摘要:

7 Aromatic Compounds ~~ By I. G. C. COUlTS Department of Chemistry and Physics Nottingham Polytechnic Nottingham NG11 8NS 1 General and Theoretical Studies Benzene and the Phenyl Ring.-As a contribution to the continuing search for methods of quantifying aromaticity in molecules Zhou and Parr' have expanded their recent suggestion that absolute hardness (or HOMO-LUMO gap) is such a measure by the introduction of a new concept of relative hardness (relative to a defined hypothetical acyclic reference structure). For over 200 cyclic conjugated molecules predictions of aromaticity using relative and absolute hardness give results in agreement with other measures of aromaticity and it is concluded that relative hardness is a particularly good index for identifying aromatic non-aromatic and anti-aromatic character.The distortion from planarity of highly substituted 1,3,5-tris(diethylamin0)-2,4,6-trinitrobenzene determined by X-ray crystallography has been discussed* in terms of steric and electronic factors; in the ground state the molecule is in a boat form the result of cooperative non-bonded steric repulsion and strong push-pull conjuga- tion while in solution it exists as boat C3 and twist C2 conformers. Application3 of supersonic molecular jet laser spectroscopy has allowed the 'trapping' and structural determination of the most stable conformers of a number of methoxyben-zenes. In each case the methoxy group lies in the plane of the ring; curiously in the methoxytoluenes the meta isomer shows a large barrier to methyl rotation but the methyl groups in the ortho and para isomers are free rotating.Results of a large MRCDI ab initio calculation show4 for the lowest triplet state of the free benzene molecule that the hexagonal conformation is unstable and lies 800cm-' above an almost cylindrical trough. The influence of a P-aryl substituent on the reactivity of aryl alkyl derivatives has long been attributed to phenyl participation in carbocation formation. Evidence for the formation of the simplest example (1) in the gas phase has recently been (1) ' Z. Zhou and R. G. Parr J. Am. Chem. Soc. 1989 111 7371. J. M. Chance B. Kahr A. B. Buda and J. S. Siege] J. Am. Chem. Soc 1989 111 5940. P. J. Breen E. R. Bernstein H. V. Secor and J. L. Seeman J. Am.Chem. Soc. 1989 111 1958. W. J. Buma J. H. van der Waals and M. C. van Hemert J. Am. Chem. Soc. 1989 111 86. 171 172 I. G. C. Courts rep~rted.~ [1-'3C]-2-Phenyl-l-chloroethanewas subjected to y-radiolysis with inter- mediates being trapped with methanol and the I3Clabel in the resulting l-methoxy-2- phenylethane was found to be equally distributed in the ethane carbons. Another archetypal species which has been produced6 in the gas phase is the dehydrophenyl anion (2) generated by abstraction of an ortho proton from fluorobenzene followed by collision-induced dissociation of the resulting anion with helium possibly via a fluoride-benzyne complex. Anion (2) is a relatively weak base and does not exchange with D20. Valence Isomers and Homoaromaticity.-A synthesis of the last elusive valence isomer of benzene 2,2'-bicyclopropenyl (3) has finally been achieved' (Scheme 1).It is stable in solution at -10 "C,but at room temperature surprisingly polymerizes rather than reverting to benzene (a very exothermic process). On treatment with silver tetrafluoroborate it is transformed into Dewar benzene and it forms a bis adduct with cyclopentadiene. By a similar route 2,l '-bicyclopropenyl can be prepared and it is claimed without experimental details that the 1,l'-isomer has also been obtained. Me3Si SiMe3 Me3Si c1 SiMe3 (31 Reagents i MeLi CH2C12;ii Bu,NF 25 mTorr Scheme 1 The ketone-sensitized ph- -Jysis of benzvalene leads to benzene formation or automerization. It has now been demonstrated' that photocycloaddition also occurs with a number of ketones to give oxetanes (4).The valence isomerization of benzoxathiete to monothio-o-benzoquinone has been investigated.' Treatment of (4) S. Fornarini and V. Muraglia J. Am. Chem. SOC.,1989 111 873. S. Gronert and C. H. DePuy J. Am. Chem. SOC.,1989 111 9253. ' W. E. Billups and M. M. Haley Angew. Chem. Int. Ed. Engl. 1989 28 1711. M. Christ1 and M. Braun Angew. Chem. Inf. Ed. EngL 1989 28 601. A. Naghipur K. Reszka A,-M. Sapse and J. W. Lown 1. Am. Chem. SOC.,1989 111 258. Aromatic Compounds hexamethyl Dewar benzene with t-butyl hypochlorite gives by a radical mechanism the chloro compound (5) the reactions of which have been reported." Ab initio calculations on the radical cation states of prismane indicate that they would be less stable than those derived from hexamethyl Dewar benzene." Although there are various theoretical and experimental results which indicate that homoaromatic stabilization is mainly a property of ionic systems with neutral molecules having a very small stabilization energies it has been suggested on the basis of heats of hydrogenation that triquinacene is homoaromatic.This view is challenged by Dewar and Holder,12 who find no evidence of homoaromatic stabiliz- ation from either AM1 or ab initio calculations on the molecule. They suggest that the discrepancy between theoretical and thermodynamic data arises from the effects of twisting in di- tetra- and hexahydrotriquinacenes. In an elegant study Prinzbach and co-~orkers'~ describe the conversion of cis-benzene trioxide into 3,6,9-tris(acceptor-substituted) cis-tris-6-homobenzenes (6) which are now available in gram quantities.They have been shown by NMR to possess C3 symmetry. A companion paper reports14 the preparation of trans-oxa-tris-6-homobenzenes(7). 2 Preparation of Benzenes from Non-aromatic Precursors Collision-induced dissociative chemisorption allows the specific conversion of methane into benzene. A monolayer of methane adsorbed on a Ni"' catalyst at low temperatures and ultra high vacuum is converted by krypton bombardment into methyl radicals. As the temperature is raised these radicals dissociate to adsorbed C2H2and then benzene." The mixed heteropolyacid H5PM~10V2040, dissolved in 1,2-dichloroethane with tetraglyme catalyses the aromatization of cyclic dienes in the presence of molecular oxygen.The reaction proceeds by successive one-electron transfers to the heteropoly system which is then reoxidized by the oxygen; conversion of limonene into p-cymene 10 C. C. Wamser D. D. Ngo,M. J. Rodriquez S. A. Shama and T. L. Tran J. Am. Chem. Soc. 1989,111 2162. K. Raghavachari and H. D. Roth J. Am. Chem. Soc. 1989 111 7132. 12 M. J. S. Dewar and A. J. Holder J. Am. Chem. SOC.,1989 111 5384. 13 W.-D. Braschwitz T. Otten C. Rucker H. Fritz and H. Prinzbach Angew. Chem. Int. Ed. EngL 1989 28 1348. 14 D.-R. Handreck D. Hunkler and H. Prinzbach Angew. Chem. Int. Ed. EngL 1989 28 1351. Is Q. Y. Yang A. D. Johnson K. J. Maynard and S.T. Ceyer J. Am. Chem. Soc. 1989 111 8748. I. G. C. Coutts is precededI6 by isomerization to endocyclic dienes. Moore and co-workers have developed ring expansion of 4-alkynylcyclobutenones as a route to benzoquinones." Compounds (8),readily available from dimethyl squarate undergo mild thermolysis to the ketenes (9) which are thought to cyclize via biradicals (10) to quinones (1 1) (Scheme 2). An alternative cyclization of (9) gives cyclopentenediones as by- products but ketenes derived from 4-alkenylcyclobutenones cyclize only to six- membered rings,18 while 4-chloro-4-aryl- (or alkenyl) cyclobutenones rearrange to p-chl~rophenols.'~ cis-5,6-Dichlorohexafluorocyclohexa-1,3-diene,available by a five-step synthesis from hexafluorobenzene has been used2' as a synthon for that molecule in Diels- Alder reactions.Cycloaddition of acetylenic esters to 1 -methoxy- cyclohexadienes produces alkylsalicylates and resorcinols.21 O\ X (9) I 0 0 R' R2fJR 0 +'0 X Scheme 2 3 Non-aromatic Compounds from Benzene Precursors The rneta-photocycloaddition of ethenes to benzene although of great synthetic potential is a process of notorious complexity. However by judicious choice of substituents on the benzene and ethene it is possible to control the nature of the products; the position of alkene attack is directed by the arene substituent while the use of trans-1,2-dichloroethene gives 6-exo-7-endoadducts such as (12).22A remarkable rate enhancement in the cycloaddition of N-methylmaleimide to the enol l6 R.Neumann and M. Lissel J. Org. Chem. 1989 54 4607. L. D. Foland J. 0.Karlsson S. T. Perri R. Schwabe S. L. Xu S. Patil and H. W. Moore J. Am. Chem. SOC.,1989 111 975. 18 S. T. Pem H. J. Dyke and H. W. Moore J. Org. Chem. 1989,54 2034. 19 S. L. Xu and H. W. Moore J. Org. Chem. 1989 54 4024. 20 W. P. Dailey R. A. Correa E. Harrison and D. M. Lemal J. Org. Chem. 1989 54 5511. 21 C. C. Kanakam N. S. Mani H. Ramanathan and G. S. R. Subba Rao J. Chem. SOC.,Perkin Trans. 1 1989 1907. 22 A. Gilbert P. Heath and P. W. Rodwell J. Chem. SOC.,Perkin Trans. 1 1989 1867. Aromatic Compounds form of 9-anthrone compared with that to anthracene is attributed23to catalytic oxyanion acceleration. Mild heating of a pyrrolo[ 3,2-elindole causes migration via a ‘disallowed’thermal 1,3-shift from oxygen to carbon giving dienone (13) in which benzene aromaticity has been unexpectedly destroyed.24 I CI (12) 4 Substitution in the Benzene Ring Electrophilic Substitution.-In a review2’ Effenberger discusses the use which his group and others have made of 1,3,5-tris(dialkylamino)benzenesas sources of stable arenium ions (a-complexes).Although the role in electrophilic aromatic substitution of such ions is wdll established the participation of .rr-complex intermediates on the potential energy surface is still a subject of debate. The behaviour of arenium ions generated in the gas phase by protonation of alkylbenzenes indicates that they coexist with related .rr-complexes.In the latter the positive charge must become localized on the alkyl moiety permitting alkyl side-chain isomerization (Scheme 3). The observation that the side chains of s-butyl and pentylbenzenium ions isomerize prior to decomposition support the existence of wcomplexes although other mechanisms (e.g. involving proton-bound carbenium ions) cannot be excluded.26 The reactions of bromide and chloride with aryl cations produced by dediazonization of arenediazonium salts is diffusion ~ontrolled.~’ f JI Since cation radicals often take part in complex reaction schemes rather than simple combinations they have been regarded as being of low intrinsic reactivity towards nucleophiles compared with related carbocations. However anodic oxida-23 M.Koerner and B. Rickborn J. Org. Chem. 1989 54 6. 24 R. E. Bolton C. J. Moody and C. W. Rees J. Chem. SOC.,Perkin Trans. I 1989 2136. 25 P. Effenberger Acc. Chem Res. 1989 22 27. 26 R. W. Holman and M. L. Gross J. Am. Chem. SOC.,1989 111 3560. 27 J. P. Lorand Tetrahedron Lett. 1989 30,7337. 176 I. G. C. Coutts tion of 9-phenylanthracene produced a cation radical which reacted an order of magnitude faster with acetate than did the corresponding cation.28 Kochi has continued his advocacy of electron transfer processes in aromatic substitution with an interesting account29 of the nitration of arenes by the reaction of molecular oxygen with arene-nitrosonium charge transfer complexes. This nitration involves initial autoxidation of the complex to a radical ion pair [ArH’+ NO2] followed by collapse to a a-complex and final proton loss.The novel procedure allows quantita- tive nuclear nitration of durene and pentamethylbenzene encouraged by specific coupling of arene cation radical with paramagnetic nitrogen dioxide. In the presence of added base prior proton abstraction leads to free-radical side-chain nitration. This last process has been further investigated in a study3’ of the decay in the presence of bases of radical cations produced by laser excitation of methylbenzene- tetranitromethane complexes. Although the nitration of naphthalene predominantly follows the arenium intermediate pathway application of 15N CIDNP techniques indicates that there is a small but significant contribution from the alternative single-electron transfer route.31 In carbon tetrachloride nitrogen dioxide nitrates naphthalene by a free radical mechanism; mononitration occurs predominantly in the 1-position and there is also appreciable formation of the unusual 1,3-and 2,3-dinitronaphthalenes.The product ratios obtained resemble those observed for nitronaphthalenes formed by atmos- pheric pollution and suggest that these may also arise by free radical processes.32 The nitro groups in microbial natural products such as chloramphenicol result from the oxidation of amine-containing precursors.However when Streptumycesfumanus was cultured in a medium containing K%l8o3 the N/O ratio in the nitro group of the metabolite dioxapyrrolomycin was the same as that in the enriched nitrate indicating that the nitro group is introduced by a process analogous to electrophilic nitration.33 The selective nitration of electron-rich substrates with tetrabromonitrocyc-lohexadienone as the nitronium carrier has been extended34 to anilines.Mononitra- tion of alkylbenzenes with benzoyl nitrate in the presence of a zeolite leads to a preponderance of the para isomer.35 The effectiveness of zeolites in controlling the selective electrophilic halogenation of alkylbenzenes is diminished by hydrogen halides but with propylene oxide as an acid scavenger toluene was para-brominated with 98% ~electivity.~~ In the presence of cetyltrimethylammonium bromide aniline N-methylaniline and N,N-dimethylaniline are brominated with an unusually high ortho/para ratio which rises with increasing bulk of the amine s~bstituent.~’ Ben-zyltrimethylammonium tribromide has been further exploited in the bromination of 28 B.Reitstoen F. Norrsell and V. D. Parker J. Am. Chem. SOC.,1989 111 8463. 29 E. K. Kim and J. K. Kochi J. Org. Chem. 1989,54 1692. 30 J. M. Masnovi S. Sankararaman and J. K. Kochi J. Am. Chem. SOL 1989 111 2263. 31 J. F. Johnston J. H. Ridd and J. P. B. Sandall J. Chem. SOC.,Chem. Commun. 1989 244. 32 G. L. Squadrito F. R. Fronczek D. F. Church and W. A. Pryor J. Org. Chem. 1989 54 548. 33 G. T. Carter J. A. Nietsche J. J. Goodman M. J. Torrey T. S. Dunne M. M. Siegel and D. B. Borders J. Chem. SOC.,Chem Commun. 1989 1271. 34 M. Lemaire A. Guy P. Boutin and J.P. Guette Synthesis 1989 761. 35 K. Smith and K. Fry Tetrahedron Lerr. 1989 30,5333. 36 F. de la Vega and Y. Sasson 1 Chem. SOC.,Chem. Commun. 1989 653. 37 G. Cerichelli L. Luchetti and G. Mancini Tetrahedron Lett. 1989 30,6209. Aromatic Compounds 177 a wide range of phenols38 and has been used to dibrominate 5-a~etoxytropolone.~~ Phenols passed down a column of a polymer-bound form of the reagent are quantitatively brominated although naphthols are oxidized.40 The selective chlorina- tion of electron-rich aromatic compounds with N-chloroamines has been the subject of mechanistic A dominant reaction pathway involves arenium ion intermediacy but electron-transfer processes may be implicated for some alkoxy- substituted benzenes.A perfluoro salt K[(C3F7)3PF3] has been advocated43 as an advantageous replacement for tetrafluoroborates in the Schiemann preparation of fluoroarenes. Aryl cations or cation radicals formed by chemical or anodic oxidation react with the fluoride of hydrogen fluoride/base complexes to yield 4,4-difluoro- cyclohexa-2,5-dienones ( 14) which can be converted4 into a range of fluorophenols (Scheme 4). Anodic oxidation of iodine in trimethyl orthoformate produces iodonium species which effect direct iodination of electron-rich ben~enes.~’ In an adaptati0x-1~~ of the classic synthesis of alkylbenzenes by Friedel-Crafts acylation followed by reduction the intermediate acylation-Lewis acid complex is reduced directly with trimethylsilane. Alkylation of metal phenolates with N-t-Boc-L- prolinal shows4’ high regio- and diastereoselectivity (Scheme 5).With magnesium as counter-ion syn-alcohols (15) are obtained possibly via a-chelation while titanium phenolates yield the anti products (16). OML, -0 + QCHO-x\ * x\ I *+ x\ Boc Boc Boc (15) (16) Scheme 5 38 S. Kajigaeshi T. Kakinami M. Moriwaki T. Tanaka S. Fujisaki and T. Okamoto BUN. Chem. SOC. Jpn. 1989 62 439. 39 T. Nagao A. Mori and H. Takeshita Bull. Chem SOC.Jpn. 1989 62 451. 40 T. Kakinami H. Suenaga T. Yamaguchi T. Okamoto and S. Kajigaeshi Bull Chem. Soc Jpn. 1989 62 3373. 41 F. Minisci E. Vismara F. Fortana E. Platone and G. Faraci J. Chem. SOC,Perkin Trans. 2 1989 123. 42 J. R. Lindsay Smith L. C. McKeer and J. M. Taylor J.Chem SOC., Perkin Trans. 2 1989 1529. 43 N. V. Pavlenko and L. M. Yagupol’skii J. Gen. Chem. USSR 1989,59,469. 44 J. H. H. Meurs D. W. Sopher and W. Eilenberg Angew. Chem. Znt. Ed Engl 1989 28,927. 45 T. Shono Y. Matsumura S. Katoh K. Ikeda and T. Kamada Tetrahedron Lett. 1989 1649. 46 A. Jaxa-Chamiec V. P. Shah and L. I. Kruse J. Chem SOC.,Perkin Trans. I 1989 1705. 47 F. Bigi G. Casnati G. Sartori G. Araldi and G. Bocelli Tetrahedron Lett. 1989 30 1121. I. G. C. Coutts The 0,O-diprotonated dication formed from 2-nitropropene in trifluoromethane- sulphonic acid reacts with benzene or naphthalene to give aryl methyl ketones.48 Bromination of (17) resulted in the formation of (18). This is formally an alkylation of a benzene the first to be initiated by bromination and a mechanism invoking a bromonium ion has been propo~ed."~ Acids of general formula ArCH2S(CH2),C02H can be formed directly from the reaction of phenols with formaldehyde and w-mercaptoalkanoic acids.50 The elec- trophilic reactivity of imidoylnitrenes ROC( =NX)N can be controlled5' by choice of nitrogen substituent.Nitrenes in which X is methanesulphonyl react with arenes containing electron-donating groups to give N-acylisoureas but do not insert into aliphatic carbon-hydrogen bonds.52 Further evidence has been presented53 for hydroxyl radicals being the major reactive species in the hydroxylation of aromatic compounds by Cur-hydrogen peroxide. Aryl halides react with F03SCF21 in the presence of copper the halide being replaced by a trifluoromethyl group in an electron transfer process.54 Aryl Radicals.Data on the relative reactivity of carbon-hydrogen bonds towards phenyl radicals have been based on a measurement of competitive reaction between the radical and carbon tetrachloride or the hydrogen donor. A new determinati~n,~~ relying on competitive abstraction of hydrogen or tritium atoms shows that at low temperatures in the liquid phase the selectivity of the phenyl radical is similar to that of the methyl radical but is less so at high temperature in the gas phase. Oxidation of arylhydrazines with Cu" salts is an interesting new source of aryl radicals,56 reaction of the radical with alkenes being controlled by the copper counter-ion. With copper halide the products (19) are those also formed by Meerwein arylation while with copper sulphate the reduced compounds (20) are formed (Scheme 6).Ar-+ CH,=CH-R .- ArCH,CH(Hal)R + ArCH,CH,R (19) (20) Scheme 6 48 K. Okabe T. Ohwada T. Ohta and K. Shudo J. Org. Chem. 1989 54 733. 49 X. Shi R. Day and B. Miller J. Chem. Soc. Perkin Trans. 1 1989 1166. 50 D. J. R. Massy and A. McKillop Synthesis 1989 253. 51 M. Kawase T. Kitamura and V. Kikugawa J. Org. Chem. 1989 54 3394. 52 H. A. Dabbagh and W. Lwowski J. Org. Chem. 1989 54 3952. 53 M. K. Eberhardt G. Ramirez and E. Ayala J. Org. Chem 1989 54 5922. 54 Q.-Y. Chen and S.-W. Wu J. Chem. SOC.,Perkin Trans. 1 1989 2385. 55 F.-D. Kopinke G. Zimmermann and K. Anders J. Org. Chem. 1989 54 3671. 56 T.Varea M. E. Gonzalez-Nunez J. Rodrigo-Chiner and G.Asesnsio Tetrahedron Lett. 1989,30,4709. Aromatic Compounds A transformation involving aryl radicals has provided an elegant solution to the problem of introducing a 10P-substituent into the 1 lp-arylandrostane series of antigestagens. Treatment of the halogenated intermediate (21) with tributylstannane to produce a free radical resulted in a high yield of (22) arising with high regio- specificity from a 6-endo-trig cy~lization.~' When the homochiral amide (23) was cyclized with tributylstannane or with Co' (salen) the diastereomeric excess of (24) was the same and was unaffected by temperature indicating that like the stannane reaction the cobalt-mediated reaction proceeds by a free radical mechanism.58 The radical reactions of polyfluoro aromatic compounds have been reviewed.59 Substitution via Aryl-Metal Complexes.The activation of arene and alkane hydrocar- bon bonds by homogeneous rhodium complexes has been reviewed.60 A photo-chemical reaction of benzene with a complex of rhodium containing ethene and carbon monoxide as ligands yields propiophenone.61 Salts of 2,6-diphenylphenol with tin62 or niobium63 undergo a facile intramolecular metallation to form (25). The addition of benzene to an otherwise unreactive tantalum(II1) alkyl complex is ~atalysed~~ by di-t-butylsilane. In the presence of tetra(triphenylphosphine)nickel benzene replaces the iodine of a-chloro-w-iodoperfluoroalkanes.65 57 E. Ottow G. Neef and R. Wichert Angew.Chem. Int. Ed. Engl. 1989 28 773. 58 A. J. Clark and K. Jones Tetrahedron Lett. 1989 30,5485. 59 L. S. Kobrina J. Fluorine Chem. 1989 42 301. 60 W. D. Jones and F. J. Feher Acc. Chem. Res. 1989 22 91. 61 C. K. Ghosh and W. A. G. Graham J. Am. Chem. SOC.,1989 111 375. 62 G. D. Smith P. E. Fanwick and 1. P. Rothwell J. Am. Chem. SOC.,1989 111 750. 63 B. D. Steffey R. W. Chesnut J. L. Kerschner P. J. Pellechia P. E. Fanwick and I. P. Rothwell J. Am. Chem. Soc. 1989 111 378. 64 D. H. Berry and Q. Jiang J. Am. Chem. SOC.,1989 111 8049. 65 Q.-L. Zhou and Y.-Z. Huang J. Fluorine Chem. 1989 43 385. I. G. C. Courts Nucleophilic displacement of hydride from arenechromium tricarbonyl complexes is of continuing synthetic use.N-Lithioamides66 add to these complexes to give ArN(R')COR* which can be hydrolysed to anilines whilst attack by the anions of Schiff bases derived from a-amino esters constitutes a route to a-aryl-a-amino esters.67 The thermodynamic control of regioselectivity of addition of carbanions to the complexes has been discussed.68 A neat synthesis of chiral 2-arylpropionic acids includes reaction of the enolate ion of (26) with benzenemanganese tricar- b0ny1.~~ Variations on the functionalization of arenes by palladium-catalysed cross-coup- ling continue to be reported. The reaction of iodobenzene with norbornene in the presence of palladium acetate gave7' (27) but the addition of potassium formate to the mixture led to high yields of (28); other formate salts were less effective.71 An unambiguous synthesis of the isomeric nitrofluorenones includes the coupling of phenylboronic acid with bromonitrotoluene~.~~ Unsymmetric biaryls are produced from aryl iodides and arylfluoro~ilanes~~ and from the reaction of arylboronic acids 66 L.Keller K.Times-Marshall S. Behar and K. Richards Tetrahedron Lett. 1989 30,3373. 67 M. Chaan J.-P. Lavergne and P. Viallefont Synth. Commun. 1989 19 1211. 68 E. P. Kundig V. Desobry D. P. Simmons and E. Wenger J. Am. Chem. SOC.,1989 111 1804. 69 W. H. Miles P. M.Smiley and H. R. Brinkman J. Chem. Soc. Chem. Commun. 1989 1897. 70 0.Reiser M. Weber and A. de Meijere Angew. Chem. Int. Ed. Engl. 1989 29 1037. 71 R. C. Larock and P. L. Johnson J. Chem. SOC.,Chem. Commun.1989 1368. 72 T. Iihama J.-M.Fu M. Bouguignon and V. Snieckus Synthesis 1989 184. 73 Y. Hatanaka S. Fukushima and T. Hiyama Chem. Lett. 1989 1711. Aromatic Compounds with aryl triflate~;~~ palladium also catalyses the reaction of the latter with cyanide75 and with trialkylaluminiums a means of converting phenolic hydroxyl into alkyl sub~tituents.~~ by cross- Monoterpenes such as p-thujaplicin have been ~btained'~ coupling of bromotropolones with organostannanes. Direct formylation7' of aryl chlorides to aldehydes with carbon monoxide is possible in the presence of an (isopropy1phosphine)propanecomplex of palladium whilst a silylative decarbonyla- tion of aromatic acid chlorides provides a new route to aryl~ilanes.~~ Arylations with organobismith reagents have been reviewed." ortho-Metallation.The use of Grignard reagents in organic synthesis has been eclipsed by the rise of organolithiums. However Hauser bases R2NMgBr and magnesium diamides (R2N),Mg easily prepared and stable effect ortho-magnesi- ation" of ester or diethylamide derivatives of benzoic acids; the resulting organo- magnesiums can be quenched by electrophiles. Snieck~s~~.~' has extended his ortho-lithiations of N,N-diethylbenzamides to the preparation of ortho silyl intermediates which can be further elaborated. Secondary P-aminobenzamide (29) is dilithiated with n-butyllithium electrophiles being directed onto the benzamide side chains4. 0 The relative ortho-directing power of methoxy and N,N'-dimethylimidazolidine substituents has been st~died;'~ in the absence of TMEDA the latter is more effective.The use of the MEM blocking group for phenolic hydroxyl in lithiation is com- promised by competing ortho-metallation.86 Further examples of the ortho-alkylation of phenols uia intermediate 1,3,2-benzodioxaborins have appeared.87 Nucleophilic Substitution.-AM1 calculations show that polynitroarenes react with hydroxide ion to form charge transfer complexes with considerable radical character on the arene; the complexes collapse to Meisenheimer intermediates the relative energies of which can be successfully predicted in spite of the neglect of correlation 74 A. Huty I. Beetz and 1. Schumann Tetrahedron 1989 45 6679. 75 K. Takagi and Y. Sakakibara Chem.Lett. 1989 1957. 76 K. Hirota Y. Isobe and Y. Maki J. Chem. SOC.,Perkin Trans. I 1989 2513. 77 M. G. Banwell M. P. Collis G. T. Crisp J. N. Lambert M. E. Reum and J. A. Scoble J. Chem. SOC. Chem. Commun. 1989 616. 78 Y. Ben-David M. Portnoy and D. Milstein J. Chem. Soc. Chem. Commun. 1989 1816. 79 J. D. Rich J. Am. Chem. Soc. 1989 111 5886. J.-P. Finet Chem. Rev. 1989 89 1487. 81 P. E. Eaton C.-H. Lee and Y. Xiong J. Am. Chem. SOC.,1989 111 8016. 82 R. J. Mills N. J. Taylor and V. Snieckus 1. Org. Chem. 1989 54 4372. 83 R. J. Mills and V. Snieckus J. Org. Chem. 1989 54 4386. 84 S. Bengtsson and T. Hogberg J. Org. Chem. 1989 54 4549. 8.5 F. M. Bevan M. E. Euerby and S. J. Qureshi J. Chem. Res. (S) 1989 116. 86 J. Mayrargue M.Essamkaoui and H. Moskowitz Tetrahedron Lett. 1989 30,6867. 87 C. K. Lau H. W. R. Williams S. Tardiff C. Dufresne J. Scheigetz and P. C. Belanger Can. J. Chem. 1989 67 1384. 182 I. G. C.Coutts and thermal energies in such calculations.88 However no spectroscopic evidence was obtained of intermediates arising from SET processes during a study of the reaction of polynitrohalogenobenzeneswith hydroxide.89 Discrepancies in reported equilibrium constants for the reaction of methoxide with 4-cyano-2,6-dinitroanisole may be explained” in part by formation of imido ester (30) Vicarious nucleophilic substitution of nitroarenes can be effected” using trihalogenomethyl carbanions produced by reaction of haloforms with t-butoxide at -70°C. The nitro group of meta-substituted nitrobenzenes is replaced9* by fluoride on reaction with KF-Ph4PBr.Solvolysis of N-tosyl- 0-phenylhydroxylamine in HF-THF leads to the regiospecific formation of 4-fluorophenol- a rare example of introduction of fluorine into an inactivated arene by flu0ride.9~ OMe C-OMe II N-N,N-Dimethyl-2,4-bis(trifluoroacetyl)-l -naphthylamine undergoes ready nucleophilic replacement of the dimethylamino group to yield the corresponding naphthol naphthyl ether or thi~ether.~~ The complexities of the S,,l reaction of sulphanions with dihalogeno benzenes have been further explored.95 A simple ~reparation~~ of 4-[alkyl(aryl)sulphonyl]benzaldehydes involves the reaction of 4-halogenobenzaldehydes with sodium sulphonates.Copper( I) salts supported on alumina or charcoal can effect halide displacement on unactivated aryl halides; notable are the conversion of bromoarenes into iodoarenesy7 and the preparation of phenyl thiocyanates without contamination by isothi~cyanates.~~ The use of perfluoroarenes as protecting groups has been reviewed.99 Hexamethyldisilane acts as a a-donor towards photo-excited benzonitriles yielding radical anions which undergo trimethylsilylation ortho or para to the nitrile.’” Oxidized Benzenes.-For the oxidative coupling of phenols iron( 111) chloride is more effective in the solid state than in solution.’” The geometric isomers of 88 R. Bacaloglu C. A. Bunton and F. Ortega J. Am. Chem. Soc. 1989 111 1041. 89 M. R. Crampton A. B. Davis C.Greenhalgh and J. A. Stevens 1. Chem. Soc. Perkin Trans. 2,1989,675. 90 P. C. M. F. Castilho M. R. Crampton and J. Yarwood J. Chem. Res. (S) 1989 370. 91 M. Makosza and Z. Owczarczyk J. Org. Chem. 1989 54 5094. 92 N. Yazawa H. Suzuki Y. Yoshida 0. Furusawa and Y. Kimura Chem. Lett. 1989 2213. 93 W. R. Dolbier L. Celewicz and K. Ohnishi Tetrahedron Lett. 1989 30 4929. 94 M. Hojo R. Masuda E. Okada and H. Miya Synthesis 1989 870. 95 C. Amatore R. Beugelmans M. Bois-Choussy C. Combellas and A. Thiebault J. Org. Chem. 1989 54 5688. 96 A. Ulman and E. Urankar J. Org. Chem. 1989 54 4691. 97 J. H. Clark C. W. Jones C. V. A. Duke and J. M. Miller J. Chem. Res. (S) 1989 238. 98 J. H. Clark C. W. Jones C. V. A. Duke and J. M. Miller J. Chem. Soc.Chem. Commun. 1989 81. 99 M. Jarman J. Fluorine Chem. 1989 42 3. 100 S. Kyushin Y. Ehara Y. Nakadaira and M. Ohashi J. Chem. Soc. Chem. Commun. 1989 279. 101 F. Toda K. Tanaka and S. Iwata J. Org. Chem. 1989 54 3007. Aromatic Compounds 3,6-dimethoxy-3,6-dimethylcyclohexa- 1,4-diene formed by anodic oxidation of p-xylene in methanol have been separated,lo2 and anodic oxidation of 4-methoxy- anilides yields N-acylated quin~neimines.'~~ Complexing the carbonyl oxygen of quinone monoketals with the aluminium compound MAD encourages 1,4-addition of organometallics to the enone ~ystem,"~ and is a key step in an elegant ~ynthesis'~' of defucogilvocarcin M. The highly functionalized naphthalene (3 1 ) a potential synthon for non-linear polycyclic aromatics has been prepared'06 by Diels- Alder addition of bisketal (32) to diethyl acetylenedicarboxylate whilst regioselective cyclization of substituted butadienes onto 4-sulphonyliminoanthracene-l,9,10-triones provides a precursor of anthracyclinone~.'~~ An uncatalysed thermal [1,3]alkyl shift in the spiro vinyl ether (33) gives'08 the dienone (34) and dienone-phenol rearrangement of (35) proceeds by nitrogen migration rather than the more usual carbon shifts."' 4-Nitroacetophenone under- goes an extraordinary disproportionation to 4-aminobenzophenone and 4-nitroben- zoic acid.'".0 0 H (33) (34) (35) 5 Condensed Polycyclic Aromatic Compounds Structure and Reactivity.-Advances in theoretical and computational techniques have allowed ab initio spin-coupled calculations to be performed on naphthalene."' These show that the correlated v-type electrons in the molecule can be described 102 I.Barba F. Alonso and F. Florencio J. Org. Chem. 1989 54 4365. 103 J. S. Swenton B. R. Bonke C.-P. Chen and C.-T. Chou J. Org. Chem. 1989 54 51. 104 A. J. Stern J. J. Rhode and J. S. Swenton J. Org. Chem. 1989 54 4413. 105 D. J. Hart and G. H. Merriman Tetrahedron Lett. 1989 30,5093. 106 K. A. Parker and S. M. Ruder J. Am. Chem. Soc. 1989 111 5948. 107 F. Farina M. C. Paredes L. hebla and V. Stefani J. Chem. SOC.,Perkin Trans. 1 1989 1597. 108 S. Wang G. W. Morrow and J. S. Swenton J. Org. Chem. 1989 54 5364. 109 Y. Kikugawa T. Kitamura and M. Kawase J. Chem Soc. Chem.Commun. 1989 525. I10 P. Wan and X. Xu J. Org. Chem. 1989 54 4473. 111 M. Sironi D. L. Cooper J. Gerratt and M. Raimondi J. Chem. SOC.,Chem. Commun. 1989 675. I. G. C.Coutts in terms of ten distinct non-orthogonal orbitals with various modes of pairing up of electron spins. The three Kekulk-type structures dominate the wave function and the difference in energy between the full molecule and that of the double-benzenoid valence bond structure is 76 kJ mol-'. Ab initio calculations have been carried out on the heats of formation of hydrocarbons ranging from benzene to coronene.112 The automerization of [1-13C]- or [3-13C]phenanthrene catalysed by an AlC1,-NaCl mixture has been followed by NMR and occurs at 160-220 "C;this contrasts with temperatures above 1000 "C necessary for most polycyclic aromatics.' l3 An updated version of the Pariser-Parr-Pople approach to molecular orbital calculations termed DEWAR-PI has been used to calculate the relative energies of a-complexes for electrophilic substitution at each carbon of a large number of alternant and non- alternant polycyclics.In most cases the positions with lowest energies correspond with those found experimentally to undergo electrophilic attack;'14 further experi- mental data on the electrophilic substitution of fluoranthrene hydrocarbons have been p~b1ished.l'~ The reactivity in the gas phase of 1- and 2-naphthalenyl and 9-anthracenyl radicals towards toluene has been examined; relative rates of arylation and of proton abstraction from methyl may be in terms of reversibility of an initial addition step.Irradiation of 9,lO-dialkoxyoctamethylanthracenesgave 9,lO-Dewar isomers which are less stable than decamethyl-9,lO-Dewar anthracene."' Synthesis.-Reviews have been published on the synthesis of benzenoid polycyclics by titanium deoxygenation118 and by aryne arylation reactions."' A recent example of the latter is the synthesis of an aristolactam alkaloid.12' Eliminative photocycliz- ation of o-methoxystilbenes to phenanthrenes occurs with regioselectivity in H2S04-Bu'OH mixtures.I2l Niobium-catalysed coupling of alkynes with aryl 1,2-dialdehydes gives good yields of 1-naphthols with high regioselectivity.'22 The adduct from homophthalic anhydride and dienone (36) undergoes dyotropic rearrangement to (37) with aromatization as the driving force for intramolecular sigmatropic hydrogen transfer.'' Higher analogues of phenalenone may be obtained'24 by ring enlargement of o-pleiadienequinones with diazoalkane and related cycloocta[ delnaphthalenes mm \ 0 0 OH 0 0 112 J.M. Schulman R. C. Peck and R. L. Disch J. Am. Chem. SOC.,1989 111 5675. 113 A. T. Balaban M. D. Gheorghiu A. Schiketanz and A. Necula 1. Am. Chem. SOC.,1989 111 734. 114 M. J. S. Dewar and R. D. Dennington J. Am. Chem. SOC.,1989 111 3804. 115 M. Minabe B. P. Cho and R. G. Harvey J. Am. Chem. SOC.,1989 111,3809. I16 R. H. Chen S. A. Kafafi and S. E. Stein J. Am. Chem. SOC.,1989 111 1418. 117 M. A. Meador and H. Hart J. Org. Chem. 1989,54 2336.'18 H.N.C.Wong Acc. Chem. Res. 1989 22 145. E. R. Biehl and S. P. Khanapure Acc. Chem. Res. 1989 22 275. J. C. Estevez R. J. Estevez E. Guitan M. C.Villaverde and L. Castedo Tetrahedron Lett. 1989,30,5785. 121 F. B. Malory M. J. Rudolph and S. M. Oh 1. Org. Chem. 1989 54 4619. 122 J. B. Hartung and S. F. Pedersen J. Am. Chem. SOC.,111 5468. 123 A. P. Marchand P. Annapurna W. H. Watson and A. Nagl J. Chem. SOC.,Chem. Commun. 1989,281. 124 J. Ikuina K. Yoshida H. Tagata S. Kumakura and J. Tsunetsugu J. Chem. SOC.,Perkin Trans. 1 1989 1305. Aromatic Compounds 185 are formed by oxidative cleavage of cyclopent[ a]acenaphthylene~.'~~ In enedione (38) available'26 from 1,8-dimethylbiphenylene,the eight-membered ring is formally a cyclooctatetraene dication with two oxyanion substituents.Electron transfer would introduce destabilizing anti-aromatic character and might account for the sluggish reaction of (38) with dienes.12' Metallated cyclopropenone ketals are versatile synthons for various cyclopro- penones including the antibiotic penitricin.'28 Heating cyclohepta[ blfuran-2-one derivatives with vinyl ethers or esters has provided a route to more than forty a~ulenes;'~~ a related strategy was employed13' in the preparation of an azuleno- annulenone. Unstable 1 -hydroxyazulene and 3-hydroxyguaiazulene have been obtained by reduction of their acetyl esters. The 1-hydroxy compound exists only as the enol while the guaiazulene changes to a mixture of its keto form and a dimer.131 Addition of tropylium cation to C3 of an allenylsilane generates a vinyl cation which cyclizes to a dihydroazulene from which the related azulene can be obtained by oxidation with excess tr~pylium.'~~ The palladium-catalysed coupling of arylzinc chlorides with the triflate ester of 2-methoxy-5-hydroxytroponeyielded 5-aryltropones useful colchicine analogues.133 In a regiocontrolled synthesis of 12a,l2b-monosecocolchicine,anion (39) acted as a synthetic equivalent for the 7-methoxy-3-tropyl anion.'34 Although 3,6benzotropone is stable only in a glass at X 00 Li+ (39) 125 D. A. Jackson P. H. Lacy and D. C. C. Smith J. Chem. SOC.,Perkin Trans. I 215. 126 C. F. Wilcox K. R. Lassila G. VanDuyne H. Lu and J. Clardy J. Org. Chem. 1989 54 2190.127 C. F. Wilcox K. R.Lassila and C. E. Young J. Org. Chem. 1989 54 5035. I28 M. Isaka S. Matsuzawa S. Yarnago S. Ejhiri Y. Miyachi and E. Nakarnura J. Org. Chem. 1989 54 4727. I29 T. Nozoe P.-W. Yang C.-P. Wu T.4. Huang T.-H. Lee H. Okai H. Wakabayashi and S. Ishikawa Heterocycles 1989 29 1225. 130 S. Kuroda S. Maeda S. Hirooka M. Ogisu K. Yamazaki I. Shimao and M. Yasunarni Tetrahedron Lett. 1989 30,1557. 13' T. Asao S. Ito and N. Morita Tetrahedron Lett. 1989 30,6693. 132 D. A. Becker and R.L. Danheiser J. Am. Chem. SOC.,1989 111 389. 133 R. M. Keenan and L. I. Kruse Synth. Cornmun. 1989 19 793. 134 M. G. Banwell G. L. Gravatt J. S. Buckleton G. R.Clark and C. E. F. Rickard J. Chem. Soc. Chem. Cornmun. 1989 865. I.G. C. Coutts 77 K its carbonyl absorption at 1506 cm-' may indicate'35 some contribution from the l0T-electron structure (40).Treatment of 9-[ 1-(2,4,6-~ycloheptatriienyl)]-9-xanthydrol with acids produced 9-benzylidenexanthene rather than tropylium cation; calculations indicate'36 that the activation energy of the observed ring-contraction pathway is favoured by 130 kJ mol-'. 0- The theoretical prediction that puckered structures of cyclobutadiene dications should be more stable than planar ones is supported by agreement between observed and ab initio calculated chemical shifts.'37 The 'H NMR of (41) a hydrocarbon analogue of the squarate dianion consists of a singlet at 6 1.7 p.p.m. suggesting aromatic character; 13' NMR techniques have been applied to studies on methylated biphenylene dianion~'~~ and the dibenzo[a,c]cyclonatetraenyl anion.'40 Tricar- bonyl(cyc1oheptatriene)iron complexes have been prepared and the synthetic uses of their anions exp10red.l~' Spectroscopic and hydrogenation experiments have previously suggested that homoazulene has aromatic character; it has now been shown'42 to undergo Friedel- Crafts acylation under very mild conditions the reaction proceeding via the u-complex (42).Rearrangements of 8,8-dimethylbenzohomotropyliumions have been rep01ted.l~~In all-cis-1,4,7,10-cyclododecatetraenethe double bonds are all co- E 135 M. Ohkita T. Tsuji and S. Nishida J. Chem. SOC.,Chem. Commun. 1989 924. 136 I. T. Badejo R. Karaman and J. L. Fry J. Org. Chem.1989 54 4591. 137 M. Bremer and P. von R. Schleyer J. Am. Chem. SOC.,1989 111 1147. 13' W.T. Thorstad N. S. Mills D. Q. Buckelew and L. S. Groves J. Org. Chem. 54 773. 139 J. W. Bausch P. S. Gregory G. A. Olah G. K. S. Prackash P. von R. Schleyer and G. A. Segal J. Am. Chem. Soc. 1989 111 3633. 140 B. Eliasson M. H. Nouri-Sorkhabi L. Trogen I. Sethson U. Edlund A. Sygula and M. Rabonivitz J. Org. Chem. 1989 54 171. 141 M. Nitta M. Nishimura and H. Miyano. J. Chem Soc. Perkin Trans I 1989 1019. 142 L. T. Scott C. A. Sumpter M. Oda and I. Erden Tetrahedron Lett. 1989 30,305. 143 R. F. Childs M. Mahendran M. Sivapalan and P. Nguyen J. Chem. SOC.,Chem. Commun. 1989 27. Aromatic Compounds planar indicating that in this molecule there is an absence of homoaromatic des- tabilization.14 7 Cyclophanes The molecular structure and strain energy of [S]metacyclophane has been calculated using the ab initio STO-3G minimal basis set.Results are in rather better agreement with the X-ray structure than those obtained from previous molecular mechanics or MNDO determination^.'^^ The family of unsymmetrical cyclophanes has been extended by the synthesis of [2,2]orthometacyclophane (43),obtained as a 4:1 syn-anti mixture from the pyrolysis of a bis-~ulphone.'~~ Although the geometries of the meta-substituted ring of both forms of (43)are calculated to be practically identical 13C NMR shows strong deshielding for the C16 in the syn isomer only. (43) Sulphone pyrolyses have also yielded fluorinated [2.2]meta~yclophanes'~~ and methylated [2.2.2]metacyclophanes; 14' the latter adopt folded rather than stepped forms to minimize st.eric repulsion among internal methyl groups.A detailed study of the nitration of [2.2]metacyclophanes has been p~b1ished.l~~ A series of highly strained helical dihetero [2.2]cyclophanes (44)have been synthesized in good yields (for this type of molecule) and the effect of increasing the size of internal substituent R on CD and NMR spectra determined."' The influence on NMR spectra of forming tricarbonylchromium complexes of dithiacyclophanes has been di~cussed.'~~ An example has been discovered of a [2.2]metacyclophanedienewhich fails to undergo spontaneous valence isomerization to a dihydropyrene.' 52 An ingenious 'one pot' 144 A.Krause H. Musso W. Boland R. Ahlrichs R. Gleiter R. Boese and M. Bar Angew. Chem. Znt. Ed. Engl, 1989 28 1379. 145 L. W. Jenneskens J. N. Louwen and F. Bikelhaupt J. Chem. SOC.,Perkin Trans. 2 1989 1893. 146 G. Bodwell L. Emst. M. W. Haenel and H. Hopf Angew. Chem. Int. Ed. Engl. 1989 28 455. 147 M. Tashiro H. Fujimoto A. Tsuge S. Mataka and H. Kobayashi J. Org. Chem. 1989 2012. 148 M. Tashiro T. Watanabe A. Tsuge T. Sawada and S. Mataka J. Org. Chem. 1989 54 2632. 149 M. Tashiro S. Mataka Y. Takezaki M. Takeshita T. Arimura A. Tsuge and T. Yamato J. Org. Chem. 1989 54 451. 150 F. Vogtle A. Ostrowicki P. Knops P. Fischer H. Reuter and M. Jansen J. Chem. SOC.,Chem. Commun 1989 1757. 151 R. H.Mitchell T. K. Vinod G. J. Bodwell and G. W. Bushnell J. Org. Chem. 1989 54 5871. 152 Y.-H. Lai and P. Chen J. Org. Chem. 1989,54 4586. I. G. C.Coutts synthesis of layered systems in which the disc-shaped subunits are bridged 14-annulenes involves the reductive alkylation of dianion (45).lS3Unlike conventional phanes the units are linked by bridging groups within the .rr-system and up to five units have been incorporated in a stack. 2-8 Carcinogenic Aromatic Hydrocarbons The carcinogenicity of aromatic amines may be due in part to their conversion into electrophilic N-aryl- 0-acylhydroxylamines. It has now been that biphenyl- hydroxylamine (46)reacts with 2’-deoxyguanosine to give adducts (47) and from model experiment^'^^ the coupling is probably by an SN2 process.0 2’-deoxy-D:ribose (47) An efficient route to dimethylphenanthrenes involves reaction of naphthynes with furan to afford phenanthrene-1-4-endoxideswhich can be deoxygenated with trimethylsilyl iodide.lS6 Further syntheses have been reported of methylene-bridged benzopyrenes ’” polycyclic phenols 1583159 epoxides 16071 and epoxide diols 162,163 Although the last are commonly regarded as being the ultimate active metabolites in mutagenesis Cavalieri and co-workers have suggested that polycyclic radical cations should also be considered and now report’64 that one-electron oxidation of benzo[ alpyrenes yields intermediates which undergo nucleophilic attack at posi- tion 6;the ease of attack correlates with carcinogenicity.153 J. Alexander M. Ehrenfreund J. Fiedler W.Huber H.-J. Rider and K. Mullen Angew. Chem. Znt. Ed. Engl. 1989 28 1531. 154 M. Famulok F. Bosold and G. Boche Angew. Chem. Znt. Ed. Engl. 1989 28 337. M. Novak K. A. Martin and J. L. Heinrich J. Org. Chem. 1989 54 5430. 156 K.-Y. Jung and M. Koreeda J. Org. Chem. 1989 54 5667. 157 R. J. Young and R. G. Harvey Tetrahedron Lett. 1989 30,6603. 158 S. Kumar P. L. Kole and R. J. Sehgal J. Org. Chem. 1989 54 5272. 159 P. L. Kole S. K. Dubey and S. Kumar J. Org. Chem. 1989 54 845. 160 R. E. Lehr P. L. Kole M. Singh and K. D. Tschappal J. Org. Chem. 1989,54 850. 161 K.L. Platt H. Frank and F. Oesch J. Chem. Soc. Perkin Trans. 1 1989 2229. 162 D. R. Bushman S. J. Grossman D. M. Jerina and R.E. Lehr J. Org. Chem. 1989 54 3533. 163 J. Pataki P. Di Raddo and R. G. Harvey J. Org. Chem. 1989 54 840. 164 P. Cremonesi E. L. Cavalieri and E. G. Rogan J. Org. Chem. 1989 54 3561.

ISSN:0069-3030    

DOI:10.1039/OC9898600171

出版商:RSC    

年代:1989

数据来源: RSC

摘要:

