摘要:

8 Aliphatic Compounds Part (i) Hydrocarbons By D. F. EWlNG Department of Chemistry The University of Hull Huii HU6 7RX 1 Alkanes The reagent lithium triethylborohydride was discovered about ten years ago but the exceptional nucleophilic power of this compound has only recently been estab- lished.' In hydrogenolysis reactions with alkyl halides this reagent has a nucleophilic reactivity ca. lo4 times greater than that of the borohydride anion. Benzyl bromide is quantitatively converted into toluene in one minute and n-octyl chloride is totally reduced in three hours. The steric effects observed over a range of reactants are typical of a SN2reaction. This reagent can be conveniently prepared in situ from LiH and Et,B in THF. Activation of the C-H bond in alkanes has been attracting renewed attention recently as several workers attempt to devise procedures which simulate the naturally occurring mono-oxygenases.A typical catalytic species is a manganese tetraphenyl- porphyrin (TPP) complex incorporating an oxidizing ligand such as iodosylben- ~ene,~,, and isobutane for example can be converted into t-butyl alcohol in 25% yield. A variant on this is a triphasic system consisting4 of an organic solvent containing the substrate and the catalyst Mn(TPP)X an aqueous solution of the salt NaX (X = I Br C1 N3 or NCO) and the sparingly soluble oxidant iodosylben- zene. With this system both RX and ROH are formed in reasonable yield. Even more interesting is the ability of Mn(TPP)Cl to activate hydrocarbons towards oxidation by molecular oxygen in the presence of sodium ascorbate in aqueous buffer containing some phase-transfer reagent.' Although none of these various systems is of practical use yet there is great potential in this area.Another example of selective oxidation of unactivated alkanes is the reaction with Pb( OCOMe) under thermal ( 18 h) or photochemical conditions (6 h).6 Acetoxyla- tion occurs exclusively at secondary sites but these derivatives are not precursors to the polymeric material that is also formed. A free-radical mechanism seems likely for this reaction. ' S. Krishnamurthy and H. C. Brown J. Org. Chem. 1983,48 3085. * J. A. Smegal and C. L. Hill J. Am. Chem. SOC.,1983 105 2920. J. A. Smegal B. C. Schardt and C. L. Hill J.Am. Chem. SOC. 1983 105 3510 3515. C. L. Hill J. A. Smegal and T. J. Henly J. Org. Chem. 1983 48 3277. D. D. Mansuy M. Fontecave and J.-F. Bartoli J. Chem. SOC.,Chem. Commun. 1983 253. R. D. Bestre E. R. Cole and G. Crank Tetrahedron Lett. 1983 24 3891. 151 152 D. E Ewing 2 Alkenes Synthesis.-From Alkynes. The B-bromo-derivative of 9-borabicyclo[3.3. llnonane (1) reacts' regioselectively (99'%0) with terminal alkynes to give the Markovnikov haloboration adduct (Scheme 1). This procedure is ineffective for internal alkynes and for all types of alkenes and provides a route to 2-halogeno-alkenes in 80-100% yield. The alkenylborane reacts with lithium acetylides to afford a 2-1-alkynyl-2-bromo-1-alkene. 2-Iodo-derivatives can also be obtained by this method.' Hydrobor- ation of alkynes with the alkyl borane complex RBHBr.SMe2 has been extended' to internal alkynes.The resulting alkylalkenylborane may be deboronated with iodine (Scheme 1) or converted via a borinate ester into an alkylalkenylalkynyl- borane" in ca. 75% yield. No doubt these novel boranes will bi further exploited. B(9-BBN) BBr + R'Cr CH -BrH9 R' R'BrC=CH (1) (9-BBN)Br Br R' RZ ii HHBR._K' H)=4BR OM R' R' R' R' Reagents i MeC02H; ii LiC=CR2; iii R*BHBr.SMe,; iv MeONa-MeOH v I,-MeOH Scheme 1 In contrast to work on catalysis by palladium and nickel complexes relatively little study has been made of iron compounds even although they are less expensive. It is now reported" that the complex Fe(PhCOCHCOPh) acts as a cross-coupling catalyst in the reaction of PhCH=CHBr with ArMgBr at -20 "C to afford substituted ' S.Hara H. Dujo S. Takinami and A. Suzuki Tetrahedron Letf. 1983 24 731. S. Hara Y. Satoh H. Ishiguro and A. Suzuki Tetrahedron Lett. 1983 24 735. H. C. Brown and D. Basavaiah J. Org. Chem. 1982 47 5407. lo H. C. Brown D. Basavaiah and N. G. Bhat Organometallics 1983 2 1468. " G. A. Molander B. J. Rahn and D. C. Shubert Tetrahedron Letf. 1983 24 5449. Aliphatic Compounds -Part (i) Hydrocarbons I53 stilbenes. Yields are 75-1 00% with the homo-coupled species as the principal by-product and although this compares unfavourably with Pd/ Ni catalysis in most cases iron catalysts of this type are worth further investigation.By Elimination. An efficient general method for the desulphonation of a,P -unsatur-ated sulphones involvesi2 preliminary addition of tributylstannyl-lithium in THF at -78 "C. Elimination of a stannyl-sulphone is then smoothly effected at 20 "C by stirring with SO2 to give the alkene in 65-98% yield. The inherent reducing ability of sulphide or hydrogen sulphide anions is often obscured by their strong nucleophilicity. Two methods of circumventing this difficulty have been described. The firstI3 relies on transferring the reaction to an aprotic solvent using a suitable phase-transfer agent. For example in favourable cases vicinal dibromides (in benzene if necessary) are converted into the corresponding alkene by NazS in water in the presence of a small amount of trioctylmethylam- monium chloride.This debromination reaction uses inexpensive reagents is stereo- specific (anti-elimination) tolerates the presence of carbonyl groups and works for a wide variety of aliphatic and cyclic systems. Another interesting appr~ach'~ to this problem involves anchoring a sulphide reagent on cross-linked polystyrene. Poly(chloromethy1styrene) is easily converted into poly(styrylmethylthio1) which as a sodium salt quantitatively produces styrene from the analogous dibromo-compound. However with 1,2-dibromo-octane a significant amount of dehydro- bromination also occurs. An extensive report has ap~eared'~ concerning the synthesis of olefins from p-nitro-esters and P-nitro-ketones. This work has been in progress for several years and involves for example the coupling of 2-bromo-2-nitropropane with anions of the type RC(CN)CO,Et followed by heating in an aprotic solvent with LiBr.Both NOz and C0,Et groups are smoothly eliminated to give an a$-unsaturated nitrile in up to 70% yield for a one-pot reaction. From Carbonyl Compounds. In recent years Barluenga and co-workers have elabor- ated a one-pot synthesis of olefins from a-chloro-carbonyl compounds. Two further extensions to this synthetic method are shown in Scheme 2. Successive addition of two different Grignard reagents to a suitable a-chloro-acid chloride (2) followed by the usual treatment with lithium powder gives a tetrasubstituted alkene.I6 A wide variety of alkyl groups R' to R4is possible and there is little contamination from double addition of either Grignard reagent.However overall yields are variable 40-100%. The second variation" uses a Nierenstein chloromethylation reaction to generate an a-chloro-ketone (3) followed by reaction with a Grignard reagent to form a terminal alkene. Both these routes to alkenes can be further extended by the use of LiAIH as the final nucleophilic reagent leading to two further types of olefin (Scheme 2). Some eighty alkenes were synthesized by these four reactions. '' M. Ochiai 1. Ukita and E. Fujita 1.Chem. SOC.,Chem. Commun. 1983 619. l3 J. Nakayama H. Machida and M. Hoshino Tetrahedron Lerr. 1983 24 3001. . V. Janout and P. Cefelin Tetrahedron Lett. 1983 24 3913. Is N. Ono R. Tamura H. Eto I. Hamamoto T.Nakasuka J. I. Hayami and A. Kaji J. Org. Chem. 1983 48 3678. l6 J. Barluenga M. Yus J. M. Concellon and P. Bernad J. Org. Chem. 1983 48 609. " J. Barluenga M. Yus J. M. Concellon and P. Bemad J. Org. Chem. 1983 48 3116. 154 D. F. Ewing 0 0 R1R2C-C // I c1 \c1 \ R' R2C =CHR3 (2) R'R~C=CH Reagents i R3MgBr -78 "C; ii CH2N2-ether HCI-ether; iii R4MgBr -60 "C;iv LiAIH,-AICI, -60 "C; v R2MgBr-MgBr, -60 "C; vi Li powder -60 to 20 "C Scheme 2 A Wittig alkene synthesis has been achieved18 by passing a stream of gaseous benzaldehyde at 150 "C over a bed of solid K2C03 mixed with a suitable phos- phonium salt and some liquid Carbowax 6000 a procedure described as 'gas-liquid phase-transfer catalysis'. The alkene is obtained by condensation from the reactor effluent and is entirely free from phosphine oxide which is retained on the solid reaction bed.Although conversion rates can be up to 100% the recovery of alkene is usually much lower. Reactions.-Recent interest in modelling the reductive activation of dioxygen that is achieved by haem-containing mono-oxygenases was noted above. A further example" of this interest is the discovery that a combination of rhodium octaphenyl- porphyrin NaBH, and O2 constitutes an excellent system for the oxygenation of alkenes. Oxidation to the alcohol (e.g. octanol cyclohexanol) is anti-Markovnikov and the catalyst has a turnover number of at least 200. Another exploration of this area involves2' anchoring the catalyst the complex manganese (TPP) acetate to a rigid polymer support.Using this solid catalyst the efficiency of epoxidation of cyclohexene by sodium hypochlorite is ca. 3 times greater than with a soluble manganese species. The site-isolating effect of the polymer is probably akin to the effect of the protein in enzymes. Two new procedures for epoxidation of alkenes with aqueous H202 have been described both relying on the high rate of reaction in an organic solvent such as CH2CI2.Using an aqueous solution of sodium tungstate sodium phosphate and hydrogen peroxide with a suitable phase-transfer catalyst alkenes in CH2CI2 are epoxidized in yields of 70-80% and the H202 is totally consumed.2' Trichloracetonitrile in 30% H202 acts as an effective oxygen transfer reagent presumably via a peroxyimidic acid intermediate.22 It is a useful alternative to m-chloroperbenzoic acid and probably a more suitable reagent for large-scale work.E. Angeletti P. Tundo and P. Venturella J. Chem. SOC.,Chem. Commun. 1983 269. l9 Y. Aoyama T.Watanabe H. Onda and H. Ogoshi Tetrahedron Leu. 1983 24 1183. 2o A. W. van der Made J. W. H. Smeets R. J. M. Nolte and W. Drenth J. Chem. Soc. Chem. Commun. 1983 1204. " C. Venturello E. Alneri and M. Ricci J. Org. Chem. 1983 48 3831. L. A. Arias S. Adkins C. J. Nagel and R. D. Bach J. Org. Chem. 1983 48 888. Aliphatic Compounds -Part ( i) Hydrocarbons In the presence of cupric acetate peroxydisulphate in acetic acid converts aryl- alkenes into the bisacetoxyl derivates in 70-90% yield.23 Donor substituents in the aryl ring increase the yield and improve the selectivity but a complex mixture of products is obtained in the absence of a catalyst.Silver ion catalysis gives benzal- dehydes. An enantioselective cis-hydroxylation catalyst has been generated24 by incorporating an osmate ester into bovine serum albumin. Oxidative hydrolysis of alkene-catalyst complex with t-butyl hydroperoxide gives the corresponding diol. The highest enantiomeric excess (68%) was observed with a-methylstyrene but the S-configuration predominates in all cases. Brown and co-~orkers~~ have evaluated dibromoborane-methyl sulphide (DBBM) (4) as a hydroborating reagent in a9 exhaustive comparison with 9-BBN (9 disiamylborane (6) and thexylchloroborane-methyl sulphide (7) using a series of 22 alkenes and five alkynes.All four boranes show about the same reactivity with terminal alkenes but P-branching results in a much greater reduction in the reactivity of (6) and (7) compared to (4) and (5). The borane DBBM shows only a small selectivity for cis-alkenes but has a high selectivity (20 times more reactive than any of the other three boranes) for tri- and tetra-substituted olefins. This new borane also shows high selectivity for internal alkynes and hence complements 9-BBN which has the opposite selectivity. Further work26 with 9-BBN has shown that it is not a specific hydroborating reagent for trans-alkenes contrary to earlier claims. In fact the relative reactivity of cis/ trans pairs towards 9-BBN is unpredictable. Catecholborane (8) has also been evaluated27 but this compound is generally less selective than other hydroborating reagents.Br,BH.SMe (Me,CHCHMe),BH (4) (6) (5) Me,CHCMe,BHCI ao\B" &LBH (7) 'd A new preparation of di-isopinocampheylborane (9) in 99% diastereomeric purity provides access to alcohols in 92-98% enantiomeric purity via the hydrobor- ation and oxidation of terminal alkenes.28 Hindered alkenes react more slowly and this results in poorer asymmetric induction. Mono-isopinocampheylborane29 is a more effective reagent with up to 92% induction for some trans-alkenes. In contrast the optical selectivity is much less for reactions involving cis-alkenes or trisubstituted 23 A. Citterio C. Arnoldi C. Giordano and G. Castaldi J.Chem. Soc. Perkin Trans. 1 1983 891. 24 T. Kokuba T. Sugimoto T. Uchida S. Tanimoto and M. Okano J. Chem. SOC.,Chem. Commun. 1983 769. 25 H. C. Brown and J. Chandrasekharan J. Org. Chem. 1983 48 644. 26 H. C. Brown D. J. Nelson and C. G. Souten J. Org. Chem. 1983,48 641. '' H. C. Brown and J. Chandrasekharan J. Org. Chem. 1983 48 5080. 28 H. C. Brown M. C. Desai and P. K. Jadhav J. Org. Chem. 1982,47 5065. 20 H. C. Brown P. K. Jadhav and A. K. Mandal J. Org. Chem. 1982 47 5075. 156 D. F. Ewing alkenes as might be expected. Reduction of activated double bonds such as that in acrylonitrile can be achieved3* in excellent yield (85-100°/~) with Zn-Cu in MeOH an improvement over NaBH or lithium amide. The reagent 12-(SCN)* has been investigated in detaiL3' Under U.V.irradiation free-radical addition to alkenes gives the vicinal iodothiocyanates. However in the absence of light regioselective ionic addition occurs to give an iodoisothiocyanate. There is no evidence that the species ISCN exists. A range of ca.20 alkenes has been employed32 to investigate the addition reactions with CF30CI and CF30F. These two compounds show strikingly different modes of reaction. With CF,OCI the results are indicative of syn-addition by an electrophilic mechanism with high selectivity for Markovnikov regiochemistry and high stereospecificity whereas CF30F appears to react via a free-radical mechanism with poor regio- and stereo- selectivity. The amination of alkenes has been surveyed.33 This review concentrates on metal-catalysed addition reactions and the use of various activated aminium radicals.The addition of carboxamides and related compounds (urethanes urea) to alkenes is effectively promoted by Hg" nitrate.34 This general reaction is fairly regioselective (Markovnikov) and probably proceeds via amidomercuration-demercuration.Suc-cessive reactions with urea can afford unsymmetrically alkylated derivatives. An attractively simple method35 for the direct bis-amination of unactivated alkenes is shown in Scheme 3. The nitrogen source cyanamide is inexpensive and diamines can be obtained in 50-70% yield with almost complete stereospecificity. This procedure also provides useful routes to aziridines and imidazoles. Br Br RCH=CH 2RLH-CH 2RLH-CH I NHCN 'NH ci HN=C / RHC-CH, \/ RHC-CH CH2 Reagents i Cyanamide-N-bromosuccinimide; ii EtOH-HCI ; iii NaOEt; iv Et,N-NaHCO ; v NaI ; vi Ba(OH) Scheme 3 3lJ R.L. Sondengam Z. T. Fomum G. Charles and T. M. Akam J. Chem. SOC.,Perkin Trans. I 1983 1219. '' R. C. Cambie P. S. Rutledge G. A. Strange and P. D. Woodgate J. Chem. SOC.,Perkin Trans. I 1983 553. 32 K. K. Johri and D. D. Desmarteau J. Org. Chem. 1983,48 242. 33 M. B. Gasc A. Lattes and J. J. Perie Terruhedron 1983 39 703. 34 J. Barluenga C. Jimenez C Najera and M. Yus J. Chem. SOC.,Perkin Tmns. I 1983 591. 75 H. Kohn and S.-H. Jung J. Am. Chem. Soc. 1983 105 4106. Aliphatic Compounds -Part ( i) Hydrocarbons Cyclic addition of dipolar species to alkenes is a common route to heterocyclic systems and is generally beyond the scope of this report.However one repod6 is of interest since it describes alkene functionalization and demonstrates how old reagents can be reinvestigated with interesting results. Both cyanogen oxide (10) and ethoxycarbonylformonitrile oxide ( 11) react with alkenes to form cyclic adducts the corresponding isoxazolines (Scheme 4). Reagent ( 10) is formed from chloral hydrate and hydroxylamine but (1 1) is more conveniently available from glycine ethyl ester hydrochloride and is the preferred dipolar species especially since it generally gives higher yields of adduct. Decarboxylative ring-opening of the isoxazo- lines affords p-hydroxy-nitriles in 70-90% yield. Another convenient source of a suitable dipole for this type of olefin functionalization is 2-nitroethanol which can be converted into (12) thus leading ultimately to p-hydroxy-carboxylic acids.R' .. ... b11 111 'CHOH I /EtO D' " C0,Et CHCN /R' [ROCH,C r k-01 (12) Reagents 1 R'CH=CHRZ-Na2C0,; ii NaOEt; iii Heat Scheme 4 A very thorough study has been reported3' of the addition reaction of benzenesul- phenyl chloride. The results are generally unexceptional and support the view that addition occurs with little charge localization at the olefinic carbon atoms. There is a significant solvent effect on the rate of addition (lo4 increase in CHC13 compared to CCl for addition to styrene) suggesting that the transition state involves substantial polarization of the S-C1 bond.Chlorotelluration with TeCl involves both syn and anti modes of addition the latter by a radical me~hanism.~~ In contrast 2-naphthyltel- luronium trichloride reacts stereospecifically giving the trans-product uia a cyclic telluronium ion. Thus both stereoisomers may be formed by choice of reagent. Complexation of an unsaturated compound (such as methacrylic acid) with cyclodextrin provides a highly asymmetric environment around the double bond.39 This results in extremely high enantiomeric excess (up to 100°/~)in addition reactions where the crystalline complex is exposed to the reagent vapour (Clz Br, HBr). Stereochemical control of this calibre is most intriguing especially since the corre- sponding homogeneous solution reaction shows much poorer enantioselectivity.36 A. P. Kozikowski and M. Adamczyk J. Org. Chem. 1983 48 366. 37 G. A. Jones C. J. M. Stirling and N. G. Bromby J. Chem. Soc. Perkin Trans. 2 1983 385. 38 J.-E. Backvall J. Bergmann and L. Engmann J. Org. Chem. 1983 48 3918. 39 Y. Tanaka H. Sakuraba and H. Nakanishi J. Chem. Soc. Chem. Commun. 1983 947. 158 D. F. Ewing This reaction is a genuine example of asymmetric induction since optical resolution of the halogeno-compounds by cyclodextrin gives rise to an excess of the other enantiomer. Two reports of substitution reactions of alkenes have appeared this year both dealing with acylation. Ethylaluminium chloride is an effective Lewis acid4* and a,P-unsaturated ketones can be obtained in 40-64% yield by acylation with acid chlorides or anhydrides using only one equivalent of the catalyst.A more unusual catalyst system is Zn-Cu-CH212. Although the precise nature of the catalyst is not known4' this system shows high selectivity for acylation of alkenes with acid chlorides (no reaction with arenes) the yields are good (over 70%) and the regiocontrol is fully Markovnikov. There may be further interesting Lewis acids to come from this area. Bis(tosy1)sulphur di-imide may be used for allylic amination but yields are low. The analogous bis(methoxycarbony1)sulphur di-imide (MeOCON),S is found4 to be more effective and convenient but yields are still only moderate. A similar shortcoming is found with the oxidation of allylpalladium complexes using a MoO,(acac)-Bu'OH catalyst.43 The selectivity for hydroxylation at the internal allylic carbon is ca.90% but overall conversion is only 50%. 3 Polyenes Synthesis.-A radically new approach44 to the synthesis of substituted allenes is shown in Scheme 5. Starting with a geminally disubstituted allene this two-step one-pot procedure effectively replaces the unsubstituted terminal carbon with the carbon moiety of an aldehyde or ketone. Although the yields are variable (50-80% over the eight examples given) this method is general in application and experi- mentally convenient. R3 RZ R4 Reagents i 15 mins at 20°C; ii R3R4C0 Scheme 5 Direct alkylati~n~~ of a 1,3-dien-2-01 phosphate with an organocuprate reagent results in a transformation to the corresponding allene (Scheme 6).A combination of a copper(r) salt (2%) and tetrakis(tripheny1phosphine)palladium (1 YO)is a good 40 B. B. Snider and A. C. Jackson J. Org. Chem. 1982 47 5393. 41 T. Shono I. Nishiguchi M. Sasaki H. Ikeda and M. Kurita J. Org. Chem. 1983 48 2503. 42 G. Kresze and H. Miinsterer J. Org. Chem. 1983,48 3561. 43 K. Jitsukawa K. Kaneda and S. Teranishi J. Org. Chem. 1983 48 389. 44 S. L. Buchwald and R. H. Grubbs J. Am. Chem. SOC.,1983 105 5490. 45 A. Claesson A. Quader and C. Sahlberg Tetrahedron Lett. 1983 24 1297. Aliphatic Compounds -Part (i) Hydrocarbons 159 Reagent i RMgBr-Cu' salt Scheme 6 catalyst for the coupling46 of allenyl bromide to an alkyne RC=CH (R = alkyl aryl or hydroxyalkyl).The yield is 70-90% and the active species are probably a r-allylic Pdo complex and a copper( I) acetylenide. Both these coupling reactions merit further investigation. Another interesting coupling reaction4' is that between the butadiene Grignard reagent CH2=CH-C(MgBr)=CH and an alkyl halide using Li,CuCl as catalyst. This catalyst is better than cuprous iodide since it requires lower reaction temperatures and gives higher yields with easier work-up. Alkyl bromides and iodides are more reactive than the chlorides and even aryl iodides react. Yields are from 40 to 85% over a wide range of substrates. Extrusion of the SO2 group from a-halogeno-sulphones results in formation of a new carbon-carbon double bond and this procedure has been adapted to convert vinylogous suphones into diene~.,',~~ Preliminary addition of bromomethanesul- phony1 bromide to an olefin gives the adduct RCH2CHBrCH2S02CH2Br.This is converted by base into the required vinylogous sulphone RCH,CH=CHS02CH2Br which eliminates SO2and HBr to form RCH=CHCH=CH2. This procedure (patent applied for) is an attractive method of inserting the methylidene group onto a ring or internally onto an alkene. Alkylation of penta-l,3-dienyl anion occurs with very little selectivity. In contrast pentadienedithiocarbamate [13 ; R2 = -(CH,),-] gives an anion which produces over 90% of the a-alkylated species in reactions with primary alkyl iodides (Scheme 7).50 However more bulky alkyl groups show reduced selectivity. The a-isomer is easily rearranged by two [3,3] sigmatropic shifts to the €-isomer and the vacated a-position can then be realkylated or allylated with even greater selectivity.This reaction looks like a versatile route to useful natural polyenes such as the all-trans- tetraene shown in Scheme 7. A one-pot process has been described" which is formally equivalent to the Wittig olefin synthesis. An aldehyde R'CHO an allylic alcohol R2CH(OH)CH=CH2 and triphenylphosphine react regioselectively in the presence of palladium acetyl- acetonate to produce a diene R'CH=CHCH=CHR2. The yields are not very high (30-65'/0) but as an alternative to the Wittig reaction this procedure has considerable potential. The diene (14) is unusually reactive in Diels-Alder reactions and a useful new route to this compound (Scheme 8) has allowed further investigation of its reaction with several dienophile~.~~ 46 T.Jeffery-Luong and G. Linstrumelle Synthesis 1983 32. 47 S. Numomoto Y. Kawakami and Y. Yamashita J. Org. Chem. 1983 48 1912. 48 E. Block and M. Aslam J. Am. Chem. SOC.,1983 105 6164. 49 E. Block M. Aslam V. Eswarakrishnan and A. Wall J. Am. Chem. SOC.,1983 105 6164 6165. 50 T. Hayashi I. Hori and T. Oishi J. Am. Chem. Soc. 1983 105 2909. 5' M. Moreno-Mafias and A. Trius Bull. Chem. SOC.Jpn. 1983 56 2154. 52 F. Zutterman and A. Krief J. Org. Chem. 1983 48 1135. 160 D. F Ewing SCNRI II R1 liii CH2CH=CH2 R'A S C N RSII IV R' SCNRz II S Reagents i Lithium diethylamide -78 "C; ii R'I; iii Reflux in toluene; iv LDA at -78 "C CH,=CHI; v MeI-LiF-Li,CO in DMF Scheme 7 Reagents i CuI-THF ally1 bromide; ii MeOS0,F; iii KOH-DMSO Scheme 8 Reactions.-A very thorough review of allene chemistry has been presented by Smadja.531tcovers reactions such as protonation halogenation epoxidation and a range of reactions of derivatives.Addition reactions of PhSeS0,Ar have been extensively studied in recent years (cJ Ann Rep. Progr. Chern. Sect. B 1981 78 152; 1982 79 145). The reaction with allene~~~ under free-radical conditions gives a quantitative yield of the adduct with the ArS0 moiety on the central carbon (Scheme 9). With alkene and alkyne adducts oxidation to the selenoxide results in elimination of PhSeOH but this does not occur with allene adducts.A [2,3]-sigmatropic rearrangement leads to a selenate which can be hydrolysed to a hydroxy-sulphone in 75-90'/0 overall yield. Direct hydrosulphonation of 1,3-dienes with a 53 W. Smadja Chem. Ret.. 1983,83 263. 54 Y.-H. Kang and J. L. Kice Tetrahedron Left. 1982 23. 5374. Aliphatic Compounds -Part (i) Hydrocarbons J OSePh I R' C H =C -CR2R30H tR'CH =C-CR2R3 I I ArSO ArSO Reagents i ArSO,SePh hv; ii H,O,; iii H20 Scheme 9 sodium alkylsulphinate is effectively catalysed by palladium chloride presumably uia a .rr-ally1 complex. The regiochemistry and stereochemistry of this addition reaction have been studied in detail.55 Sodium neophylsulphinate gave complexes with good solubility and good stereocontrol. Steric effects largely dictated which regioisomer was formed.Treatment of the complex with dimethylglyoxime always gave a 2-alkene irrespective of the initial stereochemistry. Palladium-catalysed reaction of a vinylic bromide with a conjugated diene in the presence of a base can either result in an addition reaction involving the base (such as aniline) or result in elimination from the .rr-allylic complex to form the triene corresponding to direct coupling (Scheme 10). Further of this reaction reveals that conjugation of one or both of the unsaturated moieties with a C02R group leads to the formation of trienes in improved but still variable yield. The reaction shown in Scheme 10 gives the trienoic acid in 40% yield with a small loss in stereochemical homogeneity at the terminal double bond (70% E-isomer 30% 2-isomer).Treatment of dienes with two equivalents of (15) gave a tetraene in moderate yield (52% with butadiene) and a similar reaction with hexatriene gave a pentaene in 36% yield. Polymerization is a serious problem with all of these reactions. Reagent Pd(OAc),-Ar,P-excess Et,N 100 "C 24 h Scheme 10 5s Y. Tamaru Y. Yamada M. Kagotani H. Ochiai E. Nakajo R. Suzuki and Z.-I. Yoshida J. Org. Chem. 1983 48 4669. W. Fischetti K. T. Mak F. G. Stakem J.-I. Kim A L. Rheingold and R. F. Heck J. Org. Chem. 1984 48. 948. 162 D. F. Ewing A thorough +investigation of the+ reaction of nucleophiles with the novel diene derivative Me2SCH=CHCH=CHSMe2 has been rep~rted.~' Most oxygen nitrogen sulphur and carbon nucleophiles give 1,4-addition with subsequent elimination of the sulphonium groups.Exceptionally weak nucleophiles such as the anions of enolizable carbon acids do not react. The usual mechanism seems to operate for primary amines but the resulting enamines are not stable. The final reaction to be discussed in this section is the hydroformylation of 1,6-diene~.~~ This type of compound undergoes addition specifically at the terminal olefinic bond in the presence of Rh(H)CO(PPh,), and this catalyst also shows good selectivity for the regiochemistry corresponding to the n-carbaldehyde. 4 Alkynes Synthesis.-In principle the formation of a vinyl cation by alkylation of a monosub- stituted alkyne can lead to addition or elimination products (Scheme 11).This Hl / RCECH +Ph,CHOX -r RC=C (16) \CHPhJox-1+ .J\ RC(OX)=CHCHPh RCECCHPh Scheme 11 reaction has been attempteds9 by generating the required cation from for example the triflate ester (1 6) itself prepared in situ from silver trifluoromethanesulphonate and the alkyl halide. Although significant amounts of a disubstituted alkyne were formed further development is required to make this procedure into a useful route to alkynes. A complex of propargyl acetate and Co,(CO) is effectively a source of propargyl cation. Reaction of this complex with trialkynylallanes followed by mild oxidative demetallation with cerium ammonium nitrate gives a 1,4-diyne. This is a convenient and flexible route to such compounds and several unknown derivatives were obtained in this way.60 Some chiral alkynes have been obtained by a stereo-specific bromination-double dehydrobromination sequence.,' Reactions.-Two papers62363 describe the attempted hydrocyanation of alkynes and a,w-alkadiynes without the use of HCN.The cyanocobalt complex [Co(CN),I3- in the presence of H2 gives a mixture of alkyl cyanide (60-100%) alkenyl cyanide (10-44%) alkene (5-20%) and substantial amounts of alkane. Clearly the specific- ity of this catalyst is not high but rather better results are obtained with a nickel complex in the reaction with diynes. If the reductant is Zn-H,O most diynes give high yields (over 90"/0) of the dinitrile MeCH(CN)(CH,),,CH(CN)Me with none of 57 P. J. Duggan J. K. Leng D. R. Marshall and C.J. M. Stir!ing J. Chem. SOC.,Perkin Trans. f 1983 933. R. Grigg G. J. Reiner and A. R. Wade J. Chem. SOC.,Perkin Trans. I 1983 1929. F. Marcuzzi and G. Modena J. Org. Chem. 1982,47 4577. S. Padnamabhan and K. M. Nicholas Tetrahedron Lett. 1983 24 2239. 58 59 60 6' A. M. Caporusso and L. Lardicci J. Chem. SOC.,Perkin Trans. I 1983 949. ..62 T. Funabiki Y. Yamasaki Y. Sato and S. Yoshida J. Chem. SOC.,Perkin Trans. 2 1983 1915. 63 T. Funabiki Y. Sato and S. Yoshida Bull. Chem. SOC.Jpn. 1983 56 2863. Aliphatic Compounds -Part (i) Hydrocarbons 163 the other regioisomers. Less selectivity was found with other reducing conditions such as NaBH,-H20. The solvomercuration of internal alkynes in an aliphatic amine solvent has been studied in The structure of the intermediate mercury species is postulated and the factors controlling the nature of the products (amines enamines) are described.A solvent interaction involving MeOH has been dis- covered65 in the'addition of the elements of trimethylstannane to terminal alkynes. In the presence of 60 equivalents of MeOH an 80% or greater yield is obtained with the complex Me,SnCu.Me,S in THF although the regiospecificity is not very high (up to 30% of the 1-stannyl derivatives). In the absence of MeOH the yield of adduct is much reduced. A further report66 on the addition of phenylarylselenosulphonates ArSO,SePh to alkynes confirms an earlier observation of high anti-Markovnikov selectivity and anti-stereochemistry.Conversion of the adduct into the selenoxide usually results in elimination of benzeneselenenic acid to give an alkynyl sulphone. However if no vinylic hydrogen is present in the p-position elimination with an allylic hydrogen occurs to give an allene.67 If neither vinylic nor allylic hydrogens are available the selenoxide is very stable but will undergo base-catalysed fragmentation to an allylic alcohol and other products. Following on from previous work on alkenes the reagent system PdCl,-CaCl,- HC1-CO-0,-ROH has been applied to the hydroesterification of alkynes.6s As an example acetylene is quantitatively converted into a mixture of maleic (85%) and fumaric (15%) esters. Other terminal alkynes show the same high yield of esters but with lower stereoselectivity.In contrast internal alkynes can only be converted into monoesters. This reaction appears to offer some advantage over established pro- cedures particularly the high cis-selectivity. A somewhat more unusual alkyne carbonylation reaction69 is shown in Scheme 12. The furanone derivative was formed in 87% yield using Rh4(CO),* and NaOAc but other rhodium species and other bases were inferior. This catalyst system was useful even at a relatively low pressure of CO (ca. 10 atm). R' R2 \/ czc Reagent CO-N~OAGR~,(CO),,-E~OH 125 "C Scheme 12 Specific activation of the 3-yne moiety in 1,3-diynes is produced by a l-Me3Si Thus reduction of RCrCCzCSiMe with Li(A1HBui2Bun) is totally regio- specific and stereospecific giving a 3-trans-en-1-yne in 95% yield.This is a remark- able activation towards nucleophilic reduction (hydroalumination) and increases 64 J. Barluenga F. Aznar R. Liz and R. Rodes J. Chem. Soc. Perkin Trans. I 1983 1087. 65 E. Piers and J. M. Chong J. Chem. Soc. Chem. Commun. 1983 934. 66 T. G. Back S. Collins and R. G. Kerr J. Org. Chem. 1983 48 3077, 67 T. G. Back S. Collins V. Gokhale and K.-L. Law J. Org. Chem. 1983 48 4776. 68 H. Alder B. Despeyroux and J. B. Woell Tetrahedron Lerr. 1983 24 5691. 69 T. Mise P. Hong and H. Yamazaki J. Org. Chem. 1983 48 238. 70 J. A. Miller and G. Zweifel J. Am. Chem. Soc.,#1983 105 1383. 164 D. F. Ewing the usefulness of diynes. The enyne can be desilyated (KF.2H20 in DMF) or subjected to furth,er hydroalumination to produce 1-E73-Z-butadienes.The reaction of prop-2-ynyl-lithium with various electrophiles usually gives a mixture of acetylenic and allenic products owing to the rearrangement of the prop-2-ynyl species (I 7) to the dienic species (1 8) and (19). Thus the ratio of the corresponding products (20) and (21) of the addition of propylene oxide (R2 = CH,CHOHMe) is 45 :55. However in the presence of 0.5 equivalents of hexamethyl- phosphoramide the allenic isomer (2 1) forms 87% of the products." Furthermore R'CECCH,Li R'C=C=CH,I Li 7R'C=CHLi I H (17) il8) (19) R'CrCCH2R2 RI R2C=C=C H RICH =C=C H R~ (20) (21) !22) when the lithium species (17) is maintained at -75 "C in presence of a five-fold excess of HMPA it is largely converted into the more stable species (19) and the major product of alkylation is (22) in most cases.Generation of (19) from the corresponding allenyl bromide followed by alkylation or hydroxyalkylation in the presence of HMPA shows little tendency to produce (17). It is thought that the presence of excess HMPA loosens the ion-pair structure of (17) allowing rearrange- ment to the thermodynamically preferred form (19). " C. Huynh and G. Linstrumelle J. Chem. Soc. Chem. C'ommun. 1983 1133.

ISSN:0069-3030    

DOI:10.1039/OC9838000151

出版商:RSC    

年代:1983

数据来源: RSC

摘要:

8 Aliphatic Compounds Part (ii) Other Aliphatic Compounds By B. V. SMITH Department of Chemistry Chelsea College Manresa Road London SW3 6LX 1 Alcohols and Ethers The formation of alkanes by deoxygenation of an alkyl tosylate with Bu,SnH-NaI or by pyrolysis/photolysis of an alcohol proceeds efficiently.' Appropriately sub- stituted systems underwent ring closure in a process believed to involve free-radical intermediates (Scheme 1). Chemoselective reduction of an acid group by NaBH,- N,N-dimethylchloromethyleneiminiumchloride is possible in the presence of func- tional groups e.g. Hal C02R CN and alkene; cyano- and nitro-groups in ketones and esters were not reduced by LAH-silica gel whereas the carbonyl groups were reduced in fairly good yield.' Horse liver alcohol dehydrogenase brought about rapid exchange of the pro-1-R-hydrogen in octan- 1-01.The pro-I -S-hydrogen exchanged slowly under these conditions ; both processes required the enzyme. Interestingly yeast dehydrogenase was specific for the pro-1-R-hydr~gen.~ Oxidation of alcohols by solid potassium permanganate was shown to be facilitated by sonica- tion and barium manganate was found to oxidize a wide range of alcohols (and other compounds) efficiently. Methylation of long-chain alcohols (at C-2) showed good selectivity in the presence of Ni-Pd cataly~is.~ Trialkylsilylation of a range of alcohols (and phenols and acids) was effected by Nafion-H,6 a polymeric perfluori- nated resin sulphonic acid. R (la) R = H,X = NTs; (2) (lb) R = Ph,X = 0.Reagents i Bu,SnH-Nal-AIBN-DME 80 "C Scheme 1 Y. Ueno C. Tanaka and M. Okawara Chem. Lett. 1983,795; W. Hartwig Tetrahedron 1983,39,2609. ' T. Fujisawa T. Mori and T. Sato Chem. Lett. 1983 835 Y. Kamitori M. Hojo R. Masuda T. Inoue and T. Izumi Tetrahedron Lett. 1983 24 2575. S. Shapiro T. Arunachalam and E. Caspi J. Am. Chem. SOC. 1983 105 1642. J. Yamawaki S. Sumi T. Ando and T. Hanafusa Chem. Lett. 1983 379; H. Firouzabadi and Z. Mostafavipoor Bull. Chem. SOC.Jpn. 1983 56 914. ' J. Sabadie and G. Descotes Bull. SOC.Chim. Fr. II 1983 253. G. A. Olah A. Husain and B. P. Singh Svnrhesir 1983 892. 165 166 B. V. Smith Structural and chemical evidence was advanced to confirm the identity of an unusually stable enol (3) prepared from (4).7 Several routes to unsaturated alcohols have been reported.Metallic manganese reacts with allylic bromides and the allyl group undergoes Barbier-type addition to a carbonyi group; with an a,P -enone 1,2-addition was noted and with PhCH(Me)CHO and allyl bromide the erythro threo ratio in the product was 3 1.8 Oxidation (H202 or Bu‘OOH) of zirconium-diene (isoprene) complex gave a mixture of products in which the yield of alcohol could be optimized by use of H202;diols were obtained from cyclic precursors.’ Reduction (LAH-Et20) of acetylenic alcohol (5) was 99% cis-selective [to form (6)]only when a clear solution of reagent was used since slurries gave lower selectivity. Solvent dependence in these processes has been explored.” PhC(OMe)=C(OH)Ph PhCN,COPh (3) (4) Me,Si-CH(OH)Me Me,SiCECCH(OH)Me HAH (5) (6) Enantioselective reaction of optically active diallylbis-( 2-phenylbuty1)tin and an aldehyde led to homoallyl alcohols in 2O-8O% optical yield which was independent of solvent but did vary with R.For R = C8HI7 the product (S)-homoallyl alcohol was formed in 84% yield (82% e.e.) in a process considered to involve addition of the allyl group to the re-face of the aldehyde.” a-Substituted allyl boronates with aldehydes gave homoallyl alcohols by y-attack [RCH(OH)CH,CH=CH..-X; X = C1 Br OR or SR] with surprisingly high 2 :E ratio (e.g. R = Me X = C1 2:E = 93 :7).12 Isomerization of triple bonds in alkynols has been brought about by metal salts of amines; e.g. dec-2-yn-1-01 gave dec-9-yn-1-01 (95% 0.5 h).I3 Alkynols e.g.(lo) have been prepared from (7) (see Scheme 2); in the intermediate (8) the d.s. ratio varied from 86 14 to 97 :3 and e.e. in (10) was 70-92% .I4 Addition of silylated alkyne (I 1) to a carbonyl compound was promoted by a trace of fluoride ion and led to PhCECC(OH)R1R2 in good yield.” Advances in stereochemical control in 1,2-and 1,3-diols have been summarized and optical enrichment of asymmetric diols via stannoxanes recommended.16 A useful reversal of the erythro threo ratio in reduction of a-hydroxy-ketones has ’ J. F. McGarrity W. Cretton A. A. Pinkerton D. Schwarzenbach and H. I). Flack Angew. Chem. Int. Ed. Engb 1983 22 405. T. Hiyama M. Sawahata and M. Oboyoshi Chem. Lett. 1983 1237. H. Yasuda K.Nagasuna K. Asami and A. Nakamura Chem. Letf. 1983 955. lo M. L. Mancini and J. F. Honek Tetrahedron Lett. 1983 24,4295; J. W. Blunt M. P. Hartshorn M. H. G. Munro T. S. Lee R. S. Thompson P. R. Trebilco R. W. Vannoort and J. Vaughan Ausf. J. Chem. 1983 35 581 1387. ‘I J. Otera Y. Kawasaki H. Mizuno and Y. Shimizu Chem. Left. 1983 1529. l2 R. W. Hoffmann and B. Landmann Tetrahedron Lett. 1983 24 3209. l3 S. R. Abrams D. D. Nucciarone and W. F. Steck Can. J. Chem. 1983 61 1073. l4 W. S. Johnson R. Elliott and J. D. Elliott J. Am. Chem. Soc. 1983 105 2904. l5 1. Kuwajima E. Nakamura and K. Hashimoto Tetrahedron 1983 39 975. S. Masamune and W. Choy Aldrichim. Acm 1982 15 47; A. Shanzer J. Libman and H. E. Gottlieb J. Org. Chem. 1983. 48 4612. 167 Aliphatic Compounds -Part (ii) Other Aliphatic Compounds SiMe, I c I -1 + Ill Me-*Me CI HO*Me (7) R' (8) R = alkyl R'= Me I ii HO-kCZCR' iii +--R 2Me PhC=CSiMe (11) (10) (9) Reagents i TiCI4-CH2Cl2 -78 "C; ii PCC; iii KOH-MeOH Scheme 2 been reported ;zinc borohydride reduction (0 "C) favours erythro-glycol formation whereas with NaAlH2(0R) [R = MeO(CH2)20CH20-] and the t-butyldiphenyl- silyl ether (-78 "C) the threo-isomer predominates." Regioselective cyclodehydra- tion of chiral diols by (EtO),PPh, has been studied ;(S)-(+)-propane- 1,2-diol gave methyloxirane with 82% retention of configuration.A lower figure (50%) was found for the reaction of (S)-(+)-phenylethane-l,2-diol,which was rationalized in terms of decomposition of the betaine intermediates presumed to be formed." Chirality inversion in the butane-1,3-diol system has been explored and a stereoselective synthesis of a 1,3-diol derivative used as an approach to the ansa-bridge in rifamy- cin.I9 Ally1 alcohol under conditions of the water gas reaction and with a catalyst based on [a,( CO),J,gave butane- 1,4-diol in good yield.20 Derivatization of chiral alcohols (and ketones) and their separation by high-resolution gas chromatography of metal salts have been reported.21 Among several recorded preparative methods for ethers are the use of (Me0)2CH2-Me,SiI the synthesis of alkoxyalkanones preparation of (2S)-2-O-(protected)-2- hydroxypropanals from methyl L-lactate and formation of homoallylic ethers.22 Preparative methods for oxiranes include phase-transfer reaction mediated by dilute H2O2-H3O+-W02-HP0:-(in good yields) the use of (S)-malic acid as a chiral " T.Nakata T. Takana and T. Oishi Tetrahedron Lett. 1983 24 2653. P. L. Robinson C. N. Barry S. W. Boss S. E. Jarvis and S. A. Evans jun. J. Org. Chem. 1983,48,5396. '' S. Takano C. Kasahara and K. Ogawara Chem. Lett. 1983 175; W. C. Still and J. C. Barrish J. Am. Chem. SOC.,1983 105 2487. '' K. Kaneda T. Imanaka and S. Teranishi Chem. Lett. 1983 1465. 21 V. Schurig and R. Weber Angew. Chem. Suppl 1983 1130. 22 G. A. Olah A. Husain and S. C. Narang Synthesis 1983 896; J. Koshimo T. Sugawara T. Yogo and A. Suzuki Chem. Lett. 1983,933; S. K. Massad L. D. Hawkins and D. C. Baker J. Org. Chem.1983 48 5180; H. Sakurai Y. Sakata and A. Hosomi Chem. Lett. 1983 409. 168 B. V. Smith building block a regio- and stereo-specific formation and ring closure of iodohydrins reaction of p-peroxy-substituted free radicals and epoxidation mediated by iron- porphyrin complexes with oxygen transfer from PhI0.23 In this latter report cis trans selectivity for cis-and trans-but-2-ene was -6 1 ; surprisingly trans-stilbene failed to react under conditions in which the cis-isomer gave 77% yield. With prochiral substrates and chiral complexes e.e. varied from 0% (1 -methyl- cyclohexene) to 5 1'/o (4-chlorostyrene). Palladium-catalysed reaction between a halogenocarbonyl compound and a keto- or allyl-tin gave good yields of cyclic ethers and+a small e.e.(19'/0) was reported in the most favourable case. Telluronium ylides (R,TeCHCH=CH,) with aldehydes gave oxiranes with reasonable Z-selec- tivity; e.g. C7HI4Oafforded a 68 32% Z/ E mixture.24 The adverse role of water in the Sharpless epoxidation has been stressed and a comprehensive summary of synthetic applications with an evaluation of the mechanism of tartrate-mediated reactions presented. A general review of preparative/synthetic applications has also appeared.25 Ring-opening of trans-I ,2-epoxy-3-methyl- 1,3-diphenyIbutane by BF,OEt,-C,H has been studied by stereochemical and isotopic methods ; a cautionary note was that in some cases the course of reaction depended on the batch of complex used.26 Organocuprate-mediated ring-opening of racemic and chiral oxirane precursors has been applied to the synthesis of (E)-9-hydroxydec-2-enoic acid a swarm-settling pheromone of the queen honey bee.Trialkylaluminiums with 2,3-epoxy-alcohols gave (12) and (13) as major and minor products respectively; periodate oxidation of the product of ring-opening of 2,3-epoxyoctadecan-l-ol by Me3Al gave (14) in high yield (-95%) and with 92% e.e.27 Regiospecific ring-opening by organotin reagents gave alkoxytins capable of further elaboration.28 Rearrangement of unsatur- ated epoxides e.g. (1 5) + (16) has been realized by use of SnCl,-CH,Cl,; a possible intermediate is (17).29 The direction of reaction given by an acetylenic epoxide e.g. (18) and LiNEt is a function of solvent polarity; in ether-hexane a cyclopropane alcohol was formed whereas in HMPT an enynol was produced by p-elimination and rearrangement.30 SiMe, RLOH Me ClA1 Me OH (12) (13) (14) (15) 23 C.Venturello E. Alveri and M. Ricci J. Org. Chem. 1983,48 3831; D. A. Howes M. H. Brookes D. Coates B. T. Golding and A. T. Hudson J. Chem. Res.(S) 1983 9; R. Antonioletti M. D'Auria A. De Mico G. Piancatelli and A. Scettri Tetrahedron 1983 39 1765; E. J. Corey G. Schmidt and K. Shimoji Tetrahedron Lett. 1983 24 3169; J. T. Groves et al. J. Am. Chem. Soc. 1983 105 5786 5791. 24 I. Pri-Bar P. S. Pearlman and J. K. Stille J. Org. Chem. 1983 48 4629 A. Osuka and H. Suzuki Tetrahedron Lett. 1983 24 5109. 25 J. G. Hill B. E. Rossiter and K. B. Sharpless J. Org. Chem. 1983,48 3607; K. B. Sharpless et al.Pure Appl. Chem. 1983 55 589 1823; Aldrichim. Acta 1983 16,(3); A. S.Rao S. K. Paknikar and J. G. Kirtane Tetrahedron 1983 39,2323. 26 J. W.Blunt J. M. Coxon C.-E. Lim and H. A. Schuyt Aust. J. Chem. 1983 36,97. 27 A. A. Kandil and K. N. Slessor Can. J. Chem. 1983 61 1166; W. R. Roush M. A. Adam and S. M. Peseckis Tetrahedron Lett. 1983 24 1377. 28 M. Fiorenza A. Ricci M. Taddei and D. Tassi Synthesis 1983 640. 29 I. Cutting and P. J. Parsons J. Chem. SOC. Chem. Commun. 1983 1435. 30 M. Apparu and M. Barrelle Bull. SOC.Chim. Fr. 11 1983 83. Aliphatic Compounds -Part ( ii) Other Aliphatic Compounds (16) (17) (18) (S)-(+)-and (R)-(-)-3-hydroxytetrahydrofurans have been prepared in high e.e. from chiral malate esters and 2-substituted tetrahydrofurans were obtained by chirality transfer from acyclic chiral half esters in the presence of [Pd(PPh3),]-MeCN-Et3N.31 The role of actylenic diethers as an entry to derivatives of oxocarbons C,O,"- and general routes to cleavage of ethers have been ~urveyed.~' 2 Alkyl Halides Decomposition of optically active a-phenylneopentyl chloroformate gave (R)-(+)-1-chloro-1-phenyl-2,2-dimethylpropanewith optical purity greater than that of the product from treatment of the alcohol with thionyl chloride.The stereochemistry of substitution by Ph,CHLi in THF led to 20% retention of optical activity in the product (S)-(+)-P~,CHCH(P~)BU'.~~ An alternative to the Hunsdiecker reaction has been explored ;esters from N-hydroxypyridine-2-thionewere shown to decom- pose via a radical chain mechanism in the presence of CC14 BrCCl, or CHI3 to form noralkyl halides in high yield.34 Alcohols with sodium iodide in the presence of trimethylsilyl polyphosphate (PPSE) gave alkyl iodides in good yields but in some cases the reaction failed.35 Solid-solid interaction of RBr and MeCO,K catalysed by alkylammonium salts gave alkyl acetates in excellent yield and at room temperat~re.~~ Reductive dehaloge- nation of alkyl halides (LiAlH,) has been studied; a radical intermediate was proposed and trapped in the case of 6-iodohept-1-ene.Tertiary and benzylic halides with Zn(BH,) in ether were smoothly dehalogenated ; complementary studies established the usefulness and high reactivity of LiEt3BH.37 In the last case LiEt,BD is the reagent of choice for site-specific deuteriation.Tertiary halides react with Me3SiCN under the influence of SnC1,. High chemoselectivity was noted; a primary chlorine in a dihalide was not affected. Two possibilities were considered for the mechanism (Scheme 3) of this interesting reaction which affords an entry into tertiary alkanoic acids. On balance evidence from n.m.r. studies supported formation of isocyanides as intermediate^.^^ A higher degree of asymmetric induction was found in addition of (+)-2-methyl- butylmagnesium bromide to PhCHO when (+)-1-methoxy-2-methylbutane was 3' V. K. Tandon A. M. van Leusen and H. Wynberg J. Org. Chem. 1983,48 2767; G. Stork and J. M. Poirier J. Am. Chem. Soc. 1983 105 1073. 32 F.Serratosa Acc. Chem. Res. 1983 16 170; M. V. Bhatt and S. V. Kulkami Synthesis 1983 249. 33 D. A. Bright D. E. Mathisen and H. E. Zieger J. Org. Chem. 1982,47 3521. 34 D. H. R. Burton D. Crich and W. B. Motherwell Tetrahedron Lett. 1983 24 4979. 35 T. Imamoto T. Matsumoto T. Kusumoto and M. Yokoyama Synthesis 1983 460. 36 J. Barry G. Bram G. Decodts A. Loupy P. Pigeon and J. Sansoulet Tetrahedron 1983 39 2673. 37 E. C. Ashby R. N. De Priest and T. N. Pham Tetrahedron Lett. 1983 24 2825; S. Kim C. Y. Hong and S. Yang Angew. Chem. Int. Ed. Engl. 1983 22 562; S. Brandange 0. Dahlman and J. Olund Acta Chem. Scand. (B) 1983 37 141. 38 M. T. Reetz I. Chatziiosifidis H. Kiinzer and H. Miiller-Starke Tetrahedron 1983 39 961. 170 B.V. Smith R3CC1 + Me,SiCN 4R,CCN + Me,SiCI Reagents i SnCI4-CH,CI2 r.t. Either R,CCI + SnCl,sR,C' +SnCIs-~Me,SiN~CCR3SnC15- 11 Me,SiCI + NECCR + SnCI Or Me,SiCN ++ R,C+ SnC1,-=R,C-N~CSiMe,SnCls- R,C-NECCR,=R,CN=C + + SnCl + Me,SiCI li 11 R,C+ + R3CCN Scheme 3 replaced by (-)-1-isopropyl-2-methoxy-4-methylcyclohexane as solvent.39 Coupling of a chiral 1-methylheptyl halide and a-dimethylaminophenylacetonitrile,in liquid ammonia led to partially inverted product. Racemization of reagent was dependent on structure and electron transfer in the alkylati~n.~' Lithio-isobutyrophenone and (S)-(+)-2-iodo-octane reacted with inversion of configuration; some of the halide was racemized under these conditions. Inversion was found for the system Ph3SiLi- (R)-2-chloro-4-phenylbutane in THF (0 OC)."' Alkyl bromides and chlorides were found to couple with R2CuCNLi2 (thus making the use of iodides unnecessary) at -50°C in THF; thus Br(CH2)3C1 afforded BuS(CH2),C1 (89%) with R = Bus.The presence of an alkene was not a drawback as CH,=CHCH(Me)(CH,),Br gave (R = Ph) 91% of product by regioselective reaction at the terminal halide.42 An attempt was made to improve asymmetric induction in the PhX-Bu'MgX system by using nickel complexes containing chiral phosphines; up to 50% e.e. was found and the reaction was dependent on the halide Substitution of RHal by aqueous thiocyanate in a two-phase system and ion-exchanged zeolite-mediated alcoholysis have been reported.@ Alkylation (at C and 0)of MeCOCH,CO,Et by C,H,,CH(I)Me has been studied over a range of conditions and enantiomeric purities of products have been measured.45 1,2-Dibromides (and monobromides) are formed in the reaction of tosylhydrazonzs with bromine.46 Ring closure of a,@-di-iodides by Bu'Li-Et20 gave three- four- and five-membered rings in excellent yield although it failed for I(CH2)21.47 39 L.Jalander and R. Strandberg Acra Chem. Scand. (B) 1983 37 15. 40 J. Chauffaille E. Hebert and Z. Welvart J. Chem. SOC.,Perkin Trans. 2 1982 1645. 4' L. M. Jackman and B. C. Lange J. Org. Chem. 1983,48,4789; T. Hayashi Y. Okamoto and M. Kumada J. Chem. SOC.,Chem. Commun. 1982 1072. 42 B. H. Lipschutz D. Parker J. A. Kozlowski and R.D. Miller J. Org. Chem. 1983 48 3334.43 G. Consiglio F. Morandini and 0. Piccolo Tetrahedron 1983 39 2699. 44 W. P. Reeves and J. V. McClusky Tetrahedron Lett. 1983,24 1585; M. Onaki M. Kawai and Y.Izumi Chem. Lett. 1983 1001. 45 G. Bram D. Cabaret E. D'lncan N. Maigrot and Z. Welvart J. Chem. Res.(S) 1982 86. 46 G. Palmieri Tetrahedron 1983 39 4097. 47 W. F. Bailey and R. P. Gagnier Tetrahedron Lett. 1982 23. 5123. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 171 An improved procedure for vinyl iodides has appeared.48 B-Bromo- or B-iodo-9- BBN reacts readily with alkynes chemoselectively at terminal sites ; protolysis of the products gave 2-bromo- or 2-iodo-alk-1-ene~.~~ A range of saturated and unsatur- ated alkyl bromides was smoothly dehydrohalogenated by KF-A1203 in various solvents.50 Prenylation catalysed by Lewis acids of alkenes and furans has been rep~rted.~' Rearrangement of allylic structures during oxidative hydrolysis has been interpreted as involving formation of an iodoso-intermediate which undergoes [2,3]sigmatropic rearrangement (Scheme 4).52 Vinyl bromides with organozincs (from sec-alkyl Grig- nard reagents) underwent coupling in the presence of chiral Pd" catalysts with e.e.UP to 86'/0.~~ 1ii I Reagents i ii [O]; iii OH- \o Scheme 4 Highly crowded compounds such as (19) and (20) have been prepared from Bu',SiCHBr and unusual bond lengths and angles recorded. Olah's reagent (HF- C5H5N ratio 10 1) reacted smoothly with amino-alcohols ;erythro-diastereoisomers gave a product in which threo-fluoramine pred~minated.~~ Bu',SiCH =CHSiBu' [Bu',SiCHBr] (19) (20) 3 Aldehydes and Ketones Interest in the chemistry of these systems continues unabated.Principal features of published work are reported here but it is almost impossible to do justice to the skill and ingenuity of many syntheses. Preparative routes to ketones include the use of alkyl-tins to transfer one group to an acyl chloride nickel-mediated metathesis of ArCH2X and an acyl chloride clean reduction of cy -halogenocarbonyls by NaTeH reaction of cuprates and pyridyl esters and the route shown in Scheme 5 which was applied to synthesis of the 411 D. H. R. Barton G. Bashiardes and J.-L. Fourrey Tetrahedron Lett. 1983 24 1605. 49 S. Hara H. Dojo S. Takinarni and A.Suzuki Tetrahedron Lett. 1983 24 731; Synthesis 1983 1005. so J. Yamawaki T. Kawate T. Ando and T. Hanafusa Bull. Chem. SOC.Jpn. 1983 56 1885. " H. Klein A. Erbe and H. Mayr Angew. Chem. Znt. Ed. EngL 1982 21 82; Z. M. Isrnail and H. M. R. Hoffrnann Angew. Chem. Suppl. 1983 985. 52 S. Yarnarnoto H. Itami T. Tsuji and W. Nogata J. Am. Chem. SOC.,1983 105 2909. 53 T. Hayashi T. Hagihara Y. Katsuro and M. Kurnada Bull. Chem. SOC.Jpn. 1983 56 363. 54 M. Weidenbruch and H. Flott Angew. Chem. Int. Ed. Engl. 1982 21 368; G. Alvernhe S. Lacombe A. Laurent and C. Rousset J. Chem. Res. (S) 1983 246. 172 B. V. Smith RYSMe i,ii '\ iiii R\/c=o RCH,Ts -* R'/CHTS ~ R" 'Ts R' Reagents i Bu"Li -20 "C; ii R'X -78 T;iii (MeS), -78 "C; iv CuC12-SiOz r.t.Scheme 5 Douglas fir tussock moth pher~mone.~~ 7'rimethylsilyl ethers have been used as an approach to aliphatic (and alicyclic) ketones carrying t-butyl Some success was claimed for ozonation as a route to carbonyl corn pound^.^^ Several routes have been developed to a$-unsaturated carbonyl compounds. Direct dehydrogenation of saturated aldehydes has been achieved by the use of [PdC12( PhCN),]-AgOSO,CF in the presence of N-rnethylm~rpholine.~~ Yields were good. In the same paper a one-pot route uia Sn" enolates is reported. Stereodefined reaction of alkenyl-lithium cuprate with an acyl halide at low tem- perature gave an enone with >96% Z-isomer in the most favourable case.59 Alkenyl halides were coupled to Zn salts of enol ether anions in the presence of Pd" catalyst with regiospecificity retention of alkenyl stereochemistry and in good yield; a related method used silyl enol ethers of saturated carbonyl compounds and ally1 carbonate with a palladium-phosphine catalyst in (preferably) a nitrile as solvent.Ally1 ketones were prepared by a similar method ; with stannic chloride enol silyl ethers gave stannylated ketones.60 Other routes reported are acylation (by RCOC1) of an alkene in presence of Zn compounds stereoselective ring-opening of chlorosiloxycyclopropanes formylation or acylation of isoprene (as the Cp,Zr complex) a retro-Diels-Alder reaction and oxidation (by Ce'") of alkylfurans.6' Approaches to acetylenic ketones have been made by a borane-oxidation sequence the use of lithiated 2-alkynyl- 1,3-dioxanes (as oxygenated acyl anion equivalents) and through alkynyl transfer from an alkynyl boron.62 The hydroboration route has been applied to the preparation of hydroxy-ketones (and of dihydrojasmone from the appropriate precursor); a-alkoxyalkyl carbonyls have been obtained through zinc-mediated reaction of functionalized carbonyl compounds and a -chloro-a -aceto~y-ethers.~~ This latter method was elaborated 55 J.W. Labadie D. Tueting and J. K. Stille J. Org. Chem. 1983 48 4634; S.-I. fnaba and R. D. Rieke Tetrahedron Lett. 1983 24 2451; A. Osuka and H. Suzuki Chem. Lett. 1983 119; S. Kim and J. 1. Lee J. Org. Chem. 1983 48 2608; Y. Murata K. Inomata H. Kinoshita and H. Kotake Bull. Chem. Soc. Jpn. 1983 56 2539.56 C. Lion and J.-E. Dubois Bull. Soc. Chim. Fr. 11 1983 375. 57 E. Niki Y. Yamamoto T. Saito K. Nagano S. Yokoi and Y. Kamiya Bull. Chem. Soc. Jpn. 1983 56 223. 5H T. Mukaiyama M. Ohshima and T. Nakatsuka Chem. Lett. 1983 1207. 59 N. Jabri A. Alexakis and J. F. Normant Tetrnhedron Lett. 1983 24 5081. 60 C. E. Russell and L. S. Hegedus J. Am. Chem. Soc. 1983 105,943; J. Tsuki I. Minami and I. Shimizu Terrahedron Lett. 1983 24 5635 5639; Chem. Lett. 1983 1325; E. Nakamura and I. Kuwajima ibid. p. 59. 61 T. Shono I. Nishiguchi M. Sasaki H. Ikeda and M. Kurita J. Org Chem. 1983,48 2503; J.-M. Conia and L. Blanco Noun J. Chim.,1983,7,399; M. Akita H. Yasuda and A. Nakamura Chem. Lett. 1983 217; R. Bloch Tetrnhedron 1983 39 639; L.Lepage and Y. Lepage Synthesis 1983 1018. 62 H. C. Brown N. G. Bhat and D. Basaviah Synthesis 1983 885; K. J. H. Kruithoff R. F. Schmitz and G. W. Klumpp Tetrahedron 1983,39,3073;M. Yamaguchi T. Waseda and I. Hirao Chem. Lett. 1983 35. 63 H. C. Brown D. Basaviah and U. S. Racherla Synthesis 1983 886; M. T. Reetz and H. Muller-Starke Liebigs Ann. Chem.. 1983 1726. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 173 toward synthesis of glycosides. The chemistries of 1,2- and 1,4-dicarbonyl transposi- tion have been explored and a 3-ketobutyl synthon [1-(2-methyl)- 1,3-dioxolan-2-y1-2- nitroethane] has been used to generate 1,4-diket0nes.~~ Aldehydes (not ketones) were reduced by Bu,N+ BH(OAc),- in refluxing benzene except in the case of PhCOCMe,CHO where intramolecular hydride delivery was suspected.Zn(BH,), as a stable complex with DMF reduced ketones with a speed which depended on structure.65 Borane complexed with (S)-valinol gave 65-73'/0 selectivity in reduction of a prochiral ketone and high asymmetric induction (>go%) was found in reduction of keto-esters derived from (-)-8-phenylmenthol with KB( Pr'O),H. Reactivity factors and the stereochemistry of metal borohydride and aluminohydride reduction have been surveyed.66 Prochiral a -halogeno-ketones gave with 9-BBN halohydrins in good e.e. ;these were transformed into chiral epoxides or alcohols. Yeast-mediated reactions were applied to a range of halogenated ketones (and keto-esters); high yields and optical purities were noted.67 An alternative to Wolff-Kishner reactions is the use of LiAlH4-P214 in refluxing benzene; yields were variable but excellent in some cases.68 Efficient procedures for a -deuteration or a -tritiation of ketones have appeared.69 a -Bromo-ketones can be obtained by treatment of an alkene with sodium br~mite.~' Some miscellaneous reactions include an improved route to gem-diacetates (Ac,O- FeCl,) asymmetric Strecker synthesis and selective protection of carbonyl groups using silica-supported Girard's reagent.71 General surveys of alkylation reactions metal enolates homoenolates and homoenolization have appeared.72 Aldol-type reactions continue to occupy prime interest.An efficient one-pot generation and reaction of lithiated ethers ROCH,Li has been used to explore reactivity in addition processes; Bu'OMe is a hydroxymethyl anion equivalent.' The stereochemistry of products formed from enolates of alkyl t-butyl ketones and PhCHO has been explored; syn-aldols e.g.(2I) were preferred Aldehyde t-butylhydrazones via lithiated derivatives reacted with carbonyl compounds or alkyl halides to form C-trapped t-butyl azo-compounds which by isomerization and hydrolysis gave either a -hydroxy-ketones or ketones. These reagents are thus con- 64 V. V. Kane V. Singh A. Martin and D. L. Doyle Tetrahedron 1983,39,345; T. Shono and S. Kashimura J. Org Chem. 1983 48 1939; G. Rosini R. Ballini and P. Sorrenti Tetrahedron 1983 39 4127. 6T C. F. Nutaitis and G. W. Gribble Tetrahedron Lett. 1983 24 4287; B.J. Hussey R. A. W. Johnstone P. Boehm and I. D. Entwistle Tetrahedron 1982 38 3769. 66 S. Itsuno A. Hirao S. Nakahama and N. Yamazaki J. Chem. Soc. Perkin Trans. I 1983 1673; J. K. Whitesell D. Deyo and A. Bhattacharya J. Chem. Soc. Chem. Commun. 1983 802; B. Caro B. Boyer G. Lamaty and G. Jaqueu Bull Soc. Chim. Fr. U 1983 281; H. Haubenstock Top. Sfereochem. 1983 14 23 I. 67 H. C. Brown and G. G. Pai J. Org. Chem. 1983 48 1784; M. Bucciarelli A. Forni I. Moretti and G. Torre Synthesis 1983 897; T. Kitazume and N. Ishikawa Chem. Lett. 1983 237. 68 H. Suzuki R. Mosuda H. Kubota and A. Osuko Chem. Lett. 1983 909. 69 G. Rosini and R. Ballini Synthesis 1983 228; S. Hegade R. M. Coates and C. J. Pearce J. Chem. Soc. Chem. Commun. 1983 1484. 70 T.Kageyamo Y.Tobito A. Katoh Y. Ueno and M. Okawara Chem. Lett. 1983 1481. " K. S. Kochbar B. S. Bal R. P. Deshpande S. N. Rajadhyaksha and H. W. Pinnick J. Org. Chem. 1983 48 1765; D. M. Stout L. A. Black and W. L. Matier ihid. p. 5369; T. Chihara E. Waniguchi T. Wakabayashi and K. Taya Chem. Lerr. 1983 1647. 72 J. K. Whitesell and M. A. Whitesell Synthesrs 1983 517; T. Mukaiyama Pure Appl. Chem. 1983 55 1749; N. H. Werstiuk Tetrahedron 1983 39 205. 7? E. J. Corey and T. M. Eckrich Tetrahedron Lett. 1983 24 3 163 3 165. 74 C. H. Heathcock and J. Lampe J. Org. Chem.. 1983,48. 4330. 174 B. V.Smith venient acyl anion equivalent^.^^ An electron-transfer route has been claimed in reaction between lithiated pinacolone and ethyl p-nitr~benzoate.~~ Synthetic uses of silyl enol ethers and ketene acetals have been reviewed.77 Silicon derivatives have been employed in alkylation of cyanhydrin silyl ethers allylsilane- aldehyde reactions generation of Michael adducts of cis-stereochemical addition preferential erythro-selective (kinetically controlled) aldol reaction of enamino- silanes and aldehydes and stereoselective additions of t-butyldimethyl enolsilanes and aldehydes7* In the most favourable case in this last report MeC0,Bu' and PhCH(Me)CHO gave j3-hydroxy-ester with >97O/0 d.s.The Nazarov reaction (ther- mal ring closure of divinyl ketones) has been 'silicon-directed' in the transformation of (22) and (23) into (24) and ultimately to (25). The reaction affords an interesting annelation procedure and should be capable of elab~ration.~~ Diene (26) with PhCHO-[Eu(hfc),] gave a cyclic adduct transformed into (27); when R = But 38% e.e.was observed and with diene (28) 58% e.e. was noted for (29)." Me0 Me,SiO H 0' H Me Ph (26) R = Me or But (27) (28) (29) A new chiral borane B-allyldi-isopinocampheylborane(30)' gave 83-96% e.e. in production of homoallyl alcohols (from RCHO)." Ally1 boronates a j3-alkoxy- carbanion equivalent formed homoallyl alcohols with high threo erythro ratio ; 75 R. M. Adlington J. E. Baldwin J. C. Bottaro and M. W. D. Perry J. Chem. SOC., Chem. Commun. 1983 1040. 76 E. C. Ashby and W.3. Park Tetrahedron Lett. 1983 24 1667. 77 P. Brownbridge Synthesis 1983 I 85. 78 T. Mukaiyama T.Oriyama and M. Murakami Chem. Lett. 1983,985; S. E. Denmark and E. J. Weber Helu. Chim. Actu 1983 66 1655; I. Crossland and S. 1. Hommeltoft Actu Chem. Scand. (B) 1983 37 21; W. Ando and H. Tsumaki Chem. Lett, 1983 1409; C. H. Heathcock and L. A. Flippin J. Am. Chem. SOC. 1983 105 1667 S. Kiyooka and C. H. Heathcock Tetrahedron Lett. 1983 24 4765; G. Kjeldsen J. S. Knudsen L. S. Ravn-Petersen and K. B. G. Torssell Tetrahedron 1983 39 2237. 79 T. K. Jones and S. E. Denmark Helv. Chim. Acta 1983 66 2377 2397. 80 M. Bednarski C. Maring and S. Danishefsky Tetrahedron Lett. 1983 24 3451. *' H. C. Brown and P. K. Jadhav. J Am. Chem. Soc. 1983 105. 2092. Aliphatic Compounds -Part ( ii) Other Aliphatic Compounds triallylborons with lithiated phenylselenyl ethers generate linear (3 1) or branched (32) homoallyl alcohols in which the key to the product ratio is the fate of (33).82 Divalent tin enolates of achiral aldehydes reacted with 3-acetylthiazolidine-2- thione and a chiral auxiliary to form P-hydroxy-aldehydes in which optical purities of 65-90% had been induced.83 In the presence of a palladium(0) catalyst 1-bromoalk-1-enes couple with tributyltin enolates to form P,y-unsaturated ketones in good yields.84 Enantio- and diastereo-selective syntheses using chiral glyoxylate esters and allylic tin reagents gave high erythro threo ratios; tin(1r) enolates of 1,3-dihydroxypropan-2-0nederivatives reacted with MeCOC0,Me in an anti-crossed aldol process in good yield whereas the corresponding crossed reaction with 2-bromo-2-methylpropanal and RCHO gave acceptable yields of /3 -hydroxy-aldehydes8' Penta-2,4-dienyltrimethylstannane with a,P-unsaturated carbonyls did not give Diels-Alder adducts with Lewis acids but normal (1,2) addition was noted.86 New (a-ethoxyalkeny1)tins have been employed in aldolization e.g.(34) -* (35) (71Y0).'~ General reviews of Ti- and Zr-mediated reactions have appeared. Dicarbonyl (intramolecular) coupling has been used to generate cyclic ketones or alkenes.88 Titanated butynyl carbamates (which as lithiated derivatives are synthetic equivalents of MeC=CHCHO) react with carbonyl compounds regio- and diastereo-selectively in which (36) is believed to represent the transition state.89 (34) (35) (36) ML3 = TiOPr' An interesting evaluation of the role of titanium and the stereochemistry of aldolization led to the conclusions that Lewis acids had a 'stereosteering' role and that increase of pressure could reverse threo erythro ratios observed in normal reactions.A similar re-evaluation of the boat transition state in Ti- and Sn-mediated x2 P. G. M. Wuts P. A. Thompson and G. R. Callen J. Org. Chem. 1983,48,5400; Y. Yamamoto Y. Saito and K. Maruyama ibid. p. 5408. 83 N. Iwasawa and T. Mukaiyama Chem. Lett. 1983 297. x4 M. Kosugi I. Hagiwara and T. Migita Chem. Lett. 1983 839. 85 Y. Yamamoto N. Maeda; and K. Maruyama J. Gem. Soc. Chem. Commun. 1983,774; R. W. Stevens and T. Mukaiyama Chem. Left. 1983 595; J.-I. Kato and T. Mukaiyama ibid. p. 1727. 86 Y. Naruta N.Nagai Y. Arita and K. Maruyama Chem. Lett. 1983 1683. 87 J.-P. Quintard B. Elissondo and M. Pereyre J. Org. Chem. 1983 48 1559. 88 B. Weidmann and D. Seebach Angew. Chem. Int. Ed. Engl. 1983 22 31; J. E. McMurry Acc. Chem. Res. 1983 16 405; J. E. McMurry and D. D. Miller J. Am. Chem. Soc. 1983 105 1660. 89 D. Hoppe and C. Riemenschneider. Angew. Chem. Int. Ed. Eng1 1983 22 54. 176 B. V. Smith reactions has appeared." Reetz has reported on the reaction shown in Scheme 6; high erythro :threo ratios were noted. 100% N-titanation was observed with (37) and for R' = Me X = OPr' R2 = Ph the product ratio was 91 :9.Chiral P-alkoxy- aldehydes gave 1,3-asymmetric induction in Ti-mediated addition to enolsilyl ethers ; zirconium behaved similarly.'' Methenylation of ketones (and nitriles and alkynes) occurs by means of titanocene dichloride-methylenezinc iodide.92 Aldehydes in the presence of TiCl, react with 3-phenyl-3-trimethylsilylprop-1-ene to form homoallylic alcohols which could be converted into P-hydroxy-esters; thus Bu'CHO afforded (R)-Bu'CH(OH)CH,CO,Me with 9 1'/o e.e.93 Zirconocene-induced coupling of a ketone with isoprene showed reversal of regioselectivity ;high threo-selectivity was noted for addition of e.g.(E)-C,H,ZrCICp2 to EtCHO at -1 10 "C (92% j.94 Rf\ I' R+ R'CH2CH=NNMe2 c,c\ -".N (37) NMe N-NMe / TIX3 I R' R' erythro threo Reagents i LDA 0°C; ii CITi(OPr') or BrTi(NEt,), -78°C iii R'CHO -78 to -40°C Scheme 6 Regioreversal in the addition of (E)-MeCH=CHCH,MgCl to carbonyl groups occurs in the presence of A1Cl3 to form the a-adduct prefer en ti all^.^^ The reason for this is not clear but two possibilities are shown in Scheme 7.The major product (38) from 3-phenylprop- I -enylmagnesiuln chloride and PhCHO supported the 'open chain rne~hanism'.~~ Chain lengthening (Me,SiCH,MgCl-R'COR2) is a con- venient pro~ess.~' Miscellaneous reactions include addition of ally1 or benzyl halides to aldehydes catalysed by Sm" ring-opening of oxazolidines (from ephedrine) by organocuprates to give aldehydes with modest e.e. alkylation of ketones by alkenes (with Ag2S20R) YO Y. Yamamoto K. Maruyama and K. Matsumoto J. Am. Chem. Soc. 1983 105 6963; E. Nakamura and I. Kuwajima Tetrahedron Lett. 1983 24 3343 3347.91 M. T. Reetz R. Steinbach and K. Kesseler Angew. Chem. Suppl. 1982 1899; M. T. Reetz and A. Jung J. Am. Chem. Soc. 1983 105 4833. 92 J. J. Eisch and A. Piotrowski Tetrahedron Lett. 1983 24 2043. Y3 T. Hayashi M. Konishi and M. Kumada J. Org. Chem. 1983 48 281. 94 G. Erker and U. Dorf Angew. Chem. Int. Ed. Engl. 1983,22 777; K. Mashima H. Yasuda K. Asami and A. Nakamura Chem. Lett. 1983 219. 95 Y. Yamamoto N. Maeda and K. Maruyama J. Chem. SOC.,Chem. Commun. 1983,742; J. Org. Chem. 1983 48 1564. 96 J. M. Coxon G. W. Simpson P. J. Steel and V. C. Trenerry Tetrahedron Lett. 1983 24 1427. 97 C. Burford F. C'ooke G. Roy and P. Magnus Tetrahedron 1983 39 867. Aliphatic Compounds -Part ( ii) Other Aliphatic Compounds 177 t \ I (38) Reagents iii AICI, -78 "C; iv RCHO -78 "C Scheme 7 and addition of Et,Zn to PhCHO catalysed by chiral complexes of Co and Pd.98 Catalytic activity has been noted for Pd complexes (aldolization) Fe carbonyl species (trimerization of aldehydes) and organomolybdenum (Wittig-like reaction) and chiral Rh complexes (cyclization of enal~).~~ Several papers describe Michael and related reactions.Aryl halides with either Li-ZnBr or a Pd catalyst gave products of conjugate addition (of ArH).'" LiMe2Cu gave fast conjugate addition in hydrocarbon solvents when reacting with (E)-PhCH=CHCOMe; in DMF or DMSO no conjugate addition was seen."' The stereocontrol of Michael addition was probed by addition of the p-lactone enolate (39) to (2)-dimethyl butenedioate and discussed in terms of the formation of the major product (40).Addition-cyclization was also discussed in terms of control exercised.Io2 The role of L-ascorbic acid in Michael addition to acrolein was described in stereochemical terms and speculatively proposed as a pathway for detoxifica-tion.Io3 Convenient addition (Et,Nf I-CF3CO2H) to enones formed P-iodo-ketones. lo4 H-(39) (40) YX J. Souppe J. L. Namy and H. B. Kagan Tetrahedron Lett. 1982 23 3497; P. Mangeney A. Alexakis and J. F. Normant ibid. 1983 24 373; A. Citterio F. Ferrario and S. De Bernardinis J. Chem. Res. (S) 1983 310; N. Oguni T. Omi Y. Yamamoto and A. Nakamura Chem. Lett. 1983 841. 99 J. A. Soderquist and W. W.-H. Leung Tetrahedron Lett. 1983 24 2361; J.Tsuji I. Minami and I. Shimizu ibid. p. 1793 1797; K. Ito M. Kamiyama S. Nakanishi and Y. Otsuji Chem. Lett. 1983 657; T. Kauffmann B. Ennen J. Sander and R. Wieschollek Angew. Chem. In?. Ed. Engl. 1983 22 244; B. R. James and C. G. Young J. Chem. SOC.,Chem. Commun. 1983 1215. I00 J.-L. Luche C. Petrier J.-P. Lansard and A E. Greene J. Org. Chem. 1983 48 3837; S. Cacchi and A. Arcadi ibid. p. 4236. 101 G. Hallnemo and C. Ullenius Terrahedron 1983 39 1621. I02 J. Mulzer A. Chucholowski 0. Lommer I. Jibril and G. Huttner J. Chem. SOC., Chem. Commun. 1983 869; G. Stork C. S. Shiner and J. D. Winkler J. Am. Chem. SOC.,1982 104 310. 103 G. Fodor R. Arnold 1. Mohacsi I. Karle and J. Flippen-Andersen Tetrahedron 1983 39 2137. I04 J. N. Mark Terrahedron 1983 39 1529.178 B. V. Smith 4 Carboxylic Acids and Esters Several methods for efficient esterification have been published. Acids with an alkyl chloroformate and Et,N-DMAP gave esters rapidly in high yield as did their reaction with Me,SiCl followed by addition of an alcohol. 1,l'-Dimethylstannocene is effective as a catalyst for acylation of alcohols (and amides) and for esterification of acids including hindered ones. 2-Chlor0-3~5-dinitropyridine catalysed esterifica- tion probably through anhydride formation. Bis(trimethylsily1) peroxide with ketones promoted Baeyer-Villiger-type ester formation in high yield.'05 Acid chlorides have been converted into terminal alkenes by the sequence in Scheme 8; use of LiAlD4 gave deuteriated alkenes.lo6 ... R'COCI ''I' R'COCH,CI -R'R2C(OM)CH2CI 1 R'R2C=CH2 tRiR2C(OM)CH2Li Reagents i CH,N,-Et,O; ii HCI; iii R2MgX (M = Mg); iv LiAIH,-AlCI Scheme 8 Phase-transfer catalysis of acid formation from vinyl halides led to a$ -unsatur-ated acids. lo' Prochiral a,P-unsaturated acids undergo asymmetric hydrogen transfer in achiral or chiral alcohols with chiral Ru phosphine complexes; the observed e.e. was generally low.'o8 Halogenation of a$-unsaturated acids via trimethylsilyl esters is efficient."' y,S-Unsaturated-P-0x0-esters uia dianions are alkylated exclusively at the y-position ; diketene and Grignard reagents with Co" catalyst formed 3-methylenealkanoic acids precursors for terpenoids. lo During Kolbe elec- trolysis (Z)-4-enoic acids are partially isomerized to (E)-isomers probably uia a cyclopropylcarbinyl radical.' I Preparation of optically active derivatives has employed the oxazoline/chiral auxiliary route (giving 2-chloro- or 2-phenyl-alkanoic acids in moderate e.e.) the generation of P-hydroxy-acids by addition of a chiral nitrile oxide to an alkene or by addition of RCHO to the trislithiated derivative of (R)-N-acetyl-a-phenylglycinol with improvement over previous methods."* Pig liver esterase has been used in selective hydrolysis of chiral3-hydroxy-3-methylalkanoic acid esters.' I3 Malate esters and L-serine have served as precursors for chiral building blocks.'14 S.Kim Y. C. Kim and J. I. Lee Tetrahedron Lett. 1983 24 3365; M. A. Brook and T. H. Chan Synthesis 1983,201;T.Mukaiyama J. Ichikawa and M. Asami Chem. Lett. 1983,293,683; S. Takimoto N. Abe Y. Kodera and H. Ohta Bull. Chem. SOC.Jpn. 1983 56 639; S. Matsubara K. Takai and H. Nozaki ibid. p. 2029. 106 J. Bariuenga M. Yus J. M. Concellon and P. Bernad J. Org. Chem. 1983 48 31 16. I07 J.-J. Brunet C. Sidot and P. Caubkre J. Org. Chem. 1983 48,1919. 108 K. Yoshinaga T. Kito and K. Ohkubo Bull. Chem. SOC.Jpn. 1983 56 1786. Io9 M. Beilassoued F. Habbachi and M. Gaudemar Synthesis 1983 745; T. Azuhata and Y. Okamoto ibid. p. 461. 110 J. A. M. van den Goorbergh and A. van der Gen J. R Neth. Chem. Soc. 1983 102 393; T. Fujisawa T. Sato Y. Gotoh M. Kawashima and T. Kawara Bull. Chem. SOC.Jpn. 1982 55 3555. 111 M. Huhtasaari H.-J.Schafer and H. Luftmann Acta Chem. Scund. (B) 1983 37 537. 112 S. Shibata H. Matsushita H. Kaneko M. Noguchi M. Saburi and S. Yoshikawa Bull. Chem. SOC. Jpn. 1982,55 3546; A P. Kozikowski Y. Kitagawa and J. P. Springer J. Chem. SOC. Chem. Commun. 1983 1460; M. Braun and R. Devant Angew. Chem. In?. Ed. Engl. 1983 22 788. 113 W. K. Wilson S. B. Baca Y. J. Barber T. J. Scailen and C. J. Morrow J. Org. Chem. 1983 48 3960. I14 J. D. Aebi M. A. Sutter D. Wasmuth and D. Seebach Liebigs Ann. Chem. 1983 21 14; R. Dumont and H. Pfander Helv. Chim. Acta 1983 66 814. Aliphatic Compounds -Part ( ii) Other Aliphatic Compounds 179 Synthesis and properties of a-keto-acids have been reviewed. Organocadmium reagents with CNC02Et-ZnC12 formed RCOC0,Et in fair yield.' I5 Keto-acids with a quaternary carbon at C-2 have been prepared from gem-dichlorocyclopropanes which act as masked esters; y-keto-acids were prepared by ring-opening of 2-alkoxycyclopropanecarboxylic esters.' l6 Yeast-mediated reduction of ethyl acetoace- tate gave (S)-ethyl-3-hydroxybutyrate in claimed 95-97% e.e.;use of Geotrichum candidurn gave the (R)-ester in -90% e.e.This is the first report of microbiological production of the (R)-isomer. Similar reduction of the y-chloro-ester was studied as a function of the size of the alkyl group in the ester; above C8 the rate diminished. With C1CH2COCH2CO2C8H the (-)-hydroxy-ester was formed with e.e. -96%.' '' These methods hold promise for a range of systems. Selective hydrolysis (pig liver esterase) of dimethyl esters of a range of diacids (symmetrical meso and cis-1,2-cyclic types) produced significant e.e.in the half-ester products. Thus Me02CCH,CH(Me)CH2C02Me formed a half-ester with e.e. of 90% (cJ 14% from chymotrypsin). In discussion of the mechanism it was suggested that binding to the enzyme was regulated so that in the dimethyl ester of 2,4-dimethyl-3- hydroxyglutarate the pro-S-group is hydrolysed."8 Tetraethoxyallene has been prepared and used as the synthetic equivalent of the malonate dianion ,-C(C02Et),. Copper(1)-promoted arylation of ethyl sodiocyanoacetate proceeds cleanly.' l9 5 Lactones Two useful synthetic routes are heterogeneous dehydrobromination of w -bromocar-boxylic acids and treatment of 1,n-diols with sodium bromite (NaBrO,).120 Enol-6-lactones were prepared from the Wittig reagent RO,CC( Me)=PPh and glutaric anhydride derivatives with some selectivity and p -keto-lactones via the dianion from an w -halogeno-P-keto-ester.'21 Asymmetric synthesis of bicyclic lactones was achieved in high yield (and good e.e.) from a chiral imide precursor; transformation of the appropriate lactone precursor was applied to a synthesis of (lR,3S)-cis-chrysanthemic acid (81'/o e.e.). Macrocylic lactones have been piepared from protec- ted hydroxy-aldehydes and the phosphonium ketene Ph,P-C=C=O as starting material ;transformation of the adduct was successfully achieved and exaltolide and ambrettolide were synthesized.'22 I15 A. J. L. Cooper J. Z. Ginos and A. Meister Chem.Rev. 1983,83 321; Y. Akiyama T. Kawasaki and M. Sakamoto Chem. Lett. 1983 1231. I I6 M. G. Banwell J. Chem. SOC.,Chem. Commun. 1983 1453; H. Kunz and M. Lindig Chem. Ber. 1983 116 220. I17 B. Wipf E. Kupfer R. Bertozzi and H. G. W. Leuenberger Helv. Chim. Acta 1983 66 485; B.-N. Zhou A. S. Gopalan F. Van Middlesworth W.-R. Shieh and C.J. Sih J. Am. Chem. SOC.,1983,105,5929. I I8 P. Mohr N. Waespe-SarEevik C. Tamm K. Gawronska and J. K. Gawronski Helv. Chim. Acta 1983 66 2501. II9 R. W. Saalfrank and W. Rost Angew. Chem. SuppL 1983,451; A. Osuka T. Kobayashi and H. Suzuki Synthesis 1983 67. 120 Y. Kimura and S. L. Regen J. Org. Chem. 1983 48 1583; T. Kageyama S. Kawahara K. Kitamura Y. Ueno and M. Okawara Chem. Letf. 1983 1097. 12' S.Tsuboi H. Fukumoto and A. Takeda Chem. Lett. 1983 1219; R. J. Sims S. A. Tischler and L. Weiler Tetrahedron Lett. 1983 24 253. I22 T. Mukaiyama H. Yamashita and M. Asami Chem. Lett. 1983 385; H.-J. Bestmann and R. Schobert Angew-. Chem. lnt. Ed. EngL 1983 22 780. 180 B. V. Smith y-Butyrolactones (as the disilyl enolate) react with a simple aldehyde with com- plete diastereoface selectivity as only one of four possible diastereoisomers was formed.123 Adduct (4 1) was formed with complete threo-selectivity (Scheme 9) and as shown afforded (42) or (43) by appropriate reaction. Control was considered to be due to a bicyclic (44) or acyclic (45) transition state (Scheme 9). OSiMe GOH .* 0 Me3Sio __* Me,% ii i ' H"Q -H% RZ R' R' R' R' R' Reagents i TiCI,RCHO -78 "C; ii BF,-Et,O; iii KN(SiMe& Scheme 9 Several ring-opening reactions noted are regioselective attack of alkylaminostan- nanes the use of 9-BBN to form substituted cyclopropylacetic acids from p-lactones and production of a,o-diesters of long-chain diacids by addition of Grignard reagents (from a,w-dihalides) to P-propiolactone (including synthesis of a precursor for ~ivetone).'~~ Epoxide formation was noted in attack of PhS02CH2Li on (46) which yielded (47); cyclization of (47) gave a mixture in which (48) ~red0minated.l~~ y-Butenolides reacted with KMn0,-crown ether to give principally cis-2,3-dihy- droxy-y-butyrolactone; a bulky substituent in (49) favoured formation of (50) at the expense of the other isomer.An entry into the carbohydrate series was available from such precursors.'26 I23 K.Yamamoto and Y. Tomo Chem. Lett. 1983 531. I24 A. Ricci M. Romanelli M. Taddei G. Seconi and A. Shanzer Synthesis 1983 319; M. Kawashima and T. Fujisawa Chem. Lett. 1983 1273; T. Fujisawa T. Sato T. Kawara and H. Tago Bull. Chem. SOC.Jpn. i983 56 345. I25 S. Batmangherlich A. H. Davidson and G. Procter Tetrahedron Lett. 1983 24 2889. T. Mukaiyama F. Tabusa and K. Suzuki Chem. Lett.. 1983 173. Aliphatic Compounds -Part ( ii) Other Aliphatic Compounds (47)X= PhSO HO’ OH (49) (50) 6 Amines and Amides Amination of alkenes has been reviewed.’” Synthetic routes reported include a reductive Beckmann reaction of oximes which gave good yields of secondary amines formation of functionalized tertiary amines hydroboration-alkylation of propargyl amines to form unsaturated amines a conversion of primary amines into secondary allylamines via a Wittig-type sequence and generation of tertiary propargyl- amines.”* Synthesis of primary allylic amines has been reviewed.lz9 Ally1 boronates with Schiff bases gave secondary homoallylamines.13’ Direct addition of the amino- group to an alkene was possible by use of NH2CN-NBS; trans-but-2-ene formed (*)-2,3-diaminob~tane.’~’ Primary amines have been converted into imines (and other products) by an excess of RLi into ketones (by anodic methoxylation of carbamates) and into imines by reaction with N-chlorosuccinimide followed by elimination from the formed N-chloroamine.32 An asymmetric synthesis of substituted propargylamines (and a-substituted a-amino-acids) employed in the first stage amidine formation from a chiral pyrrolidine (51) and R’R2CHNH2; the amidine (52) was a source of either product according to p -hydroxyamines were resolved kinetically by enan- tioselective N-oxide f~rmation.’~~ o*o II (51) (52) 127 M. B. Gase A. Lattes and J. J. Perie Tetrahedron 1983 39 703. 128 S. Sasatani T. Miyazaki K. Maruoka and Y. Yamamoto Tetrahedron Lett. 1983,24,4711; G. Courtois and P. Miginiac Bull. SOC.Chim. Fr. ZZ 1983 148; J. L. Torregosa M. Baboulene V. Speziale and A. Lattes Tetrahedron 1983,39,3101; R. J. Linderman and A. I. Meyers Tetrahedron Lett. 1983,24,3043; G. Boche M. Bernheim and M. Neissner Angew.Chem. Suppl 1983 34. I29 R.B. Cheikh R. Chaabouni A. Laurent P.Mison and A. Nafti Synthesis 1983 685. I30 R. W. Hoffmann G. Eichler and A. Endesfelder Liebigs Ann. Chem. 1983 2000. 131 H. Kohn and S.-H. Jung J. Am. Chem SOC.,1983 105,4106. 132 H. G. Richey jun. and W. F. Erickson J. Org. Chem. 1983 48 4349; T. Shono Y.Matsumura and S. Kashimura ibid. p. 3338; J.-C. Guillemin and J.-M. Denis Angew. Chem. Suppl. 1982 1515. 133 M. Kolb and J. Barth Liebigs Ann. Chem. 1983 1668. I34 S. Miyano L. D.-L. Lu S. M. Viti and K. B. Sharpless 1.Org. Chem. 1983 48 3608. 182 B. V.Smith Stereoselective preparation of amino-ketones (Scheme 10) gave (53) as a single isomer which afforded the threo-amino-ketone (54).'35Mannich bases have been prepared from iminium salts and silyl enol ethers and an alternative route to Mannich-functionalized amines has been presented.136 Me NHTs Me NHTs IV Me Me N-TS I MenAa iv o/ *Me I Me Me Me (53)\JJ/ (54) Reagents i TsN=S=O PhMe 0 "C ii 5% NaOH r.t.; iii 5% HCI 0 "C;iv Os0,-Na104 Scheme 10 Enamine chemistry has been re~iewed.'~' A one-pot synthesis has been reported optimization of yields has been undertaken and bicyclic enamines have been obtained from 1a~tams.I~~ a-Chloroenamines with R'C02H-R2MgX gave chemoselectively ketones in high yields; CN and OAc groups were unreactive since PhCH(OAc)CO,H gave only PhCH(OAc)COCH2CH2Ph with the appropriate reagent. 139 Very effective asymmetric synthesis was noted for Mi'chael addition of (55) to ArCH=C(CO,Et),; (56)was formed with d.s.95% and e.e. 92% .I4' Metallated enamines have been prepared and studied; nucleophilic attack of an enamine on a chiral allylic molybdenum complex formed alkenes or alkenals in good optical yield and enaminoketones with RLi gave a,@-unsaturatedketones. 14' Weak acids with RNH and P214,formed amides in excellent yield; alkylation of RCONH [by R'OH and RuC12(PPh3),]was effective and R'CHO and a secondary amine formed tertiary amides in excellent yield with Pd" cata1~st.l~~ Alkyldiphenyl-sulphonium salts proved efficient 0-alkylating agents for amides and ~reas.'~~ A chiral stationary phase (recognition model) derived from 3,5-dinitrophenyl-glycine has been applied to the resolution of N-acyl-1-amino-1-ary1alkanes.l4 Reduction of amides from MeCOC0,H and chiral amines has been studied; e.e.was low in the products and depended on the conditions used. Improved selectivity was found for reduction [Zn(BH,),] of 2-alkyl-3-oxoamides in which product with a high d.s. ratio was obtained e.g. MeCOCH(Me)CONH gave 13.' R. S. Garigipati J. A. Morton and S. M. Weinreb Tetrahedron Lett. 1983 24 987. I36 R. N. Benaud D. BCrubC and C. J. Stephens Can. J. Chem. 1983,61,1379;G.Courtois and P. Miginiac Bull. Soc. Chim. Fr. II 1982 395; ibid. 1983 p. 21. 137 P. W. Hickmott Tetrahedron 1982 38 3363. 138 R. Knorr P. Low and P. Hassel Synthesis 1983 785; R. Carlsson A. Nilsson and M. Stromquist Acta Chem. Scand. (B) 1983 37 7; J.M. McIntosh L. Z. Pillon S. 0.Acquaah J. R. Green and G. S. White Can. J. Chem. 1983 61 2016. I39 T. Fujisawa T. Mori K. Higuchi and T. Sago Chem. Letf. 1983 1791. 140 S. J. Blarer and D. Seebach Chem. Ber. 1983 116 2250; cf D. Seebach and V. Prelog Angew. Chem. Int. Ed. Engl. 1982 21 567. 141 H. Albrecht Synthesis 1983 56 58 61; J. W. Faller and K.-H. Chao J. Am. Chem. SOC.,1983 105 3893 T. Mukaiyama and T. Oshurni Chem. Left. 1983 875. I42 H. Suzuki J. Tsuji Y. Hiroi N. Sato and A. Osuka Chem. Left. 1983 449; Y. Watanabe T. Ohta and Y. Tsuji Bull. Chem. Soc. Jpn. 1983,56,2647; Y. Tamaru Y. Yarnada and Z. Yoshida Synthesis 1983 474. 143 M. Julia and H. Mestdagh Tetrahedron 1983 39 433. I44 W. H. Pirkle C. J. Welch and M. H. Hyun J.Org Chem. 1938 48 5022. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds (*)-MeCH(OH)CH(Me)CONH (syn :anti = 98:2).'45 High e.e. in the formation of amide (58) and its subsequent hydrolysis to a 2-substituted malate (59) was found; the chiral auxiliary (57) was highly effective here.'46 r---. N Me A I Primary enamides (E)-or (2)-RCH=CHNHAc have been generated by copper- catalysed decarboxylation of the acids RCH=C(CO,H)NHAc; the (2)-or (15)-isomer can be prepared by choice of ~olvent.'~' 7 Other Nitrogen Compounds Efficient conversions of acids and oximes into nitriles by ethyl polyphosphate and trimethylsilyl polyphosphate respectively have been Phase-transfer catalysis has been employed in smooth dehydration of ald~ximes.'~~ An 'acetal template' has been used in the generation of cyanhydrins in high optical yield (Scheme 1 1).I5' Oxidation of sec-alkyl cyanides (MezSO-O2-base) afforded ketones but in variable ~ie1d.l~' Stereocontrolled synthesis of 2-substituted-cu,P-unsaturated nitriles employed TiCl,-promoted condensation of an aldehyde and silylketene- imines.15 Allenic nitriles were prepared from oxime precursors.lS3 Transformation Reagents i Me3SiCN-TiC14 -40 to -20 "C:ii TsOH-dioxane Scheme 11 I45 T. Munegumi and K. Harada Chem. Lett. 1983 1225; Bull. Chem. Soc. Jpn. 1983,56,298 2774; Y. Ito and M. Yamaguchi Tetrahedron Lett. 1983 24 5385. 146 R. W. Stevens and T. Mukaijama Chem. Len. 1983 1799. 147 U. Schmidt and A. Lieberknecht Angew.Chem. In?. Ed. Engl. 1983 22 550. 148 T. Imamoto T. Takaoka and M. Yokoyama Synthesis 1983 142 J. M. Aizpura and C. Palomo Nouv. J. Chim. 1983 7 465. I49 H. Shinozaki M. Imaizumi and M. Tajima Chem. Lett. 1983 929. I 50 J. D. Elliott V. M. F. Choi and W. S. Johnson J. Org. Chem. 1983 48 2294. IS1 S. S. Kulp and M. J. McGee J. Org. Chem. 1983 48 4097. IS2 H. Okada I. Matsuda and Y. Izumi Chem. Lett. 1983 97; Bull. Chem. SOC.Jpn. 1983 56 528. J. Grimaldi and A. Cormons. Bull. Snc. Chim. Fr. 11 1983 49. 184 B. V. Smith of RN=C=O into RN=C has been followed by I3C n.m.r.; Bu'Ph,SiLi was effective and the nature of the intermediates was ~1arified.l~~ Ethoxymethylenemalonitrile served as a building block for some heterocyclic No evidence for a vinyl cation was found when (EtO),C=CH(N,+) was decom- posed in solution.156 Oxidation of R1R2CHN02 [Fe(CN);-] gave dinitro-compounds whereas reductions of unsaturated nitro-compounds afforded ketones and oxime~.'~' Convenient nitro-aldol reaction could be effected by use of alumina at room temperat~re."~ The preparation and reactions of diazomethane have been surveyed.159 8 Sulphur Compounds Simple preparative routes to and reactions of thioaldehydes have been studied.I6' Terminal alkynes via thiophenyl ethers and their reaction with HgS04-H+ can be transformed into acids. AcSH adds to a$-unsaturated carbonyl compounds in the presence of cinchonine forming adducts with variable e.e.16' Activation of azides by sulphur improved their reactivity toward organometallics ; the adducts (RNHN=NCH,SPh) by acylation and subsequent cleavage with base gave good yields of amides RNHCOR'.162 Two-phase alkylation using sulphonium salts was accelerated by Cu'; prenyl salts gave only tertiary esters in presence of CUB^.'^^ Sodium bromite was effective and selective for conversion of dialkyl sulphides into sulph~xides.'~~ The facile production of an a,p-enone from a P-oxosulphide trans- formation of methyl ketones into a-chlorosulphenyl chlorides efficient generation of chiral sulphinates and a Darzens reaction in the presence of chiral L-menthyl chloromethanesulphonate (with low e.e.in the formed epoxysulphonate) have been noted.165 Chiral (arylsulphinylmethyl) oxazolines serve as chiral enolace- tate equivalents leading to P-hydroxy-acids in moderate e.e.The d.s. ratio in the product from XC6H4CH0 and (*)-MeC6H4SOCH2CH=CH2-LDA was found not to depend significantly on the substituent X. Liquid chromatographic separation of sulphoxides and sulphoximines is possible with a chiral stationary phase [(R)-N-(3,5-dinitrobenzoyl)phenylglycine].166 I54 J. E. Baldwin A. E. Derome and P. D. Riordan Tetrahedron 1983 39 2989. I55 H. W. Schmidt R. Schipfer and H. Junek Liebigs Ann. Chem. 1983 695. I56 I. Szele M. Tencer and H. Zollinger Helu. Chim. Acta 1983 66 1691. 157 N. Kornblum H. K. Singh and W. J. Kelly J. Org. Chem. 1983 48 332; S. Torii H. Tanaka and T. Katoh Chem. Lett. 1983 607. G. Rosini R. Ballini and P. Sorrenti Synthesis 1983 1014. 159 T.H. Black Aldrichim. Acta 1983 16 3. I60 E. Vedejs and D. A. Perry J. Am. Chem. Soc. 1983 105 1683; J. E. Baldwin and R. C. G. Lopez Tetrahedron 1983 39 1487. 161 S. R. Abrams Can.J. Chern. 1983,61,2423;J. K. Gawronski K. Gawronska H. Kolbon and H. Wynberg J. R. Neth. Chem. Soc. 1983 102 479. 162 B. M. Trost and W. H. Pearson J. Am. Chem. SOC. 1983 105 1054. I63 B. Badet M. Julia M. Ramirez-Munoz and C. A. Sarrazin Tetrahedron 1983 39 31 11. I64 T. Kageyama Y. Ueno and M. Okawara Synthesis 1983 815. I65 Y. Ueno L. D. S. Yadav and M. Okawara Chem. Lett. 1983 831; G. Adiwidjaja H. Giinther and J. Voss Liebigs Ann. Chem. 1983 11 16; K. Hiroi R. Kitayama and S. Sato Synthesis 1983 1040; M. H. H. Nkunya and B. Zwanenburg J. R. Neth. Chem.Soc. 1983 102 461. I66 R. Annunziata M. Cinquini and A. Gilardi Synthesis 1983 1016; D. D. Ridley and M. A. Smal Aust. J. Chem. 1983 36 1049; S. Allenmark L. Nielsen and W. H. Pirkle Acta Chem. Scand. (B) 1983,37 325. Aliphatic Compounds -Part ( ii) Other Aliphatic Compounds 185 Alkyl allyl and benzyl sulphones by metallation and subsequent treatment with Me,SiOOSiMe, gave ketones. Ketones with LiMe3SiCHzS02Ph in DME gave a$-unsaturated sulphones chemoselectively. Dianions from P-hydroxy-sulphones reacted with alkyl halides or carbonyls to form furanones; dianions from P-keto- sulphones underwent a -and y-alkylation and by brominative cleavage alkenes were formed.16' In this way was prepared non-6-en-1-01 (fruit fly pheromone). The sulphone dianion is a synthetic equivalent of the dianion C=C.A range of dienes can be conveniently prepared from the monoanion of RCH,CH=CHSOZCH,Br by sequential intramolecular loss of Br- and SO2. Ths bis-sulphone (60) is a synthetic equivalent of the 1,3-dipole +CHzCH2CHz.169 Electrophilic cyclization-fragmentation of allenic sulphones and sulphinates led to (chiral) a,P -unsaturated sultines. Functionalized resins with hydrazinosulphonyl groups bind carbonyl compounds; when heated with alkali the formed sulphonylhy- drazones gave alkenes or in the presence of NaBH,-LiAlH, alkanes or with MeOH-KCN homologated nitriles. Some sensitivity to the steric bulk of groups in the carbonyl compound was discerned. 17* Triflates have been reviewed and their chemistry in acylation has been e~plored.'~' 9 Phosphorus Compounds Preparation and uses of chiral [160,'70,180]phosphateesters has been reviewed.17* Stable alkylidenephosphenes have been reported; the reduction of bis-arylphos- phenes gave a mixture of (*)-and me~ophosphanes.'~~ Attack by ethoxy-radicals at trivalent phosphorus occurred with net inver~i0n.I~~ Diphosphorus tetraiodide is useful for deoxygenation of benzylic alcohols and hydroxymethyl groups attached to Pv.175 A considerable volume of work on Wittig-type reactions has appeared.Wadsworth-Emmons processes have been revisited and synthetic applications sum-mari~ed.'~~ Novel and interesting reactions include the first stereoselective synthesis of 2-cqp-unsaturated esters by the Horner-Emmons reaction (Scheme 12) the successful use of heterogeneous conditions and weak bases in HzO to obtain I67 J.R. Hwu J. Org. Chem. 1983,48,4432; S. V. Ley and N. S. Simpkins J. Chem. SOC.,Chem. Commun. 1983 1281 K. Tanaka K. Ootake K. Imai N. Tanaka and A. Kaji Chem. Lett. 1983,633; D. Scholz Liebigs Ann. Chem. 1983 98. 168 E. Block et al. J. Am. Chem. SOC. 1983 105 6164 6165. I69 B. M. Trost J. Cossy and J. Burks J. Am. Chem. SOC.,1983 105 1052. I70 S. Brouerman and Y. Duar J. Am. Chem. SOC.,1061; H. Kamogawa A. Kanzawa M. Kadoya T. Naito and M. Nanasawa Bull. Chem. SOC.Jpn. 1983 56 762. 171 P. J. Stang and M. R. White Aldrichim. Acta 1983 16 15; F. Effenberger G. Epple J. K. Eberhard U. Buhler and E. Sohn Chem. Ber. 1983 116 1183. I72 G.Lowe Acc. Chem. Res. 1983 16 244. 173 M. Yoshifuji K. Toyota K. Shibayama and N. Imamoto Chem. Lett. 1983 1653; M. Yoshifuji K. Shibayama and N. Imamoto ibid. p. 585. I74 W. G. Bentrude M. Moriyama H.-D. Mueller and A. E. Sopchik J. Am. Chem. SOC.,1983 105 6053. I75 H. Suzuki H. Sani H. Kobuta N. Sato J. Tsuji and A. Osuka Chem. Lett. 1983 247; M. Yamashita K. Tsunekawa M. Sugiura T. Oshikawa and S. Ionokawa ibid. p. 1673. I76 W. J. Stec Acc. Chem. Rex 1983 16 41 I. 186 B. V. Smith a,P -unsaturated ketones and esters reaction of P -hydroxy-carboxylic acids with the phosphorane from diethyl azodicarboxylate to form alkenes+( with ste+reocontrol in some cases) and the preparation and decomposition of R3P-CF-PR3 which afforded a route to a 1,2-difl~oroalkene."~ A one-pot process leading to a conjugated diene used the palladium-promoted coupling of an aldehyde and allylic alcohol in the presence of Ph,P; penta-2,4-dienylphosphineoxide with carbonyl compounds gave conjugated trienes.'?* The rate of reaction of stabilized ylides and yield of E-alkene were increased at a pressure of 10 kbar.'79 0 R I1 (CF,CH20),PCH(R)C0,Me 2 ~1 CO,Me Reagents i R'CHO KN(SiMe3),-THF-18-crown-6, -78 "C Scheme 12 Wittig reactions have also been applied to the preparation of enamines and enol ethers of aldehydes and the stereoselective synthesis of cyclopropanes and bicyclic lactones.'" Phosphonium ylides via acylation and decomposition of the acyl ylide gave 1,2-diketones transformable into dialkylacetylenes.Ph3PC12 with lithium car- boxylates formed an acyloxyphosphonium salt ; treatment of this with Grignard reagent afforded ketones in good or very good yield.18' A boron analogue of the Wittig reaction is shown in Scheme I3 ; decomposition of the diastereoisomeric Li' Mes2BCR1R2 R'R2C-CR3R4 II Mes,B OLi Scheme 13 adducts from PhCHO and n-C8H17BMes2 gave PhCH=CHC7H, with >99.9% E-isomer. Yields were generally better at low temperatures. Mixed dior-ganoborinanes formed from a phosphonium ylide and borane undergo addition to an alkene (Scheme 14) in a scheme which can be expressed as in the equation R'CH2X + CI,CHOMe + R2CH,X + R3COR4 + R'CH2COCH(R2)CHR3R4 177 W. C. Still and C. Gennari Tetrahedron Lett. 1983 24,4405; J.Villitras and M. Rambaud C. R. Hebd. Seances Acud. Sci. 11 1983 1175; Synthesis 1983,300; J. Mulzer and 0.Lammer Angew. Chem. Suppl. 1983 887; D. J. Burton and D. G. Cox J. Am. Chem. Soc. 1983 105 650. 178 M. Moreno-Manas and A. Trins Bull. Chem. Soc. Jpn. 1983 56 2154; C. C. Santini and F. Mathey Can. J. Chem. 1983 61 21. 179 A. Nonnenmacher R. Mayer and H. Plieninger Liebigs Ann. Chem. 1983 2135. IBo J. C. Gilbert and U. Weerasooriya J. Org. Chem. 1983 48 448; A. Moupert J. Martelli R. Gree and R. Carrit Nouv. J. Chim. 1983 7 345; R. W. Saalfrank P. Schierling and P. Schatzlein Chem. Ber. 1983 116 1463. 181 H.-J. Bestmann K. Kumar and L. Kisielowski Chem. Ber. 1983 116 2378; T. Fujisawa S. Iida H. Uehara and T. Sato Chem. Lett. 1983.1267. Aliphatic Compounds -Part ( ii) Other Aliphatic Compounds RICH-GPh rRiCH-6PhS] A R'CH2BH2PPh iii 1-AH3 1 1 X R3 X / R'CH,COCHR2 -R'CH2!5CH(R2)CH' R1CH2B .PPh I CH \R4 \H R3/ \R4 Reagents i BH3-THF; ii A; iii HX; iv R2CH=CR3R4; v R'I; vi C1,CHOMe; vii LiOCEt3; viii H,O,-NaOH Scheme 14 The ylide (61) has been used to add to carbonyl groups in a Horner-type process generating E/Z-a,P-unsaturated esters in which the E-isomer predominated.'82 R,feC HC0,Et (61) It proved possible to isolate a ketophosphonium halide from a phosphorus(m) ester and an a -halogenocarbony1 compound. Decomposition via an Arbuzov reac- tion was the only observed reaction forming (RO),P(0)CH2COR1. lg3 The synthetic usefulness of Homer-Wittig reactions based on Ph2P(0)CH2R1 is well illustrated by Scheme 15 in which stereospecific elimination from (62) led to (62) Reagents i HO-H,O; ii BuLi then R'CHO then separate isomers iii NaH-DMF Scheme 15 2-alkene in good yield ;stereoselective reduction of ketone (63) gave a rhreo-product (64) which also underwent stereospecific elimination to an E-alkene.In a variation on this theme trisubstituted alkenes were prepared from the appropriate starting material.184By protecting the carbonyl group (as a dioxolane) sequences to P,y-and y,S-unsaturated ketones have been successfully employed. Full regio- and stereo-chemical control in formation of E-and 2-allylamides from /3-(acy1amino)alkylphosphine oxides was achieved. A lack of stereospecificity in elimi- nation from (63) was attributed to a fragmentation and recombination; it proved possible to use a trap (3-ClC6H4CHO) to detect formed PhCHO and isolate E-and 2-chlorostil bene~.'~~ I xz A.Pelter B. Singaram and J. W. Wilson Tetrahedron Lett. 1983,24,635; H.-J. Bestmann and T. Roder Angew. Chem. Int. Ed. EngL 1983 22 782; A. Osuka Y. Mori H. Shimizu and H. Suzuki Tetrahedron Ler?. 1983 24 2599. 183 1. Petnehazy G. Szakai and L. Toke Tetrahedron 1983 39 4229. I84 A. D. Buss and S. Warren Tetrahedron Lett. 1983 24 3931 5293 11 I; C. Earnshaw R. S. Torr and S. Warren J. Chem. Soc. Perkin Trans. 1 1983 2879 2893. ins C. A. Cornish and S. Warren Tetrahedron Lett. 1983 24 2603; D. Cavalla and S. Warren ibid. p. 295; A. D. Buss S. Warren J.S. Leake and G. H. Whitham J. Chem. SOC.,Perkin Trans. I 1983 2215. 188 B. V. Smith Diastereoisomerically pure phosphinates have been generated from an Arbuzov reaction of (2S,4S)-4-methyl-2-phenyl-I ,3,2-dioxaphosphorinane and used to pre- pare chiral phosphine oxides in high (76-1 00%) optical yield.'" p-Hydroxyalkylphosphonates underwent smooth fluoride ion-catalysed elimination; in a similar reaction scheme a-trimethylsilylalkylphosphonates gave alkenes by reaction with carbonyl compounds in the presence of CsF (the best ~atalyst).'~' By this latter approach PhCOMe afforded Ph(Me)C=CHMe with an E :2 ratio of 1 :3. Epoxidation of a$-and &?-unsaturated phosphonates has been achieved by H,02-Na2W0 or Bu~~~H-Mo(C~)~.'~~ 10 Miscellaneous A review of applications of alkali-metal fluorides in organic synthesis has appeared.lg9 IX6 M.Segi Y. Nakamura T. Nakajima and S. Suga Chem. Lett. 1983 913. I87 T. Kawashima T. Ishii and N. Imamoto Chem. Lett. 1983 1375; Tetrahedron Lett. 1983 24 739. G. Sturtz and A Pondaven-Raphalen Bull. SOC.Chim. Fr. II 1983 125. I X9 G. G. Yakobsoii and N. W. Akhmetova Synthesis 1983 169.

