摘要:

8 Aliphatic Compounds Part (ii) Other Aliphatic Compounds By A. R. TATCHELL School of Chemistry Thames Polytechnic Wellington Street London SE 18 6PF 1 Alcohols and Ethers Chiral alcohols oxirans and oxaziridines of known absolute configuration give rise to liquid-crystal-induced circular dichroism (LCICD) when added to the achiral nematic liquid crystal N-p-methoxybenzylidene-p'- butylaniline (MBBA). It has been proposed that the axes of adjacent MBBA molecules are induced to lie in a helical arrangement by virtue of the presence of the interposed chiral dopant and the direction of helicity is correlated with the molecular interactions between the substituents of the chiral dopant and the adjacent MBBA molecules.' The formation of mono-esters from symmetric 1,2- and 1,3-diols in good yields has been made feasible by their conversion into the corresponding known stann- oxanes by treatment with dibutyltin oxide and subsequent reaction with one molar equivalent of an acylating agent followed by hydrolysis.The sequential addition of two acylating agents to the stannoxane gives a mixed diester.2 Selective oxidation of a limited range of 2,2-disubstituted butane-1,4-diols using either a benzoyl peroxide-nickel(I1) bromide reagent mixture or triphenylmethyl tetrafluoroborate provides a route to the corresponding pp-disubstituted- y -butyrola~tones.~ With these reagents very little of the aa-disubstituted isomeric lactone is formed. Although (S)-1,2-O-isopropylideneglycerolis readily available from 1,2:5,6-di- 0-isopropylidene-D-mannitol uia (R)-1,2-0-isopropylideneglyceraldehyde the enantiomeric glycerol derivative (2) which could serve as the starting material for the synthesis of important drugs is less easily accessible.Ascorbic acid (1)has now been used as an inexpensive chiral source for this compound (Scheme 1); as an i-iii CH,OH (2) HO-'OH HO OK (1) Reagents i Me,CO MeCOCl; ii NaBH,; iii NaOH H'; iv Pb(OAc), EtOH; v NaBH, NaOH Scheme 1 W. H. Pirkle and P. L. Rinaldi J. Org. Chem. 1980 45 1379. * A. Shanzer Tetrahedron Lett. 1980 21 221. M. P. Doyle R. L. Dow V. Bagheri and W. J. Patrie Tetrahedron Lett. 1980 21 2795. 123 124 A. R. Tatchell HZCOMS -H CH,CN CH,CN CH,CN CH ,CO ,- (3) Reagents i TsCI Et,N; ii KCN NaI NaHCO, DMSO; iii HCI MeOH at 0 "C; iv MsCI Et,N; v KN, MeCN 18-crown-6; vi H2 Pd/C; vii H,SO Scheme 2 example of its utility its conversion into (R)-4-amino-3-hydroxybutanoicacid (3) a useful anti-epilectic and hypotensive drug has been described (Scheme 2).4 The synthesis of chiral oxirans has been the subject of several publications.Thus some monosubstituted (S)-oxirans have been formed in high optical purity from the toluene-p-sulphonate of (S)-1,2-O-isopropylideneglycerol[the enantiomer of (2)] by conversion into (S)-2,2-dimethyl-4-alkyl- 1,3 -dioxolan with lithium dialkyl- cuprates ring-opening to the acetyl derivative of the corresponding bromohydrin followed by base-catalysed cy~lization.~ The previously published synthesis of (2S,3S)-2,3-epoxybutane from (2R,3R)-tartaric acid has been shown to proceed in better than 99.9% diastereoisomeric and enantiomeric purity by employing com- plexation chromatography on nickel(I1) bis-[( 1R)-3-(heptafluorobutyryl)camphor-ate].6 In this synthesis the formation of the oxiran system also arises from a base-catalysed cyclization of an ester of a bromohydrin.The asymmetric cyclization of prochiral 1,3-dichloropropan-2-ol and racemic 2,3-dichloropropan- 1-01 using active cobalt(sa1en)-type complexes [e.g. N,N'-disalicylidene-( 1R,2R)- 1,2-cyclo- hexanediaminato-coba1t(11)],has also been de~cribed.~ t-Butyl hydroperoxide in the presence of the chiral catalyst quininium benzyl chloride converts cycohex-2-en-1-one into (2S,3S)-2,3-epoxycyclohexanonein 20% enantiomeric excess (e.e.).* The same hydroperoxide with titanium(1v) isopropoxide in the presence of optically active diethyl tartrate has been found to epoxidize a wide range of allylic alcohols with high asymmetric induction (>90% e.e.).The configurations of the epoxy-alcohols that are obtained coupled with the observation that the enantiomeric tartrates give rise to opposite configurations in the products has allowed a preliminary view to be proposed for the direction of attack of the peroxide.' Intramolecular epoxidation (noted in last year's Report) has also been the subject of further study." A convenient and highly stereospecific method for the conversion of oxirans into thiirans using potassium thiocyanate in the presence of silica gel or else supported upon it has been reported." The yields are very acceptable since the work-up procedures are simple and the thiirans are readily purified from unreacted starting material by column chromatography.M. E. Jung and T. J. Shaw J. Am. Chem. SOC.,1980,102,6304. U. Schmidt J. Talbiersky F. Bartkowiak and J. Wild Angew. Chem. In?.Ed. Engl. 1980 19 198. V. Schurig B. Koppenhoefer and W. Buerkle J. Org. Chem. 1980 45 538. 'T. Takfichi M. Arihara M. Ishimori and T. Tsuruta Tetrahedron 1980 36 3391. H. Wynberg and B. Marsman J. Org. Chem. 1980,45,158. T. Katsuki and K. B. Sharpless J. Am. Chem. SOC.,1980,102,5974. lo J. Rebek Jr. and R. McCready J. Am. Chem. SOC.,1980,102 5602. M. 0.Brimeyer A. Mehrota S. Quici A. Nigam and S. L. Regen J.Org. Chern. 1980,45,4254. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 2 Aldehydes and Ketones Although high enantiomeric purity is being achieved in the synthesis of oxirans as described above the formation of chiral cup-epoxy-aldehydes whose configurations can be mechanistically established has been little studied. A procedure that has now been reported12 arises from the development of a synthetic method for chiral CY -hydroxy-carboxylic acids which uses a stereoselective bromohctonization of for example (S)-tigloylproline; this method was noted in last year's Report. The acyl derivative (4) on bromination gives the bromo-lactone (5)contaminated with less than 8% of the diastereoisomer (6);ring-opening of the lactone with methoxide ion followed by reduction yields the ap-epoxy-aldehyde (7) (Scheme 3).The configur- ational assignment follows from mechanistic considerations and high chemical and optical yields are obtained for a representative range of unsaturated acids. -0JqBr R+ H R' R2 R2 R2 (4) Reagents i (S)-ethyl prolinate (EtO),PO(CN) Et I;ii KOH EtOH H20;iii NBS Bu'OK; iv NaO at -78 "C; v NaAIH,(OCH,CH,OMe), at 0 "C Scheme 3 (S)-2-Methoxymethylpyrrolidinecontinues to be used as an efficient chiral induc- ing reagent. On reaction with l-bromo-3-phenylprop-2-eneit forms the chiral allylamine (8) which on deprotonation forms the chiral homo-enolate equivalent (9).13 Alkylation then proceeds with very acceptable stereoselectivity (4845% e.e.) to yield the enamine (lo) which on hydrolysis gives the chiral P-alkyl-aldehyde (11)(Scheme 4).Five different alkyl halides were employed and the configurations of the products were assigned by standard procedures and from a consideration of the favoured direction of approach of the alkylating reagent. A polymer-supported reagent that is prepared by treating poly(2-vinylpyridine) with a borane-dimethyl sulphide complex when heated in benzene solution in the presence of boron trifluoride etherate reduces aldehydes and ketones in good yield.14 Swelling of the polymer-borane complex by preheating in benzene or " S. Terashima M. Hayashi and K. Koga Tetrahedron Lett. 1980 21,2733. l3 H. Ahlbrecht G. Bonnet D. Enders and G. Zimmermann Tetrahedron Left. 1980 21 3175. l4 F.M Menger H. Shinozaki and H.-C. Lee J. Org. Chem. 1980 45 2724. 126 A. R. Tatchell d P h OHC iii -H-eoMe (8) (9) (10) Reagents i Bu'Li Bu'OK light petroleum at -78 "C;ii RX at -78 "C; iii 4M-HCl Et,O Scheme 4 alternatively prior partial alkylation of the polymer leads to reagents which effect faster reductions because a less compact configuration exposes the reactive sites to the carbonyl reactant. The reduction of saturated alkyl aryl ethylenic and acetylenic ketones with a range of chiral reducing reagents continues to be explored. Two publications report the use of protected glucofuranose derivatives with sodium borohydride in the presence of a carboxylic acid.15 B-(3-Pinanyl)-9-borabicyclononanemade from either (+)-or (-)-pinene which has been used so successfully for the reduction of aldehydes to chiral 1-deuteriated primary alcohols has been found to reduce cup-acetylenic ketones to the corresponding secondary alcohols in reasonable to excellent enantiomeric excess.16 Also noted this year is the use of lithium aluminium hydride that is complexed with amino-diols derived from tartaric acid (12),17 with a mixture of (-)-N-methylephedrine and N-ethylaniline,'8 and with analogues of Darvons alcohol (13).19 In the latter instance the new chiral ligands offer some promise for elucidating the relative importance of structural features in determining the degree of selectivity and the predominant configuration that is obtained.The chiral acetylenic alcohols prepared by procedures similar to that discussed above or by the reaction of aldehydes with lithium trimkthylsilylacetylide in the presence of a chiral amino-alcohol followed by alkaline hydrolysis," have been elaborated into optically active 4-alkyl-butyrolactones (14)21 and into optically active 4-alkyl-butenolides (15) (Scheme 5).20*22The butenolide (15; R = C8HI7) on epoxidation ring-opening of the lactone with ammonia followed by oxidation Is J.D. Morrison E. R. Grandbois and S. I. Howard J. Org. Chem. 1980 45 4229; A. Hirao S. Nakaharna H. Mochizuki S. Itsuno and N. Yamazaki ibid. p. 4231. l6 M. M. Midland D. C. McDowell R. L. Hatch and A. Tramontano J. Am. Chem. SOC.,1980,102,867. l7 M. Schmidt R. Amstutz G. Grass and D. Seebach Chem. Ber. 1980,113 1691. S. Terashima N.Tanno and K. Koga Chem. Lett. 1980 981; J. Chem. Sac. Chem. Commun. 1980 1026. l9 N. Cohen R. J. Lopresti C. Neukom and G. Saucy J. Org. Chem. 1980 45,582. 2o T. Mukaiyama and K. Suzuki Chem. Lett. 1980,255. 21 J. P. Vigneron and V. Bloy Tetrahedron Lett. 1980 21 1735; M. M. Midland and A. Tramontano ibid. p. 3549. 22 J. P. Vigneron and J. M. Blanchard Tetrahedron Lett. 1980 21 1739. 127 Aliphatic Compounds -Part (ii) Other Aliphatic Compounds RCH(0H)C-CH -% RCH(OH)CrCCO,H -+ H (14) 0 RCH(OH)CH=CHCO,H __+ H C,Hl,CO CONH2 (15) (16) Reagents i BuLi at -78 "C;ii CO,;iii H,,Pd/BaSO, quinoline; iv H'; v H2, Pt Scheme 5 of the product gave (+)-tetrahydrocerulenin ( 16).22 This compound had previously been synthesized from carbohydrate precursors.High asymmetric induction has been achieved in the reaction of organometallic reagents with chiral a -alkoxy-ketones and with p-alkoxy-aldehydes that have an a-chiral For example 3-hydroxydecan-2-one as its benzyl ether (17; R' = C7H15,R2 = CH2Ph) reacts with butylmagnesium bromide in THF to give a threo (18):erythro (19) ratio of 200 1(Scheme 6 illustrates the reaction with one enan- R' R' Me R' Bu + H=H*-Me R20 0 R20 OH R20 OH (18) (19) threo erythro Scheme 6 tiomer). The erythro-isomer (19)was formed in high selectivity (100 1)by allowing the protected compound 6-hydroxytridecan-5-one to react with methylmagnesium chloride in THF. It was noted that the nature of the solvent and of the protecting group were crucial to the successful stereoselectivity that was achieved.The reagents of choice for the reactions using p-alkoxy-aldehydes (which do not show such high asymmetric inductions when they react with Grignard reagents) are the lithium dialkylcuprates when the threo-isomer predominates. The results may be rational- ized on the basis of the Cram cyclic chelate model (20) where the favourable transition state develops from attack of the nucleophile from the side that is remote from the alkyl group. Interestingly however the reaction of lithium enolates with a-alkoxy-aldehydes e.g. 2-(benzyloxy)propanal gives the predominant stereoisomer in which the Felkin model (21) for asymmetric induction appears to R' :$oR2 R' *! 9 0 I \ ,I (21) /m (20) 23 W.C. Still and J. H. McDonald 111 Tetrahedron Lett. 1980 21,1031; W.C.Still and J. A. Schneider ibid.,p. 1035. 128 A. R. Tatchell be followed.24" Here the favourable transition state develops from attack of the nucleophile in an anti-periplanar direction from the large group which in this case is regarded as being the alkoxy substituent; a theoretical justification for this criterion has been p~blished.~~' It is argued that competition between the two alternative transition states is feasible and that variations in the degree of selectivity will thus be a function of the basicity of the alkoxy-oxygen and hence of the degree of electron-donating character of R2. Electron-withdrawing groups in R2 would decrease chelation effects and promote the reaction uia the Felkin model.3 Carboxylic Acids Each of the enantiomeric forms of fluorosuccinic acid has been synthesized from (2R)- and (2S)-malate esters by the reaction with diethylaminosulphur trifluoride followed by hydroly~is.~~ The configurations were unambiguously assigned on the basis of a similar conversion of dimethyl (2S,3R)-[3-2Hl]malate (22) obtained from monosodium fumarate by fumarase-catalysed hydration with deuterium oxide into 2-fluor0-[3-~H~]succinicacid (23) and examination of the proton-fluorine coupling constants of the derived deuteriated i.e. (24) and non-deuteriated anhydrides. In this way the fluorination reaction was shown to proceed with inversion of configur-ation and (-)-(2s)-malic acid therefore gives (-)-(2R)-fluorosuccinic acid.The latter exhibited a negative c.d. curve and is therefore anomalous when compared with the bromo- and chloro-acids; this has allowed the previously assigned configur- ation of (+)-fluorosuccinic acid which is a metabolite of p-fluorophenylacetic acid that is produced by Pseudomonas species to be corrected. A new metabolite from an aqueous culture medium of Paecilomyces uariotii has been assigned the structure (25) on the basis of chemical degradation and spectroscopic studies.26 Y0,Me 70,Me D\ ,? (22) (23) (24) Reagents i Et,NSF,; ii H,O'; iii MeCOCl Scheme 7 (S)-2-(Hydroxymethyl)pyrrolidinehas been used as a chiral auxiliary agent for the synthesis of chiral 2-alkyl-carboxylic acids in high enantiomeric excess (54-95'/0).~'This reagent was first converted into the chiral amide by acylation followed by stereoselective enolization [(Z)geometry preferred] by reaction with lithium di-isopropylamide and addition of an alkyl halide followed by hydrolysis.Chiral 2-hydroxy-acids have been prepared either from cy -keto-esters by alkylation using a modified LiAlBu4 reagent,28 or by the reaction of organometallic reagents with 24 (a)C. H. Heathcock S. D. Young J. P. Hagen M. C. Pirrung C. T. White and D. VanDerveer J. Urg. Chem. 1980 45 3846; M. Chtrest H. Felkin and N. Prudent Tetrahedron Lett. 1968 2199; (6) N. T. Anh and 0.Eisenstein Nouu. J. Chim. 1977 1 61. 25 G. Lowe and B. V. L. Potter J. Chem. SOC.,Perkin Trans. 1 1980 2029. D. C. Aldridge R. M. Carman and R. B.Moore J. Chem. SOC.,Perkin Trans. 1 1980,2134. " D. A. Evans and J. M. Takacs Tetrahedron Lett. 1980 21,4233. 28 D. Abenhafm G. Boireau and B. Sabourault Tetrahedron Lett. 1980,21,3043. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 129 chiral a-keto-oxa~olines;~~ in both cases modest enantiomeric excesses were obtained. threo-2-Alkyl-3-hydroxy-carboxylic acids were formed in a highly stereoselective reaction between aldehydes and a new group of bulky propionate esters namely 2,6-dimethylphenyl and 2,6-di-t-butyl-4-methoxyphenyl propion-ate^.^' This work complements other extensive studies on stereoselective aldol-type condensation reactions which were reported last year31 and which have been further extended this year.32 The diastereoisomeric derivatives prepared from partially active methyl 2-and 3-hydroxy-carboxylates and (+)-(R)-2-me thoxy-2 -(trifluorome thy1)phenylacetic acid with [Eu(fod),] show a lanthanide-induced shift of the protons in the methoxy- carbonyl group and the methine group that may be correlated with the enantiomeric purity and absolute configuration of the parent It had previously been noted that complexes of chiral lanthanide shift reagents with the parent acids do not establish enantiomeric purity.Spme interesting amino-acids have been reported. Thus the boron analogue H3N-BH2C02Hof glycine has now been ~ynthesized~~" by a simple exchange of an amino-group between ammonia and the N-trimethyl analogue which was described This amino-acid appears to have significant anti-tumour and antihyperlipidaemic activity.An amino-acid with iron-chelating qualities avenic acid A (26) has been isolated from the root washings of plants of Avena sativa which had first been grown in an iron-containing nutrient solution and then in one which was iron-free until the plants exhibited pronounced iron-induced chloro~is.~~~ The plant washings were submitted to ion-exchange chromatography and (26)was isolated by elution with an ammonia-formic acid buffer solution. Avenic acid B (27) HO N N OH HO N H2 was also isolated and its synthesis has been The synthesis of (&)-cleonine (28) which is an amino-acid component of the family of bleomycin- phleomycin antibiotics has been accomplished from cy~lopentanone.~~ The route involves conversion into the cyanhydrin protection of the hydroxyl function by formation of an acetal reduction of the cyano-group to the corresponding aldehyde followed by a Strecker reaction of the protected amino-nitrile; finally hydrolysis and deprotection give (28).The toxic amino-acid a-methylene-P-alanine (29) isolated from a Red Sea sponge Fasciospongia cavernosa has been synthesized from 3-bromo-2-(bromomethyl)propanoicacid by sequential esterification elimination 29 A. I. Meyers and J. Slade J. Org. Chem. 1980 45 2785. 30 C. H. Heathcock and M. C. Pirrung J. Org. Chem. 1980,45 1727. 31 R. Brettle Annu. Rep. Prog. Chem. Sect. B. 1979 76 330. 32 C. H. Heathcock C. T. Buse W. A. Kleschick M. C. Pirrung J. E. Sohn and J. Lampe J.Org. Chem. 1980 45 1066; D. A. Evans and L. R. McGee Tetrahedron Lett. 1980,21 3975 and references cited therein. 33 F. Yasuhara and S. Yamaguchi Tetrahedron Lett. 1980 21,2827. 34 (a) B. F. Spielvogel M. K. Das A. T. McPhail K. D. Onan and I. H. Hall J. Am. Chem. Soc. 1980 102 6343; (b)B. F. Spielvogel L. Wojnowich M. K. Das A. T. McPhail and K. D. Hargrave ibid. 1976,98,5703. 35 (a) S. Fushiya Y. Sato and S. Nozoe Tetrahedron Lett. 1980 21 3071; (b) Chem. Lett. 1980 1215. 36 K. Kato Tetrahedron Lett. 1980 21 4925. 130 A. R. Tatchell FH2 H,NCH,CCO,H of one molecule of hydrogen bromide and nucleophilic replacement of the second bromine with an arnino-gro~p.~' Underivatized amino-acid enantiomers may be separated by h.p.l.c.using a reversed-phase column packing and a chiral eluant consisting of (S)-proline in aqueous copper(I1) acetate solution; resolution of basic neutral and acidic amino- acids was achieved.38 N-Acetyl-0-t-butyl esters of amino-acids have been separ- ated by h.p.1.c. by using a column packing of a chiral phase bonded to silica gel with an eluant of diethyl ether or methylene dichloride or chlor~form.~~ 4 Lactones and Macrolides The reactions of /3 -propiolactone may be classified as those involving substitution in the ring and those involving ring-opening. In the former category the conversion of the lactone (30) into its anion (31) and the subsequent reaction of (31) with a variety of electrophilic reagents leads to substitution products (32) that are not readily obtained by other means.4o The considerable stability of the anion in THF at -78 "C[although it undergoes p-elimination to give the alkene (33) on warming to room temperature] has been attributed to the orthogonal arrangement [shown in (34)] of the orbital at C-3 and the cT-orbital between C-4 and oxygen which -0,C H (33) Reagents i LiNPri2 at -78 "C; ii R3X;iii heat Scheme 8 precludes either anti-or syn-elimination sequences.The range of electrophilic reagents used to 'trap' the intermediate (31) was considerable and in all cases the stereoselectivity of the reaction leading to (32) was very high (usually > 98%).In the case of an analogous anion (35) the reaction with phenyl isothiocyanate afforded entry into the rare class of thietanimines (36),41as shown in Scheme 9.37 A. Holm and P. J. Scheuer Tetrahedron Lett. 1980 21 1125. 38 E. Gil-Av A. Tishbee and P. E. Hare J. Am. Chem. Soc. 1980 102,5115. 39 A. Dobashi K. Oka and S. Hara J. Am. Chem. Soc. 1980,102,7122. 40 J. Mulzer and T. Kerkmann J. Am. Chem. SOC., 1980 102 3620. 41 J. Mulzer and T. Kerkmann Angew. Chem. Int. Ed. Engl. 1980 19,466. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds PhNCS heat H,O ___, r-co21 Scheme 9 Ring-opening reactions of P-propiolactone and its analogues have been effected by lithium dialkyl~uprates~~ or by Grignard reagents in the presence of copper(I1) to give homologous acids in which the chain has been extended by three carbon atoms. The enantiomeric forms of 2-substituted y-butyro- and 8 -valero-lactones have been synthesized from the readily available 2-methyloxazoline (38).44 Scheme 10 illustrates a typical sequence for the butyrolactones; the valerolactones were pre- pared similarly but using 3-(trimethylsily1oxy)propyl bromide or iodide in place of ethylene oxide in the reaction of (38) and in place of 2-(trimethylsily1oxy)ethyl iodide in the reaction of (39).The configurations of the products (41) and (42) were deduced from their c.d.spectra and from their 'H n.m.r. spectra in the presence of chiral solvents and the enantiomeric excesses were determined by h.p.1.c. of for example the intermediate diastereoisomeric mixture derived from (40) or (43) after removal of the trimethylsilyl group.OMe (38) OMe (39) OMe 1 iv (42) Me,SiO Me0 (40) OMe (43) Reagents i BuLi 03 ;ii Me3SiC1;iii LiNPr', RX; iv LiNPr', ICH2CH20SiMe3; v H' Scheme 10 The a -methylene-y-butyrolactones (44) and (45) have been synthesized from methyl 3,5-O-isopropylidene-a -D-xylof~ranoside~~ and from 1,2-O-isopropyl-idene-a -D-xylofurano~e,~~ respectively. Previously published methods for the pre- paration of a -alkylidene-y-butyrolactones yield the (E)-isomer as the predominant product. However it has now been reported that the (E)-and (2)-isomers of 42 T. Fujisawa T. Sato T. Kawara M. Kawashirna H. Shimizu and Y. Ito Tetrahedron Left. 1980 21 2181; T. Fujisawa T. Sato T. Kawara A. Noda and T. Obinata ibid.,p. 2553; T. Fujisawa T. Sato T. Kawara and K.Naruse Chem. Lett. 1980 1123. 43 J. F. Normant A. Alexakis and G. Cahiez Tetrahedron Lett. 1980 21 935. 44 A. I. Meyers Y. Yarnamoto E. D. Mihelich and R. A. Bell J. Org. Chem. 1980,45 2792. V. Nair and A. K. Sinhababu J. Org. Chem. 1980 45 1893. "T. F. Tam and B. Fraser-Reid J. Chem. Soc. Chem. Commun. 1980 556. 132 A. R. Tatchell a-ethylidene-y-butyrolactone may be formed from the intermediate (47) (Scheme 11) according to the catalyst used in the subsequent elimination reaction. The stereoisomeric nature of the intermediate (47) formed by a titanium(1v)-chloride- catalysed aldol condensation was presumed from a consideration of the likely transition state (46)of the reaction. Subsequently the (2)-isomer (48)resulted from a boron-trifluoride-catalysed anti-elimination process and the (E)-isomer (49)from a base-catalysed syn-elimination that was induced with lithium bis(trimethy1- ~ily1)amide;~~" the stereochemical aspects of these eliminations had been established earlier.47b 0 C"" = oA '-0 3SiMe3 + .ii LMe,Si (46) (48) (49) Reagents i Me,SiOSO,CF, Et,N Et,O; ii MeCHO TIC],; iii BF,.OEt,; iv LiN(SiMe,) Scheme 11 Full details are now available of macrolide syntheses which use a palladium-catalysed intramolecular cyclization of the stabilized anions of allylic acetates and the total synthesis of several naturally occurring macrolides has been achieved by this method.48 This general method is an important alternative to methods which result from cyclization of w -functionalized carboxylic acids or their derivatives under conditions of high dilution.Recent catalysts which have found use for this lactonization reaction are cyanuric chloride4' and dibutyltin oxide;" the latter is also useful for lactam formation. The p -keto-lactone (&)-diplodialide A (50) had been synthesized previously by a lactonization pro~edure,~'" and indeed a variant of this method has been reported this year which involves the silver-perchlorate-catalysed cyclization of the S-(2-pyridyl) hydroxythioester (5l)'lbfollowed by removal of the protecting group (R') 47 (a)K. Yamamoto Y. Tomo and S. Suzuki Tetrahedron Lett. 1980,21,2861. (6) P. F. Hudrlik and D. Peterson J. Am. Chem. Soc. 1975,97 1464; P. F. Hudrlik D. Peterson and R. J.Rona J. Org. Chem. 1975,40,2263. 48 B. M. Trost and T. R. Verhoeven J. Am. Chem. SOC. 1980,102,4743. 49 K. Venkataraman and D. R. Wagle Tetrahedron Lett. 1980 21 1893. 50 K. Steliou A. Szczygielska-Nowosielska A. Favre M. A. Paupart and S. Hanessian J. Am. Chem. SOC. 1980,102,7578. 51 (a)T. Ishida and K. Wada J. Chem. SOC.,Perkin Trans. 1 1979,323; (b)A. B. Shenvi and H. Gerlach. Helv. Chim. Acta 1980 63 2426. 133 Aliphatic Compounds -Part (ii) Other Aliphatic Compounds and oxidation by manganese dioxide. However an alternative synthesis involving an intramolecular Eschenmoser sulphide-contraction reaction (see Scheme 12) has been developed employing the intermediate (52) followed by elimination of the acetoxy-residue.52 (52) Scheme 12 5 Amides and Lactams In the formation of the dilithiated derivative of an a@ -unsaturated secondary amide [e.g.(53) and (55; R = H or alkyl)] the second metallation process appears to take place at the @'-position rather than at the anticipated y-or @-positions.Subsequent reaction with a range of electrophiles E' then leads to the @'-substitution products i.e. (54) or (56)respectively (Scheme 13). Although the acyclic examples show lesser regioselectivity the reaction offers a means for substitution at a site that has not previously been regarded as being readily acce~sible.~~ CONHMe CONHMe CONHMe CONHMe 0 j,ij +R~E + (JE ~f i,ii R R (53) (54) (55) (56) Reagents i 2 molar equivalents of Bu'Li TMEDA THF at -78 "C;ii E' Scheme 13 A remarkably simple method for the cyclodehydration of y- 8- and &-amino- acids to the corresponding lactams involves heating the amino-acid in toluene in the presence of neutral alumina or silica Attention is being increasingly directed towards the asymmetric synthesis of @ -1actams.Utilizing an earlier developed cycloaddition method involving dimethyl- keten methyl trimethylsilyl acetal(57) with an imine in the presence of titanium(1v) chloride asymmetric induction has been realized at C-4 to the extent of 44-78% by employing a chiral imine. For example (S)-butylidene-(1 -phenylethyl)amine (58;R' = Pr" R2= Ph) gives (59);the configuration at C-4 was assigned as (S)on the basis of chemical degradation procedures and this was related to the probable 52 R.E.Ireland and F. R. Brown Jr. J. Org. Chem. 1980,45,1868. 53 P.Beak and D. J. Kempf J. Am. Chem. Soc. 1980,102,4550. s4 A.Blade-Font Tetrahedron Lett. 1980 21 2443. 134 A. R. Tatchell transition states of the reaction. A variant used Schiff bases that had been generated from a chiral ester of an a-amino-a~id.~~ Somewhat more modest asymmetric inductions have been found with p-lactam formation using an aryl aldimine with the lithium enolate of for example a (-)-menthy1 ester.56 Best results were obtained by using the menthyl ester from 2-phenylpropanoic acid with N-benzylideneaniline. R1CH=NCHMeR2 Ph (58) H AMe + TIC] R'C-NCHMeR2 -pr"ho OMe Me-/ Me2C=C' Me \ (59) OSiMe (57) N-Hydroxy-2-azetidinones (the elegant synthesis of which was mentioned last year and which has now been described in detail57") have been cleanly reduced with titanium(II1) chloride in buffered solution to the corresponding p -1actam; acid- sensitive protecting groups and base-sensitive chiral centres at C-3 were unaffected by these condition^.^^ 6' Amines and Imines (S)-1-Dimethoxymethyl-2-methoxymethylpyrrolidine, which was used as a reagent in the reported asymmetric synthesis of CY -alkyl-a -amino-acids last year has now been employed in the asymmetric synthesis of amine~.'~ The sequence involved the reaction of the reagent with propargylamine to give the amidine (60),which was then converted first into the 3-silylated derivative and then into the lithiated complex (61).Reaction with an appropriate alkyl halide followed by hydrolysis gave the CY -alkylated propargylamine (62);the sequence could be repeated to give dialkylated products (63). The configurations and enantiomeric excesses of mono- and di-alkyl- propargylamines were deduced by their conversion into the corresponding amino- acids. From these configurations it appeared that the alkylation takes place from a direction opposite to that observed in the asymmetric synthesis of amino-acids [cf. also (9) + (ll)].The reason for this opposite stereoselectivity in two apparently similar reactions is not at present clear. (60) (61) 55 I. Ojima and S. Inaba Tetrahedron Lett. 1980 21 2077,2081. 56 C. Gluchowski L. Cooper D. E. Bergbreiter and M. Newcomb J. Org.Chem. 1980,45 3413. 57 (a)M. J. Miller P.G. Mattingly M. A. Morrison and J. F. Kerwin Jr. J. Am. Chem. Soc. 1980,102 7026; (6) P. G. Mattingly and M. J. Miller J. Org. Chem. 1980,45 410. M. Kolb and J. Barth Angew. Chem. Int. Ed. EngI. 1980,19 725. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 135 A very convenient method for preparation of the synthetically important Mannich salt i.e. dimethyl(methy1ene)ammonium iodide has been developed. NNN’N’-Tetramethylmethylenediaminewas added to an anhydrous solution of trimethylsilyl iodide in ether when the product was rapidly precipitated in 96% yield.59 The conversion of primary aliphatic amines into azides,60 fluorides,61 and nitrate esters6’ via the appropriate pyridinium salts are further examples of this very versatile reaction methodology.7 Other Nitrogen-containing Compounds The (2)-formamidines (64) that are formed by the addition of a secondary amine to an aryl isocyanide at low temperature in the presence of silver chloride are thermodynamically unstable and they isomerize to the (E)-isomers (65) on heating or on treatment with acid. The n.m.r. spectrum of the (E)-isomer (65; Ar = rn -ClC,H,) revealed equivalent methyl signals at 34 “C but non-equivalence at -30 “C; restricted rotation about the C-N bond at the lower temperature is thus inferred. In contrast the (2)-isomer (64; Ar = m-ClC6H4) shows no such tem- perature effect over the range +34 to -80 “C and both methyl groups maintain their equivalence. The explanation offered is that the N-aryl and dimethylamino-groups are orthogonal to the N-C=N plane (66); when an ortho-substituent is present in the aryl residue two methyl signals are observed and it is suggested that in this case there is also conformational restriction about the N-aryl bond.63 H\@ H Ar H \/ \@ /C=N ,C=N C=N Me-N \Ar Me-N B \ Me Me Mi’’ \ N/Q Me (64) (65) (66) Aliphatic aldoximes may be smoothly dehydrated to nitriles by treatment with sulphuryl chloride fluoride (ClS0,F) ;64 the reductive cleavage of ketoximes with vanadium(I1) chloride offers a means of regenerating the parent ketones in good yield.65 The conversion of aliphatic and alicyclic (but not apparently aromatic) aldehydes and ketones into nitriles having one additional carbon atom has been effected by way of their corresponding 2,4,6-tri-isopropylbenzenesulphonyl-hydrazones by heating with a three-fold excess of potassium cyanide (Scheme 14).The method is particularly applicable to parent ketones or aldehydes having additionally an olefinic function; an example is given using a keto-steroid as a substrate.66 ’’ T. A. Bryson G. H. Bonitz C. J. Reichel and R. E. Dardis J. Org. Chem. 1980,45 524. 6o A. R. Katritzky G. Liso E. Lunt R. C. Patel S.S.Thind and A. Zia J. Chem. Soc. Perkin Trans. 1 1980,849. A. R. Katritzky A. Chermprapai and R. C. Patel J. Chem. Soc. Perkin Trans. 1 1980 2901. 62 A. R. Katritzky and J. Marzorati J. Org. Chem. 1980,45 2515. 63 A. F. Hegarty and A. Chandler J. Chem. Soc. Chem. Commun. 1980 130.64 G. A. Olah S.C. Narang and A. Garcia-Luna Synthesis 1980,659. 65 G. A. Olah M. Arvanaghi and G. K. Surya Synthesis 1980 220. 66 J. Jiricny D. M. Orere and C. B. Reese J. Chem. Soc. Perkin Trans. 1 1980 1487. 136 A. R. Tatchell R' R'\ KCN R'\ C-NHNHS0,Ar -[R>Cr$=N{ -R2,CHCN C=NNHSO,Ar + \ R2/ ~2' \CN Ar = 2,4,6-Pr1&H2 Scheme 14 Reductive cleavage of the cyano-group to yield the corresponding alkane may be effected by using a catalyst of potassium dispersed over neutral alumina prepared at 150 "Cunder an atmosphere of argon. Subsequently the catalyst (14%K/A120,) was used at room temperature as a hexane slurry to which the nitrile was added. The reaction is compatible with the presence of THP and other acetal-protecting groups and with the presence of an olefinic system although here migration of the double-bond may be observed in some instances.The usefulness of the method is shown by a synthesis of (Z)-dodec-9-en-l-y1 acetate the sex pheromone of Para-lobesia vitaeana (Scheme 15).67 . .. HOCH2(CH2)4CH2Br<THPOCH2(CH2)4CH2CN I THPOCH2(CH2)4CH(CH2)2CH&HEt %AcOCH,(CH&CH&HEt Reagents i NaCN phase-transfer catalyst n-C,oH22; ii 3,4-dihydro-2H-pyran Amberlyst H-15; iii LiNPr', EtCHkHCH,CH,I; iv K/Al,O,; v MeCO,H MeCOCl Scheme 15 y-Nitro-alkanoic acids which are readily prepared by a Michael addition reaction between a nitro-alkane and an acrylic ester followed by hydrolysis have been converted into cyclopentenones by treatment with a polyphosphoric acid-methanesulphonic acid system.68 Scheme 16 illustrates one mechanistic sequence that has been suggested for a reaction which ultimately yields dihydrojasmone the first intermediate being the y-nitro-acylium ion.Me PnCH,bc ___*pn3 +pnCH2Yo [-HNO,] [-H'l -z6 o+o It O//NYo 0 0 Pn = pentyl Scheme 16 8 Phosphorus Compounds A mild and selective procedure for monodemethylation of phosphate and phosphon- ate esters involving stirring with t-butylamine at room temperature has been described in two publication^.^^ Total dealkylation may be effected by employing trimethylsilyl iodide followed by hydrolysis of the intermediate trimethylsilyl ester." 67 D. Savoia E. Tagliavini C. Trombini and A. Umani-Ronchi J. Org. Chem. 1980,45 3227.68 T.-L. Ho J. Chem. SOC.,Chem. Commun. 1980 1149. 69 M. D. M. Gray and D. J. €1. Smith Tetrahedron Lett. 1980 21 859; D. J. H. Smith K. K. Ogilvie and M. J. Gillen ibid. p. 861. 70 G. M. Blackburn and D. Ingleson J. Clitw. Soc. Ptvkin Tmtts. 1 1980 1150. 137 Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 4-Acetoxyazetidin-2-one (67) (Scheme 17) when treated with a range of phosphite or phosphonite esters provides a route to 4-oxoazetidin-2-yl-phosphon-ates (68)and -phosphinates (69) whence acid hydrolysis gives a -aminophosphonic (70)and a-aminophosphinic (7 1)analoguesof aspartic acid.71 Such compounds have been incorporated into dipeptides for pharmaceutical evaluation. 0 II P-OR' - 0 II+-R-H HOZC NH2 0 (67) (68) R2= OR' (69) R2 = Me (70) R2 = OH (71) R2= Me Scheme 17 Chiral tertiary phosphines of high enantiomeric purity are required for incorpor- ation into catalysts for asymmetric synthesis.Improved optical purities have been achieved by utilizing the synthetic route illustrated in Scheme 18.72 OMen OMen OMen ... *I* I I RI--P R'--P+ cF3so3-A R'--p I 5 R'--P 4 "s 4 \SMe 4 \ 4 'RZ Ph Ph Ph Ph R' = Me or Et; Men = (-)-menthy1 Reagents i CF,SO,Me; ii Bu'SLi; iii R2Li at -50 "C Scheme 18 9 Alkyl Halides Several methods have been described for the conversion of alcohols into alkyl halides. A general reagent for bromide formation from primary secondary tertiary allylic and benzylic alcohols is lithium bromide plus trimethylsilyl chloride in acetonitrile.A useful alternative which shows regioselectivity is pyridinium bromide perbromide plus hexamet hyldisilane ;for example 2 -me th ylpentane -2,4 -diol gives 2-bromo-2-methylpentan-4-01. With (-)-octan-2-01 this latter reagent results in an 88% inversion of configuration in the alkyl Retention of configuration (>92%)in the conversion of alcohol into alkyl bromide results from a double inversion process involving first the formation of the alkyl phenyl selenide (from the alkyl methanesulphonate and sodium phenyl selenide) followed by reac- tion with a bromine-triethylamine reagent. Conformationally preferred cyclic sys- tems wherein the leaving group in either of these reactions is axial give poorer yields owing to competing elimination processes.74 The effectiveness of a range of reducing agents and the influence of solvents on the reaction course have been studied for the hydrogenolysis of alkyl halides and alkyl toluene-p-sulphonates.Lithium triethylborohydride appears to be more effective than lithium aluminium hydride for the reduction of acyclic alkyl halides and alicyclic iodides and both these reagents are superior to other complex metal 7' M. M. Campbell and N. Carruthers J. Chem. SOC.,Chem. Commun. 1980 730. 72 J. Omelahczuk W. Perlikowska and M. Mikolajczyk J. Chem. Sac. Chem. Commun. 1980 24. 73 G. A. Olah B. G. B.Gupta R. Malhotra and S. C. Narang J. Org. Chem. 1980,45 1638. 74 M. Sevrin and A. Krief J. Chem. SOC., Chem. Commun. 1980,656. 138 A. R. Tatchell hydride~.~~ However the selectivity exhibited by LiAlH4 towards hydrogenolysis of halides and tosylates is crucially solvent-dependent.Thus in diethyl ether LiA1H4 effects hydrogenolysis of alkyl tosylates but not alkyl iodides while the opposite selectivity is observed in diglyme. This selectivity is dramatically illustrated in the case of 1 1 -bromoundecyl toluene-p-sulphonate where either functionality may be reduced according to the solvent employed. The solvent effect has been attributed to poor solvation of the lithium cation in diethyl ether resulting in diminished nucleophilicity of the tetrahydroaluminate anion towards displacement of iodide. In this solvent the lithium cation could well complex specifically with the tosylate group thereby enhancing its leaving qualities; the lithium cation would be strongly solvated in diglyme solution and this could result in the reverse functional rea~tivity.~~ 10 Reviews The structural features and the symmetry properties resulting in optical activity are reviewed in an historical account which points out some of the many misconceptions (some fifty or so) that have arisen since the time of van't Hoff and Le Bel.77 A review on the resolution of racemates by chromatography is timely,78 and a discussion of resolution by direct crystallization of racemic conglomerates intere~ting.~~ A survey of the methods of stereo-control in synthetic procedures for acyclic systems80 complements a review published at the end of last year on recent advances in asymmetric synthesis.81 There is also a review on the stereochemistry of phosphorus compounds.82 Reviews have also appeared on the hydrogenolysis of organic halides,83 the use of the fluoride ion as a base in organic reaction^,^^ the thermal and photochemical decomposition of azoalkane~,~~ the conversion of the primary amino-group into other functionalities,86 and the reactions of squaric acid and its derivatives.87 75 S.Krishnamurthy and H. C. Brown J. Org. Chem. 1980 45 849. 76 S. Krishnamurthy,J. Org. Chem. 1980 45 2550. 77 J. K. O'Loane Chem. Rev. 1980,80,41. 78 G. Blaschke Angew. Chem. Int. Ed. Engl. 1980 19 13. 79 A. Collet M.-J. Brienne and J. Jacques Chem. Rev. 1980,80 215. P. A. Bartlett Tetrahedron 1980 36 3. " J. W. ApSimon and R. P. Seguin Tetrahedron 1979 35 2797.82 C. R. Hall and T. D. Inch Tetrahedron 1980,36,2059. 83 A. R. Pinder Synthesis 1980 425. 84 J. A. Clark Chem. Rev. 1980 80,429. 85 P. S. Engel Chem. Rev. 1980 80 99. 86 A. R. Katritzky Tetrahedron 1980 36 679. 87 A. H. Schmidt Synthesis 1980,961.

ISSN:0069-3030    

DOI:10.1039/OC9807700123

出版商:RSC    

年代:1980

数据来源: RSC

摘要:

9 Alicyclic Chemistry By J. M. MELLOR Department of Chemistry The University Southampton SO9 5NH 1Introduction A number of areas are the subjects of reviews. Those not discussed further in this Report include the chemistry of benzocyclobutene and related compounds;' trans-cycloalkenes and [a,b]betweenanenes;* polyep~xides;~ the uses in organic synthesis of oxycycl~propanes,~ 3-methylcyclohex-2-enonederivatives,' and azoalkanes;6 the use of the intramolecular Diels-Alder reaction' in the synthesis of natural products; and the application of bicyclic and tricyclic intermediates' to the stereocontrolled synthesis of prostaglandins. The following topics have also been reviewed but aspects are discussed further in this article cycl~butadiene,~ the dynamic stereochemistry of five- six- and seven-membered rings," and the concept of sigma-assistance and the discussion" of the importance of through-bond interac- tions.2 Synthesis Monocyclic Compounds.-A general method for synthesis of cyclopropane deriva- tives'* proceeds by the reaction of dibromomalonic esters with copper in DMSO. Addition to a variety of alkenes including acrylonitrile 1-octene and styrenes occurs in high yield but the reaction is non-stereospecific. An alternative four-stage sequence13 to similar products (Scheme 1) has the advantage of high stereo-specificity. 2-Alkoxy-cyclopropanecarboxylateshave been used as precursors of 1,4-dicarbonyI compounds. Their potential has been increased by the effective cycl~propanation'~of silyl-enol ethers with methyl diazoacetate.Tetrachloro- cy~lopropene'~ adds to alkenes with high stereospecificity suggesting that there is R. P. Thummel Acc. Chem. Res. 1980,13 70. ' J. A. Marshall Acc. Chem. Res. 1980 13 213. W. Adam and M. Balci Tetrahedron,1980 36 833. E. Wenkert Acc. Chem. Res. 1980,13,27. ' J. K. Sutherland Chem. SOC.Rev. 1980,9 265. W. Adam and 0.De Lucchi Angew. Chem. Int. Ed. Engl. 1980 19 762. ' G. Brieger and J. N. Bennett Chem. Rev. 1980 80 63; R. L. Funk and K. P. C. Vollhardt Chem. SOC.Rev. 1980,9,41. R. F. Newton and S. M. Roberts Tetrahedron,1980,36 2163. T. Bally and S. Masamune Tetrahedron,1980 36 343. lo E. Toromanoff Tetrahedron 1980,36 2809. J. W. Verhoeven Recl. Trav. Chim. Pays-Bas 1980 99 369. N. Kawabata and M.Tanimoto Tetrahedron,1980,36 3517. l3 J. Ohishi Synthesis 1980 690. l4 H-U. Reissig and E. Hirsch Angew. Chem. Int. Ed. Engl. 1980 19 813. l5 W. Weber and A. de Meijere Angew Chem. Int. Ed. Engl. 1980 19 138. 139 140 J. M. Mellor Reagents i MeSSMe SOZCl2 CH2C12 at -50 "C; ii CH,(CO,Et), EtOH EtONa; iii Me2S0,; iv EtOH EtONa Scheme 1 a carbene intermediate. The products e.g. (l),which are obtained in high yield can be dehalogenated to afford vinylcyclopropanes. Access to simple cyclobutane derivatives is still difficult. A useful two-step method16 from commercially available tosylmethyl isocyanide makes cyclobutanone available by initial alkylation with 1,3-dibromopropane and subsequent hydrolysis. Two routes to hydroxy-cyclobutenediones (derivatives of semisquaric acid) have been described.These compounds which are related to the mycotoxin moniliformin are available by [2 + 21 cycloaddition of tetraethoxyethylene to trimethylsilyl- keten17 or to methylketen,18 or by photoaddition18 of dichlorovinylene carbonate with 1,l -dichloroprop- 1-ene. Cyclobutanetetraone is unknown but the tetra-imine (3) is obtained" by the surprisingly simple experimental procedure of the reaction of (2) with nitrosobenzene in benzene. The product (3) which is a tetramer of phenyl isocyanide is a strong oxidizing agent; in the conversion of alcohols into aldehydes (4) is obtained. The intensive effort to find improved methods for the preparation of five- membered rings continues. General annelation procedures are described elsewhere.Transition-metal-catalysed intramolecular hydroacylation of unsaturated aldehydes to give cyclopentanones has attracted much attention. Full details2' of a catalytic method based on rhodium complexes have been given. The method is limited to mono- or di-substituted alkenes. Rhodium complexes2' are effective in promoting the cyclization of 1,6-dienes to give methylenecyclopentanes in high yield but again the further substitution of the double-bonds prevents cyclization. The use of alkyne-cobalt carbonyl complexes to give 2-substituted cyclopentenones has been described. The method has now been used22 to transform the alkynes (5) and (6) into the prostaglandin synthons (7a) and (7b) respectively by reaction with ethylene.Two methods relying on rearrangements (Schemes 223 and 324) provide simple routes to key synthons. l6 D. van Leusen and A. M. van Leusen Synthesis 1980 325. W. T. Brady and K. Saidi J. Org. Chem. 1980.45 727. '* D. Bellus P. Martin H. Sauter and T. Winkler Helv. Chim. Acfa 1980 63 1130. H. J. Bestmann G. Schmid and E. Wilhelm Angew. Chem. Inf. Ed. Engl. 1980,19 136. 2o R. C. Larock K. Oertle and G. F. Potter J. Am. Chem. Soc. 1980 102 190. R. Grigg T. R. B. Mitchell and A. Ramasubbu J. Chem. SOC.,Chem. Commun. 1980,27. 22 R. F. Newton P. L. Pauson and R. G. Taylor J. Chem. Res. (S),1980,277. 23 L. A. Paquette G. D. Crouse and A. K. Sharma J. Am. Chem. SOC.,1980,102 3972. 24 B. M. Trost T. A. Runge and L. N. Jungheim J. Am. Chem. Soc. 1980,102,2840.Alicyclic Chemistry 0 (7a) R = (CH2)&O2Me (7b) R = CH2CH=CH(CH2)3C02Me CHO Reagents i KH THF at room temperature Scheme 2 OCH,Ph Reagents i dioxan (Ph2PCHzCH2PPhz)zPd Scheme 3 The retro-Diels-Alder reaction has been used with great success to generate a number of interesting unstable compounds. By thermolysis2' of bridged ketones at 800°C and trapping of the products at -196"C a number of ketones e.g. (8) which are tautomers of phenols have been spectroscopically characterized. The formation of six-membered rings via initial [2 + 21 photocycloadditions has been used in a number of syntheses of natural products. Addition of cyclohexenones to methyl cyclobutenecarboxylate and subsequent thermolysis is a useful route26 to derivatives of trans-decalin.A very efficient procedure2' leading to cyclohexenones is shown in Scheme 4. The method promises to have a wide applicability to substituted alkenes and to vinyl ethers. Although an understanding of the observed regiochemistry is not yet developed a regioselectivity that is of synthetic importance has been found. Thus 1-methylcyclohexene gives predominantly (9) but 3,3-dimethylbut-1 -ene gives mainly (10). An alternative decalone synthesis2' proceeds 0 (8) (9) (10) 25 M-C. Lasne and J-L. Ripoll Tetrahedron Lett. 1980,21,463. 26 P. A. Wender and J. C. Hubbs J. Org. Chem. 1980 45 365; P. A. Wender and L. J. Letendre ibid. p. 367. S. W. Baldwin and J. M. Wilkinson J. Am. Chem. SOC.,1980,102,3634. ** R.Scheffold M. Dike S. Dike T. Herold and L. Walder J. Am. Chem. SOC., 1980,102 3642. 2' 142 J. M. Mellor 0 0 1ii Reagents i hv;ii Bu',AIH; iii base Scheme 4 Scheme 5 by a chemically catalysed [using aquocobalamine or other cobalt(II1) complexes] controlled-potential electrolysis resulting in reductive coupling of an alkyl halide with an ap-unsaturated ketone. Examples of intramolecular coupling are shown in Scheme 5. The versatility of the well-established [4 + 31 cycloaddition of allyl cations to dienes has been extended29 by the use of allyl alcohols as precursors (Scheme 6). In contrast to previous methods vinyl ethers and not ketones are directly isolated. Reagents i C,H, ZnCI, EtNPr', MeCN at room temperature Scheme 6 A procedure3' for ring expansion by three carbons is based on coupling of a P-keto-sulphone with an allyl ester.The method has been adapted inter alia for the synthesis of eight-membered rings (Scheme 7) and for a further synthesis of muscone (Scheme 8).A very simple synthesis of muscone is achieved3' by regioselec- tive aldol cyclization of hexadecane-2,15-dione. The selectivity is observed by use of the combination of a tertiary amine with a dialkylaluminium aryloxide. A metathesis reaction of a linear unsaturated ester followed by a Dieckmann con- densation of the diester product has for some time appeared to be a potential route to macrocyclic ketones. The method using W0C4 and [(Cp),TiMe2] as catalyst has been successfully applied3 to ethyl oleate in a synthesis of civetone (11).29 H. M. R. Hoffmann and J. Matthei Chem. Ber. 1980,113,3837. 30 B. M.Trost and J. E. Vincent J. Am. Chem. SOC.,1980 102,5680. 31 J. Tsuji T. Yamada M. Kaito and T. Mandai Bull. Chem. Soc. Jpn 1980,53,1417. 32 J. Tsuji and S. Hashiguchi Tetrahedron Lett. 1980 21 2955. 143 Alicyclic Chemistry CH2 cy" + Me,Si&OSO,Me S0,Ph SiMe S0,Ph OH SOzPh Reagents i NaH NaI DMF; ii Bu,NF THF; iii KH 18-crown-6 DME Scheme7 6-d iii,iv S0,Ph Reagents i NaH NaI DMF; ii Bu,NF THF; iii Hz Pd; iv Na(Hg) Na,HPO, MeOH Scheme 8 The chemistry of three interesting fluorocarbons has been reported. 1rradiatio1-1~~ of hexafluorobenzenein the presence of oxygen gives not only hexafluoro-Dewar- benzene but also the oxide (12).Thermolysis of (12) at 50°C gives mainly the dienone (13). Thermolysis of (14) at 585°C and trapping of the products at -196 "C results in the of perfluorocyclopentadienone (15). Photolysis of (15) gives perfluorocyclo-octatetraene possibly via the intermediacy of perfluorocyclobutadiene. On warming (15) gives an expected [4 + 21 dimer but interestingly the dimer appears to have an em configuration. The pyrazoline (16) has been prepared3' uia addition of perfluorotetramethyl-Dewarthiophen to trifluorodiazoethane. Thermolysis of (16) at -600 "C gives perfluoropentamethyl- cyclopentadiene (17) in 11% yield. The product (17) can be isolated by g.1.c. but is a strong acid of pK < -2 i.e. stronger than nitric acid and it is a volatile liquid that readily attacks glassware.33 M. G. Barlow R. N. Haszeldine and C. J. Peck J. Chem. Soc. Chem. Commun. 1980 158. 34 M. W. Grayston W. D. Saunders and D. M. Lemal J. Am. Chem. Soc. 1980,102,413. 35 E. D. Laganis and D. M. Lemal J. Am. Chem. Soc. 1980,102,6633. 144 J. M. Mellor F F&Jb FF F (13) Bicyclic Compounds.-A general procedure has been described36 for the prepar- ation of bicyclo[x. y.O]alkane skeletons by the dialkylation of dilithium salts of vicinal dialkyl cycloalkanedicarboxylates with cyw -dihalides. The method is a satis- factory entry to the bicyclo[3.3.0]octane skeleton. This skeleton has been the target of intensive synthetic studies. An efficient synthesis3' of a potential intermediate for synthesis of natural products is shown in Scheme 9.Using chiral phosphines modest enantioselectivity is observed in the Wittig reaction. 0 0 Reagents i [(Ph,P),Pd] DBU toluene at 80 "C;ii N-bromosuccinimide DMSO H,O; iii Ph,P; iv K&O Scheme 9 The conversion of the ethylene (18)into the doubly bridged ethylene (19) requires the conversion of an achiral system into the chiral product. Irradiati~n~~ of achiral (20) in ( + )-diethy1 tartrate afforded an intermediate ketone which was reduced to give (19) with low enantioselectivity. Alternative synthetic routes to these doubly bridged alkenes called betweenanenes by Marshall proceed by direct photo- is~merization~~ or by [2,3] sigmatropic rearrangement of a spirocyclic ylide pre- 36 K.G. Bilyard P. J. Garratt and R. Zahler Synthesis 1980 389. 37 B. M. Trost and D. P. Curran J. Am. Chem. SOC.,1980,102,5699. 38 M. Nakazaki K. Yamamoto and M. Maeda J. Chem. SOC.,Chem. Commun. 1980,294. 39 A. Nickon and P. St. J. Zurer Tetrahedron Lett. 1980,21,3527. 40 V. Cere C. Paolucci S. Pollicino E. Sandri and A. Fava J. Chem. SOC.,Chem. Cornmun. 1980 755. Alicyclic Chemistry 145 The highly unstable spiropentene (21)has been prepared41 by elimination of hydrogen bromide from (22).Polymerization occurs in the condensed phase at -78“C but (21)is moderately stable in solution (in CHCl,) at -30“C. The problems of stereo-controlled synthesis of spirocyclic natural products have stimu- lated the investigation of further approaches. The use4’ of a p -dicarbonyl system (Scheme 10) is efficient in generating a spirocycle but is untested for demanding 06N-phenylselenophthalimide opseph b Scheme 10 cases that require stereoselectivity.Semmelhack’s group43 have extended their studies by devising a synthesis of acorenone and acorenone B which relies on the key transformation of the chromium complex (23)to give (24).However the cyclization is not very efficient. Pearson’s use of cyclohexadienylium-Fe(C0)3 complexes to construct spirocyclic systems e.g. the conversion44 of (25)into (26) again has little steric control but the approach has now been extended to the synthesis of other interesting skeletons with good stereocontrol; e.g. tricothecane derivative^^^ and cis-hydrindene~.~~ 0 CN CN CN Polycyclic Compounds.-Following the development of intermolecular additions of alkenes to diynes catalysed by [(C~)CO(CO)~] Vollhardt and co-workers have now extended the method to the synthesis of tricyclic systems from acyclic precur- sors.Cyclization4’ of (27)gave (28)in 85% yield and the uncomplexed silylated diene could readily be obtained from (28).Such methods have considerable promise for the synthesis of natural products. The trachylobane series of diterpenes incorpor- ates a tricyclo[3.2.1.02~7]octanemoiety and this feature is the greatest obstacle to synthesis. Alternative strategies4* for a simple synthesis of this skeleton are shown in Scheme 11 one of the methods was used in the synthesis of trachylobane derivatives. The use of the intramolecular Wittig reaction in the construction of 41 R.Bloch and J-M. Denis Angew. Chem. Znt. Ed. Engl. 1980,19,928. 42 W. P. Jackson S. V. Ley and J. A. Morton J. Chem. SOC.,Chem. Commun. 1980 1028. 43 M. F. Semmelhack and A. Yamashita J. Am. Chem. Soc. 1980,102 5924. 44 A. J. Pearson P. Ham and D. C. Rees Tetrahedron Lett. 1980 21,4637. 45 A. J. Pearson and C. W. Ong Tetrahedron Lett. 1980,21,4641. 46 A. J. Pearson and M. Chandler Tetrahedron Lett. 1980 21 3933. 47 E. D. Sternberg and K. P. C. Vollhardt J. Am. Chem. Soc. 1980,102,4839. 48 R. M. Cory and R. M. Renneboog J. Chem. SOC.,Chem. Commun. 1980 1081; R. M. Cory D. M. T. Chan Y. M. A. Naguib M. H. Rastall and R. M. Renneboog J. Org. Chem. 1980,45,1852. 146 J. M.Mellor Reagents i H,C=CHSO,Ph THF HMPT; ii H2C=C(Me)$Ph3 X-Scheme 11 0 (unstable intermediate) [ref. 511 C’ -[ref. 521 [ref. 531 Reagents i KOBu‘; ii Et3N Scheme 12 anti-Bredt alkene~~~ has been reviewed. Such compounds are still the target of intensive synthetic studies. Recent examples are collected in Scheme 12.50-53 Syn-theses of propellanes which are another category of highly strained compounds are collected in Schemes 1354-56and 14.57 49 K. B. Becker Tetrahedron 1980 36 1717. H. Gerdes S. Javeri and H. Marschall Chem. Ber. 1980,113 1907. K. B. Becker and J. L. Chappuis Helu. Chim. Actu 1980,63,1812. ” H. 0.House M. B. DeTar R. F. Sieloff and D. Van Derveer J. Org. Chem. 1980,45,3545. 53 L.A. M.Turkenburg J. W. van Straten W.H. de Wolf and F. Bickelhaupt J. Am. Chem. SOC.,1980 102,3256 54 R. Bishop and A. E. Landers Aust. J. Chem. 1979,32,2675. ” W. F.Carroll and D. G. Peters J. Am. Chem. SOC.,1980,102,4127. 56 P. G.Gassman and G. S. Proehl J. Am. Chem. Sac. 1980,102,6862. 57 T. Tsuji Z. Komiya and S. Nishida Tetrahedron Lett. 1980,21,3583. Alicyclic Chemistry [ref. 561 Reagents i hv; ii cathode DMF; iii Na Scheme 13 The optical activity of fluxional molecules has never been examined. 2-Methyl- semibullvalene (29) has been ~ynthesized~~ in higher enantiomeric purity the absolute configuration has been determined and the observed c.d. spectrum com- pared with predictions. Access to substituted semibullvalenes is difficult but a one-pot synthesis5' (Scheme 15) has been successfully developed.Bridged [14]annulenes were first synthesized from anthracene by building in the bridging unit. This route was lengthy and not very efficient. The alternative method developed by Vogel's group based on the development of the perimeter by using the dialdehyde (30) had many improvements but was limited by the inaccessibility of (30).A much improved method of preparation of (30)has now been described,60 based on the diacylation of cycloheptatriene. The dialdehyde (30)has been conver- ted into (3l) which suffers considerable deformation from planarity. Spectroscopic data (u.v. and n.m.r.) indicated that (31) is a polyolefin and not an aromatic molecule. However X-ray data appear initially to conflict with this conclusion.In the absence of a low-temperature X-ray structure to resolve the question the view61 that (31) is a polyolefin that undergoes a fluxional valence-tautomeric '13 L. A. Paquette R. F. Doehner J. A. Jenkins and J. F. Blount J. Am. Chem. SOC.,1980 102 1188. 59 D. Paske R. Ringshandl I. Sellner H. Sichert and J. Sauer Angew. Chem. Int. Ed. Engl. 1980,19 456. 60 E.Vogel H. M. Deger J. Sombroek J. Palm A. Wagner and J. Lex Angew. Chem. Int. Ed. Engl. 1980,19,41. 61 E.Vogel H. M. Deger P. Hebel and J. Lex Angew. Chem. Int. Ed. Engl. 1980,19,919; H. Gunther H.von Puttkamer H. M. Deger P. Hebel and E. Vogel ibid.,p. 921. 148 J. M. Mellor equilibrium in the crystal at room temperature remains an unproven but attractive hypothesis.Titanium-catalysed dimerization of cycloheptatriene aff ords6* the dimers (32) and (33) which are probably obtained by an initial [6 + 21 addition to give (34) followed by [4 + 21 additions to give either (32) or (33). CHO es;QCHO (29) (30) (31) (32) (33) (34) Access to the larger diamondoid hydrocarbons has been significantly advanced. The subject has been reviewed63 by McKervey and full details have been published64 of the synthesis of triamantane (35),in five steps from norbornadiene. [8]Tritwis- tane (36) a member of a rare family of molecules of the chiral point group D3 has been synthesized6' in several steps from the photo-adduct of the p-benzoquinone-cyclohexa-1,3-dieneDiels-Alder product (37). 3 Stereochemical Consequences of Through-Bond Interactions Verhoeven" has presented a timely review of 'sigma-assistance' and described both the earlier spectroscopic observations of through-bond interactions and examples of the more recently discovered consequences of such interactions on reactivity.Although these effects can be observed in the chemistry of acyclic systems they are most dramatically exposed in reactions of rigid bridged systems. The following discussion is focussed on a limited number of topics illustrating the control of reaction pathways by through-bond interactions. [4 + 21 Cyc1oadditions.-In Table 1are collected recent examples illustrating the stereochemical control of through-bond interactions. Two important conclusions emerge from these results with dienes (38) (39) and (41)-(43)' endo-addition is 62 K.Mach H. Antropiusova F. Turecek V. Hanus and P. Sedmera Tetrahedron Lett. 1980,21 4879. 63 M. A. McKervey Tetrahedron 1980 36 971. 64 F. S. Hollowood M. A. McKervey R. Hamilton and J. J. Rooney J. Org. Chem. 1980 45,4954. 6J K. Hirao and 0.Yonemitsu J. Chem. Soc. Chem. Commun. 1980,423. A licyclic Chemistry Table 1 Stereoselectivity in [4 + 21 cycloadditions Diene Dienophile Product stereochemistry Reference N-Methyltriazolinedione Exclusively endo a N-Methyltriazolinedione Exclusively endo a N-Meth yltriazolinedione Exclusively endo a Maleic anhydride Exclusively endo b Maleic anhydride Exclusively endo b Methyl propiolate Exclusively endo b Methyl propiolate Mainly exo b Dimethyl acetylenedicarboxylate Mainly exo b Singlet oxygen Mainly endo C Singlet oxygen Mainly endo C TCNE Mainly endo d TCNE Mainly endo d Singlet oxygen Mainly endo e Singlet oxygen Mainly exo e \ / / oqcl* a OMe OMe Cl (42) (43) (44) (a) L.A. Paquette R. V. C. Can P. Charumilind and J. F. Blount J. Org. Chem. 1980 45 4922; (6) L. A. Paquette R. V. C. Carr M. C. Bohm and R. Gleiter J. Am. Chem. Soc. 1980 102 1186; M. C. Bohm R. V. C. Carr R. Gleiter and L. A. Paquette ibid. p. 7218; (c) L. A. Paquette R. V. C. Carr E. Arnold and J. Clardy J. Org. Chem. 1980 45 4907; (d) M. Avenati J-P. Hagenbuch C. Mahaim and P. Vogel Tetrahedron Left. 1980 21 3167; (e) L. A. Paquette F. Bellamy M. C. Bohm and R. Gleiter J.Org. Chem. 1980,45 4913. either observed exclusively or dominantly whereas the dienes (40) and (44) nor-mally undergo em-addition. This stereospecificity is explained not by steric factors but by orbital interactions of the bridged systems which lead to unequal availability of electrons on the two faces of the reacting diene. The second important feature is best illustrated by the behaviour of (40) with N-methyltriazolinedione. It has been concluded that the exceptionally high reactivity of this dienophile is character- ized by an unusually early transition state in which the importance of these electronic effects is magnified. Hence only with the more reactive N-methyltriazolinedione does (40) give an endo product. In (39) and other dienes the orbital interaction is always sufficiently important to control the formation of an endo product.A similar FMO analysis has been applied66 to the case of [4 + 21 additions to propellanes. In the additions of triazolinedione to (45) and to (46) the preference is for addition of the dienophile from the syn face for (45) but from the anti face for (46). 66 M. C. Bohm and R. Gleiter Tetrahedron 1980 36 3209. 150 J. M. Mellor .O (45) (46) Other Cyc1oadditions.-In cycloaddition reactions norbornene shows both an exceptional reactivity relative to other alkenes and a high preference for exo- addition. exo-Addition has been attributed in the past to torsional effects or to there being steric hindrance to endo-addition and the exceptional rates to relief of ring strain.The inadequacy of these views has been nicely exposed by measure- menf7 of the relative rates of reaction of nitrile oxides azides diazomethane a nitrone and a diene with norbornene and with the alkenes (47)-(49). When suitable allowance has been made for the relative contributions of strain relief the results show that norbornene is unusually reactive. The full explanation of this rate increase is not clear -it has been called6’ factor ‘x’,but some orbital interaction that leads to an enhanced availability of electrons from the exo-face is probable. Ab initio calculations lend support68 to this view. b (47) (49) Additions69 to 7-substituted norbornadienes have been extensively investigated. Four modes of addition (anti-exo syn-em anti-endo and syn-endo) are possible.Relative rates of addition of hexachlorocyclopentadiene to a series of dienes are shown in Table 2. The data indicate that rates of syn-endo- and anti-endo-addition Table 2 Rates and partial rate factors for the reaction of hexachlorocyclopentadiene with norbornadienes Partial rate factors Diene Overall rate 1O5k2/s-’ anti-endo syn-endo anti-exo Norbornadiene 39.8 1 1 16.9 (5O;X = OMe) 10.1 1.13 0.74 7.23 (5O;X = H) 9.85 0.85 0.97 7.05 (50;X= F) 8.26 0.86 0.63 5.95 7-Chloronorbornadiene 1.32 0.40 0.40 0.35 (50) 67 R. Huisgen P. H. J. Ooms M. Mingin and N. L. Allinger J. Am. Chem. SOC.,1980 102 3951. 68 G.Wipff Tetrahedron Lett. 1980,21,4445. 69 P.H.Mazzochi B. Stahly J. Dodd N. G. Rondan L.N. Domelsmith M. D. Rozeboom P. Caramella and K. N. Houk J. Am. Chem. SOC.,1980,102,6482. Alicyclic Chemistry are essentially identical and decrease slightly as the electronegativity of the 7- substituent increases. In contrast the rate of the anti-em mode of addition is markedly affected by the nature of the 7-substituent. Again steric factors must be unimportant but the nature of the orbital interaction that leads to these results is not clear. Electrophilic Substitution.-The suggestion that long-range orbital interactions might control reactivity in a series of bridged aromatic compounds (51)-(55) has been made by a group of Australian chemists. Relative rates of nitr?tion7' of these acenaphthylenes are shown. At this stage it appears premature to explain these results by orbital interactions.Other explanations such as the formation of a complex with the substituent in (54) leading to the observed enhanced reactivity cannot be ignored. A similar study of br~mination~' of a series of bridged aromatics e.g. (56),was interpreted on the basis of there being substantial long-range orbital interactions. (51) Relative rate of nitration is 1.00 Relative rate of nitration (52) R' = R2 = H 0.69 (53) R1 = OMe R2 = H 0.70 (54) R' = H,R2 = OMe 9.91 (55) R'R~= o 0.31 Birch Reductions.-Both product and rate studies of the reduction (by Li NH3 and Bu'OH) of a series of bridged aromatic compounds show the importance of orbital interactions. For example the double-bond in (57) is reduced much more readily (by a factor of 141) than that in n~rbornene.~' The remarkable distance over which such effects operate is shown in compounds (58)-(60).It has been c~ncluded'~ that the reduction of the double-bond in (58) is markedly accelerated 70 M. J. Oliver H. K. Patney and M. N. Paddon-Row Am. J. Chem. 1980,33,795. 71 M. N. Paddon-Row B. V. Lap H. K. Patney and R. N. Warrener Aust. J. Chem. 1980,33,1493. 72 M.N.Paddon-Row and R. Hartcher J. Am. Chem. SOC.,1980,102,662. 73 M.N.Paddon-Row and R. Hartcher J. Am. Chem. SOC.,1980,102,671. 152 J. M. Mellor by through-bond (i.e.four-bond) interactions. No acceleration is observed in (59) but the pathway (through five bonds) may be unfavourable. In (60) the modest enhancement of reactivity of the double-bond has tentatively been attributed to through-bond (i.e.six-bond) interactions.Radical Cyc1izations.-Verhoeven" has summarized the kinetically favoured modes of cyclization of alkenyl radicals and related the favoured pathways to the import- ance of through-bond interactions. Thus the preferential cyclization of hex-5-enyl radicals to give a five-membered ring and not a six-membered ring may partly be attributed to through-bond interactions. The more traditional explanation of prefer-ence for an ex0 mode of cyclization rather than an endo mode has been This analysis based on steric effects has been extended7' to rationalize the observed stereoselectivity of closure of substituted hex-5-enyl radicals.The present evidence suggests that both through-bond effects and steric effects contribute to determine the products of cyclization. In photocyclization of hexadienone~~~ it is observed that product formation via cyclization to a five-membered ring is favoured over the alternative mode to a six-membered ring. The factors controlling the mode of cyclization in the excited state are not clear. 4 Conformational Analysis of Six-Membered Rings The search continues for better methods of determination of structure in the solution phase and for more accurate methods of determination of the difference in energy between conformers. Careful analysis of lanthanide-induced shifts now permits the determination of energy difference^^^ for the conformers of 2-methyl 3-methyl- and 4-methyl-cyclohexanone.This study was based on a two-site binding model and was even effective for 2-chlorocyclohexanone. The merit of the study is that conformer energies are determined directly. However less rigorous analyses based on lanthanide-induced shifts can be unreliable and a study7' of cis-3,4-dialkyl-cyclohexanones warns of the dangers of such analyses. Full details have been published of the determinati~n~~ of the thermodynamic parameters relating to conformers of methylcyclohexane isopropylcyclohexane and some cis-1,4-dialkyl-cyclohexanes. The results were obtained by I3C n.m.r. analysis of compounds that were enriched with 13C at a single carbon atom. N.m.r. analysis of (61) shows a preference" for the trideuteriomethyl group to occupy the axial position a result which warns of possible conformational changes as a consequence of isotopic substitution.74 A. L. J. Beckwith C. J. Easton and A. K.Serelis J. Chem. SOC.,Chem. Commun. 1980,482. 75 A. L. J. Beckwith T. Lawrence and A. K. Serelis J. Chem. SOC.,Chem. Commun. 1980,484. 76 W. C. Agosta and S. Wolff J. Org. Chem. 1980,45 3139. " R. J. Abraham D. J. Chadwick L. Griffiths and F. Sancassan J. Am. Chem. SOC.,1980,102 5128. 78 A. Pons and J. P. Chapat Tetrahedron 1980,36,2297. 79 H. Booth and J. R. Everett J. Chem. SOC.,Perkin Trans. 2 1980 255. F. A. L. Anet V. J. Basus A. P. W. Hewett and M. Saunders J. Am. Chem. SOC. 1980 102 3945. 153 Alic yclic Chemistry 5 Other Stereochemical Aspects Craze and Watt have determined8* the energy barrier to hydride transfer in the ketols (62)-(64).It was observed that transfer of hydride is slowest in (62) and fastest in (64),and it is known that the two reacting centres are held closest together in (64). Hence the compounds of the series effectively represent a progression towards a transition state for hydride transfer. Reaction in (64) is fastest because the ground state is closer to the optimum geometry for transfer of hydride. The concept of 'orbital steering' was originally invoked with the implication that a misalignment of reacting groups (of the order of 10")might have profound effects upon reaction rates. The hypothesis has been effectively testeds2 for the lactonization of the hydroxy-acids (65)-(68) and for this series there is no evidence to support orbital steering.A small angular displacement is not kinetically significant. 6 Structural Aspects Neutral Species.-The X-ray structure of tetra-t-butylcyclobutadiene (69)has been Unexpectedly it is non-planar. This result both raises the question of the spin multiplicity of (69) and explains its ready conversion into tetra-t-butyl- tetrahedrane. Photoelectron spectrag4 of the diene and of a tetrahedrane have been reported. An elegant series" of experiments help to clarify the structure of cyclobu-tadiene. Deuteriated cyclobutadienes were generated by the decomposition of (70) and (71) and the products were trapped as adducts of acrylic derivatives. In the case of (71) decomposition is anticipated to give both (72) and (73).However (70) is expected to give only (72). The nature of the adducts that are trapped then depends upon the competitive rates of the trapping reaction and the equilibra- tion of (72) with (73). Experiment has established that in the decomposition of (70) there is a preferential trapping of (72). It must be concluded that cyclobu- tadiene does not have a D4,,equilibrium geometry in solution. Further experiment shows that the rate of trapping is comparable with the rate of equilibration of (72) and (73). D xc D s (73) (74) G-A. Craze and I. Watt J. Chem. SOC., Chem. Commun. 1980,147. F. M. Menger and L. E. Glass J. Am. Chem. SOC.,1980,102,5404. 83 H. Irngartinger N. Riegler K-D.Malsch K-A. Schneider and G. Maier Angew. Chem.Inr. Ed. Engl. 1980,19 211. 84 E. Heilbronner T. B. Jones A. Krebs G. Maier K-D. Malsch J. Pocklington and A. Schmelzer J. Am. Chem. SOC.,1980,102,564. 85 D. W. Whitman and B. K. Carpenter J. Am. Chem. SOC.,1980,102,4272. 154 J. M. Mellor Determinations of the microwave spectrum and dipole moment of (74) provide86 strong evidence for spiroconjugation. The observed dipole moment (p = 0.95 D) is very high for a hydrocarbon. Carbenium Ions. The study of deuterium isotope effects on the I3Cchemical shifts in the spectra of carbenium ions is an established method of structural analysis. Application to the problem of the norbornyl cation8’ indicates that this ion has a symmetrical structure. In contrast the cyclobutylcyclopropylcarbinylcation under- goesg8 a complex set of rearrangements; it has been argued89 that the 2-methyl-2- norbornyl cation has some non-classical character and again the 2-bicyclo[2.1.llhexyl cation” has non-classical character. All these results have been obtained by the powerful method of Saunders and they emphasize the need to recognize a continuum of carbenium ion behaviour ranging between classical ions through partially bridged structures that are characterized by unequal bonding to cases that are characterized by equal bonding in a symmetrical bridge. Radical Species.-Cyclopropyl radicals have been generated by the reaction of sodium naphthalene with cyclopropyl halides in tetrahydrofuran. The radicals that are generated can then undergo electron transfer to give cyclopropyl anions and hence products.It has now been established” that for both secondary and tertiary cyclopropyl radicals inversion is faster than the electron transfer. The unusual photolytic cleavage of a carbon-hydrogen bond in a hydrocarbon has been ob- in the photolysis of pentamethylcyclopentadiene to give (79 which was shown by e.s.r. spectroscopy to have D5hsymmetry. A series of cyclopentadienyl radicals have been generated93 by attack of t-butoxyl radicals on alkyl-substituted cyclopentadienyltrimethylstannanes;on the e.s.r. timescale the parent cyclopen- tadienyl radical also has DShsymmetry. Irradiation of (76) with X-rays leads to the formation of (77) in a matrix. On warming (77) is transformed into a new radical which it has been argued94 is (78).Under similar conditions the 7-norbor- nadienyl radical9’ rearranges to the tropylium radical. Jy I --a (75) (76) (77) (78) Carbanions.-A careful examination of 7-phenylnorborn-7-yl carbanions shows that the effective geometry of the carbanion depends on the counter-ion. Thus at -68 “C the lithium salt is pyramidal,96 with the major barrier to inversion being attributed to ionic dissociation. In contrast the potassium salt is effectively planar. S. W. Staley A. E. Howard M. D. Harmony S. N. Mathur M. Kattija-Ari J-I. Choe and G. Lind J. Am. Chem. SOC.,1980,102,3639. M. Saunders and M. R. Kates J. Am. Chem. SOC.,1980,102,6867. M. Saunders and H-U. Siehl J. Am. Chem. SOC.,1980,102,6868. a9 K. L. Servis and F-F. Shue J.Am. Chem. SOC.,1980,102,7233. L. R. Schmitz and T. S. Sorensen J. Am. Chem. SOC.,1980,102 1645. 91 G.Boche D. R. Schneider and H. Wintermayr J. Am. Chem. SOC.,1980,102 5697. 92 A. G.Davies and J. Lusztyk J. Chem. SOC., Chem. Commun. 1980 554. 93 M. Kira M. Watanabe and H. Sakurai J. Am. Chem. SOC.,1980,102,5202. D.Brandes F. Lange and R. Sustmann Tetrahedron Lett. 1980 21 261. ” D.Brandes F. Lange and R. Sustmann Tetrahedron Letf. 1980,21,265. 96 P. R.Peoples and J. B. Grutzner J. Am. Chem. SOC.,1980,102,4709. Alicyclic Chemistry Two related papers have established the existence of cu,a'-dianion~~~ and a-keto-dianion~~~ as intermediates. The former can be generated by treatment of a ketone with first potassium hydride (to give a monoanion) and then n-butyl-lithium and tetramethylenediamine.The latter can be prepared from a-bromo-ketones (Scheme 16). OLi -&L& ii& OLi Br Br Li Reagents i lithium hexamethyldisilazide; ii Bu'Li Scheme 16 '' J. S. Hubbard and T. M. Harris J. Am. Chem. SOC.,1980,102,2110. 9a C.J. Kowalski M. L. O'Dowd M. C. Burke and K. W. Fields J. Am. Chem. SOC.,1980,102,5411.

ISSN:0069-3030    

DOI:10.1039/OC9807700139

出版商:RSC    

年代:1980

数据来源: RSC

摘要:

10 Aromatic Chemistry By R. BOLTON Department of Chemistry Bedford College London NWI 4NS 1 General A second method for generating phenyl cation has been reported involving the spontaneous p -decay of 1,4-ditritiobenzene; the product then contains the label attached to C-4.l The synthesis of such labelled phenyl cations could also be brought about by the ring-closure method reported previously.' A novel 1,2-shift of a methyl group has been found in the reaction of (1)under the influence of base as shown in reaction ( l).3 a/ -& / ButOK,THF / / (1) 0 0 (1) Contributions towards a knowledge of the properties of aromatic compounds include a report of new binuclear lanthanide n.m.r. shift reagent^.^ Theoretical aspects of aromatic chemistry have been advanced by a general theory of chemical bonding5 as well as by theoretical approaches to the Birch reduction6 and to halogenobenzenium ions.' Reactivity-selectivity relationships in the reactions of benzyl derivatives have been discussed in terms of HOMO-LUMO interactions.* Changes in the nature of the transition state with changes in the nature of the nucleophile have been suggested from a study of the reactions of benzyl bromides,' and a paper on cation-anion interactions is appropriate in this context.lo Re-assessment of sub-stituent effects has expectedly occupied a number of workers; another extension of the Hammett equation has been announced" and perturbation theory has been applied to substituent effects providing descriptions of these in terms of changes G.Angelini M. Speranza A. L. Segre and L. J. Altman J. Org. Chem. 1980,453291. * M. Hanack and U. Michel Angew. Chem. Znt. Ed. Engl. 1979,18 870. B. Miller and A. K. Bhattacharya J. Am. Chem. SOC.,1980,102,2450. T. J. Wenzel T. C. Bettes J. E. Sadlowski and R. E. Sievers J. Am. Chem. SOC., 1980 102 5903. S. Fliszar J. Am. Chem. SOC.,1980 102 6946. A. J. Birch A. L. Hinde and L. Radom J. Am. Chem. SOC.,1980,102,3370. R. C. Binning jr. and K. M. Sando J. Am. Chem. SOC., 1980,102,2948. Y. Karton and A. Pross J. Chem. SOC.,Perkin Trans. 2 1980 250. V. P. Vitullo J. Grabowski and S. Sridharan J. Am. Chem. SOC.,1980,102 6463. lo C. D. Ritchie and T. C. Hofelich J. Am. Chem. SOC.,1980 102 7039. G. Weeks and V. Horak J. Org. Chem.1980,45,2068. 158 R. Bolton in the Coulombic integral. l2Other attempts to understand and quantify theoretically such substituent effects have used a parallel between benzyl anions and phenoxide or anilide anions,13 or have studied carbo-cation~,~~ or have sought to differentiate between field and inductive effects on the basis of their non-proportionality.ls The dual-parameter substituent constant already successfully applied to benzene chemistry,16 has been extended to the naphthalene system although the correspond- ing tests have not been made." In most cases the proliferation of parameters ensures a better fit between experimental and calculated figures although the physical significance of these new parameters (as opposed to their mathematical function) is sometimes hard to envisage.Such extensions of the Hammett equation have been regularly reported but few have reached general applicability. A parallel has been reported" between o1and the effects of substituents on the fifth overtone of the aryl C-H stretching vibration. 2 Non-benzenoid Systems Among the interesting systems reported this year the preparation of a dialkoxy- (aryl)bromane(III) (2) deserves mention (Scheme 1).l9 The BrlI1 derivative shows considerable stability towards water and other weak nucleophiles and has mild oxidizing properties. The preparations of other remarkable species include the dication ether salts A;OAi2' and the stable 4n7r-system (3)*l as well as cyclo-octa[deflfluorene. This last compound was obtained from cyclopenta[deflphenanthrene; it shows para- HO Br OH (2) Reagents i Br,.CCl,; ii OH-; iii Me,CO H'; iv 2 equivalents of Bu"Li; v (CF,),CO; vi H' H,O; vii HONO HBr Cu; viii BrF, (CH,Cl) Scheme 1 l2 R. Ponec Collect. Czech. Chem. Commun. 1980 45 1646. G. Kemister A. Pross L. Radom and R. W. Taft J. Org. Chem. 1980,45 1056. D. A. Forsyth and B. B. Sandel J. Org. Chem. 1980 45 2391. W. F. Reynolds J. Chem. SOC.,Perkin Trans. 2 1980,985. I6 M. Godfrey J. Chem. SOC., Perkin Trans. 2 1978 487. l7 M. Godfrey J. Chem. SOC., Perkin Trans. 2 1980 330. Y. Mizugai and M. Katayama J. Am. Chem. SOC.,1980,102,6424. l9 T. T. Nguyen and J. C. Martin J. Am. Chem. SOC.,1980,102 7382. P.J. Stang G. Maas and T. E. Fisk J. Am. Chem. SOC.,1980,102,6361.** A. G. Anastassiou and H. S. Kasmai Angew. Chem. Int. Ed. Engl. 1980 19,43. Aromatic Compounds 159 tropic anti-aromatic properties.’* Among unusually acidic hydrocarbons octa-fluorofluorene (see below) and 5H-perfluoro-l,2,3,4,5 -pentamethylcyclopen ta- diene (4) deserve mention. The trifluoromethyl groups in the latter compound raise the acidity of the remaining proton so that a pK value of -2 is ob~erved;’~ although inferior to the effect of five cyano-substituents the effect is nonetheless considerable. (3) (4) A new synthesis of annulenones has been described.24 In essence it combines two classical reactions for the aldol condensation of a terminal acetylenic aldehyde and a methyl ketone provides the unsaturated ketone the two ‘ends’ of which may then be linked by acetylenic oxidative coupling.Dimethylbisdehydro[ nlannulen- ones may thus be obtained where n is 15 17 19 or 21. Interest is now turning towards the properties of excited states in the annulene systems or towards the aromaticity of their anions. Thus studies of the excited states of methano-bridged [lo]- [14]- and [18]-ann~lenes~~ provided strong evidence of considerable transannular interactions while other studies have been made of the radical ions of 4,5,7,8-tetramethyl-[2.2]paracyclophane26“ and of [16lannulene dianion.266 The photoelectron spectrum of [8]paracyclophane (and those of the [6]-and [7]-analogues) suggested that the observed splitting arose from the electronic effect of methyl substituents rather than from the deformation of the ring.27 Among the contributions to azulene chemistry a shorter synthesis of the parent hydrocarbon (previously reported in a note28n) has now been described.286 The process may be used to incorporate hydrogen or carbon labels at specified positions in the system.While it has yet to be shown to be able to produce bulk quantities of azulene quickly and cheaply the main obstacle appears to be the need to follow the last stage of the reaction (see Scheme 2) by t.1.c. in order to avoid losses through the acid-catalysed decomposition of azulene. The method has however considerable ___+ _I_* [-H,OI a $cH2N2 \ [97%] \ [SO%] [30-50%] I / Scheme 2 22 I. Willner and M. Rabinovitz J. Org. Chem. 1980,45 1628.23 E. D.Laganis and D. M. Lemal J. Am. Chem. SOC.,1980,102,6633. 24 J. Ojima Y. Shiroishi K. Wada and F. Sondheimer J. Org. Chem. 1980,45 3564. 2s H. J. Dewey H. Deger W. Frohlich B. Dick K. A. Klingensmith G. Hohlneicher E. Vogel and J. Michl J. Am. Chem. Soc.. 1980,102,6412. 26 (a)J. Bruhin F. Gerson and H. Ohya-Nishiguchi J. Chem. SOC.,Perkin Trans. 2 1980 1045; (b)G.R. Stevenson and B. E. Forch J. Am. Chem. SOC.,1980,102 5985. ” R. Gleiter H. Hopf M. Eckert-Maksic and K.-L. Noble Chem. Ber. 1980 113 3401. 28 (a)L. T.Scott J. Chem. SOC.,Chem. Commun. 1973 882; (b) L. T.Scott M. A. Minton and M. A. Kirms J. Am. Chem. SOC.,1980,102 6311; (c) K. Hafner Angew. Chem. 1958,70 419. 160 R. Bolton advantages over the simple Ziegler-Hafner synthesis whose success relied upon the pyrolysis of an azulene precursor in benzidine and the concomitant distillation of the azulene in a stream of superheated steam.*" The carcinogenic hazard may be removed by the use of triethanolamine in place of benzidine but the difficulties of maintaining temperature flow of steam and regular addition of the azulene precursor remain.The synthesis of bis(perfluoroacy1)azulenes and their decomposition to give azulene-1,3-dicarboxylicacid have now been achieved.29 The observation of elec-trophilic trifluoroacetylation of azupyrene (5) has confirmed the conclusions about its aromatic character that were made from spectroscopic considerations and in the face of the 4rt~-system.~~ The synthesis of 6,6'-bis(azuleny1) has been achieved by the Ziegler-Hafner method using 4,4'-bipyridyl as starting material.The fact that each pyridine system in turn could be converted into the azulene system by this route reflects considerable improvements in the yields of individual steps of this sequence.31 The dimerization of (6) forms the dihydro-derivative (7) of some 6,12-diaryl-azuleno[1,2-b]azulenes;the parent may be obtained by oxidation with molecular bromine.32 Benz[a]indeno[ 1,2,3-cd]azulene (8) has been obtained by the photolysis of 1-X-triptycenes (X =OCOPh OPh or SMe).33 @(-Jc=c/Ar \H \/ (6) (5) (7) (8) In the cyclophane series the ready formation of a rn-xylylene system led to the formation of octamethyl[2.2]metacyclophane in 20% yield.34 The Dewar isomer of [4]metacyclophane has been and so has the quinhydrone correspond- ing to the [3.3]metacyclophane The polyphenylenicenes may be con- veniently included here; triphenylenicene (benz0[2.2]metacyclophane)~~ and penta- phenylenicene3* have been prepared along with an interesting series of systems 29 L.J. MathiasandC. G. Overberger,J. Org. Chem. 1980 45 1701. 30 A. G. Anderson jr. G. M. Masada and G. L. Kao J. Org. Chem. 1980,45 1312. 31 Ch. Jutz Synthesis 1980 31. 32 T. Toda N. Shimazaki T. Mukai and C. Kabuto Tetrahedron Lett. 1980 21 4001. 33 Y. Kawada H. Tukada and H. Iwarnura Tetrahedron Lett. 1980 21 181. 34 J. J. Gajewski M. J. Chang P. J. Stang andT. E. Fisk J. Am. Chem. Soc. 1980,102 2096. 35 L. A. M. Turkenburg J. W. van Straten W.H. de Wolf and F. Bickelhaupt J. Am. Chem. Soc. 1980,102,3256. 36 H. A. Staab C. P. Herz and A. Dohling Chem. Ber. 1980,113 233. 37 E. Hammerschmidt and F. Vogtle Chem. Ber. 1980,113 1125. E. Hammerschmidt and F. Vogtle Chem. Ber. 1980,113 3550. Aroma tic Compounds 161 such as anthra~enophane.~~ Among the chemistry of cyclophanes may be included their susceptibility to Diels-Alder reagents4’ and the formation of the significant chromium complex (712-[3.3]paracyclophane)chromium(~).41The extension of these synthetic methods culminated in the synthesis of a [2]catenane containing a 2 2 -membered heterocyclic 3 Electrophilic Reactions The process has been reviewed.43 Electrophilic attack upon benzocyclopropenes demonstrates an alternative mechanism involving attack upon a u-bond.The limitations and extent of such a mechanism deserve further definiti~n.~~ Some theoretical discussions upon the electrophilic attack by protons upon the cyclopro- penium ions also deserve mention.45 The electrophilic nature of the hydroxyl radical has again been determined by studying the distribution of products arising from the attack of Cerfontain and his workers have continued their careful studies of the mechanism of s~lphonation.~’-~~ The complicated behaviour of sulphonation involving sulphur trioxide resuits partly because of changes in the nature of the rate-determining step with changes of the solvent and also from the intervention of a number of competing processes which are reflected by changes in the nature of the reaction products.The anthracene derivatives used in the most recent work are also vulner- able to coupling reactions in strongly acidic media; such polymeric species were detected in the course of the sulphonation and were major products when anthracene pyrene naphthacene or 9,lO-dimethylanthracene were treated with aluminium(II1) chloride (loo/,) in liquid antimony(II1) chloride at 100-130 0C.55 The carbonium ion which was formed by proton attachment was held to be formed through a disproportionation reaction which may be represented by reaction (2) 6ArH + 4SbCl3 + 4(ArH.H)’ + 4C1-+ $Sb + [Ar( -H)]z (2) In this way anthracene gave anthra[2,l-~]aceanthrylene;pyrene gave 1,l’-bipyrenyl and dinaphtho[2,1,8a,8,7-defg;2’,1’,8a’,8’,7‘-ijkI]pentapheneby sub-sequent ring-closure between positions 10 and 10‘of the biaryl.39 R. Wingen and F. Vogtle Chem. Ber. 1980 113 676. 40 A. F. Murad J. Kleinschroth and H. Hopf Angew. Chem. In[. Ed. Engl. 1980 19 389; A. F. S. Murad and H. Hopf Chem. Ber. 1980,113,2358;but compare the synthesis by Diels-Alder processes described by P. G. Gassman T. F. Bailey and R. C. Hoye J. Org. Chem. 1980 45 2923. 41 R. Benn N. E. Blank M. W. Haenel J. Klein A. R. Koray K. Weidenhammer and M. L. Ziegler Angew. Chem. Znt. Ed. Engl. 1980,19 44. 42 G. Schill G. Doerjer E. Logemann and W. Vetter Chem. Ber. 1980 113 3698. 43 F. Effenberger Angew. Chem. Znt. Ed. Engl. 1980,19 151. 44 L. K. Bee P. J. Garratt and M. M. Mansuri J. Am. Chem. SOC.,1980 102,7076. 45 T.Clark and R. Weiss J. Org. Chem. 1980 45 1790. 46 N. V. RaghavanandS. Steenken J. Am. Chem. SOC.,1980,102 3495. 47 F. van de Griendt and H. Cerfontain J. Chem. SOC.,Perkin Trans. 2 1980 13. 48 F. van de Griendt and H. Cerfontain J. Chem. SOC.,Perkin Trans. 2 1980 19. 49 F. van de Griendt and H. Cerfontain J. Chem. SOC.,Perkin Trans. 2 1980 23. 50 K. Lammertsma and H. Cerfontain J. Chem. SOC.,Perkin Trans. 2 1980 28. 51 R. Brogman and H. Cerfontain J. Chem. SOC.,Perkin Trans. 2 1980 33. 52 A. Koeberg-Telder F. van de Griendt and H. Cerfontain J. Chem. Soc. Perkin Trans. 2 1980 356. ” F. van de Griendt and H. Cerfontain J. Chem. SOC.,Perkin Trans. 2 1980 904. 54 F. van de Griendt C. P. Visser and H. Cerfontain J. Chem. Suc. Perkin Trans. 2 1980 911.” A. C. Buchanan 111 A. S. Dworkin and G. P. Smith J. Am. Gem. Suc. 1980,102 5262. 162 R. Bolton The sulphodeacylation of dimesityl ketone received kinetic In 89.8% (w/w) sulphuric acid the reaction could be analysed in terms of two competing processes. The first fission of the diary1 ketone provides both mesitylene and mesitoic acid (2,4,6-trimethylbenzoic acid) whose subsequent acid-catalysed decarboxyla- tion occurs readily under these conditions; 2,4,6-trimethylbenzenesulphonicacid then arises from attack upon thk arene that is provided by these two routes. It would be interesting to detect the direct sulphodecarboxylation of mesitoic acid; the recent work was interpreted in terms of protiodecarboxylation followed by rapid sulphonation but the rates of cleavage of the reported mesityl ketones suggest that analogous cleavage of the acid might not occur too slowly to be significant.Acylation by CH3CO+ has been studied in the gas phase and has important differences from the corresponding liquid-phase pro~ess.~’ The extended study of the acylation of hydrocarbons by Gore and his workers now includes studies upon triphenylene and chrysene in which the semi-quantitative work of earlier chemists has been refined to quite remarkable limits;58 as with the earlier work upon the acylation of naphthalene and 1-chloronaphthalene the identification of quite small amounts of isomers in admixture is reported. Competition studies have been applied to the reaction of dimethylketen with arenes in the presence of aluminium(II1) chloride.’’ Quite different values for the Hammett slope (p’) were proposed depending upon whether the substituents were more ( pf = -0.92) or less (p+ = -6.6) electron-donating than hydrogen.Similar behaviour was reported to occur with diphenylketen; however the conclusions are open to the criticisms that all competition reactions are prone to as well as to the specific reservation of the paucity of the number of points comprising the first part of the plot. Mercuriation by mercury(I1) trifluoroacetate in trifluoroacetic acid has also received careful and systematic study. The results were interpreted in terms of a rapidly formed T-complex (showing only a slight hydrogen-isotope effect in its formation) followed by a slow substitution process that is characterized by a substan- tial kinetic hydrogen-isotope effect.The complexity of the reaction however operates against a full understanding of the system even under such conditions.60 In studies of exchange of hydrogen isotopes Taylor and his workers have made two significant contributions. The first involves the effect of the orientation of the substrate upon reactivity and deals with measures of hydrogen isotope exchange in polyphenylene systems where either crown or helical orientation can be found and where the interconversion of the systems is not a complication under the reaction conditions.61 The second dealt with the effect of the cyclopropyl substituent on rates of aromatic detritiation; a series of careful measurements have quantified the effect of the group and set it in the context of the behaviour of the more conventional alkyl systems.The possibility of slight hydrogen-bonding behaviour 56 J. A. Farooqi P. H. Gore E. F. Sadd D. N. Waters and G. F. Moxon J. Chem. SOC.,Perkin Trans. 2 1980 835. 57 M. Speranza and C. Sparapani J. Am. Chem. Soc. 1980,102,3120. ’* P. H. Gore F. S. Kamounah and A. Y. Miri J. Chem. Res. 1980 (S) 40 (M) 0530. 59 K. R. Fountain P. Heinze D. Maddex G. Gerhardt and P. John Can. J. Chem. 1980,58,1939. ‘’C. W. Fung M. Khorramdel-Vahed R. J. Ranson and R. M. G. Roberts J. Chem. Soc. Perkin Trans. 2 1980 267. 61 M. M. Hirschler and R. Taylor I. Chem. SOC.,Chem. Commun. 1980,967. Aromatic Compounds 163 of the three-membered ring was deduced.62 Ridd and his c011eagues~~ have made a study of N-H hydrogen isotope exchange in protonated NN-dimethylaniline systems.An interesting contrast is found in the modes of reaction of the N-deuterio- NN-dimethylanilinium ion (9)and of N-deuterio-NN-dimethyl-3,5-xylidinium ion (10). The first compound undergoes hydrogen exchange at a rate which decreases regularly as the acidity of the solvent increases; the second shows the same behaviour to levels of about 84% sulphuric acid but then shows an acceleration in the rate of exchange. This was understood to show a change of mechanism in which exchange was now occurring between the solvent and hydrogen atoms attached to sites ortho- and para- to the nitrogen atom. Substituent effects were the same suggesting a common step in which these aromatic sites undergo proton attack; the resulting Wheland intermediate may lose hydrogen however either from carbon or from nitrogen.The catalysis of this exchange of hydrogen isotopes by nitrosonium ions which depends upon the concentration of NO' and whose rate is inversely propor- tional to the acidity of the medium (H!) was explained in terms of a loose complex between NO' and the anilinium ion with consequent loss of a proton from nitrogen. DkMe DAMe, I I (9) (10) Nitration continues to show new and unexpected facets. Helsby and Ridd64 have shown that the adducts arising from ipso-attack during the nitration of aromatic amines such as N,Nf,2,4,6-pentamethylaniline may be isolated with care as the hexafluorophosphate.Fischer and his colleagues6' have studied particularly the products of ipso-nitration of some para-substituted toluenes while the rearrange- ment of some such adducts has been shown not to involve only acid catalysis;66 light also causes the formation of aromatic products (Scheme 3).67 A new mechanism of reaction could be indicated by the observation6' that the nitration of phenols is catalysed by lower oxides of nitrogen although the diastereoisomeric ethyl ethers Mfiy (70 :30 ratio) Ac hvy hv CsH, p-xylene Y Me NO Scheme 3 62 P. Fischer and R. Taylor J. Chem. SOC.,Perkin Trans. 2 1980 781. 63 (a)J. R. Blackborow D. P. Clifford I. M. Hollinshead T. A. Modro J. H. Ridd and M. C. Worley J. Chem. Soc. Perkin Trans.2 1980,632;(6) D.J. Mills and J. H. Ridd ibid.,p. 637. 64 P.Helsby and J. H. Ridd J. Chem. SOC.,Chem. Commun. 1980 926. " A.Fischer D. L. Fyles and G. N. Henderson J. Chem. SOC., Chem. Commun. 1980,513. 66 A.Fischer and J. N. Ramsey Can. J. Chem. 1974,52 3960. 67 H. Shosenji K. Esaki and K. Yamada. Tetrahedron Lett. 1980 21 91. 68 D.S.Ross G. P. Hum and W. G. Blucher J. Chem. Soc. Chem. Commun. 1980 532. 164 R. Bolton observation itself is still consistent with the classical concept of nitration through prior nitrosation. Olah6’ has demonstrated the formation and properties of two new species i.e. N-nitropyridinium ion and N-nitroquinolinium ion from the reaction of nitronium salts with the appropriate heterocyclic base. These salts then behave as sources of modified nitronium ion giving both the orientation and as a generalization the rates of attack expected from such species.Differences in the rates of reaction arising from substitution in the pyridinium system have been ascribed among other factors to changes in the N-N resonance interaction and consequent alterations in the strength of the bond being broken during reaction. Measurements of ‘thermodynamic nitration rates’ have been rep~rted.~’ The first paper deals with the nitration of benzene and some derivatives in aqueous sulphuric or perchloric acids and interprets the results in terms of a function M, whose parallel with some of the terms in the Hammett acidity function and allied param- eters reflects its origins.The intention is to derive appropriate rate constants after allowance has been made for activity-coefficient effects; the need for this new function is not in the Reporter’s opinion conclusive. The various attempts to reflect the influence of proton-donors upon the observed rates of acid-catalysed reactions have had only limited success (e.g. see ref. 71) possibly because of the need to link equilibrium positions for protonation with kinetic properties of reacting systems and the most successful of these may owe its efficacy to its emphasis upon the comparison of the effects of acids upon two reacting systems under kinetic condition^.^^ The formation of 3-bromo-4-methylpheno1 by the bromination of p-cresol in HF-SbF mixtures73 may be consistent with deactivation of the hydroxyl function in such media but n.m.r.evidence substantiates the arg~ment’~ that ipso-attack occurs and that the orientation which is observed arises from an acid-catalysed rearrangement of an intermediate dienone. Considerable interactions across large distances seem to occur in the bromination of 9-substituted hexahydro-1,4- methanobiphenylenes (ll) where the change to a 9-methoxyl substituent increases the rate by a factor of 3 x lo5 over that found for the 9-keto-cornpo~nd.~~ 9 4 Nucleophilic Aromatic Substitution Meisenheimer Complexes.-The formation of such complexes has been reported in the 1:1 interaction of sodium methoxide with picramide a number of N-substituted picramides and NN-dimethylpicramide in methanol,76 of potassium 69 G.A. Olah S. C. Narang J. A. Olah R. L. Pearson and C. A. Cupas J. Am. Chem. SOC.,1980 102,3507. 70 N. C. Marziano P. G. Traverso and G. G. Cimino J. Chem. Soc. Perkin Trans. 1 1980 574. 71 M. A. Paul and F. A. Long Chem. Rev. 1957,57 1,935. 72 J. F. Bunnett and F. Olsen J. Chem. SOC., Chem. Commun. 1965,601; Can,J. Chem. 1966,441897. 73 J. P. Jacquesy M.-P. Jouannetoud and S. Makani J. Chem. SOC., Chem. Commun. 1980 110. 74 J. M. Brittain P. B. D. de la Mare and P. A. Newman Tetrahedron Lett. 1980,21,4111. 75 M. N. Paddon-Row B. V. Lap H. K. Patney and R. N. Warrener Aust. J. Chem. 1980 33 1493. 76 M. R. Crampton and B. Gibson J. Chem. Soc. Perkin Trans. 2 1980,752. Aromatic Compounds t-butoxide with 2,4,6-trinitrotoluene in t-butyl and of methoxide ion with NN-dimethylpicramide in mixtures of dimethyl sulphoxide and methanol7' and with N-methylpicramide in the same mixture when loss of protons competes with the formation of u-complexe~.~~ When cyanide ion or isopropoxide ion attack 4-nitrobenzofuroxan (12) attack first takes place at C-7 to give (13);" however concurrent attack at both C-5 and C-7is detected with methoxide ion in methanol and the kinetics of formation of these two complexes have been determined.'l Formation of spiro-complexes might be expected with suitably substituted picryl derivatives and thus NN'-dimethyl-N'-picrylethylenediamine(14) gives the system (15) with triethylamine in aprotic solvents such as dimethylformamide or dimethyl sulphoxide; rearrangement then occurs with the displacement of a nitro-group.82 O2N MeN J 0 H (14) Even the dianion of 3-carboxy-4-nitrobenzenesulphenicacid is reported to form a stable Meisenheimer complex in 15.3M-potassium hydroxide solution.83 The reduction of halogeno-nitro- and -polynitro-benzenes with sodium boro- hydride in dimethyl sulphoxide leads in some cases to the formation of hydride Meisenheimer complexes which although unstable may be observed by 'H n.m.r.rneasurement~.~~ The rate of decomposition of a number of complexes between 1,3,5-trinitrobenzene and aliphatic monoketones in the presence of triethylamine when brought about by acid (pH 1 to 6) shows no simple dependence upon the structure of the ketone.85 It seems that under the experimental conditions the Janowski reaction does not take place.A remarkably stable Meisenheimer complex has been reported from the reaction of 2-phenylbenzopyrylium ions (flavylium ions) and hydrogen sulphite anion.86 In contrast all attempts to obtain a Meisenheimer complex from the interaction of triethylamine or diethylamine with 1,5-dimethyl-2,4,8-trinitronaphthalenein dimethyl sulphoxide-methanol mixtures failed because of the preferential formation of the benzyl ~arbanion,'~ a complication which attended the corresponding process with methoxide ion." After a detailed study of the possible contributions of elec- tron transfer and proton transfer in determining the products of reaction of 77 A. R. Norris Can.J. Chem. 1980 58 2178. E. Buncel M. Hamaguchi and A. R. Norris Can. J. Chem. 1980 58 1609. 79 E. Buncel M. Hamaguchi and A. R. Norris Can. J. Chem. 1980,58,1615. M. E. Moir and A. R. Norris Can. J. Chem. 1980 58 1691. F. Terrier H. A. Sorkhabi F. Millot J. C. Halle and R. Schaal Can. J. Chem. 1980 58 1155. E. Buncel M. Hamaguchi and A. R. Norris J. Chem. SOC., Perkin Trans. 2 1980 2205. 83 R. L. Blakeley and B. Zerner J. Am. Chem. SOC., 1980,102,6586. 84 V. Gold A. Y. Miri and S. R. Robinson J. Chem. SOC.,Perkin Trans. 2 1980,243. R. A. Renfrow M. J. Strauss and F. Terrier J. Org. Chem. 1980,45,471. 86 R. Brouillard and J.-M. el H. Chahine J. Am. Chem. SOC.,1980 102 5375. 87 E. Buckley J. E. Everard and C. H. J. Wells J. Chem. SOC.,Perkin Trans.2 1980 132. 88 S. R. Robinson B. C. Webb and C. H. J. Wells J. Chem. SOC., Perkin Trans. 2 1976 273. 166 R. Bolton p-nitrotoluene with bases the intervention of three anionic species i.e. p-nitrotoluene anion p-nitrotoluene radical anion and the p,p'-dinitrobibenzyl radical anion was deduced. The relative proportions of each depended upon the reaction conditions; mechanisms were produced to explain these SNArand SRNlProcesses.-In the latest of a series of studies seeking to test the applicability of the additivity principle to substituent effects upon the rate of reaction of picryl chloride with aniline good agreement was found with groups meta to the ieaction sitego whereas para-substituted anilines showed much poorer agreement." Miller and Morang2 have reported rates of methanolysis of both picryl chloride and of picryl methyl ether; the product in both cases is picric acid since the ether is unstable to the reaction conditions.Among other reports involving similar systems the formation of products of displacement by nucleophiles from 1,5-dichloroan- thraquinone deserves mention,93 as does the unexpected loss of a nitro-group when p-cresol is caused to react with N-methyl-4-nitrophthalimide (Scheme 4).94 A xo NMe+ 6 ooa:~e i hydrolysis I + / + products O2N / / Me / 0 Me 0 Reagents i K,CO, Me2S0 at 142"C Scheme 4 side-reaction of 3,5-dichloro-2-nitroanisolewith aniline provides both preferential displacement of chlorine that is ortho to the nitro-group (presumably from hydro- gen-bonding as with the orientation of attack of pentafluoronitrobenzene by amines) and hydrolysis of the methoxyl function although in only 6.5% yield (Scheme 5).95 Me0 0N02 xPhNH2 PhNH29at18O0C+ c:o:()2 for 3 h / NHPh C1 / NHPh CI 0n02 Scheme 5 Zoratti and Bunr~ett~~ have identified two mechanisms by which the hydroxy- dehalogenation of p-iodo p -bromo- or p-chloro-toluene may occur in aqueous hydroxide at temperatures as high as 333 "C.In the absence of catalytic quantities of metal ions the same mixture of rn-and p-cresol results from all three substrates suggesting that there are benzyne intermediates whose selectivity towards nucleophiles is the subject of a second paper.97 In the presence of copper ions but not of iron nickel manganese or cadmium a non-aryne type of displacement 89 E.Buncel and B. C. Menon J. Am. Chem. SOC.,1980,102,3499. 90 T.A.Ernokpae 0.Eguavoen and J. Hirst J. Chem. SOC.,Perkin Trans. 2 1980 829. 91 T.A. Emokpae 0.Eguavoen K.-U.-Rahman and J. Hirst J. Chem. SOC.,Perkin Trans. 2 1980,832. 92 J. Miller and P. J. S. Moran J. Chem. Res. 1980,(S)62,(M) 0501. 93 E. H.Ruediger M. L. Kaldas S. S. Gandhi C. Fedryna and M. S. Gibson J. Org. Chem. 1980 45 1974. 94 H. M.Relles D. S. Johnson and B. A. Dellacoletta J. Org. Chem. 1980,45,1374. 95 W.Ried and G. Sell Chem. Ber. 1980,113,2311. 96 M. Zoratti and J. F. Bunnett J. Org. Chem 1980,45 1769. 97 M. Zoratti and J. F. Bunnett J. Org. Chem. 1980 45 1776. Aromatic Compounds 167 occurred in which hydroxydehalogenation gave isomerically pure p -cresol.The function of the copper is still open to discussion; organometallic derivatives were considered though the metal might be acting as a specific solvent of incipient halide ions. The mechanism has presented yet another unusual aspect. Following the observation of unusual kinetic form,98 Bunnett and his school have detected a major effect that has been ascribed to the leaving group and which operates after it has left. The origin of such an effect is the free-radical character of the reaction and the reaction conditions. In a system where electrons are derived by the solution of potassium metal in liquid ammonia an electron gradient can be imagined to be set up between the surface of the metal and the molecules of the attacking aryl halide.Under normal mixing conditions this gradient may well vary in slope owing to changes in the local concentrations of the reacting species. Like a number of free-radical processes the implications are of a diff usion-controlled process in which not only the nature of the aryl halide but also its situation vis-a-vis other possible reagents is supremely important in determining its fate.99"00 The SRNl mechanism has also been used preparatively"' to provide a route to benzofurans. 5 Diazonium Ions The effect of complexation upon the rates of decomposition of aryldiazonium ions has been measured in 1,2-dichloroethane where the greatest stabilization was found with a 2 1-membered macrocyclic polyether system.lo2 A similar technique was used to measure the extent of ion-pairing between ArN2' and its gegen40n.l'~ The degree of association between various diazonium ions and 18-crown-6 has been measured by the calorimetric titration method;lo4 a comparison between results obtained using the two techniques would be a valuable extension.The 4-morpholinobenzenediazonium ion has undergone X-ray crystallographic analy- sis; the distortion of the ring that was found was explained in terms of non-quinonoidal perturbations and it was correlated with SCF cal~ulations.'~~ The reactions of anti-arylazo methyl ethers in methanol which involve ionization are catalysed by acids; the rates of a number of such reactions have been reported and they provide evidence of general acid catalysis.'06 Carbonylation occurs when aryldiazonium tetrafluoroborates are treated with carbon monoxide under slight pressure and in the presence of a palladium(0) catalyst as well as sodium acetate.Mixed anhydrides presumably formed by trapping the acylium ion by acetate anion are thought to be intermediates; the uptake of carbon monoxide has formal equivalence with the exchange of nitrogen with the aryl cation.'" 98 R. G. Scamehorn and J. F. Bunnett J. Org. Chem. 1979,44,2604. 99 R. R. Bard J. F. Bunnett X.Creary and M. J. Tremelling J. Am. Chem. Soc. 1980 102 2652. loo M. J. Tremelling and J. F. Bunnett J. Am. Chem. SOC.,1980 102 7375. 101 R. Beugelmans and H. Ginsburg J. Chem. SOC.,Chem. Commun. 1980 508. lo' R.A. Bartsch and P. N. Juri J. Org. Chem. 1980,45 1011. lo3 P. N. Juri and R. A. Bartsch J. Org. Chem. 1980 45 2028. R. M. Izatt J. D. Lamb C. S. Swain J. J. Christensen and B. L. Haymore J. Am. Chem. SOC.,1980 102,3032. lo' N. W. Alcock T. J. Greenhough D. M. Hirst T. J. Kemp and D. R. Payne J. Chem. SOC.,Perkin Trans.2 1980 8. lo6 T. H. Broxton and A. C. Stray J. Org. Chem. 1980 45 2409. lo' K. Nagira K. Kikukawa F. Wada andT. Matsuda J. Org. Chem. 1980 45 2365. 168 R.Bolton 6 Preparative Aspects Benzene Derivatives.-Elemental fluorination using dilute solutions of the halogen in nitrogen at -78 "C provides monosubstitution products by a process which seems to be electrophilic in character.'08 The preparative fluorination of benzene (61% yield) and of nitrobenzene benzonitrile benzoic acid and acetophenone can be brought about by using silver@) fluoride in n-hexane.The major initial product from benzene is 3,6-difluorocyclohexa-1,4-diene(16),arising from cis-addition across the ring the substitution product presumably arises by thermal decomposi- tion of (16).'09 Little selectivity is observed and all positions are attacked with similar ease in the cases cited. (16) (17) The synthesis of a number of alkyl and benzyl fluorides has been brought about by an application of the susceptibility of pyrylium ions to nucleophilic attack. N-Substituted 2,4,6-triphenylpyridiniumfluorides (17) arising from the reaction of the appropriate primary amine with 2,4,6-triphenylpyrylium fluoride undergo thermal decomposition to provide the appropriate aliphatic fluoride.The quaternary ammonium salt could be obtained in 72-86% yield and in all but one case the yield of benzyl fluoride was in the region of 65% .'lo Direct cyanation of arenes has been reported previously,"' but a recent communi- cation lists conditions in which the substitution is brought about in a plasma that arises from the discharge of a r.f. generator operating at 13.56 MHz. Benzene was found to give benzonitrile in 94%yield (64% based on cyanogen; 45% conversion) with small quantities of the dicyanobenzenes being formed. The process seemed to be only slightly selective; all sites in some monosubstituted benzenes including the ipso-position were attacked with similar facility.In this the process appears to be even less selective in orientation than conventional free-radical substitu- tions. l2 Photoreduction of chlorobenzene chloro-naphthalenes and chloro-biphenyls may be brought about in alkanes. The mechanism is thought to involve homolysis in the triplet state when the energy of this excited state is comparable with that of the C-C1 bond attacked. 113~1 l4 Trifluoromethanesulphonic acid ('triflic acid') has been reported to be an efficient catalyst in the Houben-Hoesch reaction bringing about the ready formation of acylation products from the reaction of nitriles with phenols or phenolic In contrast much of the reactivity of methyl and ethyl triflates under Friedel-Crafts conditions appears to depend upon this acid; the pure esters are rather weak alkylating agents.'16 lo* F.Cacace P. Giacomello and A. R. Wolf J. Am. Chem. Soc. 1980,102,3511. Io9 A. Zweig R. G. Fischer and J. E. Lancaster J. Org. Chem. 1980 45 3597. A. R. Katritzky A. Chermprapai and R. C. Patel J. Chem. Soc. Perkin Trans. 1 1980 2901. 'I1 E. Havinga and J. Cornelius Chem. Reu. 1975,75 353. Y.-H. So and L. L. Miller J. Am. Chem. Soc. 1980,102,7119. N. J. Bunce J. P. Bergsma W. De Graaf Y. Kumar and L. Ravanal J. Org. Chem. 1980,102,3798. K. H. Eichin H.-D. Beckhaus and C. Ruchardt Tetrahedron Lett. 1980,21 269. B. L. Booth and G. F. M. Noori J. Chem. SOC.,Perkin Trans. 1 1980,2894. B. L. Booth R. N. Haszeldine and K. Laali J. Chem. Soc. Perkin Trans. 1 1980 2887. Aromatic Compounds Studies of the alkylation of phenols have been extended through consideration of the conditions needed for cyclization of species such as (18)'17 and by a report of the use of magnesium derivatives to promote high specificity of attack to sites that are ortho to the phenolic group during such cyclizations."* The mechanisms deduced from the experimental evidence are not uniquely demanded by these facts and the complexity of behaviour of a@ -unsaturated ketones during addition reactions may be found to be operating in this instance as well.Metal complexes may also act in a recently reported preparation of salicylaldehydes by the attack of formaldehyde upon phenols in the presence of tin(1v) chloride and a tertiary amine such as tri-n-octylamine. '19 The yields (under favourable conditions) recom- mend this process over most alternatives.(18) (19) A much wider use of metallation is found in the reaction of an excess of n-butyl-lithium with benzyl alcohols in the presence of NNN'N'-tetramethylethyl-enediamine in pentane. The resulting lithium (0-lithio-ary1)methoxides(19) may react with electrophiles including alkylating agents and carbonyl compounds to provide a wide range of ortho-substituted benzyl alcohols.120 The 'anomalous' reactions of benzyl Grignard reagents as exemplified in reaction (3) (which represents the earliest evidence121) have been re-investigated under conditions in which an intermediate (20) can be obtained. This species decomposes to give both the hydrocarbon (21) and the product (22) (Scheme 6).lZ1 PhCH2MgX + HCHO + o-MeC6H4CH20H (3) The preparation of ortho- substituted benzoic acids has been reported using diphenyliodonium-2-carboxylate (23) and specifically copper(I1) as a necessary CH Reagents i HCHO; ii MgCl (22) Scheme 6 '17 W.S. Murphy and S. Wattanasin J. Chem. Soc. Perkin Trans. 1 1980 1555. "IW. S. Murphy and S. Wattanasin J. Chem. Soc. Perkin Trans. I 1980 1567. G. Casiraghi G. Casnati G. Puglia G. Sartori and G. Terenghi J. Chem. SOC.,Perkin Trans. 1 1980,1862. N. Meyer and D. Seebach Chem. Ber. 1980,113,1304. "' C. Bernardon and A. Deberly J. Chem. SOC.,Perkin Trans. 1 1980 2631; cf. M. Tiffeneau and R. Delange C. R. Hebd. Seances Acad. Sci. 1903,137 573 (J. Chem. SOC., 1904 A.i.48). 170 R. Bolton catalyst.The mechanism of the reaction is thought to differ from that found with copper(1) catalysts with a greater specificity in the displacement. Although such a reaction is limited to the insertion of groups through nucleophilic attack it offers a route to a number of anthranilic acid derivatives and hence to the wealth of chemistry that these provide.'22 (23) The preparation of o -alkyl-nitrobenzenes (0-RC6H,N02)through the interaction of nitrobenzene and an excess of Grignard reagent continues to arouse interest. The reaction itself is old but the preparative use of the process relies upon the reali~ation'~~ that oxidation of the reaction mixture with potassium permanganate is necessary if one is to maximize the yield of nitro-arene. Similarly the details have been published of short optimized syntheses by which derivatives of p-resorcylic acid may be prepared by conventional classical A novel synthesis of benzyl ethers and one which may prove to have mechanistic interest involves the sequential treatment of an alcohol with chloro(phenylmethy1- ene)dimethylammonium chloride and sodium hydrogen telluride.The process was applied to the synthesis of 3p-benzyloxycholest-5-ene,but the authors point out that the mild and non-basic conditions (within the limits imposed by HTe-) allow the method to be applied to carbohydrate hemi is try.'^^ Derivatives of 2-aminobenzhydrol may be obtained readily in good yield (70%) and under mild conditions by the attack of benzaldehyde derivatives upon sub- stituted anilines in the presence of phenyldichloroborane and triethylamine as shown in reaction (4).126 Two variants on the classical bromodediazoniation reaction [reaction (5)] have been proposed.In the first,12' the use of tin(I1) or ascorbic acid to reduce copper(I1) in situ has been claimed to improve the yield of aryl bromides that are formed by the Sandmeyer reaction. In the second,'28 two methods for introducing bromine into an aromatic system are combined. Copper(I1) bromide and chloride have been to introduce the appropriate halogen into highly activated systems such as anthracene and the combination of molecular bromine and copper(I1) bromide ''' R. A. Scherrer and H. R. Beatty J. Org. Chem. 1980 45 2127. 123 G. Bartoli M. Bosco and G.Baccolini J. Org. Chem. 1980,45 522. A. G. M. Barrett T. M. Morris and D. H. R. Barton J. Chem. SOC.,Perkin Trans. I 1980 2272. lZ5 A. G. M. Barrett R. W. Read and D. H. R. Barton J. Chem. SOC.,Perkin Trans. 1 1980 2184. 126 T. Toyoda K. Sasakura and T. Sugasawa Tetrahedron Lett. 1980,21 173. lZ7 C. Galli Tetrahedron Lett. 1980,21 4515. M. P. Doyle M. A. van Lente R. Mowat and W. F. Fobare J. Org. Chem. 1980 45 2570. lZ9 W. C. Alcorn F. M. Cromarty J. Flood J. M. Mancilla A. D. Mosnaim D. C. Nonhebel and I. Scullion J. Chem. Res. (S) 1980 102. Aromatic Compounds brings about multiple bromination of aromatic amines at sites that are ortho and para to the nitrogen atom. If this reaction is carried out in a solvent such as carbon tetrachloride then the subsequent addition of t-butyl nitrite to a solution that contains hydrogen bromide allows the amino-group to be replaced by bromine in a formal bromodeamination step.Oxidative bromination and partial demethylation occur when NN-dimethylaniline is subjected to these reaction conditions; when the alkyl nitrite is added nitration products are formed perhaps through a free- radical process. HONO CuBr,HBr ArNH2 +ArNiBr-ArBr (5) Two uses of peroxy-acids are important. The reaction of alkyl-benzenes with trifluoroperoxyacetic acid is reported to give only aliphatic carboxylic acids by ring-opening; no aromatic carboxylic acids arising from oxidation of the side-chain are found.130 The degradation of 'susceptible' aromatic rings such as those contain- ing hydroxyl functions has been long used to prepare such ring-fission products as in the synthesis of benzene derivatives by the oxidation of 2-naphthol but the apparently specific breakdown of an aromatic ring that is without such vulnerable sites is new.The second application of peroxy-acids is in the formation of aromatic nitro-groups by oxidation of amino-systems. Again the method is not new; for example the synthesis of 2,6-dichloronitrobenzeneinvolves such a process.'31 The novelty arises from the use of Caro's acid as a solution of hydrogen peroxide in concentrated sulphuric acid or of the equally powerful peroxytrifluoromethanesul-phonic acid. With such reagents the oxidation of polynitro-aniline derivatives has been achieved in some cases for the first time.I3* p-Diacyl-benzenes are also not readily available.However they may be prepared by the oxidation of their dihydro-derivatives which are formed by the displacement of trimethylsilyl groups from the addition products that are formed in the reaction of trimethylsilyl chloride with either benzene or p-xylene (Scheme 7).133 H. 'SiMe H COR' COR2 Reagents i Me,SiCl; ii R'COCI; iii 0 Scheme 7 Arene-metal complexes have recently featured in a number of synthetic pro- cesses. Thus the treatment of 3-[(2-bromoaryl)amino]cyclohex-2-en-1-ones (24) with a catalytic quantity of a Pd" species brings about intramolecular cyclization to give 1,2-dihydrocarbazol-4(3H)-onesvia aryl-palladium complexe~,'~~ as shown R. Liotta and W. S. Hoff J.Org. Chem. 1980,45 2887. 13' A. S. Pagano and W. D. Emmons Org. Synth. Coll. Vol V (1973) 367 (Wiley New York). 132 A. T. Nielsen R. L. Atkins W. P. Norris C. L. Coon and M. E. Sitzmann J. Org. Chem. 1980,45 2341. M. Laguerre J. Dunogues and R. Calas Tetrahedron Lett. 1980 21 831. 134 H. Iida Y. Yuasa and C. Kibayashi J. Org. Chem. 1980 45 2400. 172 R. Bolton 0 0 N AR1Q-bR' R' / N R' X R2 X R2 (24) Reagents i [Pd(OAc),(PPh,),] NaHCO, DMF Scheme 8 in Scheme 8. Arene-metal complexes are also highly activated towards nucleophilic attack whether at the ring or at a suitable site in the side-chain and the ease with which the carbon-metal bond may subsequently be broken allows groups such as -Cr(C0)3 to act as removable activating groups bringing about processes which would otherwise be difficult.Thus a synthesis of acorenone and of acorenone B has as its first stage the attack of a cyanhydrin acetal anion upon o-methylanisole that is complexed to chromium; the effect is the nucleophilic displacement of hydrogen by ultimately an acyl group (Scheme 9).13' Similarly activation of CN i/ iii-vi f--Meq 0 I CN Reagents i [Cr(CO),l; ii Li OAOA ;iii LiNR,; iv CF,SO,H; v NH3 H,O; vi H' H,O Scheme 9 styrene-like double-bonds may be achieved. 136 A preparation of 3-methoxyphthalic anhydride which is required in the synthesis of hydroxy-polyannular systems for work on carcinogenicity has been rep~rted.'~' It relies upon a Diels-Alder process [reaction (6)] with the advantage of an improved yield and minimal losses of the sort that occur in a more conventional route because of the appreciable solubility of the acid and its precursors in water.M. F. Semmelhack and A. Yamashita J. Am. Chem. SOC.,1980,102 5924. 136 M. F. Semmelhack W. Seufert and L. Keller J. Am. Chem. SOC.,1980 102,6584. 13' M. S. Newman and K.Kanakarajan J. Org Chem. 1980,45 3523. Aromatic Compounds OMe OMe qo2Et+ 0 Oc0."' 173 15O-20O0C+ [-C,H,;86%1 /C0,Et C02Et Polybenzenoid Systems.-Oxidative coupling of benzene derivatives that contain electron-withdrawing groups or those which only slightly withdraw electrons (but not -NO2 or -COX) is brought about by thallium(II1) trifluoroacetate in trifluoroacetic acid or in carbon tetrachloride or in acetonitrile that contains boron trifluoride etherate.The process seems to involve aryl cations from heterolysis of the thalliation product; these attack a second molecule of arene to give an intermedi- ate whose oxidation is achieved by Tl"'.'38 Unsymmetrical biaryls are formed when species such as (P-RC~H~)P~(OAC)~ decompose in arenes in the presence of trifluoroacetic acid.139 The reaction is speeded by aluminium(II1) salts but no rearrangement occurs even when alkyl groups are present. The substitution appears to have electrophilic requirements but does not involve the free carbo-cation p-RC,H,'; it has been suggested14' that the slow stage of the reaction involves the formation of a .rr-complex between the reagent and the arene without the fission of the C-Pb bond.Derivatives of naphthalene and of biphenyl can be obtained by the reaction of NN-dimethylformamide dimethyl acetal with 1-aryl-3-alkyl- or -aryl-propan-2- ones. Thus 1,3-diphenylpropanone gives NN-dimethyl-3-phenylnaphthalene-l-carboxamide (25) (Scheme 10) on heating with the acetal in an autoclave. Similarly CONMe Me,NCH(OMek za Z\ / /Ph (25) a; Z = H b; Z = CF3 c;z = c1 Scheme 10 1-(m-trifluoromethylphenyl)-3-phenylpropanonegives only (25b) but 1-(m -chlorophenyl)-3-phenylpropanone gives not only (2%) and the 5-chloro-isomer but also NN-dimethyl-3-(m-chlorophenyl)naphthalene-l-carboxamide. The pro- posed mechanism was justified by experiments using 13C labelling.'41*'42 A key step in the synthesis of 3,4-dihydro-2( 1H)-fluorenones and hence of the gibberellin ~keleton,'~~ rests upon the Birch reduction (using Li and NH3) of 2,5-dimethoxyben- zoic acid and the subsequent alkylation of the dianion by benzyl halide in situ.Fluorenone-1 -carboxylic acid (26) has been found to bring about transamination of amino-acids (as o-formylbenzoic acid but it has the two advantages 13' A. McKillop A. G. Turrell D. W. Young and E. C. Taylor J. Am. Chem. Soc. 1980 102,6504. 139 H. C.Bell J. R. Kalman J. T. Pinhey and S. Sternhell Tetrahedron Lett. 1974 857. H. C.Bell J. R. Kalrnan G. L. May J. T. Pinhey and S. Sternhell Aust. J. Chem. 1979 32 1531. 14' R.F.Abdulla T. L. Ernrnick and H. M. Taylor Synth. Commun. 1977,7 305;R.F.Abdulla K. H. Fuhr and H.M. Taylor ibid. 1977,7 313. 14' R.F. Abdulla K. H. Fuhr R. P. Gajewski R. G. Suhr H. M. Taylor and P. L. Unger J. Org. Chem. 1980,45,1724. 143 J. M. Hook and L. N. Mander J. Org. Chem. 1980,45 1722. 144 C.A. Panetta and A. L. Miller J. Org. Chem. 1978.43 2113. 174 R. Bolton (i) that its synthesis is easy and and (ii) that primary aliphatic amines also undergo transamination with the new reagent. The mechanism of the process however probably differs fundamentally from that achieved under enzyme con- ditions. 146 Anthracene precursors have been made by Diels-Alder addition of benzyne to diene systems such as furans and carbazoles. Initially14' the bis-aryne which is the formal intermediate was generated by the decomposition of organometallic com- pounds in which fluorine was adjacent to the metal and was expelled with it; conditions have now been reported where the much more readily obtained tetra- bromides (27b) are used su~cessfully.'~~ The greater availability of these starting materials now makes this synthetic route more attractive.Me (27) a;Z = F b;Z = Br Carcinogenic Hydrocarbons.-The mechanism of carcinogenic action of hydrocar- bons has attracted interest; the reactivity towards chemicals is compared to that as a mutagen. Access to the great collection of Professor E. Clar has allowed a wide range of hydrocarbons to be studied in an attempt to parallel the reactivity towards maleic anhydride with either theoretical measures of reactivity or with carcinogenic activity.149 Another set of investigation^,'^^ also dedicated towards comparison between theory and experiment took the hydrogenation of such poly- benzenoid systems as their type reaction.In both cases acceptable parallels were found. The application of partial hydrogenation of multi-ring aromatic systems has already been reported as a potent means of directing orientation of attack towards unusual sites; the synthesis of derivatives of dibenz[a,h]anthracene which were held to be the ultimate metabolites (for a review see ref. 151)of this hydrocarbon was achieved by first preparing 1,4,7,8,11,14-hexahydrodibenz[a,h]anthraceneby reduction with lithium in liquid amm~nia."~ Specifically labelled systems show the course of metabolism of such hydrocarbons.The synthesis of deuterium-labelled derivatives of 7,12-dimethylbenz[a]anthracene(28) has been brought about by the 14' 14' Me (28) 145 L. F. Fieser and A. M. Seligman J. Am. Chem. SOC., 1935 57,2174. 146 C. A.Panetta and A. S. Dixit J. Org. Chem. 1980,45,4503. G. Wittig and H. Harle Liebigs Ann. Chem. 1959 623 17. H. Hart C. Lai G. Nwokogu S. Shamouilian A. Teuerstein and C. Zlotogorski J. Am. Chem. SOC. 1980,102,6649. 149 D. Bierman and W. Schmidt J. Am. Chem. Suc. 1980,102,3163. P. P.Fu H. M. Lee and R. G. Harvey J. Org. Chem. 1980 45 2797. 15' D. E.Hathway and G. Kolar Chem. SOC.Reu. 1980 9,241. Is* H.M.Lee and R. G. Harvey J. Org. Chem. 1980,45,588. Aromatic Compounds hydrogenolysis of the appropriate bromo-arene.However although complete incor- poration of deuterium could be brought about by lithium aluminium deuteride when halogen in the side-chain was displaced the corresponding displacement of bromine from ring positions did not give 100°/~ labelling with deuterium unless both the reagent and the water that was used to quench the reaction were fully labelled.” The synthesis of 8-and of 1l-methoxy-7,12-dimethylbenz[a]anthracenesled to the preparation of the corresponding hydroxy-derivatives; the starting materials however were obtained by the reduction of the diols that were formed by organometallic attack upon the corresponding 7,12-dione. In this process it was noticed that the reducing agent seemed to be an organotin species when tin(I1) and hydrochloric acid were used and not a free carbo-cati~n.’~~ The reductive methyl- ation of polycyclic quinones a process that is used extensively in the synthetic chemistry of Fieser (e.g.see ref. 155) and of Newrnanls4 has been re-introduced as a route to obtaining polymethyl-polybenzenoidsystems. Organolithium com- pounds have replaced the Grignard reagents with an attendant increase in the observed yields and a diminished sensitivity to steric effects.ls6 The preparation of 8- and of l0-fluoro-3-methylcholanthrenesby the Elbs reaction has been repor- ted,lS7 together with the observation that the process fails to provide the 11-and 12-fluoro-analogues. The somewhat uneven success which has attended the use of this reaction to prepare the corresponding methoxy-derivatives suggests that its application is limited; no reasons are immediately available.The one-pot synthesis of polycyclic aromatic quinones reported by Manning in 1977 has been improved by using photochemical and not thermal conditions for the addition of quinones to the 1,l-diaryl-ethylenes. A range of polybenzenoid systems are therefore avail- able in principle and the subsequent use of photochemical annelation with iodine present to oxidize the initially formed dihydro-arene generates even larger systems. Thus 5-(2-naphthyl)benzo[b]chrysene-9,14-dione(29) itself generated by the reaction of 2-bromo-3-methoxy-l,4-naphthoquinoneand 1-(l-naphthyl)-l-(2-naphthyl)ethylene provides the quinone (30) which on reduction gives dinaphtho[l,2-c :2,3-e]pyrene (Scheme 11).lS8Kaupp and his co-workers have undertaken further studies into the diene-addition reactions of anthra~ene’~~”~~ and 9-phenylanthra~ene’~~ and of dibenz[a,c]- and dibenz[~,h]-anthracene,’~~ which are processes of some synthetic importance.The chemistry of 1,g-diphenylanthracene including an improved synthesis of the parent hydrocarbon has been described.16* Considerable differences in the steric environments of the 9-and 10-positions are reflected in the considerable differences in their chemistry. Thus reduction of 1,8-diphenylanthraquinonegives 153 S. R. Adapa Y. M. Sheikh R. W. Hart and D. T. Witiak J. Org. Chem. 1980 45 3343. M. S. Newman and K. Kanakarajan J. Org. Chem. 1980,45,2301. ”’ R. B. Sandin and L.F. Fieser J. Am. Chem. SOC.,1940,62 3098. lS6 M.Konieczny and R. G. Harvey J. Org. Chem. 1980,45 1308. lS7 M.S.Newman and V. K. Khanna J. Org. Chem. 1980,454507. 15’ K.Maruyama T. Otsuki and K. Mitsui J. Org. Chem. 1980,45,1424;W. B. Manning J. E. Tornaszewski G. M. Mushik and R. I. Sato ibid. 1977 42 3465. lS9 G. Kaupp and H.-W. Griiter Chem. Ber. 1980,113 1458. G. Kaupp and E. Teufel Chem. Ber. 1980 113 3669. G.Kaupp and H.-W. Gruter Chem. Ber. 1980,113 1626. H.0.House N. I. Ghali J. L. Haack and D. Van Derveer J. Org. Chem. 1980,45 1807. 176 R. Bolton I + + mBr \ ' 0 'OMe ZCH2 0 / Reagents i hv;ii I, hv; iii LiAlH Scheme 11 only the 9-anthrone in which the carbonyl group is flanked by the two aryl systems and only some organometallic reagents were able to react with this shielded ketone function.An addition reaction between 10-diazoanthrone or 4-diazonaphthalene- 1(4H)-one and benzyne or 1,2-naphthyne gives indazole derivatives which upon thermo- lysis provide hydroxy-derivatives of considerably complex systems such as fluoran- thene benz[a]aceanthrylene and naphth[2,1 -~]aceanthrylene.~~~ The synthesis and determination of the absolute stereochemistries of (+)-and (-)-benzo[a]pyrene 7,8-oxides have been achieved starting from the separated diastereoisomers of frans-8-bromo-7-(menthyloxy)acetoxy-7,8,9,lO-tetrahydro-benz[a]pyrene; the (+)-isomer of this bromo-ester was shown by X-ray analysis to have the absolute stereochemistry (7S,8S) and this in turn correlates the stereochemistry of a number of mammalian metab01ites.l~~ Quinones have been used as routes to a number of systems.Thus hydroquinone monomethyl ethers or substituted benzofurans may be formed in a Michael reaction involving either diethyl malonate or ethyl a~etoacetate;'~~ allylation of quinones by allyltin species in the presence of Lewis acids such as BF3 is a synthetically useful (72-'78O/0 yield) route to various vitamin and coenzyme struc- tures.166 K. Hirakawa T. Toki K. Yamazaki and S. Nakazawa J. Chem. SOC.,Perkin Trans. 1 1980 1944. 164 D.R.Boyd G. S. Gadaginamath A. Kher J. F. Malone H. Yagi and D. M. Jerina J. Chem. SOC. Perkin Trans. 1 1980 2112. 165 K.A. Parker and S.-K.Kang J. Org. Chem. 1980,45 1218. 166 Y. Naruta J. Am.Chem. SOC.,1980,102,3774. Aroma tic Compounds The electrophilic substitution reactions of 4H-cyclopenta[deflphenanthrenehave been studied further ;167 more modern analytical techniques have shown acylation to be a more complex process than the earlier reports suggested.168 The correspond- ing 8,g-dione (31) has also been studied; many of its reactions are predictable by analogy with fluorene on the one hand or with phenanthraquinone on the The possible ring-contraction reaction to give the dibenzopentalene structures does not seem to have been attempted. (31) The ozonolysis of 1,2-dichloroacenaphthylenegives two stable ozone adducts whose chemistry has not yet been fully studied. These results when the identity of the adducts are fully known may be important to the mechanism of ozoniz- ation.17' Photochemical Processes.-Photochemical reactions of benzene with furanl'l and with 1,2- 1,3- and 1,4-dienes have been reported,17* and a review of photochemical rearrangements has appeared.173 The photo-induced decomposition of peroxyacetic acid in xylenes has demonstrated an orientational preference in the attack by hydroxyl radicals which show the electrophilic properties previously found (e.g.see ref. 46) but the orientation of attack of xylenes by methyl radicals appears to be determined by the wavelength of the light that causes photolysis of the peroxy- As light of higher energy causes a preference for rnetu-alkylation the facts are reminiscent of the competition between thermodynamic and kinetic control in the heterolytic alkylation mechanism and may admit of a similar explanation.The photochemical reactions of pyridine and of 2-fluoropyridine with aliphatic amines include nucleophilic displacement in the case of the fluoropyridine but unusual compounds are formed with triethylamine including not only the dealkyla- tion product but also a second species whose identity has been discussed in terms of previously proposed mechanisms. 17' Photoresponsive crown ethers have been studied using the cis-trans isomerization of azobenzene as the test process.176 Sensitized fluorescence of 9,lO-dibromoanthracene has been the subject of some kinetic M. Yoshida K. Hishida M. Minabe and K. Suzuki J. Org. Chem. 1980,45,1783. 16' W. E. Bachman and J.C. Sheehan J. Am. Chem. SOC.,1941,63,2598. 169 M. Yoshida A. Kadokura M. Minabe and K. Suzuki Bull. Chem. SOC.Jpn. 1980,53 1179. 170 H. Seltzer S. Gab and F. Korte Angew. Chem. Int. Ed. Engl. 1980.19,474. 171 J. C. Berridge A. Gilbert and G. N. Taylor J. Chem. SOC.,Perkin Trans. 1 1980 2174. 172 J. C.Berridge J. Forrester B. E. Foulger and A. Gilbert J. Chem. SOC.,Perkin Trans. 1 1980 2425. 173 G. Kaupp Angew. Chem. Int. Ed. Engl. 1980,19,243. 174 Y. Ogata and K. Tomizawa J. Org. Chem. 1980,45,785. '" A.Gilbert and S. Krestonosich J. Chem. SOC.,Perkin Trans. 1 1980 2531. 176 S.Shinkai T. Nakaji Y. Nishida T. Ogawa and 0.Manabe J. Am. Chem. SOC.,1980,102,5860. 177 T.Wilson and A. M. Halpern J. Am. Chem. SOC.,1980,102,7272,7279. 178 R.Bolton Polyhalogeno-aromatic Chemistry.-The cycloaddition reactions of polyfluoro- derivatives of Dewarthiophen and pyrroles have been re~0rted.I~~ Decafluoro-fluoranthene is reported to be formed along with the more expected of its nucleo- philic reactions;179 a similar study has been made of the reactions of heptafluoro- 2-naphthyl-lithi~m.'~' Kinetic measurements of the nucleophilic attack of polyfluoro-arenes have been continued,181 and they have somewhat extended the previous reports of the series. Some of the most impressive chemistry of the octafluorofluorene system is attributable to the effect of the fluorine substituents which stabilize the fluorene anion and its analogues considerably.'** Polychloro-aromatic chemistry is represented by some carefully described work on the coupling reactions by which copper brings about the formation of biar~1s.I~~ Y.Kobayashi A. Ando K. Kawada A. Ohsawa and I. Kumadaki J. Org. Chem. 1980 45 2962; Y. Kobayashi A. Ando K. Kawada and I. Kumadaki ibid. pp. 2966,2968. J. Burdon H. S. Gill I. W. Parsons and J. C. Tatlow J. Chem. Soc. Perkin Trans. 1 1980 1726. J. Burdon H. S. Gill and I. W. Parsons J. Chem. Soc. Perkin Trans. 1 1980 2494. R. D. Chambers D. Close and D. L. H. Williams J. Chem. Soc. Perkin Trans.2 1980,778. R. Filler A. E. Fiebig and M. Y. Pelister J. Org. Chem. 1980,45 1290. A. G. Mack H. Suschitzky and B. J. Wakefield J. Chem. SOC.,Perkin Trans. 1 1980 1682.