8 Heterocyclic Compounds By D.E. AMES Department of Chemistry Queen Mary College London Mile End Road London El 4NS 1 Introduction The flow of publications on heterocyclic chemistry has continued to grow in 1989 so that this Report is by necessity highly selective emphasizing preparative work. Useful reviews dealing with heterocyclic sonochemistry' and with the hetero-Cope rearrangement2 have been published. Many reactions leading to phosphorus-containing heterocycles are covered in a review3 of phosphaalkynes and phos- phaal kenes. 2 Three-membered Rings A series of crystalline arenesulphonate derivatives of enantiomerically enriched glycidol have been ~repared.~ They react with nucleophiles with very high regioselec- tivity (Scheme 1). Vinyloxiranes have received much attention during the year and their SN2'addition reactions (Scheme 2) have been reviewed.' Addition of functionalized alkenes across ?H NCAOTS -io ?H 96% ii boTs Ph\j\/oTs Reagents Et,AlCN; ii PhMgBr Li2CuC1 Scheme 1 R4 R2 R3 R3 Scheme 2 ' Y.Goldberg R. Sturkovich and E. Lukevics Heterocycles 1989 29 597. 'S. Blechert Synthesis 1989 71. L. N. Markovski and V. D. Romanenko Tetrahedron 1989,45,6019. J. M. Klunder T. Onami and K. B. Sharpless J. Org.Chem. 1989,54 1295. J. A. Marshall Chem. Reu. 1989 89 1503. 189 190 D. E. Ames the epoxide unit by a radical process yields tetrahydrofurans (Scheme 3).6 Vinyl-oxiranes prepared from aldehydes and the lithium dienolate of ethyl 2-bromobut-2- enoate rearrange to dihydrofurans on thermolysis (Scheme 4).7 wAr a-AAr Me02aTAAr Me02C + -Reagents hv Ph2S2 AIBN CH2=CHC02Me Scheme 3 Br Reagents i furan-2-aldehyde; ii A Scheme 4 The preparation and reactions of dioxiranes' and of oxaziridines9 have been reviewed.A stereospecific synthesis of aziridines from diols via the cyclic sulphates has been reported (Scheme 5)." Aziridination of vinylsilanes (or vinylstannanes) with an N-acetoxyaminoquinazolone(1) followed by elimination of the trimethylsilyl and quinazolone groups gives azirines (2) (Scheme 6)." oso; NR3 iii R' TR22 R2 -LRZ R' R' 62-89% OH +NH2R3 LO Reagents i SOCl, A; ii RuCl, NaIO,; iii R3NH2 A; iv Bu"Li Scheme 5 Ph 86% N 91% N + Ph I Q QNHOAc (1) Reagents i CsF DM F; Q=3-Ethyl- 1-oxo-1,2-dihydroquinazolin-2-y1 Scheme 6 K.S. Feldman and T. E. Fisher Tetrahedron 1989 45 2969. ' T. Hudlicky A. Fleming and T. C. Lovelace Tetrahedron 1989 45 3021. * (a) W. Adam R. Curci and J. 0. Edwards Acc. Chem. Res. 1989 22 205; (b) R. W. Murray Chem Rev. 1989 89 1187. F. A. Davis and A. C. Sheppard Tetrahedron 1989,45 5703. B. B. Lohray Y. Gao and K. B. Sharpless Tetrahedron Lett. 1989 30,2623. R. S. Atkinson and B. J. Kelly J. Chem. Soc. Chem. Commun. 1989 836. Heterocyclic Compounds The first tricyclic diaziridines (3) have been prepared (Scheme7),12 but they undergo acid-catalysed rearrangement to form a bicyclic salt (4). 3,3-Dialkyl-2-diphenylphosphinoyloxaziridines by oxidation of are ~btained'~ N-diphenylphosphinoylimines with the anhydrous potassium fluoride-rn-chloroperbenzoic acid complex (Scheme 8).'H and I3C NMR spectroscopy shows that these undergo rapid inversion at N at room temperature. N-N (3) H (4) Reagents i NaOCI-NaOH-H20; ii CF,C02H Scheme 7 0 l\ R1 / / /C=N\ i_ /c-N \ R2 PPh2 R2 I1 FPh2 0 0 Reagents i anhydrous KF-MCPBA Scheme 8 Mesoionic bicyclic imine (5) is oxidized in the thiadiazole ring to give an unusual hetero-fused oxaziridine (6).14 Reaction of calcium-cyclooctatetraene complexes with a substituted di-chlorophosphine ( RPC12) produces the fused-ring phosphacyclopropane (7).15 Q P R l2 S. N. Denisenko E. Pasch and G. Kaupp Angew. Chern. Znt. Ed. EngL 1989 28 1381.l3 W. B. Jennings S. P. Watson and D. R. Boyd Tetrahedron Lett. 1989 30,235. l4 P. J. Dunn and C. W. Rees J. Chern SOC.,Perkin Trans.1 1989 2485. l5 D. S. Hutchings P. C. Junk W. C. Patalinghug C. L. Ralston and A. H. White J. Chem. SOC.,Chern. Cornmun.,1989 973. 192 D. E. Ames 3 Four-membered Rings The ester enolate-imine condensation route to P-lactams has been reviewed,I6 and development of this approach continues. The reaction of zinc enolates from amino- esters with silylated imines gives high yields of amino-substituted P-lactams (Scheme 9).17 Zinc and trimethylsilyl chloride have been used to condense 2-bromoesters with imines (Scheme lo)." -R IR2 R'R'N H Reagents i LDA; ii ZnC12; iii R3CH=NSiMe3; iv H20 Scheme 9 1 BrCHzCOzEt +PhCH=NPh -82% Reagents i Zn Me,SiCI Scheme 10 Glyoxal diimines react with lithium ester-enolates to form 4-(iminoalkyl)azetidin- 2-ones (8; X = NAr) and by acidic hydrolysis aldehydes (8; X = 0)(Scheme 1 l).19 P-Lactams have been prepared from P-aminothiol esters (9) without epimeriz- ation by heating with copper( I) trifluoromethanesulphonate and calcium carbonate in toluene (Scheme 12)." Benzoylation of thioformamides (10) gives S-H H I O-Li+ ArN /$/NAr + Me&< -Mesx 90% OMe 0 H Ar = 4-methoxyphenyl Scheme 11 A-! s H-NHCHzPh -85% H i NCHzPh SPh (9) Reagents i CF3SO;Cu+ CaCO, toluene A Scheme 12 l6 D.J. Hart and D.-C. Ha Chem. Rev. 1989 89 1447. l7 F. H. van der Steen H. Kleijn J.T. B. H. Jastnebski and G. van Koten Tetrahedron Lett. 1989,30,765. C. Palomo F. P. Cossio A. Arrieta J. Modriozola M. Oiarbide and J. M. Ontoria J. Org. Chem. 1989 54 5736. l9 B. Alcaide A. Gomez J. Plumet and J. Rodriguez-Lopez Tetrahedron 1989 45 2751. 20 N. Miyachi F. Kanda and M. Shibasaki J. Org. Chem. 1989 54 3511. Heterocyclic Compounds 193 benzoylthioimidates (1 1).These unstable intermediates have been converted directly into 4-benzoylthioazetidinones (12) (Scheme 13).2' 4,4-Dialkoxyazetidin-2-ones have been obtained by reaction of ketene acetals with isocyanates (Scheme 14).22 A new synthesis of p-lactams has been effected by stereoselective oxidative coupling of dianions of acyclic amide~.~~ For example amide (13) gave p-lactam in 58% yield 90% of which was isomer (14) (Scheme 15).XN H -SCOPh Reagents i PhCOCI Et,N; ii XCH,COCI (X = phthalimido-) Et3N Scheme 13 (OMe)2 Me + PhN=C=O -H2CXMe 90% 0P N P h Scheme 14 (PhCHJZN CO~BU' . .. H 1,Il + Ph Ph (13) (14) Reagents i Bu"Li TMEDA; ii N-iodosuccinimide Scheme 15 Turning to syntheses of fused-ring p-lactams a new route24 is based on a pal- ladium-catalysed carbonylation reaction of a bromoalkenylpiperidine salt (Scheme 16). [2 + 21 Cycloaddition of ketenes (formed in situ) to 1,3-benzoxazine and quinazoline derivatives forms a p-lactam system fused to the original hetero- cyclic ring,25 as illustrated by Scheme 17. Reagents CO Pd(OAc) PPh, Bu;N Scheme 16 21 M. P. Wentland P.E. Hansen S. R. Schow and S. J. Daum Tetrahedron Lett. 1989 30,6619. 22 M. L. Graziano and G. Cimminiello Synthesis 1989 54. 23 T. Kawabata K. Sumi and T. Hiyama J. Am. Chem. SOC. 1989 111 6842. 24 M. Mori Y. Higuchi K. Kagechika and M.Shibasaki Heterocycles 1989 29 853. 25 S. D. Sharma and V. Kaur Synthesis 1989 677. 194 D. E. Ames SMe Reagents i ArOCH,COCl Et3N; ii Raney Ni Scheme 17 l,l-Dioxo-7-substituted cephems have been prepared26 from the acid (15; R = H X = S) which is first protected as the t-butyl ester. This is oxidized with sodium tungstate and hydrogen peroxide to the sulphone (15; R = But X = SO2)and then converted into the diazo compound (16). A rhodium-catalysed reaction with methanol leads to the trans-7-methoxy compound (17) whereas reaction with triethylboron gives cis-and trans-7-ethyl derivatives (Scheme 18).0. .o COzR (15) Reagents i PrONO CF,CO,H; ii MeOH Rh2(02CC7H,&, Et,N Scheme 18 Displacement of the mesylate group of (18; R = S02Me) to prepare 3-functional- ized 3-norcephalosporins often involves isomerizations. These are avoided2' by using the trifluoroacetate (18; R = 02CCF3)so that 3-halogeno 3-pyrrolidino and other derivatives can be prepared efficiently. PhCHzCONH 0 Penicillin and cephalosporin esters (19 and 20 X = S) are conveniently oxidized to the corresponding sulphoxides (X = SO) by hydrogen peroxide formic acid and polyphosphoric acid.28 26 T. J. Blacklock J. W. Butcher P. Sohar T. R. Lamenec and E. J. J. Grabowski J.Org. Chern. 1989 54 3907. 27 V. Farina S. R. Baker and S. I. Hauck J. Org.Chern. 1989 54 4962. 28 M. Tanaka T. Konoike and M. Yoshioka Synthesis 1989 197. Heterocyclic Compounds R'CONH R'CONH C02R2 C02R2 (19) (20) Four-membered rings containing phosphorus have received particular attention during the year. Dihydrophosphetes have been obtained29 from diphenyltitanacy- clobutene as shown in Scheme 19. Earlier examples were metal complexes or P=O oxide derivatives. TiCp -ii Pfl-OEf - 66% 73% Ph Ph Ph Ph Ph Ph Reagents i RPCl,; ii EtOPCI Scheme 19 Phosphenium cations react with isocyanides to produce 1 -aza-3-phosphetine cations (Scheme 20).30 Condensation of iminophosphanes with a phosphaalkyne forms diphosphirene (21) which isomerizes to azadiphosphetine (22)31 (Scheme 21) and a novel thermal cyclotetramerization of the phosphaalkyne leads to yellow crystals of tetra-t-butyltetraphosphacubane(23).32 t Me2N NMe2 \/ P-c I I CF3SO; /c-N\ Bu'N But Scheme 20 R' NR2 \/ RIP-NR~ -It /Bu'C=P // BUT=P BUT P (21) But Reagent i R'P=NR2 (23) Scheme 21 29 K.M. Doxsee G. S. Chen and C. B. Knobler J. Am. Chem. SOC.,1989 111,9129. 30 C. Roques M. R. Mazieres J.-P. Majoral and M. Sanchez J. Org. Chem. 1989 54 5535. 31 E. Niecke and D. Barion Tetrahedron Lerr. 1989 30,459. 32 T. Wettling J. Schneider 0.Wagner C. G. Kreiter and M. Regitz Angew. Chem. Int. Ed Engl. 1989 28 1013. 196 D. E. Ames 4 Five-membered Rings An ingenious synthesis of 2-substituted 4-methylene tetra hydro fur an^^^ is based on a palladium-catalysed cycloaddition of an aldehyde to 2-(trimethylsilyloxy-methy1)allyl acetate (Scheme 22).In another palladium-catalysed (Scheme 23) an alkenyl alkynyl ether is cyclized to a 3,4-dialkenyltetrahydrofuran. MeSiO i.' AcO-Ph 1 Reagents i PhCH=CHCHO Pd(OAc), Me3SnOAc (Pr'O),P (=L) Scheme 22 Ph Reagents i (Ph,As),.Pd(OAc) complex Scheme 23 New syntheses of y-lactones have been reported. Reductive cyclization of allylic y-bromoacid esters gives 2,3-disubstituted butyrolactones (Scheme 24).35 Cobalt and ruthenium carbonyls together catalyse the regiospecific insertion of carbon monoxide into the least-substituted carbon-heteroatom bond of an oxetane or thietane to form butyrolactones or thiobutyrolactones (Scheme 25).36 In a general asymmetric syn- Ph Reagents i Bu,SnH AIBN A Scheme 24 Reagents i Co,(CO), Ru,(CO),, CO A Scheme 25 33 B.M.Trost S. A. King and T. Schmidt J. Am. Chem. SOC.,1989 111 5902. 34 B. M. Trost E. D. Edstrom and M. B. Carter-Petillo J. Org. Chem. 1989 54 4489. 35 J. L. Belletire and N. 0. Mahmoodi Tetrahedron Lett. 1989 30,4363. 36 M.-D. Wang S. Calet and H. Alper J. Org. Chem. 1989 54 21. Heterocyclic Compounds thesis of chiral butenolide~,~~ diastereocontrolled alkylation at the y-position of hydroxybutenolides is achieved using the tin enolate of a chiral thiazolidine deriva- tive (Scheme 26). R' R1&T* R' HOzC OH 0 T' Reagents i CH,=C(T*)OSnOSO,CF, T* = -N*' Scheme 26 Allenylsilanes react with acylium ions in a one-step [3 + 21 annulation process to form substituted furans (Scheme 27).38 In another annulation sequence39 indene was converted into the bromoindenyl propargyl ether (24) which was cyclized with cobaloxime-sodium borohydride to form the fused tetrahydrofuran system (25) (Scheme 28).H.. /SiMezBut Et SiMe2But _ Et 11 -Et/C=C=C \Me 71% 86% -PhCHzV M e PhCHz Reagents i AICI3 PhCH,COCI; ii HF C,H,N Scheme 27 (24) Reagents i NBS HCrCCH,OH; ii cobaloxime NaBH Scheme 28 Cyclization of silylated diynes with 2,6-dimethylphenyl isocyanide4' in the pres- ence of bis(cyclooctadiene)nickel(O) leads to iminocyclopentadienes with a fused heterocyclic ring (Scheme 29).TF-Ph 0 i, o*NAr 82% SiMe3 SiMe3 Reagents i ArNC Ni(cod), A Scheme 29 37 Y. Nagao W.-M. Dai M. Ochiai and M. Shiro J. Org. Chem. 1989 54 5211. 38 R. L. Danheiser E. J. Stoner H. Koyama D. S. Yamashita and C. A. Klade J. Am. Chem. Soc. 1989 111 4407. 39 K. Last and H. M. R. Hoffmann Synthesis 1989,901. 40 K. Tamao K. Kobayashi and Y. Ito J. Org. Chem. 1989 54 3517. 198 D. E. Ames New approaches to the synthesis of isobenzofurans include a general procedure based on reductive condensation of phthalide with a 1,l-dibromide. Under acidic conditions the resulting alkylidenephthalan (26) is in equilibrium with alkylisoben- zofuran (27) and can be trapped by reaction with dienophiles (Scheme 30).41Isoben-zofuran derivative (28) has been prepared from dialdehyde (29) and glyoxal via the dione (30) and reductive acetylation (Scheme 31)?2 Reagents i PhCHBr, Zn TiCI, TMEDA; ii MeO2CC=CCO2Me Scheme 30 0 + o%Ac ii OH I/OAc Ph OAc 0 (29) (30) (28) Reagents i (CHO),.NaHSO, C,H,N KCN H20;ii Zn Ac20 CSHsN Scheme 31 a Albidin (6-methoxy-3-methylisobenzofuran-4,5-dione) red pigment from Penicillium albidum Sopp has been synthesized from the vinyl ether (31)."3 A radical cyclization process using tributyltin hydride gives an 87% yield of cyclic ethers 70% of which is the five-membered ring product (32).Hydrolysis and then oxidation lead to the quinone albidin (33) (Scheme 32). OAc OAc OAc (32) ii,iii iv I 0 Reagents i Bu,SnH AIBN; ii OH- H20; iii H30+; iv DDQ Scheme 32 41 S.K. Meegalla and R. Rodrigo Synthesis 1989 942. 42 D. Passerieux M. Casteignan L. Lepage and Y. Lepage Bull. SOC.Chim. Fr. 1989 441. 43 S. Tennant and D. Wege J. Chem. SOC.,Perkin Trans. 1 1989 2089. Heterocyclic Compounds A palladium-catalysed carbonylation process4 gives 4-or 7-acetoxybenzofuran or the corresponding benzothiophenes (Scheme 33) in high yields. A one-pot prepar- ation of benzothiophenes is based on cyclization of an aryl zirconocene (34) with a silylated alkyne. The cyclic zirconium compound (35) is produced and this reacts with sulphur dichloride to form a benzothiophene (36) (Scheme 34).45 OAc Reagents i PdCl,(PPh,), AqO CO Et,N OAc Scheme 33 -.R2 R2 R’ R2 R3 R2 (34) (35) (36) Reagents i Cp2Zr (Me)Cl; ii Me,SiC=CR3; iii S2C12; iv Bu4N+ F- H,O;v HCI-H,O Scheme 34 Novel fused-ring thiophene systems have been reported; for example photocyliz- ation of terthiophenes (37; R = 2- or 3-thienyl) gives the tetracyclic product (38),46 and reductive dimerization of 3,4-dibromothieno [2,3-b]thiophene (39) forms 3,3’:4,4’-bis(thieno[2,3-b]thiophene)(40).47 This last fused heteroarene is a planar (37) Br )-/r I I Ny, I SR; (39) S (40) 44 M. Iwasaki J. Li Y. Kobayashi H. Matsuzaka Y. Ishii and M. Hidai Tetrahedron Lett. 1989 30,95. 45 S. L. Buchwald and Q. Fang J. Org. Chem. 1989 54 2793. 46 N. Jayasuriya J. Kagan J. E. Owens E. P. Kornak and D. M. Perrine J.Org. Chern. 1989,54 4203. 47 Y. Kono H. Miyamoto Y. Aso T. Otsubo F. Ogura T. Tanaka and M. Sawada Angew. Chem. Int. Ed. Engl. 1989 28 1222. 200 D. E. Ames centrosymmetric electron-donating component for the synthesis of organic metals. Condensation of quinoxaline with the lithium derivative of dimethyl sulphone gives cyclic sulphone (41) (Scheme 35).48 182% Reagents i Li[CH2S02Me] Scheme 35 3,4-Dimethylselenophene can be prepared efficiently by passing 2,3-dimethyl- butadiene and selenium vapour over sand in a glass tube at 450 0C.49 Diselenides (42; R = NH2or Me,) are oxidized and cyclized by hydrogen peroxide in acetonitrile to form 1,2-benzisoselenazol-3(2H) -one 1-oxide (43) and benzo[ b]selenophen-3(2H)-one 1-oxide (44).50 0 0 II II +aciHZ Se I1 0 2 Se/II 0 (43) (42) (44) (+)-(2S,5S)-Hexanediol obtained from the dione by reduction with yeast has been converted into (-)-(2&5R) -2,5-dimethylpyrrolidine (84%) by reaction of the dimesylate with benzylamine followed by catalytic debenzylation." (*)-2,3-Methanoproline a weak inhibitor of ethylene biosynthesis has been synthesized from an enaminone as summarized in Scheme 36.52 I I H COzCHzPh COZCHzPh Reagents i PhCH20COCI; ii CH2N2; iii hv; iv H,-Pd/C; v HCl-H20; vi AcO- resin Scheme 36 48 J.M. Vierfond L. Legendre J. Mahuteau and M. Miocque Heterocycles 1989 29 141. 49 G. Barbey G. Dian N. Merlet F. Outurquin add C. Paulmier Synthesis 1989 181. 50 K. Kloc J. Mlochowski and L. Syper Liebigs Ann.Chem. 1989 811. 51 R. P. Short R. M. Kennedy and S. Masamune J. Org. Chem. 1989 54 1755. 52 F. L. Switzer H. Van Halbeek E. M. Holt and C. H. Stammer Tetrahedron 1989 45 6091. Heterocyclic Compounds N-Triisopropylsilylpyrrolehas been converted successively into the 3-bromo and 3-lithio derivative^.^^ Reaction with electrophiles and removal of the N-protecting group then gave 3-substituted pyrroles conveniently. Oxidative alkoxycarbonylation of dipropargylamines generates 3,4-bis(alkoxycarbonylmethylene)pyrrolidines which are easily isomerized to pyrrolediacetic acid esters (Scheme 37).54 Zir- conocene-imine complexes react with alkyne and carbon monoxide in a new syn- thesis of trisubstituted pyrroles shown in Scheme 38.55 Another route to polyalkyl- pyrroles is based on the condensation of a ketone enolate to a nitroalkene to form a nitr~ketone.~~ Reductive cyclization of the acetic nitronic anhydride then gives the pyrrole derivative (Scheme 39).A regioselective synthesis of pyrroles (Scheme 40) by coupling a$-unsaturated imines with esters is promoted by a niobium chloride cata~yst.~' R'NLE IINZZZl:] rE Reagents i C02 air R'OH Pd/C KI; ii Et,N DMSO Scheme 37 Li R'CH2NSiMe3 + Me /CP2Zr\ [ Cp21,,,] R'CH2NSiMe3 -CH RICH -NSiMe3 Cp2Zr(THF) \/ c1 ... . N R' H Reagents i THF; ii R2C_CR3; iii CO; iv NH4Cl H,O Scheme 38 R3 R3 Reagents i LiNPr,; ii R3CH=CR4(N02); iii Ac,O; iv Zn/Cu NH,CI H20 EtOH Scheme 39 53 K.-P. Stefan W. Schuhmann H.Parlar and F. Korte Chem. Ber. 1989 122 169. 54 G. P. Chiusoli M. Costa and S. Reverberi Synthesis 1989 262. 55 S. L. Buchwald M. W. Wannamaker and B. T. Watson J. Am. Chem. SOC.,1989 111 776. 56 M. Miyashita B. Z. E. Awen and A. Yoshikoshi J. Chem. SOC.,Chem. Commun. 1989 841. 57 E. J. Roskamp P. S. Dragovich J. B. Hartung and S. F. Pedersen J. Org. Chem. 1989 54 4736. 202 D. E. Ames I I R' R' Reagents i R5C0,Et; ii NbCI,( DME) complex Scheme 40 Photo-oxygenation of tetraethylpyrromethenone (45) in methanol in the presence of dioxygen and a porphyrin photosensitizer gives the corresponding methanol- propentdyopent adduct (46) (72%).58 Methanolysis of diazasilacyclopentenes (47) produces 3-aminopyrroles (48) but with only small amounts of methanol a pyrrolo[3,2-b]pyrrole (49) is formed (Scheme 41).59 NHBu' u!ir 1 N NHBu' B ut (48) NHBu' But prN1 But (49) Scheme 41 Oxidation of 2-phenylindole with sodium tungstate-hydrogen peroxide yields 1-hydroxy-2-phenylindole(56%).60 1-Methoxyindole can be isolated by oxidizing indole similarly and methylating the unstable hydroxy compound with diazomethane.1-Methoxymethylindole-2-carboxylicacid can be lithiated at the 3-position using s-butyl lithium in the presence of hexamethylphosphoramide.613-Substitution prod- ucts are then obtained by reaction with electrophiles (Scheme 42). R.Bonnett S. Ioannu and F. J. Swanson 1. Chem. SOC.,Perkin Trans. I 1989 711. 59 H. tom Dieck U. Verfiurth K. Diblitz J. Ehlers and G.Fendesak Chem. Ber. 1989 122 129. 60 M. Somei and T. Kawasaki Heterocycles 1989 29 1251. Y.Yokoyama M. Uchida and Y. Murakami Heterocycles 1989 29 1661. Heterocyclic Compounds 203 ___* I MeOCH MeOCH2 OLi CH20Me Reagents i Bu”Li HMPA; ii electrophile (e.g. HCONMe2 X = CHO); iii H20; iv CH2N2 Scheme 42 Contrary to earlier conclusions electrochemical oxidation of 5,7-dihydroxytryp- tamine (50) at low pH gives a radical intermediate. The initial step is a le- 1H+ oxidation and the predominant form of the intermediate has an unpaired electron at C4 (51).62 Nucleophilic attack by water yields 4,5,7-trihydroxytryptamine(52) which is rapidly oxidized further to 5-hydroxytryptamine-4,7-dione (53) (Scheme 43). H 4,4’-dimers OH 0 (52) (53) Scheme 43 Indoloquinones have also been obtained by a route based on an internal trapping reaction of azomethine ylides generated from oxazolium salts.63 The sequence is summarized in Scheme 44.Benzo[f]indole-4,9-dioneshave been prepared by ther- mal condensation of 2-acetonyl-3-alkoxy- 1,4-naphthoquinones with primary amines (Scheme 45).64 Radical cyclization of allylic halogenoacetamides gives cis-fused 2-pyrrolidones and piper id one^,^^ triphenylgermanium hydride being preferable to tributyltin hydride (Scheme 46). In work on possible intermediates for the synthesis of Amaryl- lidaceae alkaloids,66 cerium (111) compound (54) was condensed with the cyclopen- 62 G. Dryhurst A. Anne M. Z. Wrona and D. Lemordant J. Am.Chem. SOC.,1989 111 719. 63 E. Vedejs and S. L. Dax Tetrahedron Lett. 1989 30,2627. 64 K. Maruyama A. Osuka K. Nakagawa T. Nabeshima and K. Tabuchi Synthesis 1989 628. 65 G. Stork and R. Mah Heterocycles 1989 28 723. 66 L. E. Overman and H. Wild Tetrahedron Lett. 1989 30,647. 204 D. E. Ames OSiMe,Bu' OSiMe2But OSiMezBut it J%fC"" 'N Reagents i Me,SiCN CsF; ii Bu~N+F-,H20; iii DDQ Scheme 44 0 0 Reagents i MeNH,; ii 2M-HCl Scheme 45 R ii iii ~ NCOCH2Br N aR aR CT;.. NCOCHzBr I H I H COCFS Reagents i (CF3C0)20 base; ii Ph3GeH AIBN; iii KF H20 Scheme 46 tanone (55) to form a single product (56). On heating with copper(I1) trifluoroacetate tandem aza-Cope and Mannich cyclization reactions gave hydroindolone (57; X = SiMe,Ph) and thence the 3-hydroxy compound (57; X = OH) (Scheme47).Isoindoles have been prepared by an ingenious sequence of cycloaddition re- arrangement and elimination reactions67 summarized in Scheme 48. Thermal reaction of triphenyl(viny1imino)phosphoranes (58) with tropones and oxidation of intermediate (59) provides a short route to 1-azaazulenes (60) (Scheme 49).68 Intramolecular Diels- Alder reaction of 3-( 3-indolyl)prop-2-enoates with olefinic substituents at the 1-position leads stereoselectively to fused indole compounds (Scheme 50).69 67 A. R. Katritzky M. H. Paluchowska and J. K. Gallor J. J. Heterocycf. Chem. 1989 26 421. 68 M. Nitta Y. Iino E. Hara and T. Kobayashi J. Chern. Soc, Perkin Trans. I 1989 51. 69 Y.Shimoji F. Saito S. Sako K. Tomita and Y. Morisawa Heterocycles 1989 29 1871. Heterocyclic Compounds4"+ao4 205 C12Ce NMe I SiMe2Ph CHzCN (54) (55) Reagents i Cu(OTf), A; ii HBF,-Et,O; iii H202 KF Scheme 47 mR3-H20%0 R2 I IRl \' HO A2 Rl Scheme 48 H (59) Scheme 49 206 D. E. Ames R'R2 = 2H(47%) (CH2),(87%) or (CH,),(20%) Scheme 50 An efficient synthesis of 1-ethoxyphosphindole oxide7' has been based on the nickel-catalysed reaction of ethyl 2-iodobenzoate with diethoxymethylphosphine (Scheme 51). 0' 'OEt Reagents i (EtO),PMe NiCI,; ii KOBu'; iii NaBH,; iv PBr,; v Et,N Scheme 51 Regioselective addition reactions of organometallic reagents with benzy-lideneimine (61) have been applied to the synthesis of pyrrolizidines.Use of a protected aldehyde group in the Grignard reagent gives (62) which on hydrolysis cyclizes to form the single isomer (63) of the hydroxypyrrolizidine (Scheme 52).71 Excellent stereoselectivity is also achieved in a synthesis of pyrrolizidin-2-ones by a radical cyclization process (Scheme 53).72 .OH 89% Ph Reagents i (1)-(CH2),MgBr; ii 1M-HCl EtOH; iii LiAIH Scheme 52 a An enantioselective synthesis of ~wainsonine,~~toxic fungal indolizidine alkaloid utilizes hydroxyester (64; X = OH) derived from 2,3- O-isopropylidene-~- erythrose. Conversion via tosylate to azide (64; X = N,) led to intramolecular 1,3-dipolar cycloaddition to give triazole (65). Loss of nitrogen forms ester (66; 70 A. Sedqui T.Lakhlifi B. Lande and-J. Amaudrut Bull. SOC.Chim. Belg. 1989 98 865. 71 D. H. Hua D. Bensoussan and A. A. Bravo J. Org. Chem. 1989 54 5399. 72 P. F. Keusenkothen and M. B. Smith Tetrahedron Lett. 1989 30 3369. 73 R. B. Bennett J.-R. Choi W. D. Montgomery and J. K. Cha J. Am. Chem. SOC.,1989 111 2580. Heterocyclic Compounds Reagents i Bu3SnH AIBN Scheme 53 R = Et) and thermal cyclization of the corresponding acid (66; R = H) gives lactam (67) which by hydration and removal of the protecting group is converted into trio1 (68) (Scheme 54). Reagents i NaN,; ii K,CO,-H,O; iii A; iv BH,; v H,O,-NaOH; vi 6M-HCl Scheme 54 Interesting sulphur heterocycles prepared from toluene-p-sulphonyl hydrazone (69) include the new welectron donor system (70) (Scheme 55).74 (70) Reagents i SOCl,; ii CS, A; iii P(OMe)3 A Scheme 55 C.Rovira N. Santa and J. Veciana Tetrahedron Lett. 1989 30,7249. 208 D. E. Ames An intramolecular aza-Wittig reaction has been applied to the synthesis of sub- stituted oxazoles (Scheme 56).75 \ N3 RZ R2 Reagents i LiNPrb; ii R3COCl; iii P(OEt), A Scheme 56 Regiospecific nucleophilic substitution reactions involving the attack of the N-atom of oximes on an epoxide have been used76 to generate nitrones; these are trapped in 1,3-dipolar cycloaddition reactions to form fused-ring isoxazolidines (Scheme 57). LiCl 60% -0 -t ,OH -N Scheme 57 Reissert compounds (71; X = 0 or S) have been prepared from the corresponding five-membered ring heterocycles (72) under non-aqueous conditions using trimethyl- silyl cyanide as the source of CN (Scheme 58).77 COR 1 Reagents i RCOCI Me3SiCN Scheme 58 Protection of pyrazole (73; R = H) as the 1-hydroxymethyl derivative (73; R = CH,OH) allows conversion into the dilithio derivative (74; X = Li) which reacts with electrophiles.For example benzaldehyde yields (74; X = CHPhOLi); treat- ment with acid then removes the metal and the protecting group to give the 5-substituted pyrazole (75).’* A review of pyrazole 1-oxides and 1,2-dioxides has been published.79 75 H. Takeuchi S. Yanagida T. Ozaki S. Hagiwara and S. Eguchi J. Org. Chem. 1989 54 431. 76 R. Grigg and J. Markandu Tetrahedron Lett. 1989 30,5489. 77 B. C. Uff Y.-P.Ho D. S. Brown I. Fisher F. D. Popp and J. Kant J. Chem. Res.(S) 1989 346. ” A. R.Katritzky P. Lue and K. Akutagawa Tetrahedron 1989 45 4253. 79 A. Kotali and P. G. Tsoungas Heterocycles 1989 29 1615. Heterocyclic Compounds 209 Cfi2% Art X = CHPhOLi b N' X N' I I R LiOCH2 (75) (73) (74) Propargyl azides undergo a base-catalysed prototropic rearrangement to short- lived allenyl azides. These rapidly cyclize to triazafulvenes which can be trapped by nucleophiles to form 1,2,3-triazoles (Scheme 59).80 H pNh 5 7% Me0-G nN3 2 [HycA~]-+ -*/ H H/ $ Nu N CH20Me CH20Me CH20Me Reagents i NaOMe; ii NuH (e.g. MeOH NH3) Scheme 59 7-Azaindolizine (76) shows lower propensity to undergo electrophilic substitution than indolizine (or other azaindolizines) and fails to undergo Vilsmeier formylation nitrosation or azo-coupling reactions." Chichibabin amination of (76) also fails but 8-halogeno and 8-methyl groups are reactive.5 Urothione (77) urinary metabolite of the molybdenum co-factor is a unique sulphur-containing pterin. Its structure has been confirmed82 by an unequivocal total synthesis of the (*)-mixture (10% overall yield in fourteen steps) (Scheme 60). It is based on thiophene annulation of chloronitrile (78) containing a protected amino group. After introduction of the methylthio group in (79) the carbonyl is converted into methoxy and the protecting group removed to give (80).Construction of the pyrimidine ring using guanidine and cleavage of the ether groups leads to the target molecule (77).In an efficient synthesis of benzoisothiazol-3-0nes~~ and benzoisoselenazol-3-ones benzanilide is dilithiated with n-butyl lithium. The salt (81) is treated with sulphur or selenium to introduce the element as in (82). Cyclization with copper(r1) bromide then gives the products (83) in good yields (X = S 44%; X = Se 63%). The selenium compound ebselen is used to treat cell damage caused by hydrogen peroxide etc. 8o K. Banert Chem. Ber. 1989 122 1963. 81 R. Buchan M. Fraser and P. V. Lin J. Org. Chem. 1989 54 1074. 82 E. C. Taylor and L. A. Reiter J. Am Chem. SOC.,1989 111 285. 83 L. Engman J. Org. Chem. 1989 54 2965. 210 D. E. Ames OMe CN / OMe + HSyOBui -x\s-(OMe12 [;I:?:: H NMe2 ii iii OBu' I (78) = X/CN \n.SMe OBu' 'OBu' (79) ix-xi. HN~I;& H ~~1:;fioMe H2N H2 N A N OBu' OH (80) (77) Reagents i EtNH2; ii LiBF, H20; iii NaOAc; iv Bu'ONO CuBr,; v NaSMe; vi NaBH,; vii HC(OMe), p-TsOH; viii MeOH p-TsOH; ix guanidine; x TFA; xi 3M-H2S04 Scheme 60 Di-t-butyldiazomethane and carbon diselenide react in hot toluene to form 2,2-di-t- butyl-5-(di-t-butylmethylene)-2,5-dihydro-l,3,4-selenadiazole (Scheme 61).84 31% I I CSe2 + Bu:C=N2 -Bu:C\ N=N /C=CBu Se Scheme 61 5 Six-membered Rings Cycloaddition reactions of heteroaromatic six-membered rings have been reviewed.85 Trimethylsilyl enol ethers of aldehydes and ketones react with carbon suboxide to form substituted 4-(trimethylsilyloxy)-2H-pyran-2-oneswhich are hydrolysed to give 4-hydroxy-2H-pyran-2-ones (Scheme 62).86 84 R.H. Berg N. Harrit E. Larsen and A. Holm Acta Chem. Scand. 1989,43 885. 85 A. R. Katritzky and N. Dennis Chem. Rev. 1989,89 827. 86 L. Bonsignore S. Cabiddu G. Loy and D. Secci Heterocycles 1989 29 913. Heterocyclic Compounds 21 1 OSiMe OH ii+ R2 0 Reagents i O=C=C=C=O; ii H,O Scheme 62 Problems arising in the synthesis of 4-chromanones by condensation of 2-hydroxyacetophenones with formaldehyde can be avoided by isolation of Mannich base hydrochloride (84) and cyclization by titration with potassium hydroxide (Scheme 63).87 Chromanochromanone (85) related to rotenone has been synthesized (Scheme 64).88 0 0 c1-(84) Reagents i HCHO-Me2NH; ii KOH Scheme 63 v vi I H (85) Reagents i Bu"Li HMPA; ii ZMeOC,H,COCl; iii Raney Ni; iv 12 EtOH; v BCI,; vi KOAc EtOH Scheme 64 Formation of a chromium complex of benzodioxin allows metallation and thence alkylation and functionalization at the 5-position (Scheme 65) whereas the uncom- plexed molecule reacts at C2.89 87 B.Cox and R. D. Waigh Synthesis 1989 709. S. M. F. Lai J. J. A. Orchison and D. A. Whiting Tetrahedron 1989 45 5895. 89 T. V. Lee A. J. Leigh and C. B. Chapleo Tetrahedron Lett. 1989 30,5519. 212 D. E. Ames Li PhCH2 Reagents i Bu"Li; ii PhCH,Br; iii I Scheme 65 OH OH I I Ph2v 2Phyo\l PhCH-0-0-CHPh + 0 40y0 0,0,CPh2 Reagents i WO,; ii CIS03H Scheme 66 172,4-Trioxanes can be obtained by treating peroxides and epoxides with tung- sten(v1) oxide and then with acid (Scheme 66).90 Conformational analysis of six-membered sulphur-containing saturated heterocycles has been reviewed." Optically active thiadecalins and thiahydrindans have been prepared by a proline-catalysed intramolecular Michael reaction (Scheme 67).92 Chiral 2,6-dithiabicyclo[3.1 .l]heptane (86) the dithia-analogue of 0 H Reagent i L-proline Scheme 67 the parent ring of the thromboxane A2nucleus has been ~ynthesized.~~ (-)-Menthy1 mercaptoester (87) adds to thiapyrone (88) to form thioether (89) and reduction then gives alcohol (90) as the major isomer (2 1 ratio).Chromatographic separation of the isomers and cyclization via the mesylate affords the (+)-enantiomer of bicyclic product (86) (Scheme 68).Selenoxanthen-9-ones are obtained by coupling benzyne intermediates with selenium-lithiated selenosalicylamides (Scheme 2-Dialkylaminopyridines can be prepared from aminonitriles and acetylene by a cobalt-catalysed process (Scheme 70) ?5 5-Alkyl-2-(p-toluenesulphony1)pyridines T.Fujisaka M. Miura M. Nojima and S. Knsabayashi 1 Chem. Soc. Perkin Trans. 1 1989 1031. 91 E. Juaristi Acc. Chem. Res. 1989 22 357. 92 A. P.Kozikowski and B. B. Mugrage J. Org. Chem. 1989 54 2274. 93 K. Steliou and G. Milot J. Org. Chem. 1989 54 5821. " M. Watanabe M. Date M.Tsukazaki and S. Furukawa Chem. Pharm. Bull. 1989 37 36. 95 A. P. Ivanov D. Z. Levin E. S. Mortikov and V. K. Promonenkov J.Org. Chem. USSR 1989,25,629 (Engl. Transl. p. 566). 213 Heterocyclic Compounds b0LSH+b S + Q-iii iv A (90) Reagents i PriNEt2; ii LS-Selectride; iii MsC1 Et,N; iv (Me3Si),NLi Scheme 68 Reagents i lithium N-isopropylcyclohexylamide;ii PhBr Scheme 69 R' I __+ NC-C-NR3R4 i QE1,R3R4 I R2 I R2 Reagents i HC-CH CoCp, A Scheme 70 +[ ]-"Q RQ SO,Ar R4+ ArSo2CN EtO S02Ar OEt Scheme 71 are formed by [4 + 21 cycloaddition of tosyl cyanide to 2-alkyl-l-ethoxybuta-1,3-dienes followed by aromatization of a dihydropyridine (Scheme 71).96 Efficient deoxygenation of heteroaromatic N-oxides can be achieved at room temperature using ammonium formate as hydrogen transfer agent and a palladium catalyst in methanol.97 96 U.Ruffer and E. Breitmaier Synthesis 1989 623. 97 R Balicki Synthesis 1989 645. 214 D. E. Ames Diastereoselective aza-Diels-Alder reaction using tetra-0-pivaloylgalac-topyranosylamine (91) as a chiral template allows the synthesis of enantiomerically pure 2-substituted piperidines e.g. tobacco alkaloid (S)-anabasin (Scheme 72).98 F& RO X-N+?c! XCs RO NH2 / RO H \ (91) = XNH,(R = Bu'CO) N ii-iv 192% Reagents i MeOCH=CHC(OSiMe,)=CH, ZnCl,; ii Selectride; iii (HSCH2)2 BF,-EtzO; iv Raney Ni; v HCI MeOH Scheme 72 Pyrimidines carrying an w-alkynyl side chain at the 2-position undergo intramolecular inverse electron demand Diels- Alder reactions across the C2 and C5 positions. Loss of hydrogen cyanide by a retro-Diels-Alder reaction then leads to annulated pyridines (Scheme 73).99 Scheme 73 The first total synthesis of the alkaloid (*)-meloscine has been accomplished by a highly stereocontrolled sequence."' This shows the value of tandem cationic aza-Cope rearrangement and Mannich cyclization reactions [(92) 4(93)] and is summarized in Scheme 74.A convenient route to chiral indolizidines is based on 1,4-addition-ring closure reactions of chiral a-sulphinyl ketimine anions with unsaturated esters (Scheme 79.''' 98 W.Pfrengle and H. Kunz J. Org. Chem. 1989,54 4261. 99 A. E. Frissen A. T. M. Marcelis G. Geurtsen D. A. de Bie and H. C. van der Plas Tetrahedron 1989 45 5151. 100 L. E. Overman G. M. Robertson and A. J. Robichaud J.Org. Chem. 1989 54 1236. 101 D. H. Hua S. N. Bharathi F. Takusagawa A. Tsujimoto J. A. K. Panangadan M.-H. Hung A. A. Bravo and A. M. Erpelding J. Org. Chem. 1989 54 5659. Heterocyclic Compounds 76% “’?OR R = CH,Ph Y = NHCOBU‘ i ii I78% ON,CO \ H (93) (92) Reagents; i Ph,P=CH2; ii KOH EtOH H20 Scheme 74 V c- 85% Reagents i Bu”Li; ii CH,=CHCO,Et; iii NaCN-BH, HOAc CF,C02H; iv Raney Ni; v LiAIH4 Scheme 75 Iminophosphorane (94) reacts with isocyanates to give 2-alkylamino-3-nitro-9- phenyl-9H-pyrido[ 2,3-b]indoles (95).’02 Annulation of the pyridine ring onto indole occurs by a tandem aza-Wittig-electrocyclization strategy (Scheme 76). Rhodium(11) acetate catalyses the decomposition of vinyl diazomethanes in the presence of N-alkoxycarbonylpyrrolesto provide a direct route to the skeleton of the tropane alkaloids (Scheme 77).’03 (3 S,4S) -3 -Carboxy-4-hydroxy-2,3,4,5-tetrahydropyridazine (96) is an unusual amino acid constituent of the anti-tumour agent Luzopeptin A.An enantiospecific synthesis (Scheme 78) of (96) has been reported. lo4 102 P. Molina and P. M. Fresneda Synthesis 1989 878. 103 H. M. L. Davies W. B. Young and H. D. Smith Tetrahedron Lett. 1989 30,4653. 104 P. Hughes and J. Clardy J. Org. Chem. 1989 54 3260. 216 D. E. Ames I Ph Ph 1 (94) 80% Q&-JQNO' NHEt I Ph Reagents i EtNCO A (95) Scheme 76 NC02Me ll C02Me COzEt COZEt Scheme 77 .. ... II 111 I K'O Me02C I NHNHp (96) Reagents i Bu'OOH Ti(OPr'), L(+)-diethyl tartrate; ii RuO,; iii CH2N2; iv K2C03 MeOH H,O; v NH2NH2.H20; vi CF3C02H H20 Scheme 78 Phthalazine forms a Reissert compound (97) on treatment with trimethylsilyl cyanide benzoyl chloride and aluminium ~hloride."~ The anion from (97) con-denses with aldehydes to give a 1-substituted phthalazine (98) (Scheme 79).Lithiation of phenoxazine (99) with butyllithium occurs regiospecifically adjacent to the oxygen atom i.e. at the 4-and/or 6-positions. This has been applied to the syntheses of 4-mOnO- and 4,6-disubstituted phenoxazines; the N-protecting group can be removed by catalytic reduction.'06 B. C. Uff,Y.-P. Ho F. Hussain and M.S. Haji J. Chem. Res.(S) 1989 24. Y. Antonio P. Barrera 0.Contreras F. Franco E. Galeazzi J. Garcia R. Greenhouse A. Guzman E. Velarde and J. hl. Muchowski J. Org. Chem. 1989 54 2159. Heterocyclic Compounds H' CN A~CHOH (97) (98) Reagents; i NaH; ii ArCHO; iii KOH H,O EtOH Scheme 79 I MeCHPh (99) 2-Substituted pyrido[3,2-e]- 1,3 -thiazin-4(4H)-ones ( 100) have been prepared from the sodium derivative of 2-chloronicotinamide (101) and thioester~.'~' Diazoalkanes react as ylides with tetrasulphur tetranitride to give red crystalline trithiadiazines ( 102).'08 0 flcoNHz NaH; RCS(0Et); H,O 63% N C1 - + 38% SXS S4N4 H Ph The tellurium heterocycle (103) has been prepared from ylide (104) and elemental tellurium. Tellurobenzaldehyde is formed and is trapped with dimethylbutadiene to obtain ( 103).'09 Te Ph3PCHPh L_ [Te=CHPh] n '(104) Ph (103) 107 A.Couture P. Grandclaudon and E. Huguerre Tetrahedron 1989 45 4153. 108 R. M. Bannister and C. W. Rees J. Chem. SOC.,Perkin Trans. 1 1989 2503. 109 G. Erker and R. Hock Angew. Chem. Znt. Ed. Engf. 1989 28 179. 218 D. E. Ames Diels- Alder reactions of cr-pyrones with phosphaalkynes yields phosphinines (Scheme 80). The process has been applied to the preparation of 2-hydroxyphos-phabenzene ( 105).110 This is a genuine heterocyclic phenol which undergoes 0-methylation not P-methylation. Me3Si0 Me3Si0 But HO But Reagents i Bu'CEP; ii H+,MeOH Scheme 80 6 Seven-membered Rings Oxepanes have been prepared by new routes. First by a rhodium( 11)-carbenoid- mediated cyclization (Scheme 81)"' and second by an acid-catalysed ring opening of hydroxyepoxides (Scheme 82).lt2In the case of (106) oxepane (107) constitutes 82% of the mixed products.Benzoxepine-3,5(2H,4H)-diones(108) have been pre- pared (Scheme 83) by a Claisen conden~ation."~ Me Scheme 81 HO H (106) (107) Reagents i camphorsulphonic acid Scheme 82 0 L "VC Et NaOEt R2 OAMe Me R3 R3 (108) Scheme 83 'lo G. Mark1 and A. Kallmunzer Tetrahedron Lett. 1989 30,5245. 111 M. J. Davies J. C. Heslin and C. J. Moody J. Chem. SOC.,Perkin Trans. 1 1989 2473. 112 K. C. Nicolau C. V. C. Prasad P. K. Somers and C.-K. Hwang J. Am. Chem. SOC.,1989 111 5335. 113 G. Gabriel R. Pickles and J.H. P. Tyman 1. Chem. Res. (S) 1989 348. Heterocyclic Compounds Flash vacuum pyrolysis of the Meldrum's acid derivative (109) at 500 "C gives good yields of lH-azepin-3(2H)-one (1 10). X-Ray studies show that the dienaminone conjugated system is approximately planar although the ring as a whole is markedly n~n-planar.''~ A synthesis of fused-ring azepine-2,Sdione (1 11) is based on a photochemical [2a + 2~1 ring expansion of a substituted N-pentenylphthalimide (1 l2).Il5 N NMe2 Me 0 Two separate Michael additions of methyl propynoate occur at the methyl group and nitrogen atom of 2-methylbenzothiazole to form a mixture of azepine derivatives (113; R = H and CH=CHCO2Me).ll6 The annual herb Isotropis forrestii poisons sheep in Australia.The nephrotoxic compound (+)-iforresthe has been isolated and shown117 by X-ray studies to be the fused-ring 1,4-diazepinedione (114). 54 MeOzC Co2Me 114 A. J. Blake H. McNab and L. C. Monahan J. Chem. SOC.,Perkin Trans. 1 1989 425. 115 M. A. Weidner-Wells A. Decamp and P. H. Mazzochi J. Org. Chem. 1989 54 5746. 116 R. M. Letcher K.-K. Cheung and D. W. M. Sin 1. Chern. Res. (S) 1989 115. 117 S. M. Colegate P. R. Dorling C. R. Huxtable T. J. Shaw B. W. Skelton P. Vogel and A. H. White Aust. J. Chem. 1989 42 1249. 220 D. E. Ames 5-( Chloromethy1)tetrazole reacts with hexamine in aqueous ethanol to give the methanoditetrazolo[ 1,3,6,8]tetrazecine (1 15) in which two seven-membered rings have an NCH2N unit in common."8 Photochemical oxidation of the pyrazine (1 16) produces endoperoxide (117) which is converted into the 1,3,6-oxadiazepine (1 18) by triphenylphosphine (Scheme 84).l19 Reagents i 02,hv Methylene Blue; ii PPh Scheme 84 Cyclization of the substituted nicotinoyl chloride (119) (Scheme 85) forms a pyrido[3,2-f]-1,4-oxazepinone(120; X = 0;Y = C1) which reacts with dimethyl- amine to give the base (120; X = 0 Y = NMe2).12' Analogues (120; X = S and CHJ were also prepared.An intramolecular Pictet-Spengler reaction of the N-hydroxytryptamine deriva- tive (121) gave the oxathiazepine system (122).121 D. Moderhack K.-H. Goos and L. Preu Liebigs Ann. Chem. 1989 689. 119 I. M. Dawson A. J. Pappin C. J. Peck and P. G. Sammes J. Chem. Soc. Perkin Trans.1 1989 453. 120 A. D. Cale T. W. Gero K. R. Walker Y.S.Lo W. J. Welstead L. W. Jaques A. F. Johnson C. A. Leonard J. C. Nolan and D. N. Johnson J. Med. Chem. 1989,32 2178. P. H. H. Hermkens J. H. van Maarseveen C. G. Kruse and H. W. Scheeren Tetrahedron Lett. 1989 30,5009. Heterocyclic Compounds 7 Larger Rings With research in the field expanding rapidly the publication of an updated volume ‘Crown Ethers and Analogs’ is welcome.’22 Macrocyclic lactones have been obtained’23 by cyclization of (a-carboxyalky1)sul- phonium salts (123) (Scheme 86). The formation of mono- and dilactones is solvent- dependent e.g. (123; n = 10) gives mainly dilactone (124) in acetonitrile but predominantly monolactone (125) in acetone. Scheme 86 Hydrolysis of racemic medium-ring lactones with horse or pig liver esterase gives the lactone with excellent enantiomeric excess and provides a general procedure for obtaining optically pure medium-ring lac tone^.'^^ The 18-membered ring lichen macrolide (+)-aspicilin (126) has been built up in fifteen steps (13% overall yield)’25 from D-mannose which provides the stereogenic centres at C4 C5 and C6.The stereogenic centre at C17 is derived from (S)-ethyl lactate. The final steps of the synthesis are summarized in Scheme 87 which shows the cyclization step and the removal of protecting groups. m-: )Me . ... 1-111 -51% H‘ Me 0 (126) Reagents i Et3N 2,4,6-trichlorobenzoyl chloride; ii pyrrolidinopyridine; iii CF3C02H MeOH Scheme 87 New methodology for the synthesis of macrolactones has been applied to the preparation of the dihydroxybislactone colletodiol ( 127).’26 The route is summarized in Scheme 88.A silver ion-induced cyclization of hydroxydithioketals (128) gives oxacene (129; X = SEt); oxidative removal of the thioether group with peracid followed by I22 E. Weber J. Toner I. Goldberg F. Vogtle D. A Laidler J. F. Stoddart R. A. Bartsch and C. L. Liotta ‘Crown Ethers and Analogs’ John Wiley New York 1989. 123 H. Matsuyama T. Nakamura and N. Kamigata J. Org. Chem. 1989 54 5218. 124 E. Fouque and G. Rousseau Synthesis 1989 661. 125 G. Quinkert E. Fernholz P. Eckes D. Neumann and G. Durner Helu. Chim. Acta 1989 72 1753. 126 G. E. Keck E. P. Baden and M.R. Wiley J. Org.Chem. 1989 54 896. 222 D. E. Ames OCH2SMe Ox O u * . M e 1+ HO “ ‘0 S d . . Me (127) Reagents i AgNO H20 2,6-lutidine ii dicyclohexylcarbodiimide;iii H+ resin H20 MeOH Scheme 88 .. I-1v + & Me (128). (129) Reagents i N-chlorosuccinimide; ii AgNO,; iii MCPBA; iv Et,SiH BF,*Et,O Scheme 89 triethylsilane then provided the product (129; X = H) in 88% overall yield (Scheme 89).’27 Two interesting routes to oxathiocine derivatives have been reported. First an intramolecular ene reaction of an unsaturated thioketone (130) gives ( 131).12’ Second in a rhodium( 11)-catalysed process tetrachlorothiophene and diazoketone (132) form the stabilized thiophenium S,C-ylide (133) which on warming rearranges to the 1,4-0xathiocine (134) (Scheme Ph Ph 127 K.C. Nicolau C. V. C. Prasad C.-K. Hwang M. E. Duggan and C. A. Veale J. Am. Chem. SOC.,1989 111 5321. 128 S. Motoki T. Watanabe and T. Saito Tetrahedron Lett. 1989 30,189. 129 0. Meth-Cohn E. Vuorinen and T. A. Modro J. Org. Chem. 1989 54,4822. 223 Heterocyclic Compounds c1 c1 67% Me 0 c1 (132) (133) (134) Reagents i Rh2(OAc), tetrachlorothiophene; ii A Scheme 90 Cycloaddition of nitrone (135) to methylenecyclobutane formed isoxazolidine (136) which on flash vacuum photolysis at 500 "C,rearranges to seven and nine- membered ring products (137; 42%) and (138; 12%) respectively (Scheme 91).130 A photochemical 1,2-addition of nitrile group to phenol provides a new route to azocinones (Scheme 92).13' N 70% a H Ph 0 Ph/ '0-Ph (135) (136) (137) Reagents i methylenecyclobutane Scheme 91 I-- Scheme 92 Oxidation of N-acylenamides of dihydrobenzazepines e.g.(139) with lead tetraacetate effects ring expansion and leads conveniently to N-acyltetrahydroben- zazocines (140).'32 76% -Me0 Pb(OAc) " T N COMe Meoq, Me0 CHI 0 I3O F. M. Cordero A. Goti F. De Sarlo A. Guama and A. Brandi Tetrahedron 1989 45 5917. 131 N. Al-Jalal J. Chem. Res. (S) 1989 110. 132 R. A. Lessor P. W. Rafalko and G. R. Lenz J. Chem. SOC.,Perkin Trans. 1 1989 1931. 224 D. E. Ames The use of methyl azidoformate in a nitrene insertion reaction with the methylene- bridged cyclopentadecaene (141) forms ester (142; R = C0,Me).Removal of the methoxycarbonyl group gives 4,9-methano-1 H-aza[ 1llannulene (142; R = H) a 12~-homologueof pyrr01e.l~~ X-Ray evidence shows that the double bonds are localized. 3,7-Diphenyl-1,5-dithia-2,4,6,8-tetrazocine ( 143) has been prepared by two routes. In the fir~t,”~ action of lithium bis( trimethylsily1)amide on benzonitrile gives amidine salt (144) which reacts with sulphur dichloride to form the heterocycle (143). In the second the product is obtained by reaction of benzamidine with bis(phtha1imido)sulphide and bis( ptoluenesulphony1)sulphurdiimide (Scheme 93). Heterocycle (143) is planar but one dimethylamino substituent group is enough to destroy the planarity of the ring.’35 (144) (143) Reagents i S2C12;ii benzarnidine; iii Ts=N=S=NTs Scheme 93 Nine-membered diazonine ring products are formed by oxidation of tetrahydro-P-carboline derivatives (145) with sodium ~eri0date.I~~ The indole ring is cleaved at the 2,3-bond but mono- or dicarbonyl compounds may be produced according to the substituents in the starting material (Scheme 94).C02Me C02Me NalO -R = H;42% -I .I %NH NalO R =Me; 62% HRR Scheme 94 133 W. Lange W. Haas H. Schickler and E. Vogel Heterocycles 1989,28 633. 134 U.Scholz H. W. Roesky J. Schimkowiak and M. Noltemeyer Chem. Ber. 1989,122 1067. 135 M.Amin and C. W. Rees J. Chem. SOC.,Chem. Comrnun. 1989 1137. 136 F.Gatta and D. Misiti J. Heterocycl. Chem. 1989,26 537. Heterocyclic Compounds 225 A one-step ring enlargement reaction with isocyanates has been used to convert P-ketoester or P-ketonitrile systems into macrocyclic imides (Scheme 95) the C-N atoms of the cyanate group being inserted into the ring.I3’ Ar - ArNCO ‘0” Scheme 95 Tetraaza[ 14lannulenes (146) have been prepared by reaction of enamine salt (147) with o-phenylenediamine.13’ Condensation of 1-ethyl-3,4-diformyl-2,5-dimethylpyrrole (148; R = Et) with 1,2-diaminoethane gives the dipyr-rolotetraazacyclohexadecine (149; R = Et; 69%). When pyrrole (148; R = H) is used the product (80%) exists predominantly as (150) a 2-azafulvene 2c10; (147) R “‘fiMe (“ ”) N OHC N Mel$:R MegMe R (148) (149) 137 V. I. Ognyanov and M. Hesse Helv. Chim.Acta 1989 72 1522.138 F. Adams R. Gompper and E. Kujath Angew. Chem. Int. Ed. Engl. 1989 28 1060. 139 S. A. N. Taheri R. 4. Jones S. S. Badesha and M. M. Hania Tetrahedron 1989 45 7717. 226 D. E. Ames The effect of 0-substituents on the synthesis of tetraphenylporphyrins has been in~estigated.'~' Improved yields of 2-alkyl- 2-alkoxy- and 2.6-dialkoxyphenyl com- pounds were obtained using boron trifluoride-ethanol co-catalysis but halogeno- substituted compounds failed to react. Photochemical cyclization of an 18r-electron open-chain precursor has been achieved141 as the key step in syntheses of two 20-methyl isobacteriochlorins and two-20-cyano-compounds (Scheme 96). H AMe = CH2C02Me PMe= CH2CH2C02Me Reagents i MeOH HC(OMe)3 CF3C02H hv H Scheme 96 140 J.S. Lindsey and R. W. Wagner J. Org. Chem 1989 54 828. 141 D. M. Amott P. J. Harrison G. B. Henderson Z.-C. Sheng F. J. Leeper and A. R. Battersby J. Chem. SOC. Perkin Trans. 1 1989 265.

ISSN:0069-3030    

DOI:10.1039/OC9898600189

出版商:RSC    

年代:1989

数据来源: RSC

摘要:

9 Organometallic Chemistry Part (i) The Transition Elements By G. R. STEPHENSON School of Chemical Sciences University of East Anglia Norwich NR4 7TJ 1 Introduction In 1989 as has been increasingly the case in previous years development of the organic chemistry of the transition metals has focused on explorations of the applications of transition metals in organic synthesis. This survey is of necessity a highly selective sampling of a topic that has now become a major field. The aim of this Report is to provide a guide only to new uses of existing methods and to emerging new reactions which contribute unusual bond-forming processes to the canon of organic synthesis. Major developments in supra-molecular chemistry and electron transfer chemistry for example which reflect the thinking more of the coordination and organometallic chemistry disciplines than organic chemistry have been omitted.2 General Synthetic Reactions Epoxidatiom-Transition metals continue to be used to great effect in many conven- tional organic reactions. There is perhaps no better example of this than the impact of asymmetric epoxidation methods on the design of organic syntheses in the 1980s. In 1989 the development of this area has continued though increasingly attention is now given to performance of epoxidation reactions in situations where functional- ity is present to promote a subsequent step. A typical example uses the original Sharpless vanadium method to control the relay of chirality in a synthesis that seeks to create a bis-epoxide unit (Scheme 1).Epoxidation however takes place between these two positions to form (l) which rearranges upon placement of a leaving group at one end of the epoxy-diol.' Other uses of epoxide products in subsequent cyclizations forming intermediates with six-membered* and five-membered rings3 have provided routes to aminoacids. Introduction of an epoxide to initiate a bio- mimetic cyclization provides a further case one which this time uses the more common titanium-mediated enantioselective Sharpless procedure. Reaction with the prochiral starting material affords an optically pure sample of (3) from (2) (Scheme 2).4 Kinetic resolution is also an important application of the titanium R. G. Salomon B. Basu S. Roy and R. B. Sharma Tetrahedron Lett.1989 30 4621. U. Schmidt M. Respondek A. Lieberknecht J. Werner and P. Fischer Synthesis 1989 256. M. E. Jung and Y. H. Jung Tetrahedron Lett. 1989 30 6637. S. Hatakeyama H. Numata K. Osanai and S. Takano J. Chem. SOC.,Chem. Commun. 1989 1893. 227 G. R. Stephenson Me OCH2(4-MeOPh) OCH2(4-MeOPh) . .. + diastereoisomer 1. I1 $OH 15% Me OSiEt OH (1) 55% 1iii-v Me OH 0 Reagents i Bu'OOH VO(acac),; ii Bu;NF; iii DEAD PPh, Zn(OTs),; iv BU'OK;v DDQ Scheme 1 y[siMe3 Hy4 R2 0 HO OH OH 82% (3) (2) R' = H; R2 = (CH,),CMe=CH(CH,),CrCCH,SiMe (4) R' = C=C(CH,),OTHP; R2 = C_CCH2Me I R' (5) Reagents i Ti(OPr'), (-)-DET Bu'OOH; ii SnCl, CHzClz; iii Ti(OPr'), (+)-DET Bu'OOH Scheme 2 Organometallic Chemistry -Part (i) The Transition Elements 229 tetraisopropoxide/dialkyl tartrate combination; an unusual example to appear this year is the enantioselective destruction of 2-thienyl~arbinols.~ The great number of synthetic chemists who have now adopted these procedures is a testimony to their generality and efficiency.Typical examples are to be found in Chamberlin's route to (9s)-dihydroerythronolide A,6 access to sex pheromones of Hyphantria c~nea,~ work on juvenoids by Zabia and co-workers,8 and terpenoid hybrids by Kutney.' Synthesis of the naturally occurring epoxide (5) from (4) by Rao's group," Wang's synthesis of a fragment of FK-506 at the Merck Frosst Centre in Canada," Crombie and Jarrett's routes to plant toxins,12 and Still's studies of podand ionophore~'~ provide further indications of the popularity of the method.All around the world this reaction is now at the forefront of synthetic thinking. Epoxidation work in Sharpless' own group centres on the mechanism of the asymmetric ep~xidation'~ and on subsequent functionalization of epoxidation prod- ucts to form for example (6).15 Others too address this theme in work leading to aziridines (7)16 and a,P-epoxysilylketones (8).17 New uses for the Sharpless titanium catalyst (for example in the asymmetric oxidations of 1,3-dithianes described by Kagan and co-workers18) or development of new catalysts for use with simple alkenes," point the way for new progress. C02Me Indeed contemporary challenges in alkene oxidation using transition metal chemistry concern the general enantioselective epoxidation of alkenes that lack OH directing groups and methods for enantioselective diol formation.This latter issue is receiving intense attention from the Sharpless team,20 while Schurig's group at Tubingen has combined forces with Kagan's laboratory in Paris to address the Y. Kitano M. Kusakabe Y. Kobayashi and F. Sato J. Org. Chem. 1989,54,994. A. R. Chamberlin M. Dezube S. H. Reich and D. J. Sall J. Am. Chem. SOC.,1989 111 6247. ' K. Mori and T. Takeuchi Liebigs Ann. Chem. 1989 453; M. T6th H. R. Buser A. Peiia H. Am K. Mori T. Takeuchi L. N. Nikolaeva and B. G. Kovalev Tetrahedron Lett. 1989,30 3405. C. Wawrzenczyk A. Zabia and M. Aniol Liebigs Ann. Chem. 1989 5.C. Carvalho W. R. Cullen M. D. Fryzuk H. Jacobs B. R. James J. P. Kutney K. Piotrowska and V. K. Singh Helv. Chim. Acta 1989 72 205. 10 A. V. R. Rao P. R. Krishna and J. S. Yadav Tetrahedron Lett. 1989 30 1669. Z. Wang Tetrahedron Lett. 1989 30 6611. 12 L. Crombie and S. R. M. Jarrett Tetrahedron Lett. 1989 30,4303. 13 T. Iimori W. C. Still A. L. Rheingold and D. L. Staley J. Am. Chem. Soc. 1989 111 3439. 14 P. R. Carlier and K. B. Sharpless J. Org. Chem. 1989 54 4016; C. J. Bums C. A. Martin and K. B. Sharpless ibid. p. 2826. l5 J. M. Klunder T. Onami and K. B. Sharpless J. Org. Chem. 1989 54 1295. 16 J. Legters L. Thijs and B. Zwanenburg Tetrahedron Lett. 1989 30,4881. M. E. Scheller W. B. Schweizer and B. Frei Helv. Chim. Acta 1989 72 264.18 0. Samuel B. Ronan and H. B. Kagan J. Organomet. Chem. 1989 370 43. 19 M. Gahagan A. Iraqi D. C. Cupertino R. K. Mackie and D. J. Cole-Hamilton J. Chem. SOC., Chem. Commun. 1989 1688. 2o J. S. M. Wai I. Mark6 J. S. Svendsen M. G. Finn E. N. Jacobsen and K. B. Sharpless J. Am. Chem Soc. 1989 111 1123; E. N. Jacobsen I. Mark6 M. B. France J. S. Svendsen and K. B. Sharpless ibid. p. 737. G. R Stephenson former. This team has produced an interesting development using molybdenum catalysts which in one case gives enantioselectivity as high as 9570.~‘ Hydrogenation and C-H Activation.-As in the previous section it is work on asymmetric methods that takes centre-stage in the development of new hydrogenation catalysts and applications.One of the most popular procedures employs the binaph- thy1 chelating phosphine BINAP with ruthenium catalysis and is valuable in the preparation of aminoacids.22 In a new development the same reagent is employed in a double asymmetric hydrogenation leading to (9) (Scheme 3).22 Rhodium catalysis another typical method has been employed with the chelating substrate (ll) again achieving high enantioselectivity in the formation of In other cases more unusual catalysts are under investigation; examples are a dinuclear system employed by Schmidt and SU~s-Fink~~ and the metallacarboranes used by Hawthorne’s Iridium catalysts are used for the reduction of aldehydes.26 Another unusual case is the semihydrogenation of alkynes and dienes using pal- ladium catalysts and a silane the products are ~is-alkenes.~’ CO2H (9) R = Me (10) R = H Reagents i Ru2C14(BINAP),NEt3 H2;ii [Rh(cod),]CIO, BCPM H2 Scheme 3 The mode of action of catalysts is an important problem.Valuable information can be gained from X-ray structural studies and a number have been reported recently; for examples see those on iridium28 and rhodium29 catalysts. Hydrogenation by homogeneous catalysts involves the formation of C-H bonds from metal-bound intermediates. The reverse process forms organometallic species by reaction of hydrocarbons at positions lacking normal activating groups. Iridium 21 V. Schurig K. Hintzer U. Leyrer C. Mark P. Pitchen and H.B. Kagan J. Organomet. Chem. 1989 370 81. 22 H. Kawano T. Ikariya Y.Ishii M. Saburi S. Yoshikawa Y. Uchida and H. Kumobayashi J. Chem. SOC.,Perkin Trans. 1 1989 1571; H. Muramatsu H. Kawano Y. Ishii M. Saburi and Y.Uchida J. Chem. SOC.,Chem. Commun. 1989 769. 23 H. Takahashi N. Yamamoto H. Takeda and K. Achiwa Chem. Lett. 1989 559. 24 G. F. Schmidt and G. Suss-Fink J. Organomet. Chem. 1989 362 179. 25 J. A. Belmont J. Soto R. E. King 111 A. J. Donaldson J. D. Hewes and M. F.Hawthorne J. Am. Chem. SOC 1989 111 7475. 26 C. S. Chin S. C. Park and J. H. Shin Polyhedron 1989 8 121. 27 B. M. Trost and R. Braslau Tetrahedron Lett. 1989 30,4657. 28 J. M. Brown P. L. Evans P. J. Maddox and K. H. Sutton J. Organomet. Chem. 1989,359 115. 29 N. W. Alcock J. M. Brown and A. P. James Acta Cryst. C Cryst. Struct. Commun. 1989 45 734.Organometallic Chemistry -Part (i) The Transition Elements 23 1 catalysts are often employed. Recent examples leading to the formation of (12) and (13) are found in a study that examines the use of liquid xenon as an inert solvent for reactions of this type (Scheme 4).30 An investigation of thermal rearrangements of platinum complexes has provided information about isotope effects in metal insertion into C-H bonds.31 Reagents i (C,Me5)IrH2PMe3 Xe hv Scheme 4 In the reactions of organometallic hydrides hydrogen transfer may not always be complete stable structures with bridging (agostic) hydrogens can be formed. Brookhart’s work using cobalt complexes provides a typical e~ample.~’ Hydroformylation Hydrosilylation and Hydroboration.-Hydroformylation com-bines hydrogenation with a carbonyl insertion step to add H and CHO across an alkene.Predominantly branched products [(15) > (16)] have been obtained from styrenes (14) with rhodium catalysts and unusual phosphole and phosphanorbor- nadiene ligand~.~~ Comparison of hydroformylation and hydrogenation with catalysts using phosphole and PPh3 ligands has also been described.34 In other cases tri- and tetra-phosphine ligands have yielded predominantly linear products (16) from (17).35A computational study of energetics of intermediates in hydrofor- mylation by cobalt catalysts has been published.36 Rhodium catalysis employed in a synthesis of unsaturated cyclic lactams combines hydroformylation with intramolecular C- N bond formation.Depending on the conditions considerable selectivity for the formation of (19) [with R~ICI(PP~~)~/PP~J or (20) [with RhCI(CO)( PPh3)JP( 0Ph)J from (18) has been a~hieved.~’ (14) R = Ph \ (17) R = Et (18) R = CH,CONH + 0 0 (19) (20) 30 M. B. Sponsler B. H. Weiller P. 0.Stoutland and R. G. Bergman J. Am. Chern. SOC. 1989 111 6841. D. C. Griffiths and G. B. Young Organornetallics 1989 8 875. M. Brookhart D. M. Lincoln A. F. Volpe jun. and G. F. Schmidt Organornetallics 1989 8 1212. D. Neibecker R. RCau and S. Lecolier J. Org. Chern. 1989 54 5208. J. Hjortkjaer and P. Toromanova-Petrova J. Mol. Catal. 1989 50 203. 31 32 33 34 35 D. E. Hendriksen A. A. Oswald G. B. Ansell S. Leta and R. V.Kastrup Organornetallics 1989,8 1153. 36 L. Versluis T. Ziegler E. J. Baerends and W. Ravenek J. Am. Chern. SOC. 1989 111 2018. 37 I. Ojima and A. Korda Tetrahedron Lett. 1989 30,6283. 232 G. R. Stephenson Two recent studies use platinum3* and palladium39 catalysts for hydrosilylation. Brunner and Obermann have used chiral pyridinyloxazolines such as (21) with the more normal rhodium catalyst [ Rh(cod)Cl] for asymmetric hydrosilylation of aceto- phen~ne.~' Two oxazoline groups flanking a pyridine in (22) have provided chiral auxiliaries with a C axis after removal of the silyl group alcohols such as (23) were obtained in optical yields as high as 95Y0.~'An unusual hydrosilylation has been performed on the carbonyl portion of a metal acyl complex.42 In another unusual reaction the combined introduction of both silyl and formyl groups by silylformylation of alkynes produces acyl-formyl-substituted vinylsilanes; Rh4(CO)12 was used as the catalyst.43 Me (21) (21) or (22) A.Ph,SiH, Rh cat. Me OH (23) R = CH2CH2C02Et A series of papers from Burgess and Ohlmeyer have probed rhodium-catalysed hydroboration. Both OH4 and NHTs groups45 have been employed in search of diastereoselectivity in the formation of (24) and (25) (Scheme 5). A model predicting the sense of diastereoselection has been proposed.46 . .. 1,11_ Ph Me 'CHI Phlx Me' OH + PMe h x OH (24) X = OCOCF (14:1) (25) X = NHTs (7:1) Reagents i catecholborane [Rh(cod)CI], PPh3 ;ii H,O,/aq. NaOH Scheme 5 38 R.Skoda-Foldes L. KollLr and B. Heil J. Organomet. Chem. 1989 366,275. 39 B. Marciniec and E. Mackowska J. Mol. Catal. 1989 51 41. 40 H. Brunner and U. Obermann Chem. Ber. 1989 122 499. 41 H. Nishiyarna H. Sakaguchi T. Nakarnura M. Horihata M. Kondo and K. Itoh Organometallics 1989 8 846. 42 M. Akita 0. Mitani and Y. Moro-oka J. Chem. SOC.,Chem. Commun. 1989 527. 43 I. Matsuda A. Ogiso S. Sato and Y. Izumi J. Am. Chem. SOC.,1989 111 2332. 44 K. Burgess and M. J. Ohlrneyer Tetrahedron Lett. 1989 30 395. 45 K. Burgess and M. J. Ohlmeyer Tetrahedron Lett. 1989 30 5857. 46 K. Burgess and M. J. Ohlrneyer Tetrahedron Lett. 1989 30,5861. Organometallic Chemistry -Part (i) The Transition Elements 233 Carbonylation and Decarbony1atioo.-The carbonylation of simple substrates such as alkyl or aryl halides is still an important field of research although the emphasis is increasingly shifting to the combination of carbonyl insertion with other processes as seen in cases appearing elsewhere in this Report.Typical examples of new work on simple carbonylation reactions however are discussed here. The use of platinum catalysts with alkyl halides is a reaction that succeeds despite possibilities for p-eliminati~n.~~ The palladium-catalysed carbonylation of aryl chlorides (26)48and sulphonyl chlorides (28)49 gives esters or other carboxylic acid derivatives (27) and (29) (Scheme 6). In the last case the OR' group was introduced in an unusual way by the use of Ti(OR')4 in the reaction mixture.Phase transfer conditions for the use of mixed Fe(CO)5/Co2(C0)8 catalysts have been examined with aryl iodide sub- strates. In addition to normal carboxylate products other coupling products were formed in minor amounts.50 In another unusual process nitrobenzene (30) is converted into formanilide (31) by the action of [HRu,(CO),,]- a reaction that effects reduction and C- N bond formation using methanol and carbon monoxide.51 Two examples of amide formation illustrate different approaches. In the first,52 with palladium catalysis an aryl halide substrate is employed while in the second,53 a cobalt catalyst opens a vinylazetidine. (27) Y = OH OMe NHPr" (26) R = H C1 Me; X = C1 0' (29) Y = OR' (28) X = S02CI (31) 80% (30) R = H;X= NO2 Reagents i Y-H Pd cat.; ii Ru,(CO),* CO MeOH Scheme 6 Decarbonylation of sugars has been examined using Wilkinson's catalyst RhC1( PPh,) .The reaction is effective not only with aldose substrates54 but even with ketoses.55 Organometallic Enolate Complexes.-Organometallic enolates formed by deproton- ation of metal acyl complexes have been extensively developed as reagents for enantioselective synthesis. The benzyloxy-substituted acyl complex (32) has featured in progress this year. By the use of either copper [(33) (34) 3 :1,88%] or aluminium reagents [(33) :(34) 1 :8 65%] to promote addition of aldehydes selective access to both diastereoisomers is possible (Scheme 7). A special feature is the removal of the entire metal acyl group from (34) to leave an a~etal.~~ The complex (32) is also 47 R.Takeuchi Y. Tsuji M. Fujita T. Kondo and Y. Watanabe J. Org. Chem. 1989 54 1831. 48 Y. Ben-David M. Portnoy and D. Milstein J. Am. Chem. SOC.,1989 111 8742. 49 M. Miura K. ltoh and M. Nornura Chem. Lerr. 1989 77. 50 J.-J. Brunet and M. Taillefer J. Organomet. Chem. 1989 361 C1. S. Bhaduri H. Khwaja K. Sharma and P. G. Jones J. Chem. SOC.,Chem. Commun. 1989 515. 52 Y. Uozumi N. Kawasaki E. Mori M. Mori and M. Shibasaki J. Am. Chem. SOC.,1989 111 3725. 53 D. Roberto and H. Alper J. Am. Chem. SOC.,1989 111 7539. 54 M. A. Andrews G. L. Gould and S. A. Klaeren J. Org. Chem. 1989 54 5257. 55 M. A. Andrews Organomerallics 1989 8 2703. 56 S. G. Davies D. Middlemiss A. Naylor and M.Wills Tetrahedron Lett. 1989 30,2971. G. R. Stephenson (32) R = OBn (35) X = H; Y = OH (Bn = CH,Ph) (36) X = 0H;Y = H I i-iii cp HFe*Yprn 0 x (33) x = OH; Y = H (34) X = H; Y = OH /O\ Reagents i BuLi; ii CuCN or Et,AICI; iii \0 ;iv Br, (CH,OH), -78°C; v MeCH-CHMe Scheme 7 useful in additions to epoxybutenes. The trans-epoxide affords the major product (35) (10:1 81%) which has a sequence of three adjacent chiral centres. A diastereoisomer (36) is formed in 90%yield with similar stereoselectivity from the ~is-epoxide.~~ The original Davies enolate reagent derived from (32; R = H) has been used to prepare a-alkylsuccinate derivatives such as (37),58 or in the enan- tiomeric series the product (38).59 A Me n (37) (38) Oxygen-bound rhodium enolates have been examined and again diastereoselec- tive addition to aldehydes can be achieved.In the case of (39),the rhodium complex is achiral.60 Enolates such as (39) are normally formed by reaction between conven- tional enolates and metal halide complexes. An unusual alternative combines metal hydrides and epoxides to form a C-bound product.61 Cuprates and Related Reagents.-Organocuprates and copper-catalysed Grignard reagents have well-established roles to play in organic synthesis. The precise details of their mode of action however still remain uncertain. The angle of attack of 57 S. G. Davies D. Middlemiss A. Naylor and M. Wills Tetrahedron Lett. 1989 30 587. 58 G. Bashiardes S. P. Collingwood S. G. Davies and S.C. Preston J. Chem. SOC Perkin Trans. I 1989 1162. 59 G. Bashiardes S. P. Collingwood S. G. Davies and S. C. Preston J. Organornet. Chem. 1989,364 C29. 60 G. A. Slough R. G. Bergman and C. H. Heathcock J. Am. Chem. SOC.,1989 111,938. 61 J. Wu and R. G. Bergman J. Am. Chem. SOC.,1989 111 7628. Organometallic Chemistry -Part (i) The Transition Elements 1 1; co PhCHO I ___3 Rh -20°C Me3P’ / \o Me3P’ / Me3P \O But Me3P (39) Ph Me cuprate reagents to a$-unsaturated esters has been the subject of a theoretical investigation by Dorigo and Morokuma.62 NMR studies in GOteb~rg~~ and at the AT&T Bell Laboratories in New Jersey64 sought to identify initial .rr-binding of the copper in additions to enones.Lithium iodide coordination at the carbonyl group in a Lewis acid fashion is also implicated in these studies. Kuwajima has raised the possibility that Me,SiCl often used in conjugate addition/enolate trapping reactions may act similarly as a Lewis acid activating the enone for nucleophile addition.65 Strong Lewis acids such as BF3.Et20 are often employed in conjunction with cuprates and this has been the subject of an NMR investigation.66 NMR spectros- copy has also been employed to probe additions to alkynyl The relative importance of 0-and .rr-bound intermediates is also at issue in allylic situations; both NMR techniques68 and stereochemical investigation^^^ have been used to address this problem. When allylic leaving groups and a$-unsaturated esters are present in the same structure SN2’displacement is preferred leading to alkenes such as (40).70New Br R1 R3 types of reagents continue to receive attention.Knochel’s team have reported results with RCu(CN)ZnI reagents in additions to nitroalkenes’l and with enones acid and ally1 halides and vinylogous acid iodides.72 Zinc diamine complexes have been used in the place of copper in the catalysis of Grignard reactions.73 Nickel-catalysed Grignard additions have been used to open cyclic vinyl ethers (41) to prepare (42)74 and (43)75in 89% and 11% yields respectively. The formation of (42; R’ = Bun R2 = Me n = 1) in 62% yield from (41; R’ = SnMe, n = 1) by reaction with 62 A. E. Dorigo and K. Morokurna J. Chem. SOC. Chem. Commun. 1989 1884. 63 M.Bergdahl E.-L. Lindstedt and T. Olsson J. Organomet. Chem. 1989 365 C11. 64 S. H. Bertz and R. A. J. Smith J. Am. Chem. SOC.,1989 111 8276. 65 Y. Horiguchi M. Komatsu and I. Kuwajima Tetrahedron Lett. 1989 30,7087. 66 B. H. Lipshutz E. L. Ellsworth and T. J. Siahaan J. Am. Chem. Soc. 1989 111 1351. 67 N. Kradse Tetrahedron Lett. 1989 30 5219. 68 B. H. Lipshutz E. L. Ellsworth S. H. Dirnock and R. A. J. Smith J. Org. Chem. 1989 54 4977. 69 T. L. Underiner S. D. Paisley J. Schrnitter L. Lesheski and H. L. Georing J. Org. Chem. 1989,54,2369. 70 C. Girard I. Rornain M. Ahrnar and R. Bloch Tetrahedron Lett. 1989 30 7399. 71 C. Retherford M. C. P. Yeh I. Schipor H. G. Chen and P. Knochel J. Org. Chem. 1989 54 5200. 72 T. N. Majid M. C. P. Yeh and P.Knochel Tetrahedron Lett. 1989 30 5069. 73 J. F. G. A. Jansen and B. L. Feringa J. Chem. SOC.,Chem. Commun. 1989 741. 74 P. Kocieriski S. Wadman and K. Cooper 1. Org. Chem. 1989 54 1215. 75 T. L. Davies and D. A. Carlson Synthesis 1989 936. G. R. Stephenson Rt R' Pl R2MgBr ' >-\ Ov(CH~) n /-OH NiCI2 RZ (CH,)n (41) (42) R' = CH2CH2CH=CMe,; R2 = Me; n = 1 (43) R' = H; R2 = (CH,),Me; n = 2 Bu2Cu(CN)Li2 and Me1 involves both nucleophile and electrophile addition to the same carbon. The same study describes the use of copper-catalysed reactions of vinyllithium reagents of type (41; R' = Li n = 1 2).76Manganese analogues of Grignard reagents have been examined both 1,2-additions and copper-catalysed 1,4-additions are possible.77 Addition of these reagents to acid chlorides is also With conventional cuprate reagents Me2CuLi and the newer Me2Cu(CN)Li2 involvement of nearby groups in the substrate to facilitate displace- ment reactions raises interesting general possibilities.The reaction has now been examined in detail in studies of stereocontrolled TsO-displacements from alkyl tosy~ates.~~ 3 Coupling Reactions Transition-metal-catalysed coupling reactions provide a remarkably versatile method for carbon-carbon bond formation. The development of applications of these coupling processes in organic synthesis has received much attention in 1989. Conven- tional nucleophiles alkenes alkynes and a number of heteroatom-substituted sub- strates can be combined in a great many ways typically using palladium catalysis.Indeed organopalladium chemistry has totally dominated this field in papers appear- ing in 1989 just as it has throughout the development of the area in the 1980s. Increasing use of organotin and organoboron substrates however has been the most notable innovation of this past year. Although work had previously established the possibility of the use of such substrates in synthesis examples of the application of these methods are now becoming far more common and receive special attention in this year's survey. General Coupling Processes.-Coupling Vinyl and Aryl Halides with Alkynes. Pal-ladium-catalysed coupling reactions have proved particularly useful in the synthesis of polyenes. Much recent work in this area has been directed towards access to polyene natural products such as leukotrienes lipoxins and HETEs.The combina- tion of two simple subunits the vinyl bromide (44; R' = CH20H X = Br) and the alkyne (45; R2 = [CH2I2CO2Me,Y = H) to form an enyne intermediate for the synthesis of a tritiated analogue of leukotriene E metabolite provides a typical example.*' A similar combination of an alkyne and a vinyl halide is used in the formation of (46) which was subsequently hydrogenated to produce the cis,trans,-trans-trienediol unit of the leukotriene target molecules." 76 P. Kocienski S. Wadman and K. Cooper J. Am. Chem. SOC.,1989 111 2363. 77 G. Cahiez and M. Alami Tetrahedron Lett. 1989 30 7365. 78 G. Cahiez and B. Laboue Tetrahedron Lett.1989 30 7369. 79 S. Hansessian B. Thavonekham and B. DeHoff J. Org. Chem. 1989 54 5831. D. Delorme Y. Girard and J. Rokach J. Org. Chem. 1989 54 3635. *' M. Avignon-Tropis and J. R. Pougny Tetrahedron Lett. 1989 30,4951. 237 Organometallic Chemistry -Part (i) The Transition Elements OH R' = CH=CHCH(OH)(CH,),Me; X = C1; R2= (CH,),CO,Me; Y = OH In an intramolecular [4 + 21 cycloaddition route towards esperamicin/ calichemicin aglycones Schreiber has also employed the coupling of alkynes and vinyl halides to prepare a key intermediate. The conditions selected namely combin- ing a palladium catalyst with the use of CuI are typical of procedures for coupling alkynes with vinyl halides.82 Similar conditions have been employed to combine a bromopyridine and an alkyne to prepare an intermediate in a route to the leukotriene antagonist (47).83 Methods to combine alkynes and halogenopyridines have also been examined.84 To achieve control in the coupling of (48) and (49) an iodopyridine was needed; the reaction fails with the substrate (50).A similar coupling with an aryl iodide was used in the same investigation to provide a product that upon hydrogenation was converted into DDATHF (5,10-dideaza-5,6,7,8-tetrahydrofolic acid) which is in preclinical trials as an anti-tumour agent.84 HO H C02Bu' + HCGC G X (48) X = I (49) (50) X = Br 65% Coupling Aryl Halides with Alkenes. The original Heck coupfing that forms styrenes from aryl halides and alkenes (for a typical recent example see Beletskaya's prepar- ations of substituted cinnamic acids") has continued to receive attention this year.The reaction has been used in the Merck Sharp and Dohme laboratories in England to prepare another cinnamic acid derivative which was converted into a substrate for a second palladium-catalysed reaction.86 82 F. J. Schoenan J. A. Porco jun. S. L. Schreiber G. D. VanDuyne and J. Clardy Tetrahedron Left. 1989 30 3765. 83 C. E. Burgos E. G. Nidy and R. A. Johnson Tetrahedron Lett. 1989,30 5081. 84 E. C. Taylor and G. S. K. Wong J. Org. Chern. 1989 54 3618. 85 N. A. Bumagin P. G. More and I. P. Beletskaya J. Organornet. Chern. 1989 371 397. 86 R. J. Alabaster I. F. Cottrell D. Hands G. R. Humphrey D. J. Kennedy and S. H. B. Wright Synthesis 1989 598.G. R. Stephenson An intramolecular example of Heck coupling can be seen in a route to (51) (Scheme 8).87 In an alternative procedure a reductive work-up using formic acid removes the alkene linkage upon detachment of the metal." A further variant of the formate reduction method combines vinyl halides and alkynes to form conjugated dienes rather than enyne~.'~ I (51) 89% Ts Reagents i Pd(OAc), Et3N,(o-tol)3P Scheme 8 Coup!ing Vinyl Halides with Alkenes. When vinyl halides are combined with simple alkenes the p-elimination step can proceed in an alternative fashion to form a non-conjugated diene such as (52) (Scheme 9). This type of process has recently been explored in detail by Larock and Gong" in an extension of earlier studies using aryl halides.A nice application of this chemistry which seems most reliable with cyclopentene substrates provides an unusual alternative to conjugate addi- tion/enolate trapping for access to prostanoid structure^.^' Two advantages are significant protection of the OH groups is not needed and enolate rearrangement and elimination of OR (a major limitation of conventional approaches) does not occur. I Reagents i Pd(OAc), Ag2C03 PPh3 Scheme 9 An intramolecular version of the alkene/vinyl halide coupling forms bicyclic products for example (53) with the p-elimination step bringing the alkene into conjugation with a second alkene linkage that was not involved in the initial addition process (Scheme 10). The alkenes in the cyclohexa-1,4-diene ring are diastereotopic providing an opportunity for an asymmetric induction.With (R)-BINAP a modest (46% e.e.) transfer of chirality was achieved providing the first example of an asymmetric Heck coupling.92 87 L. S. Hegedus M. R. Sestrick E. T. Michaelson and P. J. Harrington J. Org. Chem. 1989 54 4141. 88 A. Arcadi F. Marinelli E. Bernocchi S. Cacchi and G. Ortar J. Organomet. Chem. 1989 368,249. 89 A. Arcadi E. Bernocchi A. Burini S. Cacchi F. Marinelli and B. Pietroni Tetrahedron Lett. 1989 30 3465. 90 R. C. Larock and W. H. Gong J. Org. Chem. 1989 54 2047. 91 R. C. Larock F. Kondo K. Narayanan L. K. Sydnes and M.-F. H. Hsu Tetrahedron Lett. 1989,30,5737. 92 Y. Sato M. Sodeoka and M. Shibasaki J. Org. Chem. 1989 54 4738.Organometallic Chemistry -Part (i) The Transition Elements H (53) 68% Reagents i P~(OAC)~, AgzC03 Ph2PCH2CH2PPh2 Scheme 10 Coupling Reactions of Vinyl Trijlates Sulphoximes and Thioacetals. Triflates are commonly used in place of halides in coupling reactions. Andersson and Hallberg coupled vinyl triflates with enol ethers to form oxygenated diene~.~~ A detailed examination of the oxidative addition step initiating this coupling reaction has been performed using platinum c~mplexes?~ In cleavage of carbon-sulphur bonds the third member of the triad -nickel -has proved particularly useful. Two examples illustrate this chemistry in cases using nickel catalysts with dithioacetal” and chiral sulphoximine groups.96 In the second case transition-metal-catalysed cross-coupling was used to remove an important chiral auxiliary at the same time solving the difficult problem of control of E/Z isomer ratios in the formation of the exocyclic double bond of prostacyclins.Nickel catalysts and the use of salt-free organozinc nucleophiles were necessary in the formation of (54) (Scheme 11). H !l ULV H / (54) 74% Ru‘MeSiO Reagents i R,Zn[R = (CHz),OSiButPhz] NiCl,(L -L) [L -L = Ph2P(CHJ3PPh2] Scheme 11 Coupling Reactions of Organotin and Boron Reagents.-Coupling AryZ and Vinyl Tin Substrates. Palladium catalysis can be used to perform homocoupling of vinylstan-nanes to form symmetrical conjugated diene~.~’ Homocoupling may sometimes compete with cross-coupling reactions though generally this is not a severe limita- tion.Schreiber and Porco have applied the cross-coupling process both with bromobenzene and with acid chlorides.98 With ally1 halides on the other hand parallel formation of homocoupling products was described although cross-coupling yields were still in the range 40-75%. In a similar reaction Danilova and co-workers obtained the enone (55) in 75% yield together with only 10% of homocoupling products (Scheme 12).99 93 C.-M. Andersson and A. Hallberg J. Org. Chem. 1989 54 1502. 94 P. J. Stang M. H. Kowalski M. D. Schiavelli and D. Longford J. Am. Chem. Soc. 1989 111 3347. 95 P.-F. Yang. Z.-J. Ni and T.-Y. Luh J. Org. Chem. 1989 54 2261. 96 I. Erdelmeier and H.-J. Gais J. Am. Chem. Soc. 1989 111 1125.97 G. A. Tolstikov M. S. Miftakhov N. A. Danilova Y. L. Vel’der and L. V. Spirikhin Synthesis 1989,633. 98 S. L. Schreiber and J. A. Porco jun. J. Org. Chem. 1989 54 4721. 99 G.A. Tolstikov M. S. Miftakhov N. A. Danilova Y. L. Vel’der and L. V. Spirikhin Synthesis 1989,625. 240 G. R. Stephenson Reagents i PdC12( MeCN)2 THF PPh Scheme 12 Coupling of arylstannanes with halogenated nucleosides has been used to prepare boron-containing derivatives such as (56) for neutron capture therapy (Scheme 13). Selective substitution of tin rather than boron (see below) is notable in this reaction.loo 0 R = SiMe,Bul I I %AAAruL RO OR (56) 79% Scheme 13 Vinylstannane coupling in particular offers attractive opportunities in organic synthesis.An example that employs vinyl triflates as the second component is to be found in work on a total synthesis of anthramycin."' In the field of porphyrin synthesis ethenyl side-chains have been introduced by replacement of bromine substituents on the pyrrole rings using a palladium-catalysed reaction.'02 In studies of polycyclic cyclopentanoids Cheney and Paquette provide further examples that illustrate the power of this type of coupling pro~ess."~ Coupling Aryl and Vinylboronate Reagents. As with the tin reagents described above homocoupling of vinylboronates can provide access to symmetrical 1,3-dienes. Typical applications of both aryl and vinyl reagents however are in cross-coupling reactions. An extensive examination of cross-coupling between bromonitroarenes and arylboronates has been made.This route can give regioselective access to a wide variety of biphenyl coupling products.'04 100 Y. Yamamoto T. Seko and H. Nemoto J. Org. Chem. 1989 54 4734. 101 M. R. Peha and J. K. Stille J. Am. Chem. SOC.,1989 111 5417. 102 0. M. Minnetian I. K. Moms K. M. Snow and K. M. Smith J. Org. Chem. 1989,54 5567. D. L. Cheney and L. A. Paquette J. Org. Chem. 1989 54 3334. 103 '04 T. Iihama J.-M. Fu M. Bourguignon and V. Snieckus Synthesis 1989 184. Organometallic Chemistry -Part (i) The Transition Elements 241 With vinylboronates as with other substrates for cross-coupling processes it is selective access to either E- or 2-alkenes that constitutes the main attraction of the method.Examples of both types of product are found in applications in leukotriene synthesis. The combination of the E,E-boronate (57a) with the 2-vinyl iodide (58a) afforded a Z,E,E-trienediol upon coupling with Pd( PPh3)4-T10H. Since a racemic vinyl halide was used the product was obtained as a mixture of diastereois~mers.'~~ Nicolaou's group on the other hand have used the E,Z-boronate (57b) with an E-vinyl iodide (58b) to form the E,E unit of an E,E,Z-triene.lo6 With a vinylboronate containing both bromide and boronic ester groups stepwise elaboration has proved possible first replacing the bromine by use of an organozinc reagent then effecting palladium-catalysed carbonylation to introduce the ester.'" With aromatic sub- strates ortho-palladation can be combined with coupling reactions."' R' (57) (58) R3 a; R' = H,R2 = CH=CHCH(OSiMe2Bu')CH2CH=CH(CH2)4Me R3 = CH(OSiMe2But)(CH2),CO2Me,R4= H b; R2= CH=CHCH,CH=CH(CH2),Me,R2 = R3 = H R4= CH(OSiMe2Bu')CH(OSiMe2Bu')(CH,),C02Me 4 Transition-metal-catalysed Cyclization and Oligomerization Reactions Polyene Cyc1izations.-The transition-metal-catalysed intramolecular coupling of alkenes and alkynes has received considerable recent attention.Again palladium catalysts are most commonly used and since the reaction proceeds by direct coordination of reactants by the transition metal centre reactive functionality on the alkene is not required. A representative example can be drawn from work in Trost's laboratory leading to the formation of (59).'09 A similar cyclization has been used in a synthesis of (-)-sterepolide."' The exocyclic diene formed in this way can be used in a subsequent conventional cycloaddition step as in the formation of (60) as the major stereoisomer."' Another variant of this type of process combines the presence of an oxygen bridge with a capacity to eliminate palladium to form a 1,4-diene.Use of a triphenylarsine ligand in this cyclization has proved advantageous.' l2 105 M. Avignon-Tropis M. Trielhou J. Lebreton J. R. Pougny I. Frtchard-Ortuno C. Huynh and G. Linstrurnelle Tetrahedron Lett. 1989 30,6335. 106 K. C. Nicolaou J. Y. Ramphal J. M. Pulazon and R. A. Spanevello Angew. Chem. Int. Ed. Engl. 1989 28 587. 107 N. Yamashina S. Hyuga S.Hara and A. Suzuki Tetrahedron Lett. 1989 30 6555. 108 J. S. McCallurn J. R. Gasdaska and L. S. Liebeskind Tetrahedron Lett. 1989 30,4085; J. Dupont M. Pfeffer M. A. Rotteveel A. De Clan and Jean Fischer Organometallics 1989 8 1116; W. Tao L. J. Silverberg A. L. Rheingold and R. F. Heck ibid, p. 2550. 109 B. M. Trost D. C. Lee and F. Rise Tetrahedron Lett. 1989 30 651. 110 B. M. Trost P. A. Hipskind J. Y. L. Chung and C. Chan Angew. Chem. Int. Ed. Engl. 1989,28 1502. 111 B. M. Trost and D. C. Lee J. Org. Chem. 1989 54,2271. 112 B. M. Trost E. D. Edstrom and M. B. Carter-Petillo 1.Org Chem. 1989 54,4489. G. R. Stephenson R (59) R = CsH,,,95% OSiMe3 (60) 60% 6:1 ratio Reagents i Pd2(dba), (o-tol),P HOAc CHCI,; ii BSA 140-180 "C,R = CH(OH)(CH2)2C~CSiMe Scheme 14 Organozirconium chemistry provides a common alternative to organopalladium methods and can be applied to both the cyclization of enynes113 and a,w-dienes.l14 An extension of these methods employs imine substrates in intramolecular additions to alkenes and alkynes to form amine products such as (61) (Scheme 15)."' Addition of methylenecyclopropanes to alkynes has been examined.' l6 I NHMe N\ Me (61) 58% Reagents i Cp,ZrBu; ;ii H30+ then HO- Scheme 15 Pauson-Khand Reactions and Related Cyc1izations.-When alkene-plus-alkyne cyc- lization is combined with carbonyl insertion two rings can be formed in a single step.This type of double cyclization is most commonly performed by means of cobalt complexes and is termed the Pauson-Khand reaction.Studies of the scope of this reaction continue to be published as in the formation of products of types (62) and (64).'16 Severe hindrance reduces the yield as seen for example in the formation of (63).l17 Improved access to (alkyne)Co,(CO) complexes in a one-pot process from CoBr gave products that were used successfully in intermolecular cyclizations with alkenes."' The conventional form of the reaction has now been used in many syntheses. The intermolecular reaction for example features in the first total synthesis of furanether B,l19 and an intramolecular case is employed in a stereocontrolled route to deoxynorpentalenolactone H.'" 113 E. C. Lund and T. Livinghouse J. Org. Chem. 1989 54 4487. 114 C.J. Rousset D. R. Swanson F. Lamaty and E.4. Negishi Tetrahedron Lett. 1989 30 5105. 115 M. Jensen and T. Livinghouse J. Am. Chem. SOC.,1989 111 4495. S. A. Bapuji W. B. Motherwell and M. Shipman Tetrahedron Lett. 1989 30,7107. 117 W. A. Smit S. 0. Simonyan V. A. Tarasov G. S. Mikaelian A. S. Gybin I. I. Ibragimov R. Caple D. Froen and A. Kreager Synthesis 1989,472. 118 A. Devasagayaraj and M. Periasamy Tetrahedron Lett. 1989 30 595. 119 M. E. Price and N. E. Schore J. Org. Chem. 1989 54 5662. P. Magnus M. J. Slater and L. M. Principe J. Org. Chem. 1989 54 5148. Organometallic Chemistry -Part (i) The Transition Elements R4 (62) R' = R2 = R3 = R4 = H; X = 0;56% (63) R' = R2 = R3 = H; R4 = H Me; X = 0;48% (64) R'-R2 = (CHJ4; R3 = R4 = H; X = 0;64% Recently alternatives to the organocobalt methodologies have been the subject of increased attention.Organozirconium chemistry provides cyclization procedures which may offer great versatility allowing simple cyclizations of the type discussed in the preceding section to be combined with carbonylation to give rise to enone products. Thus while the formation of (66) from (65) reflects a zirconium version of the Pauson-Khand process alternative work-up methods can afford alkenes (67) or halides (68) (Scheme 16). Reactions of this type have been studied extensively by Negishi's group.'21 SiMe3 ii. iii @O (66) 55% SiMe cT-siMe3 i_ 111 OTjZrCp2 -d Me -(67) 90% I (68) 75% Reagents i Cp,ZrCl, Mg HgC12; ii CO; iii H,O+; iv I Scheme 16 E.4.Negishi S. J. Holmes J. M. Tour J. A. Miller F. E. Cederbaum D. R. Swanson and T. Takahashi J. Am. Chem. Soc. 1989 111 3336. 244 G. R. Stephenson By the combination of two alkynes with an isocyanide (frequently used in place of CO in insertion processes) cyclopentadienone derivative can be produced. The cyclization step was performed by means of nickel catalysis in yields ranging from 50 to In a comparison of nickel and palladium catalysts Oppolzer’s develop- ment of combined metallo-ene cyclizations with carbonyl insertion can be made to give either an enone product (the result of two carbonyl insertion steps) or an ester in which the intermediate produced by the first cyclization/carbonylation step was intercepted by the solvent before the closure of the cycl~pentenone.’’~ Intermolecular Ni(C0)4-catalysed combinations of ally1 halides alkynes and CO can also be used to form cyclopentenones but at present reactions of this type lack control giving mixtures of products.’24 Alkyne Cyc1izations.-The formation of arenes and cyclooctatetraenes has been the traditional focus of studies seeking to develop applications of transition-metal- mediated alkyne cyclooligomerization in organic synthesis.New developments in this area now generally concern the properties of novel reagent systems. The use of niobium complexes provides a good e~ample.”~ Ruthenium carbonyl alkyne com- plexes have also been found to be able to effect alkyne trimerization.’26 Butadiene Te1omerization.-The combination of two butadiene molecules with nucleophiles normally by means of palladium catalysis has also been a fruitful field of study for many years.A detailed investigation of the effect of reaction conditions on the combination of butadiene and N,N-diethylamine is indicative of the state of refinement that studies of this type have now rea~hed.’~’An intramolecular version of the reaction examined by Takacs and Zhu’28 resembles other palladium-catalysed cyclizations discussed earlier but since it involves the addition of alcohols amines or other nucleophiles to the two diene units in (69) or (70) it is mechanistically related to conventional butadiene telomerizations. X/2xcOCHzPh a (69) X = C(SO,Ph) 50-90% (70) X = NCOPh Reagents i P~(OAC)~, PPh, PhCH20H (X = C(C02Et)2:88%) Scheme 17 Insertion reactions are sometimes combined with butadiene telomerization.A nickel(0) reagent system has been used to promote the combination of three butadiene molecules and carbon dio~ide.’’~ Examples involving organozirconium 12* K. Tamao K. Kobayashi and Y. Ito J. Org. Chern. 1989 54 3517. 123 W. Oppolzer T. H. Keller M. Bedoya-Zurita and C. Stone Tetrahedron Lett. 1989 30,5883. 124 F. Camps J. Coll J. M. Moret6 and J. Torras J. Org. Chern. 1989 54,1969. 125 A. C. Williams P. Sheffels D. Sheehan and T. Livinghouse Organornetaffics,1989 8 1566. 126 E. Lindner R.-M. Jansen H. A. Mayer W. Hiller and R. Fawzi Organometalfics,1989 8 2355.127 T. Antonsson A. Langlit and C. Moberg J. Organornet. Chern. 1989 363 237. 128 J. M. Takacs and J. Zhu J. Org. Chem 1989 54 5193. 129 H. Hoberg and D. Barhausen J. Organornet. Chern. 1989 379 C7. Organometallic Chemistry -Part (i) The Transition Elements methods have been the subject of detailed inve~tigati0n.l~' With titanium complexes simple dimerization of butadienes can be achieved.131 5 Nucleophile Addition at Metal-bound Hydrocarbons Coordination of an alkene or polyene to a transition metal centre produces elec- trophilic species which can undergo synthetically useful reactions with nucleophiles. Many transition metals are efficient stabilizing groups for charged centres either within the complex itself or at adjacent positions; as one would expect these cationic species are far more potent electrophiles than neutral .rr-complexes and can offer greater versatility in synthetic reactions through compatibility with a wider range of nucleophiles.A third feature is also of great importance when unsymmetrically substituted (i.e.prochiral) ligands become n-bound to a transition metal centre the resulting complex is chiral. In many cases such complexes can be resolved and since alkylation of most metal .rr-complexes is generally completely diastereoselective relative to the fate of the ligand bearing the metal extraordinarily efficient chirality transfer is possible between the controlling chirality of the metal complex and the new chiral centres formed in the alkylation reaction.Reactions involving these key features are reflected in the most important developments of the year both in stoicheiometric and catalytic systems. q2-Complexes.-Studies by Rosenblum's group with Fp complexes [Fp = Fe(CO),Cp Cp = CSH,] the most widely used metal-ligand system for cationic q2 .rr-complexes have delineated many of the chiral aspects of chemistry of this type. Exchange etherification of (71) can be used to introduce optically active alcohol groups. Here the situation is complicated by stereochemical lability in the face selectivity of metal binding. The effect can be used to promote a fair degree of dynamic resolution in the product (72). The best results to date have been achieved with menthyl ethers which show a diastereoisomeric ratio of 4 1.The major diastereoisomer has been assigned the structure indicated for (72). Alkylation of the lithium enolate after separation of the major diastereoisomer and removal of both the chiral auxiliary and the metal centre first by treatment with acid and then by heating the resulting .rr-complex in acetonitrile produced a resolved metal-free compound (73) identified by conversion into the known ketone (74). In this same OLi R = Et (73) (74) R = menthyl Reagents i THF -78 "C;ii HBF,; iii MeCN Scheme 18 130 H. Yasuda T. Okamoto Y.Matsuoka A. Nakamura Y. Kai N. Kanehisa and N. Kasai Organomefallics 1989 8 1139. 131 H. Yamamoto H. Yasuda K. Tatsumi K. Lee A. Nakamura J. Chen Y. Kai and N. Kasei Organornetallics 1989 8 105. G.R. Stephenson paper a CD quadrant rule relating absolute configuration to circular dichroism properties was des~ribed.'~~ With a neutral q2-complex Pouilhks and Thomas have extended methods for nucleophile addition at CO and acyl transfer to metal-bound hydrocarbons. 133 Direct nucleophile addition at a ?r-bound ligand followed by a separate carbonyl insertion step has been employed for the synthesis of P-amin~acids.'~~ The Wacker oxidation converting terminal alkenes into methyl ketones by organopalladium chemistry normally involves water addition to a r-bound alkene. A new variant of this reaction involves the use of unusually reactive palladium nitro complexes and direct re-oxidation by air.'35 The same conditions were used for the oxidation of ketones to enones.In another Wacker variant water addition to a 1,Cdiene is followed by isomerization to yield a r-ally1 complex.'36 Much work has been done in Backvall's group on the palladium-catalysed addition of nucleophiles to 1,3-dienes. An example appearing this year involves the use of this stereocontrolled 1,4-difunctionalization to initiate an approach towards per-hydrohistrionicotoxin by the formation of (75). Conventional copper-catalysed Grignard addition (see Section 2) is used to relay chirality of the ally1 chloride in the introduction of the butyl substituent (Scheme 19).'37 1 OAc (75) 72% ii OAc 89% Reagents i Pd(OAc) ,LiOAc LiCl benzoquinone; ii BuMgBr CuCN Scheme 19 q3-Complexes.-In studies of stoicheiometric applications of ?r-ally1 complexes attention has recently focused on the use of alternatives to organopalladium methods.Neutral q3 Fe(C0)2N0 complexes prepared from 1,3-dienesY offer another 132 M. K. Begum K.-H. Chu T. S. Coolbaugh M. Rosenblum and X.-Y. Zhu J. Am. Chern. SOC.,1989 111 5252. 133 A. Pouilhbs and S. E. Thomas Tetrahedron Lett. 1989,30,2285. 134 G.M.Wieber L. S. Hegedus B. Akermark and E. T. Michalson J. Org. Chem. 1989,54 4649. 135 T. T.Wenzel J. Chem. SOC.,Chem. Commun. 1989,932. 136 B. Akermark B. C. Soderberg and S. S. Hall J. Org. Chem. 1989,54 1110. 137 D.Tanner M.Sellh and J.-E. Backvall J. Org. Chern. 1989,54 3374. Organometallic Chemistry -Part (i) The Transition Elements approach to 1,3-difunctionalization which culminates in a nucleophile addition step.'38 New methods for the preparation of cationic complexes both from metal carbonyls and from half-sandwich complexes by direct reactions with allylic alcohols in the presence of HBF4 have been exp10red.l~~ The preparation of neutral vinyl- substituted q3-complexes has also been de~cribed.'~' With catalytic systems the use of palladium still dominates work directed to organic synthesis.The formation of the macrocycle (76) by intramolecular nucleophile addition to an allyl intermediate occurring in the synthesis of (-)-aspochalasin B provides an excellent e~amp1e.l~~ This demonstrates with a fully functionalized system the use of methods for ring formations of this type which have been under development in the Trost group for many years.Another case of intramolecular nucleophile addition has been examined to provide a method for the further elaboration of 1,4-difunctionalized derivatives of dienes obtained using palladium methodologies discussed in the preceding ~ecti0n.l~~ In a third displace- ment of an allylic leaving group leads to the formation of C-glycopyranoside derivatives. 143 SOzPh (76)49% Reagents i Pd(PPh,), dppp Scheme 20 Palladium-catalysed methods for amination,l4 azide addition,'45 and new pro- cedures to promote nucleophilic substitution of allyl ethers by use of B203,146 have been reported. When prochiral allyl ligands are used the possibility arises that an asymmetric induction can be performed by inclusion of chiral phosphine ligands at the metal centre.In work employing chiral ferrocenyl diphosphine ligands efficient transfer of chirality has been achieved in a number of cases. The best examples give products in up to 90% e.e.14' Opening of allylic epoxides and alkylation of the resulting q3-allyl complex is an attractive method that has undergone considerable development this year. The advantages of control of relative stereochemistry and promotion of a sequence of 138 K. Itoh S. Nakanishi and Y. Otsuji Chem. Lett. 1989 615. 139 V. V. Krivykh 0.V. Gusev and M. I. Rybinskaya J. Organornet. Chem. 1989,362,351; V. V. Krivykh 0.V. Gusev P. V. Petroskii and M. R. Rybinskaya ibid. 1989 366,129. 140 G.-H. Lee S.-M. Peng F.-C. Liu D. Mu and R.S.Liu Organometallics 1989 8 402. 141 B. M. Trost M. Ohmori S. A. Boyd H. Okawara and S. J. Brickner J. Am. Chem. Soc. 1989,111,8282. 142 J.-E. Backvall J.-0. VBgberg and K. L. Granberg Tetrahedron Lett. 1989 30,617. 143 M. Brakta P. Lhoste 'and D. Sinou J. Org. Chem. 1989 54 1890. M. Takagi and K. Yamamoto Chem. Lett. 1989 2123. 145 S.-I. Murahashi Y. Tanguchi Y. Imada and Y. Tanigawa 1.Org. Chem. 1989 54 3292. 146 X. Lu and X. Jiang J. Organomet. Chem. 1989 359 139. 147 T. Hayashi A. Yamamoto Y. Ito E. Nishioka H. Miura and K. Yanagi J. Am. Chem SOC.,1989,111 6301. 248 G. R. Stephenson two substitution reactions by subsequent utilization of the second allylic C-0 bond are well illustrated by the opening of the epoxide (77).By means of a palladium- catalysed azide introduction and conventional osmylation the product (78) has been employed in a formal total synthesis of the carbocyclic nucleoside aristeromy~in.'~~ OzNW3 +++02Nu3 -(77) 00 X Reagents i MeN02 Pd(PPh,), 87%; ii Ac20 92%; iii NaN, Pd(PPh,), 61% (78) Scheme 21 Palladium-catalysed generation and utilization of trimethylenemethane derivatives has been the subject of intensified effort in 1989. Two full papers from Trost's group the originators of the method delineate most of the features of the present state of development of this approach to C-C bond f~rmation,'~~ and in direct addition to aldehydes instead of alkenes combined C-C and C-0 bond formation^.'^^ In a more recent development heteroatom replacement in the trimethylenemethane portion has been achieved.The product of reactions with alkenes however are acyl cyclopropanes resulting from a [2 + 13 cycloaddition path.'51 Bambal and Kemmitt have described a [3 +31 version of the reaction achieved by replacement of the alkene by an aziridine. Ring opening followed by intramolecular attack by nitrogen affords piperidine~.'~~ As with simple ally1 complexes trimethylenemethane complexes can be used in asymmetric inductions. In another approach that employs ferrocenyl-based diphos- phines as the chiral auxiliary (79) has been used to form (80) as the major product PhOiS S02Ph +-\ -ax ==CO LOEt X 0 (80) X = CO,Me COMe (79) in up to 75% e.e.153 Inclusion of a chiral auxiliary in the alkene component of the [3 + 21 process is also an effective strategy.'54 The utilization of q3-allyl chemistry in concert with other organometallic methods can result in attractive synthetic procedures.Palladium-catalysed coupling followed 148 D. R. Deardod M. J. Shulman and J. E. Sheppeck 11 Tetrahedron Lett. 1989,30 6625. 149 B. M. Trost P. Seoane S. Mignani and M. Acemoglu J. Am. Chem. SOC.,1989 111 7487. 150 B. M. Trost S. A. King and T. Schmidt J. Am. Chem. Soc. 1989 111 5902. 15' B. M. Trost and S. Schneider J. Am. Chem. Soc. 1989 111 4430. 152 R. B. Bambal and R. D. W. Kemmitt J. Organomet. Chem. 1989 362 C18. 153 A. Yamamoto Y. Ito and T. Hayashi Tetrahedron Lett. 1989 30,375. 154 F. Chaigne J.-P. Gotteland and M. Malacria Tetrahedron Lett.1989 30,1803; B. M. Trost B. Yang and M. L. Miller J. Am. Chem. SOC.,1989 111 6482. Organometallic Chemistry -Part (i) The Transition Elements by nucleophile addition has been used to combine three components in a preparation of unusual aminoacid structures (81) (Scheme 22).lS5 Nucleophile addition and subsequent palladium-catalysed rearrangement has been used in pyrimidine chemistry.' 56 (81) R = H,Me;52-56% Reagents i Pd(dba)2 Ph2PCH2CH2PPh2 LiCHN=CPh2 I C02Me Scheme 22 q4-Complexes.-Of the cationic v4-complexes the Mo(CO)&p system is currently at the most advanced stage of development. An interesting recent investigation explores possibilities for asymmetric induction in the addition of chiral nucleophiles to prochiral complexes of type (82).'57 Indenyl complexes are often employed with acyclic ligands.Complexes such as (83) formed in situ by complexation by ligand exchange are cyclized by intramolecular alkoxide addition.lS8 Pentamethylcyclopentadienyl(Cp') complexes are also popular alternatives to Cp derivatives for use with acyclic dienes. Recent work with Cp' complexes has revealed some unusual properties of acyclic ligands which can adopt either cis or trans geometries across the central bond of the diene.'59 Deprotonation by LiN( can form the v3-butadienyl derivative (84). The same product can be obtained by desilylation of a C-2 SiEt derivative [{CH2=CHC(SiEt3)=CH2}Mo(C0)2Cp']+.160 ii0(c0)2cp I q5-Complexes.-Work on organoiron complexes continues to dominate investiga- tions of uses of ~5-electrophiles.In a full paper'61 appearing this year many years of effort examining the use of tricarbonyliron complexes as A-ring precursors for N. Kopola B. Friess B. Cazes and J. Gore Tetrahedron Lett. 1989 30,3963. 156 M. L. Falck-Pedersen T. Benneche and K. Unheim Acta Chem Scand. 1989 43 251. 157 A. J. Pearson S. L. Blystone H. Nar A. A. Pinkerton B. A. Roden and J. Yoon J. Am. Chem. SOC. 1989 111 134; A. J. Pearson V. D. Khetani and B. A. Roden J. Org. Chem. 1989 54 5141. 158 J. S. Baxter M. Green and T. V. Lee J. Chem. SOC. Chem. Commun. 1989 1595. 159 S. A. Benyunes M. Green and M. J. Grimshire Organometallics 1989 8 2268. 160 S. A. Benyunes M. Green M. McPartin and C. B. M. Nation J.Chem. SOC.,Chem. Commun. 1989,1887. 161 A. J. Pearson and M. K. O'Brien J. Org. Chem. 1989 54 4663. 250 G. R. Stephenson trichothecene synthesis has been brought to fruition. Recently two major advances have proved crucial in improving the efficiency of routes of this type. The first arises from the discovery that tin enolates are capable of building quaternary centres. The second stems from a decision to use a silyl group as the final source of OH functionality required on the five-membered ring. Full details of the use of cycloheptadienyl complexes as electrophiles in routes to the Prelog-Djerassi lactone and a tylosin fragment have also been published.'62 The metal is used in two alkylations so affording control of relative stereochemistry a feature made possible through the use of a seven-membered ring Fe(CO),[P(OPh),] complex which allows hydride abstraction to be employed to re-form the q5-bonding mode after the first nucleophile addition.With cyclohexadienyl complexes of this type this reaction is not normally possible. Recently an alternative based on OMe removal has been described. When used with complexes obtained by microbial deoxygenation of prochiral arenes this process provides convenient access to opti- cally pure complexes for use in double alkylation sequence^.'^ Complexes capable of hydride abstraction by an electron transfer process also offer a method to overcome difficulties experienced in returning to the state.'^^ Replacement of Fe(CO) by the isoelectronic fragment Fe(C6H6) however requires work with complexes for which the development of applications in organic synthesis is less well advanced.The annelation of (85) by reaction with anisidine (86; R' = R2 = H R3 = OMe) (Scheme 23) shows great promise as an entry to alkaloid ~ynthesis.'~~ Access to aryl-substituted tricarbonyl( cyclohexadieny1)iron cation complexes has also been explored.'66 OMe I OMe 0 (85) R2 Scbeme 23 In a reaction employing alkynyl higher order cuprates Donaldson describes the preparation of (88). With silylacetylides-KI-KF and the cation (87) a transoid product is obtained. The position of nucleophile addition is also dependent on the nature of the nucleophile since malonate addition has been found to give the 162 A.J. Pearson Y.-S.Lai W. Lu and A. A. Pinkerton J. Org. Chem. 1989 54 3882. 163 P. W. Howard G. R. Stephenson and S. C. Taylor J. Organomet. Chem. 1989 370 97. '6.1 D. Mandon and D. Astruc Organometallics 1989 8 2372. 165 H.-J. Knolker R. Boese and K. Hartmann Angew. Chem. Znt. Ed. Engl. 1989 28 1678. 166 D. A. Owen G. R. Stephenson H. Finch and S. Swanson Tetrahedron Lett. 1989 30 2607. Organometallic Chemistry -Part (i) The Transition Elements 25 1 a,wallyl product (89).16' Although precedented with other metal-ligand systems [a recent example is the alkylation of the ruthenium complex (90) with methyl- lithium168] this mode of addition is new in the Fe(CO) series of acyclic diene complexes. A second example involving addition of a phosphorus nucleophile is cited in a recent review.'69 C02Me I q6-Complexes.-While historically they are the most extensively studied q6-com- plexes Cr( CO) derivatives offer relatively modest activation as electrophiles.Although the promotion of nucleophilic replacement of chlorine in chlorobenzene complexes is a popular application of the electrophilicity of these complexes the direct replacement of hydrogen in the same way is not p~ssible.'~' Nucleophile addition produces an anion that must be oxidized removing the metal to effect aromatization. A recent application of this method is the arylation of lithi~amides."~ Successful preparation of pyridine complexes by the complexation of 2,5-bis(trimethylsily1)pyridine offers methods to effect a type of nucleophile addition process that would not be possible by other means.Nucleophile addition occurred at C-2 and the resulting anionic intermediate could be alkylated at nitrogen to form (91).'72 R (ii) Me1 CN-Me I ,I Cr(CO)3 Cr(C0)3 (91) Cationic FeCp q6-complexes provide more powerful electrophilic reagents. Both nucleophile addition reactions173 and halogen substitution from aromatic rings174 167 W. A. Donaldson and M. Ramaswamy Tetrahedron Lett. 1989 30 1339; 1343. 168 J. R. Bleeke and D. J. Rauscher J. Am. Chem. SOC.,1989 111 8972. 169 R. Grie Synthesis 1989 341. 170 S. Ostrowski and M. Mgkosza J. Organomet. Chem. 1989 367 95. 171 L. Keller K. Times-Marshall S. Behar and K. Richards Tetrahedron Lett. 1989 30 3373.172 S. G. Davies and M. R. Shipton J. Chem. SOC.,Chem. Commun. 1989 995. 173 S. L. Grundy A. R. H. Sam and S. R. Stobart J. Chem. SOC.,Perkin Trans. I 1989 1663; R. G. Sutherland C. H. Zhang A. Piirrko and C. C. Lee Can. J. Chem 1989,67 137. 174 C. C. Lee C. H. Zhang A. S. Abd-El-Aziz A. Pibrko and R. G. Sutherland J. Orgunomet. Chem. 1989 364,217. G. R. Stephenson have been examined. In studies related to organometallic routes to the thyromimetic compound SK&F L-94901 addition of the anion (93) to (92) afforded a C-2 adduct that was converted into (94) by oxidation with DDQ (Scheme 24).'75 c1 + FeCp Cl (92) (93) (94) 27% Reagents i -78 "C 15 min.; ii DDQ Scheme 24 Electrophilic [Mn(CO),]+ complexes have been more widely used in organic synthesis.Most recent developments here concern the addition of chiral nucleophiles to prochiral complexes. Both 1 ,3-176 and 1,4-177 disubstitution patterns have been examined. Pearson has applied his use of the Schollkopf chiral enolate equivalent to complete a synthesis of diphenyl ether aminoacid derivatives that make double use of the metal to promote rea~ti0n.l'~ 6 Reactions Adjacent to Transition Metal w-Complexes Organometallic ncomplexes can serve as stereodirecting groups to impose control in reactions of conventional functionality. Generally the best stereocontrol is achieved when the site of reaction is adjacent to the .rr-complex. This approach provides the key to a synthesis of intermediates for 5,6-diHETE.By osmylation the unbound portion of the v4-triene unit in (95) was converted diastereoselectively into the diol (96) without removal of the Cyclization of nitrile oxides to q4-triene complexes also shows good diastereo~electivity.'~~ The reaction has been applied in a stereoselective synthesis of (+)-( S)-[6] -gingerol.18' The availability of tricarbonyliron complexes in optically active form is an important aspect of this Fe(CO)3 175 R. C. Cambie S. J. Janssen P. S. Rutledge and P. D. Woodgate J. Organomet. Chem. 1989,359 C14. I76 A. J. Pearson P. R. Bruhn F. Gouzoules and S.-H. Lee J. Chem. SOC.,Chem. Commun.,1989 659. 177 W. H. Miles P. M.Smiley and H.R. Brinkman 1. Chem. SOC.,Chem. Commun.,1989 1897. 178 A. Gigou J.-P. Lellouche J.-P. Beaucourt L.Toupet and R. Grke Angew. Chem. Int. Ed. Engl. 1989 28,755. 179 T. Le Gall J.-P. Lellouche L.Toupet and J.-P. Beaucourt Tetrahedron Lett. 1989 30,6517. 180 T. Le Gall J.-P. Lellouche and J.-P. Beaucourt Tetrahedron Letf. 1989 30,6521. Organometallic Chemistry -Part (i) The Transition Elements 253 work. Recently a survey of CD spectra of a range of complexes has been made to support assignments of absolute configuration.'81 Nucleophile addition to an aldehyde adjacent to the r-complex has been combined with a vanadium-catalysed epoxidation of the resulting ally1 alcohol to relay chirality to further oxygenated centres.'82 In a new development trimethylenemethane complexes have been employed adjacent to the aldehyde with very good diastereo~electivity.'~~ Stereoselective reaction next to q6-arene complexes is also a popular technique.The method has been extended to the use of silyl enolethers with BF3 catalysis a reaction that proceeds with excellent diastereoselectivity which is typically better than 90%.'84 [2,3]-Wittig rearrangements have also been examined.18' Microbiology and metal complexes mix when yeast reduction of ketones in arene .rr-complexes is used for the preparation of optically active benzyl alcohol com- plexes.'86 Alternative access to such compounds is provided by diastereoselective complexation of optically active benzyl alcohols. Monocyclic systems have been examined.'87 The alcohol can subsequently be displaced by nucleophiles in diastereoselective reactions that proceed by the generation of carbenium ion centres next to and stabilized by the metal complex.'8s The process has been applied to the synthesis of optically active tetrahydrobenzapines by the intramolecular intercep- tion of the carbenium ion by an electron-rich aromatic ring.'89 Use of mild conditions in the complexation step enables efficient chirality transfer during complexation to occur when the alcohol control group is at the p-position.Uemura's group has been at the forefront of work exploring long-range chirality relay from chromium complexes. Stereocontrol has now been achieved as far as five carbons along the chain by use of Claisen reactions as seen in the formation of (97) (Scheme 25). Conversion of (98) into (99) employs the chromium complex directly.Alternatively hydrolysis of the acetal in (97) alkylation of ketone and ionic reduction produced the epimer at the a-po~ition.'~~ This year several papers have been published describing reactions at carbonyl groups adjacent to Co,(CO) alkyne complexes. Enolates,'" silyl enolether~,'~ and allyl~tannanes'~~ have been employed as nucleophiles. 7 Alkylation of Organometallic Anions The use of anionic metal v-complexes in organic synthesis is less well developed than methods in which the organometallic portion is the electrophile. Nonetheless 181 F. Djedaini D. GrCe J. Martelli R. GrCe L. Leroy J. Bolard and L. Toupet Tetrahedron Lett. 1989 30 3781. M. Laabassi and R. GrCe Tetrahedron Lett. 1989 30 6683. I83 M. Franck-Neumann D.Martina and M.-P. Heitz Tetrahedron Lett. 1989 30 6679. 184 C. Mukai W. J. Cho and M. Hanaoka Tetrahedron Lett. 1989 30 7435. 185 M. Vemura H. Nishimura and Y. Hayashi J. Organomet. Chem 1989 376 C3. 186 J. Gillois G. Jaouen D. Buisson and R. Azerad J. Organomet. Chem. 1989 367 85. 187 J. Brocard L. Pelinski J. Lebibi M. Mahmoudi and L. Maciejewski Tetrahedron 1989 45 709. 188 S. J. Coote S. G. Davies D. Middlemiss and A. Naylor J. Chem. SOC.,Perkin Trans. 1 1989 2223. 189 S. J. Coote S. G. Davies D. Middlemiss and A. Naylor Tetrahedron Lett. 1989 30 3581. 190 M. Uemura T. Minami K. Hirotsu and Y. Hayashi J. Org. Chem. 1989 54 469. 191 C. Mukai K. Nagami and M. Hanaoka Tetrahedron Lett. 1989 30 5627. 192 C. Mukai K. Nagami and M.Hanaoka Tetrahedron Lett. 1989,30,5623; J. Ju B. R. Reddy M. Khan and K. M. Nicholas J. Org. Chem. 1989 54 5426. 193 J. A. Marshall and W. Y. Gung Tetrahedron Lett. 1989 30 309. G. R. Stephenson 0 1iii-v n OAc Me I\ Me O\ P OMe Reagents i mCr(CO)3; ii ClOCCH,OMe; iii LDA; iv Me,SiCl; v CH,N,; vi Me3AI \ _. Scbeme 25 many features are similar-although of course polarity is reversed. Reaction can occur either at or adjacent to the wcomplex and generally proceeds with a high degree of stereocontrol so offering attractive possibilities for synthetic applications. The anionic cycloheptatrienyl complex of Fe(CO) has been examined in reactions with 2-chlorotrop0ne.'~~ The ally1 anion complex itself [(C,H,)Fe(CO),]- under-goes a rather more unusual reaction with alkyl halides promoting carbonyl insertion and acyl transfer initiated presumably by reaction of the electrophile at the metal centre.Enone products are obtained in yields of between 60 and 90%.'95Phenoxide complexes of Cr(C0)3 react with (tol)SO,C1 or CR3COCl but with organometallic electrophiles electron transfer rather than bond formation occurs.196 Use of charge- stabilizing groups on the hydrocarbon ligand has been a popular strategy to promote useful alkylation reactions. A new example employs the unusual ketone complex (100). Formation of an enolate extends conjugation into the metal ?r-complex producing an anion that can be alkylated stereoselectively. When this technique is combined with metal-controlled reduction of the ketone and removal of the metal 194 M.Nitta M. Nishimura and H. Miyano J. Chem. Soc. Perkin Trans. 1 1989 1019. 195 M. Brookhart J. Yoon and S. K. Noh J. Am. Chem. Soc. 1989 111 4117. 196 J. A. Heppert T. J. Boyle and F. Takusagawa Organornetallics 1989 8 461. Organometallic Chemistry -Part (i) The Transition Elements the organic product (101) has a run of four adjacent alternating chiral centres (Scheme 26).'97 Anionic centres adjacent to metal arene complexes also react with good stereo~ontrol.'~~ (100) Reagents i LDA MeI; ii NaBH,; iii Br, NaSPh Scheme 26 Lithiated organometallic complexes particularly chromium arene complexes are important as anionic reagents. A typical example is the use of an organochromium intermediate in a synthesis of (+)-lambertic acid.'99 Reactions of dilithiated arene complexes (Li,C,H,)Cr(CO) ,have also been examined.200 8 Carbene Complexes Rhodium Catalysis of Reactions of Carbene Complexes.-Insertion Reactions.In its applications in organic synthesis much of the recent development of rhodium catalysis of carbene chemistry has focused on the utility of carbene insertion reactions. Generated most usually from diazoketones and esters the carbene complex is able to promote reactions at positions that are not normally reactive in synthetic bond formation reactions. This can provide a most efficient tool in organic synthesis avoiding the need for additional activating functionality. Rhodium-catalysed routes to cyclic ethers by insertion into C-H bonds provides a typical recent example.'01 The diastereoselectivity of this process has been explored.'" Insertion into 0-H bonds provides an effective route from lactones to cyclic ethers which benefits from the ease of introduction of the diazoester by addition of lithiodiazoacetate to the la~tone.~'~ A similar insertion step has been used in an approach to ~oapatanol.''~ Cyclopropanation.In the combination of carbenes with alkenes to form cyclopro- panes the use of copper catalysts is now being displaced in popularity by methods employing rhodium. Some impressive new developments have occurred this year. Vinyl ethers for example can be converted into cyclopropanes with substantial diastereoselectivity sometimes as high as 20 1.In the case of (102) the product 197 A. J. Pearson and M. W. D. Perry J. Chem. SOC. Chem. Commun. 1989 389; A. J. Pearson and R. Mortezaei Tetrahedron Let?. 1989 30 5049. 198 S. J. Coote S. G. Davies D. Middlemiss and A. Naylor J. Organomet. Chem. 1989 379 81; J. Albert and S. G. Davies Tetrahedron Lett. 1989 30 5945. 199 M. Node X.-J.Hao H. Nagasawa and K. Fuji Tetrahedron Lett. 1989 30 4141. 2oo M. E. Wright Organometallics 1989 8 407. 201 J. Adarns M.-A. Poupart L. Grenier C. Schaller N. Ouimet and R. Frenette Tetrahedron Lett. 1989 30 1749. 202 J. Adams M.-A. Poupart and L. Grenier Tetrahedron Lett. 1989 30 1753. 203 C. J. Moody and R. J. Taylor J. Chem. SOC.,Perkin Trans. 1 1989 721. 204 M. J. Davies J. C. Heslin and C.J. Moody J. Chem. SOC.,Perkin Trans. 1 1989 2473. 256 G. R. Stephenson was converted into the tmns-substituted cyclopentene (103) in 61% overall yield for the two steps (Scheme 27).205Carbene addition to pyrroles requires an electron- withdrawing group on the pyrrole nitrogen otherwise insertion into the C-H bond at C-2 is preferred.'06 Similar addition to furan rings has been used for the formation of 1,Cdiacyl diene unit in a synthesis of the antileukaemic fatty acid ostopanic acid.'07 Intramolecular examples of additions to furan rings give access to cyclopen- tenone derivatives and phenols; with thiophenes bicyclic thiophene derivatives have been obtained.208 CO2Et q;-t CO2Et -+ Bu"0 + "'1 CO,Et CO2Et Et02C' (102) (103) Reagent i Rhz(OAc),; ii distillation Scheme 27 Stoicheiornetric Carbene Complexes.-Alkyne and Carbon Monoxide Insertion.The combination of coupling of carbene complexes and alkynes with a carbonyl insertion step has provided regiocontrolled routes to polysubstituted arenes that are bcoming increasingly popular with synthetic chemists. Contributions from both Dotz and Wulff originators of the use of this chemistry in organic synthesis and Yamashita's team at Upjohn provide fine examples of new developments. Wulff's group has been exploring new routes to alkaloid synthesis; for example the formation of (104) in OMOM (,,OM I OMe I. Me Me OMe (104) 59% which creation of a quaternary centre prevents aromatization of the newly formed ring.'09 Dotz in extending the reaction to carbon-phosphorus triple bonds has described new routes to 1,3-oxaphospholes in which the carbonyl insertion step is omitted.210 Yamashita has employed the original version of the reaction which typically forms hydroquinone monoethers in his two routes for the synthesis of khellin and its analogues full details of which have now been published.'" Both 205 H.M. L. Davies T. J. Clark and L. A. Church Tetrahedron Lett. 1989 30 5057. 206 H. M. L. Davies W. B. Young and H. D. Smith Tetrahedron Left. 1989 30 4653. 207 J.-H. Sheu C.-F. Yen H.-C. Huang and Y.-L. V. Hong J. Org. Chem. 1989 54 5126. 208 A. Padwa T. J. Wisnieff and E. J. Walsh J. Org. Chem. 1989 54 299. 209 W. E. Bauta W. D. Wulff S. F. Pavkovic and E.J. Zaluzec J. Org. Chem. 1989 54 3249. 210 K. H. Dotz A. Tiriliomis and K. Harms J. Chem. SOC.,Chem. Commun. 1989 788. 211 A. Yamashita A. Toy and T. A. Scahill J. Org. Chem. 1989 54 3625. Organometallic Chemistry -Part (i) The Transition Elements employ the addition of alkynes to a furan-methoxycarbene complex. With thioether- substituted carbene complexes regioselective preparation of 4-oxygenated aryl thioethers is possible. This has the advantage of later allowing the selective removal of the sulphur substituent as seen in a synthesis of visnagan.212 Although the mechanism of the chromium carbene cyclization reactions is unproven a generally accepted proposal is that the process begins by loss of CO to allow binding of the alkyne so initiating the formation of a metallocyclobutane intermediate.A recent theoretical investigation suggests that such an intermediate should be puckered not planar a conclusion which will influence the way in which subsequent stereochemical control is explained.213 When carbenes and alkynes are combined within the same molecule heating can promote coupling with a second alkyne to promote cyclization forming either phenols or cycl~pentenediones.~~~ Alkenes can also be combined with chromium carbenes in an intramolecular fashion to form CI-(CO)~ In another complexes of indan~nes.~'~ example of the same type of reaction X-ray crystallography has been used to establish the relative stereochemistry of the product ( 105).216Intermolecular reac- tions between the chromium carbene complex and an a,w-enyne have also been examined.These reactions give rise to either 5,3-fused ring systems or phenol derivatives depending on the substitution pattern on the alkene and the length of the strap joining the two reaction centres in the hydr~carbon.~" Cyclopropanation Reactions. Studies of asymmetric cyclopropanation using stoicheiometric iron complexes which are chiral at the iron atom have received considerable attention this year. Partial resolution of methyl and ethyl phosphine complexes (106) has been followed by asymmetric transfer of the CHMe portion to vinyl acetate which proceeded in good optical yields but lacked diastereoselec- tivity in the formation of (107) and ( 108).218The carbene complex (109) has been cp\ Me Me OAc R3P-/Fe+y R' - t$* v + OC H (107) (108) (106) R' = Me (109) R' = Ph 212 A.Yarnashita A. Toy N. B. Ghazal and C. R. Muchrnore J. Org. Chem. 1989 54 4481. 213 P. Hofmann and M. Harnrnerle Angew. Chem. Int. Ed Engl. 1989 28 908. 214 Y.-C. Xu C. A. Challener V. Dragisich T. A. Brandvold G. A. Peterson W. D. Wulff and P. G. Williard J. Am. Chem. SOC.,1989 111 7269. 215 C. Alvarez A. Parlier H. Rudler R. Yefsah J. C. Daran and C. Knobler Organometallics 1989,8,2253. 214 K. H. Dotz H.-G. Erben and K. Harms J. Chem. SOC.,Chem. Commun. 1989 692. 217 T. R. Hoye and G. M. Rehberg Organometallics 1989 8 2070. 218 M. Brookhart and Y. Liu Organometallics 1989 8 1572. 258 G. R. Stephenson used for benzylidine transfer to propene again mixtures of diastereoisomers were produced.At present vinyl acetate in reaction with (109) has given the best results showing 4 1 diastereoselectivity in favour of the cis-i~orner.~~’ Use of the penta- methylcyclopentadienyl ligand in the carbene complex has improved reactivity in the cyclopropanation of alkenes.220 Another variant using chromium carbene com- plexes employs photolytic conditions to promote cyclobutanone formation rather than cyclopropane formation introducing the extra carbon by carbonyl insertion.221 Carbene Complexes US Electrophiles. Cationic carbene complexes of the type dis- cussed above in reactions with alkenes can function in general as electrophiles when exposed to nucleophilic reagents.222 An example from the work of Helquist’s group illustrates the utility of this type of reaction in synthesis when combined with other processes in this case cyclopropanation or cyclization by C-€3 insertion reactions.For example conjugate addition to cyclohexenone is followed by enolate trapping using the electrophilic carbene complex (110). The adduct (1 11) can be converted into a second carbene complex by reaction with Me,O+ so promoting the cyclization step (Scheme 28).223 iii 4 (111) 50% 90% Reagents i CuBr; ii FG=CHSPh (110); iii Me,O+ Scheme 28 Copper/zinc carbene derivatives have been used in Knochel’s group as sources of C-1 fragments first by nucleophile addition to the carbene derivative then by electrophilic attack on the ~l-intermediate that is formed.This has the overall effect of introducing a CH2 group in between the nucleophile and the ele~trophile.~~~ Carbene Complexes as Nucleophiles. Carbene complexes are converted into nucleophiles by deprotonation to form metal-stabilized carbanions which are struc- turally related to the metal acyl-derived enolates discussed in Section 2. Wulff et al. have demonstrated that pyrrolidine substitution in the carbene complex improves the efficiency of alkylation reactions; for example the formation of (112) (Scheme 29).225 219 M.Brookhart and R. C. Buck J. Organomet. Chem. 1989 370 111. 220 M. N. Mattson J. P. Bays J. Zakutansky V. Stolarski and P. Helquist J. Org. Chem. 1989 54 2467. 22 1 M. A. Sierra and L. S. Hegedus J.Am. Chem. Soc 1989 111 2335. 222 G. N. Glavee Y. Su R. A. Jacobson and R. J. Angelici Znorg. Chim. Ac~Q, 1989 157 73; S. A. Levitre A. R. Cutler and T. C. Forschner Orgunometullics 1989 8 1133. 223 S.-K. Zhao C. Knors and P. Helquist J. Am. Chem Soc. 1989 111 8527. 224 P. Knochel N. Jeong M. J. Rozema and M. C. P. Yeh J. Am. Chem. Soc. 1989 111,6474. 225 W.D. Wulff B. A. Anderson and L. D. Isaacs Tetrahedron Lett. 1989 30,4061. Organometallic Chemistry -Part (i) The Transition Elements Similar methods have been used to promote equivalents of aldol reactions by oxidative removal of the carbene complex after the nucleophile addition step. In an alternative metal removal photolysis promotes carbonyl insertion and cyclization to form a-aminolactones such as (113) (Scheme 29).226 (112) 76% NMe2 Me MetPh (113) 56% .I 80-94% Ph Reagents i LDA; ii -Me ;iii Bu"Li; iv 09 Me Scheme 29 W.D. Wulff B. A. Anderson and A. J. Toole J. Am. Chem. SOC.,1989 111 5485.

