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6 Organometallic Chemistry Part (ii)Main-Group Elements By M. G.HUTCHINGS 1.C.I. Organics Division Research Department Blackle y Manchester M9 3DA. 1 Introduction To maintain continuity with last year's Report' and its two predecessors P Se and Te are excluded as are carbaboranes. Organometallic species containing Li Be and B have been the subjects of various ab initio calculations during part of a wider attempt to develop a 'model chemistry' aimed at establishing relationships between structures and energies of simple molecules rather than merely calculating isolated absolute values. Species studied include phenyl cations,*" ethyl and vinyl cations and their isoelectronic methylboranes,2b and small compounds containing Li or Be.2' Considering the number of new organic synthetic routes based on organo-metallics which have been developed in the past twenty years or so application in larger synthetic schemes had until recently been disappointing.However the full worth of such reagents is becoming recognized as evidenced further by the syntheses mentioned below all dependent on organometallic reagents and pro- cedures which have been recently developed. The enantiomer of the macrocyclic antibiotic dilactone (-)-vermiculin and the closely related fungicide (-)-pyreno-phorin have been synthesized by modifications around lithio dithiane~.~ A 'chemo- regio- and stereo-selective' route to the sex peromone (7E,9Z)-dode- cadien-1-yl acetate in 40 '/o yield from but-1-yne and hept-1-yne has been based largely on organoboron ~hemistry.~ Key reagents are NH2(CH2)3NH-K+ SiazBH (Sia = 3-methylbut-2-yl) and EtCECLi 12 and NaOAc and' finally Sia2BH followed by HOAc.Syntheses of prostaglandins5" and loganid& have included reactions of allylsilanes with electrophiles. Without wishing to labour the point it does seem worthwhile reiterating last year's Reporter's trenchant caveat concerning overliberal interpretation of product studies when assigning structures to reactive intermediates.' Instances of prema- ture inferences based on insufficient data continue to come to light. K. Smith Ann. Reports (B),1976.73 121. (a)J. D. Dill P. von R. Schleyer and J. A. Pople J. Amer. Chem. SOC.,1977,99 1; (6)Y. Apeloig P. von R. Schleyer and J. A. Pople ibid. 1977,99 5901; (c)J.D. Dill P. von R. Schleyer J. S. Binkley and J. A. Pople ibid. 1977 99 6159. D. Seebach B. Seuring H.-0. Kalinowski W. Lubosch and B. Renger Angew. Chem. Internat. Edn. 1977 16 264. E.4. Negishi and A. Abramovitch Tetrahedron Letters 1977 41 1. B.-W. Au-Yeung and I. Fleming (a)J.C.S. Chem. Comm. 1977 79; (b)ibid. 1977 81. 136 Organometallic Chemistry -Part (ii) Main -Group Elements 137 Of a general nature a review has appeared which deals with the preparation and use in synthesis of reactive metal powders by reduction of their salts with alkali metak6 A recently published volume contains articles on organometallic synthesis via metal atoms,7a T-ligands containing organosilicon structures of organometallic compounds containing electron-deficient bridge and organome talk radical anions.7d Due to an oversight' in last year's Report' the comments concerning stabilized silicenium ions failed to include reference to a note by Mislow and co-workers.' Further evidence relating to the proposed ferrocenyl silicenium ion FcSiPh2' has forced a reappraisal of the data to the effect that this species is now no longer considered to be a necessary discrete intermediate in the observed reaction sequences. Hence the unequivocal existence of a silicenium ion in solution has yet to be demonstrated. 2 Group1 Reviews have appeared concerning the generation and reactivity of di- and poly- alkali metal derivatives of heterofunctionally substituted organic molecules,1o the structure and reactivity of alkali metal enolates," and applications of a-metallated isocyanides in organic synthesis.'* A useful correlation has been drawn between 13C-lH one-bond coupling constants in benzenoid and heterocyclic molecules and the relative reactivity of the corresponding CH moiety toward 1ithiati0n.l~ Incorrect predictions caused by heterosubstituents can be related to the propensity for Li complexation and consequent ortho-directing effects.Presumably the technique could be used in reverse to assist in n.m.r. assignments. Reagents are sometimes favourably modified merely by the change of physical form they undergo when adsorbed on a passive support and methods have been described for the preparation of Na or K in reactive forms on the high surface area of charcoal graphite or alumina.14L1 These reagents and the intercalation compound CsK react with ketones giving enolates which can be subsequently monoalkylated preferably in hexane solvent where competing side reactions are minimized through the reactive species remaining adsorbed on the support.Following a similar procedure nitriles and esters may be a-metallated hetero- geneously with CsK and monoalkylated in good ~ie1ds.l~~ Lithiation of ketone dimethylhydrazones by more conventional techniques generate useful enolate equivalents. A recent study of the mechanistic stereo- chemistry of this reaction (Scheme 1)15 showed that regardless of the hydrazone 'R. D. Riecke Accounts Chem. Res. 1977,10,301. '(a) P. L. Timms and T. W. Turney Adv. Organometallic Chem.1977 15 53; (6) I. Haiduc and V. Popa ibid. p. 113; (c)J. P. Oliver ibid. p. 235; (d)P. R. Jones ibid. p. 273. 'K. Smith personal communication. P. Bickart F. M. Llort and K. Mislow J. Organometallic Chem. 1976,116 C1. lo E. M. Kaiser J. D. Petty and P. L. A. Knutson Synthesis 1977 509. L. M. Jackman and B. C. Lange Tetrahedron 1977 33 2737. '* U. Schollkopf Angew. Chem. Internat. Edn. 1977 16 339. l3 E. B. Pedersen J.C.S. Perkin II 1977,473. 14 (a)H. Hart B. Chen and C. Peng Tefruhedron Letters 1977,3 121; (b)D. Savoia C. Trombini and A. Umani-Ronchi ibid. 1977 653. '' M. E. Jung and T. J. Shaw Tetrahedron Letters 1977 3305. M. G. Hutchings 16' cyclopentanones. Me i,ii + CD,CH2 lNMe2 kN + CD,CH2 +N ,NMe2 CH,CH2 CH,CH- Lit or It CD,CH CD,CH 111t Et Pr' NMe Reagents i.LiNEt2; ii CD31;iii CH31 Li+ Scheme 1 orientation the primary carbanion is initially generated. The second anti depro- tonation is kinetically favoured presumably because of Me2N hindrance to the alternative but the syn carbanion is thermodynamically favoured as evidenced by subsequent isomerization. Alkylation of enolates resulting from the addition of lithium organocuprates to cyclopentenones usually gives the 2,3-dialkylated cyqlopentanone with trans-orientation of the alkyl substituents. However the presence of a 3-phenyl group causes the incoming alkylating agent to attack cis,in a highly stereoselective fashion. 16a The reasons for this reversal of stereochemistry are presently unknown but a possibly related phenomenon concerns the directing effect of a 3-aryl or -benzyl group during the formation of lithium enolates of The thermodynamically favoured 2-enolate is formed pref- erentially the 3-substituent possibly acting to co-ordinate and thereby direct and stabilize the adjacent Li' by n-complexation.This model finds support from an independent theoretical study (CND0/2) which predicts Li+-C6& to exist as a pyramidal face-metallated species (c& symmetry) in contrast to H+-C6H6 (corner protonated; C2,symmetry).l6' The preference for this structure can be rationalized by the .rr-bonding ability of the unoccupied p-orbitals on Li' in conjunction with filled n-orbitals of C6H6 of suitable symmetry. An anionic equivalent of the Friedel-Crafts cycloacylation forms the basis of a general ring-forming synthesis (Scheme 2 e.g.Z = CH2CH2CH2).17a For Z = CH2 LiO OLi 0 Reagents i RLi; ii H20 Scheme 2 or CMe2 ring formation is not observed but rather reactions of an alternative type occur that for Z=CMe2 E=C02H being depicted in its most general form in Scheme 3. In principle Z and E can assume a variety of chemical identities (e.g. l6 G. H. Posner and C. M. Lentz (a) Tetrahedron Letters 1977,3215; (b)ibid. 1977,321 1 (c)D. Heidrich and D. Deininger ibid. 1977 3751. " (a) R. J. Boatman B. J. Whitlock and H. W. Whitlock jun. J. Amer. Chem. Suc. 1977 99,4822; (b) D. Hellwinkel G. Hofmann and F Lammerzahl Tetrahedron Letters 1977 3241. Organometallic Chemistry -Part (ii) Main -Group Elements 139 Oz\Eef nz-Li+ -P -b \ E-Li' ' Li \E Scheme 3 2=NR,0;E = COPh) and other examples have been gi~en."~ Furthermore if Z and E themselves are initially part of a ring the product itself will be bicyclic.The inclusion of a negative!y charged atom a to the carbonyl carbon of an a',6'-unsaturated ketone system suppresses addition of RLi to the carbonyl group with consequent preference for P'-attack as exemplified by reactions of the ylid in Scheme 4." An alternative approach to the inhibition of conventional addition to a carbonyl group relies on the effect of extreme steric hindrance to reagent attack. 0 0 .. ... +cO,tl fl.111 ,9c02Me +CozEt +PPh +PPh Bun Reagents i MeLi; ii Bu"I; iii HC-MeOH Scheme 4 Metallations at surprising sites are thereby promoted as in the generation of (la) from (lb),19" and the metallation of the Y-Me group of (3),where Y = NR S,I9' or 0.19' Reaction of any of these species with electrophiles and suitable work-up leads to products derived from the uncommon synthons HYCH2-.By formally adding two electrons to the pentadienone system electrophilic attack at the terminal 5-position ('E' activity') is enhanced at the expense of the conventional nucleophilic attack ('Ns activity'). In practice a direct E5synthon (3) has been generated by double deprotonation of allylacetophenone and shown to react regio- and stereospecifically with electruphiles.20 Studies of polymer-bound organolithium species have given interesting synthetic and mechanistic results as for instance in the reaction between @-C6H4SCH2-Lit and (4a) followed by MeI/NaI.*l" The product ratio [(4c)]/[(4b)] gives a measure of the extent of site interaction on the polymer; high PhCH 0 a N - R P r i ~ ~ o 0 ~ ~ e \/ PhCH 0 Pr' KH2)n I (1) a; R=CH2Li b; R=CH3 (3) (4) a; n =4 b;n=5 c; n=6 M.P. Cooke jun. and R. Goswarni J. Amer. Chem. SOC.,1977 99,642. l9 (a)R. Schlecker and D. Seebach Helv. Chim. Acta 1977,60 1459; (b) P. Beak B. G. McKinnie and D. B. Reitz Tetrahedron Letters 1977 1839; (c)P. Beak and B. G. McKinnie J. Amer. Chem. SOC. 1977,99,5213. 2o M. Pohrnakotr and D. Seebach Angew. Chem. Infernat. Edn. 1977,16 320. 21 (a)G. A. Crosby and M. Kato J. Amer. Chem. SOC.,1977,99,278; (b)B.J. Cohen M. A. Kraus and A. Patchornik ibid. 1977 99 4165. 140 M. G. Hutckings ratios signify ionic clustering as is in fact observed in this particular system. Polymer-bound trityl-lithium ((&CC,H4C-Ph2Li') has been used to generate the enolate from acetophenone which then reacts with an independent polymer-bound acylating agent (@-C6H3N020COPh) to give high yields of the diketone (PhCOCH2COPh).21b In contrast the corresponding reaction with wholly soluble reagents gives a much inferior yield. The reaction sequence is capable of extension by use of a third reagent giving rise to what is termed a 'chemical cascade'. Among other useful new organolithium reagents are RCC12Li (from RCC12H including CH2C12) which reacts with a variety of electrophiles,22 and cis-X-CH=CH-Li (X = OEt..NR,) which act as CHOCH2-equivalents.23 In a study of the gas phase acidities of cis- and trans-but-2-enes by pulsed ion-cyclotron resonance spectroscopy the cis-butenyl anion has been found to be 0.2 kcal mol-' less stable than its trans-is~rner.~~ This result has relevance to solution-phase studies of butenyl anions where the cis-isomer has been found to predominate to a greater extent as the electropositivity of its alkali metal coun- terion M+ increased. Since ion-separation is expected to increase with more electropositive M+,it had been assumed that the cis-preference was to be ascribed to the relative stabilities of the free anions. However it now appears to arise because of differences in interaction energies among the allylic skeleton M' and the solvent.Ab initio calculations at minimal basis and split basis levels on the species C3Li4 including geometry optimization have predicted the strange ground-state geometry depicted in (5) (C2"symmetry) where the angle between the two central Li-C bonds is only 93°.25The central Li' ions bond with the highest occupied nonbonding .rr-orbitals of the C3 chain (formally and conveniently considered a C34- ion isoelectronic to C02)(6). Li\ /c\ Li c \c / Li Li Attention is drawn to a review of the umpolung of the reactivity of carbonyl compounds with particular reference to lithiated sulphur heterocyclic reagents.26 Besides this review and work cited elsewhere in this Chapter Seebach and his prodigious group have published in 1977 a series of papers in Annalen and Chem.22 J. VilliCras P. Parriot and J. F. Normant Bull. SOC.chim. France 1977 765. 23 J. Ficini S. Falou A.-M. Touzin and J. d'Angelo Tetrahedron Letters 1977 3589; R. H. Wollenberg K. F. Albizati and R. Peries J. Amer. Chem. Soc. 1977,99,7365;L. Duhamel and J.-M. Poirier ibid. 1977,99,8356. 24 J. E. Bartmess W. J. Hehre R. T. McIver jun. and L. E. Overman J. Amer. Chem. SOC. 1977 99 1976. 25 E. D. Jemmis D. Poppinger P. von R. Schleyer and J. A. Pople J. Amer. Chem. SOC. 1977,99,5796. 26 B. T. Grobel and D. Seebach Synthesis 1977,357. Organometallic Chemistry -Part (ii) Main -Group Elements 141 Ber. which give details of previously communicated material (much of which has been highlighted in Annual Reports in previous years) but which also include new illuminating insights.3 Group I1 Magnesium.-A useful review has appeared on the one-step reaction of organic halide Mg and substrate (Barbier rea~tion).~' Species of general formula HMgR are surprisingly ill-characterized. However the preparation of a particularly active form of MgH from the reaction of LiAlH4 and Et2Mg has opened up routes to these species based on 1:1 redistribution reactions with appropriate R2Mg. Thus HMgAlkyl may be prepared in THF in which it is stable at room temperature contrary to earlier reports.28"*b The species is dimeric in dilute solution (bridging hydrogens) and is reported to give the products of both reduction and alkylation on reaction with ketones.Perhaps the most significant result from this series is the observation that HMgCl and HMgBr add to alkenes and alkynes.28c No details are yet available but hopefully we can look forward to a hydrometallation agent analogous to diborane but which leads to Grignard reagents. Other related species are HMgOAr which are highly stereoselective reducing agents,28d and HMgPh prepared directly by reaction between LiAIH4 and Ph2Mg.28e An interesting new addition reaction of organomagnesiums is the transition metal catalysed addition of Me3SiCH2MgC1 to diketene yielding Me3SiCH2C(:CH2)CH2C02H.zg The reaction provides the first example of vinyl-oxygen bond cleavage in diketene but conceivably the catalysts rather than the Grignard itself could be responsible for the mode of ring opening.Copper- promoted additions of Grignard reagents continue to offer useful synthetic sequences including the addition to 3-alken- 1-ynes predominantly at the 2-posi- tion as exemplified in a synthesis of myrcene 30a the direct stereospecific replace- ment of iodide from vinyl iodides,30b and regiospecific addition of unsymmetrical ally1 Grignards to alkyl halides used in a simple synthesis of gerani01.~'~ A purely electrophilic mechanism is proposed for the addition of 2-norbornyl- magnesium bromide to formaldehyde based on similar exo :endo ratios for product and starting material.31 In contrast an electron-transfer mechanism is believed to apply in the rare 'wrong end' addition of RMgX to the carbonyl oxygen in o-quinol acetates.32 Zinc Cadmium and Mercury.-Alkynylzinc reagents couple with alkenyl halides in the presence of Pd catalysts to give high yields of conjugated en~nes.~~~ Besides 27 C.Blomberg and F. A. Hartog Synthesis 1977 18. E. C. Ashby and A. B. Goel (a)J. Org. Chem. 1977,42,3480;(6) J.C.S. Chem. Comm. 1977,169; (c) Inorg. Chem. 1977 16 2941; (d) E. C. Ashby A. B. Goel and J. J. Lin Tetrahedron Letters 1977 3133; (e)E. C. Ashby and A. B. Goel Inorg. Chem. 1977,16,1441. 29 K. Itoh T. Yogo and Y. Ishii Chem. Letters 1977 103. 30 (a) H. Westmijze H. Kleijn J. Meijer and P. Vermeer Tetrahedron Letters 1977 869; (b) A. CommerGon J. F. Normant and J. VilliCras J. Organornetallic Chem. 1977 128 1; (c) F. Derguini-Boumechal R. Lorne and G. Linstrumelle Tetrahedron Letters 1977 1181.31 D. E. Bergbreiter and 0.M. Reichert J. Organometallic Chem. 1977 125 119. 32 B. Miller J. Org. Chem. 1977 42 1402 1408. 33 (a)A. 0.King N. Okukado and E.-I. Negishi J.C.S. Chem. Comm. 1977,683; (b)E.-I.Negishi A. 0. King and N. Okukado J. Org. Chem. 1977,42 1821. M. G. Hutchings being >97 ‘/o stereospecific the procedure is compatible with the presence of various electrophilic functionalities in the alkene precursor and is unique in allow- ing the direct preparation of terminal enynes CH,=CH-C=C-R without pro- tection-deprotection sequences. A related reaction involving aryl- or benzylzinc compounds and aryl halides leads to high yields of unsymmetrically coupled pro- ducts and is again tolerant of further substitution in the aryl halide.33b The silylated cyclohexenol (7) undergoes synthetically useful spirocyclo-propanation to (8) in the presence of excess Et2Zn-CHJ2 in concentrated benzene solution (Scheme 5).34” In contrast trimethylsiloxyrnethylenecyc’fopentanegives (9) under Simmons-Smith conditions (CH212-Zn-C~).34b In both these reactions Zn12 apparently causes ring opening of the cyclopropane and either H-or ring C- migration.Me,SiO Reagent i Et2Zn-CH212; ii ZnIz I Scheme 5 The conventional view that substituents preferentially adopt the equatorial orientation in monosubstituted cyclohexanes is no longer tenable in the light of variable temperature I3C and Ig9Hgn.m.r. studies of various cyclohexylmercury It is shown unambiguously that the mercury substituents preferentially occupy an axial position.Photolysis of ty -amino-acids with various aliphatic side chains in the presence of HgC12 leads to methylmercury chloride from an apparent fragmentation of the side chain of the amino-a~id.~~ It is tempting to infer a connection with the formation of highly neurotoxic methylmercury found in the natural environment. 4 Group I11 Boron.-A review has appeared dealing with boraheterocycles prepared via hydroboration . their use as reagents and intermediates being particularly emphasized.37 By redistribution of Me2S,BH3 with BC13 and BBr3 in the appropriate stoi- cheiometry Me2S,BHX2 and Me2S,BH2X (X = C1 Br) are made readily avail- able.38 Reagents such as these are particularly important in preparations of unsymmetrical trialkylboranes or variously substituted mono- and di-alkylboranes 34 (a) I.Ryu S. Murai and N. Sonoda Tetrahedron Letters 1977,4611; (6) I. Ryu S. Murai S. Otani and N. Sonoda ibid. 1977 1995. ’’ P. F. Barron D. Doddrell and W. Kitching J. Organometallic Chem. 1977 139 361. 36 K. Hayashi S. Kawai T. Ohno and Y. Maki J.C.S. Chem. Comm. 1977. 158. 37 H. C. Brown and E.-I. Negishi Tetrahedron 1977 33 2331. H. C. Brown and N. Ravindran (a) J. Amer. Chem. Soc. 19?7,99,7097; (6) Synthesis 1977,695; (c)J. Org. Chem.. 1977,42 2533. Organorne ta llic Chemistry -Part (ii) Main -Group E1ements all of which have their place in the repertoire of synthetic organic chemistry. Significant observations are that the bromo compounds give appreciable amounts of tertiary alkylboranes with trisubstituted alkenes and the ease with which Me2S,BHBr2 effects hydroboration in comparison with Me2S,BHC12.38" It is rele- vant that there is evidence for .rr-interaction between benzene and Me2S,BHBr2 which is absent from the chloro analogue.Reaction between BBr3 and (Me3Si)3N gives MeBBr2 essentially quantitatively and free from di- or tri-methyl derivative^.^^ Easy routes to methylboranes are always interesting since hydroboration is obviously inapplicable for their preparation. Tertiary alkylboranes are also rela- tively inaccessible so the sequence bromination (Br2-hv) and alkylation (RM) when applied inter alia to secondary alkyl boronate esters giving tertiary alkyl boron derivatives is of potential synthetic value.4o The reagent Li'Et,BH- may be used in a route to other novel boranes and borates involving nucleophilic hydro- boration of styrenes under relatively mild condition^.^^ Finally w -alkynylalkyl-boranes inaccessible by hydroboration may be prepared by prototropic iso-merization [K+NH2(CH2)3NH- catalyst] of the available internal alkynylborane itself prepared by hydroboration of a terminal nonconjugated enyne.'* The increasing problems associated with the use of racemic materials as phar- maceuticals (etc.) has heightened the need for asymmetric reagents.Therefore the renewed interest in chiral boranes as reducing agents is particularly timely and is reflected in several publications dealing with modified isopinocampheylborane systems.The reagent (10) derived from 9-borabicyclononane reduces aldehydes (10) with concommittant elimination of alkene and has been used to reduce deutero- benzaldehyde to (S)-benzyl-a-&alcohol (important for mechanistic biochemical studies) with essentially quantitative asymmetric indu~tion.