摘要:

14 Aliphatic Compounds By N. POLGAR The D yson Perrins Laboratory Oxford THEfollowing topics will be discussed :(1)alkenes ;and (2) fatty acids and related compounds. 1 Alkenes Natural Hydrocarbons.-The hydrocarbon composition of marine algae (phyto plankton benthic algae) has been the subject of detailed studies with a view to obtaining information for tracing pollutants in the marine environment and also for studies of marine processes.'Y2 In the course of these studies several new C, ,C, and C polyunsaturated hydrocarbons have been found and investigated. The polyolefin predominating in many species is a n-C hexaene formulated mainly as a result of ozonolysis and mass-spectrometric studies as all-cis-3,6,9,12,15,18-heneicosahexaene It has been stated3 that in the (l).394 i.r.spectrum of this polyolefin bands attributable to terminal unsaturation are lacking. Two C polyolefins with terminal unsaturation have been isolated5 from the marine brown alga Fucus vesiculosus. These polyolefins have been shown to have the structures (2) and (3) respectively (both all-cis). The evidence for the structure (2) assigned to the hexaene in particular of the position of the .[CH2I3. grouping includes partial hydrogenation (involving the terminal double bond) followed by ozonolysis of the product; the structure (3) for the pentaene has been confirmed by its partial ~ynthesis.~ Me[CH ,CH=CH],CH ,Me Me[CH,CH=CH],.[CH,],.CH=CH (1) (2) Me[ C H ,] 3-[ C H ,.C H =CHI,.[ CH,] ,-CH =C H (3) M. Blumer R.R. L. Guillard and T. Chase Marine Biology 1971 8 183. W. W. Youngblood M. Blumer R. R. L. Guillard and F. Fiore Marine Biology 1971 8 190. M. Blumer M. M. Mullin and R. R. L. Guillard Marine Biology 1970 6 226. R. F. Lee J. C. Nevenzel G.-A. Paffenhofer A. A. Benson S. Patton and F. E. Kavanagh Biochim. Biophys. Acta 1970 202 386. T. G. Halsall and I. R. Hills Chem. Comm. 1971 448. 449 450 N. Polgar Further reports have appeared on the methyl-branched long-chain mono- unsaturated olefins (C22-C30) isolated from various members of the bacterial family Micrococcaceae. These olefins have methyl branches in iso- or anteiso- positions at one or both ends of a long alkyl chain and contain a cis-double b~nd.~.~ The various hydrocarbon fractions include mixtures of isomers.Evidence has been presented for the exact position of the double bond in each hydrocarbon isomer isolated from two members of the above bacterial family (Sarcina lutea and S.Jlaua) ;the double bond in all isomers is in or near the centre of the molecule.8 The biogenesis of these olefins has been shown to involve head-to-head condensation of two molecules of fatty acids with decarboxylation of one of them6 according to the scheme R'CH,.C02H + R2C02H -+ R'CH=CHR2-The double bond is localized between the carbon atoms derived from C-1 and C-2 of the fatty acid which is not decarboxylated upon incorporation into the olefin; the full details of the intermediates involved in this biosynthetic pathway have not yet been established.' Synthesis.-Stereoselective and stereospecific olefin syntheses have been re-viewed.'' A new general procedure' for stereospecific olefin synthesis involves the conjugate addition of cis-or trans-1-alkenyl-cuprolithiumcomplexes to as-unsaturated carbonyl compounds.It is found that this addition occurs with retention of the double-bond geometry thus affording isomerically pure cis- or trans-yb-ethylenic carbonyl compounds. cis-and trans-1-Alkenylcuprates also react stereospecifically with alkyl halides to give cis-or trans-2-olefins. The previously reported' use of a 1,5-sigmatropic rearrangement for a stereo- specific synthesis of cis-5-methylhept-4-en-l-al has now been extended to the synthesis of its lower homologue cis-4-methylhex-3-en-l-al (6);' the key step is the rearrangement of the trimethylsilyl ether (4)to the enol ether (5).OSiMe PH20SiMe3 "r r""9Y (4) (5) (6) P. W. Albro and J. C. Dittmer Lipids 1970 5 320.' T. G. Tornabene S. J. Morrison and W. E. Kloos Lipids 1970 5 929. T. G.Tornabene and S. P. Markey Lipids 1971 6 190. P. W. Albro T. D. Meehan and J. C. Dittmer Biochemistry 1970 9 1893. lo J. Reucroft and P. G. Sammes Quart. Rev. 1971 25 135. F. Naif and P. Degen Helv. Chirn. Acta 1971 54 1939. E. J. Corey H. Yamamoto D. K. Herron and K. Achiwa J. Amer. Chem. SOC.,1970 92 6635. l3 E. J. Corey and D. K. Herron Tetrahedron Letters 1971 1641. Aliphatic Compounds 45 1 A general 1,5-diene synthesi~'~ which involves overall coupling of allyl alcohols with preservation of the position and geometry of the olefinic bonds is based upon the following sequence of reactions :(i) conversion of the allyl alcohols into allyl bromides by the action of carbon tetrabromide and triphenylphosphine (ii) quaternization of tributylphosphine with one of the allyl bromides (iii) C-alkylation of the derived ylide with the other bromide and (iv) reductive cleavage of the new phosphonium salt by means of lithium and ethylamine.Another procedure,' for the synthesis of squalene and analogues depends upon using an allylic carbanion stabilized by sulphur. The allylic oxidation of gern-dimethyl olefins by selenium dioxide has been shown' to proceed stereospecifically to give tvans-alcohols or -aldehydes. A method is thus provided for the stereospecific synthesis of functionalized tri- substituted olefins.A stereospecific method for the synthesis of phosphorus betaines applicable to the inversion of the stereochemistry of olefins has been described.' ' The method depends upon the opening of epoxides by means of lithium diphenyl- phosphide in tetrahydrofuran. Quaternization of the crude product with methyl iodide leads directly to betaines which fragment under the conditions of the quaternization ; the resulting olefins are obtained with inversion of the stereo- chemistry relative to the starting epoxide. (+)-cis-Achillene (8) and (-)-truns-achillenol (9) recently isolated from the essential oil of AchilleaJilipendulina have been synthesized,' * together with their stereoisomers starting from (S)-(+)-2,6-trans-dimethylocta-l,3,7-triene (7).2 Fatty Acids and Related Compounds Isolation and Structure of Natural Compounds.-The major occurrence of unsaturated fatty acids with the unusual position of the double bond between C-5 and C-6 has been reported" for several species of the bacterial genus Bacillus. Two highly unsaturated acids have been found to be present among the fatty acids from aje the body fat of the Mexican and Central American scale insect E. H. Axelrod G. M. Milne and E. E. van Tamelen J. Amer. Chem. Soc. 1970 92 2139. ' J. F. Biellmann and J. B. Ducep Terrahedron 1971 27 5861. l6 U. T. Bhalerao and H. Rapoport J. Amer. Chem. SOC., 1971,93,4835. '' E. Vedejs and P. L. Fuchs J. Amer.Chem. Soc. 1971,93,4070. Is K. H. Schulte-Elte and M. Gadola Helv. Chim. Acta 1971 54 1095. l9 T. Kaneda Biochem. Biophys. Res. Comm. 1971 43 298. 452 N. Polgar Llaueia axin.20 The available evidence including U.V. spectra and mass spectro- metry of the deuteriated esters indicates that both acids are conjugated pen- taenoic acids having the structures (10)and (1 l) respectively. An interesting discovery is that of the (-)-form of 3-hydroxydecanoic acid (12) named myrmicacin in the leaf-cutting ant (Atta sexdens);2’the acid has been isolated together with its lower homologues from the metathoracic gland of the ant. It appears that myrmicacin is used by these ants as a herbicide thus preventing undesirable spores from sprouting. Me[CH,],CH(OH)CH,CO,H (12) An unsaturated trihydroxy-acid suggested to be 5,8,12-trihydroxy-trans-9-octadecenoic acid (13) having an allylic hydroxy-group has been isolated from wheat bran.22 Me[CH ,] ,CH(OH)CH ,CH ACHCH( OH).[C H,] ,CH(OH).[C H ,] ,CO ,H (13) The isolation of a 12-membered-ring lactone 1 1-hydroxy-trans-8-dodecenoic acid lactone (14) from a fungus has also been described;23 the fungus appears to belong to the group Cephalosporium recqei.A series of new butenolide derivatives isolated from Umbelliferae have been shown24 to have the structures (15) (16) (17) and (18) respectively. All these butenolides differ from each other only by the extent of unsaturation of their J. Cason R. Davis and M. H. Sheehan J. Org. Chem. 1971 36 2621. ” H.Schildknecht and K. Koob Angew. Chem. Internat. Edn. 1971 10 124. ” P. W. Albro and L. Tishbein Phytochemistry 1971 10 631. 23 R. F. Vesonder F. H. Stodola L. J. Wickerham J. J. Ellis and W. K. Rohwedder Canad. J. Chem. 1971 49 2029. 24 F. Bohlmann and M. Grenz Tetrahedron Letters 1971 3623. Aliphatic Compounds side-chains and it is suggested24 that they may arise from the corresponding unsaturated c,8 fatty acids. (15) R = [CH=CH],.[CH,],Me (16) R = CH=CH-CH,CH=CH-[CH,]4Me (17) R = CH=CH.[CH,],Me (18) R = [CH=CH]3-CH,*CH2CH=CH A series of unusual fatty acids occurring as the principal components of the saponifiable lipids of Bacillus acidocaldarius a thermophilic bacterium have been found to have the structures 11-cyclohexylundecanoic and 13-cyclohexyltri-decanoic acids.25 There have been further report^'^,^^,^^ on the methyl-branched fatty acids from the preen-gland waxes of various birds ;a review on the chemistry of preen- gland waxes of waterfowl has also been p~blished.~’ The acid constituents of these waxes include series of polymethyl-substituted fatty acids with repeating -CH2CHMe-units having the structures (19)and (20)where n for the principal homologues in various cases has been shown to be 1 or 2.Most of the acids which have been studied were found to be laevorotatory having D-configuration in respect of all the asymmetric centres ; however acids with L-configuration in respect of C-2 also occur. Me[CH2],.[CHMeCH,],.CHMe.C02H (19) Me[CH,];[CHMeCH,],CHMeCO,H (20) The above acids are of particular interest in view of the fact that they represent lower homologues of the laevorotatory polymethyl-substituted acids from Mycobacterium tuberculosis var.hominis (named mycocerosic or mycoceranic acids). Another series of polymethyl-substituted fatty acids from these bacteria having the general structure (21) are dextrorotatory with L-configuration of the asymmetric centres. The literature concerning both series of acids has been recently re~iewed.~’ L L Me[CH ,];CHMe-CH ,CHMeCH=CMe.CO H (21) 25 M. de Rosa A. Gambacorta and L. Minale Chem. Comm. 1971 1334. 26 0.Bertelsen Arkiu Kemi 1970 32 17. ’’ J. Jacob and A. Glaser Z. Naturforsch. 1970 25b 1435. ’* J. Jacob and A.Zeman Z. Naturforsch. 1970,25b 1438. 29 G. Odham and E. Stenhagen Accounts Chem. Res. 1971,4 121. 30 N. Polgar ‘Topics in Lipid Chemistry,’ ed. F. D. Gunstone Logos Press London 197 1 vol. 2 p. 207. 454 N. Po[gar Another two series of dextrorotatory polymethyl-substituted fatty acids with repeating -CH2CHMe- units have now been found in a sulpholipid isolated from M. tubercul~sis.~The structures of these acids represented by the general formulae (22) and (23) have been established mainly by mass-spectrometric studies; the latter also showed homology by 42 mass units (-CH2CHMe-) for both series. A main representative of the acids (22)appears to be the penta- methyl-substituted C,,-acid (22; rn = 4). The principal hydroxy-acid (23) has been shown to be the octamethyl-substituted C,,-acid (23;rn = 7).The hydroxy- group in these acids is always adjacent to the methyl branch which is farthest away from the carboxy-group. The dextrorotation of both series indicates that they are related to the above dextrorotatory L-acids (21). Me[CH,],,~[CHMeCH,],CHMeCO,H (22) Me[CH,] ,,CH(OH).[CHMeCH,],,,HMe.CO,H (23) It has been proposed31 to name the acids (22) and (23) ‘phthioceranic acids’ and ‘hydroxyphthioceranic acids’ respectively. These names however appear confusing since phthiocerane is the hydrocarbon derived from phthio~erol,~ subsequently shown33 to be a mixture of 4-methyltetratriacontane and 4-methyl- do triacon tane. Further studies of the mycolic acids (a-branched long-chain p-hydroxy-acids) have been reported including those from Nocardia (nocardic acids).Investiga- tions of five strains of the latter organisms resulted in the isolation of a variety of acids including tetraenoic nocardic acids in the range c6246 .34 Further progress has also been made in the structural studies of the glycolipids derived from mycolic acids which are major constituents of the ‘wax D’ fractions of mycobacterial lipids. 35 In some cases differences between the lipid contents of mycobacteria grown in vivo and in vitro have been reported. It is therefore of interest that the presence of mycolic acids as well as of phthiocerol dimycocerosate has now been de- monstrated in bacteria obtained from tuberculous tiss~e.~~.~~ Naturally occurring lactones reported include those isolated from the wood of several Quercus species and shown3’ to be diastereoisomeric y-lactones derived from 3-methyl-4-hydroxycaprylic acid (24); their configurations have been deduced from n.m.r.studies. 31 M. B. Goren 0. Brokl B. C. Das and E. Lederer Biochemistry 1971 10 72. 32 L. G. Ginger and R. J. Anderson J. Biol. Chem. 1945 157 213. 33 R. Ryhage S. Stallberg-Stenhagen and E. Stenhagen Arkiv Kemi 1959 14 259. 34 M. T. Maurice M. J. Vacheron and G. Michel Chem. Phys. Lipids 1971 7,9. 35 J. Markovits E. Vilkas and E. Lederer European J. Biochem. 1971 18 287. 36 E. Kondo K. Kanai K. Nishimura and T. Tsumita Japan J. Med. Sci. Biol. 1970 23 315. 3’ K. Kanai E. Wiegeshaus and D. W. Smith Japan. J. Med. Sci.Biol.1970 23 327. 38 M. Masuda and K. Nishimura Phytochemistry 1971 10 1401. Aliphatic Compounds 455 Me[CH,],-CH(OH)CHMe.CH,.CO,H (24) An antibiotic carboxylic acid produced by a fungus believed to be Cephalo-sporium,has been assigned the structure (25) ;39 a notable feature of this structure is the presence of a p-lactone function apparently not reported previously for compounds isolated from a fungus. H OC H ,CH -CH.[ CH ,],-CH Me-CH ,.C Me =C H CMe =CHCO H II OC-0 (25) Synthesis.-Normal-chain Acids. Details of a synthesis4' of crepenynic acid (octadec-9-en-12-ynoic acid) (28) from non-3-yn-1-yl-triphenylphosphonium bromide (26) and the aldehyde-ester (27) have been published.41 +-Me[ CH ,],.C- CCH,CH,PPh,Br +0HC.[CH 2] 7.C02 Me (24) (27) I Me[CH ,],.C= CCH ,CH &CH.[ CH 2] ,.CO ,H (28) Various di- and poly-enoic acids have been synthesized according to the general procedure42 involving condensation of propargyl bromides (29) with the di-Grignard derivatives of w-acetylenic acids (30) followed by partial reduc- tion of the resulting acetylenic acids (31).The compounds ~ynthesized~~ include methyl octadeca-5,8,1 l-trienoate eicosa-10,13-dienoate and eicosa-7,10,13-trienoate as well as labelled acids44 corresponding to these esters and several closely related labelled acids. Me[CH ,Iz.[C -CCH JxBr +HCr CCH ,-[CH ,],,,-C02 H (30) (29) I Me[CH,],~[C~C-CH,], + I.[CH2],,,.C02H (31) 39 D. C. Aldridge D. Giles and W. B. Turner Chem. Comm. 1970 639.40 R.W. Bradshaw A. C. Day Sir Ewart R.H. Jones C. B. Page and V. Thaller Chem. Comm. 1967 1055. 4' R.W. Bradshaw A. C. Day Sir Ewart R. H. Jones C. B. Page V. Thaller and (in part) R.A. Vere Hodge J. Chem. Soc. (0,1971 1156. 42 J. M. Osbond P. G. Philpott and J. C. Wickens J. Chem. Soc. 1961,2779. 43 H. W. Sprecher Biochim. Biophys. Acta 1971 231 122. 44 J. Budny and H. Sprecher Biochim. Biophys. Acta 1971 239 190. 456 N. Polgar a In a new pr0cedu1-e~~variety of substituted propargyl halides (32) and (n -4) (n -1)-alkadiynoic* acids (33) have been employed for the preparation of poly-ynoic acids with four five and six triple bonds; partial reduction of the triple bonds gave the corresponding polyenoic acids. Me[CH2],.[C-CC.CH2],- ,Hal +H[C~CCH,],.[CH2],C02H (32) (33) I The alkadiynoic acids (33) were obtained46 from (n -1)-alkyn-1-01s (34) which were elongated (via their tetrahydropyranyl derivatives) with propargyl tosylate to yield (n -4) (n -1)-alkadiyn-1-01s (35); the latter are readily purified by distillation.Oxidation of the diynols (35) gave the alkadiynoic acids (33). HC-C.[CHJ,+ 10H (34) The requisite propargyl halides (32) were prepared4’ by ether cleavage of substituted propargyl methyl ethers with acetyl bromide or acetyl iodide in the presence of the appropriate zinc halide. By using dichloromethane as solvent this ether cleavage could be carried out at room temperature. Under these conditions substituted propargyl bromides and iodides with up to four triple bonds (32 ;x = 5)could be prepared in good yields.In syntheses of polyenoic acids and esters with three to six all-cis skipped double bonds by hydrogenation of poly-ynoic acids in the presence of Lindlar’s catalyst the resulting products may contain small amounts of trans-unsaturated material. The optimum conditions of the cis-hydrogenation and the mechanism and kinetics involved have now been in~estigated.~~ The cis-hydrogenation proceeds with optimum results in light petroleum ethyl acetate or acetone at room temperature in the presence of small amounts of quinoline. It is shown that trans double bonds cannot be directly formed from triple bonds but result from isomerization of cis double bonds. A synthesis of octadeca-trans-2-cis-9-cis-12-trienoic acid (39),an attractant for the honey bee has been de~cribed.~’ The starting point was linoleic acid which was converted into the tetrabromo-acid (36).Further bromination in the 45 W.-H. Kunau H. Lehmann and R. Gross Z. physiof. Chem. 1971 352 542. 46 W.-H. Kunau Chem. Phys. Lipids,1971 7 101. 47 W.-H. Kunau Chem. Phys. Lipids,1971,7 108. 4n A. Steenhoek B. H. van Wijngaarden and H. J. J. Pabon Rec. Trav. chim. 1971,90,961. 49 A. W. Starratt and R. Boch Canad. J. Biochem. 1971 49 251. * The nomenclature recommended by the 1U PAC-IU B Commission on Biochemical Nomenclature (see e.g. Biochemistry 1967 6 3287) is used; n indicates the number of carbon atoms in the chain. Aliphatic Compounds 2-position followed by reduction to the pentabromo-octadecan-1-01 (37) and debromination of the latter with activated zinc dust gave the 2-bromo-9,12- dien-1-01 (38) which was oxidized to the corresponding acid; the methyl ester of the latter was then subjected to dehydrobromination with 1,5-diazabicyclo- [5,4,0]undec-5-ene.Some double-bond isomerization was found to have occurred during the above procedures. Me[CH,],~[CHBrCHBr-CHz]z-[CHz]6-C0,H (36) Me[CH,],.[CHBrCHBrCH,I,.[CH,I,.CHBrCH20H (37) Me[CH,],.[CH LCHCH ,] ,.[CH ,] ,.CHBrCH ,OH (38) Me[CH,],.[CH ~CHCH,],-[CH,],CH ICHC0,H (39) Anew synthesis5' of trans-2-dodecene-l,l2-dioicacid (traumatic acid) (44) stated to give a product free from contaminants involves conversion of methyl undec-10-enoate (40) by the action of N-bromosuccinimide in the presence of aqueous sulphuric acid into the bromo-ester (41) and thence via (42) into the dioic acid (43).The latter on heating in uucuo yields the acid (44). XCH2CH(OH).[CHJ,.CO,R H0,CCH kH.[CH ,] ,-Co H (41) X = Br R = Me (44) (42) X = CN R = Me (43) X = C02H R = H Another synthesis of interest is that of the trans,trans-dienoic hydroxy-acid (50) a by-product of prostaglandin biogenesis. The starting point for this synthesis5' was the chloronitrile (45). Reduction of this nitrile with lithium aluminium triethoxyhydride gave the chloroaldehyde (46) which on reaction with the Grignard derivative of 4-methoxybut-3-en-1-yne gave the methoxyenynol (47 ; X = Cl). This was reduced to the dienol (48 ;X = CI) and the latter con- verted via the nitrile (48 ;X = CN) into the aldehydo-acid (49).Reaction with pentylmagnesium bromide gave the acid (50) (Scheme 1). P. H. M. Schreurs P. P. Montijn and S. Hoff Rec. Truc. chim. 1971 90 1331. 51 E. Crundwell and A. L. Cripps Chem. and Ind. 1971 767. 458 N. Polgar MeOCH=CHCH =CH-CH(OH).[CH 2I6x (48) 1 1 Me[CH,],CH(OH)CH ACHCH ACH.[CH2]6.C02H (50) Scheme 1 In connection with studies on aleuritic acid regarded as the threo-isomer of 9,10,16-trihydroxyhexadecanoicacid (51) the synthetic52 threo-acid (51) has now been re~olved.~ The resolution achieved by fractional crystallization of the (-)-ephedrine salt gave the enantiomeric acids with [alD+ 24.6" and -24.45" respectively.The natural acid stated to show a very small rotation had been earlier suggested5 to consist probably of one enantiomorph or to contain an excess of the latter. H0[CH ,],-CH(OH).CH(O H).[CH 2]7C0 2 H (51) There is an increasing interest in nitrogen and sulphur analogues of epoxy-and hydroxy-acids. A recent review54 deals with syntheses and reactions of these compounds. Cycloulkane and Cycloulkene Acids. The extensive literature on the prosta- glandins includes a review55 of the preparations of the prostaglandins El F*, F2, and E,. s2 D. E. Ames T. G. Goodburn A. W. Jevans and J. F. McGhie J. Chem. SOC.(C) 1968 268. 53 J. F. McGhie W. A. Ross J. W. Spence and (in part) F. J. James Chem. and Ind. 1971 1074. s4 G. Maerker 'Topics in Lipid Chemistry,' ed.F. D. Gunstone Logos Press London 1971 vol. 2 p. 159. 5s E. J. Corey Ann. New Ynrk Acad. Sci. 1971 180 24. 56 E. J. Corey H. Shirahama H. Yamamoto S. Terashima A. Venkateswarlu and T. K. Schaaf J. Amer. Chem. SOC.,1971,93 1490. Aliphatic Compounds The first syntheses of the prostaglandins F, (56) and E (57) in optically active naturally occurring form have now also been rep~rted.’~ These prosta- glandins were obtained from the optically active hydroxy-lactone (52) readily available from intermediates described el~ewhere,’~ via the aldehyde (53). The aldehyde was converted stereospecifically into the alcohol (54) by means of the P-oxido-ylide reagent derived from the (S)-(+)-phosphonium salt (55);the latter was obtained by a sequence of reactions starting from the readily available natural (S)-(-)-malic acid.Conversion of the bistetrahydropyranyl derivative of the alcohol (54),by reaction with di-isobutylaluminium hydride into a lactol followed by reaction of the latter with the Wittig reagent derived from 5-tri- phenylphosphonovaleric acid in dimethyl sulphoxide produced stereospecifically the bistetrahydropyranyl derivative of prostaglandin F, which was hydrolysed to give the prostaglandin F, (56). On oxidation of the bistetrahydropyranyl derivative of prostaglandin F, followed by removal of the tetrahydropyranyl group the prostaglandin E (57)was obtained. THPO (53) X = CHO (54) x = -HO THP = tetrahydropyranyl E. J. Corey S. M. Albonico U. Koelliker T.K. Schaaf and R.K. Varma J. Amer. Chem. Soc. 1971,93 149I. 460 N. Polgar The first total syntheses of the prostaglandins F1, F,, El and E as their naturally occurring optically active forms were reported last year.58 Thus the natural forms of all the known primary prostaglandins have now been syn- thesized. In studying the effect of ring size on the biological properties of the prosta- glandins two biologically active cyclohexane analogues have been ~repared.~ These compounds were found to be less active than the natural prostaglandins. Malvalic acid (58) the principal cyclopropene acid occurring in cottonseed oil has been synthesized6' with 14C at various positions. ,T Me[CH2] 7C=C.[ CH2],CO H (58) Branched-chain Acids. A large number of papers continue to be published on the Cecropia juvenile hormones.Following the demonstration6' that these hormones show dextrorotation attention has been turned to syntheses of the enantiomeric forms of these compounds. A synthesis6 (Scheme 2) of both enan- tiomeric forms of the natural trangtrans,ch-C18 hormone as well as of the tranS,tranS,tranS-isomer was carried out according to a scheme earlier described6 for the preparation of racemic juvenile hormone. The chloroketal(59) prepared in both enantiomeric forms gave on reaction with the dienol ester (60) via a Claisen rearrangement the enantiomeric forms of the chloroketone (61). Each of these chloroketones was reduced with sodium borohydride to give two pairs of diastereoisomeric chlorohydrins (62);the latter were separated by thin-layer chromatography.On treatment of the resulting four chlorohydrins with methanolic potassium carbonate the corresponding epoxy-compounds (63) were obtained the juvenile hormone (one of the dextrorotatory isomers) showing [aJD+ 12.2". In the above synthesis the enantiomeric forms of the chloroketal (59) were prepared via the ( -)-a-(1-naphthy1)ethylamide derived from cr-chloro-cc-methyl- butyric acid. The latter was obtained from a-methylbutyraldehyde which was converted by the action of cupric chloride into the a-chloro-derivative and thence by oxidation with potassium permanganate into the corresponding acid. Another synthesis,64 involving starting materials of known absolute con- figuration is based upon the preparation of both enantiomeric forms of 2,2-dimethoxy-3-methylpentan-3-ol(64).They were obtained from 3-methylpent- 1-yn-3-01 which was resolved by fractional crystallization of the brucine salt of 58 CJ N. Polgar Ann. Reports (B) 1970 67 525. 59 N. S. Crossley Tetrahedron Letters 1971 332'1. W. J. Gensler D. M. Solomon R. Yanase and K. W. Pober Chem. Phys. Lipids 1971 6 280. " A. S. Meyer and E. Hanzmann Biochem. Biophys. Res. Comm. 1970 41 891. '2 P. Loew and W. S. Johnson J. Amer. Chem. Soc. 1971,93 3765. '' P. Loew J. B. Siddall V. L. Spain and L. Werthemann Proc. Nat. Acad. Sci. U.S.A. 1970 67,1462. h4 D. J. Faulkner and M. R. Petersen J. Amer. Chem. Soc. 1971 93 3766. Aliphatic Compounds 461 its phthalate half-ester ;addition of methanol to each enantiomer using mercuric oxide-boron trlfluoride etherate-trifluoroacetic acid catalyst gave the corres- ponding ketal (64).The (-)-form was shown by conversion into the parent methyl ketone and thence into (-)-2-hydroxy-2-methylbutyric acid to possess R configuration. Reaction of the enantiomeric forms of the hydroxyketal (64) with the dienol ester (60) gave uia a Claisen rearrangement the respective enantiomers of the hydroxyketone (65). Reduction with sodium borohydride furnished the diols (66) which were converted via the monotosylates into the epoxides (63) (Scheme 3). Scheme 3 462 N. Polgar The dextrorotatory juvenile hormone resulted from the (S)-(+)-enantiomer of the hydroxyketal(64) thus indicating that the natural hormone has the lO-R 11-S configuration.The literature involving syntheses of insect juvenile hormone analogues has been recently reviewed.65 Syntheses of alkyl-branched long-chain compounds reported include those of esters of various alkenyl- and alkyl-substituted fatty acids by the Wittig reaction between alkylidene triphenylphosphoranes RCH=PPh (where R varied from H to n-C 7H35),and methyl 12-0x0-octadecanoate or 10-oxohexadeca- noate.(j6 3-Methyl- and 3,6-dimethyl-substituted fatty acids have been ~ynthesized~~ by a route involving the methyl-substituted cyclohexane- 1,3-diones (dihydro- resorcinols) (67 ; X = H) and (67 ; X = Me) respectively as chain-extenders.68 The syntheses involve C-alkylation of the 1,3-diones by means of allylic halides followed by reductive cleavage of the alkylation products.Me X Methyl 14-methyl-cis-8-hexadecenoate(71; X = C0,Me) and 14-methyl-cis-8-hexadecen-1-01 (71 ;X = CH,OH) sex attractants of Trogoderma species were prepared69 by a scheme involving the bromo-derivative (68) of 3-methyl- pent-1-yne as an intermediate. Coupling with propargyl alcohol gave the diynol (69) which was hydrogenated to yield 6-methyloctan-1-01 (70; X = CH,OH). The corresponding aldehyde (70 ;X = CHO) furnished via the Wittig condensa- tion with the triphenylphosphinylide of methyl 8-bromo-octanoate the com- pounds (71). EtCHMe-CZCBr E tCHM e.C 5CC- C-CH,OH (68) (69) EtCHMe[CH2]4X EtCHMe.[CH,],-CH=CH.[CH,],X (70) (71) 65 K. Slama Ann.Reu. Biochem. 1971 40 1079. 66 D. G. Chasin and E. G. Perkins Chem. Phys. Lipids 1971 6 8. 67 P. D. Grimwood D. E. Minnikin N. Polgar and J. E. Walker J. Chem. Sac. (C) 1971 870. 68 CJ H. Stetter ‘Newer Methods of Preparative Organic Chemistry,’ ed. W. Foerst Academic Press New York and London 1963 vol. 2 p. 51. 69 J. I. De Graw and J. 0. Rodin J. Org. Chem. 1971 36 2902. Aliphatic Compounds ( & )-4,6-Dimethylocta-trans-2-trans-4-dienoic acid (73) a degradation product of the pigment sclerotiorin has been synthesized7’ by a Wittig condensation from 2,4-dimethylhex-truns-2-enal(72) ;the latter was obtained by base-catalysed condensation of a-methylbutyraldehyde and propionaldehyde. The two rneso-forms of 2,4,6-trimethylpimelic acid (76) have been isolated7 from a mixture of stereoisomers obtained from a&-dimethylglutaric anhydride via the lactone (74) and bromo-ester (75).Their configurations were determined by X-ray analysis.72 0’ C H ,-CH Me-CH ,.CH Me-CO BrCH,CHMeCH ,CHMeCO,Me (75) (74) HO2CCHMeCH,.CHMe.CH,CHMe-CO2H (76) The biological activities of the toxic diesters of trehalose with mycolic acids (‘cord factors’) have been receiving further attenti~n.~ For studies of the relation- ship between the toxicity of these compounds and their ability to inhibit mito- chondrial oxidative phosphorylation two glycolipid analogues methyl 6-mycoloyl-a-D-glucopyranoside and 6,6’-dimycoloylsucrose have been prepared. The mycolic acids employed for these preparations were fractions isolated from virulent tubercle bacilli H37 Rv ; the fractions contained mainly acids having only one hydroxy-group and possessing cyclopropane rings.Reactions.-The complex reactions which occur on alkali fusion of various compounds74 have been subjected to further detailed studies. The products isolated on alkali fusion of long-chain epoxy-acids suggest7 the occurrence of at least four different reaction pathways one of which involves a p-elimination reaction. The results obtained on alkali fusion of 1 I-alkoxyundecanoic acids indicate that p-elimination occurs almost exclusively leading initially to undec- 10-enoic and 11-hydroxyundecanoic acid;75 thus it is shown that the above reaction observed for epoxides also occurs with ethers.Further concern ’’ R. Chong R. R. King and W. B. Whalley J. Chem. SOC.(C),1971,3566. 71 W. Keller-Schierlein M. Brufani R. Muntwyler and W. Richle HeIv. Chim. Acta 1971 54 44. 72 M. Brufani and W. Fedeli Helv. Chim. Acta 197 1 54 5 1. l3 M. Kato and J. Asselineau European J. Biochem. 1971 22 364. 74 Cf B. C. L. Weedon ‘Techniques of Organic Chemistry,’ ed. A. Weissberger Inter- science New York 1963 vol. XI p. 655. ’’ M. F. Ansell I. S. Shepherd and B. C. L. Weedon J. Chem. SOC.(C),1971 1840. 76 M. F. Ansell D. J. Redshaw and B. C. L. Weedon J. Chem. SOC.(C),1971 1846. 464 N. Polgar the alkali-fusion reactions of long-chain 2-hydroxy-acids and various 0x0-acids. In the course of these studies the alkali fusion of 9,10,16-trihydroxyhexadecanoic acid (aleuritic acid) has been reinvestigated ;it is shown that the products obtained from this trihydroxy-acid can be interpreted in terms of the known behaviour of the appropriate mono- and di-hydroxy-acids.In order to investigate certain details of the mechanism of the Varrentrapp reaction representative alkenoic alkynoic and alkadienoic acids have been subjected to alkali fusion with potassium de~terioxide.~ The deuteriated degra- dation products examined by n.m.r. and mass spectrometry were found to be consistent with a stepwise reversible migration of the double bond during the fusion reaction. The previously reported fission of 9( 10)-hydroxy-10(9)-oxo-octadecanoicacid by alcoholic potassium hydroxide to give nonanedioic and nonanoic acid has been shown to be an autoxidation rea~tion.'~ With reference to the importance of alkali isomerization for the spectro- photometric estimation of certain acids in fats and oils the isomerization of methyl linoleate and methyl linolenate with potassium t-butoxide has been investigated,' and detailed analyses of the isomerization products have been reported.A further study on the alkali cyclization of long-chain trienoic carboxylic acids has been published.80 The products (77; n + m = 11) formed by the action of potassium hydroxide in ethylene glycol at 180 "C from octadeca-9c,l2c,l5c- and -9t,12t,l St-trienoic acids (containing isolated double bonds) as well as from octadeca-9c,l lt,13t-and -9t,l1 t,l3t-trienoic acids (containing a conjugated sys- tem) have been compared.The results are shown to indicate a polycentric mechanism for the ring closure which is preceded by an ionic isomerization to give a conjugated trienic system with a central cis double bond capable of undergoing cyclization. Octadeca-9c 12c 1Sc-trienoic (linolenic) acid is found to yield primarily a cyclic acid with a propyl side chain (77; n = 3) whereas the trienoic acids without a central cis double bond give mixtures containing a wide range of isomers arising by prototropic migration of the conjugated triene system either already present or being formed during isomerization. Reports concerning the catalytic hydrogenation of unsaturated esters include a study" of the competitive hydrogenation rates of isomeric methyl octadece- " M.F. Ansell A. N. Radziwill and B. C. L. Weedon J. Chem. SOC. (C),1971 1851. M. F. Ansell I. S. Shepherd and B. C. L. Weedon J. Chem. SOC.(C),1971 1857. 79 T. L. Mounts and H. J. Dutton Lipids 1970 5 997. 8o A. N. Sagredos J. D. v. Mikusch and V. Wolf Annafen 1971 745 169. C. R. Scholfield T. L. Mounts R. 0. Butterfield and H. J. Dutton J. Amer. Oil Chemists' Sac. 1971 48 237. Aliphatic Compounds 465 noates. It involves the hydrogenation of mixtures containing a radioactively labelled and an unlabelled isomer the two isomers competing for catalyst surface and hydrogen. Another paperg2 deals with the hydrogenation on copper chromite previously shown to result in extensive double-bond isomerization. P-Eleostearate and other unsaturated esters including trans,trans-conjugated dienes were reduced with deuterium and copper chromite and the positional and geometric isomerization occurring during the reduction was studied.Monoenes were formed from conjugated trans,trans-dienes by 1,2-and 1,4-addition ; methyl oleate was not reduced but isomerized under the conditions employed. The ozonolysis of olefins in particular unsaturated fatty acids has been reviewed.8 Another reviews4 concerns olefin reactions catalysed by transition- metal compounds in particular those reactions which appear applicable to unsaturated fatty acids. Addition reactions which have been investigated include the 1,3-addition of a variety of diarylnitrones to hexadec-I-ene as well as to esters of undec- -10-enoic oleic and linoleic acids to yield i~oxazolidines.~~ The latter were reduced to amino-alcohols and alcohols.The reactivity of the homoallylic systems of the 0-toluene-p-sulphonyl ester derived from methyl ricinelaidate (78; trans double bond X = toluene-p-sulphonyl)86 and 0-methylsulphonyl ester of methyl ricinoleate (78 ;cis double bond X = methyls~lphonyl)~~ has been studied. Reactions which include the formation of a cyciopropane ring and elimination may occur. Thus it is showns7 that the 0-methylsulphonyl ester of methyl ricinoleate is readily converted into methyl 9-methoxy-l0,11-methyleneheptadecanoate(79) by reaction with meth- anol ;with water the corresponding hydroxy-derivative and with acetic acid the acetoxy-derivative are formed.Elimination is the predominant reaction under certain conditions. Me[CH,] ,.CH(OX)CH2.CH=CH-[CH2] ,CO,Me (78) 2Ft2 Me [CH 2] CH __ CH.CH(OMe).[CH J,CO,Me (79) The allylic halogenation and oxidation of unsaturated esters have been recently reviewed.88 S. Koritala and E. Selke J. Amer. Oil Chemists’ SOC.,1971 48 222. 83 E. H. Pryde and J. C. Cowan ‘Topics in Lipid Chemistry,’ ed. F. D. Gunstone Logos Press London 1971 vol. 2 p. 1. “ C. W. Bird ‘Topics in Lipid Chemistry,’ ed. F. D. Gunstone Logos Press London 1971 vol. 2 p. 247. ’’ H. Basu and H. Schlenk Chem. Phys. Lipids 1971,6,266. 86 E. Ucciani A. Vantillard and M. Naudet Chem. Phys. Lipids 1970 4 225. *’ F. D. Gunstone and A. I. Said Chem. Phys. Lipids 1971 7 121.** M. Naudet and E. Ucciani ‘Topics in Lipid Chemistry,’ ed. F. D. Gunstone Logos Press London 1971 vol. 2 p. 99. 466 N. Polgar Simple @-unsaturated acids can be reduced with lithium in liquid ammonia to give high yields of saturated acids.89 In the case of P-keto-acid enol-ethers such as acetoacetic acid methoxymethyl enol-ether (80) the enol-ether group is eliminated during this procedure. In this way a P-keto-ester can be readily converted via the keto-acid methoxymethyl enol-ether into the corresponding saturated deoxy-acid. R2 I R'-C-CO MeC=CHCO,H I' '0 I I OCH,OMe 0-so / (80) The preparation of a range of anhydrosulphites (81) by reaction of thionyl chloride with a-hydroxycarboxylic acids has been de~cribed.~' In support of a hypothesis concerning the formation of n-alkanoic acids and n-alkanes found in some meteorites the terminal chain elongation of fatty acids by reaction with free radicals has been studied." Reaction of methyl or ethyl free radicals with monolayers of potassium palmitate and n-heptadecanoate on an aqueous surface yielded straight-chain acids with longer carbon chains than those of the reactant acids.It is thus found that extension of hydrocarbon chains by free-radical reaction can be achieved if the growing chains are suitably packed in a monolayer on a surface. The oxidative degradation of saturated normal long-chain compounds by potassium permanganate has been the subject of further studies ;the results of oxidation experiments involving docosanoic acid and related compounds are reported.89 J. E. Shaw and K. K. Knutson J. Org. Chem. 1971 36 1151. 90 G. P. Blackbourn and B. J. Tighe J. Chem. SOC.(C),1971 257. 91 C. B. Johnson and A. T. Wilson Lipids 1971 6 181. q2 Nguyen Dinh-Nguyen and A. Raal Acta Chem. Scand. 1970 24 3416.

ISSN:0069-3030    

DOI:10.1039/OC9716800449

出版商:RSC    

年代:1971

数据来源: RSC

摘要:

15 Terpenoids and Steroids By B. A. MARPLES Department of Chemistry The University of Technology Loughborough THE second annual volume of the Chemical Society’s Specialist Periodical Report on Terpenoids and Steroids has recently been published. This gives compre- hensive coverage of the literature published in the period September 197& August 1971. The widening interest in organic geochemistry is indicated by two reviews in this area.2 Other reviews on stereoselective and stereospecific olefin ~ynthesis,~ and insect sex attractants4 have appeared. 1 Monoterpenoids Revised structures are presented for pinol dibromide (2) and pinol tribromide (3) which are derived from pinol(1) as shown.5 The migration of the oxygen bridge occurs during a number of electrophilic additions to the double bond.An n.m.r. study on nerol and geraniol and their acetates using the Eu(dpm) shift reagent supports the E configuration for geraniol and the 2 configuration for nerol.6 These assignments which are in agreement with early literature are in disagree- ment with those of Rummens. (1) (2) (3) The full details of the synthesis of yomogi alcohol and the rearrangement of its epoxide (4)to products of the santolinyl skeleton are now available.’ Inter- estingly the acetoxy-epoxide (5) gives the oxetan (6),and products derived from ’ ‘Terpenoids and Steroids’ ed. K. H. Overton (Specialist Periodical Reports) The Chemical Society London 1972 Vol. 2. J. R. Maxwell C. T. Pilliriger and G. Eglinton Quart. Rev. 1971,25 571 ;P.Albrecht and G. Ourisson Angew. Chem. Internat. Edn. 1971 10 209. J. Reucroft and P. G. Sammes Quart. Rev. 1971 25 135. K. Eiter Fortschr. Chem. org. Naturstofle 1970 28 204. J. Wolinsky R. 0.Hutchins and J. H. Thorstenson Tetrahedron 1971 27 753. J. W. Haan and L. J. M. van de Ven Tetrahedron Letters 1971 2703. A. F. Thomas and W. Pawlak Helu. Chim. Acta 1971 54 1822. 467 B. A. Murples a 1,2-shift of the vinyl group are not observed. Solvolysis of the artemisyl sulphonium salt (7) in aqueous acetone gives essentially yomogi alcohol whereas in methanol the chrysanthemic derivative (8) is obtained (inter aliu) in low yield.* This latter result suggests the possible intermediacy of the chrysanthemyl skeleton in the biogenesis of some non-head-to-tail monoterpenes and is possibly analogous to the presqualene alcohol to squalene conversion.Some aspects of the biosynthesis of cyclopropane compounds have been reviewed.' 'I OR (4; R = H) (5; R = Ac) The grasshopper ketone (1 1) is synthesized from the diol(9) via (lo),as shown. The biosynthesis of the allenic carotenoids fucoxanthin and neoxanthin may involve an analogous sequence of reactions. The allenic cyclopropane alcohol (12) is stereoselectively reduced with sodium in liquid ammonia to the alcohol (13) from which ( -t)-trans-chrysanthemic acid may be prepared.' ' The reduction possibly involves the intramolecular protonation of the cyclopropyl anion by the a B. M. Trost P. Conway and J. Stanton Chem. Comrn. 1971 1639.J. H. Law Accounts Chem. Res. 1971 4 199. lo S. Isoe S. Katsumura S. B. Hyeon and T. Sakan Tetrahedron Letters 1971 1089. R. W. Mills R. D. H. Murray and R. A. Raphael Chem. Comm. 1971 555. Terpenoids and Steroids (12) (13) pendant OH group. A new synthesis of rethrolones is reported,” and a new approach to the synthesis of a-and P-damascenones (14) and (15) respectively involve^'^ the initial construction of the trimethylcyclohexadiene (18). This is achieved through the 1A-addition of the ally1 ylide (16) to the enone (17) as shown. Three interesting new syntheses of cis-jasmone are reported. 14-’ The key step in the first l4 of these involves the dehydrochlorination and decarbonylation of (y-p / \ the chlorodiketone (19) to the cyclopentenone (20).The ~econd’~ employs aqueous Ti3+to convert the nitro-compound (21)to the 174-diketone (22). In the third the cuprous acetylacetonate-catalysed reaction between the diazoketone (23) and isopropenyl acetate (24) gives the cyclopropyl derivative (25) which on hydrolysis gives the diketone (22). A new total synthesis” of (+)-fenchone and ’’ G. Biichi D. Minster and J. C. F. Young J. Amer. Chem. SOC.,1971 93 4319. l3 G. Biichi and H. Wiiest Helv. Chim. Acta 1971 54 1767. l4 G. Biichi and B. Eggar J. Org. Chem. 1971 36 2021. l5 J. E. McMurry and J. Melton J. Amer. Chem. SOC.,1971 93 5309. I’ J. E. McMurry and T. E. Glass Tetrahedron Letters 1971 2575. l7 (a) P. H. Boyle W. Cocker D. H. Grayson and P. V. R. Shannon Chem. Comm. 1971,395; (6) P.H. Boyle W. Cocker D. H. Grayson and P. V. R. Shannon,J. Chem. Sor. (0,1971 2136. 470 B. A. Marples -0 + yOAc -, ~ -CHN the synthesis’ of the 9-acetoxyfenchane derivative (27) are described. The latter is formed in high yield by treatment of the ether (26) with BF,-Ac,O. The diastereomeric forms of p-menthane-8-thiol-3-one are the first natural terpenoid keto-thiols to be isolated.” The full details are available of the application of the condensation between citral and phloroglucinols to the syntheses of (&)-deoxybruceol and cannabinoids.20 Cantleyocide is a new glucoside terpenoid compound containing a loganoside and a secologanoside.2 2 Sesquiterpenoids Convincing new evidence is presented in support of the em-structure (28) for isolongifolene epoxide,22a rather than the alternative endo-structure which was suggested last year,22b from a study of its aluminium alkoxide-catalysed rearrange- ment.The absolute configuration (lOR 11s)of the CI8 juvenile hormone has ’* N. Bosworth and P. D. Magnus Chem. Comm. 1971 618. l9 (a) D. Lamparsky and P. Schudel Tetrahedron Letters 1971 3323; (6) E. Sundt B. Willhalm R. Chappaz and G. Ohloff Helu. Chim. Acta 1971 54 1801. 2o L. Crombie and R. Ponsford J. Chem. SOC.(C) 1971,788 796. ’*T. Sevenet C. Thal and P. Potier Tetrahedron 1971 27 663. ‘’ (a)L. K. Lala J. Org. Chem. 1971 36 2560; (6)cf. Ann. Reports (B) 1970 67 408. Terpenoids and Steroids 471 been established by ~ynthesis,~~,~~ and by a study of the circular dichroism of the derived glycol in the presence of Pr(d~m),.~~ Synthetic imino-analogues of the juvenile hormone have no intrinsic activity but are potentiators of juvenile- hormone activity.26 Bulnesoxide and 10-epiguaioxide have been shown to be identical (29),27and revised structures are presented for enhydrin,’* the c~riolins,~~ pyrethro~in,~’ and pyro~antonin.~ A synthesis confirms the structure and some of the stereochemistry of cyclonerodiol (30)32which is a metabolite of Gibberella ,f~jikoroi.~~ H Germacrene is cyclized with thiophenyl and trichloromethyl radicals to the selinene derivatives (31).34 The stereoselectivity of this reaction which is similar to that observed using electrophiles suggests that the C-X and C-C bonding (31 ;X = SPh or CCl,) processes are synchronous.A biogenetic model cyclization of preisocalamendiol (32) with 80% aqueous acetic acid gave isocalamendiol (33) with which it co-occurs.’ The abnormal Cope rearrangement of cis,trans-furanocyclodeca-1,5-dienes [e.g. cis,trans-furanodiene (34) to the trans-fused isofuranogermacrene 23 P. Loew and W. S. Johnson J. Amer. Chem. Soc. 1971,93 3765 5315. 24 D. J. Faulkner and M. R. Petersen J. Amer. Chem. SOC.,1971 93 3766. ’’ K. Nakanishi D. A. Schooley M. Koreeda and J. Dillon Chem. Comm. 1971 1235. ” L. M. Riddiford A. M. Ajami E. J. Corey H. Yamamoto and J. E. Anderson J. Amer. Chem. Soc. 1971 93 1815. 27 H. Ishi T. Tozyo and M. Nakamura Tetrahedron 1971 27 4263. 28 B. S. Joshi V. N. Kamat and H.Fuhrer Tetrahedron Letters 1971 2373. ’’ S. Takahashi H. Naganawa H. Inuma and T. Takita Tetrahedron Letters 1971 1955. 30 E. J. Gabe S. Neidle D. Rogers and C. E. Nordham Chem. Comm. 1971 559. 3‘ T. B. H. McMurryand D. F. Rane,J. Chem. SOC.(C),1971 1389. 32 S. Nozoe M. Goi and N. Morisaki Tetrahedron Letters 1971 3701. 33 B. E. Cross R. E. Markwell and J. C. Stewart Tetrahedron 1971 27 1663. 34 T. W. Sam and J. K. Sutherland Chem. Comm. 1971,970. 35 M. Iguchi M. Niwa and S. Yamamura Chem. Comm. 1971 974. 472 B. A. Marples (35)] is ascribed to the presence of the furan ring.36 The 4-acetoxy-3-ketone (36) rearranges in acetic anhydride and pyridine to the 2-acetoxy-derivative (37) by an intramolecular process as shown.3 The 3a-bromolongifolene derivative (38) rearranges by a 1,5-hydride shift to the olefin (39) at a rate which suggests a-bond participati~n.~~ (38) (39) A number of approaches to the synthesis of hydroazulenic sesquiterpenes are reported.39 Guaiol bulnesol and z-bulnesene were ~btained,~~'~'~~ and the observation that acetolysis of compound (40) cleanly gave the ring-expanded 36 K.Takeda 1. Horibe,and H. Minato Chem. Comm. 1971 88. 37 P. S. Aumeer and T. B. H. McMurry Chem. Comm. 1971 641. '' L. Stehelin J. Lhornrne and G. Ourisson J. Amer. Chem. Soc. 1971 93 i651. 39 (a)J. A. Marshall and A. E. Greene J. Org. Chem. l971,36 2035; (b)C. J. V.Scanio and L. P. Hill Chem. Comm. 1971 242; (c) C. H. Heathcock and R. Ratcliffe J. Amer. Chem. Soc. 1971 93 1746; (d)J.A. Marshall and A. E. Green Tetrahedron Letters 1971 859; (e) J. A. Marshall A. E. Greene and R. Ruden ibid. p. 855; (f)G. L. BuchananandG. A. R. Young Chem. Comm. 1971,643;(8)J. B. Hendrickson and R. K. Boeckman jun. J. Amer. Chem. Soc. 1971,93 1307. Terpenoids and Steroids EtO,C..$ -Et02C@ COCHN 0 compound (41) by homoallylic participation is of particular intere~t.~ 9a*b Racemic patchoulenone and epipatchoulenone have been synthesized :40 the key step involved the direct formation of the bicyclic ketone (43) by BF3-catalysed decomposition of the diazoketone (42). The tricyclic alcohol (44) is converted in high yield in sulphuric acid+ther to neoclovene (45).41This strongly supports the previously proposed mechanism for the conversion of caryophyllene to neoclovene.The syntheses of zizanoic and isozizanoic acids are reported :42 a key step is the rearrangement of the compound (46) to the compound (47) a 40 W. F. Erman and L. C. Stone J. Amer. Chem. Soc. 1971 93 2821. 41 T. F. W. McKillop J. Martin W. Parker J. S. Roberts and J. R. Stevenson J. Chem. SOC.(C),1971 3375. 42 D. F. MacSweeney and R. Ramage Tetrahedron 1971,27 1481. B. A. Marples +H,OH process which may have a biogenetic parallel. The absolute configuration of ( -)-sirenin (48) was confirmed by synthesis,43 and illudin S has been ~ynthesized.~~ The new hydrocarbon fukinane (49) has been prepared from f~kinone.~’ The isolation of paradisiol (50) from grapefruit in which nootkatone and valencene also occur supports the early hypothesis that their biosynthesis involves a 1,2-methyl shift from C-10 to C-5.However an alternative proposal involves the intermediacy of two discrete spiro-cation~.~~ A total synthesis of i~hwarane,~’ and its isolation49 from Cymbopetaium penduliforurnare reported. Davana ether (51) appears to be the odoriferous com- ponent of the oil of Artemisia pallens since davanone and artemone are odourless when pure.” The isolation of pure trans-atlantone (52) is reported for the first tirne,’l and an additional C16 terpenoid metabolite LL-Z1271/3 (53) has been isolated from an Acrostalagmus specie^.'^ Myliol(54) a new tetracyclic sesquiter- pene was isolated from Mylia t~ylorii,’~ and the new furanoterpenes dehydro- 44 T. Matsumoto H.Shirahama A. Ichihara H. Shin S. Kagawa F. Sakan and K. Mijano Tetrahedron Letters 197 1 2049. 45 K. Naya and M. Kobayashi Bull. Chem. SOC.Japan 1971,44,258. 46 H. Sulser J. R. Scherer and K. L. Stevens J. Org. Chem. 1971 36 2422. 47 D. J. Dunham and R. G. Lawton J. Amer. Chem. Soc. 1971,93,2075. 48 R. B. Kelly J. Zamecnik and B. A. Beckett Chem. Comm. 1971,479. 49 L. C. Teng and J. F. De Bardeleben Experientia 1971 27,14. 50 A.F. Thomas and G. Pitton Helu. Chim. Acta 1971 54 1890. 51 B. S. Pande S. Krishnappa S. C. Bisarga and Sukh Dev Tetrahedron 1971 27,841. 52 G.A. Ellestad R. H. Evans jun. and M. P. Kunstmann Tetrahedron Letters 1971 497; cf. Ann. Reports (B) 1970 67,412. 53 V. BeneSova P. Sedmera V. Herout and F. Sorm Tetrahedron Letters 1971 2679.Terpenoids and Steroids /c02h lasiosperman (55)and lasiosperman were obtained from Lasiosperrnurnradiaturn. Liatrin (56)” and eupacunin (57)56 are novel antileukemic germacranolide cis,&-dienes. The isolation of pacifenol (58) which contains bromine and chlorine may suggest that halogenated pesticides could be naturally det~xified.~ 54 H. Bornowski Tetrahedron 1971 27 4101. 55 S. M. Kupchan V. H. Davies T. Fujita M. R. Cox and R. F. Bryan J. Amer. Chem. SOC.,1971 93 4916. 56 S. M. Kupchan M. Maruyama R. J. Hemingway J. C. Hemingway S. Shibuya T. Fujita P. D. Cradwick A. D. U. Hardy and G. A. Sim J. Amer. Chem. SOC.,1971 93 4914. ’’ J. J. Sims W. Fenical R. M. Wing and P. Radlick J.Amer. Chem. SOC.,1971,93,3774.476 B. A. Marples 3 Diterpenoids Revised structures are presented for candicandiol and epi~andicandiol.~~ Treat-ment of methyl podocarpate with three equivalents of DDQ in methanol resulted in exclusive B-ring oxidation to give the enone (59).59The acid-catalysed dehydra- tion of manool and epimanool to yield pimaradienes and then rosadienes in a biogenetic-type process is reported in Similarly the carbonium ion (60) (or equivalent) which was generated from the appropriate amine tosylate and tosylhydrazone rearranged in biogenetic fashion to give a variety of tetracyclic and pentacyclic diterpenoids.6 The synthesis of neoatisiranone confirms the structure of the ketone (61) obtained by rearrangement of isophyllocladene epoxide.62 An unusual formic acid-catalysed rearrangement of erythroxylol A epoxide (62) to the allylic alcohol (63) is reported.63 The abietane epoxide (64) fragments with BF to give the ketone (65) (inter ulia) in an analogous manner to that observed in certain steroidal and decalin epoxide~.~~ The rearrangements by solvolysis of certain 4-mesyloxy- and 1-tosyloxy-abietane derivatives appear on balance to involve discrete carbonium ions.6s 58 F.Piozzi P. Venturella A. Bellino M. P. Paternostro B. Rodriguez Gonzalez and S. Valverde Chem. and Ind. 1971 962. 59 J. W. A. Findley and A. B. Turner J. Chem. SOC.(0, 1971 547. 6o T. McCreadie and K. H. Overton J. Chem. SOC.(0,1971 312. R. M. Coates and E. F. Bertram J. Org. Chem. 1971,36 3722. 62 P. A. Gunn R. McCrindle and R.G. Roy J. Chem. SOC.(0, 1971 1019. 63 R. D. H. Murray R. W. Mills and J. M. Young Tetrahedron Lptters 1971 2393. 64 R. C. Cambie R. A. Franich and T. J. Fullerton Austral. J. Chem. 1971 24 593; cf. ref. 130 132. ” (a)H. W. Whitlock jun. P. B. Reichardt and F. M. Silver J. Amer. Chem. Soc. 1971 93 485; (b)H. W. Whitlock jun. and L. E. Overman ibid. p. 2247. Terpenoids and Steroids OH CH,OH CH,OCHO (62) (63) Further efforts have been directed towards the synthesis of the bicyclo[3,2,1]- octane system. An intramolecular Reformatsky reaction with compound (66) gave compound (67),66and a Dieckmann reaction with the diester (68) provided a model of the kaurene class (69).67 The acid-catalysed decomposition of the Me0 H a- C0,Me CH,C02Me +QoC0,Me 66 F.E. Ziegler and M. E. Condon J. Org. Chenz. 1971 36 3707. 67 R. A. Finnegan and P. L. Bachmann J. Org. Chem. 1971,36 3196. B. A. Marples diazoketone (70) gave the tetracyclic compound (71) by an intramolecular C-alkylation.68 Photoaddition of allene to cyclopent-1-en-1-a1 gave the com- pound (72) regiospecifically and its conversion to the steviol model (74) via the tosylate (73)is notable.69 Strobic acid (75) is a new resin acid from Pinus ~trobus.~'Torulosal (76) is auto-oxidized to 18-nor-4-hydroxy-compounds (inter alia) and thus the norter- penoids isolated from Aracoria excelsa could be artefact~.~~ The full account is available of the isolation of a novel gibberellin aldehyde A24 (77) and the corre- sponding acid A, (78).'2 The hydroquinone diterpene lycoxanthol (79) was isolated from Lycopodiurn lu~idulurn,~~ and the new podolactones C (80) and D (81) are the first known terpenes to contain the sulphoxide Inumakilactones B and C were isolated from Podocarpus rnacrophyll~s.~~ Novel C0,Me 68 D.J. Beames T. R. Klose and L. N. Mander Chem. Comm. 1971 773. 69 F. E. Ziegler and J. A. Kloek Tetrahedron Letters 1971 2201. 70 D. F. Zinkel and B. P. Spalding Tetrahedron Letters 1971 2459. R. Caputo L. Mangoni L. Previtera and R. Iccarino Tetrahedron Letters 1971 373 1. 72 D. M. Harrison and J. MacMillan J. Chem. SOC.(C) 1971 631. 73 R. H. Burnell and M. Moinas Chem. Comm. 1971 897. 74 M. N. Galbraith D. H. S. Horn and J. M.Sasse Chem. Comm. 1971 1362. 75 S. Ito M. Sunagawa M. Kodama H. Honma and T. Takahashi Chem. Comm. 1971 91. Terpenoids and Steroids 4’79 CO,H (77 ; R = CHO) (78; R = C0,H) furanoditerpenes include chettaphanin I1 (82),76and the C2 compounds nitenin (83) and dihydr~nitenin,~~ and furospongin (84),” which may be derived from sesterterpenes. Further studies on Euphorbia lathyris have resulted in the isola- tion of 7-hydroxylathyrol (85),79and lathyrol(86).*’ A biogenetic scheme linking 76 A. Sato M. Kurabayashi A. Ogiso and H. Mishima Tetrahedron Letters 1971 839. 77 E. Fattorusso L. Minale G. Sodano and E. Trivellone Tetrahedron 1971 27 3909. 78 G. Cimino S. De Stefano L. Minale and E. Fatorusso Tetrahedron 1971 27 4673. 79 P.Narayanan M. Rohrl K. Zechmeister D. W. Engel W. Hoppe E. Hecker and W. Adolf Tetrahedron Letters 1971 1325. 480 B. A. Marples (85; R = OH) (86; R = H) [87 ;R = CH=CHCH=CH(CH,),Me] the lathyran tiglian casben and ingenan diterpenes of the Euphorbiaceae is proposed,80 and is supported by the isolation of the unique orthoester huratoxin (87) from Hura crepitans (Euphorbiaceae).8 4 Sesterterpenoids The full account of the structural derivation of the fungal metabolite fusicoccin is now available.82 Cheilanthatriol (89) is a new fundamental type of sesterter- pene which is formed from geranylfarnesol (88) by a cyclization initiated at the isopropylidene 5 Triterpenoids X-Ray crystallographic work has clarified a number of stereochemical problems.The unreactive olefinic bond of the triterpene enone (90) is highly twisted,84 and zeorin has the 210-H c~nfiguration.~~ The structures of kulactone (91) which 8o W. Adolf and E. Hecker Experientia 1971 27 1393. K. Sakata K. Kawazu T. Mitsui and N. Masaki Tetrahedron Letters 1971 1141. ” (a)K. D. Barrow D. H. R. Barton Sir Ernst Chain U. F. W. Ohnsorge and R. Thomas J. Chem. Soc. (C) 1971 1265; (b)K. D. Barrow D. H. R. Barton Sir Ernst Chain C. Conlay T. C. Smale R. Thomas and E. S. Waight ibid. p. 1259; (c) M. Brufani S. Cerrini W. Fedeli and A. Vaciago J. Chem. Soc. (B) 1971 2021. H. Khan A. Zaman G. L. Chetty A. S. Gupta and Sukh Dev Tetrahedron Letters 1971 4443. 84 G. H. Beasley and D. A. Cox J. Amer. Chem. Soc. 1971,93,4312.‘5 T. Nakanishi H. Yamauchi T. Fujiwara and K. Tomita Tetrahedron Letters 1971 11 57. Terpenoids and Steroids 481 AcO'* (92) (94) \ I / H has the 20P-H configuration,* and abieslactone (92) have been el~cidated.~ Abieslactone (92) is isomerized88 with BF to grandisolide (93) which is also formed by acid treatment of cyclograndisolide (94) a recently isolated cyclo- artenol deri~ative.~~ A study of the acid-catalysed rearrangement of certain neotriterpene epoxides illustrates the strong dependence of reaction course on the solvent and reactants." The Lewis acid-catalysed backbone rearrangement 86 K. W. Ma F. C. Chang and J. C. Clardy Chem. Comm. 1971,424. " J. P. Kutney N. D. Westcott F. H. Allen N. W. Isaacs 0. Kennard and W.D. S. Motherwell Tetrahedron Letters 1971 3463. H. hie S. Uyeo and K. Kuriyama Tetrahedron Letters 1971 3467. 89 F. H. Allen J. P. Kutney J. Trotter and N. D. Westcott Tetrahedron Letters 1971 283. 90 (a)G. Berti F. Bottari A. Marsili I. Morelli and A. Mandelbaum Tetrahedron 1971 27 2143; (6)G. Berti A. Marsili I. Morelli and A. Mandelbaum ihid. p. 2217. 8' B. A. Marples of a 9,l la-epoxy-5a-lanostane gave the A9(‘1),13(17)-~~mp~~nd (95).9‘ This rearrangement has not been observed previousIy in 13/?,14a-triterpenoids. Predictably 7-oxofriedelene rearranges only to the enone (96) and this supports the concept of a two-step backbone rearrangement in these compound^.^^ Further examples of mercuric acetate dehydrogenations of triterpenes are rep~rted.’~ The acidic fraction from the reaction of lupenyl acetate in chloroform- acetic acid contains the homo-acids (97) and (98)(inter aha).The chloroform acts as a source of trichloromethyl radicals which are incorporated. The absence of U.V.absorption in an independently synthesized 18,20(29)-diene supports the previously proposed twisted conformation for this system.94 A further route to 4-demethyl compounds is reported.95 Ac0 (97) (98; 18,19-dehydro) Enzymic cyclization of 6-demethyl-2,3-oxidosqualenegives 19-norlano~terol.~~ The dialdehyde (99) which is a useful intermediate for the synthesis of squalene is prepared by stereospecific selenium dioxide oxidation of 2,7-dimethyIocta- 2,6-diene.97 A new synthesis of squalene employs the reaction of farnesyl ’I I.G. Guest and B. A. Marples J. Chem. SOC.(C) 1971 1468. 92 P. Sengupta J. Mukherjee and M. Sen Tetrahedron 1971,27 2473. 93 (a)G. V. Baddeley J. J. H. Simes and T. G. Watson Austral. J. Chem. 1971,24 2639; (b) S. P. Adhikary W. Lawrie J. McLean and M. S. Malik J. Chem. Soc. (C),1971,32. A. Vystrtil and Z. Bleeha Chem. and Znd. 1971 1 172. 94 9s K. F. Cohen R. Kazlauskas and J. T. Pinhey Chem. Comm. 1971 1419. y6 (a) E. J. Corey A. Krief and H. Yamamoto J. Amer. Chem. SOC.,1971 93 1493; (b)E. E. van Tamelen J. A. Smaal and R. B. Clayton ibid.,p. 5279. 9’ U. T. Bhalero and H. Rapoport J. Amer. Chem. SOC.,1971,93,531 I Terpenoids and Steroids 483 bromide with the lithium derivative of 2-farnesylthiothiazoline as a key step.98 Presqualene alcohol (100) has been synthesized and converted microsomally into ~qualene,~~ thus confirming Rilling's earlier suggestion concerning the role of this intermediate in the biosynthesis of squalene.A biogenetic-like partial synthesis of mexicanolide is reported by two groups."' A total synthesis of lupeol,"' and the synthesis ofpreviously unknown 18~-oleanane are described. lo2 Tetrahymanol is the first example of a triterpenoid alcohol to be isolated from Green River ~ha1e.I'~ Triterpenes (and steroids) have been isolated from certain bacteria and thus the origin of such compounds in shales need not be purely botanic. lo4 A number of new nortriterpenoid bitter principles related to quassin have been isolated from Picrasma ailanthoides and Quassia africana.O5 98 K. Hirai H. Matsuda and Y. Kishida Tetrahedron Letters 1971 4359. 99 (a) R. V. Campbell L. Crombie and G. Pattenden Chem. Comm. 1971 218; (b)E. E. van Tamelen and M. A. Schwartz J. Amer. Chem. SOC.,1971 93 1780; (c) L. J. Altman R. C. Kowerski and H. C. Rilling ibid. p. 1782; (d) H. C. Rilling C. D. Poulter W. W. Epstein and B. Larsen ibid. p. 1783; (e) R. M. Coates and W. H. Robinson ibzd. p. 1785. loo (a)J. D. Connolly I. M. S. Thornton and D. A. H. Taylor Chem. Comm. 1971 17; (6)M. E. Obasi J. I. Okogun and D. E. U. Ekong ibid. p. 727. lo' G. Stork S. Uyeo T. Wakamatsu P. Grieco and J. Laboritz J. Amer. Chem. Soc. 1971,93,4945. lo' R. E. Corbett and H. L. Ding J. Chem. Soc.(0,1971 1884. lo' W. Henderson and G. Steel Chem. Comm. 1971 1331. lo4 (a)C. W. Bird J. M. Lynch S. J. Pirt and W. W. Reid Tetrahedron Letters 1971,3189; (h)C. W. Bird J. M. Lynch S. J. Pirt W. W. Reid C. J. W. Brooks and B. S. Middle-ditch Nature 1971 230 473; (c) M. de Rosa A. Gambacorta L. Minale and J. D. Bu'Lock Chem. Comm. 1971,619. Io5 (a) T. Murae T. Tsuyuki T. Ikeda T. Nishihama S. Masuda and T. Takahashi Tetrahedron 1971 27 1545 5 147 ;(b)J.-P. Tresca L. Alais and J. Polonsky Compt. rend. 1971 273 C 601. 484 B. A.Marples 6 Steroids Volumes IID and TIE of the second edition of Rodd's 'Chemistry of Carbon Compounds' covering steroid chemistry have now been published. 'O6 Other books on chemical and biological aspects of steroid conjugate^,'^' and on the total synthesis of steroids,"' are also available as is a review on anthropod moulting hormones.lo9 The side-chain double bond of compound (101) reacts regioselectively and stereospecifically with I,-AgOAc to give the iodoacetate (102). 'lo Bromoace-toxylation is similarly stereoselective and stereochemical assignments can be made to 22,23-dibromides. The 20R,22R-configuration is proposed' l1 for natural 20,22-dihydroxyecdysones and the 22&23R-configuration is proposed ' for antheridiol ;the latter has also been synthesized. A number of studies on microbiological hydroxylation are reported. Specific 1lfl-hydroxylationof 3~-hydroxy-5u,6u-epoxidesoccurs with Curuularia lunutu,' and two Rhizopus species cause 6p- 7p- and 12~-monohydroxylation of some A4-bufatrieno1ides.'l5 The presence of a 21-hydroxy-group causes Rhizopus nigricans species to hydroxylate at C-7 rather than C-1 1.' l6 14P-Hydroxylation of 5/?,14p-androstane derivatives is observed with Cercospora melonis.' l7 An 106 'Rodd's Chemistry of Carbon Compounds' ed.S. Coffey Elsevier Amsterdam 2nd edn. vol. IID 1970 and vol. IIE 1971.. 107 'Chemical and Biological Aspects of Steroid Conjugates' ed. S. Bernstein and S. Solomon Springer-Verlag. New York 1970. 108 A. A. Akhrem and Y.A. Titov 'Total Steroid Synthesis' Plenum Press New York 1970. 109 H. Hikino and Y. Hikino Fortschr. Chem. org. Naturstofe 1970,28,256. 110 D. H. R. Barton J. P. Poyser P. G. Sammes M. B. Hursthouse and S. Neidle Chem. Comm.1971 715. Ill (a) M. Koreeda D. A. Schooley and K. Nakanishi J. Amer. Chem. Soc. 1971 93 4084; (6) B. Dammeier and W. Hoppe Chem. Ber. 1971 104 1660. 112 D. M. Green J. A. Edwards A. W.Barksdale and T. C. McMorris Tetrahedron 1971 27 1199. 113 T. C. McMorris and R. Seshadri Chem. Comm. 1971 1646. 114 K. Kieslich and H. Wieglepp Chem. Ber. 1971 104 205. 115 (a) B. Gorlich and J. Wolter Annafen 1971 753 106; (6) B. Gorlich F. H. Durr and J. Wolter ibid. p. 116. 116 V. Schwarz J. Protiva and J. Martinkova Coll. Czech. Chem. Comm. 1971,36 3455. 117 F. Mukawa Chem. Comm. 1971 1060. Terpenoids and Steroids improved combined chemical and microbiological route to 15-hydroxy-steroids is reported. ' The long-range effects of some substituent groups on hydrogenation' and esterification' 2o have been reported and conformational transmission from a 9(11)-double bond favours the formation of the 2,4-dienol-3-acetate from 178-acetoxy-2a-phenylandrosta-4,9( 1 l)-dien-3-one.Last year's work on intra-molecular functionaIization of unreactive positions using steroidal benzophenone derivatives has been extended. Thus 5a-androst-9( 1 1)-en- 17p-01 and Sa-androst- 14-en-178-01 are available from the 17P-steroidal derivative (103).' 22 An interest- ing variation of this method employs a mixed complex between an appropriate steroid acid and 4-benzoylbenzoic acid. 23 Thus 3a,5a-androstanyl hemi-succinate can be used to obtain 5a-androstan-3a-ol-16-0ne. Dienol-benzene rearrangements of A-ring epoxyhydroxy-steroids are reported.'24 Similar rearrangements occur in the reactions of steroids containing three potential sites of unsaturation in rings A and B with CH3COBr-HBr.'25 Under the same conditions 17~-acetoxy-compounds possessing two potential sites of unsaturation give anthrasteroids. Thus compound (104) gives the anthrasteroids ( 105) via the spiro-cations as shown.'26 Similar conversion of 3-0xo-A~.~-dienes to to anthrasteroids and 19-nor-3-0xo-A~,~-dienesring-B aromatic steroids are de~cribed.'~~ A profound oxidative rearrangement of the compound (106) to the phenanthrene (107) is induced by DDQ treatment.12* Tetracyanoethylene reacts with 9(11)-dehydroergosteryl acetate to give the adduct ( 108).129 The 5,7,9( 11),14-tetraene intermediate in this reaction is formed J.W. Blunt I. M. Clark J. M. Evans Sir Ewart R. H. Jones G. D. Meakins and J. T. Pinhey J. Chem. SOC.(C),1971 1136. (a)K. Mori K. Abe M. Washida S.Nishimura and M. Shiota J. Org. Chem. 1971 36 231 ;(b)Y.J. Abul-Hajj Steroids 1971 18,281. I2O R. T. Blickenstaff K. Atkinson D.Breaux E. Foster Y. Kim and G. C. Wolf J. Org. Chem. 1971,36 1271. P. Toft and A. J. Liston Tetrahedron 1971 27 969. lZ2 R. Breslow and P. Kalicky J. Amer. Chem. Soc. 1971 93 3540. 123 R. Breslow and P. C. Scholl J. Amer. Chem. SOC.,1971,93 2331. J. R. Hanson Chem. Comm. 1971 1119 1343. 12' J. Libman and Y. Mazur Chem. Comm. 1971 729. J. Libman and Y. Mazur Chern. Comm. 1971 730. J. Libman and Y. Mazur Chem. Cornm.1971 1146. W. Brown and A. B. Turner J. Chem. Soc. (C),1971,2566. 129 A. Lautzenheiser Andrews R. C. Fort and P. W. Le Quesne J. Org. Chem. 1971 36. 83. 486 B. A. Marples R2 R2 R' = P-H R2= p-Me R' = /?-Me R2= P-H R' = p-Me R2 = a-H OH Ac 0 NC CN by elimination of tetracyanoethane from the originally formed ene-reaction product. Conformational effects in some epoxide rearrangements are discussed. The phenyl group in the epoxide (109) prevents the derived carbonium ion (1 10) from adopting a suitable conformation to give c-nor-D-homo-compounds and alternative products including the unsaturated aldehyde (1 1I) are obtained.' 30 The introduction of a methyl group at C-19 greatly modifies the products of rearrangement of 3P-acetoxy-Sa,6a-epoxides.Thus the products are formed through the conformation (1 12) of the carbonium ion derived from 3P-acetoxy- 5,6a-epoxy-5a-cholestane. The BF,-catalysed fragmentation of the epoxide (1 13) to the olefin (114) may have a biogenetic ~aralle1.l~~ 130 L. J. Ames A. F. H. Baines J. M. Coxon and M. P. Hartshorn Airstral. J. Chrnz. 1971 24 1899; CJ refs. 64 and 132. 13' I. G. Guest and B. A. Marples J. Chem. SOC.(C), 1971 576. 13* N. Ikekawa M. Morisaki H. Ohtaka and Y. Chiyoda Chem. Comm. 1971 1498; cJ refs. 64 and 130. Terpenoids and Steroids 487 (1131 (114) A full account of the extensive HF-catalysed backbone rearrangement of cholesterol' 33 is now available. The intermediacy of two equilibrating ion pairs [(C-5)+F-] is proposed and the formation of the 26-fluoro-compounds is envisaged through a 1,6- or 1,Shydride ion shift (115).Also full details of the similar rearrangements of a de-A-steroidal 9(1 1)-ene,'34 and of a 7-hydroxy-4- ene,' 35 have appeared. Further studies on 3or-amino-steroids are reported.' 36 (a) (115) 133 P. Bourguignon J.-C. Jacquesy R. Jacquesy J. Levisalles and J. Wagnon Bull. SOC. chim. France 1971 269. 134 J. P. Bertholet and J. Levisalles Bull. SOC.chim. France 1971 1888. 135 J.-C. Jacquesy R. Jacquesy and S. Moreau Bull. SOC.chim. France 1971 3609. 136 F. Frappier J. Thierry and F.-X. Jarreau Tetrahedron Letters 1971 1887. B. A. Marples The acid-catalysed rearrangements of androst-Sene and ~-homoandrost-5-ene gave mixtures of A8.9-compounds.'37 Thus the absence of a C-17-substituent and initial ring strain at the C/D ring junction has a profound effect.Equilibration of configurations at C-5 for the androstene derivatives and at C-5 and (2-13 for the D-homoandrostene derivatives requires the intermediacy of spiro-cations. The partial backbone rearrangement with thionyl chloride of the 9P-compound (116) to compound (117) provides evidence that such rearrangements need not be ~0ncerted.l~~ Treatment of the Westphalen diol diacetate with anhydrous 17 -4 Ac0 OAc OAc (J 16) HF induces a backbone rearrangement and a small amount of retro-Westphalen rearrangement.' 39 Similarly the 9-fluoro-compound (1 18) rearranges to the allylic alcohol (119) with BF,.14' Sulphuric acid treatment of the 17,17-dimethyl compound (120) gives the 13,17-dimethyl compound (121) by the following sequence (i) p-face protonation at C-14 (ii) P-face migration of a methyl group to C-13 and (iii) intermolecular hydride ion addition.'41 137 D.N.Kirk and P. M. Shaw Chem. Comm. 1971 948. J. M. Coxon M. P. Hartshorn and C. N.Muir Chem. Comm. 1971 659. 139 C. Berrier J.-C. Jacquesy and R. Jacquesy Tetrahedron Letters 1971 4567. 140 J.-C. Jacquesy R. Jacquesy and S. Moreau Bull. SOC.chim. France 1970,4513 14' C. Monneret P. Choay Q. Khuong-Huu and R. Goutarel Tetrahedron Letters 1971 3223. Terpenoidsand Steroids Owing to the favourable stereoelectronic arrangement and in contrast to the 17a-epimeric compounds 17fl-acetoxy-l7aa-hydroxy-17afl-methyl-~-homo-steroids dehydrate and rearrange to give the 17a,17a-dimethyl-~-homo-13-enes with a variety of acid catalysts.142 The Westphalen rearrangement reaction medium (H,SO,-Ac,O) is the most favourable for this transposition. A rearrange-ment study of &-methyl-and 4~-methyl-5a-hydroxy-compounds provides further evidence in support of a concerted methyl group migration and C-5-0 cleavage in the Westphalen rearrangement. 143 Rearrangement of the vinyl compound (122) in H2S0,-AcOH-Ac,O gave .the Ag('o)-compound (123).14 Classical ionic intermediates are proposed owing to the scrambling of deuterium labelling. AH17 HO w OAc (122) (123) The application of the rearrangement of alkyl nitrones as a useful alternative to the Beckmann rearrangement is demonstrated by the conversion of the nitrone (124)to the lactam (125).'45 Such a vinyl migration is not generally observed in the Beckmann rearrangement.The regioselectivity observed during the addition of dichloroketen to steroidal olefins is stereoelectronically ~ontrolled.'~~ Simi-larly the cleavage of the 4,5-bond in the 3fl,S-cyclocholestan-6-yl radical,' 47 and the rearrangement of the 5a-methyl-3,6-diketone (126) on silica gel to the cyclo-pentanone (127)14' are stereoelectronically controlled. Further acid-catalysed rearrangement of compound (127) surprisingly gives the aldol (128). 14' C. Monneret and Q. Khuong-Huu Bull. SOC.chim. France 1971 623. 143 J. G. L1. Jones and B. A. Marples J.Chem. SOC.(0,1971 573. 144 I. G. Guest J. G. L1. Jones and B. A. Marples Tetrahedron Letters 1971 1979. 145 D. H. R. Barton M. J. Day R. H. Hesse and M. M. Pechet Chem. Comm. 1971,945. 146 A. Hassner V. R. Fletcher and D. P. G. Hammon J. Amer. Chem. SOC.,1971,93,264. 14' A. L. J. Beckwith and G. Phillipou Chem. Comm. 1971,658. 14' R. J. Chambers and B. A. Marples Tetrahedron Letters 1971 3747. 490 B. A. Marples 161 :0J$yY0& 0 OH Trityl fluoroborate is a useful mild reagent for the removal of benzyl benzyl- oxycarbonyl tetrahydropyranyl and bismethylenedioxy protecting groups for the hydroxy-group. 149 Alternative methods are available for the regeneration of ketones from thioacetal~.'~~ Diosgenin may be degraded in good yield to 22-oxocholesterol,' 51 and dholesteryl acetate is converted in high yield to 7-oxocholesteryl acetate by a photo-oxidation employing atmospheric oxygen and mercuric bromide or N-bromosuccinimide.52 A biogenetic-like cyclization of the acetylenic triene (129) gave the tetracyclic compound (130) from which progesterone was prepared.' 53 Similarly formic acid solvolysis of the tertiary alcohols (131)154and (133)15' gave the cyclized products (132) and (134) respectively. Treatment of the allene (135) with excess 0' OH (129) p____) HC0,H 149 D. H. R. Barton P. D. Magnus G. Streckert and D. Zurr Chem. Comm. 1971 1109. I5O (a) P. R. Heaton J. M. Midgley and W. B. Whalley Chem. Comm. 1971 750; (b) W. J. Huurdeman H. Wynberg and D.W. Emerson Tetrahedron Letters 1971 3449. 151 G. A. Smith and D. H. Williams Chem. Comm. 1971,402. Is' N. Friedman M. Gorodetsky and Y. Mazur Chem. Comm. 1971 874. 153 (a)W. S. Johnson M. B. Gravestock R.J. Barry R. F. Myers T. A. Bryson and D. H. Mills J. Amer. Chem. SOC.,1971,93,4330;(b)W. S. Johnson M. B. Gravestock and B. E. McCarry ibid. p. 4332. lS4 P. T. Lansbury P. C. Briggs T. R. Demmin and G. E. DuBois J. Amer. Chem. Soc. 1971,93 1311. lS5 P. T. Lansbury and G. E. DuBois Chem. Comm. 1971 1107. Terpenoids and Steroids 491 Et EtYoCHo rn-chlorobenzoic acid leads to the pregnane (136) whereas osmium tetroxide oxidation provides the corticoid-like compound (1 37).' 56 The full account of a non-photochemical total synthesis of precalciferol is available.' '' In support of previous suggestions on the catabolism of insect moulting hor- mones it has now been shown that in Bornbyx rnori,ponasterone Ais hydroxylated to ecdysterone and inokosterone and then converted to poststerone by cleavage of the C-20-C-22 bond.'58 Acansterol (138) is a further new cyclopropane marine sterol,' 59 and 23,24-bisnor-5a-cholanic acid is the first steroid carboxylic acid to be isolated from IS' M.Biollaz W. Haefliger E. Velarde P. Crabbe and J. H. Fried Chem. Comm. 1971 1322. 57 (a)T. M. Dawson J. Dixon P. S. Littlewood B. Lythgoe and A. K. Saksena J. Chem. SOC.(0,1971,2960;(b)P. S. Littlewood B. Lythgoe and A. K. Saksena ibid.,p. 2955 (c) I. J. Bolton R. G. Harrison and B. Lythgoe ibid.,pp.2950,2944; (4T. M. Dawson J. Dixon P. S. Littlewood and B. Lythgoe ibid. p. 2352. 158 H. Hikino Y. Ohizumi and T. Takemoto Chem. Comrn. 1971 1036. Y. M. Sheikh C. Djerassi and B. M. Tursch Chem. Comm. 1971 217. 492 B. A. Marples petroleum.'60 Sterols are present in the red alga Porphyridium cruenturn,'61 and a number of withanolides of a new chemotype (Indian I) have been isolated from Withania somnifera.'62 160 W. K. Siefert E. J. Gallegos and R.M. Teeter Angew. Chem. Internat. Edn. 1971 10 747. 16' G. H. Beastall H. H. Rees and T. W. Goodwin Tetrahedron Letters 1971,4935. lb2 I. Kirson E. Glotter D. Lavie and A. Abraham J. Chem. SOC.(C),1971 2032.

ISSN:0069-3030    

DOI:10.1039/OC9716800467

出版商:RSC    

年代:1971

数据来源: RSC

摘要:

16 Atkaloids By H. F. HODSON The Wellcome Research 1aboratories Beckenham Kent BR3 3BS THIS Report is deliberately more selective than in previous years since the period under review has seen the publication of the first of the comprehensive annual Specialist Periodical Reports devoted to Alkaloids. Although this first volume covers the literature from January 1969 to June 1970 most chapters incorporate sufficient earlier references to give perspective to the newer work. Three chapters not of the annual review type are also included. One" is a timely authoritative review of studies over the past five years on the biosynthesis of the terpenoid indole alkaloids. Anotherlb provides the only comprehensive review of that fascinating group the bisindole alkaloids.The third non-recurrent chapterlc considers recent pharmacological studies and clinical applications of alkaloids. Most new alkaloids isolated during the year are either minor modifications of well-established structural types or are more remote variants which fall satisfyingly into place within accepted broad biogenetic schemes. A notable feature of the year is the number of total syntheses which incorporate new and often generally applicable annelation reactions. Several 3C n.m.r. analyses of alkaloids of established structure have been reported including gelsemine,2 nicotine and q~inine,~ amaryllidaceae type^,^,^ and steroidal alkaloids of the veratramine type ;5 by a combination of proton-decoupling techniques and consideration of chemical shifts most carbon resonances were assigned unambiguously.A study of the 3C n.m.r. spectrum of piperine6 employed Eu(dpm) as a paramagnetic-shift reagent showing the potential value of this method in 13C n.m.r. spectroscopy. 1 Pyridine and Pyrrolizidine Alkaloids Further studies'" are reported on the formation of 'unnatural' nicotine analogues by the biosynthetic incorporation of analogues of natural precursors. Thus ' (a) A. R. Battersby 'The Alkaloids' (Specialist Periodical Reports) The Chemical Society London 1970 vol. 1 p. 31; (6) A. A. Gorman M. Hesse H. Schmid P. G. Waser and W. H. Hopff ibid. p. 201 ;(c) E. Schlittler ibid. p. 464. ' E. Wenkert C.-J. Chang A. 0.Clouse and D. W. Cochran Chem. Comtn. 1970,961. W. 0. Crain jun. W. C. Wildman and J.D. Roberts J. Amer. Chem. Soc. 1971 93 990. L. Zetta G. Gatti and G. Fuganti Tetrahedron Letters 1971 4447. P. W. Sprague D. Doddrell and J. D. Roberts Tetrahedron 1971 27 4857. ' E. Wenkert D. W. Cochran E. W. Hagaman R. B. Lewis and F. M. Schell J. Amer. Chem. Soc. 1971,93 6273. ' (a)H. F. Hodson Ann. Reports (B) 1970 67 468. 493 494 H. F. Hodson feeding the appropriate pyrroline precursor analogues to Nicotiana glutinosa has provided the nicotine homologues (1 ; R' = H R2= Me) and (1 ; R' = Me R2 = H)."' Also in N. tabacum plants 5-fluoronicotinic acid is incorporated into 5-fluoronicotine (1 ; 5-flUOr0 R' = R2 = H).* Such work must eventually be of value in determining the specificity and steric requirements of the enzyme@) involved and also provides a potential general method for the preparation of close analogues of biologically active natural products.H (2) R = CH,.CH=CH*C=CH (3) R = CH2CH2-CH=C=CH2 Two remarkable acetylenic 'alkaloids' histrionicotoxin (2) and the related allene dihydroisohistrionicotoxin (3) have been isolated' from the skin of the South African arrow poison frog Dendrobates histrionicus a close relative of the species responsible for the production of the equally remarkable steroidal base batrachotoxin. lo The structure and absolute stereochemistry of (2) and (3) were deduced entirely from X-ray studies of the salts.' A synthesis' 'of the necine base ( +)-supinidine (6)depended on the formation of the pyrrolizidine system by catalytic hydrogenolysis of the isoxazolidine (4 ; R = mesyl); 0,N-cleavage was followed by spontaneous cyclization to (5).The starting alcohol (4;R = H) was readily available from the 1,3-dipolar addi- tion of methyl 4-hydroxycrotonate to the nitrone 1-pyrroline- 1 -oxide. C0,Me C02Me CH,OH 2 Isoquinoline Alkaloids A novel thermal rearrangement ' of the readily available benzocyclobutene (7) to (8) in high yield was the key step in the first reported ~ynthesis'~ (Scheme 1) ' (6) M. L. Rueppel and H. Rapoport J. Amer. Chem. Soc. 1971,93 7021. * E. Leete G. B. Bodem and M. F. Manuel Phytochemisrry 1971 10 2687. J. W. Daly I. Karle C. W. Myers T. Tokuyama J. A. Waters and B. Witkop Proc. Nut. Acud. Sci. U.S.A. 1971 68 1870; B. Witkop Experienria 1971 27 1121.lo J. A. Joule Ann. Reports (B) 1968 65 504; see also E. X. Albuquerque J. W. Daly and B. Witkop Science 1971 172 995. I ' J. J. Tufariello and J. P. Tetle Chem. Comm. 1971 469. l2 W. Oppolzer J. Amer. Chem. Soc. 1971,93 3833 3834. l3 W. Oppolzer and K. Keller J. Amer. Chem. SOC., 1971 93 3836. Alkaloids 495 of ( f)-chelidonine [10;( -)-enantiomer depicted ;( -)- ( +)- and ( +)-chelidonine all occur naturally]. Hydroboration and peroxidation of (8) gave a separable mixture of (9) and the unwanted trans-fused 4b-epimer. The synthesis was com- pleted by epimerization at C(10) uia an oxidation-reduction sequence removal of the protecting group and N-methylation to (10). I 0 (7) PhCH2*O-C0 iii-vi OH Scheme 1 Reagents i xylene 120°C; ii B,H, then H,O,; iii Cr0,-Me,CO; iv NaBH,; v H, Pd-C; vi methylation.The cyclization of (7) to (8) is only one example of a general rearrangement of unsaturated substituted benzocyclobutenes which has been studied in detail and shown to proceed via an o-quinonedimethide intermediate; in many cases e.g. (11) to (12) a high degree of stereoselectivity is observed.I2 0 bNMe (11) R' = H,R2 = C1 or R' = C1 R2 = H Considerable effort has been expended this year on the synthesis of aporphines by photochemical cyclization of bromophenolic precursors. l4 For example For an outline of earlier work in this field see S. M. Kupchan J. L. Moniot R. M. Kanojia and J. B. O'Brien J. Org. Chem. 1971,36 241 3. 496 H.F. Hodson photolysis of the phenolic bromobenzylisoquinolines (13;R' = OH,R2 = OMe ; R' = OMe R2 = H; R'R2 = OCH,.O) gave in all three cases both the aporphine (14 by path a) and the corresponding morphinandienone (15 by path b) in a combined yield of less than Other workers however report a yield of more than 50% of the aporphine (14;R' = R2 = OMe) and ,no morphinandienone by photolysis of (13;R' = R2 = OMe).I6 A second type of ring-closure has produced proaporphines such as ( f)-pronuciferine (17 ; R = and (+)-glaziovine (17; R = H)I9 by photolysis of the appropriate hydroxybenzylbromoisoquinoline (16). These types of cyclization have also been applied to phenethylisoquinoline systems to produce homoaporphines,20 homomorphinandienones,20and homoproaporphines.R2 Me Me + R2 0 Studies of the electrochemical oxidation of phenolic tetrahydroisoquinolines have shown that the results are broadly similar to those obtained in chemical and enzymatic oxidations but reactions are often cleaner and the products T. Kametani S. Shibuya H. Sugi 0. Kusama and K. Fukumoto J. Chem. Soc. (C) 1971 2446; T. Kametani H. Sugi S. Shibuya and K. Fukumoto Tetrahedron 1972 27 5375. l6 R. J. Spangler and D. C. Boop Tetrahedron Lerrers 1971,4851. T. Kametani T. Sugahara H. Sugi S. Shibuya and K. Fukumoto Chem. Comm. 1971 724; Tetrahedron 1971 27 5993. Z. Horii Y.Nakashita and C. Iwata Tetrahedron Letters 1971 1167. l9 T. Kametani H. Sugi S. Shibuya and K. Fukumoto Chem. and Ind. 1971 818; T.Kametani S. Shibuya T. Nakano and K. Fukomoto,J. Chem. SOC.(C) 1971,3818. 2o T. Kametani and M. Koizumi J. Chem. SOC.(0,1971 3976. Alkaloids 497 obtained in higher yield.2 There are however a few significant differences; for example,22 electrochemical oxidation of (18) gave not only the C(3)-C(3’) dimer previously obtained by chemical oxidation but also the dimer (19) with the skeleton of the alkaloid dauricine ; earlier attempts to obtain compounds of type (19)by chemical oxidation had been unsuccessful. Of even greater interest is the electro-oxidation of the non-phenolic benzylisoquinoline laudanosine (20) which was examined under several sets of conditions the best of which gave the morphinandienone 0-methylflavinantine (21) in 52 % yield.23 Me0qN.c02Et Me0 MeoqNMeMe0 Me0 JqOMe OMeMeoa 0 (21) Reductive cleavage with sodium in liquid ammonia has been of immense value in the structural elucidation of the ether-linked bisbenzylisoquinoline alkaloids,24 and a novel extension2’ of this method has been used to determine 21 J.M. Bobbitt K. H. Weisgraber A. S. Steinfeld and S. G. Weiss J. Org. Chem. 1970,35,2884; see also J. M. Bobbitt H. Yagi S. Shibuya and J. T. Stock ibid. 1971 36 3006. 22 J. M. Bobbitt and R. C. Hallcher Chem. Comm. 1971 543. 23 L. L. Miller F. R. Stermitz J. R. Falck J. Amer. Chem. SOC.,1971 93 5941. 24 For current examples see L. A. Mitscher W.-N. Wu R. W. Doskotch and J. L. Beal Chem. Comm. 1971,589; R. W. Doskotch and J. E. Knapp Lloydia 1971,34,292.25 M. R. Falco J. X. de Vries Z. Maccio and I. R. C. Bick Chem. Comm. 1971 1056. 498 H. F. Hodson the structure of a new alkaloid belarine (22; R = H). Cleavage of (22; R = Me) with sodium in trideuterioammonia gave a diphenol and the (largely) dideuteriated base (23) in which the position of the deuterium atoms could readily be determined by n.m.r. spectroscopy thus defining the diphenylether termini in rings B and E of belarine (22; R = H).25 H' \D 'OMe (22) (23) The preparation of (2)-cularine (25; R = Me) by a phenol-coupling route has been announced from two laboratories ;26727 in both instances alkaline ferricyanide oxidation of (24) gave the p-coupled phenol (25 ;R = H) which was methylated with diazomethane to (25; R = Me).In one case,27 however (25; R = H) was accompanied by the o-coupled phenol (26) as the major product. The two groups employed different routes to the starting diphenol (and report widely different melting-points for this compound). The sequence (24) to (25) may not necessarily represent the biosynthetic pathway to cularine; the 7,8-dioxygenated isoquinoline pattern is rare and its appearance in cularine could be accounted for by an alternative route involving open-chain bis(phenylethy1- amines) with isoquinoline ring-closure at a late stage.26 OH (24) 3 Amaryllidaceae Alkaloids A new cycloaddition reaction28 employs a 2-pyrroline-4,5-dione as a dienophile and leads to substituted tetrahydroisatins with a double bond and keto-group suitable for further functionalization.This reaction promises to find application 26 A. H. Jackson and G. W. Stewart Chem. Comm. 1971 149. 27 T. Kametani K. Fukumoto and M. Fujihara Chem. Comm. 1971 352; Bioorganic Chem. 1971 1 40. 28 Y. Tsuda K. Isobe and A. Ukai Chem. Comm. 1971 1554. A Ikaloids 499 in the synthesis of alkaloids incorporating a hydroindole partial structure such as crinine mesembrine hasubanonine and erythraline types and is exemplifiedz9 by the first total synthesis of (*)-haemanthamine [(33) as natural (+)-enan- tiomer)] an alkaloid which has played and continues to play,30 an important part in biosynthetic work on Amaryllidaceae alkaloids. Addition of butadiene to the pyrrolinedione (28) prepared and used as its ethanol adduct (27) gave a high yield of (29) which was converted by standard methods and with a high degree of stereoselectivity to the diol (30) = (31).A Pictet-Spengler cyclization of (31) gave the 5,lO-ethanophenanthridine(32; R = H) which after monotosylation to (32; R = tosyl) followed by elimination furnished ($)-haemanthamine in high yield.29 Photochemical cyclization of bromophenolic compounds (see under iso-quinolines) has also been applied to the preparation of compounds with the 1,3z For e~ample,~’ crinine ~keleton.~ irradiation of an alkaline solution of the bromophenol(34) furnished ( f)-oxocrinine (35) in a yield of about 5 %;formation 29 Y. Tsudaand K. Isobe Chem. Comm. 1971 1555. 30 A. R. Battersby J. F. Kelsey and J. Staunton Chem.Cornm. 1971 183; G. W. Kirby and J. Michael Chem. Cornm. 1971 187,415. 31 T. Kametani T. Khono S. Shibuya and K. Fukumoto Chem. Comm. 1971 774; Tetrahedron 197 1 27 544 1. 32 T. Kametani and T. Khono Tetrahedron Letters 1971 3155. H. I;.Hodson of (35) must obviously proceed via the dienone which undergoes spontaneous Michael addition. 4 Mesembrine Alkaloids The mesembrine alkaloids isolated from Sceletiurn spp. have hitherto been represented by a small but steadily growing group of bases all with the same carbon skeleton typified by mesembrine (36);despite the close structural similarity to the crinine-type Amaryllidaceae alkaloids their biosynthetic affinities are not yet clear33 and they are conveniently discussed as a separate group.A dibasic alkaloid first isolated from Channa a crude drug preparation and now from S. narnaquenseand S. tortuosurn has proved to be of a new and intriguing structural type. Sceletium Alkaloid A had veratryl and pyridine chromophores and mass-spectral fragmentations characteristic of the mesembrine bases ;34 a direct- method X-ray analysis34" established structure (37) (relative configuration). Tortuosamine also from S. tortuosurn is the corresponding seco-derivative (38). OMe OMe OMe Many syntheses of racemic mesembrine [as (36)] have been reported during the last few years but an asymmetric synthesis of this alkaloid has now been realized.35 The aldehyde (39)was prepared by standard methods and by reaction with the L-proline derivative (40),was converted to the chiral enamine (41).Annelation with methyl vinyl ketone gave a cyclohexenone enriched in the 33 P. W. Jeffs C. W. Archie R. L. Hawks and D. S. Farrier J. Amer. Chem. SOC.,1971 93 3752; P. W. Jeffs H. F. Campbell D. S. Farrier and G. Molina Chem. Cumm. 1971 228. 34 (a)P. W. Jeffs P. A. Luhan A. T. McPhail and N. H. Martin Chem. Curnrn. 1971 1466; (b)F. 0. Snyckers F. Stretlow and A. Wiechers Chem. Comm. 1971 1467. 3s S. Yamada and G. Otani Tetrahedron Letters 1971 1133. Alkaloids 50 1 enantiomer (42) which on acid hydrolysis followed by spontaneous Michael- type addition furnished an optically impure mesembrine hydrochloride from which could be obtained (+)-mesembrine enantiomeric with the natural (-)-alkaloid (36).OMe OMe OMe OoMe CHXHO I I I <.CHO n I Me (39) 5 Terpenoid Indole Alkaloids A comprehensive clas~ification~~ of monoterpenoid indole alkaloids relies on established biosynthetic pathways and in uitro interconversions together with biogenetic hypotheses ; it provides an excellent guide to the astonishing array of alkaloid structures (more than 700)formed from just two basic units tryptamine (or tryptophan) and secologanin. Two alkaloids pauridianthine and pauridianthinine from Pauridiantha callicarpoides (Rubiaceae) are formulated as (43) and (44) respectively mainly on spectroscopic e~idence.~’ A number of p-carbolines substituted with simple heterocyclic moieties have been reported recently38 but the C skeleton of the non-tryptamine portion of (43) and (44) places these new bases in a uniquely interesting biogenetic position.An intriguing structure (49 for which further evidence would be welcome is suggested for dehydr~ervatamine,~~ one of threz closely related alkaloids from Ervatamia orientalis (Apocynaceae). (43) 36 I. KompiS M. Hesse and H. Schmid Lloydia 1971 34,269. 37 J.-L. Pousset A. Bouquet A. Cave A. Cave and R.-R.Paris Compt. rend. 1971 272 C 665. 38 H. F. Hodson Ann. Reports (B) 1970 67 478. 39 J. R. Knox and J. Slobbe Tetrahedron Letters 1971 2149. 502 H. F. Hodson C0,Me G1ycosides.-One of the most interesting aspects of alkaloid chemistry during the last decade has been that concerned with the isolation and characterization of the glycosides vincoside (48)and isovincoside (= strictosidine) and the recogni- tion of the central role played by vincoside in the biogenesis of the many hundreds of monoterpenoid indole alkaloid^.^' Vincoside and isovincoside are C(3) epimers [cf.(48) and (49); indole-alkaloid numbering] in which the remaining stereochemistry is rigorously established ; vincoside but not isovincoside is known to be incorporated into alkaloids of the three main structural types and into cinchona alkaloids. On the basis of a comparison of rotational-shift differ- ences in vincoside and its derivatives with those in ipecoside and its derivatives vincoside was shown to have a C(3)configuration identical with that at the corresponding centre [C(5)] in ipecoside whose full stereochemistry had apparently been established as (47) by chemical and optical correlations with (-)-dihydro- protoemetine.Vincoside was thus assigned the 3cr-H configuration (49) which appeared to be in harmony with the biosynthetic results since vincoside but not isovincoside is known to be a precursor for Corynanthe-type alkaloids with a 3a-H configuration; the C(3)hydrogen is not lost during this transformation. . OGlu H" \o Me0,C (46) (484 (47) 5a-H (49) 3a-H 40 Ref. ](a)and references there cited. Alkaloids 503 Doubts about these formulations have been expressed,41 however and this year publications from three groups provide independent conclusive evidence that the above assignments should be reversed i.e. vincoside is (48)and isovincoside is (49).Firstly an X-ray study42 of 00-dimethylipecoside reveals that ipecoside the standard on which the rotational-shift correlations were based has the full stereochemistry (46) with a 5/3-hydrogen not 5a as previously supposed; the absolute configuration followed from the existence of an internal stereochemical standard D-glucose. Secondly,43 a glycosidic indole lactam newly isolated from Adina rubescens has been identified as vincoside lactam [(50),cf. vincoside as (48b)land by a series of hydrolytic and reductive steps converted to the triol (51). This triol was shown to be the enantiomer of a triol obtained in a predictable manner from corynantheine an alkaloid of rigorously established stereochemistry thus confirming the configuration (50) of vincoside lactam and hence that of vincoside (48).It was carefully established that no unexpected epimerizations had occurred at any stage during these transformation^.^^ In passing it may be noted that A. rubescens has also yielded a glucoside rubes~ine,~~ in which the glucose moiety of vincoside lactam is esterified by caffeic acid. Finally a meticulous chemical and spectroscopic of isovincoside (strictosidine) and derivatives incorporating two independent correlations with antirhine of known stereochemistry leaves no doubt that this glucoside has the 3a-H orienta-tion (49). The above results lead to the surprising conclusion that at an early stage in the biosynthesis of monoterpenoid indole alkaloids from their glycosidic precursor46 there is an inversion of stereochemistry at C(3)with retention of the C(3)hydrogen; a similar inversion must also take place during biosynthesis of 41 E.g.Ref. l(a),p. 42; A. I. Scott Bioorganic Chemistry 1971 1 157; Ref. 50 footnote 13. 42 0. Kennard P. J. Roberts N. W. Isaacs F. H. Allen W. D. S. Motherwell K. H. Gibson and A. R. Battersby Chem. Comm. 1971 899. 43 W. P. Blackstock R. T. Brown and G. K. Lee Chern. Comm. 1971 910. 44 W. P. Blackstock and R. T. Brown Tetrahedron Letters 1971 3727. 45 K. T. D. De Silva G. N. Smith and K. E. H. Warren Chem. Comm. 1971,905. 4b A. R. Battersby and K. H. Gibson Chem. Comm. 1971,902. 504 H. I;.Hodson the ipecac alkaloid^.^' Further developments in this area are awaited with interest.An amorphous amino-acid glycoside from Rhazya orientalis has been characterized as a 5-carboxyisovincoside (52).“* Partial synthetic studies were instrumental in establishing the depicted stereochemistry ;condensation between secologanin (53) and L-tryptophan gave the natural glycoside together with its C(3) epimer thus fixing the C(5)chirality; secologanin and D-tryptophan gave another pair of epimers and comparative studies with all four diastereoisomers defined the C(3) stereochemistry. The natural occurrence of a tryptophan-derived glycoside is interesting. Although tryptamine is known to be incorporated into many indole alkaloids via vincoside it has been pointed out that in the tryptophan analogues like (52) the 5-carboxy-group could well provide the activation necessary for ring-closure on to C(5) in the biosynthesis of alkaloids like ajmaline ;indeed last year’s biogenetically modelled synthesis of ajmaline49 provided a laboratory analogy for this step.CorynanthbStrychnosTypes.-Talbotine (54) the principal alkaloid of Pleiocarpa talbotii is unlike other alkaloids from Pleiocarpa spp. and presents a new but perhaps not surprising mode of incorporation of the unrearranged Corynanthe- type terpenoid skeleton. N.m.r. and i.r. studies on this hemiacetal alkaloid and its derivatives led to the depicted structure and relative stereochemistry which were fully in accord with the observed mass-spectral fragmentation^.^' An optical correlation of talbotine based on the then-accepted 3a-configuration 4’ A.R. Battersby and R. J. Parry Chem. Comm. 1971 901. 48 K. T. D. De Silva D. King and G. N. Smith Chem. Comm. 1971 908. 49 H. F. Hodson Ann. Reports (B) 1970,67,481. 50 M. Pinar M. Hanaoka M. Hesse and H. Schmid Helv. Chim. Acta 1971 54 15. Alkaloids 505 for vincoside indicated that talbotine should have the 3P-orientation ; the established relative stereochemistry then required that C(15) would also have the fi-configuration in conflict with the almost universal cr-configuration of this centre in the indole alkaloids.36 Further work,” however demonstrated con- clusively that the absolute configuration is (54) and the optical correlation is thus in line with the revised C(3) orientations in vincoside and isovincoside.Ochrolifuanines A and B (55),5 two isomeric amorphous bases from Ochrosia lifuana (Apocynaceae) are indole analogues of emetine and examples of a structural type hitherto unencountered in natural products surprisingly in view of their simple formal derivation from basic biogenetic building blocks. The molecular formula C2,H3,N2 of ochrolifuanine A and the presence of two indole chromophores and of a C-ethyl group (n.m.r.) immediately suggest a structure biogenetically derived from two tryptamine units and one C,-mono- terpenoid unit. This was supported by other spectroscopic studies with compel- ling evidence from the mass spectrum which exhibited four principal peaks at m/e 267 253 185 and 171 [cJ (55)]. The presence of Bohlmann bands in the i.r.spectrum indicated the presence of a trans-quinolizidine system ;assuming the 15a-H configuration on biogenetic grounds this suggested the 3cr-H orientation depicted. From n.m.r. evidence ochrolifuanine B appears to be the C, epimer of ochrolifuanine A. A completely unrelated species Strychnos usambarensis (Logianaceae) has yielded a new alkaloid usambarine of the same skeletal type; spectroscopic data were in accord with its formulation as (56).52 N-Benzoylmeroquinene (57 cis) and its trans-isomer prepared in connection with synthetic studies in the quinine series (see later) have been converted to the esters (58a*) which incorporate the well-known Corynanthe-type mono- terpenoid carbon skeleton. In parallel syntheses alkylation of (58a-c) with tryptophyl bromide followed by oxidative cyclization gave the four racemic heteroyohimbane alkaloids ajmalicine (59a) 19-epiajmalicine (59b) tetrahydro- alstonine (59c) and akuammigine (59d).53 ’’ N.Peube-Locou M. Koch M. Plat and P. Potier Compt. rend. 1971 273 C 905. 52 M. Koch and M. Plat Compt. rend. 1971 273,C 753. 53 J. Gutzwiller G. Pizzolato and M. Uskokovic J. Amer. Chem. Soc. 1971 93 5907. 506 H. F. Hodson COPh I H I H' (57) (58) a; P-H a-Me (59) a; 3a-H 20P-H 19a-Me b; P-H p-Me b; 3a-H 20P-H 19p-Me c ;a-H a-Me c; 3a-H 20a-H 19a-Me d; 3P-H 20a-H 19a-Me Gardnerine (60) from Gardneria nutans is a new alkaloid with a unique cyclic imidoester function and several other unusual features. The full structure and absolute stereochemistry followed from an X-ray studys4 on the von Braun- cleavage product although the main structural features had already been recognized by degradative and spectroscopic ~tudies.~ Mild hydrolysis of gardnerine gave the oxindole (61; R = H) the tosylate (61; R = tosyl) of which regenerated gardnerine on treatment with base ;this surprisingly ready O-alkyla- tion of the oxindole lactam function is obviously assisted by the favourable rigid steric environment.Gardnerine can thus be formally derived from an oxindole with a sarpagine-like monoterpenoid skeleton voachalotine o~indole~~ being hitherto the sole example of this type. Other features worthy of note are the OMe 18 OMe 54 N. Aimi S. Sakai Y. Iitaka and A. Itai Tetrahedron Letters 1971 2061.55 S. Sakai N. Aimi A. Kubo M. Kitagawa M. Shiratori and J. Haginiwa Tetrahedron Letters 197 1 2057. 56 Ref. 1 p. 177. Alkaloids 507 unusual 4,5,7-trimethoxyindole substitution and for an indole alkaloid the unexpected configuration of the C(19)=C(20) double bond with C(18) cis to C(21). Aspidospema Types.-Alstonisidine (62) from Alstonia muelleriuna is a bisindole alkaloid in which two well-known monomeric types resembling macroline (cf. A) and quebrachidine (cf. B) are linked in a novel manner.s7 Structure (62) (no stereochemistry assigned) was derived mainly from spectroscopic data the mass spectra being particularly informative revealing highly characteristic fragments from both ‘halves’. HO C0,Me An X-ray studys8 of obscurinervine (63)has confirmed the previously proposed unique heptacyclic structure of this and closely related alkaloids from Aspido-sperrna obscurineruum ;such confirmation was thought necessary because recent observationss8 raised doubts about the validity of the semi-synthetic sequence on which the novel dihydro-1,4-oxazine ring structure was based.The highly functionalized Aspidosperma alkaloid vindorosine (69) has been synthesizeds9 (Scheme 2) by a method which illustrates a new general approach to this pentacyclic system. The key step was a cyclization of the N-acetyl-trans- enamino-ketone (64) to a tetracyclic ketone deacetylation of which gave the most stable diastereoisomer (65); condensation with acrolein and dehydration of the resulting mixture of epimeric ketols then furnished the pentacyclic ketone (66).Standard methods were used to transform (66) to the /?-ketoester (67) the anion of which was oxidized by hydrogen peroxide in a stereospecific manner to give (68). The synthesis was completed by reduction to a separable mixture of epimeric diols and monoacetylation of the required epimer to give (+)-vindoro- sine (69). 57 J. M. Cook and P. W. LeQuesne J. Org. Chem. 1971,36 582. J. Kahrl T. Gebreyesus and C. Djerassi Tetrahedron Letters 1971,2527. 59 G. Biichi K. E. Matsumoto and H. Nishimura J. Amer. Chem. SOC.,1971,93 3301. 508 H. F. Hodson NAc lo I Me Me Me Scheme 2 6 Quinoline Alkaloids Biogenetically Derived from Indoles Since the isolation and structure determination of camptothecin some five years ago its unique structure and potent anti-tumour and antileukaemic activity have provided a powerful stimulus to synthetic efforts.Hitherto all such efforts6' have been unsuccessful many foundering in the later stages connected with the construction of the labile ring E a-hydroxylactone moiety but now two syntheses of (*)-camptothecin (79) have been announced.6f~62 The success of the first synthesis61 depended on an elegant new annelation reaction ;addition-cyclization of the ethyl carbonate (72) of an a-hydroxyester to the ap-unsaturated lactam (71) gave a pentacyclic lactam (73) with all the necessary carbon nitrogen and oxygen atoms. After hydrolysis to the acid (74) only a reduction-dehydrogenation-reduction sequence [via (75)-+(76)-+ (77)+(78)] was required to produce ( 2)-camptothecin (79).The required starting lactam was obtained by conventional methods via the diketone (70) which was inde- pendently prepared by another group63 in connection with a projected campto- thecin synthesis. 6o Listed in ref. 62. G. Stork and A. G. Schultz J. Amer. Chem. SOC. 1971,93,4074. 62 R. Volkmann S. Danishefsky J. Eggler and D. M. Solomon J. Amer. Chem. Soc. 1971,93 5576. 63 T. K. Liao W. H. Nyberg and C. C. Cheng J. Heterocyclic Chem. 1971,8 373. Alkaloids 509 EtCH.CO,Et 0 dC0,Et (72)) 0-1:::21.. Et0,C C02Et 0 Et HO (70) 0 (74) (75) R = H (77) R = AC (76) R = AC (78) R = H The second synthesis,62 very different in concept embodied a new a-pyridone- forming reaction ;64 condensation of the enamine (80)with dicarbomethoxyallene gave the or-pyridone triester (81) which was transformed to (82) in a series of conventional reactions.A Friedlander condensation between (82) and o-amino- benzaldehyde furnished the tetracycle (83)which was converted to (84);hydroxy-methylation than gave (+)-desoxycamptothecin (79 ; H instead of OH) the anion (KOBu' in Bu'OH-DMSO) of which could be oxidized to (_+)-campto- thecin (79) with hydrogen peroxide. '' S. Danishefsky S. J. Etheredge R. Volkmann J. Eggler and J. Quick J. Amer. Chem. SOC.,1971 93 5577. 510 H. F. Hodson ,CO,Et C II C C0,Et II C EtO (80) Et0,C’ (81) 9q t / / H0,C Et H C02H CO,H (84) (83) Another different approach to the camptothecin system is inspired by the biogenetic consideration that the alkaloid is almost certainly derived from I indole-alkaloid precursors.Following a demonstration6’ that substituted indoles can be autoxidized (K0Bu‘-DMF) in high yield to quinolones the model lactams (85) were thereby converted to (86); chlorination (86) with thionyl chloride was accompanied by ring D dehydrogenation to give compounds (87) with the full camptothecin chromophore.66 Following the synthesis of quinine reported last year further work in this area is reported by the Roche group. The original synthesis proceeded via N-benzoyl- meroquinene (88)for which an alternative preparati~n,~’ starting from P-collidine has now been devised ;new preparations of the trans-isomer and the corresponding 65 E.Winterfeldt Annalen 1971 745 23. 66 E. Winterfeldt and H. Radunz Chem. Comm. 1971 374. 67 M. R. Uskokovic C. Reese H. L. Lee G. Grethe and J. Gutzwiller J. Amer. Chem. SOC.,1971 93 5902. Alkaloids 51 1 0 R' (85) c1 dihydro-derivatives are also described. Another synthesis6* of quinine and quinidine again utilized (88) but differed from previous routes in that (88) was converted (Scheme 3) to a completely functionalized quinuclidine derivative (89) before incorporation of the quinoline portion of the molecule. Scheme 3 Reagents I BuiAlH and rebenzoylation; ii C1,CHLi; iii KOH. 7 Terpenoid Alkaloids I3Cn.m.r. spectroscopy played the major role in assigning a structure to arenaine a new monoterpenoid guanidine from the seeds of Plantago arenaria.A compari- son of noise-resonance decoupled and single-frequency decoupled spectra and a consideration of chemical-shift values led directly to the gross structure of (90); G. Grethe H. L. Lee T. Mitt and M. R. Uskokovic J. Amer. Chem. Soc. 1971 93 5904. 512 H. F. Hodson the illustrated relative stereochemistry followed from p.m.r. studies.69 An X-ray study has shown that the highly oxygenated vakognavine from Aconitum palmatum is a unique example of an N-C(19) secoditerpene alkaloid. The base exists as (91) with the free aldehyde group spectroscopically discernible whereas the salts have the quaternary carbinolamine structure (92).70 0 Me O T ” H H 0 H Me Me NH 1 ‘CH20R2 OH -coQ (94) R’ = X R2 = AC (95) R’ = H R2 = X X (96) R’= RZ= H 69 A.Rabaron M. Koch M. Plat J. Peyroux E. Wenkert and D. W. Cochran J. Amer. Chem. SOC.,197 1,93,6270. ’O S. W. Pelletier K. N. Iyer L. H. Wright M. G. Newton and H. Singh J. Amer. Chem. SOC.,1971 93 5942. Alkaloids 513 Last year two novel bases from Maytenus ovatus (Celestraceae) were shown to be nicotinoyl esters of a highly oxygenated se~quiterpenoid.~~ Now it has been shown that evonine (93),first isolated from Euonymus europaea (also Celectraceae) ten years ago is an alkaloid of the same general type its structure and relative stereochemistry following from extensive degradative and spectroscopic st~dies.~,,~~ Three other bases from E.sieboldiana are closely related and have been correlated with e~onine.~~ Two new alkaloids from Euphorbia millii are also terpenoid molecules with a basic ‘handle’; they are milliamines A and B [(94) and (95) re~pectively],~’ unusual basic esters of the diterpene ingenol (96) which was isolated for the first time last year (from another Euphorbia species) as an ester of hexadecanoic acid. 8 Miscellaneous Alkaloids Eight new closely related alkaloids from the leaves of Elaeocarpus kaniensis are minor variants of e.g.,elaeokanine A (99)or elaeokanine E (98).76All alkaloids previously isolated from Elaeocarpus spp. have the same basic skeleton exemplified by elaeocarpiline (97) and are conceivably biogenetically derived from ornithine and a C, polyketide.The new bases could similarly originate from ornithine and a C polyketide chain. Two other new alkaloids have novel structures also suggestive of a polyketide origin. The structure and absolute configuration of porantherine (100) from Poranthera corymbosa were established by an X-ray and the structure proposed for the isoquinoline ancistrocladine (101) was based on extensive degradative and spectroscopic The seeds of several species of Lunaria (Crucifereae) are well known as the hitherto unique source of a small group of closely related alkaloids exemplified by lunarine (102) which almost certainly arise by combination of a spermidine- like amine with a dicarboxylic acid formed by phenol coupling of two phenyl- 7’ H.F. Hodson Ann. Reports (B) 1970 67 485. 72 H. Wada Y. Shizuri K. Yamada and Y. Hirata Tetrahedron Letters 1971 2655; Y. Shizuri H. Wada K. Sugiura K. Yamada and Y. Hirata ibid. 2659 3131. 73 M. Pailer W. Streicber and J. Leitich Monatsh. 1971 102 1873. ’4 K. Sugiura Y. Shizura H. Wada K. Yamada and Y. Hirata Tetrahedron Letters 1971 2733. 75 D. Uemura and Y. Hirata Terrahedron Letters 1971 3673. 76 N. K. Hart S. R. Johns and J. A. Lamberton Chem. Comm. 1971,460. 7’ W. A. Denne S. R. Johns J. A. Lamberton and A. McL. Mathieson Tetrahedron Letters 1971 3 107. ’’ T. R. Govindachari and P. C. Parthasarathy Tetrahedron 1971 27 1013. 514 H. F. Hodson OMe OMe propide units.'".Surprisingly the bark of a completely unrelated species Codonocarpus australis (Phytolaccaceae) has furnished an alkaloid codono- carpine formulated as (103) (or this structure with the spermidine portion reversed)" which has obvious close biogenetic affinities with lunarine and its congeners. H H I H I HN-A-N yo oTT/-o H OMe OMe '9 C. Poupat and G. Kunesch Cornpt. rend. 1971 273,C,433. R. Doskotch A. B. Ray and J. L. Beal Chem. Comm. 1971 300.