ISSN:0069-3030    

DOI:10.1039/OC9898600227

出版商:RSC    

年代:1989

数据来源: RSC

摘要:

9 Organometallic Chemistry Part (ii) Main-Group Elements By P. D. LlCKlSS Department of Chemistry and Applied Chemistry University of Salford Salford M5 4WT Main-group organometallic chemistry continues to thrive with the fields of multiple bonding between heavier main-group elements and reactive intermediate chemistry continuing to grow and ‘precursor’ chemistry in which novel organometallic monomers are prepared as precursors to either ceramic materials or polymers is becoming a field in its own right. Vigorous growth also continues in the field of preparation and characterization of unusual organolithium reagents. A new book’ gives excellent coverage of most aspects of main-group chemistry. The format of this Report is the same as that of last year concentrating mainly on new structural features and novel or potentially useful reactions.Once again much of interest has been excluded because of the limited space available. 1 Group I Three new indicators N-pivaloyl-o-toluidine,2 N-pivaloyl-o-benzylamine,2and PhTeTePh,3 are proposed as reagents for the direct titration of organolithium reagents. The compounds are all stable simple to prepare give sharp end points and should prove useful to those who regularly titrate for example commercially supplied Bu”Li. The cleavage of THF by organolithium reagents is a common problem and has often limited the situations in which this very useful solvent can be used. Such cleavage is greatly reduced by the addition of Mg(CH2CH20Et) to the reaction solution allowing for example Bu‘Li and C6H11Li to be prepared readily in THF.4 The investigation of organolithium reagent structure by X-ray crystallography and NMR spectroscopy continues to reveal various novel structural features.Fast- atom-bombardment mass spectrometry has also been used to determine the degree of aggregation of RLi compound^.^ The first structural characterization of a non- conjugated 1,2-dilithioethane has been carried out.6 Treatment of tetrakis (trimethyl- sily1)ethylene with lithium metal affords 1,2-dilithio[tetrakis(trimethylsilyl)]ethane which can be isolated as a yellow crystalline THF adduct. The lithium atoms are ’ Ch. Elschenbroich and A. Salzer ‘Organometallics’ VCH Weinheim FRG 1989. J. Suffert J. Org. Chem. 1989,54 509. Y. Aso H.Yamashita T. Otsubo and F. Ogura J. Org. Chem. 1989 54 5627. C. G. Screttas and B. R. Steele J. Org. Chem. 1989 54 1013. A. K. Abdul-Sada A. M. Greenway and K. R. Seddon J. Organomet. Chem. 1989 375 C17. ‘A. Sekiguchi T. Nakanishi C. Kabuto and H. Sakurai J. Am. Chem. SOC.,1989 111 3748. 261 262 P. D. Lickless each coordinated to the two central carbons and an oxygen of a THF molecule the average C-C bond length is 1.597 A. The solid-state structure of 1-1ithio-2-methoxybenzene' consists of tetrameric units in which the four lithium atoms form a pyramid with a lithiated arylcarbon being found above each triangular face and bonded to the three lithium atoms forming the face. There also appeardo be short Li...HC interactions between a lithium and an aryl hydrogen in a different tetramer.Use of 6Li NMR spectroscopy shows that the tetrameric structure remains intact in toluene-d solution but on addition of TMEDA dimers are formed and addition of N,N,N',N',N"-pentamethyldiethyl-enetriamine leads to monomer formation. In the solid 1,l-bis[ (dimethyl- amino)methyl]-2-propyllithium' comprises dimeric units in which the lithium atoms are in an Li2C ring and are also coordinated to dimethylamino groups. In n-pentane- d12solution two dimeric species are present the major one appears to have the same structure as that in the solid state (in which the a-methyl groups are trans to each other) while the minor one is very similar but has the a-methyl groups in a cis arrangement. The first trimeric organolithium compound [2.6-bis(dimethyl- amino)phenyl]lithium has been characterized in both solid and solution states.The solid-state structure comprises a triangle of lithium atoms bridged by aryl carbanions with the NMe substituents being intramolecularly coordinated to the lithium atoms. In non-polar solvents such as toluene the trimeric structure is also favoured but in THF a monomer-trimer equilibrium OCCU~S.~ Both 2-lithiobenzofuran-TMEDA and 2-lithiobenzothiophene-TMEDA are dimeric in the solid state with benzofuryl rings bridging the lithium atoms and TMEDA acting as a chelating ligand. NMR spectroscopy also shows both com- pounds to be dimeric in solution." Surprisingly both the solid- and solution-state structures of Ph2PCH2Li-TMEDA have been shown" to be monomeric with the lithium being only three-coordinate bonded to the CH group and chelated by the TMEDA.Several a -or y-phosphorus functionalized alkyllithiums e.g. [(Li(TMEDA)(CH,PMeR)},] (R = Me or Ph) have been prepared by addition of Bu"Li to the appropriate phosphine.12 The solid-state structure of the benzyllithium adduct [q1-C6H5CH2]Li.THF.TMEDA has been found (in contrast to other adducts which are polymeric) to be monomeric with the lithium being coordinated to only the benzylic carbon of the benzyl group the oxygen of the THF molecule and the two nitrogens of the TMEDA molec~le.'~ Treatment of Me,SiCH2CN with either Bu"Li or Pr:NLi affords Li2( Me,SiCCN) (A) which co-crystallizes from the reaction solution together with one molecule ' S.Harder J. Boersma L. Brandsma G. P. M. van Mier and J. A. Kanters J. Organomet. Chem. 1989 364,1. W. Moene M. Vos F. J. J. De Kanter G. W. Klurnpp and A. L. Spek J. Am. Chem. SOC.,1989 111 3463. S. Harder J. Boersma L. Brandsma J. A. Kanters W. Bauer and P. von R. Schleyer Organomefallics 1989 8 1696. lo S. Harder J. Boersma L. Brandsma J. A. Kanters W. Bauer R. Pi P. von R. Schleyer H. Schollhorn and U. Thewalt Organometallics 1989 8 1688. G. Fraenkel W. R. Winchester and P. G. Willard Organometallics 1989 8 2308. 12 L. T. Byrne L. M. Engelhardt G. E. Jacobsen W.-P. Leung R. I. Papasergio C. L. Raston B. W. Skelton P. Twiss and A. H. White J. Chem. SOC.,Dalfon Trans. 1989 105. 13 W. Zarges M. Marsch K. Harms and G. Boche Chern. Ber.1989 122 2303. Organometallic Chemistry-Part (iii) The Main-Group Elements 263 of hexane as the complicated aggregate [(A)12(Et20)6(C6H14)],14 a structure significantly different to monolithium nitriles. Several silyllithium reagents have been investigated with the X-ray crystal struc- ture of (thf),Li(SiPh,),Li(thf) being determined15 and treatment of 2,4,6-tri-t- butylphenyllithium with halogenosilanes affording LiSiC1 .16 The bulky (mesityl),HSiLi(thf) can be prepared as a useful reagent by treatment of (mesityl),SiHCl with lithium powder.17 Methylenecyclopropane reacts with lithium powder to give the stable dilithium reagent 2,4-dilithio but- 1-ene rather than the trimethylenemethane dianion.18 The new lithium reagent Me,SiCHLiSi(OMe)Me can readily be prepared by treatment of the parent hydrocarbon with Bu'Li.The reagent effects direct conversion of enolizable or non-enolizable aldehydes and ketones into synthetically useful vinyl- silanes and promises to be a useful alternative to (Me3Si),CHLi which is only suitable for non-enolizable substrates.'' The radical anion reductive metallation of phenyl thioethers to give organolithium compounds has been reviewed.,' Reductive lithiation of (RO),( PhS)CH species and transmetallation of (RO),( Bu;Sn)CH com-pounds both yield the previously unavailable simple (dialkoxymethy1)lithium reagents (RO),CHLi (R = Me Et etc.) which are useful as one-carbon nucleophiles.21 The reaction of [( Me3Si),C5H2]Li and related lithium reagents with various Lewis bases such as ethers amines and thioethers affords crystalline adducts which are monomeric in solid solution and gas phases., In the solid state there is an unusual almost linear arrangement of the ring centroid of the cyclopentadienyl group the lithium and the oxygen of the THF molecule in [(Me3Si)3C5H2]Li-THF.The disodium compound [Ph,CCPh2]Na2.(OEt2) is formed as a green solid when Ph2C=CPh2 is treated with sodium metal. The solid-state structure of the compound is complicated with the two sodium atoms in different environments one in which the sodium is sandwiched between four aryl rings two from one dianion and two from a second and another in which the sodium coordinates with two ether molecules and one diani~n.,~ Another sodium reagent [PhNa( PMDTA)] ,in contrast to its monomeric lithium analogue LiPhSPMDTA has a dimeric structure with the ips0 carbons of the phenyl rings and the sodium atoms forming a four-membered ring and each sodium being coordinated by a single PMDTA.24 The organopotassium compound K[ q5-C5(CH2Ph)5].3THF has been prepared by treatment of pentabenzylcyclopentadiene with potassium.X-Ray crystallography gives a K-C(ring) average distance of 3.035& somewhat shorter than that in KCH (3.22 A) but similar to that in K[C5H4SiMe,] (3.00 14 W. Zarges M. Marsch K. Harms and G. Boche Chem. Ber. 1989 122 1307. l5 G. Becker H. M. Hartmann E. Hengge and F. Schrank 2. Anorg. AZZg. Chem. 1989 572 63. 16 H. Weiss and H. Oehme 2. Anorg. AZlg. Chem. 1989 572 186. D. M.Roddick R. H. Heyn and T. D. Tilley Organometallics 1989 8 324. 18 A. Maercker and K.-D. Klein Angew. Chem. Znt. Ed. EngZ. 1989 28 83. 19 T. F. Bates and R. D. Thomas J. Org. Chem. 1989 54 1784. 20 T. Cohen and M. Bhupathy Ace. Chem. Res. 1989 22 152. 21 C. S. Shiner T. Tsumoda B. A. Goodman S. Ingham S.-H. Lee and P. E. Vorndam J. Am. Chem Soc. 1989 111 1381. 22 P. Jutzi W. Leffers S. Pohl and W. Saak Chem. Ber. 1989 122 1449. 23 H. Bock K. Ruppert and D. Fenske Chem. Ber. 1989 122 1685. 24 U. Schiimann U. Behrens and E. Weiss Angew. Chem. Znt. Ed. EngZ. 1989 28 476. 25 J. Lorbeth S.-H. Shin S. Wocadlo and W. Massa Angew. Chem. Znt. Ed. EngZ. 1989 28 735. 264 P. D. Lickless 2 Group I1 The first two-coordinate organomagnesium compound ( Me3Si)3C-Mg-C(SiMe3)3 to be characterized in the solid state has an Mg-C bond length of 2.116(6) % and a linear C- Mg-C arrangement.26 A second unsolvated alkylmagnesium species [(Np2Mg)2-(NpMgBr)2], (Np = Me3CCH2) can be prepared by reaction of NpBr with magnesium in ether and has the polymeric structure shown in Scheme 1.27 Scheme 1 Several novel sodium organomagnesates e.g.[ Na(PMDTA)],[MgPh,] (1) and Na2[ Mg(C-CBu'),(TMEDA),] (2) have been prepared and characterized by X-ray crystallography.** Compound ( 1) has tetrahedral geometry at magnesium with the phenyl groups forming unsymmetrical bridges between magnesium and sodium and (2) has tram alkynyl groups coordinated to magnesium in a pseudo-octahedral environment. Each four-membered ring is perpendicular to its neighbours and the rings are unsymmetrical having Mg-C bonds between 2.20 and 2.42 A.Another example of an X-ray crystal structure determination of an alkylmag- nesium compound is [ v3-HB(3-Bu'pyz),]MgMe which can be prepared by treatment of Me2Mg with T1[ HB(3-B~'pyz)~l.~~ Surprisingly when treated with 13CH31 the methylmagnesium compound not only gives the alkylation product I3CH3CH3but also the MgL3CH3 derivative derived from alkyl exchange. The role of free radicals in the mechanism of Grignard reagent formation has been further studied and firm evidence provided that radicals are strongly adsorbed onto the magnesium metal surface and are therefore not free to diffuse in solution readily.30 A detailed study of the reaction between cycloheptyl bromide and mag- 26 s.s. Al-Juaid C. Eaborn P. B. Hitchcock C. A. McGeary and J. D. Smith J. Chem. Soc. Chem. Commun. 1989 273. 27 P. R. Markies G. Schat 0.S. Akkerman F. Bickelhaupt W. J. J. Smeets A. J. M. Duisenberg and A. L. Spek J. Organomet. Chem. 1989 375 11. 28 M. Geissler J. Kopf and W. Weiss Chem. Ber. 1989 122 1395. 29 R. Han A. Looney and G. Parkin J. Am. Chem. Soc. 1989 111 7276. 30 H. M. Walborsky and J. Rachon J. Am. Chem. Soc. 1989 111 1896. Organometallic Chemistry-Part (iii) The Main-Group Elements 265 nesium in ether provides clear evidence that cycloheptyl radicals are intermediates in the formation of cycloheptylmagnesium bromide.31 However the data could not be used to prove that the intermediate radical was not bound to the metal surface.The use of highly active magnesium allows convenient preparation of but-2-ene- 1 4-diylmagnesium compounds which are not readily available using conventional techniques and which can be used to prepare various useful cyclic products.32 The use of substituted cyclopentadienyl ligands has allowed the successful prepar- ation and structural characterization of several new organocalcium complexes. Thus treatment of Ca12 with MeSCSK results in the formation of a mixture of (77'-MeSC5)CaI(THF) and (775-Me5C5)2Ca(THF)2, from which the former can readily be isolated.33 The solid-state structure is dimeric with iodines bridging between calciums each of which is coordinated to one Me& and two THF ligands.The and complexes (775-Me5C,)2Ca.2THF [q5-1,3-(Me3C)2CSH3]2Ca-THF,[77'-(Me3Si),C5H5-,]2Ca-THF(n = 1or 2) have been prepared by treatment of calcium in liquid ammonia with the parent cyclopentadiene. X-Ray crystallography of [q5-(Me3Si),C5H312Ca.THF shows that the compound is a monomeric bent metal- locene with a THF molecule coordinated to the calcium.34 The bent metallocene structure has also been found in [qS-MeCSH4]2Ca.DME in which both DME oxygens are coordinated to the calcium.35 Co-condensation of metals Ca Sr or Ba with cyclooctatetraene (COT) and THF at -196 "C leads to formation of M(COT)(THF) species which decompose to give M(C0T) when heated to 60°C in U~CUO.~~ It is thought that the metal is bound to the ligand in a polyhapto fashion with the observed low solubility suggesting a polymeric structure.Treatment of calcium in liquid ammonia with COT also gives C a( C OT) .35 3 Group I11 Treatment of A12Br6 at -10°C with Bu'Li affords a mixture of [HAlBu:], [LiHAlBu:I2 and AlBu;. On treatment with further Bu'Li AlBu affords Li[AlBu\]. Both of the aluminium hydrides have been examined by X-ray crystallography; [HAlBu\] contains a planar six-membered Al-H ring while in [LiHA1Bu:l2 there are two lithium atoms bridging between the Al-hydrides to form an H2Li2 cyclic dimer.37 The reaction between ammonia and Me3AI and BuSAl gives the trimeric species [Me2A1NH2I3 and [BuiA1NH2l3 respectively both of which are potential precursors to aluminium nitride.38 Although the methyl derivative has a skew-boat ring conformation the tertiary butyl derivative has an unprecedented planar (AlN)3 ring which is presumably required to minimize 1,3-interactions between the bulky substituents on aluminium.The thermal decomposition of BuiAl above 470 K 3' K. S. Root C. L. Hill L. M. Lawrence and G. M. Whitesides J. Am. Chem. SOC.,1989 111 5405. 32 H. Xiong and R.D. Rieke J. Org. Chern. 1989 54 3247. 33 M. J. McCormick S. C. Sockwell C. E. H. Davies T. P. Hanusa and J. C. Huffman Organometallics 1989 8 2044. 34 P. Jutzi W. Leffers G. Muller and B. Huber Chem. Ber. 1989 122 879. 35 A. Hammel W. Schwarz and J. Weidlein. J. Organornet. Chern. 1989 378 347. 36 D. S. Hutchings P. C. Junk W. C. Patalinghug C. L. Raston and A. H. White J.Chern. SOC.,Chem. Cornrnun.,1989 973. " W. Uhl 2. Anorg. Allg. Chem. 1989 570 37. 38 L. V. Interrante G. A. Sigel M. Garbauskas C. Hejna and G. A. Slack Znorg. Chem. 1989 28 252. 266 I? D. Lickless proceeds via P-hydride elimination on an aluminium surface to give hydrogen isobutylene and a carbon-free crystalline layer of aluminium. This may therefore be a useful way to form A1 layers on electronic devices.39 Infrared spectra of matrix-isolated species provide the first good experimental evidence for an Me3Ga.AsH3 adduct the formation of which is usually proposed as the first step in the chemical vapour deposition of G~As.~' The chemistry of aminoalanes continues to attract considerable interest. The first six-coordinate alkylaluminium compound (3) has been prepared by treatment of Me,Al with N(CH,CH,OH) and comprises an A1406 array containing two six- coordinate and two four-coordinate aluminium atoms.41 A six-coordinate aluminium with octahedral coordination is also found in the product (4) of the reaction between 1,4,8,1l-tetraazacyclotetradecaneand Me3Al in the presence of ZrC14 .42 Me Me / \ Me Me Me/ 'Me (3) (4) Tetradentate amines also react with alkylaluminium compounds to form aminoalanes (5) and (6) containing Al,N and Al,NO four-membered rings and a central six-coordinate al~minium.4~ The reaction of Me3A1 with 3,3'-iminobispropy- lamine affords (7) as the sole product in which four organoaluminium units bridge between two amine ligands.44 39 B.E. Bent R. G. Nuzzo and L. H. Dubois J. Am. Chern. SOC.,1989 111 1634. 40 E. A. Piocos and B. S. Auk J. Am. Chem. Soc. 1989 111 8978. 41 M. D. Healy and A. R. Barron J. Am. Chem. Soc. 1989 111 398. 42 G. H. Robinson M. F. Self S. A. Sangokoya and W. T. Pennington J. Am. Chem. SOC.,1989,111,1520. 43 S. A. Sangokoya F. Moise W. T. Pennington M. F. Self and G. H. Robinson Orgunometullics 1989 8 2584. 44 G. H. Robinson F. Moise W. T. Pennington and S. A. Sangokoya Polyhedron 1989 8 1279. Organometallic Chemistry-Part (iii) The Main-Group Elements 267 Treatment of Me3Ga and Me,In with Me,Si-N=C=N-SiMe affords volatile 1 1 adducts but Me,AI gives a monomeric insertion product Me2Al( NSiMe,),CMe which contains a planar AlN2C ring system.45 Treatment of R3AI compounds (R = Me or Et) with (-)-ephedrine affords novel five-coordinate aluminium com- plexes in which the formation of the Al-N bond is stereospecific and leads to optical activity at the nitrogen while treatment with pyridine-2-thiol (PySH) affords crystalline head-to-head dimers [ R2AlPyS]2.47 Treatment of mesitylgallium derivatives with Cr(C0)6 or Mo(CO) leads to formation of a variety of metal complexes in which one or more M(CO) units are coordinated to mesityl groups; for example [(CO),Mb( q6-C6Me3H2),]Ga(C6Me3H2)3-n1 or 2).48 (n = The unusual tetraalkyl digallane and diindane derivatives [ { ( Me3Si),CH),Ml2 containing metal-metal bonds have been prepared by treating either Ga2Br4.2( dioxane) or In2Br4.2TMEDA with four equivalents of ( Me,Si),CHLi.The gallium compound forms yellow crystals with a Ga-Ga bond distance of 2.541 b~~~ while the indium analogue is orange-red and has an In-In bond length of 2.828 A." A series of '111-V' compounds (Me21nNR2) (R = Et Pri or Me,Si) and (M~,IIIPR~)~= But or Ph) have been prepared and shown to be dimeric in both (R the vapour and solid phase.'l Mass spectral studies indicated that increasing the size of the R group leads to a decrease in stability. The dimeric [Et,InPBu\] has also been structurally ~haracterized,~ again demonstrating the use of bulky ligands in reducing the degree of molecular association in organometallic compounds. The steric effects of the bulky mesityl group on the structures of arylindium compounds has been in~estigated.~ Trimesitylindium forms discrete monomers in the solid state with a possible agostic interaction between an ortho CH and indium the anion in [ Me,N][InCl(mesityl),] is also a discrete unit with a distorted tetrahedral geometry around indium and InCl(mesityl) forms centrosymmetric chloride-bridged dimers.Benzylindium compounds In(CH2Ph),C13- (n = 1 2 or 3) have been pre- pared.54In solution and in the vapour phase In(CH,Ph) exists as monomers while [ In(CH2Ph),C1] and [In( CH2Ph)C12] , probably contain chloride bridges. Several isopropylindium derivatives PriInCI Pr'InC1 and [ Pr\InNHBu'] have been pre- pared55 in the continuing search for simple molecules which may be used as precursors to indium in chemical vapour deposition processes.Neopentylindium compounds Np,In Np,InCl NpInCl, and Np,InMe (Np = Me3CCH2) have also been prepared using the reaction between NpMgCl and InI as a starting point. 45 R. Lechler H.-D. Hausen and J. Weidlein J. Organornet. Chern. 1989 359 1. 46 M. L. Sierra V. S. J. de Mel and J. P. Oliver Organornetallics 1989 8 2486. 47 R. Kurnar V. S. J. de Mel and J. P. Oliver Organornetullics 1989 8 2488. 48 0. T. Beachley jun. T. L. Royster jun. W. J. Youngs E. A. Zarate and C. A. Tessier-Youngs Organornetallics 1989 8 1679. 49 W. Uhl M. Layh and T. Hildenbrand J. Organornet. Chern. 1989 364,289. 50 W. Uhl M. Layh and W. Hiller J. Organornet. Chern. 1989 368,139. 5' K. A. Aitchison J. D. J. Backer-Dirks D. C. Bradley M. M. Faktor D.M. Frigo M. B. Hursthouse B. Hussain and R. L. Short J. Organornet. Chern. 1989 366,11. 52 N. W. Alcock I. A. Degnan M. G. H. Wallbridge H. R. Powell M. McPartlin and G. M. Sheldrick J. Organornet. Chern. 1989 361 C33. 53 J. T. Lernan and A. R. Barron Organornetallics 1989 8 2214. 54 A. R. Barron J. Chern. SOC. Dalton Trans. 1989 1625. 55 B. Neurniiller Chern. Ber. 1989 122 2283. 268 P. D. Lickless X-Ray crystallography shows that NpInC12 is a one-dimensional polymer [NpIn (p-Cl),lm with no interactions between polymer strands.56 Surprisingly reaction of alkylindium compounds such as Me,In and Et,In with alkyliridium complexes leads to In-C cleavage with addition products being formed. For example IrMe(PMe,) and InMe afford rner and fuc isomers of IrMe2(PMe,),(InMe2).57 Intramolecular coordination of the two nitrogen atoms to indium in Me[2,6- (Et2NCH2),C6H3]InC1 allows monomeric units with a distorted trigonal-bipyramidal geometry to be formed.,* The first example of a stable (alky1peroxo)indium com- pound Bu',InOOBu' can be prepared by the controlled addition of O2 to Bu~I~.,~ The compound is resistant to further oxidation and comprises dimers with bridging Bu'OO groups.Treatment of [2.2] paracyclophane with In[InBr,] or Tl[GaCl,] yields 1 1 adducts ( p-C6H,CH,CH2),.In[ InBr,] and (p-C6H4CH2CH2)2.fl[Gac14],respectively.60 q. Both compounds form sM(paracyc1ophane) M(paracyc1ophane)M. -one-dimensional stacks and are of high thermal and chemical stability. The solid- and gas-phase structures of the golden-yellow ($-C,Me,)In have been investigated.61 The gas-phase structure consists of monomers with the indium situated 2.288A above the ring centroid while in the solid state the structure comprises hexameric units with the six indium atoms forming an octahedral array with the Me,CF ligands coordinated around the outside with an indium-ring centroid distance of 2.302 A.The structure of [q5-(PhCH2),C5]In was found62 to be isostruc- tural with its thallium analogue comprising 'quasi-dimers' with an inversion centre between the two indium atoms and an In.-In distance of 3.631 A. Evidence for a Tl'-Tl' interaction in [(PhCH,),C,TI] is also supported by an MO analysis of the Treatment of TlCl with arylsilver reagents AgR (R = mesityl C6F3H2 or C6F5) affords complexes of the types [TlR2][T1C13R] TlClR, or TlR3 depending on the molar ratio of reagents used and the R The X-ray crystal structure of [Tl(mes),][T1C13(mes)] shows the linear [Tl(me~)~]+ cations and the tetrahedral [TlCl,(mes)]-anions to be linked by weak Tl-..Cl interactions into chains.4 Group IV Organosilicon chemistry is covered well in two new volumes65 and the crystal structure data for silicon compounds have also been the subject of a book.66 The 56 0.T. Beachley jun. E. F. Spiegel J. P. Kopasz and R. D. Rodgers Organometallics 1989 8 1915. 51 D. L. Thorn and R. L. Harlow J. Am. Chem. SOC.,1989 111 2575. 58 H. Schumann W. Wassermann and A. Dietrich J. Organomet. Chem. 1989 365 11. 59 W. M. Cleaver and A.R. Barron J. Am. Chem. SOC.,1989 111 8966. 60 H. Schmidbaur W. Bublak B. Huber J. Hofmann and G. Muller Chem. Ber. 1989 122 265. 61 0. T. Beachley jun. R. Blom M. R. Churchill K. Faegri jun. J. C. Fettinger J. C. Pazik and L. Victoriano Organometallics 1989 8 346. 62 H. Schumann C. Janiak F. Gorlitz J. Loebel and A. Dietrich J. Organomet. Chem. 1989 363 243. C. Janiak and R. Hoffmann Angew. Chem. In?. Ed. Engl. 1989 28 1688. 64 A. Laguna E. J. FernLndez A. Mendia M. E. Ruiz-Romero and P. G. Jones J. Organomet. Chem 1989,365 201. 65 'The Chemistry of Organic Silicon Compounds' ed. S. Patai and Z. Rappoport John Wiley Chichester 1989. 66 E. Lukevics 0. Pudova and R. Sturkovich 'Molecular Structure of Organosilicon Compounds' Ellis Horwood Chichester 1989.Organometallic Chemistry-Part (iii) The Main-Group Elements 269 chemistry of the Si-C bond for 198667 and 198768 has been reviewed as has the ‘direct synthesis’ of chlor0silanes,6~ the synthesis and synthetic potential of acyl- ~ilanes,~’ the steric effect of the Me3Si group in organic chemistry,” p~lysilanes,~~,~~ cyclic silicon germanium and tin comp0unds,7~ and molecular states of silicon corn pound^.^^ The addition of catalytic amounts of cyanide or thiocyanate salts such as CuCN or [Bu$N]+[SCN]- greatly promotes the reaction between Grignard reagents and chlorosilanes. For example after aqueous work up the reaction between PhSiC13 and (C6Hll)MgBr in the presence of 5% CuCN at -30°C affords 83% of PhSi(C6Hl,)20H,76 and Ph,SiCl and Bu‘MgC1 in the presence of CuCN give Ph,Bu‘SiCl in 80% yield after 5 h at reflux in THF.77 This promises to be a convenient way to improve the synthesis of simple organosilanes that are finding increasing use in organic synthesis.It has been shown that unprecedented 1,3-migration of a silyl group occurs in the 6,6-bis(trimethylsilyl)norborn-2-y1cation prior to desilylation and deprotonation. This presumably occurs via a rapidly equilibrating mixture of carbocati~ns.~~ The formation of 1,3-aryl-bridged silicocations for which there seems to be no analogue in carbon chemistry is proposed in the reactions of compounds of the type (Me3Si),C(SiMe2C6H4X)(SiMe21)= H p-OMe or p-Me) in which the y-aryl (X groups provide powerful anchimeric assistance in solvolysis reactions with for example CF3CH,0H.79 The use of chiral silanes for asymmetric induction continues to be studied.Little success has so far been achieved although the use of chiral silanes in which the chiral centre is remote from the silicon has been demonstrated to be highly enan- tioselective in the synthesis of arylcarbinols.80 Reaction of RCH=C=C (R = Me or But) with chiral naphthylphenylmethylsilaneleads to formation of chiral allenes with 3.5 and 10.5% enantiomerk excess respectively.81 Reaction of RLi reagents (R = Me But Ph etc.) with the chiral silyl thioketone (R)-(-)-Me(a-naph- thyl)PhSiC(S)Ph gives after protic work up silyl sulphides Me( a-naph- thyl)PhSiC(SR)HPh with up to -50% diastereomeric excess depending on the conditions used.82 Chiral silanes have also been used in the preparation of homoally- lic alcohols in up to 55% e.e.83 67 G.L. Larson J. Organomet. Chem. 1989 360,39. 68 G. L. Larson J. Organomet. Chem. 1989 374 1; M. P. Clarke ibid. 1989 376 165. 69 G. L. Larson J. Organomet. Chem. 1989 374 1. 70 A. Ricci and A. Degl’Innocenti Synthesis 1989 647. 71 J. R. Hwu Chem. Rev. 1989 89 1599. ’* R. D. Miller and J. Michl Chem. Rev. 1989 89 1359. 73 R. D. Miller Angew. Chem. Znt. Ed. Engl. 1989 28 1733. 74 P. D. Lickiss in ‘Rodd’s Chemistry of Carbon Compounds’ ed. M. F. Ansell Elsevier Amsterdam 1989 Vol. IVK p.1. 75 H. Bock Angew. Chem. Znt. Ed. Engl. 1989 28 1627. 76 P. J. Lennon D. P. Mack and Q. E. Thompson Organometallics 1989 8 1121.77 A. Shirahata Tetrahedron Lett. 1989 30,6393. 78 W. Kirmse and F. Sollenbohmer J. Am. Chem. Soc. 1989 111 4127. 79 C. Eaborn K. L. Jones and P. D. Lickiss J. Chem. Soc. Chem. Commun. 1989 595. 80 T. H. Chan and P. Pellon J. Am. Chern. Soc. 1989 111 8737. P. J. Stang and A. E. Learned J. Org. Chem. 1989 54 1779. 82 B. F. Bonini G. Maccagnani S. Masiero G. Mazzanti and P. Zani Tetrahedron Lett. 1989 30,2677. 83 T. H. Chan and D. Wang Tetrahedron Lett. 1989 30,3041. 270 P. D. Lickless Hydrolytic condensation of cyclohexyltrichlorosilanein aqueous acetone affords a mixture of silasesquioxanes which have structural similarities to silica surfaces and which may be useful models for such surface^.'^*^^ The tetrasiloxane {OSi[ (CH2),OHI2} appears to be the first diorganofunctional cyclosiloxane that is completely miscible with water but it could not be polymerized by ring opening with H2S04 .86 The reaction of trans-( PhMeClSi)CH=CH( SiPhMeCl) with sodium under the influence of ultrasonic irradiation produced a polymer (Mw 39 800) trans-[(PhMeSi)CH=CH(SiPhMe)l,.The polymer's Si-Si bonds are broken under irradiation by a mercury lamp and it can be cast as a film which can be doped with SbF vapour to give a highly conducting polymer film." Polymerization of 1,2- diethynyldisilanes catalysed by RhCl( PPh,) gives products such as (8) which can also be doped with SbF to give conducting polymers that have moleclar weights Mw = 119000 and 28 000 for R = Ph and Me respectively." RR -SiMeRSiMeR II 2 HCEC-Si-Si-C=CH II Me Me c=c (8) The degradation of polysilanes by UV light is becoming industrially important and new mechanistic workg9 shows that the process in solution involves reaction of (R2Si), to give silylenes R2Si and polysilyl radicals -SiR2-SiRe2.Addition of 18-crown-6 increases the rate of polymerization of MePrSiCl by sodium and also changes the molecular weight distribution from bimodal to monomodal with a molecular weight of -100OO0.90 Polymerization of 1-phenyl-7 8-disilabicyclo[2.2.2]octa-2 5-dienes by alkyllithium reagents provides a new route to polysilanes and also allows formation of block copolymers with methyl methacry- late." Treatment of 1,2,5,6-tetrasilacycloocta-3,7-diyneswith Bu"Li gives [Si(R)MeSi(R)MeC_C] polymers (R = Me Et or Ph) which also give highly conducting materials when doped with SbFs .92 A new method for the preparation of oligosilanes involves reaction of HSiC1 with silyltriflate in the presence of Et,N.For example reaction between HSiC1 and Me3SiOS02CF3or Me2Si(OS02CF3)2 affords Cl,SiSiMe and Me2Si(SiC13)2 respec- tively in yields of 72 and 62'/0.~~ Simple silyltriflates such as HSi(OS02CF3), [(CF302S0)2MeSi]2,and Ph9Si,(OS02CF3) that may be of use in such preparations can readily be made by cleavage of phenyl groups from the corresponding aryl 84 F. J. Feher D. A. Newman and J. F. Walzer J. Am. Chem. SOC.,1989 111 1741. 85 F. J. Feher and T. A. Budzichowski J. Organomet. Chem. 1989 373 153. 86 G.Kossmehl and A. Fluthwedel Chem. Ber. 1989 122 2413. 87 J. Ohshita D. Kanaya M. Ishikawa and T. Yamanaka J. Organomet. Chem. 1989 369 C18. 88 J. Ohshita K. Fuomori M. Ishikawa and T. Yamanaka Organometallics 1989 8 2084. 89 T. Karatsu R. D. Miller R. Sooriyakumaran and J. Michl J. Am. Chem. Soc. 1989 111 1140. 90 M. Fujino and H. Isaka J. Chem. SOC.,Chem. Commun. 1989,446. 91 K. Sakamoto K. Obata H. Hirata M. Nakajima and H. Sakurai J. Am. Chem. SOC. 1989 111 7641. 92 M. Ishikawa Y. Hasegawa T. Hatano A. Kunai and T. Yamanaka Organometallics 1989 8 2741. 93 W. Uhlig and A. Tzschach Z. Chem. 1989 29 335. Organometallic Chemistry-Part (iii) The Main-Group Elements 27 1 silanes by triflic acid.94 The palladium-catalysed reaction between aromatic acid chlorides and chlorodisilanes leads to decarbonylation and the formation of aryl chlorosilanes.This method proceeds in good yield is tolerant of various functional groups and should prove a useful route to numerous aromatic chlor~silanes.~~~~~ Triethylsilyl hydrotrioxide Et,SiOOOH prepared by addition of ozone to Et,SiH has been shown to be a powerful oxidizing agent reacting at -78 "C with alkenes to give 1,2-dioxetanes and oxidatively cleaved carbonyl produ~ts.~' Other potentially useful reagents are the new silicon pseudohalide Me,SiNCSe which reacts selectively with aldehydes but not ketones to give 0-trimethylsilylated cyanohydrin~,~~ (Me3Si0)2 which surprisingly reacts with 2-benzothiazolylalkyllithiums to give alkylbenzothiazoles incorporating a methyl group cleaved from one of the Me,Si moieties,99 Me,SiSSiMe3 which reacts with acylsilanes in the presence of CoC1 as catalyst to give the corresponding silylthioketones,"' and Et2PriSiC1 or Et2PriSiOS02CF3 which can be used to form silyl ethers of different stability to those of comparable Et,Si and Bu'Me2Si species.'o' The structures of two remarkably stable silanetriols (Me,Si),CSi(OH) and (Me3Si)3SiSi(OH)3,have both been found to consist of hydrogen-bonded hexameric cage units in the solid state.lo2 Kinetic evidence suggests that at high base concentra- tions the main process in the cleavage of RSiMe(OH) and RSi(OH) (R = m-ClC6H,CH2) is dissociation of the dianions RSiMe(O-)2 and R(OH)Si(O-) into Me(0-)Si=O (an acetate ion analogue) and the metasilicate ion HO(0-)Si=O re~pectively.''~ The X-ray crystal structures of hexacoordinate silicon compounds e.g.bis-[ 8-(dimethylamino)naphthyl]fluorosilaneand bis-[ 8-(dimethylamino)naphthyl]silane containing only one or no highly electronegative group have been determined and provide further evidence that such species may be intermediates in isomerization reacti~ns.''~~''~ Evidence for five-coordinate Si Sn and Pb compounds in which the metal is bonded to four carbons and intramolecularly coordinates to a nitrogen has also been reported.'06 Reaction between ICH2SiMe3 and alkoxide ions RO- does not give the expected Me3SiCH20R products but Me,SiOR and ROMe involving cleavage of a silicon-carbon bond probably via a five-coordinate silicon species.'" The first pentacoordinate silylsilicate (9) has been prepared and struc- turally characterized.'" The Si-Si bond length is 2.403 A and the geometry around the central silicon is trigonal-bipyramidal.94 W. Uhlig and A. Tzschach J. Organomet. Chem. 1989 378 C1. 9s J. D. Rich J. Am. Chem. SOC.,1989 111 5886. 96 J. D. Rich Organometallics 1989 8 2609. 97 G. H. Posner K. S. Webb W. M. Nelson T. Kishimoto and H. H. Seliger J. Org. Chem. 1989,54,3252. 98 K. Sukata J. Org. Chem. 1989 54 2015. 99 S. Florio and L. Troisi Tetrahedron Lett. 1989 30,3721. 100 A. Ricci A. Degl'Innocenti A. Capperucci and G. Reginato J. Org. Chem. 1989 54 19. 101 S. Florio and L. Troisi Tetrahedron Lett. 1989 30,6413. 102 S.S. Al-Juaid N. H. Buttrus R. I. Damja Y. Derouiche C. Eaborn P. B. Hitchcock and P. D. Lickiss J. Organomet. Chem. 1989 371 287. 103 J. Chmielecka J. Chojnowski W. A. Stanczyk and C. Eaborn J. Chem. SOC.,Perkin Trans. 2 1989 865. 104 C. Brelikre F. Cad R. J. P. Comu M. Poirier,G.Royo and J. Zwecker Organometallics 1989,8 1831. 10s C. Brelikre R. J. P. Corriu G. Royo and J. Zwecker Organometallics 1989 8 1834. 106 R. Koster G. Seidel B. Wrackmeyer K. Horchler and D. Schlosser Angew. Chem. Znt. Ed. Engl. 1989 28 918. 107 T. K. Chakraborty and G. V. Reddy J. Chem. SOC.,Chem. Commun. 1989 251. I08 M. Kira K. Sato C. Kabuto and H. Sakurai J. Am. Chem. SOC.,1989 111 3747. 272 P. D. Lickless F3C CF3 Ph3Si g% Et4N+ -rp 0 F3C CF3 A new relatively stable silene Ph2Si=C(SiMe3)2 can be prepared in solution by elimination of MX from (Me3Si)2(Ph2XSi)CM species (M = Li or Na X = F or Br) in a manner similar to that used for the Me,Si= analogue.'o9 Photolysis of acyl-silanes (Me,Si),RSiC(O)R' (R = Me But or Ph; R' = adamantyl etc.) gives silenes Me3SiRSi=C(OSiMe3)R' which rearrange further on photolysis to give various new silenes and cyclic dimeric products the nature of which depends on the size of R and R'.ll0 Treatment of acylsilanes (Me,Si),C(O)R (R = But or adamantyl) with Et3GeLi affords silaenolate species (Me,Si),Si=C(OLi)R for the first time."' The first example of a compound containing a 1-sila-3-azacyclobutane ring (10) has been prepared by addition of 2,6-dimethylphenylisocyanide to the silene (Me3Si)2Si=C(CloH15)OSiMe3 .lI2 On warming the hydrocarbon glass in which l-mesityl-2,3,4-tri-t-butyl-l-silacyclobutadiene is prepared an unusual dimerization involving a [1,5] sigmatropic shift occurs to give (ll).l13 A metal-bound silene is thought to be an intermediate in the reaction between Me3SiSi(Me2)CH=CH2 and Ni(PEt3)4 at 220°C,"4 and the formation of a metal-bound Si=C species is also implicated in the reaction between [Cp(C0)2Fe]MeSi(C1)CH=CH2 and Bu'Li which affords (12) apparently uia a head-to-tail silene dimeri~ation."~ 109 N.Wiberg M. Link and G. Fischer Chem. Ber. 1989 122 409. K. M. Baines A. G. Brook R. R. Ford P. D. Lickiss A. K. Saxena W. J. Chatterton J. F. Sawyer and B. A. Behnam Organometallics 1989 8 693.111 I. S. Biltueva D. A. Bravo-Zhivotovskii I. D. Kalikhman V. Yu. Vitkoskii S. G. Shevchenko N. S. Vyazankin and M. G. Voronkov J. Organomet. Chem. 1989,368 163. 112 A. G. Brook A. K. Saxena and J. F. Sawyer Organometallics 1989 8 850. 113 D. B. Puranik M. P. Johnson and M. J. Fink J. Chem. Soc. Chem Commun. 1989 706. 114 M. Ishikawa T. Ono Y. Saheki A. Minato and H. Okinoshima J. Organornet. Chem. 1989 363 C1. 115 N. Auner J. Grobe T. Schafer B. Krebs and M. Dartmann J. Organomet. Chem. 1989 363 7. Organometallic Chemistry-Part (iii) The Main-Group Elements 273 Reaction of Bu:Si=SiBu with the bulky BuiSiCN gives a 2,3-disila-l-azetine a [2 + 21 cycloaddition product while with BuiSiNCO a 3-aza-l-oxa-2,5-disilacyc-lopent-3-ene is formed."6 Addition of nitrosobenzene or nitrobenzene to (me~)~Si=Si(mes)~ gives the compounds (13) and (14) respectively both of which contain novel ring systems."' Ph Ph \ / N-0 0-N I.1 J\ Si(mes) (mes)2Si,0 Si(mes) (rne~)~Si-Photolysis of the trisilane (Me,Si),Si(mes) (adamantyl) gives the remarkably air- stable disilene (mes)AdSi=SiAd(mes) which has an Si=Si bond length of 2.138 A,118and disilenes with small substituents can be made in situ at a platinum centre to give some of the first T2-disilene complexes. The synthesis relies on the addition of a dihydrodisilane [(R2SiH)2(R = Pr' or Ph)] to either Pt(dppe)Cl or Pt(dppe)C,H . Unfortunately X-ray crystallographic data are not yet available for these interesting complexes.' i9 Photolysis of trisilane (15) affords (after rearrangement) silylene (16) which is remarkably stable and can be observed by UV spectroscopy (A,, 448 nm) in fluid 3-methylpentane solution at 200K.This silylene is the first to be observed under such conditions the bulky substituents presumably preventing further reaction.12' In contrast to the reaction of dimesitylsilylene with oxygen (which reportedly gave a silanone 0-oxide) the reaction of Me2% with O2in an argon matrix appears to give a dioxasilirane product,12' while insertion of O2 into the Si-Si bond of 1,l72,2-tetramesityl- 1 2-disilirane gives a cyclic peroxide species as a isolable solid which when treated with silica gel or Ph3P gives novel disiloxetane species.'21 Another transition-metal silylene complex (CO),FeSiMe,.HMPT has been struc- turally characterized the Si-Fe distance being found to be about 2.28 A.122 116 M.Weidenbruch B. Flintjer S. Pohl and W. Saak Angew. Chem. Int. Ed. Engl. 1989 28 95. 117 G. R. Gillette J. Maxka and R. West Angew. Chem. Int. Ed. Engl. 1989 28 54. 118 B. D. Shepherd D. R. Powell and R. West Organometallics 1989 8 2664. 119 E. K. Pharn and R. West J. Am. Chem. SOC.,1989 111 7667. 120 D. B. Puranik and M. J. Fink J. Am. Chem. SOC.,1989 111 5951. 121 A. Patyk W. Sander J. Gauss and D. Crerner Angew. Chem. Int. Ed. Engl. 1989 28 898. 122 C. Zybill D. L. Wilkinson C. Leis and G. Muller Angew. Chem. Int. Ed. Engl. 1989 28 203. 274 P. D. Lickless I i Si : hv -p 254 nrn The chemistry of the first silicon .rr-complex (~~-c~Me~)~Si has been explored further.'23 Different pathways seem to be followed in reactions with CS, C02,and PhNCS'24 and with Se or Te,'25 all of which give cyclic products.Reaction of a digermirane with dimethylacetylenedicarboxylate and acetylene in the presence of catalytic amounts of palladium catalyst gives ring expansion prod- ucts. However the stoichiometric reaction between the digermirane and Pd( PPh3)4 gives the palladadigermetane (17).'26 An unusual symmetrical twist-boat conforma- tion has been found in 2,2,5,5-tetramethyl-1,3-diselena-2-germacyclohexane. The barrier to interconversion of the two enantiotopic conformational isomers 34.4 kJ mol-' is surprisingly high and the reasons for this behaviour clearly require further study.12' Ar2GeAGeAr2 \/ Pd 1 PPh3 (17) Ar =2,6-Et2C,H For the first time several polycyclic oligogermanes have been reported.Reduction of (Bu~X,G~)~ (X =Br or Cl) with lithium naphthalenide affords octagermanes (18)'28and (19),12' respectively both of which have been fully structurally character- ized. The chloride can also be prepared by reduction of Bu'GeCl,. Reduction of another bulky halogenogermane (Me,Si),CHGeCl ,with lithium affords the first hexagermaprismane (2O).l3' Cyclopentadienyl complexes of Ge Sn and Pb continue to be of interest with various sandwich and half-sandwich complexes containing the 1,3-Bu:C5H3 ,131 123 P. Jutzi U. Holtmann D. Kanne C. Kriiger R. Blom R. Gleiter and I.Hyla-Kryspin Chem. Ber. 1989 122 1629. 124 P. Jutzi and A. Mohrke Angew. Chem. Int. Ed. Engl. 1989 28 762. 125 P. Jutzi A. hohrke A. Muller and H. Bogge Angew. Chem. Znt. Ed. Engl. 1989 28 1518. 126 T. Tsumuraya and W. Ando Organometallics 1989 8 2286. 127 S. Tomoda M. Shimoda M. Sanami y.Takeuchi and Y. Iataka J. Chem. SOC.,Chem. Commun. 1989 1304. 128 M. Weidenbruch F.-T. Grimm S. Pohl and W. Saak Angew. Chem. Int. Ed. Engl. 1989 28 198. 129 A. Sekiguchi H. Naito H. Nameki K. Ebata C. Kabuto and H. Sakurai J. Organomet. Chem. 1989 368,c1. 130 A. Sekiguchi C. Kabuto and H. Sakurai Angew. Chem. Znt. Ed. EngL 1989 28 55. 13 I P. Jutzi and R. Dickbreder 1. Organomet. Chem. 1989 373 301. Organometallic Chemistry-Part ( iii) The Main-Group Elements 275 R / RGe-R RGe -GeR R R-Ge-GeR /\ ~ I RGe GeR X (18) X = Br R = But (20) R = (Me,Si),CH (19) X = C1 R = But l,l'-(dimethylsilanediyl)bis-(2,3,4,5-tetramethyl-cy~lopenta-2,4-diene),~~~Me,-or C5133 ligands being prepared.The first germapyrazoline (21)has been prepared by addition of diazomethane to a Ge=C containing precursor. On heating or photolysis loss of N2 occurs to give a germirane which then decomposes to give (me~)~Ge:.'~~ Novel three- and four-membered rings e.g. in (22)and (23),containing Ge and S are formed on addition of germylenes to thio-ketones or -ketenes with subsequent o~idation.'~~,'~~ 0 II mes2Ge +&S -+ G~ MCPBA -@>O mes2 mes2 The electronic spectra of R,Ge (R = Me Et Ph etc.) species and their adducts with for example EtOH Bu3P Me2S and PhCl have been recorded in hydrocarbon matrices.The adducts show absorption bands at shorter wavelengths than the corresponding free germylene~.'~' The IR spectrum of matrix-isolated Me2Ge has 132 F. X. Kohl R. Dickbreder P. Jutzi G. Muller and B. Huber Chem. Ber. 1989 122 871. 133 P. Jutzi R. Dickbreder and H. Noth Chem Ber. 1989 122 865. 134 M. P. Egorov S. P. Kolesnikov 0. M. Mefedov and A. Krebs J. Organomet. Chem. 1989 375 CS. 135 T. Tsumuraya S. Sato and W. Ando Organometallics 1989 8 161. 136 W. Ando and T. Tsumuraya Organometallics 1989 8 1467. 137 W. Ando H. Itoh and T. Tsumuraya Organometallics 1989 8 2759. 276 P.D. Lickless also been recorded. 13' Reaction between stabilized diaminogermylene and diamino- stannylene precursors with a cyclic acetylene gives the first digerma- and distannacy- clobutene derivatives (24) re~pective1y.l~~ (24) M = Ge or Sn Photolysis of phenyl-substituted trigermanes e.g. (PhMe,Ge)*GeMe and (Me3Ge)2GePh2,occurs in a similar fashion to that of aryltrisilanes giving germy- lenes and digermenes which can be trapped by dienes.14' Reduction of (2,6- Pr;C6H3),GeCl2 (R2GeC1,) with lithium naphthalenide in DME gives digermene R,Ge=GeR which reacts further with excess reducing agent to give a vinyllithium equivalent R,Ge=GeRLi(DME) which should be a useful precursor to other digermene~.'~~ N20 or DMSO) Depending on the source of the oxygen (302 oxidation of digermenes R,Ge=GeR (R = 2,6-Et,C6H3 or 2,6-Pr&H,) gives 1,2- digermadioxetane digermoxirane and 1,3-cyclodigermoxane products respec-ti~e1y.l~~ Addition of thermally generated (mes),Ge=Ge(mes)* to paraformal-dehyde thiobenzophenone and phenylacetylene gives novel 1,2,3-oxa- and 1,2,3- thia-digermetanes and 1,2-digermetene products re~pective1y.l~~ The organometallic chemistry of tin is covered extensively in a new book,'44 the chemistry of tin cluster compounds has been re~iewed,'~' and a 'Tetrahedron Symposium in Print' covers organotin reagents in organic synthesis.'46 The trialkylstannane (PhMe2CCH2),SnH can be handled in air is soluble in organic solvents adds to activated olefins and is proposed as a new organotin reducing agent.14' A simple preparation of Me3SnH is achieved by reduction of Me,SnCl with LiAlH in triglyme at 60-68 "C in 81% yield.This convenient preparation may make Me,SnH a useful alternative to Me,SnCl Me3SnLi and Bu;SnH as a simple organotin reagent.14' The reaction between R,SnLi (R = Me or Bun) reagents with esters or thioesters provides a convenient route to various 138 J. Barrau D. L. Bean K. M. Welsh R. West and J. Michl Organometallics 1989 8 2606. 139 A. Krebs A. Jacobsen-Bauer E. Haupt M. Veith and V. Huch Angew. Chem. Znt. Ed. Engl. 1989 28,603. 140 M. Wakasa I. Yoneda and K. Mochida J. Organomet. Chem. 1989,366 C1. 141 J. Park S. A. Batcheller and S. Masamune J. Organomet. Chem. 1989 367 39. 142 S. Masamune S.A. Batcheller J. Park W. D. Davis 0. Yamashita Y. Ohta and Y. Kabe J. Am. Chem. SOC.,1989 111 1888. 143 W. Ando and T. Tsumuraya J. Chem. SOC.,Chern. Commun. 1989 770. 144 'Chemistry of Tin' ed. P. G. Harrison Blackie Glasgow and London 1989. 145 R. R. Holmes Acc. Chem. Rex 1989 22 190. 146 Tetrahedron 1989 45 pp. 909-1219. 147 A. B. Chopa A. E. Zfiiiiga and J. C. Podesta J. Chem. Res. (S) 1989 234. 148 B. H. Lipshutz and D. C. Reuter Tetrahedron Lett. 1989 30,4617. Organometallic Chemistry-Part (iii) The Main-Group Elements 277 potentially useful acylstannanes such as PhCOSnMe and C4H7COSnBu; in reason- able ~ie1ds.l~~ Reaction of [(2,4,6-Pr;C6H2)2SnBr]2 with Na2S-9H20 in air gives (25) and anaerobically gives (26) the first examples of such ring systems.In (25) the Sn-0-Sn and Sn-S-Sn bond angles are 101.7 and 80.6" re~pectively.'~' The four-membered ring compounds (BuiSnE) (E = S Se or Te) all have planar rings,151 while in (Me2SnTe)3 the six-membered ring adopts a twist-boat conformation. 152 b R2Sn'y'SnR2 R = 2,4,6-Pr;C6H (25) E = S E' = 0 (26) E = E' = S Partial hydrolysis of RSnC1 (R= Pr' or Bu') affords RSn(OH)C12-H20 species which in the solid state form dimeric units containing Sn202 rings. These units are hydrogen bonded to form chains which are further linked as 1a~ers.l~~ The use of bulky mesityl groups allows the monomeric four-coordinate tin hydroxide (mes),SnOH (Sn-0 bond length 1.999 A) and tin fluoride (mes),SnF (Sn-F bond length 1.96 A) and not polymeric species to be formed.'54 A series of seven bulky alkyl and aryl di- tri- and tetrastannanes have been investigated by X-ray crysta110graphy.l~~ As expected larger R groups increase Sn-Sn bond distances those in BukSn being 2.966(1) 8 long.The blue-violet solid 2,2,4,4,5,5-hexakis-(2,6-diethylphenyl)pentastanna[ 1.1. llpropellane has been found to have a distance of 3.367 8 between bridgehead tin atoms and no coupling between them in NMR spectra indicating that there is no bonding between the bridgehead atoms and that the compound has significant biradical ~haracter.'~~ An T2-coordination of R,SnH to a transition metal has been found in (v5-MeC5H4)-(CO),Mn(H)SnPh, prepared by photolysis of a mixture of ($-MeC5H,)Mn(CO) and Ph,SnH.X-Ray crystallography shows the Sn-H Mn-H and Sn-Mn bond lengths to be 2.16 1.37 and 2.6368, respectively with an Sn-Mn-H angle of 550 157 The crystal structure of a new diaryltin( 11) compound bis-[8-(dimethyl- amino)naphth- 1-yl- C N]tin( 11) shows distorted trigonal bipyramidal geometry at tin with nitrogen atoms of intramolecularly coordinated NMe groups in axial 149 A. Capperucci A. Degl'lnnocenti C. Faggi G. Reginato and A. Ricci J. Org. Chem. 1989 54 2966. 150 P. Brown M. F. Mahon and K. C. Molloy J. Chem. SOC.,Chem. Commun. 1989 1621. I51 H. Puff G. Bertram B. Ebeling M. Franken R. Gattermayer R. Hundt W. Schuh and R.Zimmer J. Organomet. Chem. 1989 379 235. 152 R. J. Batchelor F. W. B. Einstein and C. H. W.Jones Acta Crystallogr. Sect. C 1989 45 1813. 153 H. Puff and H. Reuter J. Organomet. Chem. 1989 364,57. 154 H. Reuter and H. Puff J. Organomet. Chem. 1989 379 223. H. Puff B. Breuer G. Gehrke-Brinkmann P. Kind H. Reuter W. Schuh W. Wald and G. Weidenbriick J. Organomet. Chem. 1989 363 265. IS6 L. R. Sita and R. D. Bickerstaff J. Am. Chem. SOC. 1989 111 6454. 157 U. Schubert E. Kunz B. Harkers J. Willnecker and J. Meyer J. Am. Chem. SOC.,1989 111 2572. P. D. Lickless position^.'^^ The reaction between Sn(AlCl,) and benzene affords the dimer (27) as the first bis(arene) complex of a Group IV element.'59 The eight-membered Sn,C1,Al2 ring has a chair conformation each pair of benzene rings are inclined to each other at about 101"and the Sn-ring centroid distances are very long (-3.2 A).Another tin-arene complex (28) is formed in the reaction between SnCl, AlC13 and Me&. It has an Sn-C&k6 distance of 2.45 A which is somewhat shorter than that found in complexes of tin with p-xylene and mesitylene.'60 The ability of 1,5,9-tristannadodecanes such as R,S(II(CH~),S~R,(CH,)~-I SnR,(CH,) (R= Me or Cl) to complex chloride ion has been studied.16' For R = C1 a single chloride ion can be complexed giving an anion in which there is a chloride bridge between two of the SnCl groups. For R= Me no significant complexation occurs. A series of bicyclic compounds (29; X = C1 or Br) can exist with either both halogens outside (an 'out-out' isomer) the macrocycle core (n = 6,7 or 8) or as a mixture of the 'out-in' isomer in which one halogen is outside and one inside (n= 10 or 12)."j2 Me \ C /+C \BPr X-Sn-(CH2) -Sn-X Me2Pb\ /c=c\ Me Pr' Triorganolead cations such as (30) can be stabilized by intramolecular coordina- tion to a CEC bond.'63 The Pb to CZEC carbon distances are 2.648 and 2.467A and the interaction may be viewed as like that of an intermediate in the addition reaction of a metal fragment to a triple bond.J. T. B. H. Jastrzebski P. A. van der Schaaf J. Boersrna G. von Koten D. Heijdenrijk K. Goubitz and D. J. A. de Ridder J. Organornet. Chern. 1989,367 55. 159 H. Schrnidbaur T. Probst B. Huber 0. Steigelrnann and G. Muller Organornetallics 1989 8 1567. 160 H. Schrnidbaur T. Probst 0.Steigelrnann and G.Muller 2. Naturforsch B 1989 44 1175. 161 K. Jurkschat H. G. Kuivila S. Liu and J. A. Zubieta Organornetallics 1989 8 2755. 162 M. T. Blanda J. H. Homer and M. Newcornb J. Org. Chern. 1989 54 4626. 163 B. Wrackrneyer K. Horchler and R. Boese Angew. Chern. Int. Ed. Engl. 1989 28 1500. Organometalfic Chemistry-Part (iii) The Main-Group Elements 279 The lead cationic species Me3PbLi can be prepared in THF solution at -78 "C by reaction between Me,PbBr and lithium. It rapidly decomposes at -20 "C but can be used at -78 "C to prepare for example Me,PbSiMe .164 Reaction between the carbaborane Na[ 2,3-( Me3Si),C2B4H5] with PbC1 affords the plumbacarbaborane closo-1-Pb-2,3-(Me3Si),-2,3-C2B4H4 in which the lead atom is q5-bonded to the C2B3 face with Pb-C distances of -2.6 5 Group V The new reagent (3,3-diisopropoxypropyl)triphenylarsonium ylide acts as a P-formyl vinyl anion equivalent and can be used to convert aldehydes into y-hydroxyenals in a three-step procedure,166 and a mixture of Bu;As and Zn has been shown to be a useful system to convert various aromatic aliphatic and heterocyclic aldehydes into alkenes in a one-pot rea~ti0n.l~~ A Wittig-type reaction is observed in the reaction between an aldehyde and BrCH2C02Me in the presence of Bu;As K2C03 and (Ph0)3P to give products of the type RCH=CHCO,Me.The novelty of this reaction lies in it being catalytic in Bu;As which is regenerated from the Bu;AsO formed in the reaction by the (PhO),P. This appears to be the first demonstration of such a catalytic Wittig-type reaction.16' In contrast to the hydrolysis of cyclo-(CH,),AsH [which affords cyclo-(CH,),As(O)OH] the hydrolysis of cyclo-(CH,),AsCl gives [cyclo-(CH,),AS(OH)~]CI.This can be considered as a cationic arsenic (v) diol or a dialkylarsenic acid in which the molecules are linked via intermolecular OH...Cl.-.HO- hydrogen bonds.169 Heating of cyclo-(AsR) (R = Me n = 5; R = Ph n = 6) with [q5-Me,C,M(CO),] (M = Mo or W) affords Me5C5M(C0),(q3- RAsAsAsR) complexes in which the RAsAsAsR acts as an isoelectronic and isolobal wallyl ligand; this is the first time that such a ligand not containing ligating carbon atoms has been found. The As-As bond lengths are -2.36 ,& with an As-As-As angle of -830.170 The asymmetric synthesis of optically active tertiary arsine (R)-(-)-EtMePhAs has been achieved via an iron complex containing the first resolved secondary arsine (31).17' 4- PF Me -Ai 4H I Ph Ph 164 B.Wrackmeyer and K. Horchler Z. Naturforsch. E 1989 44 1195. 165 N. S. Hosmane U. Siriwardane H. Zhu G. Zhang and J. A. Maguire Organometallics 1989 8 566. 166 P. Chabert J. B. Ousset and C. Mioskowski Tetrahedion Lett. 1989 30,179. 167 Y. Shen B. Yang and G. Yuan 1.Chem. Soc. Chem. Commun. 1989 144. I68 L. Shi W. Wang Y. Wang and Y.-Z. Huang J. Org. Chem. 1989 54 2027. 169 J. W. Pasterczyk A. M. Arrif and A. R. Barron J. Chem. Soc. Chem. Commun. 1989 829. 170 J. R. Harper M. E. Fountain and A. L. Rheingold Organometallics 1989 8 2316.171 G. Salem and S. G. Wild J. Organomet. Chem. 1989 370 33. 280 P. D. Lickless The X-ray crystal structures of Ar3As Ar2AsOAsAr2 and Ar2AsAsAr2 (Ar = C6F5)-the first tetraaryldiarsine to be so characterized- have been determined.'72 Annual reviews of the chemistry of antimony'73 and bismuth'74 for 1987 and a review of the use of organobismuth reagents in arylation reactions have been p~blished.'~~ Treatment of RSbBr2 compounds (R = Et Pr or Bu) with magnesium gives cyclic (RSb) and (RSb)5 products. Attempts to isolate the compounds by evaporation of the solvent lead to formation of polymeric (RSb) species. However [(mes)Sb],-C,H can be isolated and X-ray crystallography shows it to comprise Sb4...Sb4..- chains with the benzene ring bonded in an v6-fashion to one Sb of each rn01ecule.'~~ The first secondary stibane [(mes),SbH] to be structurally characterized is found to be surprisingly stable towards oxidation.X-Ray crystallography shows it to have a C-Sb-C angle of 101.7'. Treatment of (me~)~SbH with Bu"Li affords (mes),SbLi which when added to a mixture of CuCl and Me3P in THF gives [(mes),SbCu( PMe3)2]2-the first example of a late-transition-metal antimonide. The compound has a planar Sb2Cu2 four-membered ring with a Cu-Sb distance of 2.669 A new general method for the preparation of bismuthonium ylides (32) involves the treatment of Ph3Bi0 or Ph3BiC12 with sodium salts of 1,3-dicarbonyl compounds. Reaction of the ylides with sulphenes gives 1,3-0xathiole 3,3-dio~ides."~ Li+ BiPh R' (32) R-R' = CH,CMe2CH (33) R = CF R,R = Me Ph etc.To1 = p-MeC6H A series of pentaarylbismuth compounds Ar3AriBi have been prepared by treat- ment of Ar3BiX2 species with Ar'Li (X = F or C1; Ar = p-MeC6H4Ar' = C,F,; Ar = Ph Ar' = 2,6-F2CsH3 et~.).'~~ As for Ph5Bi the compounds have square- pyramidal geometry in the solid state. The first thermally stable hexacoordinate bismuthate complex (33) is prepared by treatment of a five-coordinate precursor with a dilithium reagent.18' 172 A. L. Rheingold D. L. Staley and M. E. Fountain J. Organomet. Chem. 1989 365 123. 173 L. D. Freedman and G. 0. Doak J. Organomet. Chem. 1989,360 263. 174 G. 0. Doak and L. D. Freedman J. Organomet. Chem. 1989 360,297. 17' J.-P.Finet Chem.Rev. 1989 89 1487. 176 M.AteS H. J. Breunig S. GulleG W. Offermann K. Haberle and M. Drager Chem. Ber. 1989 122 473. 177 A. H. Cowley R. A. Jones C. M. Nunn and D. L. Westmoreland Angew. Chem. Znt. Ed. Engl. 1989 28 1018. 178 T. Ogawa T. Murafuji and H. Suzuki J. Chem. Soc. Chem. Commun. 1989 1749. 179 A. Schmuck and K. Seppelt Chem. Ber. 1989 122 803. 180 K.-y. Akiba K. Ohdoi and Y. Yamamoto Tetrahedron Lett. 1989 30,953. Organornetallic Chemistry-Part (iii) The Main-Group Elements 28 1 6 Group VI The first selenoaldehyde (34) can be prepared according to the reaction shown in Scheme 2. It is an air-stable blue solid which isomerizes on melting to give the benzoselane (35).lg1 SeCN I H-$-SiMe3 A CH,CI t (34) Scheme 2 The reaction between aldehydes RCHO (R = Me Ph etc.)with (Me,Si),Se affords 1,3,5-triselenacyclohexanes(CHRSe) ,apparently via selenoaldehyde intermediates RCHSe.The cyclic selanes can be decomposed either thermally or with Lewis acid to regenerate the selenoaldehyde which can be trapped as a Diels-Alder adduct.Ig2 The formation of methyl 2H- 1-benzoselenete-2-carboxylateas a reactive inter- mediate on photolysis of 3-diazobenzo[ blselenophen-2(3 H)-one is implicated by the isolation of its dimer. This seems to be the first synthetic approach to the benzoselenete ring system.lg3 The new heterophane 2,l l-diselena[3.3](2,6)pyridinophane has been prepared in high yield and has been shown to interact with both Ni2+ and Cu2+ ions in a host-guest type complex.'84 The structure of 2,l l-diselena[3.3]orthocyclophanehas been shown to be anti rather than syn in both the solid and solution state.lg5 A new one-pot synthesis of bis(ethylenedise1eno)tetrathiafulvalene relies on the use of HMPA as solvent rather than the usual THF and gives yields of -50% of this compound which is of potential interest in the organic superconductor field.lg6 Functional species such as tetraformyltetraselenafulvalene have also been pre- pared.18' The Hammett constants a,,, and upfor PhTe PhSe Te- and Se- have been found to be (a,) 0.20 0.20 -0.57 and -0.59 respectively and (a,)0.29 0.22 -0.72 and -0.84 respectively by electrochemical reduction of various aryl chalcogenide species.lgg New selenium coronands such as 1,3,7,9-tetraselenacyclododecane and 1,3,7,9,13,15-hexaselenacyclooctadecaneand their derivatives have been fully 181 R.Okazaki N. Kumon and N. Inamoto J. Am. Chem. SOC.,1989 111 5949. 182 Y. Takikawa A. Uwano H. Watanabe M. Asanurna and K. Shimada Tetrahedron Lett. 1989,30,6047. 183 S. Yarnazaki K. Kohgami M. Odazaki S. Yarnaba and T. Arai J. Org. Che?. 1989,54 240. 184 S. Muralidharan M. Hojjatie M. Firestone and H. Freiser J. Org. Chem. 1989 54 393. 185 T. Okajima Z.-H. Wang and Y. Fukazawa Tetrahedron Lett. 1989 30 1551. 186 A. M. Kini B. D. Gates M. A. Beno and J. M. Williams J. Chem. SOC.,Chem. Commun. 1989 169. 187 M. Salk. A. Gorgues J.-M. Fabre K. Bechgaard M. Jubault and F. Texier J. Chem. SOC.,Chem. Commun.1989 1520. 188 R. hest and C. Degrand J. Chem. SOC.,Perkin Trans. 2 1989 607. 282 P. D. Lickless characterized and are shown to have different conformations to S and 0 analogues in the solid state.'89 The use of 1,4-dicyanonaphthalene as an electron acceptor enables the photo- chemical formation of the synthetically useful PhSe+ species from PhSeSePh for the first time.'" Oxidation of 1,5-diselenacyclooctane with two equivalents of NOPF gives a novel salt (36) that can oxidize 1,2-diphenylhydrazine to azobenzene and PhSH to PhSSPh.191 Bis( acyl diselenides) such as [PhC(O)Se] act as acylating reagents for such nucleophiles as R,NH Et,ONa PhSNa etc. under mild conditions and in good yield with both acyl groups 'being ~ti1ized.l~~ Similar bis( acyl) selenides [RC(O)],Se can be prepared in good yield from RC(0)Cl and Na,Se (R = Me Pr' But et~.).'~~ A versatile one-pot synthesis of unsymmetrical organoselenium compounds RSeR' [R = n-C6H13 PhCH2 PhC(0); R' = Pri PhC(O) EtOC(O) etc.] is achieved via sequential cleavage of Me,Si groups from (Me,Si),Se with Bu"Li and subsequent treatment with a suitable organic chloride or bromide.'94 A tetraalkyl Te'" compound Me,Te has been isolated for the first time as a yellow-orange pyrophoric liquid.The compound is prepared by reaction of TeC1 with 4,2 equivalents of MeLi at -78 "C. It is relatively thermally stable but decom- poses to give Me,Te after 4 h at 120 0C.195 The ditelluroethers RTe(CH,),TeR (R = Ph or Me) act as chelating ligands in Ptrl and Pd" complexes such as [Pd{PhTe(CH2),TePh)I2] and [Pt{MeTe(CH,),TeMe}Cl2].Both meso and (*) isomers can be formed.'96 The mechanism of the solvolysis of p-EtOC6H4TeC13 in for example a C&- MeOH mixture has been investigated. Such reactions give p-EtOC6H4Te(0)C1 and p-EtOC6H4Te(OMe),c1 as solid product^.'^' The X-ray photoelectron and NMR spectra of various tellurapyrans tel-lurapyranones and tellurapyrylium salts have been recorded for both Te" and Te'" compounds so that correlations between NMR chemical shift and binding energy could be in~estigated.'~~ 189 R. J. Batchelor F. W. B. Einstein I. D. Gay J.-H. Gu B. D. Johnston and B. M. Pinto J. Am. Chem. SOC.,1989 111 6582. 190 G. Pandey V. J. Rao and U. T. Bhalerao J. Chem. SOC.,Chem.Commun. 1989 416. 191 H. Fujihara R. Akaishi T. Erata and N. Furukawa J. Chem. SOC.,Chem. Commun. 1989 1789. Y.Nishiyama A. Katsuura Y. Okamoto and S. Hamanaka Chem. Lett. 1989 1825. 193 H. Kageyama H. Tsutsumi T. Murai and S. Kato Z. Naturforsch B 1989,44 1050. 194 M. Segi M. Kato T. Nakajima S. Suga and N. Sonoda Chem. Lett. 1989 1009. 19s R. W. Geddridge jun. D. C. Hams K. T. Higa and R. A. Nissan Organornetaffics,1989 8 2817. 196 T. Kemmitt W. Levason and M. Webster Inorg. Chem. 1989 28 692. 197 N. K. Adlington J. D. Miller and T. A. Tahir J. Chem. SOC.,Dalton Trans. 1989,457. 198 M. R. Detty W. C. Lenhart P. G. Gassman and M. R. Callstrom Organometaflics,1989 8 861. 19' Organometallic Chemistry-Part (iii) The Main-Group Elements 283 The hydrotelluration of acetylenes has been studied in detail.The addition of RTeH species (generated in situ) gives 1,2-substituted regioisomers exclusively with aromatic acetylenes but some 2,2-isomer is also produced on addition to aliphatic acetylenes. Use of HTe-ion allows divinyl tellurides to be made e.g. (PhCH=CH2)2Te.'99 Such vinyl and divinyl tellurium compounds can be used in the preparation of vinyllithium reagents.2oo The first stable alkyltelluryl halides have been prepared by utilizing the steric protection afforded by the bulky (Me3Si),C group. Thus treatment of [(Me3Si)&TeI2 with S02C12 Br2 or I2 affords (Me,Si),CTeX (X = C1 Br or I) in high yield. Treatment of the halides with RLi gives (Me,Si),CTeR (R = Me or Ph).201 A range of bis-(P-alkoxyalky1)ditellurideshave been made by treatment of an alkene with an aqueous mixture of Te02 an alcohol and HC1 with subsequent reduction using Na2S205.Treatment of the ditellurides with S02C12 gives crystalline (P-alkoxyalky1)tellurium trichlorides in good yield.202 Addition of activated elemental Te to Ph,P=CHPh gives the novel telluroaldehyde PhC(Te)H which can be trapped as its Diels-Alder adduct with 2,3-dimethyl- b~tadiene.~' A more general method for the preparation of telluroaldehydes and telluroketones uses (Me2Al),Te which converts RC(0)R' species such as benzal- dehyde and adamantanone into the corresponding RC(Te)R' species. Again the C=Te compounds could not be isolated but were trapped as Diels-Alder ad duct^.^'^ A corresponding reaction occurs to give selenoketones when (Me2Al)Se is used in place of (Me2Al)2Te.205 The need for volatile organotellurium compounds for MOCVD work has led to preparations of numerous new compounds.For example bis( alkyltel1uro)acetylenes RTeC-CTeR (R = Me or Et) can be prepared by treating HC-CLi-ethy- lenediamine with Te and then RI,206 and the reaction between Na2Te (made from Te and sodium naphthalenide) or LiTeMe and ally1 bromide affords (CH2=CHCH2),Te and CH2=CHCH2TeMe re~pectively.~'~ The reaction between PhCECH and Se and Te in three-phase systems comprising the metal PhCECH KOH H20 and an alkylammonium salt or selenium gives a 1,3-diselenole product but for tellurium distyryltellurium and the corresponding ditelluride are formed.208 In contrast to an earlier report the reaction between tellurium and PhCECH under strongly basic conditions has been reported to give 1 ,Cditellurafulvenes rather than a cyclic ditell~ride.~'~ Novel tellurodicarbonic acid esters [ROC( O)],Te (R = Me Pri PhCH2 etc.) can be prepared in reasonable yield by treating ROC(0)Cl compounds with Na2Te.These compounds seem to be more stable towards oxidation than diacyl tellurides 199 S. M. Barros M. J. Dabdoub V. M. B. Dabdoub and J. V. Comasseto Organometallics 1989 8 1661. 200 S. M. Barros J. V. Comasseto and J. Berriel Tetrahedron Lett. 1989 30 7353. 20 1 K. Giselbrecht B. Bildstein and F. Sladky Chem. Ber. 1989 122 1255. 202 L. Engman Organometallics 1989 8 1997. 203 G.Erker and R. Hock Angew. Chem. Int. Ed. Engl. 1989 28 179. 204 M. Segi T. Koyama Y. Takata T. Nakajima and S. Suga J. Am. Chem. SOC.,1989 111 8749. 205 M. Segi T. Koyama T. Nakajima S. Suga S. Murai and N. Sonoda Tetrahedron Lett. 1989,30,2095. 206 R. W. Geddridge jun. K. T. Kiga D. C. Harris R. A. Nissan and M. P. Nadler Organometallics 1989 8 2812. 207 K. T. Higa and D. C. Harris Organometallics 1989 8 1674. 208 V. A. Potapov S. V. Amosova and A. S. Kashik Tetrahedron Lett. 1989 30 613. 209 H. B. Singh and F. Wudl Tetrahedron Lett. 1989 30 441. 284 P. D. Lickless and attempted transesterification by for example treatment with an alcohol leads only to decomposition.210 A series of tellurocarboxylates RC(0)TeR’ (R = PhCH2 R’ = Et; R = 1-naphthyl R’ = Me) can be prepared as yellow to orange solids or liquids.The first step in the synthesis involves treatment of an acid chloride with Na2Te to give RC(O)TeNa which when treated with an alkyl or aryl iodide affords the RC(0)TeR’. This appears to be the first time that such compounds have been isolated.211 H. Suzuki and Y. Nishioka Bull. Chem. SOC.Jpn. 1989 62 2177. T. Kanda S. Nakaiida T. Murai and S. Kato Tetrahedron Lett. 1989 30 1829.