ISSN:0069-3030    

DOI:10.1039/OC9807700157

出版商:RSC    

年代:1980

数据来源: RSC

摘要:

11 Heterocyclic Compounds By T. M. CRESP Department of Chemistry University College London 20 Gordon Street London WClH OAJ 1 Three-Membered Rings Photolysis of the azimine (1) gives the triaziridine (2) which is the first authentic triaziridine to be isolated.' On standing (2) slowly (tllz= 3.5 days) reverts to azimines. Oxygen-oxygen bond homolysis followed by @-scission is the normal photochemical fate of ozonides. The reaction has been used to prepare some very y (1) unstable aziridinediones (Scheme 1).2 They were characterized by examination of their infrared spectra recorded at 77 K and of their decomposition to carbon monoxide and isocyanates on warming. On reaction with alkynyl-lithium reagents aziridones undergo ring-opening followed by ring-closure (Scheme 2) to provide a novel synthesis of pyrrolinones (4).The a-bromo-amide precursors of the aziridones R = H Me Pri or CH2CH2Ph Reagents i hv at 77K Scheme 1 0 Br Reagents i LiCzCR3; ii H,O Scheme 2 ' C. Leuenberger L. Hoesch and A. S. Dreiding J. Chem. Soc. Chem. Commun. 1980 1197. 'H. Aoyama M. Sakamoto and Y. Omote J. Am. Chem. SOC.,1980,102,6902. 179 180 T. M. Cresp afford the same products presumably but not necessarily through the intermediacy of (3).3This represents a useful synthesis of those pyrrolinones that do not tautomer- ize to pyrroles. A number of preliminary reports have been brought together in a full paper4 describing the chemistry of thiiranimines. They are readily prepared from sulphonyl isocyanates and diphenyldiazomethane the reaction involving 1,3-dipolar cyclo- addition to yield 1,2,3-thiadiazoliniminesfollowed by decomposition to the thiiran- imines (5).Ring-opening reactions are dominated by cleavage of the unusually long C(2)-S bond (1.94A).The two other ring-forming bonds are shorter than the sum of the covalent radii a situation also encountered in aziridinimines.’ In solution thiiranimines (5) rearrange to benzothiophens (7) with methanol ring- opening gives thioxosulphonamides (6). Reviews covering this chemistry and the chemistry of other heterocyclic analogues of methylenecyclopropanes6*7make fascinating reading. S \ S0,Ar (5) (7) Oxidation of the (E)-oxime carbamate (8) in a Neber-type reaction gives the 1-azirine (9).’ The corresponding (2)-isomer (lo) under the same conditions fails to yield (9);instead the monosulphoxide (11)is isolated (Scheme 3).The observed stereospecificity would seem to militate against nitrene formation at least for this qSMe MeHNfjsMe But Bu‘ S0,Me SMe (9) (8) NHMe But Bu‘ SMe S0,Me (10) (11) Reagents i KMnO Scheme 3 E. R. Talaty A. R. Clague M. 0. Agho M. N. Deshpande P. M. Courtney D. H. Burger and E. F. Roberts J. Chem. SOC.,Chem. Commun. 1980,889. G. L’abbC J.-P. Dekerk C. Martens and S. Toppet J. Org. Chem. 1980,45,4366. * H. Quast P. Schefer K.Peters and H. G. von Schering Chem. Ber. 1980,113 1921. G. L’abbC Angew. Chem. Int. Ed. Engl. 1980,19,276. ’H. Quast Heterocycles 1980 14 1677.H. G. Corkins L. Storace and E. Osgood J. Org. Chem. 1980,45,3156. Heterocyclic Compounds Neber reaction. Products from the reaction of amino-azirines (12) and ketens proceed via the intermediacy of the much-studied zwitterion (13) (see Annu. Rep. Prog. Chem. Sect. B 1979 76 224) which usually undergoes ring-cleavage to (14).9Irradiation of 3-(2-thienyl)-2,2-dimethyl-2H-azirine (15)generates the nitrile isopropylide (16) which adds to activated carbon-carbon and carbon-oxygen double-bonds to give 1-pyrrolines and 3-oxazolines respectively. lo A brief review on azirines concentrates on their conversion into other heterocyclic systems. l1 NMe K' A- n I (13) (14) R4 (15) (16) N-Heteroaryl vinylaziridines undergo thermal isomerization to azepines; for example the aziridine (17) isomerizes to (20) in refluxing xylene.l* The correspond- ing N-isothiazolo- and N-thieno-aziridines (18) and (19)also rearrange to azepines at room temperature.Electrochemical oxidation of tertiary amines usually gives iminium salts; however N-benzylaziridine affords the known tetramer (2 1)from a chain process that is initiated by formation of a radical cation.13 As would be expected oxa,aza-bis- (22) and dioxa,aza-tris-u-homobenzenes(24) undergo [2 + 2 + 21-cycloreversions to (23) and (25) respectively. l4 Cyclic polyepoxides are the subject of a concise review" that is a pleasure to read. Ar (17) Ar= GN ; (18)Ar= (19) Ar= PhJ 6 S (21) E. Schaumann S. Grabley M. Henriet L. Ghosez R.Touillaux J.-P. Declercq G. Germain and M. Van Meerssche J. Org. Chem. 1980,45,2951. lo K.-H. Pfoertner and R. Zell Helv. Chim. Acta 1980,63,645. A. Hassner Heterocycles 1980 14 1517. H. P. Figeys and R. Jammar Tetrahedron Lett. 1980,21 2995. l3 R. Kossai J. Simonet and G. Dauphin Tetrahedron Lett. 1980,21,3575. H. Prinzbach K.-H. Muller C. Kaiser and D. Hunkler Tetrahedron Lett. 1980,21 3475. Is W.Adam and M. Balci Tetrahedron 1980,36,833. 182 T.M. Cresp 2 Four-Membered Rings General.-Pyrolysis of the tosylhydrazone (26) gives oxeten.I6 It can be hydro- genated to oxetan and it smoothly rearranges in solution to form acrolein. Base- induced cyclization of the 3-methoxy-selenoxides derived from the vinyl selenide (27) gives oxetans." Carboxamides (28) which have been postulated as intermedi- ates in the photochemical ring-contraction of succinimides to azetidine-2,4-diones (see Annu.Rep. Prog. Chem. Sect. B 1979 76 225) also yield azetidinediones (29) on irradiation.'* A full account of the preparation and reactions1' of the related 4-thioxo-2-azetidinones has appeared. Oxidation of the (2)-oxime (30) with m-chloroperbenzoic acid gives the oxazete (3 1)in high yield. The correspond- ing (E)-oxime (32) fails to cyclize under the same conditions and the sulphoxide (33) is isolated.20 The fate of the carbamates derived from these oximes has also been examined (see previous Section). 0 'qYHo Li\/N=QI phseq~ R2 N\ R1%Me R2 N OH Me 0 0 Ts/ (26) (27) (28) (29) N ,OH HO\ BulssMe Bu'IqSMe Bu' %R N-0 SMe SMe SMe (30) (31) (32) R=SMe (33) R=S02Me In a careful study,21 the two oxa-azabicyclo[2.2.0]hexanones (34) and (35) have been identified as intermediates in the photochemical equilibrium between oxazinones (36) and (37).It has been suggested that the zwitterion (38) is the common intermediate. The dimer derived from the sulphine oxide (40) (the lachrymator in onions) is not (39) but the much more interesting 1,2-dithietan 1,l-dioxide (41).22 This first example of an isolable 1,2-dithietan derivative arises from a dimerization in which (40) acts both as a 1,3-dipole and as a dipolarophile. R2mO -0"N 9 R2?JJC N yo Me R' (34) R' = Ph R2 =Me (36) R' = Ph R2= Me (38) (35) R' =Me R2 = Ph (37) R' = Me R2= Ph l6 P.C. Martino and P. B. Shevlin J. Am. Chem. Soc. 1980,102,5429. M. Shimizu and I. Kuwajima J. Org. Chem. 1980 45 4063. K. Maruyama T. Ishitoku and Y. Kubo Chem. Lett. 1980,265. l9 M. D. Bachi 0.Goldberg A. Gross and J. Vaya J. Org. Chem. 1980 45 1477 1481. 2o H. G. Corkins L. Storace and E. R. Osgood Tetrahedron Lett. 1980 21,2025. *' P. de Mayo A. C. Weedon and R. W. Zabel J. Chem. Soc. Chem. Commun. 1980,881. 22 E. Block A. A. Bazzi and L. K. Revelle J. Am. Chem. Soc. 1980,102 2490. Heterocyclic Compounds 183 0-0 Et H Et Et 0-Et’ H (39) (40) (41) (42) Peroxidase-catalysed oxygenative decarboxylation of 3-indolylacetic acid gives electronically excited indole-3-carboxaldehyde,suggesting the intermediacy of the a-peroxy-lactone (42).A report23 on the ingenious but futile attempts to prepare dioxetans related to (42) makes heart-rending reading. p-Lactams.-The Merck Sharp and Dohme group has used carbene insertion as the key step in a synthesis of the carba-2-penem system (Scheme 4).24 The a0 i_ q0 I;I zoqs4NHco2R 0 CO2CH2Ph O N2 H C02CH2Ph C02CH ,Ph Reagents i [Rh,(OAc),]; ii Ts,O; iii HSCH,CH,NHCO,R PriNEt Scheme 4 1 C0,H CO,H (43) (44) efficacy of this methodology has been elegantly demonstrated by the synthesis of of (*)-thienamycin starting from diethyl acetone-l,3-dicarbo~ylate,~~ (+)-thienamycin (43) from L-aspartic acid,26 and of (-)-homothienamycin (44).” Full details of the group’s earlier synthesis of (*)-thienamycin which relies on formation of the C(2)-C(3) bond by displacement of a bromide by malonate anion (Scheme 3,have appeared.28 pSMe 2 SMe OA 0 PhCH,02C CO2CH2Ph PhCH202C CO,CH,Ph Reagents i Br,; ii NaH DMF Scheme 5 23 W.Adam and K. Takayama J. Org. Chem. 1980 45,447. 24 R. W.Ratcliffe T. N. Salzmann and B. G. Christensen Tetrahedron Lett. 1980 21 31. 25 D. G.Melillo I Shinkai T. Liu K. Ryan and M. Sletzinger Tetrahedron Lett. 1980 21 2783. 26 T. N. Salzmann R. W. Ratcliffe B. G. Christensen and F. A. Bouffard J. Am. Chem. Soc. 1980 102,6161. 27 T. N. Salzmann R. W. Ratcliffe and B. G. Christensen Tetrahedron Lett. 1980,21 1193. 28 F. A. Bouffard D..B. R. Johnston and B. G. Christensen J. Org. Chem. 1980 45 1130; S. M. Schmitt D.B. R. Johnston and B. G. Christensen ibid. pp. 1135,1142. 184 T. M. Cresp The other 'classical' route involving C(2)-C(3) bond formation by intramolecular Wittig reaction has been developed into a versatile synthesis of thienamycin analogues (45)2g as well as of analogues of the antibiotic MM13902 (46).30 Isoxazoline (48) formed from a 1,3-dipolar cycloaddition between the nitrile oxide (47) and methyl crotonate has been converted into the thienamycin precursor (49).31 Conversion of (49) into thienamycin was achieved32 by utilizing the carbene- insertion method. The promised details (see Annu. Rep. Prug. Chem. Sect. B 1979 76 227) of the synthesis of authentic 2-(alky1thio)penems (51) have been delivered twice.33 Wittig-type reaction between the phosphorane and trithiocarbonate ester of the lactam (50)was used to form the C(2)-C(3) bond.OS0,Na NHCOMe mR'= flR1 M e w S4 0 )cPPh 0 C02R2 N/ R2O2C' (45) 0 C0,Na (46) CH(OMe) 0,COPNB I MemoLe 04J-N (49) C0,PNB (50) PNB =p-nitrobenzyl The 1,l-dimethyl-1-carbapenem(53) has been prepared by an intramolecular aldol condensation taking advantage of the non-enolizable aldehyde (52).34 The cost of synthetic convenience was lack of biological activity in the product. The reaction of the unsaturated sulphoxide (54) with the Vilsmeier reagent gives via a vinylogous Pummerer rearrangement the C(2)-vinylchloro-cephem (55). The product (55) is the starting material for the synthesis of a number of novel p-lac tarn^.^^ Pyrolysis of sulphoxides to give sulphenic acids provides the basis for the conversion of simple p-lactams (56) into penam sulphoxides (57).36 Unlike penicillanic sulphone the isomeric isopenam sulphone (59) is not an inhibitor of p-la~tamase.~~ The penems (60) prepared from methyl (5R)-penicillate S-oxide 29 L.Cama and B. G. Christensen Tetrahedron Lett. 1980 21 2013. 30 A. J. G. Baxter R. J. Ponsford and R. Southgate J. Chem. SOC.,Chem. Commun. 1980,429. 31 T. Kametani S.-P. Huang S. Yokohama Y. Suzuki and M. Ihara J. Am. Chem. SOC.,1980,102,2060. 32 T. Kametani S.-P. Huang T. Nagahara and M. Ihara Heterocycles 1980,14 1305. 33 M. Lang K..Prasad J. Gosteli and R. B. Woodward Helu. Chim. Acta 1980 63 1093; S. Oida A. Yoshida T. Hayashi N. Takeda T. Nishimura and E.Ohki J. Antibiot. 1980 33 107. 34 M. Shibuya and S. Kubota Tetrahedron Lett. 1980,21,4009. 35 D. 0.Spry Tetrahedron Lett. 1980 21 1289 1293. 36 A. C. Kaura C. D. Maycock and R. J. Stoodley J. Chem. SOC., Chem. Commun. 1980,34. 37 C. M. Pant and R. J. Stoodley J. Chem. SOC.,Chem. Commun. 1980,928. 185 Heterocyclic Compounds 0 MeCONH 0qcHo C02CH2Ph C02R (53) (54) 0 PhH,CCONH R' H \I 0 R2 R2 (56) (57) R1=NHCOCHZPh R2 =H (58) R' = H R2 =C02Me 0 PhH,CONH 0 0 xx02r C02H (59) PhH,CCONH H ON^. yCOzH 0H>OMe C0,Bu' C02H C02Bu' (62) (63) (64) (58),38have pronounced biological activity. Attempted ring-closure from (61) by carbene insertion under identical conditions to those used to generate the carba- penem failed to give any of the desired 2-0x0-dinorpenicillate.Ring- closure from (62) by formation of an s-C(2) bond was more rewarding providing an entry into the 2-methoxypenem system (63).39The 1-oxa-2-oxocephalosporins (64),40designed in an attempt to enhance the reactivity of the @-lactam ring towards cleavage share an absence of significant antibacterial activity with the 2-oxocephalosporins (see Annu. Rep. Prog. Chern. Sect. B 1979,76,228). Oxidation of the tricarbonyliron-lactam complex (65) is an interesting and unusual route into the @-lactam ring sy~tern.~' Hydrogenolysis of @-lactams provides a facile entry into dipeptide~.~' 38 M. Foglio G. Franceschi C. Scarafile and F. Arcamone J. Chem. SOC.,Chem. Commun. 1980 70. 39 J.Marchand-Brynaert L. Ghosez and E. Cossement Tetrahedron Lett. 1980,21,3085. 40 M. Aratani D. Hagiwara H. Takeno, K. Hernrni and M. Hashimoto J. Org. Chem. 1980,45 3682. 41 G. D. Annis E. M. Hebblethwaite andS. V. Ley J. Chem. SOC.,Chem. Commun. 1980 297. 42 I. Ojima S. Suga and R. Abe. Tetrahedron Lett. 1980,21 3907. 186 T.M. Cresp 3 Five-Membered Rings 2,5-Bis(trimethylsiloxy)furan (66) can be readily prepared from succinimide and has been to be a useful synthetic intermediate in a number of reactions. The use of nitro-olefins in the formation of the furan ring has been refined and used in the preparation of a number of furan~terpenoids.~~ The 'one-pot' synthesis (66) (67) of 2,4,5-trisubstituted furans (67)from ketones and ethyl 3,4-dibromo-2-butenoate is a useful addition to a well-tried theme.45 A short efficient synthesis of cantharidin (68) (Spanish fly) emphasizes the importance of high-pressure Diels-Alder reactions where furan is the diene (Scheme 6).46 Q+s*L&-$ A&$$ 0 0 S (68) Reagents i 15 kbar; ii Raney nickel Scheme 6 Benzo[c]furans generated from acetals (69)47or benzalphthalans (70);' continue to provide a source of polycyclic aromatics.The trisepoxyhexaradialene (7 1)49 represents the third member in that series to be prepared and it will enable comparisons to be made with the nitrogen (72) and sulphur (73) analogues. A review of benzo[c]furans covers the literature to mid 197tL50 Tetrahydrofurans have become respectable synthetic targets because of their presence in many naturally occurring ionophores.Permanganate-promoted oxida- tive cyclization of 1,5-dienes'* and photochemical cyclization of P-allyloxy-CHAr XG X R (71) X=O (70) (72) X = NCHzPh (73) x=s 43 P. Brownbridge and T.-H. Chan Tetrahedron Lett. 1980 21 3423,3427,3431. 44 M. Miyashita T. Kumazawa and A. Yoshikoshi J. Org. Chem. 1980,45 2945. 45 L. Moubarak and R. Vessiere Synthesis 1980 52. 46 W. G. Dauben C. R. Kessel and K. H. Takemura J. Am. Chem. SOC.,1980,102,6893. 4'7 B. A. Keay D. K. W. Lee and R. Rodrigo Tetrahedron Lett. 2980 21 3663; K. Naito and B. Rickborn J. Org. Chem. 1980,45,4061. 48 J. G. Smith S. S. Welankiwar B. S. Shantz E. H. Lai and N. G. Chu J. Org. Chem. 1980,45 1817. 49 M. B.Stringer and D. Wege Tetrahedron Lett. 1980,21,3831. " W. Friedrichsen Ado. Heterocycl. Chem. 1980 26 135. 51 D. M. Walba and P. D. Edwards Tetrahedron Lett. 1980 21 3531. HeterocyclicCompounds ketoness2 represent two interesting approaches that exhibit sufficient stereochemical control to warrant further attention. In the total synthesis of lasalocid A (74)s3 the tetrahydrofuran ring is obtained by reduction of a sugar-derived y-lactone while the tetrahydrofuran rings necessary for the total synthesis of monemsin (75)s4 arise from 1,4-diols. CO,H HOH,C-H HO (75) A synthesis of pyrroles from a-diketones takes advantage of the ready amination of (r-allyl)palladium(o) complexes (Scheme 7).” N-Alkylation of pyrroles with potassium t-but~xide’~ or potassium hydroxides7 in the presence of 18-crown-6 may offer some advantages over previous methods when C-alkylation is a problem.R2 R2 I Ph Reagents i AMgBr; ii Ac,O; iii PhCH2NH2 [Pd(Ph,P),I Scheme 7 The NN’-dipyrrolylmethane (77) that results from N-alkylation using the alternative method of employing dipolar aprotic solvents to solvate the counter-ion has been converted5* (Scheme 8) into the stable aromatic anion (78) which is an analogue of the fluorene anion. The second step in the alkylation to produce (77) may proceed through the interesting azoniafulvene (76). (NN-Dimethylamino)pyridine,better known as a superior catalyst for 0-acetylation and silylation also appears to offer advantages when used for the N-acetylation of pyrroles and in dole^.^^ Full details 52 H.J. Carless and D. J. Haywood J. Chem. Soc. Chem. Commun. 1980,657. 53 R. E. Ireland S. Thaisrivongs and C. S. Wilcox J. Am. Chem. SOC.,1980,102 1155. 54 D. B. Collum J. H. McDonald 111 and W. C. Still J. Am. Chem. Soc. 1980 102 2117 2118 2120. s5 B. M. Trost and E. Keinan J. Org. Chem. 1980,45,2741. 56 W. C. Guida and D. J. Mathre J. Org. Chem. 1980,45,3172. 57 E. Santaniello C. Farachi and F. Ponti Synthesis 1979 617. 58 U. Burger and F. Dreier Helu. Chim. Am 1980,63 1190. 59 K. Nickischi W. Klose and F. Bohlmann Chem. Ber. 1980 113,2036. 188 T. M. Cresp 1ii,iii (78) Reagents i CH,Cl, HMPA; ii Bu"Li;iii CuCl,; iv MeLi Scheme 8 of the photocycloaddition of dimethyl acetylenedicarboxylate to indoles have appeared,60 and they include a detailed mechanistic study.The dianion (79) from N-methylphthalimide gives mono- e.g. (go) and di-alkylated products e.g (81). The ratio of bridgehead to benzylic alkylation is very dependent on the nature of the electrophile.6' Both pyrroles6* and is~indoles~~ give 1:2 adducts with diethyl azodicarboxylate that result from Michael additions to both a-positions. d M\- e &NMe\ +~\ N M e OLi HO RO (79) (80) (81) A historical account of the frustrations and successes in the synthesis of ergot alkaloids makes interesting reading.64 More recent efforts have resulted in an improvement in the Bowman procedure for the preparation of Uhle's ketone (82)65 and an efficient route to methyl indole-4-carbo~ylate.~~ The former is a favourite intermediate in ergot alkaloid synthesis and the latter has been used in two impressive syntheses of chanoclavine I (83).67 HOTMe NHMe (84) R=CH H H (85) R=B (82) (83) 'O P.D. Davies and D. C. Neckers J. Org. Chem. 1980 45 456; P.D. Davies D. C. Neckers and J. R. Blount ibid. p. 462. G. A. Flynn J. Chem. SOC. Chem. Commun. 1980,862. C. K. Lee S. J. Kim and C. S. Hahn J. Org. Chem. 1980,45,1692. R.Kreher D.Schmitt and K. J. Herd Tetrahedron Left.,1980 21 3471. 64 D. C. Horwell Tetrahedron 1980,36 3123. "G.S.Ponticello J. J. Baldwin P. K. Lemma and D. E. McClure J. Org. Chem. 1980,45,4236. "A. P.Kozikowski H. Ishida and Y.-Y. Chen. J. Org. Chem. 1980 45 3350. 67 A. P.Kozikowski and H.Ishida J. Am. Chem. SOC. 1980 102,4265; W.Oppolzer and J. I. Grayson Helv. Chim. Acta 1980,63 1706; W.Oppolzer Heterocycles 1980 14 1615. Heterocyclic Compounds Polycyclic polyamines can provide information about the relationship between structures conformation and angle strain. Conformational analysis of a series of tricyclic orthoamides (84)68 and the effect of angle strain on hybridization in a series of tris(amino)boranes (85)69 are two examples from this area. An extension of the known photocyclization of S-aryl vinyl sulphides to thiophens has been used to prepare benzothiophens (87)from readily available methyl 2-(ary1thio)acetoacetates(86).70 a-Bisulphenylate ketones (88)cyclize equally well presumably by the same mechanism.” Tetrachlorothiophen 1,l-dioxide undergoes addition to a wide range of dienophiles and as expected the adducts lose sulphur dioxide.72 With furans the loss of sulphur dioxide is followed by rearrangement; a process best illustrated by the reaction between 3,4-dichlorothiophen 1,l- dioxide and 2,5-dimethylfuran where the initial adduct (89) which loses sulphur dioxide and rearranges to (90) can be isolated.73 Photocyclization of 3-acetoxybenzo[b]thiophen 1,2-dioxide (91) with cycloalkanes gives [2 + 21 adducts (92) ;these undergo ring-expansion to benzo[b]thiepinones (93).74 The kinetics of intramolecular acylation of long-chain o-(2-thienyl)alkanoic acids have been and the results used to advantage in a five-step synthesis of mu~cone,~~ where the cyclization of (94) gives a 59% yield of (95) without using unnecessarily high dilution.Publications in the area of donors for organic superconductors include two new syntheses of tetramethyltetraselenafulvene (96),77 a full on the synthesis 68 G. R. Weisman V. Johnson and R. E. Fiala Tetrahedron Lett. 1980,21,3635. 69 J. E.Richman N.-C. Yang and L. L. Andersen J. Am. Chem. SOC.,1980,102 5790. 70 T.Sasaki and K. Hayakawa Tetrahedron Lett. 1980 21 1525. 71 T.Sasaki K. Hayakawa and S. Nishida Tetrahedron Lett. 1980 21 3903. 72 M. S.Raasch J. Org. Chem. 1980 45 856. 73 M. S.Raasch J. Org. Chem. 1980,45 867. 74 N.V.KirbyandS. T. Reid J. Chem. SOC.,Chem. Commun. 1980 150. C. Galli G. Illuminati and L. Mandolini J. Org. Chem. 1980,45 311. 76 G. Cantoni C. Galli and L.Mandolini J. Org. Chem. 1980,45 1906. 77 F. Wudl and D. Nalewajek J. Chem. Soc. Chem. Commun. 1980,866;L.-Y. Chiang T.0.Poehler A. N. Bloch and D. 0.Cowan ibid. p. 866. M. V.Lakshmikantham and M. P. Cava J. Org. Chem. 1980,45,2632. 190 T. M. Cresp RR (95) Se X e Fe R&/ R Ye Se ' (96) X =Se R =Me (99) 6 m (97) X=S,R=H (98) of diselenadithiafulvene (97) and a description of the synthesis of diferrocenyl- tetrathiafulvene (98).79Seleno[3,4-b]selenophen (99) originally claimed to be a product from the reaction of selenium with acetylene has been prepared for the first time by a more rational route.80 The a-diazo-ketone (101) undergoes thermal ring-contraction to form the thietanone (100). With benzene as solvent the product of irradiation of (101) is the dihydrothiophen (102),whereas in methanol the heterocyclic products are (103) and (104).'l There is obviously much mechanistic and synthetic potential left in (101).OMe 70,Me Treatment of chloro-anilines (105) with base followed by irradiation provides a conceptually if not mechanistically (an intramolecular S,,l mechanism has been proposed) straightforward route to oxindoles (106).82The 2 1 adduct from con- 79 Y. Ueno H. Sano and M. Okawara J. Chem. SOC.,Chem. Commun. 1980,28. A. Konar and S. Gronowitz Tetrahedron 1980,36,3317. J. Bolster and R. M. Kellog J. Org. Chem. 1980,45,4804. 82 J. F. Wolfe M. C. Sleevi and R. R. Goehring J. Am. Chem. SOC.,1980,102,3646. Heterocyclic Compounds densation of diphenylketen with 1-methylbenzimidazole has structure (107),83 and not (108) (as previously reported).t-Butyl(cyan0)keten adds to the C(4)-C(5) double-bond of 2-(dimethy1amino)thiazoles(109) to give the tetrahydropyranone (110y4 (110) Trimethylaluminium adds stereospecifically to the (ptosy1)pyrazolines (111)and (114) yielding (112) and (115) respectively. Oxidation provides a convenient route to trans-(113) and cis-pyrazolin-4-ones (116).85 The method of preparation of allenic esters by treatment of 3,4-dialkyl-2-pyrazolin-5-ones with thallium(II1) nitrate has been extended to include a number of cyclic allenic esters (117).86 MeR&R4 MeR4;-,.e4 Me N=N N-N N=N /Ts (111) / (117) n =6-9 Ts (114) 83 M. J. Haddadin and H.H. N. Murad J. Org. Chem. 1980 45 2518. 84 A. Dondoni A. Medici C. Venturoli L. Forlani and V. Bertolasi J. Org. Chem. 1980,45 621. 85 W. H. Pirkle and D. J. Hoover J. Org. Chem. 1980 45 3407. A. Silveira Jr. M:Angelastro R. Israel F. Totino and P. Williamsen J. Org. Chem. 1980 45 3533. 192 T. M. Cresp Acyl-amidines which are well established as isoxazole precursors and have more recently (see Annu. Rep. Prog. Chern. Sect. B 1979 76 230) been used in the preparation of 1,2,4-0xadiazoles and 1,2,4-triazoles provide a convenient route to thiadiazoles (118) isoxazoles (119) and isothiazoles (120).87 .I NMe X-N R’ A/‘n 2 Y=C + RIG >RZ Y 1. (118) X=S,Y=N (119) X=O,Y=CH (120) X=S,Y=CH Irradiation of triazolines results in extrusion of nitrogen affording a 1,3-diradical which closes to form an aziridine ring.By having the carbon radical in conjugation with an a@-unsaturated ketone radical recombination results in the formation of a five-membered ring. In the example reported,*’ the intermediate (121) undergoes a retro-Diels-Alder reaction followed by trapping of the resultant keten (122) by solvent (Scheme 9). A similarity between reactions of singlet oxygen and triazolinediones with olefins and dienes suggests that they may react by much the same mechanism. Preliminary resultss9 on the mechanism of addition of triazolinediones to olefins suggest that this is indeed the case. ‘Et li fii ’Et Reagents i hv; ii MeOH Scheme 9 Primary amines react with 4-formylbenzofuran oxides (123) to give imines which rearrange to nitro-indazoles (124).Modification to oxime or hydrazone formation can be successfully incorporated providing a route to 2-oxy- (125) and 2-amino- indazoles (126) (Scheme A full report on the formation of quinoxaline monoxides (128) and (129) from benzofuran oxide (127) enones and amines has appeared.” By-products arise from reactions of (127) with amine detracting from an otherwise attractive synthetic route. The reaction is initiated by conjugate Y.-I. Lin S. A. Lang Jr. and S. R. Petty J. Org. Chem. 1980 45 3750; Y.-I. Lin and S. A. Lang Jr. ibid. p. 4857. A. G. Schultz and C.-K. Sha J. Org. Chem. 1980,45,2040. 89 C. A. Seymour and F. D. Greene J. Am. Chem. SOC.,1980,102,6384.90 A. J. Boulton T. Kan-Woon S. N. Balasubrahmanyam I. M. Mallick and A. S. Radhakrishna J. Org. Chem. 1980,45 1653. 9‘ A. F. Kluge M. L. Maddox and G. S. Lewis J. Org. Chem. 1980,45 1909. Heterocyclic Compounds -WR I R2 N R2 \ 'N (124) R' = alkyl or Ph (123) (125) R'=OR Reagents i H2N-R' (126) R'=NR2 Scheme 10 addition of an amine to the enone the enolate acting as a nucleophile and the protonated amine subsequently being eliminated to form the quinoxaline ring. It would be interesting to know if nucleophiles other than amines could be used in the reaction. 0 t 0 t + 0 0 (127) (129) A full of the Lewis-acid-promoted reaction of a-diazocarbonyl com- pounds (130) with nitriles to give oxazoles (131) will be welcomed by those seeking optimal conditions for this general synthesis of oxazoles.Tosylmethyl isocyanide the universal precursor forms a dianion (132) which condenses with ethyl benzoate to form the oxazole (1 33).93 Orthoesters condense with a-amino-ketone hydro- chlorides to provide a reasonable general route to 2,5-disubstituted oxazoles ( 134).94 Thiazolium oxazolium and selenazolium salts bearing N-(w-chloroalkyl) side- chains undergo ring-expansion on treatment with base (Scheme 1l).95 Alkylation of chiral oxazolines followed by hydrolysis yields butyrolactones and valerolac- tones. The alkylation sequence can be chosen to provide either enanti~mer.~~ Chiral (134) 92 H. P. Doyle W. E. Buhro J. G. Davidson R. C. Elliott J. W. Hoekstra and M.Oppenhuizen J. Org. Chem. 1980,45 3657. 93 S. P. J. M. van Nispen C. Mensink and A. M. van Leusen Tetrahedron Lett. 1980 21 3723. 94 J. L. La Mattina J. Org. Chem. 1980,45 2261. '' H.-J. Federsel and J. Bergman Tetrahedron Lett. 1980 21 2429. 96 A I. Meyers Y. Yamamoto E. D. Mihelich and R.A. Bell J. Org. Chem. 1980,45 2792. 194 T.M. Cresp CHO CHO Reagents i OH Scheme 11 keto-oxazolines react with organometallics to give after hydrolysis a-substituted a-hydroxy-acids in 30-87 '/o enantiomeric excess.97 A review on 1,3-thia~olines~~ places emphasis on the 1,3-thiazolinone + hydroxy- 1,3-thiazole tautomerism. Isoxazole N-oxides (135) have been isolated by benzo fusion to disfavour the ring-opened isomer ( 136).99 -0 (135) (136) (137) X=N Y=CH (138) X=CH Y=N 4 Six-Membered Rings A review"' covers the recent work on cycloaddition reactions of pyridines with special emphasis on intramolecular cyclizations.Irradiation of pyridine N-oxide in aqueous alkali forms the nitrile"' and not the isocyanide as previously reported (see Annu. Rep. Prog. Chem. Sect. B 1977,74 273). Fusion of 3-hydroxy-2-pyridone with phosphorus pentasulphide gives in addition to 3-hydroxypyridine-2-thione,the novel isomeric betaines (137) and (138).lo2 4-Methoxy-2-pyridone forms [2 + 2]cycloadducts with alkenes when irradiated in acetone solution. The regiochemistry of addition depends on the alkene that is used electron-deficient alkenes giving (139) by addition to the 5,6 double-bond.In solvents other than acetone only photo-2-pyridone (140) is formed (Scheme 12).lo3 The 2-pyrazinone (141) undergoes photochemical [4 + 41 cyclo- dirnerization to the anti-dimer (142) in the solid state; this reaction is reversed by R tfi -"ea orR~o N H o N H o N H o N H (140) (139) Reagents i hv RCH=CH Scheme 12 '')A. I. Meyers and J. Slade J. Org. Chem. 1980 45 2785. 98 G. C. Barrett Tetrahedron 1980,36 2023. 99 A. J. Boulton and P. G. Tsoungas J. Chem. SOC., Chem. Commun. 1980,421. loo W. Sliwa Heterocycles 1980,14 1793. 101 0.Buchardt J. J. Christensen D. E. Nielsen R. R. Koganty L. Finsin C. Lohse and J. Becker Actu Chem. Scand. Ser. B 1980 34 31. '02 J. S. Davies K.Smith and J. Turner Tetrahedron Lett. 1980 21 2191.H. Fujii K.Shiba and C. Kaneko J. Chem. SOC.,Chem. Commun. 1980 537. Heterocyclic Compounds Me Me hv,solid state __L c-- Ph hv,MeOH or heat N Ph heating (142) in methanol solution or by its irradiation. The N-ethyl analogue of (141) is photochemically stable in the solid state.lo4 N-Methyl-l,2-dihydropyridinebehaves as an enamine towards electron-deficient alkenes the usually observed [4 + 21 adducts being the thermodynamic product^."^ a-Pyridinones that bear an electron-attracting 4-substituent behave as dienophiles at elevated temperatures. Thus the 4-cyano-2-pyridone (143) reacts with 2,3- dimethylbuta-1,3-diene at 170 "C to give the isoquinoline (144).lo6 Pyrimidine- dienols react with electron-deficient dienophiles providing a novel route to quinazo- lines (Scheme 13).lo7 Pyridinoquinolin-2-ones (145) can be readily prepared in a 'one-pot' procedure by treatment of an acetanilide under Vilsmeier conditions (POCl in DMF) followed by addition of a secondary amine.lo8 0 Reagents i PrlNLi; ii MeO,CC=CCO,Me Scheme 13 Formation of pyridinium salts (147) from primary amines and pyrylium salts (146) followed by nucleophilic displacement with a wide range of nucleophiles has been the subject of a fruitful study by the Katritzky group in recent years.A detailed summary109 of this work is most welcome The acetate (148) serves as a convenient precursor for the pyrylium zwitterion (149). The reactions of (149) parallel those of the better known 3-oxidopyridinium zwitterion (1SO).Its thermal T. Nishio N. Nakajima and Y. Omote Tetrahedron Lett. 1980 21 2529. lo' B. W. Weinstein L. C. Lin and F. W. Fowler J. Org. Chem. 1980,45 1657. H. Tomisawa R. Fujita H. Kato and H. Hongo Heterocycles 1980 14 11 1. lo' S. Senda T. Asao I. Sugiyama and K. Hiroto Tetrahedron Lett. 1980 21 531. 0.Meth-Cohn and B. Tarnowski Tetrahedron Lett. 1980,21 3721. lo9 A. R. Katritzky Tetrahedron 1980 36 679. 196 T.M. Cresp R2 R2 (148) (150) X=NR (151) (154) X=NMe dimer (15 1)is bristling with functionality and its potential as a synthetic intermedi- ate has already been demonstrated."' The heterocarbanions (152) (153) and (154) appear to be thermally stable and parattopic."' The thioether group directs lithiation to the 5-position of the pyridine (155) giving access to a range of imidazo[l,5-a]pyridines (156) that are difficult to obtain by other methods.With benzonitrile as the electrophile the cyclazine-(158) a novel lO?r-electron system is obtained (Scheme 14). A 3,5-didehydroimidazo[ 1,5-a]- pyridine (157) has been suggested to be an intermediate.ll2 Reagents i Bu"Li; ii electrophile; iii Raney nickel; iv Bu"Li PhCN Scheme 14 A review113 covers the major synthetic routes to the 4H-pyran ring system. Cycloreversion of the ylides (159) gives a-0x0-dithioesters (160). Trapping of these intermediates with dienes is a convenient method for the preparation of functional- ized thiopyrans (141).'14 'lo J. B. Hendrickson and J. S. Farina J. Org Chem. 1980.45 3359 3361.'I' A. G. Anastassiou H. S. Kasmai and M. R. Saadein Tetrahedron Lett. 1980,21,3743. *I2 P. Blatcher and D. Middlemiss Tetrahedron Lett. 1980 21 2195; P. Blatcher D. Middlemiss P. Murray-Rust and J. Murray-Rust ibid. p. 4193. '13 C. Seoane J. L. Soto and M. Quinterio Heterocycles 1980 14 337. 'I4 E. Vedejs M. J. Amost J. M. Dolphin and J. Eustache J. Org. Chem. 1980 45 2601. Heterocyclic Compounds R' R' 0-0 (162) (163) Two groups"' have described a one-step synthesis of 2-substituted 4H-pyran-4- ones (173) by C-acylation of P-methoxy-ap-enone enolates (162) with acid chlorides anhydrides or acyl-imidazoles. The known conversion of secondary furfuryl alcohols into maltol has been considerably improved and this represents a very convenient entry into 3-hydroxy-4H-pyran-4-0nes."~ Dehydrobromination of the germacyclohexadiene (164) proceeds uia the ger- mabenzene (165) which dimerizes or which can be trapped with dienes."' Convinc-ing spectroscopic evidence has been presented to show that the retro-ene reaction of (166) and the ester cleavage of (167) both give silabenzene which can be trapped in an argon matrix."' Isatoic anhydride (168) is a heterocycle with a long history.Its rich chemistry has been beautifully put together in an impressive review.'" Other reviews include those on 1,3-0xazines,'~~ heterocyclic betaines,12' and thiocoumarins.'** 00hfi/HiGe Ge /\ Bu'Br Bu' Si / \H O-c\ No Me QfJ 0 (164) (165) (166) (167) (168) 5 Seven-Membered and Larger Rings Cycloaddition reactions of oxepin normally proceed through benzene oxide.However with the cyclopentadienone (169) the exo-[6 +41 tr-cyclo-adduct (170) can be isolated as well as the endo-[2 +41 tr-cyclo-adduct (171).'23 A molecular orbital study of the oxepin-benzene oxide valence isomerization has been repor- The course of the reaction of the dihydroazepine (172) with dimethyl acety- 11s M. Koreeda and H. Akagi Tetrahedron Lett. 1980,21,1197;T.A. Morgan and B. Ganem ibid. p. 2773. 'I6 P.D. Weeks T. M. Brennan D. P. Brannegan D. E. Kohla M. L. Elliott H. A. Watson B. Wlodecki and R. Breitenbach J. Org. Chem. 1980,45 1109. '17 G. Mark1 and D. Rudnick Tetrahedrori Lett. 1980 21 1405. G. Maier G. Mihon and H. P. Reisenauer Angew. Chem. Znt. Ed. EngL 1980,19,52.G. M. Coppola Synthesis 1980,505. T.Kato N. Katagiri and Y. Yamamoto Heterocycles 1980 14 1333. C.A. Ramsden Adu. Heterocycl. Chem. 1980 26 1. 0.Meth-Cohn and B. Tarnowski Adu. Heterocycl. Chem. 1980,26,115. lZ3 T.Ban Y. Wakita and K. Kanematsu J. Am. Chem. SOC.,1980,102,5415. lZ4 D.M. Hayes S. D. Nelson W. A. Garland and P. A. Kollman J. Am. Chem. Soc. 1980,102 1255. 198 T. M. Cresp o+q:+$p+ Ph m+ 0 Ph 0' (169) (170) 0 R = C02Me (171) lenedicarboxylate depends markedly on the solvent. In non-polar solvents [4 + 21 cycloaddition leads to the adduct (175). In polar solvents the dipolar intermediate (173) can ring-close and the resultant [2 + 21 adduct ring-open to (176) or in a protic solvent it can be protonated leading to (174).'*' Thermal interconversion of 2-pyridylnitrene (177) $ (179) may go through the carbene (180) as previously suggested but the stable intermediate in the interconversion is the cyclic carbodi- imide (178).126 Cyclic carbodi-imides are also intermediate in other nitrene re- arrangement~.'~' R MeOH ___) + + Ill polar solvent R RR (174) 1MeCN R (175) (176) o\..= N N "%N] n*9e (177) (180) (179) The dihydro-[ 14lannulene (18l) the penultimate precursor of the aromatic imino-methano[ 14lannulene (184) is a remarkably stable (i.e.decomp. above 75 "C) 1H-azepine. On chromatography on A1203 it isomerizes to the anti-isomer (183) presumably uia the Bredt rule respecting 3H-azepine (182).'** The stability of (181) has encouraged a successful attempt to characterize the much more labile (i.e.stable for a few hours at -78 "C in solution) 1H-azepine (185).'29 If present lZ5 W. Eberbach and J. C. Carre Tetrahedron Lett. 1980,21,1145. 126 C.Wentrup and H.-W. Winter J. Am. Chem. SOC.,1980,102,6159. 12' C.Wentrup C. Thetaz E. Tagliaferi H. J. Linder B. Kitschke H.-W. Winter and H. P. Reisenauer Angew. Chem. Int. Ed. Engl. 1980,19,566. lZ8 E. Vegel U. Brocker and H. Junglas Angew. Chem. Int. Ed. Engl. 1980 19 1015. lZ9 E.Vogel H.-J. Altenbach J.-M. Drossard H. Schmickler and H. Stegelmeier Angew. Chem. Int. Ed. Engl. 1980,19 1016. Heterocyclic Compounds (181) L H @'' '/N R' (187) (188) the benzeneimine tautomer (186) is there in less than 1% concentration in agree- ment with thoeretical calculations.Condensation of 1,2,4-triazines with benzo- cyclopropene affords substituted 3,8-methanoaza[ 10]annulenes (187).130 Aza- [14lannulene (188) is diatropic has temperature-dependent 'H n.m.r. spectra and like aza[l8]annulene (see Annu. Rep. Prog. Chem. Sect. B 1979 76 246) the nitrogen atom occupies an inner ~0sition.l~~ N.m.r. studies of conformational and configurational effects in medium-sized heterocycles include investigations on the carbodi-imide (189),13* 1-thiacyclo-octan-5-one (190),'33 the 2-0x0-azocine (191),134 and trans-thiacyclo-oct-4-ene (192). 35 0 CN> N 0 Crowns and cryptands continue to be a major growth industry. The effects of modification and of functionalization on crown ethers have been reviewed.lJ6 The pyridino-crown (193) selectively forms inclusion compounds with aliphatic alcohols.13' Primary ammonium cations are complexed by the triaza-trioxa-macrocycle (194) with a ca.ten-fold stability factor over complexation of K+.138 130 M. L. Maddox J. C. Martin and J. M. Muchowski Tetrahedron Lett. 1980 21 7. 13' H.Rottele and G. Schroder Angew. Chem. Int. Ed. Engl. 1980,19,207. 13' R. Damrauer D. Soucy P. Winkler and S. Eby J. Urg. Chem. 1980 45 1315. 133 F.A. L. Anet and M. Ghiaci J. Org. Chem. 1980,45 1224. 134 F.A. L. Anet Tetrahedron Lett. 1980 21 2133. V. CerC A. Guenzi S. Pollicino E. Sandri and A. Fava J. Org. Chem. 1980,45261. 136 J. S. Bradshaw and P. E. Stott Tetrahedron 1980,36 461. 13' E.Weber and F.Vogtle Angew. Chem. Znt. Ed. Engl. 1980 19 1030. 13' J. M. Lehn and P. Vierling Tetrahedron Lett. 1980 21 1323. 200 T.M. Cresp Me / 4 / (194) 6 Monographs and Reviews Where appropriate secondary literature references have been included in the previous sections. A very useful contribution is a list of monographs and reviews on heterocyclic compounds published between 1965 and 1978.’39“ Other topics in the Advances in Heterocyclic Chemistry series that have not previously been mentioned are heterocyclic betaine~,’~~’ ring synthesis of heteroaromatic nitro- compo~nds,~~~~ and heteroaromatic radicals with heteroatoms of Group V in the ring.139d A characteristically detailed and stimulating review by Huisgen is concerned with the heterocyclic counterparts of the cyclopentenyl anion pentadienyl anion electrocyclic rea~ti0n.l~’ A review on cyclic azoalkenes concentrates on the strained ring systems that they form by elimination of nitr~gen.’~’ Equilibrium conformations of four- and five-membered heterocyclic (and carbocyclic) rings as measured by vibrational spectroscopy and electron diffraction have been reviewed.’42 A more general survey of conformational analysis of heterocyclic compounds has also appeared.’43 In the Weissberger-Taylor series the 1,2,3-triazole ring system has been reviewed.144 Under the heading of fused-ring heterocycles with three or more nitrogen atoms a new volume14’ of Rodd’s Chemistry of Carbon Compounds’ contains reviews on purines and related ring system~;’~’“ nucleosides nucleotides and nucleic acids;14” pteridines alloxazines flavins and related and the biosynthesis of plant alkaloids and nitrogenous microbial metabolites.145d 139 (a)A. R. Katritzky and P. M. Jones Ado. Heterocycl. Chem. 1979 25 303; (b)J. W. Bunting ibid. p. 2; (c) S. Rajappa and M. D. Nair ibid. p. 113; (d)P. Hanson ibid. p. 206. 140 R. Huisgen Angew. Chem. Int. Ed. Engl. 1980.19.947. 14’ W. Adam and 0.de Lucchi Angew. Chem. Int. Ed. Engl. 1980,19,762. 14* A. C. Legon Chem. Rev. 1980,80,231. 143 F. G. Riddell ‘The Conformational Analysis of Heterocyclic Compounds.’ Academic Press London 1980. 144 ‘Triazole 1,2,3,’ ed. J. A. Montgomery (Weissberger and Taylor’s ‘The Chemistry of Heterocyclic Compounds’) Wiley-Interscience New York,1980 Vol.39. 14’ ‘Rodd’s Chemistry of Carbon Compounds,’ 2nd edn. ed. S. Coffey Elsevier Amsterdam and New York,1980 Vol. IV Part L; (a) G. Shaw; (6)D. S. Jones; (c) K. Olta R.Wrigglesworth and H. C. S.Wood; (d)R.B. Herbert. Heterocyclic Compounds 20 1 A special edition of the journal ‘Heterocycles’ is dedicated to Professor Umezawa on the occasion of his 65th birthday.146 His enormous contribution in the area of antibiotics has uncovered many new heterocyclic ring systems. 14‘ Heterocycles 1979 Vol. 13.