ISSN:0069-3030    

DOI:10.1039/OC9716800493

出版商:RSC    

年代:1971

数据来源: RSC

摘要:

17 Aromatic Compounds By H. HEANEY Department of Chemistry The University of Technology Loughborough Leicestershire. LEI 7 3TU 1 General The concept of aromaticity has been discussed again.' Is it an outmoded concept or can one still conveniently classify compounds usefully in this way? The invited lectures at the international symposium on non-benzenoid aromatic compounds held in Sendai have been published,2 as have the proceedings of symposia held in Jer~salem,~ Aro-and at the I.U.P.A.C. congress in B~ston.~ maticity and the relevance to pericyclic reactions has been re~iewed,~ as has the Mobius-Hiickel concept.6 Hindered rotation about the sp2-sp3 carbonsarbon bonds in a number of bisdichloromethylbenzenes has been reported. The barrier (AG * = 17.7 kcal mol-') was particularly high in the case of the octachloro-o-xylene derivative (l).7For the rneta-isomer' three conformers were indicated by the low-tempera- ture n.m.r.spectra and two conformers for the para-is~rner.~ Relatively high energy barriers to rotation also exist in compounds such as (2)." While space- filling models suggest that severe hindrance to the rotation of the t-butyl groups in (3) should be observed no evidence was found in the n.m.r. spectrum even H ' J. F. Labarre and F. Crasnier Fortschr. Chem. Forsch. 1971 24 33. ' Papers in Pure Appl. Chem. 197 1 28 pp. 11 1-398. ' 'Aromaticity Pseudo-Aromaticity and Anti-Aromaticity,' Israel Academy of Sciences and Humanities Jerusalem 1971. Papers in Pure Appl. Chem.1971 28 supplement. M. J. S. Dewar Angew. Chem. Internat. Edn. 1971 10 761. H. E. Zimmerman Accounts Chem. Res. 1971,4 272. V. Mark and V. A. Pattison Chem. Comm. 1971 553. J. Peeling B. W. Goodwin T. Schaefer and C. Wong Canad. J. Chem. 1971,49 1489. B. H. Barber and T. Schaefer Canad. J. Chem. 1971,49 789. lo A. Mannschreck and L. Ernst Chem. Ber. 1971 104,228. 515 516 H. Heaney at -80 "C.l1 This result was ascribed to an in-plane bending of the t-butyl groups away from the phenyl substituent. The energy barrier to ring inversion in 2-(1-hydroxy-1-methylethy1)tetraphenylene has been studied and is very low compared with the barrier in cyclo-octatetraene. l2 The result was interpreted as indicating a decrease in the anti-aromaticity of the planar transition state involved in the inversion compared with the anti-aromaticity in planar cyclo- octatetraene.Protonation of aromatic aldehydes by HS0,F-SbF substantially increases the barrier to rotation about the aryl-to-carbonyl carbon bond versus that observed in the boron trifluoride c~mplexes.'~ Similar effects have also been observed in related system^.'^ Results of other studies of inversions and rotations at nitrogen' and in carbon-carbon systems16 have also appeared. The asymmetric syntheses of hexa-' and octa- and nona-helicene18 have been reported by the photocyclization of the appropriate diarylethylenes using circularly polarized light. It was shown that the optical activity did not result from partial asymmetric photodestruction.The spontaneous resolution of racemic 1,l'-binaphthyl has been achieved by heating the solid at temperatures between 105-1 50 "C. Partial resolution was also achieved during the solidifi- cation of molten samples." The chiral binaphthyl derivative (4) is readily resolved and has been used with bases some of which are normally difficult to I' B. Miller and K.-H. Lai Tetrahedron Letters 1971 2957. H. P. Figeys and A. Dralants Tetrahedron Letters 1971 3901. l3 R. Jost P. Rimmelin and J. M. Sommer Chem. Comm. 1971 879. l4 M. Rabinovitzand A. Ellencweig Tetrahedron Letters 197 1,4439; R.Jost P. Rimmelin and J. M. Sommer ibid. p. 3005. W. J. Deloughry and I. 0. Sutherland Chem. Comm. 1971 1104; M. J. S. Dewar and W. B. Jennings J. Amer. Chem.Soc. 1971 93 401 ; C. H. Bushweller J. W. O'Neil and H. S. Bilotsky ibid. p. 543; C. H. Bushweller and J. W. O'Neil Tetrahedron Letters 1971 347 1. I6 G. Markl F. Lieb and C. Martin Tetrahedron Letters 1971 1249; D. Y. Curtin P. E. Bender and D. S. Hetzel J. Org. Chem. 1971 36 565; M. Oki and M. Suda Bull. Chem. SOC.Japan 1971,44 1876; M. Oki and N. Nakamura ibid. p. 1880. A. Moradpour J. F. Nicoud G. Balavoine H. Kagan and G. Tsoucaris J. Amer. Chem. Soc. 1971,93 2353. l8 H. Kagan A. Moradpour J. F. Nicoud G. Balavoine R. H. Martin and J. P. Cosyn Tetrahedron Letters 197 1 2479. l9 R. E. Pincock and K. R. Wilson J. Amer. Chem. Soc. 1971,93 1291. 2o J. Jacques C. Fouquey and R. Viterbo Tetrahedron Letters 1971 4617. Aromatic Compounds 2 Benzene and Derivatives Mechanistic aspects of electrophilic substitutions which are of current interest have been reviewed.2 Fluorine hyperconjugation in aromatic systems has been reviewed22 and the major conclusion is reached that it is unimportant as a primary factor.A model based on polar (inductive) effects best describes sub- stituent effects of perfluoroalkyl groups. Spirodiene rearrangement^^^ and the synthesis of quinones which have a heterocyclic ring directly fused to the quinone moiety24 have been reviewed. The deuteriation of the aromatic ring of benzyldicarbonyl-n-cyclopentadienyl-iron occurs more readily than the deuteriation of anisole under comparable conditions and this suggests that the group -CH2-Fe(CO),-n-C,H is more electron releasing than is the methoxy-gro~p.~~ Partial rate data have been reported for the nitration of p-halogenoanisoles.In acetic anhydride attack para to the methoxy-group occurs to the extent of 40 31 and 28% of total attack in the series p-iodo- p-bromo- and p-chloro-anisole.26 The so-called ips0 partial rate factors for iodine bromine and chlorine are 0.18 0.07, and 0.06,. Evidence for a field effect in aromatic nitration has been adduced from the rates of nitration of 3,8-diaza[ lO]cyclophane and a related open-chain compound. The rate for the cyclophane is lower by a factor of 200.27 Except for alkylation sulphonation and iodination electrophilic substitution in aro- matic compounds is normally regarded as being irreversible ; however the bromination of NN-dialkylanilines has been shown to be reversible.Thus o-bromo-NN-dimethylaniline hydrobromide gave a mixture of products including NN-dimethylaniline and p-bromo-NN-dimethylaniline when heated at 120 "C in chloroform.28 The debromination step presumably involves the ion (5) as shown. (5) Electrophilic substitutions of aromatic compounds which proceed by way of addition-elimination reactions were mentioned in last year's report.29 Thus 5-substituted-hemimellitenesand 4-substituted-o-xylenes react with nitric acid- acetic anhydride to give 4-nitrocyclohexa-2,5-dienones in addition to normal 21 G. A. Olah Accounts Chern. Res. 1971 4 240; J. H. Ridd ibid. p. 248. 22 D. Holtz Chem. Rev. 1971 71 139. 23 D. H. Hey Quarr. Rev. 1971 25 483.24 I. Baxter and B. A. Davis Quart. Rev. 1971 25 239. 25 S. N. Anderson D. H. Ballard and M. D. Johnson Chern. Comm. 1971 779. 26 C. L. Perrin and G. A. Skinner J. Amer. Chem. SOC.,1871,93 3389. 27 G. Mossa A. Ricci and J. H. Ridd Chern. Comm. 1971 332. '* F. Effenberger and P. Menzel Angew. Chem. Internat. Edn. 1971 10,493. 29 H. Heaney Ann. Reports (B) 1970 67 331. 518 H. Heaney substitution product^.^' For example the dienone (7) was isolated in 73% yield from (6). The nitration of polyalkylbenzenes with fuming nitric acid leads to ring and side-chain substitution products together with small amounts of dinitrocyclohexenones ; thus ethylmesitylene affords (8) as a minor (2-4 %) prod~ct.~The chlorination of 3,4-dimethylphenolY 3,4-dimethylphenyl acetate (7) or 3,4-dimethylphenyl methyl ether in acetic acid gives the enone (9) which decomposes first to the dienone (10) and then to the phenols (11) and (12).32 Aromatic compounds undergo methylthiolation by treatment with methyl methanethiosulphonate in the presence of aluminium chloride.However since the introduction of an RS group activates the product to further electrophilic substitution di- and poly-substitution occurs readily.33 0 c1 Me Me Me Me C1 Me C1 Me (9) Reactions of aromatic compounds with thallium salts continue to attract attention.34 Arylthallium(II1) compounds have been shown to form biaryls when allowed to react with PdCl in acetic acid containing sodium acetate.35 The role of the sodium acetate may involve the formation of Pd" species which is more efficient than PdCl in the coupling reaction.Acetophenone and a number of its derivatives have been converted in good yield into methyl phenylacetate 30 D. J. Blackstock M. P. Hartshorn A. J. Lewis K. E. Richards J. Vaughan and G. J. Wright J. Chem. SOC.(B) 1971 1212. 31 H. Suzuki M. Sawaki and R. Sakimoto Chem. Comm. 1971 1509. 32 P. B. D. de la Mare and B. N. B. Hannan Chem. Comm. 1971 1324. 33 J. K. Bosscher E. W. A. Kraak and H. Kloosterziel Chem. Comm. 1971 1365. 34 K. Ichikawa S. Uemura T. Nakano and E. Uegaki Bull. Chem. SOC.Japan 1971 44,545; S. Uemura K. Sohma M. Okano and K. Ichikawa ibid. p. 2490; A. McKillop J. D. Hunt M. J. Zelesko J. S. Fowler E. C. Taylor G. McGillivray and F. Kienzle J.Amer.Chem.SOC., 197 1,93,484 1 ;E. C. Taylor F. Kienzle R. L. Robey A. McKillop and J. D. Hunt ibid.,p. 4841 ;A. McKillop 0.H. Oldenziel B. P. Swann E. C. Taylor and R. L. Robey ibid. p. 7331 ; K. L. Erickson and H. W. Barowsky Chem. Comm. 1971 1596. 35 S. Uemura Y. Ikeda and K. Ichikawa Chem. Comm. 1971 390. Aromatic Compounds 519 (or derivatives) using thallium(rI1) nitrate in acidic methanol.36 1,2-Aryl migra- tion occurs in an intermediate such as (13) which is formed by the oxythallation of the enol form of the initial ketone. OMe o-Quinone methide has been generated by the photolysis of the compounds (14) and (15),37 and is stable at -196 0C.38The nucleophilic cyclization of an enol ether unit on to an o-quinone methide has been used in the formation of carpanone (18).39 The required precursor (17) was obtained by the phenolic coupling of (16) using palladium dichloride and led to the direct isolation Me HI M.p7 of (18).This brilliant synthesis results in the generation of five contiguous asym- metric centres. Cyclization of the quinone methide (20) has been suggested to account for the base-catalysed formation of (21)from (19)."' Similarly the forma- tion of (25) at 250 "Cfrom (22) proceeds as shown.41 36 A. McKillop B. P. Swann and E. C. Taylor J. Amer. Chem. SOC.,1971 93 4919. 37 0.L. Chapman and C. L. McIntosh Chem. Comm. 1971 383. 38 C. L. McIntosh and 0.L. Chapman Chem. Comm. 1971,771. 39 0. L. Chapman M. R. Engel J. P. Springer and J. C. Clardy J.Amer. Chem. SOC. 197 1,93,6696. 40 E. E. Schweizer T. Minami and D. M. Crouse J. Org. Chem. 1971 36 4028. 41 R. Hug Gy. Frater H.-J. Hansen and H. Schmid Hefu. Chim. Acta 1971 54 306. 520 H. Heaney O-(CH,),-$R Br Me Me 25 + rapid 1 CIAR& R2 OR2 R' R2 (24) Intramolecular cycloadditions to o-quinodimethanes also proceed in high yield. Thus after heating the benzocyclobutene derivative (26) in toluene at 190 "C the product (28) was isolated in 85 % yield. The results obtained in a number of reactions support the view that for example the intermediate (27) is involved in the formation of (28);42this principle has been applied to the The full account of the generation and synthesis of racemic ~helidonine.~~ reactions of 1,3-diphenylisoindenone has appeared.44 o-Benzoquinone 0-phenylene sulphite and o-phenylene carbonate are known to afford the dimer of cyclopentadienone on pyrolysis.45 The deposition of the pyrolysis products 42 W.Oppolzer J. Amer. Chem. SOC.,1971 93 3833 3834. 43 W. Oppolzer and K. Keller J. Amer. Chem. SOC. 1971 93 3836. 44 J. M. Holland and D. W. Jones J. Chem. Suc. (0,1971 608. 45 D. C. De Jongh R. Y. Van Fossen and C. F. Bourgeois Tetrahedron Letters 1967 271. Aromatic Compounds 521 on an i.r. plate at -196°C has enabled the monomer to be observed.46 3,4,6- Trimethyl-1,2-benzoquinoneforms the dimer (30) when a chloroform solution is left at room temperat~re.~~ It is presumably formed via the quinone methide (29). The isomerization of hindered quinone methides such as (31) to alkenyl phenols e.g.(32) can be achieved rapidly in quantitative yield on neutral alu- mina.48 Stable 0-and p-naphthoquinone methides have been isolated and are 0 0 0 OH Me Me Me present as glucosides in the insect Aphis nerii4’ The synthesis of compounds in the triquinocyclopropane series was reported last year. The tetraquinocyclo- butane (34) has now been prepared by the thermal dimerization of the diquino- ethylene (33).” 0 C II C 0 Rearrangements of methylene cyclohexadienes bearing allyl or benzyl groups at the quaternary carbons should be capable of proceeding by symmetry-allowed concerted pathways. However the deuteriated compound (35) gave (36) in which complete equilibration of the ends of the allyl group had taken place and strongly suggesting a radical chain mechanism in which the allyl radical 4h 0.L. Chapman and C. L. McIntosh Chem. Comm. 1971 770. 47 M. F. Ansell and A. J. Bignold Chem. Comm. 1971 1562. 48 D. Braun and B. Meier Angew. Chem. Internar. Edn. 1971 10 566. 49 K. S. Brown and U. Weiss Tetrahedron Letters 1971 3501; K. S. Brown and P. M. Baker ibid. p. 3505. S. Koster and R. West Chem. Comm. 1971 1380. 522 H. Heaney MebMe Me Me\ Me Me D' (35) (37) is the chain carrier.51 The benzyl analogue (37) could only be observed by n.m.r. spectroscopy and it rearranges very rapidly to (38) also by a radical mechanism. Reaction of either the dienol (39) or the semibenzene (40) with 1% sulphuric acid in ahetic acid for 10 min gave the normal ally1 migration product (41).52 However over an extended period (20 h) using 10 % sulphuric acid the compounds (39) (40) and (41) each gave identical mixtures of (42H45).The & Mea Me Me Me (42) (43) Me Me (44) (45) surprising conclusion concerning these rearrangements is that migration of the poorest migrating group occurs. Initial protonation must occur predominantly on the carbon flanked by two methyl groups and molecular models indicate that steric strain is most effectively relieved by this process. The tosyl hydrazones (46; R = H or Me) rearrange in the presence of acids to (47; R = H or Me). The [3~,3s]-sigrnatropic shift is analogous to the dienimine-aniline type.53 51 B. Miller and K.-H. Lai Tetrahedron Letters 1971 1617. 52 K.-H. Lai and B. Miller Tetrahedron Letters 1971 3575. 53 M. Schmid H.-J. Hansen and H. Schmid Helv. Chim.Acta 1971 54 937. Aromatic Compounds ,NHTs IdNHTs HN R Me (46) (47) The monoethers of hydroquinone and catechol which are hindered towards aromatic electrophilic substitution are efficiently cleaved to the corresponding quinones and alcohols on treatment with nitrous acid.54 Thus 4-benzyloxy-2,6-di-t-butylphenol is converted smoothly into benzyl alcohol and 2.6-di-t-butylbenzoquinone. "0-Labelling experiments showed that the intermediate (48) fragments to the cation (49) which affords the quinone in the aqueous II (48) 0 (49) medium. The preparation of substituted 2,5-diamino-p-benzoquinonesby established methods in good yield is not easy.It has now been reported55that the oxidative amination of p-hydroquinones using sodium iodate in the presence of the appropriate amine gives very good yields. Indane-5,6-quinone tetrahydronaphtho-2,3-quinone, and 4,5-dimethylbenzo-1,2-quinone each react with cyclopentadiene to afford adducts in which the diene behaves as the dien~phile.~~ With a number of other o-benzoquinonesand cyclo-pentadiene the quinone acted as both the diene and the dien~phile,~' and the two products underwent intramolecular Cope interconversions. With acyclic dienes the quinone always acts as a dienophile. Using tetrachloro-or tetrabromo-o-ben~oquinone~~' acyclic dienes add to one of the carbonyl groups.For example with 2,3-dimethylbuta-l13-diene the spirodihydropyran (50) was obtained. In benzene at 80 "C (50)was converted as expected into (51) whereas in the pre-sence of 2,3-dimethylbuta-1,3-dienethe bis-adduct (52) was obtained. Treatment of the p-nitrobenzenediazonium ion with sodium methoxide in methanol affords nitrobenzene in high yield. Evidence has been presented5' 54 D. H. R. Barton P. G. Gordon and D. G. Hewitt J. Chem. Soc. (C) 1971 1206. " W. Schafer and A. Agnado Angew. Chem. Internat. Edn. 1971 10 405. 56 W. M. Horspool P. Smith and J. M. Tedder J. Chem. Soc. (C) 1971 1638. 57 (a)M. F. Ansell A. F. Gosden V. J. Leslie and R. A. Murray J. Chem. SOC.(C),1971 1401; (b) M. F. Ansell A. J. Bignold A. F. Gosden V.J. Leslie and R. A. Murray ibid. p. 1414; (c) M. F. Ansell and V. J. Leslie ibid. p. 1423. 58 W. J. Boyle T. J. Broxton and J. F. Bunnett Chem. Comm. 1971 1469. 524 H. Heaney Me c1 Me Me which supports the view that the initial product is the cis-p-nitrophenylazo- methyl ether which reacts further by a free-radical mechanism to form the nitro- benzene. The reduction of aryl diazonium salts by means of borohydride has been shown to proceed by way of aryldia~enes.~~ The diazotization of 2-amino- tetrafluorophenol in 70 % aqueous sulphuric acid gave l-diazotetrafluoro-benzene-2-oxide(53) in virtually quantitative yield.60 The decomposition of the diazo-oxide in the presence of dipolarophiles leads to the formation of products derived from the dipolar keto-carbene (54).Thus with benzonitrile the benzo- xazole (55) was obtained in 51% yield. The decomposition of the diazonium salt from 3-amino-4-t-butyl-5-nitrobenzoic acid (56) remarkably affords the benzocyclobutene (57) in good yield.61 The mechanism of this reaction is obscure C02H C02H O,N @NH2 02Nq \ but will undoubtedly be studied further. The decomposition of N-nitrosoace- tanilide in a mixture of 2,Sdimethylfuran and benzene gives rise to 2-benzyl-5- methylfuran. It was suggested that this product arises by acetate ion deprotona- 59 C. E. McKenna and J. G. Traylor J. Amer. Chem. SOC.,1971 93 2313. 6o J. M. Birchall R. N. Haszeldine J. Nikokavouras and E. S. Wilks J. Chem. SOC.(C) 1971 562. 61 M. H. Knight T. Putkey and H.S. Mosher J. Org. Chem. 1971 36 1483. Aromatic Compounds tion of the charge-transfer complex (58).62 The decomposition of N-nitroso- N-exo-bicyclo[3,1,0]hex-2-en-6-ylurea (59) in the presence of sodium carbonate results in the formation of benzene in 90% yield.63 It was suggested that the intermediates (60H62)are involved. In less-basic media bi- and tri-cyclic products were obtained in addition to benzene. The norbornenone derivative (63)is converted exclusively into 1,2,3,4-tetraphenylbenzeneunder mild alkaline condition^.^^ This reaction does not appear to involve decarbonylation and may well involve the loss of two molecules of carbon dioxide as shown in (64) NO H HI wN-coNH2 (59) Ph 'H followed by the loss of water.2-Aryl-6-oxocyclohex-1 -enylacetic esters undergo dehydrogenation to phenols with simultaneous loss of the acetate side-chain when heated at 100°Cin DMF in the presence of sodium hydride.6' The reaction of diphenylcyclobutenedione with an excess of diazomethane gives a mixture of (65) and (66). The formation of (66) from (65) occurs on heating in toluene whereas in xylene the phenol (67)was obtained.66 There is a pronounced tem- perature effect on the reaction of diazomethane with 1,3,5-trinitrobenzene. At 0 "C the product is (68),whereas at -80 "C(69) was obtained.67 62 J. I. G. Cadogan M. J. P. Harger J. R. Mitchell and J. T. Sharp Chem. Comm. 1971 1432. " W. Kirmse and F. Scheidt Angew. Chem. Internat. Edn. 1971 10 263. 64 E. A. Harrison Chem.Comm. 1971 1090. 65 D. Nasipuri A. Bhattacharyya and B. G. Hazra Chem. Comm. 1971 660. 66 W. Ried W. Kuhn and A. H. Schmidt Angew. Chem. Internat. Edn. 1971 10 736. 67 J. C. Van Velzen C. Kruk and Th. J. De Boer Rec. Trau. chim. 1971 90 842. 526 H Heaney PhB Me0 \ '"rH Me0 The full account of the reactions of organolithium compounds with aryl sulphonium salts which were reported previously68 has now been published. The ligand coupling reaction requires both units to possess a 7c-system and proceeds with the retention of configuration at carbon.69 The evidence supports the view that intermediate sulphuranes are involved. The location of the metal ion in certain aromatic carbanion systems has been studied. In for example fluorenyl-lithium 7Li n.m.r.suggests that the lithium ion is located above the n-cl~ud.~~ The n.m.r. spectrum of [3,5-2H2]phenylmagnesiumbromide has been studied7' and an extended Schlenk equilibrium used to account for the species present. Diborane has been shown to react with arylmercury halides in tetrahydrofuran to form intermediates which can be oxidized to phenols in high yield.72 A number of reports of reactions of sodium-naphthalene with organic halides have appeared. Different views have been reported for reactions with aryl halides.73 A radical coupling mechanism was suggested for reactions of alkyl halides and the observation of a CIDNP effect in the reactions of p-fluorobenzyl chloride or iodide74 suggests that the radical-radical-anion pair (70) is involved." H. Heaney Ann. Reports (B) 1969 66 329. 69 R. W. LaRochelle and B. M. Trost J. Amer. Chem. SOC.,1971,93 6077. 'O R. H. Cox H. W. Terry and L. W. Harrison J. Amer. Chem. SOC.,1971 93 3297. 71 D. F. Evans and G. V. Fazakerley J. Chem. SOC.(A) 1971 184; G. Fraenkel D. G. Adams and R. R. Dean J. Phys. Chem. 1968,72,944. 72 S. W. Breuer M. J. Leatham and F. G. Thorpe Chem. Comm. 1971 1475. 73 T. C. Cheng L. Headley and A. F. Halasa J. Amer. Chem. SOC.,1971 93 1502; G. D. Sargent Tetrahedron Letters 1971 3279. 74 J. W. Rakshys Tetrahedron Letters 1971 4745. Aromatic Compounds The cerium(1v)-catalysed decomposition of phenyldiazomethane leads to a mixture of cis- and trans-stilbene in which the cis-isomer predominate^.^^ It was suggested that radical-cation intermediates are involved although an expla- nation for the formation of the cis-isomer in high yield is obscure.The benzo- phenone ketyl radical can be generated thermally in for example decalin. a-Diketones can be reduced efficiently by this system to the a-hydroxyketone ; for example benzoin is obtained in 85 % yield from ben~il.~~ Aromatic ketones such as a-tetralone are reduced to the corresponding hydrocarbons by lithium in ammonia in a two-step process in which the benzylic alcoholate ion is formed first and this is then further reduced by excess of metal after protonation with ammonium chloride.77 Catalysis by trace quantities of cobalt was also noted. Vinyl esters of aromatic acids have been converted in high yields into diaroyl- methanes in the presence of aluminium chloride.These reactions may proceed via the diaroylacetaldehydes. '' Deuterium and tritium labelling studies have shown that the formyl proton in salicylaldehyde formed in the Reimer-Tiemann reaction is not derived from the aryl residue.79 Thus protonation of the anion (71) must occur before re-aromatization. Phthalaldehyde reacts with phenyliso- cyanate to form N-phenylphthalamidine quantitatively." It was suggested that the reaction proceeds via the iminoaldehyde (72). The oxidation of various araldehyde hydrazones with mercuric oxide in a number of solvents such as benzene gives rise to the diazoalkane. It has now been shown that arylnitriles are formed in solvents such as 1,2-dimetho~yethane.~l The reaction is thought to involve a tautomeric equilibrium between the diazoalkane and the imine.A number of very interesting sulphur trioxide oxidations of suitably protected substituted arenes have been reported." Thus for example pentachlorotoluene affords the betaine (73) from which the benzyl alcohol can be isolated. Prolonged reaction leads to (74) from which pentachlorobenzaldehyde can be isolated. Stilbene ozonides react with a number of bases including dimethylsulphoxide to afford quantitative yields of benzaldehydes and benzoic acids. Thus the 75 W. S. Trahanovsky M. D. Robbins and D. Smick J. Amer. Chem. SOC.,1971 93 2086. 76 M. B. Rubin and J. M. Ben-Bassat Tetrahedron Letters 1971 3403. 77 S. S. Hall S. D. Lipsky F.J. McEnroe and A. P. Bartels J. Org. Chem. 1971 36 2588. 78 Y. S. Rao and R. Filler J. Org. Chem. 1971 36 1447. 19 D. S. Kemp J. Org. Chem. 1971 36 202. 80 I. Yamamoto Y. Tabo and H. Gotoh Tetrahedron Letters 1971 2295. 81 D. B. Mobbs and H. Suschitzky Tetrahedron Letters 1971 361. 82 V. Mark L. Zengierski V. A. Pattison and L. E. Walker J. Amer. Chem. Sac. 1971 93 3538. 528 H. Heaney SO H / so; +o\ so; +/ 1 C,CI CH -0 C,CI -CH / \ ,so; SOJH +s (73) SO3H (74) ozonide derived from trans-2,4-dinitrostilbene gives benzaldehyde and 2,4-dinitrobenzoic acid.8 Treatment of for example benzaldehyde dimethylacetal with boron trifluoride in deuteriochloroform at room temperature results in the formation of the stable delocalized carbonium ion (75).84 The advantages of using tetra-alkylammonium salts in reactions which traditionally use metal salts have been pointed out.This has been used to good effect in the benzoin condensati~n.~~ c1 A new route to biaryls involves the elimination of hydrogen chloride from the charge-transfer complexes formed between n-excessive arenes and aryl halides which contain electron-withdrawing groups. Thus using (76)and (77) the corres- ponding biaryl was obtained in 79 % yield.86 The prediction87 that NO-diaryl- hydroxylamines should undergo benzidine-type rearrangements has been verified.88 Benzyl-N-(o-nitrophen0xy)carbonate was treated with base followed by o-nitrofluorobenzene and gave the compound (78). Attempted removal of 83 R.M. Ellam and J. M. Padbury Chem. Comm. 1971 1094. 84 M. Rabinovitz and D. Bruck Tetrahedron Letters 1971 245. J. Solodar Tetrahedron Letters 1971 287. 86 F. Effenberger K. Nagel and W. Agster Angew. Chem. Internat. Edn.. 1971 10 566. *’ M. J. S. Dewar in ‘Molecular Rearrangements’ ed. P. de Mayo Interscience New York 1963 vol. 1 p. 344. 88 T. Sheradsky and G. Salemnick Tetrahedron Letters 1971 645. Aromatic Compounds the protecting group with hydrobromic acid resulted in the rearrangement to (79). The trifluoromethyl group is frequently hydrolysed by strong bases particu- larly in arenes containing hydroxy- or amino-substituents in the para-position. Good yield conversions of trifluoromethylnitrochlorobenzenes into the phenols without hydrolysis of the trifluoromethyl group have been reported using powdered sodium hydroxide in dimethyl ~ulphoxide.~~ Reductive dehalogena- tions which occur during nucleophilic aromatic substitutions are more common than was previously thought particularly when attempting to replace iodine activated by a nitro-group with a bulky amine.” Whereas a-chloronaphthalene is not converted into a-ethoxynaphthalene with ethoxide ion in refluxing ethanol 5-chloroacenaphthylene is converted into 5-ethoxyacenaphthylene (80).Stabili-zation of the intermediate (81) was suggested to account for the change in reac- tivity.” The chemistry of Meisenheimer complexes continues to attract considerable attention.92 The complex derived by the reaction of methoxide ion with 3,5,6,8-tetranitroacenaphthenewas formulated as (82).93The potassium salt of trans-4-t-butylcyclohexanol reacts with picryl chloride to afford the styphnate (84),presumably via hydride ion abstraction from the Meisenheimer adduct (S3).94 Triarylnitrones are produced in the reactions between diphenyl- acetonitrile and certain nitrobenzenes carried out in the presence of for example OEt EtO CI OC,H Bu‘ OC,H,,Bu’ (83) *’ R.L. Jacobs J. Org. Chem. 1971,36 242. 90 F. Pietra M. Bartolozzi and F. Del Cima Chem. Cornm. 1971 1232. 91 M. J. Perkins Chem. Comm. 1971 231. 92 M. Nilsson C. Ullenius and 0. Wennerstrom Tetrahedron Letters 1971 2713; 0. Wennerstrom Acta Chem. Scand. 1971 25 789,2341 ;F. Terrier and M.-P. Simonnin Bull.Soc. chim. France 1971 677; E. J. Fendler W. Ernsberger and J. H. Fendler J. Org. Chem. 1971 36 2333; E. J. Fendler D. M. Camaioni and J. H. Fendler ibid. p. 1544; J. H. Fendler E. J. Fendler and L. M. Casilio ibid. p. 1749; F. Terrier F. Millot and M.-P. Simonnin Tetrahedron Letters 1971 2933; M. J. Straws and H. Schran ibid. 1971 2349; M. R. Crampton M. A. El Ghariani and H. A. Khan Chem. Comm. 1971 834. ’’ C. H. J. Wells and J. A. Wilson Tetrahedron Letters 1971 4521. 94 M. L. Sinnott and M. C. Whiting J. Chem. SOC.(B) 1971 965. 530 H. Heaney sodium methoxide in methanol.95 Nucleophilic displacement of hydride ion is apparently involved in the first step. The chlorination of aromatic amines by reagents such as N-chlorosuccinimide is known to proceed via the N-chloro- amine.A kinetic study has now shown that heterolytic cleavage leads to chloride ion and a nitrenium cation and hence to product.96 In the presence of alcoholic solvents varying amounts of cyclohexa-2,5-dienone derivatives for example (85) were also isolated. Bu‘ Me OMe The reactions of polymethylhalogenobenzenes which do not have an ortho-hydrogen with potassium t-butoxide at 225°C lead to products derived by dehydrobr~mination.’~ In the case of bromodurene the products show that the hydrogen is removed from an ortho-methyl group ;for example (86)was formed in the presence of cyclohexene. Full accounts of the amide-ion catalysed re- arrangements of trihalogenobenzenes in liquid ammonia have appeared.98 The so-called ‘halogen-dance’ proceeds by a positive halogen transfer.Thus for example 1,2,4-tribromobenzene rearranges in the presence of potassium anilide to give 1,3,5-tribromobenzene and disproportionates to di- and tetra- bromobenzenes. The evidence points strongly to a ‘seven-halogen’ syster- in which 1,2,3,5-tetrabromobenzeneacts as a co-catalyst. An interesting method of dichloromethylating nitroarenes involves the reaction of trichloromethyl-lithium with the nitro-compound in the presence of a trace of lithium n-butoxide. Substitution occurs ortho to the nitro-group and may involve intermediates such as (87) and (88).99 Intramolecular nucleophilic (87) (88) 95 M. Jawdosiuk B. Ostrowska and M. Makosza Chem. Comm. 1971 548. 96 P.G. Gassman and G. A. Campbell J. Amer. Chem. SOC.,1971,93,2567. 97 J. I. G. Cadogan J. K. A. Hall J. T. Sharp and A. K. Robertson Chem. Comm. 1971 1273. J. F. Bunnett and C. E. Moyer J. Amer. Chem. SOC., 1971,93 1183; J. F. Bunnett and G. Scorrano ibid. p. 1190; D. J. McLennan and J. F. Bunnett ibid. p. 1198; J. F. Bunnett and I. Feit ibid. p. 1201. 99 E. T. McBee E. P. Wesseler and T. Hodgins J. Org. Chem. 1971 36 2907. Aromatic Compounds 531 substitution in highly fluorinated compounds has been used in the synthesis of five-membered heterocyclic systems. loo Nucleophilic substitution in 1,2,3,4- tetrafluoronaphthalene occurs at the 2-position," ' and in decafluorophenan- threne at positions 2 and 7,'02 not as had been tentatively predicted at positions 9 and 10.Benzene Isomers and Homoaromatic Systems.-Full papers which describe the now well-known initial approach to the synthesis of Dewar-benzenes have appeared together with an account of non-aromatization reaction^."^ A very efficient synthesis of benzvalene and naph thvalene involves the interaction of cyclopentadienyl-or indenyl-lithium with dichloromethane and an alkyl-lithium reagent.'04 Large quantities of these two arene isomers are thus poten- tially available although benzvalene is thermodynamically very unstable. The full account of some Diels-Alder reactions of Dewar-hexafluorobenzene has appeared.'" The spectroscopic data are in accord with exo-addition and this was rationalized in terms of steric effects which operate in the transition states.Full papers have also appeared on cis-and trans-9,lO-dihydronaphthal-ene. O6 Labelling experiments have shown that the homocyclo-octatetraene dianion is protonated in polar media with a high selectivity and results in the formation of all-cis cyclonona-l,3,6-triene (89).lo7 Similarly reactions with oxygen permanganate or methyl iodide result in the formation of 5-substituted all-cis- cyclonona-l,3,6-triene derivatives."* A monocyclic bishomotropylium ion has been reported to result from the protonation of cis-bicyclo[6,1,O]nona-2,4,6-triene. The n.m.r. spectrum is consistent only with protonation at position 3 which results in the formation of the 1,3-bishomotropylium ion (9O).lo9 Metal-catalysed reactions of homotropylium ions have been discussed.''' loo G. M. Brooke W. K. R. Musgrave R. J. D. Rutherford andT. W. Smith Tetrahedron 1971 27 5653; G. M. Brooke W. K. R. Musgrave and T. R. Thomas J. Chem. SOC. (C) 1971 3596. lol P. L. Coe G. M. Pearl and J. C. Tatlow J. Chem. SOC.(C) 1971 604. O2 J. Burdon B. L. Kane and J. C. Tatlow J. Chem. SOC.(C) 1971 1601. lo3 E. E. van Tamelen S. P. Pappas and K. L. Kirk J. Amer. Chem. SOC.,1971,93,6092; E. E. van Tamelen and D. Carty ibid. p. 6102. lo4 T. J. Katz E. J. Wang and N. Acton J. Amer. Chem. SOC.,1971 93 3782. Io5 M. G. Barlow R. N. Haszeldine and R. Hubbard J. Chem. SOC.(0,1971 90. O6 E. E. van Tamelen and B. C. T. Pappas J. Amer. Chem. SOC.,1971,93,6111;E. E. van Tamelen T. L. Burkoth and R. H. Greeley ibid.p. 6120. lo' W. H. Okamura T. I. Ito and P. M. Kellett Chem. Comm. 1971 1317. lo8 T. I. Ito F. C. Baldwin and W. H. Okamura Chem. Comm. 1971 1440. lo9 P. Warner and S. Winstein J. Amer. Chem. SOC.,1971 93 1284. 'lo P. Warner Tetrahedron Letters 1971 723; L. A. Paquette Chem. Comm. 1971 1076. 532 H. Heaney 3 Thermal Elimination and Rearrangement Reactions The pyrolyses of tetrachloro-o-phenylene carbonate- and tetrachloro-o-benzo- quinone show qualitative similarities to the mass spectral fragmentations. '' ' Thus the quinone gives (91) at 650 "C whereas at 720 "C tetrachlorobut-l-ene-3-yne is the major product and presumably arises by decarbonylation of tetra- chlorocyclopentadienone. The major product obtained in the flash-vacuum- thermolysis of p-benzoquinone at 850 "Cis vinylacetylene ;(92) is the most likely intermediate ;'12' phenyl p-benzoquinone has also been studied.' 12* Pyrolysis coupled with mass spectrometry has been used to study the fragmentation of 3-bromotropolone.In the presence of methanol two major products were obtained 2-bromophenol and dimethyldicyclopentadiene dicarboxylate.' ' 0 0 0 (92) (91) The first product arises by the loss of carbon monoxide whereas the second also involves the loss of hydrogen bromide and rearrangement to the keten (93). The pyrolysis of trans-pentafluorocinnamic acid at 400 "C affords 5,6,7,8-tetrafluorocoumarin,' whereas the pyrolysis of pentafluorophenyl ally1 ether results in the formation of the stable cyclohexadienone (94).' ' The gas-phase pyrolysis of (94a) at 295 "C gave a quantitative yield of acetic acid and dimethyl isophthalate.l6 Deuterium-labelling experiments demon- strated the intramolecularity of the rearrangement and that a [1,5] or two successive [1,3] migrations occur. The thermal dimerization of phenylallene 111 D. C. De Jongh D. A. Brent and R. Y.Van Fossen J. Org. Chem. 1971 36 1469. 112 (a) H. J. Hageman and U. E. Wiersum Tetrahedron Letters 1971 4329; (b) Chem. Comm. 1971 497. 113 H. F. Grutzmacher and J. Hiibner Tetrahedron Letters 1971 1455. 11a H. Heaney and A. P. Price Chem. Comm. 1971 894. 115 G. M. Brooke Tetrahedron Letters 1971 2377. 116 J. A. Berson and R. G. Salomon J. Amer. Chem. Soc. 1971,93,4620; R. A. Baylouny ibid.p. 462 1. Aromatic Compounds results in the formation of 2,3-dimethyl- 1-phenylnaphthalene possibly via (95).' l7 A number of other interesting thermal rearrangements and extrusions which result in the formation of aromatic compounds have been reported.l18 C0,Me C0,Me QJ OAc PhH Although NNDO calculations predict that the polyene geometry of pentalene is preferred to the aromatic geometry there are indications from the calculated bond lengths and AH that there is a slight degree of aromaticity associated with pentalene (96).'19 The preparation of the fulvene derivative (97) was the key step in an attempted preparation of a derivative of pentalene.l2' Two isomeric products together with cyclopentadiene were obtained from pyrolysis of (97) at 600 "C.The flash thermolysis and collection of the products at -196 "C gave a mixture which is believed to contain (98) the first simple pentalene derivative. The vapour-phase pyrolysis of 6-vinylfulvene at 110 "C afforded a mixture of which the dihydropentalene (99) was a major product. 12' The flash thermolysis of o-nitroanisole at 900 "Cgives benzaldehyde together with a number of other products.122 The intermediacy of the phenoxymethyl and spiro-oxiran (100)radicals was suggested. (100) 'I7 J. E. Baldwin and L. E. Walker J. Org. Chem. 1971 36 1440. R. Weiss and C. Schlierf Angew. Chem. Internat. Edn. 1971 10 811; D. L. Coffen Y. C. Poon and M. L. Lee J. Amer. Chem. Soc. 1971,93,4627; R. Maruca J. Org. Chem. 1971 36 1626; W. S.Trahanovsky and P. W. Mullen Chem. Comm. 1971 102; L. F. Miller and R. F. Boyer J. Amer. Chem. Soc. 1971 93 650; M. Pomerantz T. H. Witherup and W. C. Schumann J. Org. Chem. 1971 36 2080; M. Kato T. Sawa and T. Miwa Chem. Comm. 1971 1635; R. S. Atkinson A. J. Clark and R. E. Overill ibid. p. 535. 'I9 N. C. Baird and R. M. West J. Amer. Chem. Soc. 1971 93 3072. lZo R. Bloch R. A. Marty and P. de Mayo J. Amer. Chem. SOC.,1971,93 3071. "' J. J. Gajewski and C. J. Cavender Tetrahedron Letters 1971 1057. lZ2 R. A. Marty and P. de Mayo Chem. Comm. 1971 127. 534 H. Heaney The flash-vacuum-pyrolyses of the isomeric tolyldiazomethanes all give rise to styrene and benzocyclobutene in ca. 50 % yield.123 l3C-Label1ing experiments using formyl-labelled p-tolualdehyde have confirmed the previously suggested mechanism.'24 Other pyrolytic reactions have also led to benzocyclobutene derivatives.'25 4 Non-benzene Systems Three-and Four-membered Rings.-The reaction of an excess of dimethylamine with tetrachlorocyclopropene surprisingly generates the trisdimethylamino-cyclopropenium ion (101) rather than ring-opened products in almost quanti- tative yield.' 26 Other secondary amines with the exception of diethylamine react similarly.The intermediacy of the tri-t-butylcyclopropenium ion is impli- cated in the reaction of rn-chloroperoxybenzoic acid with 1,2,3-tri-t-butylcyclo- propene,'27 which leads to di-t-butylacetylene and the mixed anhydride (102) as ..-. if? x2 Me,N NMe Ph (101) primary products.The condensation of cyanoacetic acid with diphenylcyclo- propenone leads unexpectedly to the triafulvene (103). 28 7,7-Dichlorobicyclo-[4,1,0]hept-3-ene (104) reacts with potassium t-butoxide in dimethyl sulphoxide and forms benzocyclopropene( 105)in ca.40 %yield.'29 The dehydrohalogenation of (106)provides another route to a benzocyclopropene derivative 7,7-dichloro- 2,5-diphenylbenzocyclopropene.'30 The hydrolysis of the photoadduct (107) leads to cyclobutenedione which is reasonably stable.' ' H Ph 123 B. G. Odell Ann. Reports (B) 1970 67 173. 124 E. Hedaya and M. E. Kent J. Amer. Chem. SOC.,1971 93 3283. 125 D. L. Forster T. L. Gilchrist C. W. Rees and E. Stanton Chem. Comm. 1971 695; T. L. Gilchrist C. W. Rees and E. Stanton ibid.,p.801; A. Roedig V. Kimmel and W. Lippert Tetrahedron Letters 1971 12 19. '26 Z.-i. Yoshida and Y.Tawara J. Amer. Chem. SOC.,1971 93 2573. J. Ciabattoni and J. P. Kocienski J. Amer. Chem. SOC.,1971 93 4902. E. D. Bergmann and I. Agranat J. Chem. SOC.(0,1971 1541. W. E. Billups A. J. Bakeney and W. Y.Chow Chem. Comm. 1971 1461. B. Halton and P. J. Milsom Chem. Comm. 1971 814. 13' J. C. Hinshaw Chem. Comm. 1971 630. Aromatic Compounds 535 Five- Seven- and Nhe-membered Rhgs.-Cyclopentadiene reacts with dichloro- carbene generated from chloroform using potassium t-butoxide giving as one of the products 6-chlorof~lvene.~~~ This may prove to be a new general route to 6-substituted fulvenes. The condensation of sodium cyclopentadienide with acetoxychloroalkanes such as (108) followed by the elimination of acetic acid with triethylamme affords fulvenes [(109) in this case] in good yield.133 Vilsmeier formylation of 6,6-bisdimethylaminofulveneyields the bisaldiminium salt (1 10) which on hydrolysis with sodium hydroxide affords (lll) (112) or (113) de- pending on the concentration of the base.’34 The fungal metabolite Illudin S Q AcO C1 OHC N Me OHCEHNMe2 H H (114) has been converted into the fulvenes (115) and (1 16) on brief treatment with cold sulphuric acid.The formation of dimethyl 4,5-azulenedicarboxylate (1 18) may occur by the .8 + r2scycloaddition of dimethyl acetylenedicarboxylate ”’ M. B. D’Amore and R. G. Bergman Chem. Comm. 1971,461. 133 R. Kyburz H. Schaltegger and M.Neuenschwander Helv. Chim. Acta 1971 54 1037. 134 K. Hafner and F. Schmidt Tetrahedron Letters 1971 2237. 135 S. M. Weinreb T. C. McMorris and M. Anchel Tetrahedron Letters 1971 3489. 536 H. Heaney HO-0 with (117) followed by the loss of dimethylamine.' 36 The synthesis of azulene derivatives from tropolones has been described :'37 thus 7-isopropyl-2,4-di- methylazulene was prepared from 4-isopropyltropolone. Reactions of tropone with electron-rich olefins in inverse-electron-demand Diels-Alder reactions have been re~0rted.l~' Thus (119) was formed with acenaphthylene. Reactions of a,cc'-dibromoketones with di-iron nonacarbonyl in the presence of 1,3-dienes lead to the formation of cyclohept-3-enones. Bro- mination and dehydrobromination leads to tropone derivatives.39 The mechanism of the thermal rearrangement of (120) to the tropone derivative (122) via (121) has been studied by kinetic and deuterium-labelling methods R. W. Alder and G. Whittaker Chem. Comm. 1971 776. T. Nozoe K. Takase and S. Fukuda Bull. Chem. SOC.Japan 1971,44 2210 2215. 138 T. Uyehara and Y. Kitahara Chem. and Znd.,1971 354. 13' R. Noyori S. Makino and H. Takaya J. Amer. Chem. SOC.,1971 93 1272. Aromatic Compounds and supports the view that an antara-antara [3,3]-sigmatropic process is in- v~lved.'~~ The rearrangement of tropones to m-hydroxybenzaldehydes is not confined to substrates carrying nitro-groups. The tropone derivative (123) rearranges to m-hydroxybenzaldehyde in the presence of aqueous piperidine probably via (124).14' The base-catalysed hydrolysis of 7-acetoxynorbornadiene leads to tropyl derivative^.'^^ In the presence of methanol methyl tropyl ether was obtained in 57 % yield and no deuterium incorporation was observed in the presence of methan[2H]ol and sodium deuteroxide.The suggested mechanism involves the [1,3]-sigmatropic shift of C-7 to the norcaradiene derivative (125). Heptatriafulvalene has been predicted to be polyolefinic rather than aro- rnati~.'~~ Stable salts of the type (126) have now been prepared and their spectral data are consistent with the existence of aromatic ~haracter.'~~ The reaction of tropylium perchlorate with cyclopentadiene in aqueous dioxan affords a complex mixture of alcohols.'45 However only .4 + ,2 cycloaddition occurs to form the allylic cation (127) and all of the products are derived from this ion or ions of the type (128).The reaction of antimony pentachloride with heptafulvalene results in the formation of the ditropylium salt (129) in high yield.'46 8-Cyano- 8-cycloheptatrienylheptafulvenylium fluoroborate has been prepared by the ..H, 0' 140 T. Miyashi M. Nitta and T. Mukai J. Amer. Chem. SOC.,1971 93 3441; see also J. E. Baldwin and M. S. Kaplan ibid. p. 3969. 141 G. Biggi F. Del Cima and F. Pietra Chem. Comm. 1971 1627. 142 B. Franzus W. C. Baird R. E. Felty J. C. Smith and M. L. Scheinbaum Tetrahedron Letters 1971 295. 143 H. Yamaguchi and T. Nakajima Theor. Chim. Acra 1968,12 349. 144 K. Takahashi T.Fujita and K. Takase Tetrahedron Letters 1971 4507. 145 S. It6 and I. Itoh Tetrahedron Letters 1971 2969. 146 H. Volz and M. Volz-de Lecea Annafen 1971 750 136. 538 H. Heaney abstraction of hydride ion from (130).14' Although 8-cyanoheptafulvene is unstable to acids a number of electrophilic substitution reactions have been carried out in the presence of weak bases. Thus the Vilsmeier reaction results in formylation at C-8 in 47% yield.'48 Conformational aspects of the chemistry of the 2-carboxytribenzotropylium ion (131) have been discussed assuming a chiral rapidly inverting boat-shaped ion. 149 Two tetrabenzoheptanonafulvalenes,(132) and (1 33) have been syn- thesized but both appear to be non-planar non-aromatic compounds. 50 8) -& 147 T.Otomo M. Oda and Y. Kitahara Chem. Comm. 1971 114. 14* M. Oda and Y. Kitahara Bull. Chem. SOC.Japan 1971,44,296. 14' W. Tochtermann and G. H. Schmidt Annalen 1971 754 90. lSo P. J. Garratt and K. A. Knapp Chem. Comm. 1971 1084. Aromatic Compounds 5 Cyclophanes and Annulenes The chemistry of cyclophanes has been reviewed. 51 Syntheses of layered cyclophanes' 52 and of the bridged metacyclophane' 53 (134) have been described. In the latter example extrusion of the methylamino-bridge occurs at about 200 "Cto afford (135). Full accounts of studies of ring rotations of rn-phenylene units in nietaparacyclophanes have appeared.' The solvolyses of I-tosyl-oxy[2,2]paracyclophane proceed with complete retention of configuration and are somewhat faster than those of aliphatic secondary tosylates.The results were tentatively interpreted as involving a bridged ion in which positive charge is distributed to both rings.'55 The acid-catalysed rearrangement of (+)-(S)-4-methyl[2,2]paracyclophane leads to optically pure (+)-(S)-12-methyl[2,2]-metaparacyclophane. The requirement of a fully chiral reaction co-ordinate to explain the result suggests that the intermediate (or possibly transition state) (136) is involved. '56 At relatively high temperatures all positions in metapara- cyclophane undergo hydrogen exchange at roughly the same rate with the excep- tion of that at the strongly hindered 8-position. '57 Acetylation with acetyl chloride and aluminium chloride in dichloromethane at -25 "C results in the formation of four monoacetylated derivatives of which (139) is the major product and presumably arises via the ions (137) and (138).'57 l5 ' D.J. Cram and J. M. Cram Accounts Chem. Res. 1971 4 204. 152 S. Mizogami T. Otsubo Y. Sakata and S. Misumi Tetrahedron Letters 1971 2791 ; T. Otsubo S. Mizogami Y.Sakata and S. Misumi ibid. p. 4803. 15' V. Boekelheide and R. A. Hollins J. Org. Chem. 1971 36 2437. 154 D. T. Hefelfinger and D. J. Cram J. Amer. Chem. SOC.,1971 93 4767; S. Akabori K. Shiomi and T. Sato Bull. Chem. SOC.Japan 1971 44 1346. 155 R. E. Singler and D. J. Cram J. Amer. Chem. SOC.,1971 93 4443; R. E. Singler R. C. Helgeson and D. J. Cram ibid. 1970 92 7625. 156 M. H. Delton R. E. Gilman and D. J. Cram J. Amer. Chem.SOC.,1971,93 2329. 15' D. T. Hefelfinger and D. J. Cram J. Amer. Chem. Soc. 1971 93 4754. 540 H. Heaney The n.m.r. spectroscopy of annulenes has been reviewed. 58 Dibenzocyclo-nonatetraenone does not sustain a paramagnetic ring current.lS9 Two [lo]- annulenes (140) and (141) have been prepared and are crystalline below -60 0C.160The automerization of (141) has been studied by variable-tempera- ture I3C n.m.r. spectroscopy. Neither of these substances should be regarded as aromatic compounds. Attempts to prepare quinone-like bridged [10]annu- lenes have shown that whereas the 2,5-dione exists as the norcaradiene (142) the 11,ll-difluoro-derivativedoes exist in the bicyclic forrn,l6' as does the 2,7-dione (143).162 The resolution of a number of chiral 1,6-methano[lO]-annulene derivatives has been reported.'63 An attempted synthesis of the 1,5- didehydro[lO]annulene (144) resulted in the formation of the compound (145) possibly via a Cope-like rearrangement.' 64 Similarly an attempted reaction to form (146) resulted in the formation of anthracene. The synthesis of compound 0 0 (142) (143) 15' R. C. Haddon V. R. Haddon and L. M. Jackman Forschr. Chem. Forsch. 1970/1971 16 103. Is9 M. Rabinovitz E. D. Bergmann and A. Gazit Tetrahedron Letters 1971 2671. 160 S. Masamune K. Hojo K. Hojo G. Bigam and D. L. Rabenstein J. Amer. Chem. SOC.,1971 93,4966. E. Vogel E. Lohmar W. A. Boll B. Sohngen K. Miillen and H. Giinther Angew. Chem. Internat. Edn. 1971 10 398. 162 E. Vogel W. A. Boll and E.Lohmar Angew. Chem. Internat. Edn. 1971 10 399. 163 U. Kuffner and K. Schlogl Tetrahedron Letters 1971 1773. 164 N. Darby C. U. Kim J. A. Salaiin K. W. Shelton S. Takada and S. Masamune Chem. Comm. 1971 1516. Aromatic Compounds 54 1 (147) in which one of the benzene rings in biphenylene is formally replaced by a bridged [lOIannulene ring has been re~0rted.l~~ N.m.r. data suggest "F that the unsaturated system in (148) is planar and sustains a diamagnetic ring current. 166 The synthesis and properties of the bridged methano[ lolannulene (147) analogue of phenalenone (149) has been de~cribed.'~' The annulene portion appears to be only slightly perturbed by the enone bridge. The oxidative- photocyclization of 1-(9'-anthryl)-4-phenylbuta-1,3-dieneaffords 3,4 :8,9-di-benzopyrene.It was suggested that this reaction involves the [101annulene (150).168 The full account of the synthesis of pyracylene (151) has been pub- 1i~hed.l~' In accord with predictions the peripheral 12n system sustains an induced paramagnetic ring current. Similarly the polarography of the quinone (1 52) and the e.s.r. spectrum of the semiquinone radical-anion (1 53) support the description of this [12lannulene as being antiaromatic. Other [12lannulene 165 P. J. Garratt and K. P. C. Vollhardt Angew. Chem. Internat. Edn. 1971 10 125. 166 M. 0.Riley and J. D. Park Tetrahedron Letters 1971 2871. 167 I. Murata T. Nakazawa and T. Tatsuoka Tetrahedron Letters 1971 1789. 168 R. J. Hayward and C. C. Leznoff Tetrahedron 1971 27 2085.169 B. M. Trost G. M. Bright C. Frihart and D. Britelli J. Amer. Chem. SOC.,1971 93 737. 170 P. S. Kinson and B. M. Trost J. Amer. Chem. SOC.,1971 93 3823. 542 H. Heaney systems have been rep~rted,'~' including non-planar systems. 172 Dehydro-[12]ann~lenes,'~~ have been reduced to the dianions. The and [12]ann~lene'~~ dianion from [12]annulene sustains a diamagnetic ring current is stable at + 30 "C,and does not undergo any dynamic processes of the type observed in [12]annulene it~e1f.l~~ Despite the non-planarity of the ring which is due to the presence of the inner protons the resonance energy associated with the 14 n-electrons is at least 8 kcal mol-' greater than that of the isoelectronic [14]annulene. A number of [lSlannulene derivatives have been prepared in order to study the derived cation^.'^' The annulenone (154) is best regarded as a polyenone in its ground state.However in concentrated sulphuric acid the U.V.spectrum suggests a contribution from the 14 n-electron system (155). 76 A number of [161- and [181-annulenes have been prepared,' and [181annulene undergoes an isodynamic conformational process whereby the outer and inner protons exchange their magnetic environments and become equivalent above +41 OC.17* [20]Ann~lene'~~ does show evidence for a paramagnetic ring current at -105"C and [22]ann~lene'~' a strong diamagnetic ring current in the n.m.r. spectrum. The exact limit for aromaticity in [4n + 2lannulenes 171 G. M. Pilling and F. Sondheimer J.Amer. Chem. SOC.,1971 93 1970 1977. 172 H. A. Staab F. Graf K. Doerner and A. Nissen Chem. Ber. 1971 104 11 59; A. B. Holmes and F. Sondheimer Chem. Comm. 1971 1434. 173 P. J. Garratt N. E. Rowland and F. Sondheimer Tetrahedron 1971 27 3157. 174 J. F. M. 0th and G. Schroder J. Chem. SOC.(B) 1971,904. 175 G. P. Cotterrell G. H. Mitchell F. Sondheimer and G. M. Pilling J. Amer. Chem. SOC.,1971 93 259; H. Ogawa N. Shimojo and M. Yoshida Tetrahedron Letters 1971 2013; H. Ogawa M. Kubo and H. Saikachi ibid. p. 4859. 176 H. Ogawa H. Kato and M. Yoshida Tetrahedron Letters 1971 1793. 177 T. M. Cresp and M. V. Sargent Chem. Comm. 1971 1454; K. Endo Y. Sakata and S. Misumi Bull. Chem. SOC.Japan 1971 44 2465; K. Fukui T. Okamoto and M. Nakagawa Tetrahedron Letters 197 1 3 121.178 J.-M. Gilles J. F. M. Oth F. Sondheimer and E. P. Woo J. Chem. SOC.(B) 1971 2177. 179 B. W. Metcalf and F. Sondheimer J. Amer. Chem. SOC.,1971 93 6675. 180 R. M. McQuilkin B. W. Metcalf and F. Sondheimer Chem. Comm. 1971 338. Aromatic Compounds has been calculated as being between the 22- and the 26-membered rings. Tride- hydro[26]annulene the only previously known [26]annulene derivative shows no ring current but this could be due to the presence of the three acetylenic residues. Monodehydro[26]annulene has now been prepared and is capable of sustaining an induced diamagnetic ring current."' 6 Polycyclic Compounds Full papers have appeared which describe the preparation and reactions of compounds having parallel triple bonds.'82 The reactions of a number of rhodium-complexed bisacetylenes for example from (1 56) with acetylenes yield annelated products under mild conditions :'83 thus diphenylacetylene gives (157) in 80 % yield.The norbiphenylene anion was reported recently,'84 and a benzo-derivative of the corresponding cation has been reported this year. 185 A Wittig reaction between (158) and homophthalaldehyde gave (159) in low yield and hydride abstraction gave (160). The macrocyclic compound (162) was on the other hand prepared in surprisingly good yield by the interaction of the ylide (161) with isophthalaldehyde.'86 The introduction of substituents either on the double bond or in the ortho-position of trans-stilbene reduces the melting points of the compounds to the extent that a number of them are room-tempera- ture nematic materials.'87 The /?-0x0-sulphoxide (163) undergoes rearrangement at room temperature in the presence of toluene-p-sulphonic acid to give even- tually a mixture of naphthalene derivatives.'88 In ethyl acetate solution the '" B. W. Metcalf and F. Sondheimer J. Ainer. Chem. SOC.,1971,93 5271. "* H. A. Staab and J. Ipaktschi Chem. Ber. 1971 104 1170 H. A. Staab J. Ipaktschi and A. Nissen ibid. p. 1182; A. Nissen and H. A. Staab ibid. p. 1191. lS3 E. Muller R. Thomas M. Sauerbier E. Langer and D. Streichfuss Tetrahedron Letters 197 1 52 1. H. Heaney Ann. Reports (B) 1969 66 346. P. J. Garratt and K. P. C. Vollhardt Chem. Comm. 1971 1143. C. D. Tulloch and W. Kemp Chem.Comm. 1971 747. W. R. Young A. Aviram and R. J. Cox Angew. Chem. Internat. Edn. 1971 10 410. "' Y. Oikawa and 0. Yonemitsu Chem. Comm. 1971 555. 544 H. Heaney CH CH I1 II PPh PPh compounds (165 ;XR = OEt OH and SMe) are formed possibly via the inter- mediate (164). 1,5-Dimethoxycarbonylbiphenylenehas been prepared in extremely good yield (75 %) when methyl 2,3-di-iodobenzoate was heated with copper bronze in DMF.ls9 The reduction of a number of polycyclic hydrocarbons with lithium in liquid ammonia produces anions which are alkylated by methyl iodide to afford cyclohexadiene derivatives. These cyclohexadienes are rearranged by the trityl cation. Thus 9,lO-dihydrophenanthreneaffords (166) which is rearranged to (167).I9' The abstraction of hydride ion by the trityl ion is well known and has been used to remove protecting groups from alcohols.191 Hydride ion is ab-stracted from benzyl benzyloxycarbonyl tetrahydropyranyl and bismethylene- dioxy-derivatives of alcohols.The perchlorodiphenylmethyl carbonium ion is also capable of abstracting hydride ion. However the perchlorotriphenylmethyl ion although able to convert cycloheptatriene into the tropylium ion is itself converted into the perchlorotriphenylmethyl radical. 192 This suggests that the hydride shift is a two-step process in this reaction. The 13Cn.m.r. spectrum of lS9 M. S. Newman and M. W. Logue J. Org. Chem. 1971,36 1398. I9O D. F. Lindow and R. G. Harvey J. Amer. Chem. SOC.,1971 93 3786. 19' D. H. R. Barton P. D. Magnus G.Streckert and D. Zurr Chem. Comm. 1971 1109. 192 M. Ballester J. Riera-Figueras J. Castaiier and A. Rodriguez-Siurana Tetrahedron Letters 197 1 2079. Aromatic Compounds 545 the dimer of 9-phenyl[9-' 3C]fluorenyl shows it to have the hexa-arylethane structure (168).193 The anodic methoxylation of for example 9,lO-diethyl- anthracene results in the formation of an almost 1 1 mixture of the cis-and trans-dimethoxy-compounds. It was argued that neither possible boat con-formers adequately explains the spectral data. 194 (168) Azulene derivatives are obtained by the reaction of 2H-cyclohepta[b]furan- 2-one with enamines. Thus the compound (169) gave the azulene (171 ;n = 3) with 1 -N-pyrrolidinylcyclohept-1-ene.'95 Using pyrrolidine cyclopentene the intermediate (170) was isolated and readily converted into (171 ; n = 1).The reactions of diarylketens with ethoxyacetylene lead to dihydroazulenones.' 96 a- (1 70) Thus (172) forms (173). The hydrocarbon (174) can be converted into the corresponding relatively unstable 12n-electron anion using methyl-lithi~m.'~~ High electron-density resides at position 1 in the anion since the hydrocarbon (174) is regenerated on protonation. Similarly the reaction of the anion with (172) (173) 193 H. A. Staab K. S. Rao and H. Brunner Chem. Ber. 1971 104,2634. 194 V. D. Parker J. P. Dirlam and L. Eberson Acta Chem. Scand. 1971 25 341. 195 P.-W. Yang M. Yasunami and K. Takase Tetrahedron Letters 1971 4275. 196 H. Teufel and E. F. Jenny Tetrahedron Letters 1971 1769.19' P. Eilbracht and K. Hafner Angew. Chem. Internat. Edn. 1971 10 751. 546 H. Heaney benzophenone and loss of lithium hydroxide leads to the stable compound (175). Two routes to the synthesis of benzo[4,5]cyclohepta[1,2,3-de]naphthalene (176) have been reported.'98 The carbinol (177) undergoes a Wagner-Meerwein rearrangement to the ion (178) whichcyclizes to the propellane( 179).199 Electrophilic additions to dehydro- janusene (180) give mixtures of rearranged and non-rearranged products as do the ring-opening reactions of epoxyjanusenes.200 Carbonium ion rearrange- ments occur during solvolyses of halogenojanusenes and related compounds.20 It is of interest to note that two series of doubly rearranged derivatives exist which are related by way of the achiral trans-ketone (181).202 Solvolyses of various benzobicyclanyl p-bromobenzenesulphonates have been reported.203 The rearrangement of (182) in sulphuric acid-acetic acid leads to (183).204 Rearrangements of 1,4-dihydro- 1,4-epoxynaphthalene occur during lg8 J.F. Muller D. Cagniant and P. Cagniant Tetrahedron Lerrers 1971 45; J. T. Craig K. W. Tan and A. D. Woolhouse ibid. 1971 3209. 199 G. Wittig and W. Schoch Annulen 1971 749 38. 2oo S. J. Cristol and M. A. Imhoff J. Org. Chem. 1971 36 1849. 201 S. J. Cristol and M. A. Imhoff J. Org. Chem. 1971 36 1854. *02 W. M. Macintyre M. A. Imhoff and S. J. Cristol J. Org. Chem. 1971 36 1865. 203 H. Tanida and S. Miyazaki J. Org. Chem. 1971 36 425; H. Tanida and T.hie ibid. p. 2777. 204 R. Caple G. M.-S. Chen and J. D. Nelson J. Org. Chem. 1971,36 2870. Aromatic Compounds /\ Ph 1 Ph certain cycloaddition rea~tions.~'' Thus cycloaddition with N-phenyltriazoline- dione occurs by a stepwise mechanism and aryl migration to the carbonium ion (184) results in the formation of the stabilized ion (185) which gives the final product (186). The rearrangement reactions of l-methoxybenzo barrelenes (187) are similar and give rise to a number of different product and equilibria between various products have been demonstrated in a highly alkylated 205 T. Sasaki K. Kanematsu and M. Uchide Tetrahedron Letters 1971 4855. 206 H. Heaney and S. V. Ley Chem. Comm. 1971 224; I. F. Mikhailova and V. A. Barkhash J.Org. Chem. (U.S.S.R.) 1970 6 2335. 548 H. Heaney example.207 The rearrangement of (188)in sulphuric acid leads to a quantitative yield of the lactone (189).208The reaction of (190) with palladium(I1) chloride- copper(r1)chloride in acetic acid containing sodium acetate results in the formation Me of (192) as the major product. It was suggested that the intermediate (191) is involved.209 Other examples of rearrangements in systems such as (193)210and (194)2l1 have been reported. O*O & &BPdC1 J HH 2 207 H. Hart and G. M. Love Tetrahedron Letters 1971 1342; J. Amer. Chem. SOC.,1971 73 6265. 208 H. Heaney and S. V. Ley Chem. Comm. 1971 1342. 209 C. J. R. Adderley J. W. Nebzydoski M. A. Battiste R. Baker and D. E. Halliday Tetrahedron Letters 197 1 3545.210 R. Baker and T. J. Mason J. Chem. SOC.(B),1971 1144. 211 M. A. Battiste P. F. Ranken and R. Edelman J. Amer. Chem. SOC.,1971 93 6276. Aromatic Compounds The chromium complex obtained from biphenylenyl-2,2’-dilithium and chromic chloride reacts with a number of transition-metal halides to afford two types of o-hexaphenylene one of which is screw-shaped and can be resolved.2 Dibenzo[g,p]chrysene reacts with lithium and yields the dianion (195); cis-and trans-isomers of the dihydro-derivative can be i~olated.”~ The synthesis of the interesting polycyclic hydrocarbon dibenzo[ghi,mno]fluoranthene (196) (Corannulene) has been described in full.’14 The molecule is bowl-shaped as a resuk of distortions.Low yield but simple syntheses of pyraceheptylene (197) and benzo[a]pyraceheptylene (198) have been reported.215 The heat of hydrogenation of acepleiadylene indicates that the ‘conjugation’ energy of the three non-naphthalene double bonds is approximately 18.9kcal mol-l .216 5,10-Dimethylene-5,1O-dihydroacepleiadene (1 99) and the analogue 212 G. W‘ittig and K.-D. Rumpler Annafen 1971 751 1. 213 G. W’ittig E. Barendt and W. Schoch Annalen 1971 749 24. 214 W. E. Barth and R. G. Lawton J. Amer. Chem. Soc. 1971,93 1730. C. Jutz and E. Schweiger Angew. Chem. Internat. Edn. 1971 10 808. 216 R. B. Turner W. S. Lindsay and V. Boekelheide Tetrahedron 1971 27 3341. 550 H. Heaney (200) have been prepared.217 They are readily hydrated to bridged epoxides which suggests that they are non-planar.Evidence was presented which suggested that an 18-n-electron periphery is obtained from (199) in the presence of base. *” J. W. Lown and A. S. K. Aidoo Canad. J. Chem. 1971,49 1861.