ISSN:0069-3030    

DOI:10.1039/OC9898600261

出版商:RSC    

年代:1989

数据来源: RSC

摘要:

10 Synthetic Methods By D. R. KELLY School of Pure Chemistry and Applied Chemistry University of Wales College of Cardiff PO Box 912 Cardiff CFl3TB 1 Introduction The major preoccupation in synthesis’ continues to be the development of techniques for the preparation of chiral intermediates2 for use in natural product ~ynthesis.~ Of the four main approaches available the use of naturally available chiral materials such as s~gars~-~ and amino acids’ seems to be declining whilst asymmetric synthesis (particularly using transition metals’) and the use of enzyme-catalysed reactions9-’ ’ are on the increase. For example ethyl (S)-(+) -3-hydroxybutanoate and cis-benzene glycol,’2 which both result from enzyme technology are now commonly used in synthesis.Resolution and chiral chr~matography’~ are used less frequently although the latter is now the method of choice for analytical purpose^.'^ The merits and otherwise of each approach are discussed in a review of the synthesis of insect pheromones by Mori.’’ The strategies behind contemporary synthetic routes are reviewed in the new journal Chernrrucrs and two books.16 A modestly priced C. Seoane Aldrichim. Acta 1989 22 41. * S. G. Davies J. M. Brown A. J. Pratt and G. W. J. Fleet Chem. Er. 1989 259. A.-ur-Rahman (ed.) ‘Studies in Natural Products Chemistry Stereoselective Synthesis’ Parts B and C Elsevier Amsterdam 1989. G. W. J. Fleet Chem. Er. 1989 287. D. Horton (ed.) ‘Trends in Synthetic Carbohydrate Chemistry’ ACS Symposium Series No. 386 American Chemical Society Washington DC 1989.S. Hanessian Aldrichim. Acta 1989 22 3. ’ M. J. O’Donnell W. D. Bennett and S. Wu J. Am. Chem. Soc. 1989 111 2353. * S. G. Davies Chem. Er. 1989 268; J. M. Brown ibid. p. 276; 1. Oijima N. Clos and C. Bastos Tetrahedron 1989 45 6901; S. I. Blystone Chem. Rev. 1989 89 1663. A. J. Pratt Chem. Er. 1989 282. 10 H. Davies R. H. Green D. R. Kelly and S. M.Roberts ‘Biotransformations in Preparative Organic Chemistry The Use of Isolated Enzymes and Whole Cell Systems in Synthesis Best Synthetic Methods’ Academic Press London 1989. J. R. Whitaker and P. E. Sonnet (eds.) ‘Biocatalysis in Agricultural Biotechnology’ ACS Symposium Series No. 389 American Chemical Society Washington DC 1989. 12 J. R. Gillard and D. J.Burnell 1. Chem. Soc. Chem. Commun. 1989 1439. l3 P. R. Brown and R. A. Hartwick (eds.) ‘High Performance Liquid Chromatography’ John Wiley New York 1989; S. 6.Allenmark ‘Chromatographic Enantioseparation Methods and Applications’. John Wiley New York 1989; M. Zief and L. J. Crane ‘Chromatographic Chiral Separations’ Chromato- graphic Science Series No. 40 Marcel Dekker New York 1988; E. Gruska ‘Preparative Scale Chromatography’ Chromatographic Science Series No. 46 Marcel Dekker New York 1989. 14 V. Schurig H.-P. Nowotny and D. Schmalzing Angew. Chem. Int. Ed. Engl. 1989 28 736; W. A. Konig S. Lutz G. Wenz G. Gorgen C. Neumann A. Gabler and W. Boland ibid. p. 178. l5 K. Mori Tetrahedron 1989 45 3233. 16 E. J. Corey and X.-M. Cheng ‘The Logic of Chemical Synthesis’ Wiley Chichester 1989; T.Lindberg ‘Strategy and Tactics in Organic Synthesis Volume 2’ Academic Press San Diego 1989. 285 286 D. R. Kelly encyclopaedic compilation of 15 000 reaction^'^ and a second edition of Brandsma's classic book on acetylene chemistry have been published." Wittig Cr"/Ni" OH , OH OH HOC\ Me OH Palytoxin (la) -the Everest of organic synthesis -appears to be within sight of completion following reports of the synthesis of palytoxin carboxylic acid (lb) and amide (lc) by coupling of eight subunits.'' Synthons for the ABC FG and IJK rings of brevetoxin B (2) have been prepared" and coupled,21 but the technology for the synthesis of the DE rings developed using R.C. Larock 'Comprehensive Organic Transformations A Guide to Functional Group Transformations' VCH New York 1989.18 L. Brandsma 'Preparative Acetylenic Chemistry Second Edition' Studies in Organic Chemistry No. 34 Elsevier Amsterdam 1988. 19 R. W. Armstrong J.-M. Beau S. H. Cheon W. J. Christ H. Fujioka W.-H. Ham L. D. Hawkins H. Jin S. H. Kang Y. Kishi M. J. Martinelli W. W. McWhorter jun. M. Mizuno M. Nakata A. E Stutz F. X. Talamas M. Taniguchi J. A. Tino K. Ueda J. Uenishi J. B. White and M. Yonaga J. Am. Chem. SOC.,1989 111 7525 7530. 2o K. C. Nicolaou M. E. Duggan and C.-K. Hwang J. Am. Chem. SOC.,1989 111,6666,6676,6682; K. C. Nicolaou C. V. Prasad C.-K. Hwang M. E. Duggan and C. A. Veale ibid. p. 5321. 21 K. C. Nicolaou Pacifichem Hawaii December 1989. 287 Synthetic Methods .CHO models22 failed when applied to the natural product.The nine contiguous chiral centres of streptovaricin A were constructed from a tripyran~side.~~ Arguably the most stunning natural products of the past few years are the calicheamicin (3a) and esperamicin (3b) enediyne antitumour antibiotics. The facile electrocyclie rearrangement of these compounds (3) to benzenoid biradi~als~~ is thwarted by the distance between the alkyne groups. However when a nucleophile adds to the enone (3)25 or synthetic analogues26 the geometry changes and- the biradical (4) which is capable of cleaving DNA is formed. 0 NHCOzMe 111 I (3) a; R=H (4) b; R=OH Unnatural product synthesis has also had its triumphs this year; chief amongst these must be the barrel-shaped trinacrene (9,which was constructed in two steps by six Diels-Alder reaction^.^' 22 K.C. Nicolaou C.-K. Hwang and D. A. Nugiel J. Am. Chem. SOC.,1989 111 4136. 23 D. R. Mootoo and B. 0. Fraser-Reid J. Org. Chem. 1989 54 5548. 24 J. P. Snyder J. Am. Chem. Soc. 1989 111 7630. 25 J. N. Haseltine S. J. Danishefsky and G. Schulte J. Am. Chem. SOC.,1989 111 7638; P. Magnus and R. T. Lewis Tetrahedron Lett. 1989 30 1905. 26 K. Tomioka H. Fujita and K. Koga Tetrahedron Lett. 1989,30,851; N. B. Mantlo and S. J. Danishefsky J. Org. Chem. 1989 54 2781; J. F. Kadow M. G. Saulnier M. M. Tun D. R. Langley and D. M. Vyas Tetrahedron Left. 1989 30 3499; P. Magnus and F. Bennett ibid. p 3637; F. J. Schoenen J. A. Porco jun.S. L. Schreiber G. D. VanDuyne and J. Clardy ibid. p. 3765. 21 P. R. Ashton N. S. Isaacs F. H. Kohnke G. S. D’Alcontres and J. F. Stoddart Angew. Chem. Znt. Ed. Engl. 1989 28 1261. 288 D. R. Kelly 2 C-C Connection and Disconnection 0rganometallics.-One of the most important outcomes of the synthetic work on palytoxin was the development of the Cr"/Ni" mediated coupling of vinylic halides and aldehydes. This reaction is very tolerant of oxygen functionality and can even be run in water. Allylic halides [e.g. (6)] react with rearrangement of the double bond (Scheme 1).28 H5 .pH c1 + OHC::;'" + OCHzPh OCH2Ph H H (6) Reagents CrCI, LiAIH, Pr'OH Scheme 1 Although cuprates are widely used in synthesis their structures29 and mechanisms are not clearly understood.An NMR study of bis[dimethylcopper(I) lithium] addi- tion to an a,P-unsaturated ketone (7) indicates initial formation of an q2-alkene complex (8) which ultimately results in 1,4-(9) but not 1,2-addition Lipshutz et al. have shown that in the presence of boron trifluoride etherate the copper (I) reagent heterolyses to the methyllithium complex (11) and Me3Cu2Li (12) the major 28 N. Kato H. Takeshita H. Kataoka S. Ohbuchi and S. Tanaka J. Chem. SOC.,Perkin Trans. 1 1989 165. 29 M. M. Olmstead and P. P. Power J. Am. Chem. SOC.,1989 111 4135. 30 S. H. Bertz and R. A. J. Smith J. Am. Chern. Soc. 1989 111 8276. Synthetic Methods (7) (CuMez),,Li I (Me2CuLi) e MeLi-BF +Me,Cu,Li BF3aOEt2 (11) (12) reactive species.31 In contrast the increased rate of addition of cuprates to saturated32 and unsat~rated~~ ketones engendered by trimethylsilyl chloride was interpreted only in terms of substrate-Lewis acid interactions.OH Scheme 2 Dilithiomethyl(thieny1)cyanocuprate (13) undergoes a substitution reaction with (E)-bis(tributylstanny1)ethylene (14) to give the E-vinylcuprate (15) which reacts with terminal epoxides (Scheme 2).34 2-Vinylcuprates (16) undergo cis addition 31 B. H. Lipshutz E. L. Ellsworth and T. J. Siahaan J. Am. Chem. SOC.,1989 111 1351. 32 S. Matsuzawa M. Isaka E. Nakamura and I. Kuwajima Tetrahedron Lett. 1989 30 1975. 33 Y. Horiguchi M. Kornatsu and I. Kuwajirna Tetrahedron Lett. 1989 30 7087. 34 J. R. Behling J.S. Ng,K. A. Babiak and A. L. Campbell Tetrahedron Lett. 1989 30 27. 290 D. R. Kelly with phenylthioacetylene (17) and substitution of the phenylthio group in the resultant phenyl vinyl sulphide (18) with Grignard reagents catalysed by NiCl,(dppe) gives E,Z-dienes (19) (Scheme 3).35 Reagents i RMgX NiCI,( dppe) Et,O room temperature Scheme 3 High enantioselectivity can be achieved in the addition of alkylzincs to aldehydes catalysed by chiral amino alcohols. When diethylzinc was added to benzaldehyde in the presence of 8 mol YO DAIB (20a) of only 15% e.e. (S)-1-phenylpropan-1-01 was formed with an enantiomeric excess of 95%. The reason for this remarkable result is that the homochiral dimeric precatalyst dissociates rapidly in the presence of the aldehyde or dialkylzinc to give the true catalyst whereas the heterochiral precatalyst is essentially ~nreactive.~~ Several other catalysts have also been used such as the pyrrolidine derivative (20b),37 the bis(su1phonamide) (21),38 prolin~ls;~ and amino alcohols.40 Diaminozinc complexes (22) catalyse the conjugate addition NR' RZ NHSOiCFj aOH NHS02CF3 (20) a; R' = R2 = Me b; R' = H Rz= -CH2 I Me NH( Boc) COZCH2Ph (22) a; R= Me X = C1 (23) b; R=Me,X=OBu' c; R = (S)-PhCH(Me) X =OBu' 35 V.Fiandanese G. Marchese F. Naso L. Ronzini and D. Rotunno Tetrahedron Lett. 1989 30,243. 36 M. Kitamura S. Okada S. Suga and R. Noyori J. Am. Chem. SOC.,1989 111 4028. 37 K. Tanaka H. Ushio and H. Suzuki J. Chem. SOC.,Chem.Commun. 1989 1700. 38 H. Takahashi T. Kawakita M. Yoshioka S. Kobayashi and M. Ohno Tetrahedron Lett. 1989 30 7095; M. Yoshioka T. Kawakita and M. Ohno ibid. p. 1657. 39 K. Soai and S. Niwa Chem. Lett. 1989 481. 40 M. Hiyashi H. Miwata and N. Oguni Chem. Lett. 1989 1970; K. Soai S. Niwa and M. Watanabe J. Chem. SOC.Perkin Trans. 1 1989 109. Synthetic Methods 291 of Grignard reagents to a,P -unsaturated ketones?’ The comparatively low reactivity of organozincs enables highly functionalized reagents such as the protected amino acid (23) to be prepared using s~nication.~~ The corresponding lithio carbanion requires stabilization by an adjacent ester group.43 Reformatsky reagentsw can be added to imines if the zinc is ‘activated’ by trimethylsilyl chloride45 and to acetals in the presence of titanium tetra~hloride.~~ Dimethylzinc suppresses polyalkylation in the reaction of lithium enolates and ele~trophiles~’ and has enabled for the first time the direct three-component synthesis of prostaglandin^.^^ Allylsilanes and A1lylstannanes.-The reaction of carbonyl electrophiles (24) with allyl~ilanes~~ or allylstannanes (26) in the presence of Lewis acids (Sakurai reaction) goes uia two major pathways coordination of the Lewis acid to the carbonyl (25) followed by attack of the allyl species or metathesis of the Lewis acid and the allyl moiety (27) followed by attack of the carbonyl.With boron trifluoride etherate only RL direct addition occurs; with tin tetrachloride either direct reaction or metathesis occurs depending on the stoichiometry and the structure of the carbonyl group;50 with cobalt dichloride complete metathesis seems to occur.51 The use of Lewis acids 41 J.F. G. A. Jansen and B. L. Feringa J. Chem. SOC.,Chem. Commun. 1989 741. 42 R. F. W. Jackson K. James M.J. Wythes and A. Wood J. Chem. SOC.,Chem. Commun. 1989 644. 43 J. E. Baldwin M. G. Maloney and M. North J. Chem. SOC.,Perkin Trans. 1 1989 833. 44 A. Fuerstner Synthesis 1989 571. 45 F. P. Cossio J. M. Odriozola M. Oiarbide and C. Palomo J. Chem. SOC.,Chem. Commun. 1989 74. 46 T. Basile E. Tagliavini C. Trombini and A. Uman-Ronchi J. Chem. Soc. Chem. Commun. 1989 596. 47 Y. Morita M. Suzuki and R. Noyori J. Org. Chem. 1989,54 1785. 48 M.Suzuki H. Koyano Y. Morita and R. Noyori SYNLEm 1989 22. R. G. Majetich in ‘Organic Synthesis Theory and Applications’ ed. T. Hudlicky Jai Press Greenwich 49 CT 1989. so S. E. Denmark E. J. Weber T. M. Wilson and T. M. Willson Tetradhedron 1989 45 1053. J. Iqbal and S. P. Joseph Tetrahedron Lett. 1989 30,2421. 292 D. R. Kelly can be avoided by using high temperat~re~~ pre~sure.'~ The relative or nucleophilicities of 15 allysilanes have been determined by measuring their rates of reaction with p-anisylphenylcarbenium tetrachl~roborate.~~ Allylsilanes bearing alkoxy groups (28) react with two molecules of aldehyde to give cis-tetrahydropyrans (29)? OH I OBOM (32) I iR I OBOM (33) Reagents i BF3.0Etz CH2C12 -78 "C;ii RCHO 140 "C; iii RCHO BF,.0Et2 Scheme 4 a-Alkoxyallylstannanes (30) rearrange stereospecifically to (2)-3-stannyl enol ethers (31) in the presence of boron trifluoride etherate.Upon thermolysis at 140"C with aldehydes they predominantly yield the anti adduct (32) via a syn SE2' pathway; under catalysis by boron trifluoride etherate they give the syn adduct (33) via an anti SE2'pathway (Scheme 4).56Similarly the syn adduct was also formed when N-acyliminium salts were used as the ele~trophile,~' whereas with titanium tetra- chloride both stereoisomers of the vinyl carbamate (34)give the same product (35) via the metathesis pathway.58 52 A. J. Pratt and E. J. Thomas J. Chem. SOC.,Perkin Trans. I 1989 1521; V. J. Jephcote A.J. Pratt and E. J. Thomas ibid. p. 1529. 53 Y. Yamamoto and K. Saito J. Chem. SOC.,Chem. Commun. 1989 1676. 54 H. Mayr and G. Hagan J. Chem. SOC.,Chem. Commun. 1989 91. 55 Z. Y. Wei D. Wang J. S. Li and T. H. Chan J. Org. Chem. 1989 54 5768. 56 J. A. Marshall and W. Y. Gung Tetrahedron Lett. 1989 30 2183; Tetrahedron 1989,45 1043. 57 Y. Yamamoto and M. Schmid J. Chem. SOC. Chem. Commun. 1989 1310. 58 T. Kramer J.-R. Schwark and D. Hoppe Tetrahedron Lett. 1989 30 7037. Synthetic Methods T ;20,"+ or OCb yyb OCb Me3Sn (35) (34) 0 II Cb = -C-NPr; The anionic counterpart of the Sakurai reaction in which the allysilane or -stannane is converted into a pentacoordinate speciess9 by addition of a nucleophile (typically fluoride) has been reviewed.60 If a-hydroxy ketones are used as the electrophile in the presence of triethylamine the hydroxy group acts as an internal nucleophile and the transfer of the ally1 group in th.e complex (36)so formed is highly stereoselec- tive for formation of the syn adduct (37).61 1 (37) Oxaphosphetanes (38)62 have emerged as the key intermediate9 in the Wittig reaction.63 The vinylogous oxaphosphinine (40) is postulated to be the intermediate in the decomposition of the phosphonium salt (39).64 Diphenyl ylide anions (41) Rip-0 R2~#R' R' R4 (41) 59 S.Pernez and J. Hamelin Tetrahedron Left. 1989 30,3419. 60 H. Sakurai SYNLEn 1989 1. 61 K. Sato M. Kira and H. Sakurai J. Am. Chem. SOC.,1989 111 6429.62 E. Vedejs and C. F. Marth J. Am. Chem. SOC.,1989 111 1519; E. Vedejs and T. J. Fleck ibid. p. 5861. 63 B. E. Maryanoff and A. B. Reitz Chem. Reu. 1989 89 863. 64 J. Le Roux and M. Le Corre J. Chem. SOC.,Chem. Commun. 1989 1464. 294 D. R. Kelly give a higher proportion of the 2-alkene than conventional triphenylphosphoranes and the second group is donated more readily than the first.6s Tandem Wittig reactions to give dienes (43) in which the one phosphorus atom is ‘used’ twice can be achieved with 1,l-diphenylphospholaniumperchlorate (42) (Scheme 5).66 Reagents i BU‘OK; ii C6H13CHO; iii BuLi; iv MeSSMe; v BuLi; vi C8H,,CH0 Scheme 5 Unstabilized arsonium ylides give exclusively trans epoxides with aldehydes whereas semistabilized arsonium ylides give alkenes if potassium hexamethyl- disilazide (KHMDS) is used as the base and epoxides with LiHMDS.67Arsines are comparatively expensive which restricts their use in synthesis; however a new procedure uses a mixture of the aldehyde a bromo compound and triphenyl phosphite plus a catalytic amount of tributylarsine.The arsonium salt is formed in situ and undergoes deprotonation and the Wittig reaction to yield tributylarsine oxide which is then reduced back to tributylarsine by triphenyl phosphite.68 The same techniques has also been used with dibutyl telluride.69 Cyc1oadditions.-The [2 + 21 cycloaddition of methoxymethyl vinyl ketone (44) to styrenes (and methylenecyclohexane) catalysed by Ti’” (Scheme 6) can be achieved without photochemistry although this is limited at present to highly nucleophilic alkenes.” Scheme 6 Dye-sensitized photooxygenation of 2-methoxyfurans (45) gives bicyclic adducts (46) which decompose on warming to give carbonyl oxides (47).7’This method is a useful alternative to ozonolysis.An intramolecular nitrone cycloaddition was used 65 E. G. McKenna and B. J. Walker J. Chem. SOC.,Chem. Commun. 1989 568. 66 I. Yamamoto S. Tanaka T. Fujimoto and K. Ohta J. Org. Chem. 1989 54 747. 67 J. D. Hsi and M. Koreeda J. Org. Chem. 1989 54 3229. 68 L. Shi W. Wang Y. Wang and Y.-Z. Huang J. Org. Chem. 1989,54 2027. 69 Y.-2. Huang L.-L. Shi and X.-Q. Wen J. Chem. SOC.,Perkin Trans. 1 1989 2397. 70 T. A. Engler M. H. Ali and D. V. Velde Tetrahedron Lett.1989 30 1761. ” M. L. Graziano M. R. Iesce F. Cermola F. Giordano and R. Scarparti J. Chem. Soc. Chem. Comrnun. 1989 1608. Synthetic Methods 295 I2Me C02Me C02Me -Ph-( %02Me Ph 9-0 to prepare the densely functionalized cyclohexane (48) from mannose (Scheme 7).72 The addition of Trost's trimethylenemethane equivalent (49a) to homochiral vinyl y-alkoxysulphones,74 oxa~epinediones,~~ sulph~xides,~~ or acrylate gives (48) ' Reagents i NaIO,; ii HONHMe NaHCO Scheme 7 cyclopentenes with high diastereomeric excesses. Additions to aldehydes and some ketones are possible with the tin analogue (49b) and tri-n-butyltin acetate as co- catalyst.77 A~O&R L J (49) a; R= SiMe b; R= SnBu Diels- Alder reaction of 2-vinyl- 1,4-benzodioxin (50) with dimethyl acetylenedi- carboxylate gives an adduct (51) which on treatment with base yields a 2-hydroxy bisaryl ether (52) a structural component of the vanc~mycins.~~ The use of high pressure or simply stirring with florisil enables even reluctant enophiles such as f~ran~~ to undergo the intramolecular Diels- Alder (IMDA) reaction.80 With allenic ketones" or vinyl sulphonatess2 the reaction proceeds at 72 T.K. M. Shing D. A. Elsley and J. G. Gillhouley J. Chem. Soc. Chem. Commun. 1989 1280. 73 F. Chaigne J.-P. Gotteland and M. Malacria Tetrahedron Lett. 1989 30 1803. 74 B. M. Trost P. Seoane and M. Acemoglu J. Am. Chem. Soc. 1989 111 7487. 75 B. M. Trost B. Yang and M. L. Miller J. Am. Chem. Soc. 1989 111 6842.76 P. Binger A. Brinkmann P. Roefke and B. Schafer Liebigs Ann. Chem. 1989 739. 77 B. M. Trost. S. A. King and T. Schmidt J. Am. Chem. Soc. 1989 111 5902. 78 T. V. Lee A. J. Leigh and C. B. Chapleo SYNLETT 1989 30; cf G. Mezey-Vandor M. Nogradi V. P. Novikov A. Wiszt and M. Kajtar-Peredy Liebigs Ann. Chem. 1989 401. 79 Furan ethers readily undergo the intermolecular Diels-Alder reaction see M. Korreda K.-Y. Jung and J. Ichita J. Chem. Soc. Perkin Trans. I 1989 2129. 80 B. A. Keay and P. W. Dibble Tetrahedron Lett 1989,30 1045; C. Rodgers and B. A. Keay ibid. p. 1349. H. Finch L. M. Harwood G. M. Robertson and R. C. Sewell Tetrahedron Lett. 1989 30,2585. 82 E. Bovenschulte P. Metz and G. Henkel Angew. Chem. Int. Ed. Engl. 1989 28 202.296 D. R. Kelly + Me02CC CC02Me -nor ‘0 01Q1O2Me C02Me (51) Bu‘OK 1 OH room temperature. An interesting demonstration of the effect of geometry on the IMDA reaction is provided by the quassinoid intermediate (53) in which the unactivated alkene moiety reacts in preference to the normally more reactive enone group.g3 Removable stereogenic groupsg4 and chiral Lewis acidsg5 for the generation of asymmetry in the Diels-Alder reactions6 are now frequently used devices. Kagan has reported the first example of induction of chirality by an alkaloid base (Scheme 8). Presumably this operates via a chiral ion pair (54).” Nitrosoyl hydride and nitrosoformaldehyde can be generated by thermolysis of their 9,lO-dimethylanthracene adducts; they undergo Diels-Alder reactions with dienes.” High diastereomeric excesses were achieved in the cycloadditions of chiral a-hydroxyacylnitroso compoundsg9 and iminium ions derived from amino acids.” 83 T.K. M. Shing Y.Tang and J. F. Malone J. Chem. Soc. Chem. Commun. 1989 1294. 84 I. Alsono J. C. Carretero and J. L. G. Ruano Tetrahedron Lett. 1989 30 3853; M. C. Carreno J. L. G. Ruano and A. Urbano ibid. p. 4003; R. C. Gupta D. S. Larsen R. J. Stoodley A. M. Z. Slawin and D. J. Williams J. Chem. Soc. Perkin Trans. 1 1989 739. 85 J. W. Faller and C. J. Smart Tetrahedron Lett. 1989 30 1189; N. Iwasawa J. Sugimori Y. Kawase and K. Narasaka Chem. Lett. 1989 1947. 86 M. J. Tashner in ‘Organic Synthesis Theory and Applications’ ed. T. Hudlicky Jai Press Greenwich CT 1989.87 0. Riant and H. B. Kagan Tetrahedron Lett. 1989 30 7403. 88 H. E. Ensley and S. Mahadevan Tetrahedron Lett. 1989 30 3255. 89 A. Miller T. McC. Paterson and G. Procter SYNLETT,1989 32. 90 H. Waldmann Liebigs Ann. Chem. 1989 231. Synthetic Methods q 0 V I 0 Y-NH Scheme 8 reflux2h Benzene CN CN toluene 91 M. Teng and F. W. Fowler Tetrahedron Lett. 1989 30 2481. 92 J. Barluenga M. Tomas A. Ballesteros and L. A. Lopez J. Chem. Soc. Chem. Cornrnun. 1989 1487. 93 J. Barluenga J. Joglar F. J. Gonzalez and S. Fustero Tetrahedron Lett. 1989 30 2001. 94 J. Barluenga F. J. Gonzalez and S. Fustero Tetrahedron Lett. 1989 30 2685. 298 D. R. Kelly (59).Diazocarboxylate esters (61) undergo photochemically induced cy~loaddition'~ with glycals (60) to give adducts (62) which are powerful glycosylating reagents and which can be reduced to 2-aminoglycosides (63) (Scheme 9).96 Reagents i hv (350nm) cyclohexane; ii R'OH; iii Raney Ni H2 Scheme 9 3 Functional Group Manipulation Addition Reactions.-The Cieplak theory has stimulated several groups to investigate additions to ketones and alkenes with 'remote' substituents. Electron-withdrawing equatorial substituents at the 3-position of cyclohexanones and methylenecyclo- hexanes clearly favour axial attack in a wide range of addition reaction^,^' but the results are much less clear-cut for substituents at the 2-po~ition.'~ Epoxides.-The Sharpless asymmetric epoxidation reaction continues to find new application^,^^-'^' but no ligands superior to tartrate esters have been found.lo2 Useful stereoselectivity can be achieved with other transition-metal catalyst^;'^^ for example epoxidation of norbornene by Cr"' porphyrins is highly selective for the ex0 face.'04 95 S.M.Weinreb and P. M. Scola Chem. Rev. 1989 89 1525. 96 Y. Leblanc and B. J. Fitzsimmons Tetrahedron Lett. 1989 30,2889; Y. Leblanc B. J. Fitzsimmons J. P. Springer and J. Rokach J. Am. Chem. SOC.,1989 111 2995. 97 A. S. Cieplak B. D. Tait and C. R. Johnson J. Am. Chem. Soc. 1989 111 8447. 98 E. Vedejs and W. H. Dent 111 J. Am. Chem SOC.,1989 111 6861. 99 P. N. Guivisdalsky and R. Bittman J. Org. Chem. 1989,54,2826; M. Oshima H. Yamazaki I.Shimizu M. Nisar and J. Tsuji J. Am. Chem. SOC.,1989 111 6280. 100 S. Takano Y. Iwabuchi and K. Ogasawara J. Chem. Soc. Chem. Commun. 1989 1371; S. Takano K. Samizu T. Sugihara and K. Ogasawara ibid.,p. 1344; S. Takano K. Inomata T. Sato and K. Ogasawara ibid. p. 1591. 101 M. M. L. Crilley A. J. F. Edmunds K. Eistetter and B. T. Golding Tetrahedron Lett. 1989 30,885; L. Thijs D. M. Egenberger and B. Zwanenburg ibid. p. 2153. 102 C. J. Burns C. A. Martin and K. B. Sharpless J. Org. Chem. 1989 54 2826; P. G. Potvin R. Gau P. C. C. Kwong and S. Bianchet Can. J. Chem. 1989 67 1523. 103 K. A. Jorgensen Chem. Rev. 1989,89 431. *04 T. G. Traylor and A. R. Miksztal J. Am. Chem. Soc. 1989 111 7443; J. M. Garrison and T. C. Bruice ibid. p.191. Synthetic Methods 299 Dimethyldioxirane (64)'05 is emerging as the reagent of choice for the preparation of labile epoxides such as those derived from glycals,lo6 enol esters,'" enol lac- tones,lo8 and a$-unsaturated is~nitriles,''~ although side reactions are encountered in the oxidation of benzaldehydes to carboxylic acids"' and sulphides to sul- phoxides."' Methyl(trifluoromethyl)dioxirane,which is somewhat more reactive epoxidizes enol ethers"2 and also oxidizes hydrocarbons to alcohols and ketones.113 0-0 X Me Me (64) The conversion of acid chlorides (65) into ally1 alcohols (68) is achieved in one pot by double addition of chloromethyllithium to give the alkoxide (66),nucleophilic displacement of the halogeno group and Boord-type elimination (Scheme 10).In the absence of lithium iodide the epichlorohydrin (67) is i~olated."~ Reagents i CICH,I LiBr; ii 2MeLi-LiI Scheme 10 The regiochemistry of intramolecular ring opening of epoxides by hydroxy groups can be forced into the endo mode by an adjacent alkene group (Scheme 11).This methodology was applied extensively in the synthesis of intermediates for brevetoxins A and B (2)."' peJ'-\"-J R R R Scheme 11 10s R. W. Murray Chem. Rev. 1989 89 1187; W. Adams R. Curci and J. 0. Edwards Acc. Chem. Res. 1989 205. 106 R. L. Halcomb and S. J. Danishefsky J. Am. Chem. SOC.,1989 111 6661. 107 W. Adam L. Hadjiarapoglou and X. Wang Tetrahedron Lett. 1989 30 6497. 108 W. Adam L. Hadjiarapoglou V. Jager and B.Seidel Tetrahedron Left. 1989 30,4223. 109 J. E. Baldwin D. J. Aldous C. Chan L. M.Hanvood I. A. O'Neil and J. M. Peach SYNLETT 1989 9. 110 A. L. Baumstark M. Beeson and P. C. Vasquez Tetrahedron Lett. 1989 30 5567. 111 S. Colonna and N. Gaggero Tetrahedron Lett. 1989 30 6233. 112 L. Troisi L. Cassidei L. Lopez R. Mello and R. Curci Tetrahedron Lett. 1989 30 257. 113 R. Mello M. Fiorentino C. Fusco and R. Curci J. Am. Chem. SOC.,1989 111 6749. 114 J. Barluenga J. L. Fernandez-Simon J. M. Concellon and M. Yus J. Chem. SOC.,Perkin Trans. I 1989 77. 115 K. C. Nicolaou C. V. C. Prasad P. K. Somers and C.-K. Hwang J. Am. Chem. SOC. 1989 111 5330 5335. 300 D. R. Kelly Treatment of epoxy silyl ethers (69) with an aluminium phenoxide catalyst (70) causes stereoselective anti migration of the silyloxymethyl group to the epoxide moiety to give silyloxy aldehydes (71).l16 The enantioselective deprotonation of racemic epoxides by chiral bases provides in principle a better route to chiral allylic alcohols and epoxides than the Sharpless methodology.However the enantiomeric excesses achieved thus far are inferior.' l7 Dihydroxy1ation.-The osmium tetroxide-catalysed dihydroxylation of cyclohexene and a-pinene with trimethylamine N-oxide (Scheme 12) is first order in osmium catalyst and amine oxide but zero order in alkene. The slow step is either trimethyl- amine N-oxide oxidation of the osmium(v1) ester (72) or hydrolysis of the osmium(vII1) ester (73).' l8 Independently the Sharpless group showed that the low enantioselectivity obtained in some alkaloid-catalysed dihydroxylations is due to the diversion of the osrnium(vII1) ester (73) into a second catalytic cycle which has low (and often opposite) enantioselectivity.' l9 This accords with the earlier observa- tion that when the dihydroxylation of trans-stilbene is run in the presence of a-pinene (R,R)-hydrobenzoin is produced with 3% e.e.ll*A modified experimental procedure in which the alkene is slowly added to the other reactants improves the enantiomeric excess and reduces the reaction time.' l9 The catalytically active osmium tetroxide-Cinchona alkaloid complexes12' con- tains a single coordinated amine,"l but diamines with a C2axis [e.g.(74)'22,'23 and (75)lZ4] often give better enantiomeric excesses with E -alkenes.116 K. Maruoka T. Ooi and H. Yamamoto J. Am. Chem. Soc. 1989 111 6431. 117 M. Asami and N. Kanemaki Tetrahedron Lett. 1989 30,2125. 118 E. Erdlick and D. S. Matteson J. Org. Chem. 1989 54 2742. 119 J. S. M. Wai I. Marko J. S. Svendsen M. G. Finn E. N. Jacobson and K. B. Sharpless J. Am. Chem. Soc. 1989 111 1123; B. B. Lohray T. H. Kalantar B. M. Moon C. Y. Park T. Shibita J. S. M. Wai and K. B. Sharpless Tetrahedron Lett. 1989 30 2041. 120 J. S. Svendsen I. Marko E. N. Jacobson Ch. P. Rao S. Bott and K. B. Sharpless J. Org. Chem. 1989 54 2263. 121 E. N. Jacobsen I. Marko M. B. France J. S. Svendsen and K. B. Sharpless J. Am. Chem. Soc. 1989 111 737. 122 M. Hirami T. Oishi and S.Ito J. Chem. Soc. Chem. Commun. 1989 665. 123 T. Oishi and M. Hirama J. Org. Chem. 1989 54 5834. 124 E. J. Corey P. D. Jardine S. Virgil P.-W. Yuen and R. D. Connell J. Am. Chem. Soc. 1989 111,9243. Synthetic Methods 302 D. R. Kelly Ph Ph R R (74) R = Me Et Pr etc. (75) The reaction of alkenes with permanganate (Scheme 13) gives a cyclic manganese(v) ester (76)lZ5similar to that observed with osmium tetroxide. This is rapidly oxidized to manganate(v1) (77)which undergoes base hydrolysis to the diol (78) whereas under neutral conditions disproportionation of (77) gives a manganese(vI1) ester (79) which is ultimately converted into a ketol (80).lz6 H H H H Scheme 13 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone(DDQ) stereoselectively hydroxy- lates the benzylic position of chiral phenylacetic esters (d.e.< 67%).lz7Camphoryl-sulphonyloxaziridine'28 and its derivative^'^^ effect the enantioselective hydroxyla- tion of enolates and in such a role they may supplant phenylsulphonyloxaziridine which has low diastereoselecti~ity.~~~ Reduction.-Magnesium in methanol reduces acetylenic and a,@-unsaturated esters to saturated esters,131 whereas a mixture of copper iodide lithium iodide and tin 125 T. Ogino and N. Kikuiri J. Am. Chem. SOC.,1989 111 6174. 126 D. G. Lee and T. Chen J. Am. Chem. SOC.,1989 111 7534. 127 A. Guy A. Lemor D. Imbed and M. Lemaire Tetrahedron Lett. 1989 30 327. 128 F. A. Davis A. C. Sheppard and G. S. Lai Tetrahedron Lett. 1989 30,779.129 F. A. Davis M. C. Weismiller G. S. Lai B. C. Chen and R. M. Przeslawski Tetrahedron Lett. 1989 30 1613. 130 M. J. Taschner and A. S. Aminbhavi Tetrahedron Lett. 1989 30 1029. 131 R. 0.Hutchins Suchismita R. E. Zipkin I. M. Taffer R. Sivakumar A. Monaghen and E. M. Elisseou Tetrahedron Lett. 1989 30 55. Synthetic Methods hydride effects 1 ,.l-reduction of qP-unsaturated ketones. In the presence of trimethylsilyl chloride even a,P-unsaturated aldehydes undergo exclusive conjugate addition,'32 and similar selectivity is achieved with the hexamer of triphenylphos- phine-copper h~dride.'~~ + c1-I R R= H,Me Bun (82) The binaphthyl group in its many guises [e.g. (8l)l is emerging as the pre-eminent chiral catalyst for the reduction of alkene~'~~ and ketones'35 with hydrogen although similar high efficiencies have been obtained with oxazaborolidines (82) and b0~ane-THF.l~~ Complexes involving sodium hydride zinc chloride and Chiraldt3' or rhodium and proline pho~phines'~~ offer the prospect of an equally economic system but the enantioselectivities are inferior at present.Inclusion complexes are another alternative. Acetyl ferrocene is bound in solution by P-cyclodextrin and reduced enantioselectively by sodium b~rohydride.'~~ Moreover the inclusion com- plexes of prochiral ketones with the dioxolane (83) react enantioselectively with sodium borohydride in the solid state!'40 The reagents are simply ground together in a mortar. (83) Substitution at sp3 Carbon.-Cyclic sulphates are a useful alternative to epoxides since they can be formed from diols without inversion of one centre14' and (in tandem with chiral dihydroxylation) can be used to prepare enantiomerically pure aziridine~.'~~ 13' B.H. Lipshutz C. S. Ung and S. Sengupta SYNLETT 1989 64. 133 D. M.Brestensky and J. M. Stryker Tetrahedron Lett. 1989 30,5677. 134 R. Noyori Chem. Er. 1989 883; Chern. SOC.Rev. 1989 18 187; H. Kawano T. Ikariya Y. Ishii M. Saburi S. Yoshikawa Y. Uchida and H. Kumobayashi J. Chem. Soc. Perkin Trans. 1 1989 1571. 135 K. Mashima K.-H. Kusano T. Ohta R. Noyori and H. Takaya J. Chem. Soc. Chem. Comrnun. 1989 1208. I36 E. J. Corey and J. 0. Link Tetrahedron Lett. 1989 30 6275. 137 A. Feghouli R.Vanderesse Y. Fort and P. Caubere J. Chem. Soc. Chem. Commun.,1989 224. 138 H. Takeda T. Tachinami M. Aburatani H. Takahashi T. Morimoto and K. Achiwa Tetrahedron Lett. 1989 30 363; H. Takeda T. Tachinami and K. Achiwa ibid. p. 36; H. Takahashi and K. Achiwa Chem. Lett. 1989 305. 139 Y. Kawajiri and N. Motohashi J. Chem. Soc. Chem. Comrnun.,1989 1336. I40 F. Toda and K. Mori J. Chem. SOC.,Chem. Commun.,1989 1245; F. Toda K. Kiyoshige and M. Yagi Angew. Chem. Int. Ed. Engl. 1989 28 320. 141 B. M. Kim and K. B. Sharpless Tetrahedron Lett. 1989 30 655. 142 B. B. Lohray Y. Gao and K. B. Sharpless Tetrahedron Lett. 1989 30,2623. 304 D. R. Kelly The combination of triphenylphosphine (TPP) and diethyl azodicarboxylate (DEAD)'43enables the displacement of hydroxy groups by nucleophiles under mild conditions (Mitsunobo reaction).Normally the nucleophile is a carboxylic acid or but equally carbon nitrogen (e.g.hydrazor~es'~~ and or diacylamine~'~~) halogen nucleophiles can be employed. Peracids are reduced to the corresponding carboxylic acid by the intermediate betaine.'47 Primary and secondary alcohols usually react with inversion of configuration by an SN2process whereas allyli~'~~ and benzylic alcohols'49 react via an SN1mechanism [e.g. the cis-diol (84) gives an epoxide (85) under standard Mitsunobo conditions]. Protecting Groups.-Although the use of protecting groups should be avoided wherever possible it is nevertheless often difficult to do without them. For example in the synthesis of palytoxin carboxylic acid (1b) forty-two hydroxy-protecting groups of eight different types were removed in five steps and 35% yield -an average efficiency of 97S0/0.l9Benzyl ethers are normally formed from alkoxides and a benzyl halide under strongly basic conditions; however by using phenyldiazomethane and fluoroboric acid they may be made at -40 "C,under essentially neutral conditions and in the presence of amines which react much more slowly.'5o t-Butyldimethylsilyl ethers can be cleaved in the presence of t-butyldiphenylsilyl ethers by using the mild reagent pyridinium p-toluenes~lphonate.'~~ THP-protected alcohols are cleaved by triphenylphosphine dibromide at -50 0C.152 However treatment with triphenylphosphine and carbon tetrabromide effects conversion into the corresponding bromide with inversion of ~0nfiguration.l~~ If a double bond is present cyclization via an oxonium ion occurs.'54 Ketals can be cleaved in the absence of water by aluminium trii~dide'~~ or by samarium trichloride and trimethyl chl~rosilane,'~~ and are directly converted into thioketals without affecting ketones by using magnesium bromide and ethanedithi01.I~~ Even more remarkably with 1,2-bis(trimethylsilyloxy)cyclopentene 143 For the use of polymer-bound alkyl azodicarboxylates see L.D. Arnold H. I. Assil and J. D. Vederas J. Am. Chem. SOC.,1989 111 3973. 144 P. Beraud A. Bourhim S. Czernecki and P. Krausz Tetrahedron Lett. 1989 30 325. 145 J. F. Kadow D. M. Vyas and T. W. Doyle Tetrahedron Lett.1989 30 3299. 146 P. G. Sammes and D. Thetford J. Chem. SOC.,Perkin Trans. 1 1989 655. 147 D. Crich H. Dyker and R. J. Harris J. Org. Chem. 1989 54 257. 148 V. Farina Tetrahedron Lett. 1989 30 6645. 149 E. Palomoin A. P. Schaap and M. J. Heeg Tetrahedron Lett. 1989 30 6797. L. J. Liotta and B. Ganem Tetrahedron Lett. 1989,30 4759. lS1 C. Prakash S.Saleh and I. A. Blair Tetrahedron Lett. 1989 30 19. 152 A. Wagner M.-P. Heitz and C. Mioskowski J. Chem. SOC.,Chem. Commun. 1989 1619. 153 A. Wagner M.-P. Heitz and C. Mioskowski Tetrahedron Lett. 1989 30 557. 154 A. Wagner M.-P. Heitz and C. Mioskowski Tetrahedron Lett. 1989 30 1971. 155 P. Sarmah and N. C. Barua Tetrahedron Lett. 1989 30,4703. 156 Y. Ukaji N. Koumoto and T. Fujisawa Chem.Lett. 1989 1623. 157 J. H. Park and S. Kim Chem. Lett. 1989 629. Synthetic Methods (86) and boron trifluoride etherate they are converted into cyclohexane-1,3-diones (87)? The methyl orthoformate of 1,2-benzenedimethanol readily forms benzylic ketals with ketones and aldehydes which are cleaved by catalytic hydr~genation.”~ Thioketals are normally cleaved with mercury( 11) salts such as mercuric perchlor- ate buffered with calcium carbonate16’ or by alkylation.’61 However the new reagent bis(trifluoroacetoxy)iodobenzeneis claimed to be more selective.’62 4 New Reaction Conditions Traditionally organic chemists have adopted new equipment somewhat more slowly than their physical chemistry brethren. It is much easier to buy a new reagent than to invest in a new machine! Nevertheless new opportunities should not be over- looked.There have been three major general reviews of sonochemistry (ultrasound) published in the past year’63-’65 and a specialist review devoted to heterocyclic chemistry.’66 The two major uses of ultrasound are the generation of ‘hot’ intermedi- ates and the fragmentation of heterogeneous surfaces so as to increase their surface area. Ultrasonic irradiation of a liquid causes the formation of microscopic bubbles (acoustic cavitation) of incredibly high temperatures (1000-10 000 K) which in turn give rise to free radicals and sometimes lumine~cence.’~’ Thus for example it is possible to hydrostannylate an alkyne at -50 “C using a high-power ultrasonic probe.16’ The rate of many heterogeneous reactions is limited by the reactive surface (88) (89) 158 Y.-J.Wu and D. J. Bumell Tetrahedron Lett. 1989 30,1021. 159 N. Machinaga and C. Kibayashi Tetrahedron Lett. 1989 30,4165. 160 B. H. Lipshutz R. Moretti and R. Crow Tetrahedron Lett. 1989 30,15. 161 Y. Mori and M. Suzuji Tetrahedron Lett. 1989 .u),4383. 162 G. Stork and K. Zhao Tetrahedron Lett. 1989 30,287. 163 ‘Ultrasound Its Chemical Physical and Biological Effects’ ed. K. S. Suslick VCH New York 1988. 164 R. J. Giguere in ‘Organic Synthesis Theory and Applications’ ed. T. Hudlicky Jai Press Greenwich CT 1989. 165 T. J. Mason and J. P. Lorimer ‘Sonochemistry Theory Applications and Uses of Ultrasound in Chemistry’ Ellis Horwood Chichester 1989.166 Y. Gol’dberg R. Sturkovich and E. Lukevics Heterocycles 1989 29 597. 167 E. B. Flint and K. S. Suslick J. Am. Chem. Soc. 1989 111 6987. 168 E. Nakamura D. Machii and T. Inubushi J. Am. Chem. Soc. 1989 111 6849. 306 D.R. Kelly area of the catalyst or reagent. Reformatsky reactions are often difficult to initiate using zinc powder but ultrasonic irradiation results in a change in surface mor- phology of the zinc and enhanced reaction In a careful study of the radical cyclization of 19-iodotabersonine (88) by sodium 16-epivindolinine (89) was isolated in 34% yield (54% conversion) when an ultrasonic bath was used whereas without ultrasound or using a sonic probe only a trace was formed.17’ Even PCC on silica gel oxidizes alcohols more rapidly when irradiated.”l Finally the availability of high-powered tunable microwave generators makes possible the selective ‘heating’ of one component of a mixt~re.”~ ‘69 K.S. Suslick and S. J. Doktycz J. Am. Chem. Soc. 1989 111 2342. 170 G. Hugel D. Cartier and J. Levy Tetrahedron Lett. 1989 30,4513. 171 L. L. Adams and F. A. Luzzio J. Org. Chem. 1989 54 5387. 172 L. J. Lucisano and R. P. Poska Pharm. Technol. Int. 1990 2 38.