~~" Bu'Li donates H- to the B atom of (lo) the new chiral trialkylborohydride reducing even relatively hindered ketones rapidly and q~antitatively.~~' Optical purities of products range only from 3-37 % but of more importance is the finding that the predominant enantiomers of all alcohols produced to date have the same absolute configuration. In a reaction analogous to the well known radical addition of R3B to enones and analogues B-alkynyl-9-BBN undergoes conjugate addition to those a$ -unsaturated ketones which are capable of assuming a cisoid conformation but apparently by a nonhomolytic pathway.Further elimination in the reaction with (11)leads to conjugated enynone~.~~ Dialkyldialkynylstannanes react with Et3B or 39 I<. Barlos and H. Noth Chem. Ber. 1977,110 3460. 40 H. C. Brown N. R. DeLue Y. Yamamoto K. Murayama. T. Kasahara S.-I. Murahashi. and A. Sonoda J. Org. Chem. 1977,42 4088. 41 H. C. Brown and S. C. Kim J. Org. Chem. 1977.42,1482. 42 C. A. Brown and E.-I. Negishi. J.C.S. Chem. Comm. 1977 318. *' (a) M. M. Midland A. Tramontano and S. A. Zderic J. Amer. Chem. SOC.,1977,99,5211; (b) S. Krishnamurthy F. Vogel and H. C. Brown J. Org.Chem. 1977,42,2534. 44 J. A. Sinclair G. A. Moiander and H. C. Brown J. Amer. Chem. Soc. 1977 99,954; G.A. Molander and H.C. Brown J. Org. Chem. 1977,42,3106. M. G. Hutchings Me0 (11; Bu;B to give the novel heterocyclic dienylboranes (12) which can be used for further synthetic m~dification.~~ Of relevance to the mechanism of the photo- chemically induced rearrangement of dialkyl-trans -1,3-dienylboranes is the finding that the independently generated cis-isomers rapidly cyclize with concur- rent alkyl migration to (13).46 The rearrangement is formally isoelectronic to the second migration step in the reactions between acyIating agents and alkynyl- or cyano-borates. R (12) (13) Reports of new reactions of borate salts have been few in 1977.However a reaction of great potential value in view of the number of structural features capable of modification is the Michael addition of alkynylborates to a,p-unsaturated systems depicted in general form by equation (l).47As yet only nitroethenes have given synthetically useful yields of organic products although reaction with even these is inhibited by excessive substitution [R3 = R4= Me equa- tion (l)]. R’ Li+R:BCECR2 +R3R4C=C(X)R5 + R:BL=CR2-CR3R4-CR5XLi+ (1) Following on from last year’s claim for the generation of ‘methylborylene’ (MeB:) the analogue ‘naphthylboryne’ (a-NpB:) has been proposed as a primary product in the photolysis of ~-NP,B.~~ Evidence for this species rests solely on indirect product studies. Firstly oxidation products observed were cyclohexanol when cyclohexane was solvent and cyclohexane-cis- 1,2-diol for reaction in cyclo- hexene the latter uia the assumed ‘stable’ species (14); and secondly Cl- ions and COCl were observed after hydrolysis and oxidation with CC14 as solvent If (14)is (14) indeed stable further data on its characterization are awaited but in the meantime readers are invited to make up their own minds on the rightness of the claim for the generation of a boryne.45 L. Killian and B. Wrackmeyer J. Organometallic Chem. 1977,132 213. 46 G. Zwiefel S. J. Backlund and T. Leung J. Amer. Chem. SOC.,1977.99 5192. 4’ A. Pelter and L. Hughes J.C.S. Chem. Comm. 1977,913. 48 B. G. Rarnsey and D. M. Anjo J. Amer. Chem. SOC.,1977,99 3182.Organometallic Chemistry-Part (ii) Main -Group Elements The methylated cyclopentadienylborane (15; X =BC12) prepared from (15; X = Me3Ge) and BC13 is fluxional on the 'H n.m.r. time scale down to -80°C due to rapid BCl sigmatropic shifts.49" In contrast (15; X = B12) undergoes further reac- tion with B13 yielding the novel salt (16) characterized by a full range of spec-troscopic and conductivity techniq~es.~~' The bonding of the Csvpyramidal cation in (16) is assumed to be similar to that in the dication C,(CH3b2'. An interesting (15) (16) series of 1,3-shifts has been observed for (17; Scheme 6).50Addition of MeLi to (17; R2 = Me) leads to fragmentation products resulting from migration of R' from C to B (Scheme 6). When R' # R3 R3BMe2 is also observed consistent with the rapid sigmatropic shift of the BMe unit prior to ate-complex formation.R'QR3 d- R'@R3BR~( R'@R3BRZ( A.-e*c. R' , R3 R' R3 R' R' R " BMe2 R' R' 1 ArLi L 7+ BR~+borepin R' R'BMez Ri R3 R'BMe2-Li' R3 Reagent i LiMe (R2=Me) Scheme 6 The recently published MNDO method has been employed to calculate various data for boranes (AHf geometries IP dipole moments and proton affinities) which agree much more satisfactorily with known experimental data than did the previous MIND0/3 values5* Aluminium Gallium and Thallium.-The lack of ready synthetic approaches to alkylalanes has prevented exploitation of their full potential in organic synthesis so approaches reported in 1977 which go some way in removing this deficiency open up important new areas for future research.The alkene- or alkyne-derived metal P. Jutzi and A. Seufert (a)Angew. Chem. Internal. Edn. 1977 16,41; (b) ibid. 1977 16,330. J. J. Eisch and J. E. Galle J. Organometallic Chem. 1977 127,C 9. " M. J. S. Dewar and M. L. McKee J. Amer. Chem. SOC. 1977,99 5231. 146 M. G. Hutchings complexes Cp2Zr(C1)R readily transfer an alkyl or alkenyl group respectively to AICl3. The resulting species react rapidly with acyl chlorides at -30°C to give quantitative yields of ketones whereas the starting Zr complex reacts at best only slowly.52" An even greater synthetic potential results from modifications which use the transition metal catalytically. Both AIH3 and more significantly LiAIH4 in the presence of TiC14 or ZrC14,52b as well as readily prepared (PrlNkAlH in the presence of Cp2TiC12,52c give alkylalanes or alanates on reaction with alkenes.The reactions show analogies to hydroboration with BH3 in their sensitivity to steric effects (allowing preferential reduction of the terminal alkene bond in noncon- jugated dienes) and preference for strongly basic ethers as solvents. By suitable choice of reagents further reaction generates alkane alkyl halide or alcohol (02 oxidation) in high yields. The reagents are cheap and the conditions mild but a critical limitation to the generality of the reaction is the conversion of internal alkenes to terminal alkyl groups. Of course this may be turned to advantage when mixtures of isomeric alkenes are used as starting material and the terminally substituted product is required.A further type of novel organoalane formulated as (18) is also derived by transfer of a group from the more readily formed Zr derivative Cp2Zr(CI)COR.53 0 I1 (C12Al-C -R)x (18) While masked carbonyl functionalities have found favour as one source of acyl anion equivalents the more direct progenitors of this synthon acylmetallics have proved singularly disappointing as synthetic intermediates. However the acyl moiety present in (18) is highly susceptible to electrophilic attack. Thus (18) is protonated (or deuterated) at the carbonyl carbon by water (or D20),and is both C-and 0-acylated with CH3COCl. The possible existence of a stable Group I11 acylmetallic species such as (18) is noteworthy in that no stable acylborane analogue has yet been prepared.Attempts at further structural characterization of (18)would be desirable. BukAlH reacts with Cp2ZrC12 to give (19) which acts as one of the few homo- geneous catalysts for the industrially significant Fischer-Tropsch process (reductive polymerization of CO).54 Straight chain C1-Cs alcohols are obtained remarkably from a room temperature reaction at atmospheric pressure all carbon atoms of the products being incorporated from the CO feedstock. H-AlBu; /\ cp2zrH /c' H-AIBu; (19) " (a)D. B. Carr and J. Schwartz J. Amer. Chem. SOC. 1977 99 638; (b) F. Sato S. Sato H. Kodama and M. Sato J. Organometallic Chem. 1977 142 71; (c)E. C. Ashby and S.A. Noding Tetrahedron Letters 1977 4579. 53 D. B. Carr and J. Schwartz J. Organometallic Chem. 1977 139 C 21. 54 L. I. Shoer and J. Schwartz J. Amer. Chem. SOC. 1977,99,5831. Organom eta llic Chemistry -Part (ii) Main-Group Elem en ts An unusual type of isomerism exists in the oxamide complexes (20) and (21) of Me I Thallium (111) trifluoracetate brings about nonphenolic oxidative coupling of aromatic systems. The reaction is tolerant of nitrogen- and oxygen-containing functionalities and is applicable to intramolecular couplings as in a synthesis of the aporphine alkaloid (f)-~coteine.~~ The corresponding thallium (111) acetate effects an unprecedented aromatic acetoxylation during the coupling. 5 GroupIV Silicon.-One of the archetypal components of organic chemistry the benzene ring has still to find a Si analogue.However a report in 1977 claims evidence for the generation and trapping of the first silabenzene (22; Scheme 7).57 Unfortunately an alternative route to the observed (23) involving carbanionic attack by the lithiated intermediate (24) and subsequent ring closure cannot be excluded on the evidence available. Nor are other anticipated products observed which might be indicative of the intermediacy of (22) such as dimers. In the (24) (22) Reagents i (Me3Si)zNLi -77 "C; ii CF3C=CCF3 Scheme 7 absence of more compelling data the case for a silabenzene must at best remain unproven. Two related synthetic approaches have been used to prepare species which undergo reactions now generally ascribed to ~ilaethenes.~' By varying R (Scheme 8) the silaethene can be generated in solution and trapped at tempera- tures as low as -50 "C (R =Ts) to give products resulting from initial 2 +2 2 +3 and 2 +4 cycl~additions.~~" In the absence of trapping agents dimers are formed.58 Furthermore other more stable lithiated intermediates (e.g.R = Ph2PO) can be isolated and subsequently thermolysed in vucuo the silaethene being detected 5s P. Fischer R. Graf J. J. Stezowski and J. Weidlein J. Amer. Chem. Soc. 1977 99,6131. E. C. Taylor J. G. Andrade and A. McKiIlop J.C.S. Chem. Comm. 1977,538. ''T. J. Barton and D. S. Banasiak J. Amer. Chem. SOC.,1977,99 5199. '* (a)N. Wiberg and G. Preiner Angew. Chem. Internat. Edn.1977,16,328; (b)P. R. Jones and T. F. 0. Lim J. Amer. Chem. SOC.,1977,99,2013. 148 M. G. Hutchings Br Br OR Br OR Li II II II MezSi-C(SiMe3)~ Me2Si-C(SiMe& b Me2Si-C(SiMe3)2 -% Me2Si=C(SiMe3)2 Reagents i AgOR; ii Bu"Li; iii A Scheme 8 directly by mass spe~trometry.~~" After last year's report of preparations of stable silacyclopropenes there have now been several discussions of their reactions with methanol and with ketones alkenes alkynes dienes and dimethylsilylene all leading to insertion and ring Pd catalyses dimerization to dis- ilacycl~hexadienes.~~~~' Sila-allene (25a) has been proposed as a product of the photolysis of (26) on the basis of isolation of (25b) following initial in situ cyclo-addition with solvent a~etone.~'" A convenient and eacient synthesis of Me2Si =O results from abstraction of oxygen from DMSO by dimethylsilylene.60 Intermediacy of the first oxasilacyclopropane (27) has been claimed but as usual depends solely on product analyses.61o Novel intramolecular reactions of the carbene (28) have been reported.6l6 Me,Si / Me 0 Ph \ /\ Ph Me PhCGC -SiMe2SiMe3 MezSi -CPhz Me2ii -&Ph (25) a; X=Si b;X=C In the near absence of experimental data on free sila-alkenes the latest compu- tational study of HzSi=CHz offers several useful insights.62 Ab initio calculations which take into account electron correlation effects have predicted HzSi=CH2 to be a singlet planar species in its ground state 28 kcal mol-' below the first triplet.The difference in energy between the planar and orthogonal geometries taken as a reflection of the .n-bond strength has the surprisingly high value of 46 kcal mol-' whereas the barrier to the exothermic dimerization is less than 14 kcal mol-'.The polarity (6 -C=Si S +) and low lying T*level are responsible for the experiment- ally observed reactivity of such species. Moreover the polarization causes the C 2p.n and Si 3p.n orbitals to be enlarged and contracted respectively thus vitiat- ing the conventional view that 'mismatching' of these orbitals is responsible for the weakness of the .n-bond. A cheerless prospect is that bulky substituents will be insufficient to prevent dimerization and attempts to alter the polarity will only result in counterproductive weakening of the .n-bond.A provocative note concerning ab initio calculations on divalent Si has predicted that CHz=Si is considerably more stable than HCESiH although further results predict 59 (a)M. Ishikawa T. Fuchikami and M. Kumada J. Amer. Chem. Soc. 1977,99,245;(b)H. Sakurai Y. Kamiyama and Y. Nakadaira ibid. 1977,99,3879;(c)D. Seyferth S. C. Vick M. L. Shannon T. F. 0. Lim and D. P. Duncan J. Organometallic Chem. 1977,135 C37; (d)D. Seyferth and S. C. Vick ibid. 1977 125 C 11; (e) M. Ishikawa K.-I. Nakagawa and M. Kumada ibid. 1977 131 C 15; (f)M. Ishikawa T. Fuchikami and M. Kumada J.C.S. Chem. Comm. 1977,352. 6o H. S. D. Soysa H. Okinoshima and W. P. Weber J. Orgunometallic Chem. 1977,133 C 17. '' (a)W. Ando M. Ikeno and A. Sekiguchi J. Amer. Chem. Soc.1977,99,6447; (b)W. Ando and A. Sekiguchi J. Organometallic Chem. 1977 133 2 19. 62 R. Ahlrichs and R. Heinzmann J. Amer. Chem. SOC.,1977,99,7452. Organometa11ic Chemistry -Part (ii) Main -Group Elem en ts 149 CH2=SiH2 to be somewhat more stable than H2+ CH2=Si.63 Nevertheless it was suggested that it would be yorth searching experimentally for unsaturated divalent organosilicon species. The burgeoning synthetic chemistry based on vinylsilanes has prompted several new reports of syntheses of these species. Alkynylsilanes react with hydroborating agents leading to a,P -substituted vinylsilanes useful for conversion to a-silaketone~,~~~ carboxylic and stereospecifically a-alkylated vinyl-silane~,~~' and with Cu-promoted Grignard reagent^.^' An alternative approach relies on the addition of vinyl-lithiums to Me3SiC1.66 An important reaction of vinylsilanes is their oxidation to epoxysilanes themselves precursors to carbonyl and stereochemically defined' hetero-substituted alkenes.68 a-Chloroalkylsilanes may be lithiated and react with ketones to give epoxysilanes directly.Since these may be cleaved to aldehyde the overall procedure is one of reductive nucleophilic a~ylation.~~ Because of decreased C-C1 polarity a-chloroalkylsilanes undergo anomalous nucleophilic substitution reactions both in solution (Scheme 9)69aand vapour-solid D + -n R3 i-CH2 + D3SiCH2CI -R3P-CH2SiD2-CH2 pCI -+ R3kH2SiD2CH2DCI-Scheme 9 heterogeneous phases.69b Another paper on substitution reactions at Si has poin- ted out that reagents which favour 1,2-addition to enones (hard bases charge control) substitute at Si with retention of configuration whereas others which add 1,4 to enones (soft bases frontier orbital control) react with inversion at Si.This correlation supports the hypothesis that the electronic character of the nucleophile dictates the stereochemistry of nucleophilic substitution at Si7* A range of tech-niques has shown that both a concerted dyotropic process as well as a 2-step radical process occurs in the thermal rearrangement of (29) to (30),71" whereas silylmethyl acetates are believed to rearrange (alkyl migration) via an unprecedented inverted Si ylid (31),71breminiscent of species frequently invoked in borate chemistry. 63 J.N. Murrell H. W. Kroto and M. F. Guest J.C.S. Chem. Comm. 1977 619. 64 (a)A. Hassner and J. A. Soderquist J. Organometallic Chem. 1977 131,C 1; (6)G. Zwiefel and S. J. Backlund J. Amer. Chem. SOC. 1977 99 3184; (c) K. Uchida K. Utirnoto and H. Nozaki Tetra-hedron 1977 33,2987. 65 (a) H.Westmijze J. Meijer and P. Vermeer Tetrahedron Letters 1977 1823; (b)M. Obayashi K. Utimoto and H. Nozaki ibid. 1977 1805. 66 (a)R. T. Taylor C. R. Degenhardt M. P. Melega and L. A. Paquette Tetrahedron Letters 1977 159; (6) D. Seyferth J. L. Lefferts and R. L. Lambert jun. J.Organometallic Chem. 1977 142 39. (a) C. Burford F. Cooke E. Ehlinger and P. Magnus J. Amer. Chem. SOC. 1977 99 4536; (b) F. 67 Cooke and P. Magnus J.C.S. Chem. Comm. 1977 5 13.68 P. F. Hudrlik A. M. Hudrlik R. J. Rona R. N. Misra and G. P. Withers J. Amer. Chem. SOC.,1977 99 1993. 69 (a) H. Schrnidbaur and B. Zirnmer-Gasser Angew. Chem. Internat. Edn. 1977 16 639; (6) S. P. Hopper M. J. Tremelling R. J. Ginsberg and P. C. Mendelowitz J.Organometallic Chem. 1977 134 173. 70 R. J. P. Corriu and C. Guerin J.C.S. Chem. Comm. 1977 74. 71 (a)M. T. Reetz Chem. Ber. 1977,110,954,965;(b)M. T. Reetz and N. Greif Angew. Chem. Internat. Edn. 1977 16 712. M. G. Hutchings (29) (30) (31) Further parametrization has permitted extension of empirical force field cal- culations to p~lysilanes,~~ and using this technique Ph3SiSiPh3 is calculated to adopt a D3 conformation and to be strain free unlike the unknown Ph3CCPh3.72 Ph3SiOSiPh3 has a linear Si-0-Si unit in the crystalline phase and in agreement with predictions of the above calculations has Sg symmetry (two staggered antichiral C3 propeller^).^^ Finally attention is drawn to the remarkable observation that (32) shows Me group inequivalence in its ‘H n.m.r.spectrum up to at least 150°C whereas its C and Sn analogues have much lower barriers to substituent rotation.74 What happens in the Ge and mixed derivatives? Me,Si SiMe Germanium Tin and Lead.-The rearrangements of benzylideneaminotin (IV) halides (33) to (44) are the first examples of ortho-metallation involving Sn.75 The full scope of the reaction has yet to be demonstrated but it fails in analogous Si and Ge systems. The cycloperoxidation of bistriflates by means of R3Sn02SnR3 has given a route to the bicyclic endoperoxide (35) (of relevance in the prostaglandin field) from (36).76 Me3SnLi is readily prepared and adds 1,4 to conjugated enones Vn, fifi&-JTfOyJ-OTf R \ ’R R \ ’R (33) (34) (35) (36) the resulting stannylated enolate being set up for alkylation and possible further modification (Scheme lo).” The transposition of the carbonyl group by means of oxidative cleavage of the C-Sn bond is particularly noteworthy and demonstrates the superiority of this reageqt-over Me3SiLi which otherwise reacts analogously.The Sn-substituted ylid Ph3PCHCH2SnMe3 undergoes the Wittig reaction with carbonyl compounds to give allyltrimethylstannanes which are valuable precursors 72 J.P. Hummel J. Stackhouse and K. Mislow Tetrahedron 1977 33 1925; W. D. Hounshell D. A. Dougherty J. P. Hummel and K. Mislow J. Amer. Chem. Suc. 1977,99 1916. ’’ C. Glidewell and D. C. Liles J.C.S. Chem. Comm. 1977,632. 74 D. Seyferth and S. C. Vick J. Orgunometallic Chem. 1977 141 173. ’’ B. Fitzsimmons D. G. Othen H. M. M. Shearer K. Wade and G. Whitehead J.C.S. Chem. Comm. 1977,215. 76 M. F. Salomon and R. G. Salomon (u)J.Amer. Chem. Suc. 1977,99 3500; (b) ibid. 1977,99 3501. 77 W. C. Still J. Amer. Chem. SUC.,1977 99,4836. Organometallic Chemistry -Part (ii) Main -Group Elements 151 i,ii &c5H11 &c5H11 (j,c5H11 Me SnMe SnMe 0 Reagents i Me3SnLi; ii C5Hl1I; iii MeLi; iv CrO-jZpy Scheme 10 to difficultly accessible allyllithi~ms.~~ Moreover the Sn compounds themselves are intrinsically useful in that they add to acyl chlorides with Rh catalysis giving good yields of allylket~nes.~' Hyperconjugation by CH2MMe3 (M = Si Ge Sn or Pb) has been investigated using various n.m.r.probes in naphthyf'" and styry1806 systems. The overriding conclusion is that hyperconjugative electron-release in the neutral ground-state follows the order Pb -Sn >Ge -Si in contrast to the commonly-accepted order Pb >Sn >Ge >Si based on studies of electron deficient compounds.8oa Me3M groups which are bound directly to an aromatic nucleus donate electron density by an inductive/field effect but act as negative hyperconjugative substituents.80b 6 GroupV A synthetically useful series of reactions based on lithiated alkylarsine oxides and dependent on the thermal reaction of the halogenated arsorane RPh2AsX2(X = C1 Br or I) for the critical cleavage of the R-As bond is summarized in Scheme 11.81a.6 Two-carbon homologation of alkyl halides may be effected indirectly in R4R5C= CHBr -CH~R' J R'=H ii,iii.v.vi R'R2CHR3 II I 'ii,viii R4R5C=CBr2 Ph2As-CHR' R1= Reagents i LiNPri; ii R2X; iii LAH; iv ha12 or S02C12-A; v Br2-A; vi R3(=OH-or PhS-); vii R4R5D=0; viii excess BrZ-A.Scheme 11 good yield by addition of their alkyllithium derivatives to the vinyl group of diphenylvinylarsane followed as above by bromine or sulphuryl chloride.81' The '* D. Seyferth K. R. Wursthorn and R. E. Mammarella J. Org. Chem. 1977,42 3104. 79 M.Kosugi Y.Shimizu and T.Migita J. Organometallic Chem. 1977,129,C 36. *' (a)W. Adcock D. P. Cox and W. Kitching J. Organometaiiic Chem. 1977 133 393; (b) W. F. Reynolds G. K. Hamer and A. R. Bassindale J.C.S. Perkin II 1977 971. 81 (a)T. Kauffmann H. Fischer and A. Woltermann Angew. Chem. Internat. Edn. 1977 16 53; (b)T. Kauffmann R. Joussen and A. Woltermann ibid. 1977,16 709;(c)T. Kauffmann H. Ahlers H.-J. Tilhard and A. Woltermann ibid. 1977 16 710. M. G. Hutchings + As-containing a-amino-acid analogue Me3AsCH2C0g H20 has been isolated from the western rock lobster and fully characterized. Despite its emotive charac- ter the authors say that its existence does not necessarily reflect environmental pollution.82