ISSN:0069-3030    

DOI:10.1039/OC9838000165

出版商:RSC    

年代:1983

数据来源: RSC

摘要:

9 Alicyclic Chemistry By S. A. MATLIN Chemistry Department The City University Northampton Square London EC1 V OHB 1 Three-membered Rings A stereospecific cyclopropane synthesis has been reported employing the acid- catalysed cyclization of y-stannyl alcohols (Scheme 1 ; R’ R2 = Me Ph). On treat- ment with TiCI4 the bis-ketene acetals (1) cyclize stereoselectively to dimethyl trunscyclopropane- 1,2-dicarboxyIates (2). If the reaction is carried out in the presence of acetic anhydride the cyclobutanes (3) are obtained.2 Diastereomeric excesses of 74% were observed in the cyclopropanation of the di-( /)-menthy1 or di-( d)-menthyl esters of fumaric acid with isopr~pylidenetriphenylphosphorane.~ Ph ~1 13\”6,. BF3.2AcOH Bu ,Sn Scheme 1 we R3&R4 C02Me ,TiC1,- TiCI,- ~~~&i0~Me Ie02C AcZO Me,SiO ,’OSiMe 9ciz HO Me R3 R4 Me0,C R4 (3) (1) (2) A new synthesis of substituted cyclopropylacetic acids involves hydroboration of P-alkenyl-P-propiolactones (4) with 9-borabicyclo[3.3.llnonane (9-BBN) and sub- sequent treatment with sodium meth~xide.~ (4) 2-Acylcyclopropane carbaldehydes have been obtained5 by condensation of 2-substituted 1,3-diketone anions with vinyl selenones as shown in Scheme 2. ‘ I. Fleming and C. J. Urch Tetrahedron Lett. 1983 24 4591. ’ I. H. M. Wallace and T. H.Chan Tetrahedron 1983 39 847. ’M.J. De Vos and A. Krief Tetrahedron Lett. 1983 24 103. M. Kawashima and T. Fujisawa Chem. Lett. 1983 1273. R. Ando T. Sugawara and I. Kuwajima J. Chem. Soc. Chem. Comrnun.1983 1514. 189 190 S. A. Matlin * Scheme 2 Cyclopropanation of ketene alkylsilyl acetals (5; R3 = Me or CH,Ph) or ketene disilyl acetals (5; R3 = SiMe,) leads to the synthetically versatile cyclopropanone acetal intermediates in high yields.' Cyclopropanes with an adjacent masked aldehyde group can be prepared' by cyclopropanation either with the diazoacetal (6) or by addition to the vinyl acetal (7). (5) (6) (7) The first synthesis of 1,4-di-t-butylmethylenecyclopropene (8) has been reported,8 via chlorocarbene addition to 1,3-di-t-butylallene and subsequent elimination of HCl. 'H N.m.r. of the unstable compound at -30 "C showed pronounced shifts of the olefinic protons (s4.02and 7.09) indicating a strong contribution from the resonance form (8b).Microwave studies of cyclopropyl cyanide and cyclopropylacetylene provide evidence for electron donation from the cyclopropane ring to the n-systems of the substituents.' Participation by the cyclopropane ring leading to 17-1 8% retention of configuration has been observed in the solvolysis of (R)-and (S)-1-deuterio-2- cyclopropylethyl toluene-p-su1phonates.I' Removal of an electron from tetra-alkyl- cyclopropanes by light-induced electron transfer to chloranil or fluoranil results in 'G. Rousseau and N. Slougui Tetrahedron Lerr. 1983 24 1251. ' H. Abdallah R. Cree and R. Carrie Can. J. Chem. 1983 61 217. W. E. Billups and L.-J. Lin Tetrahedron Lett. 1983 24 1683. M. D. Harmony R. N. Nandi J. V. Tietz J.-I. Choe S. J. Getty and S.W. Staley J. Am. Chem. SOC. 1983 105 3947. lo I. M. Takakis and Y. E. Rhodes Tetrahedron Lert.. 1983. 24 4959. Alicyclic Chemistry 191 radical cations by cleavage of the most substituted bond of the cyclopropane.'] 1,3-Biradicals are formed in the infrared photochemical decomposition of bicyc- lopropyl.l2 The stereomutations of cyclopropanes involving ring cleavage internal rotations and ring reclosure have received considerable attention. l3 The combination of CN with OR SR or NR2 as geminal substituents is far more effective than its combination with a geminal C02R group in lowering the activation energy for cis-trans isomeriz-ation.I4 Following ring-opening of a cyclopropane rotations about the two remaining C-C bonds may occur at dramatically different rates as the result of steric interac- tions between the substituents at the termini of the propylidene moiety.15 A new method for determining rotational propensities has been devised,14 based on chiral deuterium labelling.Thus for example the stereomutations in the cyclopropane (9) (Scheme 3) could be observed by n.m.r. from which the relative rotational pro- pensities of the CN- and isobutenyl-bearing groups was determined to be 3.9 * 0.5.16 D D HyA$ D N H C K NC Scheme 3 Cyclopropylidenes are generated as useful carbenoid intermediates by the action of methyl-lithium on gem-dibromocyc1opropanes." New studies of alternative reac- tions with other organometallic agents provide synthetic routes to cyclopropylcar- boxylic acid derivativesI8 (Scheme 4; X = 0 NH or NR) and spirocyclopropyl products19 (Scheme 5; X = 0 or CH2).Scheme 4 'I H. D. Roth and M. L. M. Schilling J. Am. Chem. Soc. 1983 105 6805. l2 W. E. Farneth and M. W. Thornsen J. Am. Chem. Soc. 1983 105 1843. l3 J. E. Baldwin and C. G. Carter J. Org. Chem. 1983 48 3912. l4 R. Mertnyi A. De Mesrnaeker and H. G. Viehe Tetrahedron Lett. 1983 24 2765. l5 W. von E. Doering L. R. Robertson and E. E. Ewing J. Org. Chem. 1983 48 4280. l6 W. von E. Doering and Y. Yarnashita J. Am. Chem. Soc. 1983 105 5368. J. Arct L. Skattebel. and Y. Stenstrorn Acta Chem. Scand. (B),1983 37 681; M. Bertrand A. Tubul and C. Ghiglione. J. Chem. Rex (S) 1983 250. I' T. Hirao Y. Harano Y. Yarnana Y. Ohshiro and T. Agawa Tetrahedron Lett.1983 24 1255. I' F. Scott B. G. Mafunda J. F. Normant and A. Alexakis Tetrahedron Lett. 1983 24 5767 192 S. A. Math \R -W + n-C,H,,Li + ClMgCu'Rl RI Scheme 5 A reassessment of the strain energy of diphenylcyctopropenone suggests that it has previously been overestimated by a large factor the new determination of ca. 80 kJ mol-' resonance stabilization supporting the view that cyclopropenone has ground-state aromatic stabilization.'' The results of studies of reactions of thiocyclopropenium ions with nucleophiles are collected in Scheme 6. RS RS SR '?.' + Me,S-cHCOR' ->c=o + >-c<--RsYsR RS RS SR SR Re$ 21 SR Ph' X = Me or OMe Re$ 22 Scheme 6 2 Four-membered Rings Continuing interest in the synthesis of cyclobutane derivatives is reflected in numerous reports covering a convenient synthesis of cyclobutanone itself by carbon- ation of 1,3-bis(brom0magnesio)propane,~~ ketene acetal [2 + 21 cycloadditions to olefins affording cyclobutanone a~etals,~~ two approaches to substituted cyclo- b~tenones,~~ intramolecular acylation of vinylsilanes leading to a-methylenecyclo- butanones26 (Scheme 7) and cycloaddition of vinyl ketenes to olefins giving 2-vinylcyclobutanones which can be rearranged to cycl~pentenones~' (Scheme 8).q +Me3 -!!!?L \ + &R CHR R Scheme 7 20 A. Greenberg R. P. T. Tornkins M. Dobrovolny and J. F. Liebrnan J. Am. Chem. Soc. 1983 105,6855. " S. Inoue and T. Hori Bull. Chem. SOC.Jpn. 1983 56 171. 22 H.Yoshida M. Nakajirna T. Ogata K. Matsumoto R. M. Acheson and J. D. Wallis Bull. Chem. SOC. Jpn. 1983 56 3015; Chem. Lerr. 1983 155. 23 J. W. F. L. Seetz R. Tol 0. S. Akkerrnan and F. Bickelhaupt Synthesis 1983 721. 24 H. W. Scheeren and A. E. Frissen Synthesis 1983 794. 25 T. Takeda T. Tsuchida K. Ando and T. Fujiwara Chem. Lett. 1983 549; A. Hassner and J. L. Dillon J. Org. Chem. 1983 48 3382. 26 K. Mikami N. Kishi and T. Nakai Tetrahedron Lett. 1983 24 795. 27 D. A. Jackson M. Rey and A. S. Dreiding Helv. Chim. Acta 1983 66 2330; Tetrahedron Leu. 1983 24 4817. AIicyclic Chemistry 0 II MeS0,H R2 R2 Scheme 8 Peracid oxidation of a-cyclopropylidene ketones followed by lithium halide rearrangement provides a new route2* for the synthesis of 2-acylcyclobutanones (Scheme 9).The rearrangement29 of 2-methylenecyclopropylcarbinolswith formic acid gives the 3-methylenecyclobutyl formate (I 0). 0 Scheme 9 Scheme 10 The microwave spectra of isotopically labelled 3,4-dimethylenecyclobutene have been analysed and the observed bond order-bond length relationships compared with theoretical models.30 The structure of tetra-t-butylcyclobutadiene has been reassessed on the basis of spectroscopic and new X-ray determinations and it is now concluded to have a rectangular rather than square ring.31 Temperature-dependent Cotton effects in the chiral cyclobutanones (R)-and (S)-(11) are indicative of puckered conformationally mobile ring^.'^ Such puckering and the consequent repulsive interactions between the 1-and 3-positions and the 2-and 4-positions makes a major contribution to the strain energy of cyclobutanes.Thus although the total strain energy of the latter is very similar to that in cyclopro- panes the origins of the excess enthalpy are different and this accounts for the greater reluctance of cyclobutanes to undergo eliminative ring fission compared with cycl~propanes.~~ Application of SCF methods to cyclobutyne it to lie ca. 320 kJ mol-' above vinylacetylene with the singlet state being more stable than the triplet by over 50 kJ mol-'. 28 A. Lechevallier F. Huet and J.-M. Conia Tetrahedron 1983 39 3329. 29 E. W. Thomas Tetrahedron Lett. 1983 24 2347. 30 R. D. Brown P. D. Godfrey B.T. Hart A. L. Ottrey M. Onda and M. Woodruff Ausr. J. Chem. 1983 36,639. 3' 0. Ermer and E. Heilbronner Angew. Chem. Int. Ed. Engl. 1983 22 402; H. Irngartinger and M. Nixdorf ibid. p. 403. 32 R. N. Harris P. Sundararaman and C. Djerassi J. Am. Chem. SOC.,1983 105 2408. 33 H. A. Earl D. R.Marshall and C. J. M. Stirling J. Chem. SOC.,Chem. Commun. 1983 779. 34 G. Fitzgerald P. Saxe and H. F. Schaefer J. Am. Chem. Soc. 1983 105 690. 194 S. A. Matlin 3 Five-rnembered Rings Cyclopentyne has been demonstrated to be an intermediate in the ring expansion of cyclobutylidenecarbene"' and appears to have an antisymmetrical singlet ground state.36 New cyclization and ring expansion methods for the formation of five-membered rings continue to appear,37 particular attention being focused on enantioselective syntheses.Examples of this include the use of natural chiral starting materials such as sugars3' and (-)-quinic acid (1 2) the latter being converted into the cyclopentenes (13;R = CH2Ph or COPh) which were used in prostaglandin syntheses.39 In another strategy the rhodium-catalysed cyclization of the 2-diazo-3-keto-esters (1 4) was shown to give cyclopentanones (1 5) with high diastereosele~tivity~~ (Scheme 1 I). (14) (15) R Diastereoselectivity ("/o ) n-C,H I 1 87 CH=CH 92 Pr 83 Bu' 83 Ph 85 Scheme 11 Cyclization of the substituted racemic pentenals (16) and (18) induced by the chiral complex [Rh(chiraphos),]Cl [chiraphos = (2S,3S)-bis(diphenylphosphino-Is J.C. Gilbert and M. E. Baze J. Am. Chem. Soc. 1983 105 664. 36 L. Fitjer and S. Modaressi Tetrahedron Lett. 1983 24 5495. 3 7 G. Stork J. D. Winkler and N. Saccomano Tetrahedron Lett. 1983 24 465; E. J. Corey and S. G. Pyne ibid. p. 2821; E. E. van Tamelen J. R. Hwu and T. M. Leiden J. Chem. Soc. Chem. Commun. 1983 62 T. H. Kim Y. Hayase and S. Isoe Chem. Lett. 1983 1421; M. Yamashita J. Onozuka G. Tsuchihashi and K. Ogura Tetrahedron Lerr. 1983 24 79; P. Eilbracht M. Acker and W. Totzauer Chem. Ber. 1983 116 238. 38 D. Horton T. Machinami Y. Takagi C. W. Bergmann and G. C. Christoph J. Chem. SOC.,Chem. Commun. 1983 1164; R. J. Ferrier P. Prasit and P. C. Tyler J. Chem. SOC.,Perkin Trans. I 1983 1641. 39 J. C. Barriere J. Cleophax S. D. Gero and M.Vuilhorgne Helv. Chim. Acta 1983 66 296 1392. 40 D. F. Taher and K. Raman J. Am. Chern. Sor.. 1983. 105 5935. Alicyclic Chemistry phq; __* PhQEt .$'.. [ Rh(chirdphos),C I] @Ph 0 0 (16) (17) (18) (19) butane)] results in asymmetric syntheses of the cyclopentanones ( 17; 52% e.e.) and (19; unknown e.e.) respective1y:l Cycl~pentenones~~ are important targets of synthetic strategy and some examples of new routes are collected in Schemes 12-16.4347 0 OSiMe, @ viii QR vii t-t-$1~" CHR R Reagents i H,Of; ii ; iii 2MeLi; iv RCHPPh,; v EtOH-H+; vi Me3SiC1; vii 600°C; viii Pd( OAc),-p-benzoquinone Scheme 12 (Ref 43) MeqR OMe OMe OSiMe 111,1\ \I + 1 I MeFKe 6.j 1 0 Reagents i RCH(OMe)2-BF,.Et,0; ii CH2PPh,; iii LiAIH,; iv Me,SiCI; v SnCI,; vi CF3CO2H Scheme 13 (Ref 44) 4' B.R. James and C. G. Young J. Chem. Soc. Chem. Commun. 1983 1215. 42 I. J. 0.Jondiko and G. Pattenden J. Chem. Soc. Perkin Trans. I 1983 467 J. D. Elliott A. B. Kelson N. Purcell R. J. Stoodley and M. N. Palfreymon ibid.,p. 2441. 43 J. Salaun and Y. Almirantis Tetrahedron 1983 39 2421. 44 E. Nakamura J. Shimada and I. Kuwajima J. Chem. SOC.,Chem. Commun. 1983 498. 45 E. Nakamura K. Fukuzaki and I. Kuwajima J. Chem. SOC.,Chem. Commun. 1983 499. 46 E. Negishi and J. A. Miller J. Am. Chem. SOC., 1983 105 6761. 47 T. K. Jones and S. E. Denmark Helv. Chirn. Acra 1983 66 2377,2397. I96 S. A. Matlin 0 Scheme 14 (Ref 45) R -C ZC-SiMe R SiMe 1- I II A ZnBr Reagents i THF 60°C; ii I, ill [Pd(Ph3P),]-C0-F.t3N Scheme 15 (Re$ 46) RL.%Me R2 Scheme 16 (Ref 47) Solvolysis of cyclopent-3-enyl tosylate in formic acid proceeds entirely with retention of configuration (demonstrated by stereospecific deuterium labelling) via the three-centre cation (20).48The same intermediate (20) has been generated by the protonation of ~yclopent-3-enylidene.~~ \ 4 Six-membered Rings Direct spectroscopic observation has confirmed the allenic structure of cyclohexa- 1,2-diene generated from bicyclo[3.1 .O]hexane-6-carbonyl chloride by vacuum pyrolysis and cold tra~ping.~' The phosphorane (21) condenses with enals in a new '3+3' cyclohexenone annula- tion (Scheme 17).5' The use of (R)-(+)-binaphthol as a chiral leaving group in the aluminium-catalysed cyclization of the neryl ether (22) leads to D-limOnene (23) in 77% enantiomeric 44 J.B. Lambert and R. B. Finzel J. Am. Chem. Soc. 1983 105 1954. 49 W. Kirmse P.V. Chiem and P. Ci. Henning J. Am. Chem. Soc. 1983 105 1695. 50 C. Wentrup G. Gross A. Maquestiau and R. Flammang Angew. Chem. lnt. Ed. Engl. 1983 22 542. 'I K. M. Pietrusiewicz J Monkiewicz and R Bodalski. I Org Chem.. 1983 48. 788. Alicyclic Chemistry R’ R’ Scheme 17 excess. Enantioselective syntheses of bisabolenes follow from similar cyclizations with chiral farnesyl ethers.52 Manoharan and Elie153 have reassessed the gauche interaction in trans-l,2-dimethylcyclohexane to be 3.05 * 0.37 kJ mol-’ in the liquid phase.5 Medium Rings The titanium-induced dicarbonyl coupling reaction has been applied to the intramolecular cyclization of keto-esters (Scheme 18) and gives good results for ring sizes of 4-14 carbon^.'^ Scheme 18 Scheme 19 Cyclo-octadienes are formed regio- and stereo-selectively by the Nio-catalysed cyclodimerization of substituted butadienes (Scheme 19; X = OSiMe or C02Me).” A general synthetic method has been reporteds6 for the construction of cyclodeca- 2,6-dienones by intramolecular alkylation of protected cyanohydrins (Scheme 20). A similar method has been employed in a humulene synthesis.57 52 S. Sakane J Fujiwara K. Maruoka and H. Yamamoto J. Am. Chem. Soc. 1983 105 6154. 53 M. Manoharan and E. L. Eliel Tetrahedron Lett.1983 24 453. 54 J. E. McMurry and D. D. Miller J. Am. Chem. SOC.,1983 105 1660. 55 P. Braun A. Tenaglia and B. Waegell Tetrahedron Lett. 1983 24,385. 56 T. Takahashi H. Nemoto and J. Tsuji Tetrahedron Lett. 1983 24 2005. 57 T. Takahashi. K. Kitamura and J. Tsuji Tetrahedron Left. 1983 24 4695. 198 S. A. Matlin I Scheme 20 A four-carbon ring-enlargement reaction has been reporteds8 for the synthesis and ring expansion of medium-ring carbocycles (Scheme 21 ; n = 5 6 or lo). 0 Q co-Scheme 21 The first synthesis of trans trans-cycloundeca- 1,5-diene has been reported,59 involving a ring contraction from trqns,trans,trans-cyclododeca-I ,5,9-triene. The reactions of cyclo-octa- 1,5-diene with halogens in various solvents may lead either to cis-and trans-l,2-additions or to transannular cyclizations and the factors controlling this behaviour remain to be explained.60 Medium-ring cis-l,2-dichlorocycloalkanes are conveniently prepared by the action of Ph3P-CC14 on the corresponding epoxides.61 Rearrangement reactions of medium-ring alkenes have been reported,62 including the photochemical ring contraction and bridging of cyclonona-1,2-diene (Scheme 22).63 Scheme 22 6 Large Rings threo-Selective cyclization of the aldehydic allylic bromide (24) with CrCI affords the cembrenoid intermediates (25) and (26).64 5n Y.Nakashita and M. Hesse Helu. Chim. Acta 1983 66,845. 59 G. Haufe Synthesis 1983 235. 60 S. Uemura S. Fukuzawa A. Toshimitsu M. Okano H. Tezuka and S.Sawada J. Org. Chem. 1983 48 270. " A. P. Croft and R. A. Bartsch J. Org. Chem. 1983 48 3353. 62 C. Glidewell and D. Lloyd J. Chem. Res. (S) 1983 180; R. W. Thies J. L. Boop M. Schiedler D. C. Zimmerman and T. H. LaPage J. Org. Chem. 1983,48,2021; see also A. C. Connell and G. H. Witham J. Chem. SOC.,Perkin Trans. I 1983 995. 63 T. J. Stierman and R. P. Johnson J. Am. Chem. SOC. 1983 105 2492. 64 W. C. Stille and D. Mobilio J. Org. Them. 1983 48 4785. AIicyclic Chemistry The 15-membered carbocyclic intermediates (27) and (28) for a muscone synthesis were obtained by Claisen-Ireland rearrangement (Scheme 23).65 An alternative approach to muscone and exaltone involves a new three-carbon ring expansion (Scheme 24; R = H or Me).66 The first hydrocarbon catenane (29) has been synthesized using the Glaser oxidation method to cyclize a 46-carbon diacetylene threaded through the 28-carbon ring.67 (27) Scheme 23 MeCO,H+ m"' R Y dR+ OH m R + OH R Scheme 24 7 Bicyclic Compounds Hydrindanes as important intermediates in the synthesis of terpenes and steroids are the subject of numerous synthetic strategies,68 including an anionic [3,3] sig- 65 R.K. Brunner and H.-J. Borschberg Helu. Chim. Acta 1983 66,2608. 66 C. Fehr Helv. Chim. Acra 1983 66,2512 2519. 67 G. Schill N. Schweickert H. Fritz and W. Vetter Angew. Chem. Int. Ed. Engl. 1983 22 889. 68 B. M. Trost and M. K.-T. Mao J. Am. Chem. SOC.,1983 105 6757; C.-P. Chuang and D. J. Hart J. Org.Them. 1983 48 1782. 200 S. A. Matlin /OCH,Ph OCH ,Ph H Me0,C C0,Me C' @ 0-N -/ matropic shift in the vinyl norbornenol (30)69and aluminium-catalysed cyclization- rearrangement of the dienone (3 The hydrazulene ring system (32) has been prepared by intramolecular nitrile oxide cycii~ation.~' Conformationai preferences of perhydroazulenes have been examined by spectroscopy and X-ray diffraction.'* Further details of the scope of the epoxyannulation reaction (Scheme 25) have now a~peared.'~ Scheme 25 Diels-Alder reactions of 1,4-benzoquinones with dienes provide a very efficient access to bicyclo[4.4.0]decadienes which are valuable synthetic intermediate^.^^ Two new designs of chirai dienophiles giving high degrees of asymmetric induction have 69 M.E. Jung and G. L. Hatfield Tetrahedron Lett. 1983 24 293 I. 70 B. B. Snider and T. C. Kirk J. Am. Chem. SOC.,1983 105 2364. 7' A. P. Kozikowski B. B. Mugrage B. C. Wang and Z. Xu Tetrahedron Lett. 1983 24 3705. 72 H.0. Hou!e P. C. Gaa and D. VanDerveer J. Org. Chem. 1983 48 1661; H. 0. House P. C. Gaa J. H. C. Lee and D. VanDerveer J. Org. Chem. 1983 48 1670. 73 M. E. Garst B. J. Mcbride and A. T. Johnson J. Org. Chem. 1983,48 8; M. E. Garst and P. Arrhenius ibid. p. 16. 74 Z. Q Jiang J. R. Scheffer A. S. Secco J. Trotter and Y.-F. Wong 1.Chem. SOC.,Chem. Commun. 1983 773; J. B. Hendrickson and V. Singh ibid. p. 837; J. Jurczak T. Kozluk M. Tkacz and C. H. Eugster Helv. Chim. Acta 1983 66 218; J. Jurczak T.Kozluk S. Filipek and C. H. Eugster ibid. p. 222; F. Orsini F. Pelizonni D. Pitea E. Abbondanti and A. Mugnoli J. Org. Chem. 1983 48 2866; P. A. Grieco K. Yoshida and P. Garner ibid. p. 3137. Alicyclic Chemistry 201 been reported. The titanium-catalysed addition of cyclopentadiene to the acrylate ester (33) gave the pure (2R)-adduct (34).7s By bringing the chiral centre one atom closer to the olefinic bond in the vinyl ketones (35; R' = cyclohexyl or But; R2 = H SiMe, or SiMe2Bu') very high diastereofacial selectivities were obtained in additions of cyclopentadiene without the need for Lewis acid catalysis.76 &-T2 (35) .H Several strategies for spiroannulation leading to spiro[4,5]decanes have been reported" and two have been applied78 to the synthesis of acoradiene (36).Tr~st'~ has devised a spirocontraction-spiroannulation,exemplified by the synthesis of the spiro[4,6]undecenone (37). The first observation of exo and (slightly more stable) endo orientations of the 7-cyano-substituent in substituted norcaradienes (38; R = H or But) has been made8' by ' H n.m.r. The allenic derivative (39) shows dual reactivity rearranging through both the cycloheptatriene (39a) and endo-norcaradiene (39b) forms.'l The dicyanodi- bromosemibullvalene (40) undergoes degenerate Cope rearrangement more slowly than the parent hydrocarbon,82 evidently as a result of distortion of the ground-state ge~metry.'~ 75 W. Oppolzer C. Chapuis and M. J. Kelly Helv. C'him. Acra 1983 66 2358. ? 6 W.Choy L. A. Reed and S. Masamune J. Org. Chem. 1983,48 1137; S. Masamune L. A. Reed J. T. Davis and W. Choy ibid. p. 4441. 77 M.-L. Roumestant B. Cavallin and M. Bertrand Bull. Soc. Chim. Fr. 11 1983 309; E. Piers C. L. Lau and 1. Nagakura Can. J. Chem. 1983 61 288 R. C. Greenwood J. Org. Chem. 1983 48 2098. 7X W. Oppolzer F. Zutterman and K. Battig Helu. Chim. Acta 1983 66 522; D. Solas and J. Wolinsky J. Org. Chem. 1983 48 670. 79 B. M. Trost and B. R. Adams J. Am. Chem. Soc. 1983 105 4849. RO K. Takeuchi T. Kitagawa Y. Senzaki H. Fujimoto and K. Okamoto Chem. Lett. 1983 69. '' T. Toda N. Shimazaki H. Hotta T. Hatakuyama and T. Mukai Chem. Left.,1983 523. 82 H. Quast and Y. Gorlach Tetrahedron Left. 1983 24 5591. 83 H. Quast Y. Gorlach J.Christ E.-M. Peters K. Peters and H. G. von Schnering Tetrahedron Lett. 1983 24. 5595. 202 S. A. Matlin I I Br+Br NC CN The bicyclic anion (41) is a widely cited example of homoaromaticity but recent theoretical investigations have provided conflicting views on the presence of homoaromatic stabilization. Deuterium isotope effects on the I3C chemical shifts in this anion have now provided clear experimental support for the presence of hom~aromaticity.~~ Bicyclo[2.1 .O]pent-2-ene (42) adds dienophiles across the central 0-bond whereas dipoles add to the ex0 face of the n-bond as illustrated by the reactions in Scheme 26.85The central bond of bicyclo[ I. 1 .O]butanes undergoes photoinduced additions of the activated C-H bond in acetone acetonitrile and ethyl acetate (Scheme 27; X = COMe CN or C02Et).8h Scheme 26 ac-dH H CH,X Scheme 27 84 M.Christ] H. Leininger and D. Bruckner J. Am. Chem. Soc. 1983 105 4843. 85 W. Adam A. Beinhauer 0.de Luchi and R. J. Rosenthal Tetrahedron Lett. 1983 24 5727. 86 P. G. Gassman and J. L. Smith. J. Org. Chem.. 1983 48 4438. Alicyclic Chemistry (431 (44) Bridgehead interactions in bicyclic compounds have been re~iewed.~’ Calcula-tions8* suggest that dehalogenation of the bridgehead di-iodide (43) should lead to ring closure to the [2.1.l]propellane (44) and evidence for the occurrence of this reaction has been pre~ented.’~ A short synthesis of [1 1.1 Ilbetweenanene (46) involves photochemical isomeriz- ation of the bicyclic olefin (45).90 UU (45) Scheme 28 (47) Strain-energy calculations (MM2) for 36 bridgehead dienes have been reported” as well as some new syntheses involving pericyclic” and elimination93 reactions.[3.3]Sigmatropic rearrangement of 1 n -divinylbicyclo[ n.m.O]alkanes results in forma- tion of meso bridgehead dienes containing a trans trans-l ,5-cycloalkadiene linkage (Scheme 28).94 Some strained bridgehead olefins e.g.(47) have been prepared using the Ramberg- Backlund reaction.95 Enones with strained bridgehead double bonds have been generated and tra.pped by nucleophilic reagents and by cycloaddition reactions.96 x7 R. W. Alder Acc. Chem. Rex 1983 16 321. 88 K. B. Wiberg J. Am. Chem. SOC.,1983 105 1227. n9 K.B. Wiberg F. H. Walker W. E. Pratt and J. Michl J. Am. Chem. SOC.,1983 105 3638. YO A. Nickon P. St. John Zurer B. Hrnjez and J. Tino Tetrahedron 1983 39 2679. 9‘ P. Warner and S. Rescock Tetrahedron Lett. 1983 24 4169. 92 K. J. Shea and J. W. Gilrnan Tetrahedron Lett. 1983,24,657;P. W. Warner I.-S. Chu and W. Boulanger ibid. p. 4165. Y7 Y. Tobe T. Kishimura K. Kakiuchi and Y. Odaira J. Org. Chem. 1983 48 551. 94 K. J. Shea A. C. Greeley S. Nguyen P. D. Beauchamp and S. Wise Tetrahedron Lett. 1983 24 4173. 9s K. B. Becker and M. P. Labhart Helu. Chim. Acta 1983 66 1090. 96 H. 0. House J. L. Haack W. C. McDaniel and D. VanDerveer J. Org. Chem. 1983 48 1643; H. 0. House R. J. Outcalt J. L. Haack and D. VanDerveer ibid.,p. 1654. 204 S.A. Marlin 8 Polycyclic Compounds Formation of the steroid nucleus in one step uia the biomimetic cyclization of an acyclic polyene precursor (48) has now been achieved."' SnCI -__ Arene-olefin cycloaddition reactionsy8 generate the tricycl0[3.3.0.0~~~]0ctene ring system which is proving to be a very versatile intermediate. Examples of the exploitation of this pathway (Scheme 29) include conversions into the iridoids (49)9" and (50),'0° steroids via (51),"' and the coriolin precursor (52).'02 -b __* H (51) MeO Scheme 29 The synthesis of polyquinanes has been a focal point of numerous publications during 1983. A useful tricyclic intermediate for polyquinane synthesis is formed'03 by intramolecular Diels-Alder cyclization of the alkenylcyclopentadiene (53).Y7 W. S. Johnson Y.-Q. Chen and M. S. Kellog J. Am. Chem. SOC.,1983 105 6653. 98 R. S. Sheridan J. Am. Chem. Soc. 1983 105 5140. YY P. A. Wender and G. B. Dreyer Tetrahedron Lett. 1983 24 4543. Ino K. Kon and S. Isoe Helu. Chim. Acta 1983 66 755. IUI G. Mikhail and M. Dermuth Helv. Chim. Acta 1983 66 2362. 102 M. Dermuth A. Canovas E. Weigt C. Kruger and Y.-H. Tsay Angew. Chem. Int. Ed. Engl. 1983 22 721. I03 D. Sternbach and J. W. Hughes Tetrahedron Lett. 1983 24 3295; D. W. Landry Tetrahedron 1983 39 2761. Alicyclic Chemistry 205 Related cyclization of the allylic cation derived from (54) has been used in a route to zizaene'04 (55). Several syntheses of the racemic antitumour sesquiterpene coriolin (56) have appeared key elements of the synthetic strategies being outlined in Scheme 30.105-107 Q5 -q5cF3c09 @ R' -R4 R" R; R4 R3 SiMe, R3 (53) (54) (55) &o-Ref 106 OH '0 PhSH __* Ref 107 SPh ORZ 0r2 Scheme 30 I04 A. J. Barker and G. Pattenden J. Chem. SOC.,Perkin Trans. I 1983 1901; see also H. M. R. Hoffmann and R. Henning Helu. Chim. Acta 1983 66 828. C. Exon and P. Magnus J. Am. Chem. SOC.,1983 105 2477. P. F. Schuda and M. R. Heimann Tetrahedron Lett., 1983 24 4267. In7 P. A. Wender and J. J. Howbert Tetrahedron Lett. 1983 24 5325. 206 S. A. Matlin There have also been syntheses of hirsutene (57)"* and the related hirsutic acid C,Io9capnellenes (58),'" and cedrene (59)."' OH r SOC1,--pyridine In an approach to the synthesis of [6S]coronane (60) the pentaspirane (61) was subjected to a "cascade" rearrangement to (62).'I* Intramolecular cyclopropanation of the diazo-ketone (63) followed by desilylation affords the long-sought tricyclo[2.1 .0.02"]pentan-3-one (64).On irradiation (64) decomposes to cyclobutadiene and cyclopentadienone with no evidence for the formation of tetrahedrane by CO extrusion.'l3 iYN2 (66) (67) R' R Me I08 B. A. Dawson A. K. Ghosh J. L. Jurlina and J. B. Stothers J. Chem. SOC.,Chem. Commun.,'1983,204. I09 A. E.Greene M.-J. Luche and J.-P. DeprCs J. Am. Chem. SOC.,1983 105,2435. I10 G. Mehta D. S. Reddy and A. N. Murty J. Chem. SOC.,Chem. Cornmun. 1983 824; A.M. Birch and G. Pattenden J. Chem. SOC.,Perkin Trans. I 1983 1913. Ill M.Horton and G. Pattenden Tetrahedron Lett. 1983,24 2125. I12 J. Fitjer M. Giersig W. Clegg N. Schorrnann and G. M. Sheldrick Tetrahedron Lett. 1983,24 5351. I I3 G. Maier M.Hoppe and H. P. Reisenauer Angew. Chem. Int. Ed. Engl. 1983,22 990. Alicyclic Chemistry The undecacylic polyquinane (65) has been synthesized and christened "pagodane".' I4 Other caged polycycles for which first or improved syntheses are reported include noriceanes (66)II5 and functionalized iceanes [e.g. (67)],' I6 penta-prismane (68),Il7 4-peristylane (69),'18 dodecahedranes (70; R = H or Me),II9 and trishomocubanediones (71; R' R2 = H Me).'20 Ring expansionI2I of trishomocubanone with diazomethane provides a series of [m.1.lltriblattanes with m=3-6. Ab initio MO calculations predict the more stable structure of fenestrane (72) to be that with DZd(72a) rather than C, (72b) symmetry.'22 New routes to the antitumour fungal metabolite quadrone (74)123 include assembly of the framework uia intramolecular Diels-Alder reaction of the triene (73)'24and rearrangement of the bicyclic alcohol (75).'25 (73) (74) T 1 HCOIH r; i Py.HCrO,.CI ii HgO H,SO, P HO' R M e MeOH -H20 0&Me 114 W.-D. Fessner and H. Prinzbach Tetrahedron Lett. 1983 24 5857. IIS 2. Majerski and M. Zuanic J. Org. Chem. 1983 48 898. I I6 P. R. Spurr and D. P. G. Harnon J. Am. Chem. SOC.,1983 105 4734. I I7 W. G. Dauben and A. F. Cunningham J.Org. Chem. 1983,48 2842. 1 In L. A. Paquette A. R. Browne C. W. Doecke and R. V. Williams J. Am. Chem. SOC.,1983 105 4113. I19 G. Mehta and M. S. Nair J. Chem. SOC.,Chem. Commun. 1983 439; L. A. Paquette R. J. Ternansky D. W. Balogh and W. J. Taylor J. Am. Chem. SOC.,1983 105 5441; L. A. Paquette R. J. Ternansky D. W. Balogh and G. Kentgen ibid. p. 5446. I20 G. Mehta A. V. Reddy W. Tacreiter and T. S. Common J. Chem. ,Soc. Chem. Commun. 1983 441; see also T. Ogino K. Awano T.,Ogihara and K. Isogai Tetrahedron Left. 1983 24 2781. I21 M. Nakazaki K. Naernura and M. Hashirnoto Bull. Chem. SOC.Jpn. 1983 56 2543. 122 J. M. Schulman H. L. Sabio and R. L. Disch J. Am. Chem. Soc. 1983 105 743. I23 S. D. Burke and C. W. Murtiashaw Tetrahedron Lett.1983 24 2949. 124 R. H. Schlessinger J. L. Wood A. J. Ross R. A. Nugent and W. H. Parsons 1.Org. Chem. 1983 48 1146; J. M. Dewanckele F. Zutterman and M. Vandewalle Tetrahedron 1983 39 3235. I25 K. Takeda Y. Shimono and E. Yoshii J. Am. Chem. SOC.,1983 105 563. 208 S. A. Mutlin The olefinic double bonds of syn- (76) and anti- (77) sesquinorbornenes deviate from planarity'26 (m-tilting) and this distortion leads to a lowering of ionization potential^.'^^ The exo-and endo-isomers of the olefin (78) also show this phenomenon.'28 Virtually no twisting of the diene units in [2.2.2]hericene (79)'29 was observed by X-ray diff ra~ti0n.I~' Gleiter and PaquetteI3' have reviewed the influence of diene distortions on the stereoselectivity of addition reactions in bridged polycyclic compounds.(79) In the [n.2.2.2]paddlane systems (80; n = 10-14) 'Hm.m.r. provides evidence for an increasingly high energy barrier to rotation of the paddle as the size of the large bridgehead loop decrease^.'^^ Gas-phase pyrolysis of cubane yields vibrationally excited cyclo-octatetraene which fragments to benzene and a~ety1ene.I~~ 126 C. A. Johnson J. Chem. SOC.,Chem. Commtm. 1983 1135; 0. Ermer and C. D. Bodecker Helv. Chim. Acta 1983 66 943. I27 R. S. Brown J. M. Buschek K. R. Kopecky and A. J. Miller J. Org. Chem. 1983,48 3692. I28 K. Mackenzie A. S. Miller K. W. Muir and L. ManojloviC-Muir Tetrahedron Lett. 1983 24 4747. I29 0. Pilet J.-L. Birbaum and P. Vogel Helu. Chim. Acta 1983 66 19.I3O A. A. Pinkerton D. Schwarzenbach 0. Pilet and P. Vogel Helv. Chim. Acta 1983 66 1532. 131 R. Gleiter and L. A. Paquette Acc. Chem. Res. 1983 16 328; see also I. Erden and A. de Meijere Tetrahedron Lett. 1983 24 3811; L. A. Paquette T. M. Kravetz M. C. Bohm and R. Gleiter J. Org. Chem. 1983,48 1250. I32 P. E. Eaton and B. D. Leipzig J. Am. Chem. Soc. 1983 105 1656. '33 H.-D. Martin P. Pfohler T. Urbanek and R. Walsh Chem. Eer. 1983 116 1415.