ISSN:0069-3030    

DOI:10.1039/OC9898600285

出版商:RSC    

年代:1989

数据来源: RSC

摘要:

11 Enzyme Chemistry By N. J. TURNER Department of Chemistry University of Exeter Exeter EX4 400 1 Introduction Several useful reviews appeared during the year dealing with both general and specific aspects of enzyme-catalysed organic synthesis. These include the use of enzymes in organic media,’ the preparation of chiral building blocks useful for the synthesis of important bioactive natural products,2 lipase-catalysed reactions in organic solvents with reference to enantio~electivity,~ general review of enzymes in organic synthesis use of enzymes to promote key transformations in organic ~ynthesis,~ use of enzymes in the synthesis of chirally labelled amino acids heterocyclic compounds,’ use of hydrolases for asymmetric synthesis,8 and biotrans- formations in organic synthesis.’ 2 Hydrolytic Enzymes Reactions in Aqueous Media.-A lipase from a Pseudornonas species has been used to effect enantioselective hydrolysis of the prochiral dithioacetal (1) to give the corresponding half-ester (2) in a chemical yield of 92% and enantiomeric excess of 98%; (2) was then converted chemically into both the (R)-and (S)-isomers of MK-0571 (3) potent antagonists of leukotriene LTD .lo The effect of high pressure on peptide formation catalysed by carboxypeptidase Y and themolysin has been studied.For example the carboxypeptidase Y catalysed substitution reaction of N-[3-(2-furyl)acryloyl]phenylalanine ethyl ester with gly- cinamide or phenylalaninamide showed a sixfold higher total peptide yield at 200 MPa than at atmospheric pressure.In the case of the reaction of N-acyldipeptide and amino acid amide both the peptide yield and substitution efficiency were improved at elevated pressure and the wasteful hydrolysis of the substrate was ’ M. W. Empie Annu. Rep. Med. Cbem. 1988 23 305. K. Mon ACS Symp. Ser. 1989 389,(Biocatal. Agric. Biotechnol.) 348. ’C. S. Chen and C. J. Sih Angew. Cbem. Znt. Ed. Engl. 1989 28 695. C. H. Wong Science 1989 244 1145. S. M. Roberts Pbilos. Trans. R SOC.London B 1989 324 577. K. J. O’Toole D. Gani and D. W. Young in ‘Synthetic Applications of Isotopes and Labelled Com- pounds’ (Proc. Int. Symp.) 1988 p. 61. ’S. M.Roberts Bog. Heterocycl. Cbem 1989 1 65. * P. Gramatica Cbem Oggi 1989 7 9. D. H. G. Crout and M. Christen Mod.Syntb. Methods 1989 5 1. D. L. Hughes J. J. Bergan J. S. Amato P. J. Reider and E. J. J. Grabowski J. Org. Chem. 1989,!54 1787. 307 308 N. J. Turner SCH2CHzCOzMe P~eudornonas ,SCH2CH2C02Me A~CH~ lipase Ar-yH SCH2CHzCOzMe SCH2CH2C02H (1) (2) I I c1 SCH2CH2CONMe (3) reduced." Griengl has provided a working model for the resolution of esters of bicyclic alcohols by Cundidu cylundriceu lipase. For alcohols containing both bicyclo[2.2. llheptane and bicyclo[2.2.2]octane units the enantioselectivity has been compared and rationalized on the basis of the proposed model.12 Lipase Amano P (from Pseudornonus Juorescens) irreversibly catalyses the ring-opening of a-substituted cyclic acid anhydrides (4; R' = Me W Ph; R2 = H Me Et; n = 1 or 2) in PriO at 20 "C.Preferential attack occurs at the less hindered carbonyl group to give monoesters with high regio~electivity.'~ Acylase I (EC 3.5.1.14) from both porcine kidney and the fungus Aspergillus has been shown to be a broadly applicable enzymic catalyst for the kinetic resolution of unnatural and rarely occurring a-amino acids. Despite accepting a wide variety of side-chains the enzyme is specific for the hydrolysis of N-acyl-L-amino acids.14 Optically active half-esters (5; X = CH=CH CO dioxolane-2,2-diyl) have been prepared by pig-liver esterase and porcine pancreatic lipase (PPL) catalysed hydroly- ses of the corresponding a-symmetric diesters. The hydrolysis with pig-liver esterase was shown to be remarkably affected by acetone as a co-solvent.The half-esters (5) are useful intermediates for the synthesis of (+)-carba~yclin.'~ By changing the alcohol moiety of L-aspartate diesters chymotrypsin can regioselectively hydrolyse either the a-or &ester. For the dimethyl isopropyl and H 'I S. Kunugi K. Tanabe K. Yamashita Y. Morikawa T. Ito T. Kondo K. Hirata and A. Nomura Bull. Chem. SOC.Jpn. 1989 62 514. 12 T. Oberhauser K. Faber and H. Griengl Tetrahedron 1989 45 1679. l3 J. Hiratake K. Yarnamoto Y. Yamamoto and J. Oda Tetrahedron Lett. 1989 30 1555. 14 H. K. Chenault J. Dahmer and G. M. Whitesides J. Am. Chem. SOC.,1989 111 6354. Y. Nagao M. Kume R. C. Wakabayashi T. Nakamura and M. Ochiai Chem. Lett. 1989 239. Enzyme Chemistry benzyl esters the enzyme almost exclusively cleaves the a-esters whereas for the dicyclopentyl and dicyclohexyl esters the hydrolysis occurs preferentially at the 1-Ferrocenylethanol (6) was esterified with high R-enantioselectivity by P.fluorexens lipase. The absolute configuration of the product was rationalized according to an active site model that has been established by examining a range of organic substrates.” The half-ester (7) has been prepared in 63% yield and 96% e.e. by PPL-catalysed hydrolysis of the corresponding prochiral diacetate. The authors note that (7) is synthetically equivalent to a desymmetrized tris(hydroxy- methy1)methane (8) and should therefore provide a useful C4 chiral building block containing a tertiary carbon.” Me / o-“ .-I-,’ OH I I Fe I OH OH Optically active binaphthols such as (1,l’-binaphthyl)-2,2’-diol(9) have been obtained using lipases.Acylation of (*)-(9) with enol esters in diisopropyl ether- acetone (9 1) gave solely (R)-2-acyloxy-2’-hydroxyl-l,l’-binaphthyl having 90-95%e.e. The unreacted (S)-binaphthol had 69-89’/0 e.e. The corresponding hydroly- sis reactions of (*)-binaphthylmonochloroacetyl esters were also carried out giving (R)-(9) in >90% e.e.I9 The optically active bicycloalcohol (10)was prepared by lipase-catalysed hydrolysis of the corresponding racemic acetate (itself available in two steps from dicyclopentadiene). The alcohol (10)was then converted into the enone (11)and then in a number of steps into (+)-cuparenone (12).Interestingly (10) (11) (12) 16 S.H. Wu L. C. Lo S. T. Chen and K. T. Wang J. Org. Chem. 1989 54 4220. N. W. Boaz Tetrahedron Lett. 1989 30 2061. G. Guanti L. Banfi and E. Narisano Tetrahedron Lett. 1989 30 2697. 19 M. Inagaki J. Hiratake T. Nishioka and J. Oda Agric. Biol. Chem. 1989 53 1879. 3 10 N. J. Turner it was shown that the recovered optically active acetate from the lipase reaction could also be converted into the key enone (1 l) thus constituting an enantioconver- gent synthesis of (12)." D-myo-Inositol 1,4,5-triphosphate (14) plays an important role in secondary messenger functions being derived by breakdown of phosphatidylinositol 43-bisphosphate. Synthetic approaches to (14) must address both the problems of enantiomeric resolution during the synthesis and the preparation of differentially protected intermediates.A useful solution to this dilemma uses cholesterol esterase to resolve the (*)-diacetate of (13) to give (-)-(13) in 86% e.e. and 34% yield. Alkaline hydrolysis of (-)-( 13) gave the (+)-diol which was recrystallized from ether-hexane (1:3) to give the diol with optical purity >98%. The diol was then converted into (-)-( 14) in seven steps in an overall yield of 45%.'l OH Enantiomerically pure sulphoxides are not readily available by either chemical or enzymatic procedures. A useful approach to this problem has been provided uia lipase (Pseudomonas sp. K-10) catalysed hydrolysis of racemic methylsulphinyl acetates (*)-(15) to give optically active products.This lipase was tolerant of a wide range of substituents (15; R = p-N02C6H4 p-C1C6H4 Ph p-MeOC6H4 Bu" cyclo- hexyl) in all cases the recovered ester having >98% e.e. and 3349% yield. The acid (16) could similarly be recovered in yields ranging from 88 to 98%." A novel application of hydrolases uiz. enantioface differentiation has been demonstrated using enol esters as substrates. When cycloalkanone enol esters (17) are exposed to the micro-organism Pichia miso in pH 6.5 phosphate buffer at 30 "C the enol esters undergo hydrolysis to give a-alkylcycloalkanones (18) with good enantiomeric purity (Scheme 1).23 Optically active 1,l -dimethyl-1-silacyclohexan-2-20 S. Takano K. Inomata and K. Ogasawara J. Chem. SOC.,Chem. Commun. 1989 271. 21 Y.-C.Liu and C.-S.Chen Tetrahedron Lett. 1989 30 1617. 22 G. Solladie J. Hutt and A. Girardin Synthesis 1987 173; K. Burgess and I. Henderson Tetrahedron Lett. 1989 30 3633. 23 H. Ohta K. Matsumoto S. Tsutsumi and T. Ihori J. Chem. SOC.,Chem. Commun. 1989 485. Enzyme Chemistry OCOR' 0 n R' R2 Yield YO e.e. % Configuration 4 Me Me 64 83 S 4 Me Et 98 94 S 4 Me Pr 85 77 S 4 Me Ph 92 41 S 4 CH,CH=CH Et 92 80 R 4 CH,Ph Me 63 83 R 6 Me Me 60 67 S Scheme 1 01s have been obtained by hydrolysis of the corresponding racemic acetates using C.cylandricea lipa~e.~~ Optically active cyanohydrins have been prepared previously using mandelonitrile lyase catalysed addition of cyanide to an aldeh~de.~' A number of research groups have now prepared these compounds using lipases e.g.hydrolysis of racemic cyanohydrin and lipase-catalysed irreversible transesterification of cyanohydrins using enol esters as acyl donors.29 Enzymes that are able to hydrolyse nitriles to amides or acids have been relatively unexplored. The number of papers appearing in 1989 reflects the growing interest in this area. Among the recent reports are those that deal with both aliphatic3' and aromatic transformation^.^'-^^ 24 K. Fritsche C. Syldatk F. Wagner H. Hengelsberg and R. Tacke Appl. Microbiol. Biotechnol. 1989 31 107. 25 F. Effenberger T. Ziegler and S. Forster Angew. Chem. Znr. Ed. Engl. 1987 26 458. 26 H. Ohta S. Hiraga K. Miyamoto and G. Tsuchihashi Agric. Biol. Chem. 1988 52 3023.27 H. Ohta Y. Miyamae and G. Tsuchihashi Agric. Biol. Chem. 1986,50 3181. 28 A. van Almsick J. Buddrus P. Honicke-Schmidt K. Laumen and M. P. Schneider J. Chem SOC. Chem. Commun. 1989 1391. 29 Y.-F. Wang S.-T. Chen K. K.-C. Liu and C.-H. Wong Tetrahedron Lett. 1989 30 1917. 30 Y. H. Lee and H. N. Chang Biotechnol. Lett. 1989 11 23. 31 M. Kobayashi T. Nagasawa N. Yanaka and H. Yamada Biotechnol. Lett. 1989 11 27. 32 J. Mauger T. Nagasawa and H. Yamada Biotechnology 1988 8 87. 33 J. Mauger T. Nagasawa and H. Yamada Tetrahedron 1989.45 1347. 312 N. J. Turner Reactions in Organic Solvents.-Many examples now exist of reactions catalysed by enzymes (especially hydrolases) in organic solvents. The advantages of carrying out these reactions in non-aqueous environments include enhanced thermostability altered specificity and the generation of new mechanistic pathways that are unavail- able when water is the solvent.Recently Klibanov and co-workers have attempted to provide some direct evidence for the nature of enzymes when suspended in organic solvents by using high-resolution solid state NMR with magic angle spinning. By monitoring the isotropic 15N chemical shifts of the imidazole nitrogens in the active site of an a-lytic protease they were able to compare the aqueous solution structure with that in an organic solvent (acetone octane DMSO). For both acetone and octane they found that the catalytic triad system at the active site remains intact whereas with DMSO the triad becomes disrupted and the enzyme loses its activity.34 Lipases from pig pancreas and Chromobacterium uiscosum (but not Cundida cylundricea) catalyse transesterification reactions between ethyl esters of carboxylic acids and Bu,Sn ethers of primary and secondary alcohols.35 By exploiting the prochiral specificity of enzymes a series of y-hydroxypimelate diesters (19) were converted into either enantiomer of y-butyrolactone substituted propionates (20).The best results were obtained with PPL and R = Et (100%yield >98% e.e.) and R = PhCHz (100%yield >95% e.e.).36 Klibanov has investigated the replacement of water by ‘water-mimics’ in protease- catalysed peptide synthesis thereby minimizing hydrolysis of the peptide bonds. He observed that thermolysin-catalysed peptide bond formation in the reaction between Z-Gly-Gly-Phe-OH and H-Phe-NH was extremely slow in anhydrous t-amyl alcohol but became more pronounced in the presence of 1% water and was further accelerated (200 times) by the addition of 3% more water.To circumvent the problem of competing hydrolysis of the Gly-Phe bond the water was replaced by formamide and ethylene glycol while still maintaining high reaction rates. Using this approach several oligopeptides were prepared by segment c~ndensation.~’ Crown ethers have been found to enhance the rate of the a-chymotrypsin-catalysed transesterification of Ac-Phe-OEt with propanol in n-octane and to a lesser degree when subtilisin is used.38 Oxime acetates and acrylates have been shown to be effective irreversible acyl transfer agents for lipase-catalysed transesterifications in organic media.39 34 P.A. Burke S. 0.Smith W. W. Bachovchin and A. M. Klibanov J. Am. Chem. SOC.,1989 111 8290. 35 M. Therisod J. Organomet. Chem. 1989,361 C8. 36 A. L. Gutman and T. Bravdo J. Org. Chem. 1989 54 4263. 37 H. Kitaguchi and A. M. Klibanov J. Am. Chem. SOC.,1989 111,9272. 38 D. N. Reinhoudt A. M. Fendebak W. F. Nijenhuis W. Verboom M. Kloosterman and H. E. Shoemaker J. Chem. SOC.,Chem. Commun. 1989 399. 39 A. Ghogare and G. S. Kumar J. Chem. SOC.,Chem. Commun. 1989 1533. Enzyme Chemistry 3 Oxidoreductases Both enantiomers of phorocantholide I a defensive secretion of the eucarypt longicorn (Phorucantha synonyrna) have been prepared using baker's yeast-mediated reduction in the key step.Thus diethyl 3-oxoglutarate was converted into the corresponding keto acid (21) which was then reduced with immobilized baker's yeast to give (22); this was subsequently converted into (23)."' The alcohol dehydrogenase from T%ermoanuerobiumbrockii reduces the keto group of the isoxazole (24) to give the (S)-isomer of (25) in >98% e.e. Bromide (25) was then converted through to (S)-(26),a potent and selective P2-adrenergic stimulant. The corresponding (R) -(26) was prepared via a highly enantioselective (97% e.e.) transesterification of the racemic bromohydrin (25) with trifluoroethyl octanoate to give (27) (catalysed by lipase P from P. fluore~cens).~~ Br 7hermoanaerobium Br NH 0 (24) (25) (26) Br Baker's yeast reduction of methyl 3-oxopentanoate normally gives the correspond- ing methyl 3-hydroxypentanoate having the D-configuration.However if the yeast is initially immobilized in magnesium alginate and the reaction is run under a high concentration of magnesium ion then the selectivity is reversed to give the isomer."^ A review has been published covering the synthetic use of amino acid dehy- drogenases hydroxy acid dehydrogenases and alcohol dehydrogenases. In addition methods for co-factor regeneration are disc~ssed.4~ 40 Y. Naoshima H. Hasegawa T. Nishiyama and A. Nakamura Bull. Chem. SOC.Jpn. 1989 62 608. 41 M. De Amici C. De Micheli G. Carrea and S. Spezia J. Org. Chem. 1989 54 2646. 42 K. Nakamura Y. Kawai S.Oka and A. Ohno Tetrahedron Lett. 1989 30,2245. 43 W. Hummell and M. R. Kula Eur. J. Biochem. 1989 184 1. 3 14 N. J. Turner The octyl ester (28) was obtained in 82%e.e. and 77% chemical yield uia reduction of the corresponding P-keto ester with baker's yeast. The nature of the ester group had a profound effect on the stereoselectivity of the reduction since with the ethyl ester the enantiomeric excess was 56% and with the t-butyl ester it was 46%. In all cases the absolute configuration of the product was S. The alcohol (28) was sub- sequently converted into (R)-(+)-a-lipoic acid (29) in five Pursuing the use of organometallic substrates in enzyme-catalysed reactions Yamazaki and Hosono have employed horse-liver alcohol dehydrogenase (HLADH) to resolve racemic 1 -formyl-2-methyl derivatives of tricarbonyl( cyclopen- tadieny1)manganese and (benzene)tricarbonylchromium as well as racemic 1-hydroxyethylferrocene -ruthenocene and -0smocene.For example (*)-(30) was reduced by HLADH and NADH at pH 7.5 and 4 "Cto give after silica chromatogra- phy (1S)-(+)-(30) in 31% yield and (-)-(31) in 35% yield. The enantiomeric purity of both the products as well as those derived from the other substrates was shown to be >99% by chiral shift 'H NMR.45 Analogous reductions have been carried out previ~usly.~~ Baker's yeast entrapped in calcium alginate beads provides a readily reusable catalyst for stereoselective reductions and has been used to prepare (52,13S)-tetradec-Sen- 13-olide an aggregation pheromone of Crytolesters grain beetle.47 I ,Mn, oc A co co 44 A.S. Gopalan and H. K. Jacobs Tetrahedron Lett. 1989,30 5705. 45 Y. Yamazaki and K. Hosono Tetrahedron Lett. 1989 30 5313. 46 S. Top G. Jaonen J. Gillois C. Baldoli and S. Maiorana J. Chem. Soc. Chem. Commun. 1988 1284. 47 Y. Naoshima A. Nakamura T. Nishiyama T. Haramaki M. Mende and Y. Munakata Chem. Lett. 1989 1023. Enzyme Chemistry 3-Fluoropyruvate has been converted into 3-fluoro-~-alanine on a large scale (space-time yield of 76 g/litre/day) with average conversion of 73%. The reactor contained in addition to the substrate alanine dehydrogenase poly(ethy1ene glycol)- modified NADH (catalytic) and formate dehydrogenase to regenerate the NADH.48 A range of P-substituted nitroalkenes has been reduced with high enantiomeric excess (6698%) using baker’s yeast.49 (-)-(2~,5R) -2,5-Dimethylpyrrolidine (32) has been prepared in optically active form (98% e.e.) using baker’s yeast in the key step.50 N 4 Carbon-Carbon Bond Formation A novel carbon-carbon bond forming reaction has been described in the baker’s yeast-mediated reduction of cyanoacetone (33).When ethanol was added to the reaction instead of obtaining the expected 3-hydroxy compound the diastereomers (34) and (35) were obtained in a combined yield of 88% [ratio (34) (35) = 66 341. Separation of (34) and (35) followed by conversion into their Mosher’s esters revealed that each had been formed in >99% e.e. Although the authors offer no explanation for the mechanism one possible clue is that if the reaction is stopped after 4 h then the 2-ethyl-3-0x0 compound is isolated in 58% yield indicating that a-ethylation is the first step in the sequence followed by red~ction.~~ baker’s OH ?H MeL C N - Me>CN + Me%CN I Et Et (33) (34) anti (35) sYn An extensive and detailed paper has been published summarizing the potential for using rabbit-muscle aldolase (RAMA) as a catalyst for stereoselective C-C bond formation.The paper demonstrates that more than 50 aldehydes are substrates for RAMA (in addition to the natural substrate D-glyceraldehyde 3-phosphate) although only two structural analogues of dihydroxyacetone phosphate are accept- able. The paper contains useful information regarding the practical requirements for these reactions including immobilization of the catalyst and isolation of the products.52 Rabbit-muscle aldolase has been used as a catalyst for the key step in the preparation of 3-deoxy-~-arabino-heptulosonic acid 7-phosphate (39) an inter- mediate in the shikimate pathway.The aldolase-mediated carbon-carbon bond 48 T. Ohshima C. Wandrey and D. Conrad Biotechnol. Bioeng. 1989 34 394. 49 H. Ohta N. Kobayashi and K. Ozaki J. Org. Chem. 1989 54 1802. so R. P. Short R. M. Kennedy and S. Masamune J. Org. Chem. 1989 54 1755. ” T. Itoh Y. Takagi and T. Fujisawa Tetrahedron Lett. 1989 30,3811. 52 M. D. Bednarski E. S. Simon N. Bischofberger W.-D. Fessner M.-J. Kim W. Lees T. Saito H. Waldmann and G. M.Whitesides J. Am. Chem. SOC.,1989 111 627. 316 N. J. Turner forming step involved coupling of the protected aldehyde (36) and dihydroxyacetone phosphate (37) yielding the desired C4-C5 threo stereochemistry in the product (38); (38) was then converted in three steps into the target (39).’3 HNAc rabbit-muscle Me02C MeOzC OH OH (36) (37) (38) 1 Since many water-soluble organophosphates are somewhat unstable and difficult to prepare in large quantities Wong and co-workers have carried out in situ formation of vanadate and arsenate esters of alcohols and examined whether they are substrates for organophosphate-requiring enzymes (equation 1). They have found that for many enzymatic reactions (e.g.phosphoglucoisomerase glycerophosphate dehydrogenase glucose 6-phosphate dehydrogenase) arsenate and vanadate esters are mimics of phosphate esters.However with aldolase reactions it was found that only arsenate can be used since with dihydroxyacetone and inorganic vanadate a redox reaction occurs that converts dihydroxyacetone into gly~eraldehyde.’~ R-OH HOASO:-enzyme HO -R-OASOS-R’-OAsO:-2,R-OH (1) By using a half-protected dialdehyde as a substrate for RAMA the ketose products obtained can be subsequently deprotected to provide aldolases with ‘inverted’ configuration. This can be illustrated (Scheme 2) by the synthesis of L-xylose (42) starting from dihydroxyacetone phosphate and diethoxyacetaldehyde (40) to give Reagents i rabbit-muscle aldolase; ii phosphatase; iii iditol dehydrogenase; iv aq.HCI/THF Scheme 2 53 N. J. Turner and G. M. Whitesides J. Am. Chem. SOC.,1989 111,624. 54 D. G. Drueckhammer J. R. Durrwachter R. L. Pederson D. C. Crans L. Daniels and C.-H. Wong J. Org. Chem 1989 54 70. Enzyme Chemistry initially (41). Diastereoselective reduction with L-iditol dehydrogenase followed by cleavage of the acetal gave ~-xylose.~~ Several papers have been published in the past few years describing the use of acylneuraminate pyruvate lyase (EC 4.1.3.3) to prepare neuraminic acid and some analogues. This enzyme catalyses the stereospecific condensation of N-acetylman-nosamine (43; R' = NHAc; R2= R3 = OH) with pyruvate to give N-acetyl-aldolase '%CO2H NANA R2& Ac~2H HO OH -t-0 OH neuraminic acid (44;R' = NHAc R2= R3 = OH).A recent communication sum-marizes the scope and limitations of this aldolase. Those substrates that are success-fully accepted together with the yields for the reactions are presented in Scheme 3.56 R' R2 R3 Yield % NHAc OH OH 100 OH OH OH 87 N3 OH OH 78 OH H OH 67 OH OH H 66 H OH OH 36 Scheme 3 5 Enzymes Acting on Carbohydrates and Oligosaccharides An excellent review by Whitesides has been published covering the use of enzymes especially aldolases glycosyl transferases and glycosidases in carbohydrate syn-thesis." Two reports have exploited the transglycosylating activity of glycosidases to prepare oligosaccharides. Thus trisaccharides have been obtained from a-and P-galact~sidase,~~ and by using two different P-galactosidases (from Escherichia coli and bovine testes) with complementary regioselectivities the synthesis of the disac-charide (45) was achieved.Initially a mixture of oligosaccharides containing pre-dominantly (45) was generated from lactose and D-GalNAc on a mmol scale by HO NHAc (45 1 55 C. W. Borysenko,A. Spaltenstein J. A. Straub and G. M.Whitesides 1.Am Chem SOC,1989,111,9275. 56 C. Augi B. Bouxom B. Cavayi and C. Gautheron Tetrahedron Lett. 1989,30 2217. 57 E. J. Toone E. S. Simon M.D. Bednarski and G. M.Whitesides Tetrahedron 1989 45 5365. 58 K. Ajsaka and H. Fujimoto Carbohydr. Res. 1989 185 139. 318 N. J. Turner transgalactosylation using /3-galactosidase from bovine testes. The unwanted oligosaccharides in the product mixture were then removed by hydrolysis with /3-D-galactosidase from E.coli. Purification on carbon-celite gave (45) in 21% yield.” A recently isolated strain of Bacillus subtilis (NCIB 11871) has been found to produce a new fructosyl transferase (EC 2.4.1.161). This transferase can catalyse formation of a wide range of a,-,-linked disaccharides; for example it is able to transfer 1,6-dichlorofructose from 1’,6-dichlorosucrose to glucose. Most importantly this transferase has a preferred tendency to transfer only a single fructose moiety thereby forming sugars only one residue longer rather than levan polymers.60 Various lipases were screened in order to find a system that was capable of regioselectively acylating either of the two hydroxyl groups present in the tetrahy- drofuran derivative (46).Out of 20 lipases examined a number gave useful selec- tivities producing the corresponding acylated products (47) and (48) using tri- chloroethyl butyrate (5 equiv.) as the acylating agent and benzene as the solvent (Scheme 4). For example with Humicula lunuginosu the ratio of (47) :(48) was 3 :97 OCOR (47) R =Pr” OH (46) Reagents i C1 ‘1Toit-OH benzene lipase (48) R =Pr” CI Scheme 4 (71% conversion) whereas using Rhizopus juponicus gave a corresponding ratio of 86:14 (96% conversion). The reactions could be carried out on a scale of up to 400 mg of (46).6l Glycosylated derivatives of 1-deoxynojirimycin (49) have been prepared using a combination of cyclodextrin glycosyltransferase and gly-coamylase.62 OH I (49) 59 L.Hedbys E. Johansson K. Mosbach P. 0.Larsson A. Gunnarsson and S. Svensson Carbohydr. Res. 1989 186 217. 60 P. S. J. Cheetham A. J. Hacking and M. Vlitos Enzyme Microb. Technol 1989 11 212. 61 F. Nicotra S. Riva F. Secundo and L. Zucchelli Tetrahedron Lett. 1989 30,1703. 62 Y. Ezure S. Marno N. Ojima K. Konno H. Yamashita K. Miyazaki T. Seto N. Yamada and M. Sugiyama Agric. Biol. Chem. 1989 53 61. Enzyme Chemistry 6 Miscellaneous Biotransformations Phosphoenol pyruvate (PEP) (50) is a valuable phosphate donor particularly in the preparation of nucleoside triphosphates (e.g. ATP CTP) from the corresponding diphosphates using adenylate kina~e.~~ It has been prepared in situ in two steps from D-( -)-3-phosphoglyceric acid using readily available enzymes.The PEP thus generated was used to convert cytidine 5’-monophosphate (CMP) to the less readily available cytidine 5’-triphosphate (CTP).64 Homochiral sulphoxides (51; R = CH,OMe Me) have been obtained in >99% e.e. via oxidation of the corresponding sulphides using Rhodococcus equi IF0 3730.65 yYzH 0-P-OH I /-\ ROCH2CH2 Ph OH Metabolism of 1,2-dihydronaphthalene indene and 1,2-benzocyclohepta- 1,3- diene by a mutant strain of Pseudornonas putida has been shown to yield benzylic monoalcohols all containing the R-configuration (along with some vicinal diols as minor products with the S-configuration at the benzylic positions). For example 1,2-dihydronaphthalene (52) gave a 3 :1 mixture of dihydronaphthalenol (53) and dihydroxytetralin (54).66 ?H -q+ \ rn*.OH \ \ OH (52) (53) (54) Hudlicky has employed the known P.putida-mediated transformation of chlorobenzene to diol (55) to provide a useful synthon for the preparation of both D-and L-erythrose derivatives. Thus diol (55) was converted into the protected hydroxy lactone (56) which by manipulation of the site of reduction allowed divergence into both enantiomeric series yielding protected forms of L-and D-erythrose (57) and (58) respectively (Scheme 5).67 P. putida has also been used to convert styrene into the corresponding cis-diol (59) which could be produced at a concentration of 900 mg per litre. The diol (59) was then converted into the cyclohexane derivative (-)-zylene (60) in 11 steps.68 63 C.Augi and C. Gautheron Tetrahedron Lett. 1988 29 789. 64 E. S. Simon S. Grabowski and G. M. Whitesides J. Am. Chem. Soc. 1989 111 8920. 65 H. Ohta S. Matsumoto Y. Okarnoto and T. Sugai Chem. Lett. 1989 625. 66 D. R. Boyd R. McMordie S. Austin N. D. Sharma H. Dalton P. Williams and R. 0.Jenkins J. Chem. Soc. Chem. Commun. 1989 339. 67 T. Hudlicky H. Luna J. D. Price and F. Rulin Tetrahedron Lett. 1989 30 4053. 68 T. Hudlicky G. Seoane and T. Pettus J. Org. Chem. 1989 54 4239. 320 N. J. Turner / xoq 0 iii,iv 0 &H OH (57) OH -OOH \ P v v1 11 (55) (56) OH Me0 OMe (58) Reagents i ;ii 03;iii NaBH,; iv Dibal; v Ph,P=CH,; vi LiAlH Scheme 5 Other examples of the use of benzene cis-glycol products include the preparation of 6-deoxycyclitol analogues of myo-inositol 1,4,5-tripho~phate.~~ Extending his work aimed at finding useful enzyme-catalysed oxidations and hydroxylations Furstoss has shown that N-phenylcarbamate derivatives of both geraniol (61) and nerol (62) undergo highly stereoselective bis-hydroxylations to give the diols (63) and (64) respectively.The conversions (yields) are respectively _____ OCONHPh OCONHPh (62) (64) S. V. Ley M. Parra A. J. Redgrave F. Sternfield and A. Vidal Teirahedron Lett. 1989 30,3557. Enzyme Chemistry 49 and 40% with >90% e.e. in both cases. Two facets of this reaction are of interest (i) if the free alcohols geraniol and nerol are used then no conversion is observed this being in accord with previously observed activating effects of suitably positioned carbonates and amides and possibly being related to the lower lipophilicity of the free alcohols; (ii) in both cases the (S)-C6 isomer is obtained and thus the reaction is independent of the C2-C3 double bond ge~metry.~' Optically active 1,2-epoxy-2-methylalkanes(65; n = 24) have been obtained from the precursor alkenes via microbial epoxidation.The usefulness of these products was demonstrated by their conversions into prostaglandin w-chains (66; R = CECH n = 3; R = I n = 4).71 The complementary enantioselective ring opening of epoxides has been achieved using microsomal epoxide hydr~lase.~~ In the presence of baker's yeast the N-allylcarbamoylanthranilonitrile(67) is cyclized initially to (68) and then to 2-methylimidazo[ 1,2-c]quinazolin-5(3 H)-one (69).The intermediacy of (68) was shown by a time course study after 24h the reaction mixture contained 75% yield of (68) and 20% of (69) whereas after 5 days there remained only 20% of (68) and the yield of (69) had risen to 70%.Unfortunately the reaction appears to show no enantio~electivity.~~ In a subsequent publication the same authors have shown that the initial reaction can also be carried out using cata~ase.~~ R R (68) (69) Dopamine P-monooxygenase has been shown to catalyse aromatization of 1-(2- aminoethyl)cyclohexa-1,4-dieneto 2-phenylethylamine in a reaction that requires stoichiometric oxygen and ascorbate.The authors postulate a mechanism involving hydrogen atom transfer.75 Purine nucleoside phosphorylase has been used to prepare a number of unnatural nucle~sides.~~ 70 J. D. Fourneron A. Archelas and R. Furstoss J. Org. Chem. 1989 54,4686. 7' 0.Takahashi,,J. Umezawa K. Furuhashi and M. Takagi Tetrahedron Lett. 1989 30,1583. 72 G. Bellucci G. Berti C. Chiappe F. Fabri and F. Marioni J. Org. Chem 1989 54 968. 73 A. Kamal and P. B. Sattur J. Chem. SOC.,Chem. Commun. 1989 835. 74 A. Kamal and P. B. Sattur Tetrahedron Lett. 1989 30,1133. 75 K. Wimalasena and S. W. May J. Am. Chem. SOC.,1989 111 2729. 76 W. J. Hennen and C. H. Wong J. Org. Chem. 1989 54 4692. 322 N. J. Turner 7 Novel Biocatalysts In parallel with the development of enzyme-based methodologies for organic syn- thesis much effort is currently being focused on the design of novel catalysts with predetermined characteristics.The relative merits of the two most promising approaches have been critically compared by Hilvert; these are (i) site-directed mutagenesis of existing proteins and (ii) the development of antibody-based catalysts employing rationally designed imm~nogens.~~ The latter field has been separately reviewed." Catalytic antibodies have been demonstrated to carry out hydrolysis of ester substrates both in aqueous media and also in reverse micelles. Thus an antibody generated against the transition-state analogue phenylphosphonate was shown to catalyse the hydrolysis of phenyl acetate in aqueous solution with k,, and K values of 18.8 min-' and 157 pM,respectively.When the antibody was solubilized in reverse micelles formed from 50 mM bis-(2-ethylhexyl)sodium sulphosuccinate in isooctane the corresponding kinetic parameters were 3.89 min-' and 569 PM.'~ Electrostatic interactions between a hapten and the complementary antibody have been exploited to generate catalytic amino acid side-chains in an antibody-combining site. Monoclonal antibodies generated to hapten (70) were capable of catalysing HF elimination from the fluorinated substrate (71). This was rationalized on the basis that the positively charged alkylammonium ion in (70) should induce a carboxylate ion at the active site of the antibody that would then facilitate deproton- ation and hence HF elimination from (71)." F Catalytic antibodies have been shown to catalyse redox reactions by raising antibodies to a fluorescyl hapten and then using them to accelerate the rate of reduction of resazurin by sulphite." Antibody catalysis of a Diels- Alder reaction has been achieved by Hilvert and co-workers.They reasoned that in a Diels-Alder cycloaddition the transition state is highly ordered and resembles the product more than it does the starting material. However the reaction product cannot be used as a suitable hapten for generating antibodies since severe product inhibition of the catalyst would be expected. Thus they concentrated on the reaction between N-ethylmaleimide (73) and tetrachlorothisphene dioxide (72) which proceeds via the unstable bicyclic intermediate (74) that extrudes SO2 to give a dihydrophthalimide (75) as product.Now the final product no longer resembles the transition state and hence product inhibition should be minimized. Five high-affinity monoclonal anti- 77 D. Hilvert ACS Symp. Ser. 1989 389 (Biocatal. Agric. Biotechnol.) 14. 78 G. M. Blackburn A. S. Kang G. A. Kingsbury and D. R. Burton Biochem. J. 1989 262 381. 79 C. N. Durfor R. J. Bolin R. J. Sugasawara R. J. Massey J. Jacobs and P. G. Schultz J. Am. Chem. Soc. 1988 110 8713. 80 K. M. Shokat C. J. Leurnann R. Sugasawara and P. G. Schultz Nature (London) 1989 338 269. 81 N. Janji and A. Tramontano J. Am. Chem. Soc. 1989 111 9109. Enzyme Chemistry c1 c1 1 \/ bodies were elicited against the hapten (76) a stable analogue of (74).When the antibodies were presented with (72) and (73) in aqueous buffer at pH 6.0 they were found to accelerate the rate of the Diels- Alder reaction significantly.82 An artificial selenoenzyme selenosubtilisin has been prepared by chemical con- version of the active site nucleophile (serine-221) in the protease subtilisin into a selenocysteine. The effect of this change of Se for 0 was that the intermediate acyl-enzyme was considerably more reactive towards amines than water (up to 14 000-fold compared with native subtilisin) thereby effectively converting the protease into an acyltran~ferase.~~ Staphyllococcal nuclease ( DNAse) is a relatively non-specific phosphodiesterase that cleaves DNA.By attaching sequence-specific oligonucleotides to a unique site on the enzyme the new hybrid nucleases were shown to hydrolyse single-stranded DNA in a catalytic fashion at specific sequences. One such hybrid nuclease was able to site-selectively cleave single-stranded M13 mp 7 DNA (1214 nucleotides) primarily at one phosphodiester bond.84 82 D. Hilvert K. W. Hill K. D. Nared and M-T. M. Auditor J. Am. Chem. Soc. 1989 111 9261. 83 Z. P. Wu and D. Hilvert J. Am. Chem. Soc. 1989 111 4513. 84 D. R. Corey D. Pei and P. G. Schultz Biochemistry 1989 28 8277.