ISSN:0069-3030    

DOI:10.1039/OC9716800515

出版商:RSC    

年代:1971

数据来源: RSC

摘要:

18 Heterocyclic Chemistry Part (i) Saturated Ring Systems” By I. D. BLACKBURNE and M. J. COOK School of Chemical Sciences University of East Anglia Norwich NOR 88C 1 Three-membered Rings The first report of nitrene intermediates in the photolysis of aziridines e.g. (l) promises to provide a useful route to other aziridines by the trapping of thenitrene with appropriate olefins.’ Whereas an example of the 1-azabicyclo[ l,l,O]butane system is known the 2-aza-isomer has yet to be isolated although evidence for its existence as an intermediate (2) has been reported;2 cf the intermediacy of 2-oxabicyclo[l,l,O]butane (3).3 The new 2,4-diazabicyclo[l,l,O]butane(4) ob-tained by condensation of formaldehyde with a primary amine and an aminating agent and the new 5-azabicyclo[2,1 ,O]pentane (5)2 have been prepared and both are relatively stable; in particular the latter unlike the highly strained carbocyclic analogue shows no tendency to react with acetylene dicarboxylate.The quantitative preparation of the oxaspiropentane (6) and its lithium iodide- T. L. Gilchrist C. W. Rees and E. Stanton J. Chem. SOC.(0,1971. 988. ’ J. N. Labows jun. and D. Swern Tetrahedron Letters 1971 4523. L. E. Friedrich and R. A. Cormier Tetrahedron Letters 1971 4761. A. A. Dudinskaya L. I. Khmelnitski I. D. Petrova E. B. Baryshnikova and S. S. Novikov Tetrahedron 1971 27 4053. * Including simple unsaturated compounds which are not ‘aromatic’ ‘antiaromatic’ etc. 551 I. D. Blackburne and M. J. Cook Me HN’JNR ~N.CO,E~ 0 U (4) Me (5) catalysed rearrangement have also been rep~rted,~ the rearrangement providing a rapid high-yield route to cyclobutanone.Studies on aziridine and oxiran ring-opening by carbon-carbon bond cleavage have continued. In the nitrogen series kinetic experiments show that rates of cycloaddition to active dipolarophiles are determined only by the first-order ring scission to the azomethine ylides.6 Azomethine ylides have been found to be amongst the few 1,3-dipoles that equal ozone in their ability to attack an aromatic double bond. Thus (7) has been shown to undergo cycloaddition with phenanthrene,’ and it also provides the first example of 1,3-dipolar addition to azobenzene forming the triazolidine (8).8 Previously azobenzene had only been observed to undergo [2+ 2]cycloadditions with keten.In the oxiran system thermal ring-opening to the carbonyl ylide [(9a) (9b)l has now been demonstrated to proceed by way of the expected conrotatory proce~s,~ cf Ar Ar J. R. Salaiin and J. M. Conia. Chem. Comm.. 1971 1579. R. Huisgen and H. Mader J. Amer. Chem. SOC.,1971 93 1777; H. Hermann R. Huisgen and H. Mader ibid. p. 1779. ’ R. Huisgen and W. Scheer Tetrahedron Letters 1971 481. E. Brunn and R. Huisgen Tetrahedron Letters 1971 473. A. Dahmen H. Hamberger R. Huisgen and V. Markowski Chem. Comm. 197 1,1192. Heterocyclic Chemistry-Part (i) Saturated Ring Systems aziridines and cyclopropyl anions. Carbonyl ylides have been trapped by acety- lenes," olefins," and carbonyl compounds' to give dihydrofurans tetra-hydrofurans and dioxolans respectively.N-Inversion in aziridines continues to be a field which attracts attention. The well-recognized slow inversion may in fact be hastened by introduction of a halogen at a ring carbon e.g. (10); the enhanced rate can be explained in terms of 'double-bond-no bond' resonance in which contributions from planar forms (lob) facilitate the inversion. l2 On the topic of positively charged three-membered rings the preparation for the first time of a solution of the unstable aziridine N-oxide system (11) by ozonolysis of the corresponding aziridines is particularly noteworthy. The decompositions of the N-oxides (12 13; X = NR)13 and of the analogous episulphoxides (12 13; X = S)I4 have been elucidated and shown to follow two distinct pathways the less facile but partially stereospecific path B is pre-ferred when the stereochemistry is unfavourable for the hydrogen-transfer reaction A.The peroxy-epoxide (14) has been suggested as a key intermediate in a unifying concept of the mechanism of ozonolysis of 01efins.l~ OHI -0 Bu' \/ R'AR2 X+ 0-I R 0-0'Io+ AR2R' 5 WR+x=o (14) LO H. Hamberger and R. Huisgen Chem. Comm. 1971 1190. A. Robert J.-J. Pommeret and A. Foucaud Tetrahedron Letters 1971 231. D. J. Anderson and T. L. Gilchrist J. Chem. SOC.(C) 1971,2273. l3 J. E. Baldwin A. K. Bhatnagar Se Chun Choi and T. J. Shortridge J. Amer. Chem. SOC.,1971 93 4082. l4 J. E. Baldwin G. Hofle. and Se Chun Choi J. Amer. Chem. SOC.1971 93 2810; K. Kondo and A. Negishi Tetrahedron 1971 27 4821. P. R. Story J. A. Alford W. C. Ray and J. R. Burgess J. Amer. Chem. SOC.,1971 93 3044. 554 I. D. Blackburne and M. J. Cook The reaction of 1-azirines (15) with hydrazine to give tetrahydro- 1,2,4-triazin- 6-ones was reported last year16 but the product is now known to be accompanied by small yields of 2-hydrazinoaziridines (16; Y = NH,).” The products of the reaction provide a sharp contrast to those of the corresponding reaction with hydroxylamine where 2-hydroxyaminoaziridine (16; Y = OH) is formed in nearly quantitative yield.’* H RNH R I \ 40 I C CONH H-C-Br I ArAAr -.A0 CONH I bisnorcholany 1 bisnorcholanyl (15) (16) (17) (18) The first preparation of optically pure a-lactams (18) of known configuration has been ~1aimed.l~ The compounds are obtained fiom the optically active a-halogenoamides (17) which cyclize with inversion of configuration.The exis- tence of a-lactones (19) evidence for which was reported last year,” has been further substantiated by the trapping of the dipolar form with methanol to give a-methoxy-acids (20).’ The precursor of the a-lactone provides an alternative to that reported previously. Oxaziridines appear to be the most widely studied three-membered rings containing two heteroatoms. A high-yield preparation involving the molyb- denum(v)-catalysed oxidation of Schiff bases with t-amylhydroperoxide has been reported and the authors suggest” that this is more convenient than the peracid procedure.A detailed examination of the oxaziridine-nitrone equili- brium (21) an analogue of the aziridine-azomethine ylide system (see above) has been ~ndertaken,~~ and it has been shown that the photocyclization of (21b) 16 Ann. Reports (B) 1970 67 434. 17 T. Nishiwaki and T. Saito J. Chem. SOC.(0,1971,2648. 18 T. Nishiwaki and S. Onomura J. Chem. SOC.(C),1971 3026. 19 S. Sarel B. A. Weissman and Y. Stein Tetrahedron Letters 1971 373. 20 Ann. Reports (B) 1970 67 436. 21 W. Adam and R. Rucktaschel J. Amer. Chem. SOC.,1971.93 557. 22 G. A. Tolstikov U. M. Jemilev V. P. Jurjev F. B. Gurshanov and S. R. Rafikov. Tetrahedron Letters 197 1 2807. 13 J. S. Splitter Tah-Mun Su H. Ono and M. Calvin J. Amer. Chem. SOC.,1971 93 407 5.Heterocyclic Chemistry-Part (i)Saturated Ring Systems 555 is stereospecific in accordance with orbital-symmetry rules. The corresponding thermal cleavage of (21a) gives a 50:50 mixture of cis-and trans-(2lb) the iso- meric products resulting from the two possible conrotatory motions of carbon- oxygen cleavage. Reaction of oxaziridines with thiourea deoxygenates the ring to a Schiff base perhaps by way of the unknown thiaziridine intermediate (22) which is postulated to eliminate sulphur spontane~usly.~~ A further paper on the oxaziridine system provides an unusual example of reversal of heteroatom basicity. Data for a series of 2-t-butyloxaziridines are suggestive of O-protona-tion :a reflection amongst other things of steric congestion about the nitrogen atom.25 0 2 Four-membered Rings Various syntheses of four-membered ring compounds containing one heteroatom have been published.These include an improved route to 3-azetidin0ls,~~ the photosensitized preparation of the polycyclic azetidine (23),2' the first prepara- tion of the parent 2-methylene-oxetan (24),28and the synthesis of the hitherto unknown 2-alkyl-(or aryl-) l-a~etines.~' A precautionary note on the synthesis of 3-thietanol-1,l-dioxide has appeared and a less hazardous procedure is ~uggested.~' Asymmetric induction has been observed in the [2 +2lcycloaddition of sulphene to optically active enamines and this appears to be the first applica- tion of asymmetric synthesis to four-membered rings.31 The thietan 1,l-dioxide (25) was produced in 6% optical purity whereas (26) which has the reverse /vMe H Me 24 D.St. C. Black and K. G. Watson Angew. Chem. Internat. Edn. 1971 10 327. 25 A. R. Butler and B. C. Challis J. Chem. SOC.(B) 1971 778. 26 E. H. Gold J. Amer. Chem. SOC.,1971,93 2793. 27 P. D. Rosso J. Oberdier and J. S. Swenton Tetrahedron Letters 1971 3947. 28 P. F. Hudrlik and A. M. Hudrlik Tetrahedron Letters 1971 1361. 29 A. B. Levy and A. Hassner J. Amer. Chem. SOC.,1971,93,2051. 30 D. C. Dittmer M. E. Christy N. Takashina R.S. Henion and J. M. Balquist J. Org. Chem. 1971,36 1324. 31 L. A. Paquette J. P. Freeman and S. Maiorana Tetrahedron 1971 27 2599. I. D.Blackburne and M. J. Cook stereochemistry was obtained in 25 % optical purity ;stereospecificity evidently increases as the number of rotational degrees of freedom is reduced.A number of rearrangements of four-membered rings have been reported. In the sulphur series,32 the cis- and trans-sulphones (27) ring-expand to the corresponding sulphinic esters (28) on treatment with t-butoxymagnesium bromide32" [cf the thermally induced isomerization (29) +(30) reported two years ago33] but in sharp contrast both isomers give the trans-diphenylcyclo- propyl derivative (31) on treatment with ethylmagnesium bromide.32b As a further contrast the cis- and trans-sulphoxides (32) both give cis-diphenyl- cyclopropyl derivatives with t-butoxide in DMF the anion (33) subsequently undergoing disprop~rtionation.~~' Reaction of trans-diphenylthietan (34) with t-butoxide probably also proceeds via a diphenylcyclopropyl derivative (39 but this was not isolated.32b Apart from the oxidation state of the sulphur atom and the strength of the base proton availability is also a parameter determining the reaction pathway in this series :it is notable that in a protic medium (methano- lic methoxide) the trans-sulphone (27) and the trans-sulphoxide (32) are merely epimerized to their cis-isomers and do not rearrange.Ph + rh+€'h 1 -PhqPh + PhqPh so Ph so- SH SO H (32) (33) A new synthesis of /I-lactams by ring expansion of cyclopropanone derivatives seemingly provides a basis for a more general route than some already realized (Scheme l).34 The photochemical conversion of some diazomalonic ester 32 (a) R.M. Dodson P. D. Hammen and R.A. Davis J. Org. Chem. 1971 36 2693; (b)R. M. Dodson P. D. Hammen E. H. Jancis and G.Klose ibid. p. 2698; (c)R. M. Dodson P. D. Hammen and J. Yu Fan ibid. p. 2703; R. M. Dodson and J. Yu Fan ibid. p. 2708. 33 Ann. Reports (B) 1969 66 431. 34 H. H. Wasserman H. W. Adickes and 0.Espejo de Ochoa J. Amer. Chem. Soc. 1971 93 5586. Heterocyclic Chemistry-Part (i) Saturated Ring Systems 557 amides into lactams e.g. (36) into (37) has now been found to give the cis- as well as the normal trans-product and offers a direct route to the nucleus of the penicillin and cephalosporin antibiotic^.^^ A further approach to new types of p-lactam antibiotics is now feasible through the isolation of the P-lactam function Scheme 1 But0,C-YN2 ‘s\l C-N 0 O4 C0,CH Ph C02CH2Ph Buto2caL (36) (37) of penicillins.36 The process involves cleavage of the S-1-C-2 bond by pyrolysis of the penicillin sulphoxide followed by treatment with diazomethane and then zinc in acetic acid (Scheme 2). R’ -Zn-HOAc -J-NH ol$;2R2 0 N Scheme 2 An unexpected difference has been observed between iodolactonization a traditional method of obtaining y-lactones from &unsaturated acids and bromolactonization which now has been shown to favour P-lactone formation. 35 G. Lowe and J. Parker Chem. Comm. 1971 577. 36 (a)D. H. R. Barton D. G. T. Greig P. G. Sammes and M. V. Taylor Chem. Comm. 1971,845 ;(b)D. H. R. Barton P. G. Sammes M. V. Taylor C.M. Cooper G. Hewitt B. E. Looker and W. G. E. Underwood ibid. p. 1137. 558 I. D. Blackburne and M. J. Cook Thus treatment of the conformationally rigid (38) with one equivalent of bromine yielded (39):37a and more remarkably open-chain acids (40) also form P-lactones (41) even when R' = R2 = H where isomerization to the up-unsaturated acid is possible.37b Me Me CO H R2 Routes to four-membered rings containing two heteroatoms include a new enamine reaction which has been reported to provide a possible general pathway to 1,2-diazetidines thus cyclohexanone enamines e.g. (42) react with diben-zoyldi-imide at room temperature to give structures of type (43) in nearly quanti- tative yield.38 Isolation of 1,2-dioxetan compounds e.g. (44),from the photo-oxidation of ole fin^,^^ and their chemiluminescence in the presence of a fluorescent hydro- carbon during thermal decomposition continues to attract interest.Activation energies for the overall luminescent process and for dioxetan cleavage of (44) are the same (24 kcal mol- ') and there is no alternative low activation energy dark pathway for decomp~sition.~~~ Thermal decomposition of trimethyl- dioxetan in the presence of lanthanide chelates has been observed to produce narrow-band chemiluminescence of moderate efficiency the wavelength of which is dependent upon the metal complex. Such systems might reasonably be used as chemical sources of 'monochromatic' light of chosen wavelength and be devised to generate a specific number of photons.40 The 1,3-dithietan ring (45) has been obtained by the first reported photocyclo- addition reactions of an alicyclic thioketone adamantanethi~ne.~' The reactive N-COPh Et0)r8 NCOPh EtO (44) 0 37 (a) W.E. Barnett and J. C. McKenna Chem. Comm. 1971 551; (b) W. E. Barnett and J. C. McKenna Tetrahedron Letters 1971 2595. 38 L. Marchetti and G.Tosi Tetrahedron Letters 1971 3071. 39 (a) A. P. Schaap Tetrahedron Letters 1971 1757; (b) T. Wilson and A. P. Schaap J. Amer. Chem. SOC.,1971 93 4126. 40 P. D. Wildes and E. H. White J. Amer. Chem. SOC.,1971 93 6286. 41 C. C. Liao and P. de Mayo Chem. Comm. 1971 1525. Heterocyclic Chemistry-Part (i) Saturated Ring Systems species is a triplet which apart from dimerizing may react to give alkene addition products (46).Other reports on the preparation of dithietan derivatives have appeared which demonstrate the versatility of carbon disulphide in synthesis.42 3 Five-memberedRings A method of heterocyclic synthesis by cyclization of olefinic amines in the presence of a mercuric salt has been reported.43 The products mercurated nitrogen heterocycles generated by trans-addition to the olefin may be demercurated by sodium borohydride. Thus (47) yields solely (48),and (49) yields both five- and six-membered ring products (50) and (5l) the relative proportions depending on the solvent and the mercury salt employed. Other cyclizations of N-substituted -N -N, INHP~ \ Pr Pr (47) (48) Me Me Me I I I m+W'gy \ \ (49) olefinic amines e.g.(52; X = NO)44"and (52; X = Cl),44b proceed via free- radical mechanisms and lead to five-membered nitrogen rings only providing convenient routes to derivatives of lesser known isomers of tropane e.g.(53)-(55) ; (54)has also been prepared by a fluoroacetic acid-catalysed cyclization of (56).45 Comparable intramolecular radical additions of olefinic thiols (57)have led to 42 Y. Hayashi T. Akazawa K. Yamamoto and R. Oda Tetrahedron Letters 1971 1781 ; P. Yates D. R. Moore and T. R. Lynch Canad. J. Chern. 1971,49 1456. 43 J. Perie J. P. Laval and A. Lattes Compt. rend. 1971 272 C 1141; J. Perie J. P. Laval J. Roussel and A. Lattes Tetrahedron Letters 1971 4399. 44 (a)Y. L. Chow R. A. Perry B. C. Menon and S. C. Chen Tetrahedron Letters.1971 1545; Y. L. Chow R. A. Perry and B. C. Menon ibid. p. 1549; (6) J.-M. Surzur L. Stella and R. Nouguier ibid. p. 903. 4s G. Esposito R. Furstoss and B. Waegell Tetrahedron Letters 1971 899. I. D. Blackburne and M. J. Cook the first syntheses of two thiabicyclo-octane systems (58)and (59),but in contrast with the amino-olefin cyclization formation of the [2,2,2]bicyclo system seems to be favoured over formation of the [3,2,1] system.46 Thus when R = H (58) is the sole product some (59) being formed along with (58) when R = Me. The Ramberg-Backlund reaction of a-halogenosulphones continues to provide synthetic routes to interesting compounds such as the strained pro- pellane (60):’ and the products (61) and (62) of a novel ‘bishomoconjugative Ramberg-Backlund rearrangement’.48 Chlorination of sulphones with sulphuryl chloride somewhat unexpectedly gives the P-chlorinated product in contrast with sulphides and sulphoxides which undergo a-~hlorination.~~ 46 J.-M.Surzur R. Nouguier M.-P. Crozet and C. Dupuy Tetrahedron Letters 1971 2035. ” L. A. Paquette and R. W. Homer J. Amer. Chem. SOC.,1971,93,4522. 48 L. A. Paquette R. E. Wingard jun. and R. H. Meisinger J. Amer. Chem. SOC.,1971 93 1047. 49 I. Tabushi Y. Tamaru and Z. Yoshida Tetrahedron Letters 1971 3893. Heterocyclic Chemistry-Part (i) Saturated Ring Systems C1 Alkylphosphonium salts normally react with base by loss of an a-proton but reaction of the small-ring salt (63) with methyl-lithium results in attack at phosphorus.This pathway relieves ring strain and yields the first stable penta- alkylphosphorane (64).50 The first resolution of a chiral cyclic phosphorus compound (65) is claimed the laevorotatory form being obtained via the (+)-9-camphorsulphonate salt.51 The recently synthesized methyleneaminophos- phanes which are novel 1,3-dipoles having high nucleophilic ~haracter,~ 2a have been shown to react with electrophilic olefins to produce compounds of type (66).52b The synthesis of the 4,5-dihydro-3-azaphosphole(67) by reaction of phenylphosphine with vinyl isocyanide has also been reported.53 Me NEt X2P-N=CPhz \ + CpP CH2=CHR x‘/\ x Some novel cleavage reactions of rings containing heteroatoms in the 1-and 3-positions should find applications in synthesis.Trityl fluoroborate cleaves 1,3-dioxolans to form a-ketols e.g. (68) 4(69),54 and ozonolysis affords esters in essentially quantitative yields e.g. (70) +(71).55 The latter reaction is general 50 E. W. Turnblom and T. J. Katz J. Amer. Chem. SOC.,1971 93,4065. s1 G.Ostrogovich and F. Kerek Angew. Chem. Internat. Edn. 1971 10 498. 52 (a)A. Schmidpeter and W. Zeiss Chem. Ber. 1971 104 1199; (6) A. Schmidpeter and W. Zeiss Angew. Chem. Znternat. Edn. 1971 10 396. ’’ R. B. King and A. Efraty J. Amer. Chem. SOC.,1971 93,564. 54 D.H. R. Barton P. D. Magnus G. Smith and D. Zurr Chem. Comm. 1971 861. 55 P. Deslongchamps and C. Moreau Canad. J. Chem. 1971 49,2465. 562 I. D. Blackburne and M. J. Cook for a range of acetals and ketals and an interesting specificity is suggested by the into conversion of methy1-2,3,4,6-tetra-0-acetyl-~-~-glucopyranoside2,3,4,6-tetra-0-acetylgluconate whilst the a-anomer remains unreacted.Milder con- ditions are now available for the generation of aldehydes and ketones from the 1,3-dithiolan ring. Basic hydrolysis of the bis-sulphoxide derivative rather than the bis-sulphone is now re~ommended,~~ and still a further improvement may lie in the use of sodium N-chlorotoluene-p-sulphonamide(Chloramine T) which rapidly and efficiently cleaves both 1,3-dithiolans’ and 1,3-oxathio- lans’ 7b directly at room temperature. Mercury(@ successfully catalyses the thiazolidine hydrolysis (72) -P (73) a key step in a scheme for aldehyde synthe- sis,” and nitrogen dioxide has proved appropriate for a novel convenient and highly efficient regeneration of ketones from doxy1 derivatives e.g.(74),59 an important class of biological spin labels. Ph 011 Ph -+ \ CH-C-Ph C6H,b3-(I) -+ C,H,,CO,CH,CH,OH Ph /Ph II 0 (71) (68) (69) (70) (72) (74) The assumption that thioketones react with amines to form Schiff bases should be treated with some caution. Thiobenzophenone has been shown to react with a number of primary amines as well as with diethylamine to yield the thermally labile thio-ozonide (75).60 Structures of the 1,2,4-trithiolan type (76) and (77) have also been assigned to the products of the oxidation of both fl-ketodithioic (75) (76) Y = RCOCH (77) Y = PhNH-N (78) 56 P.R. Heaton J. M. Midgley and W. B. Whalley Chem. Comm. 1971 750. ’’ W. J. F. Huurdeman H. Wynberg and D. W. Emerson Tetrahedron Letters 1971 3449; D. W. Emerson and H. Wynberg ibid. p 3445. L. J. Altman and S. L. Richheimer Tetrahedron Letters 1971. 4709. 59 J. A. Nelson S. Chou and T. A. Spencer Chem. Comm. 1971 1580. 6o M. M. Campbell and D. M. Evgenios Chem. Comm. 1971 179. Heterocyclic Chemistry-Part (i) Saturated Ring Systems 563 acids6' and phenyldithiocarbazic acid.62 Spectral data for (76) indicate strong conjugative interactions between the sulphur atoms and the carbonyl groups. Five-membered cyclic phosphites have been shown to exhibit greatly reduced nucleophilic reactivity compared to their acyclic analogues ; this is attributed to the increased ring strain accompanying quaternization at pho~phorus.~~ This ring strain factor can suppress the normally exothermic Arbusov-type reaction of phosphor amid ate^.^^ Contrary to assertions that phosphorus inversion in phosphochloridites is rapid configurational stability is demon- strated by (78) and it is suggested that the tendency towards inversion depends solely on sample purity.65 4 Six-memberedRings In a comprehensive study experimental evidence has been presented which clearly establishes the previously disputed equatorial quaternization of nitrogen throughout the tropane series.66 On the synthesis side a large section of a diamond-type lattice (SO) has been prepared uia treatment of (79) with ethyl a-brom~methylacrylate,~~ intramole-cular quaternization has yielded the novel heterocycle (S1),68 aluminium chloride- catalysed cyclization of substituted allylthioglycollic acid chlorides (82) to dihydrothiapyran-3-ones provided a route uia (83) to the hitherto unknown parent (84),69and a novel cyclization of ad-dibromoadipic acid dianilide for Et x-0 N Et0,C aN3 (79) X = Br C104,or picrate Et0,C P (81) (84) " P.YatesandT. R. Lynch Canad. J. Chem. 1971,49 1477. '* G. Casalone and A. Mugnoli J. Chem. Soc. (B) 1971,415. b3 C. Brown R. F. Hudson V. T. Rice and A. R. Thompson Chem. Comm. 1971 1255. 64 C. Brown and R. F. Hudson Tetrahedron Letters 1971 3191. 65 R. H. Cox M. G. Newton and B. S. Campbell J. Amer. Chem. SOC.,1971 93 528. " G. Fodor R.V. Chastain jun. D. Frehel M. J. Cooper N. Mandava and E. L. Gooden J. Amer. Chem. SOC.,1971 93 403. " H. Stetter and K. Komorowski Chem. Ber. 1971 104 75. " C. H. Chen and K. D. Berlin J. Urg. Chem. 1971,36 2791. '9 K. Sato S. Inoue and K. Kondo J. Org. Chem. 1971 36 2077. 564 I. D. Blackburne and M. J. Cook which potassium fluoride was the only successful catalyst encountered has given the bicyclic lactam (SS).” Allylic ammonium ylides normally undergo rapid sigmatropic rearrangement e.g. (86)+(87). However as expected such rearrangements are notably slowed or inhibited by unfavourable transition state geometry and this is exemplified by the alternative generation of the carbonyl-stabilized ylide (89) from (SS).” 0 0 Yh Br-/ I CHzCH=CHPh CH,CH=CHPh (88) (89) The dihydropyridine formed on condensing aniline with butanal was earlier assigned structure (90) its reaction with a dienophile being presumed to result from a concerted 1,3-hydrogen shift during cycloaddition.However this process [n2s+.2 +02s +.2,] is now recognized to be thermally forbidden and a re-investigation has revealed that the dihydropyridine possesses structure (91).72 The conclusion is reached that there is no authentic concerted diene reaction of 1,4-dihydropyridines. This is in accord with the reaction of 1.4-dihydropyridines with acetylene dicarboxylate which gives fused cyclobutene derivative^,^^" and the further observation that with acrylonitrile adducts of type (92) are formed,73b unless the 4-position is fully substituted when the ring is inert to this reagent.R’ (90) (91) (92) 70 I. Shahak S. Rozen and E. D. Bergmann J. Org. Chem. 1971 36 501. 71 S. Mageswaran W. D. Ollis I. 0. Sutherland and Y. Thebtaranonth Chem. Comm. 1971 1494. 12 G. Krow E. Michener and K. C. Ramey Tetrahedron Letters 1971 3653. 73 (a) R. M. Acheson and N. D. Wright Chem. Comm. 1971 1421; (b) R. A. Sulzbach and A. F. M. Iqbal Angew. Chem. Internat. Edn. 1971 733. Heterocyclic Chemistry-Part (i) Saturated Ring Systems 56 5 7°2Me C0,Me Pr Me (93) (94) (95) Other groups report that a 2,3-dihydropyridine (93) is formed from butanal and ammonium acetate in acetic acid,74 and that the thermal ring expansion of the 1,2-dihydropyridine (94) gives the 3H-azepine (95).75 The decomposition of cyclic diaza-alkanes continues to be a field of active interest.76 Variations reported this year include the Lewis-acid-catalysed re- organization of the N-oxide (96; Y = Nf-O-) to benzaldehyde ~xime~~ and the pyrolysis of diazabasketene itself (96; Y = N) to azocine (97) rather than to ~ubane.~' Both rearrangements proceed with loss of HCN and the inter- mediacy of structures (98 Y = N+-O-BF,) and (98 Y = N) is suggested.The high preference shown by lithium for the equatorial position in 6-lithio- sultones and 2-lithiodithia1-1~~~ provides a route for stereospecific equatorial alkylations or deuteriation of these rings. Furthermore treatment of (99 ; R = Me or Ph) with butyl-lithium followed by quenching affords the isomer (99) Li 1 R R (100) 74 H.B. Charman and J. M. Rowe Chem. Comm. 1971,476. 75 T. J. van Bergen and R. M. Kellogg J. Org. Chem. 1971,36 978. 76 Ann. Reports (B) 1970 67 448; K. Shen. J. Amer. Chem. SOC.,1971 93 3064; D. E. McGreer and J. W. McKinley Canad. J. Chem. 1971 49 105; B. M. Trost and R. M. Cory J. Amer. Chem. SOC.,1971,93 5572 5573. 77 J. P. Snyder L. Lee and D. G. Farnum J. Amer. Chem. SOC.,1971,93 3816. 78 D. W. McNeil M. E. Kent E. Hedaya P. F. D'Angelo and P. 0. Schissel J. Amer. Chem. SOC.,1971,93 3817. 79 (a) T. Durst Tetrahedron Letters 1971 4171; (b) A. A. Hartmann and E. L. Eliel J. Amer. Chem. SOC.,1971 93 2572. 5 66 I. D.Biackburne and M. J. Cook Scheme 3 ( A new heterolytic fragmentation involving the anion of 1,3-dithianyl tosylates (Scheme 3)” may have synthetic applications as may Scheme 4 which provides a means of aldehyde homologation.8 Scheme 4 Some unusual cycloadditions have been reported which include the reaction of the keten-SO adduct with (101) to yield (102),” and the capture of very weakly dipolarophilic alkyl ketones by the intermediate 174-dipole (104) resulting from the spontaneous reaction of (103) with vinyl ethers.83 An unequivocal example of a [3+ l]cycloaddition has also been described in which the 1,3- dipolar azomethine imine derived from dissociation of (105)is trapped by t-butyl isocyanide to give (106).84 Ph Ph Ph >c=N-c,H,M~-~ + C H,Me-p Ph OR I CH H,C’+ \ I Ph (104) *O J.A. Marshall and J. L. Belletire Tetrahedron Letters 1971 871. F. A. Carey and J. R. Neergaard J. Org. Chem. 1971,36 273 1. 82 J. M. Bohen and M. M. Joullie Tetrahedron Letters 1971 1815. 83 S. R. Turner L. J. Guilbault and G. B. Butler J. Org. Chem. 1971 36 2838. 84 J. A. Deyrup Tetrahedron Letters 1971 2191. Heterocyclic Chemistry-Part (i) Saturated Ring Systems Conformational Analysis.-A substantial number of papers have appeared on conformational studies of various six-membered ring compounds. Further applications of the ultrasonic relaxation method' have provided data for more- stable to less-stable chair-chair inversion barriers in 2-methoxy-l ,3-dioxanss5" and more importantly data for the twist-boat to chair (tk)inversions in some alkylated 1,3-dio~ans.~'~ Together with results for chair<hair (c-c) inversion barriers the latter results allow energy parameters for the tb Sc equilibrium to be obtained directly by experiment.Variable-temperature n.m.r. has been applied to an ever-widening range of ring compounds and an unusually low c-c barrier (AGI = 5.5 kcal mol-') has been reported for the silane (107) which is attributed to the long C-Si bonds.'6 In the low-temperature spectrum of the tetrathian (108) all three rate processes ec,c-tb and pseudorotation (twist-twist) have been observed and a lower limit of 10 kcal mol- ' is assigned to the twist-twist process" (cf 0.8 kcal mol-' in cyclohexane). /\ I Me Me F The 19F n.m.r.spectrum of the N-fluoropiperidine (109)shows that N-inversion is slow on the n.m.r. time-scale up to 60"C and the authors report a ratio of axial lone-pair to equatorial lone-pair of 95 5." 'H N.m.r. and 13C n.m.r. studies suggest that the lone pair in piperidine itself is preferentially equatorial when complexed with a shift reagent.'9 R5 ((I) G. Eccleston E. Wyn-Jones and W. J. Orville-Thomas J. Chem. Soc. (B) 1971. 1551 ; (b)G. Eccleston and E. Wyn-Jones ibid. p. 2469. 86 C. H. Bushweller J. W. O'Neil and H. S. Bilofsky Tetrahedron 1971 27 3065. " C. H. Bushweller G. U. Rao and F. H. Bissett J. Amer. Chem. Soc. 1971 93 3058. J. Cantacuzene and J. Leroy J. Amer. Chem. SOC.,1971 93 5263. 89 I. Morishima K. Okada T. Yonezawa and K. Goto J.Amer. Chem. SOC.,1971 93 3922; I. Morishima K. Okada M. Ohashi and T. Yonezawa Chem. Comm. 1971 33. 568 I. D.Bluckburne and M. J. Cook Tetrahydro-1,3-oxazines and hexahydro-1,3-diazines continue to attract study.” J(NHCH) couplings have been observedgoa in both systems and indicate that N-H protons are predominantly if not exclusively axial a result which is discussed in terms of the generalized anomeric effect cf the ‘rabbit ear effect’. N-Alkyl substituents on rings lacking a substituent at C-2 are preferen- tially equatorial and it has been suggestedgob that the ‘rabbit ear effect’ may be rather less important than was at one time thought. Presumably however dipolar effects contribute substantially to the factors which lead to the observed axial preference of the N-But group in (1 But I 0 s+ I & 0 0 The proton hyperfine splitting constants in the nitroxyl radical (1 11) have been used to show that the N-0 group is predominantly The N-oxide bond of N-methylmorpholine N-oxide also shows an axial preferen~e,~~ as do the semipolar S-0 bonds in (1 12 X = 0 or S),94 cJ sulphoxides and sulphites.Extensive research on phosphacycles has provided further evidence for the axial preferences of 2-C1 and 2-OR groups on 1,2,3-dioxaphosphorinan (1 13)95 and 1,2,3-dioxaphosphorinan-2-one (1 14)96 rings though a 2-phenyl group on the latter ring is preferentially eq~atorial.~’ Substitution of ring oxygen atoms for sulphur e.g. (115)reduces the axial preference for a 2-OPh The P-H bonds in (116; R’ = H, R2 = H) and (117),99 and the phenyl group in [116; R’ = 0 or (OMe), R2 = Ph]’oo are also predominantly axial.90 (a) H. Booth and R. U. Lemieux Canad. J. Chem. 1971,49 777; (6)E. L. Eliel L. D. Kopp J. E. Dennis and S. A. Evans jun. Tetrahedron Letters 1971 3409; (c) F. G. Riddell and D. A. R. Williams Tetrahedron Letters 1971 2073; P. J. Halls R. A. Y. Jones A. R. Katritzky M. Snarey and D. L. Trepanier J. Chem. Soc. (B),1971 1320; R. A. Y.Jones A. R. Katritzky and D. L. Trepanier ihid. p. 1300; T. A. Crabb and R. F. Newton Tetrahedron Letters 1971 3361. 91 L. Angiolini R. P. Duke R. A. Y.Jones and A. R. Katritzky Chem. Comm. 1971 1308. 92 A. Rassat and J. Ronzaud J. Amer. Chem. SOC.,1971 93 5041. 93 M. J.Cook A. R. Katritzky and M. Moreno-Mafias J. Chem. SOC.(B),1971 1330. y4 D. N. Harpp and J. G. Gleason J. Org. Chem. 1971 36 1314. 95 M. Haemers R. Ottinger J. Reisse and D. Zimmermann Tetrahedron Letters 1971 461; K. Bergesen and P. Albriktsen Acta Chem. Scand. 1971 25 2257. 96 D. W. White G. K. McEwen R. D. Bertrand and J. G. Verkade J. Chem. SOC.(B) 1971 1454. 97 J.-P. Majoral R. Pujol J. Navech and F. Mathis Tetrahedron Letters 1971 3755. 98 J. R. Campbell and L. D. Hall Chem. and Ind. 1971 1138. 99 J. B. Lambert and W. L. Oliver jun. Tetrahedron 1971,27 4245. loo A. T. McPhail J. J. Breen J. H. Somers J. C. H. Steele jun. and L. D. Quin Chem. Comm. 1971 1020; A. T. McPhail J. J. Breen and L. D. Quin J. Amer. Chem. Soc. 1971,93,2574. Heterocyclic Chemistry-Part (i) Saturated Ring Systems f'i n m-30 o\p/o o\p I 11 4\ ox o// \OPh R2 HS (113) (1 14) (1 15) (1 16) (1 17) 5 Medium-and Large-ring Compounds Syntheses of novel heterocycles and improved routes to known ones have been the subjects of a number of reports this year.These include routes to di- and tetra-hydro-2-benzazepinesand their corresponding 1,3-diones e.g. (118)," and to the benzodiazepinone (1 19) from which the diazacycloundecene ( 120) was obtained.'02 Tetra- and penta-thiepins (l2l)lo3 and (122),lo4 respectively and the first seven-membered cyclic phosphinic acid (123)"' have been pre- pared and the novel pyrrolo-benzodiazocine (124) has been synthesized from (125).'06 In contrast to the behaviour of ethylenediamine with arylideneacetone which gives 14-membered ring products 1,3-diaminopropane with benzylidene- acetone yields (126) rather than a 16-membered ring.lo7 Also unexpected was the photolytic product of (127) ; unlike many hetero-derivatives of 1,3-cyclo- heptadiene (127) failed to collapse to a bicyclic nucleus (of the penicillin type) and either dimerized or rearranged with addition of methanol to (128).'OS G.N. Walker and D. Alkalay J. Org. Chem. 1971 36 461. lo2 M. Davies P. Knowles B. W. Sharp R. J. A. Walsh and K. R. H. Wooldridge J. Chem. Soc.,(C),1971,2449. '03 F. Feher F. Malcharek and K. Glinka Angew. Chem. Znternat. Edn. 1971 10 331. F. Feher and M. Langer Tetrahedron Letters 1971 2125. J. L. Suggs and L. D. Freedman J. Org.Chem. 1971 36 2566. lo6 G. De Martino S. Massa M. Scalzo R. Giuliano and M. Artico Chem. Comm. 1971 1549. lo' K. Hideg and D. Lloyd Chem. Comm. 1971 372. lo* M. F. Semmelhack S. Kunkes and C. S. Lee Chem. Comm. 1971 698. 570 I. D. Blackburne and M. J. Cook X-Ray studies on l-azabicyclo[3,3,3]undecanehydrochloride (129) the free base of which was reported last year,"' confirm the be bc be (bc = boat-chair) conformation suggested for this system and reveal internal strain.' lo Flattening at the nitrogen accounts for the greater acidity relative to quinuclidine hydro- chloride while the free base itself exhibits an electronic absorption uncharac- teristic of a tertiary amine and this again is attributed to distortion. Syntheses conformational studies and transannular interactions between aromatic rings have been the subjects of a number of papers on heterocyclo- phanes.'' Polyether studies have also continued in depth increasing attention being directed towards the examination of complex stability. Stability constants for complexes of cyclic"2 and bicyclic"3 polyethers e.g. (130)and (131),with various cations demonstrate forcibly that ring size or more correctly the fit of log Ann. Reports (B) 1970 67 462. 'lo N. J. Leonard J. C. Coll A. H.-J. Wang R. J. Missavage and I. C. Paul J. Amer. Chem. SOC.,1971,93 4628. ''I S. Akabori K. Shiomi and T. Sato Bull. Chem. SOC.Japan 1971 44 1346; T. Sato M. Wakabayashi K. Hata and M. Kainosho Tetrahedron 1971 27 2737; B. R. Davis and I. Bernal J.Chem. SOC.(B) 1971 2307. H. K. Frensdorff J. Amer. Chem. SOC.,1971 93 600. J. M. Lehn and J. P. Sauvage Chem. Comm. 1971,440. Heterocyclic Chemistry-Part (i) Saturated Ring Systems the cation in the cavity is a key factor in determining complex stability and hence potential selectivity. For monocyclic crowns the optimum ring size for stable + + complexes is 15-1 8 for Na + 1 8 for K ,and 18-2 1 for Cs . Enhanced stability of complexes in organic solvents relative to water is also noted. Large differences in the heats of complexing (130) for the smaller cations Na' and Li' compared with K+,Cs' and NH,' are reported' l4 and these differences are shown to be solvent dependent the largest difference being in DMSO. New nitrogen- and sulphur-containing polyethers have been described.Stability constants for complexes of the alkali and alkaline-earth metals fall on replacing oxygen by N and S but the reverse order is demonstrated for Ag+ complexes where covalent bonds rather than electrostatic forces are probably involved. Crystalline complexes of macrocyclic polyethers with one to six molecules of thiourea have been prepared but the exact nature of these complexes is as yet unknown.'16 Et 7jH5 Et\'\ OH I I p-C,H,C,H,-C-D Me-C-C-Me -+ Me-C-H I /I I OMe C6H5 Et C6H 5 ( 132) (1 33) ( 134) The stereochemical fates of carbanions in the presence of a crown ether have been reported."' Optically active (132) in K0Bu'-Bu'OH undergoes D-H exchange (k,) and racemization (k,) at the relative rate k :k of 46 but in the presence of (130) both rates are enhanced and the ratio k :k is 0.9.Again the base-catalysed decomposition of (133) to (134) proceeds with 90% retention of configuration but in the presence of crown ether the reaction proceeds with 15 7; net inversion. E. M. Arnett and T. C. Moriarity J. Amer. Chem. SOC.,1971 93 4908. C. J. Pedersen J. Org. Chem. 1971,36,254;D. St. C. Black and I. A. McLean Austral. J. Chetri. 1971 24 1377 1391 1401; D. W. Allen P. N. Braunton I. T. Millar and J. C. Tebby J. Chern. SOC.(0, 1971 3454. 'I6 C. J. Pedersen J. Org. Chem. 1971 36 1690. 'I' J. N. Roitman and D. J. Cram J. Amer. Chem. SOC.,1971,93,2231.