ISSN:0069-3030    

DOI:10.1039/OC9777400136

出版商:RSC    

年代:1977

数据来源: RSC

摘要:

7 Electro-organic Chemistry By R. LINES Laboratory of Organic Chemistry The Norwegian Institute of Technology The University of Trondheim N- 7034 Trondheim NTH Norway 1 Introduction The current state and growth of electrosynthetic chemistry together with an outline of the most promising reactions of recent years is the subject of a Russian review.' Another Russian paper2 surveys current problems in the anodic fluorination of organic compounds. On the cathodic side a useful review3 written from a physical- organic standpoint has appeared concerning the electroreduction of organic compounds both in aprotic and aqueous media. 2 Anodic Processes The Anodic Oxidation of Carboxy1ates.-Alkyl benzenes are reported4 to be obtained in good yield by the Kolbe electrolysis of 1-alkyl- 1,4-dihydrobenzoic acids.Thus decarboxylation of (1)offers a useful synthetic route to the 1-alkyl naphthalenes. (1) A systematic study5 of the migratory aptitudes of the alkyl substituents (R' or R2) in the oxidation of P-hydroxy carboxylic acids (2; R3= H) revealed preferential migration of olefinic cyclopropyl or benzylic groups. OH 0 0 -2e II II R'R2CkHR3COZH -R2CCHR'R3+R1CCHR2R3 -C02/-H20 (2) Scheme 1 ' M. Ya. Fioshin Soviet Electrochem. 1977 13 1. I. N. Rozhkov Russ. Chem. Rev. 1977,45615. P. J. Elving Canad. J. Chem. 1977 55 3392. J. Slobbe J.C.S. Chem. Comm. 1977,82. ' T. Shono J. Hayashi H. Omoto and Y. Matsumura Tetrahedron Letters 1977,31 2667. 153 154 R. Lines When R3=Me however the selectivity was much diminished reflecting the importance of the conformation of the intermediate carbenium ion.The results of the study were applied to the synthesis of dl-muscone (4)via the olefinic acid methyl ester (3) (Scheme 2). 0 HO ,CH2C0,Me II The electrolysis of acylaminomalonic acid monoesters6 in acetic acid solutions has been found to produce a good yield of the useful synthetic intermediates 2-acetoxy-2-amino acid derivatives. Similarly the 3-acetoxy-3-amino acid deriva- tives were obtained from the oxidation of 3-alkoxycarbonylalanine derivatives in acetic acid-THF media. Anodic oxidation of 4,4-diphenyl but-3-enoic acid' (5; R =H) in methanol results in a readily separable mixture of isomeric diphenyl ally1 ethers (6,7; R' = H R2=Me).Similarly electrolysis of the Stobbe half-ester (5; R = C02Et) in ethanol yields the corresponding esters (6,7; R' = CO,Et R2=Et). R2 Ph HRPh CH2CO2- -2e MeOH or EtOH Ph Ph 0 R' +%HR1 Ph CH2OR' Ph (51 (6) (7) Scheme 3 The relative simplicity of the electrochemical route compared with the alter- native chemical syntheses makes this an attractive method for the preparation of these compounds. The Anodic Oxidation of Neutral Organic Compounds.-The anodic chemistry of the tropane alkaloids has been studied' in both acetonitrile and benzonitrile. Controlled potential electrolysis of tropane (8; R =Me) in acetonitrile results in the uptake of 0.79Fmol-' to yield a mixture of (protonated) tropane (57.6'/0) nortropane (8; R = H 13.6%) and the N-carboxaldehyde (8; R = CHO 5.3%).Both nortropane and the N-carboxaldehyde are believed' to be derived from the iminium ion (9). The aldehyde is the major product in the presence of hydroxide. R\ (8) (9) (10) CH2* NRQ/N-ND T. Iwasaki. H. Horikawa K. Matsumoto and M. Miyoshi J. Org. Chem. 1977,42 2419. 'F. M. Banda and R. Brettle J.C.S. Perkin f 1977 1773. B. L. Laube M. R. Asirvatham and C. K. Mann J. Org. Chem. 1977,42,670. Elec tro -organic Chemistry 155 The oxidation of nortropane results in the formation of both C-N (8;R = CH2CN) and N-N bonds (10). The cyanide is thought to arise from generation of solvent radicals formed from the oxidation of hydroxide ions. OH-CH3CN -e CH2CN+H20 Scheme 4 This is supported by the observation that binortropane (10) is the major product in benzonitrile where solvent radical formation is prevented.The anodic cyanation of t-aliphatic and heterocyclic amines has been the subject of a systematic study.' Preparative electrolysis of the amines at Pt in aqueous methanolic sodium cyanide solution yielded a-cyan0 amines in reasonable yields (30-60%). The ease of cyanation was found to be in the order (CH,) >(CH2)5>Me >Et >Pr" >Pr' = 0. This reactivity series was rationalized' by consideration of the geometry of the amine on the electrode surface. Deprotonation the key step in the reaction must occur at the a-carbon situated in a position easily accessible to the electrode. Obviously this is not the case for the isopropyl group.Similarly the configuration of the adsorbed cyclic amines encourages substitution at the a-ring-carbon and for N-isopropylpiperidine ring substitution was the sole reaction. The chemistry of the anodic oxidation of cyclohexene in the presence of cyanide ion turns out to be rather complex.'o In methanolic sodium cyanide solution at Pt not only cyanation but also methoxylation and isocyanation were observed. The isocyanation reaction was highly potential dependent. It is interesting to note that only tarry products were formed when the electrolyses were performed in acetoni- trile. Anodic cyanation reactions carried out in emulsion systems are claimed to give superior results over the more conventional solvent supporting electrolyte combinations.Eberson and HelgCe" now have demonstrated the synthetic utility of emulsion electrolysis for the preparation of 4-alkoxy-4-cyano-biphenyls;a class of liquid crystals. The electrochemical method using aqueous sodium cyanide dichloromethane and tetra n-butylammonium sulphate gave at least a four-fold yield increase over the alternative five-step chemical synthesis. A new mode of oxidative coupling of substituted bibenzyls has been reported." Anodic oxidation of (11;Z = 0)was expected to yield the aporphine skeleton whereas in acetonitrile the bridged lactone (12) was isolated. The mechanism is thought to involve formation of a cation radical in ring a followed by proton loss from the 4-position of the isochromanone ring. Further oxidation of the resulting radical to the cation then serves as an electrophile towards the veratryl ring to give (12).In acidic solution (CH2Cl-TFA) where proton loss is inhibited the spirodienone (13; 33%) is formed. A rather rare example of ortho-coupled biphenyl^'^ results from the controlled potential electrolysis of methoxylated aryl benzoates. The biphenyls are obtained T. Chiba and Y. Takata J. Org. Chem. 1977,42 2973. K. Yoshida T. Kanbe andT. Fueno J. Org. Chem. 1977,42 2313. L.Eberson and B. Helgke Actu Chem. Scund. 1977,B31,813. I. W.Elliott jun. J. Org. Chem. 1977,42 1090. M. Sainsbury and J. Wyatt J. C.S. Perkin I 1977 1750. 156 R. Lines Meorno Me0 OMe Z= 0or NMe (11) OMe (13) in high yield after the passage of 1Fmol-’. Further oxidation results in ortho- and para-quinones.An interesting detail here is that the products can be accounted for by a 2Fmol-’ scheme whereas experimentally 3Fmol-’ is needed for quinone formation. A useful synthetic route to 5,5’-disubstituted hydruillic acids (15) is reported14 from the controlled potential oxidation of 5-alkyl substituted barbituric acids (14) at a pyrolitic graphite electrode (Scheme 5). (14) R’ R2 = H or Me R3= Me Et or PhCH2 Scheme 5 Examination of the 1-methyl and 1,3-dimethyl barbituric acids over the pH range 0-13 revealed much more complex behaviour. l5 Formation of hydruillic acid (15; R3= H) remains the primary process but further oxidation at the 5-position and subsequent reaction with the parent molecule (or the anion at pH> pK,) yields an open chain trirner which by further oxidation finally gives a cyclic trimer.The first example of the electrochemical difunctionalization of saturated hydro- carbons has appeared.16 Anodic oxidation of adamantane in TFA at the potential of the second wave gives after workup adamantane-l,3-diol (70%). Similarly NN’-adamantane- 1,3-diyl bisacetamide (58%) results from oxidation in acetoni- trile. These two nucleophilic solvents are particularly suitable for the high anodic S. Kato and G. Dryhurst J. Electroanalyt. Chem. Interfacial Electrochem. 1977 79 391. l5 S. Kato and G. Dryhurst J. Electroanalyt. Chem. Interfacial Electrochem. 1977 80 181. l6 A. Bewick G. J. Edwards S. R. Jones and J. M. Mellor J. C. S. Perkin I 1977 1831.Electro-organic Chemistry potentials required Extension of the method to non-bridged hydrocarbons where concomitant olefin formation becomes important may require even more efficient nucleophiles to trap the reaction intermediates. A novel combination of light and electrochemistry has been used to effect the oxidation of organic c~mpounds.~’ A catalytic amount of a quinone is irradiated in the presence of the substrate and a graphite anode at the potential of the quinone- hydroquinone couple. The photochemical reaction produces the oxidized substrate together with the hydroquinone which is electrochemically reconverted into the quinone. Last year’s report [Ann. Reports (B) 1976,73 1431 cited the slow intramolecu- lar coupling of the dication of the [2,2]metacyclophane (16; R=OMe).In a voltammetric study of a series of alkylated [2,2]metacyclophanes Sat0 and Kamada18 suggest the involvement of a transannular cation radical of the 5,13-dimethyl derivative (17). R -@-R __ -(16) (17) Preparative electrolyses of (16; R = H or Me) resulted” in successive oxidation deprotonation reactions to give ultimately the corresponding pyrenes. The dications of the tetrathioethylenes (18; n = 2 or 3) generated in acetonitrile undergo a novel endocyclic to exocyclic rearrangementlg (Scheme 6). Rotation about the central C-C bond of the product provides the driving force of the rearrangement by minimizing the coulombic repulsion between the positive sulphur atoms. The mechanism is ~uggested’~ to be a simultaneous intramolecular migration of two u bonds an example of a dynotropic rearrangement.This same rearrangement reaction characterizes the anodic chemistry of the ortho-thio-oxalates*’ of type (19) (Scheme 7). An interesting feature is that (20) is not the primary product of the rearrangement of the cation of (19). Both the pyrolysis and photolysis of (19) give (20) directly which suggests that the electrochemical frag- mentation is directed by conformational and/or solvation effects. ” J. M. Bobbitt and J. P. Willis J. Org. Chem. 1977 42 2347. T. Sat0 and M. Kamada J. C. S. Perkin II 1977,384. l9 R.M. Harnden P. R. Moses and J. Q. Chambers J. C. S. Chem. Comm. 1977,11. ’* P. R.Moses R. M. Harnden and J. Q. Chambers J. Electroanalyt.Chem. Interfacial Electrochem. 1977,84 187. 158 R. Lines -e -e -e *-LL 77 Scheme 7 3 Cathodic Processes The Cathodic Reduction of Organic Cations.-A new class of stable cation radicals has been prepared2’ by reduction of the diphosphiacyclohexadiene salts (21; R # H). Further reduction yields the highly reactive diphosphabenzenes (22). The cation radicals are unusual in that they decompose by protonation in the presence of strong acids; a property no doubt arising from the strong carbanionic nature of the ring-carbons. Ph ,Ph Ph ,Ph Ph ,Ph +e SH 7 L -+ products Jr’r” RP R Ph/ ‘Ph Ph/ \Ph Scheme 8 The Cathodic Reduction of Neutral Organic Compounds.-Electrogenerated nitrobenzene anion radical in DMF is reported by Wagenknecht22 to react rapidly with alkyl halides to give high yields of NO-dialkylphenyl hydroxylamines.Another useful synthesis involves the electrochemical reductive acylation of electron-deficient ole fin^.'^ Reduction of ethyl cinnamate at a Hg cathode in DMF containing acetic anhydride gave ethyl 3-phenyl-4-oxopentanoate (75%) and ethyl 2-benzyl-3-oxobutanoate (2%). Anthracene however under similar conditions gives the vinyl ester (23) in 66-75% yield.24 The reductive coupling of anthracene with 1,2-and 1,3-dihalide~~~ has been shown by cyclic voltammetry to proceed catalytically. Coupling of the 1,3-dihaIides 21 R. D. Rieke R. A. Copenhafer C. K. White A. Aguiar J. C. Williams jun. and M. S. Chattha J. Amer. Chem. SOC.,1977 99 6656.22 J. H. Wagenknecht J. Org. Chem. 1977,42 1836. 23 H. Lund and C. Degrand Tetrahedron Letters 1977,40 3593. 24 H. Lund Acta Chem. Scand. 1977 B31.424. 2 25 E. Hobolth and H. Lund Acta Chem. Scand. 1977 B31,395. Electro -organic Chemistry 159 in the 1-or 2-positions of anthracene results in ring-closure to cyclo-pentanoanthracene derivatives (Scheme 9). &&, n=7-8 + / + Br(CH2),Br -\\ \\ / Scheme 9 The corresponding catalytic reductive alkylation of quinolines and isoquinolines with t-butyl halides leads to t-butylated heterocyclic compounds.26 A large percentage of the alkylation takes place in the carbocyclic ring. Although many isomers are formed and the overall yield of each isomer is low (10-20°/0) the method has the advantage of experimental simplicity.Electroreduction of halides continues to provide interesting chemistry. The tetra-bromo compound (24) exhibits two major voltammetric peaks.27 Electrolysis at the first wave consumed 3F mol-' and yielded 1,2-dibromobenzocyclobutene and polymers. It was deduced27 that the parent compound (24) is an equilibrium mixture of two conformers and that each product could be ascribed to a single conformer. Reduction of (24) at the second wave gave the tetracyclic product (25) the result of a rearrangement of the Diels-Alder benzocyclobutadiene dimer (Scheme 10). Scheme 10 The as yet unreported dimethylene cyclopropanone (27) is cited 28 as an inter- mediate in the electrolysis of the a,a '-dibromoketone (26).Electroreduction of the readily accessible 2,2,2-trichloroethanol~~~ offers a direct route to 1,l-dichloro-olefins (Scheme 12). Care must be taken to ensure an acidic solution otherwise the alcohol is the sole product. 26 C. Degrand and H. Lund Acta Chem. Scand. 1977 B31,593. 27 L. Rampazzo A. Inesi and R. M. Bettolo J. Electroanalyt. Chem. Interfacial Electrochem. 1977 83 341. L. Rampazzo A. Inesi and A. Zeppa J. Electroanalyt. Chem. Interfacial Electrochem. 1977 76 175. 29 A. Men Angew. Chem. Znternat. Edn. 1977,16,57. 160 R. Lines OH OH R'R2(!XC13 A R'R2C = CCI2 +R'R2LCHCl2 Reagents i Hg cathode 95% EtOH-Et3NHCI Scheme 12 A re-examination3* of cathodic nucleophilic substitution of p-bromobenzo-phenone [Ann. Reports (B),1974 713 2261 has led to the conclusion that the process proceeds exclusively via a bimolecular radical chain-mechanism.A.c. polarographic measurements as well as careful electrolytic experiments showed that the alternative exchange-current pathway could account for only 2% of the total products. The revised mechanism is shown in Scheme 13. (28)+ (30) + PhCOC6H4SPh+(29) (4) (30)+$ [PhC(OH)C6ff4SPh]2 (5) Scheme 13 The same authors31 have presented an efficient method for the electropinacol- ization of ketones. The process involves the use of tetra-alkylammonium salts in carefully dried acetonitrile. Under these aprotic conditions the tetra-alkylam- monium ions are thought to form tight ion-pairs with the ketyl anion radicals and allow dimerization while inhibiting further charge transfer.It is arguedY3' by consideration of the mechanism given in Scheme 13 that the pinacol is essentially a termination product and therefore pinacolization occurs in bulk solution remote from the electrode surface. Pinacol formation characterizes the primary step in the reductive coupling of 1,3-diket0nes.~~ The pinacol from 1,3-diphenyl propane-1,3-dione (31; R = H) is unstable in acidic solution and cyclizes to (32) and a tricyclotrioxanonane (33). Reduction of the corresponding substituted phenyl derivatives (3 1; R = halogen Me or OMe) leads to hexadienediones which can be further reduced to hexene- diones. Compound (33) is thought to result from the dl form of the intermediate pinacol by a double intramolecular ketalization followed by dehydration.Ph OH OH 0 pcOph p-RC6H4 uC6H,R-p ph;;&ph (31) OH (33) (32) 30 W. J. M. van Tilborg C. J. Smit and J. J. Scheele Tetrahedron Letters 1977 24 2113. 31 W. J. M. van Tilborg and C. J. Smit TefruhedronLetters 1977.41 3651. 32 A. J. Klein and D. H. Evans I.Org. Chem. 1977,42,2560. Electro -organic Chemistry 161 A new hydrogen anode33 [Ann. Reports (B) 1974 71 2281 of composite construction has been evaluated and although more efficient than its predecessors the maximum current density and life-time are still limited and need to be improved for more widespread use. An interesting example of conformational effects on fragmentation patterns has been noted in the cathodic cleavage of methyl o-alkyl substituted aryl ~ulphones.~~ Phenyl methyl sulphone is known to undergo exclusive methyl-sulphur cleavage but the introduction of ortho-substituents promotes aryl-sulphonyl fission and this becomes the major mode with the ortho-t-butyl substituted compound.Aryl- sulphonyl cleavage is characteristic of the cyclic aryl sulphones and comparison with molecular models that the conformation of the ortho-substituted sulphones approached that of the cyclic compounds. The electrochemical behaviour of DL-a-lipoic acid3' (a co-factor for a number of enzyme catalysed reactions) has been studied in order to gain some insight into its biological redox mechanism. The oxidized acid (34)cannot be reduced in water but undergoes direct reduction to the dianion in acetonitrile at -1.92 V (SCE)-an extremely negative potential.The acid is however readily reduced by elec- trochemically generated hydrogen which strongly suggests that reduction of the disulphide linkage occurs by an atom transfer-mechanism. (34) '* (34)' Scheme 14 Martigny and Sim~net~~ have devised an autocatalysed cathodic elimination using cY,a'-disubstituted 1,2-diphenyl ethanes. Reduction of (35) in DMF gives a product (trans -stilbene) which is more easily reduced than the parent. The rela- tively stabIe stilbene anion radical then undergoes a homogeneous electron- exchange with the parent molecule. Voltammetric evidence for this process includes a dramatic decay of Ep when the sweep rate is decreased. At very slow scans the Ep of stilbene is reached.PhCH(SPh)CH(O Ac)Ph (35) Labelling experiments often reveal new features of seemingly straightforward reactions. One example is the reduction of phenacyl chloride3' in DMF-l0/' D20. Recovery of the starting material after short reaction-times reveals not only the reduction product (acetophenone) but also considerable H-D exchange of the methylene hydrogens of the starting material. 33 C. P. Andrieux J. M. Dumas-Bouchiai and J. M. Saveant J. Electroanalyt. Chem. Interfacial Elec- trochem. 1977,83 355. 34 B. Lamm and K. Ankner Acta Chem. Scad. 1977 B31,375. 35 J. K. Howie J. J. Houts and D. T. Sawyer J. Amer. Chem. SOC. 1977,99 6323. 36 P. Martigny and J. Simonet J. Electroanalyt. Chem. Interfacial Electrochem. 1977 81 407.37 A. F. Diaz Y. Y. Cheng and M. Ochoa J. Amer. Chem. SOC.,1977,99,6319. 162 R. Lines Interestingly the fraction of phenacyl chloride converted into acetophenone is always less than the fraction of D incorporated into the methylene hydrogens and that the exchange is in excess of the Faraday consumption. A suggestion3' is that the exchange proceeds (at potentials2Ep of phenacyl chloride) via an anion radical which can undergo several H/D exchanges per electron transfer. Falsig and Iversen3* have scaled up the electrolytic reduction of benzotriazole to provide preparative quantities of 2-aminophenyl hydrazine dihydrochloride in 80-85% yields. Treatment of the product with ortho-esters represents a good synthetic route to the 3-substituted benzo-1,2,4-triazines.Evidence has been for the intermediacy of a carbene anion radical during the electrolysis of diphenyldiazomethane. The three isolated products diphenyl methane benzophenoneazine and diphenylmethylamine are believed to arise by a radical-chain process involving the diphenyl carbene radical anion. The observed properties of this species indicates that it behaves primarily as a radical. Although the cation radical of chlorophyll-a is stable in aprotic solvents pre- paration of stable solutions of the corresponding anionic species has proved elusive. A report has now appeared4' that in DMF which has been treated with active alumina both the anion radical and dianion of chlorophyll-a are quite stable. Chemiluminescence has also been observed4' from the reaction of the radical anion with oxygen.The electroreduction of phenylglyoxylic acid oxime in the presence of strychnine leads to opically active phenyl gly~ine,~~ the absolute configuration of which depends on the cathode potential. Thus 17.1% of the R isomer is formed at -0.95 V (SCE) whereas at -1.35 V an enantiomeric excess (1l.lY0) of the S isomer is obtained. Although many different parameters are involved the main factor is probably the protonation of the intermediate chiral carbanion (36) or (37). The product arising as a competition between inversion of the carbanion and protonation in the initial configuration at the electrode surface. PhcC02H PhCCOzH I NHOH I NH2 (36) (37) 4 Miscellaneous The use of minute working electrodes has made possible voltammetric studies in both benzene and chl~robenzene.~~ Chlorobenzene in particular appears to be an excellent solvent for the study of the redox behaviour of aromatic compounds.In benzene the very strong ion-pairing effect allows the reversible formation of the trianion radical of 1,2-bis-(9-anthryl) ethane. The potential (ca. -2.8 V SCE) required to generate this species is the most negative reversible reduction-potential yet reported for an aromatic system. In contrast a report has now appeared43 38 M. Falsig and P. E. Iversen Acta Chem. Scand. 1977 B31 15. 39 R.N. McDonald J. R. January K. J. Borhani andM. D. Hawley J. Amer. Chem. Soc. 1977,99,1268. 40 T. Saji and A. J. Bard J. Amer. Chem. Soc.1977,99 2235. 4' M. Tubault E. Raoult J. Armand and L. Boulares J. C. S. Chem. Comm. 1977 250. 42 R. Lines and V. D. Parker Actu Chem. Scand. 1977 B31 369. 43 M.Horner and S. Hunig Angew. Chem. Internat. Edn. 1977 16,410. Electro -organic Chemistry concerning r-system (38) which can exist in five oxidation states separated by four reversible one-electron transfers. R R (38) 0ther reports have described similar behaviour for two cluster compounds a and a new Pt tetrathiolene clu~ter.'~ tetrameric cyclopentadienyl iron ~ulphide~~ Oxydipropionitrile (dielectric constant = 60) commonly used as a g.1.c. phase shows promise as an electrochemical All the usual supporting elec- trolytes are soluble and at Pt using LiCIO the potential range is +2.62 to -3.9 V (SCE).The Ag/Ag' reference electrode is stable in this solvent. An interesting application of cyclic voltammetry to conformational analysis has appea~ed.~' The technique requires that the conformers be separated by significant activation barriers as well as oxidizing (or reducing) at substantially different rates. Excellent agreement was obtained between the results of low-temperature cyclic voltammetry of cyclic tetra-alkylhydrazines with the known conformational data of these compounds. The authors4' point out that for reproducible results a consistent electrode surface is required. Dia~~~ has noted some differences in stability of some surface bonded pyrazoline derivatives (39) and (40). Both compounds undergo reversible one-electron trans- fer in acetonitrile (X = OMe) but when bonded to the electrode surface (SnOz uia the silylanyl derivative) the charge transfer process becomes irreversible for (40) but not for (39).The conclusion is that the array of cation radicals bonded to the surface are less stable than in solution but that the structure of the tricyclic derivative (39) inhibits decomposition. Ph Ph Strong surface interactions with ions in the electrolyte phase characterize the behaviour of the anisotropic metallic conductor polymeric sulphur nitride (SN), when used as an electrode.49 The electrodes also exhibit unusual heterogeneous electrode process properties. The suggest that such electrodes might be more suitable for modification (chemical or electrochemical) for the fabrication of selective catalysts than for example SnOz or graphite electrodes.44 Trinh-Toan Boon-Keng Teo J. A. Ferguson T. J. Meyer and L. F. Dahl J. Amer. Chem. SOC.,1977 99,408. Boon-Keng Teo F. Wudl J. H. Marshall and A. Kruger J. Amer. Chem. SOC.,1977,99 2349. 46 J. Y. Gal and M. Persin J. Electroanalyt. Chem. Interfacial Electrochem. 1977 77,361. 47 S. F. Nelsen L. Echegoyen E. L. Clennan D. H. Evans and D. A. Corrigan J. Amer. Chem. SOC. 1977,99 1130. 48 A. Diaz J. Amer. Chem. SOC.,1977,99 5838. 49 R. J. Nowak H. B. Mark jun. A. G. MacDiarmid and D. Weber J. C. S. Chem. Comm. 1977 9.