ISSN:0069-3030    

DOI:10.1039/OC9807700179

出版商:RSC    

年代:1980

数据来源: RSC

摘要:

12 Organometallic Chemistry Part (i) The Transition Elements By H. M. COLQUHOUN and J. HOLTON ICl Corporate Laboratory The Heath Runcorn Cheshire WA7 40E and M. V. WlGG ICI Agricultural Division Billingham Cleveland TS23 1LD 1 Introduction Interest in the use of transition-metal species in organic synthesis continued at a high level during 1980. Progress has been made in obtaining a more detailed understanding of some established reactions and a number of new reactions have been described which form the basis of potentially useful procedures. Last year we highlighted the use of phase-transfer methods for convenient generation of reactive organometallic intermediates in situ and this approach has been more fully reviewed.* Other areas reviewed include palladium-catalysed allylic alkylations2” and applications of this and related palladium-catalysed reactions in the synthesis of natural products,2b oxidative addition and coupling reactions cata- lysed by the metals of the nickel triad,3 and the synthesis of intermediates by rhodium-catalysed hydroformylation reaction^.^ The extensive proceedings of the third international symposium on olefin metathesis have been published,’ and several relevant books have appeared.Topics discussed include syntheses involving carbon monoxide,6“ catalytic hydrogenation,66 and synthetic and mechanistic aspects of oxidations catalysed by palladium salts.6c Two books’ concerned with catalysis by soluble transition-metal species include descriptions of industrial synthetic pro- cesses as well as laboratory procedures.L. Cassar Ann. N.Y.Acad. Sci. 1980,333 20. (a)B. M. Trost Acc. Chem. Res. 1980,13,385; (b)J. Tsuji Top. Cum. Chem. 1980,91,29. E. Uhlig and D. Walther Coord. Chem. Rev. 1980,33,3. H. Siege1 and W. Himmele Angew. Chem. Znt. Ed. Engl. 1980,19,178. Proceedings of the 3rd International Symposfum on Olefin Metathesis ed. J. M. Basset and Y. Chauvin in J. Mol. Card. 1980,Vol. 8,Issues 1-3. (a)‘New Syntheses with Carbon Monexide’ ed. J. Falbe Springer-Verlag Berlin 1980;(6) P. Rylander ‘Catalytic Hydrogenation in Organic Syntheses’ Academic Press New York 1979;(c) P. Henry ‘Palladium Catalysed Oxidation of Hydrocarbons’ D. Reidel Publishing Company Holland 1979. ’(a)G. W. Parshall ‘Homogeneous Catalysis The Applications and Chemistry of Catalysis by Soluble Transition Metal Complexes’ John Wiley New York 1980;(b)C.Masters ‘Homogeneous Transition- Metal Catalysis’ Chapman and Hall London 1980. 203 H. M. Colquhoun J. Holton and M. V. Twigg 2 Hydrogenation A full report has appeared on the catalytic hydrogenation of polycyclic aromatic hydrocarbons.' The hydrogenation of a series of polyaromatic compounds has been examined using platinum or palladium on charcoal or platinum oxide catalysts under mild conditions (25 "C; 20-30 p.s.i. H2). Reduction over the palladium catalyst affords the internal dihydro-arene regioselectively while the analogous reaction with platinum catalysts occurs on the terminal ring to give the tetrahydro- arene.These reactions complement the Birch reduction which generally provides different hydro-aromatic products. The homogeneous ruthenium catalyst -[(Ph3P)2(Ph2PC&)RuH2]- K+CloHs.Et20 catalyses the hydrogenation of naph- thalene and of anthracene to tetrahydronaphthalene and tetrahydroanthracene with 98% selectivity.' Reduction of phenanthrene is very slow and isolated aromatic rings (as in benzene toluene tetralin or pyridine) are unaffected. This anionic hydride catalyst compares favourably with other homogeneous hydrogenation catalysts being selective and requiring only relatively mild conditions (100 "C; 6 atm). Ketones esters and nitriles are also hydrogenated. A detailed study has been made of the hydrogenation catalyst N~H/RON~/[N~(OAC>~].'O This heterogeneous catalyst is cheap easily and repro- ducibly prepared and can be stored for long periods.By monitoring the uptake of hydrogen selective reduction of alkyne to alkene and then to alkane is easily achieved particularly in the presence of quinoline. Only mild conditions (25 "C; 1atm H2; 1-1.2 mole equivalents) are required to reduce disubstituted or terminal alkynes containing a variety of functional groups (alkyl aryl hydroxyl or amine) to cis-alkenes in high yield. Similarly carbonyl compounds are readily reduced to the corresponding alcohols but selective hydrogenation of a@-unsaturated ketones can be achieved with preferential reduction of the double-bond. These reactions are influenced by steric factors and mixed products are obtained if the double-bond is too sterically hindered.Steric crowding may be used to advantage for instance to achieve high selectivity in the reduction of polycarbonyl compounds (Scheme 1). With [Pd(PPh,),] as catalyst allylic acetates can be reduced to alkenes using NaBH4 or NaBH3CN. l1 Normally carboxylate groups cannot be displaced since they are unreactive towards mild hydride-transfer reagents or they suffer attack at the carbonyl group by more powerful reagents to produce alcohols. Both NaBH4 [97%] Reagents i H2 NaH/NaOR/[Ni(OAc),] catalyst Scheme 1 P. P. Fu H. M. Lee and R. G. Harvey J. Org. Chem. 1980,45,2797. R. A.Grey G. P. Pez and A. Wallo J. Am. Chem. SOC.,1980,102 5948. lo J. J. Brunet P. Gallois and P. Caubbre J. Org. Chem. 1980,45,1937.R. 0.Hutchins K. Learn and R. P. Fulton Tetrahedron Lett. 1980 21 27. Organometallic Chemistry -Part (i) The Transition Elements and NaBH3CN are effective but the latter is favoured when sensitive functional groups are present (e.g. NOz). With aromatic substituents the corresponding conjugated alkenes are produced almost exclusively whereas mixtures of regio- isomers are obtained with aliphatic systems. The combined reagent [TiCL,]/NaB& has been examined for the reduction of a large variety of.functional groups. Carboxylic acids and acyl chlorides are reduced to alcohols and amides oximes and nitro-compounds to amines. Sulphoxides are converted into sulphides and this reagent also permits the denitrosation of nitrosamines to amines.12 A very active homogeneous catalyst for hydrogenation of alkenes has been prepared by the reaction of [Rh(PPh,),Cl] with Cs[7-butenyl-7,8-C2B9H1~].'~ The crystal structure of the product [(77 2-3,4 -H2C=CHCH2CH2) -3-H-3 -PPh3-3 1,2-RhC2B9H10] shows that the butenyl group is co-ordinated to rhodium.Addition of hydrogen leads to reduction of the double-bond creating a vacant site on the rhodium for complexation of an alkene molecule. The rhodacarbaborane has an initial hydrogenation rate for alkenes that is thirty times faster than that of [Rh(PPh3),C1] and four times faster than [Ir(cod)(py)(PPri3)]PF6 (one of the most active homogeneous hydrogenation catalysts known). A recognized route to 5p-steroids is the hydrogenation of 3-0x0-4-ene or 1,4-diene steroids using palladium black that is modified with pyridine.14 4-Methoxypyridine is however a more effective modifying agent than pyridine giving high yields (>95%) of 5P-steroids (which may contain a variety of substituents).Investigation of the mechanism of asymmetric hydrogenation has continued with the first characterization" of a hydrido(alky1)rhodium intermediate. The intermedi- ate (1)in hydrogenation of methyl (2)-a-acetamidocinnamate,using [Rh(diphos)- (MeOH)2]' has previously been characterized by X-ray crystallography. By extend- ing these studies to lower temperatures the rhodium hydrido-alkyl (2) has been r Ph l+ NH Ph Ph I h;le J (2)s= solvent identified by 'H 31P and 13C n.m.r. spectroscopy. Previously only indirect evidence has been available for species of this type because they are very reactive and do not normally accumulate in detectable concentrations.The structure of [Rh{(S S)-chiraphosxethyl (2)-a-acetamidocinnamate}]+ has been determined,16 and it is essentially similar to that of (1).Interestingly addition of hydrogen to this structure would lead to the (S)-isomer of the product whereas l2 S. Kano Y. Tanaka E. Sugino and S. Hibino Synthesis 1980,695 and 741. l3 M. S. Delaney C. B. Knobler and M. F. Hawthorne J. Chem. Soc. Chem. Commun. 1980,849. l4 N. Tsuji J. Suzuki M. Shiota I. Takahashi and S. Nishimura J. Org. Chem. 1980,45 2729. A. S. C. Chan and J Halpern J. Am. Chem. SOC.,1980,102,838. l6 A. S. C. Chan J. J. Pluth and J. Halpern J. Am. Chem. Soc. 1980 102 5952.H. M. Colquhoun J. Holton and M. V. Twigg the major reaction product is the (R)-isomer. It has been suggested that the newly characterized intermediate corresponds to the predominant diastereoisomer in solution (only one isomer is observed by n.m.r. in solution) but that the other diastereoisomer is so much more reactive towards hydrogen that it dominates the enantioselectivity of the reaction. It was therefore concluded that in this and in a related" system it is not the preferred stereochemistry of binding of the substrate to the catalyst but the difference in reactivity of the two isomeric adducts that determines which stereoisomer is produced. Accordingly at a sufficiently high pressure of hydrogen the hydrogen-transfer step is no longer rate-determining and the stereochemistry should then be dominated by the binding of substrate to catalyst leading to reversal of the stereochemistry of the product.This mechanism provides an elegant explanation for the known inverse dependence of optical yield on the partial pressure of hydrogen.18 Modification of Raney nickel with an aqueous solution of tartaric acid and sodium bromide produces an excellent catalyst for the hydrogenation of acetylacetone to optically pure pentanediol."" Using (R,R)-tartaric acid the (-)-(2R,4R)-pentane- 2,4-diol is obtained whereas the (S,S)-acid gives the (+)-(2S,4S)-diol. This catalyst system has also been used for the hydrogenation of 4-hydroxy-2-butanone to produce either (R)-or (S)-1,3-b~tanediol.'~' 3 Dimerization Oligomerization and Cycliiation of Alkenes The dimerization of propylene to 2,3-dimethylbut-1 -ene catalysed by [Ni(v- allyl)Br{P(C6H11)3}],has been re-examined and the catalyst was found to have an activity that is three orders of magnitude higher than previously reported.20 Simply by altering reaction conditions an activity of 150 x lo5kg of product per gram of nickel per hour (at ambient temperature) was obtained.The first example of the use of a cyclopentadienylnickel cluster to effect catalytic oligomerization of ethylene has been reported;21 [Ni3(q5-C5H5)3(CO)21 when supported on silica-alumina and subsequently heated to 150 "C produces a highly active catalyst for oligomerization of ethylene. The major products are mixed butenes and hexenes.Fourteen-membered cycloalkenes are readily prepared by co-oligomerization of isoprene with olefins and acetylenes in the presence of (3).22 The reaction of (3) with isoprene produces an intermediate which upon successive addition of dimethyl (3) l7 J. M. Brown and P. A. Chaloner J. Chem. SOC.,Chem. Commun. 1980,344. '* I. Ojima T. Kogure and N. Yoda J. Org. Chem. 1980,45,4728. l9 (a) K. Ito T. Harada A. Tai and Y. Izumi Chem. Lett. 1979 1049; (b)S. Murakami T. Harada and A. Tai Bull Chem. SOC.Jpn. 1980 53 1356. *' B. Bogdanovic B. Spliethoff and G. Wilke Angew. Chem. Int. Ed. Engl. 1980,19,622. *' D. L. Beach and T. P. Kobylinski J. Chem. SOC.,Chem. Commun. 1980,933. 22 R. Baker and M. G. Kelly J. Chem. SOC.,Chem. Commun. 1980,307. Organometallic Chemistry -Part (i) The Transition Elements acetylenedicarboxylate and sulphur (to remove complexed nickel) yields (4) in 30% yield.Wilkinson's catalyst [Rh(PPh,),Cl] has been shown to be effective (Scheme 2) for the cyclization of 4,4-disubstituted- 1,6-dienes (5) to methylenecyclopentanes (6).23 Simply refluxing in chloroform gives high yields of products. It is interesting to compare the effect of rhodium(1) with a similar reaction using palladium(@ which produces cyclopentenes (7),as shown also in Scheme 2. In contrast to palladium-catalysed cyclizations the rhodium-promoted reaction does not occur when the double-bonds are substituted. v2 R' R2 *2v-H Pd"+ X Y X Y X Y (5) (7) Scheme 2 Further reports have appeared on the co-cyclization of a,@-diynes and substituted alkynes in the presence of [CO(~-C~H~)(CO)~] to give annulated benzenes,24 which are useful intermediates for further functionalization.Total synthesis of racemic steroids (e.g. d,l-oestrone) demonstrates the usefulness of this procedure. Molybdenum hexacarbonyl promotes the cyclopropanation of conjugated esters and nitriles by diazocarbonyl compounds e.g. as shown in reaction (l).25 The 0 0 Me II PhCCHN + H,C< -Phb+.Me CN CN reaction is thought to proceed through a molybdenum-carbene intermediate but this has not been confirmed. Chromium hexacarbonyl exhibits much lower catalytic activity but the tungsten analogue is inactive for cyclopropanation because 1,3- dipolar addition occurs to give 2-pyrazolines.4 Carbonylation Divinyl ketones are valuable double Michael acceptors but few convenient syn- theses have previously been described. It is now reported that vinylmercuric chlorides are carbonylated at a pressure of 1atm of carbon monoxide in the presence of a rhodium catalyst to give high yields of divinyl ketones,26 as shown in reaction (2). 23 R. Grigg T. R. B. Mitchell and A. Ramasubbu,J. Chem. SOC.,Chem. Commun. 1980,27. 24 (a)E. R. F. Gesing J. A. Sinclair and K. P. C. Vollhardt J. Chem. SOC.,Chem. Commun. 1980,286; (b)R. L. Funk and K. P. C. Vollhardt J. Am. Chem. SOC.,1980,102,5245,5253. 25 M. P. Doyle and J. G. Davidson J. Org. Chem.. 1980,45 1538. 26 R. C. Larock and S. S. Hershberger J. Org. Chem.1980.45 3840. 208 H. M. Colquhoun J. Holton and M. V. Twigg Arylmercuric halides undergo a corresponding reaction giving diary1 ketones in up to 95% yield but more vigorous conditions are generally required (70°C; 100atm). The synthesis of lactones by palladium-catalysed carbonylation of halogeno- alcohols [reaction (3)] has been effected under mild conditions (2540°C; 1-4 atm CO). Catalyst efficiency is reasonably high (>250 turnovers) isolated yields are 60-90% and the reaction is general for benzyl allyl vinyl and aryl halides containing primary secondary or tertiary alcohol groups.27 WH + co [pd(PPhd~Cl~! @ HI + (3) 0 An analogous though intermolecular carbonylation [reaction (4)] has been applied28 to the synthesis of the natural product curvularin.The yield of intermediate ester (8)is ca 70%. MeO@" + co + .,3 [Pd(PPh,)zC12]h Mead](4) Me0 Me0 roI Ph 0 f0I Ph 0 (8) Alkynecarboxylic esters have been synthesized in good yield via the oxidative carbonylation of alkyne~~~ in the presence of catalytic quantities of [PdC12] as shown in reaction (5). D'dClzl 2Cu2+ + RCGCH + CO + MeOH -RC=CC02Me + 2H+ + 2Cuf (5) 'Carboacylation' describes the formal addition of an ester to a double-bond and has now been achieved by palladium-assisted attack of a carbanion on an alkene insertion of carbon monoxide into the resulting alkyl-palladium bond and finally attack of methanol to liberate the product esters (9) and (lo) as shown in Scheme 3.30By careful control of experimental conditions competing reactions (such as p-elimination of hydride from the intermediate palladium alkyl) may be suppressed OMe R' OMe (10) (9) Scheme 3 " A.Cowell and J. K. Stille J. Am. Chem. Soc. 1980,102,4193. 28 T. Takahashi H. Ikeda and J. Tsuji Tetrahedron Lett. 1980 21 3885. 29 J. Tsuji M. Takahashi and T. Takahashi Tetrahedron Lett. 1980 21,849. 30 L.S.Hegedus and W. H. Darlington J. Am. Chem. SOC.,1980,102,4980. Organometallic Chemistry -Part (i) The Transition Elements and yields of isolated purified product in excess of 80% are obtainable. With ethene propene hex-1-ene and the anion of diethyl methylmalonate high yields of a single carboacylation product [isomer (9)] were isolated only traces of the other regioisomer (10)being formed.Arylamines may be converted into arenecarboxylic acids via their diazonium salts by reaction with carbon monoxide at a pressure of 9 atm in the presence of sodium acetate and a palladium(0) ~atalyst.~' The reaction is thought to occur by arylation of palladium with elimination of N2 insertion of CO into the aryl- palladium bond and attack of acetate ion on the resulting benzoyl-palladium complex giving a mixed benzoic-acetic anhydride [reaction (6)]. Hydrolysis affords ArN; + CO + AcO-+ ArC02Ac + N2 (6) the arenecarboxylic acid in good yield and the reaction is unaffected by a variety of functional groups in the aromatic nucleus. 5 Chemistry of Synthesis Gas and Catalysis by Metal Clusters Catalysis by metallic clusters is sometimes viewed with because the active species are often poorly characterized and may not even be clusters.Thus for example it has been that cluster fragments are the active species in the [Rh6(C0)16]-CatalySed oxidation of cyclohexanone to adipic acid. This however is not so for the rhodium-catalysed formation of polyols (notably ethane-1,2-diol) from synthesis gas that occurs at high pressures. Under reaction conditions elegant high-pressure i.r. have shown that rhodium is present in the form of large carbonyl clusters though this is not the case for the corresponding reaction using ruthenium catalysts in acetic An alternative approach to the synthesis of ethane- 1,2-diol involves hydroformylation of formaldehyde to glycolaldehyde (OHCCH20H).This rhodium-catalysed reaction is markedly solvent-dependent hydroformylation only being favoured in NN-disubstituted amide~.'~~ Glycolal-dehyde is obtained in up to 50% yield (with only small amounts of hydrogenation to methanol) by using [RhCl(CO)(PPh3)2] in dimethylacetamide. In the presence of carbon monoxide and water catalysts derived from rhodium/iron and ruthenium/iron carbonyls are active for the synthesis of tertiary amines; see reactions (7) (8) and (9).34The alkyl group in the product contains one more carbon atom than the olefin and the reaction proceeds via hydroformyla-tion of the alkene. It is noteworthy that iron or ruthenium carbonyls alone are not good catalysts. The active species is thought to be a cluster. R'CH=CHZ + 2CO + H20 + R'CH2CH2CHO + C02 (7) R'CH2CH2CHO + HNR; + R1CH2CH=CHNR; + H20 (8) R1CH2CH=CHNR; + CO + H20 + R1CH2CH2CH2NR; + C02 (9) 31 (a)K.Nagira K.Kikukawa F. Wada and T. Matsuda J. Org. Chem. 1980,45,2365; (6)K.Kikukawa K.Kono,K.Nagira F. Wada and T. Matsuda Tetrahedron Lett. 1980 21 2877. 32 (a) B. C. Gates and J. Lieto Chemtech. 1980 195; (b) M. K.Dickson B. P. Sudha and D. M. Roundhill J. Organomet. Chem. 1980 190 C43. 33 (a)J. L. Vidal and W. E. Walker Znorg. Chem. 1980,19,896; (6)B.D.Dombek J. Am. Chem. SOC. 1980,102,6855; (c)A.Spencer J. Organomet. Chem. 1980,194 113. 34 R. M. Laine D. W. Thomas and L. W. Cary J. Org. Chem. 1979,44 4964; R.M.Laine ibid. 1980 45,3370. 210 H. M. Colquhoun J. Holton and M. V. Twigg A number of transition-metal cluster compounds i.e.[RU~(CO)~~], [OS~(CO)~~] and [Ir4(CO)12] act as precursors to homogeneous catalysts for alkyl-exchange reactions of tertiary amines [e.g. reaction (lo)]." Water is a necessary component of the system and the reaction is thought to involve abstraction+of hydride from the amine by the catalyst giving an iminium cation (e.g. MeCH=NEt2 from Et3N). [Ru~(CO)~~] (at 150"C) A Et3N + Pr3N . Et2NPr + EtNPr2 (10) Hydrolysis of the latter yields in this example acetaldehyde and diethylamine which can combine with dipropylamine and propionaldehyde respectively (from Pr3N). Transfer of hydride from the catalyst to the resulting iminium cations then yields the mixed amines and completes the catalytic cycle. Synthesis gas is converted into propene with high selectivity (though at low conversion) over a catalyst derived from [Fe3(C0)12] supported on magnesium Ethene is similarly converted into propene and these results may be taken as evidence for a carbene chain mechanism similar to that established for alkene metathesis.An extension of this scheme provides a new mechanism for Fischer- Tropsch synthesis of saturated hydrocarbon^.^^ Related makes use of a catalyst prepared by reducing cobalt(I1) acetylacetonate with AlEt,. In an alkyl- terphenyl solvent this converts synthesis gas (at atmospheric pressure) into a mixture of linear alkenes in the c2-c6 range and saturated hydrocarbons. Hydroformylation of ally1 alcohol to hydroxybutanals is not well documented although it is known that formation of by-products (e.g.from hydrogenation and isomerization to propan-1-01) is a serious problem. An extensive of the rhodium-catalysed reaction using a wide range of ligands (including polymer-bound systems) highlights the sensitivity of hydroformylation to ligand type ligand :metal ratio and reaction conditions. Curiously the use of the unusual ligand 1,l'- bis(dipheny1phosphino)ferrocene under appropriate conditions at 60 "C results in a clean reaction with yields of n-hydroxybutanol of up to 85%. An interesting variation on the hydroformylation theme is the use of [co2(Co)g] in the presence of Ph2PCH2CH2PPh2 to catalyse the formation of dipropyl ketones from propene carbon monoxide and water. Yields of ketones as high as 87% have been rep~rted.~' 6 Reactions of Co-ordinated Ligands Cyclopropylcarbinyl compounds are formed by the reaction of the alkenyl-iron complex (11)with electrophiles (e.g.H') or radicals (e.g. C13C Br3C or ArS02) via regiospecific attack at the 6-carbon of the butenyl ligand.41 The homolytic reaction (shown in Scheme 4) is thought to proceed by a radical chain mechanism and gives yields of ca. 6940 based on the iron complex. A novel method for the vicinal diamination of alkenes uses [(~5-C5H5)Co(NO)]2. The reaction of this complex with nitric oxide and an alkene at O'C followed by '' Y.Shvo and R. M. Laine J. Chem. SOC.,Chem. Commun. 1980,753. 36 F.Hugues B. Besson and J. M. Basset J. Chem. SOC.,Chem. Commun. 1980,719. 37 C. O'Donohoe J. K.A. Clarke and J. J. Rooney J. Chem. SOC.,Faraday Trans. I 1980,76 345. M. Blanchard D.Vanhove F. Petit and A. Mortreux J. Chem. SOC., Chem. Commun. 1980,908. 39 C. U.Pittman and W. D. Honnick J. Org. Chem. 1980,45,2132. 40 K.Murata and A. Matsuda Chem. Lett. 1980,11. 41 A.Bury M. D. Johnson and M. J. Stewart J. Chem. SOC.,Chem.. Commun. 1980,622. Organometallic Chemistry -Part (i) The Transition Elements 211 Br + Fe(CO),h-C H,) -[FeBr (CO)~(T-C, H,)] (11) Scheme 4 0 R' ,k$R2 ___ .,,fR2 LiAIH H2NTR3 R4 reduction of the intermediate complex (12) in situ with lithium aluminium hydride affords the diamine in 50-90°/0 yield (Scheme 5).42 The relative reactivity of alkenes towards [(q5-C5Hs)Co(NO)]2 increases with increasing ring-strain so that norbornene for example reacts more rapidly than cyclopentene which is more reactive than a simple acyclic alkene such as trans-hex-3-ene.The well-known susceptibility of arene-chromium tricarbonyl complexes to nucleophilic attack has been exploited in a novel synthesis of chromans (benzodihy- dropyran~).~~ The complex (13) for example [from 3-(o-fluorophenyl)propan-l-ol and tris(pyridine)tricarbonylchromium(~)] is readily cyclized by treatment with potassium t-butoxide giving the chroman complex (14). Mild oxidation by iodine in diethyl ether liberates chroman in virtually quantitative yield. Such cyclizations may also be achieved catalytically in the presence of the rhodium(II1) complex [(q5-EtMe4Cs)(q6-C6H6)Rh]2+ 2[PF6]- since the benzene ligand is readily and reversibly displaced by other arenes via an intermediate solvated species.Grubbs and co-workers have shown that the methylene-transfer agent [(q5-CSH5)2Ti(p-CH2)(p-Cl)AlMe2] originally discovered by Tebbe may be used to convert esters directly into vinyl ethers [reaction (1l)]."" The reaction is favoured by donor solvents such as THF,and is a general high-yield synthetic procedure unlike the reaction of esters with Wittig reagents. The titanium reagent is tolerant of ketal and alkene functional groups but ketones are readily methylenated. 42 P. N. Becker M. A. White and R. G. Bergman J. Am. Chem. SOC.,1980,102 5676. 43 R.P. Houghton M. Voyle and R.Price J. Chem. SOC.,Chem. Cornmun. 1980 884. 44 S. H. Pine R.Zahler D. A. Evans and R. H. Grubbs J. Am. Chem. Soc. 1980,102,3270. 212 H. M Colquhoun J. Holton and M. V. Twigg The spirocyclic sesquiterpenes acorenone and acorenone B have been synthesized by a route which uses the activating and meta-directing effects of a chromium tricarbonyl group to introduce the spirocyclopentane fragment.45 The two metal- assisted steps in this synthesis are shown in Scheme 6. MeO Cr (co) 1 1 1 1 + Me v-vii (CO)3Cr Reagents i Li ; ii I,; iii H’(aq); iv OH-(aq); v LiNR, CF,SO,H; vi NH,OH; vii H’(aq) $.“On Scheme 6 Primary aromatic amines react rapidly with the allene complex cis-[PtCI2(Me2C=C=CH2)(PPh3)] in chloroform or dichloromethane to precipitate p-ammonioalkenyl complexes (15). However if the latter are retained in solution by increasing the volume of solvent a novel rearrangement occurs to yield the corresponding enamine complexes (16).The presence of a cis-enamine ligand was confirmed (X-ray) and the enamines were liberated from their complexes by treatment with cyanide ion.46 I NHAr (16) 7 Isomerization Palladium(I1) complexes (notably [PdC12(PhCN)2] in benzene) catalyse the Cope rearrangement [reaction (12)] of many unstrained acyclic 1,5-dienes to such an extent they occur readily at room temperature giving the product distribution that 45 M. F. Semmelhack and A. Yamashita J. Am. Chem. SOC.,1980,102,5924. 46 A.de Renzi P. Ganis A. Panunzi A. Vitagliano and G. Valle J. Am. Chem. SOC.,1980 102 1722. Organometallic Chemistry -Part (i) The Transition Elements 213 results from thermodynamic In contrast the thermal reaction requires high temperatures and proceeds less stereoselectively due to partial kinetic control of the nature of the products.The catalysed isomerization requires a substituent at either C-2 or C-5 but no rearrangement takes place if both of these positions are substituted. This could be due to the intermediacy of a carbocyclic species but detailed information about the mechanism is lacking. It may be expected that this situation will change as synthetic applications of this particularly mild reaction are inv'estigated. Isomerization of allylic alcohols to ketones [reaction (13)] takes place smoothly at room temperature in the presence of catalytic amounts of [Rh(CO)2Cl]2 in dichloromethane under phase-transfer conditions with aqueous sodium hydroxide.48 This simple method for isomerizing ally1 alcohols does not always require a phase-transfer catalyst (quaternary ammonium salt) though the use of one results in the suppression of by-products.Rearrangement of N-allyl-amides OH 0 II R'CH=CH&HR2 -+ R'CH2CH2CR2 (13) H2C=CHCH2NHCOMe -B CH3CH=CHNHCOMe (14) to predominantly cis-N-propenyl-amides is catalysed by rhodium and ruthenium hydrides [e.g. reaction (14)]. Although this is a fairly general reaction? a universal catalyst is not yet available and it is necessary to match catalyst and reaction conditions with a particular substrate. Thus N-propenyl-imides can be obtained from N-allyl-imides only when iron pentacarbonyl is used as the catalyst.Acetylenic silyl ethers are selectively converted into synthetically versatile 1,3-dienol ethers in high yield [reaction (IS)] by heating at 150-180 "C in the presence of a ruthenium hydride complex.5o It is thought that the reaction proceeds uia a simple addition-elimination process and it may be for steric reasons that terminal acetylenes do not undergo reaction. R2CH2CrCCHR1(OSiMe3)+ R2CH=CHCH=CR'(OSiMe3) (15) (R2 = OSiR OR' or R') Catalysts derived from titanocene and metal hydrides are known to cause olefins to isomerize. These systems have now been useds1 to obtain almost quantitative yields of the bicyclo-conjugated diene (18) (which is difficult to prepare by any other route) from the cis-annulated diene (17).H H (17) 47 L. E. Overrnan and F. M. Knoll J. Am. Chem. Soc. 1980,102,865. 48 H. Alper and K. Hachern J. Org. Chem. 1980,45,2269. 49 J. K. Stille and Y. Becker J. Org. Chem. 1980,45 2139. K. Hirai H. Suzuki Y. Moro-oka and T. Ikawa Tetrahedron Lett. 1980,21,3413. 51 F. Turecek H. Antropiusova K. Mach V. Hanus and P. Sedrnera Tetrahedron Lett. 1980 21 637. 214 H. M. Colquhoun,J. Holton and M. V,Twigg 8 Asymmetric Synthesis Undoubtedly the most significant advance in this area has been the discovery by Katsuki and Sharplessz2 that asymmetric epoxidation of allylic alcohols may be achieved with >95'/0 enantiomeric excess in high chemical yield by using t-butyl hydroperoxide in the presence of titanium(1v) isopropoxide and (+)-or (-)-diethy1 tartrate.Reactions are carried out in chlorinated solvents at -2O"C and appear to be tolerant of a wide range of substituents with the limitation that yields decrease markedly if the product epoxy-alcohol is water-soluble. The quantities of [Ti(OPr'),] and diethyl tartrate that are required vary with the nature of the allylic alcohol so that although stoicheiometric quantities of these components are required for the epoxidation of (19),only catalytic amounts (-0.1 mol equivalent) are necessary with more reactive alkenes such as geraniol (20). Osmium tetroxide may be modified by the chiral amines (21) and (22) allowing the conversion of alkenes into chiral diols in up to 90% enantiomeric excess. Reactions are performed at -78 "C in toluene and the diastereoisomers (21) and (22) exhibit opposite stereosele~tivity.~~ An asymmetric synthesis of secondary alcohols and bromides in up to 95% enantiomeric excess has been de~eloped,~ using asymmetric hydrosilylation of alkenes with the palladium-ferrocenylphosphine catalyst (23) followed by conver- sion of the product into an alkyl pentafluorosilicate and finally stereospecific cleavage of the carbon-silicon bond to generate the optically active alcohol or bromide.R* (21) R' = H R2 = X T R'& A,1I2 (22) R' = X,R2 = H Ph P Ph (23) Stereoselective aldol condensations may be achieved by using the zirconium enolate complexes (24) which are prepared from the corresponding lithium enolate and [Zr(q'-C5H5)2C12].It has been suggested that the observed selectivity may be a result of both the enolate and the aldehyde being bound to zirconium during the reaction (Scheme 7) and hence their relative orientation being governed by the sterically demanding cyclopentadienyl ligand~.~' In all cases the zirconium enolates exhibit erythro diastereoselectivity (72-98'/0). 52 T. Katsuki and K. B. Sharpless J. Am. Chem. Soc. 1980,102 5974. 53 S.G.Hentges and K. B. Sharpless J. Am. Chem. Soc. 1980,102,4263. 54 T.Hayashi K. Tamao Y. Katsuro I. Nakae and M. Kumada Tetrahedron Lett. 1980 21 1871. " D.A.Evans and L. R. McGee Tetrahedron Lett. 1980 21 3975. Organometallic Chemistry -Part (i) The Transition Elements (X = Bu'S;RO Ph or R2N) Scheme 7 9 Miscellaneous The reaction of amines with carboxylic esters to give amides frequently requires high temperatures and/or extremes of pH.This reaction however proceeds under much milder conditions in the presence of catalytic quantities of rhodium trichloride. The synthesis of optically active 2,5-dioxopiperazines from the corresponding amino-acid esters can thus be achieved in high yield at -6O"C whereas reactions of this type at high temperatures are usually accompanied by extensive polymeriz- ation and loss of optical a~tivity.,~ Oxidation of 1-aroyl-pyrroles by palladium(I1) acetate in acetic acid affords moderate yields (3040%)of l,l'-diaroyl-2,2'-bipyrroles,which are readily hydro- lysed to 2,2'-bipyrrole~.~~ In view of the specific 2,2'-coupling observed it seems likely that this reaction proceeds via one or more ortho-palladiated intermediates.Nucleophilic attack of carbanions on 0-linalyl-NN- dimethylhydroxylamine (25) in the presence of [PdCl,(PhCN),] proceeds regioselectively to give stabilized carbopalladiation products (26). Degradation of the complexes (26) by chlorotrimethylsilane results in formation of the organic products (27) in 55-75% yield.'* Me + [R'C(COR2)(COR3)]-% (25) R3 R' COR2 COR~COR2 +"1 (26) (27) R2L R ' R' (-Nil. X \/\Ni-iX R' + R CO,\N0+ (28) + 2R L R 1 (29) &-Unsaturated ketones may be prepared in moderate yield by the reaction of 2-pyridyl esters of carboxylic acids with (wally1)nickel halides in DMF at 25 "C. Mixtures of Pr-and cup-isomers (28) and (29)are usually obtained but crotylnickel 56 Y.Yamamoto H. Yatagai and K. Maruyama J. Chem. SOC.,Chem. Commun. 1980,835. 57 T. Itahara J. Chem. SOC.,Chem. Commun. 1980,49. '' K. Hirai N. Ishii H. Suzuki Y. Moro-oka and T. Ikawa Chem. Lett. 1979 11 13. 216 H. M. Colquhoun J. Holton and M. V. Twigg bromide and 2-pyridyl benzoate afford the &unsaturated ketone (28; R’ = Me R2 = Ph) exclusively (79% yield). Esters other than 2-pyridyl carboxylates fail to give useful amounts of ketones and the authors suggest that one-electron reduction of the ester to a radical anion may be a key step in the reacfi~n.’~ Symmetrical aromatic ketones are readily obtained on treating S-(2- pyridyl) aromatic thioates (30) with the nickel(0) complex [Ni(1,5-c8H&].The thioate esters (30) are available in high yield from the reaction of aromatic carboxylic acids with 2,2‘-dipyridyl disulphide and triphenylphosphine.60 In the presence of [Pd(PPh,),] as catalyst chlorodisilanes of the type Me Si2C16- (n = 2 3 or 4) add to buta-1,3-dienes61 and to ethyne,62 with scission of the Si-Si bond. These reactions are regio- and stereo-specific so that only 1,4-addition is observed with butadienes giving cis-but-2-enes [e.g. (31)] in 50-75% yield while cis-1,2-bis(chlorosilyl)ethenes [e.g. (32)] are formed exclusively though in only moderate yield in the reaction with ethyne. C1,MeSi fi m SiMeCl CIMezSi SiMe2C1 (31) (32) Synthesis involving Iron Carbony1s.-Alcohols derived from residues capable of forming stable carbanions are deoxygenated to the parent hydrocarbon in moderate yields by formation of the alkoxide ion (using potassium in toluene) and treatment with [Fe(C0)5] followed by a~idification.~ This reaction appears to proceed via nucleophilic attack of alkoxide ion on a carbonyl ligand loss of carbon dioxide and generation of a carbanion.Treatment of the reaction mixture with alkyl halide rather than its acidification affords the corresponding alkylated hydrocarbon. Synthetic applications of the [Fe(q’- C,H,)(CO),] moiety have been extended to the preparation of fused-ring p-lac tarn^.^^ Readily available hex-5-en-2-one is thus converted into 2-methylcarbopenam in good yield by a relatively short route (Scheme 8). A feature of this procedure is that for steric reasons only one of the stereoisomeric pyrrolidine complexes (33)forms a chelate complex.Consequently the final product is a single stereoisomer corresponding to that of the natural p-lactam antibiotics. Disodium tetracarbonylferrate continues to find new applications in organic chemistry. Acyl halides and epoxides react successively with this reagent to give 59 M. Onaka T. Goto and T. Mukaiyama Chem. Lett. 1979 1483. 60 T. Goto M. Onaka andT. Mukaiyama Chem. Lett. 1980,Sl. 61 H. Matsumoto K. Shono A. Wada I. Matsubara H. Watanabe and Y. Nagai J. Organomet. Chem. 1980,199,185. 62 H. Matsumoto I. Matsubara T. Kato K. Shono H. Watanabe and Y. Nagai J. Organomet. Chem. 1980,199,43. 63 H.Alper and M. Salisova Tetrahedron Lett. 1980 21 801. 64 S. R. Berryhill and M. Rosenblum J. Org. Chem. 1980 45 1984. Organometallic Chemistry -Part (i) The Transition Elements r n-(q-C H,)Fe(CO); (v-C H5)Fe(C0)2 (334 (33b) Me Reagents i NH,; ii BH,-; iii Ag,O Scheme 8 high yields of ap-unsaturated ketones (Scheme 9). The intermediate acyl tetra- carbonylferrate anion may also be generated by the action of a Grignard reagent with iron penta~arbonyl.~' 0 /-\ R'COCI R~CH-CH, Na2Fe(CO)4-Na'[(R'CO)Fe(C0)4]-R'COCH=CHR2 Scheme 9 Palladium Chemistry.-The conversion of ap-unsaturated carbonyl compounds into dienes usually leads to stereoisomeric mixtures but a novel palladium-catalysed reaction provides a method for stereoselective synthesis of dienes (Scheme R+ R2 R2 C0,H + H __* OAc -<R3 c0,-Scheme 10 The catalytic hydration of acrylonitrile can be achieved under mild conditions by using the palladium complex [Pd(X)(OH)(bipy)(H20)] (X = halide ace-tate or hydr~xide).~' Although the yields of acrylamide are low (-22%) high regioselectivity is achieved.65 M. Yamashita S. Yamamura M. Kurimoto and R. Suemitsu Chem. Lett. 1979 1067. 66 B. M. Trost and J. M. Fortunak J. Am. Chem. SOC.,1980,102,2841. 67 G. Villain Ph. Kalck and A. Gaset Tetrahedron Lett. 1980 21 2901. H.M. Colquhoun J. Holton and M. V. Twigg Palladium (0) complexes catalyse a 1,3-alkyl shift in alkylidenetetrahydrofurans giving cyclopentanones (34) in high yield.68 The generality of the reaction has been demonstrated for a variety of substituted furans and may find applications in prostaglandin and steroid synthesis.68 B. M. Trost T. A. Runge and L. N. Jungheim J. Am. Chem. SOC.,1980,102,2840.