ISSN:0069-3030    

DOI:10.1039/OC9716800551

出版商:RSC    

年代:1971

数据来源: RSC

摘要:

18 Heterocyclic Chemistry Part (ii) Heteroaromatic Compounds By M. H. PALMER Department of Chemistry University of Edinburgh West Mains Road Edinburgh EH9 3JJ The arrangement of the heteroaromatic section this year is to concentrate on major topics rather than widespread coverage of synthetic methods. Thus a higher proportion of material of a physical-organic nature is included. 1 Ground-state Properties of the Ring Systems Molecular Structure.-There is now more interest than formerly in accurate X-ray analysis of simple heterocycles ; this is important to theoretical studies of the bonding in such molecules but much work still remains to be done on systems where microwave studies are presently impracticable. For both 4- cyanopyridine’ and pyridine N-oxide,’ the geometric features are very similar to pyridine itself but for the 4,4’-bis-quaternary salt (l) the ring is marginally larger than in neutral pyridines and perhaps slightly more similar to that of ben~ene.~ The microwave spectrum of thiazole yields a structure very close to that expected by superposition of thiophen and 1,3,4-thiadia~ole.~ The crystal structure of sulphathiazole shows the heterocyclic ring to be non-planar the thiazoline tautomer to be present and the 4,5-bond to be purely 01efinic.~ Substituents e.g.t-butyl can markedly effect ring geometry and 4,5-di-t-butyl- imidazole has a singularly long 4,5-bond for a formal double bond ;the external M. Laing N. Sparrow and P. Somerville Acta Cryst. 1971 B27 1986. D. Ulku B.P. Huddle and L. C. Morrow Acta Cryst. 1971 B27 432. J. H. Russell and S. C. Wallwork Acra Cryst. 1971 B27 2473. L. Nygaard E. Asmussen J. H. Hsg R. C. Maheshwari C. H. Nielson I. B. Petersen J. Rastrup-Andersen and G. 0. Sorensen J. Mol. Structure 1971 8 225. G. J. Kruger and G. Gafner Acta Cryst. 1971 B27 326. 572 Heterocyclic Chemistry-Part (ii) Heteroaromatic Compounds angles between the t-butyl groups are markedly distorted;6a a similar feature is present in the 2,3-bond of 2,3-di-t-b~tylquinazoline.~* In the carbocyclic ring of the latter and of a 1,2-benzothiazole derivative,' the short (orb)and long (bp) bonds are evident as in naphthalene. The N-C bonds of 8-hydroxyquinoline N-oxide' are very long and again the structure is like that of naphthalene.This is also particularly true of various thiathiophthens (1,6,6a-trithiapentalenes) where the parent compound has been redetermined' and a number of substituted systems have been investigated." Results of some of the key types are given here [compounds (2),9 (3),' (4),11and (5),12 bond lengths in A]. 1,83 'm 1.684 1.90 n (4) (5) Among molecules with related structures compounds with nitrogen and oxygen in the rings13 again demonstrate the slight differences in bond lengths. It seems to be generally agreed that these systems do exhibit bonding between classically non-bonded atoms. From the theoretical standpoint the rigid geo- metry makes this inevitable i.e. within the molecular orbital framework all electrons are attracted to all nuclei and the only question is how much electron density lies along a plane through the nuclear centres.X-ray electron spectro- scopy (ESCA) shows differences in environment at sulphur atoms in some thiathiophthens but as in the X-ray-diffraction data care in interpretation is necessary since some of these features can possibly be related to molecular orientation in the crystal." Among other condensed-ring compounds the bond lengths of molecule (6) are very similar to those resulting from fusion of a benzene ring with thiophen ; ' G. J. Visser and A. Vos Acta Cryst. (a) 1971 B27 1802 (6) 1971 B27 1793. ' A. C. Bonamartini M. Nardelli C. Palmieri and C. Pellizzari Acta Cryst. 1971 B27 1775. ' R. Desiderato J. C. Terry G. R. Freeman and H.A. Levy Acta Cryst. 1971 B27 2443. A. Hordvik and K. Julshamn Acta Chem. Scand. 1971 25 1895,2507. lo A. Hordvik Acta Chem. Scand. 1971 25 1583 1822; A Hordvik and K. Julshamn. ihid. p. 1835; R. Kristensen and J. Sletten ibid. p. 2366; T. R. Lynch I. P. Mellor. and S. C. Nyburg Acru Cryst. 1971 B27 1958; I. P. Mellor and S. C. Nyburg ibid. p. 1954; J. Sletten Acta Chem. Scand. 1971 25 3577. D. T. Clark D. Kilcast and D. H. Reid Chem. Comm. 1971 638. M. H. Palmer the bis-sulphone has more aliphatic bond lengths in the centre rings.12 Above 0 “C N-methylazepine yields two dimers ;the higher melting has a trans-piperazine system.l4 The detailed crystal structures of a tram-corrin’ and corrole’ have been published; they are very similar to that of porphin published some time ago except that the PP-bonds are longer and the ctp-bonds shorter than in the latter.Electronic Structure.-Within the hierarchy of molecular orbital calculations empirical (Hiickel and its variants such as the w-technique) semi-empirical (CNDO INDO MINDO etc.) and non-empirical (‘ab iiiitio’),the first category is now redundant. CNDO self-consistent field calculations lead to charge distributions which vary with the method of analysis,” but seem very plausible and often match those of non-empirical calculations. In the latter case ground- state properties such as ionization potential,” dipole moments,’ 8,19and often electronic spectra are being interpreted in detail.’ 8-20 A useful review of the field not cited earlier has been published.2’ CNDO calculations of reacting systems are practicable and in one such case22 various stable n-complexes were calculated for the interaction of hydrogen fluoride and benzene or pyridine.Rapid development of this approach is expected. Determination of the magnetic-susceptibility anisotropy for 2-and 4-pyranone shows that the experimental figure can be entirely accounted for in terms of local group contributions and that the molecules are thus non-ar~matic.~ This contrasts with the results for benzene furan etc. where aromaticity is inferred. The low barriers to inversion calculated for phospholes but larger for their benzo-derivatives have been interpreted in terms of (3p2p)n delocalization and thus ar~maticity.~~ 12 I.Goldberg U. Shmueli Acta Cryst. 1971 B27 2164 2173. 13 P. L. Johnson K. 1. G. Reid and I. C. Paul J. Chem. Soc. (B) 1971 946; K. I. G. Reid and I. C. Paul ibid. p. 952; F. Leung and S. C. Nyburg Canad. J. Chem. 1971 49 167. 14 S. Gottlicher and G. Habermehl Chem. Ber. 1971 104 524. 15 J. D. Dunitz and E. F. Meyer Hela. Chim. .4cra 1971 54 77. 16 H. R. Harrison 0. J. R. Hodder and D. C. Hodgkin J. Chem. Soc. (B) 1971 640. 17 D. D. Shillady F. P. Billingsley and J. E. Bloor. Thwr. Chin?.Artrr 1971 21. 1. I8 M. H. Palmer and A. J. Gaskell Theor. Chim. Acta 1971 23 52; P. Siegbahn Chem. Phys. Letters 1971 8 245. 19 D. T. Clark and D. M. J. Lilley Chem. Phys. Letters 1971 9 234. 20 M. Hackmeyer and J. H. Whitten J. Chem.Phys. 1971 54 3739. 21 ‘Quantum Aspects of Heterocyclic Compounds in Chemistry and Biochemistry,’ ed. E. D. Bergmann and B. Pullman Israel Academy of Sciences and Humanities Academic Press New York 1970 vol. 2. 22 W. Jakubetz and P. Schuster Tetrahedron 1971 27 101. 23 R. C. Benson C. L. Norris W. H. Flygare and P. Beak J. Amer. Chem. Soc. 1971 93. 5591. 24 W. Egan R. Tang G. Zon and K. Mislow J. Amer. Chem. Soc. 1971,93 6205. 575 Heterocyclic Chemistq-Part (ii) Heteroaromatic Compounds N.M.R. and Aromaticity.Xarefu1 analysis of the 'H n.m.r. spectrum of benzo- thiophen shows the similarity to naphthalene and similar diamagnetic ring currents.25 The effects of geometry on coupling constants in five-membered rings have been correlated,26 and two lines are obtained from the correlation of 3J(,,, with 2J(13C,H), which has been interpreted in terms of an aromatic series and olefinic series2' The I3C n.m.r.shifts of various 5,6-fused heterocycles with one or more nitrogen atoms and their anions and cations can be correlated reasonably well with those calculated by the CNDO procedure and average excitation energy approach.28 The 5N magnetic resonance of ~yridine~~ and 14N of both pyridine and other azines3' have been obtained ;the 14Nshifts show a nearly linear correlation with calculated n-electron density but this may be an oversimplification since for N-methylpyridinium salts other effects domi- nate the 14N ~hifts.~' An extensive survey of the 'H chemical shifts of azines their N-oxides and protonated species has been given.32 The site of substituents in monocyclic heteroaromatics is usually fairly unambiguous but extensive compilations of coupling constants which may be useful in this respect have been given for pyridine~~~ and chloromethylthiophens ;34 the former set have been correlated with CNDO calculated values.Interaction of ~yridine~~ and pyra- ~ine~~ with silyl chlorides leads to the dihydro-derivatives (7) and (8) neither of which is stable to air or from the 'H n.m.r. evidence aromatic. In contrast the long-awaited synthesis of isobenzofuran (9) by pyrolysis of two Diels-Alder adducts (10) and (11),37 shows this compound to have 'H chemical shifts (those in CDCI shown) consistent with a diamagnetic ring current and hence aro- maticity [cfi (12)].(7) X = SiCl, Y = CHSiCl (8) X = Y = NSiMe 25 K. D. Bartle D. W. Jones and R. S. Matthews Tetrahedron 1971 27 5177. 26 R. J. Abraham K. Parry and W. A. Thomas J. Chem. Soc. (B) 1971 446. '' D. M. McKinnon and T. Schaefer Canad. J. Chem. 1971,49 89. 28 R. J. Pugmire M. J. Robins D. M. Grant and R. K. Robins J. Amer. Chem. Soc. 1971 93 1887; R. J. Pugmire and D. M. Grant ibid. p. 1880. 29 R. L. Lichter and J. D. Roberts J. Amer. Chem. Soc. 1971 93 5218. 30 M. Witanowski L. Stefanik H. Januszewski and G. A. Webb Tetrahedron 1971 27 3129. " F. W. Wehrli. W. Giger. and W. Simon Helr. Chim. Acra 1971 54,229; W. Giger P. Schauwecker and W. Simon ibid. p. 2488. 32 P. Hamm and W. von Philipsborn Helc.Chim. Acra 1971 54,2363. 33 J. P. Dorie M. L. Martin S. Barnier and M. Blain Org. Magn. Rrsonance 1971 3 661. 34 T. Sone and K. Takahashi Org. Magn. Resonance 1971 3 527. 35 D. Kummer and H. Koster Angew. Chem. Internar. Edn. 1971 10 412. 36 R. A. Sulzbach and A. F. M. Iqbal Angew,. Chem. Internat. Edn. 1971 10 127. 37 D. Wege Tetrahedron Letters 1971 2337; R. N. Warrener J. Amer. Chem. Soc. 1971,93 2346. 576 M. H. Palmer \L"J PY (1 1) py = 2-pyridyl The year 1971 has seen the synthesis of several other interesting ring systems. Selenium dioxide oxidation of semicarbazones gives 1,2,3-~elenadiazoles,~~ the parent compound of which has 4-H and 5-H chemical shifts (neat liquid) at 6.66 and 7.47 6 respectively. The Group Vb homologues of pyridine phospha- (14) arsa- (15) and stiba-benzenes (16) have all been prepared from 1,l-di- n-butyl-1,4-dihydrostannabenzene (13) ;39 full details of the proton resonance have not been given but all absorb in the 'aromatic region'.The a-protons at lowest field are well separated from the others and have progressively higher values of the coupling constant J(2,3).The same starting material (13) yields (13) 0 P I Li' Ph -0 Me '* I. Lalezari A. Shafiee and M. Yalpani J. Org. Chem. 1971 36 2836. 39 A. J. Ashe J. Amer. Chem. SOC., 1971 93 3293 6690. Heterocyclic Chemistry-Part (ii) Heteroaromatic Compounds the 1-phenylborabenzene anion (17).40 This compound shows the heterocyclic protons at 3.05 T (2,6-H) 2.6 T (3,5-H) and 3.66 z(4-H) which considering that there must be some electron donation from the boron atom (i.e.an upfield shift) is strongly indicative of a diamagnetic ring current. The proton resonance of the ring protons in thiabenzene 1-oxide (18) is at very high field:' and the corresponding 13C shifts (109 50 and 89 p.p.m. from CS for a- B- and y-carbon respectively) are also at very high field compared with those of benzene (65 p.p.m.) or thiophen (68 and 66 p.p.m.). The proton coupling J(2,6)=4.4Hz must be one of the highest meta constants in proton resonance. Coupling of two thiapyrylium ions via the radical followed by oxidation yields the 4,4'-bisthiapyrylium salts whose proton resonance lies only slightly downfield of that of the rnon~cation.~~ Azocine (20) prepared by vacuum pyrolysis of diazabasketene (19),43 resinifies above -50 "C but the 2-methoxy- derivatives are rather more The latter have invariant 'H n.m.r.spectra from -75 to +185 "C and show no evidence of the bicyclic system (21) except in their reactivity. U.V. irradiation of the tetracyclo-compound (22) gives the 172-diazocine (23) which shows singlets at 6.08 and 6.936 (4:2 ratio).45 As expected none of these 871-electron rings show diagmagnetic ring currents. Although this is also the case with the 10 or 1471-electron benzo-derivatives (24)46 and (25),47 the 2-methoxydiazocine dianion obtained by reduction with potassium in THF absorbs downfield of the neutral compound rather than upfield as might have been expected from the negative charge.This does appear to be evidence of a diamagnetic ring current.48 40 A. J. Ashe and P. Shu J. Amer. Chem. SOC.,1971,93 1804. 41 A. G. Hortmann and R. L. Harris J. Amer. Chem. SOC.,1971 93 2471. 42 Z. Yoshida S. Yoneda T. Sugimoto and 0. Kikukawa Tetrahedron Letters 1971 3999. 43 D. W. McNeil M. C. Kent E. Hedaya P. F. D'Angelo and P. 0. Schissel J. Amer. Chem. SOC.,1971,93 3817. 44 L. A. Paquette T. Kakihana J. F. Hansen and J. C. Phillips J. Amer. Chem. Soc. 1971 93 152. 45 B. M. Trost and R. M. Cory J. Amer. Chem. SOC.,1971 93 5573. 46 H. J. Shue and F. W. Fowler Tetrahedron Letters 1971 2437. 47 D. L. Coffen Y. C. Poon and M. L. Lee J. Amer. Chem. SOC.,1971,93,4627. 48 L. A. Paquette J. F. Hansen and T. Kakihana J.Amer. Chem. SOC.,1971 93 168. 578 M. H. Palmer (24) X = NMe (25) X = S Tautomeric Equilibria and Conformations.-A distinction can be made by n.m.r. between the spectra of the 7H- and 9H-tautomers of xanthines and the 1-and 3-methyl derivatives appear to be the 7H-ta~tomers.~~ The protonation of purines’’ and of N-methylcarbazoleso has been studied by n.m.r. A similar study of the tautomerism of ‘dihydroxythiophens’ shows the 2,3- 2,4- and 3,4-series to be the 3-hydroxy- and 4-hydroxy-3-thiolen-2-ones, and 3-hydroxy-2- thiolen-4-ones respectively.’ The 4-hydroxyisoxazole tautomer is preferred over the cyclic oxime form.5 The nitrosation of hydroxyaminoacetonitriles yields cyclic compounds which are better represented as 5-amino-1,2,3-oxa-diazole N-oxides (26) rather than the sydnoneimine (27) since in contrast to the latter they do not form salts with Although largely in the 1H-(28)and 3H-forms the purple colour of cyclopenta[b]quinoline arises from the estimated 0.1 2)of the 4H-tautomer (29).55 0-HO \+ Various groups have studied the conformation of furan pyrrole and thiophen aldehydes and ketones by n.m.r.spectra. The nuclear Overhauser effect,56 4y D. Lichtenberg F. Bergmann and Z. Niemann J. Chem. Soc. (C) 1971 1676. ” H. J. Chen L. E. Hakka R. L. Hinman A. J. Kresge and E. B. Whipple J. Amer. Chewz. Soc. 1971 93 5102. ” R. Wagner and W. von Philipsborn Heir. Chim. Acta 1971 54 1543. ’’ J. Z. Mortensen B. Hedegaard and S. 0. Lawesson Tetrahedron 1971 27 3839.53 G. Bianchi M. J. Cook and A. R. Katritzky Tetrahedron 1971 27 6133. M. Gotz and K. Grozinger Tetrahedron 1971 27 4449. 55 J. J. Eisch and F. J. Gadek J. Org. Chrm. 1971 37 2065. 56 S. Combrisson B. Roques P. Rigny and J. J. Basselier Cunad. J. Chern. 1971 49 904; B. Roques C. Jaurequeberry M. C. Fournie-Zaluski and S. Combrisson Tetrahedron Letters 1971 2693. Heterocyclic Chemistry-Part (ii) Heteroaromatic Compounds long-range coupling,57 and low-temperature studies58 are valuable here. An attempt to use nematic-phase measurements normally good for measuring inter-proton distances e.g. for thi~phen,~~ was successful with a thiophen di- aldehyde but not for the furan analogue,60 where a negative distance was cal- culated between two hydrogen atoms ! 2 Quaternary Salts and N-Oxides Alkylation of a range of 2-(4-dimethyIaminophenyl)pyridinesoften leads to kinetically controlled attack on the exocyclic nitrogen but the thermodynamically favoured products are quaternary salts.6 A similar thermal reversal occurs with 5-phenyltetrazoles where the quaternary salts are only stable at low tem- peratures.62 The relative rates of methylation at N-4 of 2-substituted-pyrazines and 3-substituted-pyridines are constant.63 The electron densities at N-1 and N-2 in cinnolines are equal and the proportion of methylated compounds is controlled by steric effects ;64there have been further studies of the methylation of cinnolin-4-0nes.~~ An unusual cycloalkylation is the formation of (30) from 2-(4-iodobutyl)-3-methylbenzothiophen.66The N-oxide of pentachloropyridine Me where the basicity is low can be prepared from the azine by treatment with peracetic acid mixture in the presence of concentrated sulphuric acid ;apparently the peracid is protonated and hence more reactive.67 The differential solvent- induced n.m.r.shifts can be used to determine the site of N-oxidation in substi- tuted pyrazines ;68 3-methoxy- and 3-unsubstituted-l,2,4-triazines give 1-oxides whereas the 3-amino-compounds give 2-0xides.~' '' '' B. Roques and M. C. Fournie-Zaluski Org. Magn. Resonance 1971 3 305. K.-I. Dahlqvist and A.-B. Hornfeldt Tetrahedron Letters 1971 3837. 59 J.-M. Dereppe J.-P. Morisse and M. van Meerssche Org. Magn. Resonance 1971 3 583.(lo T. N. Huckley Tetrahedron Letters 1971 3497. " G. Y. Paris D. L. Garmaise and J. Komlossy J. Heterocyclic Chem. 1971 8 169. '* T. Isida S. Kozima K. Nabika and K. Sisido J. Org. Chem. 1971 36 3807. 63 L. W. Deady and J. A. Zoltewicz J. Amer. Chem. Soc. 1971 93 5475. " M. H. Palmer and P. S. McIntyre Tetrahedron 1971 27 2913 2921. h5 D. E. Ames H. R. Ansari A. D. G. France A. C. Lovesey B. Novitt and R. Simpson J. Chern. Soc. (C) 1971 3088. 6b J. A. Cotruvo and 1. Degani Chem. Comm. 1971 436. (" G. E. Chivers and H. Suschitzky J. Chem. Soc. (C),1971 2867. W. W. Paudler and S. A. Humphrey Org. Magn. Resonance 1971 3 21 7. " W. W. Paudler and T. K. Chen J. Org. Chem. 1971 36 787. M. H. Palmer 3 Aromatic Substitution Hydrogendeuterium exchange using deuterioacetic acid occurs in the 2-methyl and 3-positions of 2,6-di-methylpyrylium salts but not in the 4-position.This is ascribed to formation of the acetate (31) and ring-opened species.70 The partial rate factors for nitration of 4-phenylpyridine show all positions to be strongly deactivated with respect to benzene; this is largely a field effect.71 The rates of nitration in quinoline quinolin-4-one and cinnolin-4-one have been deter- mined.72 The hydrogen-deuterium exchange in quinoline isoquinoline and their N-oxides takes place on the protonated molecules except for the 2-H and 3-H of q~inoline.~~ The rates of exchange in deuterioacetic acid for both the 2-and 3-positions of N-methylpyrrole are higher than for the parent ring but the effect is most marked at the 2-po~ition.~~ The partial rate factors for acetylation of furan (F) and thiophen (T) have been obtained ; furan is more selective at the a-p~sition,~~ and comparison with the corresponding benzo-derivatives (BF/BT) leads to the following order of reactivity a-F >> r-T >> a-BF z B-BT > a-BT z /?-BF > P-F z /3-T.76 The rates of both H-D exchange and nitration in 3,5-dimethyl- isoxazole -isothiazole and 1,3,5-trimethylpyrazole show that the first of these reacts as the free base and the others as the conjugate acid.77 The rates of H-D exchange in the ring positions of various azaindenes correlate well with SCF x-electron calculations but apparently not with the corresponding n-localization energies; further studies of the latter type which include all valence electrons seem de~irable.~ Reduction of pyridines with lithium aluminium hydride followed by direct treatment of the reduced salt with alkyl halide or bromine gives 3-substituted- pyridines in high yield.79 Oxidation of 3-substituted-N-methyl quaternary salts by ferricyanide gives more of the 6-than the 2-pyridinone when the substituent 7" D.Farcasiu A. Vasilescu and A. T. Balaban Tetrahedron 1971 27 681. F. De Sarbo and J. H. Ridd J. Chem. SOC.(B) 1971 712. 72 D. H. G. Crout J. R. Penton and K. Schofield J. Chem. SOC.(B) 1971 1254; R. B. ' Moodie J. R. Penton and K. Schofield ibid. p. 1493. U. Bressel A. R. Katritzky and J. R. Lea J. Chem. SOC.(B) 1971 4 11. G. P.Bean Chem. Comm. 1971 421. 75 G. Ciranni and S. Clementi Tetrahedron Letters 1971 3833; S. Clementi P. Linda and M. Vergoni Tetrahedron 1971 27 4667. j6 S. Clementi P. Linda and G. Marino J. Chem. Soc. (B) 1971 79. 7' A. G. Burton P. P. Forsythe C. D. Johnson and A. R. Katritzky J. Chem. SOC.(B) 1971 2365. j8 W. Engewald M. Muhlstadt and C. Weiss Tetrahedron 1971 27 851 4171. '' C. S. Giam and S. D. Abbott J. Amer. Chem. Soc. 1971 93 1294. Heterocyclic C hemis try-Part (ii) Heteroaromat ic Compounds 581 is electron withdrawing." It seems that the rate-determining step in these reactions is formation of the ferricyanide complex rather than cleavage of the C-H bond.81 Direct alkylation of pyridine with an alkyl-lithium gives high yields of 2- and 2,6-substituted compounds even with t-butyl-lithium.82 The product from pyridine N-oxide and Grignard reagents is apparently acyclic.Addition of lithium alkyls to 2,4,6-triphenylphosphabenzene gives 1,2- dihydro-derivatives (32),which on oxidation lead to the quaternary salts (33)and then the 1-alkyl-1-alkoxyphosphabenzenes(34)on treatment with alcohols. 84 gem-Dihalides and base give benzene derivatives via a 1,2-addition sequence (Scheme l) which can be interrupted to yield (35)by the addition of an acid.85 1-Substituted-phospholes lose the substituent on treatment with alkali metals ; the solutions give e.s.r. signals from the intermediate radical-anion ;re-alkylation is readily achieved. 86 Ph Ph fi" %phn Ph "g(OAc! PhOPhPI1 P P+ P Ph I I R" 'OR' R' R' (32) (33) (34) *l 1 Ph fiPh PH I R CRCl (35) Scheme 1 8o H.Mohrle and H. Weber Chem. Ber. 1971 104 1478. 81 R. A. Abramovitch and A. R. Vinutha J. Chem. Soc. (B) 1971 131. R. F. Francis J. T. Wisener and J. M. Paul Chem. Comm. 1971 1420; F. V. Scalzi and N. F. Golob J. Org. Chem. 1971 36 2541. 83 T. J. van Bergen and R. M. Kellog J. Org. Chem. 1971 36 1705. 84 G. Markl and A. Merz Tetrahedron Letters 1971 1215; G. Markl A. Merz and H. Rausch ibid. p. 2989. 85 G. Markl and A. Merz Tetrahedron Letters 1971 1269. 86 D. Kilcast and C. Thomson Tetrahedron 1971 27 5705; E. H. Braye I. Caplier and R. Saussez ibid. p. 5523. 582 M. H. Palmer Although 3-chloro-1,2-benzisothiazolereacts normally with ethanolic sodium ethoxide with sodium cyanide in acetone (or carbanions) the reaction yields aryl thiocyanates (37) (or sulphides) by attack on sulphur (36)” There is some sitnilarity in the spontaneous cleavage of 3-lithiobenzo[h]thiophen and the metal-hydrogen exchange accompanying its8 [(38H40)] or the spontaneous cleavage of 5-lithio-1 -methyltetrazole to methyl cyanamide.89 Li (39) The rates of displacement of a fluorine atom are greater than those of chlorine for a variety of displacements by methoxide ion or piperidine.” Thus in benzo- 1,2,3-thiadiazoles although the 6-position is normally the most reactive fluorine in other positions is selectively replaced rather than a 6-chloro-sub~tituent.~~ The positional order of reactivity of halogenothiazoles to methoxide ions is 5 >2 >4 but with a rate range of 30.The 4- or 5-reactivity does not involve hetarynes since the 5-phenyl-4-chloro-compound has similar reactivity to the compounds without a substit~ent.~’ The chemistry of hetarynes has been reviewed,93 and there has been further discussion of their significance in reactions of hal~genopyridines.~~ 3-Bromothiophens can be conveniently prepared from the 2-bromo-compound by rearrangement in the presence of potassamide. 95 Benzyne adds across the 1,4-positions of ph~sphabenzene.~~ Further replacements of fluorine in perfluoroheteroaromatics have been reported ;the order of reactivity for a-substitution by hydrogen chloride in ’-D. E. L. Carrington K. Clarke and R.M. Scrowston J. Chem. Soc. (C) 1971 3262 3903. 88 R. P. Dickenson and B. Iddon J. Chem. Soc. (C) 1971 3447. 89 R. Raap Cunad J. Chem. 1971,49 2139. 90 G. B. Bressaw I. Giardi G. Illuminati P. Linda and G. Sleiter J. Chem. SOC.(B) 1971,225. 91 J. H. Davies E. Haddock P. Kirby and S. B. Webb J. Chem. SOC.(C),1971 2843. 92 M. Bosco L. Forlani P. E. Todesco and L. Troisi Chem. Comm. 1971 1093. 93 T. Kauffman and R. Wirthwein Angew. Chem. Internat. Edn. 1971 10 20. 94 H. N. M. van der Lans H. J. den Hertog and A. van Veldhuizen Tetrahedron Letters 1971 1875; J. A. Zoltewicz and A. A. Sale J. Org. Chem. 1971 36 1455. 95 M. G. Reinecke H. W. Adickes and C. Pyun J. Org. Chem. 1971 36 2690. 9h G. Markl F. Lieb and C. Martin Tetrahedron Letters 1971 1249.Heterocyclic Chemistry-Part (ii) Heteroaromatic Compounds 583 sulpholane is quinoline >> isoquinoline > ~yridine.~' The reaction of hexa- fluoropropene with fluorides and tetrafluoro-pyridazine or -pyrimidine leads to 4,5- or 4,6-substitution respectively ;the perfluoropropyl group is better able to absorb the resulting negative charge at the addition stage than the nitrogen atoms.98 Brief treatment of these perfluorinated aromatics at 580 "C or above leads to rearrangement99 of the pyridazines to the pyrimidines (44) plus a smaller amount of the corresponding pyrazines (Scheme 2). These changes are inter- preted in terms of the diazabenzvalene derivatives (45) and (46). An unusual type of cyclization with elimination of a fluoride ion is given in (47) -+ (48j.l" Scheme 2 F F F (47) (48) 4 Oxidation Reactions Examples of anodic oxidation applied to furans and thiophens in the presence of various nucleophiles have been given for example (49)-(50) where X = 0 or S."' Pyrylium and thiapyrylium ions and furans"' react in the triplet ')'R.D. Chambers M. Hole W. K. R. Musgrave and J. G. Thorpe J. Chem. Soc. (0, 1971 61. R. D. Chambers Y. A. Cheburkov J. A. H. MacBride and W. K. R. Musgrave J. ChcJm.SOC.(C) 1971 532; C. J. Drayton W. T. Flowers and R. N. Haszeldine ibid. p. 2750. OY R. D. Chambers J. A. H. MacBride and W. K. R. Musgrave J. Chem. SOC.(C) 1971 3384. loo G. M. Brook W. K. R. Musgrave and T. R. Thomas J. Chem. Soc. (0, 1971 3596. lo' K. Yoshida and T.Fueno J. Org. Chem. 1971 36 1523; K. Yoshida T. Saeki and T. Fueno rbid. p. 3673. T. Tsuchiya H. Arai and H. Igeta Tetrahedron Letters 1971 2579. 584 M. H. Palmer (49) FeOH excited state with ground-state oxygen (Scheme 3) but their ground-state molecules do not react with singlet excited oxygen,lo3 a result showing the electro- philic nature of singlet oxygen. Conversely pyrroleslo4 do react with singlet oxygen giving various products e.g. (51). Ph l* nph % P&%ph -+ PhCHO + PhCOzH Ph \ X Ph x+ + Scheme 3 NH Et Et Et Et Et&z -"Go MeaNI-Iz HO 00 Et Me H In an important series of publications Rees has described the formation and oxidation of N-aminoheterocycles. Reaction of the azine with hydroxylamine- 0-sulphonic acid or chloramine followed by treatment with lead tetra-acetate gives the nitrene which forces the loss of an adjacent carbonyl group and re- cyclization to the 1,2-diaza-systern.Thus quinoxalin-2-ones and indazoles give benzo-1,2,4- (52) and -1,2,3-triazines (53) respectively (Scheme 4). lo5 The 1,2,4- triazine-3-ones in contrast failed to give observable N-amino-derivatives but gave the ring-contracted species (54) and (55). lo6 The cinnolin-3-one and benzo- triazin-4-ones gave normal N-amino-derivatives which on oxidation yielded nitrogen and ring-contracted products ; the latter series showed intermediate '03 Z. Yoshida T. Sugimoto and S. Yoneda Tetruhedron Letters 1971 4259. G. B. Quistad and D. A. Lightner Tetrahedron Letters 1971 4417; Chem.Comm. 1971 1099. B. Adger C. W. Rees A. A. Sale and R. C. Storr Chem. Comm. 1971 695; D. J. C. Adams S. Broadbury D. C. Howell M. Keating C. W. Rees and R. C. Storr ihid. p. 828. '06 C. W. Rees and A. A. Sale Chem. Comm. 1971 (a),531 (6) 532. Heterocyclic Chemis try-Part (ii) Heteroaromatic Compounds NH I :N Scheme 4 formation of benzocyclopropenone. '06','07 In a related reaction oxidation of arylhydrazones gave the nitrile rather than the diazoalkane or sym-tetrazine. Other amine oxidations lead to benzo[c]cinnoline-N-imine'O9 and benzo-1,2,3- triazines' lo from 2,2'-diaminobiphenyl and o-aminophenyl ketone hydrazones. In contrast the oxidation of 1-aminoimidazolo[ 1,2-a]pyridinium ions gave the corresponding azo-compound perhaps showing the electrophilic nature of the nitrene.' ' 5 Reduction The only processes calling for comment are the polarographic reduction' l2 of 2-methoxyazocines directly to the dianion without evidence of the intermediate lo' J.Adamson D. L. Forster T. L. Gilchrist and C. W. Rees J. Chem. Soc. (C) 1971 981. log D. B. Mobbs and H. Suschitzky Tetrahedron Letters 1971 361. log S. E. Gail C. W. Rees and R. C. Storr Chem. Comm. 1971 1545. lo S. Bradbury M. Keating C. W. Rees and R. C. Storr Chem. Comm. 1971 827. 'I1 E. E. Glover and M. Yorke J. Chem. Soc. (C) 1971 3280. L. B. Anderson J. F. Hansen T. Kakihana and L. A. Paquette J. Amer. Chem. SOC. 1971 93 161. M. H. Palmer radical-anion a contrast to cyclo-octatetraene where the two stages are visible.This is interpreted as the first electron addition yielding a planar ring which is much more readily reduced (to a l0.n-electron system) than the neutral com- pound. In Hiickel terms the lowest vacant orbital of oxepin is antibonding and this correlates with the observation that the alkali-metal reduction of the 2,7-dimethyl compound leads to ring opening giving (56) and (57).'13 In a similar way reaction of the 4H-1,3-oxazine (58) with butyl-lithium yields an 8n-electron ring which rearranges to yield (60) and (61) via the identified species (59).'14 Me Me Me Me Me 6 Photochemical Reactions and Valency Isomerism Photolysis of various mesoionic compounds related to the sydnones gives carbon dioxide and a three-atom fragment from the ring which can be trapped by acety- lene dicarboxylic esters.Thus 3-arylsydnones give pyrazoles,' ' via the nitrili- mine and 4-aryl-l,3,2-oxathiazolinium 5-oxides yield isothiazoles via the nitrile sulphide.''6 A thermal reaction on the addition product of aldehydes or thioaldehydes to oxazolium 5-oxides also leads to loss of carbon dioxide (Scheme 5) and the formation of open-chain compounds (62).'17 Scheme 5 'I3 L. A. Paquette and T. McCreadie J. Org. Chem. 1971 36 1402. 'I4 R. R. Schmidt Angew. Chem. Internat. Edn. 1971 10 572. 'Is H. Gotthardt and F. Reiter Tetrahedron Lerters 1971 2749; M. Marky H. J. Hansen and H. Schmidt Helc. Chim. Acta 1971 54 1275; C. S. Angadiyavar and M. V George J. Org. Chem. 1971 36 1589. 'l6 H.Gotthardt Tetrahedron Letters 1971 1277 1281. '" R. Huisgen E. Funke H. Gotthardt and H.-L. Panke Chem. Ber. 1971 104 1532 E. Funke R. Huisgen and F. C. Schaefer Chem. Ber. 1971 104 1550. Heterocyclic Chemistry-Part (ii) Heteroaromatic Compounds Cyclohexa-2,5-dien-1,4-diolscan lead to either phenols or oxepins and suitable substituents such as t-butyl can force formation of the latter."* The synthesis of various oxepins and their Diels-Alder reactions through the benzene oxide form have been described.' l9 2,2,2-Trifluoroethanol is claimed to be unique in promoting nitrene (from nitrosobenzene) addition to benzene ;'2o the direction of nitrene insertion in p-disubstituted-benzenes is subject to marked steric effects. ' ' Carbon-carbon is preferred to nitrogensarbon bond fonna- tion in the photochemical cyclization of 1,2-diazepines (63),122but the latter occurs in the 6-ones (64) to yield (65).123 2-Methoxyazocines react in the form (66).44,124 Ph The photochemical rearrangement of 2-deuterioquinoline N-oxide yields 3-deuterioquinolin-2-one and indolecarbaldehyde derivatives,' whereas the related isatogen rearrangement [(67) +(70)] goes via epoxide-like intermediates (68) and (69) since ethanol fails to intercept the quinoid intermediate (71).126 'I8 A.Rieker Angew. Chem. Internat. Edn. 1971 10 425; S. Berger G. Henes and A. Rieker Tetrahedron Letters 1971 1257. W. Eberbach M. Perroud-Arguelles H. Achenbach E. Drucky and H. Prinzbach Helv. Chim. Acta 1971 54 2579. R. J. Sundberg and R.H. Smith Tetrahedron Letters 1971 267. J. M. Photis J. Heterocyclic Chem. 1971 8 167 729. G. Kan M. T. Thomas and V. Snieckus Chem. Comm. 1971 1022; J. Streith J. P. Luttringer and M. Nastasi J. Org. Chem. 1971 36 2962. 123 J. A. Moore E. J. Volker and C. M. Kopay J. Org. Chem. 1971 36 2676. L. A. Paquette and T. Kakihama J. Amer. Chem. Soc. 1971 93 174; L. A. Paquette Angew. Chem. Internat. Edn. 1971 10 11. 0. Buchardt K. B. Tomer and V. Madsen Tetrahedron Letters 1971 1311. D. R. Eckroth and R. H. Squire J. Org. Chem. 1971,36 224. M. H. Palmer (74) 0'U C N Such intermediates are however involved in the cleavage of anthranils (72) to o-aminoacetophenones (73) 12' and furazans (74) to azepines (75).128 Whereas an e.s.r. signal is obtained from the arylnitrene from the photolysis of 2-azido- acetophenone to (76) and (77) under similar conditions no signal is obtained from 3-methylanthranil where only (76) is obtained.' 29 Bicyclic products (78) arising from quinoid species such as (71) have been isolated from other photolytic reactions.30 Photochemical hydroxyalkylation of azines continues to be studied,' 31 as does the reverse reaction.' 32 27 E. Giovannini J. Rosales and B. de Souza Helv. Chim. Acta 197 1 54 21 11. 12' M. Georgarakis H. J. Rosenkranz and H. Schmid Helv. Chim. Acta 1971 54 819. 129 M. A. Berwick J. Amer. Chem. SOC.,1971 93 5780. 130 R. A. Olofson R. K. Vander Meer and S. Stournas J. Amer. Chem. SOC.,1971 93 1543; M. S. Ao and E. M. Burgess ibid. p. 5298.13' M. Natsume and M. Wada Tetrahedron Letters 1971 4503; T. J. Van Bergen and R. M. Kellogg J. Org. Chem. 1971 36 978; R. A. F. Deeleman H. C. van der Plas A. Koudijs and P. S. Darwinkle-Risseeuw Tetrahedron Letters 1971 4 159. 13' D. Elad I. Rosenthal J. Saloman and J. Sperling Chem. Comm. 1971 49. Heterocyclic Chemistry-Part (ii) Heteroaromatic Compounds (76) (77) (78) X = CO or SO 7 Ring Synthesis Asalways there has been extensive work in this field so any choice must appear arbitrary. Here it is restricted almost entirely to the most common ring systems. The condensation of aldehydes and ammonium salts leads to 1,2-dihydro-pyridines not the 2,3-isomers the ready synthesis of 3-aminoacrolein and its conversion into 3-alkylpyridines and pyrimidines has been noted.' 34 Further simple syntheses of 1,2,4-triazines and diaryl-1,3,5-triazinones have been given.l3 The cyclization of acetals in the Pomeranz-Fritsch isoquinoline synthesis and in indole synthesis can be facilitated by the use of boron trifluoride-trifluoroacetic anhydride as catalyst. '36 The reaction of 2-aminopyridine and P-ketoesters with polyphosphoric acid ethyl ester gives pyrido[ 1,2-a]pyrimidin-4-ones rather than + 1,8-naphthyridines.'37 The group [Me,N-CR=CR-CR=NMe,] X-can be readily cyclized to pyrimidines by reaction with amidines. 38 Quinazolines rather than indazoles are obtained from (79).'39 Two reactions related to the formation of isoxazoles and pyrazoles from dianions are the synthesis of 2- unsubstituted-oxazoles from metallated isonitriles and pyrazoles from trimetallated hydrazones (81).14' High yields of furans are obtained from propargylsulphonium salts and aliphatic ketones.'42 Simple syntheses of 3,2- borazaropyridines (83)'43 via the thiophens (82) and 5,1,3,4-boratriazaroles (84)'44 from amidrazones show these compounds to be fairly stable to air 133 G. Krow. E. Michener. and K. C. Ramev. Tetrahedron Letters. 1971. 3653. 134 E. Britmaier Angew. Chem. Internat. Edn:,'1971 10 268; E. Britrnaier and S. Gassen-mann Chem. Ber. 1971 104 665. T. V. Saraswathi and V. R. Srinwasan Tetrahedron Letters 1971 23 15 ; B. Singh and J. C. Collins Chem. Comm. 1971 498. 136 M. J. Bevis E. J. Forbes N. N. Naik and B. C. Uff Tetrahedron 1971 27 1253. K. Bowden and T.H. Brown J. Chem. SOC.(0,1971 2163. 138 R. M. Wagner and C. Jutz Chem. Ber. 1971 104,2975. 139 N. Finch and H. W. Gschwend J. Org. Chem. 1971 36 1463. I4O U. Schollkopf and R. Schroder Angew. Chem. Internat. Edn. 1971 10 333. 141 C. F. Bean R. S. Foote and C. R. Hauser J. Chem. SOC.(0,1971 1658. 142 J. W. Batty P. D. Howes and C. J. M. Stirling Chem. Comm. 1971 534. 143 S. Gronowitz and A. Maltesson Acta Chem. Scand. 1971 25,2435. 144 M. J. S. Dewar R. Golden and P. A. Spanninger J. Amer. Chem. SOC.,1971,93 3298. 590 M. H. Palmer R7CHLiCRZ=NNLi2 + R2 (81) H N-NR except for those where R = Me. Among large ring compounds the synthesis of 1,2,5,6,9,12-hexa-aza-l and 1,2,4,5,8,9,11,12-octa-aza-[ 121annulene'46 deriva-tives are of interest and a series of porphin-like molecules containing sulphur and oxygen in place of one or more nitrogen atoms has been de~cribed.'~~ Ethoxycarbonylnitrene inserts in the meso-ring 4,5-bond of porphyrins.' 48 145 P.Skrabel and H. Zollinger Helv. Chim. Acta 1971 54 1069. 146 H. Neunhoeffer J. Stastny and L. Motitschke Tetrahedron Letters 1971 1601. 14' M. J. Broadhurst R. Grigg and A. W. Johnson J. Chem. SOC.(c>,1971 3681; P. S. Clezy and V. Diakiw Austral. J. Chem. 1971,24,2665; M. Ahmed and 0. Meth-Cohn J. Chem. SOC.(0,1971 2104. 14' R. Grigg J. Chem. SOC.(0,1971 3664.