ISSN:0069-3030    

DOI:10.1039/OC9777400153

出版商:RSC    

年代:1977

数据来源: RSC

摘要:

8 Photochemistry By H. A. J. CARLESS Department of Chemistry Birkbeck College Malet Street London WC1E 7HX The past year has seen an increased emphasis on the use of photochemical methods for organic synthesis. The well-known cis-trans isomerization of alkenes continues to provide results of interest. Direct irradiation (185 nm) of cyclohexene or cycloheptene in pentane solution produces the highly strained trans-isomers which can be trapped by acidic methanol to form the corresponding methoxycycloalkanes.' In this way trans- cycloheptene was found to be a reasonably long-lived species at -10 "C,with a lifetime of 23 minutes. A transient U.V. absorption spectrum produced on irradia- tion (248 nm) of 1-phenyl-cycloheptene solutions can be assigned to a twisted trans-like isomer of 1-phenylcycloheptene.2 The photochemical addition of alcohols to cycloalkenes proceeding via the trans-intermediate is generally non-stereospecific.However irradiation3 of the benzocycloheptadienone (1) 'in deuteriated methanol or acetic acid leads to the product (2) of a regio- and stereo-specific syn-addition to the trans-cycloheptadienone intermediate. It has proved possible to prepare a trans-doubly bridged ethylene (3)by xylene-sensitized photo-isomerization of the cis-precur~or.~ This photochemical route to (3) \ @J*&m \ H (1) (2) a; R=Me b; R =MeCO ' Y. Inoue S. Takamuku and H. Sakurai J.C.S. Perkin ZZ 1977 1635. R. Bonneau J. Joussot-Dubien J. Yarwood and J. Pereyre TetrahedronLetters 1977,235. 'E.Dunkelblum and H.Hart J. Amer Chem. SOC.,1977,99,644. M. Nakazaki K.Yamamoto and J. Yanagi J.CS. Chem. Comm. 1977,346. 165 H. A. J. Carless compares very favourably with the non-photochemical approach to such compounds recently reported by Mar~hall,~ who would classify compound (3) as a [10,8]betweenanene. Metathetic reactions of alkenes have recently become topical and these can now be induced in a route which involves photochemical addition followed by pyrolysis. Two groups have investigated this approach to medium-ring carbo- For example [2+21 photocycloaddition of the methyl cyclo-butenecarboxylate (4) to cyclopentene gives (5) which can be cleaved on ther- molysis to the cyclononadiene ester (7) or under less vigorous conditions to the divinylcyclopentane (Q6The reaction of a cyclobutene with a cyclohexenone may H hv -\ C0,Me C0,Me (4) (5) C0,Me (7) likewise provide a useful route to the ten-membered ring of germa~radienes.~,’ Photochemical cleavage of cyclobutanes is also possible and Kaupp’ has sum- marized the photolysis of substituted cyclobutanes in terms of a ‘&-effect’ in which there is a preference for breaking of the cyclobutane bond linked to the chromo- phore and also to the substituent which interacts most strongly with the chromo- phore.Simultaneous publications by two group^^"^ discuss the photochemical re- arrangement of 3-vinylcyclopropenes to cyclopentadienes in high chemical yield. For example (8)produces the cyclopentadienes (9) and (10) in the ratio 3 :1.9 The p& hvL QPh Ph Bu‘ Ph Ph Ph But (8) (9) (10) structure of the major product is more in accord with a biradical (11) pathway rather than a carbene (12) route.In confusing contrast 3-ally1 substituted cycle-’J. A. Marshall and M. Lewellyn J. Amer. Chem SOC.,1977,99 3508. ‘P. A. Wender and J. C. Lechleiter J. Amer. Chem. Soc. 1977,99 267. G. L. Lange M.-A. Huggins and E. Neidert Tetrahedron Letters 1976,4409. G. Kaupp and M. Stark. Chem. Ber. 1977,110,3084. H. E. Zimmerman and S. M. Aasen J. Amer. Chem. Soc.,1977,99,2342. lo A. Padwa T. J. Blacklock D. Getman and N. Hatanaka J. Amer. Chem. Soc. 1977.99 2344. Photochemistry 167 ‘ (1 1) (12) propenes do seem to undergo photorearrangement via a vinyl carbene inter- mediate.” The carbene gives cycloaddition to the allyl double bond as is also found in the photochemical reactions of allyl azirines (see ref.33). Kropp et aL” have used the technique of photolysis of alkyl iodides at 254nm as a convenient means for the generation of carbocations such as the 1-norbornyl cation from 1-iodonorbornane There has been a long-standing dispute as to whether the singlet excited state of alkanones possesses reactivity towards hydrogen abstraction comparable with that of the triplet state. Henne and Fischer13 have determined the yields of various deuteriated pinacols formed in the photoreaction of deuteriated acetone-propan- 2-01 mixtures and the multiplicities of the states which give rise to the pinacols.They conclude that singlet excited acetone has a rate constant for hydrogen abstraction at least as great as that of the acetone triplet. The second excited singlet (ww*) state of adamantanethione is apparently a very indiscriminate abstractor of hydrogen from alkanes since it shows only a small kinetic isotope-effect in abstrac- tion and has little preference for abstraction from tertiary rather than primary C-H bond^.'^ A variety of methods is being used to detect and intercept the 1,4-biradicals believed to be involved in the Norrish Type I1 photochemical reactions of dialkyl and alkyl aryl ketones. Thus laser photolysis (347.1 nm) of 5-methylhexan-2-one produces transient absorption spectra (lifetime ca. 100 ns) assigned to the 1,4- biradical (13).15 The paraquat dication (l,l’-dimethyl-4,4’-bipyridylium) is able to trap such biradicals yielding the easily detected paraquat radical cation whose rate of formation allows the first estimate of the lifetime of the y-methylvalerophenone biradical (14) (7 = 97 f15 ns) in methanol at room temperature.16 The spin-trap di-t-butyl selenoketone efficiently intercepts 1,4-biradicals such as (14) which yields PhCOCHZCH2C(Me),SeC(Bu‘),Has the final product.I7 0 OH RZ @ R OH (13) R’ = R2=R3=Me (14) R’ =Ph R2= R3= Me Irradiation of 5-methyl- 1,4-naphthoquinone yields the blue photo-en01 (15) which is stable at 77 K and provides the first unambiguous example of formation of “ A. Padwa and T. J. Blacklock J. Amer. Chem. SOC.,1977,99 2345.12 P. J. Kropp G. S. Poindexter N. J. Pienta and D. C. Hamilton J. Amer. Chem Soc. 1976,98 8135. ” A. Henne and H. Fischer J. Amer. Chem. Soc.,1977,99,300. l4 K.Y. Law,P. de Mayo and S. K. Wong J. Amer. Chem Soc. 1977,99,5813. Is R. D. Small and J. C. Scaiano Chem. Phys. Lerlers 1977,50,431. l6 R.D. Small and J. C. Scaiano J. Phys. Chem. 1977,81 828. ” J. C. Scaiano J. Amer. Chem. Soc. 1977,99 1494. H. A. J. Carless a (2)-dienol in a photo-enolization reaction.18 The Norrish Type I reaction of cyclic ketones can produce unsaturated aldehydes and this route has been used in the synthesis of some prostanoids by photolysis of the appropriately substituted bicycl0[2,2,l]heptan-2-ones,’~and in production of 5-carbomethoxyhex-4-en-1-a1 for terpene synthesis from 2-carbomethoxy-2-methylcyclopentanone.20 A notably short stereoselective synthesis of the insect sex-attractant em-brevicomin (18) relies on the selective excitation (using 1-methylnaphthalene as combined sensitizer and triplet quencher) of the carbonyl group of the dihydropyranyl ketone (16) followed by hydrogenation of the resulting bicyclic compound (17).21 The absorption of visible light by a dye photosensitizer in the presence of ground-state oxygen (302) is often used to generate singlet oxygen (lo,),and the importance of ‘0 in synthetic chemistry is increasing rapidly.Singlet oxygen generally gives a 1,4-addition to cisoid conjugated dienes producing endo-perox- ides which can easily rearrange to syn-1,3-diepoxides on heating.The use of this sequence on the annulene (19) can produce an intermediate (20) which on repeti- tion of these steps yields the remarkable naphthalene pentoxide (21)., The 1,4-cycloaddition of ‘0,may even occur when one of the diene double bonds forms part of an aromatic ring as in styrenes. An ingenious synthesis of the anti-tumour agent (f)-crotepoxide (24)relies on photo-oxidation of the styrene derivative (22) to produce a bis(endo-peroxide) (23) which can be rearranged and converted into cro tepo~ide.’~ Is E. Rommel and J. Wirz Helv. Chim. Acta 1977,60 38. l9 N. M. Crossland S. M. Roberts and R. F. Newton J.CS. Chem Comm. 1977 886. G. Bidan J. Kossanyi V. Meyer and J.-P. Morizur Tetrahedron 1977,33,2193. 21 P. Chaquin J.-P. Morizur and J.Kossanyi J. Amer. Chem. SOC.,1977 99,903. 22 E. Vogel A. Breuer C.-D. Sommerfeld R. E. Davis and L.-K. Liu Angew. Chem. Internat. Edn. 1977 16 169. 23 M. Matsumoto S. Dobashi and K. Kuroda Tetrahedron Letters 1977 336 1. Photochemistry 169 The immediate biological precursors of the prostaglandins are endo-peroxides having the 2,3-dioxabicyclo[2,2,l]heptaneskeleton. One approach to the synthesis of such peroxides involves the 1,4-~ycloaddition of ‘0,to cyclopentadienes such as 1,4-diphenylcyclopentadienewhich yields the peroxide (2S).24It has now been found that the double bond of (25) can be selectively reduced by di-imide without affecting the peroxidic link a process which should increase the synthetic uses of cyclic peroxides like (25).Thus this reaction has made possible a simple synthesis of the previously unknown 2,3-dioxabicyclo[2,2,2]octane from cyclohexa- 1,3-diene.” There is a rapidly growing interest in 1,2-dioxetans and their chemistry,26 and photo-oxidation of hindered alkenes by singlet oxygen presents a good method for their synthesis. In fact the preparation of the dioxetan (26) by sensitized photo- oxidation of bis(adamanty1idene) has become a routine experiment.*’ Thermal (26) R=R=H (27) R-R= (j /O decomposition of such dioxetans has been used because it provides a chemical route to electronically excited species; ring-fission yields excited carbonyl compounds with the subsequent emission of chemiluminescent light. Wynberg and his group2* have prepared the stable and optically active dioxetan (27) by photo- oxidation of the appropriate optically active alkene and theyz9 have observed that the thermal decomposition of this dioxetan (27) produces chemiluminescence which is circularly polarized.There has been dispute as to whether dioxetan formation from ‘0,attack on an alkene occurs concertedly or via a perepoxide intermediate as calculated by Dewar et uL30 The findings of McCapra and Beheshti3’ are especially relevant to 24 D. J. Coughlin and R. G. Salomon J. Amer. Chem. SOC. 1977 99 655. 25 W. Adam and H. J. Eggelte Angew. Chem. Intemat. Edn. 1977,16 713. 26 W. Adam Advances in Heterocyclic Chem. 1977,21 437. ’’ ‘Organic Photochemical Syntheses’ Vol. 2 ed. R. Srinivasan Wiley-Interscience New York 1976 p.10. 28 H. Wynberg and H. Numan J. Amer. Chem. SOC. 1977,99,603. 29 H. Wynberg H. Numan and H. P. J. M. Dekkers J. Amer. Chem. Soc. 1977,99,3870. 30 M. J. S. Dewar A. C. Griffin W. Thiel and I. J. Turchi J. Amer. Chem. SOC. 1975,97,4439. ” F. McCapra and I. Beheshti J.C.S. Chem. Comm. 1977 517. H.A. J. Carless this question because ‘0,reacts with camphenylidene-adamantane to give the rearranged 1,2-dioxolan (28) alongside the expected dioxetan. The formation of (28) becomes most easily understood in terms of the rearrangement of a dipolar intermediate such as the perepoxide (29). Turro Adam and m-worker~~~ have R (30) a; R=Me b; R=Ph now succeeded in isolating a-peroxylactones such as (30) from reaction of ‘0,with the double bond of ketenes.The dioxetanone (30a) is stable enough to with- stand distillation below room temperature but decarboxylates with intense chemiluminescence on warming. Padwa has continued his studies on the photochemical generation of nitrile ylides from azirines by examining the intramolecular cycloaddition of the ylide to a double bond. Either 1,l -(~arbene-like),~ have been found or 1,3-~ycloaddition~~ and for some azirines both pathways are competitive as with (31)yielding (32) and (33) re~pectively.~~ Padwa and his group believe the predominant photoproduct can be understood in terms of the electronic effect of substituents on the structure of the ylide as proposed by Houk et ~1.~~ -* \ h’ PY’J +M 0 The first example of a [2+21 photocycloaddition of an alkene to an azo-bond has been noted.37 Thus the rigid unsaturated azo compound (34) where a C=C bond and the N=N bond are parallel and close is claimed to undergo ring-closure to the (34) (35) 32 N.J.Turro Y.Ito M.-F. Chow W. Adam 0.Rodriquez and F. Yany J. Amer. Chem. SOC.,1977,99 5836. 33 A. Padwa and P. H. J. Carlsen J. Amer. Chem. Soc. 1977,99,1514. 34 A.Padwa and N. Kamigata J. Amer. Chem. Soc. 1977,99 1871. 35 A. Padwa P. H. J. Carlsen and A. Ku J. Amer. Chem. Soc.,1977,99 2798. 36 P.Caramella and K. N. Houk J. Amer. Chem. Soc.,1976,98 6397;P. Caramella R. W. Gandour J. A. Hall C. G. Deville and K. N.Houk ibid 1977,99 385. ’’W. Berning and S. Hunig Angew. Chem. Internat. Edn. 1977,16 777. Photochemistry 171 remarkable isomer (35) on irradiation in acetonitrile.An unusual photocyclization of N-allyliminium salts such as (36) to yield pyrrolidines [e.g. (37)] on irradiation in \ I methanol may well be the result of an intramolecular [2+2Jphotocycloaddition of the iminium chromophore to the olefinic bond followed by C-N bond cleavage and capture of a nu~leophile.~~ Photochemical [2 +21 cycloaddition reactions of carbonyl compounds to alkenes yielding oxetans are well known. Yang and Chiang3’ have now found that the photocycloaddition of aromatic aldehydes (38) to cyclohepta- 1,3,5-triene yields a [6+2] adduct (39) as a major product besides oxetans (40). The reaction is (38) a; Ar = 1-pyrenyl b; Ar =2-naphthyl believed to occur from the singlet excited state of the aldehyde and the fact that a [4+21 adduct could not be detected may be evidence for a concerted photochemi- cal mechanism since the [27rs+27rs] and [gS +2ms] additions are allowed on the basis of orbital symmetry rules whilst the [4~s +2~s] is not.Bryce-Smith Gilbert and co-~orkers~~ have previously published useful guide- lines which rationalize the orientation and stereochemistry of cycloaddition of photoexcited benzene to olefins but the exceptions to these rules which are appearing show that there are still factors to be understood. Thus the photoad- dition of ethylene or propene to benzene (in a U.V. autoclave) gives 1,3-addition to the benzene ring as the major process rather than the expected 1,2-additi0n.~’ 1,2-addition to the benzene ring generally gives an endo-adduct for donor-substi- tuted alkenes but an exo-adduct for acceptor-substituted alkenes.For example photoaddition of 2,3-dihydropyran is the most efficient (a=0.7) cycloaddition to benzene so far known and gwes a great preference for the endo-adduct (41).42 In contrast photoaddition of benzene to 2,2-dimethyl- 1,3-dioxolen gives an em-1,2-adduct (42).43 Photocycloaddition of benzene to methyl acrylate or methacrylate shows surprisingly little selectivity yielding a mixture of em-and endo- 1,2-ad duct^.^^ 38 P. S. Mariano J. L. Stavinoha and R. Swanson J. Arner. Chern. Soc. 1977,99 6781. 39 N. C. Yang and W. Chiang J. Amer. Chem Soc. 1977,99,3163. 40 a. Bryce-Smith A. Gilbert B.H. Orger and H. M. Tyrrell J.C.S. Gem. Cornrn. 1974,334. M. F. Mirbach M. J. Mirbach and A. Saw Tetrahedron Letters 1977,959. 41 42 A. Gilbert and G. Taylor Tetrahedron Letters 1977,469. 43 H.-D. Scharf and J. Mattay Tetrahedron Letters 1977,401. 44 R. J. Atkins G. I. Fray A. Gilbert and M. W. bin Samsudin Tetrahedron Letters 1977 3597 H. A. J. Carless The photocycloaddition of an acetylene to an aromatic compound usually results in the formation of a cyclo-octatetraene via a proposed bicyclo[4,2,0]octatriene intermediate. Two have presented new evidence on these intermediates. Sket and Zupan4' have been able to isolate stable bicyclics (43) from the photo- addition of phenyl-substituted acetylenes to hexafluorobenzene whilst Tinnemans Ph C0,Me ph*FR F I- R =But Pr" or Me (44) (43) and Necker~~~ have shown that the bicyclo[4,2,0]octatriene from methyl phenyl- propiolate and benzene can undergo intramolecular photocycloaddition to yield (44).Five-membered ring heterocycles often undergo ring-atom transpositions on U.V. irradiation [e.g. the 2-alkylindazole (45)rearranges to a benzimidazole (46) via the detectable tricyclic intermediate (47).47 Until now these processes had not been observed for carbocyclic rings. However an elegant study of the irradiation of a ['3C,]-labelled cyclopentadiene (48) shows that the phototransposition of cyclo- pentadiene [(48) +(50)]occurs probably by intramolecular [2 +21 addition to yield bicyclopentene (49) followed by a 1,3-sigmatropic shift4* This pathway would account for the fact that after irradiation the bicyclopentene is found to have a " B.Sket and M. Zupan J. Amer. Chem. SOC.,1977,99,3504. 46 A. H. A. Tinnemans and D. C. Neckers J. Amer. Chem. SOC.,1977,99,6459. 47 W. Heinzelmann M. Marky and P. Gilgen Helv. Chim. Acta 1976,59 1512. 48 G. D. Andrews and J. E. Baldwin J. Amer. Chem. SOC.,1977,99,4851. Photochemistry 173 greater ratio of non-vicinal to vicinal [”C,] label than is found in the recovered cyclopentadiene. Palensky and Morrison4’ have found that a similar skeletal re- arrangement occurs on irradiation (254 nm) of alkyl substituted indenes e.g. in the interconversion of (51) and (52) and they have independently proposed a similar R‘ (53) (51) R’=Me,R2=H (52) R’ = H R2= Me mechanism.In the case of irradiation of 1,l-dimethylindene the unstable inter- mediate isoindene (53) becomes the sole product because it cannot undergo a 1,Shydrogen shift which would normally reform an indene. Barltrop Day and Samuel who had already shown the intermediacy of a zwitterion [e.g. (55)] in the photochemical rearrangement of 4-pyrones to 2-pyrones in trifl~oroethanol,~~ have now been able to isolate a further intermediate the cyclopentadienone epoxide (56) in the conversion of (54) into (57).5’ Barton and Hulshof5’ have used the related photochemical ring contraction of a 4-pyrone (58) to cyclopentenedione (59) followed by in situ reduction with sodium cyanoborohydride in the elegant synthesis of the mould metabolite terrein (60).A similar rearrangement occurs for protonated 4-pyrones (i.e. hydroxy-pyrylium cations) on irradiation in sulphuric acid. Thus the 2,3-dimethyl-4- hydroxypyrylium cation rearranges in part to the corresponding 2-hydroxypyrylium cation; however in this case Pavlik et aZ.53have shown that the major reaction- product is a protonated fury1 cation (61). A mechanism for the curious formation of (61) remains to be established. 49 F. J. Palensky and H. A. Morrison J. Amer. Chem. SOC.,1977 99 3507. so J. A. Barltrop A. C. Day and C. J. Samuel J.C.S. Chem. Comm 1976,822. ” J. A. Barltrop A. C. Day and C. J. Samuel J.C.S. Chem. Comm. 1977 598. 52 D. H. R. Barton and L. A. Hulshof J.CS. Perkin I 1977 1103.53 J. W. Pavlik D. R. Bolin K. C. Bradford and W. G. Anderson J. Amer. Chem. Soc. 1977,99 2816. H. A. J. Carless (62) RF =CF(CF,) Irradiation of perfluorinated pyridines has given the first stable examples of 2-azabicyclic isomers such as (62).54 In contrast a study of the photochemical decomposition of 1,4-[ 15N2]-s-tetrazine to nitrogen and hydrogen cyanide shows that reaction occurs without any preliminary 1,4-nitrogen bonding.” Matrix isolation techniques applied to photochemical reactions have provided some interesting results such as the first isolation of thiirene (63) by photolysis at 8 K of 1,2,3-thiadia~ole,’~the production of unstable isocyanides [e.g. (64)] on irradiation of pyridine N-oxide at 10K,57 and evidence for a process (perhaps involving a ring-opened aldoketene) which scrambles C-2 and C-6 on irradiation of a [‘3C]-labelled a-pyrone at 8 K.58 The use of chiral solvents to induce asymmetric syntheses in photochemical experiments has received some attention this year.Irradiation of 2-styrylbenzo[c]-phenanthrene in chiral solvents gives the optically active hexahelicene in optical yields up to 2‘%0,~’ whilst photochemical rearrangement of nitrones to optically active oxaziridines occurs in optical yields up to 30% on irradiation in a (+)-or (-)-2,2,2-trifluoro-l-phenylethanol and fluorotrichloromethane solvent.60 The photochemical reduction of carbonyl compounds in the presence of the optically active (S,S)-1,4-bis(dirnethylamino)-2,3-dimethoxybutane gives both mew and optically active pinacols derived from the carbonyl.For example acetophenone gives an optical yield of up to 25%0 enriched in the (R,R)-pinacol enantiomer.61 ” R. D. Chambers and R. Middleton J.C.S. Chem. Comm. 1977 154. 55 D. S. King C. T. Denny R. M. Hochstrasser and A. B. Smith J. Amer. Chem. Soc. 1977 99 271. 56 A. Krantz and J. Laureni J. Amer. Chem. SOC.,1977,99,4842. 57 0.Buchardt J. J. Christensen C. Lohse J. J. Turner and I. R. Dunkin J.CS. Chem. Comm. 1977 837. ’* B.-S. Huang R. G. S. Pong J. Laureni and A. Krantz J. Amer. Chem. Soc. 1977 99 4154. 59 W. H. Laarhoven and T. J. H. M.Cuppen J.C.S. C’hem. Comm. 1977,47. D. R. Boyd and D. C. Neill J.C.S. Chem. Comm. 1977,51. ‘* D. Seebach H.-A. Oei and H. Daum Chem. Ber. 1977,110,2316.