ISSN:0069-3030    

DOI:10.1039/OC9838000189

出版商:RSC    

年代:1983

数据来源: RSC

摘要:

10 Aromatic Compounds By H. HEANEY Department of Chemistry Loughborough University of Technology Leicestershire LE 1 1 3TU 1 General A new approach to the concept of aromaticity relates ring current and bond order.' Most of the conclusions are in agreement with those reached by a topological index based on resonance energies. Molecular orbital calculations suggest that a new class of aromatic molecules is potentially available.2 The system would have a (4n + 2)v electron perimeter with a three-centre two-electron bond -the trefoil aromatics. Calculations on the structures of the silacyclopentadienyl anion and the silacyclo- propenylium cation suggest that the former is somewhat stabilized by delocalization but that the latter is destabilized by train.^ The Diels-Alder dimer of benzene is unstable with respect to its components by virtue of their high resonance energy? With the higher homologues the readiness to undergo retro-cycloaddition should not be as pronounced because only one of the cleavage products will be aromatic.Whereas the benzene dimer decomposes at -20 "C the trimer (1) is stable at 50 "C and only decomposes to three molecules of benzene at 100 "C. Some research on polycyclic ionic species and the relationship to the criteria of aromatic and antiaromatic nature has been disc~ssed.~ The question concerning the aromaticity or otherwise of oxocarbon dianions has been reviewed briefly.6 The dimerization of 2-naphthol using a copper( 11) complex of S-( +)-amphetamine not only proceeds in high chemical yield (85%) but also with high optical purity (up to 95% ).' The absolute configuration of 2-hydroxy-1,l '-binaphthyl has been revised to R-(+).* ' K.Jug J. Org. Chem. 1983 48 1344. T. Fukunaga H. E. Simmons J. J. Wendoloski and M. D. Gordon J. Am. Chem. Sac. 1983 105,2729. M. S. Gordon P. Boudjouk and F. Anwari J. Am. Chem. Soc. 1983 105 4972. W. Grimme and G. Reinhardt Angew. Chem. Int. Ed. Engl. 1983 22 617. M. Rabinovitz I. Willner and A. Minsky Acc. Chem. Rex 1983 16 298. ti F. Setratosa Acc. Chem. Rex 1983 16 170. ' J. Brussee and A. C. A. Jansen Tetrahedron Lett. 1983 24 3261. K. Kabuto F. Yasuhara and S. Yamaguchi Bull. Chem. SOC. Jpn. 1983. 56 1263. 209 210 H. Heaney The relationship between strain enthalpy bond lengths bond and torsional angles and barriers to rotation in a range of symmetrical tetra-alkyl- 1,2-diaryl ethanes have been investigated by force-field calculations.Good agreement between calculated and experimentally determined data shows the reliability of the method.' Dimeriza- tion of a,a-dialkylbenzyl radicals leads to a,p-dimers and the related aromatized products as well as the diary1 ethanes." The amount of the latter product decreases as expected as the alkyl groups become more sterically demanding. 1,2-Di-(9- anthry1)ethanes undergo thermal and photochemical intramolecular Diels-Alder reactions to give 1,2-dihydroanthracenes which on aromatization lead to novel derivatives of triptycene.' I Dynamic n.m.r. studies on 2-naphthylethylenes and 3,4-disubstituted styrenes show the effect of a-and p-substituents on the barriers to rotation.12 Ab initio calculations on the hexahalogenobenzenes show them all to be planar molecules.The possibility of geometrical distortions due to steric overcrowding is rejected. l3 On the other hand hexa-isopropylbenzene has the six alkyl groups in a tightly interlocked tongue and groove arrangement as a result of non-bonded repulsion^.'^ Scale molecular models suggest that rotation of the isopropyl groups is essentially blocked. Hexa-isopropylbenzene evidently represents an extreme example of restricted rotation. A large number of papers that are concerned with restricted rotation in triptycenes have appeared this year and of these the most important have also been concerned with gearing effects.Dynamic gearing is the dominant mode of conformational interconversion in a series of 9-benzyltriptycenes. '5 Empirical force-field calculations and an analysis of molecular symmetry reveals that whereas dynamic gearing in bis(9-triptycy1)methane is virtually unhindered gear slippage involves an energy barrier of ca. 120 kJ mol-'.'6 Bis(2,3-dimethyl-9-triptycyl)methaneand the related carbinol have been prepared and separated into meso- and (*)-isomers which were identified by n.m.r. spectroscopy. These diastereoisomers are interconverted by gear-slippage with an energy barrier of ca. 140 kJ mol-I. The related meso-bis( 1,4-dimethyl-9-triptycy1)methane has a higher energy barrier to diastereoisomerization and even dynamic gearing involves an energy barrier of ca.56kJ mol-'.I7 The separation of the enantiomers of bis(9-triptycyl)ethers,ls bis(2- and 3-chloro-9- tripty~yl)methanes,'~ and bis( 2,6-dichloro-9-triptycyl)methane20have been achieved by h.p.1.c. using a chiral support. Rapid geared rotation in 9,10-bis(3-chloro-9- triptycy1oxy)triptycene does not remove the possibility of stereoisomerism that results from phase relationships of remote substituents.21 H.-D. Beckhaus Chem. Ber. 1983 116 86. lo G. Kratt H.-D. Beckhaus H. J. Lindner and C. Ruchardt Chem. Ber. 1983 116 3235. I' H.-D. Becker and K. Anderson Tetrahedron Left. 1983 24 3273. I* J. E. Anderson D. J. D. Barkel and C. J. Cooksey Tetrahedron Lett. 1983 24 1077. l3 J. Almlof and K. Faegri J Am. Chem. Soc.1983 105 2965. l4 J. Siege1 and K. Mislow J. Am. Chem. Soc. 1983 105 7763. l5 R. B. Nachbar W. D. Hounshell V. A. Naman 0. Wennerstrom A. Guenzi and K. Mislow J. Org. Chem. 1983 48 1227; G. Yamamoto and M. Oki ibid. p. 1233. I6 H.-B. Burgi W. D. Hounshell R. B. Nachbar and K. Mislow J. Am. Chem. Soc, 1983 105 1427. " A. Guenzi C. A. Johnson F. Cozzi and K. Mislow 1.Am.Chem. Soc. 1983 105 1438; Y. Kawada and H. Iwamura ibid. p. 1449. Y. Kawada and H. Iwamura J. Am. Chem. Soc. 1983 105 1449. l9 Y. Kawada H. Iwamura Y. Okamoto and H. Yuki Tetrahedron Lett. 1983 24 791. 20 Y. Kawada Y. Okamoto and H. Iwamura Tetruhedron Left. 1983 24 5359. 2' N. Koga Y. Kawada and H. Iwamura J. Am. Chem. Soc. 1983 105 5498. Aromatic Compounds 21 1 Stereoselective syntheses of rotational isomers of a number of peri-substituted-9- ( 1,1-dimethyl-2-phenylethyl)triptyceneshave been reported and classical kinetics of rotational isomerization studied.22 Buttressing effects on rotational barriers in various tetrahalogeno-9-substituted triptycenes have also been The remarkable feature is that the larger the halogen the lower the energy barrier.The implication of these results is that buttressing destabilizes the transition state to rotation less than it destabilizes the ground state. A similar effect was observed with 9-isopr~pyltriptycenes.~~ Restricted rotation has also been observed in a number of derivatives of 9-( 1-meth~xyethyl)triptycene,~~ 9,-dimethylamino-9,1O-dihydro-9,10- ethenoanthracene- N-oxide,26 and 9-t-butyl- and 9-isopropyl-9,lO-dihydro-1 1 -thia-9,lO-ethanoanthracene derivative^.^' Values for the barrier to rotation about the aryl-carbenium carbon bond in a series of ions have been measured by n.m.r.methods.28 A number of carbodications which have been studied under stable ion conditions are potentially aromatic. A review includes examples such as the tetramethylcyclobutadiene di~ation.~~ In the dications derived from substituted anthracenes substantial positive charge is located at positions 9 and The use of nOe difference spectroscopy demonstrates the generality of the preference for an S-trans-orientation of the carbonyl group to the ortho-position of highest double bond character in aromatic aldehydes and ketone^.^ This result is confirmed for the 1-and 2-naphthaldehydes from a study of long-range H-H spin-spin coupling constants.32 ''N and "0 N.m.r.spectral data have been reported for a number of meta -and para -substituted nitro benzene^.^^ The polar nature of the substituent is most important in determining nitrogen chemical shifts. Electron-withdrawing substituents induce upfield "N shifts (apparently through space) while the "0 shifts follow a normal direction. 2 Homoaromatic and other Ions Highly sophisticated theoretical treatments are necessary if problems associated with homoaromaticity are to be solved.34 In spite of this prediction a number of groups of workers still produce experimental evidence. Homoaromatic stabilization or otherwise of anions is the controversial area and this has been further probed by 13C n.m.r.~pectroscopy~~ and also by measuring the pk,s of a number of bicyclic hydrocarbon^.^^ Deuterium isotope effects in the anion derived from (2;X = D) favour the interpretation of the chemical shifts as being due to a single species (3) 22 G. Yamamoto M. Suzuki and M. Oki Bull. Chem. SOC.Jpn. 1983 56 306. 23 G. Yamamoto M. Suzuki and M. Oki Bull. Chem. SOC.Jpn. 1983 56 809. 24 G. Yamamoto and M. Oki Bull. Chem. SOC.Jpn. 1983 56 2082. 25 Y. Tanaka G. Yamamoto and M. Oki Bull. Chern. SOC.Jpn. 1983,56,3023; G. Yamamoto Y. Tanaka and M. Oki ibid. p. 3028. 26 F. Kakizaki N. Nakamura and M. Oki Chem. Lett. 1983 81. 27 M. Lancaster and D. J. H. Smith J. Chern. Res. (S) 1983 226. 28 R. Jost and J.Sommer J. Chem. Soc. Perkin Trans. 2 1983 927. 29 G. K. S. Prakash T. N. Randah and G. A. Olah Angew. Chem. Int. Ed. Engl. 1983 22 390. 30 G. A. Olah and B. P. Singh J. Org. Chem. 1983 48 4830. 3' L. I. Kruse and J. K. Cha Tetrahedron Lett. 1983 24 2367. 32 S. R. Salman Org. Mag. Res. 1983 21 672. 33 D. J. Craik G. C. Levy and R. T. C. Brownlee J. Org. Chem. 1983 48 1601. 34 R. C. Haddon and K. Raghavachari J. Am. Chem. SOC.,1983 105 118. 35 M. Christl H. Leininger and D. Bruckner J. Am. Chem. SOC.,1983 105 4843. 36 W. N. Washburn J. Org. Chem. 1983 48 4287. 212 H. Heaney rather than a number of species for example (4) being in equilibrium. A similar conclusion is reached when comparing the pk of (2;X = H) with (5) where the former compound has a pk at least nine units smaller than (5).This enhanced acidity corresponds to a stabilization of at least 50 kJ mol-' relative to the anion of (5). These results emphasize the importance of homoaromaticity for suitable allylic anions. Electron-electron repulsion is high in the homoaromatic dianion HCOT2- derived from cis-bicyclo[6.1 .O]nona-2,4,6-triene. Thus the heat of formation of the homoaromatic species is close to zero.37 In contrast to the well known stability of the dianion derived from cyclo-octatetraene which can be stored in solution in THF at room temperature for prolonged periods HCOT2- is not stable in this solvent except at low temperatures. Methyl-lithium and methylene chloride generate carbene which reacts with dilithiopentalene (6) to give the laterally bridged benzvalene derivative (7).This latter compound is explosive even at -40 "C. However in dilute solution a controlled rearrangement to indene (6) (7) The heats of transfer from carbon tetrachloride to fluorosulphuric acid for a series of ketones have been measured in order to evaluate the importance or otherwise of homoaromatic stabilization of the resulting cations.39 The importance of homoaromaticity in stabilizing homotropylium cations was indicated. The magnitude of the energy differences between the series of [C6HMe6]+ ions (8)-( 1 1) have been discussed in terms of the resonance energies of the ions.40 H Me H Me .. (8) (9) (10) (1 1) 37 E. Concepcion R. C. Reiter and G.R. Stevenson J. Am. Chem. SOC.,1983 105 1778. 38 W. Burger and B. Bianco Helv. Chim. Acta 1983 66,60. 39 R. F. Childs D. L. Mulholland A. Varadarajan and S. Yeroushalmi J. Org. Chem. 1983 48 1431. 40 R. F. Childs and D. L. Muiholland J. Am. Chem. SOC.,1983 105 96. Aromatic Compounds 213 The ionization of certain unsaturated [4.4.3]propellanyl-3,5-dinitrobenzoates,not-ably ( 12) and ( 13) proceed with assistance from bishomotropylium ion f~rmation.~' A novel bishomoaromatic allylic dication (14) has been generated and studied at < -100 "C. At higher temperatures it rearranges The possibility that ( 15) exists as a tris-homoaromatic cation is discounted on the basis of a comparison of the n.m.r. data for the ion and its tetrahydro-analogue.However the possibility that the two methyl groups so stabilize the allylic cation as to preclude the involvement of the tris-homoaromtic ion cannot be di~counted.~~" The ion (16) on the other hand does show bis-homoaromatic proper tie^.^^ Copper(I) catalysed decomposition of diazomethane in the presence of benzocyclobutene results in the formation of a mixture of cyclobutane-fused cycloheptatrienes by carbene insertion. Abstraction of hydride ion by means of a trityl salts affords the cyclobutane-fused tropylium ion.44 The same methodology has been applied to other mono- bis- and tris-annelated tropylium salts. 3 Quinodimethanes and Related Reactive Intermediates Regio- and stereo-controlled intramolecular Diels-Alder reactions of o-quinodi- methanes continue to attract attention in the design of synthesis.(*)-Chelidonine and (*)-norchelidonine have both been prepared by routes involving intramolecular nitrostyrene cycloaddition reactions.45 The elimination of methanol from methyl o-methylbenzyl ethers can be effected using lithium dialkylamide~.~~ However in order to avoid the subsequent addition of the dialkylamine -and this even occurs with di-isopropylamine -a highly hindered base such as lithium 2,2,6,64etramethyl- piperidide must be used. A number of o-methyl styrene derivatives that have suitably 41 L. A. Paquette K. Ohkata K. Jelich and W. Kitching J. Am. Chem. SOC. 1983 105 2800. 42 G. A. Olah M. Arvanaghi and G. K. S. Prakash Angew. Chem. Int. Ed. Engl. 1983 22 712. 43 (a) M.Glanzmann and G. Schroder Chem. Ber. 1983 116 2903; (b) p. 2914. 44 R. P. Thummel and P. Chayangkoon J. Org. Chem. 1983,48 596. 45 W. Oppolzer and C. Robbiani Helu. Chim. Ac~Q, 1983 66 119. 46 T. Tuschka K. Naito and B. Rickborn J. Org. Chem. 1983 48 70. 214 H. Heaney positioned additional double bonds have been photolysed at low temperatures using a low pressure mercury sou~ce.~' Thus the o-quinodimethane generated from (17) gave the product ( 18) in 24% yield. 0-(Propadieny1)styrene and the highly strained hydrocarbon (19) rearrange at a measurable rate even at 30 "C.The major products all arise via the o-quinodimethane derivative (20).48The formation of (20)is rate determining and can be intercepted as the adduct with N-phenylmaleimide at a rate that is consistent with those of reactions carried out in the absence of N- phenylmaleimide.Cycloprop[b]anthracenes have now been prepared by a short synthetic sequence in which they key step is the cycloaddition reaction between tetrahalogenocyc- lopropenes and an o-naphthoq~inodimethane.~~ The full paper on the generation and reactions of 1,3-diphenylbenz[fJinden-2-onehas a~peared.~' The photodecar- bonylation of adducts such as (21) yield the naphthoquinodimethane (22) which was characterized by u.v.-visible spectroscopy and by the formation of adducts with for example 4-phenyltriazoline-3,5-dione. Terpenoids containing quinone methide residues have now been identified.51 The metallic properties of charge-transfer complexes formed from 7,7,8,8-tetracyano-p-benzoquinodimethanecan be investigated more easily since a high yield (80% overall) route to this compound from p-dihydroxybenzene allows large batches to be made.'* The electrical properties of the charge-transfer complexes formed from tetracyano-p-benzoquinodimethane-aceticand -propionic acids have been studied.53 rn-Xylylene is fundamentally different from the 0-and p-isomers in that no KekulC structure fully satisfies the valency of every carbon atom without involving highly 47 J.M. Hornback and R. D. Barrows J. Org. Chem. 1983 48 90. 48 W. H. Brinker G. Wilk and K. Gomann Angew. Chem. In?. Ed. EngL 1983 22 868. 49 P. Muller and D. Rodriguez Helv. Chim. Acta 1983 66 2540. 50 D. W. Jones A.Pornfret and R. L. Wife J. Chem. Soc. Perkin Trans. I 1983 459. 5' Y. Hirose S. Hasegawa N. Ozaki and Y. Iitaka Terrahedron Lerr. 1983 24 1535. 52 R. J. Crawford J. Org. Chem. 1983 48 1366. 53 J. Baghdadchi and C. A. Panetta 1.Org. Chem. 1983 48 3852. Aromatic Compounds strained bicyclic structures. rn-Xylylene is expected therefore to be a triplet di- radical. The e.s.r. spectrum recorded at 77 K is in accord with this predi~tion.’~ The involvement of o-quinone methide intermediates in the reactions of aryloxy- magnesium bromides with aldehydes has been established by means of trapping experiments.” Thus the reaction of phenoxymagnesium bromide with 2-methylpro- panal and ethyl vinyl ether results in the formation of (23). The thermal and photochemical ring opening of benzothiet and subsequent cycloaddition reactions have been reported,s6 and a full paper on the preparation and reactions of o-quinone monosulphonimides has been published.” Napththo-2,3-quinones have been the subject of further studies.The oxidation of 1,4-di-o-tolylnaphthalene-2,3-diol by means of lead tetra-acetate at -30 “C affords the quinone (24).’* This compound is sufficiently stable to allow characterization by U.V. and i.r. spectroscopy and by the formation of the adduct (25) by interaction with norbornadiene. U-L, I’ ‘OEt 4 Benzene Derivatives Ring Syntheses.-The preparation of highly functionalized rings by rational synthesis from acyclic precursors has again attracted attention. The most important feature of this approach is the control over the regiochemistry that is incorporated into the component parts.The Diels-Alder reaction continues to be utilized in many of the syntheses where two-atom and four-atom components are combined. Some examples of the use of silyloxy-substituted 1,3-dienes are collected together as part of a review of the use of silyl enol ethers in ~ynthesis.’~ An early step in a synthesis6’ of the naphthalene nucleus of the ansamycin streptovaricin D used 1-methoxy-2-methyl-1,3-bis(trimethylsily1oxy)-buta-1,3-diene The naphthoquinone (26) was isolated in 8 1% yield. The phthalide (27) and the acetophenone (28) have both been prepared using trimethylsilyl groups to protect oxygen functions in both diene and the dienophile.61 Oxygen functionality has also been incorporated using 1,4-di-oxygenated buta- 1,3-diene~,~~.~~number of 3-arylphthalides have been prepared64 using and a 54 B.B. Wright and M. S. Platz J. Am. Chem. SOC.,1983 105 628. ” G. Casnati A. Pochini M. G. Terenghi and R. Ungaro J. Org. Chem. 1983 48 3783. ’6 K. Kanakarajan and H. Meier J. Org. Chem. 1983,48 881. 57 S. Fujita J. Org. Chem. 1983 48 177. 58 D. W. Jones and A. Pornfret J. Chem. SOC.,Chem. Comrnun. 1983 703. 59 P. Brownbridge Synthesis 1983 28; 85. 60 B. M. Trost and W. H. Pearson Terrahedron Lerr. 1983 24 269. 6’ R. Baker V. B. Rao P. D. Ravenscroft and C. J. Swain Synthesis 1983 572. 62 H. Hiranurna and S. I. Miller J. Org. Chem. 1983 48 3096. 63 H.-J. Altenbach B. Voss and E.Vogel Angew. Chem. Znt. Ed. Engl. 1983 22 410. 64 P. A. Harland and P. Hodge Svnrhesis 1983 419. 216 H. Heaney Me arMe GoMeoco2Me Ho \ HO \ Me HO \ COMe 0 cyclohexa- 1,3-diene derivatives and ethyl 4-aryl-4-hydroxybut-2-ynoates followed by thermal retro-Diels-Alder ejection of ethylene and lactonization. One of the more interesting developments concerns the possibility of utilizing multiple Diels-Alder reactions in the construction of benzannelated systems. The formation of the dihy- dronaphthol (29) in 47% is shown in Scheme 1 starting with 3-benzylidene-2,4- bis(trimethylsily1oxy)penta-1,4-die11e.~' C0,Me C0,Me MeOzC \ (29) Reagents i HC=C-CO,Me; ii MeOH Scheme 1 The use of 2,2-dimethyl-2H-pyran derivatives in the preparation of benzene derivatives has been further elaborated,66 and boron trifluoride catalysed Diels-Alder reactions of methyl vinyl ketone and a number of 3-thio- or seleno-substituted halogenobuta- 1,3-dienes provides a route to 4-substituted acetophenones that appears to be capable of further elab~ration.~~ The electrocyclic ring opening of (30) affords a 1,3-diene and reaction with 1,4-naphthoquinone with (30) in xylene containing alumina gave the anthraquinone (31) in 95% yield.68 65 0.Tsuge E.Wada and S. Kanemasa Chem. Lett. 1983 239. 66 S. Matsugo and A. Takarnizawa Synthesis 1983 852. 67 A. J. Bridges and J. W. Fischer Tetrahedron Lett. 1983 24 447. 68 A. J. Barker M. J. Begley A. M. Birch and G. Pattenden J. Chem.Soc. Perkin Trans. I 1983 1919. Aromatic Compounds The syntheses of benzene derivatives by means of inverse electron demand Diels-Alder reactions of 3-methoxycarbonyl-2-pyroneswere reported last year. Further examples result in the formation of a range of products containing differenti- ated di- and tri-oxygenated rings.69 1 ,.Q-Diaza- 1,3-diene-iron(O) complexes have been used to hold acyclic dienes in the S-cis-conformation and experiments using 4,4,7,7-tetramethylcyclo-octyneled to the formation of the benzene derivative (32) as the only The tendency of terminal acetylenes to polymerize rather than cyclo-trimerize can be controlled by using NbC1 or TaCl as catalyst^.^' Limited success has been achieved using the anion derived from (33) as a four-atom component in benzene ring syntheses.'* The preparation of 6-methoxycarbonyl- 1,2,3,4-tetrahydronaphthalene in 86% yield utilized methyl acrylate as the two-atom component.2-( Phenylsulphonyl)methylbenzyl bromide and its derivatives for example (34),undergo condensation reactions with a number of esters. The com- pound (34)gave 2-ethyl-3-hydroxy-5-methoxynaphthalene (35)with dimethyl ethyl- mal~nate.~~ A number of new biphenylenes have been prepared in good yield by the base-catalysed (DBU) condensation of benzocyclobutene- 1,2-diones with 0-bis( ~yanornethy1)arenes.~~ Benzene ring syntheses that involve the joining together of two three-atom com- ponents also continue to appear. An extension of previously established methodology for the elaboration of benzene rings from a-methylene ketones allows the synthesis 69 D.L. Boger and M. D. Mullican Tetrahedron Lett. 1983 24 4939. 70 H. tom Dieck and R. Diercks Angew. Chem. Znt. Ed. Engl. 1983 22 778. " T. Masuda Y.-X.Deng and T. Higashimura Bull. Chern. SOC.Jpn. 1983 56 2798 72 J. 9. Dickenson and W. Reusch Synth. Comrnun. 1983 13 303. 73 E. Ghera and Y. Ben-David Tetrahedron Lett. 1983 24 3533. 74 P. R. Buckland N. P. Hacker and J. F. W. McOmie J. Chem. Soc. Perkin Trans. I 1983 1443. 218 H. Heaney of catechol mono ether^.^^ The zinc ‘ate complex’ derived from ethoxyallyl-lithium and zinc chloride attacks the carbonyl group of 2-formylketone trimethylsilyl enol ethers exclusively by interaction with the a-carbon of the nucleophile.The sequence of reactions is exemplified in Scheme 2 for the conversion of the trimethylsilylether of 2-formyl-3,4-dihydronaphthalen-2H-1-one into 4-ethoxy-3-hydroxy-9,l O-dihy- drophenanthrene which was achieved in a 66% overall yield. A similar sequence has also been used for the construction of the middle benzenoid ring in m-terphenyl~.’~ OH aTMS...... _____, I,II,II1,IV & \ \ Li ~ I Reagents i EtO-CH-CH=CH2 ZnC1,; ii \ ,N-H Ts- CH2CI,; iii O, CuCI PdCI, H,O; c iv KOH EtOH Scheme 2 Double aldol condensation reactions involving methyl 4-nitro-3-oxobutyrate and a range of P-dicarbonyl compounds afford substituted 3-nitro~alicylates.~~ With unsymmetrical P-dicarbonyl compounds both regio-isomers are normally formed.However high selectivity was observed using P-ketoaldehydes. The base-catalysed (sodium ethoxide) cyclization of the bis-P-dicarbonyl compound (36) results in the formation of (37) in high yield. This latter compound was cyclized to the key intermediate (38) required for a synthesis of mycophenolic acid using n-butyl- The synthesis of benzene rings by the combination of a stabilized carbanion and a vinamidinium salt has been extended to the use of carbanions derived from ally1 pho~phonates.~~ The formation of m-aminophenols by acid-catalysed cycliza- tions of eneamino-esters achieves highly desirable functionality. The compounds (39) and (40) combine to form (41).80The synthesis has additional interest in that the structural features in the reactants may be adjusted so that the benzenoid ring is constructed from a four-carbon and a two-carbon unit.(34) (37) 75 M. A. Tius and A. Thirkauf J. Org. Chem. 1983,48 3839. 76 M. A. Tius and S. Savariar Synthesis 1983 467. 77 R. 0.Duthaler Helv. Chim. Acta 1983 66 2543. 78 S. Auricchio A. Ricca and 0. Vajna de Pava J. Org. Chem. 1983 48 602. 79 G. D. Ewen M. A. K. El-Deek D. J. H. Smith and S. Trippett J. Chem. Res. (S) 1983 14. 80 T. H. Chan and G. J. Kang Tetrahedron Lett. 1983 24,3051. Aromatic Compounds Reactions with Electrophi1es.-Partial rate factors for the proto-detritiation of a range of helicenes have been correlated with reactivity indices.8' The use of the t-butyl group to block reactive positions has been further exemplified in the preparation of 2-acylaminobiphenyls from biphenyl.82 Non-hazardous alternatives to classical chloromethylation procedures have been published.Methoxyacetyl chloride reacts with a variety of aromatic compounds in the presence of aluminium chloride to give chloromethylated produ~ts.'~ Although the nature of the electrophile has not been established unambiguously it may well be the methoxymethyl carbenium ion. Amidomethylation also constitutes a useful alternative since amidomethyl derivatives can be converted into the chloromethyl compound by reaction with phosphoryl chloride in DMF.'4 N-Hydroxymethyl-acetamide can be used as a source of the electrophile. 2-Acetamidomethyl-4- nitrotoluene can be prepared in good yield from 4-nitrotoluene.Aminomethylation using a pre-formed iminium salt85 such as Eschenmoser's salt in place of the classical conditions for phenol Mannich reactions presents significant advantages when carried out in aprotic solvents.86 Poly-aminoalkylation is avoided using solid-liquid phase transfer conditions. The phenol is dissolved in an organic solvent typically toluene or dichloromethane for phenols that bear electron with- drawing groups and is stirred with a solid base and a solid methyleneiminium salt. The phenylation of 4-iodoanisole during the thermolysis of benzenediazonium fluoroborate results in the formation of 4-iododiphenyl ether and 4-meth~xybiphenyl.~' It was suggested that the first step involves predominantly kinetic C-arylation.It is noteworthy that no intramolecular rearrangement occurs from the oxonium salt. Friedel-Crafts cyclo-alkylation reactions have been investigated using the epoxy-function as the potential electrophile. Skeletal rearrangements that charac- terize reactions of alcohols are less troublesome with epoxides. Six-membered rings are formed in high yields and seven-membered rings in moderate yields by cycliza- tions to a secondary but not to a primary carbon.88 Quinone methide ketals for ''A. S. Shawali H. M. Hassaneen C. Parkanyi and W. C. Herndon J. Org. Chem. 1983,48 4800. 82 M. Jashiro Y. Fukuda and T. Yamato J. Org. Chem 1983 48 1927. n3 A. McKillop F. Abbasi Madjdabadi and D. A. Long Tetrahedron Lett. 1983 24 1933. 84 D. R. Maudling K.D. Lotts and S. A. Robinson J. Org. Chem. 1983 48 2938. 85 H. Heaney 'Arenes and their Reactions' Chapter 2.5 in 'Comprehensive Organic Chemistry' Vol. I ed. J. F. Stoddart Pergamon Oxford 1979. 86 A. Pochini G. Pughia and R. Ungaro Synthesis 1983 906. 87 E. Eustathopoulos J. Court and J.-M. Bonnier J. Chem. SOC.,Perkin Trans. 2 1983 803. nn S. K. Taylor G. H. Hockerman G. L. Karrick S. B. Lyle and S. B. Schramm J. Org. Chem. 1983 48 2449. 220 H. Heaney Me0 m \ CJ S Me0 OMe (42) OMe (44) (45) example (42)89 and ketene dithioacetals for example (43),90 take part in acid- catalysed cyclization reactions to afford (44) and (45) respectively. Mixed anhydrides formed between arene- and alkene-carboxylic acids and triflic acid react with aromatic compounds in the absence of Lewis acids.” Further acylation to give enol esters occurs with some systems.Thus p-xylene reacts with isobutyryl chloride and silver trifluoromethanesulphonate to afford 2,Sdimethyl- isobutyrophenone in low yield together with a 48% yield of its enol ester. It has been suggested that acylations using carboxylic acids in triflic acid probably proceed via the protonated form of a mixed anh~dride.~’ The vinylogous Vilsmeier formyla- tion of nucleophilic aromatic systems such as N,N-dimethylaniline proceeds in fair to good yield using 3- N,N-dimethylaminoacrolein derivatives. The compound (46) gave the cinnamaldehyde derivative (47) in 61% yield.93 The use of magnesium methyl carbonate in the carboxylation of 1-naphthol derivatives provides a useful alternative to the classical Kolbe-Schmitt reaction.6-Amino- 1-naphthol gave the corresponding carboxylic acid in 84% yield.94 The protonation of a number of azides results in the formation of stable aminodiazonium ions.95 These ions have been shown to aminate a range of aromatic compounds in high yield. x9 A. Pelter R. S. Ward and R. R. Rao Tetrahedron Lett. 1983 24 621. 90 J. H. Rigby A. Kotnis and J. Kramer Tetrahedron Lett. 1983 24 2939. 9’ F. Effenberger E. Sohn and G. Epple Chem. Ber. 1983 116 1195. 92 R. M. G. Roberts and A. R. Sadri Tetrahedron 1983 39 137. 93 F.-W. Ullrich and E. Brcitmaier Synthesis 1983 641. 94 L. A. Cate Synthesis 1983 385. 95 A. Mertens K.Lammertsma M. Arvanaghi and G. A. Olah. J. Am. Chem. SOC.,1983 105 5657. Aromatic Compounds 22 1 Nitrogen- 14 n.m.r. spectroscopy has been used to study the equilibrium between nitric acid and the nitronium ion in sulphuric acid.96 The results obtained are in good agreement with those obtained using Raman spectroscopy. The nitration of 2-t-butylpyrene and 2,7-di-t-butylpyrene results in the formation of 1-nitro-deriva-tives. Very weak interaction between the nitro-group(s) and the aromatic r-system suggests that the orientation of the nitro-group is perpendicular to the system." Nitration reactions on a range of substrates has been reported using a nitric acid-tin( ~v) chloride complex in dichloromethane. The reactions give acceptable to very good yields in most cases but benzonitrile did not react.98 With anisole it was found necessary to carry out the reaction in dilute solution at a low temperature ion order to avoid the formation of the unexpected quinone (48).Me Me,N 0 Nitrosoarenes are not intermediates in nitration reactions for example of benzene and toluene that are carried out in trifluoroacetic acid using nitrite or nitrogen dioxide.99 The nitrous acid catalysed nitration of naphthalene can be carried out under conditions such that nitrosation does not occur.1oo Interesting papers that are concerned with ipso-nitration reactions continue to appear. New features of these reactions are still being discovered. The first report of the identification of arene adducts having a secondary nitro-group has been published."' These compounds for example (50) are formed from the more usual ipso-adducts for example (49) by rearrangements that appear to involve [1,5] and [1,3] sigmatropic nitro-shifts.Labelling studies using H15N03 support the view that the formation of 1,2,3,5-tetrachloro-4,6-dinitrobenzeneduring the nitration of 1,3,5-trichlor0-2,4-dinitroben-zene arises via the @so-Wheland intermediate in which two nitro-groups are on the same carbon atom.lo2 Similarly "N-labelling studies show that ca. 22% of the 96 D. S. Ross K. F. Kuhlmann and P.Malhotra J. Am. Chem. Soc. 1983 105 4299. 97 L. Rodenburg R. Brandsma C. Tintel J. Cornelisse and J. Lugtenburg J. Chem. SOC Chem. Commun. 1983 1039. 98 J. Einhorn S.H. Desportes P. Demerseman and R. Royer J. Chem. Rex (S) 1983 98. 99 B. Milligan J. Org. Chem. 1983 48 1495. 100 D. S. Ross K. D. Moran and R. Malhotra J. Org. Chem. 1983 48 2118. 101 G. S. Baport A. Fischer G. N. Henderson and S. Raymahasay J. Chem. SOC.,Chem. Commun. 1983 119. I02 R. B. Moodie M. A. Payne and K. Schofield. J. Chem. SOC.,Chem. Commun. 1983 233. 222 H. Heaney 2,4-dinitrophenol formed when 4-nitrophenol is nitrated in trifluoroacetic acid arises from ipso-attack at the 4-position. The 1,3-shift that follows appears to be extramolecular possibly by involvement of the radical pair ArO..NO,. lo3 These two results provide the first examples of reactions that involve nitro-denitration. The nitration of (51) affords in addition to the expected products the tricyclic adduct (52) which is formed by ipso-attack followed by cycli~ation.'~~ N N-2,4,6- Pentamethylaniline reacts with 70% nitric acid at 0 "C to form the relatively stable ipso-ion (53) which may be isolated as its hexafluor~phosphate.'~~ In more aqueous media the nitrocyclohexadienone (54) is formed.MeV MeV NHCOEt Me0 \ "Me 0 The nitration of a number of N,N-dimethylanilines in aqueous sulphuric acid gives ipso-intermediates by two mechanisms.'06 In 6&70% sulphuric acid a nitrous acid catalysed mechanism is involved while in 76-83% sulphuric acid N,N-3,4,5-pentamethylaniline results in 85% of ipso-attack at the 4-position by the nitronium ion. Rate profies and isotope effects have been determined for the rearrangements of the ipso-intermediates involved in the nitration reactions of N,N-dimethylani- lines,'o7 and the kinetics of solvolyses in aqueous sulphuric acids of the ispo-adducts derived from acetyl nitrate and p-chiorotoluene have been reported."' The 1,3- migrations of the nitro-group that occur during solvolyses of 2-cyano-3,4-dimethyl-4- nitrocyclohexa-2,5-dienyl acetate in aqueous sulphuric acid do not involve intramolecular shifts.lo9 Benzaldehyde and aromatic ketones may be hydroxylated by hydrogen peroxide in the presence of hexafluoroantimonic acid without concomitant Baeyer-Villiger 103 A. H. Clemens J. H. Ridd and J. P. B. Sandall J. Chem. Soc. Chem. Commun. 1983 343. 104 N. R. A. Beeley G. Cremer A. Dorltne B. Mompon C.Pascard and E. T. H. Dau J. Chem. SOC. Chem. Commun. 1983 1046. lo' P. Helsby and J. H. Ridd J. Chem SOC.,Perkin Trans. 2. 1983 31 1. I06 F. El-Omran and J. H. Ridd J. Chem. SOC. Perkin Trans. 2 1983 1185. 107 P. Helsby and J. H. Ridd J. Chem. SOC.,Perkin Trans. 2 1983 1191. I08 C. Bloomfield R. B. Moodie and K. Schofield J. Chem. SOC.,Perkin Trans. 2 1983 1793. I09 C. Bloomtield R. B. Moodie and K. Schofield J. Chem. SOC.,Perkin Trans. 2 1983 1003. Aromatic Compounds 223 oxidation."' Both a-and P-naphthol are hydroxylated selectively on the non-phenolic ring presumably uza the C-protonated species.' ' t-Butyl bromide activated by means of DMSO reacts with phenols to give either products of bromination or methyl thiomethylation.' I2 An appropriate choice of conditions allows a choice to be made about the direction in which the reaction proceeds.Highly activated aromatic rings are so dominated by the influence of electron-releasing substituents that a trimethylsilyl residue in a meta-position does not readily undergo ipso-halogeno-desilylation. In order to achieve regiospecific bromination of phenols it is necessary to reduce the nucleophilicity of the arene residue by conversion into the acetate. All three isomeric trimethylsilylphenyl ace- tates undergo ipso-halogeno-desilylation in good yield.' l3 The bromination of phenol and 2,5-dimethylphenol in aqueous solution has been studied by stopped-flow ultraviolet spectrophotometry.' l4 The cyclohexadienone intermediates have been detected and using p-cresol the product that results from ipso-attack can also be observed.The bromination of a number of phenols which have a p-methyl group give as the main products compounds where the bromine is meta- to the hydroxy- group. These products also arise by ipso-bromination followed by rearrangement of the bromodienone.' Electron-rich aromatic compounds such as anisole are chlorinated regioselectively by N-chloroamines."6 N-Chloropiperidine or N-chlorotriethylammonium chloride in trifluoroacetic acid at room temperature both react to give almost exclusively 4-chloroanisole. Fluoro-demetallation reactions have been used to prepare "F-labelled fluorobenzene.' l7 Reactions of fluorine with aryl-tin compounds gave the highest yields. Reactions with Nucleophi1es.-Although the reactions of aqueous base with 2,4- dinitrohalogenobenzenes is well known this type of reaction is rarely used to prepare the mono-nitrophenols which are formed in moderate yields."' In addition it has been shown that the nitroanilines undergo displacement of the amino-group presum- ably by an S,Ar mechanism.A number of copper( 1)-promoted reactions of anions with aryl iodides and bromides have been reported. Ethyl cyanoacetate is arylated in yields ranging from 50 to 90?!0,"~ and reactions of the malonitrile anion have also been reported. 2o Copper(I) arenethiocarboxylates give S-aryl thiolarenecar- boxylates in yields from CQ. 70-95% ,'*ln and arenephosphonates are obtained by interaction of phosphite anions with aryl halides in the presence of copper(1) iodide.I2' bThe amination of aryl bromides with N,N-diethylamino-tributylstannane in the presence of catalytic amounts of bis( tri- o-tolyl phosphine)palladium dichloride I10 J.-P.Gesson J.-C. Jacquesy M.-P. Jouannetaud and G. Morellet Tetrahedron Lett. 1983 24 3095. Ill J.-C. Jacquesy M.-P. Jouannetaud and G. Morellet Tetrahedron Lett. 1983 24 3099. I I2 A. Dossena R. Marchelli and G. Casnati J. Chem. SOC.,Perkin Trans. I 1983 1141. 1 I3 D. S. Wilbur W. E. Stone and K. W. Anderson J. Org. Chem. 1983 48 1542. 114 0. S. Tee N. R. Iyengar and M. Paventi J. Org. Chem. 1983,48 759. I IS A. Fischer and G. N. Henderson Can. J. Chem. 1983 61 1045. I I6 J. R. Lindsay Smith and L. C. McKeer Tetrahedron Lett.1983 24 31 17. I I7 M. J. Adam J. M. Berry L. D. Hall B. D. Pate and T. J. Ruth Can. J. Chem. 1983 61 658. 1 I8 J. S. Anderson and K. C. Brown Synth. Commun. 1983 13 233. 119 A. Osuka T. Kobayashi and H. Suzuki Synthesis 1983,67; H. Suzuki T. Kobayashi Y. Yoshida and A. Osuka Chem. Lett. 1983 193. 120 H. Suzuki T. Kobayashi and A. Osuka Chem. Lett. 1983 589. 121 (a) A. Osuka N. Ohmasa Y. Uno and H. Suzuki Synthesis 1983 68; (b) A. Oskua N. Ohmasa Y. Yoshida and H. Suzuki ibid. p. 69. 224 H. Heaney proceeds in good yield.'" The reaction with p-chlorobromobenzene did not give the disubstituted product thereby eliminating the possible involvement of an S, 1 process. The methoxylation of 5-bromovanillin occurs readily using freshly prepared sodium methoxide in DMF-MeOH in the presence of 0.4 equivalents of anhydrous copper(I1) chloride at 100 OC.lZ3 The product is obtained in 83% yield.The replace- ment of phenolic oxygen functions by means of carbon nucleophiles has been achieved in good yields using the reactions of aryl triflates with lithium cuprates.Iz4 The reported nucleophilic demercuration reactions of compounds that have mercury adjacent to a carboxylate group have been re-investigated without success. Phase-transfer catalysis has been used to carry out nucleophilic substitution reactions of weakly activated aryl halides in the preparation of alkyl arylsulphides.'26 The alkyl arylsulphides can be dealkylated using a sodium sodium methanethiolate or sodium methoxide in HMPA.'27 Selectivity among various possible alkyl groups can be achieved by the correct choice of the reagent.Sodium methoxide reacts with the dichlorobenzenes in HMPA to give chloroanisoles which are themselves demethyl- ated.'28 Dimethylformamide or dimethylthioacetamide have been used as alterna- tives to HMPA in nucleophilic substitution reactions on unactivated or weakly activated aryl halides.IZ9 In the reactions using lithium methylselenide the aryl methylselenides are themselves rapidly dealkylated by the lithium methylselenide under the reaction conditions used.'30 Carbanions which themselves contain a leaving group take part in reactions of nitroarenes in which hydride is replaced. These reactions have been called vicarious nucleophilic substitution reactions.The reactions of carbanions derived from a-chlorosulphoxides with nitroarenes give nitrobenzylsulphoxides in good ~ie1d.I~' In the analogous reactions using the anions from 1-chloroalkanesulphonic esters it proved necessary to use neopentyl- and phenyl-chloromethanesulphonatesin order to avoid nucleophilic substitution of the sulphonate anion and base induced p-elimination reactions.13* The ambident nucleophilic properties of the phenoxide ion in reactions involving the formation of Meisenheimer complexes have been known for a decade. The first report'33 that aromatic amines can act as potential carbon nucleophiles in 0-complex formation with nitroarenes has been published. The addition of aniline to one equivalent of 4,6-dinitrobenzofuran- 1-oxide (55) results in the rapid formation of the zwitterion (56).The addition of two equivalents of aniline to (55) results in the rapid formation of (57) and (58). However (57) is converted into (58) within 30 min. N,N-Dimethylaniline forms the complex (59) with (55) in the absence of base I22 M. Kosugi M. Kameyama and T. Migita Chem. Len. 1983 927. I23 D. V. Rao and F. A. Stuber Synthesis 1983 308. I24 J. E. McMurry and S. Mohanraj Tetrahedron Lett. 1983 24 2723. I25 G. B. Deacon G. N. Stretton and M. J. O'Connor Synth. Commun. 1983 13,1041. I26 D. Landini F. Montanari and F. Rolla J. Org. Chem. 1983,48 604; A. Alemagna P. Del Buttero C. Gorini. D. Landini E. Licandro and S. Maiorana ibid.,p. 605. I27 L. Testaferri M.Tingoli M. Tiecco D. Chianelli and M. Montanucci Phosphorus and Sufphvr 1983 15 263. 128 L. Testaferri M. Tiecco M. Tingoli D. Chianelli and M. Montanucci Tetrahedron 1983 39 193. 129 L. Testaferri M. Tiecco M. Tingoli D. Chianelli and M. Montanucci Tetrahedron 1983 39,751. I30 M. Tiecco L. Testaferri M. Tingoli D. Chianelli and M. Montanucci J. Org. Chem. 1983 48 4289. 131 M. Makosza J. Golihski and J. Pankonski Synthesis 1983 40. 132 M. Makosza and J. Goliftski Synthesis 1983 1023. I33 M. J. Straws R. A. Renfrow and E. Buncel J. Am. Chem. SOC.,1983 105 2473. Aromatic Compounds NO (60) ~atalysis.'~~ 7r-Excessive heteroaromatic compounds such as pyrrole form C-bonded adducts including appreciable amounts of the diastereoisomeric bis-ad duct^.'^^ The transfer of hydride ion to 1,3,5-trinitrobenzene results in the formation of relatively stable c~mplexes.'~~ It is possible that the use of less stable Meisenheimer hydride adducts could lead to the development of new mild reducing agents.2,2',4,4',6,6'-Hexanitrobibenzylforms the dianion (60) by double deprotonation using bases such as DABCO and ~iperidine.'~' 1,4-Benzoquinones normally undergo Michael addition reactions with amines. However n.m.r. results show that the first-formed adduct in liquid ammonia results from attack on a carbonyl carbon atom.I3* Reactions involving Radicals.-A common intermediate the aryl di-imide has been proposed for the anionic and free-radical dediazoniation reactions of I34 R. J.Spear W. P. Norris and R. W. Read Tetrahedron Lett. 1983 24 1555. J.-C. Halle M.-P. Simonnin M.-J. Pouet and F. Temer Tetrahedron Lett. 1983 24 2255. P.J. Atkins V. Gold and W. N. Wassef J. Chem. Soc. Perkin Trans. 2 1983 1197. I37 M. R. Crampton P. J. Routledge and P. Golding J. Chem. Res. (S) 1983 314. I38 J. A. Chudek R. Foster and F. J. Reid J. Chem. SOC.,Chem. Commun. 1983 726. 226 H. Heaney arenediazonium ions in basic alcoholic solution^.'^^ The anionic mechanism results from proton abstraction from the diary1 di-imide by the alkoxide ion and the radical process results from hydrogen abstraction by free radicals in solution. Some of the suggested steps and evidence are summarized below. ArN2++ CH,O-+ Ar-N=NH + CH,O Ar-N=NH + CH,O--* Ar-N=N-+ CH,OH Ar-N=N,--+ Ar-+ N ArN,+ + CH,O-+ Ar-N=N' + CH,O' Ar-N=N' -* Ar' + N Ar' + CD,OH -+ ArD + 'CD,OH The radicals involved can be trapped by the addition of 1,l -diphenylethene but the amount of the reaction that proceeds via the ionic process is not increased.The radical reaction cannot therefore be a chain process. The reductive dehalogenation of o-allyloxybromobenzene using lithium aluminium hydride proceeds by two competing pathways. The radical pathway which is promoted by oxygen results in the formation of cyclized products like (61).140a Various halogeno-compounds are reductively dehalogenated in high yield when solutions are photolysed in the presence of di-t-butylperoxide and lithium aluminium hydri~ie.'~'~ The incorporation of deuterium into the side chain when 1 -bromo-2,4,6- trineopentylbenzene is reduced with lithium aluminium deuteride has been inter- preted as involving radical intermediates.14' 4-Bromo-N,N-dialkylanilines react with bromine in inert solvents to give either 1 1 charge-transfer complexes or N-bromoanilinium bromides. 14* The charge-transfer complexes afford substitution and dealkylation products in polar solvents such as acetic acid. In acetone the major product resulting from the charge-transfer complex of bromine and N,N-dimethyl-aniline was N,N,N',N'-tetramethylbenzidine. It was argued that the benzidine derivative arises by debromination by acetone of the dimer formed from a radical cation whereas the dealkylation products arise after deprotonation of the radical cation.Homolytic aromatic substitution by,silyl- and germyl-radicals has been shown to be rever~ib1e.I~~ The 3,6-bis(trimethylsilyl)cyclohexadienyl radical gives 1,4-bis(trimethylsily1)benzene at 0 "C but at 130"C it gives a mixture of trimethylsilyl- benzene and 1,3-bis(trimethylsilyI)benzene. The isomer distributions obtained in aromatic hydroxylation reactions by hydroxy-radicals generated by the photolysis of a -azohydroperoxides have been correlated with the electron densities of the HOMOS of the aromatic substrates.I4 Benzene suspended in aqueous sulphuric acid containing Cu' is converted into phenol with about three times the efficiency of Fenton's reagent.145 No biphenyl was observed and it was therefore assumed that 139 T.J. Broxton and M. J. McLeish J. Org. Chem. 1983 48 191. I40 (a)A. L. J. Beckwith and S. H. Goh J. Chem. SOC. Chem. Commun. 1983 905; (b) p. 907. 141 S.-K. Chung and K. L. Filmore J. Chem. SOC.,Chem. Commun. 1983 358. I42 F. Effenberger A. Steinbach G. Epple and J. Hanauer Chem. Ber. 1983 116 3539. 143 H. Sakurai M. Kira and H. Sugiyama Chem. Lett. 1983 599. 144 T. Tezuka K. Ichikawa H. Marusawa and N. Narita Chem. Lett. 1983 1013. 145 K. Sasaki S. Ito Y. Saheki T. Kinoshita T. Yamasaka and J. Harada Chem. Lett. 1983 37 Aroma tic Compounds the percupryl ion [CuO,]+ is involved. Reactions of acetate and diethylmalonyl ions with the benzylic bromide (62) and its radical analogue (63) show that the reactions of the latter proceed faster by factors of about four with acetate and nine with the diethyl malonyl anion.'46 A biradicaloid charge-transfer interaction was postulated.Synthetic Procedures.-Anodic oxidation reactions that result in the formation of quinonebis( acetals) of benzene and naphthalene derivative~,'~' and the cleavage of ethers,'48 including examples where phenols are produced are the subjects of reviews. A number of resorcinol derivatives have been oxidized by m-chloroperben- zoic acid in dichloromethane at O°C.'49"The method results in the formation of 1,2,4-trioxygenated benzene and thus this method complements the recently described procedure that involves organocopper reagents.149b The reactions of arylmagnesium bromides and aryl-lithium reagents with the peroxyborate (64) results after the hydrolysis of an 'ate' complex in the formation of phenols in good to excellent ~ie1ds.I~' Intramolecular C-alkylation reactions of phenols that lead to spiro-dienones or phenols have been reviewed.'" A two-phase Jones oxidation procedure using ether-aqueous chromic acid has been developed for the oxidation of alkyl phenols to the corresponding quinones in large scale high yield rea~ti0ns.I~~ Aqueous hydrogen peroxide in the presence of ruthenium( 111) chloride has also been described as an efficient system for the oxidation of phen01s.I'~ 2,3,6-Trimethylphenol gave 2,3,6-trimethyl-p-benzoquinone in 90% yield.The known oxidation of 1,4-dimethyl- naphthalene with chromic oxide in acetic acid has been extended.6-Acetyl- 1,4- dimethylnaphthalene affords 1,2,4-triacetylbenzene in 40% yield.'54 The smooth oxidation of benzenoid compounds to carboxylic acids using ruthenium( 111) chloride and peri~date'~~" has been extended'55b to its use in the stereocontrolled synthesis of bridged-ring esters. The ester (66) was obtained from (65) in 85% yield after esterification using diazomethane. The conjugate base of o-iodosobenzoic acid (67) is a powerful nucleophile near pH 7. The nucleophilic properties have only now been confirmed despite the fact 146 M. Ballester J. Veciana J. Riera J. Casta;er 0.Armet and C. Rovira J. Chem. SOC.,Chem. Comrnun. 1983 982. 147 J. S. Swenton Acc. Chem. Rex 1983 16 74. I48 M. V. Bhatt and S. W. Kulkarni Synthesis 1983 249.149 (a) M. Srebnik and R. Mechoulam Synthesis 1983 1046; (b) G. J. Lambert R. P. DuWey H. C. Dalzell and R. K. Razdan J. Org. Chem. 1982 47 3350. 150 R. W. Hoffmann and K. Ditrich Synthesis 1983 107. 151 W. S. Murphy and S. Wattanasin Chem. SOC.Rev. 1983 12 213. 152 D. Liotta J. Arbiser J. W. Short and M. Saindane J. Org. Chem. 1983 48 2932. I53 S. Ito K. Athara and M. Matsumoto Tetrahedron Lett. 1983 24 5249. 154 R. Riemschneider and T. Wons Monatsh. Chem. 1983 114 1267. 155 (a) P. H. J. Carlsen T. Katsuki V. S. Martin and K. B. Sharpless J. Org. Chem. 1981 46 3936; (b) A. K. Chakraborti and U. R. Ghatak Synthesis 1983 746. 228 H. Heaney that the structure was suggested some considerable time Treatment of 2-iodobenzoic acid with potassium bromate in sulphuric acid and then with acetic anhydride gives (68) in high ~ie1d.I~’ Primary and secondary alcohols are oxidized smoothly by (68).An extension of the reported conversion of alkyl- and aryl-lithium reagents into primary amines using two equivalents of the methyl-lithium complex of methoxy- lamine involves similar reactions of the complex formed between methyl-lithium and N,0-dimethylhydroxylamine. This latter complex is the synthetic equivalent of MeNHf and results in the formation of secondary amir~es.’~~ Nitroarenes are reduced to the corresponding amines in good yields by carbon monoxide and water using the catalyst system bis( triphenylphosphine)platinum(11) chloride-tin( ~v) chloride-trieth~lamine’~~ and by the Ti” species generated by the interaction of titanium(1v) chloride with magnesium amalgam.I6’ Attempted Schiff’s base formation between primary arylamines and formaldehyde lead to mixtures containing products of carbon-nitrogen and carbon-carbon bond- forming reactions.They are all derived from the expected Schiff’s base but neither the amino1 or its dehydration product have been isolated. No reaction occurs at low temperatures. Aminols have now been isolated as their alkyl ethers by interaction of primary arylamines with paraformaldehyde and sodium alkoxides at room tem- perature.16’ When N-(methoxymethy1)aniline is treated at -60 “C successively with methyl-lithium and then n-butyl-lithium N-pentylaniline is obtained uncontami- nated with N-ethylaniline.Previous reports concerning the ease of formation of aryl-lithium reagents by the interaction of aryl bromides and lithium metal when irradiated at 40 kHz has been modified to afford diary1 zinc reagents by adding zinc bromide to the reaction mixture.I6’ The protection of the formyl group in bromobenzaldehydes by formation of the lithium morpholinoalkoxide allows lithium-bromine exchange reactions to I56 R. A. Moss K. W. Alwis and G. 0. Bizzigotti J. Am. Chem. Soc. 1983 105 681. I57 D. B. Dess and J. C. Martin J. Org. Chem. 1983,48,4155. 158 B. J. Kokko and P. Beak Tetrahedron Lett. 1983 24 561. I59 Y. Watanabe Y. Tsuji T. Ohsumi and R. Takeuchi Tetrahedron Lett. 1983 24 4121. I60 J. George and S. Chandrasekaran Synth.Cornmun. 1983 13 495. 161 J. Barluenga A. M. Bayon and G. Asensio J. Chem. SOC.,Chem. Commun. 1983 1109. I62 J.-L. Luche C. Petrier J.-P. Lansard and A. E. Greene J. Org. Chem. 1983 48 3837. Aromatic Compounds be performed efficiently. Reaction with nitrobenzene at -75 "C followed by an acidic work-up allows the introduction of a hydroxy-group 163a and carboxylation followed by treatment with aqueous acid affords phthalaldehydic The addition of functionalized organolithium reagents for example methyl lithioacetate to p-benzoquinones and cyclohexadienones proceeds in excellent yield at low tem- peratures. Jacaranone (69) was prepared by this method in 86% yield.lW Although the tetrabromo-o- and -p-dichlorobenzenes only form dilithio-derivatives in the presence of an excess of n-butyl-lithium when such solutions are allowed to interact with methyl sulphate more than two methyl groups are intr0d~ced.l~~ It appears that n-butyl-lithium and methyl sulphate do not react rapidly and hence after reaction with the aryl-lithium reagent further halogen-metal interconversion can occur.Studies that involve metallation reactions of arenes and substituted arenes have revealed a number of important new features. MNDO calculations'66 show that the most acidic hydrogens in 1-1ithionaphthalene and 9-lithioanthracene are at peri- positions. Metallation of naphthalene and anthracene by means of n-butyl-lithium in the presence of TMEDA confirm the predictions. The di-lithio species are stabilized by symmetrical bridging by the diamine.A quantitative determination of the acidities of a range of monosubstituted benzenes in THF has provided new data that are useful in obtaining an understanding of the activating strength of various substituents towards ~rtho-metallation.'~~ The most potent acidifying influence is exhibited by the N,N-diethylcarbamate derivative of pheno1.16* The presence of an alkoxy-group meta to an alkoxyalkyl group promotes metallation at the 2-position. Thus 3,4-dimethoxybenzyl methyl ether is metallated and after reaction with ethyl chloroformate affords the ester (70) in high yield.'69 The ortho-metallation of aromatic secondary and tertiary amides and oxazolines is useful for the regiospecific introduction of a number of functionalities.The use of the trimethylsilyl residue to block one of the ortho-positions in a polysubstituted arene and hence allows the iterative introduction of different groups regio~pecifically.'~~ ortho-and meta-Trialkylsilyloxybenzamidesare metalled ortho to the amido-group. The products of the reactions rearrange rapidly to afford silylated sali~ylamides."~ Thus (7 1) gives (72) intramolecularly. Oy'OMe OMe OTMS OH "I1 (a) A. K. Sinhababu and R. T. Borchardt 1. Org. Chem. 1983,48 1941; (b) p 2356. I64 A. Fischer and G. N. Henderson Tetrahedron Lett. 1983 24 131. I65 G. C. Nwokogu and H. Hart Tetrahedron Lett. 1983 24 5725. I66 W. Neugebauer T. Clark and P. von R. Schleyer Chem. Ber. 1983 116 323. I67 R. R. Fraser M. Bresse and T.S. Mansour J. Am. Chem. SOC.,1983 105 7790. I68 M. P. Sibi and V. Snieckus J. Org. Chem 1983,48 1935. 169 E. Napolitano E. Giannone R. Fiaschi and A. Marsili J. Org. Chem. 1983 48 3653. I70 R. J. Mills and V. Snieckus J. Org. Chem. 1983 4,1565. 171 R. J. Billedeau M. P. Sibi and V. Snieckus Tetrahedron Lett. 1983 24 4515. 230 H. Heaney ortho-Lithiation of benzene derivatives that contain certain electrophilic groups for example benzonitrile can be achieved using a highly congested base such as lithium 2,2,6,6-tetrameth~lpiperidide.I~~ The interaction of o-lithiated t-benzamides first with toluene-p-sulphonylazide and then with sodium borohydride provides a new short route to highly substituted anthranilamides. 173 Reduction of the triazene with Ni-A1 alloy has also been used.’74 The ortho-lithiation of N,N,N’,N’-tetramethylphenylphosphonic diamide followed by reactions involving a wide range of electrophiles has been 1-ep0rted.I~~ The addition of alkyl-lithium reagents to N-[2-(dimethylamino)ethyl]-N-methylbenzamides produce alkoxides that are ortho-metallated by further alkyl-lithium to produce for example (73).’76 Optically pure 2,2’-di-iodo-6,6’-dimethylbiphenyl reacts with n-butyl-lithium in diethyl ether to afford the optically stable di-lithiobiaryl at -10 0C.177 The activation of an 0-methoxy-group towards nucleophilic displacement by an oxazolinyl residue has been used to prepare the biaryl(74) in 92% yield.178 The conversion of l-methoxy-2- naphthoic acid into 1 -methoxy-2-naphthyloxazoline allows the methoxy group to be displaced with various organometallic reagents and hence provides a route to a range of 1 -substituted naphthalene-2-carboxylic acids and -2-methanols.179 Chiral lithiated oxazolines have been used in the synthesis of chiral phthalides,18’ and t-aromatic amides have also been utilised as substrates for ortho-metallation in phthalide syntheses.181 Methoxymethoxyarenes are also metallated ortho to the acetal function.’82 Zinc salts of enol ether anions can be coupled to aryl halides using palladium catalysts and thus allow the direct conversion of aryl halides into acetophenones in good to excellent ~ie1ds.I~~ (Di-isopropyloxymethyl-sily1)methylmagnesiumchloride has been recommended as a practically useful nucleophilic hydroxymethylating agent.Palladium-catalysed coupling with aryl bromides for example methyl o-bromobenzoate proceeds in high yield after conversion into the organozinc 172 T. D. Kruzan and J. C. Martin J. Am. Chern. Soc. 1983 105 6155. J. N. Reed and V. Snieckus Tetrahedron Lett. 1983 24 3795. I74 N. S. Narasimhan and R. Ammanamanchi Tetrahedron Lett. 1983 24,4733. I75 L. Dashan and S. Trippett Tetrahedron Lett. 1983 24 2039. I76 D. L. Comins and J. D. Brown Tetrahedron Lett. 1983 24 5465. I77 T. Frejd and J. Klingstedt J. Chern. Soc. Chern. Cornrnun. 1983 1021. I 78 H. A. Patel and D. B. MacLean Can. J. Chern. 1983 61 713. I79 A. I. Meyers and K. A. Lutomski Synthesis 1983 105. I80 A. I. Meyers M.A Hanagan L. M. Trefonas and R. J. Baker Tetrahedron 1983 39 1991. 181 M. Iwas K. K. Mahalanabis M. Watanabe S. 0.de Silva and V. Snieckus Tetrahedron 1983,39 1955. 182 R. C. Ronald and M. R. Winkle Tetrahedron 1983 39 2031. I83 C. E. Russell and L. S. Hegedus J. Am. Chem. SOC.,1983 105 943. Aromatic Compounds 231 reagent.'84a The reductive coupling of diaryliodonium salts proceeds in the presence of a stoichiometric amount of zinc and catalytic amounts of palladium compounds such as the bis(acetyla~etonate).'~~~ The reaction may be modified to give mixtures of diary1 ketones and a-diketones in the presence of carbon mon~xide.'~~' The insertion of a cyano-residue into a carbon-palladium bond ocurs when triphenyl phosphine is used to break down the dimeric complex formed with arylazo-deriva- tives.Ig5 The oxidation of arenes by thallium(II1) trifluoroacetate in the presence of catalytic amounts of palladium( 11) acetate affords biaryls in good yields.4,4'- Disubstituted biaryls are the major products whereas in the absence of the thal- lium(111) all possible isomeric biaryls are formed in similar amounts.'86 Arylmercury compounds react with a number of non-conjugated dienes and lithium tetra- chloropalladate to form 7r-allylpalladium corn pound^.'^^ Cross coupling between arylmercury compounds and vinyl halides can be achieved in the presence of a rhodium(1) catalyst.'88 The reactions may involve the intermediacy of an aryl- vinylrhodium( 111) species. The usefulness of aryl silanes in reactions with electrophiles requires that aryl halides be converted into the silanes in the presence of other functional groups.Tris(trimethylsily1)aluminium etherate and transition-metal catalysts such as bis(tripheny1phosphine)nickel dichloride allow these conversions to be carried out in reasonable ~ie1ds.l~~ The selective reduction of a range of functionalities using complex reducing agents based on sodium hydride has been reviewed."' Sodium hydride-sodium t-pentyl- oxide-nickel (11) acetate reduces aryl halides efficiently. The solvated ion-pair formed from rhodium( HI) chloride and methyl trioctylammonium chloride is an excellent catalyst system for the hydrogenation of arenes at room temperature and atmospheric pressure. Benzene toluene and N,N-dimethylaniline are all reduced to the corre- sponding cyclohexane derivative in over 90% yield."' A number of dienes which may be obtained from 1,4-di-t-butylbenzene have been hydrogenated in the presence of a rhodium catalyst and the desorbed products compared with the formation of 1,4-di-t-butylcyclohex-1-ene and cis-and trans-1,4-di-t-butylcyclohexaneformed directly."* 2,5-Di-t-butylcyclohexa-1,3-diene exhibits best the properties expected of the intermediate involved in the direct hydrogenation.The electroreduction of a number of methoxyarenes have been reported using aqueous tetrabutylammonium hydroxide solution^.'^^ Improved synthetic methods for the selective production of 1,2-dihydro- and 1,4-dihydro-naphthalenesare available as a result of a new study of the reactions of cyclohexadienes with amide ions in liquid ammonia.'94 Calcium I84 (a) K.Tamao N. Ishida and M. Kumada J. Org. Chem. 1983,48,2120; (b)M. Uchiyama T. Suzuki and Y. Yamazaki; Chem. Lett. 1983 1165; (c) p-1201. 185 K. Gehrig A. J. Klaus and P. Rys Helv. Chim. Acta 1983 66 2603. I86 A. K. Yatsimirsky S. A. Deiko and A. D. Ryabov Tetrahedron 1983 39 2381. I 87 R.- C. Larock and K. Takagi Tetrahedron Lett. 1983 24 3457. I88 R. C. Larock K. Narayanan and S. S. Hershberger J. Org. Chem. 1983 48 4377. I 89 B. M. Trost and J.4. Yoshida Tetrahedron Lett. 1983 24 4895. 190 P. Caubkre Angew. Chem. Int. Ed. Engl. 1983 22 599. 191 J. Blum I. Amer A. Zoran and Y. Sasson Tetrahedron Lett. 1983 24 4139.19* J. F. Outlaw J. R. Cozort N. Garti and S. Siegel J. Org. Chem. 1983 48 4186. K. E. Swenson D. Zernach C. Narijundiah and E. Kariv-Miller 1. Org. Chem. 1983 48 1777; E. Kariv-Miller K. E. Swenson and D. Dernach ibid. p. 4210. I94 P. W. Rabideau and D. L. Huser J. Org. Chem. 1983 48 4266. 232 H. Heaney in an equal volume mixture of methylamine and ethylenediamine reduces arenes to monoalkenes. Optimum conditions are reported for a number of preparation^.'^' 5 Photochemical and Thermal Processes Oxidative photocyclization reactions of aryl alkenes is the subject of a comprehensive review.'96 Aromatic photosubstitution reactions have been discussed both from a mechanistic and theoretical view.'97 The eosin-sensitized photo-oxidation of aminobiphenyls have been studied.19* Strong indications were obtained that the primary setp in the conversion of 4- aminobiphenyl into 4-nitrobiphenyl involves attack by singlet oxygen.Azobenzene derivatives have been prepared in which the 4- and 4'-positions are linked by a polyoxyethylene chain. The cis-isomers are isomerized thermally or by visible light to the trans-isomers which may be photoisomerized by U.V. light.199 Interestingly the trans-isomers are completely unable to bind metal ions whereas the cis-isomers can bind alkali-metal ions. Three major photoadducts are formed when 9,lO-dichloroanthracene (DCA) is irradiated in the presence of cyclohexa- 1,3-diene.'0° The products result from (2 + 2) cycloaddition to the 1,2-positions of DCA and (4 + 4) cycloaddition to the 9,lO- and 1,4-positions of DCA.The cis to trans isomerization and (4 + 4) photocyclo- addition reaction of cis-1,2-di-(9-anthryI)ethene(75) has been reported previously. A new study of the wavelength dependence of (75) [A > 392nml results in the formation of the photoisomer (76).'01 This reaction is formally a Diels-Alder reaction involving the 1,2-double bond and the 9,lO-diene system. The carbonylation of aryl (and vinyl) halides has been achieved in high yield in benzene solution using carbon monoxide and aqueous alkali under phase-transfer conditions by irradiation (350nm) in the presence of cobalt carbonyl.202" o-Bromo-P- phenyl-ethylamines and -ethanols afford lactams and lactones respectively in high 195 R.A. Benkeser F. G. Belmonte and H.-H. Yang Synth. Commun. 1983. 13 1103 R. A. Benkeser F. G. Belmonte and J. Kang J. Org. Chem. 1983 48 2796. W. H. Laarhoven Red. Trav. Chim. Pays-Bas 1983 102 185. 197 C. Parkatiyi Pure Appl. Chem. 1983 55 331. I98 T. Spee J. van Dijk-Knepper and J. Cornelisse Red. Trau. Chim. Pays-Bas 1983 102 263. I99 S. Shinkai T. Minami Y. Kusano and 0. Manabe J. Am. Chem. SOC.,1983 105 1851. 2oo W. K. Smothers M. C. Meyer and J. Saltiel J. Am. Chem. SOC.,1983 105 545. 20 I H.-D. Becker K. Sandros. and K. Anderson Angew. Chem. Int. Ed. En& 1983 22 495. 202 (a) J.-J. Brunet C. Sidot and P. Caubere J. Org. Chem. 1983 48 1166; (6) p. 1919. 19' Aromatic Compounds yields. It is thought that the initial steps proceed by an SRNl process.Carbonylation of benzyltriethylammonium halides afford phenylacetic acids.202b An account of organic plasma chemistry,203 includes a discussion of the radio- frequency cyanation of a number of substituted benzenes. The relative positions of the chlorine-carrying carbon atoms are maintained when 13-and 2,6-dichloroazulene are isomerized to dichloronaphthalenes thermolyti- ally.^'^ The known pyrolysis of (77) to give cis-2,3-divinyl succinic acid in high yield suggested that concurrent dehydrogenation should lead to benzene ring forma- tion. It has now been shown that (77) and (78) afford phthalic anhydride and styrene respectively.205 Static vacuum pyrolysis of dithiolane-5-oxides such as (79) results in the formation of benzene ethylene and carbon disulphide.Carbon disuiphide oxides may be involved.206 OSS 02s&o 0 o*ixso2 (77) (78) (79) 6 Polycyclic Systems A theoretical comparison of the structures of naphthalene and azulene has been made,207 and predictions about the stability and reactivity of the quinones of azulene have thus far been remarkably accurate.208 The intramolecular (6 + 4)7r cycloaddition reactions of a diene separated from a fulvene as in (80) allows the preparation of products that can be dehydrogenated to azulenes such as (81).209 The site-specific synthesis of [6-13C]azulene and its thermolysis at 1050 "C has been Automerization only accounts for ca. 4% of the observed rearrangements. The main product -91YO of the naphthalene formed -is [2-'3C]naphthalene.The possible involvement of the bisnorcaradiene (83) in the isomerization of (82) to (84) has been investigated. It (83) could not be 203 204 20s 206 207 208 209 210 L. L. Miller Acc. Chem. Res. 1983 16 194. E. V. Dehrnlow D. Balschukat R. Krerner and K. Drechsler J. Chem. Res. (S) 1983 268. C. M. Buchan J. I. G. Cadogan I. Gosney B. J. Harnill S. F. Newlands and D. A. Man J. Chem. SOC. Chem. Commun. 1983 725. R. W. Hoffrnann W. Barth L. Carlsen and H. Egsgaard J. Chem. Soc. Perkin Trans. 2 1983 1687. R. C. Haddon and K. Raghavachari J. Chem Phys. 1983,79 1093. L. T. Scott Pure Appl. Chem. 1983 55 363. T.-C. Wu J. Mareda Y. N. Gupta and K. N. Houk,J. Am. Chem. SOC.,1983 105 6996. H. Gugel K.-P.Zeller and C. Wentrup Chem. Ber. 1983 116 2775. 234 H. Heaney detected even at low temperatures and MIND0/3 calculations place the compound (82) about 45 kJ mol-' more stable that (83).211 The azulene bis(ammonium) salt (85) forms clathrate complexes with guests such as iodomethane.212 The iodomethane molecules lie in a cage enclosed by several host units. On the other hand a guest such as butan-1-01 forms a complex in which the host lattice has changed to form a channel-type cavity with the guest disorientated. 4,5-Bis(dimethylamino)fluorenehas the amino-groups in closer proximity than 1,8-bis(dimethylarnino)naphthalene.The former compound is therefore more basic -by slightly more than one pk unit. In the protonated form the hydrogen bond is approximately linear and the strength of the hydrogen bond is indicated by the chemical shift (6 = 18.25).*13 Sesquibiphenylenes have been prepared.214 The linear compound (86) is photo- labile.The upfield shifts of the three different proton-bearing carbon atoms in the n.m.r. spectrum of (86) when compared with those for the angularly arranged isomer may result from a reduction of the aromatic deshielding that results from paramagnetic ring-current effects in the four-membered The central ben- zene ring in (87) is extraordinarily reactive a dianion (88) is formed by reaction with potassium in THF and alkylation with n-butyl iodide affords (89).2'4b 4-Methyl- Me,Si G S i M e \ \ \ / \ \ SiMe, 9 21 I H. Durr K.-H. Pauly and K. Fischer Chem.Ber. 1983 116 2855. 212 F. Vogtle H.-G. Lohr H. Puff,and W. Schuh Angew. Chem. Int. Ed. Engf. 1983 22 409; H.-G. Lohr F. Vogtle W. Schuh and H. Puff J. Chem. Soc. Chem. Commun. 1983 924. 213 H. A. Staab T. Saupe and C. Krieger Angew. Chem. Inr. Ed. Engf. 1983 22 731. 214 (a)B. C. Berris G. H. Hovakeemian and K. P. C. Vollhatdt J. Chem. SOC.,Chem. Cornmun. 1983 502; (b)G. H. Hovakeemian and K. P. C. Vollhardt Angew. Chem. Inr. Ed. Engl. 1983 22 994; (c) J. W. Barton and D. J. Rowe Tetrahedron Lett. 1983 24 299. Aromatic Compounds 235 1,2,4-triazoIine-3,5-dioneaffords the adduct (90) by reaction with the lactone obtained after oxidation of biphenylene with manganese( 111) acetate.215 Summaries of the methods of synthesis and various reactions of 1-H-cyclo-buta[d,e]naphthalenes reveal much interesting chemi~try.~'~ The most convenient methods of synthesis of the parent hydrocarbon (91) involve either the reaction of the N,N,N',N'-tetramethylethylene diamine complex of 1,%dilithionaphthalene with dichloromethane or the reaction of naphthalene- 1,8-bismagnesiurn iodide with methylenebis(t~luene-p-sulphonate).~'~ Both methods give ca.20% yield. A number of polycyclic systems have been prepared during the past two decades using a bis- Wittig annelation reaction. Unfortunately this attractive strategy has been plagued by low yields. Significant improvements result from the use of phase- transfer catalysis in which the bis-phosphonium salt acts as the phase-transfer catalyst as well as the reagent.218 The K-region oxides have been considered to be probable precursors to in vivo reactions leading to carcinogenesis.A number of polycyclic hydrocarbons react with N-bromoacetamide in acetic acid to give K-region bromohydrin acptates. These latter compounds may be cyclized with sodium methoxide to the corresponding arene oxides.219 A K-region epoxide has also been obtained by ozonolysis of 1-(1-phenanthryl)-1-phenylethene.220 A number of pyrene derivatives that are environmental pollutants and which are potential carcinogens have been prepared from the dianion.22' I3C N.m.r. spctroscopy reveals that the dianion derived from pyrene is an unsymmetrical system with the highest charge density at position-4. A number of methylene-bridged derivatives of carcinogenic polycyclic hydrocarbons have been prepared by a new route in which o-lithiobenzamide is the key reagent.222 1,3-Dimethylisobenzofuranis the key intermediate in the synthesis of sterically congested compounds such as 1,l 1,12-trimethylben~anthracene.~~~ The full papers on the synthesis and some reactions of compounds with fused blocked aromatic rings have appeared.The anthracenone derivative (92) is 215 P. Ashkenazi M. Kaftory and D. Ginsberg Helu. Chim. Acta 1983 66 2712. 216 R. J. Bailey P. J. Card and H. Schechter J. Am. Chem. Soc. 1983 105 6096; P. J. Card F. E. Friedli and H. Schechter ibid. p. 6104. 217 L. S. Yang T. A. Engler and H. Schechter J. Chem. Soc. Chem. Commun. 1983 866. ZIR A. Minsky and M.Rabinovitz Synthesis 1983 497. 219 P. J. van Bladeren and D. M. Jerina Tetrahedron Lett. 1983 24 4903. 220 R. W. Murray and R. Banavali Tetrahedron Lett. 1983 24 2327. 22 I C. Tintel J. Cornelisse and J. Lugtenburg Recl. Trau. Chim. Pays-Bas 1983 102 14; C. Tintel M. van der Brugge J. Lugtenburg and J. Cornelisse ibid. p. 220; C. Tintel J. Lugtenburg G. A. J. Amsterdam C. Erkelens and J. Cornelisse ibrd. p. 228; C. Tintel J. Cornelisse and J. Lugtenburg ibid. p. 231. 222 J. K. Ray and R. G. Harvey J. Org. Chem. 1983,48 1352. 223 L. A. Levy and S. Kumar Tetrahedron Lett. 1983 24 1221. 236 H. Heaney remarkably stable,224a and the related blocked benzylic alcohols react particularly slowly in acidic media.224b The Diels-Alder reaction between 9-[(benzy1oxy)-methoxylanthracene and p-benzoquinones affords an adduct in which one double bond and one face of the benzoquinone are protected.This strategy was used in the stereospecific synthesis of the cyclitol conduritol A.225 The use of anthracene and its derivatives in trapping unstable alkenes is exemplified by the formation of (93) when 1,7-dehydroquadricyclaneis generated.226 & \ // OMe OMe (94) (95) Primary ozonides obtained for example by the interaction of ozone with anthracene are normally unstable. The transannular ozonide obtained from 9-t- butyl- 10-methylanthracene is a crystalline compound which is stable at room tem- perat~re.~~’ Cannithrene-2 (95) a 4,Sdisubstituted phenanthrene has been synthe- sized using the oxidative photocyclization of (94) as the key step.228 Some of the biological activity of anthracycline antibiotics has been ascribed to the ability of the anthraquinone residue to undergo enzyme-mediated reduction.Quinone methides have been suggested as being involved in the elimination reactions that then occur in the absence of oxygen. 7-Deoxydaunomycinone quinone methide is trapped efficiently by benzaldehyde and the quinone methides from 1l-deoxy-anthracyclinones have been shown to react with thiols and thiolate~.~~~ Interest in the synthesis of natural and unnatural antiturnour anthracyclines continues unabated.230 The annelation of o-bis-bromomethylarenes for example 224 (a) B. Miller and A. K. Bhattacharya J. Am. Chem. SOC.,1983 105 3234; (b)A.K. Bhattacharya and B. Miller ibid. p. 3242. S. Knapp R. M. Ornaf and K. E. Rodriques J. Am. Chem. SOC. 1983 105 5494. 225 226 0. Baumgartel J. Harnisch G. Szeimies M. Van Meerssche G. Germain and J.-P. Declercq Chem. Ber. 1983 116 2205; H.G. Zoch Ci. Szeirnies R. Romer G. Germain and J.-P. Declerq ibid. p. 2285. 227 Y. Ito A. Matsuura R. Otani and T. Matsuura J. Am. Chem. SOC.,1983 105 5699. 228 L. Castedo J. M. Saa R. Suau and G. Tojo Tetrahedron Lett. 1983 24 5419. 229 K. Ramakrishnan and J. Fisher J. Am. Chem. SOC. 1983 105 7187. 230 A. V. Rama Rao V. H. Deshpande K. Ravichandran and B. Ramamohan Rao Synth. Commun. 1983 13 1219; A. V. Rama Rao A. R. Mehendale and K. Bal Reddy Tetrahedron Lett. 1983 24 1093; Aromatic Compounds 237 (96) by reaction first with the anion (97) and then cyclization to (98) via the Grignard reagent provides a new approach to the construction of rings A and B in anthra~yclines.~~ ' The generation and subsequent reactions of quinodimethanes have also featured in the synthesis of oxygenated tetra hydro naphthalene^.^^^ Fluoride ion induced fragmentation of oxazolidinium salts such as (99) generates o-quino- dimethanes which can be trapped stereoselectively by inter- and intra-molecular processes.The observed enantioselection is ascribed to .rr-stacking in the transition state involved in the Diels-Alder reactions.233 Reactions of (99) with caesium fluoride in the presence of methyl acrylate results in the formation of (100).Diels-Alder reactions have also been employed in other methods.234 Br Me0 I Me0 q Me0 (98) SiMe, I Me,NJ I+ Me (99) 7 Cyclophanes The chemistry of calixarenes has been reviewed.235 The ' H n.m.r. spectra of a number of ethers and esters of calix[4]arenes show that all but the methyl ethers are A.V. Rama Rao K. Bal Reddy and A. R. Mehendale J. Chem. SOC. Chem. Commun. 1983 564; D. T. Davies P. S. Jones and J. K. Sutherland Tetrahedron Lett. 1983 24 519; L. A. Mitscher T.S. Wu and I. Khanna ibid. p. 4809; K. Krohn and B. Sarstedt Angew. Chem. Znt. Ed. Engl. 1983 22 875; C. M. Wong A. Q. Mi H. Y.Lam W. Haque and K. Marat Synth. Commun. 1983 13 15; E. Vedejs W. H. Miller and J. R. Pribish J. Org. Chem. 1983,48,3611; G.A. Kraus H. Cho S. Crowley B. Roth H. Sugimoto and S. Prugh ibid. p. 3439; C. E. Cobwin D. K. Anderson and J. S. Swenton ibid. p. 1455; S. Penco F. Angelucci F. Arcamone M. Ballabio G. Barchielli G. Franceschi G. Franchi A. Suarato and E. Vanotti ibid. p. 405; R. A. Russell G. J. Collin P. S. Gee and R. N. Warrener J. Chem. SOC.,Chem. Commun. 1983 994; D. J. Mincher G. Shaw and E. De Clercq J. Chem. Soc. Perkin Trans. 2 1983 613. 23 I J. F. Honek M. L. Mancini and B. Belleau Tetrahedron Lett. 1983 24,257. 232 M. Azadi-Ardakani and T. W. Wallace Tetrahedron Lett. 1983 24 1829. 233 Y. [to Y. Amino M. Nakatsuka and T. Saegusa J. Am. Chem. SOC.,1983 105 1586. 234 A. V. Rama Rao G. Venkatswamy S. M. Jawed V. H. Deshpande and B. Ramamohan Rao J.Org. Chem. 1983,48 1552; J. Tamariz L. Schwager J. H. A. Stibbard and P. Vogel Tetrahedron Lett. 1983 24 1497. 235 C. D. Gutsche Acc. Chem. Rex 1983 16 161. 238 H. Heaney conformationally rigid at room temperature.236 A new route to oxacalixarenes involves the dimer or the linear tetramer formed by the reaction of p-t-butylphenol with formaldehyde in the presence of base.237 Intramolecular cyclization of the dimer affords the dioxacalixarene whereas intramolecular cyclization of the tetramer gives the mono-oxa-compound. A novel capped calixarene that has two cavities one hydrophilic and the other hydrophobic is formed by the reaction of calixt41arene and pentan- 1,5-diol di-toluene-p-sulphonate in the presence of potassium t-b~toxide.~~* A number of oligo-oxa-derivatives of (3.4 paracyclophane quin- hydrones have been prepared.239 Enhanced charge-transfer absorption is observed with (101) in the presence of sodium ions.Chiral crown ethers have been prepared in which the chirality results from the presence of a helicene residue240 or 9,9-bifluorenyl residues.241 The chiral recognition properties depend on precise structural features. Evidence has been presented which shows that .rr-participation may be important in the complexation of some crown ethers which contain aromatic residues. The precise structure of arenediazonium complexes with crown ethers are now thought to be much more variable than was formerly The principal interaction appears to involve multiple-oxygen solvation of the a-nitrogen atom.Dediazoniation of a number of rn-and p-substituted benzenediazonium fluorobor- ates in the presence of crown ethers shows that the rate of dediazoniation is smallest and the equilibrium constant for complex formation is largest for complexes with 21-cr0wn-7.~~~ The amounts of N -Np rearrangement and exchange with external nitrogen is independent of added crown ethers. 0 Me0 In ‘la coupe du roi’ the trick is to cut an achiral object in such a way as to obtain homochiral halves. A chemical analogue of the reverse trick involves for example the stereospecific self-coupling of (+)-4-(bromomethyl)-6-(mercaptomethyl)-[2.2]metacyclophane to give the achiral cis-dimer ( 102).245 The chirality of benzo[2.2]metacyclophane ( 103) is due to helicity.Kinetic measurements show the 236 C. D. Gutsche B. Dhawan J. A. Levine K. H. No and L. J. Bauer Tetrahedron 1983 39 409. 231 B. Dhawan and C. D. Gutsche J. Org. Chem. 1983 48 1536. 238 C. Alfiieri E. Dradi A. Pochini R. Ungaro and G. D. Andreeti J. Chem. SOC.,Chem. Commun. 1983 1075. 239 H. Bauer J. Briaire and H. A. Staab Angew. Chem. Int. Ed. Engl. 1983 22 334. 240 M. Nakazaki K. Yamamoto T. Ikeda T. Kitsuki and Y. Okamoto J. Chern. SOC.,Chem. Commun. 1983 787. 24 I V. Prelog and S. Mutak Helu. Chim. Actu 1983 66 2274. 242 R. Leppkes and F. Vogtle Chem. Ber. 1983 116 215. 243 J. R. Beadle R. K. Khanna and G. W. Gokel J. Org. Chem. 1983 48 1242. 244 H. Nakazumi I. Szele K. Yoshida and H. Zollinger Helu.Chim. Acla 1983 66 1721. 245 F. A. L. Anet S. S. Miura 1. Siegel and K. Mislow J. Am. Chem. SOC.,1983 105 1419. Aromatic Compounds barrier to racemization to be 125kJ m~l-'.~~~ The chirality in the [2H3][l.l.l]-orthocyclophane (104) is due to isotopic substitution.247 Dynamic n.m.r. spectro- scopy has been used to study the interconversion of the enantiomers of a series of 1,5-naphthalenophanes. Interconversion in (105) occurs by moving the polymethyl- ene chain from one face of the naphthalene system to the other. The most stiiking result is the large negative entropy of activation.248 A comparison of the kinetic stability of cis-benzene trioxide with phane-bridged analogues shows that the bridging does not significantly affect the kinetic stability.The benzenoid ring in ( 106) suffers more bending than the trioxide ring.249 Remark- ably the conformation of the trioxonin ring produced by thermolysis is not much different from the unbridged species. The oxidative decarboxylation of the [6.2.2]pro- pellenecarboxylic acids ( 107) with lead tetra-acetate gave [6]paracyclophane and its 1,2-ipso-adduct with acetic acid.250 The high reactivity of diethyl [6]paracyclo- phane-8,9-dicarboxylate results in the formation of cis-addition products in reactions with bromine and with osmium tetr~xide.~~' The first example of a cyclophane which has a (4n)n + (4n + 2)n deck results from the reaction of [2.2]paracyclo- phane with dicyanoacetylene in the presence of aluminium chloride.252 1,2-Cyclo- addition followed by valence isomerization results in the formation of 43-dicyano[2.2]( 1,6)cyclo-octatetraenyl paracyclophane.A triple-layered [2.2]naph- thalenophane has been prepared via the tetrathia[3.3]na~hthalenophane,~~~ and photodeselenation of diselena[3.3]cyclophanes using tris( dimethy1amino)phosphine 246 M. Wittek F. Vogtle G. Stiihler A. Mannschreck B. M. Lang and H. Irngartinger Chem. Ber. 1983 116 207. 247 J. Canceill and A. Collet J. Chem. Soc. Chem. Cornmun. 1983 1145. 248 M. H. Chang and D. A. Dougherty J. Am. Chem Soc. 1983 105 4102. 249 M. Stobbe U. Behrens G. Adiwidjaja P. Golitz and A. de Meijere Angew. Chem. Int. Ed. Engl. 1983 22 867. 250 Y. Tobe K.4. Weda K. Kakiuchi and Y. Odaira Chem. Lett. 1983 1645. 25 1 J.Liebe and W. Tochtermann Tetrahedron Lett. 1983 24 2549. 252 J. E. Garbe and V. Boekelheide J. Am. Chem. SOC.,1983 105 7384. 253 T. Otsubo F. Ogura and S. Misumi Tetrahedron Lett. 1983 24 4851. 240 H. Heaney has been found to afford a number of [2.2]cyclophanes in excellent yields.254 The chiral[2.2](2,6)naphthalenophane ( 108) is formed along with its achiral diastereomer by the disulphone pyrolysis method.255 Halogen-metal exchange and hydrolysis affords the achiral hydrocarbon. Br @ \/ a COzH (107) The synthesis of 8,16-diformyl[2.2]metacyclophanesvia the corresponding 8,16-bis( bromomethyl) derivatives allow the preparation of a new range of internally functionalized compounds.256 The spontaneous oxidation of certain [2.2]metacyclo- phane derivatives for example (109) has been found to occur in solution.After about thirty days (109) was found to give (1 The reduction of [2.2]metapara-cyclophane quinone gives the corresponding tetrahydroxy-deri~ative.~~~ However this latter compound is soon converted by air into the corresponding quinhydrone which has a charge-transfer band at 490 nm. A strong dependence of charge-transfer absorptions on donor-acceptor orientations in [3.3]paracyclophane quinhydrones has been demonstrated.259 The two stereoisomeric tetramethoxy[5.5]paracyclo-phanes are not interconverted even at high temperatures. However partial oxidative demethylation leads to a rapidly equilibrating mixture of pseudo-ortho and pseudo-geminal quinhydrones.260 A number of electron donor-electron acceptor paracyclo- phanes have been synthesized.7,7,8,8-Tetracyano-p-quinodimethane is the common But i,::::, \ ;>-(-CH,Cl -254 H. Higuchi M. Kugimiya T. Otsubo Y. Sakata and S. Misumi Tetrahedron Lett. 1983 24 2593. 255 N. E. Blank and M. W. Haenel Chem. Ber. 1983 116 827. 256 M. Tashiro and T. Yamato J. Org. Chem. 1983 48 1461. 25'7 M. Tashiro and T. Yamato J. Chem. Soc. Chem Commun. 1983 617. 258 M. Tashiro K. Koya and T. Yamato 1. Am. Chem Soc. 1983 105 6650. 259 H. A. Staab C. P. Hem C. Geiger and M. Rentea Chem. Ber. 1983 116 3813. 260 H. A. Staab B. Starker and C. Krieger Chem. Ber. 1983 116 3831. Aromatic Compounds 24 1 acceptor component and N,N,N',N'-tetramethyl-p-phenylenediaminehas been utilised as the donor component.261 Titanium-mediated reductive coupling of aldehydes has been used as an alternative to the Wittig reaction in the improvement to cyclophane triene synthesis.262 A synthesis of (E,E,E,E)-[6.6]paracyclophane- 1,5,13,17-tetraene in 30% yield has been reported by way of the cyclodimerization of the product of a 1,lO-Hofmann elimination.263 The preparation of the [2.2.6]paracyclophanepentaene ( 11 1 ) actually results in the formation of (1 12) as a result of electro~yclization.~~~ 'H N.m.r.measurements place the energy barrier to rotation of the unique benzene ring in ( 1 12) at ca. 50 kJ mol-'. The Diels-Alder reaction between phenyl vinylsulphoxide and the diene (1 13) is the final step in the synthesis of [l.l.l.l]paracyclophane.265 A number of cyclophanedienes have been prepared and their photocyclization reactions studied.266 [2.2]( 2,13 )Pentahelicenoparacyclophanewas prepared by that device.8 Annulenes Spectroscopic and X-ray crystallographic evidence again dominates studies on annulenes. Thus both X-ray crystallography and the use of a chiral shift reagent show that (4,5)benzo[9]annulenone tends to adopt helically enantiomeric forms.267 A review of modern pulse methods in high resolution n.m.r. spectroscopy includes two-dimensional methods,268a and 'H and I3C shift correlations have been used for the compound (1 14).268bThe isomeric 1,2- and 2,3-annelated naphtho[l4] annulenes have been prepared and whereas the 1,2-isomer shows quite strong diatropicity in the annulene ring no evidence for a similar effect was observed for the 2,3-i~orner.~~~ 261 H.A. Staab G. H. Knaus H. E. Henke and C. Krieger Chem. Ber. 1983 116 2785; H. A. Staab R. Reimann-Haas P. Ulrich and C. Krieger ibid. p. 2808; H. A. Staab G. Gabel and C. Krieger ibid. p. 2827; H. A. Staab R. Hhz G. H. Knaus and C. Krieger ibid. p. 2835. D. Tanner and 0.Wennerstrom Acta Chem. Scand. Ser. B 1983 37 693. D. T. Glatzhofer and D. T. Longone Tetrahedron Lert. 1983 24 4413. D. Tanner 0.Wennerstrom and T. Olsson Tetrahedron Lett. 1983 24 5407. Y. Miyaharra T. Inazu and T. Yoshino Tetrahedron Lett 1983 24 5277. B. Thulin and 0.Wennerstrom Acta Chem. Scand. Ser. B,1983 37 297; 589. A. G. Anastassiou and M.Hasan Tetrahedron Lett. 1983 24 4279. 262 263 264 265 266 261 268 (a)R. Benn and H. Giinther Angew. Chem. Znt. Ed. Engl. 1983,22,350;(b) P. Schmitt and H. Giinther ibid. p. 499. 269 U. Meissner R. Bravo and H. A. Staab Liebigs Ann. Chem. 1983 687. 242 H. Heaney The dibenzo[8]annulene ( 1 15) appears to exist as a planar paratropic antiaromatic molecule.270 An opportunity to make a direct comparison of a paratropic [4n]annulene with a monobenzo-derivative is afforded by the synthesis of (1 16). It is seen that benzannelation reduces the paramagnetic ring-current by about the same percentage that benzannelation reduces the diamagnetic ring-current of several rigid [4n + 21 ann~lenes.~~' The heats of hydrogenation of 1,&methano- and 1$methano-[l Olannulene allow resonance energy comparisons with naphthalene and azulene to be made.272 A study of the configurational inversion of syn-l,6:8,13-di-imino[l4]annulene strongly supports the view that both nitrogen atoms invert syn- chron~usly.~~~ Arenediazonium salts couple with 2-and 3-alkoxy-I,6-methano[ 1Olannulenes and afford quinone hydrazones for example ( 1 I 7).274A number of reactions of these compounds have also been reported.274' The hen- decafulvadienes ( 1 18) have been prepared and on flash vacuum thermolysis give methano[ 1Olannulene and the azulenoid[ 14lannulene ( I 19).275 $s (1 19) (120) 270 H.Durr G. Klauck K. Peters and H. G. von Schnering Angew. Chem. Int. Ed. Engl 1983 22 332.27' L. T. Scott M. A. Kirms H. Giinther and H. von Puttkamer J. Am. Chem. Soc. 1983 105 1372. 272 W. R. Roth M. Bohm H.-W. Lennartz and E. Vogel Angew. Chem. Int. Ed. Engl. 1983 22 1007. 273 E. Vogel F. Kuebart J. A. Marco R. Andree H. Gunther and R. Aydin J. Am. Chem. Soc. 1983 105 6982. 274 (a) R. Neidlein C. M. Radke and R. Gottfried Cbem. Lett. 1983 653; (b) R. Neidlein and C. M. Radke Helv. Chim. Acta 1983 66 2369; (c) p. 2621. 275 A. Beck D. Hunkler and H. Prinzbach Tetrahedron Lett. 1983. 24 2151. Aromatic Compounds Me A number of bisdehydro[ 13]annulenes having a butatriene linking unit have been synthesized and the contributions of dipolar structures evaluated on the basis of spectral data.276 N.m.r. data for a number of 6,8-bisdehydro[ 13]annulenes for example (120) and (121) have been reported.277 The results suggest that (1 20) exists in the conformation shown and that (121) and its diastereoisomer exhibits little or no paratropicity.Compounds such as (122) appear to be atr~pic.~~~ An examination of a scale molecular model of [7Jcirculene (123) suggests that it should have a saddle-shaped structure. A successful synthesis in which the key steps involved the conversion of (124; R =Br) into (124; R =CHO) has been reported,279 and X-ray analysis has confirmed its expected shape. RR (125) (126) 276 M. Iyoda S. Tanake K. Nishioka and M. Oda Tetrahedron Lett. 1983 24 2861. 277 V. K. Sharma H. Shahriari-Zavareh P. J. Garratt and F. Sondheimer J. Org.Chem. 1983,48 2379. 278 J. Ojima K. Itagawa and T. Nakada Tetrahedron Lett. 1983 24 5273. 279 K. Yamamoto T. Harada and M. Nakazaki J. Am. Chem. Soc. 1983 105 7171. 244 H. Heaney Cycloarenes are defined as polycyclic aromatic compounds in which a fully annelated macrocyclic system is present enclosing a cavity into which carbon- hydrogen bonds point. Cyclododecakisbenzene ( 126),[12]kekulene the first example has been prepared'"" and physical properties reported.280b The key step was the formation of the dithiaphane (125). Attempts to synthesize [lolkekulene have not yet met with success. However the interesting helical aromatic systems (127) and (128) were prepared during the study.281 The hydrogen atoms indicated on structure (127) were observed in the 'H n.m.r.spectra in the shielding regions of the opposite ring. The data for (128) were similar. 280 (a) H. A. Staab and F. Diederich Chem. Ber. 1983,116,3487; (6)H. A. Staab F. Diederich C. Krieger and D. Schweitzer ibid. p. 3504. 28 I H. A. Staab F. Diederich and V. eaplar Liebigs Ann. Chem. 1983 2262.