ISSN:0069-3030    

DOI:10.1039/OC9716800572

出版商:RSC    

年代:1971

数据来源: RSC

摘要:

E R RATA Vol. 67 B 1970 Page 170. The work described on compound (80) should have been attributed to E. V. Dehmlow and G. C. Ezimora ,TetrahedronLetters 1970 4047. 591

ISSN:0069-3030    

DOI:10.1039/OC9716800591

出版商:RSC    

年代:1971

数据来源: RSC

摘要:

AUTHOR INDEX Abbott S. D. 580 Abe K. 485 Abegg V. P. 224 Abelson J. 439 Abley P. 278 295 365 Abola J. 426 Abraham A. 492 Abraham A. J. 42 Abraham D. J. 445 Abraham R. J. 575 Abrahamson S. A, 12 Abramovitch R. A. 234 239 257 270 581 Abrell J. W. 444 Achenbach H. 404 587 Acheson R. M. 247 262 564 Achini R. 400 Achiwa K. 450 Achmatowicz O. 19 Achter J. 433 Acton N. 340 531 Adam W. 554 Adamic K. 206 Adams D. B. 97 Adams D. G. 526 Adams D. J. C. 238 270 584 Adams P. M. 399 Adams R. M. 370 Adamson J. 238 585 Adderley C. J. R. 548 Adger B. 238 270 584 Adhikary S. P. 482 Adickes H. W. 256 362 5.56 582 Adler E. 209 381 Adolf W. 479 480 Adrian F.J. 26 31 Agarwal K. 420 Agarwal K. L. 15 429 Agata I. 222 Agnado A. 523 Agnes C. 290 Agosta W. A. 231 Agosta W. C. 277 343 Agranat I. 534 Agster W. 528 Aguiar A. M. 295 365 376 381 Ahmed F. R.,123 124 Ahmed M. 590 Aidoo A. S. K. 550 Aimi. N. 506 Ainscough E. W. 281 Ainsworth C. 384 Aiyar L. 139 Ajami A. M. 471 Akabori S. 539 570 Akazawa T. 559 Akermark B. 234 Akhrem A. A, 484 Akhtar M. 173 185 Akiba A. 160 Akutsu H. 433 Alais L. 483 Albizzati E. 275 Albonico S. M. 369 459 Albrecht P. 467 Albriktsen P. 568 Albro P. W. 450 452 Albuquerque E. X. 494 Alder R. W. 536 Aldridge D. C. 455 Aleksandrov G. G. 291 Alexander R. 192 Alford G.149 Alford J. A. 257 374 553 Alkalay D. 569 Allan C. J. 95 Allen D. W. 571 Allen F. H. 125 402 481 503 Allen L. C. 50 53 56 61 69 74 Allen L. E. 189 Allerhand A. 32 33 36 Allinger N. L. 333 337 Allison D. A. 95 Allred E. L. 157 Almenningen A. 339 Al-Shamma A. A. 125 Altman L. J. 189 248 379 396,483 562 Altman S. 420 440 Altona C. 112 339 Alworth W. L. 416 Amano K. 254 Ames D. E. 458 579 Ames L. J. 486 Amit B. 393 Amy J. W. 14 Anastassiou A. G. 150 157,227 261 Anchel M. 535 Andersen B. 339 Anderson D. J. 553 Anderson D. R. 410 Anderson H. W. 107 Anderson J. E. 41 471 Anderson L. B. 298,485 Anderson N. H. 199 Anderson R. J. 454 Anderson S.N. 517 Ando T. 367 Ando W. 239 Andreatta R. H. 172 Andreoli R. 306 Andrews G. C. 241 371 Andrews S. B. 254 Andrist A. H. 150 228 260,26 1 262 Anet F. A. L. 35 338 Anfinsen C. B. 175 Angadiyavar C. S. 159 586 Angiolini L. 568 Ansari H. R. 579 Anschutz W. 231 Ansell M. F. 463 464 521 523 Antheunis D. 27 Anthony G. M. 11 Anthony R. S. 182 Ao M. S. 272 588 Aoki K. 120 Aono T. 222 Aoyama T. 222 Appel R. 384 Appleby A. J. 317 Arai H. 217 583 Araki M. 28 Archer D. A. 241 Archie C. W. 500 Aresta M. 275 Arhart R. W. 294 Armand J. 305 307 Armarego W. L. F. 21 Armitage I. 19 Armour E. A, 284 Armstrong D. R. 80 Arnett E. M. 571 Arnone A. 174 Arold H.248 Arora K. J. S. 265 Arora P. C. 314 Arsenault G. P. 11 Artico M. 569 Asami R. 42 Ashbrook C. W. 244 Ashby E. C. 357 368 Ashe A. J. 576 577 Ashworth P. 210 Askew W. B. 14 Asmussen E. 572 593 594 Asselineau J. 463 Astrakhanov M. I. 280 Ateya A. 22 337 Atherton J. H. 232 Atkins K. E. 288 Atkins T. J. 165 166,262 284,352 Atkinson D. J. 193 Atkinson J. G. 277 Atkinson K. 485 Atkinson R. S. 163 533 Attridge C. J. 280 Aufdehaar E. 351 Augustine R. L. 274 Aumann R. 285 356 Aumeer P. S. 472 Aviram A. 543 Avram E. 290 Avram M. 290 Avrutskaya I. A. 318 Awang D. V. C. 204 Axelrod E. H. 451 Axelrod V. D. 442 Axen R. 15 Axenrod T.10 Azogu C. I. 239 Babb B. E. 266 Bacaloglu R. 136 141 Bach R. D. 368 Bachawat J. M. 371 Bachers G. E. 42 337 Bachman G. L. 228 Bachmann P. L. 477 Back T. G. 391 Baczynskyj L. 422 Baddeley G. V. 482 Bader R. F. W. 80 Badia C. 196 Baechler R. D. 140 Baer H. H. 427 Baer Y. 92 Bauerlein S. 228 Bagi G. 422 Baguley B. C. 442 Bahurel Y. 343 Bailar J. C. jun. 279 Bailey B. K. 406 Bailey M. G. 212 Bailey N. A. 223 Bailey W. F. 35 Baines A. F. H. 486 Baird M. C. 282 Baird M. S. 234 362 Baird N. C. 78. 533 Baird W. C. 537 Baitinger W. E. 14 Baizer M. M. 300 301 308 Bakeney A. J. 534 Baker B. R. 175 Baker D. J. 283 Baker P. M. 521 Baker R.548 Bakuzis P. 246 Balaban A. T. 580 Balavoine G. 516 Balch A. L. 282 Baldschwieler J. D. 16 Baldwin F. C. 531 Baldwin J. E. 150 152 157 158 160 161 228 243 244 245 259 260 261 262 269 351 533 537,553 Baldwin R. C. 189 Ballard D. H. 517 Ballard D. H. 517 Ballenegger M. 277 Ballester M. 196 375 544 Balogh V. 208 Balquist J. M. 555 Bamberger S. 202 Bamkole T. L. 135 Ban Y. 386 Bancroft K. C. C. 132 Bank J. F. 197 Bank S. 197 Banks R. E. 206 Bannister W. D. 291 Banthorpe D. V. 266 Barber B. H. 515 Barber M . 14 92 93 Barbey G. 315 Barborak J. C. 150 260 261 336 Bard A. J. 299 Barefield E. K. 281 Barendt E. 549 Bargon J. 25 30 31 Barieux J.-J.369 Barkhash V. A. 547 Barkhurst R. C. 103 Barksdale A. W. 484 Barlet R. 370 Barlex D. M. 290 Barley G. C. 406 Barlow M. G. 271 531 Barltrop J. A. 324 325 326 Barnes D. 303 Barnett J. E. G. 184 Barnett W. E. 558 Barnier S. 575 Baron S. 436 Baron W. J. 226 Baronowsky P. 177 Barowsky H. W. 518 Barr W. R. 421 Barragan L. G. R. 271 Barrell B. G. 442 Barrow K. D. 480 Barry J. 107 Author Index Barry R. J. 490 Bartak D. E. 305 308 Bartels A. P. 366 527 Barth G. 106 Barth W. E. 549 Bartle K. D. 575 Bartlett P. D. 331 Bartolini G. 241 Bartolozzi M. 529 Barton D. H. R. 255,259 351 375 397 399 480 484 489 490 523 544 557 561 Barton F. E. 31 Baryshnikova E.B. 551 Basch H. 53 82 97 Basselier J. 578 Bassinet P. 305 Bassler T. 248 Basu H. 465 Batterham T. J. 21 38 Battersby A. R. 125 401 402 403 404 405 415 493,499 503 504 Battiste M. A. 548 Battistuzzi Gavioli G. 306 Batty J. W. 589 Baudry D. 245 Bauer S. H. 339 Bauer W. 152 Baule M. 194 Baum A. A. 327 Baumgarten R. J. 246 Baxter I. 517 Bayer M. 427 Bayerl B. 277 Bayev A. A. 442,444 Bayliss R. S. 177 Baylouny R. A. 260,532 Bazant V. 280 Beak P. 574 Beal J. K. 125 Beal J. L. 497 514 Beames D. J. 349 381 478 Beam C. F. 589 Bean G. P. 132 580 Bear C. A, 127 Beard C. D. 230 Beard R. D. 391 Beardsley G. P. 224 Beasley G. H. 259 480 Beastall G.H. 492 Beaute C. 22 Beavers W. A. 103 Beck A. K. 200 Beck J. F. 401 Beck W. 281 Becker E. D. 32 Becker R. H. 28 222 241 Becker R. S. 185 Beckett A. H. 103 Author Index 595 Beckett B. A. 474 Bernasconi C. F. 137 Bilofsky H. S. 41 516 Beckey H. D. 9 Bernett W. A. 339 567 Beckley R. S. 165,285 Bernstein M.D. 368 Bingham R.C. 342 360 Beckmann J. S. 439 Bernt J. 98 Binkley R. W. 328 Beckwith A. L. J. 190 Berrier C. 488 Binks R. 13 199,489 Berry D. J. 224 Binsch G. 40 334 Beckwith J. 439 Berry R. S. 223 Biollaz M.,367,491 Bedford C. T. 408 Berson J. A. 30 41 152 Birch A. J. 278 365 Beecham A. F. 103 163 248 249 260 329 Birchall J. M.,524 Beermann C. 274 532 Bird C. W. 273,465,483 Beevers C.A. 127 Bertelli D. J. 158 Bisarga S. C. 474 Begue J. P. 245 Bertelsen O. 453 Bishop J. O. 446 Behne H. 253 Bertholet J. P. 487 Bissett F. H. 567 Behrman E. J. 427 Berti G. 481 Black D. St. C. 372 555 Belanger P. 19 23 Bertini F. 194 389 57 1 Beletskaya I. P. 383 Bertorello H. E. 219 Black H. U. 440 Belikova N. 37 Bertram E. F. 476 Blackbourn G. P.,466 Bell A. P. 290 Bertram J. 310 Blackburn G. M. 421 Bell J. A. 323 Bertrand M. 160 248 Blackmore T. 290 Bellamy F. 271 Bertrand R.D. 568 Blackstock D. J. 133 518 Belletire J. L. 566 Berwick M. A. 588 Blackstock W. P.,402,503 Bellino A. 476 Besmer P.,420,439 Blackwell J. T. 19 Belluco U. 293 Bethge P. H. 172 Blain M. 575 Bellus D. 262 Betz W. 336 Blair L.K. 66 Benam J. 390 Beug M. 134,263 Blaha K.106 Ben-Bassat J. M. 371 527 Beugelmans-Verrier M. Blake D. M. 292 Bencze L. 285 257 Blakeney A. J. 234 Bencze W. L. 107 Beuhler R. J. 10 Blanchard E. P. jun 345 Bender M. L. 168 Bevan J. W. 339 Blank B. 27 Bender P. E. 516 Bevis M. J. 589 Blankespoor R. L. 212 Benecke H. P. 241 Beynon J. H. 7 14 Bleeha Z. 482 BeneSova. V.. 474 Bezagnet A. 160 Bley P. F. 140 Benezra S. A. 15 17 129 Bezanson G. S. 412 Blicharski J. 433 327 Bezpalova Z. 106 Blickenstaff R. T. 485 Bennett E. W. 280 Bhacca N. S. 21 Blobstein S. 423 Bennett M. A. 281 Bhalerao U. T. 451 482 Bloch D. R. 219 Benson A. A. 449 Bhandari K. S. 329 Bloch R. 340 533 Benson R. C. 574 Bhatnagar A. K. 161,269 Bloor J. E. 574 Bentley M. D. 391 553 Blosse P.T. 185 Bentley T. W. 6 14 141 Bhattacharyya A.525 Blount J. F. 121 Berenguer M. J. 384 Bialecka E. 342 Blow D. M. 172 Berg A. 219 Bianchi G. 40,478 Blume G. 230 Berger A. 168 171 Bibbi G. 135 Blumer M. 449 Berger S. 264 587 Bick I. R. C. 127 497 Blunt J. W. 485 Bergesen K. 568 Bickelhaupt F. 386 Bobbitt J. M. 315 316 Bergman R. G. 248 535 Biehl E. R. 222 497 Bergmann E. D. 534 540 Biehler J. M. 255 Boch R. 456 5 64 Biellmann J. F. 162 244 Boche G. 149 150,261 Bergmann F. 578 273,277,45 1 Bock R. M. 423,444 Bergmark T. 92 Biemann K. 5 11 12,422 Bodem G. B. 494 Bergstrom D. E. 444 Bier C. J. 174 Boden R. M. 327 Berhauser J. 176 Biernbaum M. S. 243 Bodor N. 74 Berking B. 119 127 Bigam G. 341 540 Bock H. 200 Berlin A. J. 145 Bigam J. 40 Boeckman R. K. jun. 348 Berlin K.D. 23 249 Biggi G. 208 537 383.472 563 Bighi C. 306 Bohme H. 149 Berlin Yu. 121 Bignold A. J. 521 523 Boekelheide V. 241 539 Berman H. M. 432 Bigorgne M. 292 549 Bernal I. 570 Billeter M. 437 Boelema E. 252 Bernal S. 161 259 Billingsley F. P. 574 Boelhouwer C. 285 Bernardi G. 421 Billups W. E. 234 288 Boll W. A,,540 Bernardi R. 194 534 Bolsing F. 194 596 Author Index Boer F. P. 113 Boettcher R. R. 163 Bogdanovic B. 296 Bogdanowicz M. J. 346 389 Boggio R.J. 161 259 Boggs R. A. 388 Bogorad L. 415 Bohen J. M. 566 Bohlmann F. 343,452 Bol’shinskova T. A. 285 Bolton I. J. 491 Bolton J. R. 212 Bommer P. 12 Bonamartini A. C. 573 Bond A. 291 Bonhoeffer F. 447 Bonnet J. 442 Bonnier J.M. 254 Boocock D. G. B. 205 Boop D. C. 496 Boor J. jun. 296 Booth B. L. 291 Booth H. 338 568 Bor G. 292 Borch R. F. 368 Borden W. T. 367 Bordwell F. G. 141 246 252 Borghesani G. 306 Borisov A. I. 318 Bornowski H. 475 Boron W. F. 253 Boronina N. N. 290 Borowitz I. J. 383 Borrell P. 324 Boschetto D. J. 291 292 Bosco M. 135 582 Bosscher J. K. 518 Bosworth N. 470 Bottari F. 481 Boulares L. 307 Bould L.,351 Boulton A. J. 40 Boulton J. J. K. 137 Boulton M. G. 431 Bouquet A. 501 Bourgeois C. F. 520 Bourguignon P.,487 Boussu M. 388 Bowden K. 134 589 Bower H. 204 Bowie J. H. 16 Bowman C. M. 435 Bowman D. F. 206 Bowman R. E. 393 Bowman R. M.403 Bownds D. 185 Boyce C. B. 107 Boyce R. 386 Boyd D. R. 369 Boyd S. D. 376 Boyd W. A. 19 Boyer J. H.,253 Boyer P. D. 182 Boyer R. F. 266,533 Boyle P. H. 469 Boyle W.J. 141 523 Boys S. F. 47 Bradbury S.,238,270,585 Bradley C. H.,35 338 Bradshaw J. S.,219 Bradshaw R.W. 455 Bradsher C. K. 158 Brady W.T. 342 361 Brahms J. 433 Bram S. 445 Bramley R. 38 Bramwell A. F. 20 Brand T. A. T. M. 29 Brandenburg C. F. 258 Brandt J. 202 Brasen S. 209 Brassard P. 373 Braterman P. S. 274 Bratu C. 424 Brauer H. D. 195 Brauman J. I. 66,326,340 Braun D. 194 521 Braun L. M. 370 Braun P. B. 113 Braun R. A. 370 Braun W. 437 Braunton P. N. 571 Bray L. S. 290 Braye E.H. 581 Breaux D. 485 Breen J. J. 568 Breitenbach M. 315 Breitmaier E. 32 35 337 Bremner J. B. 127 Bremser W. 32 Brener L. 161 260 342 354 Brennan M. R. 15 Brent D. A. 532 Breslow R.,375 Bressaw G. B. 582 Bressel U. 580 Breuer S. W. 526 Brickell W. S. 107 Bridger W. A. 182 Brieger G. 384 Briggs J. 19 21 Briggs P. C. 350 382,490 Bright G. M. 541 Brindle J. R. 369 Briner R. C. 107 Bristol D. 207 Britelli D. 541 Britmaier E. 589 Britten R. J. 445 Britton R. W. 278 Britton W. E. 305 Broadbury S. 584 Broadhurst M. J. 590 Brockmann H. 210 Brodsky L. 151 Brokenshire J. L. 204 Brokl O. 454 Brook A. G. 231,243 Brook G. M.,583 Brooke G.M. 531 532 Brooks C. J. W. 11,483 Brown A. 107 Brown C. 563 Brown C. K. 290 292 Brown D. C. 370 Brown D. M. 427,444 Brown E. 390 Brown H. C. 213 372 374 379,388 Brown J. E. 244 Brown J. M. 287 Brown J. N. 125 Brown J. R. 406 Brown K. S.,134,263,521 Brown 0. R. 303 Brown R. F. C. 235 372 Brown R. T. 402 503 Brown T. H. 589 Brown W. 485 Browne D. T. 177 Browne P. A. 107 Browning J. 290 Brownlee G. G. 435 Broxton T. J. 523 Bruce M. I. 281 290 Bruck D. 528 Briiser W. 275 Brufani M. 463,480 Bruice T. C. 142 Brune F. 275 Brunn E. 159 552 Brunner H. 194,273 545 Brunswick D. J. 180 Brus G. J. M. 298 Bruylants A. 134 Bryan R. F. 125,475 Bryce-Smith D.154 329 330,336 Brydon D. L. 218 Bryson T. A. 350,490 Bubnov Y. N. 158 361 388 Buchanan B. G. 13 Buchanan G. L. 349,472 Buchanan G. W. 34 35 338 Buchardt O. 271 587 Buchecker R. 107 Buchi G. 380 Buckler C. E. 436 Buckley D. G. 19 Budny J. 455 Budowsky E. I. 427 Author Index Budzikiewicz H. 5 Buchi G. 344 469 507 Buenker R. J. 47 80 Buthe H. 295 Buettner A. V. 323 Bugg C. E. 432 Bugianesi R. L. 436 Bu’Lock J. D. 483 Bunce N. J. 332 Buncel E. 139 Bunnell C. A. 292 Bunnenberg E. 106 Bunnett J. F. 268 523 530 Burdon J. 531 Burdon M. G. 427 Burger K. 159 Burgers P. M. J. 430 Burgess E. M. 272 588 Burgess J. R. 257 374 553 Burgmaier G.J. 340 Burgstahler A. W. 103 105 Burke D. C. 436 Burkhalter P. G. 11 Burkoth T. L. 340 531 Burnell R. H. 478 Burnett M. G. 279 Burnett R. E. 295 365 Burrows W. J. 423 Bursey M. M. 15 17 129 327 Burton A. G. 580 Burton R. 37 42 Busch H. 435 Busetto L. 291 293 Bushby R. J. 30 Bushick R. D. 258 Bushweller C. H. 41 338 516 567 Buss V. 63 69 Butcher M. 235 Butin K. P. 303 Butler A. R. 131 132 555 Butler G. B. 566 Butler J. R. 160 230 Butterfield R. O. 464 Buys H. R. 40 339 Byers G. W. 185 Byrd J. E. 166 284 Cabell M. 269 Cacace F. 129 Cadogan J. I. G. 205,207 218 219 236 237 269 379 525 530 Cagniant D. 546 Cagniant P. 546 Cain E. N. 153 Cainelli G.389 Cairns E. J. 309 Cais M. 279 Caldow G. L. 164 286 Caldwell D. J. 102 Calo V. 392 Calvin M. 112 144 269 554 Camaioni D. M. 529 Cambie R. C. 476 Cameron A. F. 112 115 116 118 123 Camioni D. M. 137 Campbell B. S. 563 Campbell G. A. 530 Campbell H. F. 500 Campbell J. R. 568 Campbell M. M. 152,562 Campbell P. G. C. 292 Campbell R. V. M. 395 483 Canonica L. 404 408 Cantacuzene J. 339 567 Cantrell T. S. 325 Canziani F. 275 Capiomont A. 205 Capka M. 278,280 365 Caple R. 546 Caplier I. 581 Capobianco G. 303 Caputo J. F. 25 Caputo R. 478 Capwell R. J. 340 Carbon J. 442 Cardin D. J. 275 Caress E. A. 265 Carey F. A. 23 239 257 380 566 Cargioli J.D. 37 Cargle V. H. 145 Carless H. A. J. 324 325 Carlson B. A. 388 Carlson E. H. 40 Carlson T. A. 93 Carney R. L. 388 Carpino L. A. 247 Carrasquillo A. 256 Carrington D. E. L. 582 Carroll F. I. 19 Carroll M. 402 417 Carter W. A. 436 437 Carturan G. 291 Cartwright E. 435 Carty D. 531 Caruthers M. H. 420 Casalone G. 563 Casanova T. G. 385 Caserio M. C. 143 Casey C. P. 188 292 388 Cashion P. J. 420 Cashman M. P. 267 Cashmore A. R. 444 Casilio L. M. 136 138 529 Cason J. 452 Casper E. W. R. 383 Caspi E. 397 398 Cassar L. 166,284 Cast J. R. 233 Castaiier J. 196 375 544 Castells J. 384 Caubere P. 370 Cauquis G. 315 319 Cave A. 501 Cave A.501 Cavender C. J. 533 Caullet C. 315 Cedergren R. J. 428 Cekovid Z. 207 Cellura R. P. 227 Cenini S. 281 Cerefice S. A. 165 284 285 Cerlach D. H. 281 Cernohorsky I. J. 421 Cerny M. 278 365 368 Cerrini S. 480 Cescon L. A. 203 Cetinkaya B. 275 Chaffin L. J. 444 Chaiken I. M. 175 Chain (Sir) E. 480 Chait E. M. 14 Chakrabarti J. K. 252 Challis B. C. 131 555 Challis J. A. 351 Chambers R. D. 95 138 271 583 Chambers R.J. 489 Chambers R. W. 444 Chambers V. M. A. 191 Chan H. W. S. 158 Chan S. I. 432 445 Chan T. S. 440 Chang. B. 318 Chang C. H. 339 Chang C.-J.,493 Chang F. C. 126,481 Chapeville F. 175 Chapman 0. L. 325 519 521 Chappaz R.470 Chari S. 260 336 Charles R. 281 Charlton J. L. 3 1 331 Charman H. B. 565 Charney E. 105 Charpent ier- Morize M. 245 Chase J. F. A. 177 Chase T. 449 Chasin D. G. 462 Chastain R. V. jun. 563 Chattanathan N. 139 Chattha M. S. 381 Chauhan M. 209 Chauvin Y. 286 Cheburkov Y. A. 583 Chen C. H. 563 Chen C.-Y. 296 Chen G. M. S. 546 Chen H. C. 438 Chen H. J. 139 578 Chen H. L. 141 Chen J. 189 Chen J.-C. 189 190 Chen K. S. 213 Chen S. C. 559 Chen T. K. 579 Cheng C. C. 508 Cheng J. D. 267 Cheng T. C. 197 526 Cheng Y. M. 228 Chenini S. 277 Cheong L. 439 Cheradame H. 42 Cherest M. 356 357 386 Cherkofsky S. C. 345 Chestier A. 444 Chetty G.L. 480 Chheda G. B. 424 Chia H. A. 158 Chiang J. F. 339 Chiang Y. 139 141 263 Chiang Y. H. 254 Chidester C. G. 398 Childs R. F. 166 249 284 352 Childs W. V. 299 318 Chini P. 275 Chion B. 205 Chippendale K. 235 Chiraleu F. 290 Chisholm M. H. 276 Chitwood J. L. 264 Chivers G. E. 371 379 Chiyoda Y. 486 Choay P. 488 Choi S. C. 161,244,269 Chong R. 463 Chottard J. C. 192 263 Chou J. Y. 431 Chou S. 562 Choudhury A. M. 264 Chow W. Y. 234 534 Chow Y. L. 559 Christe K. O. 207 Christensen A. T. 116 124 Christensen L. W. 391 Christl M. 38 Christmann F. K. 376 Christoffersen R. E. 53,78 Christy M. E. 555 Chruma J. L. 301 Chuche J. 145 Chui K. M. 113 Chun M.C. 259 Chupina L. A. 318 Churchill M. R. 291 Chvalovsky V. 280 Ciabattoni J. 269 534 Ciardelli F. 296 Ciganek E. 148 227 336 Cimino G. 479 Cinimale F. 392 Cipollini R. 129 Ciranni G. 129 580 Ciuffarin E. 141 Clardy J. C. 126 481 519 Clark A. J. 163 533 Clark D. T. 62 63,80 92 93 95 97 98 100 573 574 Clark G. M. 344,370,389 Clark G. R. 233 Clark G. W. 219 379 Clark H. C. 276 290 Clark I. M. 485 Clark P. J. 445 Clark S. D. 107 Clark W. G. 225 Clarke K. 582 Clarke M. T. 330 Clarke T. A. 356 Claus P. 242 Clause A. O. 31 Clauss K. 274 Clayton R. B. 396 482 Cleaver R. L. 13 Clementi E. 48 50 78 87 Clementi S. 580 Clezy P. S. 590 Cliff G.R. 236,270 Clifford K. 399 Clifford P. R. 36 Clive D. L. J. 351 Closs G. L. 26 27 30 Closs L. E. 26 Clough S. C. 151 Clouse A. O. 493 Cloyd J. C. 412 Coates R. M. 324 390 396,476,483 Cochran D. W. 31 32 493 512 Cocivera M. 27 Cocker W. 469 Cockerill A. F. 19 Cocks A. T. 152 Coe P. L. 531 Coffen D. L. 257 272 533,577 Coffinet D. 376 Coggon P. 124 Cohen B. J. 302 Cohen E. 161 258 Cohen G. H. 170 Cohen K. F. 482 Cohen M. D. 330 Author Index Cohen R. L. 203 Cohen S. G. 140 Cohen-Fernandes P. 267 Cohn M. 186 Coleman J. P. 302 313 Coll J. C. 570 Collier P. D. 135 Collins C. J. 248 Collins D. J. 351 Collins J. C. 589 Collins J. H. 8 Collins P.M. 326 Collman J. P. 291 Collonges F. 343 Colonna S. 281 Colter A. K. 36 Colvin E. 380 Combrisson S. 578 Cometti G. 290 Commeyras A. 36 Condon M. E. 477 Conger R. L. 18 Conia J. M. 245,260,339 343 552 Conlay C. 480 Connolly J. D. 483 Conti F. 281 Contreras R. 434 437 Convert O. 305 Conway P. 468 Cook B. F. 233 Cook J. 218 219 Cook J. D. 224 Cook J. M. 507 Cook M. J. 478 568 Cook R. E. 116 Cook R. S. 134 Cooke M. 293 Cookson R. C. 163 260 323 345 Cooper A. 124 Cooper C. M. 557 Cooper M. J. 431 563 Cooper R. A. 31 Cooper W. F. 116 Cooperman B. S. 180 Copenhafer R. A. 298 Coppens P. 116 Copper A. 266 Coppola J. C. 114 116 Coppolino A.381 Corain C. 281 Coraor G. R. 203 Corbally R. P. 138 Corbett R. E. 483 Corey E. J. 344 346 367 369 378 379 386 388 390 396 450 458 459 47 1,482 Corfield J. R. 23 Corina D. L. 184 Corley L. 175 Author index Cormier R. A. 551 Corneo G. 446 Cornforth J. W. 399 Corradini P. 296 Cory R. M. 565 577 Coscia C. J. 401 Cosyn J. P. 516 Cote P. N. 193 265 Cotruvo J. A. 579 Cotterrell G. P. 542 Cotton F. A. 174 Cotton W. D. 241 Cottrell P. T. 307 Coulombeau C. 103 Coulson A. F. W. 179 Courchene W. L. 8 Cowan J. C. 279,465 Cowling G. J. 432 Cox D. A. 480 Cox G. B. 329 330 Cox M. L. 427 Cox M. R. 475 Cox R. H. 526,563 Cox R. J. 543 Coxon J.M. 486,488 Coyle J. D. 326 Crabb T. A. 568 Crabbe P. 102 107 367 49 1 Craddock J. H. 291 Cradwick P. D. 475 Craig J. C. 105 230 Craig L. C. 438 Crain. W. O. jun. 36 493 Cram D. J. 263 539 571 Cram J. M. 539 Cramer F. 445 Crampton M. R. 41 137 529 Crasnier F. 515 Craven B. M. 119 Crawford R. J. 188 Creasey S. E. 392 Crecely R. W. 38 Creedon P. B. 410,411 Cresp T. M. 542 Crews P. 158 221 Crick F. H. C. 420 Cripps A. L. 457 Crissman H. R. 370 Cristol S. J. 191 251 546 Crombie L. 395 413 470 Cros J. L. 315 Cross B. E. 471 Crossley N. S. 460 Crothers D. M. 434 Crouch K. 383 Crouse D. M. 519 Crout D. H. G. 580 Crow G. R. 266 Crozet M.-P.213 560 Crump D. R. 19 Crundwell E. 457 Cruse W. B. T. 125 Csunderlik C. 141 Cuddy B. D. 252 Cullen D. L. 112 Cumming W. D. 338 Cundy C. S. 290 Cunningham M. 254 Cupas C. A. 252 Currie M. 11 1 Curtin D. Y. 516 Curtis H. C. 193 Curtis R. F. 406 Curtiss L. A. 61 Cushley R. J. 410 Cyr N. 203 Dahl S. 339 Dahlberg J. E. 435 Dahlqvist K.-I. 579 Dahmen A. 159,269 552 Dahn H. 105 Dall’Asta G. 286 Dalling D. K. 34 35 338 Daly J. W. 494 Daly N. R. 14 Dammeier B. 484 D’Amore A. B. 535 Damrauer R. 254 Danchin A. 445 Danen W. C. 201 Dang T. P. 295 365 D’Angelo P. F. 271 565 577 Daniel V. 420 439 Danieli B. 204 Danishefsky S. 382 508 509 Darby N.540 Darling T. R. 361 Darwinkle-Risseeuw P. S. 588 Das B. C. 15,454 Daub J. 336 Dauben W. G. 165 324 327 328 Daver A. 304 Davidson E. H. 445 Davidson J. M. 293 Davidson N. 433 Davidson R. B. 56 Davidson R. S. 201 Davie E. S. 285 Davies A. G. 213 Davies D. I. 192 Davies D. R. 170 Davies J. E. 435 Davies J. H. 582 Davies M. 569 Davies R. J. H. 433 Davies V. H. 475 Davis B. A. 517 Davis B. R. 570 Davis D. W. 95 Davis F. A. 391 Davis R. 452 Davis R. A. 556 Davis R. E. 290 Dawans F. 290 Dawes K. 339 Dawson T. M. 491 Day A. C. 406,455 Day M. J. 255 489 Day R. A. jun. 301 Day V. W. 174 Deady L. W. 579 Dean F. M. 209 Dean P. D. G. 397 Dean R.R. 526 Deaving C. 136 De Bardeleben J. F. 474 De Bie M. J. A. 38 de Boer E. 22 De Boer Th. J. 525 De Camp E. J. 123 Decamp M. R. 158 217 327 de Clercq E. 436 437 Decora A. W. 277 Dedieu A. 80 Dedinas J. 323 Deeleman R. A. F. 588 Dees K. 225 Defay N. 38 Deganello G. 284 Degani I. 579 Degen P. 450 Degner D. 301 302 de Graaff R. A. G. 112 De Graw J. I. 462 De Haan J. W. 38 Dehmlow E. V. 229 230 342 Deitch J. 384 Dejarkis W. J. 282 De Jongh D. C. 219 520 532 De Jongh R. O. 277 Delahaye D. 315 de la Mare P. B. D. 133 252 518 Delay F. 252 Del Cima F. 208 529 537 Delhomme H. 315 Delisi D. C. 434 Deloughry W. J. 516 Delton M.H. 263 539 de Maeyer-Guignard J. 436 Demarco P. V. 19 De Martino G. 569 600 Author Index de Mayo P. 331 340,342 Dinne E. 149 DuBois G. E. 350 382 533 558 Dinulescu I. G. 290 490 de Meijere A. 342 Dirania M. K. M. 265 Dubois J. E. 380 388 De Member J. R. 36 249 Dirheimer G. 442 Ducep J. B. 162 244 451 Demmin T. R. 350 382 Dirlam J. P. 211 545 Duchamp D. J. 398 490 Ditchfield R. 75 Duck E. W. 290 den Hertog H. J. 224 582 Dittmer D. C. 555 Dudinskaya A. A. 551 den Hollander J. A. 27,29 Dittmer J. C. 450 Dudock B. S. 422 Denic M. 422 Diversi P. 284 Durr H. 226 336 Denis J. M. 245 Dixon C. 290 Diitting D. 442 Denisov E. T. 206 Dixon J. 491 Dufay P. 425 Dennis J. E. 568 Dixon J. E. 142 Duffield A. M. 13 de Ochoa 0.E. 362 Dixon W.T. 210 Duffin B. 116 Derenberg M. 227 Djerassi C. 5 13 16 102 Dufour M. 194 Derendyaev B. G. 263 106,277,491 507 Duke A. J. 80 Dereppe J. M. 579 Dobbs A. J. 199 Duke R. P. 568 de Rosa M. 453 483 Dobbs F. R. 368 Dunham D. J. 346 383 de Rossi R. H. 219 Dobler M. 111 474 Desai K. B. 229 Dobson R. C. 228 Dunitz J. D. 111 120 De Sarlo F. 130 580 Doddi G. 138 121,339,574 Deschamps J. 425 Doddrell D. 31,32,33,36 Dunlap B. E. 433 Descotes G. 343 493 Dunn G. E. 132 De Shazo M. 131 Dodson R. M. 556 Du Puy B. 435 Desider P. G. 315 Doemeny P. A. 277 Dupuy C. 213 560 Desiderato R. 573 Dopp D. 331 Durand R. 416 Desiderio D. M. 12 15 Doering W. von E. 145 Durig J. R. 340 De Silva K. T. D. 402 160,259 Durr F. H. 484 503 504 Doerner K. 542 Durr H.148 Deslongchamps P. 375 Dolata D. P. 205 Durst H. D. 368 561 Dolbier W. R. 160 188 Durst T. 245 565 de Somer P. 437 Dolby L. J. 381 Dutton H. J. 464 de Souza B. 588 Dolgoplosk B. A. 285 D’yachenko A. I. 218 Dessau R. M. 198 372 286 Dyas C. 334 Dessauer R. 203 Dolhun J. J. 11 Dzidic I. 428 De Stefano S. 479 Dolling U. H. 225 229 Deutsch A. S. 203 Dolman D. 139 Eaborn C. 133 140 Devon T. K. 104 Dolnakov Y. P. 318 Eadon G. 16 de Vries J. X. 497 Done J. N. 192 Earnshaw D. G. 277 de Waal W. 278 Donnelley J. A. 265 Eastmond R. 140 de Wachter R. 437 Doolittle F. G. 277 Eaton P. E. 166 253 284 Dewar M. J. S. 40,44 74 Doorakian G. A. 153 285 78 140 143 144 145 Dorie J. P. 575 Ebel J. P. 435 442 160 258 260 334 335 Dorn H. C. 38 Eberbach W. 587 352 515 516 528 589 Doskotch R.W. 125,497 Eberhard P. 159 Dewar P. S. 193 514 Eberson L. 196 293 298 Dewhurst P. B. 185 Doty P. 434 313 373 545 Dewick P. M. 413 DOU H. J.-M. 194 Ebina K. 289 Deyrup J. A. 163 566 Doubleday C. E. 26 Eccleston G. 567 Diakiw V. 590 Douglass I. B. 391 Eckes H. 231 Dianzani F. 436 Doupeux H. 304 Eckroth D. R. 587 Dias J. R. 369 Dourlent M. 433 445 Eckstein F. 433 Dickenson R. P. 582 Doyle G. 277 Edelman R. 548 Dickerman H. W. 442 Draggett P. T. 293 Edelson S. E. 361 Diehl P. 42 Drake A. F. 107 Eder U. 347 Diekman J. 16 Dralants A. 516 Edge D. J. 199 Dillon J. 471 Drayton C. J. 583 Edge M. D. 432 Dimmel D. R. 243 Drenth J. 169 Edmond J. 395 Diner U. E. 378 Drenth W. 37 38 Edmonds J. W. 116 Dinerstein R. J.205 Dromey R. G. 8 13 Edwards J. A. 484 Dines M. B. 378 Drucky E. 585 Effenberger F. 517 528 Ding H. L. 483 Dryhurst G. 308 317 Efraty A. 282 561 Dingwall J. G. 271 Duax W. L. 124 Efremov E. S. 106 Author Index Egami F. 430 Egan W. 574 Eggar B. 469 Egger B. 344 Eggerer H. 174 Eggers B. 380 Eggler J. 508 509 Eglinton G. 467 Eguchi S. 255 Ehrenberg L. 422 Ehresmann C. 435 Ehret C. 401 Ehrlich S. D. 421 Eiben K. 210 Eidenschink R. 159 Eikenberry J. M. 24 Eilbracht P. 545 Eisch J. J. 578 Eisen H. N. 180 Eisenberg R. 290 Eisenstadt A. 251 Eisenstein O. 155 156 Eisinger J. 434 Eitelman S. J. 391 Eiter K. 467 Ejchart A. 19 Ekong D. E. U. 483 Elad D. 588 El Ghariani M.A. 41 137 529 Elian M. 290 Eliel E. L. 35 334 565 568 Ellam G. B. 140 Ellam R. M. 528 Ellencweig A. 516 Ellestad G. A. 474 Elliot R. M. 14 Ellis. J.. 386 Ellis J. J. 452 Ellis. J. E. 381 Ellis. L. E. 340 Elzey T. K. 19 Emerson D. W. 379 490 562 Emerson G. F. 294 Empsall H. D. 281 Emsley J. W. 42 Endo K. 542 Endres R. 279 Engel D. W. 479 Engel M. R. 519 Engelman C. 334 Engewald W. 133 580 Engler E. M. 360 Englert M. 289 Englund P. T. 446 Engstrom L. 182 Enzell C. R. 374 Epstein M. J. 261 Epstein W. W. 248 396 48 3 Erdmann V. A. 435 Erickson B. W. 379 390 Erickson K. L. 518 Erickson W. F. 245 386 Erman W. F. 280 349 381,473 Ermer O.339 Ernsberger W. 42 136 529 Ernst L. 515 Eron L. 439 Eschenmoser A. 392 Espejo de Ochoa O. 256 556 Esposito G. 559 Etheridge S. J. 509 Etzold G. 426 Eugster C. H. 107 Evans D. A, 371 Evans D. D. 393 Evans D. F. 526 Evans D. H. 299 Evans J. 293 Evans J. A. 290 Evans J. M. 485 Evans M. G. 143 Evans R. H. jun. 474 Evans S. A. jun. 568 Evenson G. N. 219 Evgenios D. M. 562 Eyring H. 6 102 Faber D. H. 339 Fahlman A. 92 98 Fahnestock S. 435 Failli A. 277 Fairlie J. C. 408 Faita G. 298 Falbe J.. 292 Falck J. R. 316 497 Falco M. R. 497 Fales H. M. 10 Falk J. C. 279 Fanning A. T. jun. 217 Fanta W. I. 280 Fantucci P. 275 Farcasiu D.580 Fareed G. C. 431 Farenholtz. S. R. 27 Farid S. 22 337 Farkas G. L. 422 Farmer J. B. 225 Farnum D. G. 161 272 565 Farnia G. 303 Farrar T. C. 32 Farrier D. S. 500 Fatiadi A. J. 373 Fattorusso E. 479 Fad W. H. 277 Faulkner D. J. 351 377 460,471 Faulkner R. D. 422 Fauth G. 202 Favero G. 281 Favier R. 373 Favre A. 444 Fazakerley G. V. 526 Fearon F. W. G. 197 Fedeli W. 463,480 Fedorcsak I. 422 Fedorynski M. 230 Feeney J. 34 Feher F. 569 Fehlmann M. 117 Fehn J. 159 Feichtinger H. 292 Feigenbaum E. A. 13 Feinberg A. M. 423 Feit I. N. 268,530 Feldman H. 442 Felix R. A. 390 Felkin H. 356 357 386 Feller D. R. 412 Fellner P. 435 Felsenfeld G.433 445 Felty R. E. 537 Fendler E. J. 42 136 137 138 529 Fendler J. H. 42 136 137 138 529 Fenical W. 149 475 Fenoglio R. A. 360 Ferguson G. 123 Ferguson J. B. 178 Fernandez J. 384 Ferrer-Correia A. J. 16 Ferris J. P. 107 Fessenden R. W. 200 Fetizon M. 104 208 Field F. H. 7 10 Field K. W. 255 Fields D. L. 271 Fields E. K. 218 Fields R. 232 Fiers W. 434 437 Figeys H. P. 516 Filby W. G. 210 Filipescu N. 324 Filler R. 527 Finch N. 107 589 Findley J. W. A. 476 Fink L. M. 422 Fink W. 280 Finn F. 177 Finnegan R. A. 477 Fiore F. 449 Fioshin M. Y. 316 Firl J. 158 Fischer D. 429 Fischer E. O. 274 Fischer H. 25,26,27,202 213,267 Fischer M.S. 112 602 Fischer R. D. 337 Frankel F. 422 Fisher J. 124 Franklin J. L. 7 Fisher L. P. 145 Franzus B. 587 Fisher R. P. 388 Frappier F. 487 Fitton P. 281 Fraser R. R. 19 140 Fitzgerald R. 141 Fraser-Reid B. 233 Flandt M. 439 Frater Gy. 519 Fleet G. W. J. 181 Frater-Schroder M. 31 Fleischmann M. 303 310 Frazer W. J. 349 315 Freedman H. H. 41 153 Fleischmann R. 279 Freedman L. D. 569 Fleming I. 23 253 Freedman R. B. 186 Fletcher I. J. 40 Freeman G. R. 573 Fletcher V. R. 489 Freeman J. P. 555 Fleury D. 307 Freeman P. K. 229 254 Fleury J. P. 255 Freeman R. 32 33 34 Fleury M. B. 307 308 Frehel D. 563 Fliegl E. 136 Freier R. D. 386 Fliszar S. 308 Frensdorff H. K. 570 Flood T. C. 231 Freppel C.19 23 373 Floss H. G. 402 416 417 Fresco J. R. 442 Flowers M. C. 146 160 Freude K. A. 444 Flowers W. T. 583 Frey H. M. 146 152 Fluck E. 42 FriC I. 106 Flygare W. H. 574 Friderici K. H. 433 Fodor G. 563 Fridkin M. 420 Folk W. R. 442 Fried J. H. 367 491 Foote C. S. 331 Friedman L. 10 Foote R. S. 589 Friedman N. 490 Forbes E. J. 589 Friedrich E. C. 190 Ford P. W. 152 Friedrich L. E. 269 551 Forde T. 410,411 Fries D. C. 127 Forlani L. 135 582 Frihart C. 541 Formoso C. 432 Fritsch H. 413 Forrester A. R. 193 210 Frost G. H. 19 Forsen S. 42 Fruton J. S. 171 172 178 Forster D. L. 217 238 Fry A. J. 305 534 585 Fryberg E. C. 368 Forsythe P. P. 580 Frydman B. 415 Fort R. C. 252,485 Frydman R. B. 415 Foster A.M. 231 Fuchs P. L. 376 379,451 Foster E. 485 Fueno T. 156 3 18 583 Foucaud A. 553 Fuganti C. 127 404 Fougler B. E. 330 Fuganti G. 493 Fouquey C. 516 Fuhrer H. 471 Fournie-Zaluski M. C. Fujihara M. 498 578 579 Fujii S. 171 Fowden L. 107 Fujimoto T. 214 Fowler F. W. 577 Fujita T. 475 537 Fowler J. S. 131 518 Fujiwara T. 480 Fox H. M. 318 Fukuda S. 536 Fox J. J. 426 Fukui K. 44 143,258,542 Fraenkel D. 279 Fukumoto K. 496 498 Fraenkel G. 526 499 Frajerman C. 356 386 Fukuoka S. 277 France A. D. G. 579 Fukuzumi K. 279 Francis R. F. 581 Fuller W. 444 Franich R. A. 476 Fullerton T. J. 476 Frank J. 246 Funabiki T. 279 Frank R. 247 Funamizu M. 422 423 Franke W. H. 202 Funke E. 586 Frankel E. N. 279 Furatachi N.423 Author Index Furnta T. 278 Furstoss R. 559 Furukawa J. 156 230 287,296 Furusato M. 368 Furutach N. 422 Gaal O. 422 Gaal W. 140 Gabe E. J. 122,471 Gadek F. J. 578 Gadola H. 451 Gaumann T. 277 Gaffield W. 105 Gafner G. 572 Gagosian R. B. 361 Gail S. E. 585 Gajewski J. J. 159 533 Galard R. M. 384 Galbraith M. N. 478 Galetto W. G. 105 Gall M. 383 Gallagher R. T. 127 Gallegos E. J. 492 Galli R. 194 Gallo R. C. 420 Gambacorta A. 453,483 Gangloff J. 442 Gansow 0.A. 34 Garapon J. 254 Garbisch E. W. 39 Gardner C. L. 225 Garg C. P. 372 Gariano P. 385 Garmaise D. L. 579 Garnett J. L. 273 280 Garratt P. J. 538 541 542 543 Garst J. F.31 Gartland G. L. 119 Garza A. 290 Gaskell A. J. 574 Gassen H. G. 430 Gassenmann S. 589 Gassman P. G. 144 165 166 256 262 284 352 360 361 530 Gast L. E. 282 Gatehouse B. M. 119 127 Gatti G. 36 493 Gaudry M. 383 Gawronski J. K. 103 Gazdar A. F. 437 Gazit A. 540 Gear J. R. 41 1 Gebreyesus T. 507 Gefter M. L. 439 447 Gehlaus J. 232 Gehrke C. W. 421 Geier M. R. 420 Author Index 603 Geise H. J. 339 Gelius U. 92 95 98 Gender W. J. 460 Genson D. W. 53 Georgarakis M. 588 George M. V. 159 586 Georgiou D. 290 Gerdil R. 339 Gerlock J. L. 21 1 Gero S. D. 15 Gerry M. C. L. 225 Gershanov F. P. 371 554 Gerson F. 198 Gestbloom B. 42 Gharpure S.B. 243 Ghera E. 357 386 Giam C. S. 580 Giannini U. 275 Giardi I. 582 Gibbons A. R. 146 160 Gibbons C. S. 329 Gibson D. H. 294 Gibson H. H. jun. 233 Gibson K. H. 125 402 503 Giessner B. G. 8 Giger W. 140 575 Gilardi R. D. 118 Gilbert A, 154 329 330 336 Gilbert B. C. 199 204 Gilbert E. J. 10 Gilbert J. C. 160 230 Gilchrist D. L. 217 Gilchrist T. L. 223 238 239 534 551 553 585 Gileadi E. 302 Giles D. 455 Giles W. B. 155 Gilham P. T. 420,435 Gill D. F. 280 Gill D. S. 277 Gillan T. 206 Gillard J. 127 Gilles D. G. 42 Gilles J. M. 40 542 Gilman N. W. 268 367 Gilman R. E. 263 539 Gilmore C. J. 275 Gilow H. M. 131 Giner-Sorolla A. 427 Ginger G.L. 454 Ginsberg T. 442 Giordano F. 120 Giovannini E. 588 Giuliano R. 569 Giumanini A. G. 28 222 24 1 Givens R. S. 21 1 Givol D. 180 Glaser A,,453 Glaser R. 252 Glass T. E. 230 380 469 Glazer E. 321 Gleason J. G. 468 Gleiter R.. 88 100 153 Glick M. D. 116 Glinka K. 569 Glockner P. 356 Glogowski M. E. 266 Glotter E. 492 Glover E. E. 585 Glusker J. P. 122 Glusko V. 32 Godfrey M. 140 Goering H. L. 24 Gorlich B. 484 Goetzl E. J. 180 Goggin C. B. 267 Goh M. 38 Goh S. H. 225 Goi M. 471 Gold E. H. 555 Goldberg I. 574 Golden H. J. 283 Golden R. 140 589 Golding B. T. 287 Goldman L. 425 Goldschleger N. F. 280 Goldschmidt Z. 160 Goldstein A.W. 412 Goldstein G. 439 Goldstein J. H. 37 38 Goldstein M. J. 335 Golfier M. 208 Goller E. J. 386 Golob N. F. 581 Gomez-Gonzales L. 293 373 Gontarz J. A. 359 Goodall B. L. 281 Goodburn T. G. 458 Goode G. C. 16 Gooden E. L. 563 Goodwin B. W. 515 Goodwin T. W. 397 399 492 Goody R. S. 427,428,431 Gopal H. 373 Gorbachevskaya W. V. 29 1 Gorden B. J. 333 Gordon A. J. 373 Gordon M. P. 425 Gordon P. G. 523 Gore J. 369 Goren M. B. 454 Gorman A. A. 493 Gorodetsky M. 490 Gosden A. F. 523 Gosser L. W. 283 Goto K. 567 Goto M. 423 Goto T. 422 423 Gotoh H. 527 Gott P. G. 264 Gotthardt H. 159 586 Gottlicher S. 574 Gotz M. 578 Gougoutas J. Z.124 Goulian M. 447 Goutarel R. 488 Govindachari T. R.,5 13 Gowling E. W. 223 Graf F. 542 Graf U. 406 Graham J. R. 286 Graham W. A. G. 282 Gramaccidi C. M. 115 Grandi G. 306 Granstrom E. 14 Grant D. 252 Grant D. M. 35 37 338 575 Grant D. W. 34 35 Grasselli P. 389 Graveling F. J. 223 Graves R. E. 271 Gravestock M. B. 350,490 Gray C. J. 172 Gray G. A. 38 191 Grayson D. H. 469 Graziani M. 291 293 Gschwend H. W. 589 Greaves P. M. 377 Greber G. 431 Greeley R. H. 340 531 Green D. M. 484 Green F. D. 224 Green G. 433 Green G. H. 19 Green L. J. 10 Green M. 281 290 291 293 Green M. L. H. 276 281 Green W. H. 340 Greenberg G. R. 174 Greene A. E. 348,472 Greene J.L. 24 Greenwood G. 391 Greig D. G. T. 557 Greig J. B. 397 Gregory U. A. 281 Grenz M. 452 Grethe G. 510 51 1 Greve H. 210 Gribble M. Y. 138 Grieco P. 483 Griffin B. E. 429 Griffin G. W. 229 Griffith J. 447 Griffith M. G. 39 Grifith R. C. 150 157,261 Grifiths J. S. 391 Grigg R. 152 165 261 284 354 590 Grignon J. 308 Grillot G. F. 262 Grimberg J. I. 439 Grimm K. 363 382 Grimme W. 149 Grimwood P. D. 462 Gringore O. 344 387 Grisdale P. J. 140 266 Grisebach H. 413 Gronowitz S. 589 Gros F. 439 Gross F. 444 Gross M. H. 99 Gross M. L. 8 17 Gross R. 456 Groters A. M. 22 Groth P. 339 Grozinger K. 578 Grubbs E. J. 141 Grubbs R.H. 278 365 Gruber G. W. 222 Gruber P. 385 Gruber W. 248 Grutzmacher H. F. 532 Grunberger D. 422,423 Grundon M. F. 369 Grutzner J. B. 410 Grynkiewicz G. 130 Gryte C. 427 Grzonka J. 336 Guarnaccia R. 401 Giinther. E.. 540 Gunther H. 148 336 Giinther P. 286 Guest I. G. 482 486 Guibe-Jampel E. 385 Guilbault L. J. 566 Guilford H. 408 Guillard R. L. 449 Gullotti M. 281 Gulyas A. 422 Gunn P. A. 476 Gunstone F. D. 465 Gunther K. 210 Gupta A. S. 480 Gupta R. N. 410,411,412 Gupton P. 414 Gurd F. R. N. 32 Gurnos Jones 236 Guschibauer W. 433 445 Guss M. 356 Guthrie R. D. 392 Gutsche C. D. 228 361 Gutteridge N. J. A. 351 Gutzwiller J. 505 510 Haan J.W. 467 Haas C. K. 230 Haas F. 286 Haas G. 107 Habermehl G. 574 Habraken C. L. 267 Hach V. 368 Hackett P. 327 Hackmeyer M. 574 Haddad Y. M. Y. 280 Haddock E. 582 Haddon R. C. 540 Haddon V. R. $63 540 Haefliger W. 367,491 Haegeman G. 437 Haelwy M. D. 308 Haemers M. 468 Hafner K. 535 545 Hafner W. 292 Hagaman E. W. 493 Hagashi T. 296 Hageman H. J. 532 Hagihara N. 280 Haginiwa J. 506 Hahlbrock K. 413 Hahn R. C. 264 Haidukewych D. 247 Haimovich J. 180 Haines A. H. 108 Haines L. M. 282 Hair N. J. 115 116 118 Hajdu J. 303 Hakka L. E. 139 318 Halasa A. F. 197 526 Hales R. H. 219 Hall D. T. 252 Hall G. E. 148 336 Hall H. K. jun. 345 Hall J.H. 159 Hall J. K. A. 530 Hall L. D. 19 37 42 568 Hall R. 436 Hall R. H. 419 Hall S. S. 366 527 Hallcher R. C. 315 497 Halle J. C. 41 136 Halliday D. E. 548 Halls P. J. 568 Halpern B. 105 351 Halpern J. 166 277 284 Halpern Y. 36,41 Halsall T. G. 449 Haltiwanger R. C. 125 Halton B. 534 Hamada K. 140 Hamano Y. 286 Hamasaki T. 410 Hamberger H. 159 269 552 553 Hamelin J. 188 Hamilton L. R. 327 Hamlett P. 10 Hamm P. 575 Hammar C.