ISSN:0069-3030    

DOI:10.1039/OC9777400165

出版商:RSC    

年代:1977

数据来源: RSC

摘要:

9 Aliphatic Compounds Part (i) Hydrocarbons By D. R. TAYLOR Department of Chemistry University of Manchester Institute of Science and Technology Manchester M60 1QD 1 Acetylenes The catalytic cyclotrimerization of acetylenes has been reviewed with special reference to the co-oligomerization of a,w-diynes with silylacetylenes to produce fused ring systems.’ A new general method for the synthesis of 1,3-enynes which is stereo- and regio-selective involves the reaction of an alkynylzinc chloride with a vinyl halide in the presence of a palladium(0) complex (Scheme l).’ Alkynyl-lithium reagents R’ H R’ H \/A ‘c=c / c=c R2/ \x R2/\CrCR3 Reagents i R3C-CZnCI (R3=H or Bu”) Pd(PPh3)4-THF Scheme 1 are unsuitable for the reaction but are easily converted into the alkynylzinc chlorides which are stable to disproportionation and do not attack functional groups such as esters.Since enynes are themselves readily converted into dienyl- mercurials recently shown to dimerize smoothly in contact with rhodium salts,3 a new route to conjugated tetraenes has been opened up (Scheme 2). Reagents i (cyclo-C6H1 1)2BH; ii Hg(0Ach; iii aq. NaCl; iv [ClRh(COh]2-LiC1-(Me2N)3P0 Scheme 2 K. P. C. Vollhardt Accounts Chem. Res. 1977 10 1. * A. 0.King N. 0.Okukado and E.-i. Negishi J.C.S. Chem. Comm. 1977,683. R. C. Larock and J. C. Bernhardt J. Org. Chem. 1977.42 1680. 175 176 D. R. Taylor Enynes bearing remote functionality [e.g. (l),required for the synthesis of a sex pheromone of the grape-vine moth] can be obtained by an elegant combination of methods discovered by C.A. and H. C. Brown (Scheme 3).4 It features the use of the acetylene 'zipper' [KNH(CH2XNH2] which has also been used to effect the migration of the CEC bond in alkynylborate~.~ iii,iv 1 CzCEt -/ EtCEC H R2B H \/ v vi \/ c=c c=c /\ /\ H (CH2 )6 OAc H (CH2)60Ac (1 1 Reagents i KNH(CH2),NH2; ii Ac20; iii (Pr'MeCHkBH; iv EtCrCLi; v 12; vi H202-NaOAc Scheme 3 The stereospecific syn-addition of organometallic compounds (e-g. RCu) to the CEC bond continues to provide fascinating examples of synthetic value. However treatment of a terminal acetylene (but not C2H2) with lithium dialkylcuprates in THF leads to quantitative metal-hydrogen exchange.This undesirable reaction can be avoided (i) by using diethyl ether as solvent or better (ii) by adding lithium bromide to the reaction mixture in THF when deprotonation is completely suppressed (Scheme 4).6 Organocopper-magnesium halide complexes may also be Reagents 1 R2R3CuLi-Et20 (X =Li) or R2R3CuLi-LiBr-THF (X=Li,LiBr); ii Df(E =D) or BrCN-THF (E =Br) or N-chlorosuccinimide-(Me2N)3P0 (E =CI); (R' =alkyl or aryl R2 R3 =alkyl) Scheme 4 used to prepare vinylcuprates (2; R3=Br or R2 X =MgHal) a reaction which may usefully be followed by copper-halogen exchange using N-halogenosuc~inimide~ or cyanogen bromide or iodide,8 or by copper-nitrile exchange using cyanogen chloride or an arenesulphonyl cyanide.8 If a silylacetylene is used in this type of reaction sequence organocopper addition proceeds with the opposite regioselec- tivity so providing a route to 1-substituted 1 -silylalkenes (Scheme 5).9710 E.4 Negishi and A.Abramovitch Tetrahedron Letters 1977,411. C. A. Brown and E.4. Negishi J.C.S. Chem. Comm. 1977,318. H. Westmijze H. Kleijn and P. Vermeer Tetrahedron LetZers 1977 2023. 'A. B. Levy,P. Talley and J. A. Dunford Tetrahedron ktters 1977 3545. * H. Westmijze and P. Vermeer Synthesis 1977 784. M. Obayashi K. Utimoto and H. Nozaki Tetrahedron Letters 1977 1805. lo H. Westmijze J. Meijer and P. Vermeer Tetrahedron Letters 1977 1823. Aliphatic Compounds-Part (i) Hydrocarbons R13Si H MgY % c=c E'\/ 'R2 Reagents i R2CuMgBr2 (R' = Me R2 = Pr" n-C5HI1 or n-C6H13 X = Y = Br) or R22CuMgY (R' = Ph Y =CI or Br X = R2 = Et Pr' cyclo-C6H1 1.or Bu'); ii H20 (DzO) (E = H or D) or N-halogenosuccinimide (E =halogen) or iodoalkane (E = Me Pr" n-C5HIl or n-C6H13 erc.) Scheme 5 Vinylcoppers may also be obtained from alkyne-hydrozirconation products by transmetallation;" the overall process is both regio- and stereo-specific. Copper(1) arylacetylides react with arylcoppers to yield mixed diarylacetylenes (Ar'CGCAr2) via the formation of well-defined and isolable organo-cluster species Ar',Cu,(C_CAr2),. The highly selective formation of mixed acetylenes was shown to result from the detailed structure of the organo-cluster compounds in which triangular copper faces are occupied exclusively by one Ar' and. two Ar2C?C ligands.12 The synthesis of acetylenes and allenes uia polymetallation usually Iithiation of alkynes continues to receive attention.l3-I5 Perlithiopropyne the structure of which has been determined by ab initio cal~ulation,'~ reacts with iodoethane to afford a low yield of an ene-diyne (3) whereas with trimethyl-silyl or -germyl chloride or with diethyl sulphate it yields allenic and/or acetylenic derivatives by straightforward substitution (Scheme 6).13 But- 1-yne and but-2-yne are converted CH3ECH I* C3Li4% (Me3X)2C=C=C(XMe3)2 Et,CC=CEt +Et2C=C=CEt2 EtCrCCEt=CEtC=CEt (3) Reagents i Bu"Li-hexane; ii Me3XCI (X = Si or Ge); iii EtZSO,; iv EtI Scheme 6 by excess alkyl-lithium into the same trilithiated material but the 2-yne reacts much more slowly.A trilithiated product is also obtained by lithiation of hexa-2,4- diyne; it is a source of some exotic alkylated silylated or germylated allenynes including the hexasilylbisallene (4). l3 (Me3SihC=C=C(SiMe3)C(SiMe3)=C=C(SiMe3)2 (4) Several publications have appeared reporting investigations into the bromination of acetylenes. Solvent effects on the ratet6 and kinetic product distribution" are M. Yoshifuji M. J. Loots and J. Schwartz Tetrahedron Letters 1977 1303. G. van Koten R. W. M. ten Hoedt and J. G. Noltes J. Org. Chem. 1977,42,2705. l3 W. Priester R. West and T. L. Chwang J. Amer. Chem. SOC.,1976 98 8413; W. Priester and R. West ibid. pp. 8421 8426. I4 E. D. Jemmis D. Poppinger P. von R. Schleyer and J. A. Pople J. Amer. Chem. Soc. 1977,99,5796.Is N. M. Libman P. A. Brestkin and S. G. Kuznetsov J. Org. Chem. U.S.S.R., 1976,12 2480. I6 M.-F. Ruasse and J.-E. Dubois J. Org. Chem. 1977 42 2689. G. D. Mel'nikov and S. P. Mel'nikov J. Org. Chem. U.S.S.R. 1977 13 625. 178 D. R. Taylor considered to be compatible with the formation possibly via a fast reversibly formed v-complex of a bromovinyl cation in which the empty p-orbital is con- jugated with the benzene .rr-orbitals and therefore coplanar with the &carbon's a-bonds (5). The last-mentioned structural element implies hyperconjugation an (5) interaction which would explain the greater difference between bromination rates of similarly substituted olefins and acetylene^^^*^'*'^ than are found for rates of acid-catalysed hydration:20 the &bromine atom is more destabilizing in (5) than in the corresponding intermediate bromocation from styrene.The AdEC1 mechanism (a variant of AdE2)is thus confirmed. It should be noted that the nature of any substituents attached to their w-bonds greatly affects the relative bromination rates of correspondingly substituted olefins and acetylenes; indeed some olefinic acids appear to react more slowly than their acetylenic counterparts," though this may be misleading since allowance may have to be made for example for their different acidities which may affect ionic strength. Triethylammonium hydrogen dichloride appears to be the best reagent for achieving the addition of hydrogen chloride to the CGC bond no catalyst is required.The alkynes studied with the exception of phenyl-t-butylacetylene,all reacted stereoselectively to give syn-adducts an observation attributed to the powerfully nucleophilic anion HC12-forcing the adoption of an AdE3mechanism.21 Hydrogen chloride also without catalyst is adequate for hydrochlorination of sulphur-and selenium-substituted acetylenes an addition which proceeds exclusively in an anti-orientation.22 Mixed acetylenes of the type R'SCzCSeR2 react regiospecifically by protonation next to selenium presumably because sulphur is better able to stabilize an adjacent cation. Ph/ \R c1 R (<lo%) + \c=c / a R 'c=c / Ph/ \a (mainly) Reagents i CuCI2-LiCI (40-fold excess) MeCN (R.= H Me Pr" or Ph); ii CuC1,-KI or -I2 (five-fold excess) MeCN (R = H Me Et Pr" or Pr') Scheme 7 S.De Young S. Ehrlich and E. Berliner J. Amer. Chem. SOC.,1977,99 290. l9 G.H. Schmid A. Modro,and K. Yates J. Org. Chem. 1977,42 2021. 2o G. Modena F. Rivetti G.Scorrano and U. Tonellato J. Amer. Chem Soc. 1977,99 3392. 2' J. Cousseau and L. Gouin LCS. Perkin I 1977 1797. 22 S. I. Radchenko and A. A. Petrov J. Org. Gem. U.S.S.R. 1977 13 36. Aliphatic Compounds-Part (i) Hydrocarbons 179 Full details have now appeared of the anti-chlorination of acetylenes using copper(I1) chloride-lithium chloride in large excess in acetonitrile and the tech- nique can also be applied to iodochlorination (using CuCl,-12 or CuC1,-KI) with good regioselectivity (Scheme 7).23 Electrophilic attack upon the C=C bond by both mercurinium and sulphenium cations proceeds almost exclusively to form anti-adducts via bridged vinyl cations; in the latter addition the intermediate episulphonium ions [e.g.(6)] have been isolated as stable antimonates or tetrafluor~borates.~~ Me \c=c /Me \/ S+ SbCl6-I Me (6) New reducing agents termed complex reducing agents (CRA) have been developed by treating sodium hydride with metal salts such as iron(II1) chloride (FeCRA) or nickel(r1) acetate (NiCRA) in the presence of alko~ide.~~,~~ Triple bonds may either be reduced to 2-alkenes or fully reduced to alkanes by a judicious choice of reagents and conditions which are generally mild enough to leave carbonyl groups unaffected.26 Conversions of acetylenes into allenes by substitutions which are accompanied by the well-known propargyl rearrangement are often poorly understood in mechanistic terms.The complexities which can arise are exemplified by the reac- tion of the diphenylbutynol (7;R = Ph2COH) with lithium aluminium deuteride (Scheme 8). Whereas in dialkyl ethers the main product is the allene (8) none of this product appears to be formed when the solvent is only slightly altered to THF.27 Me D LiAID4 -/ I-RCGCMe -Ph,C-C=C + Ph2C-C=CMe I (7) OAID3 OAlD3 [A’D/ -OAID3 1.. I Ph2C=C=CDMe H Me R H R Me (8) \/c=c \/c=c \c=c / /R \D D/ \Me D/ \H [R = Ph,C(OH)] Scheme 8 23 S. Uemura H. Okazaki A. Onoe and M. Okano J.C.S. Perkin I 1977,676. ’* G. Capozzi V. Lucchini G. Modena and P.Scrimin Tetrahedron Letfers 1977,911. ’’ J. J. Brunet L. Mordenti B. Loubinoux and P. Caubere Tetrahedron Letters 1977 1069. ’‘ J. J. Brunet and P.Caubere Tetrahedron Letters 1977 3947. *’ M. P. Hartshorn R. S. Thompson and J. Vaughan Aushal. I.Chem. 1977.30.865. 180 D. R. Taylor Two I3C n.m.r. studies of acetylenic compounds have recently been reported. One establishes correlations for chemical shifts in a@-acetylenic ketones,28 and the other claims to show that chiral recognition is possible across the CEC bond in molecules such as 2,5-di~hlorohex-3-yne.~~ 2 Alkanes A review has appeared dealing with the conformations of hydrocarbon chains.30 The synthe~is,~’ thermal stability,31 and thermodynamic properties3* of some strained alkanes have been reported 13C n.m.r.spectra can be used to study conformational and rotational barriers in such Two new syntheses of alkanes have been developed. The first uses the addition of alkyimercury(I1) halides or acetates to electron-deficient olefins to generate the saturated C-C linkage and is followed by sodium borohydride reduction to cleave the C-Hg bond.34 The second technique is to convert an alcohol into a chloro- formate which may then be conveniently reduced under free-radical conditions by a trial kyl~ilane.~~ Further examples have appeared36 of oxyfunctionalization of alkanes using pro- tonated ozone [see Ann. Reports (B) 1976 73,1721. As an alternative hydrogen R3CH [R3C--+:H l& R3COH + HOR3CCH3 ____+ H OH 3R3CCH20H.+I R R2ii ‘O-CH2R 4 -H20 R2C-CH2R I O+ aR,&H2R -HO +2R2C-CH2~OH2 H’ ‘OH Scheme 9 G.A. Kalabin A. G. Proidakov L. D. Gavrilov and L. 1. Vereshchagin J. Org. Chem. U.S.S.R.,1977. 13,449. ” A. J. Jones and P. J. Stiles Tetrahedron Letters 1977 1965. 30 M. A. Winnik Accounts Chem. Res. 1977 10 173. 31 H.-D. Beckhaus and C. Ruchardt Chem. Ber. 1977,110,878. ’’D. N. J. White and M. J. Bovill J.C.S. Perkin 11 1977 1610. 33 S. Brownstein J. Dunogues D. Lindsay and K. U. Ingold J. Amer. Chem. SOC.,1977,99 2073. 34 B. Giese and J. Meister Chem. Ber. 1977 110 2588. ’’N. C. Billingham R. A. Jackson and F. Malek J.C.S. Chem. Comm. 1977 344. A liphatic Compounds-Part (i ) Hydrocarbons 181 peroxide may be used either in superacid~~~,~~ or in concentrated trifluoroacetic Studies by 'H n.m.r.in superacid suggest that the Ceaction proceeds via electrophilic attack by HO' (or the incipient cation H0.0H2) on the weakest available C-H u-bond followed by nucleophilic attack by hydrogen peroxide upon the carbenium ion and subsequent alkyl migration to oxygen (Scheme 9). Predominantly branched alkanes were studied. Reactions between n-alkanes and hydrogen peroxide in trifluoroacetic acid yield alkan-2-01s and -3-ols with negli- gible amounts of terminal 3 Allenes An exhaustive review of the synthesis and chemical reactions of the interesting phospha-allene ylides has appeared.39 These ylides yield allenes when subjected to the Wittig reaction with carbonyl compounds. An extension of earlier work [see Ann.Reports (B) 1976 73 1731 on the synthesis of allenes via allenylcoppers has been rep~rted.~' Electrophilic attack upon the intermediate (9) by iodine yields optically active iodoallenes if optically active propargyl esters are used as starting materials. However when the elec- trophile is an acid anhydride or chloromethyl methyl ether (Scheme 10) only R1R2C(OAc)C_CH 5 [R'R2C=C=CHCuR32] (9) Kd Li \ R1R2C(COR4)C=H RZ=Y R'R~C(CH~OM~)C=CH R'R~C=C=CHI R'C(COR4)=C=CH2 (10) Reagents i R32CuLi (R3 = alkyl); ii 12 (MeOCH2)2; iii CICH20Me; iv (R4CO)20 (R4= Me n-CSH11 or Ph) Scheme 10 acetylenic products are formed initially although these may isomerize to for example allenones (10). An alternative synthesis of allenes operates upon the same type of starting material [R,C(OAc)CrCH] but generates intermediate allenylborates which can be converted into a wider variety of functionalized allenes by prot~lysis~~ or hydrolysed with a retro-propargyl rearrangement to acetylenes (Scheme 11).Full details have appeared of the syntheses of higher cumulenes by flash-pyroly- tic retro-Diels-Alder and by Skattebgl's method,43 described in last 36 N. Yoneda and G. A. Olah J. Amer. Chem. SOC.1977,99,3113. 37 G. A. Olah N. Yoneda and D. G. Parker J. Amer. Chem. SOC.,1977,99,483. 38 N. C. Deno E. J. Jedziniak L. A. Messer M. D. Meyer S. G. Stroud and E. S. Tomezsko Tetrahedron,1977,33 2503. 39 H. J. Bestmann Angew. Chem. Internat. Edn. 1977 16 349. 4" J.-M. Dollat J.-L. Luche and P.Crabbe J.C.S. Chem. Comm. 1977 761. 41 M. M. Midland J. Org. Chem. 1977 42 2650. 42 J. C. Ripoll and A. "huillier Tetrahedron,1977,33 1333. 43 G. Karich and J. C. Jochims Chem. Ber. 1977 110 2680. 182 D. R. Taylor R'CECCHR2 R'CH=C=CRZ2 Scheme 11 year's Report (pp. 176-177). As the number of cumulated double bonds increases the rotational barrier decreases uniformly and not in an alternating fashion which would have suggested a dependence upon molecular planarity.44 A number of allenes of potential commercial interest have been synthesized this year.4547 These included 2,4,5-trienamides regarded as potential insecticides in which a Wittig reaction was used to introduce the non-allenic C=C bond:' and the synthesis of allenic barbiturates from allenylmalonates.The latter derivatives were prepared by an addition-elimination sequence using malonate and 1-halogeno-allenes (Scheme 12) but the correct choice of base to generate the malonate anion must be made otherwise acetylenic or dienic isomers of the desired allenes may pred~minate.~~ R'R2C=C=CHCR3(C02Eth (11) ii [R'R2C=C=C] % R'R2CCR3(C02Et)2+ (1 1) I C=CH R3=H 1 R'R2C=CHCH=C(C02Et)2 Reagents i NaH-C6H6-R3CH(C02Eth (R3= H or Et); ii NaOEt-EtOH; iii R3CH(C02Eth Scheme 12 Reactions of magnesium or lithium with 1,3-dihalogenopropanes yield cyclo- propanes and not 1,3-propane-dimetaI compounds. Hence the importance of the discovery that hydroboration of propadiene followed by mercuration yields pro- pane- 1,3-dimercury(11) chloride which although it cannot be transmetallated directly may nevertheless be converted into propane- 1,3-dirnagnesium(11) halide in two steps (Scheme 13).48 This interesting bis-Grignard reagent has so far only been used to generate glutaric esters propane- 1,3-distannyl derivatives and more significantly two silacyclobutanes in good yield.Propadiene has also been used as a precursor in propenyl ketone synthesis; the required C-2 acylation was effected with sodio a1 kylironte tracarbonyl .49 K. Bertsch G. Karich and J. C. Jochims,.Chem. Ber. 1977 110 3304. 45 P. D. Landor S. R. Landor and 0.Odyek. J.C.S. Perkin I 1977,93. 46 S. R. Landor P. D. Landor and P. F. Whiter J.C.S. Perkin I 1977 1710. 47 L. A. van Dijck B. Thankwerden and J.G. C. M. Vermeer Rec. Trau. chim. 1977 % 200. 48 L. C. Costa and G. M. Whitesides J. Amer. Chem. Soc.,1977,99 2390. 49 A. Guinot P. Cadiot and J. L. Roustan J. Organometallic Chem. 1977 128 C35. Aliphatic Compounds-Part (i)Hydrocarbons .. CH2=C=CH2 -R1HgCH2CH2CH2HgR’ BrMg(CH,),MgBr // Me02C(CH2)3C02Me Me3Sn(CH2hSnMe3 Reagents i BzH,; ii Hg(0Ach; iii NaCl; iv 2R’Li-THF; v Mg-MgBr2-THF; vi CO,; vii H+-MeOH; viii CH2N2; ix Me3SnC1; x R22SiC12 (R2 = Ph or Me) Scheme 13 Further additions of resonance-stabilized enolates to allenic sulphonium salts have been investigated.” When the addend is a cyano-stabilized enolate a cyano- furan is formed; this and earlier furan syntheses are shown to proceed by a direct substitution mechanism rather than via addition-elimination.Other uni- and bi-dentate nucleophiles were found to yield products of addition-substitution (Scheme 14). When the attacking nucleophile is a malonate anion the isolable allylic adducts [12; Z=R3C(C0,Et)2 R3=H or Me] are converted by alkoxide into ylides which undergo [2,3] sigmatropic shifts.51 Me2kH=C=CH2 I,Me~;2 lii \ Me2SCH2CZ=CH2 + Reagents i R2COCHR’ (R’ = Ac ArSO, C02R3 or CN;R2= Ph); ii HXCH2CH2X- (X = S or SO,); iii Z-(Z= CN or PhS02); iv Z-(-Me2S) Scheme 14 Further examples of ene reactions of alkylallenes have been reported. The acyclic enophile Et02CN=NC02Et reacts with allenes including cyclonona-l,2- diene to produce the expected 2-bicarbamyl- 1,3-dienes in excellent yield,52 whereas the cyclic enophile N-phenyltriazolinedione induces apparent prototropic shifts in some allenes.The ene reactions of such allenes are found to be two to five times faster than those of comparably substituted mono-olefins presumably as a result of lower steric hindrance and developing resonance interactions in the B. S. Ellis G. GrifFiths P. D. Howes C. J. M. Stirling and B. R.Fishwick J.C.S. Perkin I 1977 286. ” G. Griffirhs P. D. Howes and C. J. M. Stirling JCS. Perkin I 1977 912. ’’ C. B. Lee and D. R. Taylor J.CS. Perkin I 1977 1463; J. Chem Res. (S) 1977,136; (M)1601. 