ISSN:0069-3030    

DOI:10.1039/OC9807700203

出版商:RSC    

年代:1980

数据来源: RSC

摘要:

12 Organometallic Chemistry Part (ii) Main-Group Elements By J. L. WARDELL Department of Chemistry University of Aberdeen Meston Walk Old Aberdeen AB9 2UE 1 Introduction The powerful combination of a prolific research area and a keen commercial sense has resulted in Volume 200 of the Journal of Organometallic Chemistry appearing just sixteen years after the Journal's inception. To mark the occasion a special issue was produced of papers by twenty-two eminent chemists giving in the main personal accounts of their research. Several of these articles too many to itemize here are concerned with Main-Group compounds but the whole volume is well worth a look. The plenary lectures delivered at the Tenth International Organometallic Chemistry Conference at Dijon have also been printed.' These include the mechan- isms of the reactions between Grignard reagents and ketones,'" the role of electron transfer and charge transfer in organometallic reactions," reactive intermediates in the synthesis and chemistry of organo-silacycles," optically active organotin compounds,ld and nickel- and palladium-catalysed cross-couplings of organometal- lic reagents with organic halides." Review articles on silicon chemistry were concer- ned with synthetic applications of Me3SiX (X = CN I N3 or SMe),2" silylated synthons,2b and organosilicon chemistry in general.*' In addition a review concerned with the synthesis structures and vibrational spectra of methylmetal compounds has been p~blished.~ 2 Group1 Two new indicators 2,5-(Me0)2C6H3CH20H and (PhCH2)2C=NNHS02C6H4-~ -Me have been used to determine concentrations of organolithium c~mpounds.~ Several theoretical calculations have been carried out on methyl-lithium oligomers.' (a) E.C. Ashby Pure Appl. Chem. 1980,52,545;(b)J. K. Kochi ibid. p. 571;(c)T.J. Barton ibid. p. 615;(d)M. Gielen ibid. p. 657;(e)M. Kumada ibid. p. 669. * (a)W. C. Groutas and D. Felker Synthesis 1980,861;(b)L. Birkofer and 0.Stuhl Top. Cum Chem. 1980,88,33;(c) R. West and T. J. Barton J. Chem. Educ. 1980,57 165. 'E. Maslowsky Jr. Chem. SOC.Rev. 1980,9,25. M. R. Winkle J. M. Lansmger and R. C. Ronald J. Chem. SOC.,Chem. Commun. 1980 87; M.F. Lipton. C. M. Sorensen A. C. Sadler and R. H. Shapiro J. Orgunornet. Chem. 1980,186 155. ' (a)G.D. Graham S. Richtsmeier and D. A. Dixon,J. Am. Chem. SOC.,1980,102 5759; (6) G. D. Graham D. S. Marynick and W. N. Lipscomb ibid. p. 4572; (c) T. Clark J. Chandrasekhar and P. von R. Schleyer J. Chem. SOC.,Chem. Commun. 1980 672; (d)J. B. Collins and A. Streitwieser Jr. J. Comput. Chem. 1980 1,81. 219 220 J. L. Wardell An approximate M.O. calculation (PRDDO) indicated stable planar arrangements of lithium and carbon atoms for (MeLi) (2 < n < 6) in addition to a condensed tetramer (Tdsymmetry) and a hexamer (D3dsymmetry). An INDO treatment of 7Li-'3C coupling constants pointed to particularly large values of these constants for the MeLi monomer consistent with a covalent carbon-lithium bond. Ab initio calculations6 indicated involvement of the metal 2p orbital in the stabilization of linear singlet carbenes M-C-M and of the anions MCH2- and MCH2CH2- (M = Li or BeH).The anions MCH2- were suggested to be planar (C2"symmetry) and more stable than CH3- in contrast to the highly destabilized and pyramidal anion NaCH2-. Minimum-energy structures that were calculated from other studies were the distorted partially bridged structure (1) for C2H2Li2 in contrast to a classical structure for vinyl-lithium,' and the three structures (2) (3) and (4) for LiCH2CN of which the last two can be considered as an ion-pair (CH2Li'CN-) and a complex (CH2:LiCN) respectively.8 Racemization occurs during the formation of the organolithium compound from [2,2,6-2H3]cyclohexy1 bromide and lithium probably either on the surface of the lithium or during the lifetime of a short-lived radical ir~termediate.~ The cleavage reaction of alkoxy-substituted organotin compounds by RLi has been further studied." Organolithiums prepared by this route include LiCH=CHCH20Li Li(CH2)30Li and enantiomerically pure EtCHLiOCH20CH2Ph.While cleavage of Bu3SnCH20H by RLi does lead to a compound that is capable of hydroxymethyl- ating electrophiles," it was considered to be more complex e.g. (9,than LiCH20Li. Bu3SnCH20H + 2BuLi --+ ii ('CH,)" HCd -1 (6) IZ = 2-5 lC\ \J I The products of reaction of (cycloalkeny1)benzenes (6) with Bu'Li in the presence of THF or TMED were found to be polymers for n = 2 both those of allylic deprotonation and of addition to the double-bond [see reaction (l)]for n = 3 products of allylic deprotonation for n = 4 and finally for n = 5 of metallation of the ring." The rotational barriers of the aryl-C bonds in the compounds (7) (a) T.Clark H. Korner and P. von R. Schleyer Tetrahedron Lett. 1980 21 743; (6) A. Pross and L. Radom Aust. J. Chem. 1980,33,241;(c)W. W. Schoeller I. Chem. SOC.,Chem. Commun. 1980 124. Y. Apeloig T.Clark A. J. Kos E. D. Jemmis and P. von R. Schleyer Zsr. J. Chem. 1980 20,43. J. B. Moffat J. Chem. SOC.,Chem. Commun. 1980,1108. J. B. Lambert M. W. Majchrzak B. I. Rosen K. P. Steele and S. A. Oliver Isr. J. Chem. 1980 20 177. (a) W.C.Still and C. Sreekumar J. Am. Chem. SOC.,1980,102,1201;(6)S.D.Burke S. A. Shearouse D.J. Burch and R. W. Sutton Tefrahedron Lett. 1980,21,1285;(c)N.Meyer and D. Seebach Chem. Ber. 1980 113 1290. G.Fraenkel D.W. Estes and M. J. Geckle J. Organomet. Chem. 1980,185 147. Organometallic Chemistry -Part (ii) Main-Group Elements 22 1 Bu' Li + Pha + Bu'Li + . , .-' Ph Li+ Li + YoCzMe + Bu'Li +Y -CH2 CH But (7) which were prepared by the addition of Bu'Li to a-methylstyrenes [reaction (2)] and in p-MeC6H4CHC6H4SiMe~-p Li+(8) depend on the substitutents; e.g. at 255 K,the p-MeC6H4 ring in (8) rotates ca 200 times faster than the p-Me3SiC6& group i.e. there is more delocalization of the charge into the silylated ring.I2 An interesting intramolecular 1,4-migration of a Me3Si group occurs in 9,9-(Me3Si)2- 10-lithio-9,10-dihydroanthraceneto give 9,10-(Me3Si)2-9-lithio-9,10-dihydroan-thracene protonation of which provides the cis-product." Other rearrangements occur14 in the (Me3Si-substituted alky1)-lithiums Me3Si(CH2),Li in THF solution but not in Et20; e.g.reactions (3) and (4). Me3Si(CH&Li Me2PrSiCH2Li (3) Me,Si(CH2)5Li -Me,Si + MeLi + Me2(n-C5H,,)SiCH2Li (4) Metallations of 1,3-dithiolans (see Scheme 1)provide a complex range of prod- ucts in contrast to the simple 2-lithiation of 1,3-dithians.15 The lithiated 2-lithio-2- methyl-l,3-dithian-TMED complex crystallizes as a centrosymmetric dimer (9). Lithium bridging leads to a central ring in which the lithium is bonded equally strongly to carbon and to sulphur.16 "S) -* [RCH=S] + H,C=CHSLi HS BuLi yy/ lBUhRCH2SLi R(BuS)CHBu ,BuLiR(BuS)CHLi RCHSLi I Bu Scheme 1 Me n Me (9) l2 G.Fraenkel and M. J. Geckle J. Am. Chem. SOC.,1980,102,2869. l3 M.Daney R. Lapouyade B. Labrande and H. Bouas-Laurent Tetrahedron Lett. 1980,21,153. l4 A. Maercker M. Eckers and M. Passlack J. Organomet. Chem. 1980,186,193. Is S.R. Wilson G. M. Georgiadis H. N. Khatri and J. E. Bartmess J. Am. Chem. SOC.,1980,102 3577. R. Amstutz D. Seebach P. Seiler B. Schweizer and J. D. Dunitz Angew. Chem. Int. Ed. Engl. 1980,19,53. 222 J. L. Wardell High-field 13C n.m.r. spectroscopy of isotopically labelled CH3CHZl3CHz6Li in cyclopentane revealed the existence of hexamer octamer and nonamer units all undergoing rapid intra-aggregate C-Li bond exchanges.Above 250 K the hexamer is the predominant aggregate. Inter-aggregate exchanges also occur at higher temperat~res.~' For allyl-lithium a n-bridged structure rather than rapidly equilibrating a-bonded unsymmetrical structures was indicated from the 13C n.m.r. spectrum of [1-2H]allyl-lithium in THF using the Saunders isotope-perturbation met hod. l8 Solid PhCHLiS(O)Me obtained from lithiating PhCH2S(0)Me in THF reacts with methyl iodide vapour at 250°C to give one diastereoisomer of PhCHMeS(0)Me [(RS) and (SR)]; no selectivity is obtained from the reaction with H20 nor when liquid Me1 is used.lg 3 Group2 Reactions of atomic magnesium with MeX (X = C1 Br or I) in argon matrices and with a number of organic chlorides2' at 77K have been reported.From the i.r. and e.s.r. spectra the following steps were proposed for the organic chloride reaction Mg + RCl + RCl'Mg+ + RMgCl Mg + RCI + + MgCl' MgCl' + RCI (RXt + R' R' + Mg + RMg' RMgCl + R' (st = matrix-stabilized) The mechanisms of the more traditional Grignard formation in solution have been also considered.2' In general the rates of reaction of alkyl halides RX with magnesium are proportional to [RX] and to the surface area of the magnesium. For RI and for most RBr transport to the magnesium is overall rate-limiting while reactions with RCl are slower. Either (i) an initial transfer of an electron from Mg to RX or (ii) a collision of RX and Mg followed by extractions of halogen were possible critical steps. Specifically for the reaction of cyclopentyl bromide (10) in Et,O it was established that -d[(lO)]/dt is proportional not only to [(lo)] and the surface area of magnesium but also to the rate of stirring of the solution and it is inversely proportional to the viscosity.Only for the less reactive RX compounds such as Me3CCH2Br [but not (lo)] are the rates also dependent on the dielectric constant. " G. Fraenkel M. Heinrichs J. M. Hewitt B. M. Su and M. J. Geckle J. Am. Chem. SOC., 1980 102 3345. W. Neugebauer and P. von R. Schleyer J. Organomet. Chem. 1980 198 C1;M.Schlosser and M. Stahle Angew. Chem. Int. Ed. Engl. 1980 19,487. I9 J. F.Biellmann J. F. Blanzat and J. J. Wicens J. Am. Chem. SOC.,1980,102 2460. 2o B. S. Auk J. Am. Chem. SOC.,1980 102 3480; G.B.Sergeev V. V. Smirnov and V. V. Zagorskii J. Organomet. Chem. 1980 201 9. tI. R. Rogers G. L. Hill Y. Fujiwara R. J. Rogers H. L. Mitchell and G. M. Whitesides J Am. Chem. SOC.,1980,102 217; H. R. Rogers J. Deutch and G. M. Whitesides ibid. p. 226;H. R. Rogers R. J. Rogers H. L. Mitchell and G. M. Whitesides ibid. p. 231;J. J. Barber and G. M. Whitesides ibid. p. 239. -/ Organometallic Chemistry -Part (ii) Main-Group Elements 223 Hammett p values were found to be similar for the reactions between ArBr and Mg and between ArBr and Bu3SnH in EtzO (but not in THF). The rate-determining step of the reaction between ArBr and Mg in EtzO was one of the following (i) transfer of an electron to ArBr (ii) formation of Ar’ radical or less probably (iii) insertion of Mg into the Ar-Br bond.Reactions in THF and more polar solvents like the reactions between ArI and Mg even in Et20 are mass-transport-limited. At least 80% of (10) reacts with magnesium via free radicals.22 The reaction of (10) with magnesium produces a radical precursor to cyclopentylmagnesium bromide (1l),which is trapped by 2,2,6,6-tetramethylpiperidinenitroxyl(R2N0) as cyclo-C5H90NR2 even in the presence of Bu‘OH. The Crignard reagent (ll) on the other hand reacts preferentially with Bu‘OH. Evidence was also gained from the simultaneous reactions of RBr (e.g. R = Et) and of p-XC6H4CH2Br with Mg in THF-C6D6 that radicals are generated in the Grignard formation itself rather than in side-reactions such as Wurtz couplings or metal-halide exchange^.'^ The exchange reaction shown in reaction (3,which is catalysed by [(Cp)2TiC12] provides good yields of allyl-Grignards; styrene similarly reacts to give a-phenyl- ethylmagnesium [(Cp)2TiCI21 +PrMgBr -MeCH=CH + MeCH=CHCH,MgBr (5) CH,-PMe, / \ Li BH2 \ CH,-PdIe (12) A set of tetrahedral complexes (12; M = Be Mg Zn Cd or Hg) were prepared as shownz5 in reaction (6).The preparation and properties including structures in solution and in the solid state of bis-(2,4-pentadienyl)M (M = Be Mg or Zn) and related compounds have been investigated.26 The acyclic compounds are terminally a-bonded species under- going rapid 1,3-exchange in solution. The zinc compounds are the least thermally stable. The first example of electron-transfer in reactions of primary Grignard reagents with ArzCO has been rep~rted.’~ The cyclized product (13) in reaction (7) can only be obtained from a radical source.Cross-coupling reactions of alkenyl OH Ph CCH PhZCO ‘ QMe (7) (i) Et20 at r.t. Me (13) H2C=CH(CH,),CMe2CH,MgC1 (ii) H20 + H,C = CH (CH2),CMe,CH2CPh20H 22 L. M. Lawrence and G. M. Whitesides J. Am. Chem. SOC.,1980,102,2493. 23 B. J. Schaart C. Blomberg 0.S. Akkerman and F. Bickelhaupt Can. J. Chem. 1980,58,932. 24 F.Sato H. Ishikawa and M. Sato Tetrahedron Lert. 1980 21 365. ” H.Schmidbaur and G. Miiller Monarsh. Chem. 1980,111,1233. 26 H.Yasuda Y. Ohnuma A. Nakamura Y. Kai N. Yasuda and K. Kasai Bull. Chem. SOC.Jpn. 1980 53,1101;H.Yasuda M. Yamauchi A. Nakawara T.Sei Y. Kai N. Yasuoka and N. Kasai ibid. p. 1089. ” E.C.Ashby J. Bowers and R. Depriest Tefrcihedron Lett. 1980 21 3541. 224 J. L. Wardell aryl and allylic28 selenides with RMgX are catalysed by [NiC12{Ph2P(CH2)3PPh2}]; some rearrangements occur with ally1 selenides. A reactivity sequence of PhSeMe >> PhCl > PhSMe was established. The compounds {(Me3Si)3C}2M (14) (M = Zn or Cd) have appreciable thermal and chemical stability; e.g. (14; M = Zn) can be steam-distilled and it does not react with concentrated HCl or with Br2 in CCl,.29 Good yields of alkenes R'R2C=CH2 are obtained from the reaction of CH2Br2 R'R2C=0 and zinc in THF in the presence of TiC14 [R' = R2 = C8H17 or R'R2 = -(CH2)ll-etc.]; in a related manner (2)-and (E)-R'W2C=C(C1)CO2Me are produced from CC13C02Me R1R2C0 and Zn plus Et2AlCl in THF [for R' = Me R2 = Ph (2) (E) = 91 9].30 The mechanism of mercuriation of ArH by Hg(OCOCF3)2 in CF3C02H involves a rapidly formed r-complex which slowly converts to products [reaction (S)]."" ArH + Hg"(OCOCF3)2& ArH+ Hgx1(OCOCF3)2 ArHgOCOCF3 (8) Some values (at 25 "C) of K1/l mol-' and of k2/103 s-' for ArH in reaction (8) are 0.8 1 for PhCl 8.2 3.53 for PhH and 10 52 for PhMe.On standing changes in product composition of the PhMe reaction were monitored by 'H n.m.r. spec-trometry the equilibrium distribution at 18"C was established as 31 38 31 for 0- m- p-MeC6H4HgOCOCF3. Addition of CF3S03H to CF3C02H provides a much more effective medium.31b Acetoxymercuriation of PhCzCR (17) in HOAc occurs in a trans manner but is not regioselective [see reaction (9)] as by PhCZCR + Hg(OAc)z + Ph(AcO)C=C(HgOAc)R + Ph(AcOHg)C=C(OAc)R (9) (17) (15) (16) the ratios of products i.e.[(15)]:[(16)] for R of 3 for Me 5 for Et 11for Pr and 16.5 for Bun. Only (15; R = Pi) is obtained from (17; R = Pri) and no reaction occurs if R is But. Monocyclic peroxides have been produced from the peroxymer- curiation of dienes [reaction (lo)];"" a preparation of 2,6-dimethyl-18-crown-6 the reaction of (H2C=CHCH2)20 and tetraethylene glycol with Hg(OAc)2 followed by reductive demercuriation using NaBH4 and OH-. Replace- ment of mercury in vinyl-mercurials R'CH=CHMgX has been achieved34 by various functional groups including S02R2 OP(OR2)2 and (stereospecifically) by OAc and YR2 (Y = S Se or Te using R2XYR2; see Scheme 2 for the proposed mechanism).CH,H~OAC 28 H. Okamura M. Miura K. Kosugi and H. Takei Tetrahedron Lett. 1980,21 87. 29 C. Eaborn M. Retta and J. D. Smith J. Organomet. Chem. 1980 190 101. 30 K. Takai Y. Hotta K. Oshima and H. Nozaki Bull. Chem. SOC.Jpn. 1980 53 1698. 31 (a) C. W. Fung M. Khorramdel-Vahed R. J. Ransom and R. M. G. Roberts J. Chem. SOC.,Perkin Trans. 2,1980,267; (b)G. B. Deacon and M. F. O'Donoghue J. Organomet. Chem. 1980,194 C60. 32 S. Uemura H. Miyoshi and M. Okano J. Chem. SOC.,Perkin Trans. 1 1980 1098. 33 (a)A. J. Bloodworth and J. A. Khan J. Chem. SOC.,Perkin Trans. I 1980,2450 (6)A. J. Bloodworth D. J. Lapham and R. A. Savva J. Chem. SOC.,Chem. Commun.1980,925. 34 R. Clarock K. Oertle and K. M. Beatty J. Am. Chem. SOC.,1980,102 1966; J. Hershberger and G. A. Russell Synthesis 1980,475;J. Am. Chem. SOC.,1980,102 7603. Organometallic Chemistry -Part (ii) Main-Group Elements R2YYR2 2R2Y-H R'CH=CHHgX + R2Y.+ [R'CH-A-YR2 +R'CH=CHYR2 + HgX Agx 1 .HgX + (R2Y)2 + R2YHgX + R2Y* Scheme 2 4 Group3 Reactions of R3Al (R = Me or Et) or of R2AlCl with aza-aromatics (such as 2,2'-bipyridyl) and alkali metals lead to persistent free radicals e.g. (18);large 27Al coupling constants were measured.35 Treatment of PhCGC-CECPh with RzAICl (R = Me or Et) and lithium in ether at -25"C a tetrasubstituted product (19). Reactions of (19) that were studied were its hydrolysis to + RJAl % + NaAlR L L J .c PhC R2A1 AIR2 Li I I +PhC-CEC-CPh + I I R2Al AlR2 t t L L (19) (L PhCH=CHCH=CHPh and its dimerization to (20).Other organo-aluminium heterocycles were obtained as shown3' in Scheme 3. The complex formed from [Ni(aca~)~] and DiBAH catalyses the conjugate addition of R2AlCGCR (obtained from RCECLi and Me2AlCl) to ap-en~nes;~~ 3-alkynyl ketones are obtained on hydrolysis. Scheme 3 Trimethylsilylmethyl-indiumand -gallium compounds M{CH(SiMe3)2}3 (M = In or Ga) and Ga(CHzSiMe3) have been obtained from the organo-lithium or -magnesium compound and MC13. In contrast LiCHPh2 has been shown to reduce 3s W. Kairn J. Organomet. Chem. 1980 201 C5. 36 H. Hoberg and F. Aznar J. Organomet. Chem. 1980,193,155 161. 37 H.Hoberg and W.Richter J. Organomet. Chem. 1980,195,347. 38 J. Schwartz D. B. Cam R. T. Hansen and F. M. Dayrit J. Org. Chem. 1980.45 3053. 226 J. L. Wardell InC13 to indium. Sterically crowded In{CH(SiMe,),} (21) is the first reported monomeric trialkyl-indium.39 In addition to these M"' compounds some associated M' species have been prepared; see reaction (11).Examples of these hydrocarbon- soluble compounds are [KGa(CH2SiMe3)2] (22) and [NaGa(CH2SiMe3)2]3; ether-ates (via complexation with the alkali metal) were also produ~ed.~' PhH Ga(CH2SiMe3)3+ MH +MGa'(CH2SiMe3)2+ SiMe4 (11) DME (22) R = Me3SiCH2 The reactivity of PhR towards Tl"' (OCOCF3)3 in CF3C02H was in the sequence R = But > Me > H. The reversible thalliations (whose progress was followed by n.m.r.) are ca 10-100 times slower than mercuriations.As in mercuriations a large primary isotope effect was found (ca 5.0).41Thalliation using TI"'203 in C13CC02H was also st~died,~' at 70°C. In addition to all the usual replacement reactions ArC6H4Tl"'(OCOCC13)2 was shown to react with H2C=CMeCN in the presence of PdC12 and NaOAc to give H2C=C(CH2Ar)CN and (2)-and (E)-ArCH=C(CN)Me. A synthesis of esters from ArH utilizes the PdCl,-catalysed carbonylation of ArTl(OCOCF3)2 (Scheme 4).No additional oxidant is required to oxidize Pd" to Pd" since the T1"' that is present does this.43 A new hydrodethalliation agent is N-benzyl-1,4-dihydronicotinamide(Scheme 5);its use unlike that of NaBH4 does ArH A ArTl(02CCF3)2-% ArCOzMe Reagents i Tl(O,CCF,), CF,CO,H; ii CO (1atm) LiCl MgO MeOH PdCl Scheme 4 RCH=CH2 A RCH(OMe)CH2Tl(OAc)2 RCH(OMe)CH3 & ii iv RCH(0Me)CHzOH Reagents i Tl(OAc), MeOH; ii N-benzyl-1,4-dihydronicotinamide; iii MeOH N,;iv MeOH 0 Scheme 5 not lead to any regenerated alkene amongst the In the presence of oxygen PhCH(OMe)CH20H is formed instead.The radical PhCH(0Me)CH; can be trapped. The TI-C bond in RCH(OM~)CHDTI(OAC)~ (23) can be cleaved by Cu'X in MeCN in both ionic and radical routes; the stereochemistry of the products RCH(0Me)CHDX from threo-(23) depends on R and the temperat~re.~' 39 A. J. Carty M. J. S. Gynane M. F. Lappert S. J. Miles A. Singh and N. J. Taylor Inorg. Chem. 1980,19,3637; 0.T. Bleachley and R. G. Simmons,ibid.p. 1021. 40 0.T. Bleachley and R. G. Simmons Inorg. Chem. 1980,19,3042. 41 R. M. G.Roberts Tetrahedron 1980 36 3281. 42 S. Uemura H.Miyoshi M. Wakasugi M. Okano 0.Itoh T. Izumi and K. Ichikawa Bull. Chem. SOC.Jpn. 1980,53 553. 43 R. C. Larock and C. A. Fellows J. Org. Chem. 1980,45,363. 44 H.Kurosawa H. Okada and M. Yasuda Tetrahedron Lett. 1980 21 959. 4s J. E.Backvall M. U. Ahmad S. Uemura A. Toshimitsu and T. Kawamura Tetrahedron Lett. 1980 21 2283. Organometallic Chemistry -Part (ii) Main-Group Elements 5 Group4 Many reactions of dimethylsilylene (Me2Si; usually generated photolytically from Mel2%,) with oxygen-containing substrates e.g. aUp -unsaturated epoxides and oxetans proceed via 1,2-mitterionic complex intermediate^^^ (e.g.Scheme 6). SiMe, H + Me,Si % MeCH=CHCH,OSiMe,H Me -&vJ Me H SiMe, I Me Me Scheme 6 Reactions af Me2Si are more selective in ethereal solution than in hydrocarbons as a result of its complexation with the ether to produce a less reactive species; e.g. the relative reactivities towards EtOH and Bu‘OH (giving Me2SiHOR) are 1.8,4.7 and 9.6 in cyclohexane Et,O and THF re~pectively.~’ Addition of Me2Si to 2-butenes occurs stereospecifically; as the resulting silirans are cleaved by MeOD stereospecifically one (MeOSiMe2)CHMeCHDMe. diastereoisomer is produced from each 2-butene isomer.48 The addition of Me2Si to alkenes has been to be reversible on heafing; e.g. hexamethylsiliran (24) decomposes at 75°C to Me2C=CMe2 and Me2Si which can combine with (24) to provide octamethyl-1,2- disilacyclobutane.The reaction of MePhSi (generated photolytically from Me3SiSiPhMeSiMe3) with the conjugated diene H2C=CMeCMe=CH2 initially provides products from 1,2-addition e.g. vinylsiliran (25) from 1,4-addition e.g. 1-silacyclopent-3-ene (26) and from insertionSo into the C-H bond of the methyl group e.g. (27). Me H2C \ Si + /si -&eMe+ Me0Me Ph /\ MeSiH Ph Me I Ph H2C=CMeCMe=CH2 (27) The radicals Ar3M’ (Ar = 2,6-Me2C6H3 or 2,4,6-Me3C6H2; M = si Ge Of Sn) have been directly detected when Ar3MCl are irradiated in the presence of (RNCH2CH2NRC+j=2 Whereas Ar3Ge‘ have (R = Me or Et) in toluene ~olution.~* 46 D. Tzeng and W. P. Weber J. Am. Chem. SOC.,1980,102 1451; T.Y. Yang and W. P. Weber ibid. p. 1641. 47 K. P. Steele and W. P. Weber J. Am. Chem. Soc. 1980,102 6095. 48 V. J. Tortorelli and M. Jones J. Am. Chem. SOC.,1980,102 1425. 49 D. Seyferth D. C. Annarelli S. C. Vick and D. P. Duncan J. Organomet. Chem. 1980,201,179. 50 M. Ishikawa K. I. Nakagawa R. Enoxida and H. Kumada J. Organomet. Chem. 1980,201,151. ’’ M. J. S. Gynane M. F. Lappert P. I. Riley P. RiviBre and M. RiviBre-Baudet J. Organomet. Chem. 1980 202 5. 228 J. L. Wardell appreciable thermal stability (tl is several hours at 20 "C) both Ar3Si' and Ar3Sn' are only detected under constant irradiation at -20 "C. The two competing reac- tions of Me3Si' [see reactions (12) and (13)] were investigated in three kdi Me3SiH + [H2C=SiMe2] (12) 2Me3Si' 57Me3SiSiMe3 (13) krccomb These studies following different routes to Me3Si' [namely from Me3SiH on mercury-sensitized photolysis (gas-phase reaction) and on reaction with Bu'O' (in the liquid phase) and also from photolysis of (Me3Si)2Hg] all proved the occurrence of the disproportionation step but did not agree on kdisp:krecomb values.An electron- diffraction study of Me2Si=CH2 (dimethylsilaethylene; generated via pyrolysis of 1,l-dimethyl-1 -silacyclobutane) has been made;53 bond lengths (re values) were calculated to be 1.83 f 0.04 (Si=C) and 1.91 f 0.02A (Si-C). Two separate Russian groups have reported54" the i.r. spectra of Me2Si=CH2 and (CD3),Si=CH2 in argon matrices at low temperatures; the v(C=Si) stretch was given as 1001 and 1003.5 cm-'.The i.r. and mass spectra of MeHSi=CH2 H2Si=CH2 [v(Si-C) 1155 cm-'I and D2Si=CH2 were also studied; it was quoted that H2Si=CH2 can be stored at -196 "C for several months.54b Prochiral silaethylenes PhR'Si=CH2 (R' = Et or Bu') produced by irradiatiod5 of 1-R-1-phenyl-1-silacyclobutaneat 2537& react with chiral alcohols (R20H) to give unequal amounts of diastereoisomeric pairs of R'PhSiHOR2; this was reported to be the first example of asymmetric induction involving a trigonal silicon species to be observed at a silicon centre. As well as routes to silaethylenes from silacyclobutanes the following have been employed (i) the reaction56 of H2C=CHSiMe2C1 and Bu'Li in hexane (forms Bu'CH2CH=SiMez in contrast to the stable organolithium adduct Bu'CH,CHLiSiMe2C1 which forms in THF) and (ii) (Me3Si)2C=SiPh2 (28) from thermolysis of (Me3Si)3CSiPh2F at 450 "C;the silaethylene (28) takes part in rapid equilibriation prior to internal cyclizations," involving addition of C6H4-H to Si=C bonds as shown in Scheme 7.Flash therrnolysi~~~ of (29; Y = CH2CH=CH2 R = H or Me) or of (29; Y = OAc R = H) and co-deposition of the products (Me3Si)(Ph2MeSi)C=SiMe2$(Me3Si)(PhMe2Si)C=SiMePh Jt .lt (Me3Si)2C=SiPh2 (Me2PhSi)2C=SiMe2 (28) Scheme 7 52 S.K. Tokach and R. D. Koob J. Am. Chem. SOC.,1980,102 376; B. J. Cornett K. Y. Choo and P. P. Gaspar ibid. p. 377; L. Gammie I. Safarik 0.P. Strausz R. Roberge and C. Sandor ibid. p. 378. " P. G. Mahafly R. Gutowsky and L. K. Montgomery J.Am. Chem. Soc. 1980,102,2854. 54 (a) 0.M. Nefedov A. K. Maltsev V. N. Khamashesku and V. A. Korolev J. Organomet. Chem. 1980 201 123; L. E.Gusel'nikov V. V. Volkova V. G. Avakyan and N. S. Nametkin ibid. p. 137; (6) N. Auner and J. Grobe Z. Anorg. Allg. Chem. 1979,459 15. " G. Bertrand J. Dubac P. Mazerolles and J. Amchelle J. Chem. SOC.,Chem. Commun. 1980,382. 56 P.R.Jones T. F. D. Lim and R. A. Pierce J. Am. Chem. SOC.,1980,102,4970. 57 C.Eaborn D. A. R. Harper P. B. Hitchcock S. P. Hopper K. D. Safa S. S. Washburne and D. R. M. Walton J. Organomet. Chem. 1980 186,309. G. Maier G. Mihm and H. P. Reisenauer Angew. Chem. Int. Ed. Engl. 1980 19 52; B. Solouki D. Rosmus H. Bock and G. Maier ibid. p. 51; H. Bock R. A. Bowling B. Solouki T. J. Barton and G.T. Burns J. Am. Chem. Soc. 1980 102 429; C.L.Kreil 0.L. Chapman G. T. Burns and T. J. Barton ibid. p. 841. Organometallic Chemistry -Part (ii) Main-Group Elements with argon on a nearby spectral window at low temperatures was carried out. The spectral data (u.v. i.r. and mass) indicated5' the presence of (30). In addition the photoelectron spectra were also obtained after generating (30) close to the ioniz- ation region of the spectrometer. The ionization potentials that were obtained were 8.0 and 9.3 eV for (30; R = H) and 7.7 and 9.16 eV for (30; R = Me). Trapping of (30; R = Me) by MeOH its dimerization and the photoconversion of (30; R = H) into Dewar-silabenzene were also reported. On heating (Me3Si)2C=C(SiMe3)2(31) in decalin solution at 150"C the e.s.r.spectrum of RH (Me3Si)2C=C(SiMe3)2 $(Me3Si),C-C(SiMe3)~ -(Me3Si)2CH-C(SiMe3) (31) (32) (32) was ~bserved.'~ An unusually rapid (2)-(E)isomerization of the tetrasilyl- ated ethylene (PhMe2Si)(Me3Si)C=C(SiMe2Ph)(SiMe3) occurs in THF with an activation energy of ca 30 kcalmol-l; at 68"C = 3.7 x lOP4s-' and K[(E)/(Z)] The = 0.6. The isomerization could also be induced phot~chemically.~~ isomerization of the readily available (2)-RCH=CHSiMe3 compounds to the (E)-isomers also occurs on U.V. irradiation in the presence of NBS and pyridine.60" Another new route to (E)-Me,Si-substituted alkenes is illustrated in reaction (14)?Ob (Me3Si)3Al+ HCECR -+ (E)-Me3SiCH=CHR (14) (R=aryl or CH20H) The cuprate (MezPhSi)&uLi*LiCN prepared from Ph'MeSiLi and BuCN has been used6'" in the synthesis of various (alkeny1)silanes (see Scheme 8); addition of the cuprate (Me3Sn)(PhS)CuLi to cup-acetylenic esters has also been reported; some control of the stereochemistry of the products R'(Me3Sn)C=CHC02R2 can be achieved.61b cu ii X \ /SiMe2Ph ' \ PMezPh (Me2PhSi)2CuLi.LiCN -P c=c /c=c\ /\ R H R H Reagents i RCECH; ii X' = H' or X-Y = Me-I I, etc.Scheme 8 Direct routes from toluene and m-xylene to 2,5-(Me3Si)2-toluenes and -m-xylenes (33)are possible6' by utilizing the sequence (i) treatment with Me3SiC1 and lithium in THF [which gives 2,5-R2-2,5-dihydrotolueneand 2,5-R2-m-xylene (34) 59 H. Sakurai H. Tobita M. Kira and Y. Nakadaira Angew. Chem. Int. Ed. Engl. 1980,19 620.6o (a) G. Zweifel and H. P. On Synthesis 1980 803; (b) G. Altnau L. Rosch F. Bohlmann and M. Lomitz Tetrahedron Lett. 1980 21 4069. 61 (a) I. Fleming and F. Roessler J. Chem. SOC.,Chem. Commun. 1980 276; (6) E. Piers and H. E. Morton J. Org. Chem. 1980 45,4263. 62 M. Laguerre J. Dunogues and R. Calas Tetrahedron Lett. 1980 21 831; G. Felix M. Laguerre J. Dunogues. and R. Calas J. Chem. Res. (S) 1980 236. 230 J. L. Wardell (R = Me3Si)] followed by (ii) oxidation e.g. by air. Either (33) or (34) can be used as regiospecific precursors of other functional groups; e.g. (34) as a source of 2,s -(MeC0)2 derivatives. Germaethylenes (or germene~)~~ e.g. Ph2Ge=CHR1 (prepared from Ph2Ge and diazomethanes R1CHN2) have been trapped by MeOH [as Ph2Ge(OMe)CH2R1)] by R2CH0 and by PhNO (see Scheme 9).Diphenylger-Ph2Ge-CHR [Ph2Ge=CHR] + PhNO __* I I -[Ph2GeO] + PhN=CHR 0-NPh Scheme 9 mylene (Ph,Ge:) was obtained from Ph2GeClH and excess NEt3. Dimethylgermyl- ene has been prepared by two thermoly~es,~~ i.e. (i) of Me3GeGeMe2H at 250°C and (ii) of the 7,7-dimethyl-7-germanorbornadienes(35) (see Scheme 10)-a route used previously for stannylenes; r4 = 0.67 and 120 h at 70 "C for (35; R = H) and (35 ;R = Me) respectively. Dehydrobromination of 1,4-di-t-butyl-1-bromo-1-germacyclohexa-2,4-diene,using Bu'Li or LiNPri2 produces transient 1,4-di-t- butyl-1 -germabenzene which will dimerize unless intercepted (e.g. by dienes in Diels-Alder reaction^).^^ Me Me \/ Ph Ph R4 + Me,Ge Ph R (35) R = MeorH Reagents i R,benzyne; ii heat Scheme 10 Partial resolution66 has been achieved of tri(organo)germanium hydrides and chlorides as well as of tetra(organo)tins e.g.Me(neophyl)Ph(Ph3C)Sn by inclusion chromatography on microcrystalline cellulose triacetate. The "J(Sn-D) coupling constants easily deduced from the triplet observed by l19Sn Fourier-transform n.m.r. spectroscopy with proton decoupling have been used for the direct identification of isomeric and diastereoisomeric organotin corn pound^.^^ Reactions of allyltin compounds have continued to find use in organic syntheses; e.g. the Pd"-catalysed cross-coupling6'" of allyltin with ally1 bromides or acetates and the erythro-selective addition of crotyltin,68b either (E)or (Z),to aldehydes [reaction (1 5)].This reaction contrasts with the rhreo-selective addition of (E)-MeCH=CHCH2BR13 Li' to R2CH0.68' The tran~formation~~ of -CH=C(SnMe3)-into -CH=C(N02)- in cyclic derivatives has been made using C(NOZ)4 in DMSO at 25 "C. 63 P. RiviCre A. Castel and J. SatgC J. Am. Chem. SOC., 1980 102,5413. E. C. L. Ma D. P. Paquin and P. P. Gaspar J. Chem. SOC.,Chem. Commun. 1980 381; W. P. Neumann and M. Schriever Tetrahedron Lett. 1980,21,3273. G. Mark1 and D. Rudnick Tetrahedron Lett. 1980 21 1405. 66 I. van den Eynde and M. Gielen J. Organornet. Chem. 1980,198,(255. 67 J. P. Quintard M. Dequeil-Castaing G. Dumartin A. Rahm and M. Pereyre J. Chem. SOC., Chem. Commun. 1980,1004. 68 (ti) J. Godschalx and J. K. Stille Tetrahedron Lett.1980 21 2599; B.M.Trost and E. Keinan ibid. p. 2595;(6) Y.Yamamoto H. Yatagai Y. Naruta and K. Maruyama J. Am. Chem. SOC., 1980 102 7107;(c) Y.Yamamoto H. Yatagai and K. Maruyama J. Chem. SOC., Chem. Commun. 1980,1072. 69 E. J. Corey and H. Estreicher Tetrahedron Lett. 1980 21 1113. Organometallic Chemistry -Part (ii) Main-Group Elements 231 OH + R2CH0 (i) BF,. CHzClz R~pp *SnR13 il (ii) H,O+ (R2 = Me or Ph) Me [ >90% erythro] The photochemically induced iodinolysis of tetra(alky1)tins (36) with iodine in CCl solution is a radical chain process with a long chain length.70 The homolytic substitution (SH2)is a two-step process (Scheme 11)in which the activation process (fast) R4Sn + I' [R4Sn+ I-] -R3SnI + R' Scheme 11 is an electron transfer having a similar selectivity to that shown in the reaction of (36) with IrCls2-.Reactions with molecular halogens and with HgC12 involve charge-transfer mechanisms the rate-determining step being the unimolecular decay of the charge-transfer complex by transfer of an electron from &Sn to the electrophile. Rate constants for other electron-transfer reactions of R4Sn (as well as of %Pb and R2Hg) with (NC),C=C(CN) and Fell1 compounds have been discussed in terms of inner-sphere and outer-sphere mechanism^.^^ Alk~ltin-mediated~l carbo-cyclizations[e.g. reaction (16)] have been carried out. SnMe 6 Group5 The persistent radical [(Me3Si),CHI2As' (ti = 10 d at 300 K) was obtained by U.V. irradiation of [(Me3Si)2CH]2AsC1 in the presence of the electron-rich olefin (Et16CH2CH2NEt-d=)=2.72 Further compounds containing isolated As=C bonds have been obtained (Scheme 12); on irradiation (37)forms a dimer.73 Organobis- muth compounds have been used in organic synthesis; e.g.Ph5Br will o-phenylate phenols and 6-phenyl-2,6-dimethylcyclohexa-2,4-dieneis formed with 2,6-Me2C6H30H. In addition Ar3BiV carboxylates oxidize glycols and allylic RAs(SiMe,) RAs(SiMe3)COBu' -B RAs=C(OSiMe3)Bu' R = Me But Ph or o-Me3SiOC6H4 (37) Scheme 12 70 S.Fukuzumi and J. K. Kochi J. Org. Chem. 1980,45,2654;J. Am. Chem. SOC.,1980 102 2141; S.Fukuzumi C. L. Wong and J. K. Kochi ibid. p. 2928;S.Fukuzumi and J. K. Kochi J. Phys. Chem. 1980,842246,2254;Inorg. Chem. 1980,19,3022;J. Am. Chem.SOC.,1980,102,7290. 71 T. L. MacDonald and S. Mahalingam J. Am. Chem. SOC.,1980,102,2113. 72 M. J. S.Gynane A. Hudson M. F. Lappert P. R. Power and H. Goldwhite J. Chem. SOC.,Dalton Trans. 1980 2428. 73 G. Becker and G. Gutekunst Z. Anorg. Allg. Chem. 1980,470,131 144;J. Heinicke B. Raap and A. Tzschach J. Organomet. Chem. 1980,186 39. '' D. H. R. Barton J. C. Blazejewski B. Charpiot D. J. Lester W. B. Motherwell and M. T. B. Papoula J. Chem. SOC.,Chem. Commun. 1980 827; D.H. R.Barton D. J. Lester W. B. Motherwell and M. T. B. Papoula ibid. p. 246.

ISSN:0069-3030    

DOI:10.1039/OC9807700219

出版商:RSC    

年代:1980

数据来源: RSC

摘要:

13 Organosulphur Organoselenium and Organotel lu rium Chemistry By S. V. LEY Department of Chemistry Imperial College of Science and Technology London SW7 2AY Introduction.-The author has been set the difficult task of highlighting the past four years’ literature on sulphur selenium and tellurium chemistry; consequently this Report must be highly selective! Emphasis is placed on synthetic applications of organo-sulphur -selenium and -tellurium compounds rather than on novelty of structure or preparation although some of the newer preparative methods are covered. Organosulphur chemistry continues to be of importance both in developing new synthetic methodology and in the preparation of useful sulphur-containing heterocyclic systems. On the other hand the toxicity of organoselenium compounds has meant that they are by and large only used as reagents.Despite this limitation their advan- tages particularly in their achieving synthetic transformation where more conven- tional methods are often poor can be impressive. The enormous growth in literature of organoselenium chemistry over the past seven years is some indication of its synthetic utility. By comparison organotellurium chemistry has developed much more slowly and reflects to some extent a lack of appreciation of how different the more metallic tellurium species are compared with both sulphur and selenium compounds and also a reluctance to use elements which have historically had bad reputations. Several excellent recent reviews on organo-sulphur,’ -selenium,’b*1e*2 and telluriuml b,l e2e.3 chemistry are now available.(a)E. Block ‘Reactions of Organosulfur Compounds’ Academic Press London 1978; (b)‘Compre-hensive Organic Chemistry’ Vol. 3 Part 11 ed. D. N. Jones Pergamon Press Oxford 1979; (c) L. Field Synthesis 1978,713;(d)‘Organic Chemistry of Sulphur’ ed. S. Oae Plenum Press New York 1977; (e) ‘Organic Compounds of Sulphur Selenium and Tellurium’ ed. D. R. Hogg (Specialist Periodical Reports) The Chemical Society London 1979 Vol. 5 and previous volumes and references therein; (fl B. M. Trost Acc. Chem. Res. 1978 11 453; (g) R. Mayer 2.Chem. 1976 16 260; (h) ‘Themen der Chemie des Schwefels’ ed. K. Mass Huethig Heidelberg 1975; (i) S. Sharma Synrhesis 1978 803. * (a)‘Organic Selenium Compounds Their Chemistry and Biology’ ed.D. L. Klayman and W. H. H. Gunther Wiley London 1973; (6)D. L. J. Clive Aldrichimica Acta 1978 11 43 and Tetrahedron 1978 34 1049; (c) H. J. Reich Ace. Chem. Res. 1979 12 22 and ‘Oxidation in Organic Chemistry’ Part C Academic Press New York 1978; (d)K. B. Sharpless K. M. Gordon R. F. Lauer D. W. Patrick S. P. Singer and M. W. Young Chem. Scr. Part A 1975,8,9;(e)J. Martens and K. Praefcke J. Organomet. Chem. 1980,198,321. K. J. Irgolic (a) ‘The Organic Chemistry of Tellurium’ Gordon and Breach New York 1974; (b)J. Organomet. Chem. 1975 103,91; (c) ibid. 1977 130,411; (d)ibid. 1978 158 235; (e)ibid. 1978 158 267; (f) ibid. 1980 189 65; (g) ibid. 1980 203 367. 233 234 S. V.Ley 1 Organosulphur Chemistry Su1phides.-The use of sulphides as chemical control elements in synthesis continues to play a major role in research.Much of the chemistry results from carbanions Q to the stabilizing thio moiety. For example the anion of (phenyl-thiomethy1)trimethylsilanecan be alkylated with halide~,4*~ epoxides; or amides.6 The beauty of this as a reagent derives from the fact that after oxidation by m-chloroperbenzoic acid (MCPBA) and sila-Pummerer rearrangement aldehydes can be unmasked under unusually mild conditions (Scheme 1). Br Reagents i THF at 0 "C; ii MCPBA iii H20 Scheme 1 Additional stabilization of the Q -thio-carbanions by electron-withdrawing groups has also found numerous applications. Thio-substituted acetonitrile carbanions add conjugatively to enones,' while dianions of (pheny1thio)propionic acid have been used in the synthesis of the butenolide antibiotic metabolite lepiochlorin.' In an elegant synthesis of the ionophore A-23 187 Evans employed a phenylthiohydrazone carbanion as a butanone equivalent; this was regiospecifically alkylated with a chiral i~dide.~ A new synthesis of p -1actams involves bis-alkylation of an Q -thioacetamide dianion by methylene iodide." The use of a-thio-carbanions that are additionally stabilized by a carbonyl group is common." An interesting application'* to synthesis of macrolide rings has been reported and it is outlined in Scheme 2.SPh I Reagents i Na[N(SiMe,),]; ii Raney nickel Scheme 2 P. J. Kocienski Tetrahedron Lett. 1980 21 1559.'D. J. Ager and R. C. Cookson Tetrahedron Lett. 1980 21 1677. G. T. Agawa M. Ishikawa M. Komatsu and Y. Ohshiro Chem. Lett. 1980,335. N. Wang S. Su,and L. Tsai Tetrahedron Lett. 1979 1121. J. R. Donaubauer and T. C. McMorris Tetrahedron Lett. 1980 21 2771. D. A. Evans C. E. Sacks W. A. Kleschick and T. R. Taber J. Am. Chem. SOC.,1979,101,6789. lo K. Hirai and Y. Iwano Tetrahedron Lett. 1979 2031. l1 B. M. Trost Chem. Rev. 1978,78 363. l2 T. Takahashi S. Hashiguchi K. Kasuga and J. Tsuji J. Am. Chem. SOC.,1978 100,7424. Organosulphur Organoselenium and Organotellurium Chemistry 235 Unsaturated sulphides are becoming popular in synthesis. Phenylthioacetylene reacts with sodium derivatives of allylic alcohols to give adducts which after oxidation and pyrolysis afford a new synthesis of 2,4-dienals.l3 Allenyl sulphides can be used to prepare ap-unsaturated ket~nes.'~ a-Lithiovinyl phenyl sulphide reacts with a series of electrophiles to give dithio- thioseleno- thiosilyl- and thios tannyl- keten ace tals.' 1-Nitro-1 -phenylthiopropene has recently been recommended as a new reagent for synthesis of 3-methylfurans16 (Scheme 3). d,+ jJJ=-T-sph% JO2L Reagents i KF; ii NaIO,; iii CCI, heat Scheme 3 The use of hetero-substituted butadienes in the Diels-Alder reaction is attractive as the reactions proceed with high regioselectivity at lower temperatures. In a detailed study of 2-alkoxy(or -acyloxy)-3-alkylthio(or -arylthio)-butadienes sul- phur was shown to be the regio-control element in the Diels-Alder reaction with a variety of dien0phi1es.l~ The products of the reactions were useful for further transformations (Scheme 4).Similar 1,4-disubstituted 1,3-dienes have also been investigated." MeOr + p-Mead 032 --+ ii,iii PhS \ PhS PhS iv*YJ "x" Carvone Reagents i heat (neat); ii Wittig reagents; iii THF HCl; iv NaH MeI; v MCPBA heat Scheme 4 An efficient regiospecific 1,2-transposition of a carbonyl group involving a one-pot conversion of a ketone tosylhydrazone into an enol thioether should find applications.l9 A useful a-methylenation procedure for lactones esters,20 and ketones21 has been reported; the key step involves alkylation of intermediate regiospecific l3 R. C. Cookson and R. Gopalan J. Chem. SOC.,Chem.Commun. 1978,924. '* R. C. Cookson and P. J. Parsons J. Chem. SOC.,Chem. Commun. 1978,822. lS B. Harirchian and P. Magnus J. Chem. SOC.,Chem. Commun. 1977,522. l6 M. Miyashita T. Kumazawa and A. Yoshikoshi J. Chem. SOC., Chem. Commun. 1978,362. l7 B. M. Trost W. C. Vladuchick and A. J. Bridges J. Am. Chem. SOC.,1980,102,3554. '* B. M. Trost S. A. Godleski and J. Ippen J. Org. Chem. 1978,43 4559. l9 T. Nakai and T. Mimura Tetrahedron Lett. 1979,531. 2o I. Paterson and I. Fleming Tetrahedron Lett. 1979 993. I. Paterson and I. Fleming Tetrahedron Lett. 1979,995. 236 S. V.Ley Reagents i Me,SiCl Et,N DMF at 130“C; ii PhSCH,Cl TiCl,; iii NaIO, heat; iv LiNPr’,; v Me,SiCl Scheme 5 trimethylsilyl enolates with chloromethyl phenyl sulphide in the presence of Lewis acids (Scheme 5).Sulphenyl Halides.-Various new methods of preparation of sulphenyl halides have appeared such as chlorinolysis of thiirans” or halogenation of thiols with N-chloros~ccinimide.~~ This last method which was a modification of the original Harpp pr~cedure,’~ led to an improvement in the chlorosulphenylation reaction of olefins. The adducts of these reactions could be smoothly dehydrohalogenated using DBU (1,5-diazabicyclo[5.4.0]undec-5-ene)as a base. The addition of sul- phenyl halides to unsaturated systems has been reviewed.*’ Recent uses of sulphenyl halides in synthesis include the addition to vinyltrimethylsilane to afford a range of vinyl sulphides which were useful as two-carbon building blocks,26 and for sulphenylating various amino-cephalosporins and -penicillins which led to a novel synthesis of methoxylated derivatives via intermediate sulphenimines (Scheme 6).” H RS H Me0 H Reagents i RSCl (3 equivalents) propylene oxide; ii PPh3 silica gel; iii Hg” MeOH Scheme 6 Adducts of aminosulphenyl halides with alkenes react with lithium aluminium hydride at low temperature to form episulphides upon work-up.28 Thioaceta1s.-The concept of Umpolung reactivity is now well understood and is frequently applied in synthesis,” the use of dithian carbanions to act as acyl anion equivalents being the most common appli~ation.~’ It is very appropriate to illustrate 22 P.A. Gurbanov M. M. Movsumzade M. A. Seidov and G. K. Khodzhaev Azerb. Khim. Zh. 1977 61 (Chem.Abstr. 1978 88 37 190). 23 P.B. Hopkins and P. L. Fuchs J. Org. Chem. 1978,43 1208. 24 D. N. Harpp and P. Mathiaparanam J. Org. Chem. 1972 37 1367. 25 L. Rasteikiene D. Greiciute M. G. Linkova and I. L. Knunyants Usp. Khim. 1977,46 1041. 26 F. Cooke R. Moerck J. Schwindeman and P. Magnus J. Org. Chem. 1980,45,1046. 27 E. M. Gordon H. W. Chang C. M. Cimarusti B. Toeplitz and J. Z. Gougoutas J. Am. Chem. Soc. 1980,102,1690. 28 M. U. Bombala and S.V. Ley J. Chem. SOC., Perkin Trans. 1 1979 3013. 29 (a)D. Seebach and D. Enders Angew. Chem. Int. Ed. Engl. 1975 14 15; (6)U. Schollkopf ibid. 1977 16,339; (c) 0. W. Lever Jr. Tetrahedron 1976 32 1943; (d) D. Seebach Angew. Chem. Int. Ed. Engl. 1979 18,239. 30 B.-T. Grobel and D. Seebach Synrhesis 1977 357.Organosulphur Organoselenium and Organotellurium Chemistry 237 their use with a recent example from the Corey group in which the coupling of two important fragments was accomplished and the product was later used in maytansenoid synthesis (Scheme 7).31 MEM = B-methoxyethoxymethyl Scheme 7 Other groups have studied bis(ary1thio)acetal carbanions. They can be used to prepare cyclopropanoid compounds by intramolecular cyclization3* or can be added to ketones and aldehydes in the normal way.33 The hydroxy-thioacetal products of this latter reaction undergo further useful synthetic transformations. Rearrangement of p-hydroxydithians using KH in HMPA34 or P~(OAC)~,~’*~~ have been reported. With Pb(OAc)s oxidative seco-rearrangement takes place to give cyclic thioesters; upon reaction with various cuprates followed by oxidative syn-elimination these afford enones (Scheme 8).36 Various new methods for the conversion of thioacetals into the corresponding carbonyl derivatives now exist all of which claim some advantage over conventional meth~dology.~~ Unsaturated 1,3-dithioians can be reductively silylated to give 31 (a) E.J. Corey L. 0. Weigel A. R. Chamberlin and B. Lipshutz J. Am. Chem. SOC.,1980 102 1439; (b)E. J. Corey L. 0.Weigel A. R. Chamberlin H. Cho and D. H. Hua ibid. p. 6613. 32 T. Cohen W. M.Daniewski and R. B. Weisenfeld Tetrahedron Left. 1978,4665. 33 P. Blatcher and S. Warren J. Chem. SOC.,Perkin Trans. 1 1979 1074. 34 S. R.Wilson R. N. Misra and G. M. Georgiadis J.Org. Chem. 1980 45 2460. 35 W. Lottenbach and W. Graf Helu. Chim. Acta 1978,61 3087. 36 B. M.Trost K. Hiroi and L. N. Jungheim J. Org. Chem. 1980,45,1839. 37 (a)G. A. Olah S.C. Narang G. F. Salem and B. G. B. Gupta Synthesis 1979,273; (b) 0.Hoshino S.Sawaki and B. Umezawa Chem. Pharm. Bull. 1979 27 538; (c) G. A. Olah Y.D. Vankar M. Arvanaghi and G. K. S. Prakash Synthesis 1979 720; (d)R. A. J. Smith and D. J. Hannah Synth. Commun. 1979 9 301; (e)Q. N. Porter and J. H. P. Utley J. Chem. Soc. Chem. Commun. 1978 255; (fl E. Fujita Y.Nagao and K. Kaneko Chem. Pharm. Bull. 1978,26,3743; (g) M. Platen and E. Steckhan Tetrahedron Lett. 1980,21,5 11. 238 S. V.Ley 1ii-iv Reagents i Pb(OAc),; ii R2CuLi.Me2S; iii H2S; iv Ac20; v MCPBA; vi heat Scheme 8 Reagents i Me,SiCl Li THF; ii (AcOH)~BF Scheme 9 allylic bis-silanes; when treated with Lewis acid these give products resulting from desilylation (Scheme 9).38 A new synthesis of thioesters has appeared involving sequential reaction of 1,3-dithiolans with sodium hydride and methyl iodide.39 Dithioacetals have also been used recently in a novel preparation of cyclic lactams and imino-thioethers Reagents i IN,; ii CF,CO,H; iii SnCI W Scheme 10 Su1phoxides.-The chemistry of optically active sulphur compounds has attracted considerable attention over the years.41 One important application of the aldol 38 D.Pandy-Szekeres G. Diltris J.-P. Picard J.-P. Pillot and R. Calas Tetrahedron Len. 1980,21,4267. 39 N. C. Gonnella M. V. Lakshmikantham.and M. P. Cava Synth. Commun. 1979,9 17. 40 B.M. Trost M.Vaultier and M. L. Santiago J. Am. Chem. SOC.,1980,102,7929. (a) A. Nudelman Phosphorus Sulfur 1980,9,1; (b)G.SolladiC. Synthesis 1981 185. Organosulph ur Organ ose len ium,and Organ ote 11urium Chemistry Reagents i Bu'MgBr THF at -78 "C; ii Al amalgam; iii KOH H20 Scheme 11 condensation of (R)-(+)-t-butyl toluene-p-sulphinylacetate with ketones led to a-hydroxy-acids in good chemical and optical yields (Scheme 1l).42 Thermal syn -elimination of sulphoxides and the selenoxide elimination at lower temperatures (see later) are powerful synthetic methods for the introduction of carbon-carbon double-bonds. Of the very many literature examples the synthesis of a-methylenecyclobutanes (Scheme 12) demonstrates the In this example the (pheny1thio)keten therefore acts as an equivalent of methyleneketen.+ Q__* ..o& PhSyMe -+ PhS i,ii. H2C& C II 0. ' 0 H H Reagents i MCPBA; ii heat at 150"C Scheme 12 Carbanions a to the sulphinyl group especially when these are additionally stabilized by a conjugating carbonyl unit,'' are useful in synthesis. A convenient procedure for annelation of phenols which exploits both the utility of a-sulphinyl carbanions and the syn -elimination reaction of sulph~xides,~~ is shown in Scheme 12 Scheme 13 The conversion of ketones into homologated aj3-unsaturated enals by a modified Darzens reaction using chloromethyl phenylsulphoxide carbanion is also a syn- thetically useful rea~tion.~' Ketones react with the anion of methyl phenylsulphoxide to give products which were subsequently transformed into allylic alcohols (Scheme 14).46 42 C.Mioskowski and G. Solladie Tetrahedron 1980,36,227. 43 T. Minami M. Ishida andT. Agawa J. Chem. SOC.,Chem. Commun. 1978 12. 44 D. L. Boger and M. D. Mullican J. Org. Chem. 1980,45 5002. 45 V. Reutrakul and W. Kanghae TetrahedronLett. 1977 1377. 46 S. Goldman Synthesis 1980,640 240 S. V.Ley R' R3 R2 R3 R3 Ph A Reagents i PhS(O)CH,-; ii N NSiMe ;iii LiNPr',; iv KH L/ Scheme 14 The Pummerer reaction commonly used to convert sulphoxides into sulphides can be achieved at much lower temperatures (s0"C) by using trifluoroacetic anhydride and this is now the recommended procedure.47 A novel phenyl shift occurred upon treatment of the dienylsulphoxide (1)with methyl-lithium; however this reaction is unlikely to find general application (Scheme 15).48 MeLi {#fixe __* EtO J (1) Ph Scheme 15 Primary and secondary ally1 alcohols add to allenyl phenylsulphoxides to form enol ethers that undergo Claisen rearrangement and elimination of benzenesul- phenic acid to afford a new synthesis of 2,4-dienone~.~' A useful review on activated dimethyl sulphoxide reagents in organic synthesis has been published.The review concentrates on their use for selective oxidation of structurally diverse alcohols to the corresponding carbonyl Su1phones.-The use of sulphones in synthesis is now well recognized and this continues to be a developing area." 47 H.Sugihara R. Tanikaga and A. Kaji Synthesis 1978 881. 48 G. Neef U. Eder and A. Seeger Tetrahedron Lett. 1980. 21 903. 49 R.C. Cookson and R. Gopalan J. Chem. SOC.,Chem. Commun. 1978,608. 50 A. J. Mancuso and D. Swern Synthesis 1981 165. 51 P. D. Magnus Tetrahedron 1977,33 2019. Organosulphur Organoselenium and Organotellurium Chemistry 24 1 Application of the cheletropic elimination of SOz from dihydrothiophen dioxides to unmask dienes is a useful procedure especially when it is coupled with the possibility of an intramolecular Diels-Alder Two interesting applica- tions of this process to alkaloid synthesis have appeared recently (Scheme 16).54*55 The use of pyrolysis reactions of sulphones in synthesis has been comprehensively reviewed.56 0'02sp % (2.;Aspidospermine N H 0u YH 0-(ref.55) (*)-Elaeokanine A td Scheme 16 Allylic sulphones are regioselectively desulphonylated using organotin hydrides to afford allyl-stannanes after migration of the d~uble-bond.~' These products can be used in further transformations as in the synthesis of (*)-lavandulol (Scheme 17).58 OH Reagents i Bu,SnH azobis(isobutyronitri1e); ii (CH20)3 BF,.Et,O Scheme 17 Julia one of the pioneers of sulphone chemistry has shown that allyl sulphones can be coupled with Grignard reagents in the presence of [Cu(aca~)~] as a catalyst to give substituted olefins as This procedure is therefore a suitable alternative to the normal reaction involving alkylation of the a -sulphone anion followed by reductive removal of the sulphone moiety.Allylic sulphones as synthons for 1,l- and 1,3-dipoles via organopalladium chemistry have been studied. For example Trost has reported chemoselective alkylation of some simple allyl sul- phones by soft nucleophiles in the presence of catalytic amounts of a Pdo species.6o '* W. Oppolzer D. A. Roberts and T. G. C. Bird Helv. Chim. Actu 1979,62,201'7. 53 K.C.Nicolaou and W. E. Barnette J. Chem. SOC.,Chem. Commun. 1979,1119. 54 S. F. Martin S. R. Desai G. W. Phillips and A. C. Miller J. Am. Chem. SOC.,1980,102,3294. 55 H. F. Schmitthenner and S. F. Weinreb J. Org. Chem. 1980,45,3372. 56 F.Vogtle and L. Rossa Angew. Chem. Int. Ed. Engl. 1979 18 515. 57 Y.Ueno S.Aoki and M. Okawara J.Am. Chem. SOC.,1979,101,5414. '* Y.Ueno S. Aoki and M.Okawara J. Chem. SOC.,Chem. Commun. 1980,683. 59 M. Julia A. Righini and J.-N. Verpeaux Tetrahedron Lett. 1979 2393. 6o B. M. Trost N. R. Schmuff and M. J. Miller J. Am. Chem. SOC.,1980,102,5979. 242 S. V. Ley Conjugate addition to vinyl sulphones continues to be of interest. Recent examples include the addition of highly functionalized aryl-lithium reagents6' and of a methoxyethoxymethyl-directedaddition of methyl-lithium to a trimethylsilylvinyl sulphone6* (Scheme 18).This latter reaction was employed in a synthesis directed towards maytansine. S02Ph SOzPh MeLi - Me3Sil\i- -Me OMEM PMEM Ph Ph' Scheme 18 Enolates have also been added conjugatively to vinyl ~ulphones,~~ and in one novel example the product can further undergo intramolecular cyclopropanation (Scheme 19).64 Not unexpectedly vinyl sulphones act as good dienophiles in the Diels-Alder reaction.3-Methylsulphonyl-2,5-dihydrofuranreacts with oxazoles thus providing an efficient synthesis of vitamin B6 after concomitant loss of methanesulphinic acid (Scheme 20).65 Scheme 19 /IN< \ + hSozMe ++ VitaminB6 Scheme 20 Phenyl vinyl sulphone behaves as an equivalent of ethylene or a terminal olefin in a variety of [4 + 21 cycloaddition reactions.66 The vinyl sulphone (2) underwent Diels-Alder reaction with Danishefsky's diene; however here the carbonyl group acted as the regio-control element rather than the sulphone moiety.Sulphinic acid was also spontaneously eliminated to create the desired double-bond in the product which was subsequently converted into (*)-tazettine (Scheme 21).67 Benzenesulphonylnitrile oxide undergoes 1,3-dipolar addition reactions with alkenes to give products which were readily reduced with sodium amalgam to cis-cyanhydrins (Scheme 22).68 61 D. L. Barton P. C. Conrad and P. L.Fuchs Tetrahedron Lett. 1980,21 1811. " M. Isobe M. Kitamura and T. Goto Tetrahedron Lett. 1979 3465. K. Takaki K.Nakagawa and K.Negoro J. Org. Chem. 1980,45,4789. 64 R. M. Corey and R. M. Renneboog J. Chem. SUC.,Chem. Commun. 1980,1081. 65 W. Boll and H. Konig Liebigs Ann. Chem. 1979,1657. 66 R. V. C. Carr and L. A. Paquette J. Am. Chem. SOC.,1980,102,853. '' S.Danishefsky J. Morris G. Mullen and R. Gammill J. Am. Chem. SOC.,1980,102 2838. P.A. Wade and H. R. Hinney J. Am. Chem. SOC.,1979,101 1319. Organosulphur Organoselenium and Organotellurium Chemistry Me,SiO Br (2) Scheme 21 0 I S0,Ph S02Ph Scheme 22 Other methods of removing the sulphonyl group to unmask double-bonds have been One of these procedures was used with effect in the synthesis of moenocinol (Scheme 23).72 Over the past four years there has been steady usage of a-sulphonyl carbanions in synthesis; however the space here available does not permit a detailed review. Most noteworthy contributions in this area come from the Trost group. . .. I 11 - Reagents i Bu",N'F-; ii Li NH Scheme 23 In a new approach to macrolide synthesis anions from a-sulphonyl esters react intramolecularly with intermediate (r-ally1)palladium complexes to form carbocyc- lic rings.Most surprising was the observation that the formation of the larger ring over the smaller ring was preferred. The method was extended to the synthesis of a number of natural products. The construction of (&)-recifeiolide illustrates the cyclization process (Scheme 24).73 By ingeniously amalgamating the chemistry of LY -sulphone carbanions with a new procedure for annelation of methylenecyclopentanes a three-carbon 69 S.Torii K. Uneyarna and H. Ichimura J. Org. Chem. 1979 44 2292. 'O P. J. Kocienski Tetrahedron Lett. 1979 2649. " K. Takai Y. Hotta K. Oshima and H. Nozaki Tetrahedron Lett. 1978 2417.72 P. J. Kocienski J. Org. Chem. 1980,45 2037. 73 B. M. Trost and T. R. Verhoeven J. Am. Chem. SOC.,1980,102,4743. 244 S.V.Ley Recifeiolide e c Reagents i NaH [Pd(PPh,),] Scheme 24 Reagents i F-; ii Pd/BaSO, H,; iii Na amalgam Na,HPO Scheme 25 ring-expansion can be achieved (Scheme 25).-74This reaction has been used to synthesize muscone. Another important group of papers by the Lythgoe group elegantly describe the exploitation of the use of (Y -sulphonyl car bani on^.^^ Other uses include the synthesis of (*)-noris~ambreinolide~~ The sodium and a novel preparation of p~ridinediols.~~ anion of dimethyl N-(toluene-p-sulphony1)sulphoximehas recently been used in a convenient one-step synthesis of 2,2-disubstituted oxetans from ketones (Scheme 26).78 Thiocarbonyl Compounds and Thio1esters.-Since the discovery that thiolesters are especially useful in the synthesis of macrocyclic lac tone^,'^ interest in these compounds has grown.Stork'sE0 synthesis of cytochalasin B for example nicely links up with a relay synthesis that was previously established by Masarnune,'l in 74 B. M. Trost and J. E. Vincent J. Am. Chem. SOC.,1980,102,5680. '' (a) P. J. Kocienski B. Lythgoe and S. Ruston J. Chem. SOC.,Perkin Trans. 1 1979 1290; (6) B. Lythgoe and I. Waterhouse ibid. p. 2429; (c) P. J. Kocienski and B. Lythgoe ibid. 1980 1400. 76 S. Torii K. Uneyama and H. Ichimura J. Org. Chem. 1978,43,4680. 77 W. Junemann H.-J. Opgenorth and H. Scheuermann Angew. Chem. Int. Ed. Engl. 1980,19 388.78 S. C. Welch and A. S. C. P. Rao J. Am. Chem. Soc. 1979,101,6135. 79 S. Masamune G. S. Bates and J. W. Corcoran Angew. Chem. Znf. Ed. Engl. 1977 16 585; K. C. Nicolaou Tetrahedron 1977 32 683;T. G. Back ibid. p. 3041. G. Stork Y. Nakahara Y. Nakahara and W. J. Greenlee J. Am. Chem. SOC.,1978,100,7775. 81 S. Masamune Y.Hayase W. Schilling W. K.Chan and G. S. Bates J. Am. Chem. SOC.,1977,99,6756. Organosulphur Organoselenium and Organotellurium Chemistry Scheme 26 ,OR Ph Hh Scheme 27 which the later steps involved a silver(1)-assisted coupling of a hydroxyl group with a thiolester (Scheme 27). New methods of preparing thiolesters from acyl chlorides using organotin mer- captides have been reportedS8* S-Pyridyl thiolesters are reductively coupled in the presence of nickel complexes to give symmetrical 1,2-di0nes.~~ There is considerable current interest in achieving stereoselective aldol condensa- tions.The use of boron enolates of thiolesters to achieve this transformation looks particularly attra~tive.~~*~~ Stereoselective condensation of (E)-and (2)-boronates with aldehydes affords threo-and erythro-isomers respectively (Scheme 28). The same strategy has also been applied to a short synthesis of the Prelog-Djerassi lactone.86 The spiro-methylene lactone moiety of bakkenolide-A has been constructed by using a combination of sulphur-mediated reactions including thiolesters (Scheme 291.'' Reagents i RCHO; ii aq. H202 Scheme 28 D. N. Harpp T. Aida and T. H. Chan TetrahedronLett.1979,2853. 83 M. Onaka Y. Matsuoka and T. Mukaiyama Chem. Lett. 1980,905. 84 D. A. Evans E. Vogel and J. V. Nelson J. Am. Chem. SOC.,1979,101,6120. 8s M. Hirama and S. Masamune Tetrahedron Lett. 1979,2225. 86 M. Hirama D. S. Gamey L. D.-L. Lu,and S. Masamune Tetrahedron Lett. 1979,3937. '' D. A. Evans C. L. Sims and G. C. Andrews J. Am. Chem. SOC.,1977,99,5453. 246 S. V. Ley I H sYsMe N T~N' H Reagents i NaH; ii HgCl, H,O; iii H2Se03 Scheme 29 Routes to thiocarbonyl compounds which do not involve basic media will find immediate application. One such method involves the use of g-methoxy-phenylthionophosphine sulphide.88 This reagent was used in a convenient procedure for the selective reduction of amides to amines; the method is compatible with the presence of isolated and conjugated double-bonds esters nitro-groups and sul-phonamides (Scheme 30).89 0 II II R'CNR2R3 b R'CNR2R3 /t30+ BF4- SEt NaBH + R1CH2NR2R3t-R'C=NR2R3 BF4-Scheme 30 A review containing sixty-eight references of the thio-Claisen rearrangement has recently been published.90 Thioketones and thioamides are effectively desulphurized to the corresponding hydrocarbons or amines by using hydridotetracarbonylferrate ani~n.~' 2 Organoselenium Chemistry While many of the reactions of organoselenium compounds have counterparts in organosulphur chemistry many important differences do arise.In fact there are a number of useful and unique reactions of organoselenium species that are not found in sulphur or tellurium chemistry.Here only a very brief coverage of the more recent literature is presented. Preparation and Reactions of Se1enides.-Many new ways of introducing selenium into organic substrates have been reported although the primary sources of selenium such as diphenyl diselenide and selenyl halides still feature extensively. 88 (a) S. Scheibye B. S. Pedersen and S.-0. Lawesson Bull. SOC.Chim. Belg. 1978 87 229; (6) G. L'abbi J. Flkmal J.-P. Declercq G. Germain and M. Van Meerssche ibid. 1979 88 737; (c) R. Shabana Now. J. Chim. 1980,47; (d)S. Scheibye J. Kristensen and S.-0. Lawesson Tetruhedron 1979,35,1339. 89 S. Raucher and P. Klein Tetrahedron Lett.,1980,21,4061. 90 L. Morin J. Lebaud D. Paquer R. Chaussin and D.Barillier Phosphorus Sulfur 1979,7 69. 91 H. Alper and H.-N. Paik J. Org. Chem. 1977,42,3522. Organosulphur Organoselenium and Organotellurium Chemistry The formation of primary selenides directly from alcohols using PhSeCN and triphenylphosphine is an important de~elopment,~~ as is the ruthenium-catalysed displacement reaction of amines with phenylselenate anions (Scheme 31).93 ?q)) ic% 0 + PhSe \ OMe \ OMe / OMe OMe mph SiMe 2+QQ::ph Reagents i PhSe-Na' Ru; ii PhSe-Li' Ru Scheme 31 The use of thallous phenylselenide as a nucleophile toward various halogen- substituted compounds has also been inve~tigated.~~ Other useful carriers of the phenylseleno moiety are N-phenylselen~phthalimide,~~ phenyl areneselenosul- phonate^,^^ and tri~(phenylse1eno)borane.~~ Many other methods for the introduc- tion of selenium are based upon the addition of selenating agents to alkenes typical examples being those of hydroxy~elenation,~~.~~ and acyloxy- amino~elenation,~~ selenation.26*2c"00 Cleavage of alkyl-oxygen bonds of lactones by sodium phenylsel- enolate has led to a general synthesis of olefinic esters (Scheme 32).lo1 i,ii (-J -G + ce iii,i" M' SePh Reagents i PhSe-Na' DMF; ii CH,N,; iii 0,;iv heat Scheme 32 Diazo-ketones react well with phenylselenium chloride to give a-chloro-a -phenylseleno-ketones which can be selectively transformed into a-chloro- or a-phenylseleno-aa -unsaturated ketones'02 or reduced by tri-n-butyltin hydride to 92 P.A.Grieco S.Gilman and M. Nishizawa J. Org. Chem. 1976,41 1485. 93 S.-I. Murahashi and T. Yano J. Am. Chem. SOC.,1980,102,2456. 94 M. R. Detty and G. P. Wood J. Org. Chem. 1980,45 80. 95 K. C. Nicolaou D. A. Claremon W. E. Barnette and S. P. Seitz J. Am. Chem. SOC.,1979 101 3704. 96 (a) R. A. Gancarz and J. L. Kice Tetrahedron Lett. 1980 21 1697; (b)T. G. Back and S. Collins ibid. p. 2215. 97 D. L. J. Clive and S. M. Menchen J. Org. Chem. 1979,44 (a)p. 1883; (b)p. 4279. 98 (a)T. Hori and K. B. Sharpless J. Org. Chem. 1978 43 1689; (b)H. J. Reich S. Wollowitz J. E. Trend F. Chow and D. F. Wendelborn ibid. p. 1697; (c) D. Labar A. Krief and L. Hevesi Tetrahedron Lett. 1978 3967. 99 A. Toshimitsu T. Aoai S. Uemura and M. Okano J. Chem. SOC.,Chem. Commun. 1980 1041.loo (a) N. Miyoshi S. Furui S. Murai and N. Sonoda J. Chem. SOC. Chem. Commun. 1975 293; (b) A. Toshimitsu T. Aoai S. Uemura and M. Okano J. Org. Chem. 1980,45 1953. lo' R. M. Scarborough Jr. B. H. Toder and A. B. Smith 111 J. Am. Chem. SOC.,1980,102,3904. D. J. Buckley S. Kulkowit and A. McKervey J. Chem. SOC.,Chem. Commun. 1980,506. 248 S. V.Ley -N C0,R C0,R C0,R Reagents i PhSeC1; ii Bu",SnH Scheme 33 remove the PhSe group (Scheme 33).lo3 Cyclohexenones react with phenylselenium chloride to lead directly to cr-(phenylseleno)cyclohexenones.104 Introduction of the selenium moiety via selenium-mediated cyclization reactions is of synthetic interest. Conceptually the reaction involves the intramolecular trapping of a presumed intermediate seleniranium ion formed by addition of a selenating reagent to an alkene bond by a nucleophile (Nu) as shown in Scheme 34.If the nucleophile in this process is an alcohol,105 a thi01'~~"*'~~ (or a thioacetate) 'PhSec' --Gef / SePh Ph Scheme 34 an ret thane,"^ or an a~id,~~,"~ smooth cyclization to the corresponding heterocyclic product is achieved. Recently alkenyl-substituted @ -dicarbonyl compounds have been similarly cyclized using selenating reagents with non-nucleophilic counter- ions.'09 Representative examples of these reactions are shown in Scheme 35. Other selenium-mediated cyclization reactions that are of interest are the conver- sion of cyclonona-l,5-diene into bicyclo[4.3.0]nonane systems'l0 and a biogenetic- type process which ultimately led to a synthesis of safranal."' The use of a-seleno-carbanions in organic synthesis is now well established; however as space here does not permit a proper representation of this important area the reader is directed towards the recent extensive review by Krief.'12 @ -Hydroxy-selenides are particularly versatile synthetic intermediates and they can be prepared by a number of different routes.They can be selectively transformed Io3 P. J. Giddings D. I. John and E. J. Thomas Tetrahedron Lett. 1980 21,399. lo4 G. Zima and D. Liotta Synth. Commun. 1979,9 697. (a)K. C. Nicolzou R. L. Magolda W. J. Sipio W. E. Barnette Z. Lysenko and M. M. Joullib J. Am. Chem. SOC.,1980 102 3784; (b)D. L. J. Clive G. Chittattu N. J. Curtis W.A. Kiel and C.-K. Wong J. Chem. SOC.,Chem. Commun. 1977 725; (c)D. L. J. Clive G. Chittattu and C.-K. Wong Can. J. Chem. 1977 55 3894; (d) Z. Lysenko F. Ricciardi J. E. Semple P. C. Wang and M. M. Joullik Tetrahedron Lett, 1978 2679. lo' K. C. Nicolaou W. E. Barnette and R. L. Magolda J. Am. Chem. SOC., 1978 100 2567. lo' D. L. J. Clive V. Farina A. Singh C.-K. Wong W. A. Kiel and S. M. Menchen J. Org. Chem. 1980,452120. (a) K. C. Nicolaou S. P. Seitz W. J. Sipio and J. F. Blount J. Am. Chem. SOC., 1979 101 3884; (6)D. L. J. Clive C. G. Russell G. Chittattu and A. Singh Tetrahedron 1980 36 1399. (a)W. P. Jackson S. V. Ley and J. A. Morton J. Chem. SOC., Chem. Commun. 1980 1028; (6)W. P. Jackson S. V. Ley and A. 3. Whittle ibid. p. 1173. "" D.L. J. Clive G. Chittattu and C.-K. Wong J. Chem. SOC.,Chem. Commun. 1978,441. T. Kametani K. Suzuki H. Kurobe and H. Nemoto J. Chem. SOC.,Chem. Commun. 1979 1128. 'I2 A. Krief Tetrahedron 1980 36 2531. Organosulphur Organoselenium and Organotellurium Chemistry Ho7s. 077-OR OR [~OYO] [81"/o ] [87%] &o SePh oJiii ~ + __* OH \ ..A0 H PhSe (E = C02Me) [82%] [75'/0] Reagents i PhSeC1; ii PhSeC1 SiO,; iii PhSe+SbF,-Scheme 35 into a large variety of derivatives that are free of selenium such as ally1 alcohols a@-unsaturated carbonyl compounds olefins epoxides bromides rearranged ketones and LY -hydroxylated ketones."' Reich has reported unambiguous evidence that seleno- and thio-substituted enolates can undergo significant or even predominant alkylation at the heteroatom to afford ylide intermediate^."^ Reduction of the carbon-selenium bond is obviously synthetically important and can be achieved by either Raney nickel or lithium in eth~lamine,"~ or best of all by triphenyl- or trialkyl-tin hydride.'" By using the tin hydride method selective reduction can be achieved in the presence of other functional groups such as lactones ethers urethanes hydroxides and even some compounds that contain bivalent Benzeneselenol has been shown to be useful reagent for the dealkylation of amines.The dealkylation process involves heating in an inert atmosphere at 150"C in sealed tubes (Scheme 36).l16 Aryldiazonium fluoroborates are reduced to arylhydrazone salts by benzene- selenol in refluxing methylene chloride."' '13 H.J. Reich and M. L. Cohen J. Am. Chem. SOC.,1979,101 1307. 'I4 e.g. M. Sevrin D. Van Ende and A. Krief Tetrahedron Lett. 1976 2643. 'Is D.L.J. Clive G. J. Chittattu V. Farina W. A. Kiel S. M. Menchen C. G. Russell A. Singh C. K. Wong and N. J. Curtis J. Am. Chem. SOC.,1980,102,4438. '" H.J. Reich and M. L. Cohen J. Org. Chem. 1979,44,3148. F.G. James M. J. Perkins 0.Porta and B. V. Smith J. Chem. SOC.,Chem. Commun. 1977,131. 250 S. V.Ley 'Me N NH-HCI Reagents i PhSeH; ii HCI Scheme 36 Selenoxides and the syn-Elimination Reaction.-Without doubt the syn -elimina-tion reaction of alkyl aryl selenoxides first recognized by Huguet,'18 is an extremely powerful method for the introduction of carbon-carbon double-bonds into organic substrates.Very many examples of this process which occurs at temperatures approximately 100"Clower than is the case for the corresponding sulphoxide are now Practical improvements to the reaction such as the addition of tertiary amine base or the use of electron-withdrawing groups in the aromatic portion have previously been recommended. Recent developments employ the use of Bu'OOH and silica gel as an oxidant (for selenoxide formation)"' and the use of 2-pyridyl selenides which appears to be especially useful for the formation of terminal alkenes (Scheme 37).'*' Elimination via selenonium salts has also been investigated. 12' p-0 -SeAr H,Oz I 4 k?:,]-C14H29 C14H29 [Cl4H2' Ar = 2-pyridyl;87% Ar = Ph; 5% 1 Scheme 37 Generally syn -elimination of selenoxides shows a preference for elimination towards the less substituted carbon and away from polar groups in the p-position.Branching at the a-carbon increases the rate while branching at the p-position decreases the rate of elimination; non-polar aprotic solvents are also preferred.12' Where there is no choice for the selenoxide elimination towards polar groups will take place and this has been successfully used in a synthesis of a macrolide (Scheme 38).123 0 Reagents i NaIO, NaHCO,; ii heat; iii Claisen rearrangement Scheme 38 '18 J. L. Huguet Ada Chem. Ser. 1967 76 345. '19 D. Labar L. Hevesi W. Dumont and A. Krief Tetruhedron Lett. 1978 1141. 120 A. Toshimitsu H. Owada S.Uemura and M. Okano Tetrahedron Lett. 1980 21 5037. 12' S. Halazy and A. Krief Tetrahedron Lett. 1979,4233. '22 H. J. Reich S. Wollowitz J. E. Trend F. Chow and D. F. Wendelborn J. Org. Chem. 1978,43 1697. 123 M. Petrzilka Helv. Chim. Actu 1978,61 3075. Organosulphur Organoselenium and Organotellurium Chemistry 25 1 Recent applications of the selenoxide syn -elimination reaction to the synthesis of natural products include those of ~upinidine,"~ periplanone-B,'*' pseudomonic acid C,126 and marasmic In the synthesis of marasniic acid the elements of PhSeOMe were added to an unsaturated lactone; this was subsequently converted into the natural product (Scheme 39). Go -0"' H PhSe 0 HR HR \ (R = C02Me) YimoMe H PhSe Marasmicacid + +-WHO t iii,iv CHO R R OH Reagents i PhSeBr MeOH; ii Bu',AlH; iii MCPBA at -78 "C; iv room temperature Scheme 39 A useful method whereby 3-(phenylseleno)orthopropionate may be used as a synthon for the preparation of either 2-substituted acrylates or (Y -methylene-y-butyrolactones via Claisen rearrangement of an orthoester with allylic alcohols followed by oxidative syn -elimination of PhSeOH has been reported (Scheme 40)."* SePh 0 C0,Me H CH SePh SePh Reagents i PhSe(CH,),C(OMe), Me,CCO,H; ii LiI; iii PhSeCl; iv H,02; v heat Scheme 40 The preparation of homologated enals from ketones has been achieved utilizing selenium-based methodology.In this manner a carbocyclic analogue of throm- boxane A2 was subsequently synthesized (Scheme 41).lZ9 OMe SePh -+ etc.Reagents i Ph,P=CHOMe; ii PhSeCl; iii aqueous work-up; iv MCPBA at -78°C; v Pr',NH at room temperature Scheme 41 lZ4 D. J. Robins and S. Sakdarat J. Chem. SOC.,Perkin Trans. 1 1979 1734. lZ5 W.C. Still J. Am. Chem. SOC.,1979 101 2493. lZ6 A. P. Kozikowski R. J. Schmiesing and K.L. Sorgi J. Am. Chem. SOC.,1980,102,6577. 12' R.K. Boeckmann Jr. and S. S. KO,J. Am. Chem. SOC.,1980 102 7146. S. Raucher K.-J. Hwang and J. E. Macdonald Tetrahedron Lett. 1979 3057. K. C. Nicolaou R. L. Magolda and D. A. Claremon J. Am. Chem. SOC.,1980,102 1404. 252 S. V.Ley Although vinyl selenides have been known for some time their oxidation to vinyl selenoxides and their subsequent behaviour were investigated only fairly re~ently.'~~ Even more recently under the right conditions i.e.in the presence of DABCO (1,4-diazabicyclo[2.2.2]octane),they have been used to prepare acetylenes (Scheme 42).131 0I1 0 SeII -F3C0 / ii Ill + Ph HO Ph Reagents i MeCO(CH,),Ph DABCO; ii heat at 85 "C Scheme 42 Aryl vinyl selenoxides are versatile reagents for the transfer of an ethylene unit to enolates and thus provides a new method for forming cyclopropyl ketones (Scheme 43).13* Similar methodology has been used in a novel preparation of 3-methoxy-oxetans (Scheme 44). 133 0 II 0 Scheme 43 ,OMe Reagents i RM; ii MCPBA (2 equivalents) MeOH; iii NaOH aq. MeOH Scheme 44 The full paper on the use of a-lithio-selenoxides for the preparation of olefins ally1 alcohols and dienes has appeared.134 Mild deoxygenation of selenoxides (and sulphoxides) can be achieved by (phenylse1eno)trimethylsilanein very high ~ie1ds.l~' Selenoxides which lack p -hydrogen atoms (and which therefore cannot undergo the syn -elimination reaction) fragment by a Pummerer process when heated affording carbonyl compounds. In this way benzyl phenyl selenoxide at 110- 130 "C,gave benzaldehyde and diphenyl di~e1enide.l~~ The 1,3-transposition of primary allylic alcohols via intermediate selenoxides is a useful procedure in that it achieves a 'contrathermodynamic' transformation (Scheme 45).13' 130 M. Sevrin W. Dumont and A. Krief Tetrahedron Lett. 1977 3835. 13' H. J. Reich and W. W. Willis Jr. J. Am. Chem. SOC.,1980 102,5967.M. Shimizu and I. Kuwajima J. Org. Chem. 1980 45 2921. 133 M. Shimizu and I. Kuwajima J. Org. Chem. 1980 45,4063. 134 H. J. Reich S. K. Shah and F. Chow J. Am. Chem. SOC., 1979,101,6648. 135 M. R. Detty J. Org. Chem.. 1979 101,4528. 13' I. D. Entwistle R. A. W. Johnstone and J. €I. Varley J. Chem. SOC., Chem. Commun. 1976 61. 13' D. L. J. Clive G. Chittattu N. J. Curtis and S.M. Mencken J. Chem. SOC.,Chem. Commun. 1978 770. Organosulphur Organoselenium and Organotellurium Chemistry Reagents i ArSeCN Bu,P; ii H202 Scheme 45 Organoselenium Oxidizing Agents.-Modern synthetic chemistry has demanded the discovery and development of more mild and selective oxidizing agents. It has long been recognized that SeOz has played a major role as an organic oxidant and it is not surprising therefore that other selenium oxidants would prove equally useful.Over the past few years many advances have been made in this area. Dimethyl selenoxide was shown to be an excellent oxidant for various phos- phorus(Ir1) compounds converting them into the corresponding oxide in very high ~ie1d.l~' and certain thiocarbonyl corn pound^'^^^'^^ were Phosphine sulphide~'~~,'~~ similarly converted into their oxygen counterparts by using selenoxide reagents. The mildness of the method is best illustrated by the conversion of an unprotected nucleotide derivative into its corresponding 0x0-analogue (Scheme 46).13' 0 HO OH Scheme 46 A series of early papers by Balenovik demonstrated the use of diphenyl selenoxide as an oxidant for a number of nitrogen-containing compounds.Acyl hydrazides are converted into symmetrical hydrazine~'~' while phthaloyl hydrazide gives bis- phtha1a~inone.l~~ Arylamines produce azo-compounds when treated with selenoxides in the presence of ZnC12.'43 Tertiary amines give the corresponding oxides in respectable yield (e.g.,strychnine N-oxide ~OYO).~~~ 13' M. Mikolajayk and J. Luczak J. Org. Chem. 1978,43 2132. 139 S.Sakaki and S. Oae Chem. Lett. 1977 1003. 140 S.Tamagaki I. Hatanaka and S. Kozuka Bull. Chem. SOC. Jpn. 1977 50 3421. 14' K.BalenoviC R. LaziC V. Polak and P. Stern Bull. Sci. Cons. Acad. Sci. Arts RSF Yougosl. Sect. A 1972,17,147. 14* N. Bregant I. Perina and K.BalenoviC Bull. Sci. Cons. Acad. Sci.Arts RSF Yougosl. Sect. A 1972 17,148. 143 V. I. Naddaka V. P. Gar'kin and V. I. Minkin Zh. Org. Khim. 1976 12 2481. 144 M. Poje and K. Balenovii. Bull. Sci. Cons. Acad. Sci. Arts RSF Yougosl. Sect. A 1975 20 1. 254 S. V.Ley Ascorbic and catechol~'~~ are also readily oxidized. A recent interesting application of the oxidation of catechol using selenoxides provided an entry to the synthesis of alkaloids related to aporphine (Scheme 47).147Of importance is the fact that simple phenols are not oxidized under the reaction conditions. J 0 OH Scheme 47 The use of selenenic oxidants is gradually increasing. Deliberate generation of the unstable benzeneselenenic acid in situ followed by subsequent trapping with olefins is useful for the preparation of allylic alcohols.95~98 Suitably oriented dienes react with two equivalents of 'PhSeOH' to afford cyclic ethers (Scheme 48).148 Electrochemical routes to a number of selenenic equivalents have recently been reported.14' Oxidation of diphenyl diselenide with t-butyl hydroperoxide leads to the proposed formation of benzeneselenenic anhydride PhSeOSePh which can subsequently be used to convert olefins directly into a-(phenylseleno)-ketones (Scheme 49).The same reagent was also generated by comproportionation of diphenyl diselenide with benzeneseleninic anh~dride.'~' Reagents i 'PhSeOH'; ii 0,;iii heat Scheme 48 145 I. Perina N. Bregant and K. BalenoviC Bull. Sci. Cons. Acad. Sci. Arts RSF Yougosl. Sect. A 1973,18,4. (a) K.Balenovik N.Bregant and I. Perina Synthesis 1973 172; (6) I. Perina N. Bregant and K. BalenoviC Bull. Sci. Cons. Acad. Sci. Arts RSF Yougosl. Sect. A 1973,18,3. J. P.Marino and A. Schwartz TetrahedronLen. 1979,3253. (a) R. M. Scarborough Jr. A. B. Smith 111 W. E. Barnette and K. C. Nicolaou J. Org. Chem. 1979,44,1742;(b)S. Uemura A. Toshimitsu T. Aoai and M. Okano Chem. Lett. 1979,1359. (a) S.Torii K. Uneyama and M. Ono Tetrahedron Lett. 1980,21,2741;(b)A. Bewick D. E. Coe G. B. Fuller and J. H. Mellor ibid. p. 3827. M.Shimizu R. Takeda and 1. Kuwajima Tetrahedron Letr. 1979,419. 14' 14' 14' Organosulph ur Organoselen iu m and Organo tellurium Chemistry BU'OOH Ph2Se2 (-Bu'O&) [PhSeOSePh] Ph2Se2+ (PhSe0)zO [PhSeOSePh] 0 PhSeOSePh LSePh Ph--Ph Scheme 49 Highly selective anti-Markownikoff -type oxidation of olefinic bonds of allylic alcohol derivatives especially of bulky t-butyldimethylsilyl ethers is also possible using benzeneselenenic anhydride that is generated in situ (Scheme 50).15* Primary alcohols may be oxidized cleanly to aldehydes by using a catalytic amount of dimesityl diselenide and an excess of t-butyl hydroperoxide.The mechanism of the reaction is uncertain but is likely to involve either selenenate or seleninate esters as intermediate^.'^^ SiMe2Bu' PhSeOSePh -Ph+CHO Ph SePh Scheme 50 Benzeneseleninic anhydride (PhSeO)*O which is readily prepared by oxidation of diphenyl diselenide has been shown to be a very versatile oxidizing agent.It can be used to oxidize phenols to o-hydroxy-dienoneslS3 or quinoneslS4 under very mild conditions. Additionally oxidation of phenols with benzeneseleninic anhydride in the presence of hexamethyldisilazane gave novel selenoimines as products with high ortho-selectivity (Scheme 51).These imines could be reduced by benzenethiol to amino-phenols thus constituting a new procedure for the amination of Regeneration of carbonyl compounds from hydrazones oximes and semicar- bazones is also possible using benezeneseleninic anhydride and in some cases it can be achieved when conventional methods faiIed.ls6 Reagents i (PhSeO),O (Me,Si),NH; ii PhSH Scheme 51 lS1 M. Shimizu R. Takeda and I. Kuwajima Tetrahedron Lett. 1979,3461. M. Shimizu and I.Kuwajima Tetrahedron Lett. 1979 2801. D. H. R. Barton S. V. Ley P.D. Magnus and M. N. Rosenfeld J. Chem. Soc. Perkin Trans. I 1977,567. (a)D. H. R. Barton A. G. Brewster S. V. Ley and M. N. Rosenfeld J. Chem. Soc. Chem. Commun. 1976,985; (b)K. B. Sukumaran and R. G. Harvey J. Org. Chem.. 1980,45,4407. lSs D. H. R. Barton A. G. Brewster S. V. Ley and M. N. Rosenfeld J. Chem. Soc. Chem. Commun. 1977,147. D. H. R.Barton D. J. Lester and S. V. Ley J. Chem. Soc. Perkin Trans. I 1980 1212. 256 S. V. Ley Oxidation of hydrazine~,'~~.~'~ and amines15' have also been hydroxylamine~,~~~ reported. The oxidation of acylhydrazines by benzeneseleninic acid affords a novel synthesis of seleno-esters RC(0)SePh.l" New methods for deprotecting thioacetals to yield the parent carbonyl compounds are always welcome in synthesis and especially so if these procedures show advan- tages over existing methodology.Benzeneseleninic anhydride is a suitable new reagent to effect this transformation.'60"61 Other sulphur- or selenium-containing compounds such as thiocarbonyl species,'62 vinyl ~elenides,'~~ and sul- thi~ls,'~~ phinic acids,16s react well with the anhydride or with the corresponding benzene- seleninic acid. Dehydrogenation of ketones can be achieved in high yield by using the anhydride in chlorobenzene at 95 0C.166In some cases hydroxylation cy to the carbonyl group occurs affording a synthetically useful variation (Scheme 52).16' n (PhSeO),O ___) RO-Scheme 52 Oxidation of alcohols to the corresponding carbonyl compounds is also possible using (PhSeO)20 and when coupled with dehydrogenation this allows direct oxida- tion to enones.168 Oxidation of an aromatic side-chain is an important transformation for which the use of benzeneseleninic anhydride has recently been investigated (Scheme 53).16' The generation of benzeneperoxyseleninic acid PhSe(O)OOH in situ by treat- ment of the selenenic acid with H202, is possible.The reagent can subsequently lS7 T. G. Back J. Chem. SOC., Chem. Commun. 1978 278. 158 M. R. Czarny J. Chem. SOC.,Chem. Commun. 1976,81. lS9 T. G. Back and S. Collins Tetrahedron Lett. 1979,2661. 160 N. J. Cussans S. V. Ley and D. H.R. Barton J. Chem. SOC., Perkin Trans. 1 1980 1654. 16' A.Burton L. Hevesi W. Dumont A. Cravador and A. Krief Synthesis 19?9,877. 16' N. J. Cussans S. V. Ley and D. H. R. Barton J. Chem. SOC.,Perkin Trans. 1 1980 1650. 16' A. Cravador and A. Krief J. Chem. SOC.,Chem. Commun. 1980,951. 164 J. L. Kice and T. W. S. Lee J. Am. Chem. SOC.,1978 100 5094. R. A. Gancarz and J. L. Kice Tetrahedron Lett. 1980,21 1697. 166 D. H. R. Barton D. J. Lester and S. V. Ley J. Chem. SOC.,Perkin Trans. 1 1980 2209. K. Yamakawa T. Satoh N. Ohba R. Sakaguchi S. Takita and N. Tamura Tetrahedron 1981,37,473. 168 D. H. R. Barton A. G. Brewster R. A. H. F. Hui D. J. Lester S. V. Ley andT. G. Back J. Chem. SOC.,Chem. Commun. 1978,952. 169 D. H. R. Barton R. A. H. F. Hui D. J. Lester and S. V. Ley Tetrahedron Lett. 1979 3331. 16' Organosulphur Organoselenium and Organotellurium Chemistry Scheme 53 be used to effect epoxidation reaction^"^ or the Baeyer-Villiger o~idation,'~~ and in certain examples was superior to other methods.A new rearrangement of N-aryl-hydroxamic acids catalysed by benzeneseleninic acid has been reported (Scheme 54).172 PhCON ,OH PhCONH 6 0 PhSeO25 OH Scheme 54 3 Organotellurium Chemistry Although the literature on organotellurium species is extensive and continues to in~rease,~ application towards organic synthesis is still very limited. One of the problems of organotellurium compounds that of sensitivity to light [particularly of alkyLtellurium(I1) derivatives] can be overcome by the use of a photographic red light. In this way Clive has been able to cause PhTe- (or MeTe-) to react with various epoxides and to isolate and fully to characterize the resulting telluride^.'^^ These tellurides could be reduced under mild conditions using triphenyltin hydride.The overall sequence is therefore one of reduction of an epoxide in the presence of a ketonic group (Scheme 55). TePh Reagents i PhTe-; ii Ph,SnH Scheme 55 Some of the chemistry of dibenzyl ditelluride also prepared under red light has been in~estigated;'~~ most of the reactions involve extrusion of tellurium (Scheme 56). The hitherto unknown o-nitrophenyltellurenyl bromide can be prepared by controlled addition of bromine to benzyl o-nitrophenyl telluride. The deep red 170 P. A. Grieco Y. Yokoyama S. Gilman and M.Nishizawa J. Org. Chem. 1977,42,2034. 17' P. A. Grieco Y. Yokoyama S. Gilman and Y. Ohfune J. Chern. SOC.,Chem. Commun. 1977 870. 172 T. Frejd and K. B. Sharpless Tetrahedron Lett. 1978 2239. 173 D. L. J. Clive G. J. Chittattu V. Farina W. A. Kiel S. M. Menchen C. G. Russell A. Singh C. K. Wong and N. J. Curtis J. Am. Chem. SOC.,1980 102,4438. 174 H. K. Spencer and M. P. Cava J. Org. Chern. 1977,42 2937. 258 S. V.Ley PhCHO + PhCH20H PhCH3 + PhCH2CH2Ph PhCH2TeTeCHzPhI! PhCHzTeCH2Ph kPhCHZieCH2Ph-% 2PhCHzBr + TeBr4 I Br Reagents i hv 0,; ii hv CDC13 or at 120"C;iii Br Scheme 56 product is relatively stable and was prepared for later use in Other potentially useful tellurium-containing compounds e.g. 0-nitrophenyl phenyl and p-methoxyphenyl tellurocyanates have recently been obtained for the first time.176 Benzyl tellurocyanate can be prepared by the reaction of benzyl chloride with alkali-metal tellurocyanate solutions and reactions with selected reagents (oxygen bromine hydroxide ion hypophosphorous acid and benzyl mercaptan) have been ~ep0rted.l~~ The reaction with oxygen afforded benzaldehyde (60%) and benzyl alcohol (40%).Sodium hydrogen tell~ride'~' has been shown to be useful as a debrominating reagent for 1,2-dibromides in a limited number of examples (Scheme 57).179 Vilsmeier salts also react with sodium hydrogen telluride affording a novel synthesis of benzyl ethers.lS0 For example 1,2:5,6-di-O-isopropylidene-~-~-glucofuranose (3) after successive treatment with chloro(phenylmethylene)dimethylammonium chloride and NaTeH (from NaBH4 + Te) gave the known benzyl ether (4) in 64% yield.The mezhanism of the reaction was thought to involve the intermediacy of tellurobenzoates and electron-transfer processes (Scheme 58). 23298 (3) R=H 23299 (4) R=CHZPh 17' P. Wiriyachitra S. J. Falcone and M. P. Cava J. Org. Chem. 1979 44 3957. 176 S. J. Falcone and M. P. Cava J. Org. Chem. 1980,45 1044. H. K.Spencer M. V. Lakshmikantham and M. P. Cava J. Am. Chem. SOC.,1977,99,1470. 17' D. H. R. Barton and S. W. McCombie J. Chem. SOC.,Perkin Trans. I 1975 1574. 179 K. Ramasamy S. K. Kalyanasundaram and P. Shanmugam Synthesis 1978 311. A. G. M. Barrett R. W. Read and D. H. R. Barton J. Chem. SOC., Perkin Trans. I 1980,2184.17' Organosu lph ur Organ aselen ium and Organo tellu rium Chemistry H H HTe-I I H atom ROCPh +RO-C-Ph H+ RO-C-Ph RO-F-Ph -ROCH2Ph ll I I. transfer Te Te-Te Scheme 58 Under favourable circumstances the novel telluro-esters could be isolated and fully characterized.lgl When pure these esters were stable and were unaffected by oxygen in the dark by anaerobicphotolysis or by water. Other types of telluro-ester Ar'C(0)TeCH2Ar2 have also recently been prepared using a phase-transfer technique. Epoxides can be usefully deoxygenated to olefins by using alkali-metal 00-diethyl phosphorotelluroates (5). These reagents can be generated stoicheiometri- cally in situ or generated continuously in a process which is approximately catalytic in tellurium.The deoxygenation is stereospecific; (2)forms tend to react faster than (E)isomers and deoxygenation favours terminal epoxides in some examples (Scheme 59).lS3 0 4, (EtO)*P\;_ M+ Te (5) Scheme 59 Aryltellurium trichlorides upon treatment with Raney nickel in diglyme undergo coupling to form biaryls (Scheme 6O);ls4 however when treated with tetracarbonyl- nickel in DMF at 70 "C they give carboxylic acids in moderate yield on aqueous Reagents i TeCI, heat at 110"C; ii Raney nickel heat for 2 hours Scheme 60 Certain aryltellurium(1v) halides upon photolysis in benzene give aryl halides by 'a-elimination'. With p-methoxyphenyltellurium trichloride a 70% yield of p-methoxychlorobenzene was obtained.Ig6 A similar reaction can be achieved by warming tellurium trihalides in the presence of t-butyl hydroperoxide.Alkyltel- lurium trihalides readily available from alkenes and TeC14 yield dihalides (Scheme 61).lS7 This reaction might find application if mixed 1,2-dihalides were required. "' A. G. M. Barrett R. W. Read and D. H. R. Barton J. Chem. Sac. Perkin Trans. I 1980 2191. in2 J. Bergman and L. Engman Z. Naturforsch. Ted. B 1980 35 217. D. L. J. Clive and S. M. Menchen J. Org. Chem. 1980,452347. J. Bergman and L. Engman Tetrahedron 1980 36,1275. ln5 J. Bergman and L. Engman J. Organomet. Chem. 1979,175,233. lS6 S. Uemura and S. Fukuzawa Chem. Lett. 1980 943. '13' S. UemuraandS. Fukuzawa J. Chem. Soc. Chem. Commun. 1980,1033. 260 S. V.Ley Tellurium tetrachloride reacts rapidly with alkylphenylacetylenes to give (2)-(2-chlorovinyl)tellurium(Iv) trichlorides which in turn can be halogenodetellurated using I2 in acetonitrile or NBS in carbon tetrachloride (Scheme 62).lg8 Reagents i TeCl,; ii Bu'OOH 1,4-dioxan HOAc Scheme 61 Ph R R PhCZCR +TeC14 --* >-( k Ph>=( C1 TeCI C1 I Scheme 62 Diaryltellurium dichlorides couple with alkenes to give the corresponding arylated alkenes in the presence of Pd" species.If suitable co-oxidants are additionally used the process is catalytic in pailadi~m.'~~ Thiols can be coupled with TeC14 via intermediate (RS)4Te species which decompose on warming (Scheme 63).l9' Scheme 63 Glycols also react with tellurium alkoxylates to afford cyclic telluroacetals.'91 It is conceivable that these could be removed under mild conditions and therefore might constitute a new method of protection of 1,2-diols.Telluroxides as reagents have received some attention. Tellurium dioxide is used industrially in the oxidation of ethylene to ethylene This reaction has recently been investigated mechanistically. 193 Diary1 telluroxides such as (6) are relatively stable and odourless and can be used as mild selective oxidizing agents. They can be used to oxidize thiols thiocar- bony1 compounds hydroquinones catechols and acylhydrazines while many other functional groups remain inert.194 It is additionally possible to convert thiocarbonyl compounds into their 0x0-derivatives catalytically in a cycle which involves the (6) '" S.Uemura H. Miyoshi and M. Okano Chem. Lett. 1979 1357. '*' S. Uemura M. Wakasugi and M. Okano J. Organomet. Chem. 1980 194,277. B. Nakhdjavan and G. Klar Liebigs Ann. Chem. 1977 1683. M. Wieber and E. Kaunzinger J. Organomet. Chem. 1977,129,339. lg2 Jpn. Kokai Tokkyo Koho 79 70 207 (Chem. Abstr. 1979,91,192 813). 193 J. Bergman and L. Engman J. Organornet. Chem. 1979 181 335. D. H. R. Barton S. V. Ley and C. A. Meerholz J. Chem. SOC.,Chem. Commun. 1979,755. Organosulphur Organoselenium and Organotellurium Chemistry 261 S 0 II II R-C-R R-C-R Ar2Te=0 Ar2Te + S ArzTeBr2 Reagents i Base H,O; ii Cl,CBrCBrCI Scheme 64 use of 1,2-dibromotetrachloroethane as a brominating agent for Te’’ species (Scheme 64).195 A number of interesting applications of Te02 in synthesis have been repor- ted,196,197 Engman has recently shown that certain ketones are regenerated from their corresponding semicarbazones azines and hydrazones by treatment with TeOz in acetic acid in the presence of lithium bromide.”* Prior to 1977 compounds containing Te-N bonds were scarce.However a number of examples now exist e.g. (7),199 (8),200(9),200 and (11).202Very little is known of the chemistry of these potentially useful compounds. Tetra-aryltellurium species decompose upon heating giving good yields of diary1 tellurides and biaryls. Tetra-aryltellurium compounds appear to exchange ligands rapidly via a non-radical process prior to decomposition to tellurides and biaryls. The decomposition process is concerted and does not involve radicals (Scheme 65).203 R\ -[R,Te:::i] R,Te ,R 120°C R\ +R\ Te + R-R R R’ Scheme 65 We can expect continued growth in the use of organotellurium chemistry over the next few years.However the acceptance of organotellurium compounds as reagents will depend upon the discovery of more selective or unique transformations that cannot be achieved by conventional methodology. 19’ S.V. Ley C. A. Meerholz and D. H. R. Barton Terruhedron Let?. 1980,21 1785. 19‘ J. Bergman and L. Engman Tetrahedron Lerr. 1978,3279. 19’ J. Bergman and L. Engman Tetrahedron Lett. 1979,1509. 19* J. Bergman and L. Enmian Z. Nutzuforsch. Teil. B 1980 35 882. lg9 V.I. Naddaka V. P. Gar’kin I. D. Sadekov and V. I. Minkin Zh. Org. Khim. 1977,13 220 *O0 L.N. Markovskii E. A. Stukalo and G. P. Kunitskaya Zh. Org. Khim. 1977,13,2055. 201 L.N.Markovskii E. A. Stukalo and G. P. Kunitskaya Zh. Org. Khim. 1977 13 2514. 202 Ref. 3g.p. 391. 203 (a) D. H. R. Barton S. A. Glover and S.V. Ley J. Chem. SOC.,Chem. Commun. 1977 266; (b) S.A.Glover J. Chem. SOC.,Perkin Trans. 1 1980 1338.