-G. 11 Hammen P. D. 556 Author Index Hammon D. P. G. 489 Hammond G. S. 87 Hammond W. B. 361 Hampson P. 140 Hamrig V. 100 Hamrin K. 92 98 Hanack M. 248 Hanaoka M. 504 Hanase H. 318 Handloser L. 146 Hanessian S. 425 Hanifin J.W. 161 258 Hanna I. 104 Hannan B. N. B. 133 518 Hannaway C. 123 Hansen B. H. 317 Hansen H.-J. 159 258 265,519,522,586 Hansen H. N. 127 Hansen J. F. 148 298 577 585 Hanson A. W. 113 Hanson E. M. 231 Hanson J. R. 399 Hanson K. R. 403 Hanson S. W. 23 Hanzmann E. 460 Hara M. 280,288 Harada F. 442 Hardie J. A. 160 Harding D. R. K. 161,259 Hardy A. D. U. 475 Hardy J. P. 338 Harfenist M. 268 Harger M. J. P. 218 219 525 Hargret A. 74 Harmon C. A. 160 188 Harpp D. N. 391,568 Harris J. M. 140 Harris M. M. 107 Harris R. L. 577 Harris R. O. 161 259 Harris T. M. 380 Harris W. C. 340 Harrison D. A. 326 Harrison D. M. 478 Harrison E. A. 525 Harrison H.R. 116 574 Harrison J. F. 67 224 Harrison L. W. 526 Harrison P. G. 406 Harrison R. G. 491 Hart F. A. 19 21 Hart H. 22 249,262 263 548 Hart N. K. 513 Hart-Davis A. J. 282 Hartley B. L. 172 Hartmann A. A. 565 Hartmann F. C. 179 Author Index Hartshorn M. B. 133 Hartshorn M. P. 484,486 518 Hartshorn S. R. 129 Hartsuck J. A. 172 Hartzler H. D. 227 Harvey R. G. 544 Hase T. 351 Haselbach E. 74 Hashimoto H. 230 342 Hashimoto M. 392 Hashimoto N. 392 Haslam E. 403 Hassal C. H. 406 Hassmann V. 219 Hassner A. 235 237 489 555 Hasty N. M. 41,248,249 329 Haszeldine R. N. 206 232 271 291 524 531 583 Hata K. 570 Hata T. 429 Hauptman H.124 Hauser C. R. 391 589 Havlicek S. C. 15 Hawks R. L. 500 Hawley D. M. 115 121 Hawley M. D. 305 Hayasaka T. 222 Hayashi H. 440 Hayashi T. 280 Hayashi Y. 559 Hayatsu H. 424 427 428 Hayes D. 435 Hayes D. M. 228 Hayes E. F. 159 Hayes F. 435 Hayes L. J. 239 257 Hayes R. 14 165 261 284 354 Haynie E. C. 160 Hayward P. J. 291 Hayward R. J. 541 Hazen E. E. 174 Hazra B. G. 525 Headley L. 197 526 Heaney H. 221 517 526 532 543 547 548 Heathcock C. H. 381 Heathcock C. P. 472 Heaton P. R. 379 490 562 Hecht S. M. 423 Hecker E. 479,480 Heckner K.-H. 315 Hedaya E. 232 254 271 534 565 577 Hedegaard B. 578 Heden P. F. 92 98 Hedman J. 92 98 Hetflege J.365 Heerma. W. 15 Hetzel D. S. 516 Hefelfinger D. T. 263 539 Heusler K. 206 Hefflegs J. 278 Hewitt D. G. 209 523 Hefter H. J. 194 Hewitt G. 557 Hegarty A. F. 267 Hewlins M. J. E. 116 Hehre W. J. 48,49 53,61 Hey D. H. 192 193 207 66 75 262 265 517 Heiba E. I. 372 Hey H. 154 Heil B. 292 Heyd W. E. 252 Heimbach P. 273 287 Heyn A. S. 386 Heimler D. 315 Hibbert F. 141 Heindel N. D. 259 Hibbert P. G. 207 219 Heine H. G. 245,266,268 Hicks A. A. 105 Helene C. 445 Hicks R. E. 24 Helgeson R. C. 539 Hidai M. 281 Helser T. L. 435 Hideg K. 569 Hemingway J. C. 475 Higo A. 326 Hemingway R. J. 475 Higo K. 435 Hemmer H. 273 Higuchi S. 383 Henbest H. B. 280 Hiiragi M. 222 Henderson J. 233 Hikino H. 484 491 Henderson R.E. L. 421 Hikino Y. 484 Henderson W. 483 Hill H. D. W. 32 33 Henderson W. A. 144 Hill J. 265 Hendler S. 447 Hill L. P. 348 472 Hendrick M. E. 160 226 Hill R. E. 412 232,253 Hills I. R. 449 Hendrickson D. N. 97 Hilt H. 9 Hendrickson J. B. 348 Hinckley C. C. 18 19 22 383,472 Hindley J. 437 Hendry J. B. 131 Hindley K. 209 Henes G. 264 587 Hinkley R. K. 65 Henion R. S. 555 Hinman R. L. 578 Henning D. 435 Hinshaw J. C. 343 534 Henningsson A. 444 Hintsche R. 426 Henrici-Olive G. 274 Hirai H. 278 Henry P. M. 292,293,377 Hirai K. 390 483 Henry T. J. 150 151 Hiraoker T. 19 Henson W. L. 248 Hirata Y. 513 Henzel R. P. 165 262 Hirota N. 213 284 352 Hirsh D. 440 Hepler L. G. 141 Hirst J. 135 Herberich G.H. 294 Hirtenstein M. D. 185 Herisson J. L. 286 Hisada R. 208 Hermann H. 159 552 Hites R. A. 12 Hermolin J. 302 Hixson S. S. 177 Herndon W. C. 155 Hlubucek J. R. 23 337 Herold B. J. 245 Ho F. F. L. 19 Herout V. 474 Ho P. C. 106 Herron D. K. 378 450 Ho Y. K. 411 Hershman A. 291 Hobbs J. 433 Hertel I. 7 Hobbs W. E. 233 Hertz H. S. 12 Hodder 0.J. R. 110.574 Hertz J. E. 19 Hodge P. 227 Herzberg M. 439 Hodge R. A. V. 406 Hess B. A. jun. 217 Hodges R.,127 Hess G. P. 172 Hodges R. J. 280 Hesse M. 493 501 504 Hodgins T. 530 Hesse R. H. 255 489 Hodgkin D. C. 110 574 Hessling R. 11 Hodgson A. 444 Hodgson G. L. 381 Hodson H. F. 493 501 504 513 Hofle G. 244 H0g J. H. 572 Hoff S. 457 Hoffee P.184 Hoffman A. K. 311 Hoffman J. M. 373 Hoffman M. K. 129,327 Hoffman R. 43 321 Hoffman R. A. 42 Hoffman R. V. 231 Hoffmann H. M. R. 391 Hoffmann M. K. 17 Hoffmann R. 44 88 143 148 153,217,228 335 Hoffmann R. W. 229,232 Hofle G. 161 553 Hogberg S. 100 Hogfeldt E. 139 Hoggett J. G. 433 Hojabri F. 282 Hojo K. 40 341 540 Hokosami T. 235 Hole M. 583 Holladay D. W. 440 Holland G. W. 388 Holland J. M. 520 Hollander J. M. 95 97 Hollaway M. R. 168 Hollins R. A. 539 Hollosi M. 106 Holmes A. B. 542 Holmes G. D. 188 Holmstead R. L. 190 Holt P. T. 318 Holtz D. 517 Holy N. L. 196 Hong C. I. 424 Honig M. L. 147 Honma H. 478 Hooker T. M. 106 Hopff W.H. 493 Hopkins R. G. 146 Hopkinson J. A. 7 Hoppe I. 270 Hoppe W. 479,484 Hopper S. P. 230 Hordvik A. 573 Horeau A. 385 Horecker B. L. 183 184 Horibe I. 472 Horii Z. 496 Horn D. H. S. 478 Hornemann U. 412 Horner L. 295 301 302 Hornfeldt A. B. 579 Hornstra J. 113 Horrocks W. D. 23 Horsewood P. 392 Horsley J. A. 43 Horspool W. M. 523 Hortmann A. G. 577 Horton D. 268 Horvath G. 245 Horwell D. C. 238 270 Horwitz J. P. 428 Hosogai T. 202 Hosokami T. 270 Hotta Y. 446 Houbiers J. P. M. 107 Houk K. N. 156 House H. O. 383 Houser R. W. 247 560 Howe G. R. 132 Howe I. 13 Howell D. C. 584 Howes P. D. 589 Hoyermann K. 210 Hranilovic J. 306 Hsieh W.C. 249 Hsu K. 80 Hsu Y. L. 156 Huang W. M. 432 Hubbard R. 531 Huberman J. A. 447 Huckin S. N. 384 Huckley T. N. 579 Huddle B. P. 572 Hudec J. 103 163 260 323 Hudrlik A. M. 555 Hudrlik P. F. 555 Hudson D. W. 114 Hudson R. F. 205 563 Huebert J. 298 Hubner J. 532 Huvos P. 422 Hug R. 519 Hug W. 105 Hughes M. T. 103 Hughes R. P. 290 Hughes W. B. 164,286 Huing C. 315 Huisgen R. 149 159 269 552 553 586 Huk F. 274 Hulbert P. B. 107 Hulett L. C. 93 Hull S. E. 223 Huml K. 113 Humm D. G. 422 Humm J. H. 422 Humphrey J. S. 265 Humphrey S. A. 579 Hunt J. B. 233 Hunt J. D. 131 132 373 518 Hunter D. H. 276 Hunziker E. 129 Hurley L. H. 416 Hursthouse M.B. 484 Hurwitz E. 180 Author Index Husain S. S. 177 178 Husbands J. 280 Hutchins R. O. 368 369 467 Hutton R. S. 224 Huurdeman W. J. F. 490 562 Huxol R. F. 346 389 Huysmans W. G. B. 19 Hybl A. 122 Hyeon S. B. 468 Hyvonen M. L. 135 Ibekwe S. D. 275 281 Iccarino R.. 478 Ichihara A. 474 Ichikawa K. 518 Iddon B. 235 582 Ife R. 403 Igeta H. 583 Iguchi M. 471 Ihler G. 439 Iida S. 427,428 Iitaka Y. 120 127 506 Ikeda H. 440 Ikeda M. 144 152 Ikeda T. 483 Ikeda Y. 445 518 Ikehara M. 426,430 Ikekawa N. 486 Ikeuchi T. 281 Illuminati G. 138 582 Imafuku K. 140 Imamoto T. 140 256 Imazawa M. 428 Imhoff M. A. 251 546 Immirzi A. 127 Imoto I.385 Inamoto T. 202 Ingold K. U.,201,204,206 213 Ingraham L. L. 224 Ingrosso G. 290 Innorta G. 6 Inoue M. 428 Inoue S. 563 Inoue Y. 42 Inouye H. 401 Inubushi Y.,342 Inuma H. 471 Ipaktschi J. 543 Ippen K. 439 Iqbal A. F. M. 564 575 Iqbal M. Z. 281 Irie H. 481 Irie T. 546 Irvine P. 6 Irving C. S. 185 Isaacs N. W. 117 125 127,402 48 1 503 Author Index Isaksson L. 444 Isbrandt L. R. 25 Isenhour T. L. 12 Ishi H. 471 Ishibe N. 271 Ishijura H. 442 Ishikura H. 423 Isiyama S. 362 Islip P. J. 393 Isobe K. 498 499 Isoe S. 468 Isola M. 141 Issleib K. 289 Itai A. 127 506 Ito S. 478 537 Ito T. I. 531 Ito Y. 342 Itoh I. 537 Itoh M.388 Ivanov V. T. 106 Iversen P. E. 242,306,308 Iwamura H. 28 222 241 27 1 Iwamura M. 28,222,241 27 1 Iwasaki T. 307 Iwashita Y . 292 Iwata C. 496 Iwata R. 428 Iyer K. N. 512 Izumi Y.,296 366 Jablonski J. M. 221 Jackman L. M. 263 540 Jackson A. H. 498 Jackson H. L. 203 Jackson W. R. 191 369 Jacob J. 453 Jacobs R. L. 529 Jacot-Guillarmod A. 275 Jacques J. 516 Jacquesy J. C. 487 488 Jacquesy R. 487,488 Jaffe M. H. 247 Jaguoztyn-Grochowska J. M. 135 Jakubetz W. 574 James B. R. 273 James F. J. 458 James M. N. G. 125 James V. J. 339 Jamieson G. 112 Jancis E. H. 556 Janiga E. R. 346 389 Janik B. 419 Janousek Z. 385 Jansonius J. N. 169 Janssen J.F. 263 Janssen J. W. A. M. 267 Jantzen R. 339 Januszewski H. 575 Janzen E. G. 205 Jarczak J. 19 Jarreau F. X. 487 Jarvie A. W. P. 213 Jary J. 106 Jaurdosiuk M. 135 Jaurequeberry C. 578 Jawdosiuk M. 530 Jay E. 420 Jeck R. 176 Jefford C. W. 252 Jeffs P. W. 500 Jemilev U. M. 371 554 Jeminet G. 308 Jenevein R. M. 301 Jenkins C. S. P. 108 Jenkins D. K. 290 Jenkins P. N. 42 Jenkins W. T. 173 Jennings K. R. 9 14 16 Jennings W. B. 40 516 Jenny E. F. 545 Jensen F. R. 338 Jeppesen P. G. N. 437 Jesson J. P. 281 Jevans A. W. 458 Jewess P. J. 137 Jindal S. P. 358 Jira R. 292 Johanson R. G. 36 Johansson G. 92 95 98 Johansson N. G. 234 Johns S.R. 103 513 Johnson A. L. 157 Johnson A. P. 152 Johnson A. W. 152 590 Johnson B. F. G. 293 Johnson C. B. 466 Johnson C. D. 140 580 Johnson C. R. 116 343 346 358 387,389 390 Johnson G. L.. 372 Johnson L. F. 23 35 337 338,410 Johnson M. D. 517 Johnson P. L. 117 574 Johnson P. W. 428 Johnson R. A. 106 Johnson W. F. 434 Johnson W. S. 350 378 460,47 1,490 Johnston D. E. 351 Johnstone R. A. W. 5 6 7 8 14 15 141 Jolly P. W. 286 289 Jolly W. L. 97 Jones A. J. 35 Jones A. S. 428 43 1,432 Jones C. W. 233 Jones D. H. 219 Jones D. N. 338 Jones D. W. 260,520,575 Jones (Sir) E. R. H. 406 455,485 Jones G. 270 Jones G. H. 193,265 Jones G. W. 264 Jones I. W. 245 Jones J.G. Ll. 489 Jones K. W. 446 Jones M. 158 160 253 327 Jones M. jun. 217 226 227,232 Jones P. F. 231 Jones P. R. 386 Jones R. A. Y. 568 Jones R. H. 406 Jones T. K. 368 Jones W. M. 232 377 Joosting P. E. 332 Jordan B. R. 435 Jordan P. 173 Jorgensen E. C. 15 Jorgensen W. L. 56 Joseph-Nathan P. 19 Joshi B. S. 471 Jost R. 516 Jotham R. W. 223 Joule J. A. 494 Joullie M. M. 566 Jreissaty S. N. 338 Judd G. F. 426 Juers D. F. 327 Julia M. 192 263 342 Julia S. 253 Jullien P. 436 Julshamn K. 573 Jung G. 32 35,337 Jung M. J. 277 Junk G. A. 6 11 Jurjev V. P. 371 554 Jurs P. C. 12 Just G. 254 272 Justin B. 206 Jutz C. 549 589 Kabalka G. W.374 Kagan H. 516 Kagan H. B. 107 295 365 Kagan J. 326 Kagawa S. 474 Kahrl J. 507 Kai K. 424 Kainosho M. 570 Kaiser E. M. 391 Kaiser G. V. 244 Kaiser I. I. 444 Kaiser K. L. 156,284 352 Kajtar M. 106 Kakihana T. 148 298 577 585 587 Kalechits I. V. 274 285 608 Author Index Kalicky P. 375 485 Kaufman D. 342 Kalidas C. 139 Kaufman E. E. 444 Kalinin V. N. 28 Kaupp G. 154 328 Kalli M. 377 Kaurov A, 106 Kallos J. 179 Kavanagh F. E. 449 Kalman A. 116 Kavunenko A. P. 430 Kalvoda J. 206 Kawamura T. 214 Kamachi M. 205 Kawazu K. 480 Kamat V. N. 471 Kawdzoe Y.,28 Kameoka I. 296 Kazansky B. A. 361 Kamerling J. D. 15 Kazlauskas R. 482 Kametani T. 222 496 Keana J. F. W. 205 498,499 Kearney J.A. 267 Kampmeier J. A. 187 188 Kearns D. R. 152,445 219 379 Keating M. 238,270 584 Kan G. 587 585 Kan J. 440 Keda A. 312 Kanai K. 454 Keeler B. T. 124 Kanai T. 265 Keese R. 340 Kane A. R. 281 Kefurt K. 106 Kane B. L. 531 Kefurtova Z. 106 Kaneda T. 45 1 Keith G. 442 Kanematsu K. 547 Keller E. B. 422 Kang J. W. 277 Keller K. 147 494 520 Kannelakopulos B. 337 Keller T. 148 336 338 Kanojia R. M. 495 Keller-Schierlein W. 463 Kaplan L. 154 329 330 Kellett P. M. 531 Kaplan L. A. 138 Kelley D. P. 36 Kaplan M. S. 160 259 Kellie G. M. 35 537 Kellman R. 191 Kapovits I. 422 Kellogg R. M. 272 565 Kaptein R. 26 27 29 31 58 1 588 Karger M. H. 385 Kelly J. F. 148 Karim A. 360 Kelly K. K. 254 Kariv E.302 Kelly R. B. 474 Karle I. 494 Kelly W. S. 446 Karle I. L. 118 Kelmers A. D. 440 Karlsson S.-E.,92 Kelsey D. R. 248 Karmann H.-G. 296 Kelsey J. F. 499 Karoglan J. E. 363 382 Kemball C. 285 Karriker J. M. 340 Kemmitt R. D. W. 290 Kasai H. 423 Kemp C. M. 107 Kashiwagi T. 281 Kemp D. S. 527 Kasukhin L. F. 28 Kemp J. E. 163,260 323 Katchalski E. 171 Kemp W. 543 Katekar G. F. 346 389 Kende A. S. 160 Kato H. 542 Kennard C. H. L. I17 Kato M. 221 463 533 Kennard O. 114,116 125 Kato S. 270 127,402,481 503 Katritzky A. R. 19 40 Kennedy J. D. 191 568 578 580 Kenner G. W. 15 Katsuhara Y.,325 Kenney M. E. 25 Katsumata S. 197 468 Kenny N. C.,116 Katz G. 422 Kensler T. T. 201 Katz H. 143 322 Kent M. C.,577 Katz T.J. 113 165 284 Kent M. E. 232,254 271 340 531 561 534 565 Katzenellen bogen J. A. Kentaro Hoffmann A.,307 367 Kenyon R. S. 280 Kauffman W. J. 386 Kerek F. 561 Kauffmann T. 159 223 Kern F. 281 582 Kernaghan G. F. P. 391 Kerr D. A. 245 Kerrinnes H. J. 289 Kershaw J. R. 21 Keske R. G. 21 1 Kessler H. 42 140 334 Keszthelyi C. P. 299 Ketley A. D. 145 Kettle S. F. A. 223 Keyhani E. 439 Kezdy F. J. 168 Khan H. 480 Khan H. A. 41 137 529 Khan 0. R. 191 Khan W. A. 369 Khidekel M. L. 274 285 Khmelnitski L. I. 551 Khokhar A. Q. 103 Khono T. 499 Khorana H. G. 420 429 43 1,439,445 Khuong-Huu Q. 488,489 Kieczewski M. A. 103 Kienzle F. 131 132 518 Kieslich K. 484 Kigasawa K.222 Kiji J. 287 Kikukawa O. 577 Kilbourn B. T. 281 Kilcast D. 92,95,98 100 573 581 Kim C. U. 540 Kim S. H. 432,445 Kim Y.,485 Kime D. E. 338 Kimling H. 341 Kimmel V. 534 Kimura F. 442 Kimura K. 197 Kimura Y.,312 Kindley L. M. 324 King D. 504 King J. F. 161 259 King R. B. 282 561 King R. R. 463 Kinson P. S. 541 Kira M. 197 Kirby G. W. 392 404 499 Kirby P. 582 Kirchner P. 15 Kirk B. E. 158 Kirk D. N. 488 Kirk K. L. 340 531 Kirmse W. 229 248 525 Kirsch G. 149 Kirsch P. 279 Kirschner S. 144 Kirson I. 492 Kiryushkin A. A. 10 Kishida Y.,19 390 483 Kisis B. 107 Kiso Y.,280 Author Index Kispert L. D. 334 Kissinger P.T. 318 Kita Y. 254 Kitagawa M. 506 Kitahara Y. 536 538 Kitaura. Y. 331 Kito N. 200 201 Kittleman E. T. 286 Klanderman B. H. 219 379 Klav R. 346 Klein H. F. 281 Klein J. 379 Klein M. P. 92 Kleinstuck R. 384 Klemm L. H. 298 Klette A. 174 Kloek J. A. 346 478 Kloos W. E. 450 Kloosterziel H. 518 Klose G. 556 Klose T. R. 349 381 478 Klotz, I. M. 186 Klotz M. R. 22 Klumpp G. W. 386 Klunder A. J. H. 257 Klunklin G. 330 Klyne W. 102 105 107 Knapp J. E. 497 Knapp K. A. 538 Knappenberger M. H. 171 Kneen G. 260 Knight M. H. 524 Knittel P. 408 Knoeber M. C. 35 Knolle W. R. 212 Knorre D. G. 429 Knowles J. R. 171 177 179 181 Knowles P. 569 Knowles P.J. 281 Knowles W. S. 295 Knox J. R. 501 Knutson K. K. 466 Kobayashi M. 208,474 Kober H. 148 336 Kobuke Y. 156 Kobylecki R. J. 302 Koch M. 505 512 Koch V. R. 313 Kochetkov N. K. 427 Kochi J. K. 214 388 Kocienski J. P. 534 Kodama M. 478 Koehl W. J. jun. 372 Koehn W. 153 Koekoek R. 169 Koelliker U. 344 369,459 Koeng F. R. 39 Konig F. 404 Koenig K. E. 390 Koermer G. S. 24 Kossel H. 429 Kogan G. A. 106 Koh C. 421 Koike T. 430 Koizumi M. 496 Kojima H. 280 Kolomnikov I. S. 291 Kolshorn H. 290 Koltzenberg G. 153 Komlossy J. 579 Komorowski K. 563 Kompis I. 501 Konaka R. 201 Kondo A. 161 Kondo E. 454 Kondo K. 553 563 Kondo Y. 134 Konz W.E. 149 Koob K. 452 Kooyman E. C. 214 Kopay C. M. 587 Kopp L. D. 568 Koppel J. A. 382 Koptyug V. A. 263 Koreeda M. 471,484 Korinek K. 315 Koritala S. 465 Korn K.-D. 194 Kornberg A. 447 Kornberg T. 447 Kornblum N. 376 Kornrumpf B. 248 Korver O. 105 Korzan D. G. 257 Kosbahn W. 158 Kosfeld R. 42 Kosower E. M. 303 Kost A. A. 427 Kost D. 40 Koster H. 575 Koster S. 521 Kouba J. E. 139 Kouijs A. 588 Kovacic P. 255 256 Kovacs J. 282 Kowalski S. 442 Kowerski R. C. 248 396 48 3 Kowollik G. 426 Kozerski L. 19 Kraak E. W. A. 518 Kraft K. 153 Krakower G. W. 124 Kramer J. M. 223 Kramer L. N. 92 Kratky O. 445 Kraus J. L. 384 Krause D.L. 232 Krauskopf M. 444 Krayuschkin M. M. 38 Krebs A. 341 Krebs E.-P. 340 Kreishman G. P. 432 Krepski L. 230 244 Kresge A. J. 139 141,263 386 578 Krespan G. W. 229 Kresze G. 158 Kretchmer R. A. 349 Krief A, 396 482 Krieger J. K. 188 388 Kriegler A. B. 406 Krishnappa S. 222 474 Kristensen R. 573 Kroll L. C. 278 365 Kroll W. R. 277 Krone H. 9 Kropacheva E. N. 286 Kroszczynski W. 408 Krow G. 564 589 Krow G. R. 152 Krueger W. C. 106 Kruger G. J. 572 Kruk C. 525 Krukonis A. P. 196 Krusic P. J. 214 Krutak J. J. 264 Krutilina A. I. 442 Kubicek D. H. 286 Kubik D. 385 Kubo A. 506 Kubo M. 542 Kubota M. 292 Kubota T. 407 Kucan I. 444 Kucan Z. 444 Kuchitsu K.339 Kuck V. J. 224 Kucsman A. 116 Kuhle T. 343 Kuffner U. 540 Kuhlman D. P. 223 Kuhn S J. 129 Kuhn W. 525 Kuivila H. G. 191 Kulik S. 236 269 Kumada M. 280 Kumagai Y. 355 Kumanda M. 296 Kumar A. 420 Kummer D. 575 Kunau W.-H. 456 Kundu K. K. 139 Kunesch G. 514 Kunkes S. 569 Kuntsmann M. P. 474 Kuo Y. N. 384 Kupchan S. M. 367 475 495 Kuper D. G. 229,254 Kurabayashi M. 479 Kuriyama K. 481 Kurland R. J. 36 Kuroda H. 158,220 610 Author Index Kuroki T. 290 Kurosawa H. 290 Kurosawa K. 140 Kurts A. L. 383 Kurz M. E. 372 Kusama O. 222,496 Kushner A. S. 329 Kusuda K. 336 Kuszmann J. 245 Kutney J. P. 401 481 Kuwajima I.274 Kuwano H. 19 Kuwata K. 205 Kwan T. 296 Kyba E. P. 234 257 Kyburz R. 535 Laarhoven W. H. 298 Labarre J. F. 515 L'Abbe G. 235 Lablanche-Combier A. 268 Laboritz J. 483 Labows J. N. jun. 551 Lacadie J. A. 391 Lai C. Y. 184 Lai K. H. 263 516 522 Laing M. 572 Lajzerowicz J. 205 Lakings D. B. 421 Lala L. K. 470 Lalanchette J. M. 369 Lalezari I. 576 Lalyre Y. 444 La Mar G. N. 34 Lambert J. 39 Lambert J. B. 39 568 Lamberton J. A. 103 513 Lammens H. 286 La Monica G. 277 281 Lamparsky D. 470 Lamson D. W. 368 Lancaster J. E. 330 Landesberg J. M. 355 Landgrebe J. A. 233 Landor P. D. 377 Landor S. R. 377 Landy A. 439 Lane C. F. 379 Lang C.-C.140 Langen P. 426 Langer E. 290 543 Langer M. 569 Lanks K. W. 422,423 Lansbury P. T. 350,382,490 Lanscheid M. E. 313 Laporte P. 428 Lappert M. F. 275 La Rochelle R. W. 230 244 526 Larsen B. 248 396 483 Larson A. C. 114 Larue B. 428 Lastity D. 444 Latham W. A. 49 53 6 Lattes A. 559 Laurent A. 318 Laursen R. 177 Lautzenheiser Andrews A. 485 Laval J. P. 559 Lavie D. 492 Law J. H. 406,468 Lawesson S. O. 578 Lawler R. G. 25 26 31 Lawrie W. 482 Laws E. A. 68 334 Lawson A. J. 131,205 Lawson A. M. 14,428 Lawson D. F. 21 1 Lawson P. J. 32 Lawton R. G. 346 383 474 549 Lazzeretti P. 37 Lhomme J. 472 Lea J. R. 580 Leatham M. J. 526 Lebel N. A. 361 Lecourt M.J. 41 136 Lederberg T. 13 Lederer E. 15 454 Ledlie D. B. 370 Ledon H. 253 Lee C. S. 569 Lee E. 408 Lee G. K. 402 Lee G. K. J. 132 Lee H. B. 277 Lee H. L. 510 511 Lee K. S. 117 Lee L. 161,272 565 Lee M. L. 272 533 577 Lee R. F. 449 Lee T. B. K. 392 Lee V. F. 425 Lee W. W. 425 Leedy D. W. 303 Leenhouts J. I. 113 Leermarkers P. A. 185 Leete E. 403,410 494 Leeuwestein C. H. 112 Leffler J. E. 207 Lefour J.-M. 156 Legon A. C. 339 Le Guillanton G. 303,304 Lehmann H. 456 Lehn J. M. 62 334 570 Lehnert W. 384 Lehnig M. 27 Leibfritz D. 140 Leicht C. L. 246 Leistner E. 406 Leitich J. 5 13 Lelandais D. 22 314 Lemieux R. U. 568 Lemke P.A, 410 Leng M. 433 le Noble W. J. 239 Lenoir D. 252 Leonard N. J. 421 423 424,444 570 Le Pecq J. B. 446 Lepley A. R. 28 30 222 241 Lepri L. 3 15 Le Quesne P. W. 485 507 Lerch U. 427 Leroy J. 567 Leslie V. J. 523 Lessard J. 204 Lester G. R. 7 Letham D. S. 424 Letsinger R. L. 429 Leung F. 574 Levi E. M. 256 Levin R. H. 227 . Levin Y. 17 1 Levina E. S. 444 Levine M. D. 434 Levine S. G. 24 124 Levisalles J. 273 487 Levison J. J. 281 Levitan P. 268 Levitin I. Y . 290 Levy A. B. 257,555 Levy B. 50 Levy G. C. 37 Levy H. A. 573 Levy H. B. 436,437 Levy M. 197 Lewandos G. S. 164 286 Lewis A. J. 133 518 Lewis D. W. 24 Lewis I. C. 195 Lewis J.293 Lewis J. R. 414 Lewis R. B. 19,493 Ley S. V. 547 548 Leyshon L. J. 234 235 Leznoff C. C. 541 Li L. 442 Liao C. C. 331 558 Liao T. K. 508 Libby W. F. 10 Libert M. 315 Libman J. 485 Lichtenberg D. 578 Lichter R. L. 575 Lieb F. 222 516 582 Liedhegener A. 231 Liehr A. D. 333 Liem R. K. H. 172 Lienhard G. E. 173 Lifshitz C. 6 Author Index Liggero S. H. 251 Lightner D. A. 103 584 Liler M. 139 Lilley D. M. J. 63,95 574 Lillien I. 146 Lim P. K. K. 237,269 Lin W. C. 203 Linda P. 580 582 Lindberg B. 100 Lindberg B. J. 92 98 Lindert A. 384 Lindgren I. 92 Lindow D. F. 544 Lindsay W. S. 549 Ling. V. 437 Linhart F. 315 Linschitz H. 323 Linstrumelle G.253 Lion C. 380 388 Lippert W. 534 Lippmaa E. 37 38 Lippmaa E. T. 158 252 Lipscomb W. N. 68 172 334 Lipsett M. N. 444 Lipsky S. D. 366 527 Lipsky S. R. 410 Lister J. H. 419 Liston A. J. 485 Littauer U. Z. 420 439 Littler J. S. 13 372 Littlewood P. S. 491 Liturri V. 135 Litwack M. 444 Liu J. H. 256 Liu K. T. 372 Liu M. S. 188 Lloyd D. 132 233 569 Lloyd R. V. 200 Lobeeva T. S. 291 Lockard J. P. 343 390 Loffler H. P. 191 Loew P. 378 460 471 Loewen P. C. 420 Loffgren M. 158 221 Logue M. W. 544 Lohmar E. 540 Loken H. Y. 31 Lombardo L. 158,221 Long F. A. 141 Long W. F. 436 Longchamp S. 315 Longoni G. 275 Looker B. E. 557 Looker J.J. 237 Lopez L. 392 Lorenzi G. P. 296 Louder P. L. 291 Louick D. J. 40 Louw R. 379 Love G. M. 22,249 548 Lovesey A. C. 579 Lovrecek B. 306 Lowe G. 169 172 177 557 Lowe R. 243 Lowery M. K. 255 Lown J. W. 144,268,378 5 50 Lowrance W. C. 385 Lowry C. V. 435 Lozach N. 100 Lozeron H. 439 Lu S.-H. 416 Lucacchini A. 178 Lucken E. A. C. 205 Luckhurst G. R. 195,205 Ludger E. 19 Ludmer Z. 330 Luetzow A. E. 268 Luhan P. A. 500 Lui C. Y. 36 249 Luke M. O. 277 Lumb J. T. 262,284 Lunazzi L. 215 308 Lund H. 303 Lund W. 298 Luskus L. J. 156 Luttringer J. P. 587 Lutz R. P. 161,259 Lutz W. K. 120 Lwowski W. 234 257 Lynch I. R. 118 Lynch J. M. 483 Lynch T.R. 559 563,573 Lynd R. 344 Lyons J. E. 282 377 Lythgoe B. 491 Ma K. W. 126 481 Maag H. 392 Maas A. 9 Mabry T. J. 326 McAdams L. V. 247 McAllister D. L. 308 McBee E. T. 530 MacBride J. A. H. 583 McBride J. M. 30 McCall D. M. 42 McCall J. M. 327 McCall M. T. 327 Maccagnani G. 215 308 McCarry B. E. 490 Maccio Z. 497 McCloskey J. A. 14,428 McConnell H. M. 20,186 McConnell J. F. 339 McCormick A. 14 McCoy J. J. 292 McCreadie T. 165 285 476 586 McCreary M. B. 436 McCrindle R. 476 McDonald E. 368 61 1 McDonald J. J. 421,424 McDonald W. S. 277 McDonnell J. J. 21 1 McDowell C. A. 225 McEnroe F. J. 366 527 McEwen G. K. 568 McFarland B. G. 186 McFarlane N.R. 137 McGhie J. F. 458 McGillivray G. 131 518 McGreer D. E. 565 MacGregor R. A. 164 286 MacHattie L. 439 Machowicz E. 421 McHugh J. L. 405 Macias A. 383 Maciel G. E. 38 McInnes A. G. 410 McIntosh C. L. 325 519 52 1 McIntyre P. S. 579 Macintyre W. M. 546 Mackay I. R. 123 McKellar J. F. 332 McKelvey R. D. 198 McKenna C. E. 524 McKenna J. C. 558 McKennis J. S. 161 260 342 McKervey M. A. 252 351 360 Mackey J. K. 420 McKierhan J. E. 294 McKillop A. 131 132 373 518 519 McKillop T. F. W. 473 McKinley J. V. 41 McKinley J. W. 565 McKinnon D. M. 575 MacLachlan A. 203 McLafferty F. W. 6 17 MacLean D. B. 41 1 McLean I. A. 571 McLean J.482 McLennan D. J. 268 530 MacLeod J. K. 16 Macmillan J. 13 478 McMorris T. C. 484 535 McMurray J. E. 370 McMurry J. E. 230 380 381,469 McMurry T. B. H. 471 472 McNeil D. W. 27 I 565,577 McNicholas M. W. 161 259 MacNicol D. D. 109 McPhail A. T. 124 500 568 McQuilkin R. M. 342 542 612 Author Index McQuillin F. J. 278 295 Mann C. K. 307 Maruca R. 533 365 Manne R. 92,98 MaruSiC R. 121 McRae J. 204 Manning C. 330 Maruyama H. 392 MacSweeney D. F. 381 Mannschreck A. 515 Maruyama K. 290 473 Manojlovic- M uir L. J. Maruyama M. 475 Mader H. 159 275 Marwede G. 286 Madsen V. 271 587 Manson D. 267 Maryanoff B. E. 368 369 Madyastha K. M. 401 Mantione R. 391 Masaki N. 480 Maeda K. 280 Manuel M.F. 403,494 Masamune S. 40 165 Mader H. 552 Manyama M. 367 166 262 284 325 341 Maekawa K. 368 Manyik R. M. 288 352 354 540 Maerker G. 458 Mao S. W. 213 Masaracchia J. 153 Markl G. 232 516 582 Maoz N. 279 Maskasky J. E. 25 Mageswaran S. 161 243 Marcali K. 203 Mason J. 37 564 Marchetti L. 558 Mason K. G. 221 Maggio M. 22 337 Marcum J. D. 196 Mason P. 192 Maggiova G. M. 53 Margult A. 383 Mason R. 356 Magnus P. D. 259 351 Marino G. 15 580 Mason S. F. 107 375,470,490 544 561 Marino J. P. 242 Mason T. J. 548 Maheshwari R.-C. 572 Mark V. 515 527 Mass G. 433 Mahler H. R. 433 Markey S. P. 450 Massa S. 569 Mahler J. E. 294 Marki L. 282 Masse B. 425 Mai V. A. 233 Markl G. 222 581 Masters C. 277 Maier C. A. 121 Marko L. 285 Masuda M. 454 Maier D.P. 219 379 Markovits J. 454 Masuda S. 483 Maiorana S. 272 555 Markowski V. 159 269 Masui K. 287 Mair A. C. 237 552 Masui M. 315 Mair H. J. 339 Marks A. 439 Mateescu G. D. 99 Maitlis P. M. 166 273 Marks L. 292 Mathew M. 122 123 277,284 352 Marks T. J. 275 Mathias A. 140 Majerski Z. 19 146 251 Markwell R. E. 471 Mathieson A. McL. 103 Majoral J.-P. 568 Marky M. 159 586 513 Maki Y. 224 235 270 Marmor J. 444 Mathis F. 568 Makino S. 287 355 536 Marmor R. S. 232 Mathur N. K. 371 Makosa M. 230 Marples B. A. 482 486 Matschiner H. 289 Makosza M. 135 342 489 Matsuda H. 390 483 530 Marshall D. R. 132 Matsuda S. 286 Makovetskii K. L. 285 Marshall J. A. 347 348 Matsueda R. 392 Malassine B. 192 387,472 566 Matsu K. 265 Malatesta V. 204 Marshall J.P. 351 Matsui T. 141 Malcharek F. 569 Marsili A. 481 Matsumato K. 307 Malcolm M. J. 41 1 Marsmann H. 334 Matsumoto K. 144 268 Malek J. 368 Martens D. 149 Matsumoto K. E. 507 Malik M. S. 482 Martin A. R. 25 Matsumoto T. 474 Mallaby R. 399 Martin C. 222 516 582 Matsumura H. 140 Mallory F. B. 88 Martin C. W. 233 Matsumura N. 385 Maloy J. T. 299 Martin F. H. 434 Matsumura Y. 310 Maltesson A. 589 Martin H. A. 277 Matsuoka M. 307 Maltz H. 284 Martin J. 473 Matsura S. 423 Mamatyuk V. I. 263 Martin J. C. 219 264 Matsuura T. 331 Manassen J. 278 Martin J. R. 412 Matthews J. S. 254 Manchand P. S. 385 Martin L. L. 412 Matthews R. S. 349 Mandava N. 563 Martin M. L. 575 575 Mandelbaum A. 48 1 Martin N. H. 500 Mattingly T. W. 330 Mandell L. 301 Martin R.H. 38 516 Maurice M. T. 454 Mander L. N. 349 381 Martin R. J. 351 Maurizot J. C. 433 478 Martin V. I. 285 Maxwell J. R. 467 Mangini A. 2 15 Martinet P. 304 Maydea E. A. 312 Mango F. D. 164 286 Martinez A. P. 425 Mayer-Ruthardt I. 200 352 Martinkova J. 484 Mays M. J. 293 Mangoni L. 478 Martin-Ramos V. 159 Mazur S. 331 Manitto P. 204 404 Marty R. A. 340 533 Mazur Y.,385,485,490 Author Index Mazza M. 404 Middleton W. J. 205 229 Mazzani G. 308 Midgley J. M. 379 490 Mazzanti G. 215 562 Mazzarella L. 120 Midland M. M. 213 374 Mazzochi P. H. 20 Mighaed M. D. 9 Meakins G. D. 485 Migita T. 239 Medlik A. 379 Mijano K. 474 Meehan T. D. 450 Mijlhoff F. C. 339 Mehl J. 78 Mikhailov B. M-. 158,361 Mehta U. R. 298 388 Meiboom S.42 Mikhailova I. F. 547 Meier B. 521 MikloS D. 121 Meier H. 290 Mildvan A. S. 186 Meinwald J. 144 222 Miles D. H. 350 Meisels G. G. 8 Milewski C. A. 368 369 Meisinger R. H. 247 560 Milks J. E. 144 Meister B. 296 Millar I. T. 571 Melcher G. 445 Miller B. 263 516 522 Melli M. 446 Miller D. 301 Mellon F. A. 6 7 8 Miller F. A. 340 Mellor I. P. 118 573 Miller G. R. 20 Mellor J. M. 359 Miller J. 282 Mellows G. 397 399 Miller J. C. 179 Meloche H. P. 184 Miller L. F. 533 Melton J. 370 469 Miller L. L. 196 266 312 Menapace H. R. 282 313 316,497 Mencel P. 517 Miller M. A. 333 337 Mendenhall G. D. 204 Miller R. C. 439 Menet A. 343 Miller R. G. 223 283 Menijnse J. D. 40 Miller V. 421 Mennereau G. 305 Millie P.217 Menon B. C. 559 Millie P. H. 62 Mercer J. F. B. 424 427 Millot F. 529 Merda J. P. 22 Mills D. H. 490 Merigan T. C. 436 Mills 0. S. 114 Merregaert J. 437 Mills R. W. 468 476 Merril C. R. 420 Milne G. H. 426 Merritt M. V. 138 Milne G. M. 451 Merz A. 232 581 Milne G. W. A. 5 10 Meshcheryakova E. N. Milsom P. J. 534 I06 Mimun A. 115 Metcalf B. W. 342 542 Minale L. 453 479 483 Minami T. 519 Metelitsa D. I. 210 Minato H. 208,472 Meteyer T. E. 349 Minetti R. 134 Meth-Cohn O. 590 Minisci F. 194 Metzger H. 175 180 Min Jou A. 437 Metzger J. 194 Minn F. L. 324 Meyer A. S. 460 Minnikin D. E. 462 Meyer E. F. 574 Minster D. 469 Meyer E. F.,jun. 11 1 112 Mirzabekov A. D. 442 Meyer G. R. 262 284 444 352.Mishima H. 479 Meyers A. I. 377 Mislow K. 140 574 Meyerson S. 218 Mison P. 252 Michael J. 404 499 Misra R. 124 Michel G. 454 Missavage R. J. 570 Michelson A. M. 433 Misumi S. 539 542 Michener E. 564 589 Mitani M. 302 344 366 Michl J. 144 322 Mitchard L. C. 276 Michnowicz J. 10 Mitchell A. R. 429 Middleditch B. S. 11 483 Mitchell G. H. 542 Mitchell J. R. 219 379 525 Mitchell R. H. 241 Mitchell R. W. 278 Mitchell T. J. 439 Mitchell T. R. B. 280 Mitra D. K. 368 Mitscher L. A. 412 497 Mitsudo T. 292 Mitsui T. 480 Mitsyasu T. 288 Mitt T. 51 1 Miura K. 428 Miwa T. 221 533 Miyake H. 209 Miyamoto N. 362 Miyano S. 230 342 Miyashi T. 160 259 537 Miyaura N. 388 Miyazaki S.546 Mizogami S. 539 Mizoroki T. 290 Mobbs D. B. 527 585 Mock W. L. 377 Modro T. A. 131 Mohrle H. 373 Moersch G. W. 384 Moffatt J. G. 426,427 Moffitt W. 102 Mohammad M. 303 Mohammedi-Tabrizi F. 15 Mohrle H. 581 Moinas M. 478 Molina G. 500 Monastyrskaya G. S. 427 Money T. 381 408 Monier R. 435 Moniot J. L. 495 Monneret C. 488 489 Monso J. M. 196 Monti D. 404 Monti S. A. 257 Montijn P. P. 457 Moodie R. B. 129 580 Moore D. R. 559 Moore H. W. 257 Moore J. A. 587 Moore W. R. 107 Moradpour A. 516 Morales O. 247 Moreau C. 375 561 Moreau J. 370 Moreau S. 487 488 Morelli I. 481 Moreno-Mafias M. 568 Morgan A. R. 446 Mori K.. 485 Mori M. 386 Mori T.383 Moriarty T. C. 571 Moriarty R. M. 257 614 Author Index Moriaty R. M. 40 Morihara K. 172 Morisaki M. 486 Morisaki N. 471 Morishirna I. 567 Morisse J.-P. 579 Morita T. 265 Moritani I. 225 Morozova E. N. 430 Morreau M. C. 50 Morrill T. C. 191 Morris,D. G.,28 115 116 245 Morris J. I. 31 Morrison H. 321 Morrison J. D. 8 13,295 365 Morrison R. J. 279 Morrison S. J. 450 Morrow C. J. 295 365 Morrow L. C. 572 Morse D. E. 183 Mortensen J. Z. 578 Moscowitz A. 102 Mosher H. S. 106 243 524 Mosher M. W. 332 Moss G. P. 19 21 Moss J. R. 282 Moss R. A. 225,229 Mossa G. 130 517 Motherwell W. D. S. 114 116 125 127 402 481 503 Motitschke L. 590 Motroni G. 286 Moulijn J.A. 285 Moulineau C. 380 Mounts T. L. 464 Mowat W. 274 275,292 Moyer C. E. 268 530 Moyer R. W. 182 Muck D. L. 303 Mullen K. 198 540 Muller B. 400 Muller E. 290 543 Muller H. 294 Miiller J. 274 Muetterties E. L. 281 Mugnoli A. 115 563 Muhlstadt M. 133 580 Muir C. N. 488 Muir K. W. 275 Mukai T. 160 259 537 Mukai Y. 286 Mukaiyama T. 368 392 429 Mukawa F. 484 Mukherjee J. 482 Mukherjee R. 40 Mulheirn L. J. 397 Mullen P. W. 583 Muller C. 230 Muller J. F. 546 Muller W. 436 Mullin M. M. 449 Munchausen L. 265 Munemo E. M. 241 Muneyuki R. 246 Munsch B. 62 Munson B. 10 Muntwyler R. 463 Murae T. 483 Murahashi S. 205 Murata I. 541 Murphy G. P. 380 Murphy J. J. 265 Murphy W.S. 366 386 Murray R. D. H. 468 476 523 Murrell J. N. 38’ Murrill E. 141 Murto J. 135 Musgrave W. K. R. 95 98 138 271 531 583 Myatt J. 275 Myers C. W. 494 Myers R. F. 350,490 Myerscough T. 206 Myhre P. C. 134,263 Mylonakis S. G. 139 Nadjo L. 304 Naf F. 450 Nagai T. 194 Naganawa H. 471 Nagano K. 120 Nagarajan R. 108 Nagel A. 116 Nagel K. 528 Nahlovska Z. 335 Nahlovsky B. D. 335 Naik N. C. 105 Naik N. N. 589 Naik S. R. 428 Naito T. 383 Nakagawa M. 542 Nakagawa Y. 310 Nakahira T. 360 Nakajima T. 537 Nakama S. 140 Nakamura A. 277,289 Nakamura K. 213 Nakamura M. 471 Nakamura N. 516 Nakanima M. 296 Nakanishi K. 318 422 423 471 480,484 Nakano T. 496 5 18 Nakaoka K.209 Nakashita Y. 496 Nakayama J. 28 222 241 Nakazawa T. 541 Namba H. 201 Nandi D. L. 184 Naono S. 439 Narasaka K. 368 Narayanan K. V. 252 Narayanan P. 479 Nardelli M. 573 Naruto S. 265 Nash C. H. 410 Nasielski J. 279 Nasipuri D. 525 Nastasi M. 587 Natsume M. 588 Naudet M. 465 Navech J. 568 Navozio G. 277 Naya K. 474 Naylor R. D. 373 Neale R. S. 204 Nebzydoski J. W. 548 Neergaard J. R. 380 566 Nefedov 0. M. 218 Negishi A. 161 553 Negishi E. 388 Neidle S. 471 484 Neilson T. 431 Neiman L. A. 158,252 Nekrasov Y.S. 158 252 Nelander B. 56 Nelson G. L. 37 344 387 Nelson J. A. 562 Nelson J. D. 546 Nemec J. 106 Nenitzescu C. D. 290 Nesmeyanova 0.A. 361 Neta P. 200 Neuenschwander M.535 Neuffer J. 344 Neugebauer F. A. 202 267 Neuman M. A. 113 Neuman R. C. 188 Neumann H. 171 Neunhoeffer H. 590 Neuss N. 410 Nevenzel J. C. 449 Newman H. 389 Newman M. S. 544 Newton M. G. 512 563 Newton R. F. 568 Ng Lim L. S. 254 Nguyen-Dinh-Nguyen 466 Niblack J. F. 436 Nicholas K. 290 Nicholas K. M. 378 Nickon A. 246 Nicoud J. F. 516 Nieboer H. 332 Nielson C. H. 572 Niemann Z. 578 Nieuwenhuyse H. 379 Nikokavouras J. 524 Author Index Nilles G. P. 245 Nilsson M. 529 Ninomiya I. 383 Nishida T. 28 222 241 246,271 Nishigachi T. 279 Nishihama T. 483 Nishimura H. 507 Nishimura J. 230 Nishimura K. 454 Nishimura S. 423 442 485 Nishiwaki T. 554 Nissen A.542 543 Nitta M. 160 259 537 Niwa M. 471 Nixon J. F. 281 Noguchi I. 316 Noguchi S. 222 Nolte R. 430 Nomura M. 435 Nonaka T. 301 Nordberg R. 92,98 Nordham C. E. 471 Nordling C. 92,98 Norman R. 0.C. 199,204 Norris C. L. 574 Northington D. J. 377 Norton D. A. 124 Nougiuer R. 213 559 560 Novikov S. S. 551 Novitt B. 579 Nowlan V. 386 Noyori R. 287 355 390 536 Nozaki H. 230 362 Nozoe S. 127 471 Nozoe T. 536 Nussel H.-G. 296 Nusslein V. 447 Nummela L. 135 Nutzel K. 286 Nyberg K. 310 Nyberg W. H. 508 Nyburg S. C. 118 573 574 Nygaard L. 572 Nyholm (Sir) R. S. 275 Nyhus B. A. 339 Nyi K. 253 Nylan W. L. 421 Nyman C. J. 291 Oae. S. 200 201 Obasi M. E. 483 Oberdier J.555 Oberhansli W. E. 127 Oberkirch W. 286 O’Brien J. B. 495 Occolowitz J. L. 423 Ochterbeck E. 9 O’Connell E. L. 179 Oda M. 538 Oda R. 559 Odaira Y. 325 Odajima K. 428 Odani M. 271 Odell B. G. 153 534 Odham G. 453 O’Donovan D. G. 410 41 1 ofele K. 275 Oehlschlager A. C. 392 Ostman B. 134 263 Oeullette R. J. 338 Offengand J. 444 Offord R. E. 179 Ogawa H. 542 Ogino N. 239 Ogiso A. 479 Ogura K. 379 Ohashi M. 322 567 Ohizumi Y. 491 Ohloff G. 107 470 Ohnishi Y. 200 201 Ohno A. 200,201 Ohno K. 280,288 Ohnsorge U. F. W. 480 Ohoto Y. 265 Ohta T. 289 Ohtaka H. 486 Ohtsuka E. 420,430 Oikawa Y. 543 Oishi T. 386 Okada A. 197 Okada K. 567 Okajima T. 292 Okamoto T.289 542 Okamoto Y. 221 Okamura W. H. 531 Okano M. 518 Okazaki R. 202 Oki M. 516 Okinoshima H. 280 Okogun J. I. 483 Okumura K. 307 Olah G. A. 36 41 99 129,249 517 Oldenziel 0.H. 518 OlivC S. 274 Oliver A. J. 282 Oliver W. L. jun. 568 Oliver W. R.. 327 Ollis W. D. 161 243 564 Olmstead H. D. 383 Olofson R. A. 242 588 Olsen J. F. 217 Olson R. D. 298 O’Malley R. M. 16 Omelka L. 210 Omilianowski D. R. 444 Ona H. 165,325 Onderka D. K. 402,417 O’Neal C. H. 438 O’Neil J. W. 41 516 567 O’Neill I. 406 Ono H. 144,269 554 Onoda T. 279 Onomura S. 554 Ookuni I. 265 Oosterhoff L. J. 26 27 29 31 144 Oppenauer M. 370 Oppolzer W. 147,494,520 Orchin M. 291 292 Orenski P. J. 280 Oreshkin I.A. 285 O’Riordan E. A. 386 Orlov V. V. 215 Ortwerth B. J. 422 Orville-Thomas W. J. 567 Osawa Y. 124 277 Osbond J. M. 455 Osborn C. L. 153 Osborn J. A. 277 Osborn R. S. 112 Osborne M. R. 427 Ostrogovich G. 136 141 561 Ostrowska B. 530 O’Sullivan M. 266 Otani G. 500 Oth J. F. M. 19 40 42 149 251 542 Otomo T. 538 Otsubo T. 539 Otsuka S. 281 289 Otsuyi Y. 385 Ottenbrite R. M. 376 Ottenheym H. 15 Otter B. A. 426 Ottinger Ch. 7 Ottinger R. 568 Otto B. 447 Otto H. H. 268 Ourisson G. 366 467,472 Ovchinnikov Yu. A. 106 Overill R. E. 163 533 Overman L. E. 476 Overton K. H. 476 Owen G. R. 430 Oxford A. W. 393 Ozaki A. 290 Ozaki K. 296 Paasivivta J. 37 Pabon H. J. J. 456 Pacakova V.421 Pace B. 435 Pace N. R. 435 Pachler K. G. R. 34 Pachter I. J. 390 Padbury J. M. 528 Padwa A. 151 153 159 321 361 616 Paetkau V. H. 445,446 Paffenhofer G.-A. 449 Page C. B. 455 Paiaro G. 273 296 Pailer M. 513 Paladini J. C. 145 Palazzi A. 291 Palenik G. J. 122 123,233 Palmer K. J. 117 Palmer M. H. 574 579 Palmieri C. 573 Palyi G. 285 Pampus G. 286 Pananzi A. 296 Pande P. S. 474 Panetta C. A. 385 Panke H.