184 D. R. Taylor transition state. Ene adducts were not however obtained when cyclonona- 1,2- diene was treated with acetylenic enophiles; the 1 1 adducts obtained were simple [2 + 21 cycloadducts (Scheme 15).R CH2CR2 =C=CR3R4 R 'CH=CR2C=CR3R4 I N(CO2Et)NHC02Et Reagents i Et02CN=NC02Et [R' = H R2-R4 = Me or R1 = R3 = R4 = H R2 = Me or R2 = R3 = H R1R4 = (CH,)5]; ii ECECE [E = CF3 or CO,Et R2 = R3 = H R'R4 = (Cf-I2)=J; iii N=NCONPhCO (R' = H R2-R4 = Me) Scheme 15 Further uses of allenes in synthesis have appeared. Allenic nitriles undergo Michael additions when treated with phenylhydrazine conjugated adducts cyclize thermally to 5-aminopyrazoles whereas unconjugated adducts give 3H-indoles via a [3,3]sigmatropic shift.53 Ketene cycloadducts of cyclohexanylideneallene have also been found useful since their thermal isomerization leads to annelated pro- ducts (Scheme 16).54 & Me,C=C=O s"; + HZ 0 boo "C 0 Scheme 16 4 Olefins and Dienes Advances in the following areas relevant to olefin chemistry have been reviewed recently stepwise [2 + 21 cycloadditions of enol industrial Wittig reac- tion~,~~ the Prins ~eacfion,~' structural effects in acid-catalysed hydrati~n,~' and the 53 S.R. Landor P. D. Landor Z. T. Fornum and G. M. Mpango Tetrahedron Letters 1977 3743. 54 M. Bertrand G. Gil A. Junino and R. Maurin Tetrahedron Letters 1977 1779. " R. Huisgen Accounts Chem. Res. 1977 10 117. '' H. Pommer Angew. Chem. Internat. Edn. 1977 16,423. '' V. J. Nowlan and T. T. Tidwell Accounts Chem. Res. 1977 10 252. 58 D. R. Adam and S. P. Bhatnagar Synthesis 1977 661. Aliphatic Compounds-Part (i) Hydrocarbons 185 synthesis of insect sex pheromone^.^^ The last-mentioned review includes useful discussion of the control of stereochemistry in Wittig and related reactions.Aspects of organometallic olefin chemistry which have also been reviewed include olefin insertions in catalysis6' and the applications of organosilicon compounds6' and organopalladium compounds62 in synthesis. Olefin metathesis reactions continue to receive enthusiastic attention and besides numerous individual research report~,6~~~ the proceedings of a symposium have been p~blished.~' The excellent new olefin synthesis which involves the coupling of two molecules of a carbonyl compound by low oxidation states of titanium7' (TiC13-LiAlH, TiC1,-K or -Li or TiC1,-Zn) has been used successfully in several laboratorie~.~~-'~ It is especially useful for symmetrical tetrasubstituted olefins for which a Wittig reaction would be unsuitable.Since the reaction involves a pinacol-type reductive dimerization as the first step (Scheme 17) it is not obvious that unsymmetrical R'R~C=O -+R'R~C-O s R'R~C-O R'R~C=CR'R~ t 2~ -R R C-0 Scheme 17 olefins (R'R2C=CR3R4) could be prepared from a mixture of two carbonyl compounds. However McMurry's group has now shown that the use of an excess of acetone with for example a cycloalkanone gives synthetically useful yields of isopropylidene-cycloalkanes. With mixtures of acetone and diaryl ketones essen- tially only mixed olefins (Me,C=CAr,) are obtained; since the reduction potentials of diaryl ketones are lower than that of acetone a radical coupling pathway (path a) is deemed less likely than the formation of aryldianions (Ar2c-03 which attack acetone preferentially (path b).75 The procedure is exceptionally useful for the preparation of very hindered olefins such as adamant~lideneadamantane~' and led to another first-time achievement the synthesis and successful resolution by h.p.1.c.59 C. A. Henrick Tetrahedron 1977,33 1845. " G. Henrici-Olivk and S. Olive Topics Current Chem. 1976 67 107. 61 S. S. Washburne J..Organometallic Chem. 1976 123 1. 62 B. M. Trost Tetrahedron 1977,33,2615. 6' E. Verkuijlen F. Kapteijn J. C. Mol and C. Boelhouwer J.C.S. Chem Comm. 1977 198. 64 J.-P. Laval A. Lattes R. Mutin and J. M. Basset J.C.S. Chem. Comm. 1977 502. 65 P. G. Gassman and T. H.Johnson J. Amer. Chem. Soc. 1977,99,622. 66 T.J. Katz and J. McGinnis J. Amer. Chem. SOC. 1977 99 1903. 67 J. L. Bilhou J. M. Basset R. Mutin and W. F. Graydon J. Amer. Chem. SOC. 1977,99,4083. " R. Baker and M. J. Crimmin Tetrahedron Letters 1977,441. 69 T. J. Katz and W. H. Hersh Tetrahedron Letters 1977 585. 70 Proceedings of the International Symposium on Metathesis Noordwijkerhout Sept. 1977 Rec. Trao. chim. 1977,96 ml. 71 J. E. McMurry and M. P. Fleming J. Amer. Chem. SOC. 1974,96,4708; J. Org. Chem. 1976,41 896. 72 B. Feringa and H. Wynberg J. Amer. Chem. Soc.,1977,99,602. 73 D. Lenoir Synthesis 1977 553. 74 G. A. Olah and G. K. S. Prakash J. Org. Chem. 1977,42,580. 75 J. E. McMurry and L. R. Krepski J. Org. Chem 1976,41,3929. 186 D.R.Taylor on alumina-(+)-TAPA [2-(2,4,5,7-tetranitro-9-fluorenylideneamino-oxy)pro-pionic acid] of the (*)-cis-and (*)-trans-bi-hexahydrophenanthrylidenes(13a and b) in which chirality stems solely from torsional di~tortion.~~ (1 3a) (13b) Tetrakis(neopentyl)ethylene synthesized by the Ti" coupling reaction is unaffected by bromine in carbon tetrachloride and is not even protonated in FS03H-S02C1F although the more powerful Magic Acid cleaves the neopentyl groups.74 Another exceptionally unreactive olefin (14) named [ 10,101-betweenane has been reported; it has a doubly trans-cycloalkene 7r-bond and so has no accessible face for attack upon the olefinic Another alternative to the Wittig reaction in this case suitable for preparations of terminal alkenes is the interaction of a Grignard reagent with Eschenmoser's salt (15) (Scheme 18).77The intermediates are amine oxides which decompose at somewhat higher temperatures than the intermediate betaines of the Wittig pro- cedure.CH -he21-2R'R2CHCH2NMe2 '-( 15) ii 1 R'R2C=CH2 2 R'R2CHCH2$Me2 I 0- Reagents 1 R'R2CHMgX or R'R2CHLi; ii H202; iii 150 "C Scheme 18 Further papers on the useful olefin synthesis technique based on diphenyl-phosphinoyl migrations have a~peared.~' The main limitations foreseen for this approach are (i) that the necessary Ph,P(O) migration no longer occurs when an alternative tertiaky migration origin is present and (ii) that aryl groups at the 76 J. A. Marshall and M. Lewellyn J. Amer. Chem Soc. 1977,99 3508.77 J. L. Roberts P. S. Borromeo and C. D. Poulter Tetrahedron Letters 1977 1299. 78 A. H. Davidson I. Fleming J. I. Grayson A. Pearce R. L. Snowden and S. Warren LCS. Perkin I 1977 550; A. H. Davidson C. Earnshaw J. I. Grayson and S. Warren ibid p. 1452. Aliphatic Compounds-Part (i ) Hydrocarbons 187 migration terminus or four- or five-membered alicyclic rings at the migration origin tend to produce substantial amounts of vinyl- rather than allyl- phosphine oxides (Scheme 19). A Wittig-Horner route to vinyl ethers and hence ultimately applicable to ketone synthesis has also appea~ed.’~ R2 I I ,R’ migration Ph (0)-c-c-c +/ R2 R’ 2 ‘ A1 \ R‘ OH P migration R2 \+ I I c-c-c-/I I Ph2P(O) R2 \ I \I I c=c-c-c-c-c-I /I I /Ph21&3) PhJW Scheme 19 Olefin syntheses via vinylsilanes should prove more easy to undertake now that vinysilanes are accessible from ketones by a two-step procedure (Scheme 20).80 0 NNHTs Li SiMe3 TsNHNH~ BuLi Me3SiX I *c/H \ C-q \ Scheme 20 Trisubstituted vinylsilanes produced stereospecifically or with a stereochemistry subsequently determined by for example 13C n.m.r.spectroscopy may be con- verted by a variety of electrophilic reagents into trisubstituted alkenes of known structure (Scheme 21).81 The hydrolysis of vinylsilanes which leads to the replacement of Si by H has been found to occur readily in wet acetonitrile with toluenesulphinic acid as catalyst but in this reaction the geometry about the double bond is not retained.” ’’C.Earnshaw C. J. Wallis and S. Warren J.CS. Chem. Comm. 1977,314. 8o R.T.Taylor C. R. Degenhardt W. P. Melega and L. A. Paquette Temahedron Lefters 1977 159. T. H. Chan P. W. K. Lau and W. Mychajlowskij Tetrahedron Letters 1977 3317; T. H.Chan W. Mychajlowskij and R. Amouroux ibid. p. 1605. G.Buchi and H. Wiiest Tetrahedron Letters 1977,4305. 188 D. R. Taylor R CHzR' RCHO 4RCH(OH)C(SiMe3)=CH2 % \/ C=C I H' \SiMe3 iv. iii 1. Reagents 1 CH2=C(Li)SiMe3 -78 "C;ii Ac20; iii R'&uLi; iv SOC12-Et20 25 "C;v Br2 or I2 or AcCI-AICl or Cl2CHOMe-AICl3 Scheme 21 The alkenylboranes derived by syn-addition of 9-borabicyclononane (9-BBN) to terminal acetylenes have been found to be much more reactive towards carbonyl groups than saturated organoboranes.Their addition to aldehydes followed by oxidative hydrolysis in the usual way provides an ultra-mild pseudo-Grignard synthesis of allylic alcohols of known geometry (Scheme 22).83 Terminal olefins ~~ H' \CHRl I OH Reagents i 9-Borabicyclononane (9-BBN); ii R'CHO-THF; iii NaOH-H202 Scheme 22 have been prepared by a two-carbon homologation procedure commencing with the reaction of vinylmagnesium bromide with a trialkylborane yielding a vinylborate(1 -) which is cleaved with alkali and iodine.84 Borate esters formed quantitatively from a secondary alcohol and boric acid feature in a mild procedure for olefin formation which is effectively a two-step dehydration of the alcohol. The esters are decomposed by boron trifluoride etherate at 100"C,and olefin yields are excellent; isomeric mixtures of compositions similar to those obtained by other dehydration methods are formed.85 Ally1 alcohols can be converted into olefins by replacement of the hydroxy-group by alkyl or aryl residues on treatment with the appropriate alkyl- or aryl-magnesium halide in the presence of nickel(I1) complexes though the formation of 83 P.Jacob and H. C. Brown J. Org. Chem. 1977,42,579. K. Utimoto. K. Uchida M. Yarnaya and H. Nozaki Tetrahedron 1977,33 1945. M. P.Doyle S. B. Williams and C. C. McOsker Synthesis 1977 717. Aliphatic Compounds-Part (i) Hydrocarbons 189 mixtures of isomers indicated that allylic rearrangement accompanied the substitu- tion.86 A more reliable technique for achieving this rather unusual hydroxyl replacement would seem to be that based on the initial conversion of the alcohol into a lithium allyloxyalkylcuprate a source of the allyloxy nucleophile for reaction with the phosphonium iodine (16) (Scheme 23).87 \ II Ill \ II C=C-C-OH -% [ y=C-F-OCuR C=C-C-R / I / I + Reagents i MeLi; ii Cur; iii 3RLI; iv Ph3PNMePh I-(16) -78 to i2.5 “C Scheme 23 Some elegant syntheses of naturally occurring compounds have been reported which are based upon the use of butadiene telomers as starting materials.Exam- ples include the synthesis of cis-civetone88 and queen ~ubstmce.~~ Tidwell and co-workers have previously shown that the rates of acid-catalysed hydration of 1,l -disubstituted alkenes can be satisfactorily correlated with the sum of the up+constants of the l-sub~tituents,~~ according to the equation This correlation also applies to the rates of hydration of 2-substituted buta-1,3- dienes vinyl acetates and vinylphosphates and successfully provides a correlation for literature data on hydration rates of 22 substituted styrene~.’~ This finding is taken to confirm the Ads,2 (rate-determining C-protonation) mechanism.Hydra- tion rates of 1,2-disubstituted olefins require the mathematical model to be slightly m~dified.~’ An alternative procedure for effecting the uic-addition of halogens to olefins which avoids the use of elemental bromine or chlorine has been reported. Positive halogenonium ions are formed from the mixed reagent HX-H202 and the addition of phase-transfer catalyst (PTC) to the two-phase brew minimizes halohydrin formation:92 aq.HX-H,O R’CH=CHR2 AR’CHXCHXR2+ 2H20 ca4-pTc Suitable conditions for vicinal anti-addition of I’ -OH- I+-Cl- and 1’-OCOR-to alkene~~~ and for vicinal alkoxyselenation (addition of RO-SePh) of olefins?’’ have been reported. 86 C. Chuit H. Felkin C. Frajerman G. Roussi and G. Swiernewski J. Organometallic Chem. 1977 127,371. 87 Y. Tanigawa H. Kanamaru A. Sonoda and S.-1. Murahashi J. Amer. Chem. Soc. 1977,99 2361. 88 J. Tsuji and T. Mandai Tetrahedron Letters 1977 3285. 89 J. Tsuji K. Masaoka and T. Takahashi Tetrahedron Letters 1977 2267. 90 W. K. Chwang P. Knittel K. M. Koshy and T. T. Tidwell J. Amer. Chem. SOC.1977,99,3395; S. Y. Attia J. P. Berry K. M..Koshy Y.-K. Leung E. P. Lyznicki V. J. Nowlan K. Oyama and T. T. Tidwell ibid. p. 3401. 91 P. Knittel and T. T. Tidwell J. Amer. Chem Soc. 1977,99 3408. 92 T.-L. Ho B. G. B. Gupta and G. A. Olah Synthesis 1977 676. 93 R.C. Cambie D. Chambers P. S. Rutledge and P. D. Woodgate J.C.S. Perkin I 1977 2231; R. C. Cambie W. I. Noall G. J. Potter P. S. Rutledge and P. D. Woodgate ibid. p. 226. 94 A. Toshirnitsu S. Uernura and M. Okano J.C.S. Chem. Comm. 1977 166. 95 N. Miyoshi S. Murai and N. Sonoda Tetrahedron Letters 1977 851 190 D. R. Taylor There have been two useful advances in olefin hydroboration both stemming from H. C. Brown’s group. Firstly the relatively stable reagent Me,S,BH is commercially available and makes an excellent starting material for generating borane for addition to hindered olefins or for the preparation of ~atechylborane.~~ Secondly it is possible to add 9-BBN selectively to one (usually the less-hindered) double bond of non-conjugated dienes and hence to introduce functionality at the site of carbon-boron bond formation a procedure which should find numerous applications in synthesis (Scheme 24).97 Scheme 24 This year has not been noteworthy for novel developments in olefin cyclo- additions although major papers on the application of the concept of hard and soft acids and bases to the Woodward and Katz model of the Diels-Alder reaction and to [2+2] cycloadditions have appeared.98 The basis for this treatment of the Diels-Alder reaction is that unsymmetrical reagents will unite to form the two new 0-bonds non-synchronously via a non-symmetrical transitiou state hence predic- tion of the orientation of addition may be made by determining which 0-bond should be formed faster.The assumption is made that this bond will be that linking the softest centres i.e. the terminal atoms with greatest overlap stabilization. This leads for electron-deficient (low LUMO) and electron-rich (high HOMO) reac-tants to the rule that atoms with the largest coefficients in these MOs will bond preferentially. Note that all four frontier orbitals must be considered if both reactants have similar electron densities at their terminal atoms. Applications of Diels-Alder reactions to complex synthetic problems continue to impress this Reporter.Examples which should illustrate this are (i) the use of inter-and intra-molecular Diels-Alder additions of cyanodienes formed in situ by elec- trocyclic ring-opening of benzocyclobutenes (Scheme 25)99 and (ii) a sequence which may involve the first known example of a bimolecular pericyclic reaction in natural biosynthesis. loo Ene reactions have proved a more fruitful area for new developments. A series of conjugated dienes which undergo the ene reaction and cycloaddition simul- taneously were treated with a variety of enophiles (maleic anhydride azo-esters 96 H. C. Brown A. K. Mandal and S. U. Kulkarni J. Org. Chem. 1977,42 1392. 97 R. Liotta and H. C. Brown J. Org. chem. 1977,42 2836. 98 0.Eisenstein.J. M. Lefour N. T. Anh and R. F. Hudson Tetrahedron 1977 33 523; C. Minot and N. T. Anh ibid. p. 533. 99 T. Kametani Y. Hirai F. Satoh and K. Fukumoto J.C.S. Chem. Comm. 1977 16. loo R. D. Stipanovic A. A. Bell D. H. O’Brien and M. J. Lukefahr Tetrahedron Letters 1977 567. Aliphatic Compounds-Part (i) Hydrocarbons &,H28 Me0 ' -OEt Reagents i isoprene 180 "C,2h; ii NaNH, liq. NH3; iii 210-215 "C,toluene sealed tube Scheme 25 etc.). The product distributions indicated that steric factors were not of prime importance in the partitioning of a given diene between the two pathways.'" However the relative reactivities of different dienes towards a given eno-phile/dienophile were explicable on a steric basis; for example (17) is ten times more reactive than (18)towards diethyl azodiformate at 25 "C,because its reactive face is less hindered than either face of (18) in spite of the statistical advantage of (18) which has a suitably placed axial hydrogen on both sides of the ring.A concerted ene reaction seems therefore to be occurring a conclusion also reached after a kinetic study of ene reactions between maleic anhydride and a series fbr \ii Reagents i PhSO,N=SO; ii SO,; iii allylic rearrangement; iv retro-ene -SO2 Scheme 26 lo' B. M. Jacobson A. C. Feldstein and J. I. Smallwood I. Org. Chem 1977,42 2849. 192 D. R. Taylor of acyclic mono-olefins. lo' Some novel enophiles have been reported they include N-sulphinylbenzenesulphonamide(PhSOZN=S=0)lo3 and sulphur dioxide,lo4 the latter causing rapid thermal isomerization of thermodynamically unstable olefins such as P-pinene (Scheme 26).Other novel ene reactions were those induced by the acyl cation (from acetyl hexachloroantimonate) in which a carbocation addi- tion-elimination sequence was precluded by the absence of rearrangement pro- duct~,~~~ and the ally1 anion (Scheme ,,).''' -+ products Scheme 27 Catalytic ene reactions of chloral have been the subject of an elegant investiga- tion. Lewis acids which complex with chloral lower the required temperature for ene insertion which becomes a relatively clean reaction though not always free from by-product formation. Subsequent functional group modification may make this a useful technique for attacking the allylic position in synthesis (Scheme 28).1°' Pr"CH2CH=CH2 Pr"CH=CHCH2CH(0H)CCl3 y iv-vi Pr"CH=CHCH=CHC02Et Pr"CH=CHCH2 CH( OH)CH ii'y I Pr"CH2 CH2CH2C02H Reagents i CC13CHO-SnC14 (1-5%) CC14; ii NaH-TsCI; iii NaOEt-EtOH; iv Pd/C-H*; v Cr03; vi aq.NaOH; vii Bun3SnH Scheme 28 With a chiral olefin such as P-pinene choice 0f.a suitable Lewis acid catalyst enables stereochemical control of the reaction to be achieved. An improved technique for allylic oxidation by selenium dioxide uses mainly t-butyl hydroperoxide as the oxidant with only 1-2% SeO, unless the olefin is very unreactive when higher proportions may have to be used."' A detailed study of chromyl chloride oxidation of olefins has shown that all of the three primary products namely expoxide chlorohydrin and vicinal dichloride arise by syn-addition.lo9 These observations necessitate a revision of earlier mechanistic pro- F.R. Benn J. Dwyer and I. Chappell J.CS. Perkin ZZ 1977 533. G. D6l&ris,J. Kowalski J. Dunogues and R. Calas Tetrahedron Letters 1977 4211. '0.1 M. M. RogiC and D. Masilamani J. Amer. Chem. SOC.,1977,99 5219. lo' H. M. R. Hoffmann and T. Tsushima J. Amer. Chem. Sac. 1977,99,6008. 1mJ. H. Edwards and F. J. McQuillan J.CS. Chem. Comm. 1977 838. lo' G. B. Gill and B. Wallace J.C.S. Chem. Comm. 1977,380,382. M. A. Umbreit and K. B. Sharpless J. Amer. Chem. Soc.,1977,99,5526. '09 K. B. Sharpless A. Y. Teranishi and J.-E. Backvall J. Amer. Chem SOC.,1977,99,3120. Aliphatic Compounds-Part (i) Hydrocarbons posals based on the intermediate formation of cations and a scheme involving organochromium(v1) species was advanced (Scheme 29).By contrast evidence that hindered olefins may react with singlet oxygen via a cationic perepoxide pathway was obtained by the detection of substantial amounts of cationic rear- rangement products from camphenylideneadamantane.' '' J J Scheme 29 A new variety of polymer-bound hydrogenation catalyst uses rhodium(II1) chloride or other metal halides complexed to a phosphine which is chemically bonded to silica. ' Photoelectron spectroscopy bas shown that ethylene chemi- sorbed on tungsten has essentially sp3-hydridized carbon atoms with a carbon- carbon bond length stretched to 1.54 a further manifestation of the diverse applications of this recently developed analytical technique.'Io F. McCapra and I. Beheshti J.C.S. Chem. Comm. 1977,517. '" K. Kochloefl W. Liebelt and H. Knozinger J.CS. Chem. Comm 1977,510. T. V. Vorburger B. J. Waclawski and E. W. Plummer Chem. Phys. Letters 1977,46,42.