ISSN:0069-3030    

DOI:10.1039/OC9807700233

出版商:RSC    

年代:1980

数据来源: RSC

摘要:

14 Synthetic Methods ByR. BRE'ITLE Department of Chemistry The University Shefield S3 7HF 1 Introduction This Report like those of the two previous years is highly selective. Priority has been given to truly original methods that are thought to be capable of wide general use and to significant modifications of earlier procedures; full accounts of work that has previously been reported in outline have generally not been reported. 2 Alkanes The hydrogenolysis of organic halides has been reviewed,' and a comparison of many hydride reducing agents shows that the best for the reduction of halides are lithium tetrahydridoaluminate and triethylhydridoborate.2 Certain modified molyb- denum carbonyl species are good reagents for the desulphurization of thi01s.~ Esters of the type (l),preparable in conventional ways from the carboxylic acids undergo reductive cleavage to the alkanes on treatment with tributyltin hydride in a refluxing aromatic s~lvent.~ Similar conditions also convert the readily accessible phenyl- selenoesters into hydrocarbons; many common functional groups are unaffected.' /p \ (1) X = C1or SPh The conversion of tertiary halides into alkanes can be accomplished in rather good yields by dimethyltitanium(1v) dichloride; mixed-order dihalides react selec- tively at the tertiary site and other functionality (alkene ester) is tolerated.6 The whole range of methodologies for the construction of quaternary carbon centres has been reviewed.' * A.R. Pinder Synthesis 1980,425. S. Krishnamurthy and H.C. Brown J. Org. Chem. 1980,45,849. ' H. Alper and C. Blais J. Chem. SOC.,Chem. Commun. 1980,169. D. H.R. Barton H. A. Dowlatshahi W. B. Motherwell and D. Villemin J. Chem. SOC. Chem. Commun. 1980,732. J. Pfenninger C.Henberger and W. Graf Helv. Chim. Acta 1980,63 2328. M. T.Reetz J. Westermann and R. Steinbach Angew. Chem. Znt. Ed. Engl. 1980,19 900. S. F.Martin Tetrahedron 1980 36,419. 263 264 R. Brettle 3 Alkenes Allylic alcohols can be regiospecifically deoxygenated by conversion into the xan- thates followed by a [3,3] sigmatropic rearrangement and treatment with tributyltin hydride; protonolysis of the resultant allyltin gives the alkene.8 (See Scheme 1). R' R' Reagents i NaH CS,; ii MeI heat; iii Bu,SnH; iv H' Scheme 1 Lithium dialkylcuprates react with allylic sulphoxides and sulphones (2) to give trisubstituted alkenes (3);the reaction shows considerable regio- and stereo-selec- tivity.' Enol trifluoromethanesulphonates which are stable and easily available from ketones react with lithium dialkylcuprates to give alkenes." A similar and perhaps more convenient approach uses silyl enol ethers readily available regio- specifically which couple with Grignard reagents in the presence of dichlorobis- (triphenylphosphine)nickel(II) as a catalyst." Both reactions proceed regio- specifically with retention of the geometry of the double-bond.(2) n = 1or 2 (3) [major product] Reduction of alkynes with a zinc-copper couple in boiling methanol gives the (Z)-alkenes.12 The hexamethylphosphoric-trimiade-catalysed elimination of vicinal threo-bromo-trifluoromethanesulphonatesat last seems to have provided a satisfactory solution to the problem of converting threo -bromohydrins into the (Z)-alkenes with complete stereo~pecificity.'~ Krief has provided a survey of synthetic methods using Q -heterosubstituted ~rganometallics,'~ which naturally covers many alkene-forming reactions.Bestmann has reviewed" old and new ylide chemistry including the transylidation sequence leading to trisubstituted alkenes that is shown in Scheme 2. Several Wittig reactions which would not proceed at lower temperatures occurred when the I SiMe3 Reagents i Me,SiCI; ii transylidation; iii R'X; iv F-; v R3CH0 Scheme 2 Y. Ueno,H. Sano and M.Okawara Tetrahedron Lett. 1980,21 1767. 'Y.Masaki K.Sakuma and K.Kaji J. Chem. SOC.,Chem. Commun. 1980,434. J. M. McMurry and W. J. Scott Tetrahedron Lett. 1980 21,4313. T. Hayashi Y.Katsuro and M. Kumada Tetrahedron Lett.,1980,21,3915. B.L.Sondengam G. Charles and T. M. Akam Tetrahedron Lett. 1980 21 1069. l3 E. J. Corey A. Morfat J. R. Falck and J. 0.Albright J. Am. Chem. SOC.,1980,102 1433. I4 A. Krief Tetrahedron 1980,36,2531. H. J. Bestmann Pure Appl. Chem. 1980,52 771. Synthetic Methods reaction mixtures were heated to 160"C in acetonitrile in a pressure vessel.16 The preparation of cycloalkenes by the intramolecular Wittig reaction has been reviewed.17 The direct Peterson methylenation using trimethylsilylmethyl-lithium becomes more attractive with the discovery of a less tedious route to the silicon- based reagent.I8 The reaction of a@ -epoxy-silanes with Grignard reagents leads via a -trimethylsilyl-substitutedcarbonyl compounds to predominantly the erythro-p-hydroxy-silanes which can then be transformed stereospecifically into either (E)-or (2)-alkenes by the standard methods.'' Methods for the inversion of alkene geometry have been reviewed.20 Very large rate accelerations are observed when alkylaluminium chlorides are used to catalyse ene reactions.Moreover when dimethylaluminium chloride is used in the reaction with aldehydes the resultant alcohol-Lewis acid complex breaks down to give methane and a non-acidic aluminium oxide so that acid-sensitive products can be made in this way.Ipsenol (4) can be made in one step as shown g.";u-,= (4) though only in low yield owing to a competing [4 + 21 cycloaddition.21 The first example of an ene-reaction that produces chiral centres in a 1,3-relationship proved to be very stereospecific22 (Scheme 3). A strikingly high asymmetric induction and a very high 1,2-diastereoselectivity have also now been recorded in a low-temperature alkylaluminium-chloride-promotedintramolecular cyclization of the ene type.23 C1 EtAICI2 ~ &co2Me -tH2C AC02Me PhH at 25 "C CH2 [85% of product mixture] Scheme 3 The 'ate' complexes formed by the action of sodium methoxide on appropriate alkenyldialkylboranes which are accessible with either geometry of the alkene react with copper(1) bromide and dimethyl sulphide to give alkenylcopper intermedi- ates; at 0 "C,these couple to give 1,3-dienes with retention of the geometry of the alkene in the original borane~.*~ At -15 "C the intermediates can be trapped by ally1 halides to give 1,4-diene~;~' prenyl bromide gives 75% of the a-coupled T.F. Tam and B. Fraser-Reid J. Org. Chem. 1980,45 1344. '' K.B. Becker Tetrahedron 1980,36,1717. l8 D. E.Seitz and A. Zapata Tetrahedron Lett. 1980,21,3451. l9 P. F. Hudrlik A. M. Hudrlik R. N. Misra D. Peterson G. P. Withers and A. K. Kulkami J. Am. Chem. SOC. 1980,102,4444. 2o P. E. Sonnet Tetrahedron 1980,36,557. 21 B. B. Snider Acc. Chem. Res. 1980,13,426;B. B. Snider and D. J. Rodini Tetrahedron Letr. 1980 21 1815; B. B. Snider D.M. Roush D. J. Rodini D. Gonzalez and D. Spindell J. Org. Chem. 1980,452773. 22 B. B. Snider and J. V. DunEia J. Am. Chern. SOC. 1980,102,5926. 23 W.Oppolzer and C. Robbiani Helv. Chim. Acta 1980 63 2010; W. Oppolzer C. Robbiani and K. Battig ibid. p. 2015. 24 J. B. Campbell Jr. and H. C. Brown J. Org. Chem. 1980,45,549. 25 H.C. Brown and J. B. Campbell Jr. J. Org. Chern. 1980,45,550. 266 R. Brettle product. Many functional groups are tolerated. Alkenyl-zirconium species couple with (?r-ally1)palladium complexes of alkenes to give 1,4-dienes; the complex from a steroidal 17(20)-alkene undergoes coupling mainly at C-20 to give the product with the natural steroid configuration at that position.26 The palladium-catalysed elimination of acetic acid and carbon dioxide from the easily constructed p -acetoxy-y6-alkenoic acids shows a high preference for the (E) configuration at the new double-bond irrespective of the relative stereochemistry of the acetoxy and car- boxyl groups whereas earlier related syntheses normally required pure diastereoisomers; the stereochemistry of the 76-double-bond is ~naffected.'~ These first examples of palladium-catalysed decarboxylation occur in preference to loss of acetic acid to give a dienoic acid although the palladium-catalysed route from allylic acetates to dienes is now well established.Acyclic 1,3-dienes are available from cyclobutanone by known selenium chemistry the crucial step being the regiospecific formation of the cyclobutene by base-catalysed elimination of a selenonium salt.28 This provides another short route to ipsenol (4) as shown in Scheme 4.An example of the increasing importance.of tin derivatives in synthesis is provided by the use of a trimethylstannyl-transfer agent to prepare both the (2)-and (E)-forms of P-(trimethylstannyl)alk-2-enoates from alk-2-ynoates; further transformations including transmetallation then pro- vide a versatile route to substituted dienes (Scheme 5).29 Reagents i MeSeH ZnC1,; ii BuLi; iii m0 ;iv M;I,AgBF,; v KH DMSO; vi heat Scheme 4 -i-iii MeHCHO % MeC-CCO,R + Me,Sn H Li H EH Reagents i PhS(Me,Sn)CuLi kinetic control at -100 "C; ii MeOH; iii DIBAL; iv Ph,P=CH,; v MeLi; vi E' (E= electrophile) Scheme 5 Dienes can be prepared by the reaction of organocopper(1) species with the methanesulphinates of allenic alcohols as shown in the synthesis of myrcene (5).30 1,3-Dienyl esters are formed by the isomerization of prop-2-ynylic esters with silver trifluoroacetate in boiling benzene.,l Pearson has shown in a series of papers,32 how the iron tricarbonyl complexes of cyclohexa-1,3-dienes can be used to provide routes to quite complex structures.26 J. S. Temple and J. Schwartz J. Am. Chem. Soc. 1980,102,7381. 27 B.M. Trost and J. M. Fortunak J. Am. Chem. Soc. 1980,102,2841. S. Halazy and A. Krief Tetrahedron Lett. 1980 21 1997. 29 E.Piers and H. E. Morton J. Org. Chem. 1980,45,4263. 30 H. Kleijn H. Westmijze J. Meijer and P. Vermeer Reel. Trau. Chim. Pays-Bas 1980,99 340. 31 R. C. Cookson M.C. Cramp and P. J. Parsons J. Chem. Soc. Chem. Commun. 1980,197. 32 A. J. Pearson and P. R. Routhby J. Chem. Soc. Perkin Trans. 1 1980 395; A. J. Pearson ibid. p. 400;A. J. Pearson and M. Chandler ibid. p. 2238;A. J. Pearson E. Mincione M. Chandler and P. R. Raithby ibid. p. 2774;A. J. Pearson and M. Chandler Tetrahedron Lett. 1980 21 3933; A. J. Pearson and D. C. Rees ibid. p. 3937;A. J. Pearson ,P. Ham and D. C. Rees ibid. p. 4637;A. J. Pearson and C. W. Ong ibid. p. 4641. Synthetic Methods 267 (5) The derived complexes of hexadienyl cations are susceptible to stereospecific nucleophilic attack in both inter- and intra-molecular processes; the sequence chosen for illustration in Scheme 6 shows a route to cis-hydrindenes. The import- ance of this metholology would be further increased by the use of chiral tricarbonyl- cyclohexadienyliumiron salts so that Birch's resolution of tricarbonyl( 1-carboxy-cy~lohexa-l,3-diene)iron,~~ and the determination of the absolute configuration of the enantiomers points the way forward.C0)3Fea A (CO)3Fea \ -CH(C02Me)2 BF4-CH20H iv-vi/ -(cO),,a vii,viii CH,OAc * .* I CH-CHz-CH(C02Me)z Y H ,OAc Reagents i N_a+CH(CO,Me),; ii DIBAL; iii Tl(O,CCF,),; iv C,H,SO,Cl C,H,N; v K+CH(CO,Me),; vi HBF, Ac,O; vii DBU at -78 "C; viii Me,NO Scheme 6 4 Alkynes A considerable improvement in the conversion of methyl ketones into terminal alkynes through the enol phosphates results from the use of lithium tetramethyl- piperidide in the elimination Two new routes to 1,Senynes have been reported.In one cobalt complexes of propargyl cations are coupled with allyl-silanes (Scheme 7),35and the other employs the palladium-catalysed cross-coupling of alkenyl halides with homopropargylic organozinc ~hlorides.~~ R' R' R2 6' BF,-WR3 =+OH a RZ (CO)6C0z RZ R4 RS Reagents i Co(CO),; ii HBF, at -45 "C; iii Me3Si*R' ;iv Fe(NO,) R3 R4 Scheme 7 5 Alcohols Interest in the protection of hydroxyl groups continues. The use of allyl-silanes as silylating agents for alcohols has some advantages in terms of the by-products over the use of the trialkylsilyl chloride-tertiary amine method;37 catalysis 33 A. J. Birch and B. M. R. Bandara Tetrahedron Lett. 1980,21,2981. E.-I. Negishi A. 0. King W.L. Klima W. Patterson and A. Silveira Jr. J. Org. Chem. 1980,45 2526. 35 J. E. O'Boyle and K. M. Nicholas TetrahedronLen.,1980,21 1595. 36 E-I. Negishi L. F. Valente andM. Kobayashi J. Am. Chem. SOC., 1980,102 3298. 37 T.Morita Y. Okamoto and H. Sakurai Tetrahedron Lett. 1980,21.835. 268 R. Brettle especially by dimethyl sulphoxide makes the older method effective for tertiary The p-(trimethylsily1)ethoxymethyl group has been recommended as a new ether-type protecting group; it survives under acidic conditions which would cleave trialkylsilyl and tetrahydropyranyl ethers but is readily removed by treatment with fluoride ion.39 Two additional reagents for the cleavage of silyl ethers have been reported uiz. lithium tetraflu~roborate~' and N-bromosuccinimide in aqueous dimethyl sulphoxide,"' the latter being a very mild cheap system which is useable in the presence of many functions including tetrahydropyranyl ethers.A (2-methoxyethoxy)methyl (MEM) ether was cleaved through an intermediate 0-isopropylthiomethyl ether using conditions which did not cleave a t-butyldimethyl- silyl ether or a dithi~acetal.~' A comprehensive review of photo-removable protecting groups covers inter alia protection of hydroxyl groups in the carbohydrate field.43 Aldehydes react with methyltri-isopropoxytitaniumto give secondary alcohols under conditions where ketones esters epoxides and nitriles do not react; cinnamaldehyde gives only the allylic Markovnikov hydration of an isopropenyl group was only finally achieved in the total synthesis of picrotin by the route shown in Scheme 8 but the low yield shows the desirability of finding a -__* '"O& iii,iv ~0%~ i,ii HgCl Reagents i (CF,CO,),Hg; ii KCl; iii Bu3SnH; iv NaHCO, H,O MeOH Scheme 8 better demercuriation proced~re.~' Anti-Markovnikov hydration of alkenes can be achieved conveniently by the use of titanium tetrachloride with sodium borohy- dride.46 The epoxide group in (6) has been reductively opened in the presence of the ketone function by using tellurium hemi is try.^^ Two mild methods for the hydrolysis of primary iodides avoiding the expense of silver salts use copper(1) Me Me 38 R.G. Visser H. J. T. Bos and L. Brandsma Red. Trav. Chim. Pays-Bas 1980,99,70. 39 B.H. Lipshutz and J. J. Pegram Tetrahedron Lett. 1980 21 3343. 40 B. W. Metcalf J. P. Burkhart and K. Jund Tetrahedron Lett. 1980,21 35. 41 R. J. Batten A. J. Dixon R. J. K. Taylor and R. F. Newton Synthesis 1980 234. 42 E. J. Corey L. 0. Weigel A. R. Chamberlin H. Cho and D. H. Hua J. Am. Chem. SOC.,1980 102,6613. 43 V. N. R. Pillai Synthesis 1980 1. 44 B. Weidmann and D. Seebach Helv. Chim. Acta 1980 63 2451. 45 E. J. Corey and H. L. Pearce TetrahedronLett. 1980,21 1823. 46 S. Kano Y. Tanaka and S. Hibino J. Chem. SOC.,Chem. Commun. 1980,414. 47 D. L. J. Clive G. J. Chitattu V. Farina W. A. Kiel S. M. Menchen C. G. Russell A. Singh C. K. Wong and N. J. Curtis J. Am. Chem. SOC.,1980 102 4438. Synthetic Methods 269 oxide and methyl toluene-p-sulphonate as the iodide ~cavengers.~’ The reduction of aldehydes and ketones to alcohols by ammonia-borane and t-butylamine-borane has been compared with their reduction by borane and sodium b~rohydride.~~ The reagent prepared from N-isopropylcyclohexylamine and methylmagnesium iodide (MICA) is the best ever for the conversion of epoxides into allylic alcohol^.'^ The di-isobutylaluminium hydride-butyl-lithium ‘ate’ complex selectively reduces an cup-olefinic ester to the allylic alcohol in the presence of a carboxyl A more direct Wittig route to (2)-trisubstituted allylic alcohols has been de~eloped.~’ Homoallylic alcohols are formed when allyl-tin compounds obtainable by the reduction of allylic sulphones with tributyltin hydride are treated with trioxad2 (cf.Scheme 1).The syn-hydroxylation of alkenes by osmium tetroxide has been comprehensively reviewed;53 addition of trimethylamine N-oxide and pyridine results in a high yield even with a tetrasubstituted alkene.54 The methodology for the stereocontrolled construction of acyclic molecules continues to develop rapidly spurred on by the desire to synthesize complex ionophore and macrolide antibiotics where the stereochemical problems can often be reduced by convergency to the formation of vicinal stereo-relationships with control by pre-existing stereo-relationships. Fortunately a timely review appeared at the start of the year.55 Many of the reactions are of the aldol type. Chelation- controlled (or anti-Cram) nucleophilic addition to a-alkoxycarbonyl compounds received a lot of attention and highly stereoselective procedures for the preparation of both threo- and erythro-1,2-diols are now available and have been used in the synthesis of natural p -Hydroxy-acids and substituted homoallylic alcohols which can be converted into p -hydroxy-ketones by palladium-catalysed oxidation have been further in~estigated,~’ as have direct routes to p -hydroxy-ketone^,^' where the relative py-stereochemistry can now be controlled by the use of a new highly enantioselective chiral reagent59 which counteracts the normally small selectivity of aldehydes in the formation of the a@-bond.Diastereoselectivity has also been observed in the Michael addition of a doubly deprotonated chiral 48 M.Yoshioka T. Tsuji S. Uyeo S. Yamamoto T. Aoki Y. Nishitani S. Mori H. Satoh Y. Hamada H. Ishitobi and W. Nagata Tetrehedon Lett. 1980 21 351. 49 G. C. Andrews and T. C. Crawford Tetrahedron Lett. 1980,21 693 697. ” B. M. Trost G. T. Rivers and J. M. Gold J. Org. Chem. 1980,45 1835. 51 C. Sreekumar K. P. Darst and W. C. Still J. Org. Chem. 1980,45,4260. 52 Y.Ueno S. Aoki and M. Okawara J. Chem. SOC.,Chem. Commun. 1980,683. 53 M. Schroder Chem. Rev. 1980,80,187. ” R. Ray and D. S. Matteson Tetrahedron Len.,1980,21,449. 55 P. A. Bartlett Tetrahedron 1980,36 2. 56 W.C. Still and J. H. McDonald Tetrahedron Lett. 1980 21 1031; W.C. Still and J. A. Schneider ibid. p. 1035;D. B. Collum J. H. McDonald and W. C. Still J. Am. Chem. SOC.,1980 102 2117 2118,and 2120;C.H.Heathcock S. D. Young J. P. Hagen M. C. Pirrung C. T. White and D. Van Derveer J. Org. Chem. 1980,45,3846;K. C.Nicolaou D. A. Claremon and W. E. Barnette J. Am. Chem. Soc. 1980,102,6611. ” M.C.Pirrung and C. H. Heathcock J. Org. Chem. 1980 45 1727; H.Yatagai Y. Yamamoto and K. Maruyama J. Am. Chem. SOC.,1980,102,4548; R. W.Hoffmann and H-J. Zeiss Angew. Chem. Int. Ed. Engl. 1980 19 218; Y. Yamamoto H. Yatagai and K. Maruyama J. Chem. SOC.,Chem. Commun. 1980 1072; Y. Yamamoto H. Yatagai Y. Naruta and K. Maruyama J. Am. Chem. SOC. 1980,102,7107. 58 I. Kuwajima M. Kato and A. Mori Tetrahedron Lett. 1980 21 4291; Y. Yamamoto and K. Maruyama ibid. p. 4607;D. A. Evans and L. R. McGee ibid. p. 3975. 59 S. Masamune Sk. A. Ali D. L. Snitman and D.S. Garvey Angew. Chem. Znt. Ed. Engl.. 1980 19 557. 270 R. Brettle @ -hydroxy-ester to a nitro-alkene,60 and in the cyclic hydroboration of non-conju- gated dienes to give diolsm61 6 Ethers In a synthesis of a very labile epoxide leukotriene A methyl ester (8) from the chiral hydroperoxide (7) conditions were established62 which generated an elec- trophilic oxygen centre by loss of a good leaving group in the presence of a hindered base at low temperatures thereby minimizing both a competing carbonyl- forming elimination and the acid-catalysed decomposition of the product (8). (7) (8) Ally1 ethers can conveniently be isomerized to vinyl ethers by heating them with palladium charcoal (Pd/C) in an aromatic solvent.63 Phenyl and vinyl allyl ethers isomerize more slowly than alkyl allyl ethers thus permitting the preparation of the vinyl allyl ether (9) by the route shown.TOT pd/c.+yoy PhH for 3 5 h (9) Milder catalytic conditions using trimethylsilyl trifluoromethanesulphonate have been developed for the condensation of acetals with enol silyl ethers and allyl-silanes to give substituted 7 Halides Trialkylboranes react with iodine chloride in methanol that contains sodium acetate to give alkyl iodides; this is a milder and more economical method than earlier related ones.65 It had been reported earlier that trimethylsilyl chloride-sodium iodide or hexamethyldisilane-iodine converted alcohols into iodides. Now it has been shown that trimethylsilyl chloride-sodium bromide or hexamethyldisilane- pyridinium tribromide similarly convert alcohols into bromides;66 the second reagent converts a secondary-tertiary diol into the hydroxylated tertiary bromide selectively.1 1 -Bromoundecyl tosylate is reduced by lithium aluminium hydride in diglyme to undecyl tosylate but if the solvent is changed to diethyl ether the reduction product is undecyl bromide; this is a remarkable effect of the solvent on chemo~electivity.~' 6o M. Zuger T. Weller and D. Seebach Helv. Chim. Acra 1980,63,2005. " W. C. Still and K. P. Darst J. Am. Chem. Soc. 1980,102,7385. E.J. Corey A. E. Barton and D. A. Clark J. Am. Chem. SOC.,1980 102,4278. 63 H.A.J. Carless and D. J. Haywood J. Chem. Soc. Chem. Commun. 1980,980. 64 T.Tsumoda M. Suzuki and R.Noyori Tetrahedron Lett. 1980.21,71:S. Murata M.Suzuki. and R. Noyori J. Am. Chem. SOC.,1980 102 3248; Tetrahedron Lett. 1980,21,2527. " G. W. Kabalka and E. E. Gooch J. Org. Chem. 1980,45,3578. " G. A.Olah B. G.B. Gupta R. Malhotra and S. C. Narang J. Org. Chem. 1980,45 1638. 67 S.Krishnamurthy J. Org. Chem. 1980,45,2550. Synthetic Methods 27 1 8 Nitriles Phenyl cyanate for which an improved preparation has been developed is a convenient source of electrophilic cyanide in the preparation of acetylene nitriles from lithium acetylides; with lithio-alkenes the substitution occurs stereospecifically with retention of configuration.68 A rapid and efficient procedure for the dehydration of saturated ap-olefink and aromatic primary amides involves the addition of the amide to a pre-formed suspension of the Vilsmeier reagent chloro-NN-dimethyl- forminium chloride in acetone at 0°C; the addition of pyridine then leads to the formation of the nitrile within a few minutes.69 Reduction of a hexaquinane bis(aP -0lefinic nitrile) by Corey's magnesium and methanol method unexpectedly gave a p-p -coupled saturated dinitrile but the use of Semmelhack's copper hydride complex used earlier on enones gave the desired saturated dinitrile with no formation of a transannular bond.70 9 Nitro-compounds The synthesis and reactions of nitro-compounds in genera171 and of cyclic a-nitro- ketones in particular7* have been reviewed.An effective mild and selective method for the conversion of ketoximes into secondary nitro-compounds has been reported (Scheme 9).73Conjugated olefinic nitro-compounds can be prepared from the Reagents i HOCl benzene/H,O pH 5.5 at 25 "C; ii Bu',N'OCI- benzene/H,O; iii Mg THF then CH3C02H,or Zn aq.THF NH30H'C1- or H2 Pd/C aq. MeOH NaOH then CH3C02H Scheme 9 saturated compounds by a selenation-selenoxide elimination route,73 or from vinyl- stannanes obtainable from ketones by a modified Shapiro reaction by treatment with tetranitromet hane in dimet hyl ~ulphoxide.~~ 10 Amines The synthesis of allylic amines from allylic alcohols via imidic esters has been reviewed;75 the review75 also covers the use of trichloroacetamido-l,3-dienesin cycloaddition reactions. Organocopper reagents like other organometallics react with Mannich reagents to give aminomethylated products.Alkenyl-copper and cuprate reagents give the tertiary allylamines with cis geometry; alkenyl-alanes and alanates give the trans-amines (Scheme Saturated amines can be prepared by the reductive alkylation of amines with carbonyl compounds under very mild 68 R. E. Murray and G. Zweifel Synthesis 1980 150. 69 T.M.Bargar and C. M. Riley Synth. Commun. 1980,10,479. 70 M. E. Osborn J. F. Pegues and L. A. Paquette J. Org. Chem. 1980,45 167. 71 R.H. Fischer and H. M. Weitz Synthesis 1980 261. 72 D.Seebach E. W. Colvin F. Lehr and T. Weller Chimia 1979,33 1. 73 E.J. Corey and H. Estreicher Tetrahedron Lett. 1980,21 1117. 74 E. J. Corey and H. Estreicher Tetrahedron Lett. 1980 21 1113. 75 L.E.Overmann Acc. Chem.Res. 1980,13 218. 76 C. Germon A. Alexakis and J. F. Normant Tetrahedron Lett. 1980 21 3763. 272 R. Brettle HCGCH RC=CH li 1iii R+ (RdguLi AIBu', 1ii 1iv Rm CHZNEt R Reagents i R,CuLi; ii PhSCH,NEt,; iii DIBAL; iv Bu'OCH,N Scheme 10 conditions by using phenylselenol as the reducing agent; alkene nitrile amide and ester functions are not reduced by this reagent.77 Carboxamides can be reduced to amines in the presence of alkene ester nitro and sulphonamide functions by the method shown in Scheme 11.78 Reaction times are shorter than in other procedures S SEt II I R3CONR'R2 R3-C-NR'R2 A R3-&R'R2 -!!+ R3CH2NR'R2 Reagents i Ar,P2S (Ar = p-MeC,H,); ii Et,O'BF,-; iii NaBH Scheme 11 RCOCl ,0SiMe3 R-C -% RNCO 2RNH2 RCONHOH \NOSiMe3 Reagents i Me,SiONHSiMe,; ii (Me,Si),NH; iii heat at 120"C; iv conc.H,SO,; v ice Scheme 12 and primary amides are reduced without any competing dehydration. Amines can be prepared cleanly from acid derivatives by the routes shown in Scheme 12 incorporating an improved procedure for the hydrolysis of iso~yanates.~~ An excel-lent general method for the preparation of vicinal primary amines (Scheme 13) 0 0 I1 N N R3 H,N NH, /\ II RiR3 11 x:41 + cp-co-co-~p .Lcp-cy ' A R'R3C-CR2R4 Rz R4 \/ N N II II R2 0 0 (CP = 77-C5H5) Reagents i NO at 0 "C; ii LiAlH Scheme 13 77 K. Fujimari H. Yoshimoto and S. Oae Tetrahedron Lett. 1980,21 3385. S. Raucher and P. Klein Tetrahedron Lett. 1980 21,4061. 79 J. Rigaudy E.Lytwyn P. Wallach and N. K. Cuong Tetrahedron Lett. 1980,21,3367;F. D. King S. Pike and D. R. M. Walton J. Chem. SOC.,Chem Commun. 1978,351. Synthetic Methods 273 results from following up some earlier organometallic work; unfortunately the reaction shows rather poor stereoselectivity." 11 Aldehydes and Ketones In a new synthesis treatment of a primary azide with 'magic methyl' (FS03Me) followed by the action of an aqueous buffer at pH4 generated an aldehyde at room temperature.'l New methods for the conversion of highly hindered ketones into the next higher aldehyde have been reported which employ ingenious variants of the Peterson and Wittig reactions to generate enol ethers.82 Acyl chlorides can be reduced to aldehydes satisfactorily by tributyltin hydride provided that a pal- ladium catalyst is alternative new reducing systems are sodium borohydride -dimethylformamide in acetonitrile in the presence of cadmium(I1) ions84 or the cyanoborohydride (10) under neutral ~onditions.~~ The anion (1 1) is an improved equivalent of the formyl anion with greater nucleophilicity; regeneration of the aldehyde occurs under much milder conditions than in the better-known 1,3-dithian procedure .86 (P~~P)~CUBH~CN PhSCHSiMe3 (10) (11) Sodium hypochlorite is a cheap convenient reagent for oxidizing secondary alcohols to ketone^;^' the transformation can also be accomplished under very mild conditions by the complex formed from dimethyl sulphoxide and chlorosul- phony1 isocyanate at -78 0C.88Alternative methods for the conversion of secondary nitro-compounds into ketones have been de~eloped,~~ and the oxidative desul- phonylation of secondary sulphones to give ketones has been achieved" with molybdenum peroxide; the use of molecular oxygen led to an explosion in one case.Sodium hydrogen telluride reduces the carbon-carbon double-bond in conju- gated olefinic ketones (and related systems) without affecting isolated double- bonds." The same reduction when conducted using lithium in ethylamine contain- ing 2-methylpropan-2-01 is considerably improved9* by lowering the reaction temperature to -78 "C. Ketones or their enol silyl ethers or enol acetates react with cobalt complexes of propargyl cations (cf.Scheme 7)to give after demetalla- tion acetylenic ketones.93 Site-specific monoalkyl-substituted acyclic ketones can so P.N Becker M. A. White andR. G. Bergmann J. Am. Chem. SOC.,1980,102 5676. 81 E.J. Corey J. W. Ponder and P. Ulrich Tetrahedron Lett. 1980,21 137. 82 E.J. Corey and M. A. Tuis Tetrahedron Lett. 1980 21 3535; E.J. Corey M. A. Tuis and J. Das J. Am. Chem. SOC.,1980,102 1742. 83 F. Ginke P.Four and H. RivBre J. Chem. Soc. Chem. Commun. 1980,432. 84 I. D.Entwistle P. Boehm R. A. W. Johnstone and R. P. Telford J. Chem. Soc. Perkin Trans. 1 1980,27. R.0.Hutchins and M. Markowitz Tetrahedron Lett. 1980,21 813. 86 P. J. Kocienski Tetrahedon Lett. 1980,21 1559; D. J. Ager and R. C. Cookson ibid. p. 1677. " R. V. Stevens K. T. Chapman and H. N. Weller J. Org. Chem. 1980,45,2030. G.A. Olah Y. D. Vankar and M. Arvanaghi Synthesis 1980 141. 89 G. A. Olah and B. G. B. Gupta Synthesis 1980,44;G. A. Olah M. Arvanaghi Y. D. Vankar and G. K.S.Prakash ibid. p. 662. 90 R. D. Little and S. 0.Myong Tetrahedron Left. 1980 21 3339. 91 M. Yamashita Y. Kato and R. Suemitsu Chem. Left. 1980,847. 92 A. W. Burgstahler and M. E. Sanders Synthesis 1980,400. 93 K. M. Nicholas M. Mulvaney and M. Bayer J. Am. Chem. SOC.,1980,102 2508; S.Padmanabhan and K. M. Nicholas Synth. Commun. 1980 10 503. 274 R. Brettle be obtained from the specific enol boranes routes to which are available by the use of alkyl halides in the presence of lithium 2-(dimethylarnino)etho~ide.~~ a -Allyl-substituted ketones can be prepared by the decarboxylation of ally1 0 -keto-esters as shown in Scheme 14.95 0 Reagent i [Pd(PPh,),] DMF at 20 OC Scheme 14 Alkenyl- (but not alkyl-) zirconium species undergo conjugate addition to ap-olefinic and acetylenic ketones in the presence of a catalyst prepared from nickel acetylacetonate and DIBAL followed by quenching with acid.96 A lot of attention has been given to the reactions of organocopper compounds and organocuprates with cup-olefink carbonyl compounds especially with conjugated olefinic aldehydes leading to /3 -alkylation or conjugate red~ction.~' Selenium-based methodology for the synthesis of ap-olefinic aldehydes and ketones continues to develop.For the preparation of ap-olefinic aldehydes the reaction of an enol silyl ether,98 en~l-borane,~~ or enamine"' with phenylselenyl chloride occurs readily at low temperatures to give the a -phenylselenyl-substituted aldehyde; subsequent oxidative elimination then introduces the conjugated olefinic bond.These methods avoid the problems sometimes encountered in the direct selenylation of aldehydes. The direct selenylation of ketones (and esters) can be conducted through the reaction of selenium metal with lithium enolates,"' as shown in Scheme 15.The regiospecificity that is observed in the addition of phenylselenyl chloride to allylic alcohols is vital to a new 1,3-enone transposition procedure,"' an example of which is shown in Scheme 16. Reagents i LDA 3 moles of HMPT; ii black selenium; iii Me1 Scheme 15 94 J. Hooz and J. Oudenes Synth. Commun.1980,10,139. 95 T. Tsuda Y.Chujo S-i. Nishi K. Tawara and T. Saegusa I. Am. Chem. Soc. 1980,102,6381. 96 J. Schwartz M. J. Loots and H. Kosugi J. Am. Chem. Soc. 1980,102,1333. 97 C. Chuit J. P. Foulou and J. F. Normant Tetrahedron 1980,36 2305;M. Suzuki T. Suzuki T. Kawagishi and R. Noyori TetruhedronLett.,1980,21,1247;S. H. Bertz ibid. p. 3151;A. B. Smith B. A. Wexler and J. S. Slade ibid. p. 3237;T. Ibuka H. Minakata Y. Mitsui K. Kinoshita and Y. Kawami J. Chem. SOC., Chem. Commun. 1980,1193;T.Ibuka H. Minakata Y. Mitsui K. Kinoshita Y. Kawarni and N. Kimura Tetrahedron Lett. 1980 21 4073; T.Tsuda T.Fujii K. Kawasaki and T. Saegusa J. Chem. Soc. Chem. Commun. 1980 1013. 98 K. C. Nicolaou R. L. Magolda and W. J. Sipio Synthesis 1979,982;K. C. Nicolaou R.L. Magolda and D. A. Claremon J. Am. Chem. Soc. 1980,102,1404. 99 J. Hooz and J. Oudenes Synth. Commun. 1980,10,667. loo D. R. Williams and K. Nishitani Tetrahedron Lett.. 1980 21,4417. D. Liotta G. Zima C. Barnum and M. Saindane Tetrahedron Lett. 1980 21 3643. D. Liotta and G. Zima J. Org. Chem. 1980,45,2551. Synthetic Methods C1 OH Reagents i LiAlH,; ii PhSeC1 at -78°C; iii 0,; iv Et,NH CH2Cl2 heat; v MeCOCl C5H5N; vi Hg(02CCHA CFSCOzH Scheme 16 Reagents i MeOS0,F; ii BuLi; iii at -20°C; iv MCPBA at -4O"C then work up; v (CO2H), THF-water at 20 "C Scheme 17 A new synthesis of Py-olefinic aldehydes (Scheme 17) is related to the synthesis of saturated aldehydes using the reagent (ll),that is described above and the synthesis involves a [2,3] sigmatropic rearrangement of a silicon-stabilized sulphur ~1ide.l'~ The selectivity in the acetylenic oxy-Cope arrangement of 3-hydroxy-alk-5- en-1-ynes is much improvedlM by carrying out the reaction in boiling N-methyl- pyrrolidinone in the presence of a halogen catalyst such as iodine and has led to an industrial-scale synthesis of pseudoionone (12).P-Diketones can be prepared from ap-epoxy-ketones in a rather slow reaction conducted at elevated temperatures in the presence of a palladium(0) catalyst (Scheme 18).'05 1,SDiketones result from the addition of (1-alkyny1)trialkylborates lo' P. J. Kocienski J. Chem. SOC.,Chem. Commun. 1980 1096. '04 Y. Fujita T. Onishi K.Hino and T. Nishida Tetrahedron Lert. 1980 21 1347 M. Suzuki A.Watanabe and R. Noyori J. Am. Chem. SOC.,1980,102 2095. 276 R. Brettle 0 00 Reagents i [Pd(PPh,),] (Ph2PCH2)2 PhMe at 80-140 "C Scheme 18 to butenone in the presence of titanium(1v) chloride followed by oxidation with alkaline hydrogen peroxide. lo6 New syntheses have been developed for Q -keto-esters (from a-a~ido-esters),~'' for certain P-keto-esters108 (see Scheme 19),for y-keto-ester~"~ (see Scheme 20) and for y-substituted-& keto-esters"' (see Scheme 21). R' *C02Me \ R2 R2+ C02Me R' Reagents i [Pd(PPh,),] (Ph2PCH2), MeOCH2CH20Me reflux Scheme 19 C02Me R' i h4e3!3iO&R3 R,* C02Me Me3si0wR3 0 R2 -R1 R2 R2 R3 Reagents i N2CHC02Me [Cu(acac),] at 90 "C; ii Et,NH+F- THF at 20 "C Scheme 20 OSiMe Me Me Me Reagents i ,MeCN; ii RCHCl(SPh) ZnBr,; iii Raney nickel MeO'OSiMe3 Scheme 21 12 Carboxylic Acids and their Derivatives Recent developments in methods for the protection and esterification of the carboxyl group have been reviewed."' P -Chloroethyl esters can be cleaved reductively with zinc (or electrochemically) in the presence of catalytic amounts of aquocobalamin or synthetic analogues of vitamin B12.Since the end of the reduction is signalled by a colour change from red to green it has been dubbed the 'traffic-light reac- '06 S.Hara K. Kishimura and A. Suzuki Chem. Lett. 1980 221. lo7 P. A. Manis and M. W. Rathke J. Org. Chem. 1980,454953. lo' B. M. Trost T. A. Runge and L. N. Jungheim J. Am. Chem. SOC.,1980,102,2841; cf.G. Valavoine and F. Guibe Tetrahedron Lett. 1979 3949. lo9 H-U. Reissig and E. Hirsch Angew. Chem. Znt. Ed. Engl. 1980 19,813. 'lo Y. Kita J. Segawa J. Haruta T. Fujii and Y. Tamura Tetrahedron Lett. 1980 21 3779. '11 E. Haslam Tetrahedron 1980 36 2409. Synthetic Methods tion'.'12 The /3 -chloroethyl group and a second new carboxyl-protecting group,l13 the p -methoxycarbonylbenzyl group (which can be removed by electrochemical reduction) have both been used to protect sensitive /3 -1actam antibiotic acids. Continued interest in the activation of carboxylic acids by their conversion into thiol esters has led to some further methods for achieving this with advantages in terms of mildness cheapness and procedural ~0nvenience.l~~ -0lefinic acid CUP derivatives including thiolesters can be prepared by using the phosphorus-based route exemplified in Scheme 22.l" Trimethylsilyldiazomethane which is thermally stable has been recommended in preference to diazomethane for the Arndt-Eistert homologation of acids.116 ..... +-+-Ph3P-CHC02Me 5Ph,P-C=C=O aR2CH=CHCOYR' Reagents i Na[N(SiMe,),]; ii R'YH (e.g.PhSH); iii R'CHO Scheme 22 a-Phenylselenylation of a hindered ester as part of an ap-desaturation pro- cedure was only successful with diphenyl diselenide and potassium hydride which is a convenient combination for general use."' Following earlier work on thioamides it has now been shown that certain organometallic reagents undergo Michael addition to relatively lightly substituted a@ -0lefinic amides and trimethyl- hydrazides and that the initially formed anion can then be trapped by electrophiles; e.g.see (13).'18A wider range of conjugated olefinic amides can be reduced to the saturated amides by magnesium in The dimetallation of ap-0lefinic amides is possible too and the reaction of the dianion gives substitution at the P'-position; the procedure has been used as part of a route to a-methylene-lactones (see Scheme 23).'*' Another route to a-methylene-lactones is based on [2-(alkoxy- carbonyl)allyl]trimethylsilanes (Scheme 24).12' The Baeyer-Villiger oxidation of P-(trimethylsilyl)cycloalkanones,followed by hydrolytic ring-opening gives esters that contain a remote P -trimethylsilyl alcohol function which is easily convertible (by standard methods) into a double-bond.A '" R. Scheffold and E. Amble Angew. Chem. Int. Ed. Engl. 1980,19,629. 'I3 D. F.Corbett and A. J. Eglington J. Chem. SOC.,Chem. Commun. 1980 1083. 0. Piepers and R. M. Kellog J. Chem. SOC. Chem. Commun. 1980 1147; H-U.Reissig and B. Scherer Tetrahedron Lett. 1980,21,4259;H-J. Lui and S. I. Sabesan Can. J. Chem. 1980,58,2645. '15 H.J. Bestmann G. Schmid and D. Sandmeier Chem. Ber. 1980,113 912; H. J. Bestmann and D. Sandmeier ibid. p. 274;cf. H. J. Bestmann Angew. Chem. Int. Ed. Engl. 1977,16 348. '16 T.Aoyama and T. Shioiri Tetrahedron Lett. 1980,21,4461. '" A. L. Cossey L. Lombardo and L. N. Mander Tetrahedron Lett. 1980 21,4383. '" J. E.Baldwin and W. A. Dupont Tetrahedron Lett. 1980,21,1881; G. B. Mpango K. K.Mahalanabis Z. Mahdavi-Damghani and V. Snieckus Tetrahedron Lett. 1980,21,4823;S. Knapp and J. Calienni Synth. Commun. 1980,10 837. '19 R. Brettle and S. M. Shibib Tetrahedron Lett. 1980 21 2915. 120 J. J. Fitt and H. W. Gschwend J. Org. Chem. 1980,45,4257;P. Benk and D. J. Kempf J. Am. Chem. SOC.,1980,102,4550. '" A. Hosomi H. Hashimoto and H. Sakurai Tetrahedron Lett. 1980,21,951. 278 R. Brettle Reagents i 2 moles of BuLi TMEDA THF at -70 "C;ii PhCOPh; iii H20; iv xylene reflux Scheme 23 Me,SiCH,C=CH i HzC=C-CH2CHR2 ii,iii I -* I I C02R' C02R' OR3 Reagents i RZCH(OR3)2 BF,*Et20; ii Me,SiI; iii MeOH Scheme 24 Me,SiI Me,Si Reagents i MCPBA in phosphate buffer; ii MeOH MeONa; iii BF3-Et,0 Scheme 25 simple example is shown in Scheme 25.'22 The use of cuprates on (Z)-vinyl- substituted lactones leads to chirality transfer with inversion and it provides for example a route to the olefinic acid (14).12,An earlier palladium-catalysed process using stabilised anions went with retention.H Me Me2CH(CH2),CHZCuCN O W H ether at -20 to0 'C \ ' H02C1 (14) Me A development of a synthesis of ap-olefinic esters that uses the Claisen orthoester rearrangement (reported last year) uses trimethyl @ -methoxyorthopropionate in the reaction with the allylic alcohol; base-catalysed elimination of methanol from the rearrangement product gives an a-substituted acrylic ester.'24 The use of diethyl oxomalonate in the ene-reaction has been extended and routes to olefinic acids that are based on it (see Scheme 26) have been deve10ped.l~~ In a new route to y6-olefinic acids the key step is the Claisen rearrangement of vinyl-substituted silyl ethers of lactones which can be constructed by a variety of methods.The example shown (Scheme 27) is a step from a synthesis of widdrol and it illustrates the control of remote relative chirality which can be achieved.'26 cyp -0lefinic esters 122 P. F. Hudrlik A. M. Hudrlik G. Nagendrappa T. Yimenu E. T. Zellers and E. Chin J. Am. Chem. Soc. 1980 102,6894. B. M. Trost and T. P. Klun J. Org. Chem. 1980,45,4256. lZ4 S. Raucher J. E. Macdonald and R. F. Lawrence Tetrahedron Lett. 1980,21,4335. lZ5 M. F. Salornon S. N. Pardo and R. G. Salomon J. Am. Chem. SOC.,1980,102 2473. S. Danishefsky R. L.Funk and J. F. Kerwin Jr. J. Am. Chem. SOC.,1980,102,6889; S. Danishefsky and K. Tsuzuki ibid. p. 6891. Synthetic Methods C0,Me 7-+ -v+ C0,Me Reagents i OC(CO,Et), at 180°C for 48h; ii KOH H20; iii HCI; iv NaIO, H20 C,H,N; v CH,N2; vi OC(CO,Et), SnCI, for 5 min at 0 "C Scheme 26 Reagents i toluene at 110OC; ii Bu,N+F- Scheme 27 unlike cup-olefinic ketones cannot be alkylated by allyl-silanes but very good yields of alkylated products are obtained in the reaction of allyl-silanes with ap-0lefinic acyl cyanides in the presence of titanium(1v) chloride;'*' the products can readily be transformed into esters and other acid derivatives by standard methods. Silver silicate was used to oxidize a lactol to a lactone after bromine water had proved unsatisfactory.12' Aldehydes and ketones react regiospecifically with metal- lated keten thioacetals to give products which can readily be converted into y-lactone~.'~~ The palladium-catalysed carbonylation of halogeno-alcohols is a very general route to lactones which is particularly useful for the preparation of ap-butenolides from (Z)-p-(hydroxymethy1)vinyl iodides. 130 Another route to ap-butenolides starts from ap-olefink aldehydes the 0-trimethylsilyl cyanohydrins of which are oxidized by pyridinium dichromate to give the lactones;131 the reaction is restricted to those cases where the p-position is disubstituted and there is a hydrogen at the y-position. The reaction of a Grignard reagent (which unlike lithium di-isopropylamide does not introduce an amine into the system) with an aa-diphenylsulphenylated lactone generates the magnesium enolate of the monosulphenylated lactone which can successfully be condensed with an aldehyde when prepared in this way (see Scheme 28).132 The bis-lactonization of unsaturated 0 OMgBr 0 SPh o*sph SPh '-0 3SPh __* ii,iii o* OH Reagents i EtMgBr Et20; ii MeCHO; iii H,O+ Scheme 28 lZ7 A.Jellal and M. Santelli Tetrahedron Lett. 1980 21 4487. 12' A. Pierdet L. Nedelec V. Delaroff and A. Allais Tetrahedron 1980,36 1763. lZ9 A. P.Kozikowski and Y.-Y. Chen J. Org. Chem. 1980,452236. 130 A. Cowell and J. K. Stille J. Am. Chem. SOC.,1980,102,4193. 13' E.J. Corey and G. Schmidt Tetrahedron Lett. 1980,21,731. 13' B.M.Trost and M. K. T. Mao Tetrahedron Lett.1980.21 3523. 280 R. Brettle Reagents i Bu,N'OH-; ii dry; iii Pb(OAc) (6-15equivalents) MeCN ?t 75-80"C Scheme 29 diacids that was reported last year can be controlled to produce efficient syn-addition of the two carbonyl groups to the double-bond (Scheme 29).133 Macrocyclic lactones containing a p-keto function for example diplodiolide A can be synthesized by using a modification of the Eschenmoser sulphide contraction (see Scheme 30) in which the bond that is being formed in the ring-closure step is actually a carbon-sulphur bond.134 Olefin metathesis has been used for the forma- tion of the carbon-carbon double-bond in the synthesis of olefinic macrocyclic lactones (see Scheme 31).13' A further method for the lactonization of w-hydroxy- acids uses the cyanuric chloride-triethylamine combination in acetone at room temperature.136 FrJrMe] ii,iii _3 (170 0 0 Reagents i Pr',NEt; ii (EtO),P; iii H,O' Scheme 30 Reagents i WC16 Me& in PhCl at 75"C; very high dilution Scheme 31 13 Alkylation A description of a simple preparation of lithium di-isopropylamide (LDA) which does not require an alkyl-lithium reagent has appeared and this should facilitate the many uses of LDA for example in the formation of en01ates.~~' Alkylation through tris(dialky1amino)sulphonium enolates has been in~estigated.'~~ The prob- lems with traces of water that are encountered with quaternary ammonium salts are avoided and as there is negligible interaction with the cation what is in effect a naked enolate anion is produced.An example of this methodology is shown in Scheme 32. Freeze-dried potassium fluoride shows enhanced catalytic activity over 13' E. J. Corey and A. W. Cross Tetrahedron Lett. 1980 21 1819. 134 R. E.Ireland and F. R. Brown Jr. J. Org. Chem. 1980,45 1868. D. Villemin Tefrahedron Left. 1980 21 1715. 136 K. Venkataraman and D. R. Wagle Tetrahedron Lett. 1980,21 1893. "'M. T.Reetz and W. F. Maier Liebigs Ann. Chem. 1980 1471. R. Noyori I. Nishida J. Sakata and M. Nishizawa J. Am. Chem. Soc. 1980 102 1223; R. Noyori I. Nishida and J. Sakata Tetrahedron Lett. 1980,21,2085. ''13 281 Synthetic Methods Scheme 32 other sources of fluoride ion in alkylation reactions; pentane-2,4-dione (15) for example undergoes C-alkylation at room temperat~re.'~~ Another simple system for the alkylation of p -dicarbonyl and related compounds uses potassium hydroxide in dimethyl sulphoxide that contains some trifluoromethanesulphonic acid; no special precautions to exclude water are necessary and elimination is not a problem with secondary halides.14' Bis(pentane-2,4-dionato)nickel is at least as good a catalyst as alkoxide for the Michael reaction;141 an interesting Knoevenagel-Michael reaction has been reported using this catalyst.(15) Trost has given full details of his work on inter- and intra-molecular allylic alkylation through the palladium-catalysed substitution of allylic carbo~ylates,~~~ and has reviewed the selectivity observed in such A review covering this and wider aspects of displacement reactions of allylic compounds has also appeared.144 A recent example,14' which illustrates the very high regio- and stereo- selectivity of these palladium-catalysed processes is shown in Scheme 33.In a new CHC0,Me OH OAc Reagents i Na[CH(CO2Me)SO2PhI;ii [Pd(PPh,),] Scheme 33 route to conjugated trienone~,~~~ an initial displacement of this type is followed by a palladium-catalysed elimination reaction (see Scheme 34). Scheme 34 shows the allylation of a sulphone-stabilized anion. Ally1 sulphones can themselves act as the allylating agent in this type of rea~fion,'~~ even though in the absence of catalysis by palladium the phenylsulphinyl group is not normally displaced as a leaving group.An example of this is given in Scheme 35. A modification of the Trost procedure permitting the use of lower temperatures has been reported and N. Ishikawa T. Kitazume and M. Nakabayashi Chem. Lett. 1980 1089. '*' R. A.W. Johnstone D. Tuli and M. E. Rose J. Chem. Res. (Sj,1980 283. 14' J. M. Nelson P. N. Howells G. C. DeLullo G. L. Landen and R. A. Henry J. Org. Chem. 1980 45 1246. B. M. Trost and T. R. Verhoeven J. Am. Chem. SOC.,1980,102,4730,4743. 143 B.M. Trost Acc. Chem. Res. 1980 13 385. R. M. Magid Tetrahedron 1980.36 1901. 14' J. P.Genet F. Piau and J. Ficini TetrahedronLett. 1980 21 3183. B.M. Trost N. R. Schmuff and M.J. Miller J. Am. Chem. Soc. 1980,102 5979. 282 R. Brettle S0,Ph i-iii @-0 0 Reagents i NaH; ii ,[Pd(PPhJ,]; iii DBU [Pd(PPh,),l OAc Scheme 34 Me0,C H2C S0,Ph Reagents i Na[CH(CO,Me),l; ii [Pd{(Ph2PCH2)2121 Scheme 35 successfully applied using the cyclopentadienyl anion as the n~cleophile.'~' Another modification uses stannyl enol ethers rather than the usual stable anions thus allowing the allylation of ketones.Simple enolates or enol silyl ethers were consider- ably less satisfactory but the tin derivatives led quite generally to monoallylation with toleration of a range of f~nctiona1ity.l~~ Regiospecific formation of a carbon-carbon bond at the y-position of allylic halides occurs when a-(thiomethyl)carbonyl compounds are used in a two-phase alkaline system (see Scheme 36).14' Electrophiles whether reactive halides or ' 'Me COR COR Reagents i MeSCH,COR; ii K2C03 Scheme 36 carbonyl compounds react regiospecifically at the a-position of the aluminium 'ate' complexes of heterosubstituted allylic carbanions; the uncomplexed carbanions may react at either the a-or the y-position depending on the heteroatom and the nature of the ele~trophile.'~' The use of enol and dienol silyl ethers leads to excellent regiospecificity in the Mannich reaction with Eschenmoser's and in ureidoalkylation using N-chloromethyl-N-methyl-urethanesin conjunction with titanium(1v) chloride.'52 14' J.C. Fiaud and J. L. Malleron Tetrahedron Lett. 1980 21,4437. B. M. Trost and E. Keinan Tetrahedron Lett. 1980,21,2591. 149 K. Ogura S. Furukawa and G-i. Tsuchihashi J. Am. Chem. SOC.,1980,102,2125.150 Y. Yamamoto H. Yatagai and K. Maruyama J. Org. Chem. 1980,45 195. 151 S. Danishefsky M. Prisbylla and B. Lipisko Tetrahedron Lett. 1980,21,805. S.Danishefsky A. Guingant and M.Prisbylla Tetrahedron Lett. 1980 21 2033. 14' Synthetic Methods 283 14 Ring Synthesis The Diels-Alder reaction continues to achieve new levels of sophistication par- ticularly in its intramolecular mode which has been reviewed.lS3 By using a bis-diene and a bis-dienophile in both of which the duplicated functional groups differ in reactivity a sequential reaction can occur in which first the more reactive diene reacts with the more reactive dienophile intermolecularly after which under altered conditions the remaining groups undergo an intramolecular reaction.''* The final product is tricyclic. An application in the reduced fluorenone system is shown in Scheme 37. It is not unknown for the diene component or the dienophile to be incorporated in a protected form from which the required group is liberated when the compound is heated to bring about the intramolecular cycloaddition. For example benzo[c]thiophen dioxide is a useful masked o -quinodimethane unit'" and acylnitroso-groups can be masked as their adducts with 9,lO-dimethyl- anthracene.ls6 Two new syntheses'" illustrate cases where both components of an intramolecular Diels-Alder addition are in masked forms (Scheme 38). The first R2 R2 R' ii 4 RQD2 R3 0 Reagents i CC14 at 78 "C;ii toluene at 240 "C Scheme 37 i,ii -Conditions i at 185 "C for 30 min; ii at 170-180 OC for 2.5 h in a sealed tube; iii at 370-390 "C in toluene Scheme 38 lS3 G.Brieger and J. N. Bennett Chem. Rev. 1980,80,63. lS4 G. A. Kraus and M. J. Taschner J. Am. Chem. SOC.,1980,102 1974. 155 K. C. Nicolaou W. E. Barnette and P. Ma J. Org. Chem. 1980 45 1463; W. Oppolzer and D. A. Roberts Helu. Chim. Acta 1980 63 1703; R. L. Funk and K. P. C. Vollhardt Chem. SOC.Rev. 1980,9,41. 156 G. E. Keck and D. G. Nickell J. Am. Chem. SOC.,1980 102 3632; G. E. Keck Tetrahedron Lett. 1978,4767. 157 A. Ichihara R. Kimura S. Yamada and S. Sakamura J. Am. Chem. SOC.,1980 102 6353; H. F. Schmitthenner and S. M. Weinreb I. Org. Chem. 1980,45 3372. 284 R. Brettle significant example of the effect of catalysis by a Lewis acid on an intramolecular Diels-Alder reaction has been reported acceleration of the rate and enhanced stereoselectivity were observed (Scheme 39).The use of phenyl vinyl sulphone as a dienophile has been investigated systematically; it reacts regiospecifically with unsymmetrical dienes and the sulphone group in the product permits a variety of further synthetic operation^.^'^ Me0,C Me0,C -0 +& H H Conditions no catalyst at 150 "C 60 parts 40 parts EtAICI, at 23 "C sole product Scheme 39 Reagents i Bu,SnH at 80 "C Scheme 40 The stereoselectivity of the ring-closure of substituted hex-5-enyl radicals has been studied (cf. Scheme 40) and the results with others have been generalized to provide some guidelines that are of predictive use.'6o The synthesis of (17) is an example of an ScN' reaction with its stringent geometrical requirements in which the nucleophile attacking the allylic MEM-ether is the radical anion that is produced by reduction of the ketone (16).161 The first example of addition of a cuprate to an enone together with intramolecular reaction of the resultant enolate with an ester group has been reported (Scheme 41).16' W.R. Roush and H. R. Gillis J. Org. Chem. 1980 45,4264. lS9 R.V.C. Carr and L. A. Paquette J. Am. Chem. SOC.,1980,102,853. A. L. J. Beckwith T. Lawrence and A. K. Serelis J. Chem. SOC. Chem. Commun. 1980 484; A. L. J. Beckwith C. J. Easton and A. K. Serelis ibid. p. 482. M. Bertrand P. Teisseire and G. Pelerin Tetrahedron Lett..1980 21 2051 2055. A. J. Pearson Tetrahedron Lett. 1980 21 3929. 16' Synthetic Methods Reagents i H2C=CH(CH,),Mgbr CuBr THF at -28 to -12 "C; ii aq. NHiCl Scheme 41 The cyclocarbonylation of unsaturated tosylates that was reported last year (see Annu. Rep. Prog. Chem. Sect. B. 1979,76,359)turns out to be exceptional since in general the method is only applicable to monosubstituted 01efins.l~~The intramolecular addition of sulphur ylides to ketones has been studied in detail by two groups,'64 and the limits of its applicability have been defined. Cyclic compounds can be prepared from triphenyl(phenyliminoviny1idene)phosphorane and keto- acids. The octalone synthesis shown in Scheme 42is an alternative to the Robinson annelation procedure with the advantage that none of the non-conjugated isomer is formed.165 A new alkyl-tin(1v)-mediated carbo-cyclization can be used to prepare spiro-ketones or bicyclic ketones from cup -0lefinic ketones.166 The requisite w -stannyl-substituted side-chain can easily be introduced using either electrophilic or nucleophilic methods of alkylation.The latter procedure is illustrated in Scheme 43.The intramolecular addition of the 1:2 complex of an cup-olefinic ketone with Ir(M>2 nl(M) iii,iv 00HO O ,c,o Ph,P CONHPh Reagents i Ph,$-C=C=NPh; ii EtOAc reflux; iii PhMe reflux; iv EtOH (to remove PhNCO) Scheme 42 Reagents i. Me,Sn(CH,),MgCl THF; ii H20 H2S04;iii TiCl,; iv HzO Scheme 43 ethylaluminium chloride to an alkene proceeds with high regio- and stereo- specificity as the example in Scheme 44 The palladium-catalysed intramolecular cyclization of /3 -keto-esters with allylic phenol ethers is particularly useful for the preparation of five-membered rings,'68 although six-membered rings can also be prepared by this method.An example of J. E. McMurry and A. Andrus Tetrahedron Lett. 1980 21,4687. 164 J. K. Crandall H. S. Magaha R. K. Widener and G. A. Thorp,Tetrahedron Lett. 1980,21,4807. 16' H.J. Bestmann G. Schade and G. Schmid Angew. Chem. Znr. Ed. Engl. 1980 19 822. 166 T. L.Macdonald and S. Mahalingam J. Am.Chem. SOC.,1980 102 2113. 16' B. B.Snider D. J. Rodini and J. van Straten J. Am. Chem. SOC.,1980,102 5872. 168 J. Tsuji Y. Kobayashi H. Kataoka and T. Takahashi Tetrahedron Lett.1980 21 1475 3393. 286 R. Brettle Reagents i EtAICl, CH,Cl, at 20 OC Scheme 44 ,OPh Reagents i [Pd(OAc),J Ph3P MeCN reflux Scheme 45 the preparation of a percursor for rings c and D of a steroid is shown in Scheme 45. Alkenyl-substituted /3 -dicarbonyl systems can be cyclized by phenylselenylating agents in which the counter-ion is non-nucleophilic. 169 Sometimes the products are carbocyclic but in other cases cyclization occurs via an enolic form and an oxygen heterocycle is produced; some of these can be rearranged by tin(1v) chloride to give carbocyclic products as in the palladium-catalysed reactions discussed earlier in this Report. An example of direct cyclization to a carbocyclic product is shown in Scheme 46.The product from the 1,4-addition of Me,AlSPh to an a@-olefinic 0 0 Ztiiii -SePh Reagents i PhSe'SbF,- CH,CI, at -78 "C; ii warm to 20 OC; iii NaHCO, H,O Scheme 46 SPh Reagents i Me,AlSPh; ii NaIO,; iii silica gel Scheme 41 ketone undergoes an aldol condensation with an aldehyde. An intramolecular example is shown in Scheme 47 together with its conversion into a desulphurised product. 170 An unusual three-carbon ring-expansion sequence171 has been applied in a short synthesis of muscone from dodecanone (see Scheme 48). 169 W. P. Jackson S. V. Ley and A. J. Whittle J. Chem. SOC.,Chem. Commun. 1980 1173. 170 A. Itoh S. Ozawa K. Oshima and H. Nozaki Tetrahedron Lett. 1980 21 361. 17' B. M. Trost and J. E. Vincent J. Am. Chem.SOC.,1980,102,5680. Synthetic Methods SiMe v,vi muscone t S0,Ph CH Reagents i Br,; ii PhS0,Na; iii,Me,Si&OMes ;iv Bu,N+F-; v H, Pd/C; vi NaHg Na,HPO Scheme 48