ISSN:0069-3030    

DOI:10.1039/OC9898600307

出版商:RSC    

年代:1989

数据来源: RSC

摘要:

Author Index Abbas S. A. 31 Abboud J.-L. M. 57 72 Abd-El-Aziz A. S. 251 Abdel Hady A. F. 48 Abdul-Sada A. K. 261 Abia L. 70 Abraham M. H. 57 Aburatani M. 303 Acemoglu M. 151 248 295 Achiwa K. 230 303 Adam W. 52 110 190 299 Adams F. 225 Adams J. 255 Adams L. L. 306 Adams W. 299 Adlington N. K. 282 Adlington R. M. 81 Agrafiotis D. K. 39 56 Ahlberg P. 42 Ahlrichs R. 187 Ahmad-Junan S. A. 77 Ahmar M. 234 Aida T. 166 Aitchison K. A. 267 Ajsaka K. 317 Akaishi R. 282 Akasaka K. 11 hermark B. 246 Akiba K.-y. 280 Akiboye J. 12 Akimoto N. 126 Akita M. 232 Akita S. 20 Akkerman 0. S. 264 Akutagawa K. 208 Alabaster R. J. 237 Alami M. 123 236 Alanaine A.I. D. 49 Alauddin M. M. 99 Albert J. 255 Alberts I. A. 37 Alcaide B. 192 Alcock N. W. 230 267 Alder R. W. 58 Aldous D. J. 299 Albman C. 42 62 Alessi T. R. 169 Alexakis A. 105 123 Alexander A. J. 29 Alexander J. 188 Alexandrescu A. T. 18 Alfonso M. M. 129 Ali M. H. 294 Ali M. H. A. 70 Al-Jalal N. 223 Al-Juaid S. S. 264 271 Allen L. C. 36 Allen R. P. 73 Allenmark S. G. 285 Allinger J. A. 34 Allinger N. L. 34 Almond H. R. jun. 133 Al-Omair A. S. 28 Alonso C. M. 105 Alonso F. 183 Alonso I. 48 296 Alonso R. 80 Alper H. 125 128 196 233 Alvarez C. 257 Alvarez R. M. 132 Amato J. S. 307 Amatore C. 182 Amaudrut J. 206 Amer I. 125 Amin M. 63 224 Amornraksa K.50 Amosova S. V. 283 Amrollah-Madjdabadi A. 11 1 Amyes T. L. 59 Anderegg R. J. 23 Anders E. 38 46 Anders K. 178 Andersen M. W. 118 Anderson B. A. 258 258 Anderson D. R. 134 Anderson L. M. 66 Anderson C.-M. 239 Ando W. 274 275 276 Andres J. 42 Andrews M. A. 233 Andrews S. W. 167 Andrus M. B. 120 Angelici R. J. 258 Angelini G. 62 Angle S. R. 137 AngyPn J. G. 37 Aniol M. 229 Annapurna P. 184 Anne A. 203 Ansell G. B. 231 Antonio Y. 216 Antonsson T. 244 Aoyama T. 49 161 Apeloig Y. 60 Arad D. 60 Arai T. 281 Araldi G. 177 Arase A. 91 Arbogast B. 23 Arcadi A. 238 Archelas A. 321 Archibald T. G. 128 Arimura T. 187 Armstrong R.W. 286 Armstrong S. K.,'128 Armstrong W. P. 50 Am H. 229 Arnold J. R. P. 12 Arnold L. D. 304 Arnott D. M. 226 Arrieta A. 192 Arrif A. M. 279 Arrowsmith C. H. 18 Arteca G. A. 43 Arvantis A. 168 Arya R. 122 Asami M. 300 Asano F. 109 Asano K. 128 Asano T. 46 71 Asanuma M. 281 Asao T. 185 Asaoka M. 166 Asensio G. 178 Ashby E. G. 11 1 Ashcroft J. 79 Ashton P.R. 287 Ashwell S. 76 Asmus K. D. 74 Aso Y. 199 261 Assil H. I. 304 Ast T. 29 Astrab D. P. 158 Astruc D. 250 Ate$ M. 280 Atkinson R. A. 17 Atkinson R. S. 89 190 Auchter A. 125 Auditor M.-T. M. 48 323 Aufrand M. 125 325 AugC C. 317 319 Auk B. S. 266 Auner N. 272 Austin S.319 Avignon-Tropis M. 236 241 Awen B. Z. E. 201 Awinbhavi A. S. 302 Ayala E. 178 Azerad R. 253 Azzena U. 124 Baba A. 116 129 Baba N. 128 Babiak K. A. 105 289 Bacaloglu R. 182 Bach R. D. 37 46 Bachi M. D. 84 Bachovchin W. W. 312 Bachrach S. M. 36 Baciococchi E. 115 Back T. G. 93 Backer-Dirks J. D. J. 267 Badejo I. T. 186 Baden E. P. 221 Bader R. F. W. 41 Badesha S. S. 225 Backvall J.-E. 161 246 247 Bar M. 187 Baerends E. J. 231 Barhausen D. 244 Bahr U. 20 Bailey J. E. 28 Bailey W. F. 153 Baines K. M. 272 Baker J. 35 Baker S. R. 194 Baklouti A. 112 Bakshi R. K. 118 Balaban A. T. 184 Baldoli C. 314 Baldridge K. K. 35 Baldwin J.E. 49 81 291 299 Baldwin M. A. 19 27 Balicki R. 132 213 Ballatore A. 25 Ballester M. 57 Ballesteros A. 297 Ballini R. 132 Ballistreri A. 31 Ballou L. 31 Bambal R. B. 248 Bamberger M. 18 Banait N. S. 60 Banert K. 209 Banfi L. 108 309 Bannister R. M. 217 Banwell M. G. 144 181 185 Bapuji S. A. 149 242 Baran J. 47 51 Barba I. 183 Barber M. 24 Barbey G. 200 Baringa C. J. 28 30 Barion D. 195 Barlow S. E. 67 Barluenga J. 116 127,129,297 299 Baron M. 14 Barr D. A. 50 Barrau J. 276 Barrera P. 216 Barrett A. G. M. 133 Bamsh J. C. 165 Barron A. R. 266,267,268,279 Barros M. T. 105 Barros S. M. 283 Barthelat M. 34 Bartlett R. J. 35 Bartmess J. E. 23 Bartsch R.A.221 Barua N. C. 304 Bashiardes G. 234 Bade T. 291 Bassolino D. A. 16 Bastos C. 285 Basu B. 227 Batcheller S. A. 276 Batchelor R. J. 277 282 Batcho A. D. 165 Bates T. F. 263 Battersby A. R.,226 Batty D. 83 165 Bauer W. 262 Bauld N. L. 46 164 Baum K. 128 Baumstark A. L. 299 Bausch J. W. 186 Bauta W. E. 256 Bax A. 11 12 13 18 Baxter J. S. 249 Bayly C. I. 41 Bays J. P. 258 Bazureau J. P. 130 Beachley 0. T. jun. 267 268 Bean D. L. 276 Bean M. F. 26 27 Beau J.-M. 286 Beaucourt J.-P. 252 Beavis R. C. 20 Bechgaard K. 281 Becker D. 52 Becker D. A. 185 Becker G. 263 Beddell C. R.,4 Bednarski M. D. 315 317 Bedoya-Zurita M. 150 244 Bedworth P.V. 122 Beeson M. 299 Beetz I. 181 Begum M. K. 246 Behar S. 180 251 Behling J. R. 105 289 Behnam B. A. 272 Behrens U.,263 Belanger P. C. 181 Beletskaya I. P. 237 Bell D. J. 24 Bell J. D. 5 9 10 Author Index Bell P. 48 Bellamy F. 117 Bellassoued M. 118 Belletire J. L. 196 Bellucci G. 321 Bellus D. 126 Belmont J. A. 230 Belson D. J. 65 Ben-David Y. 181 233 Bending M. R. 10 Bengtsson S. 181 Benneche T. 249 Bennett F. 287 Bennett J. M. 65 Bennett M. A. 99 Bennett R. B. 206 Bennett W. D. 130 285 Beno M. A. 281 Benoussan D. 206 Benson L. M. 28 Bent B. E. 266 Bentley T. W. 58 Benyunes S. A. 249 Beraud P. 304 Berberich D. W. 24 Beress L.16 Berg R. H. 210 Bergan J. J. 307 Bergdahl M.,?35 Bergman N.-A. 42 Bergman R. G. 231 234 Berman S. S. 22 Bernardi F. 39 46 Bernasconi C. F. 63 Bernocchi E. 238 Bernstein E. R. 171 Bemel J. 283 Berry D. H. 179 Berson J. A. 52 Berti G. 321 Bertram G. 277 BertrPn J. 35,38,41,42,46,62 Bertrand M. P. 75 Bertz S. H. 235 288 Best W. M. 76 Bestmann H. J. 88 112 Beugelmans R. 182 Bevan F. M. 181 Bhaduri S. 233 Bhalerao U. T. 282 Bharathi S. N. 214 Bhupathy M. 263 Bianchet S. 298 Bickelhaupt F. 52 187 264 Bickerstaff R. D. 277 Biehl E. R.,184 Biemann K. 29 30 Bierbaum V. M. 67 Bigi F. 177 Bildstein B. 283 Billeter M. 17 Billington D. C. 160 Billups W.E. 172 Biltueva I. S. 272 Author Index Binder J. 129 Binger P. 295 Bird C. W. 161 Birdsall B. 12 Bisacchi G. S.,146 Bischofberger N. 3 15 Bishofberger K. 161 Bittmann R. 109 298 Bjamason A. 24 Blackbum G. M. 322 Blacklock T. J. 194 Blackstock S. C. 52 Blagoeva I. B. 71 Blair I. A. 108 304 Blake A. J. 219 Blake J. F. 38 41 46 Blanda M. T. 278 Blandamer M. J. 72 Blechert S. 189 Bleeke J. R. 251 Bloch R. 234 Blom R. 268 274 Bloodworth A. J. 83 Blystone S. I. 285 Boaz N. W. 309 Bocelli G. 177 Boche G. 135 188 262 26 i3 Bock H. 269 Bock J. L. 5 Bock U. 263 Bodwell G. 187 Boeckman R. K. 168 169 Bogge H.,274 Boehler M. A. 161 Boehshar M.99 Boelens R. 13 14 Boersma J. 262 278 Boese R. 187 250 278 Bogusky M. J. 18 Bois-Choussy M. 182 Boivin T. L. 84 Boland W. 124 187 285 Bolard J. 253 Bold G. 130 Bolin R. J. 322 Bolton J. L. 58 Bolton R. E. 175 Bonini B. F. 269 Bonke B. R. 183 Bonner F. W. 7 8 Bonner M. P. 160 Bonner R. F. 21 Bonnesen P.V. 48 Bonnett R. 202 Bonser S. M. 142 Bonsignore L. 210 Bookhart M. 257 258 Bordas-Nagy J. 32 Borden W. T. 89 Borders D. B. 176 Bordwell F. G. 60 Borysenko C. W. 317 Bosch E. 35 84 Bosold F. 188 Bott S. 300 Bottoni A. 39 46 Boubia B. 117 Boucher J.-L. 161 Bouguignon M. 180 Boumendjel A. 115 Bourguignon M. 240 Bourhim A. 304 Boutin P.176 Bouxom B. 317 Bovenschulte E. 295 Bowry V. W. 85 Boyd D. R. 191 319 Boyd J. 12 17 Boyd R. J. 36 41 Boyd R. K. 29 Boyd S. A. 247 Boyle T. J. 254 Bradley D. C. 267 Brajter-Toth A. 27 Brakta M. 247 Brand M. 87 Brandes E. B. 55 Brandi A. 48 223 Brands K. M. J. 164 Brandsma L. 262 286 Brandvold T. A. 153 257 Braschwitz W.-D. 173 Braslau R. 100 230 Brauman J. I. 67 Braun M. 110 118 172 Braun W. 17 Bravdo T. 312 Bravo A. A. 206,214 Bravo P. 113 Bravo-Zhivotovskii D. A. 272 Brean L. 134 Breen P. J. 171 Breg J. N. 14 Breitmaier E. 213 Brelikre C. 271 Bremer M. 37 186 Breneman C. M. 36 Brennan P. J. 26 Brenton A. G. 31 Brestensky D.M. 303 Breuer B. 277 Breulet J. 39 Breunig H. J. 280 Brickhouse M. D. 64 Brickner S. J. 247 Bridon D. P. 111 Brieva R. 132 Briffett N. E. 67 Briggs J. M. 42 Brinkman H. R. 180 252 Brinkmann A. 295 Brocard J. 253 Brook A. G. 272 Brookhart M. 231 254 Brooks B. 13 Brown A. L. 68 Brown D. S. 208 Brown F. K. 38 46 Brown H.C.,88 111 112 116 118 Brown J. C. C. 5 9 10 Brown J. M. 230 285 Brown P. 277 Brown R. D. 66 Brown S. C. 14 Bruckner R. 11 1 Bruhn P. R. 252 Bruice T. C. 298 Bruins A. P. 21 Bruneau C. 110 Brunet J.-J. 233 Brunner H. 125 232 Bryant T. 70 Buback M. 49 Bublak W. 268 Buchan R. 209 Buchwald S. L. 93 153 199 201 Buck R. C. 258 Buckelew D.Q. 186 Buckleton J. S. 144 185 Buckman B. O. 75 Buda A. B. 39 171 Budde W. L. 23 Buddrus J. 31 1 Budzichowski T. A. 270 Buisson D. 253 Bull J. R. 161 Bullock R. M. 85 Buma W. J. 171 Bumagin N. A. 237 Buncel E. 62 72 Bunnett J. F. 63 Bunting J. W. 67 Bunton C. A. 182 Burdisso M. 48 Burgess K. 91 126 130 135 232 310 Burgos C. E. 237 Burini A. 238 Burke P. A. 312 Burkes L. J. 23 Burlingame A. L. 30 Bumell D. J. 49 137 285 305 Bums B. 153 Bums C. J. 229 298 Burton D. R. 322 Burton L. E. 14 Busacca C. A. 48 159 162 Busch K. L. 29 Buser H.R. 229 Bush C. A. 18 Bushby R. J. 48 Bushman D. R. 188 Bushnell G. W. 187 Butcher J. W. 194 Butler A.R. 66 Buttrus N. H. 271 Byme L. T. 262 Byun H.-S., 109 Cabiddu S. 210 Cacchi S. 238 Cahiez G. 123 236 Caldwell G. 67 Caldwell K. A. 24 Cale A. D. 220 Calet S. 196 Callstrom M. R. 282 Cambie R. C. 252 Campbell A. L. 105 289 Campbell I. D. 12 14 Campbell Burk S. 12 Camps F. 244 Cannavo P. 48 Capdevielle P. 133 Caple R. 242 Capon B. 68 Capperucci A. 271 277 Caprioli R. M. 25 Cardenas R. 42 Carey J. 18 Caringi J. J. 102 169 Carless H. A. J. 164 Carlier P. R. 89 229 Carlson D. A. 95 234 Carlson R. 118 Carpenter J. E. 36 Carpenter N. E. 98 Carpita A. 134 Carr J. M. 9 Carrt F. 271 Carreno M. C. 48 161 296 Carrera G. 313 Carretero J.C. 48 296 Came R. 143 Carroll M. T. 41 Carter G. T. 176 Carter G. W. 17 Carter-Petillo M. B. 196 241 Cartier D. 306 Cartledge F. K. 34 Carvalho C. 229 Carvalho E. 132 Casida J. E. 6 Casnati G. 177 Cassidei L. 299 Castedo L. 184 Casteignan M. 198 Castellino S. 120 Castilho P. C. M. F. 182 Castle P. L. 112 Castro A. 70 71 Castro M. E. 25 Casu A. 115 Caubere P. 303 Cauliez P. 125 Cavalieri E. L. 188 CavayC B. 317 Cazes B. 249 Cederbaum F. E. 152 243 Celewicz L. 182 Cerichelli G. 176 Cermola F. 294 ternusik I. 42 Ceyer S. T. 173 Cha J. K. 206 Chaabouni M. M. 112 Chaari M. 180 Chabert P. 279 Chadha N. C. 165 Chadikun F. 31 Chaigne F.248 295 Chait B. T. 20 21 Chakraborty T. K. 271 Challener C. A. 153 257 Challis B. C. 71 Chalmers R. A. 5 10 Chamberlin A. R. 229 Chan C. 241 299 Chan T. H. 103 104 122,269 269 292 Chance J. M. 171 Chancharunee S. 140 Chaney M. O. 92 Chang C. 41 Chang C. T. 73 Chang H. N. 3 11 Chang V. H.-T. 81 Chang V. K. 148 Chang V. K.-T. 169 Chapleo C. B. 211 295 Charles B. 31 Charumilind P. 48 Chatgilialoglu C. 73 112 Chatterton W. J. 272 Chava S. P. 162 Chaves A. 52 Chazin W. J. 16 17 Cheeseman J. R. 41 Cheetham P. S. J. 318 Chehidi I. 112 Chen B. C. 302 Chen C.-P. 183 Chen C. S. 110 307 310 Chen G. S. 195 Chen H. G. 234 Chen J. 245 Chen M.-H.73 137 Chen P. 187 Chen Q.-Y. 178 Chen R. H. 184 Chen S.-T. 309 311 Chen T. 302 Chenault H. K. 308 Cheney D. L. 240 Cheng X.-M. 285 Cheon S. H. 286 Chewinski A. Yu. 63 Chesnut R. W. 179 Cheung K.-K. 219 Chiang Y. 68 98 Chiappe C. 321 Chiarelli M. P. 26 Chiba N. 128 Childs R. F. 186 Chin C. S. 230 Chinn R. L. 50 Chiusoli G. P. 201 Chmielecka J. 271 Cho B. P. 184 Author Index Cho I. H. 109 Cho S. G. 34 Cho W. J. 253 Choi J.-R. 206 Choi J. Y. 38 46 Choi S.-C. 76 77 Chojnowski J. 271 Chopa A. B. 276 Chou C.-T. 183 Choudary B. M. 100 Christ W. J. 286 Christen M. 307 Christ] M. 172 Chu K.-H. 246 Chuchani G. 63 Chuck C. C. 251 Chung J.Y. L. 241 Chung S. 109 Church D. F. 176 Church L. A. 256 Churchill M. R. 268 Cieplak A. S. 40 48 298 Cieslar C. 13 Cimminiello G. 193 Cioslowski J. 36 Clardy J. 185 215 237 287 Clark A. J. 76 179 Clark D. R. 67 Clark G. R. 144 185 Clark J. D. 55 Clark J. H. 182 Clark T. 49 Clark T. J. 256 Clarke M. P. 269 Cleaver W. M. 268 Clive D. L. J. 83 84 Clore G. M. 11 12 13 16 17 Clos N. 285 Coda A. C. 48 Cody R. B. 24 29 Coello A. 70 Cohen M. P. 128 Cohen T. 263 Colegate S. M. 219 Cole-Hamilton D. J. 229 Coll J. 244 Collingwood S. P. 234 Collis M. P. 181 Colonna S. 299 Comasseto J. V. 283 Combellas C. 182 Concellon J. M. 299 Conlettes J. L. M.165 Connell R. D. 91 106 300 Connor S. C. 5 Conrad D. 315 Conte V. 135 Contreras O. 216 Cooke R. M. 14 Cooks R. G. 24 25 29 Coolbaugh T. S. 246 Cooper D. L. 36 183 Cooper K. 234 236 Cooper P. J. 64 Author Index Coote S. J. 253 255 Corboni B. 143 Cordero F. M. 223 Corey D. R. 323 Corey E. J. 91 103 106 162 163 285 300 303 Corey E. R. 49 Correa R. A. 174 Comu R. J. P. 271 Cossio F. F. 291 Cossio F. P. 192 Cossy J. 131 Costa M. 201 Cotter R. J. 24 26 Cottrell I. F. 237 Cottrell J. S. 28 Couture A. 217 Couturier D. 125 Covey T. R. 21 22 28 Cowley A. H. 280 Cox B. 211 Cox N. J. G. 82 169 Cox R. A. 64 Cozzi P.-G. 122 Crampton M. R.66 182 Crane L. J. 285 Crans D. C. 316 Cremer D. 273 Cremonesi P. 188 Crich D. 83 165 304 Crilley M. M. L. 298 Crimmins M. T. 158 Crisp G. T. 181 Crombie L. 229 Crookes M. J. 64 Crout D. H. G. 307 Crow R. 305 Crudden C. M. 149 Cullen W. R. 229 Cupertino D. C. 229 Curci R. 87 190 299 Curran D. P. 73 137 Curtis J. M. 31 Curtis R. J. 83 Curtis L. A. 34 Cutler A. R. 258 Czernecki S. 304 Dabbagh H. A. 178 Dabdoub M. J. 283 Dabdoub V. M. B. 283 Dahmer J. 308 Dai W.-M. 197 Daigneault S. 83 Dailey W. P. 174 D’Alcontres G. S. 287 Dalton D. R. 34 Dalton H. 319 Damja R. I. 271 Damrauer R. 67 Danheiser R. L. 185 197 Daniels L.,316 Danilova N. A. 94 239 Danishefsky S.J. 54 79 169 287 299 Dannenberg J. J. 38 39 46 Daran J. C. 257 Dartmann M. 272 Daruwala K. P. 97 Da Silva Jardine P. 163 Date M. 212 Dauben W. G. 111 Daum S. J. 193 Daumas M. 131 Davidson A. H. 162 Davies A. G. 76 Davies C. E. H. 265 Davies D. B. 11 Davies H. 285 Davies H. M. L. 215 256 Davies M. J. 218 255 Davies S. E. C. 10 Davies S. G. 233,234,251,253 255 285 Davies T. L. 234 Davis A. B. 66 182 Davis F. A. 190 302 Davis T. L. 95 Davis W. A. 153 Davis W. D. 276 Dawson I. M. 220 Dax S. L. 203 Day R. 178 De Amici M. 313 De Amicis C. V. 148 Dean D. C. 50 Deardortl D. R. 248 de Bie D. A. 214 Decamp A. 219 De Clan A. 241 Degl’Innocenti A.269 271 277 Degnan 1. A. 267 Degrand C. 281 DeHoff B. 236 Deinzer M. L. 23 De Kanter F. J. J. 262 De Kimpe N. 144 de Koning L. J. 62 Delaney T. E. 23 de la Vega F. 176 Del Bene J. E. 35 Delogu G. 124 Delorme D. 236 Dembech P. 99 de Meijere A. 180 de Mel V. S. J. 267 De Mesmaeker A. 81 De Micheli C. 313 Demolliens A. 37 Denisenko S. N. 191 Denmark S. E. 55,120,135,291 Dennington R. D. 41 184 Dennis N. 46 210 Dent W. H. 111 298 DePuy C. H. 67 172 de Ridder D. J. A. 278 De Rosa M. 66 Derouiche Y. 271 De Sarlo F. 223 Desimoni G. 48 Desobry V. 180 Deterding L. J. 28 Detter L. D. 24 Detty M. R. 282 Deuter J. 48 Devasagayaraj A.242 Devillers J. 34 Devos A. 111 Dewar M. J. S. 33 38 39 41 42 69 173 184 De Witt P. 109 de Wolf W. H. 52 Dezube M. 229 Dhar R. K. 118 Dian G. 200 Dibble P. W. 164 295 Diblitz K. 202 Dickbreder R. 274 275 Diener H. 69 Diercksen G. H. F. 42 Dietrich A. 268 Dietze P. 61 DiFuria F. 135 Dimock S. H. 234 D’Innocenti A. 135 Di Raddo P. 188 Disch R. L. 184 Di Stefano D. L. 11 Ditrich K. 118 Dixneuf P. H. 110 Djedaini F. 253 Doak G. O. 280 Dobson C. M. 18 Dodt J. 17 Dotz K. H. 256 257 Doherty R. M. 57 Doktycz S. J. 306 Dolbier W. R. 54 182 Dominguez R. M. 63 Donaldson A. J. 230 Donaldson W. A. 251 Donegan G. 50 51 Dorigo A. E. 40 41 235 Dorling P.R. 219 Dorta R. L. 82 Dostalek R. 88 112 Dotz K. H. 151 Doubleday C. 52 Dougherty R. C. 23 Dowd P. 76 77 Dowle M. D. 148 Doxsee K. M. 195 Doyle T. W. 304 Drager M. 280 Dragisich V. 153 257 Dragovich P. S. 55 79 99 201 Drakenberg T. 17 Dresely S. 118 Drewello T. 32 Driscoll P. C. 13 16 17 Drueckhammer D. G. 316 Dryhurst G. 203 Dubey S. K. 188 Dubois L. H. 266 Durner G. 221 Duffin H. C. 66 Dufresne C. 181 Duggan M. E. 222 286 Duisenberg A. J. M. 264 Duke C. V. A. 182 Dulik D. M. 27 Dunach E. 105 Duncan M. W. 25 Dunn E. J. 62 Dunn P. J. 191 Dunne T. S. 176 Dunning T. H. 34 Dupont J. 241 Duran M. 42 62 Durfor C. N. 322 Durrwachter J.R. 316 Durst F. 113 Duthaler R. O. 121 124 130 Dutler R. 37 Dyke H. J. 174 Dyker H. 304 Eaborn C. 58 264 269 271 Eads C. D. 11 Eason C. T. 7 8 Eaton P. E. 181 Ebata K. 274 Ebeling B. 277 Eberhardt M. K. 178 Eckes P. 221 Edlund U. 186 Edmonds C. G. 27 28 30 Edrnunds A. J. F. 298 Edstrom E. D. 196 241 Edwards J. O. 190 299 Edwards L. G. 149 Effenberger F. 65 311 Effenberger P. 175 Egenberger D. M. 298 Egorov M. P. 275 Eguchi S. 208 Ehara Y. 182 Ehlers J. 202 Ehrenfreund M. 188 Eichelberger J. W. 23 Eilenberg W. 177 Einstein F. W. B. 277 282 Eisenstein O. 37 Eistetter K. 298 Ejiri S. 185 Eley C. N. 134 Elgendy S. 117 Eliasson B. 186 Elisseou E.M. 302 Ellestad G. A. 79 Ellison G. B. 62 Ellsworth E. L. 235 289 Elschenbroich Ch. 261 Elsley D. A. 158 295 Elsworth E. 105 Empie M. W. 307 Emsley J. 67 Emziane M. 110 Engberts J. B. F. N. 72 Engelhardt L. M. 262 Englander S. W. 11 Engler T. A. 294 Engrnan L. 104 209 283 Enholm E. J. 155 157 158 Ens W. 21 Ensley H. E. 296 Epiotis N. D. 38 EPP 0.9 17 Erata T. 282 Erben H.-G. 151 257 Erdelmeier I. 239 Erden I. 186 Erdlick E. 300 Erker G. 217 283 Ermer O. 48 Emst B. 81 126 Ernst L. 52 187 Emst R. R. 12 13 Erpelding A. M. 214 Eskelinen S. 9 Essamkaoui M. 181 Estevez J. C. 184 Estevez R. J. 184 Eurby M. E. 181 Evans P. A. 18 Evans P.L. 230 Everett J. R. 5 Ewing A. G. 27 28 Ezure Y. 318 Faber K. 126 308 Fabre J.-M. 281 Fabri F. 321 Faegri K. jun. 268 Faggi C. 277 Faita G. 48 Faktor M. M. 267 Falck-Pedersen M. L. 249 Falick A. M. 25 Faller J. W. 296 Fallis A. G. 48 155 161 Falorni M. 116 Farnulok M. 188 Fananas F. J. 129 Fang Q. 199 Fantani P. 143 Fanwick P. E. 179 Faraci G. 177 Farina F. 183 Farina V. 194 304 Farooq O. 87 Faruya T. 145 Fassberg J. 63 Fasseur D. 125 Fawzi R. 244 Feeney J. 12 Feghouli A. 303 Feher F. J. 179 270 Author Index Feichter C. 126 Feldman K. S. 83,145 156,190 Fendebak A. M. 312 Fendesak G. 202 Feng Y. 11 Fenn J. B. 21 22 Fennen J.38 Fenneu J. 46 Fenselau C. 24 27 Fenske D. 263 Feringa B. L. 107 234 291 Fernindez E. J. 268 Fernandez-Simon J. L. 299 Fernholz E. 221 Fesik S. W. 13 Fessner W.-D. 315 Fettinger J. C. 268 Fiandanese V. 94 290 Fiedler J. 188 Finch H. 250 295 Finet J.-P. 181 280 Fink M. J. 272 273 Finn M. G. 90 229 300 Finney N. S. 55 99 Fiorentino M. 87 299 Firestone M. 281 Firestone R. A. 46 Firth J. 28 Fischer G. 272 Fischer J. 241 Fischer P. 187 227 Fisher I. 208 Fisher R. A. 153 Fisher T. E. 83 190 Fishwick C. W. G. 49 Fitton J. E. 14 Fitzsimrnons B. J. 298 Fleck T. J. 133 293 Fleet G. W. J. 285 Fleischer U. 37 60 Fleming A. 190 Fleming I. 128 Flint E.B. 305 Flintjer B. 273 Florencio F. 183 Florio S. 271 Fluthwedel A. 270 Foland L. D. 174 Folkers P. J. M. 17 Foltz R. L. 23 Fontana F. 74 Ford R. R. 272 Forkner M. W. 97 Fornarini S. 172 Forschner T. C. 258 Forsen S. 16 Forster S. 311 Fort Y. 303 Fortana F. 177 Fortt S. M. 83 165 Fossel E. T. 9 Foubelo F. 129 Fountain M. E. 279 280 Fouque E. 221 Author Index 33 1 Fourneron J. D. 321 Fournier J. 110 Fowler F. W. 297 Fox D. J. 34 Fox D. N. A. 96 Fox R. O. 18 Foxall P. J. D. 10 Fraenkel G. 262 Fraile A. G. 132 France M. B. 229 300 Francisco C. G. 82 Franck R. W. 39 Franck-Neumann M. 253 Franco F. 216 Frank H. 188 Frank R.W. 46 Franken M. 277 Fraser M. 209 Fraser-Reid B. 80 165 287 Frater G. 167 FrCchard-Ortuno I. 241 Freedman L. D. 280 Frei B. 229 Freiser H. 281 French A. D. 31 Frenette R. 255 Fresneda P. M. 162 215 Friedichsel W. 161 Frierson M. R. 34 Friess B. 131 249 Frigo D. M. 267 Fringnelli F. 110 Frisch M. J. 35 Frisque-Hesbain A.-M. 11 1 Frissen A. E. 214 Fritsche K. 311 Fritz H. 173 Fritzberg A. R. 130 Froen D. 242 Fronczek F. R. 176 Fry J. L. 186 Fry K. 176 Fryxell G. E. 49 Fryzuk M. D. 229 Fu J.-M. 180 240 Fuchikami T. 124 Furstner A. 135 291 Fugami K. 101 112 Fuhry M. A. M. 99 Fuji K. 255 Fujihara H. 282 Fujimoto H. 187 317 Fujimoto T. 294 Fujino M.61 270 Fujioka H. 286 Fujisaka T. 212 Fujisaki S. 128 177 Fujisawa T. 123 133 304 315 Fujita H. 287 Fujita M.,233 Fujiwara K. 79 169 Fujiwara M. 129 Fujiwara T. 79 Fukazawa Y. 169 281 Fukumoto K. 165 Fukunaga T. 79 80 158 Fukushima S. 180 Fukuzawa Y. 79 Funakoshi K. 155 Fuomori K. 270 Furber M. 115 Furstoss R. 321 Furuhashi K. 321 Furukawa N. 282 Furukawa S. 212 Furusawa O. 182 Furuta K. 48 164 Fusco C. 87 299 Fustero S. 127 297 Futagawa T. 144 Fuwa T. 14 Gabler A. 285 Gabriel G. 218 Gaggero N. 299 Gahagan M.,229 Gais H.-J. 155 239 Gajewski J. J. 46 53 Galeazzi E. 216 Galema S. A. 72 Gallagher T. 96 Gallor J. K. 204 Gallucci J.C. 34 Gambaro M.,105 Gampe R. T. 13 Ganem B. 109 304 Gani D. 307 Gao L. 110 Gao Y. 190 303 Garbauskas M. 265 Garbow J. R. 18 Garcia J. 216 Gardner G. J. 22 Garozzo D. 31 Garrison J. M. 298 Gartland K. P. R. 4 7 8 10 Garvie D. 10 Gasdaska J. R. 49 241 Gaskell S. J. 30 Gasni V. 34 Gassman P. G. 141 142 162 282 Gates B. D. 281 Gatta F. 224 Gattennayer R. 277 Gau R. 298 Gaudemar M. 118 Gauss J. 273 Gautheron C. 317 319 Gay I. D. 282 Gazes B. 131 Geddridge R. W. jun. 282,283 Gehrke-Brinkmann G. 277 Geise B. 137 Geise H. J. 34 Geissler M. 264 Gennari C. 122 Gennani R. 110 Gero T. W. 220 Gerratt J. 36 183 Geurtsen G. 214 Geyer E.109 Ghazal N. B. 257 Gheorghiu M.D. 184 Ghogara A. 312 Ghosez L. 49 111 Ghosh C. K. 179 Ghosh D. 31 Giacomelli G. 116 Giannis A. 128 Giese B. 73 75 76 81 Gigou A. 252 Giguere R. J. 305 Gilbert A. 174 Gill G. B. 76 Gillard J. R. 49 285 Gillette G. R. 273 Gillhouley J. G. 158 295 Gillies C. W. 51 Gillies J. Z. 51 Gillois J. 253 314 Giomi D. 49 Giordano F. 294 Girard C. 234 Girard Y. 236 Girardin A. 310 Giselbrecht K. 283 Giuffrida M. 31 Glaser R. 37 Glavee G. N. 258 Gleiter R. 99 187 274 Glidewell C. 66 Glish G. L. 29 Godhino L. 105 Gorger G. 124 Goering H. L. 234 Gorlitz F. 268 Goldberg I. 221 Gol’dberg Y. 189 305 Golding B. T. 76 298 Goldstein E.34 Gomez A. 192 Gompper R. 225 Gong W. H. 238 Gonzalez C. 35 41 Gonzalez F. J. 127 297 Gonzalez-Nunez M.E.,178 Goodfellow C. L. 253 Goodman B. A. 263 Goodman J. J. 176 COOS K.-H. 220 Gopalan A. S.,314 Goralski C. T. 88 Gordon I. M. 59 71 Gordon M. S. 35 Gore J. 131 249 Gorgen G. 285 Gorgues A. 281 Gossalek J. 113 Gotar V. 132 Goti A. 223 Gotteland J.-P. 248 295 Goubitz K. 278 Gould G. L. 233 Gountzos H. 127 Gouzoules F. 252 Grabowski E. J. J. 194 307 Grabowski S. 52 319 Graden D. W. 133 Graf E. 125 Graham W. A. G. 179 Gramatica P. 307 Granberg K. K. 247 Grandclaudon P. 217 Gravatt G. L. 144 185 Graziani M. 104 Graziano M.L. 193 294 GreC D. 253 GreC R. 251 252 253 Green M. 249 Green R. H. 285 Greenberg M. M. 52 Greenhalgh C. 66 182 Greenhouse R. 216 Greenway A. M. 261 Gregory P. S. 186 Grein F. 41 Greiner A. 122 Grellier P. L. 57 Grenier L. 255 Grev R. S. 34 Grieco P. A. 55 Griengl H. 126 308 Griesbeck A. 110 Griesinger C. 12 13 Griffiths D. C. 231 Grigg R. 49 50 51 153 208 Griller D. 112 Grimm C. 23 Grimm F.-T. 274 Grimme W. 47 Grimshire M. J. 249 Grimsrud E. P. 23 Grobe J. 272 Gronenborn A. M. 11 12 13 16 17 Gronert S. 37 67 172 Gross F. 125 Gross M. L. 24 26 175 Grossman S. J. 188 Grotemeyer J. 26 Groth-Andersen H. 68 Groves J. T. 87 Groves L.S. 186 Griitzmacher H. 134 Grundy S. L. 251 Gruska E. 285 Gu J.-H. 282 Guanti G. 108 309 Guama A. 223 Guay D. 102 Guazzaroni M. E. 104 Gullec S. 280 Guerrini A. 99 Guest M. F. 33 Guette J. P.,170 Guevremont R. 31 Guitan E. 184 Guivisdalsky P. N. 298 Gulec B. 69 Gunaratne H. Q. N. 50 Gung W. Y. 120 253 292 Gunnarsson A. 318 Gunther W. 167 Guo H. 34 Gupta R. C. 48 296 Gusev 0.V. 247 Guthrie R. D. 45 57 Gutman A. L. 312 Guy A. 176 302 Guzman A. 216 Gybin A. S. 242 Ha DX. 192 Haas R. 30 Haas W. 224 Haazawa Y. 161 Habaue S. 123 Hacking P. S. J. 318 Haddad N. 52 Hadjiarapoglou L. 299 Haberle K. 280 Hammerle M. 257 Haenel M. W. 187 Hansele E.49 Hagan G. 292 Hagiwara S. 208 Hahn C. S. 109 Haider K. 52 Hail M. E. 24 Haji M. S. 216 Hakansson P. 21 22 Halcomb R. L. 299 Hale K. J. 84 Haley M. M. 172 Hall R. W. 31 Hall S. S. 246 Hallberg A. 239 Halling K. 132 Ham W.-H. 286 Hamanaka S. 282 Hamelin J. 124 293 Hammel A. 265 Hammerum S. 31 Han CX. 67 Han R. 264 Hanack M. 125 132 Hanaoka M. 253 Hand 0. W. 24 25 Handreck D.-R. 173 Hands D. 237 Handy N. C. 35 Hanessian S. 236 285 Hania M. M. 225 Hanley C. 18 Hansen G. 24 Hansen P. E. 193 Hamson L. 118 Hanusa T. P. 265 Hao X.-J.,255 Author Index Hara E. 204 Hara R. 122 Hara S. 125 241 Harada K. 133 Harada T. 144 Haramaki T.314 Harder S. 262 Hare D. R. 16 Hargiss L. O. 27 Harirchian B. 164 Harkers B. 277 Harlow R. L. 268 Harmata M. A. 55 135 Harms K. 151 256 257 262 263 Harper J. R. 279 Harrelson J. A. 60 Hamngton P. J. 238 Hamngton P. M. 99 Hams D. C. 282 283 Hams R. J. 304 Hamson A. G. 31 Hamson B. 93 Harrison E. 174 Hamson M. E. 27 Hamson P. J. 226 Harrison R. J. 33 Harrit N. 210 Hart D. 66 Hart D. J. 183 192 Hart H. 184 Hartmann H. M. 263 Hartmann K. 250 Hartung J. B. 76 184 201 Hartung Y. 101 Haruta J.-I. 96 Haruyama H. 17 Harvey R. G. 184 188 Harvey T. S. 14 Harwood L. M. 295 299 Hasegawa H. 313 Hasegawa M. 127 Hasegawa Y. 270 Haseltine J.N. 54 79 169 287 Hashimoto Y. 127 Hatajima T. 142 Hatakeyama S.,227 Hatakeyoma S. 158 Hatanaka Y. 99 180 Hatano T. 270 Hatsuya S. 131 Hattori K. 144 Hauck S. I. 194 Hauer C. R. 29 Haupt E. 276 Hausen H.-D. 267 Havlas Z. 42 Hawkins L. D. 286 Hawthorne M. F. 230 Hayakawa S. 133 Hayashi T. 91,92,103,247,248 Hayashi Y. 39 147 253 Hayashida H. 117 Author Index Hay-Motherwell R. 76 He J. 76 Head-Gordon M. 34 35 Healey T. 23 Healy E. F. 33 Healy M. D. 266 Heaney F. 51 Heath P. 174 Heathcock C. H. 234 Heck R. F. 241 Hedbys L. 318 Hedin A. 21 22 Heeg M. J. 304 Heerma W. 30 Hegedus L. S. 146 238 246 Hehnchen G. 48 Hehre W.J. 36 Heijdenrijk D. 278 Heil B. 232 Heinrich J. L. 188 Heitz M.-P. 253 304 Hejna C. 265 Heller D. N. 26 Helquist P. 153 168 258 Hemmerle H. 155 Henderson D. 49 Henderson G. B. 226 Henderson I. 126 135 310 Hendrickson J. B. 99 Hendriksen D. E. 231 Hengelsberg H. 31 1 Hengge E. 263 Henion J. D. 21 22 23 28 Henkel G. 295 Hennen W. J. 321 Heppert J. A, 254 Herbert J. M. 115 Hercules D. M. 26 Hermkens P. H. H. 220 Hernandez I. T. 51 Hernandez L. M. 31 Herndon J. W. 145 151 Herold P. 124 Hemng F. G. 9 Herschlag D. 62 Hersh W. H. 48 Hershberger P. M. 148 Heslin J. C. 218 255 Hesse M. 225 Hewes J. D. 230 Heyn R. H. 263 Hibbert F. 59 67 Hiberty P.C. 37 42 Hidai M. 199 Higa K. T. 282 283 Higham D. P. 8 Higuchi Y. 193 Hilbers C. W. 18 Hildebrandt B. 118 Hildenbrand T. 267 Hill C. L. 265 Hill J. A. 30 Hill K. W. 48 323 Hillenkamp F. 20 Hiller W. 244 267 Hillmer M. J. 25 Hiltunen Y. 9 Hilvert D. 48 322 323 Hino T. 123 Hintzer K. 230 Hipskind P. A. 241 Hiraga S. 311 Hirama M. 79 91 106 169 Hirami M. 300 Hirao K. 42 112 Hirata H. 270 Hirata K. 308 Hiratake J. 308 Hirohara Y. 158 Hirooka S. 185 Hirota K. 181 Hirotsu K. 253 Hiroya K. 165 Hirst G. C. 137 Hisamichi H. 145 Hitchcock P. B. 264 271 Hites R. A. 23 Hiyama T. 99 180 193 Hiyashi M. 290 Ho Y.-P. 208 216 Hoberg H. 244 Hochstrasser R.68 98 Hock R. 217 283 Hockstein D. R. 146 Hogberg T. 181 Honer P. 47 Honicke-Schmidt P. 3 11 Hoffman R. W. 118 Hoffmann H. M. R. 197 Hoffmann P. 81 Hoffmann R. 268 Hoffmann R. W. 135 Hofmann J. 268 Hofmann P. 257 Hofmann T. 17 Hojjatie M. 281 Hojo M. 182 Holak T. A. 16 Holcomb R. 163 Holder A. J. 33 173 Holdgriin X. 130 Holland J. F. 25 Hollander D. 30 Holloway M. K. 42 Holm A. 210 Holman R. W. 175 Holmes J. L. 31 32 Holmes P. J. 152 Holmes R. R. 276 Holmes S. J. 243 Holtmann U. 274 Honeychuck R. V. 48 Hong Y.-L. V. 256 Hop C. E. C. A. 32 Hopf H. 52 187 Hoppe D. 132 292 Horchler K. 271 278 279 Horiguchi Y. 113 235 289 Horihata M.232 Hornbuckle S. F. 50 Homer J. H. 278 Homer L. 109 Hoshi M. 91 Hosrnane N. S. 279 Hosomi A. 117 Hosono K. 314 Houk K. N. 38 39 41 46 56 Howard P. N. 137 Howard P.W. 250 Hoye T. R. 257 Hoz S. 72 Hsi J. D. 294 Hsu F. F. 27 HSU M.-F. H. 155 238 Hsu S.-H. 23 Hua D. H. 206 214 Huang H.-C. 256 Huang T.-S. 185 Huang Y.-Z. 87 117 179 279 294 Huang Y. C. J. 46 Huber B. 265 268 275 278 Huber R. 17 Huber W. 188 Huch V. 276 Hudlicky T. 190 319 Hudson A. J. 49 Hubsh T. 49 Hunig S. 119 Huban J. C. 265 Hug P. 81 Hugel G. 306 Hugel-Le Goff C. 134 Hughes D. L. 307 Hughes P. 215 Huguerre E. 217 Huisgen R.,51 Hummell W. 313 Humphrey G. R. 237 Hundt R.277 Hung M.-H. 214 Hunkler D. 173 Hunt D. F. 25 29 30 Hunt P. A. 34 Hur C.-U. 155 Hursthouse M. B. 267 Hussain B. 267 Hussain F. 216 Hussoin M. S. 99 Huston S. E. 42 Hutchings D. S. 191 265 Hutchins R. O. 302 Hutt J. 310 Hutter O. 76 Huty A. 181 Huxtable C. R. 219 Huynh C. 241 Hwang C.-K. 218 222 286 287 299 Hwu J. R. 269 Hyla-Kryspin I. 274 Hyuga S. 241 334 Iataka Y. 274 Ibragimov I. I. 242 Ibrahim M. R. 37 Ibuka T. 126 Ichikawa J. 113 Ichinose Y. 101 112 Ichits J. 295 Ido Y. 20 Iesce M. R. 294 Iglesias E. 68 70 Ihori T. 310 Iihama T. 180 240 Iimori T. 229 Iino Y. 204 Ikariya T. 230 303 Ikeda K. 177 Ikuina J.184 Ikura T. 11 Iles R. A. 5 10 Iley J. 71 132 Im J. G. 9 Imada M. 129 Imada Y. 247 Imamoto T. 142 Imbert D. 302 Impallomeni G. 31 Imwinkelreid R. 162 Inaba M. 128 Inagaki F. 14 Inagaki M. 309 Inamoto N. 281 Inata I. 109 Ingendoh A. 20 Ingham S. 263 Ingold K. U. 85 Inomata K. 298 310 Inoue J. 127 Inoue M. 114 162 Interrante L. V. 265 Inubushi T. 305 Inukai N. 145 Ioannu S. 202 Iqbal J. 104 291 Iraqi A. 229 Imgartinger H. 48 Isaacs L. D. 258 Isaacs N. 66 Isaacs N. S. 287 Isaka H. 270 Isaka M. 185 289 Isayama S. 103 Ishibuchi S. 129 Ishida M. 49 161 Ishii H. 113 Ishii Y. 96 124 199 230 303 Ishikawa M. 270 272 Ishikawa S.185 Ishizuka T. 129 Islamain M. A. 22 Ismail I. M. 4 Isobe Y. 181 Ito S. 185 300 Ito T. 308 Ito Y. 91 101 103 197 244 247 248 Itoh H. 275 Itoh K. 97 116 232 233 247 Itoh M. 135 Itoh T. 133 315 Ivanov A. P. 212 Iwabuchi Y. 298 Iwasa S. 84 157 Iwasaki M. 199 Iwasawa N. 133 162 296 Iwata S. 182 Iyer S. 150 Iyoda M. 98 Izawa H. 159 Izumi Y. 100 115 232 Jackson D. A. 185 Jackson R. F. W. 291 Jackson W. R. 127 Jacob G. S. 18 Jacobs G. A. 146 Jacobs H. 229 Jacobs H. K. 314 Jacobs J. 322 Jacobsen E. N. 90 229 Jacobsen G. E. 262 Jacobsen-Bauer A. 276 Jacobson E. N. 300 Jacobson R. A. 258 Jager V. 299 Jain R. K. 31 James A. P. 230 James B.R. 229 James K. 291 Jameson R. F. 72 Janata E. 74 Janiak C. 268 Janji N. 322 Jansen J. F. G. A. 107,234,291 Jansen M. 187 Jansen R.-M. 244 Janssen S. J. 252 Jaonen G. 314 Jaouen G. 253 Jaques L. W. 220 Jardetzky O. 18 Jardine I. 26 28 Jardine P. D. 91 106 300 Jarman M. 182 Jarrett S. R. M. 229 Jastrzebski J. T. B. H. 192,278 Jaszay J. M. 131 Jaxa-Chamiec A. 177 Jayasuriya N. 199 Jeffery ,105 Jeffs P. W. 14 Jencks W. P. 45 57 58 59,61 62 Jenkins R. O. 319 Jenkins T. E. 162 Jenneskens L. W. 187 Jennings W. B. 191 Jensen F. 40 Author Index Jensen M. 242 Jenson F. 53 Jenson M. 152 Jeong N. 258 Jephcote V. J. 292 Jerina D. M. 188 Jescchke R.126 Jiang J. 128 Jiang Q. 179 Jiang X. 247 Jie C. 33 38 Jiminez Barbero J. 12 Jin H. 286 Joglar J. 297 Johansson E. 318 Johns A. 83 Johnson A. D. 173 Johnson A. F. 220 Johnson C. R. 40 48 298 Johnson D. N. 220 Johnson M. P. 272 Johnson P. L. 180 Johnson R. A. 237 Johnson R. D. 18 Johnson R. P. 93 Johnson R. S. 29 30 Johnson W. S. 102 Johnston B. D. 282 Johnston J. F. 176 Jokisaari J. 9 Jones A. D. 49 Jones C. H. W. 277 Jones C. W. 182 Jones D. S. 130 Jones D. W. 55 56 Jones K. 76 179 Jones K. L. 58 269 Jones M. 52 Jones M. E. 62 Jones N. D. 92 Jones P. G. 52 233 268 Jones R. A. 225 280 Jones W. D. 179 Jorgensen K. A. 90 298 Jorgensen W.J. 57 Jorgensen W. L. 37 38,41,42 46 Jorgenson J. W. 28 Joseph S. P. 104 291 Joshi N. N. 112 Ju J. 123 253 Juaristi E. 212 Jubault M. 281 Jump J. M. 49 161 Jung K.-Y. 188 295 Jung M. E. 227 Jung Y. H. 227 Junk P. C. 191 265 Jurkschat K. 278 Jutzi P. 263 265 274 275 Kabalka G. W. 103 Kabe Y.,276 Kabuto C. 261 271 274 Author Index 335 Kaczmarek L. 132 Kadow J. F. 287 304 Kammerling H. T. 47 Kafafi S. A. 184 Kaspar J. 104 Kastrup R. V. 231 Kataoka H. 288 Kataoka Y. 123 Kim H.-D. 159 Kim K. S. 109 Kim M.-J. 315 Kim N. K. 9 Kagan H. B. 134,229,230,296 Kagan J. 199 Kagechika K. 193 Kagel J. R. 46 Kageyama H. 282 Kahr B. 171 Katayama S. 135 Kato M. 282 Kato N. 55 288 Kato S. 49 161 282 284 Katoh S.177 Katritzky A. R. 46 128 204 Kim S. 137 304 Kimura Y. 182 Kind P. 277 King R. E. 111 230 King S. A. 151 196 248 295 Kingsbury G. A, 322 Kai Y. 245 208 210 Kini A. M. 281 Kaila N. 39 46 Katsuhira T. 144 Kinoshita M. 108 Kajigaeshi S. 128 177 Katsuura A. 282 Kinsinger J. A. 24 Kajtar-Peredy M. 295 Kaupp G. 191 Kinugawa M. 148 Kakinami T. 128 177 Kaur S. 30 Kira M. 54 123 271 293 Kakiuchi K. 148 Kaur V. 193 Kiratake J. 309 Kalantar T. H. 91 106 300 Kautz R. A. 18 Kirby A. J. 59 71 Kalatzis E. 70 Kawabata H. 79 Kiriazis L. 70 Kalikhman I. D. 272 Kawabata T. 193 Kirmse W. 269 Kalinoski H. T. 27 Kawai Y. 313 Kishi Y. 168 286 Kallel E. A. 39 56 Kawajiri Y. 303 Kishikawa K. 125 Kallmuenzer A. 218 Kawakita T. 290 Kishimoto T. 271 Kamada T.177 Kawamura F. 125 Kita Y. 96 Kamakura S. 184 Kawano H. 96 230 303 Kitaguchi H. 312 Kamal A. 321 Kawasaki N. 233 Kitamura M. 290 Kamata M. 50 Kawasaki T. 202 Kitamura T. 99 178 183 Kambara H. 21 Kawase M. 178 183 Kitano Y. 229 Kambe N. 132 Kawase Y. 296 Kitazune T. 121 Kametani T. 165 Kay L. E. 13 18 Kitchen D. B. 16 Kamigata N. 221 Kayser M. M. 134 Kiviniitty K. 9 Kamimura A. 133 Keay B. A. 164 295 Kiyoshige K. 116 303 Kamiya Y. 142 Kebarle P. 22 24 42 67 112 Kjellberg J. 22 Kamlet M. J. 72 Keck G. E. 120 221 Kjortkjaer J. 23 1 Kanagasabapathy V. M. 60 Keenan R. M. 185 Klade C. A. 197 Kanai F. 126 Keller L. 180 251 Klaeren S. A. 233 Kanakam C. C. 174 Keller T. H. 150 244 Klamer F.-G. 47 Kanaya D. 270 Kellner G. 23 Kleijn H. 192 Kanda F.192 Kelly B. J. 89 190 Klein K.-D. 263 Kanda T. 284 Kelly D. R. 285 Klibanov A. M. 312 Kanehisa N. 245 Kemmitt R. D. W. 248 Kline A. D. 17 Kaneko C. 145 161 Kemmitt T. 282 Kloc K. 200 Kanemaki N. 300 Kennedy D. A. 50 Kloosterman M. 312 Kanematsu A. 48 164 Kennedy D. J. 237 Huger R. 57 Kanematsu K. 163 Kennedy R. M. 200 315 Klumpp G. W. 262 Kanemoto S. 149 Kenny C. 157 Klunder J. M. 189 229 Kang A. S. 322 Kerschner J. L. 179 Knobler C. 257 Kang S. H. 286 Kang S. O. 9 Keusenkothen P. F. 206 Kevill D. N. 58 Knobler C. B. 195 Knochel P.,234 258 Kanne D. 274 Khan M. 123 253 Knolker H.-J. 250 Kant J. 208 Khan M. N. 69 Knops P. 187 Kanters J. A. 262 Khanapure S. P. 184 Knors C. 153 258 Kaptein R. J. 13 14 Khetani V. D. 249 Knowles P. J. 35 Karaman R.186 Karas M. 20 Khwaja H. 233 Kibayashi C. 116 305 Kobara S. 114 Kobayashi H. 113 187 Karash C. B. 49 Kiengle F. 161 Kobayashi K. 101 197 244 Karatsu T. 270 Kikuchi O. 42 Kobayashi M. 311 Karge P. 48 Kikugawa V. 178 Kobayashi N. 132 315 Karlsson J. O. 174 Karplus M. 34 Kasai N. 245 Kikugawa Y. 183 Kikuiri N. 302 Killion R. B. 63 Kobayashi S. 120 121 290 Kobayashi T. 204 Kobayashi Y. 161 199 229 Kashik A. S. 283 Kim B. H. 106 Kobrina L. S. 179 Kashimura S. 92 Kim B. M. 91 303 Koch A. 76 Kashiwagi K. 119 131 Kim D. 73 137 Koch W. 37 60 Kasina S. 130 Kim E. K. 176 Kochi J. K. 11 1 176 Kocienski P. 95 234 236 Koehler S. 17 Koerdel J. 16 Koerner M. 175 Koster G. 118 Koster R. 271 Koga K. 159 287 Koga N. 40 54 Kohda D.14 Kohgami K. 281 Kohl F. X. 275 Kohlbrenner W. E. 13 Kohmoto S. 84 125 157 Kohnke F. H. 287 Kol M. 87 Kole P. L. 188 Kolesnikov S. P. 275 Kollir L. 232 Komatsu M. 235 289 Kondo F. 155 238 Kondo K. 132 Kondo M. 232 Kondo T. 233 308 Konig W. A. 285 Konno K. 318 Kono Y. 199 Konoike T. 194 Konopelski J. P. 161 Kooper K. 95 Kopasz J. P. 268 Kopf J. 147 264 Kopinke F.-D. 178 Kopola N. 131 249 Kopp G. 47 Kopping B. 73 Korda A. 231 Koreeda M. 188 294 Kornack E. P. 199 Korreda M. 295 Korte F. 201 Koseki S. 35 Kossmehl G. 270 Kostenko L. I. 63 Kosukegawa O. 124 Kotali A. 208 Koumoto N. 304 Kovalev B. G. 229 Kowalczyk B. A. 111 Kowalski M.H. 239 Kowasaki H. 159 Koyama H. 197 Koyama T. 283 Koyano H. 291 Kozaki T. 42 Koziara A. 109 Kozikowski A. P. 212 Kraakman P. A. 52 Kramer T. 292 Kraulis P. J. 13 Krause A. 187 Krause N. 235 Krausz P. 304 Kreager A. 242 Krebs A. 275 276 Krebs B. 272 Kreiter C. G. 195 Kresge A. J. 68 98 Krishna P. R. 229 Krivykh V. V. 247 Kriiger C. 274 Krumpe K. E. 50 Kruse C. G. 220 Kruse L. I. 177 185 Kubis A. J. 26 Kucera D. J. 98 Kundig E. P. 180 Kuhn A, 12 Kuivila H. G. 278 Kujath E. 225 Kula M.R. 313 Kulik W. 30 Kumai A. 270 Kumar G. S. 312 Kumar R. 267 Kumar S. 188 Kume M. 308 Kumobayashi H. 230 303 Kumon N. 281 Kunieda T.129 Kuntz I. D. 11 Kunugi S. 308 Kunz E. 277 Kunz H. 214 Kuo E. Y. 55 Kurata K. 133 Kuroda S. 185 Kurusu Y. 121 Kusabayashi S. 212 Kusakabe M. 229 Kusano K.-H. 303 Kutney J. P. 229 Kutzelnigg W. 37 Kuwajima I. 113 137,235 289 Kuwatani Y. 98 Kwok F. C. 68 Kwong P. C. C. 298 Kyushin S. 182 Laabassi M. 253 Laboue B. 236 Lacher B. 81 169 Lacy P. H. 185 Laguna A. 268 Lai E. K. Y. 93 Lai G. S. 302 Lai S. M. F. 211 Lai Y.-H. 187 Lai Y.-S. 250 Lai Z.-G. 61 Laidig K. E. 36 Laidler D. A. 221 Laine R. A. 31 Lakhlifi T. 206 Lakhmiri P. 109 La Mar G. N. 18 Lamaty F. 97 152 242 Lambert J. N. 181 Lamenec T. R.,194 Author Index Lamy-Schelkens H.49 Lande B. 206 Lane A. N. 18 Lange W. 224 Langhals E. 51 LanglCt A. 244 Langley D. R. 287 Lardicci L. 116 Larock R. C. 155 180 238 286 Larsen D. S. 48 296 Larsen E. 210 Larsen L. 163 Larson G. L. 269 Larsson P. O. 318 Lassila K. R. 185 Last K. 197 Lathbury D. 96 Lau C. K. 181 Laumen K. 311 Lautens M. 149 Lavergne J.-P. 180 Lavigne A. 133 Lawrence L. M. 265 Layh M. 267 Le J. C. 25 Le N. A. 52 Learned A. E. 269 Lebibi J. 253 Leblanc Y. 298 Lebreton J. 241 Lechler R. 267 Lecolier S. 231 Le Corre M. 130 293 Lectka T. 88 Lee C. 141 142 Lee C.-H. 181 Lee C. C. 251 Lee D. C. 241 Lee D. G. 302 Lee E. 155 Lee E. D. 23 28 Lee G.-H.247 Lee H. Y. 169 Lee I. 38 46 Lee J. 48 161 Lee K. 245 Lee S.-H. 252 263 Lee T.-H. 185 Lee T. J. 37 Lee T. V. 21 1 249 295 Lee Y. H. 311 Leeper F. J. 226 Lees W. 315 Leffers W. 263 265 Lefour J.-M. 37 42 Le Gall T. 252 Legendre L. 200 Le Goffic F. 131 Legters J. 229 Lehr R. E. 188 Leigh A. J. 211 295 Leipert T. K. 153 Leis C. 273 Author Index Leis J. R. 65 70 71 Leitner W. 125 Lellouche J.-P. 252 Lemaire M. 176 302 Lemal D. M. 174 Leman J. T. 267 Lemor A. 302 Lemordant D. 203 Lenarda M. 104 Lendvay G. 43 Lenfers J. B. 147 Lenhart W. C. 282 Lenn N. D. 141 Lennon P. J. 269 le Noble W. J. 46 55 71 Lenoir D. 88 Lenz G.R.,223 Leonard C. A. 220 Leonard E. 105 Lepage L. 198 Lepage Y. 198 Le Roux J. 293 Leroy L. 253 Lesage M. 112 Lesheski L. 234 Lessor R. A. 223 Leta S. 231 Letcher R. M. 219 Leumann C. J. 322 Leung W.