ISSN:0069-3030    

DOI:10.1039/OC9777400175

出版商:RSC    

年代:1977

数据来源: RSC

摘要:

9 Aliphatic Compounds Part (ii) Other Aliphatic Compounds By R. S. WARD Department of Chemistry University College of Swansea Swansea SA2 8PP Many recent developments in aliphatic chemistry can be directly attributed either to the continued search for new synthetic methods or to attempts at rationalizing mechanistic or stereochemical principles. Consequently current research reflects a strong interest in the following topics (a) new and improved asymmetric syntheses of chiral compounds; (b) the development of new methods for preparing lactones; (c) investigations of reversed (umpolung)reactivity and equivalent reagents; (d) the generation and reactions of regiospecific enolates; (e) studies of the stereochemistry of reactions in organo-phosphorus compounds; (f) investigations of new reactions of organo-sulphur compounds.1 Amines and Imines The polyether antibiotic lasalocid produced by Streptomyces lusuliensis has been used to resolve racemic amines by fractional crystallization of their salts.' High enantioselectivity is observed ("/o R :S-90 :10) in cases where the asymmetric carbon atom is attached directly to the primary amino-group (e.g. 1,2). When the asymmetric centre is separated from the amino-group by a methylene group (e.g. 3,4) the efficiency of the resolution is reduced (YOR :S -25 :75) and the enan- tiomer in excess has the opposite configuration (cf. 1and 4). Many enzyme-catalysed reactions involve the oxidation or reduction of nitrogen containing compounds by NAD(P) or NAD(P)H. Model studies have shown that amines can be oxidized by pyridinium salts.2 Furthermore imines can be reduced by 1,4-dihydropyridine derivatives in the presence of metal complexes (Scheme l).3 ' J.W. Westley R. H. Evans and J. F. Blount J. Amer. Chern. Soc. 1977,99,6057. 'Y.Ohnishi Tetrahedron Letters 1977,2109. U.K.Pandit H. van Dam and J. B. Steevens Tetrahedron Letters 1977,913;see also R.A. Gase and U. K. Pandit J.C.S. Chem. Comm. 1977,480. 194 Aliphatic Compounds-Part (ii) Other A lipha tic Compounds ArCH=NR HH C0,Et EtOlcQCO2 Et Eto2cj-7J Me Me Me Me H Scheme 1 The metal-ion catalysed synthesis of a-amino-esters from a-keto-esters and amines in the presence of 1,4-dihydropyridines has also been rep~rted.~ These reactions can be regarded as models for the enzyme-catalysed interconversion of a-keto- and a-amino-acids.Indeed they serve to demonstrate the importance of electrophilic catalysis in NAD(P)H mediated reduction reactions. The anions derived from dialkylallylamines (5) are useful P-acyl carbanion equivalents.' With alkyl halides the y-substituted products (6) are formed while with aldehydes and ketones a mixture of the cyclized y-adduct (7) and the a-adduct (8) is obtained. The lithium reagent (9) gives approximately equal amounts of (7) and (8)while the analogous zinc reagent (10)gives mainly the a-adduct (8). (5) (9) M=Li (10) M=Zn The anions derived from N-nitrosoamines also react with electrophilic reagents (Scheme 2).6 The reactions are regio- and stereo-selective and can be used to effect Li E LiNPr; I E+ I R CH2R' -78°C R CHR'--+R CHR' '\ N / 'N/ 'N/ I I I NO NO NO Scheme 2 electrophilic substitution at the a-carbon atom of secondary amines.The anions derived from N-nitrosoallylamines undergo alkylation at the a-position but react K Nakamura A. Ohno and S. Oka Tetrahedron Letters 1977,4593. ' S. F. Martin and M. T. DuPriest Tetrahedron LRtrers 1977 3925. D. Seebach D. Enders and B. Renger Chem. Ber. 1977,110,1852;B. Renger H.-0. Kalinowski and D. Seebach ibid. 1866; D. Seebach D. Enders R. Dach and R. Pieter ibid. 1879; B. Renger and D. Seebach ibid. 2334. 196 R. S. Ward with aldehydes and ketones reversibly to give a mixture of 0-and y-substituted products.Although reactivity at the a-position is kinetically favoured the y- products are formed exclusively under conditions which favour thermodynamic control. The vinyloxycarbonyl group (VOC) has been shown to be a versatile protecting group for amino-compounds. Amino-acids can be easily converted into their N-VOC derivatives by treating them with vinyl chloroformate. The protecting group can be selectively removed by treatment with HCI HBr or bromine in dichloromethane followed by warming in alcohol. Since vinyl chloroformate also attacks tertiary amines it provides a method for selective dealkylation of tertiary amines (1 1+E).' i HCI HBr -izz-+ H A new procedure for the NN-dimethylation of primary amines involves the preparation and reduction of the bis(alkoxymethy1)amine [RN(CH20CH3)2],8 while N-alkylation of secondary amines by alcohols can be accomplished in high yields (94-98 "/o) in the presence of aluminium t-butoxide and Raney nickel.' The conversion of primary amines into esters (13 -P 14) can be carried out by treating Ph Ph 'h'fiPh I BF4-CHzR BF4-the amine with 2,4,6-triphenyl-pyrylium tetrafluoroborate to give a pyridinium salt which is then heated in vacuo with the sodium salt of a carboxylic acid." Secondary enamines (15) are thermodynamically unstable since they exist in equilibrium with the tautomeric imines (16).However secondary enamines can be prepared by partial methanolysis of organo-tin or magnesium salts of imines." R2 R2 H R2 H I M 1H I H (15) (16) R.A. Olofson Y. S. Yamamoto and D. J. Wancowicz Tetrahedron Letters 1977 1563; R. A. Olofson R. C. Schnur L. Bunes and J. P. Pepe ibid. 1567. H. Kapnang G. Charles B. L. Sondengam and J. Hentchoya Hemo Tetrahedron Letters 1977,3469. M. Botta F. De Anngelis and R. Nicoletti Synthesis 1977 722. '" U. Gruntz A. R. Katritzky D. H. Kenny M. C. Rezende and H. Sheikh J.C.S. Chem. Comm. 1977 701. " B. De Jeso and J.-C. Pommier J.C.S. Chem. Comm. 1977 565. Aliphatic Compounds-Part (ii) Other Aliphatic Compounds They are stable at -80°C but completely isomerize within one hour at room temperature. Optically active oxaziridines (18) can be prepared by oxidation of imines (17) with m-chloroperbenzoic acid in (S)-(+)-2,2,2-trifluoro-1-phenylethanol,’* or by photochemical rearrangement of nitrones (19)in the same chiral s01vent.l~ In both cases the enantioselectivity of the reaction is increased by lowering the tempera- ture.The optical yields obtained by both methods compare favourably with those obtained by oxidation of imines with chiral peroxyacids. In the case of an optically active imine (e.g. 20) the diastereoselectivity of the reaction is not dependent upon the nature or chirality of the peroxyacid or the solvent. Indeed the configuration of the major product depends only on the configuration of the starting imine. If the substituent has the R configuration attack from the Si face is referr red.'^ 0 m-CPBA * hu Ph,C=NR -PhzC-NR 7PhZC=N 7 CF3CHPhOH CF3CHPhOH ‘0’ ‘R (17) (18) (19) Ph H Ph H H H I&’ A/‘/ (20) (21) The enantioselective alkylation of the cyclohexanone imine (22) gives a product of high optical purity (81 YO)due to the presence of a suitably situated ether group which reduces the flexibility of the metallated intermediate (23).15 The alkylation of a chiral enamine of cyclohexanone gives a product of equally high optical purity (83 O/O).~’ (22) (231 The cycloaddition of chiral carbodi-imides to achiral ketenes provides an asym- metric synthesis of p-lactams while 173-dipolar cycloaddition of chiral nitrones to achiral alkenes affords optically active isoxazolines.l6 12 A. Forni I. Moretti and G. Torre J.C.S. Chem. Comm. 1977,731; M. Bucciarelli A. Forni I. Moretti and G. Torre J.C.S. Perkin II 1977 1339.13 D. R. Boyd and D. C. Neill J.C.S. Chem. Comm. 1977,51. 14 D. Mostowicz and C. Belzecki J. Org. Chem. 1977,42,3917. 15 J. K. Whitesell and M. A. Whitesell J. Org. Chem. 1977 42 377; J. K. Whitesell and S. W. Felman ibid. 1663. 16 C. Belzecki and Z. Krawczyk J.C.S. Chem. Comm. 1977 302; C. Belzecki and 1. Panfil ibid. 1977 303. 198 R. S. Ward 2 Nitriles and Isocyanides Achiral carbocations generated from racemic alcohols react with chiral nitriles to give a mixture of diastereoisomeric amides which can be hydrolysed to give optic- ally active amines (Scheme 3).17 1 R3R4H+CHOH Scheme 3 trans-p-(1-Pyrrolidiny1)acrylonitrilereacts with lithium di-isopropylamide at -105°C to give the P-metallated derivative but at higher temperatures the a-metallated derivative is formed (Scheme 4).'' Both vinyl-lithium reagents react with electrophiles with retention of the configuration of the double bond. Scheme 4 The thermal rearrangement of nitrile oxides (24) to isocyanates (25) is limited as a preparative method by competition from the dimerization reaction. However the rearrangements can be carried out in exceilent yields under mild conditions by using a suitable catalyst such as sulphur dioxide which participates in the reaction as a dip~larophile.'~ R-CN+O * *R-N=C=O (24) (25) 4so2 t " W. Tomasik and C. Belzecki J.C.S. Chern. Comm. 1977 86. R. R. Schmidt and J. Talbiersky Angew. Chem. Internat. Edn. 1977 16 853. l9 G. Trickes and H. Meier Angew.Chetn. Internat. Edn. 1977 16,555. Aliphatic Compounds-Part (ii) Other Aliphatic Compounds N-Acyl isocyanides (26) can be prepared by treating carboxylic acid iodides with silver cyanide.20 They react with ynamines to give adducts (27) and undergo cycloaddition to electron-deficient alkynes to give heterocyclic products (28). N-Imidoyl-isocyanides have also been prepared from N-phenyl-imidoyl bromides. Me PhCOMNEt2CN +# (27) RCOI AgCNb RCONC-(26) % PhYNhx N' N(COPh) (28) (X= ester) a-Metallated isocyanides undergo cycloaddition to polar double bonds and also act as synthons for a-metallated primary amines (Scheme 5).*' They contain a Scheme 5 nucleophilic centre (the metallated carbon atom) and an electrophilic centre (the isocyanide carbon atom) and therefore undergo cycloaddition with imines e-g.,to give 2-imidazolines.The reaction with alkyl halides leads to chain extension of the amine equivalent. The reactions of metallated alkenyl isocyanides with elec- trophiles and 2-isocyanoacrylic esters with carbanions have also been studied. 3 Nitro-compounds The powerful nucleophilic toluene p-thiolate anion can displace a nitro-group from simple unactivated primary and secondary nitroalkanes yielding alkyl p-tolyl sulphides apparently by a conventional SN2displacement process.22 Several methods for converting nitroalkanes into carbonyl compounds are available including the acid-catalysed hydrolysis of nitronate salts (Nef reaction). 2o G. HoRe and B. Lange Angew. Chem.Infernat. Edn. 1977,16,262 and 727. " U. Schollkopf Angew. Chem. Infernal. Edn. 1977 16 339; U. Schollkopf K.-W. Henneke K. Madawinata and R. Harms Annalen 1977,40; U. Schollkopf D. Stafforst and R. Jentsch ibid. 1167; U. Schollkopf and R. Meyer ibid. 1174; R. Meyer U. Schollkopf and P. Bohme ibid. 1183. '' M. Benn and A. C. M. Meesters J.CS. Chem. Comm. 1977,597. 200 R. S. Ward The oxidative cleavage of nitronate anions under very mild conditions using t- butylhydroperoxide and VO(acac) as catalyst affords a simple approach to the prostaglandin intermediate (29).23The nitro to carbonyl conversion can also be (EtO),CH (EtO),CH Q-CH(OE1) fiNO VO(acac)2 -A- NO2 0 (29) achieved using basic silica gel. The usefulness of silica both as a reaction medium and as a reagent is illustrated by the synthesis of dihydrojasmone (30) from n-he~tylamine.’~ /-/-/-wNH2 nc::a* ’ /-v-4-4N02 St02 I (30) mi-Nitro-compounds are oxidized to olefinic dimers by silver ions.For example tetramethyl 1,3,5-hexatriene- 1,1,6,6-tetracarboxylate(31) is obtained by heating the silver salt of dimethyl 3-aci-nitro-l-propene-l,l-dicarboxylate (32) in aceto- nitri~e,’~ X X X ).C-CH=NO,-Ag+ 4 )= CH-CH=CH-CH =( X X X (X = C0,Me) A total synthesis of the naturally occurring azoxyalkene ‘elaiomycin (33)has been dary nitroalkanes have been reported.26 The dianions are powerful carbon nucleophiles unlike the simple monoanions which undergo 0-alkylation. 4 Azo-and Diazo-compounds A total synthesis of the naturally occurring azoxyalkene elaiomycin (33) has been rep~rted.’~ The azoxy function is generated by nitrosation of the protected 23 P.A. Bartlett F. R.Green and T. R. Webb Tetrahedron Letters 1977 33 1. 24 E. Keinan and Y. Mazur .I. Org. Chem. 1977,42 844 and J. Amer. Chem. SOC.,1977,99 3861. 2s T. Severin I. Brautigarn and K.-H. Brautigarn Chem. Ber. 1977 110,1669. 26 D. Seebach R. Henning F. Lehr and J. Gonnerrnann Tetrahedron Letters 1977 1161. 27 R. A. Moss and M. Matsuo J. Amer. Chem. SOC.,1977,99 1643. Aliphatic Compounds-Part (ii) Other Aliphatic Compounds urethane (34) followed by cleavage with potassium t-butoxide and alkylation of the diazotate so formed. HWH CH,OMe n-C,H, ."=NW.CH3 0 '0H HH (33) (34) 1-Phenyl- 1,2-diaza-allyl-lithium (35) reacts with primary alkyl halides at N-1 to give formaldehyde alkylphenylhydrazones (36) and with aldehydes and ketones at C-3 to give a-hydroxyaldehyde phenylhydrazones (37).*' R Li+ \,N-N=CH N Me /N.\\.-+,-,CHZ Ph Ph/ \N/ ph N k O (36) OH (35) I PhNHNZCHCR (37) The copper-catalysed thermolysis of a-diazo-P-dicarbonyl compounds in the presence of enol ethers provides a useful approach to p-methylfurans and their methylenelactone equivalent^.^^ The reaction of enol ether (38) with dimethyl diazo-malonate for example in the presence of trimethoxyphosphine copper(r)iodide gives the diester (39) which on treatment with sodium hydride followed by lithium aluminium hydride and finally acid yields menthofuran (40).ii,i NaH LiAIH4 (%. iii H+ (40) 5 Alcohols and Ethers A comparison of the acidities of alcohols and thiols in DMSO reveals that replacing the hydroxy group by SH results in a 16-20 kcal/mol increase in the enthalpy of T. Kauffmann D. Berger B. Scheerer and A. Woltermann Chem. Ber. 1977,110 3034. 2y E. Wenkert M. E. Alonso B. L. Buckwalter and I(.J. Chou J. Amer. Chem SOC.,1977 99,4778. 202 R. S. Ward depr~tonation.~' However while the acidity order for alcohols in DMSO is MeOH >EtOH >i-PrOH >t-BuOH the acidity order for thiols shows no apparent trend. The reversal of the acidity order for alcohols relative to the gas-phase apparently results primarily from the effect of the alkyl substituent on the heat of solvation of the alkoxide anion.The increased bulk of the alkyl residue hinders solvation of the anion and destabilizes it relative to the alcohol. In water there is apparently a complete reversal of the acidity order for both alcohols and thiols relative to the gas-phase. The main factor responsible for the reversed acidity order for thiols is the entropy of ionization in aqueous Alcohols react with diphenylphosphoryl azide along with triphenylphosphine and diethyl azodicarboxylate to give azides in 60-90 yield.32 The reaction is stereospecific involving inversion of configuration but is sensitive to steric hindrance. Trimethylsilyl iodide converts alcohols into iodides (with inversion of onf figuration).^^ The latter reagent can also be used to cleave ethers and esters under neutral conditions.The oxidative cleavage of alkyl and cycloalkyl ethers to carbonyl compounds can be accomplished using nitronium tetrafluoroborate or iodine pen tafluoride. 34 The reactions of optically active (R 2) allylic alcohols with NN-dimethyl- formamide dimethyl acetal proceeds stereoselectively via a [2,3]-sigmatropic re- arrangement to give optically active (R,E) amides with 100% transfer of chirality (Scheme 6).3' Me H Me-(MrO)zCHNM? Me,NCO HH Scheme 6 The reactions of epoxides with the sodium salts of malonate esters afford a novel approach to a-methylene y-lactones. Bis(a-methylene y-lactones) can be pre- prepared by treating diketones with 2-(bromornethyl)a~rylate.~~ 6 Aldehydes and Ketones Complete kinetic stereoselectivity can be achieved in aldol condensations of pre-formed lithium enolates (Scheme 7).37The erythro :threo ratio equals the (2):(E) ratio under appropriate conditions.By using the lithium enolate derived from a ketone containing a large alkyl group (e.g. R =But) one can obtain exclusively the erythro aldol since such ketones yield only the (2)enolate on deprotonation. '(' E. M. Arnett and L. E. Small J. Amer. Chem. SOC.,1977,99,808. 31 J. E. Bartmess and R.T. McIver J. Amer. Chem. SOC.,1977,99 4163. 32 B. Lal B. N. Pramanik M. S. Manhas and A. K. Bose Tetrahedron Letters 1977 1977. 33 M. E. Jung and P. L. Ornstein Tetrahedron Letters 1977,2659; M. E. Jung and M. A. Lyster J. Amer. Chem. SOC.,1977,99,968;see also T.-L.Ho and G.A. Olah Synthesis 1977,417 and M. E. Jung and M. A. Lyster J. Org. Chem. 1977 42 3761. 34 T.-L.Ho and G. A. Olah J. Org. Chem. 1977,42,3097; G. A. Olah and J. Welch Synthesis 1977,419. 35 K. K. Chan and G. Saucy J. Org. Chem. 1977,42,3828. 36 H. Marschall F. Vogel and P. Weyerstahl Annalen 1977 1557; N. Bensel K.-D. Klinkmiiller H. Marschall and P. Weyerstahl ibid. 1572. " W. A. Kleschick C. T. Buse and C. H. Hcathcock J. Amer. Chem. SOC.,1977,99 247; C. T. Buse and C. H. Heathcock ibid.,8109. Alipha tic Cornpounds-Part (ii ) Other Alip ha tic Compounds 203 Scheme 7 The stereoselectivity of the reaction can however be completely reversed by using the tetra-alkylammonium enolate derived from the same ketone. The stereoselective condensation of the lithium enolate (R =But) with a chiral aldehyde yields only two of the four possible diastereo-isomeric products.As a preparation reaction the aldol condensation suffers from the disadvantage that self-condensation products and a@-unsaturated carbonyl compounds are invariably formed. The aldol condensation between enol silyl ethers and carbonyl compounds (e.g. 41 +42) in the presence of tetrabutyl ammonium fluoride 38 (or titanium tetra~hloride~~) proceeds in a regiospecific manner and gives only minor quantities of the usual by-products. The use of dimethyl(methylene)ammonium trifluoroacetate and the corresponding iodide to quench regiospecifically generated enoiates affords a convenient route via the Mannich intermediate (e.g.44) to a-methylene ketones esters and lac tone^.^' OSiMe PhCHO Bu4N+F-* OSiMe 0 eNMe2 (43) (44) It has been demonstrated that the intramolecular Condensation of 1$diketones can be directed to give either of the two possible products (45 and 46) depending upon whether conditions favouring kinetic or thermodynamic control are empl~yed.~' 38 R. Noyori K. Yokoyama J. Sakata I. Kuwajima E. Nakamura and M. Shimizu J. Amer. Chem Soc. 1977,99 1265. 39 T. Mukaiyama Angew. Chem. Internat. Edn. 1977,16 817. 40 N. L. Holy and Y. F. Wang J. Amer. Gem. Soc. 1977 99 944; J. L. Roberts P. S. Borromeo and C. D. Poulter Tetrahedron Letters 1977 1621. 41 M. Larcheveque G. Valette and T. Cuvigny Synthesis 1977,424. 204 R. S. Ward 0 0 @OH Me &OH CHzR (45) (44) A difficulty which frequently arises in the alkylation of P-dicarbonyl compounds is the concurrent formation of C-and O-alkylated products.In addition the attempted monoalkylation of P -dicarbonyl compounds often gives low yields due to competition from dialkylation and othcr base-catalysed reactions. Several attempts have been made to overcome these difficulties by shielding the oxygen atom by association with a metal cation or a hydrogen-bonding solvent. A new procedure which gives high yields of mono- C-alkylated products with no apparent O-alkylation or other side reactions involves the use of monosolvates of 6-dicar-bony1 compounds with tetra-alkylammonium The oxygen atom is shielded not only by the large cation but also by the enol hydroxy-fluoride bond.Furthermore the reactivity of the P-dicarbonyl compound is enhanced by transfer of electron density from the fluoride anion via the hydrogen bond. The overall result therefore is to shield the oxygen atom while at the same time increasing the effectiveness of the molecule as a nucleophile. An n.m.r. study has shown that the anions derived from aldehyde dimethyl- hydrazones are formed with substantial stereoselectivity and do not equilibrate under the conditions usually employed for alkylation and acylation reaction^.^^ However a study of the stereospecificity of deprotonation and alkylation of ketone dimethylhydrazones has revealed a large kinetic preference for formation of the anti-anion followed by isomerization to give the thermodynamically more stable syn -anion (Scheme 8).44 In the case of unsymmetrical ketone dimethylhydrazones a primary carbanion is formed in preference to a secondary one irrespective of the hydrazone stereochemistry but subsequently isomerizes (in the case of an anti- anion) to give the syn-anion.The enantioselective alkylation of a metallated chiral hydrazone forms the basis of an asymmetric synthesis of chiral aldehydes4’ Doubly unsaturated carbonyl compounds react with nucleophiles at C-5. However this reactivity can be reversed by using the dianion formed from the 42 J. H. Clark and J. M. Miller J.C.S. Chem. Comm. 1977 64 and J.C.S. Perkin I 1977 1743. 43 M. Newcomb and D. E. Bergbreiter J.C.S. Chem. Comm. 1977,486. 44 M. E. Jung and T.J. Shaw Tetrahedron Letters 1977 3305. 45 D. Enders and H. Eichenauer Tetrahedron ktters 1977 191. Aliphatic Compounds-Part (ii) Other Aliphatic Compounds 205 analogous y8-unsaturated carbonyl compound (Scheme 9).46 The configuration of the product depends.upon the'nature of the electrophile used. 0 LE Scheme 9 There is a continued interest in the asymmetric reduction of carbonyl groups. The homogeneous hydrogenation of a-keto-esters using rhodium compIexes of chiral diphosphines gives a-hydroxy-esters with an enantiomeric excess of 66-76%.*' The complex produced by treating lithium aluminium hydride with two equivalents of a chiral amino-alcohol reduces acetylenic ketones to give chiral acetylenic alcohols with an enantiomeric excess of 60-84 YO.4H 7 Carboxylic Acids Dynamic n.m.r.spectroscopy has been used to study C-S p-pv-bonding and conformational equilibria (47 S 48) of thioacetic acid.49 The high rotational bar- Me S Me S I H (47) (48) rier that is observed is taken as evidence for an appreciable contribution from charged resonance forms and indicates that C-S and C-N p-pn-bonding are of similar importance in thioacetic acid and acetamide. Contrary to the generally accepted explanation for the activation of thiol esters the available da'ta suggests that such conjugation is less important in acetic acid itself. Two new methods for converting carboxylic acids into thiol esters have been reported The first involves treating the acid with carbonyl di-imidazole (CDI) or carbonyl di- 1,2,4-triazole (CDT) to give an activated intermediate which is then treated with the thi01.~' The second involves treating the carboxylic acid with a tris(alky1thio)borane (Scheme The kinetics and activation parameters for lactonization of a whole series (n = 3-23) of o-bromoalkanoic acids BT(CH~)"-~CO~H with strong bases in 99 Oh aqueous dimethyl sulphoxide have now been The reactivities span six " M.Pohmakotr and D. Seebach Angew. Chem. Internat. Edn. 1977,16 320. ''I. Ojima T. Kogure and K. Achiwa J.C.S. Chem. Comm. 1977,428. 48 R. S. Brinkmeyer and V. M. Kapoor J. Amer. Chem. Soc. 1977,99,8339. 49 E. A. Noe J. Amer. Chem. SOC.,1977,99 2803. '' H.-J. Gais Angew. Chem. Internat. Edn. 1977 16 244. 51 A. Pelter T.E. Levitt K. Smith and A. Jones J.C.S. Perkin I 1977 1672. 52 C. Galli G. Illuminati L. Mandolini and P. Tamborra J. Amer. Chem. Soc. 1977 99,2591 206 R. S.Ward WR’b Scheme 10 powers of ten the most reactive compound being the one for n = 5 and the least reactive being the one for n = 8. Comparison of the enthalpies of activation for ring-closure with those for the corresponding intermolecular reactions provides a quantitative estimate of the strain energies accompanying ring-closure. The highest strains are experienced for n =3 and 8. The entropies of activation confirm Ruzicka’s hypothesis that the probability of mutual approach of the two ends of a bifunctional chain decreases as the length of the chain increases. The reactions of unsaturated carboxylic acids with phenyl selenenyl halides or benzene sulphenyl halides afford a mild lactonization procedure which has the added advantage that the versatile phenylselenenyl or phenylsulphenyl group is incorporated into the product (e.g.49 + 50).53The PhSe or PhS group can then be removed by reduction to give the saturated lactone or by oxidation followed by elimination to give the unsaturated lactone (51). 8 Esters and Lactones It has been found that the order of introducing aIkyl groups (by alkylation using lithium di-isopropylamide ) into esters containing highly hindered a-carbon atoms is crucial in determining the overall yield of product ~btained.’~ Thus the yields of i-Pr,EtCCO,Et obtained by two complementary routes are shown +,:<n Scheme 11.i-Pr,CHCO,Et -f$b i-PrCH,CO,Et FK i-Pr2EtCC02Et EtI i-PrCHEtC0,Et Scheme 11 This and a number of similar examples demonstrate that a higher overall yield is obtained when the more bulky group is introduced last which is the reverse of the situation observed in the alkylation of ketones using sodium amide. The low reactivity of hindered esters may be due to the inability of the ester to form an enolate ion or to the lack of reactivity of the enolate once formed. Even highly s3 K. C. Nicolaou and Z. Lysenko J. Amer. Chem. SOC.,1977,99 3185 and J.C.S. Chem. Comm. 1977 293; D. L. J. Clive and G. Chittattu ibid. 484. s4 J. A. MacPhee and J.-E. Dubois J.C.S. Perkin I 1977 694. Aliphatic Compounds-Purt (ii) Other Aliphatic Compounds hindered esters such as i-Pr,CC02Et can be prepared in good yield (68 “/o) when hexamethylphosphoramide is present during both the.enolization and alkylation steps of the reaction. Various procedures for the mild cleavage of esters and lactones are available (e.g trimethylsilyl iodide33). The base-catalysed hydrolysis of esters by anhydrous hydroxide ions (KOBu‘:H20,2 :1)affords a very effective method for hydrolysing hindered The reaction has been shown to involve 0-acyl cleavage. Alternatively the phenylselenide anion can be used. The latter reagent provides a useful method for converting lactones (e.g. 52) into o-vinyl carboxylic esters (54) via the o-phenylselenenyl derivative (53).56 0 SePh (52) (53) (54) The rapid developments being made in the area of asymmetric synthesis have increased the need for methods for measuring enantiomeric purities.A useful method for determining the enantiomeric purity of a chiral lactone involves treating the lactone with (-)-(2R 3R )-2,3-butanediol to give a mixture of diastereoiso- meric ortho esters which can be analysed by g.1.~~’ The Pd’ catalysed cyclization of ally1 acetates provides a useful method for synthesizing large ring compounds (e.g. macrolides) by carbon-carbon bond formation (e.g. 55 -B 56).58 The reactions of a-bromo-esters of w-hydroxy-aldehydes (e.g. 57) with activated zinc and diethylaluminium chloride can also be used to prepare p -hydroxy-lactones (58).5’ Ly((fH2jn 11 (PhsP)4PdLNaH ,h H 2 ) nC0,Me CHC02Me OAc I S0,Ph SOzPh (55) G; OH 0 Br (57) ” P.G. Gassman and W. N. Schenk J. Org. Chem. 1977,42,918. 56 R. M. Scarborough and A. B. Smith Tefruhedron Letters 1977,4361; D. Liotta W. Markiewin and H. Santiesteban ibid. 4365 and 4369. ” G. Saucy R. Borer and D. P. Trullinger J. Org. Chem. 1977,42 3206. 58 Y. Kitagawa A. Itoh S. Hashimoto H. Yamamoto and H. Nozaki J. Amer. Chem. SOC.,1977 99 3864; B. M. Trost and T. R. Verhoeven ibid. 3867. 59 K. Maruoka S. Hashimoto Y. Kitagawa H. Yamamoto. and H. Nozaki. J. Amer. Chem.SOC.,1977.99 7705. 208 R. S. Ward 9 Amides and Lactams The barrier to internal rotation about the central C-N bond of NN-dialkyl-thioamides is considerably higher than in NN-dialkylamides themselves presume- ably indicating a greater contribution from polar resonance structures in the former case.A linear correlation in fact exists between the activation energy for C-N bond rotation and the 15N chemical shift in NN-dimethylamino derivatives.60 The increased polarization of thioamides also facilitates deprotonation of the NH group in N-alkylthioamides and reduces the rate of protonation of thioamides relative to amides6' Relatively few reliable methods are available for the mono-N-alkylation of amides. It has however been shown that simple amide methylols (59) can be directly coupled with trialkylaluminium reagents to produce good yields of the N-alkyl compounds (60).62 R R R CH20 N I N I N I H CHzOH CH,R' (59) (60) An efficient method for converting primary amides into nitriles involves treating the amide with trifluoroacetic anhydride and ~yridine."~ Primary thioamides on the other hand can be converted into nitriles by treating them with diethyl azodicar- boxylate and triphenylpho~phine.'~ + The reactions of various amides with phosgeniminium salts (Cl,C=NMe,CI-) have been investigated.Dicarboxamides react to give dicyanines which can be hydrolysed to give bis-malonamides and react with hydrazine to give dipyrazoles.6' N-A1 kylamides also react with phosgeniminium salts to give intermediates which on treatment with strong bases yield ynamides. Diamides (and dinitriles) can be converted into thiono- and dithio-esters of dicarboxylic acids (Scheme 12).66 i Et30+BF4-S S Me2NCO(CH2),CONMe2 -EtOy(cH2)n-f ii H~S-CSHSN OEt Scheme 12 60 G.J. Martin J. P. Gouesnard J. Dorie C. Rabiller and M. L. Martin J. Amer. Chem. SOC.,1977,99 1381. 61 B. G. Cox and P. de Maria J.C.S. Perkin 11 1977 1385. 62 A.Basha and S. M. Weinreb Tetrahedron Letters 1977 1465. 63 F.Campagna A.Carotti and G. Casini Tetrahedron Letters 1977 1813. 64 M. D.Dowle J.C.S. Chem. Comm. 1977,220. 65 M. Huys-Francotte Z.Janousek and H. G. Viehe J. Chem. Research 1977 100; E. Goffin Y. Legrand and H. G.Viehe ibid. 105;see also H.G. Viehe Chem. and Ind. 1977 386. 66 R.Hoffmann and K. Hartke Annalen 1977 1743. Aliphatic Compounds-Part (ii) Other Aliphatic Compounds 10 Anhydrides and bides Bis(thioacy1) sulphides (61) can be prepared by treating aliphatic dithiocarboxylic acids with dicyclohexylcarbodi-imide.6' They can be used to prepare sterically hindered dithio-esters (62).Acyl-thioacyl sulphides have also been prepared by treating sodium or piperidinium dithiocarboxylates with acetyl chloride. DCC t-BuSNa RCS2H --+ R-C-S-C-R -R-C-SBU' II II II ss S (61) (62) Enolate anions derived from acid anhydrides can be prepared by treating the anhydride with a sterically hindered base such as lithium l,l-bis(trimethylsilyl)-3-methyl- l-butoxide.68 Such anions react with aldehydes to give p-carbomethoxy y-butyrolactones (Scheme 13). Scheme 13 It is possible to reduce 1,3,3-trisubstituted succinimides regiospecifically at the least hindered carbonyl group by using dib~rane.~~ This should be contrasted with the reduction of the same compounds by sodium borohydride which attacks the most hindered carbonyl group.The optically active succinimide (63)is reduced by sodium borohydride to give a mixture of the diastereo-isomeric hydroxy-lactams (64) which react with methyl diethylphosphonoacetate and sodium hydride in dimethoxyethane to give a mixture of diastereo-isomeric esters (65).70This reac- tion affords a useful asymmetric synthesis of piperidine derivatives. The nature of the solvent influences the diastereoselectivity of the reaction. 0 ti-NaBH4 (EtO)ZPCHCO*Me R R 0Qo-0 O R O H oO:H2c0*Me (631 (64) (65) [R= (S)-1-phenylethyl] 11 Phosphorus Compounds Phosphinothioic methanesulphonic anhydrides react with aluminium chloride to form complexes which can be decomposed by water or methanol to give phos- 67 S.Kato T. Takagi T. Katada and M. Mizuta Angew. Chem. Internat. Edn. 1977,16,786; S. Kato A. Hori T. Takagi and M. Mizuta ibid. 787; S. Kato K. Sugino M. Yamada T. Katada and M. Mizuta ibid. 879. 68 N. Minami and I. Kuwajima Tetrahedron Letters 1977 1423. 69 R. Suess Helv. Chim. Acta 1977,60 1650. 'O T. Wakabayashi and M. Saito Tetrahedron Letters 1977,93. 210 R. S. Ward phinothioic halides with retention of configuration at the phosphorus atom.71 The reaction affords a stereoselective synthesis of the phosphinothioic halides. The assignment of configuration to the product is achieved by correlation of its optical rotation with that of the halide obtained by treating the phosphinothioic acid with phosphorus pentachloride which is known to involve inversion of configuration (Scheme 14).t-Bu S t-Bu S '\\ // i. AIC13 '\\ P// P ii H20 Ph' \OS02Me Ph' \CI t-Bu S t-Bu C1 '\\ // PCIS '\\ / P ____+ P Scheme 14 A new synthesis of imidate esters of phosphorus from amidates has been used to prepare the chiral phosphinimidate (67) from (66).72 Me-\ /NHBu' Et30+ Me NHBu' Me,, put PFg-' '\\+/ KH P P ___ P Ph' \O Ph' 'OEt Ph' \OEt The acid-catalysed alcoholysis of a series of phosphinic amides containing different leaving groups has been studied. At low concentrations of HCl the reactions proceed with inversion of configuration but at higher concentrations retention becomes increasingly important and eventually exceeds inversion for (68) and (69).73At a given acid concentration the proportion of the reaction proceeding with retention of configuration depends on the nucleophilicity of the leaving group.Ph 0 Ph 0 (68) R=Ph (69) R = P-O~NC~H~ A stereospecific route to chiral OS-dialkylphosphoramidothioateshas been devised and their acid-catalysed alcoholysis Once again two competing reactions are evident one involving inversion of configuration and favoured by low 71 J. Michalski and Z. Skrzypczynski J.C.S. Chem. Comm. 1977,66. 72 K. E. DeBruin and L. L. Thomas J.CS. Chem. Comm. 1977,33. 73 M. J. P. Harger J.C.S. Perkin I 1977 2057. 74 C. R. Hall and T. D. Inch Tetrahedron Letters 1977 3761 and 3765.Aliphatic Compounds-Part (ii) Other Aliphatic Compounds 211 acid concentrations the other involving retention of configuration and unaffected by acid strength. 12 Sulphur Compounds Enolate anions react with allenic sulphonium. salts to give a variety of products (e.g 70 and 73).75 *3C-Labelling experiments have shown that formation of the furan (70) involves attack on the a,rather than the y-carbon atom in the cyclization step. The initial adducts (71) formed with monosubstituted malonic esters undergo proton abstraction by sodium ethoxide to form an ylide (72) which then undergoes a [2,3]sigmatropic rearrangement to give (73). In the case of unsubstituted malonic esters the ylide rearrangement is preceded by a [1,3]prototropic shift to give the conjugated tautomer.+ + NCCH2COPh MezSJ ,-'='HZ CH Me2SCH=C=CH2 -OEt OLL-CN Mee(C02Et)~ I 'H I OEt Ph (70) 4 + Me2S-CH-C=CH2 -OEt ~ I -+ MeSCH2CH2C=CH2 MeC(CO,Et) I MeC(C02Et) MeC(C02Et)2 (72) (73) The anions derived from alkylphenylsulphides react with electrophiles to give a-substituted product^.'^. The anions derived from allylphenylsulphides on the other hand react with electrophiles at either the a-position (with alkyl halides) or the y-position (with carbonyl corn pound^).^' Allylphenylsulphides also readily undergo a heat light or acid catalysed [1,3]rearrangement of the phenylthio group which further increases the variety of products which can be formed from such compounds. Selenium stabilized carbanions have also acquired a justifiable reputation as useful reagents for carbon-carbon bond formation.Phenyl-propargylselenide for example reacts with two equivalents of lithium di-iso- propylamide to give a dianion which reacts with electrophilic reagents at both the a-and y-positions (attack occurring first at the a-position) to give a disubstituted product (Scheme 15)." Oxidation of the selenide affords the corresponding selenoxide which readily undergoes rearrangement leading to a selenoenone. 0 2LiNh'a /Li i,E' PhSe-* -,80c+ PhSey+ ii E2* z phseP PhSe @,' Li E' H Scheme 15 75 B. S. Ellis G. Griffiths P. D. Howes C. J. M. Stirling and B. R. Fishwick J.C.S. Perkin I 1977,286; G. Griffiths P. D. Howes and C. J. M. Stirling ibid.912. '' T. M. Dolak and T. A. Bryson Tetrahedron Letters 1977 1961. 77 P. Brownbridge and S. Warren J.C.S. Perkin I 1977 1131. H. J. Reich and S. K. Shah J. Amer. Chem. SOC.,1977,99 263. 212 R. S. Ward The double deprotonation of ally1 thiols gives thiocarbonyl dianions which react with electrophiles preferentially at the y-position leading to cis-vinyl sulphides (Scheme 16).79 SLi E' SE2 SE2 qsH'92 + +El R R R R Scheme 16 A new asymmetric synthesis of P-hydroxy-esters (75) involves condensation of the chiral a -sulphinyl ester enolate anion (74) with achiral aldehydes or ketones.80 In a similar manner reaction of the anion (76) derived from a chiral sulphoxide with undecanal forms the basis of a stereospecific synthesis of (+)-disparlure (77) the female sex pheremone of the gypsy moth.81 OH OH 0 H / 'CHR -t-BuSO ,,' RH t *.-.-s R'CHO C'-R (4 steps) .. .- - -I t-Bu (77) R = Me2CH(CH2)4 R' = Me(CH2)9 The synthesis of diselenoacetals (78)affords a convenient route to vinyl selenides (79) which can in turn be converted into a-halogenoalkylselenides(80). The latter yield selenium stabilized carbanions on treatment with n-butyl-lithium.82 RSe SeR K' SeR R'R2CHCOR3 5R'R'CH-CR DMF \ /3 Me1 RZ)=(R3 +RSeMe H2S04 orZnC12 (78) (79) SeR SeR SeR 79 K.-H. Geiss D. Seebach arid B. Sewing Chem. Ber. 1977,110 1833. 8o C. Mioskowski and G. SolladiC J.CS. Chem. Comm. 1977 162. " D. G. Famum T. Veysoglu A. M. Cardt B. Duhl-Emswiler T.A. Pancoast T. J. Reitz and R. T. Cardk Tetrahedron Letters 1977,4009. '' M. Sevrin W. Dumont and A. Krief Tetrahedron Letters 1977 3835; W. Dumont and A. Krief Angew. Chern. Internat. Edn. 1977 16 540; W. Dumont M. Sevrin and A. Krief ibid. 541. Aliphatic Compounds-Part (ii) Other Aliphatic Compounds The preparation and reactions of a series of 0-alkyl selenoesters have also been 13 Halogen Compounds Two useful extensions of the well known Gabriel synthesis have been described which allow primary secondary and t-Boc amines to be prepared from alkyl halides. Thus diphenylphosphinic amide reacts with alkyl halides in the presence of a phase-transfer catalyst to give N-monoalkyl derivatives which can be con- verted into primary amines or treated with a second alkyl halide molecule (Scheme 17).84 The potassium salt of t-butyl methyl iminodicarboxylate undergoes smooth 0 0 0 It Rx II II Ph2PNH2 -Ph2PNHR Ph2PNRR' -+ RR'NH Scheme 17 N-alkylation to give derivatives which can be converted by treatment with alkali into t-Boc amine~.'~ The use of an insoluble polymer support as a monoblocking agent to prepare mono-protected derivatives of dicarboxylic acid halides has been reported.86 83 D.H. R. Barton P.-E. Hansen and K. Picker J.C.S. Perkin I 1977 1723. 84 A. Zwierzak and I. Podslawczynska Angew. Chem. Internst. Edn. 1977,16,702. J. D. Elliot and J. H. Jones J.C.S. Chem. Comm. 1977,758. C. C. Leznoff and J. M. Goldwasser Tetrahedron Letters 1977 1875; see also D. M. Dixit and C. C.Leznoff J. CS. Chem. Comm. 1977 798.