ISSN:0069-3030    

DOI:10.1039/OC9807700263

出版商:RSC    

年代:1980

数据来源: RSC

摘要:

15 Biological Chemistry Part (i) Biosynthesis By J. R. HANSON School of Molecular Sciences University of Sussex Brighton BN 1 9QJ Despite the fact that only a two-year period has elapsed since the last Report,’ the volume of published work necessitates a highly selective treatment of secondary metabolism. Many of the advances depend on n.m.r. methods in which high-field spectrometers have made a significant contribution. An interesting article2 describes n.m.r. methods for tracing the fate of hydrogen in biosynthesis. Some stereochemical consequences of enzymic reactions particularly at allylic carbon atoms have been reviewed in a published le~ture.~ The stereochemistry of allylic pyrophosphate metabolism which plays an important role in terpenoid cyclizations has also been e~arnined.~An extensive review has appeared5 on chiral methyl-group methodology.1 Polyketide Biosynthesis Arachidonic acid (1) has been shown to be a key precursor not only for the biosynthesis of the prostaglandins and thromboxanes,6 but also uiu 5-hydroperoxy-eicosatrienoic acid (5-HPETE)(2),of the leukotrienes A (3) and the ‘slow reacting I substances of anaphylaxis’ (SRS-A’s) leukotrienes C-1 (4; R = Glu-Cys-Gly) D I I (4; R = Cys-Gly) and E(4;R = CYS).~ The biosynthesis of the unusual unsaturated acid (2E,4E,6E)-5-(acetoxy-methyl)tetradeca-2,4,6-trienoicacid formed by the plant Eremophilu oppositifoliu has been shown’ to follow the acetate:malonate pathway. Studies on the biosynthesis of [6]-ginger01 (9,which is a pungent principle of ginger (Zingiber oficinale) have demonstrated’ that it arises from dihydroferulic acid malonate and hexanoic acid.’ J. R. Hanson Annu. Rep. Prog. Chem. Sect. B 1978,75,329. * M. J. Garson and J. Staunton Chem. SOC. Rev. 1979 8 539. K. H. Overton Chem. SOC. Rev. 1979,8,447. D. E. Cane Tetrahedron 1980 36 1109. H. Floss and M.-D. Tsai Adv. Enzymol. 1979,50 243. ‘P. R. Marsham in ‘Aliphatic and Related Natural Product Chemistry’ ed. F. D. Gunstone (Specialist Periodical Reports) The Chemical Society London 1979,Vol. 1,p. 170. ’S. Hammarstrom B. Samuelsson D. A. Clark G. Goto A. Marfat C. Mioskowski and E. J. Corey Biochem. Biophys. Res. Commun. 1980,92 946; ibid. 1980 94 1133. E. L. Ghisalberti P. R. Jefferies and R.F. Toia Phytochemistry 1979.18 65. I. MacLeod and D. A. Whiting J. Chem. SOC. Chem. Commun. 1979,1152; P. Denniff I. MacLeod and D. A. Whiting J. Chem. SOC.,Perkin Trans 1 1980 2637. 289 290 J. R. Hanson H-OOH +C02H OH (6) -and = [13C2]acetatecoupling A computer optimization of the 13Cn.m.r. FID data has enabled" a two-bond C-I3C coupling (C-2-C-8) to be detected in asperlactone (6) that had been biosynthesized from [1,2-13C2]acetate and thus it was established that these two carbon atoms have their origin in the same [13C2]acetate unit. This sophisticated application of 13C n.m.r. techniques promises to have quite wide application in detecting rearrangements. The biosynthesis of citrinin (8) by Penicillium citrinum has continued to attract attention and has also been the subject of several n.m.r.studies. Evidence concern- ing the origin of the hydrogen atoms in citrinin has been obtained by producing the metabolite from protium-labelled carbon sources on a deuterium oxide medium." The methylation steps appear to precede'* the formation of the aromatic ring. Deuterium-labelling ~tudies'~ have shown that the aldehyde (7) plays an important role in the biosynthesis. A sequence based on the feeding of potential late precursors has been proposed.14 Ascochitine (9) is a phytotoxic metabolite of Ascochytu fabae in which methylation of the polyketide chain also appears" to precede aromatization. & HO/ \ O&-H02C \ \ 0 H02CH O\o W OH CHo OH 0 (7) (8) (9) lo R.G. Brereton M. J. Garson and J. Staunton J. Chem. SOC., Chem. Commun. 1980 1165. R. H. Carter M. J. Garson and J. Staunton J. Chem. SOC., Chem. Commun. 1979 1097; J. Barber and J. Staunton ibid. p. 1098; J. Barber and J. Staunton J. Chem. SOC.,Perkin Trans. I 1980 2244. J. Barber and J. Staunton J. Chem. SOC., Chem. Commun. 1980 552. l3 J. Barber and J. Staunton J. Chem. SOC., Chem. Commun. 1980 1163. l4 L. Colombo C. Gennari F. Aragozzini and C. Merendi J. Chem. SOC., Chem. Commun. 1980,1132. '*L. Colombo C. Gennari G. S. Ricca C. Scolastico and F. Aragozzini J. Chem. SOC., Perkin Trans. 1 1980 675; L. Colombo C. Gennari C. Scolastico F. Aragozzini and C. Merendi ibid. p. 2549. Biological Chemistry -Part (i) Biosynthesis 291 The detection of l8Olabels by studying the isotope effect on 13C n.m.r.shifts has been used16 in determining the origin of the oxygen atoms in the biosynthesis of averufin (10).The conversion of averufin into the mycotoxin aflatoxin Bt (11)has been examined," using material biosynthesized from [1,2-13C2]acetate. Full papers have appeared on the role of versiconal acetate in aflatoxin biosynthesis," on the biosynthesis of the mycotoxin ochratoxin A,19 and on the phenalenone metabolites of Penicillium herquei.*' (10) (11) (12) R = H02C-A/ (14) R = H02C In a study of the biosynthesis of mycophenolic acid (12) by Penicilliurn brevicorn- pactum it has been that the farnesylphthalide (13)and the prenylogue of mycophenolic acid (14) are formed under conditions commensurate with their probable role in the biosynthesis.2 Terpenoids and Steroids Considerable attention has been on prenyl transferase (the enzyme system responsible for the oligomerization of isoprene units) and on the mechanism of the coupling reaction in terpenoid bio~ynthesis,~~ whilst the substrate specificity l6 J. C. Verderos and T. T. Nakashima J. Chem. SOC.,Chem. Commun. 1980 183. 17 A. E. De Jesus C. P. Gorst-Allman P. S. Steyn R. Vleggaar P. L. Wessels C. C. Wan and D. P. H. Hsieh J. Chem. SOC.,Chem. Commun. 1980,389. IS P. S. Steyn R. Vleggaar P. L. Wessels and De Buys Scott J. Chem. SOC.,Perkin Trans. I 1979,460. l9 A. E. De Jesus P.S. Steyn R. Vleggaar and P. L. Wessels J. Chem. SOC.,Perkin Trans. 1 1980 52.2o T. J. Simpson J. Chem. SOC.,Perkin Trans. 1 1979 1233. 21 L. Colombo C. Gennari D. Potenza C. Scolastico and F. Aragozzini,J. Chem. SOC., Chem. Commun. 1979,1021. 22 D. L. Doerfler L. A. Ernst and I. M. Campbell J. Chem. SOC.,Chem. Commun. 1980 329. 23 H. C. Rilling Pure Appf. Chem. 1979 51 697. 24 C. D. Poulter E. A. Marsh J. Argyle 0. J. Muscio and H. C. Rilling J. Am. Chem. SOC. 1979 101,6761. 292 J. R. Hanson of farnesyl pyrophosphate synthetase has also been e~amined.~’ The C-10-methyl group (trans to the chain) of geraniol has been shownz6 to arise from C-2 of mevalonate. In the redox interconversion of geraniol and nerol the 1-pro-S hydro- gen atom appearsz7 to be lost in the formation of nerol whereas the reverse isomerization involves the loss of the 1-pro-R atom.Some evidence has been presentedz8 supporting the preferential participation of linaloyl rather than neryl pyrophosphate in the biosynthesis of cyclic monoterpenoids in higher plants. The oxidation of limonene to carvone in Me;ztha spicata a shift of the endocyclic double-bond whilst studies on the biosynthesis of the carane skeleton show3’ that it is constructed from its monocyclic precursor with the migration of the double-bond and an unexpected 1,2-shift of a proton to the site of the original double- bond. The enzymatic conversion of farnesyl pyrophosphate into nerolidyl pyrophos- phate and the role of the latter in the biosynthesis of cyclonerodiol has been examined.31 [G-13C6]G1~~ose has been as a source of acetate units in a study of the biosynthesis of pentalenolactone (16),with results suggesting that the carbon skeleton arises by the folding of farnesyl pyrophosphate (15) as shown.Deuterium n.m.r. methods have been used to define the fate of mevalonoid hydrogen atoms in the biosynthesis of fomanno~in,~~ and dihydr~botrydial.~~ capsidi01,~~ Studies on the enzymatic biosynthesis of ent-~andaracopimaradiene~~ and of ent-ka~rene,~~ using stereospecifically labelled geranylgeranyl pyrophosphate and copalyl pyrophosphate (17) have shown that the cyclization of the latter occurs with anti stereochemistry. The labelling of ring D of ent-kaurene (18) by [3,6-(17) (18) ” T. Koyama A. Saito K. Ogura and S. Seto J. Am. Chem. SOC. 1980,102 3614.A. Akhila and D. V. Banthorpe Phytochemistry 1980 19 1429. 27 D. V. Banthorpe and I. Poole Phytochemistry 1979 18 1297. 28 T.Suga T. Shishibori and H. Morinaka J. Chem. SOC. Chem. Commun. 1980 167. 29 A. Akhila D. V. Banthorpe and M. G. Rowan Phytochemistry 1980,19 1433. 30 A. Akhila and D. V. Banthorpe Phytochernistry 1980,19 1691. 31 D.E.Cane and R. Iyengar J. Am. Chem. SOC. 1979,101,3385. 32 D. E.Cane T. Rossi and J. P. Pachlatko Tetrahedron Lett. 1979 3639. 33 D.E.Cane and R. B. Naschbar Tetrahedron Lett. 1980 21 437. 34 Y. Hoyano A Stoessl and J. B. Stothers Can. J. Chem. 1980,58 1894. 35 A. P.W. Bradshaw and J. R. Hanson J. Chem. SOC. Chem. Cornmun. 1979,924. 36 K.A. Drengler and R. M. Coates J. Chem. SOC. Chem. Commun. 1980,856. 37 R.M.Coates and P.L. Cavender J. Am. Chem. SOC. 1980,102,6358. Biological Chemistry -Part (i) Biosynthesis '3C2]mevalonolactone is with the currently accepted biosynthetic scheme. ent-Kaur-15-ene rather than the normal gibberellin plant hormone inter- mediate ent-kaur-16-ene is by dwarf-5 mutants of maize whilst ent- kauran 16@,17-epoxide is an inhibitor of the biosynthesis of gibberellic acid.40 The biosynthesis of the secokauranoid enmein41 and the relationship of the kaurenol- ides4* in Gibberella fujikuroi have been examined whilst the lack of substrate specificity of G. fujikuroi has also been used to prepare biosynthetically pentacyclic analogues of the gibber ell in^,^^ ati~agibberellins,~~ and fl~orogibberellins.~~ Studies of the substrate specificity of lanosterol-2,3-oxidosqualene cyclase have the requirement for an epoxide and at least two appropriately oriented double-bonds.(RS)-Epoxysqualene has been cy~lized~~ by various cell-free systems to mixtures of 3a- and 3P -hydroxy-triterpenes. The incorporation of a 3P-hydrogen atom in the non-oxidative cyclization of squalene in tetrahymanol biosynthesis has been studied,48 utilizing *H n.m.r. Incubation49 of 14a-(hydroxymethyl)-5a -cholest-7-en-3P-o1(19) with rat liver microsomes gives 5a -cholest-8( 14)-en-3@ -01 and requires only an NADH/NADPH generator to afford formic acid. The sugges- tion was made that the loss of the hydroxymethyl group occurs by an oxygen- independent process uia dehydrogenation to the 14-aldehyde. The subsequent hydrolytic removal of formic acid may be assisted by the double-bond.Evidence has been presented5' suggesting the possible intervention of the 7a -alcohol 5a-cholest-8( 14)-en-3&7a -diol in the 14a-demethylation reaction. (19) (20) The hydrogen atom at C-28 in the alkylated sterol poriferasterol which arises from S-adenosylmethionine has been shown" to assume the pro-S position whilst the pro-R hydrogen atom comes from the reducing agent. In contrast the C-23 olefinic methyl group of dinosterol retains5' three deuterium atoms from methion- 38 K. Honda T. Shishibori and T. Suga J. Chem. Res. (S) 1980 218. 39 P. Hedden and B. 0.Phinney Phytochemistry 1979,18,1475. 40 J. R. Hanson C. L. Willis and K. P. Parry Phytochemistry 1980 19 2323. T.Fujita S. Takao and E. Fujita J. Chem. SOC.,Perkin Trans. 1 1979 2468. 42 J. R. Hanson and F. Y. Sarah J. Chem. SOC. Perkin Trans. 1,1979,3151. 43 J. R. Bearder J. MacMillan A. Matsuo and B. 0.Phinney J. Chem.SOC.,Chem. Commun. 1979,649. 44 J. R. Hanson F. Y. Sarah B. M. Fraga and M. G. Hernandez Phytochemistry 1979,18 1875. 45 B. E. Cross and P. Filippone J. Chem. Soc. Chem. Commun. 1980 1097. 46 E. E. van Tamelen and R. E. Hopla J. Am. Chem. SOC.,1979,101,6112. 47 M. Rohmer C. Anding and G. Ourisson Eur. J. Biochem. 1980,112 541 48 E. Caspi Acc. Chem. Res. 1980 13 97; D. J. Aberhart and E. Caspi J. Am. Chem. Soc. 1979 101,1013. 49 R. A. Pascal P. Chang and G. J. Schroepfer J. Am. Chem. SOC.,1980,102,6599. M. Galli-Kienle M. Anastasia G.Cighetti G. Galli and A. Fiecchi Eur. J. Biochem. 1980,110 93. 51 F. Nicotra B. M. Ranzi F. Ronchetti G. Russo and L. Toma J. Chem. SOC.,Chem. Commun. 1980 752. '* N. W. Withers R. C. Tuttle L. J. Goad and T. W. Goodwin Phytochemistry 1979 18 71. 294 J R. Hanson ine. Phytophagous insects obtain their dietary cholesterol by the dealkylation of phytosterols such as fucosterol utilizing the (24R,28S)-epoxides but not their (24S,28R)-i~omers.~~ The stereochemistry of hydroxylation of cholesterol at C-22 during pregnenolone biosynthesis occurss4 with retention of configuration to give the (22R)-stereoisomer. The deuterium and carbon-13 enrichment patterns of samples of the fungal metabolite demethoxyviridin (20) derived from labelled acetate and mevalonates are consistent with its triterpenoid origin in which lanosterol rather than cycloartenol is an intermediate.” The structures and labell- ing patterns of the side-chain fragments that the cleavage of the side-chain follows a mammalian rather than a bacterial route.Full papers on the biosynthesis of wortmannin from [1,2-’3C2]a~etate57 and on various lanosterol derivatives as possible intermediates in viridin biosynthesisS8 have appeared. The stereochemistry of elimination of the 12-hydrogen atoms in the formation of olean- and urs-12-enes has been examined.” The chemical and enzymological aspects of the biosynthesis of the carotenoids have been reviewed.60 The stereochemical origin of the C-1-methyl groups of zeaxanthin in the cyclization of carotenoid precursors has been studied by 13C n.m.r.methods.61 3 Shikimic Acid The normal route for tyrosine biosynthesis involves 4-hydroxyphenylpyruvate. However arogenic acid (2l),(pretyrosine) has been shown62 to act as a precursor in some micro-organisms. L-Phenylalanine is a precursor of caffeic acid in Ocimum ba~ilicum.~~ OH (21) (22) The fungal flavanoid chlorflavonin (22) is unusual both as a fungal flavanoid and in its origin via a c& (benzoate) and four acetate A number of stereochemical aspects of the late stages of rotenone biosynthesis and its relation- ship to amorphigenin have been e~amined.~’ Full papers have appeared on the 53 F. Nicotra F. Ronchetti G. Russo and L. Toma J. Chem. SOC.,Chem. Commun. 1980,479.54 C. Duque M. Morisaki N. Ikekawa and M. Shikita Tetrahedron Lett. 1979 4479. 55 J. R. Hanson and H. Wadsworth J. Chem. SOC.,Chem. Commun. 1979,360. 56 J. R. Hanson M. A. O’Leary and H. Wadsworth J. Chem. SOC.,Chem. Commun. 1980,853. ST T. J. Simpson M. W. Lunnon and J. MacMillan J. Chem. SOC.,Perkin Trans. 1 1979,931. 58 W. S. Colder and T. R. Watson J. Chem. SOC.,Perkin Trans. 1 1980 422. 59 S. Seo Y. Tomita K. Tori and Y. Yoshimura J. Chem. SOC.,Chem. Commun. 1980,.1275. 6o T. W. Goodwin Pure Appl. Chem. 1979,51,593; J. W. Porter and S. L. Spurgeon ibid.,p. 609. G. Britton T. W. Goodwin W. J. S. Lockley A. P. Mundy N. J. Patel and G. Englert J. Chem. SOC., Chem. Commun. 1979,27. 62 L. 0.Zamir R. A. Jensen B. H. Arison A. W. Douglas G. Albers-Schonberg and J.R. Bowen J. Am. Chem. SOC.,1980,102,4499. 63 L. Canonica P.Gramatica P. Manitto and D. Monti J. Chem. SOC.,Chem. Commun. 1979 1073. 64 M. K. Burns J. M. Coffin I. Kurobane and L. C. Vining J. Chem. SOC., Chem. Commun. 1979,426. 6s L. Crombie I. Holden G. W. Kilbee and D. A. Whiting J. Chem. SOC.,Chem. Commun. 1979 1143,1144. Biological Chemistry -Part (i) Biosynthesis 295 biosynthetic relationships involved in pterocarpan and isoflavan phytoalexin biosyn- thesis in Medicago sativa and between the aryl-benzofurans of Vigna unguiculata.66 Labelling studies have that the anthraqui,ione lucidin obtained from Galium mollugo arises from 1,4-dihydroxy-3-prenyI-2-naphthoic acid. 4 Alkaloid Biosynthesis The biosynthesis of the alkaloids has been reviewed.68 The 13C-labelling patterns of nicotine and of cocaine bio~ynthesized~~ from ornithine are in accord with a symmetrical precursor for the pyrrolidine ring whilst a symmetrical C4-N-C4 unit derived from ornithine is also implicated7’ in the formation of the retronecine rings of the pyrrolizidine alkaloids The conversion of isoleucine into the necic acids involves the loss of the 4-pro-s hydrogen atom.71 The formation of the simplest of the harman alkaloids (23) involves the decar- boxylation of 1-methyl-1,2,3,4-tetrahydro-~-carboline-l-carboxylic acid.” Stric-tosidine (24) plays a key role in indole alkaloid biosynthe~is.~~ Enzyme systems have been obtained from Catharanthus roseus that mediate its formation from tryptamine and sec010ganin.’~ 4,2 1-Dehydrogeissoschizine is an intermediate75 in heteroyohimbine alkaloid biosynthesis.Geissoschizine (25) is into 19-epi-ajmalicine and (16R)- is~sitsirikine~~ by cell-free extracts of C. roseus. Tissue cultures which will carry out this biosynthesis have been from the same plant. Vindoline and catharanthine are precursors of the dimeric alkaloid A15(20’)-20‘-deoxyvinblastine which in turn is converted into ~inblastine.~~’~’ Strictosamide is the penultimate precursor of camptothecin.81 OT%H. H= \o .Glu aj-q (24) /N Me0,C (23) 66 P. M. Dewick and M. Martin Phytochemistry 1979,18,591 597 1309; 1980,19 2341. 67 K. Inoue Y. Shiobara H. Nayeshiro H. Inouye G. Wilson and M. H. Zenk J. Chem. SOC.,Chem. Commun.1979,957. 68 R. B. Herbert in ‘The Alkaloids’ ed. M. F. Grundon (Specialist Periodical Reports) The Chemical Society London 1979,vol. 9 p. 1. 69 E. Leete and M.-L. Yu Phytochemistry 1980 19 1093; E. Leete J. Chem. Soc. Chem. Commun. 1980 1170. 70 D. J. Robins and J. R. Sweeney J. Chem. Soc. Chem. Commun. 1979,120. 71 R. Cahill D. H. G. Crout M. B. Mitchell and U. S. Miller J. Chem. Soc. Chem. Commun. 1980,419. 72 R. B. Herbert and J. Mann J. Chem. Soc. Chem. Commun. 1980,841. ” N. Nagakura M. Ruffer and M.H. Zenk J. Chem. Soc. Perkin Trans. 1 1979 2308. 74 J. Stockigt Phytochemistry 1979,18 965. 75 M. Rueffer C. Kan-Fan H.-P. Husson J. Stockigt and M. H. Zenk J. Chem. Soc. Chem. Commun. 1979,1016. 76 J. Stockigt G. Hofle and A. Pfitzner Tetrahedron Lett.1980,21 1925. 77 S. L. Lee T. Hirata and A. I. Scott Tetrahedron Left. 1979 691; T. Hirata S. L. Lee and A. I. Scott J. Chem. Soc. Chem. Commun. 1979 1081. 78 A. I. Scott H. Mizukami T. Hirata and S. L. Lee Phytochemistry 198@,19,488. 79 R. L. Baxter C. A. Dorschel S. L. Lee and A. I. Scott J. Chem. Soc. Chem. Commun. 1979 257. F. Gueritte N. V. Bac Y. Langlois and P. Potier J. Chem. Soc. Chem. Commun. 1980,452. ” C.R.Hutchinson A. H. Heckendorf J. L. Straughn P. E. Daddona and D. E. Cane J. Am. Chem. Soc. 1979 101 3358. 296 J. R. Hanson N-Methylation precedes’’ the final cyclization in the construction of the tetracyc- lic ergoline ring system. The isoprenylation steps in echinulin biosynthesis have been showns3 to involve an inversion of configuration at the allylic pyrophosphate of isopentenyl pyrophosphate.During the biosynthesis of the neurotoxin roquefor- tine (26) the 3-pro-S hydrogen atom of histidine is removed in the formation of the dehydro-amino-acid moiety.84 Full papers have appeared on the biosynthesis of some Erythrina and benzylisoquinoline alkaloidss5 and on the Cephalotaxus a1 kaloids. s6 5 Porphyrin Biosynthesis Some aspects of the biosynthesis of the porphyrins have been the subject of controversy. Their biosynthesis has been the subject of a number of review^.^' Considerable use has been made of 13C n.m.r. techniques particularly those involv- ing the direct observation of biosynthetic intermediates in living cells in the n.m.r. tube and of 15N-13Ccoupling patterns.The stepwise binding of 6-aminolaevulinic acid in the formation of porphobilinogen has been examined,” whilst 13C n.m.r. experiments have shown that the order of assembly of the pyrrole rings in uro’gen I11 (30) is A -+D.89The biosynthesis of uro’gen I11 by the enzyme system deaminase:cosynthetase involves the head-to-tail assembly of the four porpho- bilinogen units (27) followed by intramolecular rearrangement. The function of deaminase is to assemble a linear bilane which in the absence of cosynthetase is released into the medium as a hydroxymethyl-bilane (28).90 The latter cyclizes ’’ H. Otsuka J. A. Anderson and H. G. Floss J. Chem. SOC., Chem. Commun. 1979,660. 83 J. K. Allen K. D. Barrow and A. J. Jones J. Chem. SOC.,Chem. Commun.1979 280. 84 K. D. Barrow P. W. Colley and D. E. Tribe J. Chem. SOC.,Chem. Commun. 1979,225; R. Vleggaar and P. L. Wessels ibid. 1980 160. D. S. Bhakuni S. Jain and R. Chaturvedi Tetrahedron 1979 35 2323; D. S. Bhakuni A. N. Singh and S. Jain ibid. 1980 36 2149; D. S. Bhakuni and S. Jain ibid. p. 2153; D. S. Bhakuni S. Jain and S. Gupta ibid. p. 2491; D. S. Bhakuni S. Jain and R. S. Singh ibid. p. 2525. 86 A. Gitterman R. J. Parry R. Dufresne D. D. Sternbach and M. D. Cabelli J. Am. Chem. SOC. 1980,102,2074; ” A. R. Battersby and E. McDonald Acc. Chem. Res. 1979,12 14. P. M. Jordan and J. S. Seehra J. Chem. SOC.,Chem. Commun. 1980,240. 89 A. R. Battersby C. J. R. Fookes G. W. J. Matcham E. McDonald and K. E. Gustafson-Potter J. Chem. SOC.,Chem. Commun.1979 316; A. R. Battersby C. J. R. Fookes G. W. J. Matcham and E. McDonald ibid. p. 539; A. R. Battersby C. J. R. Fookes E. McDonald and G. W. J. Matcham Bio-org. Chem. 1979,8,451. 90 A. I. Scott G. Burton and P. E. Fagerness J. Chem. SOC.,Chem. Commun. 1979 199; G. Burton P. E. Fagerness S. Hosozawa P. M. Jordan and A. I. Scott ibid. p. 202; P. M. Jordan G. Burton H. Nordlov M. M. Schneider L. Pryde and A. I. Scott ibid. p. 204; A. R. Battersby C. J. R. Fookes, K.E. Gustafson-Potter G. W. J. Matcham and E. McDonald ibid. p. 1155; A. R. Battersby R. G. Brereton C. J. R. Fookes E. McDonald and G. W. J. Matcham ibid. 1980 1124; A. I. Scott G. Burton P. M. Jordan H. Matsumoto P. E. Fagerness and L. M. Pryde ibid. p. 384; see also Can. J. Chem. 1980,58,1839.Biological Chemistry -Part (i) Biosynthesis chemically to uro’gen I (29) without rearrangement of ring D. In the presence of cosynthetase rearrangement occurs with the formation of uro’gen I11 (30). The decarboxylation of uro’gen I11 to coproporphyrinogen I11 takes place91 in a sequence starting with the acetic acid moiety on ring D and followed in a clockwise order by the acids on the rings A B and C. A series of methylated metabolites of uro’gen I11 have been detected92 as intermediates in the biosynthesis of vitamin BI2. The controversy which surrounded the structure of one of these 20-methylsirohydro- chlorin has now been Inthe ring-contraction of the trimethylisobacterio- chlorin to the corrin system of cobyrinic acid the C-20-methyl group is lost and not transferred to C-1.6 Other Metabolites derived from Amino-Acids The direct 13Cn.m.r. observation of the conversion of (L-a-amino-6-adipy1)-L- cysteinyl-D-valine (31)into isopenidin N (32) by a cell-free system derived from Cephalosporium acremonium has been reported.93 The biosynthesis of the epi- dithiodioxopiperazines such as gliotoxin has been reviewed.94 The reductive methylation of the sulphur bridge of gliotoxin has been reported.95 Feeding experi- ments with cyclo-(L-tyrosyl-L-serine)and phomamide (33) have led96 to a scheme for the formation of sirodesmin PL (34) in Phoma lingam. The unusual amino-acid 91 A. H. Jackson H. A. Sancovich and A. M. Ferramola de Sancovich Bioorg. Chem. 1980,9 71. 92 A. R. Battersby G. W. J.Matcham E. McDonald R. Neier M. Thompson W.-D. Woggon V. Y. Bykovsky and H. R. Morris J. Chem. Soc. Chem. Commun. 1979 185; N. G. Lewis R. Neier G. W. J. Matcham E. McDonald and A. R. Battersby ibid. p. 541; A. R. Battersby E. McDonald R. Neier and M. Thompson ibid. p. 960; G. Muller K. D. Gneuss H.-P. Kriemler A. I. Scott and A. J. Irwin J. Am. Chem. Soc. 1979 101,3655. 93 J. E. Baldwin B. L. Johnson J. J. Usher E. P. Abraham J. A. Huddleston and R. L. White J. Chem. Soc. Chem. Commun. 1980 1271. 94 G. W. Kirby Pure Appl. Chem. 1979,51,705. 95 G.W. Kirby D. J. Robins M. A. Sefton and R. R. Talekar J. Chem. Soc. Perkin Trans. 1 1980 119. 96 J.-P. Ferezou A. Quesnaeu-Thierry C. Servy E. Zissrnann and M. Barbier J. Chem. Soc. Perkin Trans. 1 1980 1739.298 J. R. Hanson HO 0YHNH (33) (34) (35) 3-amino-5-hydroxybenzoicacid initiates the formation of the polyketide chain in the ansamycin and maytansinoid group of antibiotics and is also an important precursor of porfiromycin (35).97 Reports have appeared on the biosynthesis of a number of Streptornyces antibio-tic~.~~ Streptolydigin is unusual for this group in that the polyketide portion contains propionate Malonomicin is a tetramic acid with an unusual amino-malonic acid moiety. It is derived"' from 2,3-diaminopropanoic acid acetate and succinate. The C-nucleoside antibiotic pyrazofurin contains a rare pyrazole ring which is derived'" from glutamic acid. Reports have appeared on the biosynthesis of spectinomycin,"* ~treptonigrin,''~ aplasrn~mycin,'~~ berninamy~in,''~ and indol- mycin.lo6 7 Miscellaneous Metabolites Using chirally labelled material it has been shown'" that the introduction of sulphur at C-4 into desthiobiotin proceeds with retention of configuration and with no loss of tritium from the adjacent position.In contrast the sulphur of lipoic acid which is introduced at C-4 of the parent octanoic acid is inserted with overall inversion of configuration.lo8 97 U. Hornemann J. H. Eggertand and D. P. Honer J. Chem. SOC.,Chem. Commun. 1980 11; J. J. Kibby I. A. McDonald and R. W. Rickards ibid. p. 768; M. G. Anderson J. J. Kibby R. W. Richards and J. M. Rothschild ibid.,p. 1277. 98 L. H. Hurley Acc. Chem. Res. 1980 13 263. 99 C. J. Pearce S. E. Ulrich and K.L. Rinehart J. Am. Chem. SOC.,1980,102,2510. loo D. Schipper J. L. van der Baan and F. Bickelhaupt J. Chem. SOC.,Perkin Trans. 1 1979,2017. J. G. Buchanan M. R. Hamblin G. R. Sood and R. H. Wightman J. Chem. SOC.,Chem. Commun. 1980,917. lo' H. Otsuka 0.A. Mascaretti L. H. Hurley and H. G. Floss J. Am. Chem. SOC., 1980 102 6817. S. J. Gould and C. C. Chang J. Am. Chem. Soc. 1980 102 1702; S. J. Gould C. C. Chang D. S. Darling J. D. Roberts and M. Squillacote ibid. p. 1707. lo4 T. S. S. Cheng C.-J. Chang and H. G. Floss J. Am. Chem. Soc. 1979 101 5826. lo' C. J. Pearce and K. L. Rinehart J. Am. Chem. SOC., 1979,101,5069. R. W. Woodard L. Mascaro R. Horhammer S. Eisenstein and H. G. Floss J. Am. Chem. Soc. 1980,102,6314. lo' D. A. Trainor R. J. Parry and A.Gitterman J. Am. Chem. SOC.,1980 102 1467; R. J. Parry and M. V. Naidu Tetrahedron Lett. 1980 21 4783. lo* R. H. White J. Am. Chem. Soc. 1980 102 6605; Biochemistry 1980 19 15.

ISSN:0069-3030    

DOI:10.1039/OC9807700289

出版商:RSC    

年代:1980

数据来源: RSC

摘要:

15 Biological Chemistry Part (ii) Nucleic Acids (a) Nucleosides and Nucleotides By G. SHAW School of Chemistry University of Bradford Bradford BD7 1DP 1 Nucleoside Antibiotics and Constituents of tRNA 1-Methylisoguanosine (1)(doridosine) has been isolated from the marine sponges Tedunia digitutu ’,* or Anisodoris nobilis3 by different workers and reported to have powerful muscle-relaxant and cardiovascular activity when administered orally in mammals; since it is resistant to adenosine deaminase it is thought to act as a long-acting adenosine. It has been synthesized* from the imidazole nucleoside (2) (Scheme 1)or by methylation of isoguanosine with methyl iodide and potassium AcO OAc AcO OAc (2) IH (Rf= P-D-ribofuranosyl) Rfs (1) Reagents i MeNCO; ii NH, H,O Scheme 1 A novel and reportedly highly efficient synthesis of showdomycin (3) from the cyclobutene derivative (4)has been recorded5 (Scheme 2) and an interesting cine-substitution reaction in a 1,4-dinitropyrazole nucleoside (5) has led6*’ to a new J.Bairdlambert J. F. Marwood L. P. Davies and K. M. Taylor Life Sci. 1980 26 1069. R. J. Quinn R. P.Gregson A. F. Cook and R. T. Bartlett TetrahedronLett. 1980 21 567. F. A. Fuhrman G. J. Fuhrman Y. H. Kim L. A. Pavelka and H. J. Moshe Science 1980,207 193. A. F. Cook and R. T. Bartlett J. Org. Chem. 1980,45 4020. T. Inoue and I. Kuwajima J. Chem. SOC.,Chem. Commun. 1980,251. J. G. Buchanan A. Stobie and R. H. Wightman Can.J. Chem. 1980,58 2624. ’J. G. Buchanan A. R. Edgar R. J. Hutchinson A.Stobie and R. H. Wightman J. Chem. Soc. Chem. Commun. 1980,237. 299 300 G. Shaw uoSiMe3 -& phCOO,o~ OSiMe NOH OSiMe (4) rl PhCOO OCOPh PhCOO 7PhCOO OCOPh 0 Reagents i 2,3,5-tri-O-benzoyl RB-1-acetate SnCI,; ii LiN(SiMe,), Me,SiCI NOCI; iii at room temperature for 2 days; iv NH,,MeOH (CF,CO),O Scheme 2 AcO AcO OAc AcO OAc (5) ii 1 6AcO (6) AcO OAc (7) Reagents; i KCN; ii HJPd; iii NH,CH=&H AcO- NaOMe MeOH Scheme 3 route to formycin (6) (Scheme 3). A new synthesis of pyrazofurin (pyrazo- mycin) (8) from the aminopyrazole nucleoside (7)via photolytic replacement of a diazonium group with hydroxyl has been reported.8 D-Ribose and L-glutamate have been found’ to be the principle precursors in the biosynthesis of both pyrazofurin and formycin.(8) J. G. Buchanan A. Stobie and R. H. Wightman J. Chem. SOC.,Chem. Comrnun. 1980,916. ’J. G. Buchanan M. R. Hamblin G. R. sod and R.H. Wightman J. Chem. SOC.,Chem. Commun. 1980.917. Biological Chemistry -Part (ii)a Nucleosides & Nucleotides 301 5-(Methylaminomethyl)-2-thiouridine(9) a rare nucleoside of tRNA has been synthesized" (Scheme 4)and a new route" to wyosine (10) involves the amino- imidazole nucleoside (11)(Scheme 5). 0 H 1ii SN Rf (9) AcO OAc Reagents i HCO,Et NaH NH,CSNH,; ii CF3C02H HN(SiMe,), 1,2,3,5-ribofuranosyl tetra-acetate SnCI,; iii NH, MeOH Scheme 4 0 (11) (10) Reagents i CNBr BrCH,COMe Scheme 5 9-p-D-Ribopyranosylhypoxanthine(12) has been isolated" from Streptornyces antibioticus and synthesized by conventional means.The pyrazole structure assigned to polyoxin N and described in the previous Report has been revised13 to the imidazolone (13),similar to nikkomycin B (14) which was obtained from the culture filtrate of S. tendae. The structure of the latter was confirmed by synthesis of a diastereoisomeric mixture of the attached amino-acid (15). 0 (N' p N /IH N RBp (12) (R = 0-D-ribopyranosyl) H. Vorbruggen and K. Krolikiewicz Liebigs Ann. Chem. 1980 1438. T. Itaya T. Watanabe and H. Matsumoto J. Chem. SOC.,Chem. Commun. 1980 1158. l2 D. L. Kern P. D. Cook and J. C. French J. Heterocycl. Chem. 1980 17,461. 13 M. Uramoto K. Kobinata K.Isono T. Higashijima T. Miyazawa E. E. Jenkins and J. A. McCloskey Tetrahedron Lett. 1980,21 3395. l4 W. A. Konig W. Hass W. Dehler H. P. Fiedler and H. Zahner Liebigs Ann. Chem. 1980 622. 302 G. Shaw C O NCO,H H T HO I I HCMe H,NCH IHOCH HO OH CH-CH-CH-CO,HI I OH NH OH 0 @* 0 HO OH OH OH A new cytokinin (16) containing a o-hydroxybenzyl group has been isolated" from Zantedeschia aethiopica (cuckoo-pint) ; 2-deoxyuridine and thymidine have been extracted16 from the starfish Acanthasterplanci and the C-nucleoside agropine (17) has been isolated from crown gall tumours.17 Adenomycin has been assigned'* the structure (18) and X-ray crystallography of furanomycin which can be regarded as a C-nucleoside shows it to have the structure (19).l9 Neplanocin A a carbocyclic nucleoside analogue with anti-tumour activity obtained from Ampullariella regularis has the structure (20).20 HOCH,m o w -b A d e OCOCH(NH,)CH,OH HO OH HO OH (18) HO OH 15 H.J. Chaves das Neves and M. S. S. Pais Tetrahedron Lett. 1980 21 4387. 16 T.Komori Y. Sanechika Y. Ito J. Matsuo T. Nohara and T. Kawasaki Liebigs Ann. Chem. 1980 653. 17 D. T.Coxon A. M. C. Davies G. R. Fenwick R. Self J. L. Firmin D. Lipkin and N. F. James Tetrahedron Lett. 1980 21,495. 18 T.Ogita N. Otake Y. Miyazaki and H. Yonehara Tetrahedron Lett. 1980,21 3203. 19 M. Shiro H.Nakai K.Tori J. Nishikawa Y. Yoshimura and K. Katagiri J. Chem. SOC., Chem. Commun. 1980,375. 20 M. Hayashi S.Yaginuma N.Muto and M. Tsujino Proc. 8th Symp. Nucleic Acids 1980,IRL Press London New York. Biological Chemistry -Part (ii)a Nucleosides & Nucleotides 2 Nucleosides Reviews have appeared describing the new bicyclic ketone route to C-nucleosides2' and the photochemistry of purine nucleosides.22 The former method has been applied23 to the synthesis of 2-methylated C-nucleosides and a 9-deazapurine nucleoside namely the inosine analogue (21) has now been synthesized from ribo~ylacetonitrile~~ (Scheme 6). Ph,CO CH2CN + 00 X Reagents i (Me,N),CHOBu'; ii CF,CO,H H20 CHCl,; iii MeSO,CI Et,N CHCl,; iv PhCH,NHCH,CO,Et DMF; v NaOEt; vi Me,NCH(Oneopentyl),; vii NH, MeOH; viii sodium naphthylide THF at 20 OC for 18 h Scheme 6 Other novel C-nucleosides which have been described2' include the C-nucleoside isomer (22) of bredinin the indole derivative (23) which was prepared by dehydra- tion of a 2-(pentahydro~ypentyI)indolone,~~ and the purine analogue (24)27 (Scheme 7).Ribofuranosyl-pyrazoles,including (25) have been prepared from the ribofuranosyl-ethyne (26) and hydrazine28 and from al10se.~' N OH H O M Rf<-)CONH,N HO N H (22) (23) " R. Noyori and T. Sato Kaguku No Ryoiki Zokan 1980 169. '' M. Rufalska and G. Wenska Wiad. Chem. 1980 34.9. 23 T. Sato H. Kobayashi and R. Noyori Tetrahedron Lett. 1980,21 1971. 24 M. I. Lim R. S.Klein and J. J. Fox Tetrahedron Left. 1980 21 1013. 25 M. S.Pwnian and E. F. Nowoswiat. J. Org. Chem. 1980,45,203. 26 F. G. Gonzalez Carbohydr.Res. 1980,80 37. 2' C. K. Chu K. A. Watanabe and J. J. Fox J. Heterocycl. Chem. 1980,17 1435. 28 J. G. Buchanan A. R. Edgar R. J. Hutchinson A. Stobie and R. H. Wightman J. Chem. SOC. Perkin Trans. 1,1980 2567. 29 J. G. Buchanan M.E. Chacon-Fuertes A Stobie and R. H. Wightman J. Chem. SOC. Perkin Trans. 1 1980 2561. 304 G. Shaw CHO PI,COyycN +i JJNNHCONH2CN ii 4 00X Reagents i NH,NHCONH,; ii NaOEt; iii CH(OEt), HC1 Bu”0H Scheme 7 An interesting new route3’ to arabinofuranosyladenine (27) involves cyclization of 8-carbamoyl-2’-O-tosyladenosine(28). In pyridine-water the amide group acts as an 0-nucleophile to form the cyclic nucleoside (29);after hydrolysis and decarboxylation this produces (27). In contrast in the more alkaline N ‘N ‘N 3N’-tetramethyl-guanidine solution the amide is a N-nucleophile and the stable derivative (30)is the sole product (Scheme 8).Full details3’ of the synthesis of arabinofuranosyladenine(27) and of hypoxan-thine (31)by cyclization of the appropriate aminoimidazole arabinosides (32)and Ho (30) Reagents i pyridine water; ii N1N1N3N3-tetramethylguanidine Scheme 8 30 K. J. Divakar and C. B. Reese J. Chem. SOC.,Chem. Commun. 1980,1191. K. Kadir G. Mackenzie and G. Shaw J. Chem. SOC.,Perkin Trans. I 1980,2304. Biological Chemistry -Part (ii)a Nucleosides & Nucleotides 0 I HO I (32) X = CN *’ (31) (33) X = CONHz (33) respectively with formamidine or with triethyl orthoformate and ammonia have been published.The hitherto unknown 3-methyl-2’-deoxyadenosine(34) has been prepared32 by methylation of the (formy1amino)imidazole deoxyriboside (35) followed by reduc- tion to the formamidine (36),which cyclizes. The adenosine (34) is!abile at pHs7.0 when it produces 3-methyladenine (37) whereas at pH 8.98 the N-(formy1)- aminoimidazole nucleoside (36) is obtained. C(NH,)=NOCH,Ph C(NH,)=NH NMeCHO (34) R = dRf dR$ (35) dRC (36) i37j R = H -(dRf = 2‘-deoxy-P -D-ribofuranosyl) An improved synthesis33 of 2,3,5-tri-O-benzoylribofuranosyl azide in 98% yield from the l-O-acetate and trimethylsilyl azide has been described. The azide has been used in one3 of two syntheses3’ of 8-aza-3-deazaguanosine (38). 3’-Alkyl-uridines have been prepared36 in conventional manner from the ribose derivative (39) which was obtained from the keto-sugar (40) with either a Grignard reagent or an alkyl-lithium followed by deblocking and treatment with periodate and borohydride.A useful route to 5’-deoxy-5’-azido-nucleosides, including 5‘-deoxy-5’-azidothymidine in one step from thymidine and Ph3P CBr, and LiN3 in 90% yield has been described.37 5’-Deoxy-5‘-iodoadenosine has been shown3* to cyclize with zinc in pyridine to a 7,8-dihydro-5’,8-cyclo-5’-deoxyadenosine (41) with an R configuration at C-8. ’’ T. Fujii T. Saito and T. Nakasaka J. Chem. SOC.,Chem. Commun. 1980,758. 33 W. Schorkhuber and E. Zbiral Liebigs Ann. Chem.. 1980 1455. 34 R. A.Earl and L. B. Townsend. Can. J. Chem. 1980,58.2550. 35 R. B. Meyer G.R. Revankar P. D. Cook K. W. Ehler M. P. Schweizer and R. K. Robins J. Heterocycl. Chem. 1980.17 159. 36 A. Rosenthal and S. N. Mikhailov. Carbohydr. Res. 1980,79,235. 37 I. Yamamoto M. Sekine and T. Hata J. Chem. SOC.,Perkin Trans. 1 1980,306. 38 J. Zylber R. Pontikis A. Merrien C. Merrienne M. Baran-Marszak and A. Gaudemer Tetrahedron 1980.361579. 306 G. Shaw The novel synthesis of an analogue of NAD that was described in the previous Report has been extended3’ to include the preparation of the ribosylpyridinium salt (42) from 2,3-0-isopropylideneribofuranosylamineand a 1-(2,4-dinitro-phenyl)-3-benzoylpyridiniumsalt and further examples of the use of tetraisopropyl- disiloxane as a protecting group with cytosine arabinoside and 1-(6-deoxy-a-~-talofuranosy1)uracil have been de~cribed.~’ Other novel 0-protecting groups include the pyridine N-oxide group (43) which may be removed under mild and the use of zinc bromide to remove methoxytrityl groups in nucleoside and nucleotide chemistry has been reviewed.42 Trimethylsilyl iodide has been used for the first time43 in nucleoside synthesis to prepare 2,3,5-tri-O-benzoylribosyl iodide from the acetate and it may be condensed with a silylated base in situ to give nucleosides.The use of hydroxylamine acetate for the regioselective 2’-0-deacylation of purine and pyrimidine ribonucle~sides~~ and of pentafluorophenyl benzoate4’ for the rapid acylation of 2‘-deoxycytidine in 90% yield at room temperature during a day have been recommended Further examples of the use of fluorine in acetic acid for the fluorination of nucleosides have been given.46 S-P-Rf (45) Me,N 1 0 mN-0 CHN~ (43) (44) 39 Ch.R. Winne J. A. Lepoivre and F. C. Alderweireldt Bull. Soc. Chim. Belg. 1980,89,67. 40 W. T. Markiewicz N. S. Padyukova Z. Samek and J. Smrt,Collect. Czech. Chem. Commun. 1980 45,1860. 41 Y. Mizuno T. Endo A. Takahashi and A. Inaki Chem. Pharm. Bull. 1980,28,3041. 42 V.Kohli H. Blocker and H. Kosler Tetrahedron Lett. 1980,21,2683. 43 Z.Tocik R. A. Earl and J. Beranek Nucleic Acids Res. 1980,8,4755. 44 Y.Ishido N. Sakairi K. Okazaki and N. Nakazaki J. Chem. Soc. Perkin Trans. 1 1980 563. 45 J. Igolen and C. Morin J. Org. Chem. 1980,45,4802. 46 B.Schwarz. D. Cech A. Holy and J.Skoda Collect. Czech. Chem. Commun. 1980,45,3217. Biological Chemistry -Part (ii)a Nucleosides & Nucleotides 307 Alkylation of nucleosides continues to excite attention. Guanosine has been shown4’ to produce the C-8-substituted derivative (44) by treatment with benz[a]anthracene 5,6-oxide at pH 9.5 over 4 days at 37°C and to ben~ylate~~ with the carcinogen N-nitroso-N-benzylurea mainly on 0-6 and N-2. An examination of the methylation of various nucleosides in the presence of t-butyl peracetate has that C-methylation occurs at pH 1-4 but that at pH4-10 there is increasing N-methylation in all the common pyrimidine and purine nucleosides. Permethylation of adenosine and guanosine has been a~hieved,~’ using trimethylaniliniwn methoxide but inosine and xanthosine are cleaved by the reagent to produce methyl aglycones.Further applications5’ of the sulphur-extrusion method to nucleosides have been outlined including the conversion of 4-thiouridine into various 4-(substituted a1kyl)pyrimidine nucleosides uia 4-alkylthio-derivatives using triphenylphosphine and a strong base and further details of the replacement of the 6-amino-group of an acylated adenosine in an appropriate anhydrous medium by photolysis in the presence of pentyl nitrite have appeared.” N.m.r. relaxation studies of 13C-labelled uracil in tRNA have been reported53 and an n.m.r. study of 5-substituted uridines has that the substituent affects the N-1-C-1’ and the C-1’-0-1’ bonds in opposite ways. Ultrasonic relaxation studies have shownss that the syn-anti glycosyl conformational barrier is reduced when 2’-deoxyadenosine is bound to ethidium bromide and this is considered to be a relevant model for intercalation studies.3 Nucleotides Phosphoryl tris-triaz~le’~ have been proposed as and tri( 1-imidaz~lyl)phosphine~~ phosphorylating agents that are especially useful for the preparation of nucleoside 3‘-phosphotriesters the latter after oxidation wit) iodine water. g-Chlorophenyl phosphorodichloridate followed by oxidation of intermediate phosphite esters with iodine has also been used58 to prepare mononucleotides and a similar system has been applied” to the formation of inter-nucleotide bonds. Side-reactions in nucleo- tide synthesis using phosphorochloridates are reported to be diminished by using molecular sieves as acid scavengers,6o 06-phosphorylation or -thiophosphorylation of guanosine derivatives is aided6’ by the use of 4-(dimethy1amino)pyridine as a catalyst and selective 5’-0-phosphorylation especially of oligonucleotides has 47 K.Nakanishi H. Komura I. Miura and H. Kasai J. Chem. Soc. Chem. Commun. 1980,82. 48 R. C.Moschel W. R. Hudgins and A. Dipple J. Org. Chem. 1980,45,533. 49 M. F.Zady and J. L. Wong J. Org. Chem. 1980,451,2375. ’O G. R. Pettit R. M. Blazer J. A. Einck and K. Yamauchi J. Org. Chem. 1980,45,4073. ” A.Yamane H. Inoue. and T. Ueda Chem. Pharm. Bull. 1980,28,157. ” V.Nair and S. G. Richardson J. Org. Chem. 1980,45,3969. ” W. D. Harnill Jr. W. J. Horton and D. M. Grant J. Am. Chem. SOC.,1980,102,5454.s4 E.Egert H. J. Lindner W. Hillen and M. C. Bohrn J. Am. Chem. SOC.,1980,102,3707. ” F.Jordan S. Nishikawa and P. Hernrnes J. Am. Chem. SOC.,1980,102,3913. ” A.Kraszewski and J. Stawinski Tetrahedron Lett. 1980 21 2935. 57 T.Shimidzu K. Yarnana A. Murakarni and K. Nakamichi Tetrahedron Lett. 1980,21,2717. ’’ D. Molko R. B. Derbyshire A. Guy A. Roget and R. Teoule Tetrahedron Lett. 1980 21 2159. s9 K.E.Ogilvie and M. J. Nerner Tetrahedron Lett. 1980,21,4145. 6o V.Kohli H. Blacker and H. Koster Tetrahedron Lett. 1980.21 501. ” H. P.Daskalov M. Sekine and T. Hata Tetrahedron Lett. 1980.21 3899. 308 G. Shaw been achieved6* using 5 -chloro-8-quinolyl phosphate in the presence of (PySe) and Ph3P at room temperature over twelve hours in 92% yield.The methyl group has been found to be as a protecting group for phbsphate esters in nucleotide synthesis and it may be removed by t-butylamine at 46 "Cover fifteen hours. Interest in cyclic phosphates continues. The enzymatic synthesis and configur- ational analysis of the (R,)and (Sp)diastereoisomers of [a-"0]-2'-dADP from (Sp)and (Rp) diastereoisomers of cC1'0]-2'-dAMP using an adenylate cyclase from Breuibacterium Ziquefaciens has been achieved.64 c[ '*0]-2'-dAMP has also been ~ynthesized~~ from the P-anilidates of c-2'-dAMP and C'802 with retention of configuration and a stereospecific synthesis of cAdo-3',5'-(Sp)-[180]mono-phosphate has been Mass spectrometry has been used to identify cAMP in plant tissue Calculations of the geometrical stabilization of 3'3'-and 2',3'-cyclic nucleotides have been made and they show68 that hydrolysis of cAMP is more exothermic owing to trans ring fusion (4-5 kcalmol-' of strain energy) and unfavourable 0-C-C-0 interactions that are relieved after cleavage of the phosphate ring.A quantum-chemical study6' has examined the effect of hydration and of pucker- ing of the ribose ring on the enthalpy of hydration of CAMP; the bridge between 0-1' and 0-5' is an important hydration site for 1 molecule of water. Syntheses and configurational assignments of diastereoisomers of the 4-nitrophenyl esters of thymidine 3'-and 5'-N-phenylphosphoramidateshave been reported," and the absolute configuration at the phosphorus atom has been determined. A novel reaction of ribose 5-phosphate and barbituric acid gives amongst other compounds the nucleotide (43 which is an inhibitor of orotidine 5'-phosphate decarboxylase." The transport of nucleotides through chloroform using diammonium diazabicyclo-octane as a carrier has been rep~rted.~' Raman perturbation difference spectroscopy has been applied73 to a study of heavy-metal-nucleotide interaction and a new fluorescent labelling agent for nu~leofides~~ is the isoquinoline (46) which alkylates UMP at the phosphate ester group to give a highly fluorescent material with an excitation maximum at 353 nm and an emission maximum at 523 nm.X-Ray crystal structures that have been determined include those of pseudocytidine hydr~chloride,~~ 5-hydroxymethyl-2'-5-acety1-2'-deoxy~ridine,~~ '' H.Takaku M. Kato M. Yoshida and R. Yamaguchi J. Org. Chem. 1980,45 3347. 63 D. J. H. Smith K. K. Ogilvie and M. E. Gillen Tetrahedron Lett. 1980,21 861. 64 J. A.Coderre and J. A. Gerlt J. Am. Chem. Soc. 1980 102,6594. '' J. A.Gerlt and J. A. Coderre J. Am. Chem. SOC., 1980 102,4531. '' J. Baraniak K. Lesiak M. Sochaki and W. J. Stec J. Am. Chem. Soc. 1980 102,4533. " R.P. Newton N. Gibbs C. D. Moyce J. L. Wiebers and E. G. Brown Phytochemism 1980,19,1909. " F.J. Marsh P. Weiner J. E. Douglas P. A. Kollman G. L. Kenyon and J. A. Gerlt J. Am. Chem. SOC.,1980 102 1660. 69 M. M. E. Scheffers-Sap and H. M. Buck J. Am. Chem. Sac. 1980,102,6422. 70 J. A.Gerlt S. Mehdi J. A. Coderre and W. 0.Rogers Tetrahedron Lett. 1980,21,2385.71 H.Komura K. Nakanishi B. W. Potuin H. J. Stern and R. S. Krooth J. Am. Chem. SOC., 1980 102 1208. '' I. Tabushi Y. Kobuke and J.-I. Imuti J. Am. Chem. SOC.,1980,102 1744. 73 M. R. Moller M. A. Bruck T. O'Connor F. J. Armatis Jr. E. A. Knolonski. N. Kottman and R. S. Tobias J. Am. Chem. SOC., 1980,102,4589. 74 S. Nishimura and M. Saneyoshi Chem. Pharm. Bull. 1980,28,1695. G. 1. Birnbaum K. A. Watanabe and J. J. Fox Can. J. Chem. 1980,SS 1633. '' P. J. Barr P. Chananont T. A. Hamor A. S. Jones M. K. O'Leary and R. T. Walker Tetrahedron 1980,36,1269. Biological Chemistry -Part (ii)a Nucleosides & Nucleotides 309 6-methy1-2’-deoxy~ridine,7~ de~xyuridine,~~ and 4-amino-l-[4-amino-2-oxo-1(2H)-pyrimidinyl]-l,4-dideoxy-P-D-glucopyranuronic (C-substance -the nucleoside fragment of gougerotin).G. I. Birnbaum R. Deslauriers T.-S. Lin G. T. Shiau and W. H. Prusoff,I. Am. Chem. Soc. 1980 102,4236. 78 G. I. Birnbaum F. E. Hruska and W. P. Niemczura I. Am. Chem. SOC.,1980,102,5586. 79 P.Swaminathan J. McAlister and M. Sundaralingam Acta Crystallogr. Secr. B 1980 36 878.

ISSN:0069-3030    

DOI:10.1039/OC9807700299

出版商:RSC    

年代:1980

数据来源: RSC