ISSN:0069-3030    

DOI:10.1039/OC9838000209

出版商:RSC    

年代:1983

数据来源: RSC

摘要:

11 Heterocyclic Compounds By E. H. SMITH Department of Chemistry Imperial College of Science and Technology London SW7 2AY 1 Introduction Comprehensive Heterocyclic Chemistry,’ published during this year joins the two other comprehensive treatises. Three new volumes in the series Advances in Heterocyclic Chemistry have also appeared.2 Two publications deal with the photo- chemical heterocyclization of systems isoelectronic with the pentadienyl anion.3 @R i Y = MgX T Reagents i RX NiClz[(Ph2PCH2)2CH2]; ii RMgX NiC12[(PhzPCH2)2CH2]; iii Me3Si -= PdC12(PPh3)2 CUI Et3N Scheme 1 A number of papers are concerned with the chemistry of a range of heterocyclic compounds spanning the sections of this report. Thus attachment of side-chains to azine rings may be achieved under mild conditions using nickel- or palladium- complex catalysis (Scheme l).4Palladium(I1) acetate in combination with sodium nitrite serves as a useful means of nitrating some heterocyclic compounds including thiophene 2-pyridone and ~racil.~ A novel benzoannulation procedure which produced a variety of heterocyclic types from fluorobenzene tricarbonylchromium complexes (Scheme 2) regrettably did not realize the full potential anticipated by its designers.6 However a number of constraints were defined which should help in possible future applications or adaptations.‘Comprehensive Heterocyclic Chemistry,’ ed. A. R. Katritzky and C. W. Rees Pergamon Oxford 1984. * Adv. Heterocyf. Chem. 1382 31 32; 1983 33. (a)A. G. Schultz and L.Motyka in ‘Organic Photochemistry’ ed. A. Padwa Marcel Dekker New York 1983; (b) A. G. Schultz Acc. Chem. Res. 1983 16,210. K. Tameo S. Kodama I. Nakajima M. Kumada A. Minato and K. Suzuki Tetrahedron 1982 38 3347; T. Sakamoto M. Shiraiwa Y. Kondo and H. Yamanaka Synthesis 1983 312; M. Yamaguchi and I. Hirao Tetrahedron Lett. 1983 24 1719; see also F. Babudri S. Florio L. Ronzini and M. Aresta Tetrahedron 1983 39,1515. T. Itahara R. Ebihara and K. Kawasaki Buff. Chem. SOC. Jpn. 1983 56,2171. M. Ghavshou and D. A. Widdowson J. Chem. SOC.,Perkin Trans. 1 1983 3065. 245 246 E. H. Smith 7) Y = PhNCO PhNCS or 0 n, 0 Scheme 2 2 Three-memberedRings The stabilizing influence of the CF,-group is seen yet again in the argon matrix isolation of an unstable compound purported to be the oxirene (l)7aand the diazirine (2)7b both obtained from the same diazoketone by irradiation at different wavelengths.N U N=N (1) (2) On a more practical note the Payne epoxidation of olefins (RCN + H202)using trichloroacetonitrile in a biphasic system (CH2C12 + H20) is an improvement on earlier methods and may be competitive with the use of rn-chloroperbenzoic acid,8 and 2H-azirine may be made on a 0.1 molar scale by consecutive gas-phase dehydrochlorination and flash vacuum pyrolysis (FVP) of /3-chloroethyl azide.' This method obviates the danger of isolation of the intermediate vinyl azide (Scheme 3). CI KOBu'(s) N3 80"C.0.1 mmHg. N3 o.l mmHg N Scheme 3 A simple high-yielding route to derivatives of the same ring involves rearrangement of isoxazoles catalysed by palladium on carbon." It is necessary to poison the catalyst in order to avoid over-reduction to the amine (Scheme 4).0 Rid0R3 + Ri&oR3 N RZ NH 0 Scheme 4 '(a)M. Torres J. L. Bourdelande A. Clement and 0.P. Strausz J. Am. Chem. Soc. 1983,105,1698; (b) E. D. Laganis D. S. Janik T. J. Curphy and D. M. Lemal ibid.,1983 105 7457. L. A. Arias S. Adkins C. J. Nagel and R. D. Bach J. Org. Chem. 1983 48 888. J.-C. Guillemin J.-M. Denis M.-C. Lasne and J.-L. Ripoll J. Chem. Soc. Chem. Commun. 1983,238. S. Auricchio and 0.Vajna de Pava J. Chem. Res. (S) 1983 132. Heterocyclic Compounds Three new syntheses of aziridines involve the addition of one-carbon fragments to the imine double-bond phase-transfer catalysis mediates the addition of dimethyl-sulphonium methylide a procedure which may be applied to hydrazones as well," addition of phenyldiazomethane requires the assistance of zinc iodide,12 and in a mechanistically different approach the radical anion of glyoxal bis-t-butylimine is trapped by dichloroalkanes to give the imino-derivative of aziridine-2-carboxal-dehyde (Scheme 5).' R' = H iii R2 = CH=NR3, R3 = But I N+ Reagents i PhCHN2 Zn12 Et20; ii Me,S+I- Bu","HSO; CH2C12 aq.NaOH; iii K C12CHR4 THF Scheme 5 3H-Diazirines are useful precursors of carbenes. It is therefore welcome news that the fluorinated examples (3) can be made without recourse to the use of hazardous direct fluorination methods of old simply by halogen exchange in the chloro- or bromo-analogues using tetrabutylammonium fluoride.l4 The thermally unstable cyano-3H-dkzirines were also obtained in the same manner. R F Xi >(-7x B I R = Ph or PhO Me (3) (4) A new three-membered heterocycle to be reported is the air- and moisture- sensitive but thermally stable borirene (4).15 A book has been devoted to the subject of three-membered heterocycles16 and a chapter in a book on reactive intermediates reviews the production of nitrile ylides and nitrenes from 2H-azirines." R. S. Tewari A. K. Awasthi and A. Awasthi Synthesis 1983 330. l2 R. Bartnik and G. Mloston Synthesis 1983 924. 13 H. tom Dieck and E. Haupt Chem. Ber.1983,116 1540. 14 D.P. Cox R. A. Moss and J. Terpinski J. Am. Chem. SOC.,1983 105 6513. 15 S.M.van der Kerk P. H. M. Budzelaar A. van der Kerk-van Hoof G. J. M. van der Kerk and P. von R. Schleyer Angew. Chem. Int. Ed. Engl. 1983,22,48. l6 'Chemistry of Heterocyclic Compounds. Small Ring Heterocycles Part 1,'ed A. Hassner Academic New York 1983. 17 A. Padwa and J. H. J. Carlsen in 'Reactive Intermediates,' ed. R. A. Abramovitch Plenum New York 1982 vol. 2. 248 E. H. Smith 3 Four-membered Rings General.-Two groups have reported conditions for the reduction of 2-azetidinones to azetidines without over-reduction to the open-chain amino-alcohol." In both cases aluminium based reagents appear better than their boron counterparts chloroalane18" and alane'8b being most effective.FVP of aromatic and heteroaromatic carboxylic acids substituted in the ortho-position by a heteroatom group provides a general route to benzo-fused oxetanones thietanones and azetinones (5) to (8) some of which have been prepared for the first time." These compounds show a range of stability from (5; X = S) which is stable indefinitely in the crystalline state to (5; X = 0)and (6) which decompose at -40 "C. 0 The 1,3-thiazetidine-2-thione(9) has proven to be a versatile precursor of other ring systems (Scheme 6),20insertion of the new atoms generally occurring between the C=S and S groups. TsN NBu' NTs Reagents i MeC=CNEt2 CHCI,; ii Bu'NC CHC13 reflux; iii NaN, CS, DMF Scheme 6 p-Lactams.-A common ploy in the synthesis of p-lactams involves reaction of an arylimine with an acyl halide.Japanese workers have now shown that p-nitroben- zoate esters21" or toluene-p-sulphonic-carboxylicanhydrides21* of activated acetic 18 (a)M. Yamashita and I. Ojirna J. Am. Chem. SOC.,1983,105,6339; (6)M. B. Jackson L. M. Mander and T. M. Spotswood Aust. J. Chem. 1983 36 779. 19 C. Wentrup and G. Gross Angew. Chem. Znt. Ed. Engl. 1983 22 543. 20 G. L'abbC P. Vangheluwe and S. Toppet Bull. SOC.Chim. Belges 1983 92 61. 21 (a) M. Miyake N. Tokutake and M. Kirisawa Synthesis 1983 833; (b) N. Tokutake M. Miyake and M. Kirisawa ibid. 1983 66. Heterocyclic Compounds acids may serve as the acyl component (Scheme 7) the latter allowing a one-pot synthesis of a number of p-lactams including the bicyclic examples (10).Reagents i Ar'CH=NAr2; ii TsCl Et,N R3CH=NR4 Scheme 7 X = OorS R' = Me,R2 = Hor R' = H,R2 = Me (10) (11) Ring-contraction processes continue to play a part in p-lactam synthesis and this year sees three new additions. Thermolysis or photolysis of the 1,l-dioxo-4- thiazolidinones (1 1) results in extrusion of sulphur dioxide the two procedures being complementary in that the thermal reaction results in high yields of the trans-isomer from substrate of either geometry whereas photolysis exhibits moder- ate stereospecificity but is somewhat inefficienL2* However low-temperature photo- lysis of the 4-diazopyrrolidine-2,3-dione(12) readily available from penicillamine and mucochloric acid efficiently gave the 6,7-truns-derivative (13) (Scheme 8),23 a reaction of potential use as a model of thienamycin synthesis.This method represents an interesting alternative to the known ring contraction of the isomeric 3-diazopyrrolidine-2,4-diones. Finally treatment of the chloro-isothiazolidine (14) with phenyl-lithium results in rearrangement to the p-lactam (15) in high yield,24 Ph CI Ph SPh phtJ 0 + P"-p;-px (15) (14) 22 M. R. Johnson M. J. Fazio D. L. Ward and L. R. Sousa J. Org. Chem. 1983 48 494. 23 H. W. Moore and M. J. Arnold J. Org. Chem. 1983 48 3365. 24 C. J. Easton J. Chem. SOC.,Chem. Commun. 1983,1349. 250 E. H. Smith a process which mimics one of the proposed biosynthetic pathways to this ring and which has been sought previously without success.On the other side of the coin a new carbonylrhodium catalysed ring-expansion of aziridines results in regiospecific insertion of carbon monoxide into the more substituted C-N bond in quantitative yields (Scheme 9).2s An important proviso in this synthesis is that the N-substituent must be tertiary (in one case %Me3 was used successfully). Scheme 9 The 5,6,8-trans-erythro relationship found in thienamycin (16) has prompted three more groups to attempt the construction of monocyclic analogues with this stereochemistry using an aldol reaction. All three found that a combination of the use of N-silyl groups for protection and the lithium enolate of the P-lactam led to mixtures of stereoisomers.This dilemma could be partially resolved however by resort to alternative combinations namely the novel (N'-pyrrolidinylmethyl) N-protecting group and lithium enolate ( trans-specific diastereoselectivity not given),26a the methoxymethyl N-protecting group and tetrabutylammonium enolate (trans-specific 52 48 threo erythro),266 or the t-butyldiphenylsilyl N-protecting group and zirconium enolate (96 4 trans cis; 87 9 erythro threo).26c OH base. Me fi:2' MeCHO 0 R' = vinyl or allyl R2 = CH2N or R' = S-trityl,R2 = CH20Meor R' = Bun,R2 = SiPhzBu' The increased resistance of penicillins bearing an a-halogeno or a-methoxy group at C-6 (and C-7 of cephalosporins) towards P-lactamase activity has given impetus to the synthesis of these derivatives.In an intriguing ring-forming approach photo- lytic cleavage of cyclohexyl benzoylformates results in the transient formation of hydroxy phenyl ketene which is trapped with aryl imines to give the desired compounds with good stereoselectivity (Scheme In contrast an intramolecular photocyclization of the pyruvamide ( 17) is non-stereoselective.28 7a-Methoxy- cephalosporins are produced in moderate yield from the parent compounds by 25 H. Alper F. Urso and D. J. H. Smith J. Am. Chem. Soc. 1983 105 6737. 26 (a)A. B. Hamlet and T. Durst Can. J. Chem. 1983,61 411; (b)A. Martel J. Collerette J. Banville J.-P. Daris P. Lapointe B. Belleau and M. Menard ibid. 1983 61 613; (c)J. d'Angelo and F. Pecquet-Dumas Tetrahedron Lett. 1983 24 1403.27 H. Aoyama M. Sakumoto K. Yoshida and Y. Omote J. Heterocycf. Chem. 1983 20 1099. 28 S. C. Shim and D.-W. Kim Heterocycles 1983 20 575. Heterocyclic Compounds 25 1 oH Ar ArCH=NCH,Ph ' phfTLCH2Ph 0 major isomer Scheme 10 Ph / 0 0 Ph ESOMe 0 Ph (17) activation of the 7a-hydrogen in a novel way (Scheme 11).29 Some double-bond isomerization occurs in this process. The corresponding 7a -hydroxy congeners (and 6a-hydroxy penicillins) proved to be no more stable towards p-lactamases than the parent compounds.30 ii iii 1 Reagents i PCI,; ii Me0 CA-0-; iii MeOH A Scheme 11 Ghosez and his co-workers have shown that azetic 2-iminium salts make ready precursors of the thioxo-derivatives (18) which in turn provide the imino-analogues (19) by reaction with ammonia or meth~larnine.~~ Some recent aspects of the chemistry of p-lactams have been covered in a Tetrahedron Sympo~ium-in-Print,~~ and a correlatory approach to defining the 29 K.Iwamatsu K. Shudo and T. Okamoto Heterocycles 1983 20 5. 30 G. Kinast and W. Schrkk Tetrahedron Lett. 1983 24 283. 31 J. Marchand-Brynaert M. Moya-Portuguez I. Huber and L. Ghosez J. Chem. SOC.,Chem. Commun. 1983 818. 32 Guest Editor J. E. Baldwin Tetrahedron 1983 39 2445. 252 E. H. Smith RS= HorMe (19) geometrical requirements for biological activity in P-lactams has been published.33 Finally an account of the history of penicillin by one of the protagonists should make rivetting reading and from its reviews makes one wonder whether the ring is truly enchanted or perhaps bewitched.34 4 Five-membered Rings An approach to furans has been described whose novelty lies in the mode of construction formally a [3+ + 21 cycloaddition of a methylthio-stabilized a-ketoca- tion with an alkyne (Scheme 12).35 What appears to be a more general route accrues from the reaction of tri-n-butyltin enolates with cu-brom~ketones.~~ The substitution pattern in the resultant furan suggests that the initial step is an aldol reaction rather than a C-alkylation (Scheme 13).MeS C1 R' I SnCI Mex0 + Illi2 -Scheme 12 Bu;Sn MR2 R' R' 0 R' R3 R1 OSnBu; Scheme 13 Any synthesis of 3-functionalized furans is welcome and it is therefore a pleasure to report that hydromagnesiation of 1-trimethylsilyl propargyl alcohols followed by reaction of the intermediate vinyl Grignard with nitriles gives good yields of the valuable 3-trimethylsilyl derivatives (Scheme 14).37 The trimethylsilyl group also forms the focus of work on the photolytic ring-cleavage of furans to allenes a process remarkable for its lack of side reactions in comparison with the photolysis 33 N.C. Cohen J. Med. Chem 1983,26,259. 34 J. C. Sheehan 'The Enchanted Ring. The Untold Story of Penicillin' MIT Press Cambridge Massachusetts 1982. 35 H. Ishibashi S. Akai H.-D. Choi H. Nakagawa and Y. Tamura Tetrahedron Lett. 1983 24 3877. 36 M. Kosugi I. Takamo I. Hoshino and T. Migita J. Chem. SOC.,Chem. Commun. 1983 989. 37 F. Sat0 and H.Katsuno Tetrahedron Lett. 1983 24 1809. Heterocyclic Compounds Me,Si Me,Si -Me3Si-~< I OH 2Bu' MgBr Cp,TiCI, 25 "C BrMg%R1 OMgBr i R~CN ii H,O' R2 Scheme 14 0 R = H Me or SiMe3 of non-silylated analogues.38 The full impact of silicon on the chemistry of furans has no doubt yet to be realized but another example of its use in the form of trimethylsilyl iodide is in the mediation of conjugate addition of furans to a,P-enones a reaction which results in 2-substitution of the furan (Scheme 15).39 An alkene trap for the hydrogen iodide released is often necessary. 0 Br Scheme 15 The application of high pressure has allowed the first realization of a Diels-Alder reaction of furan with a simple benz~quinone,~' and has facilitated the cycloaddition of dichloromaleic anhydride to f~ran,~~ and a mixture of copper(I1) tetrafluoro- borate and hydroquinone should be added to the list of catalysts for such reactions at atmospheric pressure.42 Acyl-lithiums generated in situ at very low temperature (-100 "C) by reaction of alkyl-lithiums with carbon monoxide react with 5-chloropentan-2-one to give 2-acyl-2-methyltetrahydrofurans (Scheme 16).43 0 R = Bun Bus or But 0 Scheme 16 Cleavage of 2,5-dimethoxytetrahydrofuran(20) with trimethylsilyl halide gives a 1,4-dihalogeno- 1,4-dimethoxybutane (21) ,44 the chloro-derivative being of con- siderable use as a mild progenitor of N-alkylated pyrroles (Scheme 17).45 38 T.J. Barton and G. P. Hussmann J. Am. Chem. Soc. 1983 105 6316.39 G. A. Kraus and P. Gottschalk Tetrahedron Lett. 1983 24 2727. 40 J. Jurczak T. Kozluk S. Filipek and C. H. Eugster Helv. Chim. Acta 1983 66 222. 41 Y. Okamoto S. Giandinoto and M. C. Bochnik J. Org. Chem. 1983 48 3830. 42 J. A. Moore and E. M. Partain J. Org. Chem. 1983 48 1105. 43 R. M. Weinstein W. Liang and D. Seyferth J. Org. Chem. 1983 48 3367. 44 T. H. Chan and S. D. Lee Tetrahedron Lett. 1983 24 1225. 45 T. H. Chan and S. D. Lee J. Org. Chem. 1983 48 3059. 254 E. H.Smith MeO Me0 OMe Amberlyst A-21 R (20) (21) Scheme 17 A simple alternative to metallatioq to effect electrophilic substitution at the @position in pyrroles is provided by N-protection with the tri-isopropylsilyl group which sterically hinders attack at the a-position and is easily removed by tetra- butylammonium fluoride.46 The cyclopropylphosphonium salt (22) has been used in the past as a cyclopentane annulating agent by virtue of its ring-opening with nucleophiles to generate an ylide followed by intramolecular Wittig reaction.Now this same sequence using diacyl- amides as the nucleophiles provides 1H-pyrroline-3-carboxylic acids (23) in moder- ate yields.47 Although the reaction is regioselective this selectivity is not predictable. 6ph3 + HN'R' + K,OEt DcCO Et oA BF4-OAR2 (22) (23) The 1,3-dipolar cycloaddition of azomethine-ylides to dipolarophiles to give pyrrolidines is well known to require charge-stabilizing substituents in the dipole. The preparation and trapping of non-stabilized versions of these ylide~,~~",~ as well as analogues derived from f~rrnimidates,~~" and thioformimidate~,~~"~ for-ma mi dine^,^'^ has now been recorded (Scheme 18).The alkoxy- or alkylthio-ylides Me,SinN @X x/ LDA THF Me NCnNnSiMe, I Me-N+Me Lh I 0-Scheme 18 46 J.M. Muchowski and D. R. Solas Tetrahedron Left. 1983 24 3455. 47 W. Flitsch K. Pandl and P. Russkamp Liebigs Ann. Chern 1983 529. 48 (a)R. Beugelmans G. Negron and G. Roussi J. Chem. SOC.,Chem. Commun. 1983,31; (b)A. Padwa and Y.-Y. Chen Tetrahedron Lett. 1983 24 3447; (c) A. Padwa G. Hoffmanns and M. Tomas. ibid. 1983 24 4303; (d)T. Livinghouse and R. Smith J. Chem. Soc, Chem. Commun. 1983 210. Heterocyclic Compounds give pyrrolidines which decompose to 1H-2-pyrrolines or pyrroles (from addition to olefins and acetylenes respectively).Pyrrolidines are also obtained in a Hofman-Loffler-Freytag reaction in which the nitrogen-centred radical produced by photolysis of an N-iodoamine is stabilized by a dialkylphosphoro-group.49The advantage of this improvement is that the phos- phoro-group is readily removed to give N-unsubstituted pyrrolidines obtained in poor yields in the classical reaction. Yields at least in the rigid steroidal examples chosen are good. The presence of the 3-acyltetramic acid moiety (24) in a number of biologically active natural products and the dearth of suitable synthetic routes to the same has led to further developments in the field. Thus a sequence based on hydroxyalkylation of the vinyl-lithium derivative (25) and subsequent oxidation provides a new approach,’’ whilst two substantial improvements on existing methods are also recorded.’laYb R2 (24) (25) A palladium-catalysed cyclization procedure complementary to the method reported last year (Annu.Rep. Prog. Chem. Sect. B 1982 79 220) probably 15 CO.Pd(OAc), ) PPh,,Bu:N HN ‘Ph 146% L = PPh3 00+oo I I Scheme 19 \Ph \Ph 49 C. Betancor J. I. Concepcion R. Hernandez J. A Salazar and E. Suarez J. Org. Chem,1983,48,4430. 50 R.C.F.Jones and G. E. Peterson Tetrahedron Lett. 1983,24,4751. 51 (a)R. C.F. Jones and G. E. Peterson Tetrahedron Lett. 1983,24,4757;(b) P.DeShong N. E. Lowmaster and 0.Baratt J. Org. Chem. 1983,48 1149.256 E. H. Smith involves carbonylation of a vinyl palladium species followed by intramolecular trapping of the resultant acyl-palladium by NH (Scheme 19),52and is analogous to a much earlier butenolide synthesis. The method is also applicable to the preparation of six- and seven-membered lactams as well as bicyclic examples. Improvements to three classical routes to indoles derive from (a) the addition of silica-gel to the reduction of a,@-dinitrostyrenes (26) with iron-acetic which procedure uniformly produces yields in excess of 75‘/o even for benzyloxy derivatives (b) the substitution of the cyclic lactim ethers (27) for amino-aldehydes in the Fischer indole synthesis of tryptamine derivative^,^^ and (c) the use of tripiperidinomethane as a cheap replacement for dimethylformamide acetals in the conversion of o-nitrotoluene into d-nitrophenylacetaldehydeenamine~.~~ R2 R3wN02 fit xrJxm;;, “Ht R4 ‘ NO Me0 N R5 R’ H R’ = COPh COMe CO,Me or (26) (27) S02C6H,Me Wierenga and his colleagues have elaborated on their improved route to P-methyl indoles from anilines by way of the readily preparable a-thiomethyl- or a-hydroxy- oxindoles (28) (Scheme 20).56Dimethyl sulphide-borane is far superior to lithium aluminium hydride as the reductant in the last step.Me Y Me ABH Me S X xaNH H H (28) Y = SMe or OH Scheme 20 A convenient synthesis of 4-nitroindoles which serve as useful starting materials for many 4-substituted indoles of pharmacological importance results from base- catalysed cyclization of the modified Reissert precursors (29) and ( 30).572-Acylin-52 M.Mori Y. Washioka T. Urayama K. Yoshiura K. Chiba and Y. Ban J. Org. Chem. 1983,48,4058. 53 A. K. Sinhababu and R. T. Borchardt J. Org. Chem. 1983 48 3347. 54 T. Shono Y. Matsumura and T. Kanazawa Tetrahedron Lett. 1983 24 1259. 55 D. H. Lloyd and D. E. Nichols Tetrahedron Lett. 1983 24 4561. 56 W. Wierenga J. Griffin and M. A. Warpehoski Tetrahedron Lett. 1983 24 2437. 57 J. Bergman P. Sand and U. Tilstam Tetrahedron Lett.. 1983 24 3665. Heterocyclic Compounds 257 doles may be nitrated or nitrosated at C-3 depending on the conditions used (Scheme 21).58 'y-J-q;,ixT,JTJiy 'yJ-q; HO + 0 x NC ONO Reagents i KOH MeCN dibenzo-18-crown-6 12 h; ii KOH MeCN dibenzo-18-crown-6 reflux 24 h Scheme 21 A book on the Fischer indole synthesis has been p~blished.~' A publication ostensibly concerned with a new route to isoindoles gives details of an efficient preparation and crystal structure of only one member of the family l-cyano-2- methylisoindole (31).60 0 q: KCN,MeNH,.HCI MeOH 90% 1 0 50,ph (32) Although indole-2,3-quinodimethaneshave been used as reactive intermediates in synthesis none is stable enough to isolate.The furo[3,4-b]indole (32) isolated this year represents the exception.6' *-.--rn;.P..Jp1iii iv \ / \/ 0 (33) 0 Reagents i CpCo(CO), rn-xylene A hv; ii (EtO),CO KH toluene; iii (C02H), EtOH HzO; iv N-(2-aminobenzylidene)-p- toluidine TsOH PhMe Scheme 22 '' A.Gonzalez and C. Galvez Synthesis 1983 212. 59 B. Robinson 'The Fischer Indole Synthesis,' Wiley-Interscience New York 1982. 60 J. J. D'Amico B. R. Stults P. G. Ruminski and K. V. Wood J Heferocycl. Chern. 1983 20 1283. 61 M. G. Saulnier and G. W. Gribble Tetrahedron Lett. 1983 24 5435. 258 E. H. Smith In an extension of the cobalt-catalysed [2 + 2 + 21 cycloaddition of alkynes and nitriles pioneered by Vollhardt and his co-workers replacement of the nitrile and one alkyne by a o-isocyanatoalkyne allows the ready synthesis of 5-indoli~inones.~~ The almost obligatory trimethylsilyl group on the other alkyne invariably ends up next to the carbonyl group. A short formal synthesis of the antitumour alkaloid camptothecin (33) was used to illustrate the synthetic power of the method (Scheme 22).When the synthesis of thiiranes from ketones and the lithio-oxazoline (34) is applied to the n-butylthioenones (35) the resultant vinyl congeners ring expand and eliminate n-butanethiol (on heating) to give 3,4-dialkylthiophenes (Scheme 23).63 L SCH Li (35) (34) 1 SRu Scheme 23 Another versatile thiophene synthesis resulting from rearrangement of a different heterocyclic ring provides the alternative 2,4,5-substitution pattern and relies on the addition of lithium enolates to boron trifluoride activated 3-thiazolines (Scheme 24).64 Scheme 24 Two syntheses of 3,4-diaminothiophenes have been reported the first from thiolates (36) and br~monitromethane,~' a method also applicable to the synthesis of 3-aminobenzothiophenes and the second which gives the parent diamine (37) which is a precursor of a number of fused azinothiophenes.66 H H R"9CN+BrCH,NO +'VH2 R2 S-RZ NO2 (36) 62 R.A. Earl and K. P. C. Vollhardt J. Am. Chem SOC.,1983 105 6991. 63 C. A. H. Rasmussen and Ae. de Groot Synthesis 1983 575. 64 C. N. Meltz and R. A. Volkmann Tetrahedron Lett. 1983 24 4507. 65 B. R. Fishwick D. K. Rowles and C. J. M. Stirling J. Chem. Soc. Chem. Commun. 1983 834. 66 F. Outurquin and C. Palmier Bull. SOC.Chim. Fr. 1983 155 159. Heterocyclic Compounds Dutch workers have shown that metallation of terminally methyl-substituted 1,3-diynes (and trapping with CS2) and metallation of isopropenylacetylene (and trapping with Se or Te) provide routes to thieno[2,3-b]thiophene (38)67" and 3-methylseleno(telluro)phenes67brespectively.(37) (38) Radical addition of 173-dioxolane to activated68a and simple68b olefins has been demonstrated; acyclic acetals do not react. Base-catalysed ring-opening of 1,3-dithiolane- 1,l -dioxides69 complements the earlier procedure for generating thiocar- bony1 compounds reported by other workers for the anions of 1,3-dithiolanium salts (Annu. Rep. Prog. Chern. Sect. B 1980 77,197). LDA HMPA or -R,C=S + SO + I( KOBu' Et,N'[W(CO),I]; 7 -Y-.f-f s-s-s s-s s s s-s / (39) w(co)s W(CO) 1,6,6aA4-Trithiapentalenes, e.g. (39) are bicyclic compounds with no evidence for their existence as the monocyclic thiocarbonyl valence tautomers.It has now been reported that the pentacarbonyl tungsten( 0)complexes of these heterocycles exist in the crystalline state in the monocyclic form and show fluxional behaviour (intramolecular) in sol~tion.~' In another incursion of metal carbonyls into heterocyclic chemistry epoxides aziridines and thiiranes react with iron manganese or ruthenium carbonyls and iron thiocarbonyls to give the carbene complexes (40) (Scheme 25)71which are saturated counterparts of those reported last year (Annu.Rep. Prog. Chern. Sect. B 1982 79 227) which were obtained in a cognate manner. [(CO)(L)CPM(CX)I++ Y3 -M = Fe; X = S or 0,L = CO or PPh M = MnorRu;X = 0,L = NOorCO Y = NH 0,or S Scheme 25 67 (a) R.L. P. de Jong and L. Brandsma J. Chem. SOC.,Chem. Commun. 1983 1056; (b)W. Kulik H. D. Verkruissje R. L. P. de Jong H. Hommes and L. Brandsma Tetrahedron Lett. 1983 24 2203. 68 (a) Y. Watanabe Y. Tsuji and R. Takeuchi Bull. Chem. SOC.Jpn. 1983 56 1428; Cb) 0. G. Safiev D. E. Kruglov S. S. Zlotskii N. N. Pustovit and D. L. Rakhmankulov J. Org. Chem. USSR (Engl. Transl.),1983 19 208. 69 E. Schaumann U. Wriede and G. Ruhter Angew. Chem. Int. Ed. EngL 1983 22 55. 70 P. J. Pogorzelec and D. H. Reid J. Chem. SOC.,Chem. Commun. 1983 289. '' M. M. Singh and R. J. Angelici Angew. Chem. In?. Ed. Engl. 1983 22 163. 260 E. H. Smith The practicable preparation of a few simple yet useful imidazole derivatives has occupied the attention of chemists during the year and includes 2-vin~1,~~" 4(5)-and 2-formyl and 2-a~etyl~~" derivatives.An adaptation of a previous photolytic rearrangement of N-acylimidazoles to a mixture of 2- and 5-acyl- imidazoles produces solely the 5-acyl congeners (41) on blocking C-2 with an alkyl Although yields are only moderate (34-50 %) the method appears to offer a general way of making these otherwise difficultly accessible materials. ,R R3 The isomeric 4H-imidazoles (42) are also available from alkenyltetrazoles by a photolytic method.74 When unsubstituted at C-5 the products are highly susceptible to nucleophilic attack at that position and to rearrangement by a 1,2-alkyl shift to the 1H-isomers on heating (Scheme 26). R' AlR' = H R3 = Me Scheme 26 The additions of nitrones to dipolarophiles to give 5-substituted isoxazoles is LUMO(dipo1e)-HOMO(dipolarophi1e)controlled.A prediction that electron-donating groups on the nitrone should result in the alternative frontier orbital control has been substantiated by two groups who show that the amount of the 4-substituted isoxazole derived by such control is increased in the product mixture using C-cycl~propyl-~~" and C-alko~y-~" nitrones. A novel rearrangement of the 5-substituted isoxazole (43) has been reported in which transformation to a 5-oxidopyridazinium betaine (44) occurs with elimination of a nitrile,76 an unpreceden- 72 (a)A. S. Rothenberg D. L. Dauplaisse and H. P. Panzer Angew. Chem. Int. Ed. Engl. 1983 22 560; (b)J.M. Kokosa R.A. Szafasz and E. Tagupa J. Org. Chem. 1983 48 3605; (c) F. Ricciardi and M. M. Joullie Org. Prep. Proced. Int. 1983 15 17. 73 J. L. Mattina R. T. Suleske and R. L. Taylor J. Org. Chem. 1983 48 897. 74 M. Casey C. J. Moody and C. W. Rees J. Chem. SOC.,Chem. Commun. 1983 1082. 75 (a)A. Z. Bimanand and K. N. Houk Tetrahedron Lett. 1983,24,435;(b)J. B. Hendrickson and D. A. Pearson ibid. 1983 24 4657. 76 C. Caristi M. Gattuso A. Ferlazzo and G. Stagnio d'Alcontrez Tetrahedron Lett. 1983 24 1285. Heterocyclic Compounds 26 1 ted event under these relatively mild conditions. The fused heterocycle (45) is a proposed intermediate. R' R' R' I I + f"<o-+R20 I 7 X -"0 R2 xx (43) Br Br (44) (45) 5,5-Diphenyl-2-oxazolin-4-ones (46) may be prepared in good yield in a new reaction between diphenylketene and N-acylsulphilimines (Scheme 27).77The full scope of this type of reaction has yet to be realized.Ph 0 R2 RiS=NCOR2 + Ph,C=C=O -+ phTz 0 (46) Scheme 27 In a synthesis of 4-aminothiazoles (47),which has formal analogies in the thioph- ene synthesis from bromonitromethane discussed above and in a thiadiazole synthesis discovered some years ago a-bromoketones react with potassium ethoxy( thiocar- bony1)cyanamide in an efficient manner (Scheme 28).78A limited number of the rare isothiazole-1,1 -dioxides (48) have been prepared through the availability of the 3-ethoxy-4-chloro-derivative (48; X = OEt Y = Cl).79 CN +'$R 4 EtO EtO S-0 0 147) Scheme 28 77 D.M. Ketcha M. Abou-Gharbia F. X. Smith and D. Swern Tetrahedron Lett. 1983 24 2811. 78 T. Fuchigami and T. Nonaka J. Org. Chem. 1983 48 3340. 79 S. F. Britcher D. W. Cochran B. T. Phillips J. P. Springer and W. C. Lumma J. Org. Chem. 1983 48. 763. 262 E. H.Smith Two new heterocyclic systems incorporating tellurium are the isotellurazoles (49)" and the 1,3-benzotellurazoles (50),'l both types obtainable in only low to moderate yields. 1,3-Dipolar cycloaddition of diazoalkanes to thioketenes gives the 2-alkylidene-l,3,4-thiadiazolines(51).'* The process is regrettably limited in the type of diazoalkane which may be used those illustrated being successful. However in view of the ready cheletropic elimination of nitrogen and sulphur from the corresponding 2,2-dialkyl derivatives of this heterocycle to give olefins it would be interesting to see if (51) could produce allenes in the same manner.R' R3 R' R3 >-=S+ )=k=N--* *'\ic,, RZ R3 R2 NzN R3 = Me or But (51) The fluorinated 1,3,4-dioxazo1-2-ones (52) represent a potentially hazardous class of heterocycle undergoing detonations when heated,83 and are therefore unlikely substitutes for the explosive acyl azides for which they were originally designed. New mesoionic rings include the 1,4,3-thiadiazolium thiolates (53)84and the bicyclic compounds (54).85 Me\q s-N<. -R+$O N-KKRf 00 SR Rf = CF3,C3F7,or C7F (53) Me 0 R = HorMe (52) (54) Finally some fascinating chemistry has emerged from a study of the 'bi-perifunc- tional' compound (55) which can function as either an azomethine ylide (A) or thiocarbonyl ylide (B).86 In most of its cycloadditions with dipolarophiles the latter form dominates although in one case it appears that addition to form A is kinetically controlled whereas the thermodynamic product derives from addition across form B (Scheme 29).5 Six-membered Rings The versatility of a -0xoketene dithioacetals highlighted last year (Annu. Rep. Prug. Chern. Sect. B 1982 79,217 232) has been further demonstrated by their use as progenitors of a-pyrones either simple or annulated in a series of reactions resulting in overall 1,3-carbonyl transposition (Scheme 30)." " F. Lucchesini and V. Bertini Synthesis 1983 824.ni M. Mbuyi M. Evers G. Tihange A. Luxen and L. Christiaens Tetrahedron Lett. 1983 24 5873. 82 E. Schaumann H. Behr and J. Lindstaedt Chem. Ber. 1983 116 66. 83 W. J. Middleton J. Org. Chem. 1983 48 3845. n4 J. Adachi H. Takahata K. Nomura and K. Masuda Chem. Pharm. Bull. 1983 31 1746. 85 W. Friedrichsen A. Bottcher and T. Debaerdemaeker Heterocycles 1983 20 23 845 1271. nh 0. Tsuge S. Kanernasa and T. Hamamoto Chem. Lett. 1983 85 763; 0.Tsuge S. Kanemasa and T. Hamamoto Heterocycles 1983 20 647. 87 R. K. Dieter and J. R. Fishpaugh. J. Org. Chem. 1983 48 4439. Heterocyclic Compounds c-) 55 “C EtOoOEt EtO OEt 00 ex0 + endo Scheme 29 0 0 Alternative functionalization of the pyrone ring occurs when the products of metallation and subsequent hydroxyalkylation of 1-methoxybut-1-en-3-yne are hydrolysed.88 Benzothiete (56),readily obtained by ring contraction of a number of benzothio- phene derivatives undergoes photochemical or (better) thermal cycloreversion to a thioquinone-methide which can be trapped by dienophiles to give a range of 4H-1-benzothiapyrans (57).89With relatively unreactive dienophiles such as cyclo- hexenone considerable amounts of the dimer (58) contaminate the product.88 M. T. Crimmins and D. M. Bankaitis Tetrahedron Lett. 1983 24 5303. 89 K. Kanakarajan and H. Meier J. Org. Chem. 1983 48 881. 264 E. H. Smith (56) (57) OMe 0 cB (pJyBr S \ 0 ’0 OMe (58) (59) In an attempt to convert the 3-bromochromone (59) into the corresponding pyrrolidinyl amine a novel ring-contraction of the pyrone ring was discovered which also occurred in the simpler case (60) but using primary amines (Scheme 31).90 R = alkyl or OH Scheme 31 As expected the incorporation of the more electropositive tellurium into the heterocyclic ring in the dye series (61; X = Group VI element) results in a bathochromic shift.” The telluroflavones (62; R = Ph) and tellurochromones (62; R = H or Me) have been prepared from the unsaturated acids (63).”* The synthesis required the presence of electron-donating groups in the position meta to the tellurium atom to favour ortho-rather than ipso-acylation.NMez I Most papers on pyridines this year have been concerned with their reactions rather than their synthesis.An exception is the new synthesis of 4-pyridones (64) which is said to be more convenient than existing routes.93 In a series of three YO R. B. Gammill S. A. Nash and S. A. Miszak Tetrahedron Lea. 1983 24 3435. 91 M. R. Detty and B. J. Murray J. Org. Chem. 1982 47 5235. 92 M. R. Detty and B. J. Murray J. Am. Chem. SOC.,1983 105 883. y3 J. Barluenga F. Lopez Ortiz F. Palacios and V. Gotor Synth. Commun. 1983. 13 41 1. 265 Heterocyclic Compounds Ar I I er Ph AICl, "Qph I ,P,+*A,,, R2 R2 0 (64) papers Vorbriiggen and Krolikiewicz have shown that pyridine-N-oxides interact with trimethylsilyl based reagents to give ~yridines,~~" 2-alkenyl-( or benzy1)-pyridine~,~~' and 2-cyano-pyridines (Scheme 32).94' R R Me,Siv Bu; NF Rc-3N+ I 0- Scheme 32 Pyridine-N-oxides also feature in an extensive survey of the products of bromina-tion of some mono-substituted azine-N-~xides,~~ which draws some general con- clusions concerning the preferred site of reactivity.The conversion of pyridinium-2-carboxylates into 2-pyridthiones on heating with sulphur in xylene is a useful alternative to existing routes to these compound^.^^ Direct lithiation at C-2 of simple pyridines followed by trapping with electrophiles as a means of introducing substituents at that position is plagued by competing addition of the lithiating agent to the ring or self-condensation of the resulting lithio-derivative. Two procedures which help overcome these problems are lithiation under carefully controlled conditions of either the complex (65),formed from the pyridine and hexafluoroacetone (at -107 "C using lithium tetrameth~lpiperidide),~~" or the N-(t-butyloxycarbonyl)-1,4-dihydropyridines (66) (at -42 "C using s-butyl- lithium).97b In both instances chelation of lithium in the resultant intermediate is believed to occur.The carbamoyl analogues (67) of the latter starting materials undergo Friedel- Crafts acylation at the relatively electron-rich C-3 position.98 Since the products 94 (a)H. Vorbriiggen and K. Krolikiewicz Tetrahedron Lett. 1983 24 5337; (b)H. Vorbriiggen and K. Krolikiewicz ibid. 1983 24 889; (c) H. Vorbriiggen and K. Krolikiewicz Synthesis 1983 316. 95 W. W. Paudler and M. V. Jovanovic J.Org. Chem. 1983,48 1064. 96 A. R. Katritzky and H. M. Faid-Allah Synthesis 1983 149. 97 (a)S. L. Taylor D. Y. Lee and J. C. Martin J. Org. Chem. 1983 48 4156; (b)D. L. Comins Tetrahedron Lett. 1983 24 2807. 98 D. L. Comins and N. B. Mantlo Tetrahedron Lett. 1983 24 3683. 266 E. H. Smith R RH fi 0 N+ N Bu'O Et,N (65) may be dehydrogenated to 3-acylpyridines the overall transformation accomplished a reaction which has proven extremely difficult in the parent ring. The 1,4-dihydropyridines used above were derived by the CuI-catalysed addition of Grignards to N-alkoxycarbonyl pyridinium salts. Without the presence of the copper salt these organometallics add indiscriminately to C-2(mainly) and C-4 of the pyridine ring.It has now been shown that this is not true however of alkenyl- and alkynyl-Grignards which add exclusively to give the 1,2-dihydropyridine~.~~ In contrast addition of silyl enol ethers of ketones to the readily available 2-cyano- 1,2,5,6-tetrahydropyridines(68) proceeds in a 1,4-sense under catalysis by boron trifluoride. Thus (68) act as equivalents (or precursors) of the 5,6-dihydropyridinium ions (69).'0° R' k' R' I R' R3 I l Vilsmeier's reagent has proven of use in the synthesis of a few quinolines from P-anilino-butenoates (Scheme 33),'*' which reaction shows little influence of the aromatic substituents on the cyclization step. 0 RaNcOEt DMF,CHCI,,POCI,.,5 "C R e E t Me H Scheme 33 A mild version of the classical Pomeranz-Fritsch synthesis of isoquinolines uses titanium tetrachloride as the cyclocondensing agent and an a-aminophosphonate generated in situ as the imine equivalent (Scheme 34).lo2 Although attempts to use the aminophosphonate in Horner-Wittig reactions were successful the expansion of the scope of the isoquinoline synthesis which was expected to accrue thereby did not materialize because the products failed to cyclize.99 R. Yamaguchi Y.Nakazono and M. Kawanisi Tetrahedron Lett. 1983 24 1801. I00 A. Koskinen and M. Lounasmaa J. Chem. SOC.,Chem. Commun. 1983 821. 101 D. R. Adams J. N. Dominguez and J. A. Perez Tetrahedron Lett. 1983 24 517. 102 J. B. Hendrickson and C. Rodriguez J. Org. Chem. 1983,48 3344. Heterocyclic Compounds /N c1-O OP(OMe)2 Scheme 34 Jefford and his co-workers have devised and executed in good order a general synthesis of 1,2,4-trioxan-5-ones (Scheme 35),103abased on their observations of the formation of this ring system on trapping P-peroxy cations with aldehydes.103b The presence of this heterocyclic system in the potent antimalarial natural product qinghaosu (70) provided the stimulus for this work.H 0-0 R2 R2yR3 Me,SiOTf -78 to -20°C 0 R' 0 0 Scheme 35 Me 0 (70) 1,4-Peroxy compounds are also involved in a first demonstration of a thermal ring-contraction of oxygenated pyrazines to imidazoles (Scheme 36).lo4The isolation NFOMe R2 R2 / " Rl R' Me0,C R' SN Me0 X NANC02 Me N t R2 -0Me N+OMe \\/$"OMe R2 R2 (71) Scheme 36 103 (a)C.W. Jefford J.-C. Rossier and G. D. Richardson J. Chem. Soc. Chem. Commua 1983 1064; (b) C. W. Jefford D. Jaggi J. Boukouvalas and S. Kohmoto J. Am. Chem. Soc. 1983,105 6497; C. W. Jefford S. Kohmoto J. Boukouvalas and U. Burger ibid. 1983 105 6498. 104 A. J. O'Connell C. J. Peck and P. J. Sammes J. Chem. Soc. Chem. Commun. 1983 399. 268 E. H. Smith in one case of an intermediate diazoxepine (71) substantiates the proposed mech- anism by way of a pyrazine oxide. We have already seen the use of a-aminonitriles as the equivalents of iminium ions in the section on pyridines. Given a geminal alkyl group they can also act as precursors of enamines and an elegant use of this trick in the synthesis of octahy-droquinoxalines involves an isolable 5,6-dihydropyrazine-2,3-diquinomethide(72) (Scheme 37).lo5 X = CO,Me CN COMe CHO or Ph Scheme 37 A synthesis of 2,6-diarylpyrimidines proceeds regioselectively by a formal [2 + 2 + 21 cycloaddition of two molecules of aryl nitrile and one molecule of acetylene under boron trifluoride catalysis.lo6 A pyrimidine was embedded in the novel 1,3-diazabiphenylene (73),lo7 which underwent quantitatively a complex acid- catalysed rearrangement to the isoquinoline (74) possibly through the intermediacy of a benzodiazocine and an isoquinolinoazete (Scheme 38).~1-r-R* + 2ArCN 85% H,PO, ArcAr BF,.OEt \N R’ MeHqH. p3siMe3 N-\ SiMe OMe (73) Me0vsiMe3 -HCN NwSiMe N\ SiMe e- LN SiMe OMe OMe (74) Scheme 38 The well known utilization of a-diazocarbonyl compounds for the preparation of ethers by insertion of the derived carbenoids into the OH bond has now been 105 H.Ahlbrecht M. Dietz and W. Raab Synthesis 1983 231. 106 A.-A. Pourzal Synthesis 1983 717. 107 M. d’Alarcao and N. J. Leonard J. Am. Chem. Soc. 1983,105 5958. Heterocyclic Compounds 269 used intramolecularly in a synthesis of 1,4-oxazines (75),lo8 a principle already in use in p-lactam chemistry which deserves wider attention in heterocyclic chemistry as a whole. (75) Heterocycles of some novelty reported this year include the first 1,4,2,3-dioxadiazines (76) which decompose on heating (to 100 "C)in an unexpected manner to give the bis-carbonate ROC0.0CH2CH20-C0.0R,109and the 2,1,3-benzothiadiazine derivative (77) which contains the hitherto unknown dithiosul- phone group.' lo S (77) 6 Seven- and Eight-membered Rings Addition of a lithio a-diazophosphonyl derivative to a 4-methylpyrylium salt followed by catalytic (allylpalladium chloride dimer) expulsion of nitrogen provides a new route to the 2,7-di-t-butyloxepines (78)."' No valence tautomerism occurred in these oxepines as evidenced by chemical and spectroscopic studies a situation akin to the corresponding non-phosponylated thiepine reported last year (Annu.Rep. Prog. Chem. Sect. B 1982 79,236). MeP ..o (78) Although the valence tautomers of oxepine and 2,7-dimethyloxepine behave as dienes the larger ring tautomer can act as a dienophile towards the inverse electron demand tetrazines and triazines to give novel fused oxepines (79).l12 108 D.E. McClure P. K. Lumma B. H. Arison J. H. Jones and J. J. Baldwin J. Org. Chem. 1983 48 2675. 109 D. K. W. Dixon R. H. Weiss and W. M. Nelson Tetrahedron Len. 1983 24 4393. 110 R. M. Acheson M. R. Bryce S. Das Z. Dauter A. J. Rees and C. D. Reynolds J. Chem. SOC.,Chem. Commun. 1983 1002. 111 K.-L. Hofmann and M. Regitz Tetrahedron Lett. 1983 24 5355. 112 R.Dhar W. Huhnermann T. Kampchen W. Overheu and G. Seitz Chem. Ber. 1983,116 97. 270 E. H. Smith C0,Me c:+ C0,Me ZAY -N* HN / 7% / NYN R Y Y R = H or Me X = Nor CHC0,Me (79) Y = C0,MeorCN A simple route to benzo[b]oxepin-5-ones uses a strategy common in medium ring carbocyclic chemistry namely [2 + 2]photocycloaddition of an olefin to a P-acyloxy-a,P-enone followed by retro-aldol reaction (Scheme 39).l l3The alterna- tive cycloaddition protocol of putting a five-membered ring onto a four-membered Scheme 39 one results ultimately in the formation of the 1,2-diazotropones (80) from the reaction of cyclobutenones with diazoalkanes (Scheme 40),' l4 and of 3H- 1,3- benzodiazepines (81) from reaction of 2-phenylbenzazete with 1,3-oxazo1-5-ones (Scheme 41).lI5 R3q:. + R4CHN2 + R' Scheme 40 r Ph Ar2 1 Scheme 41 Heating the 3-azatricyclo[4.1 .0.0235]heptanes (82) prepared in three steps from pyridine results in ring-opening in high yield to give the heteroazepines (83),l l6 113 J.H. M. Hill and S. T. Reid J. Chem. SOC.,Chem. Commun. 1983 501. '14 H.-D. Martin R. Iden F.-J. Mais G. Kleefeld A. Steigel B. Fuhr 0.Rummele A. Oftring and E. Schwichtenberg Tetrahedron Lett. 1983 24 5469. 11' P. W.Manley C. W. Rees and R. C. Storr J. Chem. SOC.,Chem. Commun. 1983 1007. 116 J. Kurita K. Iwata M. Hasebe and T. Tsichiya J. Chem. Soc. Chern. Commun. 1983 941 Heterocyclic Compounds 27 1 the first examples of seven-membered monocycles in which the heteroatoms are 1,4-related. NC0,Me X = O,NCO,Me,orS C0,Me 'Y Y = H,H or 0 X = H C1 or Br (82) (83) (84) The previously unknown 2H-1,5-benzodioxepines (84)are relatively easily obtainable by dihalogenocarbene cyclopropanation and subsequent ring expansion of the corresponding benzodioxenes.' l7 Oxidative ring-opening of the imidazalo-imidazoles (85) allows the preparation of the 1,3,5,7,-tetrazocines (86) another rare class of heterocycle.'" RH /)=N OEt -R Et0qNTN)-Bu'OCl YOEt NN KOBu' EtO'N<N HR R = Me or Ph R (85) (86) 7 Macrocycles and Crown Ethers Two groups have reported examples of the pentapyrrole analogues of the porphyrins and corrins termed pentaphyrinsl '9aib and sapphyrins' 19' respectively and one hexapyrrole macrocycle has also been made.' '9b Three sexipyridines (87) represent the first examples of this long-sought ring.Interestingly the parent compound was reported as the free ligand12' whereas the R = H p-MeC6H4,or p-EtC,H (87) I17 G.Guillaumet G. Coudert and B. Loubinoux Angew. Chem. Int. Ed. EngL 1983 22 64. 118 R. Gompper and M.-L.Schwarzensteiner Angew. Chem. Int. Ed. Engl 1983 22 543. 119 (a) H. Rexhausen and A. Gossauer J. Chem. SOC.,Chem. Commun. 1983 275; (6)A. Gossauer Chimia 1983 37,341; (c) V. J. Bauer D. L. J. Clive D. Dolphin J. B. Paine F. L. Harris M. M. King J. Loder S.-W. C. Wang and R. B. Woodward J. Am. Chem. Soc. 1983,105,6429. lZo G. R. Newkome and H.-W. Lee J. Am. Chem. SOC.,1983 105 5956. 272 E. H.Smith substituted derivatives were obtained in a similar manner only as the Na+-complexes the metal ion apparently deriving from the g1assware!l2l The synthesis of syn-1,6 8,13 -diamino[ 14Jannulene (88) probably set a record for desperation in that conversion of the OH groups in the intermediate diol (89) into suitable leaving groups could only be achieved using oleum (65% S03)!122 The 'H n.m.r.spectrum of (88) indicates that it possesses a delocalized T-electron system. OH HO (89) The dark red dodecahydro-18,21-dioxoniakekulene salt (90) is the first heterokekulene derivative to be ~ynthesized.'~~ 2x- 12' J. L.Toner Tetrahedron Lett. 1983 24 2707. 122 E. Vogel F. Kuebart J. A. Mario R. Andrei H. Gunther and R. Aydin J. Am. Chem SOC.,1983 105,6982. 123 A. R. Katritzky and C. M. Marson J. Am. Chem. Soc. 1983 105 3279.

ISSN:0069-3030    

DOI:10.1039/OC9838000245

出版商:RSC    

年代:1983

数据来源: RSC

摘要:

12 Organometallic Chemistry Part (i) The Transition Elements By M. BOCHMANN Department of Chemical Sciences University of East Anglia. Norwich NR4 7TJ R. A. HEAD ICI New Science Group The Heath Runcorn Cheshire WA7 4QE M. D. JOHNSON Department of Chemistry University College London 20 Gordon Street London WCl H OAJ 1 Introduction 1983 was a year of consolidation in most areas of organotransition-metal chemistry a highlight being the surge of development in intermolecular activation of carbon- hydrogen bonds of both aliphatic and aromatic hydrocarbons. A great many reviews of interest to organic chemists have appeared notably on asymmetric hydrogena- tion,' rhodium-catalysed enantioselective hydrogenation,2 hydrogenation of carbon monoxide to ethanol and ethylene glycol,3 catalytic hydrocarbonylation of alcohols co-ordination chemistry of ylide~,~ 7r-complexes of cobalt( I) transition-metal nitrosyls in organic ~ynthesis,~ transition-metal formyl complexes,' electron-rich half-sandwich complexes,' homolytic displacement of transition-metal complexes from carbon," homolytic and radical pathways in the reactions of organo-chromium(111) compounds,' 'titanium-induced dicarbonyl coupling reactions,12 the organometallic complexes of titanium and zirconium as selective nucleophilic reagents in organic ~ynthesis,'~ and the organic chemistry of gold,14 as well as two reviews on the role of metal clusters in In addition the main papers presented at the Conference on Organometallic Chemistry Directed Towards Organic Synthesis held in Dijon in September have already been published." A review on ' W.S. Kennedy Acc. Chem. Rex 1983 16 106. H. Brunner Angew. Chem. int. Ed. Engl. 1983 22 897. D. B. Dornbek Adv. Cutul. 1983 32 326. M. E. Fakley and R. A. Head Appl. Catal. 1983 5 3. W. C. Kaske Coord. Chem. Rev. 1983 48 1. T. Funabiki Rev. Inorg. Chem. 1982 4 329, 'K. K. Pandey Coord. Chem. Rev, 1983 51 69. J. A. Gladysz Adv. Organomet. Chem. 1983 20 1. H. Werner Angew. Chem. In?. Ed. Engl. 1983 22 927. I" M. D. Johnson Acc. Chem. Rex 1983 16 343. I' J. H. Espenson hog. inorg. Chem. 1983 30,189. I' J. E. McMurry Acc. Chem. Rex 1983 16 405. I3 B. Weidmann and D. Seebach Angew. Chem. Int. Ed. Engl. 1983 22 31. G. K. Anderson Adv. Organomet. Chem.1982 20,40. Is R. D. Adam Acc. Chem. Rex 1983 16 67. l6 E. L. Muetterties and M. J. Krause Angew. Chem. in?. Ed. Engl. 1983 22 135. Pure Appl. Chem. 1983 55 1669. 273 274 M. Bochmann R. A. Head and M. D. Johnson the reactions of heteroaromatic transition-metal complexes with base clearly confirms that extensive earlier descriptions of covalent hydration of N-heteroaromatic ligancls has little foundation.18 2 Intermolecular Activation of Aliphatic and Aromatic Hydrocarbons The early observations of low-temperature homogeneous activation of alkenes and arenes by transition-metal complexes were made in 1965. Subsequently many examples of intramolecular activation e.g. cyclometalation have been described. In the past two years however clear examples of intermolecular activation including catalytic processes have been reported and our understanding of the nature of the reactive intermediates has grown.The dihydro-complex (1 ; R1= Ph)19 extrudes dihydrogen on irradiation in ben- zene and reacts with the solvent to give (2; R1= R2 = Ph). The corresponding complex (1; R' = Me)** reacts not only with benzene but also with cyclohexane and with neopentane to give (2; R'= Me R2 = cyclohexyl or neopentyl). Although the corresponding thermal process is also possible the thermal reductive elimination of the alkane from (2; R1= Me R2 = Alkyl) becomes dominant at higher tem- peratures. Competition experiments show that the relative reactivities of the organic substrates towards the transient intermediate formed from (I ; R' = Me) expressed as reactivity per available C-H bond are benzene (4) > cyclopropane (2.65) > cyclopentane (0.96) > neopentane (0.57) > cyclohexane (0.5) > cyclodecane (0.27) > cyclo-octane (0.04).(T-c :) 5(7-C M~,)wPR:)R~ M~,)I~H,(PR (1) (2) Phosphine ligands are by no means an absolute requirement for C- H activation. The related carbonyl complex (3)2' on irradiation with cyclohexane benzene per- deuteriobenzene or even methane in perfluorohexaneZ2 gives the alkyl or aryl complex (4) (R = neopentyl cyclohexyl phenyl C6D5 or methyl). These species are stable only at low temperatures but can be converted by reaction with carbon tetrachloride or N-bromosuccinimide into the corresponding more stable chloro- or bromo-alkyl complexes (5).The relative rates of reaction per available C-H bond observed using (3) are benzene (5) > neopentane (1.25) > cyclohexane (1). It is suggested that the pentamethylcyclopentadienyl ligand not only increases the electron density on the metal but also reduces the possibility of intramolecular C -H activation. The relative reactivity of the co-ordinatively unsaturated intermedi- ate is thus (q-C5Me5)Ir(PMe3)> (q-C,Me,)Ir(CO) > (q-C5H5)Ir(CO). However overall reactivity is likely to depend not only on the rate of reaction of the unsaturated complex but also on its rate of formation and the reverse. hv RH CHBr (~-C,Me,)1r(C0)~ (T-C,M~,)I~H(CO)R (7)-C,Me,)IrX(CO)R (3) (4) (5) X = Br or C1 l8 N. Serpone G.Ponterini M. A. Jamieson F. Bolletta and M. Maestro Coord. Chem. Rev. 1983,50,209. '' A. H.Janowicz and R. G. Bergman J. Am. Chem. SOC.,1982 104 352. 20 A. H. Janowicz and R. G. Bergrnan J. Am. Chern. SOC.,1983 105 3929. 2' J. K. Hoyano and W. A. G. Graham J. Am. Chem. SOC.,1982 104 3723. 22 J. K. Hoyano A. D. McMaster and W. A. G. Graham J. Am. Chem. Sor. 1983 105 7190. Organometallic Chemistry -Part (i) The Transition Elements 275 The corresponding rhodiurn(~rr) complex (6a)23 gives the aryl complex (7a) on reaction with PhMgBr in THF at -40°C. Reaction of (7a) with Li[HBBuS3] gives the hydridoaryl complex (7b) which undergoes arene exchange on heating with other aromatic compounds. On heating with toluene for example a mixture of meta- and para-substituted isomers (8a) and (8b) is formed the former under kinetic control the mixture under thermodynamic control.It is suggested that the rearrange- ment of (8a) into (8b) takes place without dissociation of the arene i.e. viu a q-arenerhodium(1) complex (9),or possibly via a dihydro-q2-benzynerhodium(~rr) complex (1 0). hu RH CHBr (v-C5Me5)RhX2(PMed -(v-C5Me5)RhX(PMe3)Phor~~1; (v-CSMeS)RhH(PMe3)Ar (6) a; X = C1 (7) a; X = Br (8) a; Ar = 4-MeC,H4 b;X=H b;X=H b; Ar = 3-MeC6H The thermal elimination of methane from the corresponding methyl complex (q-C5Me5)Rh(PMe3)(H)(Me)24 at -17 "C in deuteriobenzene is first order with a rate constant k = 6.5 x s-'. Irradiation of the dihydride (6b) in liquid propane at -55 "C gives exclusively the primary n-propylrhodium complex (q-C5Me5)-Rh( PMe,)( H)(Pr") which regenerates propane at -15 "C but which can be converted into the more stable bromoalkyl complex (q-C5Me5)Rh(PMe3)(Br)( Pr") on treatment with CHBr,.T2-Arene complexes (12) have been characterized in the low-temperature reaction of the arylrhenium complexes (1 la-c) with HBF4.Et20 in CH2C12.2' In the case of (12; Ar = Ph) the singlet C6H6 resonance at 87.23 in the 'H n.m.r. spectrum is unaffected by addition of free benzene which gives a separate resonance at 87.33; in the protonation of the 0- m- and p-tolyl complexes (1 Ib) the same q2-toluene cation (1 2; R = Me) is formed. Protonation of (1 lc) is more difficult and requires fluorosulphonic acid at -78 "C. In all cases deprotonation by bases such as triethyl- amine regenerates the q' -aryl complex (1 1).Similar stereochemically non-rigid q2-arene complexes (12; R = CHPh2)and (12; R = cycloheptatriene) are formed26 in the reaction of trityl or tropylium hexafluorophosphate with (7-C,H,)Re(NO) (C0)H in CH2CI2 at -78 "C. The temperature dependence of the 'H n.m.r. spectrum between -40 and -70 "C indicates that the rhenium moves around the six-membered ring of the former complex via a series of q'-arenium structures (13) corresponding to the Wheland intermediates long postulated in aromatic substitution reactions. 23 W. D. Jones and F. J. Feher J. Am. Chem. SOC. 1982 104,4240. 24 W. D. Jones and F. J. Feher Organomefallics 1983 2 562. 25 J. R. Sweet and W. A. G. Graham J.Am. Chem. Soc. 1983,. 105 305. 26 J. R. Sweet and W. A. G. Graham Organometallics 1983 2 135. M. Bochmann R. A. Head and M. D. Johnson Another q2-arene complex (15) has been identified in the reaction of the fac- complex (14) with anthra~ene.~' The rate of disappearance of (14) to (15) and to associated reduction products is independent of the concentrations of anthracene and dihydrogen indicating that the co-ordinatively unsaturated complex [RuH(Ph,P),]-is a common reactive intermediate. The trihydride IrH,(CO)(dppe) also loses dihydrogen both on heating and on irradiation yielding IrD,(CO)(dppe) in the presence of D2 and IrH(CO),(dppe) in the presence of CO. H/D Exchange takes place in the presence of C6D6 and when CO is also present benzaldehyde is also formed.28 (14) P = PPh (15) The analogy with electrophilic substitution is more evident with some complexes than with others.For example the square-planar octaethylporphyrinrhodium(1) cation prepared in situ from the corresponding chloro-complex and silver ion reacts with aromatic hydrocarbons predominantly at the para-position. The selectivity determined by competition methods anisole (1) > toluene (0.15) > benzene (0.14; statistically corrected) > chlorobenzene (0.002) is in the direction expected for an electrophilic substitution reaction but is lower than is observed in nitration or bromination. Using the substituent constant u+the reaction has a p-value of ca. -2.5; the more negative value quoted by the authors29 appears to be from use of the less appropriate U-values.The analogy with electrophilic substitution is clearly much less in the case of the complexes (1) and (3) and is certainly not exclusive because the reaction of cyclopentane with the aquated chromium(I1) ion in the presence of hydrogen peroxide takes place by (i) reaction of chromous ion with hydrogen peroxide (ii) reaction of a hydroxyl radical with cyclopentane and (iii) capture of a cyclopentyl radical by chromous ion to give the penta-aquacyclopen- tylchromium(r1r) ion.,' Selectivity in the case of (r)-C6H,)RuH2(Pri3P) (16),' is dominated by the fact that on irradiation in cyclohexane at room temperature reaction does not appear to take place with the solvent. Instead an intramolecular cyclometallation takes 27 R.Wilczynski W. A. Fordyce and J. Halpern J. Am. Chem. SOC.,1983 105 2066. 28 B. J. Fisher and R. Eisenberg Organornefallics 1983 2 764. 29 Y. Aoyama T. Yoshida K. Sakurai and H. Ogoshi J. Chem. SOC.,Chern. Cornrnun. 1983 478. 30 J. H. Espenson P. Connolly D. Meyerstein and H. Cohen Inorg. Chem. 1983 22 1009. 3' H. Kletzin and H. Werner Angew. Chem. Inr. Ed. Engl. 1983 22 873. Organometallic Chemistry-Part (i) The Transition Elements place through activation of one of the methyl groups of the tri-isopropylphosphine. The four-membered metallocycle (1 7) does react with benzene (and perdeuterioben- zene) at room temperature to give the hydridoarylruthenium complex (18). Arene exchange takes place when (I 8) is heated with other hydrocarbons such as toluene.It is suggested that the apparent absence of reaction with alkanes is a result of the ready reductive elimination of the hydridoalkyl complexes. The corresponding aryl complex in which the benzene ligand is replaced by the hexamethylbenzene ligand does not undergo exchange with other arenes. (16) [Ru] = (q-C,H,)Ru(PPr;) A (18) Me H (17) Two studies reveal the potential of lanthanide complexes in C-H activation. Thus complex (19) (R = H or Me) reacts thermally with pyridine and with tetramethylsilane in hydrocarbon solvents to give isolable products of C-H activa- tion (20) and (21).32 The reaction of (20; R = Me) with '3C-labelled methane in [2HI,]cyclohexane at 70 "Cresults in the exchange of labelled and unlabelled methyl groups in the complex.33 Kinetic studies indicate that the exchange takes place by simultaneous unimolecular and bimolecular paths the former via a cyclometallated intermediate (22) and the latter by a concerted reaction through the four-centre transition state (23).It is also significant that the complex (19; R = Me) exists in the solid state as an unsymmetrical dimer. (T-C,Me,)&uR (q-CSMe,)2LuCH,SiMe3 + RH "CH (21) (~-CSMes),L~'3CH, + CH 32 P. L. Watson J. Chem. SOC.,Chem. Commun. 1983 276. 33 P. L. Watson J. Am. Chem. SOC..1983 105 6491. M. Bochmann R. A. Head and M. D. Johnson The dehydrogenation of cycloalkanes by the complex ReH,(R,P) (24) in the presence of 3,3-dimethylbutene as a hydrogen acceptor was described in 1982.34 With cyclopentane the product was a cyclopentadienylrhenium complex but with higher cycloalkanes the un-co-ordinated cycloalkene was obtained.The dehydrogen- ation is catalytic under mild conditions; thus 3 mM catalyst (24; R = 4-FC,H4) and dimethylbutene (50 mM) in cyclo-octane as solvent gives 5.3 mM cyclo-octene within 10 min at 30 "C and 30 mM cyclo-octene within 10 min at 80 0C.35 Methylcyclohexane gives 29% 3-methylcyclohexene 65% 4-methylcyclohexene and 6% of the exocyclic olefin. The activity of the catalyst is less with (24; R = Ph) or (24; R = 4-MeC,H4). The complex [IrH2S2L2]+ (S = water or acetone L = Ph3P) also dehydrogenates cyclopentane and cyclopentene to give cyclopentadienyliridium complexes; they dehydrogenate cyclo-octane and cyclo-octene to give cyclo-octadieneiridium com- p~exes.~~ Two examples of intramolecular C-H activation are of interest.Whereas catalytic deuterium/ hydrogen exchange takes place at the a-carbon of alkylamido-complexes of zirconium hafnium and niobium the corresponding exchange in alcohols cata- lysed by alkoxy-complexes of the same metals takes place exclusively at the p-carbon.37 The cyclometallation process also serves as the basis of the catalytic aminomethylation of terminal olefins. In an unrelated process substituted cyclopen- tanes can be formed enantioselectively through activation of a remote carbon chain as in Scheme 1.38 The enantioselectivity is achieved through suitable adaptation of the substrate (25) with a removable second chiral centre on the ester group thus allowing the intermediate to cyclize diastereoselectively through a highly ordered transition state derived from the intermediate (26).Scheme 1 The details of the temperature dependence of the I3C and 'Hn.m.r. spectra of tricarbonylcyclohexadienylmanganese(28 ; X = H)demonstrated most elegantly and persuasively the existence of intramolecular C-H-Mn interactions and the associated dynamic eq~ilibria.~~" This work has been extended:39bic (a) using 2H 34 D. Baudry M. Ephritikhine and H. Felkin J. Chem. Soc. Chem. Commun. 1982 606. 35 D. Baudry M. Ephritikhine H. Felkin and R. Holmes-Smith J. Chem. Sac. Chem Commun.,1983,788. 36 R. H. Crabtree M. F. Melleas and J. M. Mihelcic J. Am. Chem. SOC.,1982 104 107.31 W. A. Nugent D. M. Ovenall and S. J. Holmes Organometallics 1983 2 161. 38 D. F. Taber and K. Raman J. Am. Chem. SOC.,1983 105 5935. 39 M. Brookhart W. Lamanna and M. B. Humphrey J. Am. Chem. SOC.,1982 104 2117; M. Brookhart W. Lamanna and A. R. Pinhas Organometallics 1983. 2.638; M. Brookhart and A. Lukacs ibid. p. 649. Organometallic Chemistry -Part (i) The Transition Elements n.m.r. spectroscopy to show that deuteriation of the hexadienemanganate(1) complex (27) takes place with endo-stereospecificity to give (28; X = D); (b) that the bridging hydrogen is acidic; (c) that the methylation of (27) with for example methyl iodide gives two isomers (30a) and (30b) via an intermediate (29) in which the methyl group is bonded to the metal; and (d) that deprotonation of (30a) and of (30b) leads to the same diene complex (31) which (e) on further methylation in the presence of carbon monoxide gives two products (33) and (34) the former being derived from the complex (32) which is unable to manifest the appropriate C-H-Mn bridging (Scheme 2).Several dynamic processes have been studied with these and related more highly substituted complexes. The cyclic dienes can be liberated from the dienyl complexes such as (27) and (31) by reaction with molecular oxygen and the cycloalkenes can be released from the enyl complexes such as (28) (30) and (34) by reaction with LiBEt,H under 1 atm CO. H (32) (34) Scheme 2 3 Rearrangements Related to Coenzyme BI2 Chemistry Three organometallic rearrangements related to bio-organic rearrangements cata- lysed by coenzyme BI2have been described two of which relate to the diodehydrase conversion of diols into aldehydes.Three diastereoisomeric 6,7-dihydroxycycloun- decyl iodides (35) have been synthesized and converted into cycloundecanone by reaction with borohydride ion in the presence of catalytic amounts of cobalt chelates and even of cobalt(r1) chloride (Scheme 3).40 The maximum yield of cycloundecanone P. Muller and J. Retey J. Chem. Soc. Chem. Comrnun. 1983. 1342. M. Bochmann R. A. Head and M.D. Johnson “-0 Om -HO (38) “ 0 Om Reagent iBH; trace.(CO)I,[(CO) = 2,3,9,10-tetramethyl-1,4,8,1 l-ol-I-tetra-azaundeca-l,3,8,lO-tetraen-l olatocobalt] Scheme 3 (75%) was obtained using the chelate 2,3,9,lO-tetramethyl- 1,4,8,1 l-tetra-azaundeca- 1,3,8,lO-tetraen-ll-ol-olato (36) the yield being almost independent of the concentra- tion of the organic substrate but being decreased by high concentrations of the cobalt complex.It is proposed that the cyclic ketone is formed by rearrangement of the conjugate base of the 1,2-dihydroxycycloundecylradical (38) which is formed by a transannular hydrogen atom transfer from the first-formed 6,7-dihydroxycyc- loundecyl radical (37) rather than by a cobalt-mediated process. Indeed it is also suggested that the organocobalt complex (39) formed by capture of cobalt(r1) by (38) is the precursor of 2-hydroxyundecanone which is formed as a by-product. Similar conclusions are drawn from an extremely thorough study of the kinetics and products of decomposition of the previously unknown 1;2-dihydroxyethyl- (40) and protected 1,2-dihydroxyethyl-cobalt(r1~)complexes [also containing the chelate ligand (36)] in alkaline methanol (Scheme 4).41 High (>95%) yields of acetaldehyde are obtained through the formation of the 1,2-dihydroxyethyl radical which is 4’ R.G. Finke W. P. McKenna D. A. Schiraldi B. L. Smith and C. Pierpont J. Am. Chern. SOC.,1983 105 7592 R. G. Finke and D. A. Schiraldi ihid. p. 7605. Organometallic Chemistry-Part (i) The Transition Elements 28 1 (Co)CH(OH)CH,(OH) (CO")+ .CH(OH)CH20H 2.CH(O-)CH,OH -+ (40) 1ii (Co)CH,CHO ~t+ MeCHO (Co) as in Scheme 3 above. Reagents i -OMe:ii A hydrogen atom source probably solvent methanol.Scheme 4 substantially more acidic than the parent ligand and rearranges through its conjugate base directly without cobalt mediation to acetaldehyde. It is clearly demonstrated that the formylmethyl complex (41) is not an intermediate on the reaction path leading to aldehyde. In contrast Golding4* has synthesized several racemic ethoxycarbonyl-substituted but-3-enyl (42) and (43) and cyclopropylcarbinyl (44) and (45) cobaloximes which rearrange in the presence of trifluoroacetic acid to an equilibrium mixture containing predominantly (43) (Scheme 5). These rearrangements are not only much slower than were observed in the corresponding methyl-substituted complexes but the most stable species also differs confirming the rather special stability of the carbon-cobalt bond in alkoxycarbonylmethylcobalt(Irr) complexes.C0,Et + EtocoY EtOCO EtOCOfro) b-cco (44) (45) (Co) = Co(dmgH),Py Reagent i CF3CO2H 1.0 M. Scheme 5 4 Diels-Alder Reactions Diazadieneiron(0) complexes catalyse the Diels-Alder reaction between 1,3-dienes and disubstituted alkynes to give hexa- 1,4-dienes (46) and (47) at moderate conver- sions and high selectivities. The catalyst can be prepared in situ for example from Fe( acac),/2 diazadiene/6 EtMgBr. Diene dimerization which is the reaction product in the absence of alkynes is not observed.43 The intramolecular Diels-Alder reaction of (48) to give (49) is catalysed by the weakly Lewis-acidic complexes of MC1(q3-allyl)(CO),(MeCN) (M = Mo or W) preferably in alcoholic solvents -which stabilize the catalyst.# 42 B.T. Golding and S. Mwesigye-Kibende J. Chem. SOC.,Chem. Commun. 1983 1103. 43 H. tom Dieck and R. Diercks Angew. Chem. 1983,95 801. 44 M. S. Bailey B. J. Brisdon D. W. Brown and K. M. Stark Tetrahedron Lett. 1983 24 3037. M.Bochmann R A. Head and M.D. Johnson (48) (49) Vinyl-substituted chromium and tungsten Fischer-carbene complexes (50) react with dienes lo4 times faster than methyl acrylate the nearest analogue. The reaction is stereoselective; for example the chromium complex reacts with isoprene to give the cyclohexenes (5 1a and b) in a 92 :8 ratio. The reaction of (50)with cyclopentadiene is complete within 3 min at 25 "C and gives the endo-product in 94% selectivity.The M(CO)5fragment can be replaced by =0,H2,or =CH2 under mild condition^.^' 5 Cross-coupling Reactions The palladium or nickel-catalysed cross-coupling reactions of carbanions with aryl vinyl benzyl or ally1 halides have continued to be versatile methods for C-C bond formation and efforts have now been made to introduce building blocks carrying functional groups in this way. Enol ethers are metallated by t-butjl-lithium. Trans- metallation with ZnClz is necessary to achieve a reaction with aryl iodides and vinyl bromides and iodides in the presence of a palladium(0) catalyst and subsequent protonation converts the products into acyl compounds. Allenic ether anions react similarly; acidic work-up gives a$-unsaturated ketones in moderate to good yield (Scheme 6).46 OEt Reagents i Bu'Li; ii ZnCI,; iii RI-Pd; iv H+ Scheme 6 Alkenylmetal complexes containing a-alkylthio or a-trialkylsilyl substituents react with vinylic iodides to give hetero-substituted dienes (52) in good yield.Zinc is again preferred as electropositive metal though vinyldialkylaluminium compounds 45 W. D. Wulff and D. C. Young J. Am. Chem. Soc. 1983 105 6726. 46 C. E. Russel and L. S. Hegedus J. Am. Chem. Soc. 1983 105,943. Organometallic Chemistry -Part (i) The Transition Elements and trialkylborates are equally useful. However organometallics derived from Me,S Me,SO MeN02 and others do not react. The exact nature of the palladium(0) catalyst does not appear to be critical in these reactions.47 Z = OEt SEt or SiMe,; (52) M = ZnC1 AIB& or BR;Li+ High optical yields have been obtained in cross-coupling reactions of a11y1 phenyl ethers with Grignard reagents catalysed by nickel complexes with (-)-( S,S)-2,3 -bis(dipheny1phosphino)butane as the asymmetric chelating phosphine ligand.Com- plexes of structure (53) are postulated as intermediates. Reaction of (54) with EtMgBr gave (55) in 85% yield and 98% optical yield.48 Attempts have been made systematically to determine those reaction parameters responsible for chemical and optical yield in nickel-catalysed cross-coupling reac- tions. The coupling of aryl halides with s-butylmagnesium halides was used as a model reaction with NiC12L [L = asymmetric I ,2-bis(diphenylphosphino)ethane derivative].Solvent concentration relative reactant ratios and most important the nature of the halide in the Grignard reagent influence the optical yield. The best results were obtained with aryl and magnesium bromide (up to 50.7 e.e.).49 6 Titanium Alkylations with organotitanium reagents have attracted much interest recently," and have now been applied to the synthesis of (57) in a one-pot reaction from the ketone (56) using a 1 :1 mixture of MeTiC1 and Me,TiC12. Compound (57) is a precursor to the tetrahydrocannabinoid (58)? 47 E. Negishi and F. T. Luo J. Org. Chem. 1983 48 1560. 48 G. Consiglio F. Morandini and 0.piccolo J. Chem. SOC.,Chem. Commun. 1983 112. 49 G. Consiglio F. Morandini and 0. Piccolo Tetrahedron 1983 39 2699.50 For reviews see M. T. Reetz Top. Curr. Chern. 1982 106 1; and ref. 13. M. T. Reetz and J. Westerrnann J. Org. Chern. 1983. 48 254. M. Bochmann R. A. Head and M. D. Johnson (58) Titanium compounds react very much faster with aldehydes than with ketones.I3 The selective alkylation of keto-groups with lithium reagents in the presence of aldehydes can be achieved if the latter are protected by reaction with Ti(NEt,) at low temperatures (Scheme 7). For differentiation between ketones the more reactive Ti(NMe2) is more suitable ; treatment of cyclohexanone and heptan-4-one mixtures with the titanium compound followed by lithium or Grignard reagents gives (59) in 99% selectivity (Scheme 7). The compound Mn(NEt,) is also a very mild protecting agent.52 0 OTi(NR,) ~ ,k + Ti(NR2) R,"R RR R HO + PrJ,Pr 8 -ii iii 6+ Pr.TPr R (59) Reagents i -78 "C; ii Ti(NR2)4; iii LiR Scheme 7 The cyclic titanium alkyl complex (60) is known to cleave isobutene to give the unstable methylidene complex (61) which can be thought of as an analogue of a Wittig reagent.With acid chlorides however the enolate (62) a non-Wittig product is formed. There is no isomerization of the double bond. Protonation gives ketones in near-quantitative yields even with sterically hindered acid ~hlorides.~~ Cp,Ti 3< -Cp,Ti=CH + A 7 Miscellaneous An improved method for the synthesis of unsymmetrically substituted dibenzofurans (64) involves treatment of o-bromophenyl-phenyl ethers (63) (from substituted fluorobenzene and sodium o-bromophenolate) in N,N-dimethylacetamide with base in the presence of 0.1 equivalent of palladium a~etate.'~ 52 M.T. Reetz B. Wendworth and R. Peter J. Chem. SOC.,Chem. Commun. 1983 406. 53 J. R. Stille and R. H. Grubbs J. Am. Chem. SOC. 1983 105 1664. 54 D. E. Ames and A. Opalko Synthesis 1983 234. Organometallic Chemistry -Part (i) The Transition Elements 285 0 OTiCICp, 'dC1 '& + Cp,Ti=CH2-(63) (64) R = NO, CN H CH20H Me or C02H The activities and selectivities of rhodium acetate palladium acetate and copper trifluoromethanesulphonate as catalysts in the cyclopropanation of large numbers of dienes and trienes with diazoacetic ester were subject to a systematic Rhodium acetate gives the highest yields and works especially well with electron-rich double bonds for example in alkyl-disubstituted 2-olefins.Palladium acetate is less active and cyclopropanates preferentially terminal double bonds where steric hindrance is minimized. Copper is a better catalyst than palladium. The diqerent behaviour patterns are taken as an indication that a carbenoid mechanism operates for rhodium with no co-ordination of the olefin to the metal whereas olefin co- ordination is important with palladium. Rhodium is the best catalyst for the cyclo- propanation of 1,1-dichlorodienes e.g. (65). cl\ c1>-?=("' + Me (65) The transfer of co-ordinated nitrene to an olefin to give aziridines has been achieved with manganese c~mplexes.~~ Photolysis of (5,10,15,20-tetramesitylpor-phyrinato)manganese(rIr) azide gives the very stable Mn" nitride complex (66).Reaction with trifluoroacetic anhydride generates the intermediate (67); the now labilized nitrene is transferred to cyclo-octene in a stoicheiometric reaction to give (68) in near-quantitative yield. Treatment with base or extraction with dilute hydro- chloric acid converts (68) into the parent compound. Tetrahydrofurans react with HSiR and CO in the presence of CO~(CO)~ and under drastic conditions (140 "C/50 atm) to give ring-opened products such as R3SiO(CH2)4CH0 and R3SiO(CH2)4C(OSiR3)=CHOSiR3 depending on the 55 A. J. Anciaux A. Demonceau A. F. Noels R. Warin A. J. Hubert and P. Teyssie Tetrahedron 1983 39 2 169. 56 J. T. Groves and T.Takahashi J. Am. Chem. Soc. 1983 105 2073. M. Bochmann R. A. Head and M. D. Johnson ,COCF THF:HSiR ratio. It has now been found that a similar reductive ring-opening proceeds at room temperature under 1 atm CO to give (69). A variety of substituted tetrahydrofurans react similarly. It has been suggested that R,S~CO(CO)~ and R3SiO(CH2)4Co(C0)4 are intermediates.” HSiMe,Et (3 equiv.) R,SiO CO (1 atm) Co,(CO) OSiR (69) 8 Phase-transfer Catalysis Phase-transfer catalysis is that which is typically effected in an aqueous/organic two-phase system with an anion transfer agent such as a crown ether or a quaternary ammonium salt. The benefits of such reactions include both mild conditions and ease of product isolation.Free radicals have been proposed as intermediates in several transition-metal- catalysed phase-transfer reactions but now their formation is confirmed in the conversion of a-phenylethyl bromide exclusively into 2,3-diphenylbutane (70) under an atmosphere of C0.58 In CH,Cl as solvent both CO,(CO)~ and Pd(dba) (dba = dibenzylideneacetone) afford meso and racemic forms of the product in equal proportions which is satisfactorily explained only by the intermediary of a planar a-phenylethyl radical. CO-Pd(dba),-[PhCH,N(C,H,),]CI PhCH(Me)CPhH(Me) 2PhCH(Me)Br CHZCl2-SN-NaOH,20 h 25 “C ’ (70) A striking example of how a change in organic solvent can alter the course of a reaction is provided when the cobalt-catalysed carbonylation of a-phenylethyl chloride and bromide as described above in CH2Clz solution is carried out in highly polar solvents such as alcohols or ethers.59 Hydratropic acid (71) is isolated in over 90% yield after acidification of the aqueous phase and since it has the opposite absolute configuration to the starting benzyl halide it appears that the reaction proceeds by an SN2mechanism rather than a free-radical pathway.Double carbonylation is unexpectedly achieved using a two-phase system comprising t-amyl 57 T. Murai Y. Hatayama S. Murai and N. Sonoda Organometallics 1983 2 1883. V. Galamb and H. Alper J. Chem. SOC.,Chem. Commun. 1983 88. 59 F. Francalanci A. Gardano L. Abis T. Fiorani and M. Foa J. Organomeial. Chem. 1983. 243 87. Organometallic Chemistry-Part ( i) The Transition Elements Ph Ph Ph Me +02H Me 0 (72) alcohol and 20% aqueous NaOH where >80% a-keto-P-butyric acid (72) is recovered from the aqueous phase via the sodium salt.Carbonylation reactions involving aryl halides are generally considered difficult to perform with metals other than palladium but full details of the use of cobalt catalysts under phase-transfer conditions have now been published.60 In a mixture of benzene and 5M aqueous NaOH with tetrabutylammonium bromide as transfer agent various aryl chlorides and bromides were converted into their corresponding carboxylic acids (73) in high yield under very mild conditions (65 "C 1 atm CO). Interestingly the carbonylation only proceeds when the reaction is irradiated with visible light typically from a commercial 125 W sunlamp.CO (I atm)-Co,(CO),~Bu,N]CI ArBr # ArC02Na C6H,-5N-NaOH 14.5 h 65 "C hv ArBr = PhBr 2-or 4-BrC6H4Me 2-or 4-BrC6H40Me 4-BrC6H,COMe 4-BrC6H4No2 4-BrC&&I or 1-or 2-bromonaphthalene Benzolactams and lactones e.g. (74) are conveniently prepared from aryl halides bearing amino- or hydroxy-functionalized groups on a side chain a-to the halogen. While some details of the mechanism are unclear evidence suggests a SRN1 condensa-tion of [Co(CO),]- with the aryl halide to form ArCo(CO), from which the product is formed by CO insertion followed by nucleophilic attack of hydroxide ion on the aryl carbonyl carbon atom. &m +co+ Qo d (74) (92%) Bromostyrenes are smoothly carbonylated to acids (75) in good yields using mild conditions (50°C 1 atm CO) with either Pd(Ph3P) or Pd(dppe)2 as catalyst.The reactions exhibit high retention of stereochemistry ; thus E-bromostyrene affords only E-cinnamic acid in 9 1 YO yield.6' H CO-W(PPh,),-[PhCH,NEt,]Cl ArM ArHH b C,H,-SN-NaOH 17.5 h 50°C then H,O+ H Br H CO,H (El Ar = Ph p-ClC6H4 3,4-(MeO)2C,H J. J. Brunet C. Sidot and P. Caubere J. Org. Chem. 1983 48 1166. 6' V. Galamb and H. Alper Transition Met. Chem. 1983 8 271. 288 M. Bochmann R. A. Head and M. D. Johnson Vinylic dibromides readily prepared from aromatic aldehydes react under car- bonylation conditions with Pd(d~pe)~ as catalyst to give either substituted buta- 1,3- diynes or carboxylic acids depending upon the organic solvent used (Scheme 8).62 When benzene is used as organic phase and benzyltriethylammonium chloride as transfer agent reasonable isolated yields of the diyne (76) are obtained.However under the same conditions aliphatic vinylic dibromides are converted into their corresponding mono- and di-carboxylic dcids. By replacing benzene as solvent by t-amyl alcohol benzalmalonic acids (77) are obtained in very good yield (87-93'/0). ArCH=C(CO,H) &!-ArCH=CBr + CO -ArCrC-CECAr (77) (87-93%) (76) (2O-68%) Ar = Ph p-MeC,H, or p-MeOC,H Reagents i Pd(dppe)2-[PhCH2NEt,]cl-c6H6-5N-NaoH, 50-70 "C; ii Pd(dppe),-[PhCH2NEt3]CI-t-amyl alcohol-5N-NaOH 50-70 "C Scheme 8 Palladium-catalysed conjugate addition of 0-hydroxyarylmercury(r1) compounds to a,p-enones gives convenient starting materials from which to prepare 2-chromanols and 2-chr0menes.~~ The acid conditions employed for the addition have precluded the use of amino-functionalized arylmercurials but it has now been found that by using suitable protecting groups a wide range of 4-phenylbutan-2-ones (78) can be prepared under phase-transfer conditions (Scheme 9).64The 4-phenylbutan-2- ones (78) themselves are valuable synthetic intermediates from which to prepare dihydroquinolinium salts (79) quinolines (80) or 1,2,3,4-tetrahydroquinolines(8 1).Highly desirable reactions of C-H bonds in unactivated alkanes are now available using the very simple two-phase system comprising an organic solvent such as CH2C12 containing alkane and Mn(TPP)X as both catalyst and transfer agent together with a saturated aqueous solution of NaX (X = NO2 N, C1 Br or I; Scheme In the presence of an oxidizing agent such as iodosylbenzene only one of the alkane hydrogen atoms is replaced by X in what appears to be a free-radical process.Hydrocarbons shown to undergo the reaction include cyclohexane isobutane 2,3-dimethylbutane and t-butylbenzene where in all cases iodosylben- zene is the preferred oxidant. Although there are very few known homogeneous catalysts for the hydrogenation of arenes it has now been found that the simple ion-pair [(C,H,,),NMe]+ [RhC14]- is exceptionally efficient under very mild phase-transfer conditions (Scheme 1 1).66 Deuterium labelling experiments indicate that the water hydrogen atoms are not present in the saturated product.However the presence of water is essential as the catalyst is totally inactive in dry CH2C12. Partial hydrogenation also takes place with arenes and acetylenes ; for instance naphthalene affords tetralin (99'/0) and diphenylacetylene gives only cis-and trans-stilbene (ratio 78 :22). 62 V. Galamb M. Gopal and H. Alper Organometallics 1983 2 801. 63 S. Cacchi D. Misiti and G. Palmieri J. Org. Chern. 1982 47 2995. 64 S. Cacchi and G. Palmieri. Tetrahedron 1983 39 3373. 65 C. L. Hill J. A. Smegal and T. J. Henly J. Org. Chern. 1983 48 3277. 66 J. Blum I. Amer A. Zoran and Y. Sasson Tetrahedron Lett. 1983 24 4139. Organometallic Chemistry -Part (i) The Transition Elements HgCl li eR2 NHZ (78) (8693%) (79) (80) (81) For R' = H R2 = Me; Z = CO,CH,Ph; X = Me C1 HgCI or MeCO R' = H R2 = Et; Z = CO,CH,Ph;X = Me R' = Ph R2 = Me; Z = CO,CH,Ph;X = C1 I = C0,Et; X = Me or CI Z = COCF,;X = C1 R' = R2 = Ph; Z = CO2CH,Ph;X = Me Reagents i PdCI2-[Bu4N]CI-CH2C1,-3N-.HC1 25 "C 5-9 h; ii 37% HBr-AcOH or 1N-NaOH-EtOH then HBr(aq); iii HBr-MeNO, 40°C; iv Zn-37% HBr-AcOH 25 "C Scheme 9 55% 21 '/o (X = N3) Reagent i Mn(TPP)X-PhIO-CH,C12-sat.NaX(aq) 25 "C 12 h Scheme 10 X X 27-1 00% X = H Me Et F OH NMe, COMe or C02Me Reagent i RhCl3.3H,O-[(C,H ,,),NMe]CI-CH2C12-H20-H2 (I atrn) 30 "C 5 h Scheme 11 290 M. Bochmann R. A. Head and M. D. Johnson 9 Heterocyclic Chemistry Cyclic nitrones have proved to be valuable intermediates in the synthesis of many biologically active nitrogen heterocycles although they are invariably prepared by stoicheiometric reactions.The catalytic oxidation of N N-disubstituted hydroxyl- amines has been achieved using either palladium black or IUICI(PP~~)~ where the nitrone (82) is isolated in very high yield.67 Pd-H,O 80°C <'> <:> +H2 I I OH 0-(82) (57-80%) R = (CH2)2-,(CH,), or o-C,H,CH2 When the reaction is carried out in the presence of alkenes a 1,3-dipolar addition takes place isoxazoles (83) being obtained in excellent yield. The reaction proceeds with high regioselectivity ; thus with ethyl crotonate and N-hydroxypiperidine 2-methyl-3-ethoxycarbonylhexahydropyridinoisoxazole (83) ; R' = CO,Et R2 = Me) is isolated in 85% yield in entirely the trans,trans-stereochemistry (established by n.m.r.).The nature of the substituent on the alkene determines its ultimate position in the isoxazole. Electron-withdrawing groups give 3-substitution whereas electron- donating groups are found to give 2-substituted products. RZ (83) R' = C02Et R2 = H or Me R' = H R2 = Ph or OBu" Imidazoles substituted in 2,5-positions (84) are prepared under mild conditions from a-halogeno-oximes and amidines using Fe3(CO) as deoxygenating agent.68 Several iron catalysts were examined and the trinuclear cluster was found con- sistently to give good yields of imidazoles which appear to be formed by deoxygena- tion of intermediate oxadiazines (85). NH II R'-C-CH,X + R~-c-N-11 I NOH Me R' = Ph or Me X = C1; R2 = Ph R' = Ph p-MeC,H, p-BrC,H, or EtOCO; X = Br; R2 = Ph R' = Ph; X = Br; R2 = rn-MeC,H 67 S.Murahashi H. Mitsui T. Watanabe and S. Zenki Tetrahedron Lerr. 1983 24 1049. 6U S. Nakarishi. i. Nantaku and Y. Otsuji Chem. Lett.. 1983 341. Organometallic Chemistry -Part (i) The Transition Elements 29 1 Oxidation of butan- 1,4-diols with a combination of molecular bromine and nickel(I1) alkanoate affords the corresponding 8-butyrolactone (86) with a high degree of regio~electivity.~~ The solvent employed for the reaction has a remarkable influence on oxidation selectivity. Using trimethylacetonitrile or CH2C12 a ratio (86a):(86b) of 2 1 is observed but with acetonitrile-CH2C1 (20/80) of DMF the selectivity increases to 4 1 (R'= R2= Me).R' R' M. P. Doyle R.L.Dow,V. Bagheri and W. P. Patrie J. Org. Chern. 1983 48 476.

ISSN:0069-3030    

DOI:10.1039/OC9838000273

出版商:RSC    

年代:1983

数据来源: RSC

摘要:

12 Organometallic Chemistry Part (ii) Main-Group Elements By John D. KENNEDY Department of Inorganic and Structural Chemistry University of Leeds Leeds LS2 9JT 1 Introduction The two journals specializing in organometallic chemistry continue to thrive. Organornetallics is now well established and in this the Editor’s book reviews are recommended reading. Journal of Organornetallic Chemistry has reached its 250th volume and its 20th year and its Editor has been pleased to note an increase in the number of papers from groups in continental Europe. In both journals about 20% of the papers continue to be concerned principally with main-group chemistry. This is reasonable in terms of quantity but in general 1983 seems not to have been the greatest year in terms of the overall quality of organometallic main-group chemistry.Although there is fortunately lively activity in a variety of areas much of the other work this year has left this reporter with a feeling of dkjh uu. Too much of the chemistry seems very routine and in an increasing proportion of the genuinely innovative work the directing interest derives not from the organometallic chemistry itself but for example from the establishment of synthetic routes for organic chemists or from the chemistry of transition-metal centres which have main-group organometallic moieties as ligands. It is not clear whether this is a symptom or a cause of what appears to be a malaise in main-group chemistry in general. It is clear that main-group chemists in the U.S.A.feel that there are problems in maintaining the identity of and the momentum of work in the sub-discipline,’ and in the U.K. there has been dismay among main-group chemists at what they regard as disproportionately massive support for transition-metal chemistry. A large component of the solution to this problem either real or imaginary must rely on the continuous generation of innovative chemistry by the practising main-group chemists. Fortunately strong pockets of creativity are still present and as mentioned in last year’s report,2 a variety of areas ripe for expansion and/or exploitation can be readily identified. 2 Group I Covalent organometallic chemistry of the alkali metals other than lithium remains largely ill-defined and is generally limited to the observation of ‘short’ metal-to- carbon distances in compounds in which the metal is associated mainly with a more ’ A.H. Cowley Chem. Br. 1983 19 480.. ’J. D. Kennedy ARR.Rep. Prog. Chem. Secr. B 1982 79 257. 293 J. D. Kennedy electronegative element. In this context the short Na-C distance of 265.6 (1) pm has been reported this occurs in the trimeric species [(Me3SiNNa)2(SiMe2)]3 in which it is comparable with the longest Na-N bond of 260.1 (3) pm. Progress in organolithium chemistry has remained steady. The influence of ethereal solvents and also of lithium halides on organolithium reactivity is well recognized. Two pieces of work are of significance in this The structure of [(PhLiOEt2),LiBr] is based on a cubic-type framework as in structure (l) in which the atoms C are the ips0 carbons of the phenyl group^.^ The lithium atom opposite to the bromine is the one not co-ordinated to Et20.The distances to carbon from the ether-free lithium at 215 pm are some 13 pm shorter than from ether-bound lithium which may be related to the reactivity. Aryl-lithiums are generally held to be dimeric in solution. This work now suggests that tetrameric units may also be quite stable (unless particularly strong multidentate donors such as TMEDA are present) and indicates that further work on the solution structure of aryl-lithiums is warranted .4 The structure of the intramolecularly etherated tetrameric 3-lithio- 1 -methoxybutine (2; only one organyl group represented) is useful in view of the failure so far to obtain crystalline samples of straightforward alkyl-lithium-ether ad duct^.^ The dimensions are taken to suggest that bond lengths of tetrahedral organolithium clusters are not significantly affected by co-ordination of Lewis bases and that accelerations of reactions may therefore derive rather from strong effects on transition states by the ether additives.’ The compound [LiC(SiMe3)3(THF)2] a substance commonly used to attach the very bulky {C(SiMe,),} group has been shown to be [Li(THF)4][Li{C(SiMe3)3}2] the anionic lithiate unit having a linear C-Li-C system with Li-C (mean) 218 and Si-C (mean) 182 pm; it is the first lithiate species to be structurally character- ized.6 The bulky species [LiC(SiMe,Ph),(THF)] is uniquely monomeric (3).7 The metal atom is covalently bound to the THF oxygen and to the central carbon atom [212 (2) pm] of the {CSi,} unit and interacts strongly with the ips0 carbon atom of one of the phenyl groups [240 (2) pm].The aromatic hybridization at the ips0 carbon appears not to be significantly distorted (compare the aluminium species reported last year2). D. J. Brauer H. Burger W. Geschwandtner G. R. Liewald and C. Kriiger J. Organomet. Chem. 1983 2441. H. Hope and P. P. Power J. Am. Chem. SOC.,1983 105 5320. G. W. Klumpp P. J. A. Geurink A. L. Spek and A. J. M. Duisenberg 1.Chem. SOC.,Chem. Commun. 1983 814. C. Eaborn P. B. Hitchcock J. D. Smith and A. C. Sullivan J. Chem. SOC.Chem. Commun. 1983 827. ’ C. Eaborn P. B. Hitchcock J. D. Smith and A.C. Sullivan J. Chem. SOC.,Chem. Commun.. 1983 1390. Organometallic Chemistry -Part (ii) Main-Group Elements A series of metallocenes [(ba~e)LiC~H~(SiMe~)~] [e.g. (4)] has been characterized (base = quinuclidene TMEDA etc.).8These are air-sensitive crystalline solids and constitute the nearest approach yet to the simplest possible metallocene [Li(C,H,)]. The silylated lithiocenes have been used to prepare yellow crystalline polysilylated plumbocenes from PbC12.9 Other interesting organolithium work reported in 1983 includes the synthesis of optically active 2,2'-dilithio-6,6'-dimethylbiphenyl(5) prepared from the optically pure di-iodo-species and BuLi in Et20 solution." It is stable towards racemization at -10"C and has potential for the synthesis of optically active biphenyl series.Me Me \ 3 Group I1 Although organomagnesium compounds as Grignard reagents pervade the whole of chemistry the organic chemistry of the alkaline earths and of beryllium is not well represented. 1983 has been disappointing for organoberyllium chemistry but it has been interesting to see a report on the preparation and reactions of the solvent-free arylcalcium halides ArCaX." These are made by the reaction between ArX and calcium in the vapour phase and their reactions have been assessed under a variety of conditions that have been found useful for Grignard and organolithium reagents. In general however yields are lower than for these last two better- established reagent types. The organobarium compound [Ba(CMe2Ph)2] has also been reported,12 together with its use as a novel initiator in anionic polymerization.Over the past few years there has been an increasing incidence of the use of lithium organocuprates in organic synthesis and they are now reasonably well recognized as useful reagents. More recently the corresponding organomagnesium cuprates (Normant reagents) derived from the interaction of Grignard reagents with cuprous halides have attracted interest and have been used imaginatively in P. Jutzi E. Schluter C. Kriiger and S. Pohl Angew. Chem. Znt. Ed. Engl. 1983 22 994. P. Jutzi and E. Schluter J. Organomer. Chem. 1983 253 313. lo T. Frejd and T. Klingstedt J. Chem. Soc. Chem. Commun. 1983 1021. 'I K. Mochida and H. Ogawa J. Organomet. Chem. 1983 243 131.'' L.-C. Tang C. Mathis and B. Francois J. Organomet. Chem. 1983 243 359. J. D. Kennedy synthetic work (see other references cited in reference 13). Structurally these reagents have been generally represented as [RCuMgX,] [R2CuMgX] etc. but now solutions in THF have been found to contain species [CU~M~~M~,~+~] 1, where rn = n = 1-4 and 6 and where rn = 2 n = 3.13 Of these [CuMgMe,] is monomeric and [Cu2MgMe4] dimeric. The others are too unstable to be investigated but where n is large it is thought that the compounds are probably based on copper clusters. Another area more familiar in Group I chemistry is that of aromatic radical anions Ar’- and related benzenoid dianions A?-. This now has been more thoroughly examined for magnesium in THF solution and the deep blue anthracene radical anion and its yellow dianion have been characterized with {MgBr}+ co~nterions.’~ There seems to be the germ of a renaissance in organozinc chemistry although much of this is associated with the generation of transition-metal complexes.For example the mixed organozinc-tantalum species (6) is obtained by the use of [Zn(CH2CMe3)2] as a hydrogen-abstracting agent on [TaC13(CHCMe3) (MeOCH,CH20Me)].’S There may be a small but increasing underswell of the use of organozincs in synthesi~,’~”’ for example in P-unsaturated a-amino-ester forma- tion.” In organomercury chemistry steady work continues in the area of polymer- curiomethanes and related compounds u.v. i.r. and Raman spectra together with some preparative work have been reported for the mercuriomethanes them-selves.18-20 An interesting result is the crystal structure of the trimercurated acetal- dehyde species [(OHg,CCHO)( N0,)(H20)].2’ This compound is the product of the mercuration of acetaldehyde by aqueous mercury oxyacid salts and is also obtained from acetylene under similar conditions.The {Hg3CH=O} units are interconnected by oxonium oxygen atoms to form a polymeric columnar [OHg3CCH=O]:+ cation. The {Hg,O} oxonium pyramid is quite flat with the angles HgOHg averaging at 1 16°.21 4 Group I11 There have been few innovative developments in the organic chemistry of the Group I11 metals in 1983. The reaction in benzene solution between A1Me3 and sodium cacodylate Na[AsMe202] yields [A~Me,l~[Me~A10AlMe~]~.~~ This is of interest because firstly it demonstrates the complete methylation of the cacodylate anion l3 E.C. Ashby and A. B. Goel J. Org. Chem. 1983 48 2125 and references cited therein. 14 P. K. Freeman and L. L. Hutchinson J. Org. Chem. 1983 48 879. l5 A. W. Gal and H. van der Heijden J. Chem. SOC.,Chem. Commun. 1983 420. l6 G. A. Molander J. Org. Chem. 1983 48 5409 and references cited therein. 37 M. Bourhis J.-J. Bosc and R. Golse J. Organomet Chem. 1983 256 193. D. K. Breitinger and W. Kress J. Organornet. Chem. 1983 256 217. Iy D. K. Breitinger W. Kress R. Sendelbeck and K. Ishiwada J. Organomet. Chem. 1983 243 245. 20 J. Mink Z. MeiC M. Gil and B. Korpar-eolig J. Organornet. Chem. 1983 256 203. 21 D. Grdenit M. Sikirica D.Matovic&logoviE and A. Nagl J. Organornet. Chem. 1983 253 283. 22 J. L. Atwood and M. J. Zaworotko J. Chem. SOC.,Chem. Commun.. 1983 302. Organometallic Chemistry -Part (ii) Main-Group Elements 297 (one of the first organometallic species known) to the [AsMe4]+ cation and secondly there is the novel anion (7) to fit into the wide range of known aluminoxide structures. Another newly established organoaluminoxide anion is [A1706Me16]- which is encountered on the decomposition pathways of high-oxygen-content organoaluminium compounds such as K[A12Me602].23 Its structure is an open {A1606} cage capped by the seventh aluminium atom (8); each aluminium atom has two methyl groups bound to it and each oxygen one. Me o/A’,oP‘, A1 /\ A] ,A’rA ‘ /A Me,Al-0 ,0-AIMe 88 Al II Me* Al ,Al 0 (7) (8) A novel benzene sandwich complex of gallium [((C6H6)2Ga.GaC14}2( C6H6)3] may be crystallized from a solution of Ga,C14 in benzene under carefully controlled condition^.^^ It contains a quasi-tetrahedral gallium centre in a bent sandwich structure (9) the distances from the metal atom to the carbon plane averaging at ca.284 pm. Other new organogallium species include gallium(Ir1) porphyrins of general structure (10) ;these species are prepared by the reactions of LiR or RMgX on the appropriate chlorogallium( 111) p~rphyrin.~~ Gas-\? 5 Group IV As in last year’s report Group IV chemistry constitutes the bulk of 1983 published material in main-group organometallic chemistry and within this area organosilicon chemistry is predominant.There is a continuing general interest in the use of Group IV species as effective ligands in transition-metal chemistry and in processes such as the transition-metal catalysed reactions of silanes but the predominant interest in these fields is in directions other than the study of the Group IV organometallic chemistry itself. This also applies to the use of Group IV species as reagents for organic syntheses which is also a major field of research. The book ‘Silicon Reagents for Organic Synthesis’ was published in 1983. This seems to deal comprehensively 23 J. L. Atwood D. C. Hmcir R. D. Priester and R. D. Rogers Organornetallics 1983 2 985. ” H. Schmidbaur U. Thewalt and T. Zafiropoulos OrganornetaNics 1983 2 1550.25 A. Coutsolelos and R. Cuilard J. Organornet. Chern. 1983 253 273. 298 J. D. Kennedy with most aspects of the field implied by its title except for the silylation of OH SH and NH (which is reasonable) and it should be a useful information resource for the synthetic organic chemist.26 There are also more specific reviews on methods of preparaing siloxycyclopropanes and their use in organic ~ynthesis,,~ and on rhodium catalysts for enantiomeric hydrosilylation.28 Polymeric species other than silicones have attracted some attention. Alkylsilanes bound to silica gel are of interest because of the potential usefulness of their surface properties. Of this work to cite one example solid-state CP/MAS n.m.r. spectros- copy has been carried out on the product of the silylation of silica gel using dimethyloctadecylchlorosilane(DMODCS) in order to examine the surface struc- tural en~ironment.,~ Another polymeric species poly-( 1-trimethylsilyl)prop-1-yne prepared from the monomer using niobium and tantalum halide catalysts is of interest because of its exceptionally high permeability to 0 gas -an order of magnitude greater than that for [( Me,SiO),] for example.30 Disilene chemistry is now well established and 1983 has seen some consolidatory work in this area.New disilenes reported include tetra-ne~pentyl~' and tetra-t- b~tyl,~, and the structural type has now been characterized by a single-crystal X-ray diffraction analysis on the original tetramesityl deri~ative.~~ The Si=Si distance is 216.0 pm some 18-20 pm shorter than typical Si-Si single bonds the difference (in pm) being greater than that between C=C and C-C.In percentage terms the contraction is some 8-9% for disilicon and ca. 12% for dicarbon. By contrast ditin species such as [Sn,(N(SiMe,),},] exhibit intertin distances no shorter than those typical of intertin single bonds which is taken to indicate a significant T-bonding component for the intersilicon bond. There is however some pyramidaliz- ation at silicon with an angle of 162" rather than the planar 180°.33The 29Si nuclear shielding anisotropy in tetramesityldisilene [Mes2Si=SiMes2] is similar to that of 13C in ethylene whereas that in [Mes2HSi-SiHMes2] is similar to that of 13C in ethane also consistent with the conclusion that the electronic structures of the Si=Si and C=C double bonds are closely similar.34 Associated with this type of work some additional cyclotrisilanes [(SiR2)3] have been made.3',35*36 A tin analogue of these the cyclotristannane [(SnAr2)3] where Ar is {2,6-Et2C6H3} has also now been ~haracterized.~~ It is an orange crystalline compound m.p.(dec.) 175 "C obtained from the reaction between [Ar2SnC1,] and lithium naphthalene. The intertin distances average at ca. 286 pm and aromatic group rotation is slow on the n.m.r. time-scale. All that is now needed to complete the Group IV set is a cyclotriplumbane. 26 'Silicon Reagents for Organic Synthesis' W. P. Weber Springer Verlag 1983. 27 S. Murai I. Ryu and N.Sonoda J. Organornet. Cbem. 1983 250 121. 28 H. Briinner Angew. Chem. Int. Ed. Engl. 1983 22 897. 29 D. W. Sindorf and G. E. Maciel J. Am. Chem. SOC.,1983 105 1848. 30 T. Masuda E. Isobe T. Higashimura and K. Takada J. Am. Chem. Soc. 1983 105 7473. 3' H. Watanabe T. Okawa M. Kato and Y. Nagai J. Chem. Soc. Cbem. Commun. 1983 781. 32 S. Masamune S. Murakami and H. Tobita Organomeiallics 1982 2 1464. 33 M. J. Fink M. J. Michalczyk K. J. Haller R. West and J. Michl 1.Chern. SOC.,Cbem. Commun. 1983 1010. 34 K. W. Zilm D. M. Grant J. Michl M. J. Fink and R. West Organomeiallics 1983 2 193. 35 S. Masamune H. Tobita and S. Murakami J. Am. Chem. SOC.,1983 105 6524. 36 S. Masamune S. Murakami H. Tobita and D. J. Williams J. Am. Cbem. SOC.,1983 105 7776.37 S. Masamune L. R. Sita and D. J. Williams J. Am. Chem. SOC.,1983 105 630. Organometallic Chemistry -Part (ii) Main-Group Elements Other new silicon multiple-bond chemistry is the isolation of the second example of a stable silaethene [Me2Si=C(SiMe3)(SiMeBut2)] (1l) prepared by the 'thermal salt elimination' reaction of equation ( 1).38 It is a crystalline compound which decays within a few days at room temperature and probably lies at the limit of isolatability for these types of compound under normal conditions. Me SiMeBu' Me II /SiMeBu'2 Me-Si-C-SiMe d'Si=C (1) -LiF II F Li Me' 'SiMe (1 1) There is a certain fascination about trying to generate other stable multiply bonded silicon species. The true silicones {R,Si=O} are often postulated by inference trapping experiments et~.~~ but have not yet been detected directly.Corresponding species [Me,Ge=S] and [Me2Si=S] however formed in the thermolysis of [(Me2GeS)J and [(Me,SiS),] respectively have been detected by photoelectron spectroscopy.a Attempts to prepare silicenium ylides such as [R2Si= NBu'] have so far been unsuccessful although the work has generated some other interesting species such as [But&( NBu')C1AlCl2] (12).4' This however has a straightforward a-bonded framework. Ph\ SiMe An elegant piece of work has been the planned synthesis and characterization of the ethenyldisilacyclopropane species ( 13) an air-stable yellow crystalline com- pound m.p. 203°C.42 It was previously thought to be a disilacyclobutane.It is formed in 14% yield from the cophotolysis of [PhC=CSiMes,SiMeJ with [Me3SiSiMes2SiMe3]. Since photolysis of the first of these starting materials is presumed to yield Ph(Me3Si)C=C=SiMes2 and the second Mes,Si it was reasoned that their cophotolysis would yield the adduct of these two products as indeed it does. Much of this novel multiply bonded and smaller polysilane work utilizes bulky stabilizing groups on silicon. The use of such bulky groups on silicon or organosilicon moieties themselves as bulky groups forms the continuing basis of a lot of interesting chemistry in other areas but space considerations preclude the detailing of these this year. A review 'Steric Effects in Organosilicon Chemistry' may however be noted in this c0ntext.4~ N.Wiberg and G. Wagner Angew. Chem Znt. Ed. EngL 1983,22 1005. 39 G. Hussmann W.D. Wulff and T.J.Barton. J. Am. Chem Soc. 1983 105 1263. 40 C. Guimon G. Pfister-Guillouzo H. Lavayssiere. G. Dousse. J. Barrau qnd J. Satge J. Organomet. Chem 1983,249 C17. 41 W. Clegg U. Klingebiel J. Neernann and G. M. Sheldrick J. Organomer. Chem 1983,249,47. 42 M. Ishikawa H. Sugisawa M. Kumada T. Higuchi K. Matsui K. Hirotsu and J. Iyoda Organometallics 1983 2 174. 43 M. Weidenbruch and A. Schafer Rev. Silicon Germanium Tin Lead Comps. 1983 7 127. 300 J. D. Kennedy In larger polysilane chemistry a new class of polyfunctional silanes obtained from Bu,PCl-catalysed Si-Si/Si-Cl bond redistribution in methylchlorodisilanes has been reported.44 Products have polycyclic structures with about seven rings per molecule e.g.[( Me,Si),(MeSi) 17C15] ( 14) and alkylation arylation amination reduction and alcoholysis of the residual Si-Cl bonds have been examined. Other interesting classes of compounds synthesized in 1983 include a number of rotanes [(CH,),Si], such as (15p and some macrocyclic species based on combinations of polysilane units {(SiMe,),) and acetylene units {-C=C-} as ring components; of these last the species (16) is the smallest known cyclic diine.& Me Me I I \I Si Me The stability of the Si-0 bond remains the basis of a lot of chemistry much of which is routine. An interesting rearrangement is that afforded by the photolysis of trimethylsilylfuran [equation (2)] to give a formallenylsilane in high yield,"7 rather than a siloxane species which might otherwise be naively expected.The correspond- ing alkylfurans give complex mixtures of products in low yields under similar conditions. 0 I1 C H SiMe hu pentane -78 "C H/ \ c=c=c/ (2) 0 87% / \ H SiMe Readers will be excited to learn that it has been found that sila- and germa-tranones [for example as in (17)] can be readily made for example by straightforward transesterification reactions and so forth.48349 It is stated that in contrast to the widely studied metallatranes of the Group IV elements their carbonyl-containing derivatives have received only scant attention so fur (this reporter's italics). Does this presage a metallatranone mountain to rival the metallatrane one? A transesterification process has been used to synthesize the 'silacrowns' [R'R2Si( OCH,CH,),O] from polyethylene glycols and simple alkoxysilanes such as [R'R2Si(0Et),] mostly in yields of 50-80°h.50 This easy synthesis in principle enables the introduction of organic moieties that are without precedent in other crown ether systems.So far however the cation solubility enhancements found 44 R. H. Baney J. H. Gaul and T. K. Hilty Organometallics 1983. 2 859. 45 C. W. Carlson X.-H. Zhang and R. West Organometallics 1983 2 453. 46 H. Sakurai Y. Nakadaira A. Hosomi Y. Eriyama and C. Kabuto J. Am. Chem. Soc. 1983 105 3359. 47 T. J. Barton and G. Hussmann J. Am. Chem. SOC. 1983 105 6316. 48 E. KupEe E.Liepins A. Lapsina G. Zelchan and E. Lukevics J. Organomet. Chem. 1983 251 15. 49 G. I. Zelchan A. F. Lapsina and E. Lukevics Zh. Obshch. Khim. 1983 465. 50 B. Arkles K. King R. Anderson and W. Peterson Organometallics 1983 2 454. Organometallic Chemistry -Part ( ii) Main-Group Elements 301 Ph,Sn fiSnPh, I I R seem in general similar to those obtained by more conventional crown ethers. An interesting converse of the principle of Lewis-base crown ethers is afforded by the concept of Lewis-acid crown species as potential complexing agents for anions. This has led to the synthesis of the tin crown compound [Ph,Sn(CH,),] (18) via straightforward Grignard and lithium processes with the final cyclization performed under dilute condition^.^ No anion co-ordination of this twenty-membered ring species has been reported however.Electronegative substituents such as chlorine on tin would presumably enhance this type of behaviour. At the other extreme of cyclostanna-alkane chemistry is the four-membered {SnC,} ring of the first stannacyclobutane [Me2Sn(CH2)2CMe2]. This compound has been isolated in 5% yield as a colourless air-unstable liquid from the straightforward reaction between [Me,C( CH,MgBr),] and [Me2SiC12] at room temperature., A second novel four-membered ring is that in the tin( 11) species 1,3-dibutyl-2,2- dimethyl- 1,3,2,4h 2-diazasilastannetidine (19). This gives an adduct (20) with cyclo- pentadiene [equation (3)] but with cyclohexa- 1,3-diene an unexpected redox process occurs with a quantitative formation of C6H6 metallic tin and [Me,Sn( NHBu'),].~~ Other work noted in tin(I1) chemistry in 1983 is the exchange of the apical tin atom in the nido-cluster [SnC,Me,]+ as summarized in equation (4).54 Usually the apical tin in these species is attacked by nucleophiles.The process of equation (4) however is believed to occur via a more complex reaction sequence initiated by electrophilic attack on the cyclopentadienyl ring. In any event this M. Newcornb Y. Azurna and A. R. Courtney Organometallics 1983 2 175. 52 J. W. F. L. Seetz G. Schat 0.S. Akkerman and F. Bickelhaupt 1.Am Chem SOC.,1983 105 3336. 53 M. Veith and F. Tollner J. Organomet. Chem 1983 246 219. 54 F. Kohl and P. Jutzi Angew. Chem. Int. Ed. Engl, 1983 22 56.J. D. Kennedy novel type of reaction may provide a general access to a variety of other cyclopen- tadienyl element compounds with the nido-cluster structure.54 As usual there has been in 1983 a variety of synthetic and structural work in permutational chalcogenide chemistry of the Group IV elements. Much of this is now routine. In stannoxane chemistry two more [(R,SnO)3] ring systems have been reported in which the tin atoms are four-co-~rdinate.~~*~~ This low co-ordination number arises because the groups R are bulky [{2,6-EtzC6H3} and {(Me,Si),C}]. In related organogermanium chemistry hydrolysis of [Bu'GeCl,] yields [But2Ge( OH),] which is of straightforward four-co-ordinate tetrahedral geometry with inter- molecular H-bonding. Dehydration gives [(Bu',GeO),] which has a planar rather than a puckered {Ge303} ring.56 Hydrolysis of [Bu'GeC13] gives [(BUf2Ge)609] 'the first Group IV sesquichalcogenide [(RM),,Y,,] with n = 3'.This has two cyclic {Ge303} units joined by three Ge-0-Ge linkages (21).57 Other germanium work includes that involving the perfluorophenylgermanium unit {Ge(C,F,),}. In a truly main-group organometallic reaction involving mercury thallium germanium and lithium the treatment of [{ (C6F,)3Ge}3Hgfl( DME) .,] with lithium in dimethoxyethane (DME) is found to give what is believed to be the covalent species [{ (C6FS)3Ge}3HgLi( DME),] other metals generally produce ionic compounds of the [{ (C6F5)3Ge}3Hg]-M+ type.58 Some related work reports the synthesis of what may be Ge-TI bonded species uia the reaction of [(C6F5),GeH] with [TlEt,] [equation (5)].59 [(C,F,),GeH] + [TlEt,] -* [(C6F,),GenEt2] + CH,CH (5) There has been interest in the possibility that hydrogen atoms in positions antiperi- planar to Sn-C bonds may be an active source of hydrogen in redox processes.w2 This has led to the synthesis of inter alia the adamantane-like compound (22).This species has elements of strain not present in adamantane itself because the organic residue has to span the large {Sn3S3} ring and consequently the bridgehead carbon is apparently one of the most flattened methine groups known as well as being effectively antiperiplanar to three Sn-C bonds6 It is not yet clear however what general chemical effects this may have. 55 V.K. Belsky N. N. Zemlyanski I. V. Borisova N. D. Kolosova and I. P. Beletskaya 1. Organomet. Chem. 1983 254 189. " H. Puff S. Franken W. Schuh and W. Schwab J. Organomet. Chem. 1983,254 33. 57 H. Puff S. Franken and W. Schuh J. Organornet. Chem. 1983,256 23. 58 G. A. Razuvaev M. N. Bochkarev and L. V. Pankratov J. Organomet. Chem. 1983. 250 135. 59 M. N. Bochkarev T. A. Basalgina G.S. Kalinina and G.A. Razuvaev J. Organomet. Chem.. 1983,243 405. 60 A. L. Beauchamp S. Latour M. J. Olivier and J. D. Wuest J. Organomet. Chem 1983 254 283. 61 S. Chandrasekhar S. Latour J. D. Wuest and B. Zacharie J. Org. Chem 1983,48 3810. 62 A. L. Beauchamp S. Latour M. J. Olivier and J. D. Wuest J. Am. Cfiem. Soc. 1983 105 7778. Organometallic Chemistry -Part (ii) Main-Group Elements H I Organolead chemistry is not well represented in 1983.The linear relationship between the n.m.r. chemical shifts S('''Pb) and S( "'Sn) for equivalent straightfor- ward organolead and organotin species has been redisc~vered:~ and the synthesis of [Pb( SiMe3)J 'the first organosilicon-lead compound' has been reported.64 The preparation of this latter species [equation (6)] makes use of the silicon Grignard-type reagent [Mg( SiMe,),]. These reagents and corresponding aluminium derivatives may be made by the reaction of [Hg(SiMe3)2] with Mg turnings or Al powder,6' and have not yet been exploited fully as synthetic reagents. 2PbC1 + 2[Mg(SiMe3),J Et70* [Pb(SiMe3),J+ Pb + 2MgCI2 (6) 6 Group V As usual much of organoarsenic chemistry is directed at the synthesis of ligands for transition-metal complexes.An interesting example of these is the strained small-ting species [Ph2As2C2Ph2] (23). This is formed in the reaction of the cyclohexa- arsane species [(AsPh),] with excess PhCECPh which gives a 13.5% yield of the tetraphenyldiarsetine product. In this compound the interarsenic distance is 247 pm the intercarbon 136 pm and the arseniocarbon 196 pm.W Some reactions with transition-metal complexes have been investigated. Ph ph\ c=c / I\ ,As-As Ph 'Ph In terms of organoarsenic chemistry proper the principal innovations also appear to be in the area of multiply bonded chemistry. The first unsupported diarsene [(~,~,~-BU'~C,H,)AS=AS{CH( SiMe,),)] has been made by the reaction between [(2,4,6-Bu1,C6H2)hH2] and (Me2Si)2CHAsC12.67 The interarsenic distance is 222.4(2) pm and the angles AsAsC which average at 96.7(3)" are smaller than angles PPC in similar diphosphenes.Double bonds to phosphorus from both arsenic and antimony have been made similarly by the reactions of [(Me3Si)2CHMC12] (M= As or Sb) with [(2,4,6-Bu',C6H2)PH,] in the presence of DBU in THF. The products (~,~,~-Bu',C~H~)P=MCH(S~M~,)~ are orange crystalline compounds. The 63 T. N. Mitchell J. Organornet. Chem. 1983. US,279. 64 L. Rosch and U. Starke Angew. Gem Inr Ed EngL 1983. 22 557. 65 D. W. Goebel J. L. Hencher and J. P. Oliver Oganornetullics 1983 2 746. 66 G. Sennyey F. Mathey J. Fischer and A.Mitschler Orgonornetollics 1983 2 298. 67 A. H. Cowley J. G. Lasch N. C. Norman and M. Pakulski J. Am. Chem Soc.. 1983. 105. 5506. 304 J. D. Kennedy new starting stibine [(Me3Si)2CHSbC12] was prepared by treatment of SbCl with [( Me3Si)2CHMgC1] in Et20 solution.68 Other arsenic multiply bonded chemistry reported in 1983 includes some work on the aromatic 1 H-1,3-benzarsa~oles.~~ In contrast to the arsabenzenes these .rr-excess species can be alkylated at the arsenic atom as well as lithiated at positions shown in (24) and (25) without a high incidence of lithium reagent addition across the As=C double bond. Alkylations and acylations of the ambident 1-1ithio-deriva-tives (24) and substitution reactions of 2-lithiobenzazarsole species have been de~cribed.~~ Li R (24) (25) There is continuing interest in tetraorganyl-distibines and dibismuthines much of which is stimulated by the thermochromic properties of these Various tetravinyldistibines [R$b2] have been made uia the scheme in equation (7).These are generally yellow in the liquid phase but where R = CH2=CH the compound freezes to a violet solid. When R = isopropenyl an brange solid is formed.70 M(NaorK) CH ClCH CI R,Sb -R,SbM -R,SbSbR (7) N" A variety of dibismuthines has now been made; all are red in solution but the tetramethyl and tetraisopropenyl derivatives together with the bi(bismuthacyc1open- tyl) species (26) freeze to give blue solids.71 Tetraphenyldibismuth is the first crystallographically determined tetraorganyl deri~ative.~~ It is made in 50% yield as an orange solid by the reaction of Ph2BiC1 and Na in NH solution.At liquid nitrogen temperatures it is yellow and the solid-state structure has no significant intermolecular interbismuth interactions. The molecule has a staggered transoid conformation (27) ; all angles approximate to right angles indicating lone-pair s-~haracter.~~ 'I Bi'LBi I' Two other aspects of organobismuth work have been noted in 1983. The first is the synthesis of the metallochiral triorganobismuthines [BiAr'Ar2Ar3]. These are formed by the cleavage of [BiAr1Ar2,] with HBr in methanol to give [BiAr'Ar2Br] 68 A. H. Cowley J.G. Lasch N.C. Norman M. Pakulski and B. R. Whittlesey J. Chem. SOC.,Chem. Commun. 1983 881. 69 J.Heinicke A. Petrasch and A. Tzschach J. Organornet. Chem. 1983 258 257. 70 A. J. Ashe E. G. Ludwig and H. Pommerening Organornetallics 1983 2 1573. 7' A. J. Ashe E. G. Ludwig and J. Oleksyszyn Organometallics 1983 2 1859. 72 F. Calderazzo A. Morvillo G. Pelizzi and R. Poli J. Chem. SOC.,Chem. Commun. 1983 507. 73 H. J. Breunig and D. Muller J. Organornet Chem. 1983 253 C21. 74 H. J. Breunig and D. Miiller Z. Naturforsch. B Anorg. Chem. Org. Chem. 1983 38 125. 305 Organometallic Chemistry -Part (ii) Main-Group Elements followed by treatment with an appropriate Grignard reagent [eMgBr]. The results suggest stable pyramidal structures but enantiomers have not yet been resol~ed.~' The second is the characterization of the six-co-ordinate species [Ph,BiX( MeOx)] (X = halogen MeOx = methyloxinate) which are readily made in yields of 40-70% from [Ph3BiX2] and Na[MeOx].The compounds can be regarded as a straight- forward octahedral bismuth(v) complexes (28) although the B-N bond is readily cleaved in polar solvents which can result in decornp~sition.~~ 7 Group VI Organotellurium chemistry continues to be a lively area both from the chemical and from biological and biomedical points of view. Structural work of note includes the observation uia X-ray diffraction at low temperatures of tellurium(1v) lone-pair and bonding electron-density in Me2TeC1,.77 Reassuringly the results are consistent with classical bonding models for AB4E compounds and there is also support for a donor-acceptor bonding model involving C1 lone-pair density and an empty Te orbital.Organotellurium compounds in synthesis continue to be of importance. One example is their use in the synthesis of a number of olefins allylic alcohols and allylic ethers in a process facilitated by the ready elimination of s-alkylphenyl- telluroxides from the product prec~rsors.~~ A novel involvement of tellurium is in the formation of benzylic chlorides by rearrangement of cycloheptatrienes [equation (8)~'~ 0 R' R2 I \-TeC'a @\ :HCl + {TeCl,} - R3 R' Another interesting organotellurium reaction involves the compound 2,Sdiphenyl- 1,6-dioxa-6a-tellurapentalene(29) which is prepared by reaction (9)." This species oxidatively adds Br or C1 at low temperatures to give the 12-Te-5 pertelluranes (30).These last species can function as mild oxidants and they are also of interest 75 P. Bras A. van der Gen abd J. Wolters J. Organornet Chem. 1983 256 CI. 76 G. Faraglia R. Graziani L. Volponi and U. Casellato J. Organornet. Chem. 1983 253 317. 77 R. F. Ziolo and J. M.Troup J. Am. Chew. SOC.,1983 105 229. 78 S. Uemura and S. Fukuzawa J. Am. Chem. SOC.,1983 105 2748. 79 M. Albeck T. Tamari and M. Sprecher. J. Org. Chem. 1983,48 2276. 80 M. R. Detty and H. R. Luss J. Org. Chem. 1983,48 5149. J. D. Kennedy in that structural studies indicate some intermolecular tellurium-halogen interaction (e.g. Te-e-Br ca. 355 pm) in addition to the direct bonding (average Te-Br 256 pm).80 CI -Te-O' 0 II uph + PhCCl + NEt, Me 0-Te-0 Ph Ph (9) O-pTe-;) Ph U '' Ph There is also interest in mechanistic work.To cite one example the stereochemistry of the addition of TeCl and of [(2-naphthyl)TeC13] to a variety of linear olefins has been studied.81 In this work [(naphthyl)TeC13] ia found to add completely anti-stereospecifically whereas TeC14 gives syrt and anti mixtures. In these reactions p-benzoquinone is highly effective in promoting syn-addition when present in catalytic amounts of 15-20%. The results have been taken to suggest an ionic mechanism involving a telluronium ion intermediate for [(2-naphthyl)TeC13] whereas competing syn-addition and free-radical chain reactions are proposed for the TeCl processes.'' *' J.-E. Backvall J.Bergman and L. Engman,J. 0%.Chem. 1983.48 3918.

ISSN:0069-3030    

DOI:10.1039/OC9838000293

出版商:RSC    

年代:1983

数据来源: RSC

摘要:

13 Synthetic Methods By A. P. DAVIS Department of Chemistry Trinity College Dublin 2,Ireland 1 Introduction As in previous years this report has to be highly selective. An attempt has been made to include fairly comprehensive views of some of the areas of greatest concern to those interested in synthetic methodology. Aside from this the selection has been made principally on the basis of the apparent breadth of applicability of the methods reported. The report is divided into two major sections. The first is concerned with reactions in which carbon atoms are connected or disconnected and the second with functional group modifications. The former is further divided in an essentially topological manner (connection of separate fragments cyclization cycloaddition etc.)” the latter into oxidative reductive and non-redox conversions.2 C-C Connection and Disconnection Connection of Separate Fragments.-Enolates and their Equivalents. This continues to be an area of intense interest. Reviews have appeared on the chemistry of two of the most important types of enolate equivalent (i) silyl enol ethers’ and (ii) nitrogen derivatives of aldehydes and ketones (enamines metallated imines etc.).2 The regioselective deprotonation of unsymmetrical ketones to give a single enolate has been a long-standing problem. Methods for giving the less-substituted ‘kinetic’ enolate by removal of the less-hindered proton are well established but the more- substituted ‘thermodynamic’ enolate is less accessible. The situation has been improved by two groups.The silyl enol ether (1) can be made from 2-methyl- cyclohexanone by treatment with (i) bromomagnesium di-isopropylamide and trimethyl~hlorosilane~ (giving 97 % regiochemical purity) or (ii) potassium hydride/THF followed by triethylborane then trimethylchlorosilane (to give 93 (3” regiochemical p~rity).~ The enoxyborate (2) an intermediate in the latter procedure also undergoes regiospecific alkylation. Other methods of enolate synthesis may involve skeletal modification of a molecule. The reaction of a titanium methylidene complex with an acyl halide ’ P. Brownbridge Synthesis 1983 I 85. * J. K. Whitesell and M. A. Whitesell Synthesis 1983 517. M. E. Krafft and R. A. Holton Tetrahedron Lett. 1983 24 1345. E.4.Negishi and S. Chatterjee Tetrahedron Lett. 1983 24 1341. * Note that reactions such as the Beckmann Rearrangement have been included in the fragmentation section as no new C-C bond is made. 307 308 A. P. Davis RCOCl results in a titanium enolate (3) of the corresponding methyl ket~ne.~ The reductive insertion of carbon monoxide into the alkyl-oxygen bond of an acetate can give a silyl en01 ether as in Scheme 1.6 Reagents i HSiR, CO Co,(CO) (cat.) Scheme 1 The usefulness of the many specific methods of enolborane synthesis has been extended by the discovery that their treatment with N-trimethylsilylimidazole will exchange -BR for -SiMe without stereo- or regiochemical scrambling.' An area which attracts much attention is the incorporation of a removable chiral centre into an enolate equivalent and the application of the resulting molecule in enantioselective syntheses.Chiral sulphinyl groups have often been exploited in this way most recently in positions (Y to hydrazone' and amide9 carbons. In both cases the derived enolates underwent enantioselective aldol condensations with aldehydes. In the latter case excellent selectivities were reported when magnesium was used as a counter-ion. In particular the /3-hydroxyamide (4)was made in greater than 99% enantiomeric excess by the route shown in Scheme 2. . .. ... Me p-MeC,H (4) 299% ee Reagents i Bu'MgBr THF; ii MeCHO; iii 10% Na/Hg MeOH NaH2P0 Scheme 2 The enolate (5) has also been used for aldol reactions." The enantiomeric excesses of the products were only in the region of 50-60% but this is relatively high for an enolate with no P-substitution.Enolates derived from (6) have been exploited by Enders and co-workers over the past few years and have now been applied to Michael additions. After hydrazone cleavage the products (7) have enantiomeric excesses 396% .'I J. R. Stille and R. H. Grubbs 1.Am. Chem. SOC.,1983 105 1664. N. Chatani S. Murai and N. Sonoda J. Am. Chem. SOC.,1983 105 1370. J. Hooz and J. Oudenes Tetrahedron Lerr. 1983 24 5695. L. Colombo C. Gennari G. Poli C. Scholastico R. Annunziata M. Cinquini and F. Cozzi J. Chem. SOC.,Chern. Commun. 1983 403. R. Annunziata M. Cinquini F. Cozzi F. Montanari and A. Restilli J. Chem. SOC.,Chem. Commun.1983 1138. M. Braun and R. Devant Angew. Chem. Int. Ed. Engl. 1983 22 788. D. Enders and K. Papadopoulos Tetrahedron Lett.. 1983 24 4967. Synthetic Methods Aldol diastereoselectivity is another area of continuing concern. Kuwajima and co-workers have described the reactions of two new types of ketone-derived enolate trichlorostannyl enolatesI2 and trichlorotitanium en01ates.I~ Both are available from the interaction of the metal tetrachlorides with silyl enol ethers. The tin ‘enolates’ for which n.m.r. evidence suggests metallo-ketone structures as in (8),14 give syn*- selective aldol reactions irrespective of the geometry of the starting enol ether (e.g. Scheme 3). In the titanium enolates the metal is thought to reside on the oxygen; the stereochemical results appear to be less useful but again there is a general preference for syn-aldols.The results are used as the basis for the proposition that a ‘bent-boat’ transition state such iis (9) is quite common in aldol reactions par- ticularly of E-enolates. (8) 95% this isomer Reagents i SnCl, CH,CI,; ii PrCHO -7O”C 7 rnin Scheme 3 Good syn-selectivity has also been observed in the aldol reactions of two new enolate equivalents at the carboxyl oxidation level. The silylated thioamide (10) reacts with benzaldehyde under the influence of tetrabutylammonium fluoride giving 95 ‘/o syn -stereochemistry in the product p -hydroxythioamide.’’ The enolates derived from (1 1) are similarly effective; the heterocyclic moieties can be displaced by oxidation of the sulphur to sulphone followed by methanolysis.I6 As part of a systematic study of the stereochemistry of aldol reactions of lithium enolates a report from Heathcock’s laboratory indicates that the enolates derived from (12) (9) ’’E.Nakarnura and I. Kuwajima Tetrahedron Lett. 1983 24 3347. l3 E. Nakamura and I. Kuwajima Tetrahedron Lett. 1983 24 3343. l4 E. Nakamura and I. Kuwajima Chem. Lett. 1983 59. C. Goasdoue N. Goasdoue and M. Gaudemar Tetrahedron Lett. 1983 24 4001. l6 F. Babudri L. DiNunno and S. Florio Tetrahedron Left. 1983 24 3883. * The convention of Masarnune is followed here; see S. Masamune S. Ali D. Snitman and D. Gamey Angew. Chem. Int. Ed. EngL 1980 19 557. 310 A. P. Davis (n = 0-3) all give virtually complete syn-selectivity in aldol reactions.However the products from the longer-chain examples are more subject to isomerization. I' Good diastereofacial selectivity (obeying Cram's rule) has been found for the Lewis acid-catalysed reaction of t-butyldimethylsilyl enol ethers with chiral aldehydes (e.g. Scheme 4). The method is considerably more stereoselective than the analogous reactions of lithium enolates possibly because of a steric influence of the Lewis acid in the transition state.'** The stereochemistry of some titanium tetrachloride-catalysed reactions of 1-phenyl-1-trimethylsiloxyethene with sub-stituted cyclohexanone acetals has been studied. A methyl group in any position on the cyclohexane ring is sufficient to ensure that attack is from the equatorial direction (>92%).l9 0-SiMe,Bu' / I \ OBu' 36 1 Reagents i BF,.Et20 CH,C12 -78 "C Scheme 4 A new 'a-acrylate anion' equivalent relies on the generation of an enolate by the reversible addition of DABCO ( 1,4-diazabicycl0[2.2.2]octane) to an acrylate.The enolate is capable of aldol reaction with a wide variety of aldehydes (Scheme 5).*' Snider and co-workers have extended their hydroxymethyl-methylation of cyclic enol ethers to the acyclic case discovering in the process a useful degree of stereoselectivity (e.g. Scheme 6).*' AZZyZ Anions and their Equivalents. A lot of attention is currently focused on the use of ally1 anion equivalents in synthesis particularly on their reactions with carbonyl compounds (Scheme 7).Several stereo-and regio-chemical issues arise (i) " C. H. Heathcock and J. Lampe J. Org. Chem. 1983 48,4330. l8 C. H. Heathcock and L. A. Flippin J. Am. Chem. SOC.,1983 105 1667. 19 E. Nakamura Y. Horiguchi J. Shimada and I. Kuwajima J. Chem. SOC.,Chem. Commun. 1983,796. 20 H. M. R. Hoffmann and J. Rabe Angew. Chem. Int. Ed. Engl. 1983 22 795. 21 B. B. Snider and G. B. Phillips J. Org. Chem. 1983 48 2789. * For diastereofacial addition to alkoxy-substituted aldehydes see the discussion of references 23 and 49 on page 317. Synthetic Methods 31 1 (1) +R_XOH CO,R Scheme 5 MeWOR Me#c OH +"IeZ Me OH R = EtorMe,Si Me >10 1 Reagent i H,CO Me,Al CH2ClZ,0 "C Scheme 6 X (13) Scheme 7 stereofacial selection controlling the stereochemistry at C* in an absolute sense or relative to a chiral centre in R';(ii) vicinal diastereoselection controlling the relative configurations of C* and Ct; (iii) regioselectivity of attack [formation of product (13) or (14)]; (iv) the stereo'.llemistry of the olefinic bond in the product.The first two run parallel to the important questions of aldol stereochemistry especially as oxidative cleavage of the olefinic bond in (13) or (14) will give an aldol. Stereofacial selection has attracted considerable attention in the past year. Reac- tion of the aldehydes (15) (17) and (19) with allyltrimethylsilane and SnCl gave preferentially the products (16) (1 8) and (20) in good diastereomeric excesses (ratios 35 :1 12:1 and 9 1 respectively) (Scheme S).22The product stereochemistry could be predicted by the assumption of ally1 attack on the less-hindered side of an SnC1,-P-alkoxyaldehyde chelate.Another group got very similar results on substrate ( 19) employing TiCI catalysis and observed diastereoselectivity in the S.-i. Kiyooka and C. H. Heathcock Terrahedron Left. 1983 24 4765. 312 A. P. Davis - (0 OH Ph Ph (19) Reagent i hSiMe, SnCI Scheme 8 same sense when the unprotected aldol was treated with tetra-allylzirc~nium~~ (see also p. 317). The allyltrimethylsilane/TiC14 combination has been applied to the chiral acetals (21) to give ultimately optically active alcohols (22) of around 70% enantiomeric excess.24 Crotyltri-n-butylstannane reacts with chiral glyoxylate (23) under Lewis acid catalysis to give predominantly isomer (24) (Scheme 9)25 (the vicinal stereochemistry is as expected on the basis of earlier literature).Allyldi-isopinocam- phenylborane reacts with aldehydes to give homoallylic alcohols of between 83% and 96% enantiomeric excess.26 R Reagent i BF3.0Et, CH2C12,-78 "c' Scheme 9 23 M. T. Reetz and A. Jung J. Am. Chem. Soc. 1983 105 4833. 24 P. A. Bartlett W. S. Johnson and J. D. Elliott J. Am. Chem. Soc 1983 105 2088. 25 Y. Yamamoto N. Maeda and K. Maruyama J. Chem. SOC.,Chem. Commun. 1983 774 26 H. C. Brown and P. K. Jadhav J. Am. Chem. Soc. 1983. 105 2092. Synthetic Methods 313 The question of vicinal diastereoselection is already fairly well resolved in the case of additions to aldehydes.It has now been shown that control is possible when X # H (Scheme 7). In the example shown in Scheme 10 the alternative diastereomer was not detected.27 Scheme 10 Several papers have appeared which are concerned principally with either or both of issues (iii) and (iv) the stereochemistry of the new double bond in (13) and the regioselectivity of the allyl system. It is found that allyl bromides (25) can be converted into alcohols (26)via a mixture of allylstannanes (Scheme 1 It appears that all the intermediate stannanes give the same regio- and stereo-chemistry in the product. Selectivity for the 2 product is also observed in the reactions of the boronates (27) (X = CI Br or OR)29and of the titanium ally1 (28) with aldehydes.In the latter case useful regio- and diastereo-selectivity was also observed (Scheme 1 2).30 Crotyl organometallics (29) will usually react with unhindered carbonyl compounds at the y-carbon. Two methods have been reported in which M is apparently substituted in situ by Al with allylic inversion so that subsequent reaction with the carbonyl compounds occurs at what was originally the a-carb~n.~'~'~ Another potentially useful application of allyl organometallics is their addition to alkynes (allyl-metallation). Addition to internal alkynes has proved difficult but SnMe Reagents i Me,SnM M = metal (various); ii PhCHO SnCI Scheme 11 '' Y. Yamarnoto T. Komatsu and K. Maruyama J. Chem. SOC.,Chem. Commun. 1983 191. 28 Y. Naruta and K.Maruyama J. Chem. SOC. Chem. Commun. 1983 1264. 29 R. W. Hoffmann and B. Landrnann Tetrahedron Lett. 1983 24 3209. 30 F. Sato M. Uchiyarna K. Iida Y. Kobayashi and M. Sato J. Chem. SOC.,Chem. Commun. 1983 921. '' Y. Yamamoto and K. Maruyama .I.Org. Chem. 1983,48 1564. 32 Y. Yamarnoto N. Maeda and K. Maruyama J. Chern. SOC.,Chem. Commun. 1983 742. 314 A. P. Davis (28) Reagents i Bu'Li HMPA -78 "C;ii (C5H5),TiCI; iii EtCHO THF Scheme 12 (29) (30) (31) it has now been reported that trimethylsilylalkynes will react cleanly with allylzinc bromide the metal adding to the silicon-bearing carbon. Furthermore internal acetylenes will react with diallylzinc in the presence of I,Z~CP,.~~ Miscellaneous. The application of Group VIII transition elements to the coupling of organic residues particularly vinyl aryl and allyl ones is of continuing interest.Palladium appears to be particularly useful ;certain aspects have been reviewed.34 One of several new developments is the conversion of R-X into RCHO by treatment with carbon monoxide tributylstannane and a Pdo catalyst.35 The reaction is applicable to R = alkenyl aryl allyl and aralkyl. Another example is the coupling of alkenyl halides with alkenyl organometallics carrying a-heteroatom substitu- tion36,37 (e.g. Scheme 13). Reagents i Pd" catalyst; ii 5% HCI aq. Scheme 13 When chiral nickel complexes are used to mediate coupling reactions asymmetric induction may be observed. A series of new optically active ligands (30) has been synthesized from readily-available a -amino-acids.Catalysis of the coupling of a-phenylethylmagnesium chloride and vinyl bromide by the derived nickel com- plexes gave products with enantiomeric excesses of up to 83% .38 Similarly the complex (31) catalysed the allylic substitution shown in Scheme 14 to give the product (32) with the remarkable enantiomeric excess of 97% (unfortunately other examples were much less su~cessful).~~ 33 E.-i. Negishi and J. A. Miller J. Am. Chem. Soc. 1983 105 6761. 34 I. P. Beletskaya J. Organornetallic Chem. 1983 250 551. 35 V. P. Baillargeon and J. K. Stille J. Am. Chem. SOC.,1983 105 7175. 36 C. E. Russell and L. S. Hegedus J. Am. Chem. SOC.,1983 105 943. 37 E.4. Negishi and F.-T. Luo J. Org.Chem. 1983 48 1560. 38 T. Hayashi M. Konishi M. Fukushima K. Kanehira T. Hioki and M. Kumada J. Org. Chem. 1983 48 2195. 39 G. Consiglio F. Morandini and 0.Piccolo J. Chem. Soc. Chem. Comrnun. 1983 112. Synthetic Methods Reagent i EtMgBr catalyst (31) Scheme 14 A related area is the generation of alkenylorganometallics by additions to acetyl- enes. One new example which should prove useful is the regio- and stereo-selective hydromagnesiation of silylacetylenes (Scheme 15):' Another is the halogenobor- ation of terminal acetylenes to give intermediates (33);4' the BBN unit can be replaced by hydrogen or an alkynyl Reagents i Bu'MgBr Cp,TiCI2; ii R21 or R21 CuI Scheme 15 BBN = B RHsiMe3 ,X= BrorI X BBN (33) In principle a trivalent boron should be an excellent carbanion-stabilizing group.In practice removal of an a-proton in a borane is generally prevented by the susceptibility of the boron to nucleophilic attack. An early solution was to use boronic esters where attack at boron was prevented by 0-P B .rr-donation. A new approach which is said to have certain advantages is the use of dimesitylboranes where the boron is protected by steric crowding. Thus the anions (34) generated by the action of mesityl-lithium or lithium dicyclohexylamide on the parent borane can be alkylated by primary alkyl halides or undergo 'Boron Wittig' reactions (Scheme 16).43Note that in the latter case the stereochemistry is the reverse of that expected from the simple Wittig reaction. HoxR1Mes2BJ-R' (R'=G Ph\ Mes i,ii e-__ iii = Me 4 R2 (34) C7H15 Me Reagents i R2Br or R21(primary R2); ii H202 MeOH NaOH aq.; iii PhCHO Scheme 16 40 F.Sato H. Watanabe Y. Tanaka T. Yamaji and M. Sato Tetrahedron Lett. 1983 24 1041. 4' S. Hara H. Dojo S. Takinami and A. Suzuki Tetrahedron Lett. 1983 24 731. 42 S. Hara Y. Satoh H. Ishiguro and A. Suzuki,Tetrahedron Lett. 1983 24 735. 43 A. Pelter B. Singaram L. Williams and J. W. Wilson Tetrahedron Lett. 1983 24 623 and succeeding papers. 316 A. P. Davis A notable application of boron in synthesis is Matteson’s use of pinanediol boronic esters such as (35) to homologate a carbon chain with control over the absolute stereochemistry of the new carbon. A full paper has appeared,44 and also a communication in which a modification of the original procedure is given.Catalysis by zinc chloride of the rearrangement step exemplified by (36) +(37) makes the levels of diastereoselectivity quite outstanding. In the example shown a synthesis of exo-brevicomin (39) intermediate (38) was formed with 99.5% diastereoselectivity (Scheme 17).45 1i ii iv Ph n v vi vii ___ B 0’ ‘0 (39) Reagents i LiCHCI, -100°C; ii ZnCl,; iii LiOCH,Ph; iv EtMgBr V H,02 NaOH; vi H+ SiO,; vii HJPd Scheme 17 In the section covering ally1 anion equivalents mention was made of the use of pentane-2,4-diol acetals (2 1) as ‘enantioselective electrophiles’ with allyltrimethyl- silane-TiCI,. They have also been shown to react stereospecifically with silylacety- lenes (40) and TiCl to give eventually the propargylic alcohols (41) in around 90% enantiomeric excess (Scheme 18).46 44 D.S. Matteson R. Ray R. R. Rocks and D. J. Tsai Organomeiallics 1983 2 1536. 45 D. S. Matteson and K. M. Sadhu J. Am. Chem. SOC.,1983 105 2077. 46 W. S. Johnson R. Elliott and J. D. Elliott J. Am. Chem. Soc.. 19x3. 105. 2904. Synthetic Methods 3 17 R' SiMe .. ... II I11 JJ-. R2 I (41) (40) Reagents i TiCI, CH2C12 -78 "C; ii pyridinium chlorochromate; iii KOH MeOH H20 Scheme 18 Analogous ring-openings with trimethylsilylcyanide-TiC1 met with roughly equal success giving initially the cyanohydrin ethers (42).47 The improvement in stereoselectivity relative to the allylsilane examples was thought to be related to the distance between the trimethylsilyl group and the chiral centre in the transition states.The 8-phenylmenthyl group is widely used as a chiral auxiliary. An application involving the glyoxylate (43) (R = H) was given earlier (Scheme 9). In general it is found that nucleophilic attack on this molecule occurs on the si face (the front side as drawn). It is now reported that this is also true for (43) (R = Ph or Me) when treated with PhMgBr MeMgBr K(Pr'O),BH or hex- 1-ene-SnC1 (an ene rea~tion).,~ Diastereofacial selectivity in the addition of organometallic reagents to chiral aldehydes and ketones may in principle be influenced by neighbouring alkoxy groups via 'chelation control'. Previously effective control had only been observed with a-alkoxy groups but a number of recent publications indicate that 'Lewis acidic' organometallic reagents will show good diastereoselectivity with 2- 3- and 4-alkoxyaldehydes.* Reetz and co-workers have investigated the reactions of MeTiCl with a variety of alkoxy-aldehydes and of allylsilanes silyl enol ethers and dialkyl- zincs with the TiC14 complexes of the For aldehydes (15) and (19) the major products appear to result from attack on the unsubstituted face of a titanium chelate such as (44); the diastereomeric ratios are all 9 1 or better.For aldehyde (45) attack by Me,Zn appears to have occurred preferentially on the substituted face of the titanium chelate (diastereomeric ratio 85 15) (Scheme 19). The less acidic reagent M~T~(OPI-')~ reacts with (15) to give predominantly (46) the product of 'non-chelation control'.47 J. D. Elliott V. Choi and W. S. Johnson J. Org. Chem. 1983 48 2294. 48 J. K. Whitesell D. Deyo and A. Bhattacharya J. Chem. Soc. Chem. Comrnun. 1983 802. 49 M. T. Reetz K. Kesseler S. Schmidtberger B. Wenderoth and R. Steinbach Angew. Chem. Int. Ed. Engl 1983 22 989. * Mention was made earlier (pp. 31 I and 312) of work involving ally1 nucle~philes.~~~~~ 318 A. P. Davis H Ph Ph L LO Me H L. Me R (15) Ph (44) Ph Ph '0 --+ '0 OH Me Me (19) Ph Ph Scheme 19 Ph LO MeHoH Me The Sharpless asymmetric epoxidation of allylic alcohols has generated consider- able interest in the reactions of the resulting epoxy-alcohols.Until recently it was not generally possible to direct the attack of an organometallic to the epoxide carbon adjacent to the hydroxy-group. Fair to good selectivity has now been obtained by employing a Grignard reagent with copper( I) catalysis (e.g. Scheme 20).50 Me OH 3.3 1 Reagent i MeMgI THF Et,O CuI (catalytic amount) -40 "C Scheme 20 SO M. A. Tius and A. H. Fauq J. Org. Chern. 1983 48 4131. Synthetic Methods 319 Reviews have appeared on two classes of ‘Umpolung’ reagent homoenolate anions and their equivalent^,^' and cyanohydrin-derived acyl anion equivalent^.^^ A new formamidoyl anion equivalent is derived by insertion of an isonitrile into a titanium-chlorine bond of Tic& (Scheme 21).53 Reagents i R’R2C=O; ii 2M-HCI aq.Scheme 21 A useful modification of the Horner-Emmons synthesis of a$-unsaturated esters has been described. In its usual form where equilibration of the intermediate adducts analogous to (48) is faster than elimination to the final product the more stable E-isomer is commonly formed. However the trifluoroethylphosphonates (47) (R’= H or Me) give fairly reliable 2-selectivity particularly when used with a highly dissociated base system (Scheme 22).54 0 R’ . .. I II 0 - [ R14- (cF3 CH 2°)2p I/ YR1 (CF,CH,O),P /=( ~2 C02Me C0,Me C0,Me R2 (47) Reagents i KN(Me,Si), 18-crown-6 THF; ii R2CH0 Scheme 22 Radical reactions may offer particular advantages for carbon-carbon bond forma-tion.Radical intermediates need not conform to the polarity bias assumed in a regular retrosynthetic dissociation so that Umpolung may be achieved fairly simply. They may also show useful functional group compatibility. Both points are illustrated by the reductive addition of the selenoglucoside (49)to methyl acrylate shown in Scheme 23. The drawback of this type of reaction is the difficulty of controlling the fate of such reactive intermediates. Competing reactions are the reduction of (50) and addition of (51) to further acrylate molecule^.^^ In a similar vein a simple and direct ‘nucleophilic acylation’ of electron-deficient olefins has been reported (e.g. Scheme 24). The mechanism is assumed to involve photochemical cleavage of Co-acylated vitamin B,2 to give an acyl species which adds to the alkene.The reductive equivalents required may be supplied by an electrode or by zinc The titanium-induced reductive coupling of carbonyl compounds has been reviewed by McM~rry.~~ 51 N. H. Werstiuk Tetrahedron 1983 39 205. 52 J. D. Albright Tetrahedron 1983 39 3207. 53 M. Schiess and D. Seebach Helu. Chim. Acta 1983 66 1618. 54 W. C. Still and C. Gennari Tetrahedron Lett. 1983 24 4405. 55 R. M. Adlington J. E. Baldwin A. Basak and R. P. Kozyrod J. Chem. SOC.,Chem. Commun. 1983,944. 56 R. Scheffold and R. Orlinski J. Am. Chem. Soc. 1983 105 7200. 57 J. E. McMurry Acc. Chem. Rex 1983 16 405. 320 A. P. Dat3is OAc I__* AcO AcTc% AcO (49) 1 * SnBu C0,Me t OAc / AcOG O PH-SnBu3 AcO (50) Reagent i Bu,SnH methyl acrylate toluene reflux Scheme 23 Reagent i Vitamin BIZ hv (400-550nm.) e-(cathode at -1.OV or Zn dust) DMF Scheme 24 Cyc1ization.-A new development of the McMurry reaction is its application to keto-esters.Instead of the alkenes produced when only ketones or aldehydes are employed the keto-ester coupling results in cyclic vinyl ethers which are generally hydrolysed on work-up to cycloalkanones. The rings formed may be any size from 4 up to 14 and the reaction is likely to be particularly useful for forming medium and large ringss8 An example is its use in a short synthesis of isocarophyllene (53) (Scheme 25). The (unintended) isomerization of the double bond in (52) was thought to have occurred on the surface of an insoluble titanium particle.59 Titanium is involved in another cyclization which appears to be unusually effective for medium-sized rings.The intramolecular Mukaiyama reaction shown in Scheme i ii 111 ___* + 38% (53) Reagents i TiCI3 LiAIH,, Et,N; ii H,O' iii Ph,P=CH, DMSO Scheme 25 58 J. E. McMurry and D. D. Miller J. Am. Chem. SOC.,1983 105 1660. 59 J. E. McMurry and D. D. Miller. Tetrahedron Let?. 1983 24. 1885. Synthetic Methods 32 1 26 was accomplished without recourse to high-dilution conditions. It is suggested that the titaniumIv catalyst is acting as a template co-ordinating to both acetal and enol ether oxygens.60 O-) I Scheme 26 Intramolecular palladium-catalysed allylic alkylations have been employed to great effect in the synthesis of macrocycles particularly by Trost and co-workers.In a new development the palladium is bound to a polymer. This enables the cyclization to take place at relatively high concentrations and results in remarkably high yields for very large rings (e.g. Scheme 27). It was found that the nature of the nucleophilic end of the acyclic precursor was critical -the bis(su1phone) system was effective whereas analogous sulphonyl ester systems were completely ineffective.61 0 Reagent i Polymer-bound Pd' THF reflux Scheme 27 There is continuing interest in the use of free radicals in cyclization. Recent contributions from Stork and co-workers concentrate particularly on the use of the 2-bromoacetal moiety as the source of a radical centre.Thus abstraction of bromine from (54) leads to the cyclized radical (55) which may be trapped by reduction to give (56)62or cyanation to give (57)(Scheme 28).63 In an elegant extension of this work cyclization onto an acetylene generated a vinyl radical positioned so that it too could cyclize giving the butenolide (58) (Scheme 29).64 In work aimed at the biomimetic synthesis of tetracyclic triterpenoids quite spectacular multiple cyclizations of carbocationic intermediates have been achieved. However the construction of the complete non-aromatic steroid nucleus in reason- able yield from an acyclic precursor has only recently been reported (Scheme 30). 60 G. S. Cockerill and P. Kocienski J. Chem.Soc. Chem. Commun. 1983 705. " B. M. Trost and R. W. Warner J. Am. Chem. SOC.,1983 105 5940. 62 G. Stork R. Mook jun. S. A. Biller and S. D. Rychnovsky J. Am. Chem. Soc. 1983 105 3741 63 G. Stork and P. M. Sher J. Am. Chem. SOC.,1983 105 6765. 64 G. Stork and R.Mook jun. J. Am. Chem. SOC.,1983 105 3720. 322 A. P. Davis (57) Reagents Product (56) Bu3SnH; Product (57) (Ph,Sn), hv (quartz) Bu'NC Scheme 28 I ii iii iv (58) Reagents i Bu,SnH AIBN; ii Na THF NH3 -78 "C; iii pyridinium chlorochromate CH,CI,; iv DBU THF Scheme 29 The particular feature of this reaction is the use of a trimethylsilyl group to direct the reactivity of the terminal double bond such that the 5-membered ring D is formed.65 Another cationic ring closure the Nazarov cyclization has been reviewed.66 65 W.S. Johnson Y.-Q.Chen and M. S. Kellogg J. Am. Chem. SOC.,1983 105 6653. 66 C. Santelli-Rouvier and M. Santelli Synthesis 1983 429. Synthetic Methods I @. H U O7 34% Reagent i SnCI, pentane Scheme 30 A simple high-yielding synthesis of 4 5 and 6-membered cyclic alkenylsilanes has been reported. The treatment of compounds (59) (n = .2 3 or 4) with t-butyl- lithium gave the corresponding cycloalkenes (60) irrespective of the geometry of the starting material. The presence of the trimethylsilyl group in (59) is necessary for the reaction to The rhodium-induced cyclization of a-diazo-P-ketoesters by carbenoid insertion into an unactivated C-H had been found to give 5-membered rings selectively.In a recent development incorporation of a chiral auxiliary in the molecule has made the reaction enantioselective (Scheme 3 I). The diastereoisomeric ratios of the products were approximately 85 15 the preferred diastereomer being shown in Scheme 31.68 R Reagent i Rh,(OAc), CH,Cl Scheme 31 Cycloadditions and Annu1ations.-Diels-Alder Reactions. The Diels-Alder continues to be heavily exploited and developed as a synthetic method. A new type of chiral dienophile has been introduced exemplified by (61). In cycloadditions with a number of dienes the diastereoselectivity is generally excellent; in the example shown in Scheme 32 the product (62) was formed in >98% diastereomeric excess. Lewis acid catalysis often improves the selectivity but is not generally necessary.69 67 E.4.Negishi L. D. Boardman J. M. Tour H. Sawada and C. L. Rand J Am. Chem. SOC.,1983 105 6344. 68 D. F. Taber and K. Raman J. Am. Chem. SOC.,1983 105 5935. 69 S. Masamune L. A. Reed 111 J. T. Davis and W. Choy J. Org. Chem. 1983 48 4441. 324 A. P. Davis (42) Reagents i BF,.OEt, toluene -78 “C,0.5 h; ii LiBH4 THF; iii NaIO, MeOH H20 Scheme 32 Intramolecular Diels-Alder reactions have been employed to great effect in the construction of complex polycyclic molecules. A relatively unusual application is the formation of macrocycles but the strategy had been noted to be potentially applicable to the cytochala~ans.~~ This has now been demonstrated in a synthesis of cytochalasin B (65) where the key step is the cyclization of (63) to (64) in about 30% yield (Scheme 33).” Use of the intramolecular Diels-Alder reaction to make smaller-ring lactones had been limited by a decelerating influence of the unconju- gated ester linkage in acyclic precursors such as (66).It has now been found that replacement of this by an acetal as in (67) allows the reaction to proceed success- fu11y.72 (J+yoa / ’HN 0 OH Reagent i 0.005-Mmesitylene 180-190 “C,6 days (45) Scheme 33 S. J. Bailey E. J. Thomas S. M. Vather and J. Wallis J. Chem. Soc. Perkin Trans. I 1983 851. ” G. Stork and E. Nakamura. J. Am. Chem. Snc. 1983 105 5510. ’’ R. K. Boeckman jun. and C. J. Flann Tetrahedron Lett. 1983 24 5035. Synthetic Methods (66) (67) Trost and co-workers have been exploring the potential of the diene (68) for 'tandem annulations' in which new rings are built on either side of the central C-C bond.Examples are shown in Scheme 34. The pathway leading to (70) via two Diels-Alder reactions had been reported earlier. The new developments are the oxidation of (69) to (71) allowing construction of the five-membered ring in (72),73 and the oxidation of (68) to (73) which is susceptible to a two-step dipolar annulation pr0cedu1-e.~~ CSiMe + "'yYSiMe ii +R1fl /j\,SiMe (68) I I vi iii SiMe Lr Br (73) vii I lv SiMe SO Ph viii OH ED "m SO,Ph +R2 S02Ph Reagents i R'CH=CHR*; ii NBS ow THF -100" + -78 "C; iii R3CH=CHR4; iv Br, ow,CuBr, THF; v NaH DMF diethyl malonate; vi NBS ow THF,-78 "C; 0 vii PhSO NaH DME; viii Bu,NF-or EtAICI2 Scheme 34 73 B.M. Trost and M. Shimizu J. Am. Chem. SOC.,1983 105 6757. 74 B. M. Trost and R. Remuson Tetrahedron Lett. 1983 24 1129. 326 A. P. Davis Alkynes are normally relatively unreactive in Diels-Alder reactions but it has been reported that catalysis by a mixture of the iron complex (74) and a Grignard or organoaluminium 'activator' will enable internal alkynes to add to simple dienes at room temperature. For example isoprene and dicyclohexylacetylene gave cyclo- hexadiene (75) in 72% yield.75 I N :FeCI N I R (74) A series of transition-metal complexes (76) (M = Cr Mo or W) have been found to be remarkably potent dienophiles taking part in Diels-Alder reactions ca.lo4-times faster than methyl acrylate. The transition-metal carbenoid centre can undergo a variety of useful transformations in the product cyclohexenes e.g. Scheme 35.76 + Me0SMKOh I--+ OMe OMe I1'" H OMe Reagents i C,H, 25 "C 1.5 h; ii Me2S0 3.5 h 25 "C iii HBr CH,CI,; iv CH2N2 Et,O Scheme 35 It has emerged relatively recently that water is an excellent solvent for Diels-Alder reactions presumably because of hydrophobic interactions between the reactants. Now it is reported that not only the rate but the endolexo selectivity are improved by conducting the reaction in water. Thus in the reaction of butenone with cyclopen- tadiene the endolexo ratio is 3.85 with excess diene as solvent and 21.4 in aqueous solution.The addition of detergents was not generally advantageo~s.~~ Other Reactions Forming 6-Membered Rings. Danishefsky and co-workers continue their investigations into the cycloaddition reactions of silyloxydienes concentrating most recently on the Lewis acid-catalysed cycloadditions with aldehydes. They have 75 H. tom Dieck and R. Diercks Angew. Chem. Inr. Ed. EngZ. 1983 22 778. 16 W. D. Wulff and D. C. Yang J. Am. Chem. SOC.,1983 105 6726. 77 R. Breslow U. Maitra and D. Rideout Tetrahedron Lett. 1983 24 1901. Synthetic Methods found that even the Lanthanide 'shift reagents' used in n.m.r. spectroscopy are capable of catalysing the reaction; use of such unusually mild conditions facilitates the isolation of the initial adducts such as (78).In most cases the relative stereochemistry in the products is that which would result from a concerted endo cy~loaddition.~' Particularly noteworthy is the fact that chiral shift reagents are capable of inducing optical activity in the product cycloadducts. A selection of the results is presented in Scheme 36. The first two entries show that increasing the bulk of R in diene (77) OR OR 1 EuL ____* PhCHO Me,SiO 'Ph Me,SiO Ph (77) (78) (79) R L Me hfc 42 58 But hfc 30 70 (+)-menthy1 fod 45 55 (+j-menthyl hfc 41 59 (-)-menthy1 fod 55 45 (-)-menthy1 hfc 8 92 Bu' fod n-C,F Scheme 36 improves the enantioselectivity. In these cases the selectivity was measured by degradation of the mixture of (78) and (79) to (80) and its enanti~mer.~~ The remaining entries demonstrate that the correct combination of chiral catalyst and chiral R can give quite good selectivity (assessed after desilylation to (81) and (82)).Curiously in the example that was particularly successful (final entry) the chiral catalyst appeared to reverse the 'natural' bias of the menthyloxy substituent as indicated by the results from Eu( fod)3 catalysis.80 78 M. Bednarski and S. Danishefsky J. Am. Chern. SOC. 1983 105 3716. 79 M. Bednarski C. Maring and S. Danishefsky Tetrahedron Left. 1983 24 3451. 80 M. Bednarski and S. Danishefsky J. Am. Chern. SOC.,1983 105 6968. 328 A. l? Davis Another development is the discovery that the cycloaddition can still occur when the terminal alkoxy in (77) and its congeners is replaced by an alkyl substituent.This has been utilized in a strategy for spiroketal synthesis (e.g. Scheme 37).81 Et3Si0A Et,SiOuR 1 ii iii 0 Reagents i Yb(fod), RCHO CHCI,; ii Pd(OAc)* MeCN; iii AcOH H20 THF; iv Alz03 Scheme 37 The hetero-Diels-Alder reactions undergone by the various possible types of azadiene have been reviewed systematically.82 ii iii Ti 1 ‘Transposed Robinson’ Reagents i K,CO, DMF; ii TiCI, AcOH H20 CHzCIz; iii DBU Scheme 38 S. Danishefsky and W. H. Pearson J. Org. Chem. 1983,48,3865. D. L. Boger Tetrahedron 1983 39,2869. Synthetic Methods 3 29 Two reports have appeared of cyclohexenone syntheses which are complementary to the Robinson annulation.In one case the '4 + 2' format of the Robinson is retained but the position of the functionality in the product is displaced (Scheme 38). The reagent (83) is generated in the presence of the substrate by base-induced elimination of triphenylphosphine from (84).83 The second method involves con- struction of the ring from two 3-carbon units (Scheme 39). Success is dependant upon the two reacting species interacting initially as 00 0 IC LHYR2 1 I R' R' Reagents i NaH THF; ii H20 (1-3 drops); iii H30t Scheme 39 5-Membered Rings.An improved method for generating azomethine ylides for [3 + 21 cycloadditions has been reported. Thiolactams such as (85) are readily alkylated on sulphur.The resulting thioimidate salt can be desilylated by fluoride ion in the presence of a dipolarophile. Cycloaddition is followed by loss of thiol to give (86) (Scheme 40). An earlier version employing a lactam was less successful probably because the initial 0-alkylation was less favourable and because of difficulties caused by the eliminated alcohol; in the new variant the thiol is scavenged by the dip~larophile.~' There has been a lot of interest in the use of nitrile oxide cycloadditions to olefins as a route to P-hydroxycarbonyl compounds. Conditions have been developed in which reduction and hydrolysis of the intermediate isoxazolines such as (87) can take place without loss of stereochemistry at C-4. In a new modification a chiral group based on glyceraldehyde is attached to the nitrile oxide generating not only relative but also absolute stereochemistry in the product ester (Scheme 41).Unfortu- nately the extent of asymmetric induction is modest; the ratio of (87) to its diastereomer (88) is only 2.9 :1 and the selectivity is reduced to zero if a monosub- stituted olefin is used.86 83 R. J. Pariza and P. L. Fuchs J. Org. Chem. 1983 48 2304. 84 K. M. Pietrusiewicz J. Monkiewicz and R. Bodalski J. Org. Chem. 1983 48 788. 85 E. Vedejs and F. G. West J. Org. Chem. 1983 48 4773. 86 A. P. Kozikowski Y. Kitagawa and J. P. Springer J. Chem. SOC.,Chem. Commun. 1983 1460. 330 A. P. Davis SMe 0 -% c,&.('OMe (86) Reagents i MeOSO,CF,; ii CsF methyl acrylate Scheme 40 Reagents i H,-Raney Ni AICI, MeOH H,O; ii NaIO, NaHCO,; iii CH2N2 Scheme 41 A clear potential handicap of this strategy for P-hydroxycarbonyl compounds is the question of regioselectivity when a 1,2-disubstituted olefin is used.The reactions of olefins (89) (R= Pr' or But) with a number of nitrile oxides have been investigated. For R = But the 5-t-butylisoxazoline was generally formed; for R = Pr' the Z-isomer of (89) gave only isoxazolines (90) but the E-olefin gave a mixture of regiois~mers.~~ Me Pr' In related processes the nitrile oxides (91) and (92) have been used for the vicinal cis-hydroxycyanation and cis-hydroxycarboxylation of olefins (Scheme 42),88 and the addition of nitrile oxides to vinyl ethers has been employed to make P-diketones.87 S. F. Martin and B. Dupre Tetrahedron Len. 1983 24 1337. 88 A. P. Kozikowski and M. Adamczyk J. Org. Chern. 1983.48 366. Synthetic Methods 33 1 - . .. Et0,c-c-rj-O I I1 (91) OTHP THP = Cb Reagents i cis-but-2-ene; ii NaOH; iii melt; iv pyH' TsO- MeOH; v H2-Raney Ni AICI, MeOH H,O; vi HI04 HZO MeOH; vii CH,N2 Scheme 42 OEt OEt OH + . .. Et Reagents i H2-Raney Ni; ii H30+ Scheme 43 In the latter case the reaction can tolerate a hydroxy-group in the vinyl ether such that 3(2H)-furanones can result after hydrogenolysis (e.g. Scheme 43).89 Other Ring Sizes. A [2 + 21 cycloaddition has also been developed as a synthesis of p -hydroxycarbonyl compounds. The photoaddition of aldehydes to furans gives 'head-to-head' regiochemistry and exo-stereochemistry to give adducts exemplified by (93) essentially protected forms of hydroxydicarbonyl compounds (95).90 In the example shown in Scheme 44,further elaboration of (93) resulted in an elegant synthesis of the asteltoxin analogue (94).9' In a development which may herald the appearance of asymmetric cyclopropana- tion reagents chiral iron-carbene complexes such as (96) have been reported to react with styrene to give 1-methyl-2-phenylcycloproptines in good enantiomeric excess (Scheme 45).92 A draw-back of this particular system is the modest diastereoselectivity of the reaction.A macrocyclic annulation employing ketenylidenetriphenylphosphorane(97) has been reported. Protected hydroxyaldehydes (98) (n = 7 9 or 11) react with (97) to give stabilized ylides (99).Deprotection and cyclization give macrolides (100) (Scheme 46).93 8Y D. P. Curran and D. H. Singleton Tetrahedron Lett. 1983 24 2079. yo S. L. Schreiber A. H. Hoveyda and H.-J. Wu J. Am. Chem. SOC.,1983 105 660. 9' S. L. Schreiber and K. Satake J. Am. Chem. SOC. 1983 105 6723. 92 M. Brookhart D. Timmers J. R. Tucker G. D. Williams G. R. Husk H. Brunner and B. Hammer J Am. Chem. SOC.,1983 105 6721. 93 H.-J. Bestmann and R. Schobert Angew. Chern. Inr. Ed. EngL 1983 22 780. 332 A. l? Davis Me Me Me OM'+ i. W""] HpoBzl 0 H (93) Bzl = PhChz-(94) Reagents i Benzene Et,O hv; ii m-CPBA NaHCO, CH,CI Scheme 44 t -I MevPh + Mb,,Ph 1 3.5 e.e. 84% e.e.88% (96) R* = (S)-2-methylbutyl Reagent i Ph-CH=C H2 Scheme 45 Rearrangements.-This section brings together those reactions in which the formation of a carbon-carbon linkage is tied to the breaking of a bond elsewhere in the molecule. One field in which such transformations are especially useful is the synthesis of macrocycles. By a ring-expansion reaction a cyclic starting material can be used to generate a larger ring avoiding the need for a difficult macrocycliz- ation. New applications of this strategy are shown in Schemes 4794and 48.95 In the latter case dehydration of the product (101) followed by hydrogenation gave the 94 R. C. Ronald and T. S. Lillie J. Am. Chem. SOC.,1983 105 5709. 95 C. Fehr Helu. Chim. Acta 1983 66 2512.Synthetic Methods (99) ( 100) Reagents i HCI aq.; ii toluene aq. buffer (pH 8.4) Scheme 46 Bs-= p-BrC,H,SO n = 4,5,6,8 or 10 Reagents i 90% H202 KHP04.3H20,THF; ii p-MeC6H4S03H.H20 Scheme 47 (101) Reagents i LiNPr', THF -40 "C 5 min; ii AI/Hg THF Scheme 48 valuable perfumery component muscone. Another method for muscone synthesis involved a Claisen rearrangement in which a 15-membered macrocyclic lactone was converted into a 15-membered carb~cycle.~~ The Claisen rearrangement has long been appreciated as one of the most powerful methods for stereocontrol in acyclic system^.^' An interesting development is shown in Scheme 49 where a chiral auxiliary is incorporated in an aza-Claisen rearrange- ment giving an enantioselective synthesis of (102) (87% enantiomeric purity).A demonstration has also been given of how 1,2-diastereoselection in the aldol reaction can be combined with 1,3-diastereoselection in the Claisen rearrangement to give effective I ,4-~tereoselection.~* Related to the Claisen [3,3] sigmatropic rearrangement is the Wittig [2,3] sig- matropic rearrangement of ally1 ethers. Among others Nakai and co-workers have been developing the potential of this reaction as a method for acyclic stereocontrol. 96 R. K. Brunner and H. J. Borschberg Helu. Chim.Acta 1983 66 2608. 97 M. J. Kurth and 0. H. W. Decker Tetrahedron Lett. 1983 24 4535. 98 C. H. Heathcock and B. L. Finkelstein. J. Chem. Soc. Chem. Commun. 1983 919. 334 A. P. Davis (102) Reagents i BuLi THF -78°C; ii Decalin 155 "C Scheme 49 In a recent publication examples have been assembled and a transition-state structure has been proposed to explain the results.99 In general 2-ally1 ethers (103) (R = aryl alkenyl or alkynyl) give syn products with good to excellent selectivity while E-ally1 ethers (104) give anti products with variable selectivity (Scheme 50).Modification of the method such that the initial carbanion is stabilized by an oxazine as in (105) changes the stereoselectivity dramatically; both E and 2 isomers gave the syn product ( 106).'00 Reagent i BuLi THF Scheme 50 Two new methods have appeared which employ pinacol-type [ 1,2] rearrangements. The ring contraction-spiroannulation shown in Scheme 51 is based on the un- precedented departure of a sulphinate anion under electrophilic catalysis.lo' The reaction has been tried for n = 3,4 and 8 giving yields 395%.The migration of an alkenyl group in intermediates related to (107) is the key step in an apparently general p-alkenyl alcohol synthesis exemplified in Scheme 52.lo' Fragmentation.-In this section are reviewed those synthetic methods which involve the cleavage of a carbon-carbon linkage without the concomitant formation of 99 K. Mikami Y. Kimura N. Kishi and T. Nakai J. Org. Chem. 1983 48 279. 100 K. Mikami K. Fujimoto and T. Nakai Tetrahedron Lett 1983 24 513. 101 B. M.Trost and B. R. Adams J. Am. Chem. Soc. 1983 105 4849. I02 P. A. Wender D. A. Holt and S. M. Sieburth J. Am. Chem. Soc. 1983 105 3348.Synthetic Methods + c;Ms (CHZ0S0,Ph -5 ( C H GSiMe SOzPh Reagents i KOH KI (Bu,N),SO, CH2<:12,H20; ii Et2AICI CH2C12 reflux Scheme 51 I cw Reagents i Li-EJ ; ii LiAIH, NaOMe THF Scheme 52 another. Such reactions often involve the opening of strained cyclic systems among which the cyclopropane ring is pre-eminent. Electron donation from an oxy-sub- stituent is often an aid to cleavage. For instance the variety of ring-opening reactions undergone by silyloxycyclopropanes has been reviewed,Io3 and two examples of their apparent conversion into homoenolate anions have appeared. In one case the titanium homoenolates (108) were formed by treatment of the cyclopropanes ( 109) with titanium tetrachloride and were shown to undergo 1,2-addition to aldehydes.*04 In a related series of reactions it was suggested that the homoenolates ( 1 10) (M= Ag or CuBF,) were intermediates in the formation of the 1,6-diones (1 11) from silyloxy- cycIopropane~.'~~ 103 S. Murai 1. Ryu and N. Sonoda J. Organornet. Chem. 1983 250 121. 104 E. Nakamura and I. Kuwajima J. Am. Chem. Soc. 1983 105 651. 1. Ryu M. Ando A. Ogawa S. Murai and N. Sonoda. J. Am. Chem. Soc. 1983 105 7192. 336 A. P. Davis R’ R’ R’ Substitution of electron-withdrawing groups on a cyclopropane also promotes ring-cleavage. A new and highly versatitle reagent designed to exploit this is 1,l- bis(phenylsulphony1)cyclopropane (1 12). It is susceptible to attack by a wide variety of nucleophiles (thiolates alkoxides amines enolates Grignard reagents and organocuprates) giving anions (1 13) which may be alkylated in situ.Reductive removal of the sulphonyl groups gives .products (1 14) such that the cyclopropane has effectively acted as a ‘propylene 1,3-dipole’ synthon. (Scheme 53).’06 S0,Ph N + phsk -Nd;02ph +-N~R (1 14) Reagents i RX; ii Na/Hg MeOH Na2HP0 Scheme 53 Unsubstituted cyclopropanes can be attacked by mercury( 11) ions and it has been reported that carboxy or ester groups can participate in this process (e.g. Scheme 54). The regio- and stereo-selectivity of the reaction have been studied in detail. Selectivity is normally good although highly dependent on conditions and substrate. The authors notesa particular preference for the formation of the larger of two possible lactones.’” Reagents i Hg(02CCF3)2,CCI, 25 “C; ii.Bu,SnH Scheme 54 The Beckmann rearrangement considered as a fragmentation here (see earlier) has received considerable attention from Yamamoto and co-workers. When per- formed on an oxime sulphonate and initiated by an organoaluminium of the form R,AlX the intermediate nitrilium ion can be trapped by transfer of X from aluminium to carbon. X may be an alkyl group (giving an imine) alkynyl cyano alkylthio or alkylseleno.’Os An example is given in Scheme 55 the final product (1 15) being the I06 B. M. Trost J. Cossy and J. Burks J. Am. Chem. SOC. 1983 105 1052. I07 D. B. Collum F. Mohamadi and J. Hallock J. Am. Chem. SOC.,1983 105 6882. I08 K. Maruoka T.Miyazaki M. Ando Y. Matsumura S. Sakane K. Hattori and H. Yamamoto J. Am. Chem. SOC..1983 105 2831. Synthetic Methods I __* N OTs Reagents i Pr,AI; ii Bu',AIH Scheme 55 active alkaloid pumiliotoxin C. It has also been shown that nitrilium ions generated in a similar fashion can be trapped intramolecularly by olefinic bonds"' or inter- molecularly with enol silanes."' A closely related reaction is the fragmentation of oxime derivatives to give nitriles and olefins. It has been shown that a trimethylsilyl group placed /3 to the oxime directs the fragmentation by acting as a powerful electrofugal leaving group (Scheme 56).' ' ' Reagent i Me3SiOS02CF3 CH,CI, 0 "C Scheme 56 Two new decarboxylation reactions have been reported by Barton and co-workers.Both employ esters of the form ( 116). These are susceptible to radical attack on sulphur resulting in N-0 bond cleavage loss of carbon dioxide and formation of an alkyl radical (Scheme 57). If the reagent employed is tri-n-butylstannane (X. = Bu,Sn.) the alkyl radical is reduced to alkane (generating a new stannyl radical).Il2 If the reagent is a halomethane (e.g. X = C13C-) the alkyl radical is converted into an alkyl halide." The latter is a convenient alternative to the Hunsdiecker reaction. 0 ?-) -&%7/326-+ R* + CO + N\ 9 3 (116) 1-x cc,,y/I/..."'" RY + CI,C-RH + Bu,Sn-zz x. sz X. (Y = CI or Br) Scheme 57 109 S. Sakane Y. Matsumura Y. Yamamura Y. lshida K. Maruoka and H. Yamamoto J. Am.Chem. Soc. 1983 105 672. I10 Y. Matsumura J. Fujiwara. K. Maruoka and H. Yamamoto J. Am. Chem. Soc. 1983 105 6312. Ill H. Nishiyama K. Sakuta N. Osaka and K. Itoh Tetrahedron Lett. 1983 24 4021. I I2 D. H. R. Barton D. Crich and W. B. Motherwell J. Chem. Soc. Chem. Commun. 1983,939. 'I3 D. H. R. Barton D. Crich and W. B. Motherwell Tetruhedron Lett. 1983 24 4979. 338 A. P. Davis 3 Functional Group Modifications Oxidation.-Additions to C=C. Current interest in the synthesis of complex acyclic and macrocyclic polyhydroxy-compounds has stimulated research into the stereochemical aspects of alkene hydroxylation and epoxidation. Recently the hydroxylation of allylic alcohols and derivatives (1 17) by osmium tetroxide has been examined in detail by Kishi and co-workers.l14 They find that the relationship between the substituent -OR2 and the new vicinal hydroxy-group is always erythro in the major product.Stereoselectivity is relatively good for R2 = H or alkyl but poor for R2= acyl. Scheme 58 shows examples which demonstrate (a) that replace- ment of -OR2 by methyl destroys the selectivity and (b) that the selectivity is greater for 2-than for E-olefins. R (OH R OH + PhCH,O& -L PhCHzO&oH PhCH,O G O H OH OH R R = OCH,Ph = Me 6 1 I 1 R PhCH,OLOH R OH PhCHzOxOH + PhCH,O&OH I OH OH R = OCHzPh 4.2 1 R = Me 1 .s I Reagent i Os04 Scheme 58 The suggested explanation for these results is that attack occurs on conformation (1 18) of the substrate (presumed to be the most stable) from the side opposite to the -OR2 substituent.Some support for this view comes from results in cyclic .. . . "'x=< g2 (1 18) I4 J. K. Cha W. J. Christ and Y. Kishi Tetrahedron Lett. 1983 24 3943 3947 Synthetic Methods OH OH -H HO<) OG Scheme 59 systems where attack clearly occurs from the side opposite to the substituent (e.g. Scheme 59). Kishi’s group have also investigated the hydroxylation of a$-unsaturated car-bony1 compounds (1 19). For the E-isomers the stereochemical result was the same R R1L 0 3 (1 19) as for (1 17) though the selectivity was generally rather lower. However for the 2-isomers the stereochemical preference was reversed so that the new vicinal hydroxy group was threo to -OR2.Similar results were obtained by Stork and Kahn for the trisubstituted alkenes (120) and (121) (Scheme 60). In these cases only the products shown were repotted.’l5 A+/0 Reagent i OsO cat. 0 acetone H20 Scheme 60 The epoxidation and osmylation of a number of medium-ring alkenes have been studied by Vedejs and co-workers. All the examples have an allylic methyl sub- stituent and for the most part the results can be explained by the assumption that this dominates the local conformation of the ring in the vicinity of the double bond. Thus the 2-cycloalkenes (122) were epoxidized and osmylated to give (123) and (124) respectively consistent with addition to the external face of a conformation with a pseudoequatorial methyl group as shown (Scheme 61).’16The same mode 1 I5 G.Stork and M. Kahn Tetrahedron Lett. 1983 24 3951. I6 E. Vedejs and D. M. Gapinski J. Am. Chem. Soc. 1983 105 5058. 340 A. P. Davis H ( 122) n = 3,5,7 or 10 0 S (1 25) Reagents i m-CPBA; ii OsO, 0/-ye ; iii OsO, w '0 Scheme 61 of attack was observed in the more complex example (125)."' The behaviour of the E -cycloalkenes employed was somewhat less predictable. A review has appeared on recent advances in the preparation and synthetic applications of epoxides.' l8 A new vicinal bis-amination of alkenes has been reported. The method adds primary amino-groups stereospecifically cis to either end of the double bond thus constituting a nitrogen-analogue of the Os04 hydroxylation (e.g.Scheme 62).I19 Reagents i H,N-CGN N-bromosuccinirnide; ii EtOH HCI; iii NaOEt or NaOH; iv Nal; v Ba(OH) Scheme 62 An elegant method has been developed for the stereospecific hydroxyamination of one double bond in a diene. Its application to a synthesis of threo-sphingosine (128) is shown in Scheme 63.l2' The transformation of (126) to (127) through a sulphoxide-sulphenate allylic rearrangement is presumed to take place via an 117 E. Vedejs J. M. Dolphin and H. Mastalerz J. Am. Chem. SOC.,1983 105 127. 118 A. S. Rao S. K. Paknikar and J. G. Kirtane Tetrahedron 1983 39 2323. 119 H. Kohn and S.-H. Jung J. Am. Chem. SOC.,1983 105 4106. 120 R. S. Garigipati and S. M. Weinreb J. Am. Chem. SOC.,1983 105 4499. Synthetic Methods 'envelope' transition-state (129) in which the alkyl group controlling the stereochemistry takes a pseudo-equatorial position.An intramolecular cycloaddition is used in this case to control the regiochemistry; intermolecular examples are also given. ,Ova roYo l-? 1iii 1v +-Y n-CI 3H2 7 Reagents i SOCI, py; ii room temperature 14 h; iii PhMgBr -60 "C THF; iv (MeO),P MeOH 60 "C:v Ba(OH), dioxan H20 Scheme 63 The homolytic intramolecular addition of N-chloroamines to carbon-carbon double bonds has been reviewed,12' as has the general topic of amination of alkenes.'22 Other Oxidations. Although widely used in organic synthesis the oxidation of alcohols with chromium( VI) reagents often has practical disadvantages particularly during work-up.The situation can be ameliorated by employing bis-trimethylsilyl peroxide as co-oxidant with a catalytic quantity of pyridinium dichromate. Primary and secondary alcohols give aldehydes and ketones in good yields. Use of RuC12( PPh3)3 in place of the dichromate gives an oxidizing system which has useful selectivity for primary hydroxy-groups in the presence of secondary ones.'23 ''I L. Stella Angew. Chem. Int. Ed. Engl. 1983 22 337. N. B. Gasc A. Lattes and J. J. Pierre Tetrahedron 1983 39 703. S. Kanemoto K. Oshima S. Matsubara K. Takai and H. Nozaki Tetruhedron Lett. 1983 24 2185. 342 A. P. Davis The conversion of anion-stabilizing functional groups into carbonyl groups has attracted considerable attention as it enables the former to be used in 'Umpolung' reagents.A recent example is a new method for the oxidative cleavage of sulphones shown in Scheme 64.'24The reaction can be used to synthesize both aldehydes and ketones. A similar cleavage of nitro-compounds (an oxidative Nef reaction) can be accomplished by oxidation of the derived nitronate anions with the iodoxy salt (130). The nitro-compounds can be deprotonated by an excess of the guanidine base used to make (130). This method is reported to be milder than earlier ones.'25 R1 H R' R' rS02Ph R1 \/ \/ \ ' C-S02Ph -L \-C-S02Ph 2 C -/ / R' R2 R2/ '3-SiMe3 2 + OSiMe Reagents i BuLi THF -78 "C; ii Me,Si-0-0-SiMe Scheme 64 Another oxidation which has attracted interest is the a$-dehydrogenation of carbonyl compounds.One well-established method is the oxidation of trimethylsilyl enol ethers with palladium(I1). A convenient catalytic version of this has been reported in which an ally1 carbonate re-oxidizes the palladium. With addition of an organotin co-catalyst the method can also be applied to enol acetates.'26 0 rn3 1 I RZ R -' RL H R' H Reagents i p-MeC,H,SO,H; ii RjCOCI Et,N; iii NaOAc AcOH H,O C,H Scheme 65 J. R. Hwu J. Org. Chem. 1983 48 4432. '25 D. H. R. Barton W. B. Motherwell and S. Z. Zard Tetrahedron Lett. 1983 24 5227. I26 J. Tsuji I. Minami and 1. Shimizu Tetrahedron Lett.. 1983 24 5635 5639. Synthetic Methods A new method has been reported for introducing an acyloxy-group in the a-position of an aldehyde.Conversion of the aldehyde into an N-t-butyl nitrone is followed by acylation on oxygen and (presumed) sigmatropic rearrangement to an acyloxyimine (Scheme 65).12’ Bis(methoxycarbony1)sulphur di-imide (1 3 1 R = COOMe) has been used to introduce nitrogen into allylic positions via ene reaction followed by 2,3-sigmatropic rearrangement (e.g.Scheme 66). Hydrolysis of the initial products (132) to allylic amines is accomplished relatively easily using aqueous base; this is an important advantage with respect to an earlier version employing (131 R = Ts).l2* r Ai Scheme 66 Finally a review has been published on the uses of peroxydisulphate one of the strongest one-electron oxidizing agents available to the organic chemist.129 Reduction.-Hydrogenation of Carbon-Carbon Multiple Bonds. Relatively little has been reported on the stereocontrol of homogeneous hydrogenation by neighbouring polar substituents. Recently two groups have found that hydrogenations with [Ir( cod)PCy,py]PF,” as catalyst may be powerfully directed by a hydroxy-group within the substrate. Thus in a variety of cyclohexenols hydrogen was delivered virtually exclusively cis to the hydroxy-gr~up.’~~~’~’ Another example is shown in Scheme 67,l3’ where the directing effect of the hydroxy-group is capable of reversing the usual preference of indenones such as (133). OH OH 0a 0CD H Reagents i H2 [Ir(cod)PCy,py]PF, CH,C12; ii H,,Pd/C MeOH Scheme 67 I27 C. H. Cummins and R. M. Coates J. Org.Chem. 1983 48 2070. I28 G. Kresze and H. Munsterer J. Org. Chem. 1983 48 3561. I29 F. Minisci A. Citterio and C. Giordano Acc. Chem. Rex 1983 16 27. I3O G. Stork and D. E. Kahne J. Am. Chern. Soc. 1983 105 1072. R. H. Crabtree and M. W. Davis Organornerallics 1983 2 681. *cod = cyclo-octadiene py = pyridine Cy = cyclohexyl 344 A. P. Davis A number of papers deal with the partial reduction of acetylenes. Although Lindlar catalyst (Pd-CaC0,-PbO) is usually employed to convert acetylenes into 2-alkenes it has been found to be only moderately selective. This is particularly so if analytical grade PbO is used and it appears that traces of transition-metal ions improve the performance considerably. MnC12 is reported to be the most effective additive.’32 The reagent system NaBH4-PdC1,-CH2C12-polyethyleneglycol has also been repor- ted to be efficient and convenient for the cis-monohydrogenation of a~ety1enes.I~~ A phase-transfer system consisting of RuCl and methyltrioctylammonium chloride in water-I ,2-dichloroethane is reported to be an unusually powerful hydro- genation catalyst.Only two atmospheres of hydrogen are required to hydrogenate a variety of benzene derivatives in 20 hours at room temperat~re.’~~ Knowles has reviewed concisely the field of asymmetric hydrogenation catalysed by rhodium complexes with chiral ph~sphines.’~~ Hydrogenation of Carbonyl Compounds. As in other additions to carbonyl com-pounds the question of stereofacial selection is of major importance in the reduction of ketones.Where there is an asymmetric centre adjacent to the carbonyl group the stereochemistry of attack by hydride reducing agents can generally be understood by invoking the Felkin-Anh reinterpretation of Cram’s rule. The transition state is supposed to result from nucleophilic attack on the substrate as represented in (134) (L = large M = medium S = small substituents). Recently Houk and co-workers have provided further support for this by calculating the preferred geometry of attack by hydride ion on propene. They have also calculated the geometry of attack by borane an electrophilic reagent finding the same conformation about the C-2-C-3 bond of the propene but a rather different line of approach (see structure 135).’36 -I1 R,B-H L H L The latter result aids the rationalization of some ‘anti-Cram’ stereochemistries observed in alkene hydroborations assuming (136 X = CR2) to be the preferred reaction geometry.* It also suggests that boranes might be capable of reducing ketones in an anti-Cram fashion as in (136 X = 0),and it has indeed been found by Midland and Kwon that reduction of a 20-ketosteroid with hindered boranes gives good selectivity for the anti-Cram product (Scheme 68).137 Reduction with hindered borohydrides gave the opposite result as expected.‘32 J. Rajaram A. P. S. Narula H. P. S. Chawla and S. Dev Terrnhedron 1983 39 2315. ‘33 N. Suzuki T. Tsukanaka T. Nomoto Y. Ayaguchi and Y. Izawa J. Chem. Soc. Chem. Commun. 1983 515. 134 J. Blum I. Amer A. Zoran and Y.Sasson Tetrahedron Lett. 1983 24 4139. 13’ W. S. Knowles Acc. Chem. Res. 1983 16 106. I36 M. N. Paddon-Row N. G. Rondan and K. N. Houk J. Am. Chem. Soc. 1982 104 7162. 137 M.M. Midland and Y. C. Kwon J. Am. Chem. Soc. 1983 105 3725. * Examples are discussed on p. 349. Synthetic Methods 10 I anti-Cram Cram Reagent i disiamylborane Scheme 68 The stereochemistry of hydride reduction of a-hydroxy-ketones of type ( 137) can generally be predicted by assuming attack on the less-hindered face of a metal chelate to give predominantly erythro-diols (138) (Scheme 69). Recently it has been reported that zinc borohydride is particularly selective for this transformation giving erythro-threo ratios of 6 or better in most of the examples studied.The reverse stereochemistry could be attained by t-butyldiphenylsilylation of the hydroxy-group and reduction with sodium bis(2-methoxyethoxy)aluminiumhydride ; this result is consistent with the Felkin-Anh model if the silyloxy group is the largest a-substit~ent.'~~ There have been a large number of publications on the enantioselective reduction of ketones. The most popular substrate for testing the various methods is aceto- phenone. Reduction to give R-1-phenylethanol occurs in (a) 87% e.e. with diphenyl- silane and a catalyst comprising [(cod)RhCl] and (139),'39 (b) 94% e.e. with a complex derived from borane and amino-alcohol ( 140),140 and (c) 84% e.e. with the borane-amine complex ( 141).14' 00 (139) \/ R /\ NHMe HO/\j\/NHPh ""c ( 142) (141) NO I 3n T.Nakata T. Tanaka and T. Oishi Tetrahedron Lert. 1983 24 2653. I39 H. Brunner G. Riepl and H. Weitzer Angew. Chem. Int. Ed. EngL 1983 22 331. 140 S. Itsuno K. Ito A. Hirao and S. Nakahama J. Chem. SOC.,Chem. Commun. 1983 469. 141 H. Suda S. Kanoh N. Umeda T. Nakajo and M. Motoi Tetrahedron Lerr. 1983 24 1513. 346 A. P. Davis The boranes derived from 9-borabicyclononane and (+) or (-)-a-pinene are well established as reagents for asymmetric reductions. Their use has now been extended to a-halogenoketones making chiral halogenohydrins available.14* Modification of LiAlH4 with the diaminoalcohol (142) gives a reagent which was earlier reported to reduce alkyl phenyl ketones enantioselectively. It has now been applied to a,P-unsaturated ketones; the results are variable but a remarkable 100% e.e.is reported for the reduction of ~yclohex-2-enone.'~~ Rather than use a chiral reagent an alternative strategy for enantioselective reduction is to place a removable chiral auxiliary in the substrate. Two such examples are shown in Schemes 70 and 71. In the former the final product (143) was formed in 95% e.e.144 In the latter the reduction of the mixture of ketones (144) gave (145) in 98% diastereomeric purity. It was presumed that the basic conditions allowed equilibration of the diastereomers of (144) and that one of them was reduced stereoselectively much faster than the Reagents i (-)-( 2&4R)-2,4-pentanediol MeC6H4S0,H ;ii AIBr,H ;iii DMSO oxayl chloride; iv K,CO, MeOH Scheme 70 3AT SAr SAr H Ar = p-MeC,H (144) (145) Reagents i NaH PhC02Et; ii NaBH, MeOH c.NH aq.; iii py Ac,O; iv CuCI, AcOH Scheme 71 Among the chemoselective carbonyl reductions reported pyridine-borane ad-sorbed on alumina seems to be a convenient method for the reduction of aldehydes in the presence of ketones,'46 and LiBH in diglyme-methanol reduces amides to amines in the presence of carboxylate Finally the use of enzymes to perform selective carbonyl reductions is dependant in practice on the availability of methods for regenerating the cofactors consumed most usually NADH.Methods have now been developed for introducing deuterium '42 H.C. Brown and G. G. Pai J. Org. Chem. 1983 48 1784. I43 T. Sato Y. Gotoh Y.Wakabayashi and T. Fujisawa Tetrahedron Lett. 1983 24 4123. '44 A. Mori J. Fujiwara K. Maruoka and H. Yamamoto Tetrahedron Lert. 1983 24 4581. 14' K. Ogura M. Fujita T. Inaba K. Takahashi and H. Iida Tetrahedron Lett. 1983 24 503. 146 J. H. Babler and S. J. Sarussi J. Org. Chem. 1983 48 4416. 147 K. Soai A. Ookawa and H. Hayashi .I. Chem. SOC.,Chem. Commun. 1983 668. Synthetic Methods into these systems facilitating the synthesis of a variety of specifically deuterated corn pound^.'^^ Other Reductions. Brown and co-workers have published detailed studies of the reduction of alkyl halides and epoxides by lithium triethylboride an exceptionally powerful hydride donor.149 Vinyl sulphones can be hydrogenolysed with retention of stereochemistry by Grignard reagents with nickel or palladium salts as catalyst^.'^' The use of sodium hydride-sodium alkoxide-metal salt systems as reducing agents has been reviewed.' 51 Non-Redox Conversions.-Substitution at sp3-Hybridized Carbon.In the absence of chelating effects acid-catalysed epoxide ring-opening reactions are understood to occur usually at the carbon remote from an electronegative substituent. The reaction of the chiral benzyloxyoxirane ( 146') with acetone does not conform to this generaliz- ation. The acetonide (147) is formed with the absolute stereochemistry as shown implying nucleophilic attack of the carbonyl oxygen at the epoxide carbon adjacent to the alkoxy substituent (Scheme 72).'52 Reagent i acetone BF,-Et20 Scheme 72 Monosubstituted epoxides react with stannyl compounds Me3SnX (X= NR2 OR C1 or I) to give specifically the stannoxanes (148) derived from cleavage at the substituted carbon.The stannyl group can be removed by treatment with malonic Methods for the cleavage of ethers in general have been reviewed.'54 Ether synthesis cannot generally be accomplished by simply reacting alkyl bromides and alcohols. A convenient way of promoting the reaction is by adding mercuric oxide and tetrafluoroboric acid to the mixture.155 Macrolide formation via cyclization of w -bromocarboxylic acid anions requires high dilution like most macrocyclizations. An elegant way of achieving this is to I48 C.-H. Wong and G. M. Whitesides J. Am. Chem. SOC.,1983 105 5012. I49 S.Krishnamurthy and H. C. Brown J. Org. Chem. 1983 48 3085; H. C. Brown S. Narasimhan and V. Somayaji ibid 1983 48 3091. Is' J.-L. Fabre and M. Julia Tetrahedron Lett. 1983 24 4311. P. Canbire Angew. Chem. Int. Ed. Engl. 1983 22 599. I52 E. W. Colvin A. D. Robertson and S. Wakharkar J. Chem. SOC.,Chem. Commun. 1983 313. '53 M. Fiorenza A. Ricci M. Taddei and D. Tassi Synthesis 1983 640. IS4 M. V. Bhatt and S. U. Kulkarni Synrhesis 1983 249. I55 J. Harluenga L. Alonso-Cires P. J. Campos and G. Asensio Svnthesis 1983 53. 348 A. P. Davis suspend the acid salt in a non-polar solvent and solubilize a small proportion of it using a phase-transfer ~ata1yst.l~~ Substitution at sp2-Hybridized Carbon. An extremely powerful acetylating system has been reported comprising acetic anhydride and chlorotrimethylsilane.Tertiary alcohols are acylated and methyl and methylthiomethyl ethers are cleaved.’’’ Benzoyl triflate is a similarly powerful benzoylating agent; tertiary alcohols are acylated and acetals are cleaved.’’* The use of 4-dialkylaminopyridines to catalyse acylations (and certain alkylations) has been reviewed.Is9 Reagents i Amberlyst A-21 resin; ii MeONa MeOH reflux Scheme 73 Two new methods for cleaving amides have been introduced. 174-Dichloro- 1,4- dimethoxybutane (149) reacts with primary amides to give pyrroles (150) which are subject to attack by a variety of nucleophiles (e.g. Scheme 73).I6O Secondary amides may be derivatized with di-t-butyl dicarbonate then cleaved with lithium hydroxide in THF or sodium methoxide in methanol (e.g.Scheme 74).161 The steric influence of the t-butyl group in intermediates such as (151) directs nucleophilic attack away from the carbamate carbonyl.Reagents i (tBu‘O,C),O Et,N 4-N,N-dimethylaminopyridine; ii NaOMe MeOH Scheme 74 Addition to C -C Multiple Bonds. The stereoselective hydroboration of chiral acyclic alkenes has played an important role in a number of major syntheses. When the asymmetric centre directing the reaction is in an allylic position it is reasonable to describe the modes of addition as ‘Cram’ or ‘anti-Cram’ as in the analogous carbonyl additions. Although the situation is complicated by the variety of olefinic substitution patterns possible evidence is emerging of a general tendency towards the anti-Cram I56 Y.Kimura and S. L. Regen J. Org. Chem. 1983 48 1533. Is’ N. C. Barua R. P. Sharma and J. N. Baruah Tetrahedron Lett. 1983 24 1189. 158 M. Koreeda and L. Brown J. Chem. SOC.,Chem. Commun. 1983 1113. 159 E. F. Scriven Chem. SOC.Rev. 1983 12 129. I60 S. D. Lee M. A. Brook and T. H. Chan Tetrahedron Lett. 1983 24 1569. 161 D. L. Flynn R. E. Zelle and P. A. Grieco J. Org. Chem. 1983 48 2424. Synthetic Methods stereochemistry in hydroboration. As mentioned earlier this can be rationalized with the aid of Houk's calculation^,'^^ which suggest a geometry of attack as in (136 X = CR,). A particularly clear example described by Midland and Kwon is shown in Scheme 75.13' 54 1 Reagents i bis( trans-2-methylcyc1ohexyl)borane; ii oxidation Scheme 75 A study of the stereoselective hydroboration of allylic alcohols and derivatives (152) may be rationalized in the same way assuming that the OR group is the 'medium' substituent.Bulky boranes such as thexylborane or 9-borabicyclononane were the most selective giving diols and derivatives ( 153) with diastereoselectivity >10 1 in many cases.'62 R1+rR3 OR R2 ( 152) A new method for placing two selected alkyl groups on boron follows the sequence shown in Scheme 76. In an earlier procedure the borane-phosphine complex (154) had been used to hydroborate two molecules of alkene. The present modification employs a phenol to consume one of the active hydrogens in (154) so that only one remains for the subsequent hydr~boration.'~~ H I J;" Ar R3 R' 'C I Ar Ar = 2,4,6-trimethylphenyl Reagents i BH,.THF; ii heat; iii ArOH; iv R2HC=CR3R4 MeI; v C1,CHOMe; vi LiOCEt,; vii H20Z NaOH Scheme 76 I62 W.C. Still and J. C. Barrish J. Am. Chem. SOC.,1983,105,2487. I63 H. J. Bestmann and T. Roder Angew. C'bem. Int. Ed. Engl. 1983,22,782. 350 A. P. Davis Dimesitylborane is reported to be a highly selective hydroborating agent. It reacts very much faster with alkynes than alkenes and shows excellent regioselectivity in its additions to unsymmetrical alkynes.I6" Miscellaneous. Ene reactions of carbon-nitrogen double bonds are relatively rare. Scheme 77 shows an intramolecular example which may have applications in alkaloid synthesis.'65 OEt OEt Reagent i flash pyrolysis at ru.440 "C Scheme 77 A method for differentiating between two carbonyl groups in a molecule has been described by Kuwajima and co-workers. After formation of the bis(sily1 enol ether) desilylation with Bu3SnF catalysed by a palladium complex occurs highly selectively at the less-hindered position. An example is the formation of (156) from (I 55) in 91 '!o yield (Scheme 78).166 OSiMc I Reagent i Bu,SnF PdClz [P(o-MPC,H,),]~ Scheme 78 The combination of triphenylphosphine and carbon tetrachloride is well-estab- lished as a convenient and mild reagent for dehydrations and hydroxy-halogen exchanges. Replacement of the carbon tetrachloride with hexabromoethane or 1,2-dibromotetrachloroethane is reported to increase the potency of the system considerably.Secondary formamides are converted into isonitriles primary amides into nitriles and ureas into carbodi-imides in less than a minute at 0 OC.I6' There is a long history of interest in reaction sequences which effect [1,2]carbonyl transposition. The area has been reviewed quite comprehensively by Kane et Finally lack of space prohibits a serious consideration of advances in the use of protecting groups but a paper concerning carboxylic acid protection should be mentioned. Bridged orthoesters ( 158) are useful masked carboxy-groups being stable to strongly basic conditions but readily hydrolysed by acid. Previously they I64 A. Pelter S. Singaram and H. c'. Brown Tetrahedron Lett.1983 24 1433. 165 K. Koch J.-M. Lin,,and F. W. Fowler Terrahedron Lett. 1983 24 1581. I66 H. Urabe Y. Tanako and I. Kuwajima J. Am. Chem. SOC.,1983 105 5703. I67 G. Bringmann and S. Schneider Synthesis 1983 139. t 68 V. V. Kane V. Singh A. Martin and D. L. Doyle Tetrahedron 1983 39 345 Synthetic Methods 35 1 could not be made simply and directly from carboxylic acids but this problem has now been solved by Corey and Raju (Scheme 79). The rearrangement of the intermediate esters (157) is presumably promoted by angle strain in the oxetane ring. Reagents i RCOCI pyridine CH,CI,; ii BF,.Et,O CH,CI Scheme 79 I hY E. J. Corey and N. Raju Terruhedron L.ett. 1983 24 5571.

ISSN:0069-3030    

DOI:10.1039/OC9838000307

出版商:RSC    

年代:1983

数据来源: RSC

摘要:

14 Host-Guest Chemistry By J. F. STODDART Department of Chemistry The University Sheffield 53 7HF 1 Introduction This is the first occasion on which this field has been the subject of a Report. The level of current research activity is such that the reviewer has decided in the limited space available to highlight some of the contributions that have appeared in the literature during the past twelve months making reference to earlier publications only where they are appropriate in the context of the recently published results. For the sake of convenience the discussion of molecular inclusion phenomena will be presented in Sections on crown ethers and cryptands cavitands cyclodextrins clathrates and other miscellaneous hosts. First of all however a few brief comments on the historical and general background to this rapidly developing field will be made.2 Historical and General Background Although clathrates and cyclodextrins have been the subjects of active research investigations for many decades now there is little doubt that the arrival in 1967 of the so-called crown ethers’ on the scene as readily available synthetic molecular receptors provided the timely fillip for the rapid development of supramolecular chemistry. Following immediately on the heels of Pedersen’s accidental discovery,* significant early contributions were made by Lehn3 and Cram.4 It was soon apparent that a relatively new area of chemistry which straddles the sub-disciplines of the subject in an immensely challenging manner for the active research investigator was beginning to emerge.Some5 recognized immediately a rosy future for synthetic molecular receptors as enzyme mimics and analogues ;others6 reacted to the euphoria with notes of caution. For a number of years now international conferences covering all aspects of host-guest chemistry have been commonplace and 1983 saw the launch of a specialist journal.’ A number of reviews have also appeared during this year; they include a general review of inclusion compounds,8 focusing on the past ‘ C. J. Pedersen J. Am. Chern. Soc. 1967 89 2495 7017. ’C. J. Pedersen Aldrichirn. Acta 1971 4 I. J.-M. Lehn Struct. Bonding (Berlin) 1973 16 1. D. J. Cram Science 1974 183 803. Lord Todd Chern. Ind. (London) ICZ at 50 Suppl. 1967 31; Chern.Ind. (London) 1981 317; C. J. Suckling and H. C. S. Wood Chern. Br. 1979 15 243. M. L. Sinnott Chern. Br. 1979 15 293 P. L. Luisi Naturwissenschafren 1979 66 498. ’ Journal of Inclusion Phenomena 1983 Volume 1 No. 1 ed. J. L. Atwood and J. E. D. Davies published by Reidel Dordrecht Holland. J. E. D. Davies W. Kemula H. M. Powell and N. 0. Smith J. Incl. Phenorn. 1983 1 3. 353 354 J. F. Stoddart present and future a highly readable and contemporary account of abiotic recep- tor~,~ accounts of the relevant literature on crown ethers as enzyme analogues’” and of receptor molecules that form molecular complexes with anions ’ authoritative reviews on cavitands,’* calixarene~,’~ and synthetic macrocyclic carbonyl com-pound~’~ as structural models of the naturally occurring ionophores and a compre- hensive account of the synthesis of chemically modified cyclodextrins,” as well as reviews on their development as enzyme models by leadersi6.” in the field.3 Nomenclature Not surprisingly in a developing subject new and loose terminology abounds. A proposal for the classification and nomenclature of host-guest-type compounds has been put forward.18 In this review it would be futile to try to be too precise with terms and names; indeed it will even be useful to employ a number of well recognized abbreviations in referring to the trivial names of some compounds. For the common crown ethers such as 15-crown-5 18-crown-6 etc. it will be useful to refer to them as 15C5 18C6 erc. The letters B DB CH and DCH preceding the macrocycle descriptor will stand for fused benzo dibenzo cyclohexano and dicyclohexano respectively.The well known trivial nomenclature system employed with macrobicyc- lic compounds e.g. [2.2.2]cryptand will also be used. Additionally cyclotriveratry- lene and cyclodextrin will be identified as CTV and CD respectively. The Group IA and IIA metal cations will be referred to as M+ and M2+ ions respectively. 4 Crown Ethers (Chorands) and Cryptands The interaction of polyethers and crown ethers (12C4 15C5 and 18C6) with the smallest cation i.e. H+ has been examined” by thermochemistry in the gas phase. It was found that in the smallest compounds (e.g. MeOCH,CH,OMe) the stabiliz- ation is small whereas in the larger ones [e.g.Me(OCH,CH,),OMe and the crowns] the hydrogen bond approaches its full intermolecular strength. Similar measurements of enthalpy and entropy changes for complex dissociation reactions of RNH3+ (R = Me or cyclo-C,H ,) with polyethers and crown ethers reveal” that multiple [N-H+...O] bonding can contribute up to 18 kcal mol-’ to the bonding in RNH3+.Me(OCH,CH2),OMe and 2 I kcal mol-’ in RNH3+. 18C6. Large negative entropies with RNH,+.acyclic polyether complexes compared with RNH,+.crown ether complexes also render the former less efficient ligands. R. C. Hayward Chem. Soc. Rev. 1983 12 285. 10 J. F. Stoddart in ‘The Chemistry of Enzyme Action,’ ed. M. I. Page Elsevier Amsterdam 1984 p. 529. J.-L. Pierre and P. Baret Bull. SOC.Chim. Fr. IZ 1983 367. l2 D.J. Cram Science 1983 219 1177. l3 C. D. Gutsche Acc. Chem. Rex 1983 16 161. l4 A. Shanzer Bull. Soc. Chim. Belg. 1983,92,41I ;A. Shanzer J. Libman and F. Frolow Acc. Chem. Rex 1983 16 60. I5 A. P. Croft and R. A. Bartsch Tetrahedron 1983 39 1417. l6 R. Breslow Chem. Br. 1983 19 126. M. Komiyama and M. L. Bender in ‘The Chemistry of Enzyme Action’ ed. M. I. Page Elsevier Amsterdam 1984 p. 505. ’* E. Weber and H.-P. Josel J. Incl. Phenom. 1983 1 79. I9 M. (Mautner) Meot-Ner J. Am. Chem. Soc. 1983 105 4906. 20 M. (Mautner) Meot-Ner J. Am. Chem. Soc. 1983 105 4912. Host-Guest Chemistry 355 Molecular mechanics calculations had been carried out previously" on 18C6 and its M' ion complexes using X-ray co-ordinates as input geometries.Two additional approaches have now been rec~mmended.'~?~~ One uses the distant matrix to generate a set of Cartesian co-ordinates that satisfy the original set of distances -the so-called distance geometry method.22 It turns out to be a powerful method and when applied to 18C6 predicted an additional low-energy conformation (C:)to the previously identified D3d and C structures. This could explain the observed dipole moment of ca. 1 D for 18C6 and its temperature dependence. The Table present^'^ relative Table Relative total energies (kcal mol-') of 18C6 Conforma tion D d c c c2 c Uncomplexed 11 0.0 3.0 11.6 9.4 Na' Complex 31 26.1 9.1 11.9 0.0 K+ Complex 00 15.1 12.0 12.3 7.1 total energies for five conformations of 18C6 as its Na+ and K+ ion complexes as well as in its uncomplexed state.In a low dielectric constant solvent the C conformation found in the crystal is preferred; in more polar environments (e.g. polar solvents and in complexes with cations and neutral molecules) the D, conformation is preferred. The other approach23 involves identifying all the ideal crown ether rings on the diamond lattice. The lowest-energy conformation of 24C8 is predicted to be ag'a ag+a ag-a ag-a ag+a ag+a ag-a ag-a. Molecular mechanics calculations on the [2.2.2]cryptand reveal24 that the out-out isomer is only 6 kcal- mol-' higher in energy than the in-in isomer observed in the solid state. U.V. photoelectron spectroscopy has been used25 to measure the valence shell ionization potentials of ligands including 12C4 15C5 18C6 CH 14C4 B14C4 B 15C5 and DBI 8C6 and [2.2.1]- and [2.2.2]-cryptands.Appreciable heteroatom lone-pair orbital interactions produce relatively high energy HOMOS and so render chorands and cryptands softer ligands than the corresponding open-chain com- pounds. This has consequences for the complexation of hard guests in particular. The oxymethylene hexamer has been isolated26 as crystals containing the [(CH20)6Ag2]2+ cation from the reaction of (CH20)3 with AgAsF,. The X-ray structural analysis' indicates that the two Ag+ ions each co-ordinate to alternate oxygens in the twelve-membered ring macrocycle which possesses approximate D311 symmetry. The X-ray crystal structures of B13C4.LiSCN and DBI4C4.LiSCN reveal2' that in both cases the Li+ ion is penta-co-ordinated to the four oxygens and to the nitrogen of the SCN-ion.The CH-bis-1 5C5 (1) forms28 2 :2 complexes in '' M. J. Bovill D. J. Chadwick I. 0. Sutherland and D. Watkin J. Chem. Soc. Perkin Trans. 2 1980 1529; G. Wipff P. K. Weiner and P. A. Kollman J. Am. Chem. Soc. 1982 104 3249. I2 P. K. Weiner S. Profeta jun. G. Wipff T. Havel 1. D. Kuntz R. Langridge and P. A. Kollman Tefrohedron 1983 39 1 113. 23 J. W. H. M. Uiterwijk S. Harkema B. W. van de Waal F. Gobel and H.T. M. Nibbeling J. Chem. Soc. Perkin Trans. 2 1983. 1843. '' G. Wipff P. A. Kollman and J.-M. Lehn J. Mml. Siruci. 1983 93 153. 2s A. D. Baker G. H. Armen and S. Funaro J. Chem. SOC.,Dalton Trans. 1983 2519. 26 H. W. Roesky E. Peymann J. Schimowiak M.Noltemeyer W. Pinkert and G. M. Sheldrick J. Chem. Soc. Chem. Commun. 1983 981. '' G. Shoham W. N. Lipscomb and U. Olsher J. Am. Chem. Soc. 1983 105 1247; J. Chem. SOC.,Chem. Commun. 1983 208. 2x J. D. Owen J. Chem. Soc. Perkin Trans. 2 1983 407. 356 J. F. Stoddart the solid state with KSCN Ba(SCN),.2H20 and NH4SCN such that the cations are sandwiched between 15C5 rings of two molecules of (I). X-Ray crystallography of the 1 :1 complexes reveals29 that the linear [TlMe,]' ion is threaded through the rings of DB18C6 and DCH 18C6 (cis-cisoid-cis-and cis-transoid-cis-isomers). In the Mg(C10,),.H20 complex with the [3.2.2]cryptand (2) the Mg2+ ion is co-ordinated3' to H20 as well as to the seven oxygens of (2). The crystal structures of the KSCN complex with the cyclic heptamer3' of acetonitrile oxide and of the hexathia analogue of 18C6 both free3 and complexed to have been reported.Hexathia-18C6 has both endo and ex0 dentate sulphurs; in the Nil' complex the ligand is co-ordinated to the metal ion octahedrally. H 18C6 and 12C4 have found34 a novel use in CI mass spectrometry. When N-H- containing sample (S) compounds (e.g. an amide amino-acid purine or pyrimidine) are mixed with the crown ether (C) abundant [C + H + S]+ ions are observed on account of strong intramolecular hydrogen bonding. 13 C N.m.r. T values for the tetra-aza-12C4 derivative (3) and its complexes with M+ and M2+ ions have been measured35 in CDCI3 CD,N02 CD30D and DzO. The side arms show varying degrees of internal motion depending on the nature of the cation (e.g.Ca2' binds all four arms) and of the solvent. C.d. studies on three isomeric dimethyl-B 15C5 derivatives (4)-(6) (synthesized from ethyl L-lactate) and their complexes with M+ and M2+ ions in MeOH have been carried Analysis of the spectra leads to conformational assignments to the macrocyclic rings when (4) and (5) are free and when (4)-(6) are complexed with Na+ ions. A Li' ion template effect has been claimed3' in the synthesis of DB14C4 (and meta-substituted derivatives) and Na+ ions have been useful in directing cyclic-oligomer formation towards 18- rather than 12-membered rings in macrocycles 29 J. Crowder K. Hendrick R.W. Mathews and B. Podejma J. Chem. Res. (S) 1983 82; D. L. Hughes and M.R.Truter Acta Crystallogr. 1983 B39 329. 30 J. D. Owen Acra Crystallogr. 1983 C39 579. 3' G. Casini F. de Sarlo D. Donati A. Guarna and P. Orioli J. Chem. Rex (S) 1983 2. 32 J. R.Hartman. R.E. Wolf B. M. Foxman and S. R. Cooper J. Am. Chem. Soc. 1983 105 131. 33 E. J. Hintsa J. R. Hartman and S. R.Cooper J. Am. Chem. Soc. 1983 105 3738. 34 A. K. Bose 0.Prakash G. Y. Hu and J. Edasery J. Org. Chem. 1983 48 1780. 35 D. S. B. Grace and J. Krane 1. Chem. Res. (S) 1983 162. 36 M. P. Mack R.R.Hedrixson R. A. Palmer and R.G. Ghirardelli J. Org. Chem. 1983 48 2029. 37 C. S. Chen S. J. Wang and S. C. Wu J. Heterocycl. Chem. 1983 20 795. 38 F. Vogtle and F. Ley Chem. Ber. 1983 116 3000. 357 Host-Guest Chemistry 5' R' -=r HO i033 0 R' HO OH R2 (3) (4) R' = Me;R2 = R3 = H (5) R2 = Me;R' = R3= H (6) R3 = Me;R' = R2 = H containing pyridyl units.M' and M2' ions39 exert a remarkable catalytic effect on the cyclization of o-hydroxypheny1-3,6,9,12-tetraoxa-14-bromotetradecyl ether (ArOH) to B18C6. However the proximity effect brought about by templating is tempered by a rate-retarding factor arising from interaction of the ArO- ion with the metal cation. Much interest continues to surround the synthesis and complexing properties of the so-called lariat ether^.^"^' Derivatives (7) containing a methyl group at the quaternary pivot carbon atom have been prepared42 from methallyl chloride and shown to bind Na+ ions better than the non-methylated species. Enhanced Na' ion binding by electrochemically reduced nitrobenzene-substituted derivatives (8) has also been observed.43 This represents a new switching mechanism for lariat ether complexes.A number of facile syntheses of hydroxymethyl and substituted-hydroxy- methyl chorands have been reported.@ In some of these epichlorohydrin and the commercially available allylglycidyl ether are key starting materials. Similar synthetic approaches have been employed in the preparation of hydr~xy-,~~ dihydr~xydiaza-,~~ (7) R' = Me; Y = 0 NH or S; R2 = Alkyl or (CH2CH20),,Me (8) R' = H;Y = 0; R2 = 0-or p-N02C,H 3Y G. Illuminati L. Mandolini and B. Masci J. Am. Chem. SOC.,1983 105 555; 6146; cf L. Mandolini and B. Masci ibid. 1984 106 168. 40 G. W.Gokel D. M. Dishong and C. J. Diamond J. Chem. SOC.,Chem. Commun. 1980 1053. 4' D. M. Dishong C. J. Diamond M. I. Cinoman and G. W. Gokel J. Am. Chem. SOC.,1983 105 586. 42 Y. Nakatsuji T. Nakamura M. Okahara D. M. Dishong and G. W. Gokel J. Org. Chem. 1983,48 1237. 43 A. Kaifer L. Echegoyen D. A. Gustowski D. M. Goli and G. W. Gokel J. Am. Chem. SOC.,1983 105 7168. 44 1. Ikeda H. Emura and M. Okahara Synthesis 1984,73; S. J. Jungk J. A. Moore and R. D. Gandour J. Org. Chem. 1983,48 1116; B. Czech A. Czech and R. A. Bartsch Tetrahedron Lerr. 1983,24 1327; B. Czech S. I. Kang and R. A. Bartsch ibid. p. 457; B. Czech B. Son and R. A. Bartsch ibid. p. 2923; K. Kimura H. Tamura and T. Shono .\. Chem. SOC.,Chem. Commun. 1983,492. 45 R. A. Bartsch Y. Liu S.I. Kang B. Son G. S. Heo P. G. Hipes and L.J. Bills J. Org. Chem. 1983 48 4864. 46 T. Kikui H. Maeda Y. Nakatsuji and M. Okahara Synrhesis 1984 74. 358 J. F. Stoddart (9) n = 0 or 1 ono c3 0 R'-N N-R2 c,LJ OJ (1 1) R' = R2 = CH2CH20H (10) R = H Me Et or C,H,,; (12) R' = R2 = CH2C02H m = 0-2; n = 1 or 2 (13) R' = Me(CH,),,CO; R2 = CH2CH,C02H (14) R' = RZ= CH,OMe and bi~(aminomethy1)~' crown ethers e.g. (9) and (10). The 1 ,lo-diaza- 18C6 constitu- tion has been a much studied one of late. Recently an X-ray crystal structure of a Na+ ion complex of the N,N'-bis-(2-hydroxyethyl)derivative (1 I) has demon- ~trated~~ the involvement of both side arms in cation binding. Although weaker binders of M' and M2+ ions than the related cryptand these nitrogen pivot lariat ethers have the attractions of being dynamically much better complexers.Two applications of this property are worthy of special mention. Bis(carboxy-methyl)diaza-l8C6 (12) is a highly efficient solubilizer of BaSO in water and could find applications in the de-scaling of oil-wells in the Noith Sea.49 The anion-capped diaza- 18C6 derivative (13) exhibid' both proton-driven ion-transport and M2+-assisted transport of RCH(C02-)NH2 ions. The latter has intriguing possibilities and the former is characterized by a pH-rate profile with a maximum at ca. pH 5. This is rationalized in terms of enforced ion release by protonatinn of the ring nitrogen and the highly lipophilic nature of the zwitterion at pH 5. In passing it should be mentioned that the N,N'-bis(methoxymethy1) derivative ( 14) is a reactive aminomethylating reagent.5' A wide range of acyclic polyethers chorands and spiro crown ethers have been synthesized by standard procedures starting from 2-alkoxypropane- I ,3-di0ls,~~ from 47 H.Maeda T. Kikui Y. Nakatsuji and M. Okahara Synrhesis 1983 185. 48 F. R. Fronczek V. J. Gatto R. A. Schultz S. J. Jungk W. J. Colucci R. D. Gandour and G. W. Gokel J. Am. Chem. Soc. 1983 105 6717. 49 F. de Jong A. van Zon D. N. Reinhoudt G. J. Torny and H. P. M. Tomassen Red. J. R. Neth. Chem. SOC.,1983 102 164. SO S Shinkia H. Kinda Y. Araragi and 0.Manabe Bull. Chem. SOC.Jpn. 1983 56 559; cf Y. Nakatsuji H. Kobayashi and M. Okahara J. Chem. SOC.,Chem. Commun.1983 800. 5' A. V. Bogatsky N. G. Lukyanenko V. N. Pastushok and R. G. Kostyanovsky Synthesis 1983 992. 52 J. Skarzewski and J. MXochowski Terrahedron 1983 39 309. Host- Guest Chemistry 359 1,1,1-(trishydr~xymethyl)ethane,~". The 20C6 derivative and from pentaerythrit~l.~~ (15) and related compounds behave55 in aqueous solutions as surfactants exhibiting micelle formation and cloud points. (15) R = n-C,,H, (16) n = 1-5 The crown ether acetals (16) have been prepared56 from MeCHO and the corre- sponding diols ; the rate of acid-catalysed hydrolysis of (1 6) in dioxan-water is decreased5' markedly by the addition of M' and M2+ ions of the appropriate size to be complexed by (16). Presumably electrostatic repulsion between M+/M2+ ions and the proton added to the acetal in the first step of the hydrolysis is the reason for this effect.Many crown ether derivatives incorporating a range of different units (e.g. pipera~ine,~'"i~oxazole,~~~ etc.) have been prepared by pre~ocene,~'' b~lvalene,~~~ Williamson-type syntheses. The derivative (17) binds59 Ag+ ions as a result of wparticipation by the phenylene rings. A number of oligo-oxa derivatives (18) of [3.m]paracyclophanes exhibit6' cation-induced charge-transfer absorption; in the case of (1 8).NaSCN the effect is reversed by [2.2. llcryptand. Intermolecular charge transfer also plays6' an important role in the ability of DB3nCn (n = 9-12) hosts to form stable 1 :1 complexes with the diquat dication in solution (n = 10 > 1I > P' SCN--0 Ol J' dMe (17) (18) .NaSCN 53 W.Offermann and E. Weber Chem. Ber. 1984 117 234. 54 M. Ouchi Y. Inoue H. Sakamoto A. Yamahira M. Yoshinaga and T. Hakushi J. Org. Chem. 1983 48 3 173. 55 E. Weber Liebigs Ann. Chem. 1983 770; cf Angew. Chem. Inr. Ed. Engl. 1983 22 616. 56 V. Gold and C. M. Sghibartz J. Chem. SOC.,Perkin Trans. 1 1983 453. 57 D. S. Baker V. Gold and C. M. Sghibartz J. Chem. SOC.,Perkin Trans. 2 1983 1121. 58 (a) R. Chinevert and R. Piante Synthesis 1983 847; (6) S. Auricchio S. Briickner L. Malpezzi and 0.Vajna de Pava J. Chem. Res. (S) 1983 112; (c) F. Camps J. Coil and S. Ricart J. Heterocycl. Chem. 1983 20 249; (d) K. Sarma W. Witt and G. Schroder Chem. Ber. 1983 116 3800. 59 R. Leppkes and F.Vogtle Chem. Ber. 1983 116 215. 60 H. Bauer J. Briaire and H. A. Staab Angew. Chem. Inr. Ed. Engl. 1983 22 334. " H. M. Colquhoun E. P. Goodings J. M. Maud J. F. Stoddart D. J. Williams and J. B. Wolstenholme J. Chem. SOC.,Chem. Commun. 1983 1140. 360 J. F. Stoddart 12 > 9) and in the solid state. Derivatives of 27C9 (ie. B and asyrn-DB) show62 an optimum fit for encapsulation of the guanidinium cation by relying upon six [N(+'-H. -.O] bonds and three -01interactions. The complexing abilities of "'+'a several 18C6 and 20C6 chorands towards Mf and RNH3+ ions have been qualita- tively ~orrelated~~ with the degree of preorganization of the binding sites. It has been possible64 to extend the range of polyether-diester compounds [e.g.(1 9)] by reacting oligoethyleneglycols with appropriate esters (e.g.dimethyl pyridine- 2,6-dicarboxylate) in the presence of catalytic amounts of M' methoxide. The stereoselectivity of binding of a-amino-alcohols towards chiral 9,9'-spirobi- fluorene crown ethers has been and novel chiral chorands [e.g. (M)-(20)] incorporating helicene frameworks have been synthesized;66 (M)-(20) selects the (S)-isomer of (RS)-PhCH(CO,H)NH,+ ions by a factor of 3 I during membrane transport. By contrast in a range of B15C5 derivatives of carbohydrates no enan- tiomeric differentiation in the transport of (RS)-PhCHMeNH3PF was observed." Chiral cryptands [e.g. (2 l)] derived from carbohydrates have been prepared68 in high yield from diaza- 18C6 derivatives by quaternizing them under high pressure and then demethylating (Scheme 1).This novel method of synthesizing cryptands has great appeal given the necessary specialized equipment. Host-guest complexes of 18C6 with neutral molecules (e.g.cyanamide and methyl 4-aminobenzoate) possessing the structural element XH (X = 0 N or C) have been in the solid and solution states ;the best guests have a complementary hydrogen atom arrangement to oxygens in the host hydrogen atoms rmdered acidic by a neighbouring polar group a large dipole moment and a low mass. Larger 67 J. A. A. deBoer J. W. H. M. Uiterwijk J. Geevers S. Harakerna and D. N. Reinhoudt J. Org. Chem. 1983 48 4821. 63 T. W. Bell G. M. Lein H. Nakarnura and D. J. Cram J. Org. Chem. 1983 48 4728. 64 J. S.Bradshaw B. A. Jones R. B. Nielson N. 0. Spencer and P. K. Thompson J. Heterocycl. Chem. 1983 20 957; J. S. Bradshaw N. 0.Spencer G. R. Hansen R. M. Izatt and J. J. Christensen ibid. p. 353. 65 V. Prelog and S. Mutak Helu. Chim. Acta 1983 66 2274. 66 M. Nakazaki K. Yamamoto T. Ikeda T. Kitsuki and Y. Okamoto J. Chem. Soc. Chem. Commun. 1983 787. 67 A. H. Haines. I. Hodgkinson and C. Smith J. Chem. SOC.,Perkin Trans. I 1983 31 I. 68 M. Pietraszkiewicz P. Salanski and J. Jurczak J. Chem. SOC. Chem. Commun. 1983 1184; M. Pietraszkiewicz and J. Jurczak ibid. p. 132. 69 A. Elbasyouny H. J. Brugge K. von Deuten M. Dickel A. Knochel K. U. Koch J. Kopf D. Melzer and G. Rudolph J. Am. Chem. Soc. 1983 105 6568. Host-Guest Chemistry 36 1 Me \_I_A Reagents i O(CH2CH21)2-Me2C0 8 kbar 25 "C ii Ph,P-DMF Scheme 1 chorands some containing pyridyl units form7" complexes with aliphatic alcohols (e.g.MeOH EtOH Pr'OH etc.). Often however the neutral guests are included7' in the crystalline host lattice in the solid state rather than in the host cavity! Interest is rapidly increasing in the various areas of overlap between crown ethers transition metals and organometallic compounds. A one-pot synthesis of some polyoxa[n]ferrocenophanes (22) and their acyclic analogues from 1,l'-diacetoxyfer-rocene has been reported;72 some of the ligands bind TI' ions preferentially. In the conden~ation~~ of 1,l '-bis(chlorocarbony1)ferrocene with I 10-diaza-18C6 at con- centrations well below the effective molarity," temperatures from -20 to 100 "C favour cryptand formation (i.e.monomer) whereas dimer formation is preferred at -70 "C. By careful design of macrocyclic ligands it is possible" to construct cluster cryptates of a desired structure e.g. (23).Rh,(CO), by rational approaches. A phosphine-aza- 15C5 derivative has been synthesi~ed'~ by a modification of the Mannich reaction using Ph,PH HCHO and monoaza-I 5C5. This compound reacts with CpFe(CO),Me to give the acyl complex (24a) thermally and the methyl complex Fe 0 (22) fi = 04 (24a) R = COMe (24b) R = Me 70 E. Weber F. Vogtle H.-P. Josel G. R. Newkome and W. E. hckett Chem. Ber. 1983 116 1906; G. Weber and P. G. Jones Acra Crystallogr. 1983 C39 1577. " F. Vogtle W. M. Miiller H.Puff,and EJ. Friedrichs Chem. Ber. 1983 116 2344. 72 S. Akabori Y. Habat Y. Sakamoto M. Sato and S. Ebine Bull. Cbern. SOC.Jpn. 1983 56 537; S. Akabori M. Ohtomi M. Sato and S. Ebine ibid. p. 1455 1459. 73 P. J. Hammond P. D. Beer and C. D. Hall J. Chem. SOC.,Chem. Commun. 1983 1161. 74 G. IJJumjnati and L. Mandohi Acc. Chern. Rex 1981 14 95. 75 J.-P. Lecomte J.-M. Lehn D. Parker J. Guilhem and C. Pascard J. Chem. SOC.,Chem. Commun. 1983 296. 76 S. J. McLain J. Am. Chem. SOC.,1983 105 6355. 362 J. F. Stoddart (24b) photochemically. Solutions of (24a) and (24b) in CH2C12 produce homogeneous solutions of M+ and M2+salts rapidly. Both the kinetic and thermodynamic stabilities of (24a).NaPF6 relative to (24b).NaPF6 are greater reflecting the contribution of the acyl-Na+ bond to binding.Investigations also continue77 on phosphorus-donor crown ether hybrid ligands as a route to CO activation. A macrocyclic polyether (25) with soft and hard sites side-by-side has been prepared7* from 2,9-diphenyl- 1,lO- phenanthroline (26). This large chorand has also been employed79 in the highly imaginative synthesis (Scheme 2) of a metallo-catenane (27).CuBF4 the excellent yield [42% based on (25)] being the result of a template mechanism. Crown ethers also serve" as second sphere ligands for transition-metal amines e.g. [W(CO)S(NH~>I, trans-[PtC12(PMe,>(NH,)1 trans-[RCl2(NH3)2I [Co(NH&I[PF6I3 [CU(NH~),(H,O)][PF~]~, and [R(H2NCH2CH2NH2)2][PF6]2,in aqueous and non- aqueous solutions uia [N-H.-01bond formation. DB 18C6 affords 1 :1 adducts and 18C6 either 2 :1 (metal complex :crown) or polymeric 1 :1 adducts in the solid state. Such adduct formation provides the basis for a novel method of separating transition metals ;e.g. 18C6 selectively precipitates the Cu" complex as a polymeric 1 :1 adduct in the presence of the Co"' amine. Allosteric effects have been demonstrated in macrobicyclic polyethers*' and in chorands containing 2,2'-bipyridyl residues.82 In (28) Hg(CF3)2 formss2 a rotaxane- type complex with the 22-membered ring; the dissociation of this complex is slowed down by a factor of 7 when PdC12 is bound to the bipyridyl function reflecting the fact that passage of the CF3 group through the ring is impeded when the ring size is decreased.In macrobicyclic polyethers it has been demonstrated" that allosteric co-operativity can arise from purely entropic effects. The simple chemical reaction of Fe3+ oxidation of dithiols to disulphides has been exploiteda3 in the production of 'switched-on' crown ethers. 3,6,9,12-Tetraoxatetradecane-I 14-dithiol and 3,6,9,12,15-pentaoxaheptadecane-1,17-dithiol are pro-ionophores which can be con- verted into analogues of 15C5 and 18C6 on addition of K,Fe(CN),. The disulphide chorands exhibit ionophoric properties. The reversible photoresponsiveness of azobenzenophane-type crown ethers (29) causes them to acts4 as 'switched-on7 77 J. Powell M. Gregg A. Kuksis a3d P. Meindl J. Am. Chem. SOC.,1983 105 1065. 78 C. 0. Dietrich-Buchecker and J.-P.Sauvage Terrahedron Lerr. 1983 24 5091. 79 C. 0. Dietrich-Buchecker J.-P. Sauvage and J. P. Kintzinger Tetrahedron Lett. 1983 24 5095. 80 H. M. Colquhoun D. F. Lewis J. F. Stoddart and D. J. Williams J. Chem. SOC.,Dalton Trans. 1983 607; cf H. M. Colquhoun G. Jones J. M. Maud J. F. Stoddart and D. J. Williams hid. 1984 63. " K. Onan J. Rebek jun. T. Costello and L. Marshall J. Am. Chem. SOC.,1983 105 6759. 82 J. Rebek jun. and L. Marshall J. Am. Chem. Soc.. 1983 105 6668. 83 M. Raban J. Greenblatt and F. Kandil J. Chem. Soc. Chem. Commun. 1983 1409. 84 S. Shinkai T. Minami Y. Kusano and 0. Manabe J. Am. Chem. SOC. 1983 105 1851; S. Shinkai Y. Honda. T. Minami K. Ueda 0. Manabe and M. Tashiro Bull. Chem. SOC.Jpn. 1983 56 1700. Host- Guest Chemistry 0 + N 1-3 a 0-> 0 / 0 x 364 J.F. Stoddart trans-(29) n = 1-3 ~i~-(29) = 1-3 n receptors with an ‘all-or-nothing’ change in M+ ion binding; trans-(29) totally lacks affinity towards M+ ions whereas cis-(29) binds considerable amounts. Very interestingly divinyloxy-compounds [CH2=CHOCH2(CH20CH2).-CH20CH=CH2; n = 1-41 undergo” intramolecular photocycloaddition in the presence of 1,4-dicyanonaphthaIene in benzene to afford cis-and trans- cyclobutano- crown ethers (30) in good (61-80%) yields. H H n n cis-(30) n = 1-4 truns-(30) n = 1 4 18C6 has found use as a solid-liquid phase-transfer catalyst for more than a decade now. Recent examples include its use in the formation of cyanohydrin derivatives,s6 in the Reissert reaction,87 and in the intramolecular Wadsworth- Emmons reaction.88 Employing the dynamic protection procedure of Barrett et uL,~~ hexahydropyrimidine has been acetylated” selectively at the secondary amino function on the ring prior to complexation of the primary amino-group (as its tosylate salt) with an equimolar amount of 18C6 to give N’-acetylspermidine.An evaluation of the dediazoniation kinetics of various meta- and para-substituted benzenediazonium tetrafluoroborates in (CH2C1) at 50 “C in the presence of 18C6 21C7 and DCH 18C6 demonstratesg1 that the rate constant for dediazonation within 85 K. Mizuno T. Hashizume and Y. Otsuji J. Chem. SOC.,Chem. Commun. 1983 977. 86 R. Chhevert R. Plante and N.Voyer Synth. Commun. 1983 13 403. 87 R. ChOnevert E. Lernieux and N. Voyer Synth. Commun. 1983 13 1095. 88 P. A. Aristoff Synth. Commun. 1983 13 145. 89 A. G. M. Barrett and J. C. A. Lana J. Chem. SOC.,Chem. Commun. 1978,471 :A. G. M. Barrett J. C. A. Lana and S. Tograie ibid. 1980 300. 90 C. M. Tice and B. Ganern J. Org. Chem. 1983,48 2106. 91 H. Nakazumi I. Szele K. Yoshida and H. Zollinger Helv. Chim. Acta 1983 66,1721; J. R. Beadle R. J. Khanna and G.W. Gokel J. Org. Chem. 1983,48 1242. Host-Guest Chemistry the complex is smallest and the equilibrium constant for complex formation largest for 21C7. Polyethyleneglycol-grafted copolymers have been shown to be catalysts for dehy- drohalogenation9* and alkylati~n~~ under two- and three-phase conditions.The practical applicability of oligoethers can be improved by supporting them on poly- styrene resins. If the oligomers are terminated94 with rigid donor groups (e.g. 8-quinolyl) their ability to bind M+ and M2+ ions is enhanced and their effectiveness as solid-liquid phase-transfer catalysts similarly improved. Membranes formed95 from esters of hydroxymethyl-12C4 -15C5 and -18C6 with an alternating copoly- mer of ethylene and maleic anhydride function as effective proton-driven M+ ion pumps. Macrocyclic polyamines are excellent potential binders of anions ' ' two significant publications96397 have appeared recently. Hexa-aza- 18C6 as its triprotonated species forms96 stable 1 1 complexes with catechol and many of its biologically important derivatives (e.g.Dopa adrenaline); the proposed binding mode of dopamine with the host is shown in Figure la. A fully protonated hexa-azadioxa-24C8 macrocycle an efficient molecular catalysis of ATP hydrolysis displaying the following characteristics (i) it binds ATP ADP and AMP; (ii) it enhances the rate of ATP hydrolysis by a factor of lo3 at pH 8.5; (iii) the products of the hydrolysis are orthophosphate and ADP; and (iv) the reaction follows first-order kinetics. A possible mode of binding of ATP to the host is shown in Figure Ib; the intracomplex reaction involves a combination of nucleophilic or acid catalysis with electrostatic catalysis. (a) (b) Figure 1 Possible modes of binding of (a) dopamine to triprotonated hexa-aza-18C6 and (b) ATP to protonated hexa-azadioxa-24C8 (X = lone pair or HC) 5 Cavitands Cram has coined the term cavitand to describe hosts with enforced cavities of dimensions matching those of appropriately chosen guest ions atoms or molecules.'* Y. Kimura and S. L. Regen J. Org. Chem. 1983 48 195. 93 Y. Kimura P. Kirszensztejn and S. L. Regen J. Org. Chem. 1983 48 385. 94 J. G. Heffernan and D. C. Sherrington Tetrahedron Letf. 1983 24 1661. 95 K. Kimura H. Sakamoto M. Yoshinaga and T. Shono J. Chem. Soc, Chem. Commun. 1983 978. 96 E. Kimura A. Watanabe and M. Kodama J. Am. Chem. SOC.,1983 105 2063. 97 M. W. Hosseini J.-M. Lehn and M. P. Mertes Helv. Chim. Acm 1983 66 2454. 366 J. F. Stoddart In a highly readable review,12 he has drawn attention to the fact that in enzymes functional groups which act co-operatively and catalytically are held in relative orientations that converge upon substrate binding sites usually located within a cavity.Spherands.-Whereas the flexible chorands and cryptands fill their own cavities when free of guest species and reorganize during complexation spherands such as (31) contain rigid cavities that are organized during their synthesis. Although the anisyl unit is a poor binder of metal ions (31) forms very strong complexes with Li' and Na' ions; it rejects K+ Rb+ Cs+ Mg2+ and Ca2+ ions completely! This amazing complexing ability and the preorganized cavity of (1) is lost98 on substitution two of the anisyl units for methoxycyclohexane units in compound (32).The ye Me (31) (32) [Me* groups pointing inwards] n-ray crystal structure has shown that the two methyl groups on the methoxycyclo- hexyl units are turned inwards such that they fill the cavity Even in the presence of Li' ions the steric barrier to this conformation undergoing the necessary confor- mational change to accommodate the Li' ion was too high to be climbed at 60°C. Scheme 3 which outlines the preparation of compound (32) shows the type of -(32) Reagents i Ni(CO),-DMF; ii Br(CH,),Br-Bu'OK-Bu'OH; iii LiAIH,-THF; iv Mel-NaH-DMF; v Bu"Li-Me2NCHzCH2NMez-Etz0 then CNBr; vi Bu"Li-THF; vii Fe(acac),-THF; viii HzO-MeOH (3:1 v/v) 120 "C 5 days to generate the host from its LiCl complex Scheme 3 'I1 D. J. Cram J. R. Moran E.F. Maverick and K. N. Trueblood J. Chem. Soc. Chem. Commun. 1983 645. Host-Guest Chemistry synthetic approaches that have to be employed in preparing spherands and their derivatives. The existence of an inward-turned methoxy-group has also been ob- served99 in modified hemispherands (33) containing a methoxycyclohexane unit. X-ray crystal structure analyses of (33) and of the complexes (33).NaBPh4.H20 and (33).Bu'NH3C10 reveal that ail three methoxy-groups of (33) must undergo ring inversion before they attain the conformations present in the crystalline complexes. IH N.m.r. spectroscopy reveals that a similar situation exists in solution. Hemi- spherand (34) by contrast behaves as a cavitand in these experiments and expresses its rigid characteristics by forming stronger complexes with M+ and RNH3+ (R = H Me or But) ions than does (33).Cram concludes that (33) should be classed as a chorand rather than as a hemispherand! 'Me Me (33) [Me* group pointing inwards] (34) A hemispherand (35) incorporating three cyclic urea units two anisyl residues and a 3'-hydroxymethyl- 1,l '-biphenyl unit has been synthesized'" as part of an incremental approach to hosts that will mimic serine proteases. By collecting and orienting L-alanine p-nitrophenyl ester cation in CDC13 (35) was acylated ca. 10" times faster than the non-complexing model compound 3-phenylbenzyl alcohol under the same conditions. The much greater rate of reaction of (35) relative to that of the non-complexing model can be interpreted in terms of (35) complexing L-MeCH(CO,C,H,-p- N02)NH3+ in its transition state for transacylation by means of three [N-H*.-O=C] bonds at the binding site (Scheme 4).This places the -CO2C,H,-p-NO carbonyl of the guest perfectly oriented for nucleophilic attack by the -CH20- group on the host. This investigation which was subsequently highlighted in Chem. Eng. News,'o1led to an exchange of opinions in the same quarter" between Breslow and Cram on calculating and interpreting enzymic accelerations. The decomplexation rate constants between Bu'NH3+ ions (as picrate salts) and a series of seven urea hemispherands have been determinedIo3 in CDC13 (saturated with D,O) by dynamic 'H n.m.r. spectroscopy using a guest host ratio of 2 1 and the But signal as probe.In the knowledge of the association constants for the same complexes at 25 "C in CDC13 (saturated with DzO) the rate constants VY D. J. Cram J. R. Moran E. F. Maverick and K. N. Trueblood J. Chem. SOC.,Chem. Commun. 1983,647. I00 D. J. Cram and H. E. Katz J. Am. Chem. SOC.,1983 105 135. in1 J. L. Fox Chem. Eng. News 1983 Feb. 14 p. 33. I02 R. Breslow Chem. Eng. News 1983 April 11 p. 4; D. J. Cram ibid. p. 4. I03 T. Anthonsen and D. J. Cram J. Chem. Soc. Chem. Comrnun. 1983 1414. 368 J. F. Stoddart P- b-x + m 5 U Y I-r 0 rl U Host-Guest Chemistry for association were obtained. The values of 1010-10'2 1 mol-' s-' indicate that complexation is diffusion controlled in keeping with a model in which the guest Bu'NH,+ ion perches on the binding sites (the CO groups) of the host.By contrast the association rate constants for the spherand (31) complexing Li' and Na+ ions in the same situation were in the range 104-105 1 mol-' s-l indicating that these guests are encapsulated much more slowly. Cyc1osexipyridines.-After numerous attempts over the past fifty years the pyridine analogue of (3 l) 'cyclosexipyridine' (36) has finally been synthesized (Scheme 5) by Newkome and Lee.lo4 The molecular rigidity is irreversibly introduced in this synthesis following an initial macrocyclization to give a flexible polyfunctional intermediate. The final step relies upon the conversion of 1,5-diketones into a pyridine nucleus with hydroxylamine under acidic conditions.Just before this publication appeared Tonerlo5 reported the synthesis (Scheme 6) of the NaOAc Iii uH H" Jiv (36) Reagents i Se0,-AcOH; ii CH,(CH2SH),-p-TsOH-PhMe; iii Bu"Li-CH,(CH,Br),-THF; iv NBS-THF-MeOH; v HONH,Cl-AcOH Scheme 5 I04 G. R. Newkome and H.-W. Lee J. Am. Chem. SOC. 1983 105 5956. lo' J. L. Toner Tetrahedron Lett. 1983 24 2707. 370 J. F. Stoddart Q? Y Qd A 0 I U P4 0 d X -40 0 d Host- Guest Chemist ry 37 1 complexes of the disubstituted cyclosexipyridines (37; R = Me or Et) using the Krohnke synthesis. In each case the excellent yield (42% and 57'/0 respectively) in the final step might arise from NH,+ (or Na+?) ion templation of the intermediate quinquepyridine.The fact that the isolated complexes are of NaOAc rather than NH,OAc (37) raises the intriguing possibility that cyclosexipyridines (37) can strip Na+ ions out of glass! Ca1ixarenes.-Another group of hosts which have potential cavitand character are those such as (38; R = But Y = OH) which is obtained when 4-t-butylphenol is treated with HCHO and base. The story behind the recent dramatic developments surrounding the so-called calixarenes has been summarized expertly by Gutsche in a recent review.I3 Calix[4]arenes are conformationally flexible and can in principle equilibrate between the four conformations illustrated schematically in Figure 2. In g5-$ R d Cone Partial cone 1,2-Alternate 1,3-Alternate Figure 2 The four possible diastereoisomeric conformations of the calix[4]arenes practice the parent calix[4]arenes (38; R = H Bul or CH2=CHCH2 Y = OH) exist preferentially in the cone conformation and at room temperature in solution they invert at ca.100 s-'. They have been converted'06 into various tetra-substituted derivatives (Y = OMe OEt OCH2CH=CH2 OCH,Ph OSiMe ethers or the acetates). All but the methyl ethers are conformationally rigid at room temperature and the preferred conformations in most cases are the cone and partial cone I Ilh C. D. Gutsche B. Dhawan J. A. Levine K. H. No and L. J. Bauer Tetrahedron 1983 39 409. J. F. Stoddart conformations depending on the nature of the derivative. By appropriate choice of reagent and reaction conditions a given constitution can be fixed in either of these two rigid conformations i.e.they are cavitands which can be contoured. Many substituted calix[n]arenes (n = 4 5 6 or 8) form" inclusion compounds with neutral organic molecules; they also act as metal ion transporting agents in an un- usually interesting fashion.'" p-t-Butyl-calix[4]arene (38; R = But Y = OH) -calix[6]arene and -calix[8]arene although ineffective towards transporting cations in neutral solutions (as metal nitrates) exhibit considerable transport capabilities in basic solutions (metal hydroxides) (cf 18C6). The p-t-butylcalix[ nlarenes are most effective at transporting Cs' ions amongst the M+ ions with the selectivity decreasing in the order [4] > [6] > [8] for [n]. The desirable features of calixarenes as ion carriers include their low water solubility their ability to form neutral complexes through loss of a proton and their potential for coupling cation transport to the reverse flux of protons.A crowned p-t-butylcalix[4]arene (39) is also able to act as a neutral ligand with K+ > NH,+ > Na+ > Cs+ > Li+ and Ba2+ >> Ca2+ selec- tivities for the transport of picrate salts through a CH2CI2 membrane.*os The X-ray crystal structure shows that (39) possesses two cavities a hydrophilic one and a + (39) lipophilic one. Further potentially interesting candidates for complexation studies are the o~acalixarenes,'~~ where some of the CH groups between the aromatic rings have been replaced by CH20CH2 units. Gutsche' holds out the prospect at the end of his review that an appropriately substituted (with six C02H and two NH groups) calix[4]arene rigidly fixed in a partial cone conformation might serve as an aldolase model.Cyclotriveratrylene (CTV) Hosts.-Other useful building blocks that have emerged' lo recently as potential cavitand precursors are the chiral (C,)derivatives [e.g.R' = Br I07 R. M. Izatt J. D. Lamb R. T. Hawkins P. R. Brown S. R. Izatt and J. J. Christensen J. Am. Chem. Soc. 1983 105 1782. I08 C. Alfieri E. Dradi A. Pochini R. Ungaro and G. D. Andreetti J. Chem. SOC.,Chem. Commun. 1983 1075. Io9 B. Dhawan and C. D. Gutsche J. Org. Chem. 1983 48 1536. I10 J. A. Hyatt J. Org. Chem. 1978 43 1808; J. Gabard and A. Collet J. Chem. Soc. Chem.Commun. 1981. 1137. Host-Guest Chemistry R' = OMe or R' = C02H R2 = OMe in (40)] of CTV [R'= R2 = OMe in (40)]. These molecules adopt exclusively the crown conformation shown in (40). An important derivative cyclotriguaiacyclene (40; R' = OH R2 = OMe) has been synthesized"' from vanillyl alcohol via the readily accessible intermediate tris-( 0-al1yl)cyclotriguaiacyclene (40; R' = OCH2CH=CH2 R2 = OMe). These saucer- shaped molecules have been incorporated as a rigid lipophilic unit into a number of synthetic hosts,"' some of which are capable of binding small organic guests e.g. MeNH,+. Dibenzofuran Hosts.-Cavitands with cleft- and collar-shaped voids have been synthesized' starting from dibenzofuran (Scheme 7) a highly suitable precursor since it readily undergoes electrophilic substitution at C-2 and C-8 and metallation at C-4 and C-6.The macrocycles (41) and (42) were obtained in 11'10 and 1.6% yields respectively and are more soluble in benzene toluene and the xylenes than in CHC1 or CH2C12. This observation correlates well with the excellent fits by molecular models of these aromatic guests within the cavities of (41) and (42) assuming they have DZdand D3dsymmetries respectively. Substituents at C-2 and C-8 on the dibenzofuran units are located on the peripheries of the cavities and so can be used to control host solubility and binding of guests and ultimately to act as catalytic sites. Cucurbituri1.-This novel collar-shaped cavitand (43) is a cyclic hexamer of dimethanoglycoluril and is ~btained"~ in good yield (40-70%) from a reaction mixture containing (NH,),CO (CHO)' and HCHO.[Its trivial name has been coined because of its resemblance to a pumpkin (Cucurbitaceae)!] Its structure was estab- lished from the X-ray of the crystals of a calcium sulphate complex obtained from sulphuric acid solution. It has a hollow core of ca. 5.5 A diameter with access being provided from the 4A diameter portals defined by the carbonyl oxygen atoms at each end. In aqueous formic acid solution many amines are encapsulated"' as evidenced by upfield shifts in their 'H n.m.r. spectra. Exchange with excess of RNH3+ ions is slow at 40 "Con the n.m.r. time-scale. Dissociation constant measure- ments reveal that the n-butyl- isopentyl- and cyclopentylmethyl-ammonium ions are strongly bound.Of the (methylbenzy1)ammonium ions only the para-isomer is Ill J. Canceill J. Gabard and A. Collet J. Chem. Sac. Chem. Commun. 1983 122. I I2 J. Canceill A. Collet J. Gabard F. Kotzyba-Hibert and J.-M. Lehn Helu. Chim. Acfa 1982 65 1894. I13 R. C. Helgeson M. Lauer and D. J. Cram J. Chem. SOC.,Chem. Commun. 1983 101. I14 W. A. Freeman M. L. Mock and N.-Y. Shih J. Am. Chern. SOC.,1981 103 7367. M. L. Mock and N.-Y. Shih 1. Org. Chem. 1983 48 3618; M. L. Mock T. A. Irra J. P. Wepsiec and T. L. Manimaran J. Org. Chem. 1983,48 3619. 374 J. F. Stoddart 4J h N W w Y -gc c,w c,w c,w LJ w w -44 >-.- c .....- 4Jw -4 c,w 3 w w > -d -4 -4 -4 Host-Guest Chemistry bound; the exclusion of the ortho- and meta-isomers is striking! Binding is even stronger for H,N+(CH,) NH3+ dications and peaks when n = 6 suggesting specific "+-He -O=C] interactions at each portal with the hydrophobic effect providing additional stabilization.The 1,3-dipolar cycloaddition (Scheme 8) of the alkyne (44) with the azide (45) to afford the triazole (46) is not only rendered completely regioselective but is also accelerated by a factor of 5.5 x lo4 under the catalytic influence of (43). Kinetic studies reveal a number of enzyme-like features (saturation behaviour substrate inhibition and stabilization of the transition state relative to the ground state) in this catalysis. It is claimed'" to be the first time that the Pauling principle of catalysis has been demonstrated in a non-biochemical host-guest system.Reagents i (43)-HC02H-H,0 40 "C Scheme 8 6 Cyclodextrins Not surprisingly these readily available hosts continue to attract a lot of attention. Symmetry rules for the determination of the intercalation geometry of aromatic guests with CDs using induced circular dichroism by the chiral hosts have been proposed.'16 The cavity of y-CD can be adapted1I7 for the binding of small guest molecules by appending a space-regulating naphthalene residue to the host ;this naphthalene-appended y-CD will also associate' with p-CD. The optimization of 116 P. E. Schipper and A. Rodger J. Am. Chem. SOC. 1983 105 4541; M. Ata and H. Yamaguohi J. Chem. SOC.,Chem.Commun. 1983 3. 117 A. Ueno Y. Tomita and T. Osa J. Chem. Soc. Chem. Commun. 1983,976. 118 A. Ueno Y. Tomita and T. Osa J. Chem. Soc. Chem. Commun. 1983 1515; see also Tetrahedron Lett. 1983 24 5245. J. F. Stoddart ferrocene substrates for p-CD reactions has been pursued"' to the extent that one of the enantiomers of (€)-3 -(carboxyethylene)-I ,2-ferrocenocyclopentene acylates p-CD 5 900 000 times faster in H,O-Me,SO than it hydrolyses under the same conditions. (The other enantiomer reacts 62 times more slowly.) A study of the volume profiles of such reactions carried out at high pressures promises12' to shed light on their structural requirements. a-CD and p-CD have been employed catalyti- callyI2' to direct attack of dichlorocarbene regioselectively at the para-position of phenolates ; thus 4-hydroxy- and 2,4-dihydroxy-benzaldehydeshave been prepared with 100% selectivities from the corresponding phenols.Enantioselective (22%) epoxidation of trans-chalcone has been achieved',' with NaOCl as oxidizing agent in the presence of catalytic amounts of p-CD. Two new molecular receptors based on CD cavities have been described one is a diaza-crown capped p-CD,'23 the other a tailor-made 'cyclodextrin' ~ynthesized'~~ from starch using Methylene Blue as a template 7 Clathrates X-Ray structural analysis of inclusion complexes with mesitylene rn-xylene and toluene has revealed'25 that (2R,SR,SR,1 1 R)-1,4,7 10-tetrabenzyl-2,5,8,11 -tetraethyl- 1,4,7,l0-tetra-azacyclododecaneforms a triangular cavity most suitable for mesity-lene; this cyclene host can also be used to separate a mixture of m-from p-xylene.Hexakis-(3,5-dimethyIphenyloxy)benzene forms'26 crystalline 1 I adducts with MeCN MeNO, and PhMe; the X-ray structure of the MeCN adduct reveals a novel interaction between host and guest involving short [Me. -01distances. 9,9'-Spirobifluorene-2,2'-dicarboxylicacid provides'27 two CO2H groups for co-ordina- tion to two molecules of DMF by intermolecular [C02H...0HC] hydrogen bonding inside the host lattice. A novel type of bisammonium clathrand (47) has been described*28which forms a wide range of inclusion compounds with organic guests (ROH RSH RI RNO, RCN RC02H etc.); crystallographic data for several clathrates suggest that the host conformation is essentially steered by the enclosed I I9 R.Breslow C. Trainor and A. Ueno J. Am. Chem. SOC.,1983 105 2739. I20 W. J. LeNoble S. Srivastava R. Breslow and G. Trainor J. Am. Chem. SOC.,1983 105 2745. M. Komiyama and H. Hirai J. Am. Chem. SOC.,1983 105 2018; see also ibid. 1984 106 174. I22 S. Banfi and S. Colonna Synth. Commun. 1983 13 1049. I23 I. Willner and Z. Goren J. Chem. SOC.,Chem. Commun. 1983 1469. I24 S. Shinkai M. Yamada T. Sone and 0. Manabe Terrahedron Lett. 1983 24 3501. I25 T. Sakurai K. Kobayashi T. Kanari T. Kawata I. Higashi S. Tsuboyama and K. Tsuboyama Acta Crystallogr. 1983 B39 84. I26 C. J. Gilmore D. D. MacNicol A. Murphy and M. A. Russell Tetrahedron Lett. 1983 24 3269. I27 M. Czugler J.J. Stekowski and E. Weber J. Chem. SOC.,Chem. Commun. 1983 154. I28 F. Vogtle H.-G. Lohr H. Puff and W. Achuh Angew. Chem. Int. Ed. Engl. 1983 22. 409; J. Chem. SOC.,Chem. Commun.. 1983 924. Host-Guest Chemistry 377 guest molecules. Crystallization of tri-o-thymotide from solutions of appropriate racemic guests chiral single crystals of clathrate inclusion complexes in which different proportions of guest enantiomers are incorporated ;after extraction of the guests the highest e.e.s were observed for 2,3-dimethyl-trans-oxirane(47%) 2,4-dimethyl-truns-oxetane (38%) and 2-bromobutane (37%). Numerous examples of reactions in the solid state have been reported in one of these report^,'^' irradiation of inclusion complexes of truns-chalcone derivatives with 1,1,6,6-tetraphenylhexa-2,4-diyne- 1,6-diol give only the syn-head-to-tail cyclobutane derivative.8 Miscellaneous Hosts A number of novel cyclophane hosts have been described recently. One involve^'^' the linking of two 4,4’-bipyridinium moieties via two ortho- or two meta-xylene bridges (o,o-48; m,rn-48) or uia one orrho- and one meta-xylene bridge (o,rn-48); these are all potential hosts. Another tetracationic host (49) formsI3* 1 1 complexes with pyrene (and other water-insoluble aromatic hydrocarbons) in aqueous solution. .+ 4 c1-+Q Me ,Me A Me-Me R’NLzJN‘R z = /-?onon R = n-C8H, 4 c1-I29 R. Arad-Yellin B. S. Green M. Knossow and G. Tsoucaris J. Am. Chern. SOC.,1983 105 4561. I 30 K. Tanaka and F. Toda J.Chern. SOC.,Chem. Commun. 1983 593. 131 W. Geuder S. Hunig and A. Suchy Angew. Chem. int. Ed. EngL 1983 22 489. I32 F. Diederich and K. Dick Angew. Chem. Int. Ed. EngI.. 1983 22 715. 378 J. F. Stoddart The neutral triazinophane (50) which is easily prepared’33 from 2,4,6-trichloro-s- triazine acts as a phase-transfer catalyst binding M+ions in the order Na’ > K+ > Cs+ >> Li+. Acyclic ligands containing amide functions are also presently attract- ing134 a lot of attention as ion carriers. Interest continues to grow in the use of microgels as matrices for molecular receptor and catalytic sites the synthesis and reactivity of cavities in microgels possessing amino functions has been described recently.‘35 9 Concluding Remarks Unfortunately the scientific predilections of the reviewer have conspired with the lack of space to deny even a mention of some important topics and to treat others in a somewhat cursory fashion.Fortunately a number of monograph^,'^^ multi-author and authoritative review^'^'-'^^ are available. 133 P. L. Anelli F. Montanari and S. Quici J. Chem. SOC.,Chem. Commun. 1983. 194. I34 A. Shanzer D. Samuel and R. Korenstein 1.Am. Chem. SOC.,1983,105,3815; L. H. Craine J. Greenblatt S. Woodson E. Hortelano and M. Raban ibid. p. 7252; F. Vogtle T. Kleiner R. Leppkes M. W. Laubli D. Ammann and W. Simon Chem. Ber. 1983 116,2028; M. Delcanale R. Marchelli A. Mangia A. Dossena and G. Casnati Angew. Chem. Int. Ed. Engl. 1983 22 563. I35 A. Hopkins and A.Williams J. Chem. SOC.,ferkin Trans. 2 1983 891. I36 G. W. Gokel and S. H. Korzeiowski ‘Macrocyclic Polyether Synthesis’ Springer-Verlag Berlin 1982 M. Hiraoka ‘Crown Compounds’ Elsevier New York 1982; M.L. Bender and M. Komiyama ‘Cyclo- dextrin Chemistry’ Springer-Verlag Berlin 1978 ; J. Szejtle ‘Cyclodextrins and their Inclusion Com- plexes’ Akademiai Kiado Budapest 1982; M. Dobler ‘Ionophores and their Structures’ Wiley New York 1981. 137 ‘Synthetic Multidentate Macrocyclic Compounds’ ed. R. M. Izatt and J. J. Christensen Academic Press New York 1978; ‘Progress in Macrocyclic Chemistry’ ed. R. M. Izatt and J. J. Christensen Wiley New York 1979,Vol. I ; I98 I Vol. 2; ‘Coordination Chemistry of Macrocyclic Compounds’ ed. G. A. Melson Plenum Press New York 1979; ‘The Chemistry of the Functional Groups.Supplement E. The Chemistry of Ethers Crown Ethers Hydroxyl Groups and their Sulphur Analogues’ Part 1 ed. S. Patai Wiley Chichester 1980; ‘Host-Guest Chemistry I and 11’ in ‘Topics in Current Chemistry 98 and IOI’ ed. F. Vogtle Springer-Verlag Berlin 1981 and 1982; ‘Inclusion Compounds, ed. J. L. Attwood J. E. D. Davies and D. D. MacNicol Academic Press London 1984 Vols. 1-3. I38 J.-M. Lehn Acc. Chem. Res. 1978 11 49; Pure Appl. Chem. 1979 51 979; 1980 52 2303 2441. I39 D. J. Cram and J. M. Cram Acc. Chem. Res. 1978 11 8. I40 J. F. Stoddart Chem. SOC.Rev. 1979 8 85. 141 F. de Jong and D. N. Reinhoudt Adv. Phys. Org. Chem. 1980 17 279. I42 J. S. Bradshaw and P. E. Stott Tetrahedron 1980 36 461.143 V. Prelog Pure Appl. Chem. 1978 50 893. 144 D. D. MacNicol J. J. McKendrick and D. R. Wilson Chem. SOC.Rev. 1978 7 65. 145 J. W. Cornforth Roc. R. SOC.London Ser. B 1978 203 101.

ISSN:0069-3030    

DOI:10.1039/OC9838000353

出版商:RSC    

年代:1983

数据来源: RSC

摘要:

Abassi Madjdabadi F. 219 Abbate G. 31 Abbondanti E. 200 Abdallah H. 190 Abe N. 178 Abell K. W. Y. 81 Abis L. 286 Abour-Gharbia M. 26 1 Abraham R. J. 14 Abrams S. R. 166 184 Acheson R. M. 192 269 Achuh W. 376 Acker M. 194 Acquaah S. O. 182 Adachi J. 262 Adam M. A. 168 Adam M.-J. 223 Adam W. 149 202 Adamczyk M. 56 156 330 Adams B. R. 201 334 Adams D. R. 266 Adams G. F. 38 39 Adams R. D. 273 Adamsky F. 63 Adiwidjaja G. 184 239 Adkins S. 154 246 Adlington R. M. 174 319 Aebi J. D. 178 Agawa T. 191 Agosta W. C. 148 Ahlberg P. 38 Ahlbrecht H. 268 Ahlrichs A. 45 Ahlrichs R. 31 Ahmed S. N. 34 102 Aizpura J. M. I83 Akaba R. 126 Akabori S. 361 Akai S.252 Akam T. M. 156 Akhmetova N. W. 188 Akiba E. 108 Akita M. 172 Akiyama Y. 179 Akkerman 0. S. 192 301 Alagona G. 43 Albeck M. 305 Albrecht H. 182 Albright J. D. 319 Author Index Alder H. 163 Alder R. W. 203 Aldersley M. F. 1 I Alemagna A. 224 Alemany L. B. 17 Alexakis A, 172 177 191 Alexander S. A. 34 Alfieri C. 238 372 Alger T. D. 17 Allen L. C. 45 Allenmark S. 184 Allman B. J. 143 Alma N. C. M. 17 Almirantis Y. 195 Almlof J. 44 210 Alneri E. 154 Alonso-Cites L. 347 Alper H. 250 286 287 288 Alston P. V. 49 Altenbach H.-J. 215 Alveri E. 168 Alvernhe Ci. 171 Alwis K. W. 228 Amer I. 23 I 288 344 Ames D. E. 284 Amin N. V. 56 Amino Y.50 237 Ammanamanchi R. 230 Ammann D. 378 Amsterdam G. A. J. 235 Anastassiou A. G. 64 241 Anciaux A. J. 285 Anderson D. K. 237 Anderson Ci. K. 273 Anderson J E. 210 Anderson J S. 223 Anderson K. W. 223 Anderson R. 300 Andersson A 16 Andersson K. 210 232 Ando K. 192 Ando M. 3.35 336 Ando R. 189 Ando T. 165 171 Ando W. 121 174 Andree R. 242 Andreeti G. D. 238 372 Andrei R. 272 Andruskiewicz C. A. 107 379 Anelli P. L. 378 Anet F. A. L. 238 Angeletti E. 154 Angelici R. J. 259 Angelucci F. 237 Annunziata R. 184 308 Anthonsen T. 367 Anthony M. C. 39 Anton D. R. 75 Antonioletti R. 168 Anwari F. 41 209 Aoyama H. 146 147 250 Aoyama Y. 154 276 Apeloig Y.20 38 105 Apparu M. 168 Arad-Yellin R. 145 377 Araragi Y. 358 Arbiser J. 221 Arcadi A. 177 Arcamone F. 237 Arct J. 107 191 Aresta M. 245 Arias L.A. 154 246 Arison B. H. 269 Aristoff P. A. 364 Arita Y. 175 Arkles B. 300 Armand J. 126 Armen G. H. 355 Armet O. 227 Am H. 21 Arnett E. M. 71 Arnold D. R. 40 Arnold M. J. 249 Arnold R. 177 Arnoldi C. 155 Arhhenius P. 200 Arrington C. A. 120 Arunachalam T. 165 Arvanaghi M. 73 213 220 Arzoumanian H. 15 Asada H. 95 Asami K. 166 176 Asami M. 178 179 Asensio G. 228 347 Ashby E. C. 169 174 296 Ashe A. J. 304 Ashkenazi P. 235 Ashworth D. M. 13 Aslam M. 159 Aspiala A, 43 Ata M. 375 Athara K.227 Atkins P. J. 225 Atkinson J. G. 144 Atkinson R. C. 79 Atwood J. L. 296 297 Auchter G. 74 Audit M. 14 Auricchio S. 2 18 246 359 Avenati M. 54 Awano K. 207 Awasthi A. 247 Awasthi A. K. 247 Ayaguchi Y. 344 Aydin R. 242 272 Azadi-Ardakani M. 237 Aznar F. 163 Azuhata T. 178 Azuma Y. 301 Baban J. A, 90 Babbitt B. W. 127 Babler J. H. 346 Baboulene M. 181 Babudri F. 245 309 Baca S. B. 178 Bach R. D. 154 246 Bacher A, 9 Baciocchi E. 126 Back T. G. 163 Bacquet C. 137 Badet B. 78 184 Backvall J.-E. 157 306 Baettig K. 148 Baghdadchi J. 214 Bagheri V. 291 BaignCe A. 96 Bailey M. S. 281 Bailey R. J. 235 Bailey S. I. 124 Bailey S.J. 324 Bailey W. F. 170 Baillargeon V. P. 314 Baird M. S. 115 Baizer M. M. 123 130 131 Baker A. D. 355 Baker D. C. 167 Baker D. S. 80 359 Baker R. 2 15 Baker R. J. 230 Bal B. S. 173 Balaban R. S. 4 Balandrin M. F. 6 Baldwin J. E. 174 184 191 Baldwin J. J. 269 Baht I. 30 32 Baht-Kurti G. 30 Ballabio M. 237 Ballatore A. M. 25 Ballester M. 227 Ballini R. 173 184 Balogh D. W. 207 Bal Reddy K. 236 237 Balschi J. A, 14 Balschukat D. 233 Ban M. I. 30 32 Ban T. 49 Ban Y. 123 133 146 256 Banavali R. 235 Banerjee A, 32 Baney R. H. 300 Banfi S. 376 Bank S. 125 Bankaitis D. M. 263 Banville J. 250 Banwell M. G. 179 Bapat G. S. 63 Baport G. S. 221 Baratt O.255 Barbe W. 99 Barber M. 24 25 Barber Y. J. 178 Barchielli G. 237 Barclay L. R. C. 93 Barcus R. L. 110 Bardo R. D. 45 Baret P. 354 Baretz B. H. 96 Barfield M. 18 Barkel D. J. D. 210 Barker A. J. 205 216 Barluenga J. 153 156 163 178 228 264 347 Barofsky D. F. 23 Barone V. 31 Barrau J. 299 Barrelle M. 168 Barrett A. G. M. 364 Barriere J. C. 194 Barrish J. C. 167 349 Barron R. P. 27 Barrow P. D. 105 Barrows R. D. 214 Barry C. N. 167 Barry J. 169 Barth J. 181 Barth W. 233 Barthelat J.-C. 42 Batlett P. A. 312 Bartlett R. J. 31 34 38 39 Bartner P. L. 27 Bartnik R. 146 247 Bartoli J.-F. I5 I Barton D. H. R. 87 169 171 337 342 Barton J.W. 234 Barton T. J. 120 143 253 299 300 Bartram R. H. 38 Bartsch R. A, 75 198 354 357 Barua N. C. 348 Baruah J. N. 348 Barzaghi M. 35 Basak A, 319 Author Index Basavaiah D. 152 172 Basalgina T. A. 302 Bashiardes G. 171 Basilevsky M. V. 32 Bass L. S. 54 Bastein A. G. T. M. 17 Batmangherlich S. 180 Battersby A. R. 12 Battig K. 201 Baudler M. I5 Baudry D. 278 Bauer H. 238 359 Bauer L. J. 238 371 Bauer V. J. 271 Baughman S. A, 92 Bauld N. L. 39 40 54 143 Baumgartel O. 236 Bax A. 5 6 7 8 9 12 Baxter H. N. 111 91 Bayon A. M. 228 Baze M. E. 113 194 Beadle J. R. 238 364 Beak P. 228 Beauchamp A. L. 302 Beauchamp P. D. 203 Beck A. 242 Becker H.-D.210 232 Becker K. B. 203 Beckhaus H.-D. 99 210 Beckner C. F. 25 Beckwith A. L. J. 87 90 226 Bedford G. R. 14 Bednarski M. 53 174 327 Beeley N. R. A. 222 Beer P. D. 361 Begley M. J. 216 Behr H. 262 Behrens U. 239 Beinhauer A. 202 BejtoviC Z. 138 Bekhazi M. 110 113 Belanger P. C. 144 Beletskaya I. P. 302 314 Belford R. L. 39 Bell G. A. 110 Bell T. N. 104 Bell T. W. 360 Bellamy A. J. 125 127 Bellassoued M. 178 Belleau B. 237 250 Bellec C. 126 BelluS D. 60 Bellville D. J. 39 40 54 Belmonte F. G. 232 Beloeil J. C. 21 Belsky V. K. 302 Benati L. I17 Benaud R. N. 182 Bendall M. R. 12 Ben-David Y. 217 Bender M. L. 354 378 Benders P. H. 47 Benkeser R.A. 232 Benn R. 241 Author Index Benson W. R. 27 Bent G. D. 38 Bentrude W. G. 185 Benzel M. A. 39 Bergman J. 157 256 306 Bergman R. G. 274 Bergmann C. W. 52 194 Bernad P. 153 178 Bernardi F. 42 Bernd M. 9 Bernheim M. 181 Berris B. C. 234 Berry J. M. 223 Bertini V. 262 Bertozzi R. 179 Bertrand M. 113 191 201 Bertranne M. 21 Berube D. 125 182 Bestmann H.-J. 179 186 187 33 I 349 Bestre R. D. 151 Betancor C. 255 Beugelmans R. 55 254 Bezoari M. D. 22 Bhacca N. S. 6 Bhalla K. C. 39 Bhat N. C. 152 172 Bhatt M. V. 169 227 347 Bhattacharye A, 65 173 317 Bhattacharya A. K. 236 Bianco H. 105 212 Bicerano J. 37 40 Bick I. R. C. II Bickelhaupt F.39 192 301 Biemann K. 23 24 Bieri. J. H. 58 Billeadeau R. J. 229 Biller S. A. 87 321 Bills L. J. 357 Billups W. E. 190 Bimanand A. Z. 57 260 Hinkley J. S. 37 102 Birbaum J.-L. 208 Birch A. M. 206 216 Bird P. 139 Birdsall B. 10 Bischofberger N. 106 Bizzigotti C. O. 228 Black L. A. 173 Black T. H. 184 Blackwell G. B. 58 Bladon G. M. 53 Blair B. A, 24 Blanchard M. 49 Blanco L. 172 Blank N. E. 240 Blarer S. J. 182 Bleekmann K. 58 Bloch R. 172 Block E. 159 185 Bloecker H. 24 Bloomfield C. 222 Blount J. F. 54 Blumich B. 10 Blum J. 231 288 344 Blunt J. W. 166 168 Boardman L. D. 323 Boatz J. A. 40 Boche G. 181 Bochkarev M. N. 302 Bochnik M.C. 253 Bock C. W. 44 Bodalski R. 196 329 Bodecker C. D. 208 Bodenhausen G. 9 Bockman R. K. jun. 324 Bohm H.-J. 45 Bohm M. 242 Bohm M. C. 54 Boehm P. 173 Boekelheide V. 239 Bottcher A, 262 Bogatsky A. V. 358 Boger D. I-. 217 328 Boggs J. E. 43 44 Bohm M. C. 208 Bolletta F. 274 Bolton R. 67 BonaEiE-Kouteck9 V. 38 117 Bondybey V. E. 40 Bonini B. F. 119 Bonnacorsi. R. 44 Bonnier J.-M. 219 Boop J. L. 198 Borchardt R. T. 229 256 Borden W. T. 34 38 Bordoli R. S. 24 25 Borisova 1. V. 302 Borschberg H.-J. 199 333 BOSC J.-J. 296 Bosch R. J. 105 Bose A. K.. 27 356 Boss S. W. 167 Botschwina P. 34 Bottaro J. C. 174 Boudjouk F. 41 209 Boukouvalas J. 267 Boulanger W.203 Boulares L. 126 Bouma W. .I. 19 36 40 Bourdelande J. L. 246 Bourhis M. 296 Bovill M. J. 355 Boyd R. J. 40 Boyer B. 173 Bradley C. V. 25 Bradshaw J. S. 360 378 Bram G. 169 170 Brand J. C. 90 Brandange S. 169 Brandsma L. 259 Brandsma R. 221 Bras P. 305 Brauer B.-E. I12 Brauer D. J.. 294 Braun M. 178 308 Braun P. 197 Braun W. 4 38 1 Braunschweiler L. 8 Bravo R. 241 Breitinger D. K. 296 Breitmaier E. 220 Breslow R. 54 326 354 367 376 Bresse M. 229 Breunig H. J. 304 Brevard C. 15 17 Briaire J. 238 359 Bridges A. J. 50 216 Briggs A. J. 83 Bright D. A, 169 Bringmann G. 350 Brinker U. H. 114 115 Brinker W. H. 214 Brinkley J.S. 36 Brisdon B. J. 281 Britcher S. F. 261 Brittain W. J. 93 Bromby N. G. 157 Brook M. A, 178 348 Brookes M. H. 168 Brookhart M. 278 331 Brooks P. W. 25 Brooks W. 12 Brouerman S. 185 Brown D. W. 281 Brown F. B. 34 Brown H. C. 151 152 155 172 173 174 312 346 347 350 Brown J. D. 230 Brown K. C. 223 Brown L. 348 Brown P. R. 372 Brown R. D. 193 Brown R. S. 208 Brownbridge P. 174 215 307 Browne A. R. 207 Brownlee R. T. C. 21 I Brownsey B. G. 25 Broxton T. J. 226 Bruck W. 104 Bruckner D. 202 21 1 Bruckner S. 359 Brugge H. J. 360 Brunner H. 273 298 331 345 Brundish D. E. 14 Brunet J.-J. 144 178 232 287 Brunner R. K. 199 333 Bruno A. E. 43 Brussee J.209 Bryant R. G. 13 Bryce M. R. 269 Bucciarelli M. 173 Buchan C. M. 233 Buchs A. 21 Buchwald S. L. 158 Buckland P. R. 217 Budzelaar P. H. M. 247 Buhler U. 185 Burger H. 294 Burgi H.-B. 210 Bueuker R. J. 39 Buice T. C. 80 Buko A. M. 24 Bunce N. J. 147 Buncel E. 224 Bung Lee W. 104 Buck J. J. 98 Burfield I). R. 86 Burford C. 176 Burgen A. S. V. 10 Burger V. 105 267 Burger W. 212 Burgers P. C. 19 20 Burinsky D. J. 23 Burke S. D. 207 Burkey T. J. 98 Burkle S. E. 73 Burks J. 185 336 Burland D. M. 141 Burnier R. C. 27 Burns G. T. 120 Burton D. J. 186 Burton G. W. 37 97 Burton P. G. 30 31 Busch K. L. 19 25 Buschek J. M. 208 Buser H.R. 21 Buss A. D. 187 Buzik K. 13 Cabaret D. 170 Cacace F. 22 Cacchi S. 177 288 Cadogan J. I. G. 233 Cajon H. D. 125 Calderazzo F. 304 Callen G. R. 175 Cambie R. C. 156 Camp R.N. 33 Campos P. J. 347 Camps F. 359 Canada E. D. 18 Canceill J. 239 373 Canovas A. 204 Caplar V. 244 Caple R. 73 Caporusso A. M. 162 Caprioli R. M. 24 25 Carballeira N. 149 Card P. J. 10 235 Caristi C. 260 Carless H. A. J. 146 Carlsen J. H. J. 247 Carlsen L. 233 Carlsen P. H. J. 227 Carlson C. W. 300 Carlsson R. 182 Caro B. 173 Carr R. V. C. 51 Carrie R. 186 190 Carroll D. I. 27 Carrupt P.-A. 86 Cirsky P. 37 Carter C. G. 191 Casal H. L. 147 Casellato V.305 Caserio M. C. 23 Casey M. 260 Casini G. 356 Casnati G. 215 223 378 Caspi E. 165 Castaldi G. 155 Castafier J. 227 Castaiio O. 30 Castedo L. 236 Castelhano A. L. 98 Castle R. N. 10 Cate L. A. 220 Caubere P. 144 178 23 I 232 287 347 Cava M. P. 68 Cavalla D. 187 Cavallin B. 201 Cavell R. G. 15 Cebulska Z. 146 Cederbaum L. S. 39 Cefelin P. 153 Cervilla M. 21 Cha J. K. 21 I 338 Chaabouni R. 181 Chabaud B. 138 Chadwick D. J. 355 Chae W.-K. 92 Chait B. T. 26 Chakraborti A. K. 227 Chan T. H. 178 189 218 253 348 Chandrasekaran S. 228 Chandrasekhar J. 30 Chandrasekhar S. 302 Chandrasekharan J. 155 Chang M. H. 239 Chang S. 72 Chanon M.141 Chao K.-H. 182 Chapman 0. L. 117 Chapuis C. 52 201 Charles G. 156 Charumilind P. 54 Chatani N. 308 Chatellier D. 78 Chatterjee S. 307 Chatziiosifidis I. 169 Chauffaille J. 170 Chawla H. P. S. 344 Chayangkoon P. 213 Cheikh R. B. 181 Chen B. C. 12 Chen C. N. 12 Chen C. S. 356 Chen S. 55 Chen T. 94 Chen Y.-Q, 204 322 Chen Y.-Y. 55 254 Chfnevert R. 359 364 Chenier J. H. B. 94 Chianelli D. 69 224 Chiba K. 256 Author Index Chiba T. 129 Chiem P. V. 114 196 Chihara T. 173 Childs R. F. 212 Cho H. 237 Choe J.-I. 190 Choi H.-D. 252 Choi H. K. J. 104 Choi V. 317 Choi V. M. F. 183 Chong J. M. 163 Chou C. S. 138 Chow J. F. 77 85 Choy W. 52 166 201 323 Christ J.201 Christ W. J. 338 Christie K. O. 15 Christensen J. J. 360 372 Christensen K. A. 16 Christiaens L. 262 Christl M. 202 21 1 Christoph G. C. 194 Chu I.-S. 203 Chuang C.-P. 199 Chucholowski A. 177 Chudek J. A. 225 Chung S.-K. 226 Cimiraglia P. 44 Cinoman M. I. 357 Cinquini M. 184 308 Ciommer B. 19 20 Ciranni G. 22 Citterio A. 155 177 343 Claesson A. 158 Clardy J. 54 Claridge R. F. C. 97 Clark H. C. 17 Clark R. J. H. 96 Clark T. 30 36 39 42 105 126 229 Clarke T. 35 Clarke T. C. 17 Cleary M. 48 Clegg W. 206 299 Clemens A. H. 222 Clement A. 117 246 Clementi E. 30 Cleophax J. 194 Clive D. L. J. 271 Coates D. 168 Coates R.M. 60 173 343 Cobwin C. E. 237 Cochran D. W. 261 Cockerill G. S. 321 Cody R. B. 27 Cofinio W. P. 39 Cohen H. 276 Cohen N. C. 252 Cohen T. 49 103 Cole E. R. 151 Coleman B. 41 Coll J. 359 Colle R. 32 Collerette J. 250 Author Index Collet A. 239 372 373 Collin G. J. 237 Collins C. J. 74 Collins S. 163 Collum D. B. 336 Colombo L. 308 Colonna S. 376 Colquhoun H. M. 359 362 Colucci W. J. 358 Colvin E. W. 347 Colvin M. E. 37 40 Comins D. L. 230 265 Common T. S. 207 ConcellBn J. M. 153 178 Concepcion E. 212 Concepcion J. I. 255 Conia J.-M. 172 193 Conlin R. T. 119 Connell A. C. 198 Connolly P. 276 Consiglio G. 170 283 314 Constantin E. 27 Contreras R.11 Contreras R. H. 30 Cook C. M. 45 Cook M. J. 20 Cooke F. 176 Cooks R. G. 19 23 25 Cooksey C. J. 210 Cooper A. J. L. 179 Cooper I. L. 31 Cooper S. R. 356 Cordell F. R. 44 Corey E. J. 87 168 173 194 35 1 Cormons A. 183 Cornelisse J. 221 232 235 Cornforth J. W. 378 Cornish C. A. 187 Cortes D. S. 138 Cossy J. 185 336 Costello C. E. 23 Costello T. 362 Cotter R. J. 26 Coudert G. 271 Court J. 219 Courtneidge J. L. 95 Courtney A. R. 301 Courtois G. 181 182 Coutsolelos A. 297 Cowley A. H. 293 303 304 Cox D. G. 186 Cox D. P. 72 103 104 247 Coxon B. 10 Coxon J. M. 168 176 Cozort J. R. 231 Cozzi F. 210 308 Crabtree R. H. 75 278 343 Craik D.J. 21 1 Craine L. H. 378 Cram D. J. 353 354 360 366 367 373 378 Cram J. M. 378 Crampton M. R. 325 Crank G. 151 Crawford R. J. 214 Cremer G. 222 Cretton W. 166 Crich D. 87 169 337 Crimmins M. T. 263 Cristau H. J. 138 Cristoph G. C. 52 Croft A. P. 75 198 354 Cross T. A. 18 Crossland I. 174 Crouse G. D. 51 Crow W. D. 108 Crowder J. 356 Crowley S. 237 Cruse W. B. T. 114 Csizmadia I. G. 32 36 41 43 Cummins C. H. 60 343 Cunkle G. T. 126 Cunningham A. F. 207 Curphy T. J. 246 Curran D. P. 56 331 Curtiss L. A. 45 Cutting I. 168 Czech A. 357 Czech B. 357 Czugler M. 376 Dahlman O. 169 Dahmane H. 92 d’Alarcao M. 268 Dalzell H C. 227 D’Amico I.J. 257 d’Angelo J. 49 250 Danieli B. 134 Danishefsky S. 52 53 174 327 328 Dann J. G. 10 Daris J.-P. 250 Das S. 269 Dashan L. 230 Dau E. T. H. 222 Dauben M‘.G. 207 Dauplaisse D. L. 260 D’Auria M. 168 Dauter Z. 259 Davidson 4. H. 180 Davidson E. R. 29 34 37 38 Davidson R. S. 141 Davies A. G. 90 95 96 Davies D. E. 54 Davies D. T.,237 Davies J. A. 17 Davies J. E. D. 353 Davis F. J. 95 Davis J. T. 52 201 323 Davis M. W. 343 Dawson B. A. 206 Deacon G. B. 224 Dean F. M. 11 Debaerdemaeker T. 262 De Bernardinis S. 177 de Boer J. .4.A. 360 De Brouckire G. 30 Decker 0. H. W. 333 De Clercq E. 237 Declercq J.-P. 236 Decodts G. 169 De Frees D. J. 37 de Groot A.258 Dehmlow E. V. 233 Deiko S. A. 231 de Jong F. 358 378 de Jong R. L. P. 259 de la Mare P. B. D. 67 79 Delaunauy J. 124 Delbecq F. 39 del Bene J. 44 Del Buttero P. 224 Delcanale M. 378 Dell A. 24 del Re G. 31 De Lucci O. 52 de Luchi O. 202 Demark G. 43 de Mare G. R. 43 de Mayo P. 147 de Meijere A, 208 239 Demerseman P. 14 221 De Mesmaeker A. 191 de Meyer C. 20 De Mico A. 168 Demonceau A. 285 Demou P. C. 15 Deng Y.-X., 217 Denis J.-M. 181 246 Denmark S. E. 174 195 De Pauw E. 24 Depke G. 38 74 Deprks J.-P. 206 De Priest R. N. 169 Dermuth M. 204 Derome A. E. 184 de Rossi R. H. 84 de Ruiter G. M. J. 142 Desai M. C. 155 de Sarlo F.356 Descotes G. 165 Deshong P. 57 255 Deshpande R. P. 173 Deshpande V. H. 50 236 237 de Silva S. O. 230 Desmarteau D. D. 156 Despax B. 149 Despeyroux B. 163 Desportes S. H. 221 Dess D. B. 228 Dessort D. 27 Detty M. R. 264 305 Dev S. 344 Devant R. 178 308 De Vos M. J. 189 Dewanckele J. M. 207 Dewar M. J. S. 101 de Weck G. 107 de Wolf W. H. 39 Deyo D. 65 173 317 Dhar R. 269 Dhawan B. 238 371 372 Diamond C. J. 357 Dick K. 377 Dickel M. 360 Dickenson J. B. 217 Iliederich F. 244 377 Diercks R. 217 281 326 Dieter R. K. 262 Dietrich-Buchecker C. O. 362 Dietz hl. 268 Pillon J. L. 192 D’Incan E. 170 DiNunno L. 309 Disch R. L. 44 207 Dishong D.M. 357 Ditrich K. 227 Dixon D. A, 42 Dixon D. K. W. 269 Djerassi C. 193 Doba T. 97 Dobler M. 378 Dobrovolny M. 192 Dobson B. 75 Doddrell D. M. 12 Doecke C. W. 207 Doering W. von E. 191 Dojo H. 171 315 Dolbier W. R. jun. 43 Dolphin D. 271 Dolphin J. M. 340 Dombek D. B. 273 Dominguez J. N. 266 Domke W. 39 Donati D. 356 Doornbos J. 4 Dorf V. 176 Dorltne A. 222 Dossena A. 223 378 Dougherty D. A. 239 Dousse G. 299 Dow R. L. 291 Doyle D. L. 173 350 Doyle M. P. 291 Dradi E. 238 372 Drakenberg T. 16 Drechsler K. 233 Dreiding A. S. 58 113 192 Drenth W. 154 Dreyer G. B. 204 Duar Y. 185 Dubois J.-E. 172 Duch W. 31 Duffley R. P. 227 Duggan P.J. 162 Duisenberg A. J. M. 294 Dujo H. 152 Dumasia M. C. 25 Durnont R. 178 Dunkin I. R. I 10 1 I7 Dunning T. H. jun. 41 42 Dupre B. 330 Dupuis M. 30 33 36 37 39 Durr H. 104 234 242 Durst T. 250 Duthaler R. O. 218 Dykstra C. E. 39 Dziobak M. P. 88 Eaborn C. 294 Eades R. E. 42 Earl H. A. 193 Earl R. A. 258 Earnshaw C. 187 Easton C. J. 90 249 Eaton P. E. 208 Eberhard J. K. 185 Eberson L. 126 Ebihara R. 245 Ebine S. 361 Echegoyen L. 357 Eckart K. 25 Eckrich T. M. 173 Edasery J. 356 Effenberger F. 185 220 226 Effio A. 91 Egger N. 58 Egsgaard H. 233 Eguchi S. 103 Eichler G. 181 Eilbracht P. 194 Einhorn J. 137 221 Eisch J. J. 176 Eisenberg R.276 Elbasyoung A. 360 El-Deek M. A. K. 218 Elgy G. M. 134 Eliel E. L. 197 Elissondo B. 175 Ellinger Y. 43 Elliott G. J. 24 Elliott J. D. 166 183 195 312 316 317 Elliott R. 166 316 El-Omran F. 222 El-Taliawi G. M. 90 Emura H. 357 Enders D. 308 Endesfelder A. 18 1 Enemark J. H. 16 Eng S. L. 147 Engel P. S. 92 Engels R. 125 Engler T. A. 235 Engman L. 157 306 Ennen B. 177 Entwistle I. D. 173 Ephritikhine M. 278 Epple G. 185 220 226 Erbe A. 171 Erden I. 208 Erhardt R. L. 83 Erickson W. F. 181 Eriyama Y. 300 Erkelens C. 235 Erker G. 176 Ermer O. 193 208 Ernst R. R. 3 7 8 9 Author Index Esaki T. 103 Espenson J. H. 273 276 Eswarakrishnan V.159 Eto H. 153 Eugster C. H. 53 200 253 Eustathopoulos E. 219 Evans B. S. 98 Evans C. M. 83 Evans D. H. 126 129 Evans S. A. jun. 167 Evers M. 262 Ewen G. D. 218 Ewing E. E. 191 Exon C. 205 Fabre J.-L. 347 Facelli J. C. 30 Faegri K. jun. 414 210 Faid-Allah H. M. 265 Fakley M. E. 273 Faller J. W. 182 Fantucci P. 30 Faraglia G. 305 Fargin E. 149 Farnell L. 38 Farneth W. E. 191 Farnum D. G. 71 Fauq A. H. 318 Fauvarque J.-F. 130 Fazio M. J. 249 Fedotov M. A, 17 Feeney J. 10 Feher F. J. 275 Fehr C. 199 332 Feigel M. 8 Fekarurhobo G. K. 146 Felkin H. 278 Feller D. 34 37 38 Feng P. 25 Fenselau C. 25 Ferguson I. E. G. 53 Ferlazzo A, 260 Fernlndez Alonso J.I. 30 35 Fernkndez Rico J. 30 35 Ferrario F. 177 Ferretti J. A. 4 Ferrier R. J. 194 Fessner W.-D. 207 Fiaschi R. 229 Field F. H. 21 26 Field J. 12 Figari G. 31 Filipek S. 53 200 23 Filmore K. L. 226 Finch P. 22 Fink M. J. 298 Fink W. H. 32 Finke R. G. 280 Finkelstein B. L. 333 Finzel R. B. 196 Fiorani T. 286 Fiorenza M. 168 Fiori G. 134 Firouzabadi H. 165 Author Index Fischer A. 63 221 223 229 Fischer H. 97 Fischer J. 3G3 Fischer J. W. 50 216 Fischer K. 234 Fischetti W. 161 Fisher B. J. 276 Fisher J. 236 Fishpaugh J. R. 262 Fishwick 9. TI. 258 Fitjer J. 206 Fitjer L. 59 113 194 Fitzgerald G. 33 37 193 Flack H.D. 166 Flammang R. 196 Flann C. J. 324 Fleischhauer I. 114 Fleming I. 189 Fleming S. A. 143 Fliege W. 56 Flippen-Andersen J. 177 Flippin L. A. 174 3 10 Flitsch W. 254 Florio S. 245 309 Floss H. G. 9 Flott H. 171 Flurry R. L. 29 Flynn D. L. 348 Foa M. 286 Fodor G. 177 Fogarasi G. 43 Fohlman J. 26 Fomum Z. T. 156 Fontecave M. 151 Foote C. S. 142 Ford G. P. 101 Fordyce W. A. 276 Forni A. 173 Forsen S. 16 Foster R. 225 Fourrey J.-L. 171 Fowler F. W. 65 350 Fox D. J. 31 33 Fox D. P. 105 Fox J. L. 367 Fox K. 12 Fox M. A. 126 14 Foxman B. M. 356 Francalanci F. 286 Franceschi G. 237 Franchi G. 237 Franck-Neumann M. I16 Francois B.295 Frank R. 24 Franken S. 302 Fraser R. R. 229 Freeman P. K. 296 Freeman R. 6 7 8 9 12 Freeman W. A, 373 Frei B. 106 107 Freiser B. S. 27 Frejd T. 230 295 Frenkiel T. A, 6 9 Frenking G. 20 35 38 Frey M. H. 18 Frey P. A. 13 Frey R. 42 Friedli F. E. 235 Friedrichs E. 361 Friedrichsen W. 262 Frisch M J. 36 44 Frissen A. E. 192 Fritz H. 199 Frolow F ,354 Fronczek F. R. 358 Frouczek F. R. 58 Fry A. 75 76 Fuchigami T. 261 Fuchs K.-A. 74 Fuchs P. L. 329 Fueno T. 38 117 Fuentes J. J. 144 Fuhr B. 270 Fujii K. 137 Fujimoto H. 201 Fujimoto K. 334 Fujisawa T. 165 178 180 182 186 189 346 Fujita E. 153 Fujita M. 346 Fujita S. 215 Fujiwara J.197 337 346 Fujiwara T. 192 Fukuda Y. 219 Fukumoto H. 179 Fukunaga T. 209 Fukushima M. 314 Fukutome H. 32 Fukuzaki K. 195 Fukuzawa S. 198 305 Funabiki T. 162 273 Funaro S. 355 Fyfe C. A. 17 Gaa P. C. 200 Gabard J. 372 373 Gabe E. J. Ill Gabel G. 241 Gauman T. 21 Gaffney A. 78 Gagneux A. R. 22 Gagnier R. P. 170 Gagnon S. D. 143 Gal A. W. 296 Gal M. 296 Galamb V. 386 287 288 Galvez C. 257 Gammill R.B. 264 Gandour R. D. 357 358 Ganem B. 364 Gannett P. M. 126 Gano D. R. 40 Gano J. E. 102 Canter C. 79 Ganzer G. A. 117 Gapinski D. M. 339 Garbe J. E. 239 Garcez W. S. 9 Garcia de la Vega J. M. 30 35 Gardano A. 286 Garigipati R. S.62 65 182 340 Garlick P. B. 4 Garner P. 54 200 Garratt P. J. 243 Garst M. E. 200 Garti N. 231 Gasc N. B. 341 Case M. B. 156 181 Gaskell S. J. 25 Gassmann P. G. 42 67 202 Gatto V. J. 358 Gattuso M. 260 Gaudemar M. 178 309 Gaul J. H. 300 Gawronska K. 179 184 Gawronski J. K. 179 184 Gee P. S. 237 Geevers J. 360 Gehrig K. 231 Geike W. A. 17 Gennari C. 186 308 319 Geoffroy P. I16 George J. 228 George P. 44 Gerlt J. A. 15 Germain G. 236 Gero S. D. 194 Geschwandtner W. 294 Gesson J.-P. 223 Getty S. J. 190 Geuder W. 377 Geurink P. J. A, 294 Ghatak V. R. 227 Ghavshou M. 245 Ghera E. 2 17 Ghiglione C. 113 191 Ghirardelli R. G. 356 Ghosez L. 251 Ghosh A.K. 206 Giacomello P. 22 Giammatteo P. 125 Giandinoto S. 253 Giannone E. 229 Giersig M. 206 Giese B. 104 Giessman U. 23 Gilardi A, 184 Gilbert 9. C. 95 Gilbert J. C. 113 186 194 Gilchrist T. L. 54 Giles J. R. M. 90 94 Gill H. S. 109 Gill R. S. 119 Gillaspey W. D. 149 Gillespie D. G. 71 Gilman J. W. 203 Gilmore C. J. 376 Gingrich H. L. 51 Ginos J. Z. 179 Ginsberg D. 235 Author Index Giomini C. 129 Giordano C. 155 343 Girard Y. 144 Gisin B. F. 26 Gladysz J. A. 273 Glanzmann M. 213 Glatzhofer D. T. 241 Gleiter R. 54 208 Glenn R. 83 Glidewell C. 41 42 94 198 Glish G. L. 19 Goasdoue C. 309 Goasdoue N. 14 309 Goddard W. A. 111 43 Godfrey P. D. 193 Goebel D. W. 303 Gobel I. 355 Goel A.B. 296 Golitz P. 239 Goh S. H. 87 226 GrdeniC D. 296 Gr6e R. 186 190 Greeley A. C. 203 Green B. N. 24 25 Green B. S. 145 377 Green J. R. 182 Greenberg A. 43 192 Greenblatt J. 362 378 Greene A. E. 177 206 228 Greenwood R. C. 201 Gregg M. 362 Gregory A. R. 37 Grev R. S. 40 Gribble G. W. 173 257 Grieco P. A. 54 200 348 Griend L. V. 15 Griffey R. H. 9 12 Griffin J. 256 Grigg R. 162 Griller D. 91 98 104 110 Hacker N. P. 103 104 217 Hackett P. 147 Hada M. 33 Haddon R. C. 37 40 42 44 Haenel M. W. 240 Haffmanns G. 55 Hafner K. 101 Hagihara T. 171 Hagiwara I. 175 Hahn M. 16 Hails M. 18 Haines A. H. 360 Hakushi T. 141 359 Halim H. 19 Hall C. D. 361 Hall L. D. 1I 223 Hall M. B. 29 Halle J.-C.,225 Haller K. J. 298 45 21 I 233 Gokel G. W. 238 357 358 364 378 Grimaldi J. 183 111 Hallnemo G.177 Hallock J. 336 Gokhale V. 163 Grimaldo C. I1 Halpern J. 276 Gold V. 80 225 359 Grimes R. N. 8 Haltiwanger R. C. 52 Golding B. T. 168 281 Grimme W. 209 Halton B. 101 Golding P. 225 Grimshaw J. 123 127 Hamada Y. 121 Goli D. M. 357 Grimshaw J. T. 127 Hamaguchi H. 132 Golinski J. 224 Groenen E. J. J. 17 Hamamoto I. 153 Golse R. 296 Gropen O. 30 Hamamoto T. 262 Gomann K. 214 Gross B. A. 73 Hamill B. J. 233 Gommer B. 38 Gross G. 196 248 Hamlet A. B. 250 Gompper R. 271 Gonzalez A. 257 Gross M. L. 20 22 27 Grossi L. 93 Hammer B. 331 Hammond P. J. 361 Goodings E. P. 359 Gopal M. 288 Grossman J. 85 Groves J. T. 168 285 Hamon D. P. G. 207 Hanack M. 74 Gopalakrischnan G. 83 Grubbs R. H. 158 284 308 Hanafusa T. 165 171 Gopalan A. S. 179 Gordon M.D. 49 209 Grue-S~rensen,G. 14 GrujiC Z. 138 Hanagan M. A. 230 Hanamoto T. 50 Gordon M. S. 40 41 209 Guanti G. 80 Hanauer J. 226 Goren Z. 376 Guarna A. 356 Hancock R. A, 22 Gorki C. 224 Gulacar F. O. 21 Handy N. C. 31 Gorleach Y. 201 Gunther H. 184 241 242 27 2 Hansen G. R. 360 Gosavi R. K. 42 102 Guenzi A. 2 10 Haque W. 237 Goskinski O. 38 Gosney I. 108 233 Gossauer A. 271 Goto J. 146 Guerin P. 21 Guest M. F. 34 Gugel H. 233 Guilard R. 297 Hara K. 106 Hara S. 152 171 315 Harada J. 226 Harada K. 26 183 Gotoh Y. 178 346 Guilhem J. 361 Harada T. 108 243 Gotor V. 264 Guillaume A. 90 Harakema S. 360 Gottfried R. 242 Guillaumet G. 271 Harano Y. 191 Gottlieb H. E. 166 Gottschalk P. 253 Guillemin J.-C. 181 246 Guimion C. 299 Harding L. B. 33 Hardinger S. A. 56 Could I.R. 96 103 104 Gupta Y. N. 58 233 Hardy P. M. 14 Could T. J. 59 Gustowski D. A. 357 Hariharan P. C. 30 45 Govindan S. V. 106 Guthrie J. P. 67 Harkema S. 355 Cower J. L. 25 Gutsche C. D. 237 238 354 Harland P. A, 215 Grace D. S. B. 356 371 372 Harmony M. D. 190 Graden D. W. 4 Harnisch J. 236 Graham W. A. G. 274 275 Haack J. L. 203 Harris F. 30 Grant D. M. 17 298 Haakansson P. 26 Harris F. L. 271 Grasse P. B. 112 Haasnoot C. A. G. 4 Harris R. N. 193 Gray G. A. 7 Habat Y.,361 Harrison J. A. 125 Gray P. D. 30 31 Habbachi F. 178 Harrison J. F. 34 Graziani R. 305 Habitz P. 30 Harrison R. J. 31 Author Index Hart B. T. 193 Hart D. J. 199 Hart H. 102 108 229 Hartling S. 134 Hartman J. R. 356 Hartshorn M. P.166 Hartwig W. 165 Hartz G. 135 Harvey D. J. 20 Harvey R. G. 235 Harwood L. M. 60 Hasan M. 241 Hasan T. 76 Hase W. L. 39 Hasebe M. 270 Hasegawa A. 94 95 Hasegawa S. 214 Hashimoto K. 166 Hashimoto M. 207 Hashizume T. 364 Haskins N. J. 23 Haslinger E. 6 Hassaneen H. M. 219 Hassel P. 182 Hassner A. 192 Haszeldine R. N. 58 Hatakuyama T. 201 Hatano M. 15 Hatayama Y. 286 Hatfield G. L. 200 Hattori K. 336 Haubenstock H. 173 Haufe G. 198 Haupt E. 8 247 Havel T. 355 Havriliak S. 38 Hawkes G. E. 16 Hawkins B. L. 9 12 Hawkins L. D. 167 Hawkins R. T. 372 Hay P. J. 41 Hayami J. I. 153 Hayase Y. 194 Hayashi H. 346 Hayashi N. 112 Hayashi T.159 170 171 176 314 Hayes P. C. 54 Hayes P. J. 17 Hayes R. A. 117 Hays G. R. 17 Hayward R. C. 354 Hazard R. 129 He Z. 54 Head R. A. 273 Heaney H. 219 Heath W. F. 68 Heathcock C. H. 173 174 310 311 333 Heavner G. A. 8 Hebert E. 170 Heck R. F. 161 Hedrixson R. R. 356 Heerma W. 25 Heerschap A. 4 Heffernan J. G. 365 Hegade S. 173 Hegarty A. F. 45 Hegarty D. 30 Hegedus L. S. 172 230 282 314 Hehre W J. 29 119 Heilbronner E. 193 Heimann M. R. 205 Heinicke J. 304 Helgeson R. C. 373 Heller D. N. 26 Hellmann. J. 15 Helsby P. 222 Hencher .I.L. 303 Henderson G. N. 63 221 223 229 Hendewerk M. L. 42 Hendrick K. 356 Hendrickson J. B. 54 200 260 266 Henin F.147 Henke H.-E. 241 Henly T. .I.,15 I 288 Henning 1’. G. 114 196 Henning K.,205 Heo G. S. 357 Herman 2. S. 29 Hernandez R. 255 Herndon W. C. 219 Hershberger S. S. 231 Herz C. P. 240 Hess B. A jun. 37 64 Hess T. C. 117 Hesse M. I98 Hewgill F. R. 124 Hiberty P. C. 37 Hickmott P. W. 182 Hicks M. G. I18 Higashi I. 376 Higashimuta T. 217 298 Higuchi H 240 Higuchi K 182 Higuchi T. 299 Hilbers C. W. 4 Hill C. L. 151 288 Hill J. G. I68 Hill J. H. M. 270 Hillier I. H. 34 Hillson P. J. 127 Hilton C. 48 Hilty T. K. 300 Hinchliffe A 45 Hintsa E. J 356 Hinz R. 241 Hioki T. 3 14 Hipes P. G. 357 Hirai H. 376 Hiranuma I-i. 215 Hirao A, 173 345 Hirao I.50 172 245 Hirao K. 40 Hirao T. 191 Hiraoka M. 378 Hiroi K. 61 63 184 Hiroi Y. 182 Hirose Y. 214 Hirotsu K. 299 Hirst D. M. 34 Hishida S. 26 Hitchcock P.B. 294 Hiyama T. 166 Hockerman G. H. 219 Hodge P. 215 Hodgkinson I. 360 Hoesch L. 58 Hoffer B. L. 144 Hoffmann H. M. R. 70 171 205 310 Hoffmann M. R. 41 Hoffmann R. W. 166 181 227 233 313 Hoffmanns G. 254 Hofmann K.-L. 269 Hogg J. L. 83 Hoinkis J. 45 Hojo M.,165 Holmes J. L. 19 20 Holmes S. J. 278 Holmes-Smith R. 278 Holt D. A. 334 Holt D. E. 16 Holton R. A, 307 Homanen L. 43 Hommeltoft S. I. 174 Hommes H. 259 Honda Y. 362 Honek J. F. 166 237 Hong C. Y. 169 Hong P.163 Honour J. W. 25 Hooz J. 308 Hope H. 294 Hopkins A. 378 Hopkinson A. C. 41 Hoppe D. 175 Hoppe M. 206 Hore P. J. 9 Hori I. 159 Hori T. 192 Horiguchi Y. 310 Hornback J. M. 214 Horner L. 124 Horning E. C. 27 Hortelano E. 378 Horton D. 52 194 Horton M. 206 Hosar R. V 8 Hoshino I. 252 Hoshino M. 153 Hosomi A. 167 300 Hosseini M. W. 365 Hotokka M. 36 Hotta H. 201 Houghton E. 25 Houk K. N. 35 38 53 57 58 102 105 233 260 344 Hoult D. I. 12 Hounshell W. D. 210 Houriet R. 86 House H. O. 200 203 Hovakeemian G. H. 234 Hoveyda A. H. 147 331 Howard D. K. 148 Howard J. A. 92 94 96 Howbert J. J. 144 205 Howes D. A. 168 Hoyano J.K. 274 Hmcir D. C. 297 Hrjez B. 203 Hsu H. L. 39 Hu G. Y. 356 Huan Z. 109 Huang G. T. 49 Huang H. B. 40 Huang M. B. 38 Hubbard J. L. 16 Huber I. 251 Hubert A. J. 285 Hudlicky T. 106 Hudson A. T. 168 Huhnermann W. 269 Hummer W. 74 Hunig S. 377 Huet F. 193 Hughes D. L. 356 Hughes J. W. 204 Hughes L. 97 Huhtasaari M. 178 Huis R. 17 Huisgen R. 56 57 Hull W. E. 8 9 Humphrey M. B. 278 Hunkler D. 242 Hunt C. A. 144 Hunter B. K. 11 Huntsman W. D. 115 Husain A. 165 167 Huser D. L. 231 Husk G. R. 331 Hussey B. J. 173 Hussmann G. P. 143 253 299 300 Hutchins M. 127 Hutchins R. O. 69 Hutchinson L. L. 296 Huttner G. 177 Hutton W.C. 4 8 Huy P. T. 105 Huynh C. 164 Huyser E. S. 38 Hwu J. R. 112 185 194 342 Hyatt J. A. 372 Hyun M. H. 182 Ichikawa J. 178 Ichikawa K 226 Iden R. 270 Igawa A. 32 Iida H. 346 Iida K. 313 Iida S. 186 Iitaka Y. 214 Ikeda H. 158 172 Ikeda I. 357 Ikeda T. 238 360 Ikehira T. 50 Ikuta S. 22 45 Illuminati G. 357 361 Imai K. 185 Imaizumi M. 183 Imamoto N. 185 188 Imamoto T. 169 183 Imanaka T. 167 Inaba S.-I. 172 Inaba T. 346 Inazu T. 241 Inesi A. 129 Ingold K. U. 91 96 97 Innes D. I. 127 Inokawa S. 185 Inokueki T. 135 Inomata K. 172 Inoue K. 133 134 Inoue M. 80 Inoue S. 192 Inoue T. 165 Inoue Y. 141 359 Ireland R. E. 59 Irngartinger H.193 239 Irra T. A. 373 Ishibashi H. 252 Ischida N. 231 Ishida Y. 337 Ishiga O. 131 Ishiguro H. 152 3 15 Ishii T. 188 Ishikawa M. 299 Ishikawa N. 173 Ishiwada K. 296 lshizaki K. 131 Isimura A, 137 Ismail Z. M. 171 Isobe E. 298 Isoe S. 194 204 Isogai K. 207 Itagawa K. 243 Itahara T. 245 Itami H. 61 171 Ito K. 177 345 Ito S. 226 227 Ito Y. 50 183 236 237 Itoh K. 337 Itsuno S. 173 345 Ivor A. S. 25 Iwamatsu K. 251 Iwamura H. 118 210 Iwao M. 10 Iwas M. 230 Iwasawa N. 175 Iwata K. 270 Iyengar N. R. 223 Iyer P. S. 91 Iyoda J. 299 Iyoda M. 243 Author Index lzatt R. K.,360 372 Izatt S. R. 372 Izawa Y. 112 344 Izumi T. 165 Izumi Y.170 183 Jabri N. 172 Jackman L. M. 170 Jackson A. C. 158 Jackson D. A. 192 Jackson M. B. 248 Jacobson K. A. 18 Jacquesy J.-C. 223 Jadhav P. K. 155 174 312 Jaggi D. 267 Jalander L. 170 James B. R. 177 195 Jamieson M. A,. 274 Janda M. 135 Janik D. S. 246 Janout V. 153 Janowicz A. H. 274 Jansen A. C. A. 209 Jaouannet S. 129 Jaqueu G. 173 Jarman M. 19 22 Jarvis S. E. 167 Jashiro M. 219 Javeed S. M. 50 237 Jeffrey-Luong T. 159 Jefford C. W. 105 114 267 Jeger O. 106 107 Jelich K. 213 Jencks W. P. 76 Jenkins T. C. 98 Jenner G. 72 Jennings M. 147 Jennings W. B. 134 Jerina D. M. 235 Jiang Z. Q. 142 200 Jibril I. 177 Jimenez C. 156 Jitsukawa K.158 Jodhan A. 104 J~rgensen,P. 32 33 Johannis J. P. 25 Johne S. 134 Johnson A. T. 200 Johnson C. A. 208 210 Johnson M. D. 273 Johnson M. R. 249 Johnson R. P. I1 5 198 Johnson W. S. 166 183 204 312 316 317 322 Johnstone R. A. W. 25 173 Johri K. K. 156 Jondiko 1. J. O. 195 Jones B. A. 360 Jones C. R. 143 Jones D. W. 214 215 Jones G. 118 362 Jones G. A, 157 Jones J. H. 269 Jones M. 41 Author Index Jones P. G. 361 Jones P. S. 237 Jones R. C. F. 255 Jones T. K. 174 195 Jones W. D. 275 Jonsall G.,38 Jonvik T. 44 Jordan K. D. 105 Josel H.-P. 354 361 Jost R. 21 1 Jouannetaud M.-P. 223 Joullie M. M. 260 Jovanovic M. V. 265 Jug K. 209 Juillard M.141 Julia M. 78 182 184 347 Junek H. 184 Jung A. 176 3 I2 Jung,M. E. 200 Jung S.-H. 156 181 340 Jungk S. J. 357 358 Jurczak J. 53 200 253 360 Jurlina J. L. 206 Jutzi P. 295 301 Kabuto C. 300 Kabuto K. 209 Kadoya M. 185 Kampchen T. 269 Kaftory M. 235 Kagan H. B. 177 Kageyama T. 173 179 184 Kagotani M. 161 Kahn M. 339 Kahne D. E. 343 Kaifer A. 357 Kaiserman H. 77 Kaji A, 153 185 Kakiuchi K. 203 239 Kakizaki F. 21 I Kalcher J. 40 Kalchhauser H. 6 Kalinina G. S. 302 Kallenbach N. R. 4 Kallmerten J. 59 Kambara H. 26 Kamensky I. 26 Kameyama M. 224 Kamitori Y. 165 Kamiya Y. 93 172 Kamiyama M. 177 Kamiyama N. 143 Kamogawa H. 185 Kanakarajan K.215 263 Kanari T. 376 Kanemoto S. 341 Kang G. J. 2 I8 Kang J. 232 Kang S. I. 357 Kang Y.-H. 160 Kanoh S. 345 Kanzawa. A. 185 Kaptein R. 9 Ksradakov P. 30 Kariv-Miller R. 23 1 Karle I. 177 Karni M. 20 38 105 Karpf M. 113 Karrick G. L. 219 Karwowski J. 31 Kasahara C. 167 Kase K. 125 Kashefi-Naini N. 80 Kashimura S. 131 132 135 136 173 181 Kaske W. C. 273 Kasmai H. S. 64 Kata I. 141 Kates M. R. 73 Kato H. 40 Kato J.-I.. 175 Kato M. 298 Katoh A. 173 Katoh T. 184 Katritzky A. R. 20 265 272 Katsuki T. 227 Katsuno H. 252 Katsuro Y.,171 Katz H. E. 367 Katz T. J.. 17 Kauffmann T. 177 Kaufman J. J. 30 45 Kaufmann K. J. 112 Kaulen J.130 Kaur G. 145 Kaur N. 145 Kawada hi. 106 Kawada Y. 210 Kawahara S. 179 Kawai M. 170 Kawakami Y. 159 Kawanisi M. 266 Kawara T. 178 180 Kawasaki K. 245 Kawasaki T. 179 Kawasaki Y. 166 Kawashima M. 178 180 189 Kawashima T. 188 Kawata T. 376 Kawate T. 171 3 89 Kemmer D. 4 Kempsell S. P. 8 Kemula W. 353 Kendric J. 34 Kennard O. 114 Kennedy J. D. 293 Kennedy W. S. 273 Kentgen G. 207 Ken;,on G. L. 13 15 Keough T. 21 25 Kerr R. G. 163 Kesseler K. 176 317 Kessler H. 9 Kestner N. R. 45 Ketcha D. M. 261 Khackik F. 148 Khait I. 18 Khanna I. 237 Khanna R. K. 238 364 Khemani K. C. 13 Kice J. L. 160 Kidd K. G. 37 Kidoura K.I19 Kikui T. 357 358 Kim D.-W. 250 Kim J.-I. 161 Kim J. K. 23 Kim K. S. 102 Kim S. 169 172 178 Kim T. H. 194 Kim Y. C. 178 Kimura E. 368 Kimura K. 357 365 Kimura Y. 62 179 334 348 365 Kinast G. 25 1 Kinda H. 358 King H. F. 30 33 38 King J. F. 13 King K. 300 King M. M. 271 King R. B. 32 Kingham A. D. 6 Kinney W. A. 51 Kinoshita H. 172 Kinoshita M. 95 Kinoshita T. 226 Kintzinger J. P. 362 Kira M. 226 Kirby A. J. 67 81 82 83 Kirby G. W. 53 Kirisawa M. 248 Kirk T. C. 200 Kirms M. A, 242 Kirmse W. 114 196 Kanazawa T. 256 Kanda K. 33 1,. Kazansky P. 17 Kirszensztejn P. 365 Kebarle P. 22 Kirtane J. G. 168 340 Kandil A. A. 168 Kandil F. 362 Kane V.V. 173 350 Kaneda K. 158 167 Kanehira K. 3 I4 Kaneko H 178 Kanemasa S. 2 16 262 Keeffe J. R. 76 Keller P. J. 9 Keller S. M. 92 Kellogg M. S. 204 322 Kelly M. J. 52 201 Kelly W. J. 184 Kelson A. H. 195 Kishi N. 62 192 334 Kishi Y.,338 Kishimura T. 203 Kisielowski L. 186 Kitagawa T. 71 201 Kitagawa Y. 178 329 Kitamura K. 179 197 Author Index Kitaura K. 43 Kitayama R. 63 184 Kitazume T. 173 Kitching W. 213 Kito T. 178 Kitsuki T. 238 360 Kiyooka S. 174 31 1 Kjeldsen G. 174 Klarner F.-G. 63 Klauck G. 242 Klaus A. J. 231 Kleefeld G. 270 Klein H. 171 Kleiner T. 378 Klett M. W. 115 Kletzin H. 276 Klingebiel V. 299 Klingler L.148 Klingstedt J. 230 Klingstedt T. 295 Klumpp G. W. 172 295 Knapp S. 55 236 Knaus G. H. 241 Knochel A. 360 Knorr R. 182 Knossow M. 377 Knowles W. S. 344 Knudsen J. S. 174 Kobayashi H. 358 Kobayashi K. 376 Kobayashi N. 15 Kobayashi T. 179 223 Kobayashi Y. 313 Koch H. F. 75 Koch J. G. 75 Koch K. 65 350 Koch K. U. 360 Koch N. H. 75 Kochbar K. S. 173 Kocienski P. 321 Kodama M. 365 Kodama S. 245 Kodera Y. 178 Kohler H.-J. 41 Konig P. 58 Koga N. 210 Kogler H. 9 Kohda A. 142 Kohl F. 301 Kohler F. H. 17 Kohmoto S. 267 Kohn H. 156 181 340 Kokko B. J. 228 Kokosa J. M. 260 Kokuba T. 155 Kolb M. 181 Kolbeck W. 56 Kolbon H. 184 Koller M.113 Kollman P. A, 355 Kolos W. 44 Kolosova N. D. 302 Komatsu T. 3 13 Komiyama M. 354 376 378 Komori T. 138 Komornicki A. 43 Kon K. 204 Kondo Y. 245 Kong S. Y. 22 Konig L. 114 115 Konishi M. 176 314 Kopecky K. R. 208 Kopf J. 360 Koppel H. 39 Koreeda M. 348 Korenstein R. 378 Kornblum N. 184 Korpar-Colig B. 296 Korpela T. K. 67 Kortbeek A. G. T. G. 17 Korth H. G. 97 Korzeiowski S. H. 378 Kos A. J. 35 37 39 44 Koshimo J. 167 Koshkinen A. 266 Kostyanovsky R. G. 358 Kosugi M, 175 224 252 Koszyk F. J. 106 Kotake H. 172 Kotnis A, 220 Kotzyba-Hibert F. 373 Koutecki J. 38 117 Kovacic P. 22 Koya K. 240 Koyama K. 141 Kozikowski A. P. 56 156 178 200 329 330 Kozlowski J.A. 170 Kozluk T. 53 200 253 Kozyrod R. P. 319 Krafft M. E. 307 Kralj B. 24 Kramer J. 220 Kramer V. 24 Krane J. 356 Kratt G. 210 Kraus G. A. 237 253 Krause M. J. 273 Kravetz T. M. 54 208 Kremer R. 233 Kresge A. J. 83 Kress W. 296 Kresze G. 158 343 Krief A. 159 189 Krieger G. 234 240 241 244 Krimmer H.-P. 101 Krishna N. R. 8 Krishnamurthy S. 15I 347 Krishnamurthy V. V. 91 Krohn K. 237 Krolikiewicz K. 265 Kruger C. 204 294 295 Kruglov D. E. 259 Kruithoff K. J. H. 172 Kruse L. I. 21 1 Kruzan T. D. 230 Kubota H. 173 185 Kudo T. 41 42 Kuebart F. 242 272 Kunzer H. 169 Kugimiya M. 240 Kuhlmann K. F. 221 Kuksis A. 362 Kulik W.259 Kulkarni S. U. 169 227 347 Kulp S. S. 183 Kulp T. 106 Kumada M. 170 171 176 231 245 299 314 Kumagi T. 119 Kumar A. 7 Kumar B. 145 Kumar K. 186 Kumar S. 235 Kunishi T. 95 Kuntz I. D. 355 Kunz H. 179 KupEe E. 300 Kupfer E. 179 Kurita J. 270 Kurita M. 158 172 Kuroda T. 141 Kurth M. J. 333 Kusano Y. 232 362 Kusumoto T. 169 Kuwajima I. 166 172 176 189 195 309 310 335 350 Kwart H. 78 Kwon Y. C. 344 Laarhoven W. H. 232 Labadie J. W. 172 L'abb6 G. 248 Labhart M. P. 203 Lacombe S. 171 Laubli M. W. 378 Laganis E. D. 246 Lahousse F. 16 La John L. A. 42 Lam H. Y. 237 Lamanna W. 278 Lamaty G. 173 Lamb J. D. 372 Lambert G. J.227 Lambert J. B. 105 196 Lami A, 31 Lammer O. 186 Lammerink B. H. M. 119 Lammertsma K. 35,44 220 Lampe J. 173 310 Lana J. C. A. 364 Lancaster M. 21 1 Landgrebe J. A. 109 Landini D. 224 Landmann B. 166 313 Landry D. W. 204 Land B. M. 239 Lange B. C. 170 Langell M. A. 73 Langridge R. 355 Lansard J.-P. 177 228 La Page T. H. I98 Author Index Lapointe P. 250 Lapsina A. F. 300 Lardicci L. 162 Larock R. C 231 Larsen D. S. 79 Larson E. G. 105 Larson E. R. 52 Lasch J. G. 303 304 Lasne M.-C. 246 Latour S. 302 Lattes A. 156 181 341 Lau C. L. 201 Lauer M. 373 Laurent A. 146 171 181 Laurent E. 137 Lavayssiere H. 299 Law K.-L. 163 Lay J. O.Jr. 22 Layton W. J. 10 Leake J. S. 187 Lebioda L. 106 Lechevallier A. 193 Lecomte J.-P. 361 Lee D. Y. 265 Lee H.-W. 271 369 Lee J.-G. 43 Lee J. H. C. 200 Lee J. I. 172 178 Lee K. H. 4 Lee L. 14 Lee M. L 10 Lee S. D. 253 348 Lee T. S. 166 Lefour J. M. 39 Leginus J. M. 57 Lehmen J. 25 Lehn J.-M. 353 355 361 365 373 378 Lehner D. 16 Lehni M. 97 Leibfritz D. 8 Leiden T. M. 194 Lein G. M. 360 Leininger H. 202 21 1 Leipzig B. D. 208 Lelandais D. 137 Lemal D. M. 246 Lemieux E. 364 Leng J. L. 162 Lengsfield B. H. HI,36 Lenkinski R. E. 14 Lennartz H.-W. 242 le Noble W. J. 72 376 Leonard J. M. 30 Leonard N. J. 268 Lepage L. 172 Lepage Y.172 Le Page Y. 11 1 Leppkes R. 238 359 378 Leroy G. 30 38 Lesch D. A 16 Lesma G. 134 Lester W. A. jun. 36 Leuenberger H. G. W. 179 Leung W. W.-H. 177 Levine J. A. 238 371 Levsen K. 19 Levy G. c. 21 1 Levy L. A. 235 Lewis I). F. 362 Lewis E. S 92 Lewis F. D. 148 Lewis I. A. S. 25 Ley F. 356 Ley S. V. 185 Liang W. 253 Liberato D. 25 Libman J. 166 354 Licandro E. 224 Liebe J. 239 Lieberknecht A. 183 Liebman J. F. 43 192 Liepins E. 300 Lier J. G. 25 Lieu M. H. 41 Liewald G. R. 294 Lillie T. S. 332 Lim C.-E. 168 Lin C.-Y. 58 Lin J.-M. 65 350 Lin L.-J. 190 Linderman R. J. 181 Lindig M. 179 Lindner H. J. 210 Lindsay D. A. 96 Lindsay Smith J.R. 223 Lindstaedt J. 262 Linstrumelle G. 159 164 Lion C. 172 Liotta D. 227 Liotta D. C. 85 Lipschutz B. H. 170 Lipscomh W. N. 355 Lishka H. 41 Little R. D. 130 Liu B. 36 37 Liu M. T. H. 104 112 Liu Y. 357 Livinghouse T. 55 254 Livingston R. 97 Liz R. 163 Lloyd D. 198 Lloyd D. H. 256 Lochead A. W. 53 Locke S. J. 93 Loder J. 271 Lohr H.-G. 234 376 Low P. 182 Lohmann J. J. 116 Lommer O. 177 Lommes P. 97 Long D. A. 219 Longone D. T. 241 Lopez A. 149 Lopez R. C. G. 184 Lopez Ortiz F. 264 Losing F. P. 19 98 Lotts K. I). 219 391 Loubinoux B. 271 Lounasmaa M. 266 Loupy A. 169 Louw R. 98 Lowe G. 13 185 Lowmaster N. E. 255 Lu L.D.-L. 181 Lucchesini F. 262 Luche J.-L. 177 228 Luche M.-J. 206 Ludwig E. G. 304 Luedtke A. E. 92 Luftmann H. 178 Lugtenburg J. 221 235 Luisi P. L. 353 Lukacs A. 278 Lukacs G. 9 Luke B. T. 34 44 Luken W. L. 30 Lukevics E. 300 Lukyanenko N. G. 358 Lumma P. K. 269 Lumma W. C. 261 Lunazzi L. 93 96 Lund A. 40 Lunnell S. 40 LUO F.-T. 50 283 314 Luss H. R. 305 Lusztyk E. 96 Lusztyk J. 95 96 Lutomski K. A. 230 Lutz G. 24 Luxen A. 262 Lynch D. 32 Lyle S. B. 219 Lynden-Bell R. M. 12 Lynn D. G. 4 Mabbott G. A. 123 Mcbride B. J. 200 Maccagnani G. 119 McClelland R. A. 67 McClure D. E. 269 McClusky J. V. 170 McDaniel C. R. 18 McDaniel W. C. 203 MacDonald J.G. 58 McDougall D. C. 53 McGamty J. F. 72 166 McGee M. J. 183 Machida H. 153 Machinami T. 52 194 Maciel G. E. 5 298 McIntosh J. M. 182 McIntosh T. J. 93 Mclver J. W. jun. 33 Mack M. P. 356 McKee M. L. 34 102 McKeer L. C. 223 McKendrick J. J. 378 McKenna W. P. 280 MacKenzie A. R. 118 Mackenzie K. 208 McKillop A, 219 McKinnon D. M. 108 MacKirdy I. S. 125 Mackor A, 142 McLain S. J. 361 McLean A. D. 37 MacLean D. B. 230 McLeish M. J. 226 McLennan D. J. 75 Macleod J. K. 19 McMahon R. J. 117 McMaster A. D. 274 McMaster B. N. 38 McMurchie L. E. 29 34 McMurry J. E. 175 197 224 273 319 320 McNeal C. J. 26 McNeil J. M. 93 MacNicol D.D. 376 378 Macomber R. S. 81 McOrnie J. F. W. 217 McPhail A. T. 71 McPherson D. W. 102 McQuarrie I). A. 29 Macura S. 3 McWeeny R. 32 Maeda H. 357 358 Maeda N. 175 176 3 12 3 13 Makela M. J. 67 Maernoto K. 142 Maerk T. D. 19 Maestro M. 274 Mafunda B. G. 191 Maggiora G. M. 44 Magnasco V. 31 Magnus P. 176 205 Mahalanabis K. K. 230 Maier G. 206 Maigrot N. 170 Maillard B. 96 Maiorana S. 224 Mais F.-J. 270 Maitra U. 54 326 Majerski Z. 207 Mak K. T. 161 Makino K. 92 Makosza M. 224 Malatesta V. 147 Malherbe R. 60 Malhotra R. 221 Mallett J. M. 78 Malpezzi L. 359 Mametsuka 66 Manabe O. 232 358 362 376 Mancini M. L. 166 237 Mandai T. 106 Mandal A.K. 155 Mandelbaum A. 20 Mander L. M. 248 Mandolini L. 357 361 Mangeney P. 177 Mangia A. 378 Mangini A. 42 Manirnaran T. L. 373 Manley P. W. 270 Mann B. E. 11 18 Manoharan M. 197 Manojlovic-Muir L. 208 Mannschreck A, 239 Mansour T. S. 229 Mansuy D. D. 151 Mantlo N. B. 265 Mao M. K.-T. 199 Maquestiau A. 20 196 Marat K. 237 Marchand-Brynaert J. 25 1 Marchelli R. 223 378 Marco J. A, 242 Marcuzzi F. 162 Mareda J. 35 58 105 233 Margaretha P. 131 Mariano P. S. 55 149 Maring C. 53 174 327 Mario J. A. 272 Mark J. N. 177 Marschke G. E. 92 Marschner T. M. 13 Marshall D. R. 162 193 Marshall J. A. 106 Marshall J. L. 18 Marshall L. 362 Marsili A. 229 Marson C.M. 272 Martel A. 250 Martelli J. 186 Marti V. P. J. 94 96 Martin A, 173 350 Martin C. W. 109 Martin G. E. 10 Martin. H.-D. 208 270 Martin J. C. 228 230 265 Martin J. P. 98 Martin R. J. 82 Martin S. A, 23 Martin S. F. 330 Martin S. W. 88 Martin V. S. 277 Maruoka K. 181 197 336 337 346 Marusawa H. 226 Maruyama. K. 175 176 312 3 I3 Marvell E. N. 48 Marzin C. 16 Masamune S. 52 166 201 298 323 Masci B. 357 Mashirna K. 176 Mason J. 15 Massad S. K. 167 Mastalerz H.,340 Masuda K. 262 Masuda R. 165 Masuda T. 217 298 Mathews R. W. 356 Mathews W. R. 25 Mathey F. 186 303 Mathis C. 295 Mathisen D. E. 169 Author Index Matier W. L. 173 MatoviC-CalogoviC D.296 Matsen F. A. 34 Matsubara S. 178 341 Matsuda I. 183 Matsugo S. 216 Matsui K. 299 Matsurnoto K. 176 192 Matsumoto M. 227 Matsumoto T. 169 Matsurnura Y. 133 134 136 181 256 336 337 Matsushita H. 178 Matsuura A. 236 Matsuura T. 236 Matteson D. S. 316 Mattina J. L. 260 Mattox V. R. 25 Matulewicz M. C. 22 Maud J. M. 359 362 Maudling D. R. 219 Maurice A. M. 39 Maverick E. F. 366 367 Mavridis A. 34 May D. D. 89 Mayer I. 30 Mayer R. 186 Mayne J. M. 125 Mayr H. 171 Mazzanti G. 119 Mazzocchi P. H. 148 Mbuyi M. 262 Meador M. A. 102 Mechoularn R. 227 Medinger K. S.,43 Mehendale A. R. 236 237 Mehta G. 206 207 Mehta R. 131 MeiC Z.296 Meier H. 58 215 263 Meili J. 23 Meindl P. 362 Meintzer C. P. 90 Meissner U. 241 Meister A. 179 Melius P. 102 Melleas M. F. 278 Meltz C. N. 258 Melzer D. 360 Menard M. 250 Mendenhall G. D. 88 90 Menger F. M. 77 85 Meot-Ner M. 354 Meou A. 113 Merknyi R. 97 191 Mermoud F. 21 Merrifield R. B. 68 Merry S. 39 Mersh J. D. II Mertens A. 220 Mertes M. P. 365 Mestdagh H.,182 Mettee H. D. 44 Meyer G. 130 Author Index Meyer H. 31 Meyer M. C. 144 232 Meyers A. I. 101 181 230 Meyerstein D. 276 Meyn S. 38 Mezey P. G. 32 39 43 Mi A. Q. 237 Michalczyk M. J. 298 Michl J. 120 203 298 Middleton W. J. 262 Midland M. M. 344 Miertiis S.44 Miginiac P. 181 182 Migita T. 175 224 252 Mihelcic J. M. 278 Mikami H. 132 Mikarni K. 62 192 334 Mikhail G. 204 Mile B. 92 94 Miller A. J. 208 Miller A. S. 208 Miller B. 236 Miller D. D. 175 197 320 Miller D. L. 20 22 Miller J. A. 163 195 314 Miller L. L. 233 Miller R. D. 170 Miller S. I. 215 Miller T. A. 40 Miller W. H. 32 37 237 Milligan B. 221 Mills R. J. 229 Minami I. 172 177 342 Minami T. 50 232 362 Minamikawa S. 148 Minato A, 245 Miccher D. J. 237 Minelli M. 16 Minisci F 343 Mink J. 296 Minsky A, 209 235 Miranda J. F. 147 Mise T. 163 Misiti D. 288 Mislow K. 210 238 Mison P. 18 I Misumi S. 239 240 Miszak S. A. 264 Mitani M.141 Mitchell J. C. 93 Mitchell T. N. 303 Mitscher L. A, 237 Mitschler A. 303 Mitsui H. 290 Miura S. S. 238 Miura Y. 95 Miyaharra Y. 241 Miyake M. 248 Miyano S. 181 Miyazaki K. 147 Miyazaki T. 181 336 Mizuno H. 166 Mizuno K. 143 364 Mlochowski J. 358 Mloston G. 247 Mobilio D. 198 Mochida K. 295 Mock M. L. 373 Modaressi S. 59 113 194 Modena G. 52 162 Mohacsi I. 177 Moharnadi F. 336 Mohanraj S. 224 Mohr P. 179 Molander G. A. 152 296 Molter K. E. 71 Mompon B. 222 Monego T. 71 Monkiewicz J. 196 329 Montanari F. 224 308 378 Montanucci M. 69 224 Monte W. T. 130 Montevecchi P. C. I17 Montgomery C. R. 104 Moodie R. B. 221 222 Moody C. J. 60 118 260 Mook R.jun. 87 321 Moore 13. W. 249 Moore J. A. 253 357 Moore S. 127 Mooring A. 143 Moran J. R. 366 367 Moran K. D. 221 Morandini F. 170 283 3 14 Morellet G. 223 Moreno-Mafias M. 159 186 Moretti I. 173 Mori A, 346 Mori M. 256 Mori T. 165 182 Mori Y. 187 Moriyama M. 185 Morris CI. A. 6 12 Morris H. 92 Morris H. R. 23 24 Morrow C. J. I78 Morrow S. D. 56 Mortezaei R. 147 Morton J. A. 65 182 Morton 1'.H. 20 Morukuma K. 43 Morvilli A. 304 Moss R. A, 85 103 104 111 228 24:' Mossoba M. M. 92 Mostafavipoor Z. 165 Mosuda K. 173 Motherwell W. B. 87 169 337 342 Motogama Y. 86 Motoi M. 345 Motyka L. 245 Moupert A 186 Moya-Portuguez M. 251 Mrozek J.38 Muchowski J. M. 254 Miiller D. 304 Mueller H.-D. 185 Muller P. 214 Mueller P. H. 102 Muller W. M. 361 Muller-Starke H. 169 172 Munsterer H. 158 343 Muetterties E. L. 273 Mugnoli A. 200 Mugrage B. B. 56 200 Muir K. W. 208 Mukai T. 119 201 Mukaiyama T. 172 173 174 175 178 179 180 182 183 Mulholland D. L. 212 Mullally D. 33 Muller N. 125 Muller P. 279 Mullican M. D. 217 Mulzer J. 177 186 Munegumi T. 183 Munro M. H. G. 166 Murahashi S. 290 Murai S. 286 298 308 335 Murai T. 286 Murakami K. 143 Murakami M. 174 Murakarni S. 298 Murata S. 118 Murata Y. 172 Murphy A. 376 Murphy R. C. 25 Murphy W. S. 227 Murray B. J. 264 Murray R. K. 107 Murray R.W. 235 Murtiashaw C. W. 207 Murto J. 43 Murty A. N. 206 Musso G. F. 31 Muszkat K. A, 18 145 Mutak S. 238 360 Mwseigye-Kibende S. 28 1 Nachbar R. B. 210 Naemura K. 207 Nafti A. 181 Nagai H. 129 Nagai N. 175 Nagai Y. 298 Nagakura I. 201 Naganawa H. 26 Nagano K. !72 Nagarajan K. 12 Nagase S. 41 42 Nagasuna K. 166 Nagata W. 61 Nagayarna K. 7 Nagayoshi K. 142 Nagel C. J. 154 246 Nagl A. 296 Nair M. S. 207 Naito K. 213 Naito T. 185 Nkjera C. 156 Nakada T. 243 394 Nakadaira Y. 300 Newcomb M. 301 Nakagawa H. 252 Newkome G. R. 27 I 36 1 369 Nakahama S. 173 345 Newlands S. F. 233 Nakai T. 62 192 334 Newton M. D. 45 Nakajima I. 245 Nguyen M.T. 45 Nakajima M. 192 Nguyen S. 203 Nakajima T. 188 Niangoran C. 138 Nakajo E. 50 161 Nibbeling H. T. M. 355 Nakajo T. 345 Nicholas K. M. 162 Nakamura A. 166 172 176 Nichols D. E. 256 177 Nichols J. 32 Nakamura E. 166 172 176 Nicholson J. K. 16 195 309 310 324 335 Nickon A. 203 Nakamura H. 360 Nielsen L. 184 Nakamura N. 107 21 I Nielsen R. B. 360 Nakamura T. 357 Niessner M. 181 Nakamura Y.,188 Niki E. 93 172 Nakanishi H. 157 Nilsson A. 182 Nakanishi S. 177 290 Nishiguchi I. 158 172 Nakashima N. 118 Nishiguchi T. 106 Nakashita Y. 198 Nishimura S. 9 Nakata F. 103 Nishioka K. 243 Nakata T. 167 345 Nishiyama H. 337 Nakatsuji H. 33 39 Niven C. E. 125 Nakatsuji Y. 357 358 Nixdorf M. 193 Nakatsuka M.50 237 Nkunya M. H. H. 184 Nakatsuka T. 153 172 No K. H. 238 371 Nakayama J. 153 Nobes R. H. 19 36 Nakazaki M. 207 238 243 Noels A. F. 285 360 Nogata W. 171 Nakazono Y.,266 Noguchi M. 178 Nakazumi H. 238 364 Nogusa H. 132 Naman V. A. 2 I0 Nokami J. 106 123 136 Namy J. L. 177 Nolte R. J. M. 154 Nanasawa M. 185 Noltemeyer M. 355 Nandi R. N. 190 Nomoto T. 344 Nantaku J. 290 Nomura K. 262 Napolitano E. 229 Nonaka T. 138 261 Narang S. C. 167 Nonhebel D. C. 98 Narasimhan N. S. 230 Nonnenmacher A. I86 Narasimhan S. 347 Norman N. C. 303 304 Narayanan K. 231 Norman R. D. C. 95 Narijindiah C. 23 I Normant J. F. 172 177 191 Narita N. 226 Norris W. P. 225 Narula A. P. S. 344 Northcott D. J. 1 I I Naruta Y. 175 313 Nowlin J.G. 27 Nash S. A. 264 Nozaki H. 178 341 Nassal M. 103 Nozaki Y. 108 Navaro O. 45 Nozawa T. 15 Nazran A. S. 110 11 1 Nucciarone D. D. 166 Neemann J. 299 Nudelman N. S. 84 Negishi E. 50 195 283 307 Nugent R. A. 207 314 323 Nugent W. A. 278 Negron G. 55 254 Numomoto S. 159 Neidlein R. 135 242 Nutaitis C. F. 173 Nelsen S. F. 126 Nwokogu G.C. 102 229 Nelson D. J. 155 Nelson W. M. 269 Oakes D. B. 73 Nemer M. J. 26 Obayashi M. 166 Nemoto H. 197 Ochiai H. 161 Neszmelyi A. 9 Ochiai M. 153 Nethercott W. 115 O’Connell A. J. 267 Neugebauer W. 229 O’Connell K. M. 129 Neuhaus D. I I O’Connor M. J. 224 Author Index Oda M. 243 Odaira Y. 203 239 Olund J. 169 Offermann W. 359 Oftring A, 270 Ogata T.192 Ogawa A. 335 Ogawa H. 295 Ogawara K. 167 Ogihara T. 207 Ogilvie K. K. 26 Ogino T. 207 Ogle C. A. 88 Ogoshi H. 154 276 Oguni N. 177 Ogura F. 239 Ogura K. 194 346 Ohanessian G. 37 Ohashi M. 27 Ohkata K. 2 13 Ohkubo K. 43 178 Ohmasa N. 223 Ohshima M. 172 Ohshiro Y. 191 Ohsumi T. 182 228 Ohta H. 178 Ohta K. 39 95 Ohta T. 182 Ohtomi M. 361 Oi R. 135 Oishi T. 146 159 167 345 Ojima J. 243 248 Okada H. 183 Okahara M. 357 358 Okamoto K. 71 201 Okamoto T. 251 Okamoto Y. 170 178 210 238 253 360 Okano M. 155 198 Okawa T. 298 Okawara M. 165 173 179 184 Oki M. 210 21 1 Okimoto M. 129 Okita M. 133 Oku A. 108 Olah G. A. 35 73 91 165 167 211 213 220 Oleksyszyn .I.,304 Olbrich G.40 Oliver J. P. 303 Olivier M. J. 302 Ollis W. D. 65 Olsen J. 32 Olsher U. 355 Olsson T. 241 Omi T. 177 Omote Y. 146 147 250 Onaki M. 170 Onan K. 362 Onda H. 154 Onda M. 193 Ono N. 153 Onozuka J. 194 Author Index Ookawa A. 346 Ootake K. 185 Opalko A. 284 Opella S. J. 18 Oppenheimer N. J. 13 15 Oppolzer W. 52 148 201 213 Orioli P. 356 Oriyama T. 174 Orliac-Le Moing M.-A, 124 Orlinski R. 319 Ormiston R. A. 108 Ornaf R. M. 55 236 Orsini F. 200 Osa T. 15 375 Osaka N. 337 Osamura Y. 33 Oshikawa T. 185 Oshima K. 341 Osuka A. 168 172 173 179 182 185 187 223 Otani R. 236 Otera J.166 Otsubo T. 239 240 Otsuji Y. 143 177 290 364 Ottenbrite R. M. 49 Ottrey A. L. 193 Ouchi M. 359 Oudenes J. 308 Outcalt R. J. 203 Outlaw J. F. 231 Outerquin F. 258 Ovenall D. M. 278 Overheu W. 269 Overman L. E. 49 Owen J. D. 355 356 Oxman J. D. 148 Ozaki N. 214 Ozment J. 32 Pabon R. 143 Pabon R. A. 54 Pacansky J. 39 42 43 Paddon-Row M. N. 38 105 344 Padmanabhan S. 162 Padwa A. 55 58 247 254 Page A. D. 20 Pai G. G. 173 346 Paillons N. 149 Paine J. B. 271 Paknikar S. .K 168 340 Pakulski M. 303 304 Pala P. 44 Palacios F. 264 Palfreymon M. N. 195 Palik E. C. 11 1 Palleros 84 Palmer M. H. 40 Palmer R. A. 356 Palmier C. 258 288 Palmieri G.170 Palmisano G. 134 Palomo C. 183 Pandey K. K. 273 Pandl K. 254 Panetta C. A. 214 Paniagua M. 35 Panico M. 23 24 Pankonski J. 224 Pankratov L. V. 302 Pansegrau P. D. 101 Panzer H. P. 260 Papadopoulos K. 308 Paquette L. A. 51 54 207 208 2 13 Paraskevopoulos G. 98 Pardi A. I Pardini. V. L. 131 Pariza R. J. 329 Park J. M. 1 I1 Park W.-S. 174 Parkanyi C. 143 219 232 Parker D. 170 361 Parker V. D. 123 Parr V. C. 25 Parsons P. J. 108 Parsons W. H. 207 Partain E. M. 253 Pascard C. 222 361 Pastushok V. N. 358 Pate B. D. 223 Patel H. A. 230 Pattenden G. 195 205 206 216 Patrie W. P. 291 Pau C. F. 119 Paudler. W. W. 265 Pauly K.-H.234 Pauzat F. 43 Paventi M. 223 Payne M. A. 221 Payne I’. W. 31 Pearce C. J. 173 Pearlman P. S. 168 Pearson. D. A, 260 Pearson W. H. 184 215 328 Peck C. J. 267 Pecquet-Dumas F. 250 Pedersen C. J. 353 Pedler A. E. 134 Pedrini P. 119 Peel J. l3. 45 Pegg D. T. 12 Pelizzoni F. 200 Pelizzi G. 304 Pelter A. 187 220 315 350 Penco S. 237 Penning M. L. M. 47 Pereyre M. 175 Perez J. A. 266 Perez L. A. 103 104 Perichon J. 130 Perie J. J. 156 181 PerKins M. J. 98 Perry D A. 53 184 Perry M. W. D. 174 Peseckis S. M. 168 Pete J.-P. 145 147 Peter R. 284 Peters E.-M. 201 Peters K. 201 242 Peters K. S. 11 1 Peterson G. E. 255 Peterson J. C. 106 Peterson K.109 Peterson M. R.,32 36 43 Peterson P. 26 Peterson W. 300 Petnehizy I. 187 Petrasch A. 304 Petrier C. 177 228 Petter R. C. 93 Petty C. B. 49 PeyerimhofT S. D. 39 Peymann E. 355 Pfander H. 178 Pfister-Guillouzo G. 299 Pfohler P. 208 Pham T. N. 169 Phillips B. T. 261 Phillips G. B. 310 Phillips L. R. 24 Phillips N. J. 4 Piancatelli G. 168 Piccolo O. 170 283 314 Pierpont C. 280 Pierre J. J. 341 Pierre J.-L. 354 Piers E. 163 201 Pietraszkiewicz M. 360 Pietro W. J. 29 119 Pietrusiewicz K. M. 196 329 Pigeon P. 169 Pike M. M. 14 Pilet O. 208 Pillay M. K. 56 Pillon L. Z. 182 Pinhas A. R. 278 Pinkert W. 355 Pinkerton A. A. 166 208 Pinnick H. W. 173 Pinson J.126 Pinto A. C. 9 Piotrowski A, 176 Piricova N. 135 Pirkle W. H. 182 184 Pirrung M. C. 112 Pitea D. 200 Pitzer R. M. 29 Placucci G. 93 Plante R. 359 364 Platz M. S. 102 104 110 111 112 215 Platzer N. 14 Pletcher D. 123 Plieninger H. 186 Poch G. K. 116 Pochini A. 215 219 238 372 Podejma B. 356 Pogorzelec P. J. 259 Pohl S. 295 Poirer J. M. 70 169 Pokier R. A, 43 Poli G. 308 Poli R. 304 Pomfret A. 214 215 Pommerening H. 304 Ponaras A. A. 60 Pondaven-Raphalen A. 188 Pongor G. 43 Ponterini G. 274 Pope S. A. 34 Pople J. A. 34 35 36 38 44 102 Porskamp P. A. T. W. 52 Porter N. A. 93 Postel M. 15 Pottinger D. 40 Pouet M.-J.225 Poulter C. D. 9 Pounder C. N. M. 31 Pourzal A.-A. 268 Powell H. M. 353 Powell J. 362 Powell M. 139 Powell M. F. 36 Power P. P. 294 Pradere J. P. 86 Prakash G. K. S. 211 213 Prakash O. 356 Pramanik B. N. 27 Prasad G. 143 Prasit P. 194 Pratt W. E. 203 Prelog V. 182 238 360 378 Prewo R. 58 Pri-Bar I. I68 Pribish J. R. 237 Priester R. D. 297 Prinzbach H. 207 242 Procter G. 180 Profeta S. jun. 355 Pross A. 67 69 Prugh S. 237 Puckett W. E. 361 Puff H. 234 302 361 376 Pughia G. 219 Pugmire R. J. 17 Pulay P. 33 43 Purcell N. 195 Purvis G. D. 111 31 34 38 39 Pustovit N. N. 259 Puzo,G. 21 Pyne S. G. 194 Quader A, 158 Quang le Van 9 Quast H.117 201 Quici S. 378 Quinga E. M. Y. 90 Quiniou H. 86 Quintard J.-P. 175 Raab W. 268 Raban M. 362 378 Rabe J. 70 310 Rabideau P. W. 231 Rabinovitz M. 209 235 Racherla U. S. 172 Radke C. M. 242 Radom L. 19 36 38 40 102 Rasanen M. 43 Raggon J. W. 108 Raghavachari K. 36 37 40 42 44 21 I 233 Rahn B. J. 152 Raine G. P. 37 45 Rajadhyaksha S. N. 173 Rajaram J. 344 Raju N. 102 351 Rakhmankulov D. L. 259 Ramakrishnan K. 236 Ramamohan Rao B. 50 236 237 Raman K. 106 194 278 323 Rarna Rao A. V. 50 236 237 Rambaud M. 186 Ramirez-Munoz M. 184 Rand C. L. 323 Randah T. N. 21 1 Randall C. J. 101 Ranu B. C. 106 Rao A. S. 168 340 Rao D. V. 224 Rao R.R. 220 Rao V. B. 215 Rapoport H. 7 Rappe A. K. 43 Rasrnussen C. A. H. 258 Rauchfuss T. B. 16 Rauscher S. 21 Ravenscroft P. D. 2 15 Ravichandran K. 236 Ravn-Petersen L. S. 174 Rawal V. H. 68 Ray J. K. 235 Ray R. 3 16 Raymahasay S. 63 221 Razdan R. K. 227 Razuvaev G. A. 302 Read R. W. 225 Rebek J. jun. 362 Reddy A. V. 207 Reddy D. B. 106 Reddy D. S. 206 Reddy G. S. 10 Redfield A. G. 7 Reed D. W. 90 Reed J. N. 230 Reed L. A. 52 201 323 Reents W. D. Jr. 27 Rees A. J. 269 Rees C. W. 118 260 270 Reetz M. T. 169 172 176 283 284 3 12 3 17 Reeves W. P. 170 Regen S. L. 179 348 365 Regitz M. 269 Author Index Reich H. J. 62 Reid D. G. 12 Reid D. H.259 Reid F. J. 225 Reid S. T. 270 Reimann-Haas R. 241 Reiner G. J. 162 Reinhardt G. 209 Reinhoudt D. N. 47 63 358 360 378 Reinsch E. A, 34 Reisenauer H. P. 206 Reiter R. C. 2 I2 Remuson R. 325 Remy D. C. 144 Renaud R. N. 125 Renfrow R. A. 224 Rentea M. 240 Rescock S. 203 Restilli A. 308 Retey J. 279 Reusch W. 217 Revial G. 49 Revol J.-M. 106 Rexhausen H. 271 Rey M. 65 192 Reynolds C. D. 269 Reynolds C. H. 101 Reynolds M. A, 13 15 Rheingold A. L. 161 Rhodes Y. E. 190 Ribo J. 117 Ricard R. 147 Ricart S. 359 Ricca A, 218 Ricci A. 168 180 347 Ricci M. 154 168 Ricciardi I. 260 Richards W. G. 29 Richardson G. D. 267 Richey H. G. jun. 181 Rickborn B.213 Ridd J. H. 222 Rideout D. 54 326 Ridley D. D. 184 Rieke R. D. 172 Riemenschneider C. 175 Riemschneider R. 227 Riepl G. 345 Riera J. 227 Riess J. G. 15 Riesz P. 92 Rigby J. H. 220 Rinaldi P. L. 6 Rinehart K. L. Jr. 23 Riordan P. D. 184 Ripoll J.-L. 246 Risbood P. A. 113 Rist G. 60 Ritchie I. M. 124 Robbiani C. 213 Roberts B. P. 90 94 Roberts G. C. K. 10 Roberts R. M. G. 220 Author Index Roberts T. G. 54 Robertson A. D. 347 Robertson 1. R. 47 Robertson L. R. 191 Robinson B. 257 Robinson J. A. 13 Robinson P. L. 167 Robinson S. A. 219 Rocks R. R. 316 Rodenburg L. 221 Rodes R. 163 Rodger A. 375 Rodriguez C. 266 Rodriguez D.214 Rodrigues K. E. 55 236 Roder T. 187 349 Roeggen I. 32 Roellgen F. W. 23 Romer R. 236 Rosch 303 Roesky H. W. 355 Rogers R. D. 297 Rohling C. M. 45 Rokach J. 25 144 Rol C. 126 Rolla F. 224 Rollin Y. 130 Romanelli M. 180 Ronald R. C. 230 332 Rondan N. G. 35 38 53 102 105 344 Ronzini L. 245 Rooney C. S. 144 Roos B. 36 Rosenthal R. J. 202 Rosini G. 173 184 Rosmus P. 34 Ross A. D. 29 Ross A. J. 207 Ross D. S. 221 Rossier J. C. 114 267 Rossiter B. E. 168 Rost W. 179 Roszak S. 30 Roth B. 237 Roth H. D. 191 Roth W. R. 242 Rothenberg A. S. 260 Roumestant M.-L. 201 Roush D. M. 51 Roush W. R. 168 Rousseau G. 190 Rousset C. 171 Roussi G.55 254 Roussilhe J. 149 Routledge P. J. 225 Rovira C. 227 Rowe D. J. 234 Rowles D. K. 258 Roy G. 176 Royer R. 221 Rubin M. B. 9 Rudolph G. 360 Ruchardt C. 99 210 Rufenacht H. 86 Ruhter G. 259 Rummele O. 270 Ruminski P. G. 257 RUO,T. C.-S. 90 Russell C. E. 172 230 282 314 Russell J. G. 13 Russell M. A. 376 Russell R. A. 237 Russkamp P. 254 Ruth T. J. 223 Rutledge P. S. 156 Ruzsicska B. P. 104 Ryabov. A. D. 231 Rychnovsky S. D. 87 321 Rys J. 30 Rys P. 231 Ryu I. 298 335 Saa J. M. 236 Saalfrank R. W. 179 186 Sabadie. J. 165 Sabahi M. 64 Sabio M. L. 44 207 Saburi M. 178 Saccomano N. 194 Sadhu K. M. 316 Sadler P. J. 16 Sadri A.R. 220 Saebei S. 38 44 Saegusa. T. 50 237 Safiev 0. G. 259 Saheki Y. 226 Sahlberg C. I58 Saindane M. 227 Sainsbury M. 127 139 St. John Zurer P. 203 Saito T. 93 172 Saito Y. 175 Saitoh N. 123 Sakamoto H. 359 365 Sakamoto M. 146 147 179 Sakamoto T. 245 Sakamoto Y. 361 Sakane S. 197 336 337 Sakata Y. 167 240 Sako H. 50 Sakumoto M. 250 Sakuraba H. 157 Sakurdi H. 167 226 300 Sakurai K. 276 Sakurai T. 376 Sakuta K. 337 Salamone S. J. 13 Salanski P. 360 Salaun J. 195 Salazar J. A. 255 Salman S. R. 21 1 Salomon. R. G. 6 141 Saltiel J. 144 232 Salvetti O. 32 Sammes P. G. 267 Sammons R. D. 13 Samuel D. 378 Sand P. 256 Sandall J. P. B. 222 Sander J.177 Sanders J. K. M. 3 II Sandros K. 232 Sani H. 185 Sank V. J. 12 Sano M. 40 Sansoulet J. 169 Santelli M. 322 Santelli-Rouvier C. 322 Santiesteban F. I1 Santini C. C. 186 Santry L. J. 67 Sapse A. M. 45 Sarma K. 359 Sarrazin C. A. 184 Sarstedt B. 237 Sarussi S. J. 346 Sasaki K. 226 Sasaki M. 158 172 Sasaki S. 43 Sasaki T. 103 Sasatani S. 181 Sasoaka M. 123 Sasson Y. 231 288 344 Satake K. 119 33 1 Satge J. 42 299 Sato F. 252 313 315 Sato M. 15 313 315 361 Sato N. 125 182 185 Sato S. 61 63 184 Sato T. 142 165 178 180 182 186 346 Sato Y. 162 Satoh Y. 152 315 Saulnier M. G. 257 Saunders M. 73 Saunders W. H. jun.$ 76 Saupe T. 234 Sauvage J.-P.362 Savariar S. 218 SavCant J. M. 123 Sawada H. 323 Sawada S. 198 Sawahata M. 166 Saxe P. 31 33 37 38 193 Scaiano J. C. 91 96 104 1 10 147 Scallen T. J. 178 Scettri A. 168 Schaad L. J. 37 Schaap A. P. 143 Schade U. 23 Schafer A. 299 Schaefer H. F. 111 31 33 34 37 38 40 41 42 45 102 I93 Schafer H.-J. 130 132 178 Schafer L. 32 Schatzlein P. 186 Schardt B. C. 15I Scharp J. I13 Schat G. 301 Schaumann E. 259 262 Scheek R. M. 9 Scheeren H. W. 192 Scheffer J. R. 200 Scheffold R. 319 Scheiner S. 42 45 Schepartz A. 125 Schiebel H. M. 26 Schiedler M. 198 Schier A. 42 Schierling P. 186 Schiess M. 319 Schill G. 199 Schilling M.L. M. 191 Schimowiak J. 355 Schimpf R. 17 Schipfer R. 184 Schipper P. E. 375 Schiraldi D. A, 280 Schlegel G. 132 Schlegel H. B. 37 39 41 45 Schlessinger R. H. 207 Schleyer P. von R. 30 34 35 36 37 39 44 105 229 247 Schlosser K. 98 Schliiter E. 295 Schmid G. 20 Schmidbaur H. 297 Schmidt G.,87 168 Schmidt H. W. 184 Schmidt J. 38 Schmidt R. R. 50 Schmidt T. 15 Schmidt U. 183 Schmidtberger S. 3 17 Schmitt P. 241 Schmitt R. E. 124 Schmitz C. 78 Schmitz R. F. 172 Schneider S. 350 Schobert R. 179 331 Schoberth W. 74 Schoeller W. 29 Schofield K. 221 222 Scholastico C. 308 Scholler D. 145 Scholz D. 185 Schormann N. 206 Schowen R. L. 68 Schrader B.39 Schramm S. B. 219 Schreiber S. L. 147 331 Schrobilgen G.J. 16 Schrock W. 251 Schroder G. 213 359 Schubert W. M. 86 Schuda P. F. 205 Schuh W. 234 302 Schulman J. M. 44 207 Schulten H. R. 26 Schultz A. G. 245 Schultz R. A, 358 Schumacher G. A. 16 Schurig V. 167 Schuster G. B. I12 Schuyt H. A. 168 Schwab W. 302 Schwager L. 237 Schwarz H. 19 20 25 38 74 Schwarzenbach D. 166 208 Schwarzensteiner M.-L. 27 1 Schweickert N. 199 Schweig A. 31 Schweitzer D. 244 Schwichtenberg E. 270 Scopes D. I. C. 127 139 Scott F. 191 Scott L. T. 233 242 Scriven E. F. 348 Secco A. S. 200 Seconi G. 180 Sedgwick R. D. 24 25 Seebach D. 175 178 182 273 319 Seetz J. W.F. L. 192 301 Segi M. 188 Seibl J. 20 23 Seiferling B. 117 Seifert K. 134 Seitz G. 269 Sekiguchi A. 121 Sekine T. 125 Sekino H. 31 Semmelhack M. F. 138 Sendelbeck R. 296 Senff U. E. 30 Sennyey G. 303 Sen Sharma D. K. 22 Senthilnathan V. I12 Senzaki Y. 201 Serpone N. 274 Serratosa F. 169 209 Seshadri S. 90 Setiloane B. P. 90 Seyferth D. 253 Sghibartz C. M. 359 Shaad L. J. 64 Shackleton C. H. L. 25 Shaefer A.-G. 54 Shahriari-Zavareh H. 243 Shaik S. S. 29 67 68 Shaka A. J. 9 Shanzer A. 166 180 354 378 Shapiro S. 165 Sharma R. P. 348 Sharma V. K. 243 Sharp J. T. 47 Sharpe R. W. 32 Sharpless K. B. 168 181 227 Shaw G. 237 Shawali A. S. 219 Shea K.J. 203 Schechter H. 235 Sheehan J. C. 252 Sheldrick G. M. 206 299 355 Sheng S. J. 91 Shepard R. 34 Author Index Sheppard P. W. 14 Sheppard R. N. 11 Sher P. M. 87 321 Sheridan R. S. 117 204 Sherrington D. C. 365 Sheth J. P. 106 Shevlin P. B. 34 102 Shibata S. 178 Shibayama K. 185 Shieh W.-R. 179 Shields C. J. 117 Shih N.-Y. 373 Shillady D. D. 29 32 Shim S. C. 250 Shimada J. 195 3 10 Shimazaki N. 201 Shimizu H. 187 Shimizu I. 172 177 342 Shimizu M.,325 Shimizu Y. 166 Shimoji K. 87 168 Shimono Y.,207 Shin J.-S. 85 Shiner C. S. 177 Shinkai S. 232 358 362 376 Shinozaki H. 183 Shiraiwa M. 245 Shmidbaur H. 42 Shoham G. 355 Shono T. 131 132 133 134 135 136 158 172 173 181 256 357 365 Short J.W. 227 Short R. P. 106 Shubert D. C. 152 Shudo K. 251 Sibi M. P. 229 Sicking W. 97 Sidot C. 144 178 232 287 Sieburth S. M. 334 Siegbahn P. 36 42 Siegel J. 210 238 Siegel S. 23 1 Sih C. J. 179 Sikirica M. 296 Simmons H. E. 209 Simon J. D. 11 1 Simon W. 378 Simonet J. 123 124 Simonetta M. 35 Simonnin M.-P. 225 Simons J. 32 33 Simpkins N. S. 185 Simpson G. W. 176 Simpson I. 40 Sims L. B. 75 76 Sims R. J. 179 Sindona G. 24 Sindorf D. W. 298 Singaram B. 187 315 350 Singh B. P. 91 165 211 Singh H. K. 184 Singh M. M. 259 Singh V. 54 173 200 350 Author Index Singleton D. H. 331 Sinhababu A.K. 229 256 Sinnott M. L. 353 Siroi T. 123 Sita L. R. 298 Skancke A. 43 Skarzewski J. 358 Skattebd L. 107 191 Skell P. S. 89 90 91 Skonieczy S. 13 Slessor K. N. 168 Slougui N. 190 Smadja W. 160 Smal M. A. 184 Smeaton A. A. 79 Smeets J. W. H. 154 Smegal J. A. 151 288 Smit C. J. 125 Smith B. L. 280 Smith C. 360 Smith D. J. H. 211 218 250 Smith F. X. 261 Smith J. D. 294 Smith J. L. 202 Smith J. M. 90 Smith L. A. 24 Smith N. O. 353 Smith R. 55 254 Smith S. L. 10 Smith V. H. jun. 38 Smithers R. H. 86 Smothers W. K. 144 232 Snider 9.B. 158 200 310 Snieckus V. 229 230 Soai K. 346 Soderquist J. A, 177 S~rensen,0. W. 9 Sohn E. 185 220 Sokalski W.A. 30 45 Solas D. 201 Solas D. R. 254 Somayaji V. 347 Sommer J. 21 I Son B. 357 Sondengam B. L. 156 Sondheimer F. 243 Sone T. 376 Sonada N. 286 298 308 335 Sonoda T. 136 Sopchik A. E. 185 Sorrenti P. 173 184 Soulier J. L. 137 Souppe J. 177 Sousa L. R. 249 Souten C. G. 155 Spagnolo P. 117 Spahic B. 143 Spear R. J. 225 Spee T. 232 Spek A. L. 294 Spencer C. 18 Spencer N. O. 360 Spenser I. D. 14 Speziale V. 18I Spik G. 25 Spitznagel G. W. 30 Splinter D. E. 22 Spotswood T. M. 248 Sprecher M. 305 Springer C. S. 14 Springer J. P. 178 261 329 Spurr P. R. 207 Srebnih M. 227 Srivastava S. 72 376 Srogl J. 135 Staab H. A. 234 238 240 241 244 359 Stagnio d’Alcontrez G.260 Stahl I). 21 Staib R. R. 52 Stakem F. G. 161 Staley S. W. 190 Stang P. J. 105 185 Stanton R. E. 30 Stark K. M. 281 Starke U. 303 Starker. B. 240 Stead M. J. 96 Stec W. J. 185 Steck W. F. 166 Steel P. J. 16 176 Steele W. V. 79 Steenken S. 98 Steer R. P. 43 Steffek D. J. 126 Steigel A. 270 Steinbach A. 226 Steinbach R. 176 317 Steiner S. 45 Steinmetz M. G. 116 Stekowski J. J. 376 Stella L. 341 Stenstrom Y. 107 191 Stephens C. J. 125 182 Sternbach D. 204 Stevens R. W. 175 183 Stevenson G. R. 212 Stewart L. C. 96 Stibbard J. H. A. 237 Stibor I. 135 Stiehl C. 104 Stierman T. J. 115 198 Still B. 106 Still W. C.167 186 198 319 349 Stille J. K. 168 172 314 Stille J. R. 284 308 Stillwell R.N. 27 Stirling C. J. M. 157 162 193 258 Stoddart J. F. 354 359 362 378 Stobbe M. 239 Stogniew M. 25 Stohrer W.-D. 70 Stoll R. 23 Stone J. A. 22 Stone W. E. 223 Stoodley R. J. 195 Stork G. 70 87 169 177 194,321 324 339,343 Storr R. C. 270 Stothers J. B. 13 206 Stott P. E. 378 Stout D. M. 173 Stowasser B. 101 Strandberg R. 170 Strange G. A. 156 Straub T. S. 83 Strauss M. J. 224 Strausz 0. P. 42 102 104 1 17 246 Strecker G. 25 Stretton G. N. 224 Stromquist M. 182 Stromberg A. 30 Stuber F. A. 224 Stiihler G. 239 Stults 9.R. 257 Sturtz G. 188 Stutz H. 74 Suarato A.237 Suarez E. 255 Suau R. 236 Suchy A. 377 Suckling C. J. 353 Suda H. 345 Suga S. 188 Sugawara M. 131 Sugawara T. 118 167 189 Sugimoto H. 237 Sugimoto T. 155 Sugisawa H. 299 Sugiura M. 185 Sugiyama H. 226 Suleske R. T. 260 Sullivan A. C. 294 Sumi S. 165 Sundararaman P. 193 Sundberg R. J. 106 Sundqvist B. 26 Surya Prakash G. K. 73 Sustmann R. 97 Sutcliffe R. 92 94 Sutherland I. O. 355 Sutherland J. K. 237 Sutter M. A. 178 Suzuki A. 152 167 171 315 Suzuki H. 168 172 173 179 182 185 187 223 Suzuki K. 180 245 Suzuki M. 26 21 1 Suzuki N. 344 Suzuki R. 161 Suzuki T. 23 I Swain C. J. 2 15 Swanstrom P. 32 Sweet J. R. 275 Swenson K. E. 231 Swenton J.S. 134 227 237 Swern D. 261 Sykes 9.D. 14 400 Symons M. C. R. 94 95 Szafsz R. A. 260 Szakrii G. 187 Szeimies G. 236 Szejtle J. 378 Szele I. 184 238 364 Szeverenyi N. M. 5 TabakoviC I. 178 Taber D. F. l(6 194 278 323 Tabet J. C. 21 Tabusa F. 180 Tacreiter W. 207 Taddei M. 168 180 347 Taffer I. M. 69 Tago H. 180 Tagupa E. 260 Tajima M. 183 Takada K. 298 Takada T. 33 39 Takagi K. 231 Takagi Y. 52 194 Takahashi K. 346 Takahashi M. 15 Takahashi T. 197 285 Takahata H. 262 Takai K. 178 341 Takakis I. M. 190 Takamizawa A. 216 Takamo I. 252 Takano S. 167 Takaoka T. 183 Takata Y. 129 Takeda A. 179 Takeda E. 146 Takeda K. 207 Takeda T. 192 Takeshita H.66 Takeuchi K. 71 201 Takeuchi R. 228 259 Takiguchi H. 90 Takimoto S. 178 Takinami S. 152 171 315 Tallec A. 129 Tam J. P. 68 Tamao K. 231 Tamari T. 305 Tamariz J. 237 Tamaru Y. 161 182 Tameo K. 245 Tamm C. 179 Tamura H. 357 Tamura R. 153 Tamura Y. 252 Tan S. L. 90 Tdnaka C. 165 Tanaka F. S. 144 Tanaka H. 123 184 Tanaka K. 185 377 Tanaka N. 185 Tanaka T. 167 345 Tanaka Y. 157 21 1 315 Tanake S. 243 Tanako Y. 350 Tandon V. K. 169 Tang L.-C. 295 Tanida M. 103 Tanimoto S. 155 Tanner D. 241 Tanner D. D. 90 Tao Y.-T. 76 Tardivel R. 137 Tashiro M. 240 362 Tassi D. 168 347 Tayak K. 173 Taylor C. K. 91 Taylor D. R. 58 Taylor H. 32 Taylor L. C. E. 25 Taylor R. L.260 Taylor S. K. 219 Taylor S. L.,265 Taylor W. J. 207 Tea-Gokou C. 86 Tee 0. S. 223 Tenaglia A. 197 Tencer M. 112 184 Teranishi S. 158 167 Terenghi M. G. 215 Terlouw J. K. 19 20 Ternansky R. J. 207 Terpinski J. 103 247 Terrier F. 225 Tessier D. 123 Testaferri L. 69 224 Tewari R. S. 247 Teyssie P. 285 Tezuka H. 198 Tezuka T. 226 Thea S. 80 Theriault N. Y. 26 Thewalt U. 297 Thiebaut H. 137 Thies R. W. 198 Thirkauf A. 218 Thole €3. T. 30 Thomas E. J. 324 Thomas E. W. 193 Thompson N. 127 Thompson P. A. 175 Thompson P. K. 360 Thompson R. S. 166 Thompson-Colon J. A. 126 Thomsen M. W.,191 Thomson C. 39 40 41 42 Thornton E. R. 107 Thulin B. 241 Thulin E. 16 Thummel R. P. 213 Tian S.J. 27 Tice C. M. 364 Tichy M. 86 Tidwell T. T. 67 Tiecco M. 69 224 Tietz J. V. 190 Tihange G. 262 Tilstam U. 256 Author Index Timberlake J. W. 92 Timmers D. 331 Tingoli M. 69 224 Tinnemans A. H. A. 142 Tinnemans P. J. J. A. 142 Tino J. 203 Tintel C. 221 235 Tischler S. A. 179 Tissot P. I3 1 Tius M. A. 218 318 Tkacz M. 53 200 Tlumak R.L. 90 Tobe Y. 203 239 Tobita H. 298 Tobito Y. 173 Tochtermann W. 239 Toda F. 377 Toda T. 201 Todd Lord 353 Toke L. 187 Tollner F. 301 Tograie S. 364 Tojo G. 236 Tokutake N. 248 Tol R. 192 Tomas A. 55 Tomas M. 254 Tomasi J. 43 44 Tomassen H. P. M. 358 Tombo G. M. R. 79 tom Dieck H. 217 247 281 326 Tomioka H. I12 Tomita Y.375 Tomkins R. P. T. 192 Tomo Y. 180 Tonachini G. 42 Toner J. L. 272 369 Toone E. J. 147 Toppet S. 248 Topsom R. D. 29 Torii S. 123 135 137 184 Torny G. J. 358 Torr R. S. 187 Torre G. 173 Torregosa J. L. 181 Torres M. 117 246 Torssell K. B. G. 174 Toshimitsu A. 198 Totzauer W. 194 Tour J. M. 323 Tourne C. M. 17 Tourne G. 17 Toyota K. 185 Trachtamn M. 44 Trainor G. 376 Traldi P. 27 Traynham J. G. 67 Trebilco P. R. 166 Trefonas L. M. 230 Trenerry V. C. 176 Trinquier G. 42 Trippett S. 21 8 230 Trius A. 159 186 Author Index Trost B. M. 184 185 199 201 215 231 321 325 334 336 Trotter J. 200 Troughtoti E. B. 71 Troup J. M. 305 Troupel M. 130 Trueblood K. N.366 367 Truter M. R. 356 Tsai D. J. 316 Tsai M. D. 13 Tsay Y.-H. 204 Tsichiya T. 270 Tsoucaris G. 377 Tsuboi S. 179 Tsuboyama K. 376 Tsuboyama S. 376 Tsuchida T. 192 Tsuchihashi G. 194 Tsuge O. 216 262 Tsuji J. 172 177 182 185 197 342 Tsuji T. 61 171 Tsuji Y. 182 228 259 Tsukanaka T. 344 Tsumaki H. 174 Tsunekawa K. 185 Tsutsumi K. 107 Tubul A. 113 191 Tucker J. R. 331 Tueting D. 172 Turnas W. 75 Tundo P. 154 Turner C. J. 4 Turner D. L. 8 Turro N. J. 96 103 104 Tuschka T. 2 I3 Tyler A. N. 24 25 Tyler P. C. 194 Tzschach A. 304 Uccella N. 24 Uchida T. 155 Uchiyama M. 231 313 Ueda K. 362 Uehara H. 186 Uemura S. 198 305 Ueno A. 375 376 Ueno K. 121 Ueno Y. 165 173 179 184 Ueoka T.141 Uiterwijk J. W. H. M. 355 360 Ukita I. 153 Ullenius C. 177 Ullrich F.-W. 220 Ullrich J. W. 55 Ulrich P. 241 Umeda N. 345 Uneyama K. 137 Ungaro R. 215 219 238 372 Unger S. E. 25 Uno Y. 223 Urabe H. 350 Urayama T. 256 Urban M. W. 88 Urbanek T. 208 Urch C. J. 189 Urso F. 250 Utley J. H. P. 123 131 Uzar H. C. 12 Vail P. D. 56 Vajna de Pava O. 218 246 359 van Bladeren P. J. 235 van Boom J. H. 4 van den Goorbergh J. A. M. 178 van der Brugge M. 235 van der Gen A. 178 305 van der Heijden H. 296 van der Kerk G. J. M. 247 van der Kerk S. M. 247 van der Kerk-van Hoof A. 247 van der Made A. W. 154 Van Derveer D. 200 203 Van der Velde G. 30 van de Waal B. W. 355 Vandewalle M.207 Van Dijk B. G. 63 van Dijk-Knepper J. 232 Van Dorsselaer A. 27 van Duijnen P. Th.,30 van Haverbeke Y. 20 Vangheluwe P. 248 van Lenthe J. H. 30 van Leusen A. M. 169 Van Meerssche M. 2.76 Van Middlesworth F. 179 Vannoort R. W. 166 Van Saun W. A. 51 van Tarnelen E. E. 194 Van Tilborg W. J. M. 125 van Zon A, 358 Varadarajan A, 212 Vargha A 43 Varney M. D. 59 Vasquez P. C. 77 Vather S. M. 324 Vaughan J. 166 Vaughan W. R. 73 Vaughn .I.B. 8 Veciana J. 227 Vedejs E. 53 55 184 237 329 339 340 Veglia A 84 Veith M.. 301 Venable T. L. 8 Venkatswamy G. 50 237 Venturella P. 154 Venturello C. 154 168 Verboorn W. 47 63 Verkruissje H. D. 259 Vetter W. 199 Vickerman J. C. 25 Viehe H.G. 97 191 Viertler H. 125 401 VilliCras J. 86 186 Vincendon G. 27 Vincent M. A. 33 34 42 Vincze A. 25 Visser G. W. 47 Viti S. M. 181 Vlazny K. 135 Vliegenthart J. F. G. 25 Vogtle F. 234 238 356 359 361 376 378 Vogel E. 215 242 272 Vogel P. 54 86 208 237 Volkmann R. A. 258 Vollhardt K. P. C. 234 258 Volponi L. 305 von Deuten K. 360 von Niessen W. 39 von Philipsborn W. 12 von Puttkarner H. 242 von Schnering H. G. 201 242 Vorbriiggen H. 265 Voss B. 215 Voss J. 184 Voyer N. 364 Vrscaj V. 24 Vuilhorgne M. 194 Wada E. 216 Wade A. R. 162 Wade P. A, 56 Wade R. 14 Waegell,-B. 197 Waespe-SarEevik N. 179 Wagenknecht J. H. 123 Wagner A. 50 Wagner G. 299 Wahlgren U. 30 Wakabayashi S.136 Wakabayashi T. 173 Wakabayashi Y. 346 Wakamatsu T. 133 Wakharkar S. 347 Walker B. J. 71 Walker F. H. 203 Walker R. 7 Wall A. 159 Wallace I. H. M. 189 Wallace T. W. 237 Walling C. 90 Wallis J. 324 Wallis J. D. 192 Walsh R. 208 Walter S. R. 18 Walton J. C. 98 Waltz W. L. 39 Wan C. S. K. 147 Wang B. C. 56 200 Wang S. J. 356 Wang S.-W. C. 271 Waniguchi E. 173 Ward D. L. 102 249 Ward R. S. 220 Warin R.,285 Waring M. J. 12 402 Warkentin J. 110 113 Warner P. W. 203 Warner R. W. 321 Warpehoski M. A, 256 Warren S. 187 Warrener R. N. 237 Waseda T. 172 Washburn W. N. 21 1 Washioka Y. 256 Wasmuth D. 178 Wassef W. N. 225 Wasylishen R. E. 17 Watanabe A.365 Watanabe H. 298 315 Watanabe M. 15 230 Watanabe T. 154 290 Watanabe Y. 182 228 259 Watkin D. 355 Watson P. L. 277 Wattanasin S. 227 Wayner D. D. M. 40 Webb M. 16 Weber D. W. 8 Weber E. 354 359 361 376 Weber E. J. 174 Weber G. 361 Weber R. 167 Weclawek K. 24 Weda K.-I. 239 Weedon A. C. 147 Weeks I. 98 Weerasooriya U. 186 Weidenbruch M. 171 299 Weidmann B. 175 273 Weigel H. 22 Weigt E. 204 Weiler L. 179 Weiner P. K. 355 Weinreb S. M. 52 62 65 182 340 Weinstein R. M. 253 Weiss R. H. 269 Weisz A. 20 Weitzer H. 345 Welch C. J. 182 Welvart Z. 170 Wender P. A. 144 204 205 334 Wenderoth B. 284 3 17 Wendoloski J. J. 209 Wennerstrom O. 210 241 Wentrup C. 196 233 248 Wepsiec J.P. 373 Werner H. 273 276 Werstiuk N. H. 67 173 319 West F. G. 55 329 West R. 120 298 300 Westermann J. 283 Wezenberg J. 20 Whan D. A. 233 White G. S. 182 White M. R. 185 Whitesell J. K. 65 173 307 317 Whitesell M. A. 173 307 Whitesides G. M. 347 Whitham G. H. 187 198 Whittle E. 98 Whittlesey B. R. 304 Wiberg K. B. 203 Wiberg N. 299 Widdowson D. A. 245 Wider G. 4 7 8 Wieghardt K. 16 Wien R. G. 144 Wierenga W. 256 Wiersum U. E. I13 Wieschollek R. 177 Wife R. L. 214 Wilbur D. S. 223 Wilczynski R. 276 Wilhelm D. 36 Wilk G. 214 Wilk K. A. 78 Wilkins C. L. 27 Willcott M. R. 10 Williams A. 80 378 Williams D. H. 12 25 Williams D. J. 298 359 362 Williams G. D. 331 Williams 1.H. 36 44 Williams L. 315 Williams R. V. 51 207 Willner I. 209 376 Wilson D. R. 378 Wilson J. W. 187 315 Wilson P. 148 Wilson W. K. 178 Wilt J. W. 92 Winkle M. R. 230 Winkler F. J. 21 Winkler J. D. 177 194 Wipf B. 179 Wipff G. 355 Wise S. 203 Witt W. 359 Wittek M. 239 Woell J. B. 163 Wolf H. R. 107 Wolf R. E. 356 Wolfe S. 42 Wolff S. 148 Wolinsky J. 201 Wolkoff A. W. 20 Wollowitz S. 62 Wolstenholme J. B. 359 Wolters J. 305 Wong C.-H. 347 Wong C. M. 237 Wong 0. S.-L. 68 Wong P. C. 104 Wong S. S. 23 Wong Y.-F. 200 Wons T. 227 Wood G. W. 26 Wood H. C. S. 353 Wood J. L. 207 Wood K. V. 257 Author Index Woodgate P. D. 156 Woodruff M. 193 Woodson S. 378 Woodward R.B. 271 Wrackmeyer B. 11 Wreesmann C. T. 4 Wriede U. 259 Wright B. 14 Wright B. B. 110 215 Wright D. R. 75 WU H.-J. 147 331 WU J.-C. 58 Wu S. C. 356 WU T.-C. 233 Wu T.-S. 237 Wuebbels G. G. 141 Wuest J. D. 302 Wiithrich K. 4 7 8 Wulff W. D. 52 282 299 326 Wuts P. G. M. 175 Wydila J. 107 Wynberg H. 169 184 Xingya L. 57 Xu Z. 56 200 Yadav L. D. S. 184 Yakobson G. G. 188 Yamada M. 376 Yamada Y. 161 182 Yamaguchi H. 375 Yamaguchi M. 172 183 245 Yamaguchi R. 266 Yamaguchi S. 209 Yamaguchi Y. 33 Yamahira A. 359 Yamaizumi Z. 9 Yarnaji T. 315 Yamamoto G. 210 21 1 Yamamoto H. 197 336 337 346 Yamamoto K. 180 238 243 360 Yamamoto S. 61 171 Yamamoto Y. 141 172 175 176 177 181 312 313 Yamamura Y.337 Yamana Y. 191 Yamanaka H. 245 Yamasaka T. 226 Yamasaki A. 15 Yamasaki Y. 162 Yamashita H. 179 Yamashita M. 185 194 248 Yamashita Y. 159 191 Yamato T. 219 240 Yamawaki J. 165 171 Yamazaki H. 163 Yamazaki N. 173 Yamazaki Y. 231 Yang D. C. 52 326 Yang H.-H. 232 Yang L. S. 235 Yang S. 169 Author Index Yannoni C. S. 17 Yarkony D. R. 39 Yarmush D. M. 14 Yasuda H. 166 172 176 Yasuhara F. 209 Yates K. 43 Yatsimirsky A. K. 231 Yeager D. L.,32 Yelle L.,25 Yelm K. E. 62 Yen H.-K. 56 Yen Y.-P. 116 Yergey J. 26 Yeroushalmi S. 212 Yin T.-K. 115 Yogo T. 167 Yokoi S. 172 Yokoyama M. 169 183 Yonezawa T. 33 39 Yoshida H. 192 Yoshida J.-I. 231 Yoshida K.54 146 200 238 250 364 Yoshida S. 162 Yoshida T. 276 Yoshida Y. 223 Yoshida Z. 182 Yoshida Z.-I. 161 Yoshifuji M. 185 Yoshihara K. 118 Yoshii E. 207 Yoshikawa S. 178 Yoshimine M. 37 42 Yoshinaga K. 178 Yoshinaga M. 359 365 Yoshino T. 241 Yoshioka Y. 41 Yoshiura K. 256 Young C. G. 177 195 Young C. M. 11 1 Young D. C. 282 Young T. E. 127 Yu L.-C. 103 Yuki H. 210 Yurtsever E. 29 32 Yus M. 153 156 178 Zacharie B. 302 Zafiropoulos T. 297 Zarbock J. 9 Zard S. Z. 342 Zaworotko M. J. 296 Zayas J. 1I1 Zelchan G. I. 300 Zeldes H. 97 Zelle R. E. 348 Zeller K.-P. 233 Zernlyanski N. N. 302 Zenki S. S. 290 Zernach D. 231 Zeuli E. 129 Zhang X.-H. 300 Zhao C. 90 Zhou B.-N.179 Zieger H. E. 169 Ziessow D. 10 Zilm K. W. 17 298 Zimmerman D. C. 198 Zimmerman H. E.,143 Ziolo R. F. 305 Zittlau W. 31 Zlotskii S. S. 259 Zoch H.-G. 236 Zollinger H. 184 238 364 Zollinger M. 20 Zoran A. 231 288 344 Zountsas J. 58 Zuanic M.,207 Zuber J. A. 114 Zubieta J. 125 Zupancic J. J. I12 Zutterman F. 148 159 201 207 Zwanenburg B. 52 119 184 Zweifel G. 163

ISSN:0069-3030    

DOI:10.1039/OC9838000379

出版商:RSC    

年代:1983

数据来源: RSC