-L. 586 Pankowski M. 292 Pantke R. 207 Paoletti J. 446 Pappas B. C. T. 340 531 Pappas S. P. 340 531 Paquette L. A. 148 153 165 221 247 260 261 262 268 272 274 284 285 298 328 352 354 531 555 560 577 585 586 587 Parham J. C. 427 Parikh I. 175 Paris G.Y. 579 Paris R.-R. 501 Park J. D. 541 Parker J. 557 Parker R. B. 17 Parker V. D. 209,309 545 Parker W. 473 Parrington B. 249 Parry D. R. 406 Parry F. H. tert. 361 Parry K. 40 575 Parry K. P. 570 Parry R. J. 350 401 402 504 Parshall G. N. 283 Parshall G. W. 277 281 Parsons G. 140 Parthasarathy P. C. 513 Pascoe J. D. 243 Pasto D. J. 359 Patchornik A. 393 Patel D. J. 445 Paternostro M. P. 476 Patil F. 22 Patrick J. E. 161 Patrick J. W. 243 Patrick T. B. 160 Patrushin Y. U. 286 Pattenden G. 395 483 Pattison V. A. 515 527 Patton S. 449 Paudler W. W. 579 Paukstelis J. V. 246 Paul H. 213 Paul I. C. 117 121 356 570,574 Paul J. M. 581 Paulik F. E. 291 Paulin D. 445 Paulsen H.253 Paulson D. R. 26 27 Pautet F. 343 Pauwells D. J. S. 34 Pawiak W. 467 Payne M. A. 141 Pearce B. W. 229 Pearce D. S. 257 Pearl G. M. 531 Pearson H. 41 Pearson J. M. 197 Pearson M. J. 259 351 Pearson R. G. 44 143 Pearson R. L. 440 Pechet M. M. 255 489 Pedersen C. J. 571 Pedriali R. 306 Pedulli G. F. 195 215 Peeling J. 515 Peet. J. H. J.. 368 Pehk T. J. 38 158. 252 Pelczar F. L. 191 Pelletier S. W. 512 Pellizzari C. 573 Penton J. R. 129 580 Perchinummo M. 194 Pereira W. E. 105 Perez G. 129 Perie J. 559 Perjessy A. 303 Perkins E. G. 462 Perkins M. J. 138 193 205 265 529 Perrin C. L. 130 517 Perroud-Arguelles M. 587 Perry R. A. 559 Peterkofsky A. 444 Petersen I. B. 572 Petersen M.R. 460 471 Petersen P. E. 253 Peterson C. E. L. 219 Peterson M. R. 19 Petricciani J. C. 420 Petrova I. D. 551 Petrovich J. P. 300 Petter J. M. 393 Pettit G. R. 369 Pettit R. 161 164 260 286 290 294 342 354 378 Petty R. 141 Peube-Locou N. 505 Peyerimhoff S. D. 47 80 Author Index Peyroux J. 512 Pfitzner K. E. 242 Pfleiderer G. 176 Philips. J. C. 148 247 577 Phillipou G. 190 489 Phillips C. 295 365 Phillips D. C. 172 Phillips G. T. 399 408 Phillips L. 42 Phillips R. E. 141 Phillips T. R. 241 Philpott P. G. 455 Photis J. M. 238 587 Pichat L.. 425 Pickett H. M. 333 Pierre G. 319 Piers E. 278 Pietra F. 135 208 529 537 Pilati T. 115 Pilgrim W. R. 277 Pilipovich D. 207 Pilling G.M. 542 Pillinger C. T. 467 Pilz I. 445 Pinar M. 504 Pincock R. E. 516 Pinder A. R. 410 Pine S. H. 241 Pinhey J. T. 482 485 Pinke P. A. 283 Pinnick H. W. 376 Pino P. 296 Pinschmidt R. K. 157 Pinson J. 305 307 Piozzi F. 476 Piperno G. 421 Pirt S.J. 483 Piskala A. 376 Pitha J. 431 Pitha P. M. 431 432 436 43 7 Pittman C. U. 334 Pitton G. 474 Pizzolato G. 505 Placucci G. 21 5 Plashkin V. S. 318 Plat M. 505 512 Plate A. 37 Platzek U. 194 Playtis A. J. 423 Plescia 0. J. 437 Pletcher D. 303 3 10 3 15 Pletcher J. 120 Plinkie G. 19 Ploner K. J. 287 Pluscec J. 415 Pobedimskii D. G. 206 Pober K. W. 460 Pochon F. 433 Pochopien D. J. 21 1 Author Index Podder S.K. 434 Pointer D. J. 113 Polgar N. 453 460,462 Pollard D. R. 124 Polonsky J. 483 Polston N. L. 370 Pomerantz M. 533 Pommeret J. J. 159 553 Poncet A. 343 Ponomarchuck M. P. 28 Ponpipom M. M. 425 Ponsford R. 470 Poon Y. C. 272 533 577 Pope P. 392 Popjak G. 395 Pople J. A. 48 49 53 61 63 66 75 Poppleton B. J. 127 Porret J. 275 Porri L. 284 290 Porter Q. N. 351 Porter R. D. 36 249 Porter R. R. 181 Porter T. H. 326 Portheine J. C. 124 Portnoy N. A. 376 Potapov V. K. 429 Potier P. 470 505 Potrafke E. M. 203 Poulter C. D. 248 396 48 3 Poulton G. 401 Poupat C. 514 Pousset J. L. 501 Powell G. P. 103 Powell J. 290 Powell R. E. 14 Powers J. C. 170 Poyser J. P. 484 Prager R.H. 388 Prange U. 251 Pratt D. R. 219 Praud L. 217 Pregosin P. S. 37 Prelog V. 107 121 333 Preuss H. 47 Previtera L. 478 Price A. P. 532 Price C. C. 209 Price M. J. 134 Price N. C. 179 Price R. 338 Priddle J. D. 179 Prigge H. 292 Prinzbach H. 328 587 Pritzhow W. 282 Probst W. J. 160 Protiva J. 484 Prox A. 15 Pryde E. H. 465 Pschigoda L. M. 106 Puckett R. T. 107 127 Puddephatt R. J. 290 Pugh E. L. 184 Pugmire A. D. 36 Pugmire R. J. 37 575 Pujedas J. 196 Pujol R. 568 Pulidon F. 306 Punch W. E. 327 Putkey T. 524 Putze B. 251 Pyun C. 582 Quast H. 247 Queiroga J. J. R. P. 245 Quick J. 509 Quigley G. 445 Quin L. D. 568 Quiocho F. A. 172 Quistad G. B. 584 Qureshi.1. H. 107 Raal A. 466 Raap R. 582 Raban M. 40 Rabason A. 512 Rabenstein D. L.. 40 341 540 Raber D. J. 252 385 Rabinovitz M. 516 528 540 Rackham D. M. 19 Radda G. K. 179 186 Radlick P. 149 475 Radom L. 49 53 63 75 Radunz H. 510 Radziwill A. N. 464 Rafikov S. R. 371 554 Ragault M. 390 Raghavan R. S. 229,254 Raghunathan P. 225 Rahman A. 426 Rahman M. B. 105 Raimondi M. 115 RajBhandary U. L. 420 422 Rakshys J. W. 41 526 Ramage R. 473 Ramain L. 285 Ramaley R. F. 182 Ramasseul. R. 206 210 Ramey K. C. 40,260,564 589 Randall E. W. 21 37 38 42 337 Rane D. F. 471 Ranken P. F. 548 Ranzi B. M. 408 Rao J. U. 567 Rao K. S. 194 545 Rao K. V. 446 Rao S. T. 127 426 432 445 Rao V.N. M. 336 Rao Y. S. 527 Raper G. 277 Raphael R. A. 468 Rapoport H. 415 451 482,494 Rapp E. 233 Raskova J. 437 Rasod G. 184 Rassat A. 103 205 206 315 366,568 Rastrup-Andersen J. 572 Ratcliffe R. 472 Rathke M. W. 384 Rausch H. 581 Rautenstrauch V. 107 162,244 Ravet J. P. 315 Ravindranathan T. 346 386 Rawn J. D. 338 Ray A. B. 514 Ray G. J. 36 Ray N. K. 74 Ray W. C. 257 374 553 Read R. E. 203 Reagan M. 139 Reddy G. V. R. 447 Reddy R. 435 Reddy T. B. 307 Red’kina L. I. 285 Redmore D. 361 Redshaw D. J. 463 Reed B. 62 Reed J. O. 257 Reed R. I. 5 Reeke G. N. 172 Rees B. 62 74 Rees C. W. 40 217 223 238 239 534 551 584 585 Rees H. H. 492 Reese C. 510 Reese C.B. 430 Reeves P. C. 222 Regan T. H. 271 Regitz M. 148 231,. 336 Rehder-Stirnweiss W. 279 Rehk T. 37 Reich H. J. 38 Reichardt P. B. 401 476 Reichmann M. E. 421 Reid D. H. 100 573 Reid K. I. G. 117 356 574 Reid N. W. 8 Reid W. W. 483 Reiding J. 214 Reifer I. 421 Reiffers S. 384 Reihsfeld V. O. 280 Reil S. 415 Reilley C. N. 318 618 Reimen-Schneider J. L. 99 Reinecke M. G. 582 Reischig G. 279 Reiser A. 234 235 Reisse J. 568 Reiter F. 159 586 Remijnse J. D. 338 Remy D. C. 19 Remy M. A. 268 Renaud R. N. 140 Rengaraja S. 23 249 Renoe B. W. 281 Rentzea C. N. 222 Rentzea M. 222 Reucroft J. 377 450 467 Reusch W. 362 363 382 Reutov 0.A. 383 Reynolds G. F. 146 Rhoads S.J. 258 Ricci A. 130 517 Riccio P. 135 Rice V. T. 563 Rich A. 445 Rich W. E. 298 Richards J. A. 299 Richards K. E. 133 518 Richards W. G. 43,65,92 Richardson C. C. 431 Richardson D. C. 174 232,253 Richardson J. S. 174 Richardson M. 446 Richer J. C. 19 23 373 Richerzhagen T. 195 200 Richey H. G. 386 Richheimer S. L. 379 562 Richle W. 463 Rick E. A. 281 Rickborn B. 358 387 Ridd J. H. 129 130 517 5 80 Riddell F. G. 35 568 Riddiford L. M. 471 Ridgway T. H. 298 Ried W. 525 Rieder W. 242 Rieke R. D. 298 Rieker A. 264,587 Riem R. H. 203 Riemann J. M. 160 Riera J. 196 Riera-Figueras J. 196 375,544 Riezebos G. 20 Rifi M. R. 304 305 Rigau J. J. 116 Rigny P. 578 Rigo P. 281 Riley M.O. 541 Rilling H. C. 248 396 483 Rimmelin P. 516 Author Index Rindone B. 408 Rose Z. B. 173 Riordan J. F. 176 Rosen L. S. 122 Ristagno C. V. 197 Rosenberg D. 37 Ritchie E. 19 380 Rosenberg I. E. 265 Robbins M. D. 527 Rosenberg M. 435 Robec G. 305 Rosenfeld I. S. 406 Robert A. 159 553 Rosenkranz H. J. 588 Robert J. B. 334 Rosenstock H. M. 6 Roberts B. P. 213 Rosenthal I. 588 Roberts D. R. 107 Roskos P. D. 256 Roberts J. D. 36 38 43 Ross C. H. 159 148 336,493 575 Ross D. A. 291 Roberts J. R. 201 Ross J. A. 328 Roberts J. S. 473 Ross W. A. 458 Roberts P. J. 125,402 503 Rossi P. 284 Roberts R. J. 442 443 Rossi R. 290 Roberts T. D. 217 265 Rossi R. A, 219 Robertson A. K. 530 Rosso P. D. 555 Robertson A. V. 13 Roth H.D. 30,,160 Robertson R. E. 20 Roth J. F. 291 Robey R. L. 518 Roth R. J. 113 Robins M. J. 37 428 Roth W. R. 160 575 Rottman F. 433 Robins R. K. 37 426 575 Rouessac F. L. 344 Robison B. 445 Rouessai F. 387 Robinson D. A. 154 329 Rouget P. 175 Robinson M. 209 Roughley P. J. 406 Robinson P. W. 291 Roundhill D. M. 281 Robinson S. D. 281 Roussel J. 559 Robinson W. H. 396,483 Rowan M. G. 397 Rocher P. 11 Rowe J. M. 565 Rochester C. H. 138 Rowe M. J. 430 Ro Choi T. S. 435 Rowell F. J. 412 Rodionov W. Ya. 215 Rowland N. E. 542 Rodriguez V. M. 19 Rowley P. T. 183 Rodriguez Gonzalez B. Roy R. G. 476 476 Roychoudhury R. 429 Rodriguez -Siurana A. Royer G. P. 186 196 375 544 Royer J. 257 Roe R. jun. 361 Rozantsev E. G. 205 Roedig A.534 Rozen S. 564 Rohrl M. 479 Rua L. 368 Rogers D. 112 127,471 Rubin I. B. 439 Rogers M. T. 25 Rubin J. 445 Rogg H. 442 Rubin M. B. 371 527 Rohwedder W. K. 452 Rubinstein I. 302 Roitman J. N. 571 Rucktaschel R. 554 Roller R. S. 265 Rudashevskaya T. Yu. Roman S. A. 367 361 Romanin A. 303 Ruddick J. D. 278 Romers C. 112 124 Ruden R. A. 387 472 Ronca G. 178 Rudqvist U. 194 Ronchi A. U. 389 Ruchardt C. 200,207,219 Rondeau R. E. 24 337 Ruehlen F. N. 318 Ronlan A. 209 Rumpler D.. 198 Ronzaud J. 568 Riimpler K. D. 549 Rooney J. J. 351 Rueppel M. L. 494 Ropp M. 173 Ruf A. 277 Roques B. 578 579 Rufford E. L. 66 Ros R. 291 Rupilus W. 292 Rosales J. 588 Rupley J. A. 172 Rose I. A. 173 179 Russell D. R. 281 290 Author Index 619 Russell G.A.,211 212 Russell J. H. 572 Russo G. 204 Rutherford K. Ci. 376 Rutherford R. J. D. 531 Ryang M. 277 Ryhage R. 454 Rynbrandt R. H. 247 Rys P. 136 Ryvolova-Kejharova D. 303 Sabacky M. J. 295 Sacchi C.,36 Sachdev G. P. 171 Saegusa T. 342 Saeki T. 318 583 Saenger W. 426 Saettone M. F. 178 SafThill R. 430 Sagatys D. S. 141 Sagredos A.N. 464 Said A.I. 465 Saikachi H. 542 Sailer K. H. 331 Saitner H. 158 Saito T. 554 Sakai M. 165 166 262 284 352,354 Sakai S. 506 Sakai Y. 324 Sakan F. 474 Sakan T. 468 Sakata K. 480 Sakata Y. 539 542 Sakimoto R. 518 Saksena A. K. 491 Sakuraba M. 292 Sakurai H. 197 324 Sakurai T. 445 Salaiin J. A.,540 Salaun J.R. 260 343 552 Sale A. A, 223 238 270 582 584 Salem L. 43 80 259 Salemnick G. 266 528 Saloman J. 588 Salomon R. G. 260 532 Saltiel J. 193 324 Sam T. W. 471 Sammes P. G. 255 377 450 467 484 557 Samuel G. 112 Samuelson G. E. 144 Samuelsson B. 14 Sanchez M. 404 Sandermann H. 186 Sanderson A. P. 132 Sandler S. R. 392 Sandvini P. 277 Sanerbier M. 290 Santelli M. 160 248 Saquet M. 233 Saraswathi T. V. 589 Sarel S. 554 Sargent F. P. 212 Sargent G. D. 526 Sargent M. V. 542 Sarid S. 439 Sartori G. 286 Sasaki T. 255 547 Sasaki Y . 38 Sasse J. M. 478 Satchell D. G. 421 Sato A. 479 Sato K. 563 Sato S. 28 271 Sato T. 254 539 570 Sato Y. 139 Sauer G. 347 Sauerbier M. 543 Saunders J.K. M. 19 22 23 337 Saunders M. 41 247 249 252 Saussez R. 581 Sauvage J. P. 570 Savage D. S. 123 Saveant J. M. 304 Savoic J. Y. 373 Sawa T. 533 Sawaki M. 518 Sayo H. 315 Sax M. 120 Scalzi F. V. 581 Scalzo M. 569 Scamehorn R. G. 246 Scanio C. J. V. 347 348 381,472 Scarpa I. S. 186 Scarzafava E. 61 Schaad L. J. 217 Schaaf J. V. D. 386 Schaaf T. K. 369,458,459 Schaal R. 136 Schaap A. P. 269 33 1,558 Schachtschneider J. H. 286 352 Schaefer F. C. 586 Schafer H. 196 298 Schaefer J. 36 Schaefer J. P. 339 Schaefer T. 42 337 515 575 Schafer W. 275 523 Schaller H. 447 Schallhorn C. H. 165 328 Schallner O. 342 Schaltegger H. 535 Scharf H. D. 346 Scharf K. H. 402 417 Schauer R.,184 Schauwecker P.575 Schechter I. 168 Scheer W. 159 552 Scheffer J. R. 329 Scheffler K. 202 Scheidt F. 525 Scheinbaum M. L. 378 390,537 Schell F. M. 493 Schell P. L. 436 Schellman J.,A.,106 Schenk H.,112 Schenk H. P. 246 Scheraga H. A.,172 Scherer H.,148 336 Scherer J. R. 474 Scheur P. J. 15 Schibecki R. A.,386 Schildknecht H. 452 Schilling P. 242 Schirch L. 173 Schissel P. O. 271 565 577 Schittenhelm D. 373 Schittenhelm W. 34 Schlenk H. 465 Schlessinger R. H. 373 Schleyer P. von R. 63 69 74 146 150 251 252 260 261 336 342 358 3 60 Schlierf C. 533 Schlittler E. 493 Schlogl K. 540 Schlosser M. 376 Schlott R. J. 279 Schmid. H.. 159 265 493 501 504 519 522 586 588 Schmid H.V. 417 Schmid J. 15 Schmid M.,265 522 Schmidpeter A. 561 Schmidt A.H. 525 Schmidt D. E. 179 Schmidt E. K. G. 145 Schmidt F. 535 Schmidt G. H. 538 Schmidt R. 195 Schmidt R. R. 586 Schmidt Th. 160 Schmitt E. 247 Schmitz A.,136 Schmitz K.S. 432 Schmitz R. Y. 423 424 Schnegg U. 149 Schneider G. 150 261 Schneider H.-J. 338 Schneller P. 292 Schoch W. 546 549 Schodey D. A. 471,484 Schoeller W. W. 266 334 Schonefeld J. 230 342 Schofield K. 129,264,580 Scholfield C. R. 464 Scholl P. C. 485 Schollkopf U. 270 589 Schon N. 286 Schorpp K. 281 Schott H. 431 Schrader L. 226 Schran H. 529 Schrauzer G. N. 277 356 Schreck J. O. 141 Schreiber W. L. 277 343 Schreurs P.H. M. 457 Schrieber J. 392 Schroder G. 19 42 149 251 542 Schroder R. 589 Schroeck C. W. 389 Schroeder B. 327 Schubert W. M. 248 Schudel P. 470 Schuetz R. D. 245 Schulman E. M. 239 Schulte-Elte K. H. 451 Schultz A. G. 384 508 Schumann W. C. 328,533 Schurr J. M. 432 Schuster G. B. 269 Schuster P. 574 Schwartz J. A. 153 Schwartz J. H. 182 Schwartz M. A. 248 483 Schwartz M. M. 207 Schwarz R. A. 391 Schwarz V. 484 Schwarzhaus K. 42 Schweiger E. 549 Schweizer E. E. 519 Schweizer M. P. 432 445 Scolastico C. 408 Scopes P. M. 105 107 Scorrano G. 268 530 Scott A. I. 104 401 408 503 Scott F. L. 267 Scott M. 367 Scrowston R. M. 582 Se Chun Choi 553 Sedlar J. 324 Sedmera P. 474 Sedor E.A. 242 Seebach D. 200 379 Seeman N. C. 127,432 Segal D. M. 170 Segre A. 281 Seidl H. 226 Sekine T. 301 Selke E. 465 Author Index Selvarajan R. 253 Shepherd R. A. 221 Selwood P. W. 18 Sheppard R. C. 15 Semmelhack M. F. 569 Sheppard W. A. 345 Sen M. 482 Sheradsky T. 266 528 Senatore L. 141 Sherrod S. A, 248 Sengupta P. 482 Shershneva L. P. 430 Senyavina L. B. 106 Shevlin P. B. 24 Serenain J. P. 368 Shibaev V. N. 427 Serid S. 420 Shibano T. 280 Serre J. 217 Shibuya S. 222 475 496 Serridge P. 257 497,499 Serve D. 315 Shields T. C. 288 289 Seshadri R. 484 Shields T. M. 308 Seter J. 360 Shigemitsu Y. 325 Seto H. 409 Shih S. 47 Setzer D. W. 225 Shilin V. V. 106 Sevenet T. 470 Shillady D. D. 574 Sevostjanova V.V. 38 Shilov A. E. 280 Seyferth D. 228 230,23 1 Shima K. 324 232,233,254 Shimidzu T. 429 Sgaramella V. 431 Shimojo N. 542 Shabarova Z. A. 429 Shin H. 474 Shafer J. 177 Shine H. J. 197 267 Shafiee A. 576 Shioiri T. 399 Shahak I. 564 Shiomi K. 539 570 Shakshooki S. K. 281 Shiota M. 485 290 Shirafuji T. 230 Shani A. 326 Shirahama H. 458 474 Shannon P. V. R. 469 Shiraton M. 506 Shapiro B. L. 23 337 Shirley D. A. 95 Shapiro J. 439 Shishido K. 445 Shapiro S. A. 139 263 Shizuka H. 265 Sharma M. 163,260 323 Shizuri Y . 513 Sharp B. W. 569 Shmueli U. 574 Sharp J. J. 379 Shoe L. I. 422 Sharp J. T. 218 219 525 Sholle V. D. 205 530 Shono T. 298 302 310 Sharples G. 223 312 344 366 Sharpless N. E. 107 Shortland A. 275 Shaw B. L.277,280,282 Shortridge T. J. 161 269 Shaw D. 34 553 Shaw E. 176 Shoua S. 357 386 Shaw J. E. 372,466 Shu P. 577 Shaw K. P. 179 Shudo K. 256 Shaw P. M. 488 Shue H. J. 577 Shchervakov V. I. 230 Shulman R. G. 445 Shebaldova A. D. 274 Shvetsov Y.A. 276 285 Siddall J. B. 460 Shechter H. 231 Siddall T. H. 42 Sheehan J. C. 393 Siddiqui M. A. Q.. 444 Sheehan M. H. 452 Siderova N. 420 Sheikh Y. M. 491 Sidikaro J. 43.5 Shelton G. 165 354 Sieczkowski J. 355 Shelton K. W. 540 Siedle A. R. 138 Shemin D. 184 Siefert W. K. 492 Shemyakin M. M. 158 Siegbahn H. 95 2 52 Siegbahn K. 92 95 98 Shen K. 565 Siegbahn P. 574 Shen K.-W. 157 Siegel H. 295 Shen T. Y. 436 Sieja J. B. 343 345 Sheng J. J. 372 Sievers R. E. 337 Shepherd I. S. 463,464 Siffert J.286 Author Index Sillion B. 254 Silver F. M. 476 Silverman J. 196 Silversmith E. F. 203 Sim G. A. 114 127,475 Simamura O. 187 Simes J. J. H. 482 Simon W. 575 Simonet J. 304 308 Simonetta M. 115 Simonnin M. P. 136 529 Simonyi M. 206 Simounin M. P.,41 Simpson R. 579 Sims C. L. 371 Sims H. L. 437 Sims J. J. 475 Singer G. M. 270 Singer L. A. 188 189 Singer L. S. 195 Singer M. F. 431 Singer M. I. C. 233 Singer S. J. 175 Singh A. 133 Singh B. 589 Singh H. 512 Singh P. 205 345 Singh S. 107 Singh S. P. 326 Singler R. E. 539 Sinnott M. L. 529 Sioumis A. A. 103 Sipe J. P.,23 Siu A. K. Q. 159 Sivers R. E. 24 Skapski A. C. 274 Skatlebol L. 146 Skelton D. 213 Sketchly J.M. 221 Skinner G. A. 130 517 Skoog F. 423,424 Skrabel P. 590 Skuballa W. 343 Skulnik D. N. 239 Slama J. 432 Slama K. 462 Slatcher R. P. 427 Slaugh L. H. 286 Slaytor M. 351 Slaytor M. B. 401 Sleiter G. 582 Slessor K. N. 38 Sletten J. 573 Slobbe J. 501 Sluyterman L. A. A. 169 Smaal J. A. 396,482 Smale T. C. 480 Smick D. 527 Smid T. 22 Smidt J. 292 Smith A. 19 Smith B. C. 442 Smith C. D.. 345 Smith D. G. 410 Smith D. W. 454 Smith G. 351 375 561 Smith G. A. 490 Smith G. N. 402 503 504 Smith G. V. 19 Smith G. W. 126 Smith H. E. 105 106 Smith J. C. 537 Smith J. D. 420 439 444 Smith M. 428 Smith M. A. 430 Smith M. J. 152 287 Smith P. 523 Smith R. F. 160 Smith R.G. 376 Smith R. H. 238 587 Smith S. A. 292 Smith S. M. 222 Smith T. W. 531 Smolanoff J. 159 Smutny E. J. 287 Snarey M. 568 Snatzke G. 106 107 Snedden W. 17 Sneeden R. P. A. 290 Snieckus V. 587 Snow J. T. 388 Snyckers F. O. 500 Snyder J. P. 161 272 565 Snyder L. C. 42 Sodano G. 479 Sodini G. C. 15 Sohngen B. 540 Soll D. 440 444 Sogin M. 435 Sohar P.,245 Sohma K. 518 Sohn Y. S. 282 Sohoni S. S. 358 Solodar J. 392 528 Solomon D. M. 460 508 Soloway S. 188 Solter L. E. 391 Soltzberg L. J. 196 Solymosy F. 422 Somers J. H. 568 Somerville P.,572 Sommer J. M. 516 Sondheimer F. 40 278 342 356 542 543 Sone T. 575 Sonnenbichler J. 422 Sonoda A. 225 Sood R. S. 401 Sorensen G.O. 572 Sorensen H. C. 224 Sorm F. 474 Souchay P. 307 621 Southard G. L. 393 Southern E. M. 429 Sowerby R. L. 390 Spaeth D. S. 277 Spain V. L. 460 Spalding B. P. 478 Spangler R. J. 496 Spanninger P. A. 589 Sparrow N. 572 Speck J. C. 183 Spector L. B. 182 Speedie M. K. 416 Spence J. W. 458 Spencer D. G. 384 Spencer T. A. 562 Spenser I. D. 410,411,412 Sperling J. 588 Spiegelman S. 438 Spiewak J. W. 247 Spillane W. J. 267 Spitzer W. A. 327 Splitter J. S. 144 269,554 Sprague P.W. 493 Spratt R. 40 Sprecher H. W. 455 Sprecher N. 286 Spring M. S. 406 Springer J. P. 519 Spry D. O. 108 Squire R. H. 587 Squires C. 442 Srinivasan R. 155 330 Srinivasan T. K. K. 234 Srinwasan V.R. 589 Srivastava K. C. 271 Staab H. A. 194 542,543 545 Stackhouse J. 140 Stachelin M. 442 Stallberg-Stenhagen S. 454 Staley S. W. 150 151 Staniforth M. L. 19 Stanton E. 217 238 239 534 551 Stanton J. 468 Staples D. H. 437 Staples P.J. 139 Starken J. W. 434 Staroscik J. 358 387 Starratt A. W. 456 Starrett R. M. 347 381 Stastny J. 590 Stauffer R. D. 283 Staunton J. 402 403 404 405,408,499 Steck W. 406 Steel G. 483 Steele J. C. H. jun. 568 Steenhoek A. 456 Stefanik L. 575 Stefanini F. P. 293 Steffen E. K. 229 Stegel F. 138 Steglich W. 385 Stegmann H. B. 200 202 Stehelin L. 472 Stein Y. 554 Steiner P. R. 37 42 201 Steinfeld A. S. 497 Steinmann A. A. 280 Steinschneider A.427 Steirl P. 343 Steitz T. A. 172 Stella L. 559 Stenhagen E. 453 454 Stensio K. E. 372 Stepanov B. I. 215 Stephenson L. M. 326 Sterenzat D. E. 286 Stermitz F. R. 497 Stern H. 446 Sternbach H. 433 Sternbach L. H. 268 Sternitz F. R. 316 Stetter H. 252 462 563 Steur R. 38 Stevens D. N. 246 Stevens I. D. R. 152 Stevens K. L. 474 Stevens M. F. G. 237 Stevens R. M. 50 68 334 Stevenson G. R. 212 Stevenson J. R. 473 Stewart G. W. 498 Stewart H. F. 243 Stewart J. C. 471 Stewart J. M. 120 Stewart R. 139 Stewart R. F. 48 Stewart T. S. 442 Stewart W. E. 42 Stillwell R. N. 14 428 Stilwell W. G. 11 Stirling C. J. M. 589 Stock J. T. 497 Stocker J. H. 301 Stockton J. D. 361 Stodola F.H. 452 Stockel K. 356 Stocker F. 202 Stohrer W. D. 335 Stokes J. R. 406 Stone F. G. A. 274 281 290 Stone L. C. 349 381 473 Stork G. 344 380 384 387 390,483 508 Storr R. C. 238 270 584 585 Story P. R. 257 374 553 Stothers J. B. 34 Stournas S. 588 Stout M. G. 426 Stowell J. C. 165 260 285 St. Pyrek J. 19 Strating J. 252 384 Strausbach P. H. 180 Strauss H. L. 333 Strauss M. J. 529 Streckert G. 375 490 544 Strehlke B. 188 Streicher W. 513 Streichfuss D. 290 543 Streith J. 271 587 Streitweiser A. 43 Stretlow F. 500 Strohmeier W. 279 Strominger J. L. 186 442 Struckhov Y. T. 291 Strzaka K. 421 Stuart A. 422 Stuart E. 431 Sturtz G. 384 Su S. R. 291 SU T.-M. 144 150 261 269 554 Subbaraman L.R. 427 Suck D. 426 Suda M. 516 Suddath F. L. 445 Sueoka N. 440 Sugahara T. 496 Suggs J. L. 569 Sugi H. 496 Sugimoto T. 577 584 Suginome H. 254 Sugiura K. 513 Suhr H. 218 Sukharevich V. 430 Sukh Dev 474,480 Sullivan D. F. 366 Sullivan G. R. 23 337 Sulser H. 474 Sulzbach R. A. 564 575 Sumitani K. 280 Sun K. K. 15 Sunagawa M. 478 Sunami M. 271 Sunco D. E. 19 Sundaralingam M. 127 426,432 445 Sundberg R. J. 140 238 587 Sundholm F. 205 Sundholm G. 31 1 Sundt E. 470 Surzur J.-M. 213 559,560 Suschitzky H. 235 371 527 579 585 Sussman J. L. 432 Sustmann R. 74 155 159 Sutherland G. L. 13 Sutherland I. O. 161 243 516,564 Author Index Sutherland J. K. 471 Sutherland R.G. 239 Suzuki A. 388 Suzuki H. 518 Suzuki M. 38,235,270 Suzuki T. 282 355 Svanholm U. 40 Svec H. J. 6 Svensson I. 444 Sverdlov E. D. 427 Svoboda P. 278 280 365 Swallow J. C. 158 Swaminathan S. 153 252 Swann B. P. 373 518 519 Swanwick M. G. 206,276 Sweeney A. 165 252 261 284 354 Sweeny J. G. 401 Sweetman L. 421 Swen H. M. 169 Swenton J. S. 555 Swen-Walstra S. C. 113 Swern D. 551 Swisher J. V. 247 Switkes E. 68 334 Sykes R. J. 410 Symons E. A. 139 Symons M. C. R. 203,204 Symons R. H. 427 Szabo A. 218 Szybalski W. 439 Tabacchi R. 275 Tabner B. J. 213 Tabo Y. 527 Tabushi I. 220 233 560 Tachikawa R. 406 Tacker M. M. 14,428 Taddei F. 37 Tanzer. C. 35 Tajima K.429 Takada S. 540 Takahashi H. 254 Takahashi K. 42,537,575 Takahashi N. 233 Takahashi S. 280 471 Takahashi T. 478,483 Takaki M. 42 Takase K. 536 537 545 Takashina N. 555 Takaya H. 287 355 536 Takaya M. 224 Takaya T. 377 Takeda K. 472 Takeda Y. 401 Takegami Y. 282,292 Takemoto T. 491 Takemura S. 423 Takeuchi H. 194 Takita T. 471 Tallec A. 305 Author Index 623 Tamao K. 280 Tamara K. 279 Tamaru Y.,560 Tamburin H. J. 20 Tamm Ch. 400 Tamura M. 388 Tamura Y. 152,254 Tan C. C. 219 Tan K. W. 546 Tanabe M. 409 Tanaka M. 292 Tanase M. 410 Tang B. K. 376 Tang R. 574 Tani K. 289 Tanida H. 546 Taniuchi H. 175 Tarasova A. J. 38 Tardivel R. 3 18 Tarpley A. R. 37 Tatlow J.C. 531 Tatsumi S. 296 Tatsuno Y. 281 Tatsuoka T. 541 Taube A. 426 Tawara Y. 534 Taylor D. A. H. 483 Taylor D. R. 158 Taylor E. 446 Taylor E. C. 131,132,373 518 519 Taylor K. G. 233 Taylor M. V. 557 Taylor P. 291 Taylor R. 140 Taylor W. C. 19 380 Tebbe F. N. 277,281 Tebby J. C. 571 Tedder J. M. 523 Teeter R. M. 492 Tegawa H. 430 Templeton D. H. 112 Teng L. C. 474 Terabe S. 201 Terahara A. 423 Teramura K. 367 Terashima M. 254 Terashima S. 346 386 458 Terrier F. 41 136 529 Terry H. W. 526 Terry J. C. 573 Testa A. C. 331 Tetle J. P. 494 Teufel H. 545 Thakore A. N. 392 Thal C. 470 Thaller V. 406 455 Thawley A. R. 11 Thebtaranonth Y. 161 243 564 Thedford R.432 Thiebe R. 422 Tliiele D. 433 Thiele K.-H. 274 275 Thielecke W. 252 Thierry J. 487 Thiery J.-P. 421 Thies R. W. 345 378 Thio J. 19 251 Thirsk H. R. 303 Thoai N. 22 Thomel F. 287 Thom E. 11 6 124 268 Thomas A. F. 467,474 Thomas B. R. 374 Thomas D. 410 Thomas E. J. 253 Thomas F. L. 279 Thomas J. M. 330 432 Thomas M. T. 587 Thomas R. 127 290 406 480 543 Thomas R. N. 105 107 Thomas T. D. 95 Thomas T. R. 531 583 Thomas W. A. 575 Thomasson J. E. 291 Thompson A. R. 563 Thomsen A. D. 303 Thomson C. 581 Thomson J. 282 Thomson R. H. 193 Thornburrow P. R. 338 Thorne R. L. 370 Thornton B. 303 Thornton I. M. S. 483 Thorpe F. G. 526 Thorpe J. G. 583 Thorstenson J. H. 467 Thrierr J.C. 433 Thummel R. P. 358 Thyes M. 328 Tidwell T. T. 358 Tiecco M. 195 215 Tien R. Y. 191 Tighe B. J. 466 Tikhomirova-Sidorova N. S. 430 Tillett T. G. 133 Timms C. H. 370 Tin K. C. 245 Tindal P. K. 199 Tinoco I. 432,434 Tinyakova E. I. 285 Tishbein L. 452 Titchener E. B. 444 Titov Y.A. 484 Tittensor J. R. 43 1 432 Tizane D. 19 23 Tjabin M. B. 280 TkaC A. 210 Tkatchenko I. 286 Tochtermann W. 538 Todd A. 252 Todd M. 405 Todesco P. E. 135 392 582 Toft P. 485 Tohier J. 308 Tokoroyama T. 407 Tokumaru K. 187 Tokura N. 134 141 194 Tokuyama T. 494 Tolman G. L. 444 Tolstikov G. A. 371 554 Tomer K. B. 271 587 Tomic L. 19 Tomic M. 19 Tomita K. 480 Tomita S. 342 Tomkiewicz M.27 Toniola C. 107 Toniolo L. 290 Torii S. 200 318 Tornabene T. G. 450 Torssell K. 194 Toru K. 255 Torzo F. 303 Toscano V. G. 259 Tosi G. 558 Totty R. N. 103 Touchard D. 204 Touet J. 390 Tove S.B. 406 Towns R. L. R. 125 Townsend L. B. 426 Tozyo T. 471 Tracey A. S. 38 Traeger J. C. 8 Trahanovsky W. S. 527 533 Trambouze Y.,285 Traunmiiller R. 273 Traylor J. G. 524 Trecker D. J. 153 Trefonas L. M. 125 Tremelling M. 30 Trepanier D. L. 568 Tresca J. P. 483 Tribble M. T. 333 337 Trifunac A. D. 26 27 Triggs C. 293 Tripathy P. B. 281 Trippett S. 23 Trivellone E. 479 Troisi L. 135 582 Trong Anh N. 155 156 Trost B. M. 164,230,244 346 389 468 526 541 565 577 Trotter J.329 481 Trotter W. 331 Trozzolo A. M. 27 Truce W. E. 188 391 Tsai L. 105 Tso P. 0. P. 432 Tsou K. C. 430 Tsoucaris G. 516 Tsuboi M. 433 Tsuboyama K. 14,428 Tsuchihashi G. 379 Tsuchiya T. 583 Tsuda Y. 498,499 Tsuji J. 280 288 Tsumita T. 454 Tsunjimoto N. 152 Tsuno Y. 140 Tsuto Y. 256 Tsutsumi S.,277 Tsuyuki T. 483 Tsuzuki H. 172 Tubbs P. K. 177 Tudos F. 206 Tufariello J. J. 494 Tulloch C. D. 543 Tunggal B. D. 148 336 Turnblom E. W. 561 Turner A. B. 476,485 Turner J. C. 299 Turner J. O. 258 Turner L. P. 421 Turner P. H. 332 Turner R. B. 549 Turner S.R. 566 Turner W. B. 455 Turro N. J. 339 361 Tursch B. M. 491 Twitchett P. J. 330 Tyminski I. J. 191 333 Tyssee D.A. 308 Ubasawa M. 430 Uccella N. 13 Ucciani E. 465 Uchida A. 286 Uchida T. 430 Uchida Y. 281 Uchide M. 547 Udell W. 228 Ueda S.,289 401 Ueda T. 428 Uegaki E. 518 Ueki M. 392 Uemura D. 513 Uemura S.,518 Uff B. C. 589 Ugo R. 281,290 Uhkir M. 314 Uhlenbeck 0.C. 434 Ukai A. 498 Uhkin L. Yu. 276 Ulku D. 572 Ullenius C. 529 Ullman E. F. 144,205 Underwood W. G. E. 557 Uneyama K.,200,201,318 Ungar G. 15 Uosaki K. 134 Urban E. J. 203 Ushio M. 214 Uskokovic M. R. 505,510 51 1 Utimoto K. 362 Utley J. H. P. 302 313 Uyehara T. 536 Uyeo S. 48 1,483 Uziel M. 421 434 Vacheron M. J. 454 Vaciago A. 480 Vajtner Z. 306 Valasinas A. 415 Valente L. 15 Valentine D. 291 Valentine J.291 Vallee B. E. 176 Valverde S.,476 Van Bekkum H. 40 338 van Bergen T. J. 565 581 588 van Boom J. H. 430 Van Brederode H. 19 Vance C. J. 303 Van Cleve W. C. 131 Vandemark F. L. 191 Vandenberghe A, 437 Vanderheiden B. S.,425 van der Lans H. N. M. 224 582 van der Lugt W. Th. A. M. 144 164 Vander Meer R. K. 588 van der Plas H. C. 588 van de Sande J. H. 420 431 van Deursen F. W. 38 Van de Ven L. J. M. 38 467 Van Dongen J. P. C. M. 88 Van Drunen C. 317 Van Fossen R. Y. 520 532 Van-Ham J. 332 van Lear G. 423 van Meersche M. 579 Van Peppen J. F. 274 Van Saun W. A. 19 van Tamelen E. E. 248 340 396 451 482 483 53 1 Vantillard A. 465 van Veldhuizen A. 224 582 Van Velzen J.C. 525 Van Wazer J. R. 334 van Wijngaarden B. H. 456 Van Zwet H. 214 Author Index Varma K. R. 397 Varma R. K. 369,459 Vashi D. B. 328 Vasilescu A. 580 Vaughan J. 133 518 Vaughan R. J. 177 Vavra N. 242 Vedejs E. 161 221 342 376 379,451 Veeflcind A. H. 386 Vegar M. R. 24 Veillard A. 53 62 74 80 Velarde E. 107 367 491 Venkataramani P. S.,362 363,382 Venkateswarlu A. 458 Venkstern T. V. 430 442 Venturella P. 476 Vere Hodge R.A. 455 Vergoni M. 580 Verheus F. W. 29 Verheyden J. P. H. 426 Verkade J. G. 568 Vernin G. 194 Vernon C. A. 252 Vesety K. 210 Vesley G. F. 385 Vesonder R. F. 452 Vestal M. 6 Viehe H. G. 385 Vilkas E. 454 Vincent A. T. 116 Vincow G. 195 Vineyard B.D. 295 Vining L. C. 410,412 Vinutha A. R. 581 Visser G. J. 113 573 Viterbo R. 516 Vittimberga B. M. 193 265 Vitullo V. P. 139 Vizzini E. A. 119 Vliegenhart J. F. G. 15 v. Mikusch J. D. 464 Voelter W. 32 35 106 337 Vogel E. 149 198 540 Vogel P. 41 247 249 252 Volker E. J. 587 Volkmann R. 508 509 Volkova L. G. 290 Vollhardt K. P. C. 541 543 Vollmer J. J. 163 Volman D. H. 200 Vol'pin M. E. 290 291 Volz H. 537 Volz-de Lecea M. 537 von Ammon R. 337 Von Der Haar F. 445 Vonnahme R. L. 294 von Niessen W. 50 78 Author Index von Philipsborn W. 42 337,575 578 Vo Quang Y. 370 Vos A. 573 Voss J. 212 Voynick I. M. 172 Vycudilik W. 242 VystrCil A. 482 Waal G. H. 19 Wachs T.6 Wada H. 208 513 Wada M. 588 Wada N. 187 Waddell W. 185 Wade A. M. 372 Waegell B. 559 Wagner A. F. 436 Wagner D. 426 Wagner J. J. 35 338 Wagner P. J. 326 Wagner R. 578 Wagner R. M. 589 Wagniere G. 105 Wagnon J. 487 Wahrhaftig A. L. 6 Waight E. S. 480 Wailes P. C. 290 Waite M. G. 114 127 Wakabayashi M. 570 Wakamatsu T. 483 Wakatsuka H. 254 Wakefield B. J. 224 Wakselman M. 385 Walborsky H. M. 189 Wald G. 185 Waley S. G. 179 Walker G. N. 569 Walker J. E. 462 Walker R. T. 427 428 431,432 Walker K. A. M. 278 365 Walker L. E. 527 533 Walker P. M. B. 445 Walker T. E. H. 65 Walker W. E. 288 289 Wallenstein M. B. 6 Walling C. 30 207 Wallwork S. C. 572 Walsh C. T. 182 Walsh R.J. A. 569 Walthers K. 339 Walton D. R. M. 140 Wampler D. L. 114 Wander J. D. 21 Wang A. H.-J. 570 Wang E. J. 340 531 Wang J.-L. 282 Wangen L. E. 12 Ward C. K. 257 Ward G. A. 292 Ward H. R. 25 26 31 Ward J. S. 161 260 342 Ward P. 193 Ward R. S. 264 Ward S.D. 8 Warden K. 326 Warne T. M. jun. 347 Warner P. 221 340 531 Warren K. E. H. 402 503 Warrener R. N. 424 575 Wartiovaara I. 135 Waser P. G. 493 Washburne S. S.,254 Washida M. 485 Wasserman E. 224 234 Wasserman H. H. 256 362,410 556 Wasson J. S. 160 Watanabe T. 312 Watanabe Y. 292 Watawabe N. 318 Wataya Y. 424 Waters E. A. 141 Waters J. A. 494 Waters J. M. 127 Waters T. N. 127 Waters W. A. 206 209 274 Waters Y.A. 314 Watson D. G. 114 Watson J. M. 258 Watson K. G. 555 Watson T. G. 482 Wawzonek S. 298 Weaver D. C. 391 Webb C. F. 359 Webb D. 437 Webb G. A. 575 Webb P. G. 187 Webb S. B. 582 Weber H. 581 Weber J. 252 Weber W. P. 390 Webster D. E. 280 Webster R. E. 440 Wedegaertner D. K. 188 Weedon B. C. L. 313,463 464 Weeks C. M. 124 Wege D. 158,221 575 Wehrli F. W. 140 575 Wehrli W. 442 Weigold H. 290 Weiler L. 384 Weinberg N. L. 307 31 1 Weingarten G. G. 255 Weinreb S. M. 535 Weinshenker N. M. 224 Weinstein A. J. 437 Weinstein I. B. 422 423 Weisgraber K. H. 316,497 Weiss C. 133 580 Weiss G. 370 Weiss R. 74 112 533 Weiss R. G. 145 Weiss U. 107 521 Weissman B. A. 554 Weissman S.M. 435 Weissman C. 437 Wells C. H. J. 137 529 Wells P. 321 Wells P. B. 280 Wells R. D. 20 Wells R. J. 24 Welzel P. 202 Wendling L. A. 329 Wenkert E. 19 31 32 246,493 5 12 Wennerstrom O. 529 Wepster B. M. 40 338 Werme L. O. 92 Werner R. 447 Werstiuk E. S.,431 Werthemann L. 460 Wertz D. H. 333 Wesseler E. P. 530 West C. T. 201 West P. R. 199 West R. 243 336 521 West R. M. 533 Westberg H. H. 165 166 262,284 352 354 Westcott N. D. 401 481 Westerman I. J. 158 Westhead R. 140 Westheimer F. H. 177 179 Westley J. W. 105 121 Wetzel P. 266 Weyerstahl P. 230 Weygand F. 15 Whalen D. L. 165 328 Whalley W. B. 379 463 490 562 Whan D. A. 285 Wharen M. 277 Wheatley P. J. 116 Whipple E.B. 578 White A. M. 36 White C. 277 White D. N. J. 121 White D. V. 298 White D. W. 568 White E. H. 558 White P. A. 15 White W. N. 262 Whitehurst P. W. 40 Whitesides G. M. 24 188 291 292 388 Whitesides T. H. 294 Whitfield C. 446 Whitfield H. O. 446 Whiting D. A. 406 413 Williams V. Z. 360 Whiting M. C. 529 Williamson K. L. 156 Whitlock H. W. jun. 476 Willis J. N. 340 Whitney C. C. 388 389 Willis M. R. 203 Whittaker G. 536 Willis T. C. 106 Whitten D. G. 327 Wilputte-Steinhert L. 279 Whitten J. H. 574 Wilson A. T. 466 Whitten J. L. 78 217 Wilson D. A. 245 Whittle J. R. 229 Wilson F. B. 109 Whittle P. R. 21 1 Wilson F. M. 393 Wiberg K. B. 340 360 Wilson H. R. 426 Wiberg N. 392 Wilson J. A. 137 529 Wickens J.C. 455 Wilson K. R. 516 Wickerham L. J. 452 Wilson L. A, 99 Wickramsinghe J. A. F. Wilson M. S. 428 3 98 Wilson S. E. 165 262 Widdowson D. A. 397 284 352 354 399 Wilson S. T. 277 Wiechers A. 500 Wilson T. 558 Wiechert R. 347 Wilt E. M. 431 Wiegehaus E. 454 Wilzbach K. E. 154 329 Wieglepp H. 484 3 30 Wieland D. M. 358 387 Wing R. M. 475 Wiersum U. E. 532 Wingard R. E.. 247 560 Wigfield Y. Y. 19 Winkler F. W. 120 Wightman R. H. 403 Winkler M. F. 416 Wikel J. H. 241 Winkley M. W. 426 Wilchek M. 180 Winstein S. 21 1 251 531 Wilcott M. R. 145 Winter R. E. K. 147 Wilcox C. F. 140 Winterfeldt E. 510 Wilcox P. E. 170 Winters R. E. 8 Wilde R. E. 234 Wirsam B. 47 Wilder P. 249 Wirthwein R. 223 582 Wildes P. D.558 Wise W. B. 40 Wildman W. C. 493 Wisener J. T. 581 Wildsmith E. 370 Wiskott E. 252 Wilford J. B. 113 Wisse J. A. 332 Wilhelm S. 140 Witanowski M. 575 Wilhite D. L. 78 217 Witherup T. H. 533 Wilke G. 286 289 296 Witkop B. 314,494 Wilkins C. L. 8 Witte J. 286 Wilkinson G. 274 275 Wittig G. 198 222 241 278,290 292 546 549 Wilkinson P. J. 280 Woenckhaus V. C. 176 Wilks E. S. 524 Woese C. R. 435 Wilks M. A. J. 203 Wofsy L. 175 Willard A. K. 390 Wojcicki A. 291 Willcott M. R. 19 Wolf A. P. 251 Willhalm B. 470 Wolf G. C. 188 485 Williams D. A. R. 568 Wolf J. F. 312 313 Williams D. H. 5 7 13 Wolf V. 464 19 337,490 Wolfe S. 204 292 Williams D. J. 127 197 Wolinsky J. 467 Williams D. M. 22 Wolkowski Z. W. 19 22 Williams E. A. 360 Wolovsky R.278 Williams F. J. 165 262 Wolter J. 484 284 352 560 Wolthers J. M. 169 Williams J. E. 74 Wong C. 515 Williams J. L. R. 266 Wong R. Y. 117 Williams J. O. 330 Wong S.-M. 395 Williams J. R. 361 Woo E. P. 40 278 542 Williams V. P. 395 Wood D. E. 200 Author Index Woodward P. 275 Woodward W. S. 12 43 102 143 390 393 Woodworth C. W. 252 Wooldridge K. R. H. 569 Woolford R. G. 314 Woolhouse A. D. 546 Wormald J. 291 Worsley M. 378 Wostradowski R. A. 329 Wright A. 243 Wright G. J. 133 518 Wright J. J. 399 Wright L. H. 512 Wright M. E. 421 Wright N. D. 564 Wristers J. 354 Wrixon A. D. 104 Wu F. 333 Wu R. 446 WU W.-N. 497 Wudl F. 116 392 Wiiest H. 469 Wuesthoff M. T. 333 Wulfman D.S. 229 Wybrandt E. 177 Wynberg H. 107 252 268 379 384 490 562 Wyn-Jones E. 567 Wyse K. J. 338 Yagen B. 398 Yager W. A. 224 Yagi H. 316 497 Yagi T. 367 Yagupsky G. 275 292 Yahnev J. A. 384 Yalpani M. 576 Yamada H. 158,220 Yamada K. 5 13 Yamada S. 426 500 Yamada Y. 423,442 Yamaguchi H. 165 166 262 284 325 352 354 537 Yamamoto H. 296 396 450,458,471,482 Yamamoto I.. 527 Yamamoto K. 280 292 296 559 Yamamoto Y. 230,291 Yamamura S. 471 Yamanaka H. 367 Yamane T. 442 Yamauchi H. 480 Yamazaki A. 429 Yamazaki H. 291 Yamazaki N. 289 Yamazaki T. 197 Yanase R. 460 Yang K. S. 376 Author Index Yang N. C. 326 Yang P. W. 545 Yaniv M. 442 444 445 Yannoni N. F. 196 Yarrow D.J. 293 Yasunami M. 545 Yates P. 559 563 Yeo A. N. H. 7 Yip K. F. 430 Yokali E. 150 Yokoyama Y. 208 Yokozeki A. 339 Yonath A. 174 Yoneda S. 577 584 Yonemitsu O. 265 543 Yonezawa K. 197 342 Yonezawa T. 214 322 567 Yoo c.s.,120 Yorke M. 585 Yoshida K. 318 583 Yoshida M. 28 222 241 542 Yoshida T. 281 Yoshida Z. 158 220 233 534 560 517 584 Yoshimoto M. 19 Yoshino A. 322 Yoshioka H. 326 Young A. E. 41 Young C. W. 436 Young G. A. R. 349,472 Young H. 424 Young J. C. 197 Young J. C. F. 469 Zeman A. 453 Young J. M. 476 Zemlicka J. 428 Young L. B. 66 Zengierski L. 527 Young W. R. 543 Zenk M. H. 402,416,417 Youngblood W. W. 449 Zetta L. 493 Yu s.,357 Zheltov A. Ya. 215 Yu Fan J. 556 Zhukova S.V. 158,252 Yukawa Y. 140,256 Ziegler F. E. 346 477 Yun-Chi Yeh. 174 478 Yurkevich A. M. 290 Ziehn K. D. 384 Yuthavong Y. 169 Ziman S. D. 164 Zimmer J. P. 299 Zabrowsky B. R. 393 Zimmerman D. 38 568 Zacharova-Kalavska D. Zimmerman H. E. 44 303 143 198 327 515 Zachau H. G. 422,442 Zimmerman T. P. 445 Zador M. 373 Zinder N. D. 440 Zalkin A. 112 Zinkel D. F. 478 Zaman A. 480 Zollinger H. 129 136 590 Zambelli A. 36 Zoltewicz J. A. 223 579 Zamecnik J. 474 582 Zander M. 202 Zon G. 574 Zandomeneghi M. 296 Zubay G. 439 Zarutova V. F. 429 Zubiana G. 389 Zdero C. 343 Zucchini U. 275 Zdunneck P. 275 Zuech E. A. 286 Zdysiewicz J. R. 213 Zuman P. 303 Zechmeister K. 479 Zurr D. 375 490 544 Zehetner W. 272 561 Zeiss H.H. 290 Zwanenburg B. 257 Zeiss W. 561 Zweifel G. 344 370 388 Zelensky I. 303 389 Zelesko M. J. 131 518 Zweig A. 330 Zeltner M. 133 Zwiesler M. L. 384

ISSN:0069-3030    

DOI:10.1039/OC9716800593

出版商:RSC    

年代:1971

数据来源: RSC