-P. 262 Levason W. 282 Levin D. Z. 212 Levin S. G. 160 Levitre S. A. 258 Levy J. 306 Levy R. M. 16 Lewis A, 161 Lewis E. S. 60 Lewis R.T. 79 287 Ley S. V. 320 Leyrer U. 230 Lhoste P. 109 247 Li J. 199 Li J. S. 292 Li Y. 41 Liberato D. J. 26 Licini G. 135 Lickiss P. D. 58 269 271 272 Lieberknecht A. 227 Liebeskind L. S. 241 Lii J.-H. 34 Lilla G. 62 Limbach H.-H. 42 Lin K.-C. 93 168 Lin M.-H. 55 Lin P. V. 209 Lincoln D. M.231 Lindberg T. 285 Lindner E. 244 Lindner H. J. 81 Lindon J. C. 4 Lindsay Smith J. R. 66 177 Lindsey J. S. 226 Lindstedt E.-L. 235 Linert W. 72 Link J. O. 103 303 Link M. 272 Linstrumelle G. 241 Linz G. 48 Liotta C. L. 221 Liotta L. J. 109 304 Lipscomb W. N. 35 Lipshutz B. H. 105 235 276 289 303 305 Lisek C. A. 28 Lissel M. 174 Liu B. 37 60 Liu F.-C. 247 Liu H.-W. 141 Liu K. K.-C. 31 1 Liu R.-S. 247 Liu S. 278 Liu X. 161 Liu Y. 257 Liu Y.-C. 110 310 Livinghouse T. 152 242 244 Lledbs A. 42 62 Lluch J. M. 35 42 Lo L. C. 309 Lo Y. s.,220 Loebel J. 268 Lohray B. B. 91 106 190 300 303 Loncharich R. J. 38 46 Longford D. 239 Loo J. A.28 Looney A. 264 Lopez J. C. 80 Lopez L. 112 299 Lopez L. A. 297 Lorand J. P. 60 175 Lorbeth J. 263 Lorimer J. P. 305 Lottenbach W. 124 Louwen J. N. 187 Lovas F. J. 51 Lovelace T. C. 190 Lovett M. B. 52 Lown J. W. 172 Lowy c.,10 Loy G. 210 Lu H. 185 Lu W. 250 Lu X. 115 125 247 Lu Y. 115 Lubman D. M. 26 Lucchini V. 110 Luchetti L. 176 Lucisano L. J. 306 Lue P. 208 Lucking K. 47 Luh T.-Y. 239 Lukevics E. 268 305 Lum R. T. 153 Luna H. 319 Lund E. C. 242 Lusztyk J. 85 Lutz S. 285 Luzzio F. A. 306 Lwowski W. 178 Lys I. 26 Ma D. 115 125 Mabud M. A. 29 McAllister M. 64 Macaulay J. B. 48 161 Maccagnani G. 269 McCain D. C. 18 McCallum J.S. 241 McCann S. 55 McCauley J. P. jun. 84 McClelland R. A. 58 60 McCloskey J. A. 27 McCormick F. 12 McCormick M. J. 265 McDonagh J. 9 McDouall J. J. W. 35 37 46 McDougal P. G. 49 161 McDowall M. A. 25 McGahren W. J. 79 McGeary C. A. 264 McGhee C. N. J. 23 McGlohon E. S. 30 McGrath M. P. 36 Machida S. 127 Machii D. 305 Machinaga N. 116 305 Maciejewski L. 253 McIver J. W. 52 Mack D. P. 269 McKee M. L. 40 46 McKeer L. C. 66 177 McKenna E. G. 294 Mackie R. K. 229 McKillop A. 178 Mackowska E. 232 Macleod A. F. 10 McLuckey S. A. 29 McMahon A. W. 31 McMordie R. 319 McMurray J. E. 88 169 McNab H. 219 McNeil M. 26 McNicolas C. 89 McPartlin M.249 267 McWhorter W. W. jun. 286 Maddox P. J. 230 Maeda S. 185 Maer G. 161 Maercker A. 263 Maerkl G. 218 Magers D. H. 35 Magnin D. R. 81 169 Magnus P. 79 242 287 Maguire J. A. 279 Mah R.,203 Mahadevan S. 296 Mahendran M. 186 Mahler H. 118 Mahmoodi N. O. 196 Mahmoudi M. 253 Mahon M. F. 96 277 338 Mahuteau J. 200 Main D. E. 21 Maiorana S. 314 Majerski K. M. 142 Majeyich R. G. 291 Majid T. N. 234 Majoral J.-P. 195 Maki Y. 181 Makosza M. 182 251 Makuta T. 125 Malacria M. 248 295 Malet-Martino M. C. 5 Maligres P. 79 Malik A. A, 128 Malikayil J. A. 11 Malinowski M. 132 Mallis L. M. 30 Mallory F. B. 184 Malone J. F. 50 164 296 Maloney B.A. 162 Maloney M. G. 291 Maltby D. A. 23 25 Mancini G. 176 Mandon D. 250 Mangeny P. 105 Mani N. S. 174 Mann M. 21 22 Mantlo N. B. 79 287 Marcelis A. T. M. 214 March R. E. 31 32 Marchand A. P. 184 Marchese G. 94 290 Marchetti M. 116 Marciniec B. 232 Marcos E. S. 41 Marek I. 105 Marel D. 125 Marinelli F. 238 Marion D. 13 Marioni F. 321 Mark C. 230 Markandu J. 51 208 Markey S. P. 25 Markies P. R. 264 Markley J. L. 18 Markb I. 90 229 300 Markovski L. N. 189 Marmon R. J. 55 Marno S. 318 Marples B. A. 110 Marquez M. 66 Marsch M. 262 263 Marschner C. 119 Marshall J. A. 92,120,189,253 292 Martelli J. 253 Marth C. F. 293 Martin C.A. 229 298 Martin I. 63 Martin K. A. 188 Martin S. A. 29 Martin W. B. 26 Martha D. 253 Martinez A. G. 132 Manino R.,5 Maruoka K. 113 300 Maruyama K. 203 Maryanoff B. E. 49 87 133 135 293 Maryanoff C. A. 49 Masaki Y. 109 Masamune S. 200 276 315 Masci B. 65 Maseras F. 42 62 Mashima K. 303 Masiero S. 269 Maskill H. 59 71 Masnovi J. M. 85 176 Mason S. A. 48 Mason T. J. 305 Massa W. 263 Massey R. J. 322 Massiot G. 115 Massy D. J. R.,178 Masuda R. 182 Masuda Y. 91 123 Masuyama Y. 121 Mataka S. 187 Matinelli M. J. 286 Matlay J. 161 Matsubara S. 102 169 Matsuda H. 116 129 Matsuda I. 100 115 232 Matsuda S. 96 Matsui K. 99 Matsui S. 119 131 Matsumoto K.112 113 310 Matsumoto S. 319 Matsumoto Y. 91 103 Matsumura Y. 177 Matsunaga S.-I. 101 112 Matsuoka Y. 245 Matsuura T. 79 Matsuyama H. 221 Matsuzawa S. 185 289 Matsuzuka H. 199 Matta K. L. 31 Matteson D. S. 106 300 Matthews B. R. 127 Mattson M. N. 258 Mauger J. 31 1 Maumy M. 133 Maxka J. 273 May S. W. 321 Maycock C. D. 105 Mayer H. A. 244 Mayers A. I. 162 Maynard J. C. 66 Maynard K. J. 173 Mayr H. 47 51 292 Mayrargue J. 181 Mazieres M. R. 195 Mazzanti G. 269 Mazzochi P. H. 219 Meador M. A. 184 Meegalla S. K. 198 Mefedov 0.M. 275 Meier 1. K. 88 Author Index Meijide F. 70 Melhuish M. W. 65 Mello R.,87 299 Melloni G. 124 Mende M.314 Mendia A. 268 Meng C. K. 21 22 Menger F. M. 43 Mercier F. 134 Mergelsberg I. 161 Merger R. 99 Merino I. 116 Merlet N. 200 Memman G. H. 183 Mertes J. 161 Men K. M. 42 Meth-Cohn O. 222 Metz P. 295 Metzler W. J. 16 Meurs J. H. H. 177 Meyer J. 277 Meyers A. I. 48 159 Mezey P. G. 43 Mezey-Vandor G. 295 Michaelson E. T. 238 246 Michl J. 269 270 276 Middlemiss D. 233 234 253 255 Midgley J. M. 23 Midland M. M. 129 Miftakhov M. S. 94 239 Migdal C. A. 63 Mignani G. 125 Mignani S. 248 Mikaelian G. S. 242 Miksztal A. R.,298 Miles W. H. 180 252 Miller A. 296 Miller B. 178 Miller J. A. 152 243 Miller J. D. 282 Miller J. M. 182 Miller M. L. 248 295 Miller R.D. 269 270 Miller U. 167 Millington D. S. 23 Millis K. K. 5 Mills G. A. 9 Mills N. S. 186 Mills R. J. 181 Mills S. D. 82 169 Milot G. 212 Milstein D. 181 233 Mimura M. 128 Min B. G. 9 Minabe M. 184 Minami T. 253 Minamikawa H. 133 Minato A. 272 Minisci F. 74 177 Minnetian 0. M. 240 Minton M. A. 56 Miocque M. 200 Mioskowski C. 111 113 117 279 304 Author Index Misiti D. 109 224 Misslitz U. 127 Mistry N. 83 Mitani O. 232 Mitchell M. B. 49 Mitchell R. H. 187 Miura H. 247 Miura M. 212 233 Miwa Y. 48 Miwata H. 290 Miya H. 182 Miyachi N. 192 Miyachi Y. 185 Miyake H. 105 Miyake T. 14 Miyamae Y. 311 Miyamoto H.199 Miyamoto K. 311 Miyano H. 186 254 Miyashi T. 50 Miyashita M. 201 Miyazaki K. 318 Miyoshi N. 126 Mizuno M. 286 Mizuno T. 132 Mlochowski J. 200 Mloston G. 51 Moberg C. 244 Mochida K. 276 Mock K. 28 Modena G. 135 Moderhack D. 220 Modriozola J. 192 Modro T. A. 222 Mohrke A. 274 Moene W. 262 Mohr P. 126 Moise F. 266 Molander G. A. 157 167 Molina P. 215 Molinari F. 122 Mollison K. W. 17 Molloy K. C. 96 277 Monaghan J. J. 24 Monaghen A. 302 Monahan L. C. 219 Mongkolaussavaratana T. 50 Montaudo G. 31 Montelione G. T. 14 Montero V. A. 51 Montgomery W. D. 206 Moodie R. B. 65 Moody C. J. 175 218 255 Moon B. M. 300 Moore H. W. 174 Mootoo D.R. 287 Morales A. 24 Moran J. R. 51 Morden W. E. 24 More P. G. 237 Moreno M. 35 Moret6 J. M. 244 Moretti R. 305 Mon A. 55 177 Mon E. 233 Mori K. 128,229,285,303,301 Mori M. 193 233 Mori Y. 92 107 305 Moriarty R. M. 143 Morihashi K. 42 Morikawa S. 101 Morikawa Y. 308 Morimoto T. 303 Morisawa Y. 204 Morita N. 185 Morita Y. 291 Moriwake T. 128 158 Moriwaki M. 177 Morokuma K. 40 41 54 235 Moro-oka Y. 232 Moms I. K. 240 Moms M. 24 Morrow G. W. 183 Mortezaei R. 255 Mortikov E. S. 212 Morton G. O. 79 Mosbach K. 318 Mosely M. A. 28 Moskowitz H. 181 Motezaei R. 166 Motherwell W. B. 149 242 Motohashi N. 303 Motoki S. 222 Moustrou C. 75 Moyano A.38 Mu D. 247 Muchmore C. R. 257 Muchowski J. M. 216 Muck W. 28 Mullen K. 188 Muller A. 274 Muller G. 265 268 273 275 278 Mueller L. 11 14 Mugrage B. B. 212 Mukai C. 253 Mukai I. 109 Mukaiyama S. 108 Mukaiyama T. 103 119 120 121 122 131 Munakata Y. 314 Munyemana F. 11 1 Murafuji T. 280 Muraglia V. 172 Murahashi S.-i. 247 Murai A. 110 Murai S. 283 Murai T. 282 284 Murakame S. 132 Murakami Y. 202 Muralidharan K. R. 93 Muralidharan S. 281 Muramatsu H. 96 230 Murphee S. S. 93 Murphy C. M. 24 26 Murphy J. A. 83 Murray R. W. 190 299 Musso H. 187 Mwesigye-Kibende S. 76 Myers A. G. 55 79 99 Nabeshima T. 203 Nadler M. P. 283 Nagami K.253 Nagao T. 177 Nagao Y. 197 308 Nagasawa H. 255 Nagasawa T. 311 Nagashima H. 109 Nagashima S. 163 Nagata R. 79 Naghipur A. 172 Nagl A. 184 Naito H. 274 Nakaahima M. 162 Nakadaira Y.,182 Nakagawa K. 203 Nakaiida S. 284 Nakaji D. 36 Nakajima H. 128 Nakajima M. 270 Nakajima T. 282 283 Nakamura A. 245 313 314 Nakamura E. 52,113,185,289 305 Nakamura K. 313 Nakamura T. 221 232 308 Nakanishi S. 97 116 247 Nakanishi T. 261 Nakata M. 286 Nameki H. 274 Naoshima Y. 314 Naperstkow A. M. 48 161 Narahara O. 158 Narasaka K. 126 133 147,296 Narasaku N. 162 Narayanan K. 155 238 Nared K. D. 48 323 Narisano E. 108 309 Naso F. 94 290 Nation C. B. M. 249 Naylor A.233 234 253 255 Neary A. P. 156 Necula A. 184 Neef G. 179 Negishi E.4 97 140 150 152 242 243 Neibecker D. 231 Nelson D. J. 64 Nelson S. J. 11 Nelson W. M. 271 Nemoto H. 240 Nettesheim D. G. 17 Neumann C. 285 Neumann D. 221 Neumann R. 174 Neumuller B. 267 Newcomb M. 278 Newell D. R. 9 Newlands M. J. 48 161 Newman D. A. 270 Ng J. S. 105 289 Ngo D. D. 173 Nguyen P. 186 Ni Z.-J. 239 Nibbering N. M. M. 62 Nicholas K. M. 123 253 Nicholson J. K. 4 5 7 8 10 Nicol G. 22 Nicolaou K. C. 79 241 286 287 299 Nicolau K. C. 218 222 Nicotra F. 318 Nidy E. G. 237 Niecke E. 195 Nielsen R. B. 93 Nietsche J. A. 176 Nijenhuis W. F. 312 Nikolaeva L.N. 229 Nilges M. 16 Nisar M. 298 Nishi K. 96 Nishida S. 186 Nishiguchi T. 109 Nishii S. 126 Nishimura M. 186 254 Nishioka E. 247 Nishioka T. 309 Nishioka Y. 284 Nishiyama H. 232 Nishiyama T. 313 314 Nishiyama Y. 282 Nissan R. A. 282 283 Nitta M. 186 204 254 Niwa S. 122 290 Noashima Y. 313 Node M. 255 Noth H. 275 Nogradi M. 295 Noh S. K. 254 Nojima M. 212 Nolan J. C. 220 Noltemeyer M. 224 Nomoto T. 93 Nomura A. 308 Nomura M. 233 Norberto F. 71 132 Norman R. E. 9 Normant J. F. 105 123 Norrsell F. 176 North M. 291 Norwood T. J. 12 Nouri-Sorkhabi M. H. 186 Novak M. 188 Novikov V. P.,295 Nowotny H.-P. 285 Noyori R. 290 291 303 Nozaki H.114 Nozoe T. 185 Nudelman N. S. 66 Nugent W. A. 97 152 Nugiel D. A. 287 Numata H. 158 227 Nunn C. M. 280 Nuwaysir L. M. 26 27 Nuzillard J.-M. 115 Nuzzo R. G. 266 Oak 0. Z. 164 Obata K. 270 Oberhauser T. 308 Obermann U. 232 O’Brien M. K. 249 Occhiucci G. 62 Ochiai M. 197 308 Oda J. 128 308 309 Oda M. 98 186 Odaira Y. 148 Odazaki M. 281 O’Donnell M. J. 130 285 Odriozola J. M. 291 Oehme H. 263 Oehrlein R. 126 Oertle K. 124 Oesch F. 188 Offermann W. 280 Ogasawara K. 99 298 310 Ogawa A. 132 Ogawa M. 124 Ogawa T. 280 Ogino T. 302 Ogiso A. 100 232 Ogiso I. 115 Ogisu M. 185 Ognyanov V. I. 225 Oguchi T. 124 Oguni N. 290 Ogura F.199 261 Oh S. M. 184 Oh S. M. N. Y. F. 70 71 Ohanessian G. 37 42 Ohashi M. 182 Ohbuchi S. 288 Ohdoi K. 280 Ohkita M. 186 Ohlmeyer M. J. 91 130 232 Ohmori M. 247 Ohnishi K. 182 Ohno A. 313 Ohno M. 290 Ohshima T. 315 Ohshita J. 270 Ohta H. 112 113 132 310 311 315 319 Ohta K. 294 Ohta T. 178 303 Ohta Y. 276 Ohwada T. 178 Oiarbide M. 192 291 Oishi T. 91 106 300 Ojima I. 231 285 Ojima N. 318 Oka S. 313 Okabe K. 178 Okabe M. 144 Okada E. 182 Okada S. 290 Okai H. 185 Okajima T. 281 Okamoto T. 128 177 245 Author Index Okamoto Y. 282 319 Okawara H. 247 Okazaki E. 79 Okazaki R. 281 Okinoshima H. 272 Oku A. 144 Okudo M. 126 Olabarrieta R.51 Olah G. A. 87 186 Olefirowicz T. M. 27 Oliva A. 38 46 122 Olivella S. 33 Oliver J. P. 267 Olivucci M. 46 Olmstead M. M. 288 Olson L. 52 Olsson T. 235 Omachi N. 165 Onami T. 92 189 229 O’Neil I. A. 299 Ono N. 133 Ono T. 272 Ontoria J. M. 192 Ooi T. 113 300 Oppolzer W. 137 150 244 Orchison J. J. A. 211 Oris C. 161 Orlando R. 24 Ortar G. 238 Ortega F. 182 Ortiz de Montellano P. R. 85 Osanai K. 227 Osani K. 158 Oschkinat H. 13 16 Oshima K. 92 101 112 Oshima M. 125 298 Osman R. 41 Ostler G. 12 Ostrowicki A, 187 Ostrowski S. 251 Osuka A. 203 Oswald A. A. 231 Oswald R. E. 18 Otera J. 114 O’Toole K. J. 307 Otsubo T. 199 261 Otsuji Y.97 116 247 Otten T. 173 Ottow E. 179 Ouimet N. 255 Oumar-Mahamat H. 75 Ousset J. B. 279 Outurquin F. 200 Ovaska T. V. 153 Overman L. E. 98 137 203 214 Owczarczyk Z. 182 Owen D. A. 250 Owens G. D. 23 Owens J. E. 199 Ozaki K. 132 315 Ozaki T. 208 Padwa A. 49 50 93 256 Page M. 52 Author Index Page P. C. B. 122 Paisley S. D. 234 Palacios F. 116 Pale-Grosdemange C. 131 Pallente-Morel] S. L. 27 Palorno C. 192 291 Palornoin E. 304 Paluchowska M. H. 204 Panangadan J. A. K. 214 Pandey G. 282 Pandiarajan P. K. 118 Pandit V. K. 164 Panichi K. M. 31 Papasergio R. I. 262 Papastavros M. Z. 12 Pappin A. J. 220 Paquette L. A, 34 48 49 240 Pardi A.16 Paredes M. C. 183 Parish D. W. 18 Park C. Y. 91 106 300 Park J. 276 Park J. H. 137 155 304 Park S. C. 230 Parker K. A. 162 183 Parker V. D. 176 Parkes H. G. 11 Parkin G. 264 Parlar H. 201 Parlier A. 257 Parr G. 36 Pam R. G. 171 Parra M. 320 Parsons P. J. 156 Pasch E. 191 Passerieux D. 198 Pasterczyk J. W. 279 Pasto D. J. 47 56 Pastor S. D. 131 Pataki J. 188 Patalinghug W. C. 191 265 Patel H. M. S. 70 Paterson T. McC. 296 Patil S. 174 Pattenden G. 76 82 169 Patyk A. 273 Paulmier C. 200 Paventi M. 65 Pavkovic S. F. 256 Pavlenko N. V. 177 Pazik J. C. 268 Peach J. M. 299 Pearson A. J. 166 249 250 252,255 Pearson R. G. 36 72 Pearson W.H. 93 Peck C. J. 220 Peck R. C. 184 Pedersen S. F. 101 184 201 Pederson R. L. 316 Pei D. 323 Pekerar S. 63 Pelinski L. 253 Pellechia P. J. 179 Pellon P. 269 Pellou A. 103 Pelter A. 117 Peiia A. 229 Peiia M. E. 65 70 71 Peiia M. R. 240 Peng S.-M. 247 Pennington W. T. 266 Pentony S. L. jun. 28 Percy J. M. 59 Perepichka I. F. 63 Perera I. 22 Periasamy M. 242 Pericas M. A. 38 Perichon J. 105 Pernez S. 124 293 Perri S. T. 174 Perrin C. L. 69 Perrine D. M. 199 Perry M. W. D. 255 Person D. 130 Peters K. 119 Peterson G. A. 153 257 Peterson K. B. 46 Petnehazy I. 131 Petrini M. 132 Petroff 0. A. C. 5 Petroskii P. V. 247 Petter R. C.143 Pettus T. 319 Pfeffer M. 241 Pflieger P. 113 ffrengle W. 214 Pham E. K. 273 Pham T. N. 111 Phanstiel O. 54 Phillips P. S. 9 Pi R. 262 Piccolo O. 124 Pickles R. 218 Pietroni B. 238 Pietrusiewics K. M. 48 Pikul S. 162 Pinkerton A. A. 250 Pinkston X.X.,23 Pinto B. M. 282 Piocos E. A. 266 Pibrko A. 251 Piotrowska K. 229 Piovosi E. 113 Pirmng M. C. 148 Pitchen P. 230 Pizzo F. 110 Platone E. 177 Platt K. L. 188 Plumet J. 192 Podesta J. C. 276 Podlogar B. L. 34 Pohl S. 263 273 274 Pohmakotr M. 140 157 Poirier M. 271 Pojarlieff I. G. 71 Poll T. 48 Pollitt R. J. 128 Pomerantz S. C. 27 Poolsanong C. 157 Poon Y.-F. 93 Pople J. A. 34 35 Popov A.F. 63 Popp F. D. 208 Popuang S. 140 Porco J. A. jun. 237 239 287 Porter N. A. 81 169 Portnoy M. 181,233 Poska R. P. 306 Posner G. H. 271 Potapov V. A. 283 Pottie M. 126 Potvin P. G. 298 Pougny J. R. 236 241 Pouilhks A. 246 Poulter L. 29 Poupart M.-A. 255 Powell D. R. 273 Powell H. R. 267 Power P. P. 288 Prackash G. K. S. 186 Prakash C. 108 304 Prakash O. 143 Prasad C. V. C. 218 222 286 299 Prasad G. 155 Pratt A. J. 285 292 Preiss U. 124 Prest R. 281 Preston S. B. 128 Preston S. C. 234 Preu L. 220 Price J. D. 319 Price M. E. 150 242 Price S. L. 33 Principle L. M. 242 Prinzbach H. 173 Pritchard P. H. 9 Pritzkow H.,134 Probst T. 278 Procter G.296 Profeta S. 34 Promonenkov V. K. 212 Pross A. 42 62 72 Proteau P. J. 79 Pryor W. A. 176 Przeslawski R. M. 302 Puckett C. L. 48 Pudova O. 268 Puebla L. 183 Puff H. 277 Pulay P. 37 Pulazon J. M. 241 Puranik D. B. 272 273 Pyckhout W. 34 Pyun C. 112 Qian Y.-Q. 17 Quinkert G. 221 Quint J. F. 28 Quintero L. 83 Quirion J. C. 123 Qureshi S. J. 181 Rabenstein D. L. 5 Raber D. J. 34 Rabinovitz M. 186 Rachon J. 264 Radom L. 68 Rader H.-J. 188 Rafalko P. W. 223 Rafter J. E. 10 Raghavachari K. 34 173 Rahman S. S. 148 Raimondi M. 36 183 Rajagopal S. 72 Rajagopalan K. 55 RajanBabu T. V. 79 80 158 Raley T. J. jun. 26 Ralston C.L. 191 Ramachandran P. V. 116 Ramakrishnan V. T. 55 Ramanathan H. 174 Ramaswamy M. 251 Ramirez G. 178 Ramphal J. Y. 241 Ramponi G. 17 18 Randall E. W. 10 Rangaishenvi M. V. 88 Rao A. V. R. 229 Rao Ch. P. 300 Rao K. K. 100 Rao V. J. 282 Rappoport Z. 63 Raston C. L. 262 265 Ratananukul P. 50 Rauk A. 37 Rauscher D. J. 251 Ravenek W. 23 1 Rbau R. 231 Rebiere F. 134 Rebolledo F. 132 Reddy B. R. 123 253 Reddy G. S. 80 158 Reddy G. V. 271 Reddy V. P. 49 Redfield A. G. 12 Redgrave A. J. 320 Redlich H. 147 Rees C. W. 175 191 217 224 Reetz M. T. 129 130 Reggelin M. 132 Reginato G. 271 277 Regitz M. 195 Rehberg G. M. 257 Reich S. H. 229 Reider P.J. 307 Reike R. D. 97 Reilly M. H. 30 Reinhoudt D. N. 312 Reiser O. 180 Reiter L. A. 209 Reitstoen B. 176 Reitz A. B. 87 133 135,293 Ren H. 58 Renneboog R. 67 Rese M. 47 Resnati G. 113 Respondek M. 227 Reszka K. 172 Retherford C. 234 Reum M.E. 181 Reuter D. C. 276 Reuter H. 187 277 Reutrakul V. 157 Reverberi S. 201 Reydellet V. 168 Reynolds C. H. 42 Reynolds S. 76 Rhee C. K. 116 Rheingold A. L. 229 241 279 280 Riant O. 296 Ricci A. 99 135 269 271 277 Rice J. E. 37 Rich J. D. 181 271 Richards K. 180 251 Richardson W. H. 34 52 Rickard C. E. F. 144 185 Rickborn B. 175 Rico J. C. 49 Rico J. G. 88 161 169 Ridd J. H. 65 66 176 Riediker M.121 124 130 Rieke R. D. 96 265 Righetti P. 48 Rigo B. 125 Rihs G. 131 Rinderknecht E. 14 Rippel H. C. 88 112 Rise F. 161 241 Riva S. 318 Robb M. A. 39 46 Roberto D. 233 Roberts B. P. 73 Roberts G. C. K. 12 Roberts K. A. 58,64 Roberts S. M. 148 285 307 Robertson G. M. 214,295 Robertson J. 81 Robichaud A. J. 214 Robinet G. 34 Robinson E. D. 92 Robinson G. H. 266 Roboz J. 25 Robyr C. 133 Roddick D. M. 263 Roden B. A. 249 Roder H. 11 Rodgers C. 295 Rodgers R. D. 268 Rodrigo R. 198 Rodrigo-Chiner J. 178 Rodriguez M. J. 173 Rodriguez-Lopez J. 192 Rodwell P. W. 174 Roefke P. 295 Rohrig D. 130 Roesky H. W. 224 Rosslein L. 126 Rogan E. G. 188 Rogers C.164 Author Index Rogers R. D. 49 Rogers-Evans M. 110 Rohde J. J. 183 Rohlfing C. M. 37 46 Rojas C. 49 161 Rokach J. 236 298 Romain I. 234 Romanelli A. L. 83 156 Romanenko V. D. 189 Ronan B. 229 Ronzini L. 94 290 Root K. S. 265 Roques C. 195 Rosa E. 71 132 Rosenberg R. E. 36 Rosenblum M. 246 Roskamp E. J. 201 Rossi K. 153 Rossi R. 134 Rossky P. J. 42 Roth H. D. 173 Roth K. 12 Rothwell I. P. 179 Rotinov A. 63 Rotteveel M. A. 241 Rotunno D. 94 290 Rousseau G. 221 Rousset C. J. 97 150 152 242 Rovira C. 207 Rowlands M. 117 Rowley M.,168 Roy P. 64 Roy S. 227 Royo G. 271 Royster T. L. jun. 267 Rozema M. J. 258 Rozen S. 87 Ruano J.L. G. 48 161 296 Ruasse M.-F. 71 Ruckle R. E. jun. 83 156 Ruder S. M. 162 183 Rudler H. 257 Rudolph M. J. 184 Riicker C. 173 Ruffer U. 213 Ruiz-Romero M. E. 268 Rulin F. 319 Rumpel H. 42 Ruppert K. 263 Russell D. H. 25 30 Russo N. 18 Ruster H. V. 47 Rutledge P. S. 252 Ruzziconi R. 115 Rybinskaya M. I. 247 Ryu I. 132 Rzepa H. S. 33 34 39 56 Saak W.,263 273 274 Saburi M. 96 230 303 Sadhu K. H. 106 Sadler P. J. 5 8 9 10 Saegusa T. 101 Sahali Y. 52 Author Index Saheki Y. 272 Saigo K. 127 Saito F. 204 Saito I. 79 Saito K. 133 292 Saito S. 128 158 Saito T. 222 315 Sakaguchi H. 232 Sakai K. 155 Sakairi M. 21 Sakaki J.-i. 161 Sakakibara Y.181 Sakamoto A. 128 Sakamoto K. 270 Sakashita S. 23 Sakurai H. 54 123 261 270 271 274 293 Salaun J. P. 113 Saleh S. 108 304 Salehpour M. 22 Salem G. 279 Sall D. J. 229 SallC M. 281 Salomon R. G. 227 Salzer A. 261 Sam A. R. H. 251 Samizu K. 99 298 Sammes P. G. 220 304 Samsel E. G. 85 Samuel O. 229 Sanami M. 274 Sanchez M. 195 Sandall J. P. B. 176 Sander W. 273 Sandhoff K. 128 Sangokoya S. A. 266 Sangwan N. K. 48 Sanins S. M. 4 Sankararaman S. 176 Sano T. 121 Santa N. 207 Sapse A.-M. 172 Sarkar A. 106 Sarma M. R. 100 Sarmah P. 304 Sartori G. 177 Sasson Y.,176 Sato F. 229 Sato K. 137 271 293 Sato M. 145 161 Sato S. 100 115 232 275 Sato T.114 298 Sato Y. 238 Satoh T.,135 Satoh Y.,125 Sattur P. B. 321 Saudek V. 17 18 Saulnier M. G. 287 Savelli G. 110 Sawada M. 61 199 Sawada T. 187 Sawyer J. F. 272 Saxena A. K. 272 Scahill T. A. 256 Scaiano J. C. 52 Scamuzzi B. 134 Scanlan G. F. 26 Scarparti R. 294 Schaap A. P. 304 Schaefer H. F. 34 37 39 Schaefer J. 18 Schafer T. 272 Schafer B. 295 Schaller C. 255 Schamp N. 144 Schat G. 264 Scheeren H. W. 220 Scheigetz J. 181 Scheller M. E. 229 Schepp N. P.,68 Schiavelli M. D. 239 Schickler H. 224 Schiketanz A. 184 Schimkowiak J. 224 Schindler M. 37 Schinzer D. 119 Schipor I. 234 Schlagg E. W. 26 Schlegel H. B. 35,37,39,41,46 Schleyer P.von R. 37 60 186 262 Schlosser D. 271 Schlosser M. 11 1 Schmalzing D. 285 Schmid M. 292 Schmidbaur H. 268,278 Schmidt G. F. 230 231 Schmidt T. 151 196 248 295 Schmidt U. 227 Schmitter J. 234 Schmitz A. 130 Schmuck A. 280 Schneider H.-J. 48 Schneider J. 195 Schneider M. P. 311 Schneider S. 144 167 248 Schnur D. M. 34 Schollhorn H. 262 Schoenen F. J. 237 287 Scholz U. 224 Schoning A. 161 Schore N. E. 150 242 Schotz K. 37 Schow S. R. 193 Schrank F. 263 Schreiber S. L. 165 237 239 287 Schubert U. 102 277 Schiimann U. 263 Schuh W. 277 Schuhmann W. 201 Schulman J. M. 184 Schulte G. 79 169 287 Schultz P. G. 322 323 Schumann H. 268 Schumann I.181 Schurig V. 230 285 Schwabe R.,174 Schwark J.-R. 292 Schwartz H. 60 Schwartz J. 88 Schwarz H. 32 Schwarz W. 265 Schweizer E. J. 79 Schweizer W. B. 229 Schwemlein H. P. 99 Scoble J. A. 181 Scola P. M. 46 298 Scott D. M. 81 Scott L. T. 186 Scott W. J. 112 Screttas C. G. 261 Scuseria G. E. 35 Sears L. J. 23 Secci D. 210 Seconi G. 99 Secor H.V. 171 Secundo F. 318 Seddon K. R. 261 Sedqui A. 206 Seebach D. 127 Seeman J. L. 171 Segal G. A. 186 Segi M. 282 283 Sehgal R. J. 188 Seidel B. 299 Seidel G. 271 Seifert W. E. jun. 25 Sekiguchi A. 261 274 Seko T. 240 Self M. F. 266 Seliger H. H. 271 SellCn M. 246 Sengupta S. 303 Seoane G.285 319 Seoane P. 248 295 Seppelt K. 280 Sestrick M. R. 238 Sethson I. 186 Seto T. 318 Sewell R. C. 295 Shabanowitz J. 25 29 30 Shah V. P. 177 Shaik S. S. 37 42 62 72 Shama S. A. 173 Sharkey A. G. 26 Sharma G. V. M. 100 Sharma K. 233 Sharma N. D. 319 Sharma R. B. 227 Sharma S. D. 193 Sharpless K. B. 89,90,91 106 189 190 229 298 300 303 Shavitt I. 35 Shaw T. J. 219 Sheehan D. 244 Sheffels P. 244 Sheldrick G. M. 267 Shen Y. 88 279 Sheng Z.-C. 226 Shepherd B. D. 273 Sheppard A. C. 190 302 344 Sheppeck J. E. jun. 248 Sherburn M. S. 83 Sherrod M. J. 43 Sheu J.-H. 256 Shevchenko S. G. 272 Shevlin P. B. 40 Shi L. 87 117 279 Shi L.-L.294 Shi X.,178 Shi Z. 41 Shibasaki M. 192,193,233,238 Shibata I. 116 Shibata T. 91 106 300 Shida N. 158 Shigematu K. 79 169 Shih M.-C. 25 Shih Y. 141 Shimada I. 14 Shimada K. 281 Shimao I. 185 Shimizu I. 113 125 298 Shimizu M. 149 Shimizu S. 48 Shimoda M. 274 Shimoji Y. 204 Shin J. H. 230 Shin S.-H. 263 Shine H. J. 66 Shiner C. S. 263 Shing T. K. M. 158 164 295 296 Shipman M. 149 242 Shipton M. R. 251 Shi-Qi P. 113 Shirahata A. 269 Shirai R. 159 Shiro M. 197 Shish Y.-N. 169 Shishodo K. 165 Shoemaker H. E. 312 Shokat K. M. 322 Shono T. 92 177 Short R. L. 267 Short R. P. 200 315 Shoup T. M. 103 Shudo K. 178 Shulman M. J.248 Shushan B. I. 21 22 Siahaan T. J. 235 289 Siegel C. 48 122 Siegel J. S. 171 Siegel M. G. 82 Siegel M. M. 27 176 Sierra M. A. 146 258 Sierra M. L. 267 Sigel G. A. 265 Sih C. J. 307 Silly L. 26 Silverberg L. J. 241 Simmons D. P. 180 Simon E. S. 315 317 319 Simon H. 124 Simonyan S. O. 242 Simpson R. E. 83 145 Sin D. W. M. 219 Singaram B. 88 112 118 Singh H. B. 283 Singh M. 188 Singh V. K. 229 Sini G. 37 42 Sinou D. 109 110 247 Siriwardane U. 279 Sironi M. 36 183 Sita L. R. 277 Siu K. W. M. 22 Sivakumar R. 302 Sivapalan M. 186 Skancke P. N. 40 54 Skelton B. W. 219 262 Skoda-Foldes R. 232 Skokotas G. 79 Skrabal P. 69 Slack G. A. 265 Sladky F.283 Slater M. J. 242 Slawin A. M. Z. 48 122 296 Slough G. A. 234 Slusarchyk W. A. 146 Smart C. J. 296 Smeets W. J. J. 264 Smiley P. M. 180 252 Smit W. A. 242 Smith A. B. 111 84 Smith B. J. 68 Smith D. B. 165 Smith D. C. C. 185 Smith G. D. 179 Smith G. M. 46 Smith H.D. 215 256 Smith J. D. 264 Smith K. 117 176 Smith K. M. 18 240 Smith M. B. 206 Smith P. J. 63 Smith R. A. G. 18 Smith R. A. J. 234 235 288 Smith R. D. 28 30 Smith S. 0..312 Snider B. B. 75 Snieckus V. 180 181 240 Snow K. M. 240 Snyder J. K. 48 161 Snyder J. P. 54 79 287 Soai K.,122 290 Sockwell S. C. 265 Sodeoka M. 238 Sodupe M. 38,46 Soderberg B. C. 246 Soejima T. 92 Sollenbohmer F.269 Soerensen 0. W. 12 13 Soga T. 119 Sohar P. 194 Solladie G. 310 Somayajula K. V. 26 Somei M. 202 Somers P. K. 218 299 Sonada S. 166 Author Index Song B. D. 58 61 Song I. C. 9 Sonoda N. 132,282,283 Sonoda T. 113 Sooriyakumaran R. 270 Sopher D. W. 177 Slbrensen P. E. 68 Sorensen T. S. 37 Sosa C. 41 Soto J. 230 Soundararajan R. 64 Spaltenstein A. 317 Spanevello R. A. 241 Sparks S. W. 12 13 Spek A. L.,262 264 Speranza M. 62 Spezia S. 313 Spiegel E. F. 268 Spiers K. J. 59 67 Spilling C. D. 133 Spirikhin L. V. 94 239 Sponsler M.B. 231 Sporn M.B. 14 Springer D. M. 169 Springer J. P. 298 Squadrito G. L. 176 Squicciarini M. P. 53 Squires R.R. 64 Sridar V. 82 Sridharan V. 50 153 Srinivasan A. 130 Srinivasan P. C. 55 Staab E. 110 Stadweiser J. 161 Stahl I. 113 Stahl W.,51 Staley D. L. 229 280 Stammer C. H. 200 Stan H.-J. 23 Stariczyk W. A. 271 Standing K. G. 21 Stang P. J. 64 99 239 269 Stankovich M. T. 141 Stanton J. F. 35 Stavber S. 87 Steams R. A. 85 Steckler R. 35 Stedman G. 70 Steele B. R. 261 Steenken S. 60 Stefan K.-P. 201 Stefani M. 17 18 Stefani V. 183 Stefanidis D. 67 Steffey B. D. 179 Steigelmann O. 278 Stein S. E. 184 Steinke T. 49 Steiou K. 212 Stejskal E. O. 18 Stella L. 161 Stemmler E. A. 23 Stephenson G. R. 250 Stem A. J. 183 Author Index Sternfield F.320 Stevens J. A. 66 182 Stevenson P. 153 Stewart J. J. P. 33 Still W. C. 229 Stille J. K. 155 240 Stobart S. R. 251 Stoddart J. F. 221 287 Stolarski V. 258 Stoll T. 125 Stone C. 244 Stone K. J. 52 Stoner E. J. 197 Stoodley R. J. 48 296 Storch D. M. 42 69 Store C. 150 Stork G. 88 203 305 Stoutland P. O. 231 Strachan A. N. 65 Straub J. A. 317 Strauss E. J. 5 Streitwieser A. 36 37 Strunk S. 111 Stryker J. M. 303 Sturkovich R. 189 268 305 Stunner R. 118 Stutz A. E. 286 Su Y. 258 Suarez E. 82 Subba Rao G. S. R. 174 Subramanian G. 55 Subramanian R. 132 Suchismita 302 Suenaga H. 177 Suenram R. D. 51 Suss-Fink G. 230 Suffert J. 261 Suga S.282 283 290 Sugai T. 319 Sugasawara R. J. 322 Sugihara T. 99 298 Sugimori J. 296 Sugimon T. 162 Sugimoto A. 135 Sugimura T. 144 Sugiyama H. 79 Sugiyama M.,318 Sugiyama S. 55 Sukata K. 271 Sukirthalingam S. 153 Sulmon P. 144 Sumi K. 193 Sumpter C. A. 186 Sun R.-C. 144 Sundqvist B. U. R. 21 22 Sunner J. 22 24 Surendrakumar S. 51 Surzur J.-M. 75 Suslick K. S. 305 306 Sustmann R. 47 Sutherland J. K. 163 Sutherland R. G. 251 Sutowardoyo K. 110 Sutton K. H. 230 Suzaki N. 145 Suzuki A. 125 241 Suzuki H. 182 280 284 290 Suzuki M. 107 161 291 305 Svendsen J. S. 90 229 300 Svensson P. 42 Svensson S. 318 Swaminathan S. 55 Swanson D. R. 97 152 242 243 Swanson F.J. 202 Swanson S. 250 Swartzendruber J. K. 92 Sweat M. P. 155 Sweatman B. C. 4 Swenton J. S. 183 Switzer F. L. 200 Sworin M. 168 Sydnes L. K. 155 238 Sygula A. 186 Syldatk C. 311 Syper L.,200 Szantay C. 49 Taber D. F. 97 152 Tabet J.-C. 31 Tabuchi K. 203 Tacconi G. 48 Tachinami T. 303 Tacke R. 3 11 Taddei M. 99 Taffer I. M. 302 Taft R. W. 57 72 Tagata H. 184 Tagliavini E. 291 Taheri S. A. N. 225 Tahir T. A. 282 Tai A. 144 Tai J. C. 34 Taillefer M. 233 Tait B. D. 40 48 298 Takacs J. M. 244 Takagi K. 181 Takagi M. 247 321 Takagi Y. 133 315 Takahara J. P. 121 Takahashi H. 142,230,290,303 Takahashi O. 321 Takahashi T. 243 Takahashi T.A. 152 Takai K. 123 Takano S.,99,158,227,298,310 Takaoda S. 164 Takata Y. 283 Takaya H. 303 Takayama H. 93 Takeda H. 230 303 Takei H.,166 Takenoshita H. 119 Takeshita H. 55 177 288 Takeshita M. 187 Takeuchi H. 208 Takeuchi. R.. 233 Takeuchi; T.,’ 229 Takeuchi Y. 274 Takeyama Y. 101 Takezaki Y. 187 Taki T. 54 Takikawa Y. 281 Takusagawa F. 214 254 Talamas F. X.,286 Tamao K. 101 197 244 Tamino K. 137 Tamm C. 126 Tamura A. 11 Tamura Y. 96 Tanabe K. 39 308 Tanabe Y. 127 Tanaka A. 123 Tanaka K. 20 182 290 Tanaka M. 126 155 194 Tanaka S. 288 294 Tanaka T. 177 199 Tang P. C. 165 Tang Y. 164 296 Tang Y.-S. 68 Tanguchi Y. 247 Tanigawa Y.247 Taniguchi M. 286 Tanner D. 246 Tao W. 241 Tapia O. 42 Tappin M. J. 14 Tarasov V. A, 242 Tardiff S. 181 Tasaka A. 113 Taschner M. J. 302 Tashev D. T. 71 Tashiro M. 187 Tashner M.J. 296 Tato J. V. 70 Tatsumi K. 245 Tatsuta K. 108 Taura Y. 155 Tayano T. 125 Taylor E. C. 209 237 Taylor J. M. 66 177 Taylor J. W. 24 Taylor L. C. E. 29 Taylor N. J. 181 Taylor R. J. 115 255 Taylor S. C. 250 Tebben P. 132 Tecklenberg R. E. jun. 25 Tecle B. 6 Tee 0. S. 65 Tenaglia A. 87 Tendler S. J. B. 12 Teng M. 297 Tennant S. 198 Teresa J. de P. 51 Terlouw J. K. 30 Terranova E. 87 Tessier-Youngs C. A. 267 Tetler L. W. 24 Texier F. 281 Thanabal.V. 18 nangaraj K. 55 Author Index Thatcher G. R. J. 57 Thavonekham B. 236 Therisod M. 312 Thetford D. 304 Thewalt U. 262 Thianpatanagul S. 50 Thiebault A. 182 Thijs L. 229 298 Thoma G. 75 Thomas E. J. 292 Thomas M. T. 158 Thomas R. D. 263 Thomas S. E. 246 Thompson Q. E. 269 Thomsen I. 132 Thomson B. A. 22 Thorn D. L. 268 Thornton E. R. 48 122 Thorstad W. T. 186 Tidwell T. T. 64 Tietze L. F. 38 46 49 Tilley T. D. 263 Timbrell J. A. 7 8 Times-Marshall K. 180 251 Tino J. A. 146 286 Tiriliomis A, 256 Tius M. A. 158 Tobe Y. 148 Toda F. 182 303 Todd J. F. J. 28 Todo F. 116 Toke L. 131 Togni A. 131 Tokunaga Y. 165 Tolstikov G. A. 94 239 Tomas M. 297 tom Dieck H.202 Tomer K. B. 28 30 Tominaga Y. 117 Tomioka K. 287 Tomita K. 204 Tomoda S. 112 274 Tonachini G. 39 46 Toner J. 221 Toole A. J. 258 Toone E. J. 317 Top S. 314 Torchia D. A. 12 13 18 Tornaletti N. 48 Toromanova-Petrova P. 231 Torras J. 244 Torrey M. J. 176 Torssell J. B. G. 132 Toshima K. 79 108 Tost W. 49 TBth M. 229 Toullec J. 64 Toupet L. 252 253 Tour J. M. 122 152 243 Toy A. 256 257 Tramontano A. 322 Tran T. L. 173 Tran V. D. 56 Traylor T. G. 298 Treat-Clemons L. 18 Trielhou M. 241 Tripathy P. B. 106 Trivellas A. 157 158 Trogen L. 186 Troisi L. 112 271 299 Trombini C. 291 Trost B. M. 100 102 137 144 151 163 167 169 196 230 241 247 248 295 Trovarelli A. 104 Truhlar D.G. 35 42 Tsarbopoulos A. 26 Tschappal K. D. 188 Tsoungas P. G. 208 Tsuchihashi G. 311 Tsuda T. 101 Tsuge A. 187 Tsuji J. 298 Tsuji T. 186 Tsuji Y. 233 Tsujimoto A. 214 Tsukamoto M. 168 Tsukazaki M. 212 Tsumoda T. 263 Tsumuraya T. 274 275 276 Tsunetsugu J. 184 Tsuno Y. 61 Tsushima S. 92 Tsutsumi H. 282 Tsutsumi S. 310 Tsuzuki S. 39 Tucker S. C. 42 Tukaoka S. 48 Tulip K. 7 Tun M. M. 287 Turchi I. J. 49 Turnbull K. D. 137 Turner N. J. 316 Turner S. U. 145 Twiss P. 262 Tyler J. W. 5 Tyman J. H. P. 218 Tzschach A. 270 271 Uchida K. 128 Uchida M. 202 Uchida Y. 96 230 303 Uchimara T. 39 Uchino H. 120 Udseth H. R. 28 30 Ue M. 148 Ueda K. 286 Uemura M. 253 Uenishi J.286 Uff B. C. 208 216 Uggerud E. 60 Uhl W. 265 267 Uhlig W. 270 271 Uhlmann P. 127 Ukaji Y. 123 304 Ulman A. 182 Ulrich E. L. 18 Um I. H. 72 Uman-Ronchi A. 291 Umezawa J. 321 Underiner T. L. 234 Ung C. S. 303 Unheim K. 249 Unwalla R. J. 34 Uozumi Y. 233 Ura T. 124 Urankar E. 182 Urata H. 124 Urban M. 42 Urbano A. 48 161 296 Urogdi L. 128 Uruma T. 84 157 Ushio H. 290 Uskokovic M. R. 165 Usuki Y. 112 Utimoto K. 101 112 123 Uwano A. 281 Uy 0. M. 26 Uyehara T. 158 VHgberg J.-O. 247 Vaid R. K. 143 Valenti E. 38 van Almsick A. 3 11 van Breeman R.B. 25 Vanderesse R. 303 Van der Eycken J. 126 van der Plas H. C. 214 van der Schaaf P. A. 278 van der Steen F. H.192 van der Waals J. H. 171 Van de Ven F. J. M. 18 Vandewalle M. 126 VanDuyne G. D. 185,237,287 Van Eldick R. 46 71 Van Halbeek H. 200 van Hemert M. C. 171 van Koten G. 192 van Maarseveen J. H. 220 van Mier G. P. M. 262 Vanucci C. 49 Varea T. 178 Vasapollo G. 125 128 Vasquez P. C. 299 Vaultier M. 162 Vautier M. 143 Veale C. A. 222 286 Veciana J. 207 Vedejs E. 133 203 293 298 Vederas J. D. 304 Veith M. 276 Velarde E. 216 Velde D. V. 294 Vel’der Y. L. 94 239 Veltwisch D. 74 Venkatramanan M. K. 49 Venturello C. 105 Verboom W. 312 Verfiirth U. 202 Versluis L. 231 Viallefont P. 180 Victoriano L. 268 Author Index Vidal A. 320 Vierfond J. M. 200 Vilar E. E. 132 Villaverde M.C. 184 Vinod T. K. 187 Virgil S. 91 106 300 Virtanen S. 9 Visigalli M. 48 Viski P. 87 Vismara E. 74 177 Vitkoskii V. Yu. 272 Vlitos M. 318 Vogtle F. 187 221 Vogel E. 224 Vogel P. 219 Volatron F. 37 Volk K. J. 27 Volpe A. F. jun. 231 von Koten G. 278 von Schnering H. G. 119 Vo-Quang L. 131 Vo-Quang Y. 131 Vomdam P. E. 263 Voronkov M. G. 272 Vos M. 262 Voss E. 49 Voss M. E. 168 Vuister G. W. 13 Vuorinen E. 222 Vyas D. M. 287 304 Vyazankin N. S. 272 Wade K. E. 7 Wadgaonkar P. P. 103 Wadman S. 95 234 236 Waegell B. 87 Wagner A. 11 1 304 Wagner F. 311 Wagner G. 14 Wagner O. 195 Wagner R. W. 226 Wai J. S. M. 90 91 106 229 Waigh R. D. 211 Wakabayashi H. 185 Wakabayashi R.C. 308 Wakasa M. 276 Wakefield B. J. 148 Waki H. 20 Walborsky H. M. 264 Wald W. 277 Waldmann H. 296 315 Waldner A. 162 Waldraff R. 47 Walker B. J. 294 Walker K. R. 220 Walker V. 9 Walkington A. J. 77 Wallbridge M. G. H. 267 Wallingford R. A. 27 28 Walsh E. J. 256 Walton R. A. 24 Walzer J. F. 270 Wamser C. C. 173 Wan P. 183 Wand A. J. 11 Wandrey C. 315 Wang D. 104 269 292 Wang K. T. 309 Wang L.-C. 36 Wang M.-D. 196 Wang S. 183 Wang T.-C. L. 25 Wang W. 87 117 279 294 Wang W.-H. 68 Wang X.,299 Wang Y.,39 87 117 279 294 Wang Y.-F. 3 11 Wang Z. 229 Wang Z.-H. 281 Wannamaker M. W. 201 Ward D. E. 116 Warner P. M. 89 Warnock W. J. 51 Wassermann W. 268 Watanabe H.281 Watanabe M. 212 290 Watanabe T. 135 187 222 Watanabe Y. 233 Watson B. T. 201 Watson D. G. 23 Watson K. G. 127 Watson S. P. 191 Watson W. H. 184 Wawrzehczyk C. 229 Webb K. S. 271 Weber E. 221 Weber E. J. 291 Weber M. 180 Weber P. L. 11 Webster M. 282 Weetman J. 48 Wege D. 198 Wei Z. Y. 292 Weiber G. M. 246 Weidenbruch M. 273 274 Weidenbriick G. 277 Weidert P. J. 109 Weidlein J. 265 267 Weidner-Wells M. A. 219 Weigl D. 13 Weil D. A. 24 Weiller B. H. 231 Weinreb S. M. 46 298 Weinstein H. 41 Weismiller M. C. 302 Weiss E. 263 Weiss H. 263 Weiss W. 264 Weissbart D. 113 Weitz M.-P. 111 Welsh K. M. 276 Welstead W. J. 220 Wen X.-Q. 294 Wendebom S. 79 Wender P. A. 162 169 Wenger E.180 wentland M. P. 193 Wenz G. 285 Wenzel T. T. 246 Werner J. 227 West R. 273 276 Westaway K. C. 61 Westmoreland D. L. 280 Westwood D. 122 Wettling T. 195 White A. H. 191 219 262 265 White J. B. 286 White K. S. 55 135 Whitehouse C. M. 21 Whitesell J. K. 56 Whitesides G. M. 265,308,3 15 316 317 319 Whiting D. A. 77 211 Whitworth S. M. 37 Wiberg K. B. 36 52 Wiberg N. 272 Widdowson D. A. 76 112 Wiechert R. 179 Wienorek M. 48 Wierschke S. G. 41 Wilcox C. F. 185 Wild H. 203 Wild S. G. 279 Wiley M. R. 221 Wilhelm R. S. 169 Wilkening D. W. 130 Wilkins C. L. 26 27 Wilkinson D. L. 273 Will B. 110 Willard P. G. 262 Willcom P. P. 169 Williams A. 69 Williams A. C. 244 Williams D.J. 48 122 296 Williams D. L. H. 64,68,70,71 Williams H. W. R.,181 Williams J. M. 281 Williams P. 319 Williams R. J. P. 17 18 Williams R. V. 161 Williard P. G. 153 Willis C. R. 73 Willnecker J. 277 Wills M. 233 234 Willson T. M. 120 291 Wilson R. M. 52 Wilson I. D. 4 5 Wilson S. R. 104 Wilson T. 120 Wilson T. M. 291 Wimalasena K. 321 Winchester W. R. 262 Winger B. E. 25 Wingert H. 99 Wingfield P. T. 12 13 Winkler J. D. 82 148 Winkler M. E. 14 Winkler T. 81 Winston S. 29 Winterfeldt E. 113 Wintgens V. 52 Wirtz J. 47 Win J. 68 98 Wisnieff T. J. 256 Wiszt A. 295 Witulski B. 52 Wocadlo S. 263 Wolber G. J. 37 46 Wong,C.-H. 307,311,316,321 Wong G. S. K. 49 237 Wong H.N. C. 184 Wong S. F. 21 Wood A. 291 Woodgate P. D. 252 Woodnutt G. 5 Woods M. D. 24 Worakun T. 153 Wormald M. R. 17 Wovkalich P. M. 165 Wrabletz F. 113 Wrackmeyer B. 271 278 279 Wright J. L. C. 31 Wright M. E. 255 Wright P. E. 11 Wright S. C. 36 Wright S. H. B. 237 Wrona M. Z. 203 WU A.-H. 87 Wu C. 151 WU C.-P. 185 Wu J. 234 Wu R.,122 Wu S. 130 285 WU S.-W. 178 Wu S. H. 309 WU Y.-J. 137 305 WU Z.-P. 68 323 Wudl F. 283 Wuthrich K. 11 17 Wulff W. D. 153,256,257,258 Wunde C. 125 Wutz K. 125 Wythes M. J. 291 Xiang Y. B. 162 Xie Y. 37 Xiong H. 96 265 Xiong Y. 181 Xu S. L. 174 Xu X. 183 XU Y.-C. 153 257 Yadav J. S. 229 Yadav V. 155 Yagi M. 116 303 Yagupol’skii L.M. 177 Yaksh T. L. 28 Yamabe S. 281 Yamada H. 311 Yamada J. 131 Yamada K. 84 125 157 Yamada N. 318 Yamada T. 92 103 133 162 Yamago S. 52 185 Yamaguchi Y. 92 Yamakawa K. 135 Yamamoto A, 247 248 Yamamoto 48 113 123 164 245 $6 Yamamoto I. 294 Yamamoto K. 122 247 308 Yamamoto M. 84 125 Yamamota N. 122 230 Yamamotcp T. 121 Yamamow Y. 126 128 131 158 240 280 292 308 Yamamura K. 105 Yamanaka H. 79 Yamanaka T. 270 Yamashina N. 241 Yamashita A. 256 257 Yamashita D. S. 197 Yamashita H. 261 318 Yamashita K. 308 Yamashita O. 276 Yamato T. 187 Yamauchi M. 135 Yamazaki H. 298 Yamazaki K. 185 Yamazaki S. 109 281 Yamazaki T. 121 Yamazaki Y. 109 314 Yan L. Q. 34 Yanagi K. 247 Yanagida S.208 Yanagisawa A. 123 Yanaka N. 3 11 Yang B. 88 248 279 295 Yang P.-F. 239 Yang P.-W. 185 Yang Q. Y. 173 Yang S.-H. 47 56 Yarwood J. 182 . Yasuda H. 245 Yasunami M. 185 Yates J. R.,111 25 29 Yazawa N. 182 Yefsah R. 257 Yeh M. C. P. 234 258 Yen C.-F. 256 Yeske P. E. 93 Yeung B.-W. A. 165 Yi M. Y. 33 Yoh S.-D. 61 Yokoyama Y. 202 Yonaga M. 286 Yoneda I. 276 Yoon J. 254 Yoon K. B. 111 Yoshida K. 184 Yoshida T. 20 116 Yoshida Y. 20 182 Yoshikawa M. 144 Yoshikawa S. 230 303 Yoshikoshi A. 201 Yoshioka H. 149 Yoshioka M. 194 290 Author Index Yost R. A. 24 27 Young A. B. 32 Young C. E. 185 Young D. W. 307 Young G. B. 231 Young M. G. 146 Young P. E. 12 Young R.J. 188 Young W. B. 215 256 Youngs W. J. 267 Yuan G. 88 279 Yuan K. 112 Yuen P.-W. 91 106 300 Yugari H. 124 Yuh Y. H. 34 Yukawa Y. 61 Yus M. 129 299 Zablocka M. 48 Zabia A. 229 Zahler R.,146 Zakutansky J. 258 Zaluzec E. J. 256 Zani P. 269 Zapata A. 92 Zappa G. 109 Zarate E. A. 267 Zare R. N. 28 Zaretskii Z. V. I. 31 Zarges W. 262 263 Zein N. 79 Zeitz H. G. 81 Zhang C. H. 251 Zhang G. 279 Zhang Y. 140 Zhao K. 88 305 Zhao L. 143 Zhao S.-K. 153 258 Zhi L. 50 Zhou Q.-L. 179 Zhou Z. 36 171 Zhu H. 279 Zhu J. 244 Zhu N.-Z. 25 30 Zhu X.-Y. 246 Zichi D. A. 42 Zief M. 285 Ziegler F. E. 54 Ziegler T. 231 311 Zimmer R.,277 Zimmermann G. 178 Zipkin R. E. 302 Zoebisch E.G. 33 Zollinger H. 69 Zubieta J. A. 278 Zuccarello G. 79 Zucchelli L. 318 Zuiderweg E. R. P. 13 17 Zifiiga A. E. 276 Zupan M. 87 Zwanenburg B. 229 298 Zwecker J. 271 Zybill C. 273

ISSN:0069-3030    

DOI:10.1039/OC9898600325

出版商:RSC    

年代:1989

数据来源: RSC