ISSN:0069-3030    

DOI:10.1039/OC9777400194

出版商:RSC    

年代:1977

数据来源: RSC

摘要:

10 Aromatic Compounds By R. G. COOMBES Department of Chemistry The City University St. John Street London EC1 V 4PB 1 Introduction The graph-theoretical approach'" to conjugation and resonance energies of hydrocarbons involving the concept of conjugated circuits [see Ann. Reports (B) 1976 73 p. 2231 has been developed as a new approach to the aromaticity" of polycyclic systems those having only conjugated circuits with (4n +2) r-electrons when the Kekulk structures are examined being defined as aromatic. The approach allows the prediction of the relative aromaticity of some systems contain- ing both (4n +2) and (4n) conjugated circuits. Resonance energies obtained2" using Clark aromatic sextet theory correlate well with the Dewar-type resonance energies from graph theory [see Ann.Reports (B) 1976 73 p. 201],26 and the latter approach has been applied to a wide range of systems.*" An essentially identical graph-theoretical approach derived however as the result of a different line of argument has also been rep~rted.~ The degree of electron delocalization in cyclic systems has been propo~ed,~ with theoretical justification to be a function both of orbital phase continuity requirements and of the disposition of donor and acceptor component systems. The condition under which the normal criterion for delocalization based on the number of m-electrons becomes invalid in 'effectively discontinuous systems' has been presented. An interesting polycyclic system with different possible delocalized structures is the dicyclo-octatetraenot 1,2 :4,5]benzene dianion which has been shown' not to sustain a localized 14welectron diamagnetic ring current.It is probably best described by the planar 20m-electron structure (l) where the electrostatic repul- sion is adequate to overcome the strain energy and the antiaromatic character of the ion. The diamagnetic susceptibility exhalt at ions of several 7-substituted cyclo- heptatrienes vary as a function of the size of the substituent are very large and are indicative of a substantial ring current.6 It has been suggested that in view of the low resonance energies and the bond alternation these systems should simply be M. RandiC (a) Tetrahedron 1977,33 1905; (6)J. Amer. Chem. SOC.,1977,99.444. J.-I. Aihara (a) Bull.Chem. SOC.Japan 1977 50 2010; (b) ibid. p. 3057; (c) J. Amer. Chem. Soc. 1977,99,2048. I. Gutrnan M. Milun and N. TrinajstiC J. Amer. Chem. Soc. 1977 99 1692. S. Inagaki and Y. Hirabayashi,J. Amer. Chem. SOC.,1977,99,7418. L. A. Paquette G. D. Ewing S. Traynor. and J. M. Gardlik I. Amer. Chem. Soc. 1977,99 6115. R. F. Childs and I. Pikulik Canad. J. Chem. 1977,55259. 215 R. G. Coombes (3) R =P-NO~C~H~ (2) described as diatropic rather than homoaromatic and the authors question whether diatropicity is a useful or even valid criterion of aromaticity. Two homoaromatic ions have been reported' which involve the interruption of the cyclic conjugated system by a three-carbon bridge. The benzannelated homocyclopentadienyl anion (2) is formed by treatment of the parent hydrocarbon with butyl-lithium.Examination of several systems' has provided no evidence for trishomoaromatic stabilization. Kinetic and product studies of the hydrolysis of (3) for example indicate86 no participation of the double bonds. A mathematical model has been devised which enables the magnitude of the interaction between homoaromatic centres to be evaluated.8c The sites of protonation of simple substituted benzenes in the gaseous phase have been receiving attention. Ring protonation of phenol has been calculated9 by ab initio MO theory to be 63 kJ mol-' more favourable than 0-protonation and a deuterium-exchange experiment gave an approximate value in agreement with this. Measurements of N1,core ionization energy suggest that aniline is protonated on nitrogen in the gaseous phase but anomalies exhibited by NN-dimethylaniline may be due to ring protonation.lo" Pulsed ion cyclotron resonance spectroscopy confirms1ob the former result although ab initio MO theory suggests that ring protonation is only 4-13 kJ mol-' less favourable. After comparison of the rela- tive base strengths of some rneta- and para-substituted anilines in the gaseous phase with the values for these compounds in aqueous solutions it has been suggested that for rn-toluidine and m-anisidine protonation occurs on the ring."' The opposing views concerning the nature of aryl "F n.m.r. polar field effects have now been largely reconciled. Calculations (CND0/2) on the 1-substituted 4-p-fluorophenylbicyclo[2,2,2]octaneshave indicated"" the dominance of 7r-polarization effects direct field effects accounting for only about 25% of the polar effects on "F chemical shifts.In this connection the distinction between T-polarization and the 7r-inductive effect has been emphasized."b 13CN.m.r. data A. Dagan D. Bruck and M. Rabinovitz Tetrahedron Letters 1977 2995. (a) L. A. Paquette M. J. Kukla S. V. Ley and S. G. Traynor J. Amer. Chem. SOC.,1977,99,4756;L. A. Paquette H. C. Berk C. R. Degenhardt and G. D. Ewing ibid. p. 4764; (6)L. A. Paquette P. B. Lavrik and R. H. Summerville J. Org. Chem. 1977 42 2659; (c) L. A. Paquette T. G. Wallis T. Kempe G. G. Christoph J. P. Springer and J. Clardy J. Amer. Chem. SOC.,1977 99 6946. D. J. DeFrees R.T. McIver and W. J. Hehre 1.Amer. Chem. Soc. 1977,99 3853. (a) R. G. Cave11 and D. A. Allison J. Amer. Chem. SOC.,1977,99,4203; (b)S. K. Pollack J. L. Deviin tert K. D. Surnrnerhays R. W. Taft and W. J. Hehre ibid. p. 4583; (c)K. D. Summerhays S. K. Pollack R. W. Taft and W. J. Hehre ibid. p. 4585. (a)W. F. Reynolds Tetrahedron Letters 1977 675; (6) W. Kitching M. Bullpit D. Gartshore W. Adcock T.-C. Khor D. Doddrell and I. D. Rae J. Org. Chem. 1977 42 2411; (c) D. F. Ewing S. Sotheeswaran and K. J. Toyne Tetruhedron Letters 1977,2041; (d)W. Adcock andT.-C. Khor ibid. p. 3769. Aromatic Compounds 217 provide unequivocal supporting evidence for 7r-polarization in the phenyl group of 1-substituted phenylbicyclo[2,2,2]octanes although there is not quantitative agreement with the above calculations."' The relative importance of the w-polarization and direct field effects has also been estimated by comparison of 19F n.m.r.data on the para-fluoro- and meta-fluoro-systems and the result is in good agreement with the estimate mentioned above."d Reversed I9Fn.m.r. polar field effects are realized in the orrho-fluoro-analogues. The modified version of the general theory of structure-property relationships previously proposed,'2n has been applied'26 to the problem of the relationships between substituent chemical shifts and substituent reactivity parameters and some success has been achieved in predicting whether a single parameter or a pair of parameters should be utilized in a particular situation. The non-additive behaviour of I3C chemical shifts in para-disubstituted benzenes [see Ann.Reports (B) 1976,73,p. 2031 has been reinter~reted.'~ The data for the 1-and 2-positions are in fact predicted additively and those for the 4-positions may be accurately described by linear proportionality relationships with the appropriate substituent chemical shifts in monosubstituted benzenes. The proportionality relationships were interpreted in terms of localized changes in the excitation term of the paramagnetic shielding expression for 13Cshifts determined largely by the ion- ization potential of the 4-substituent. Substituent effects on the 13C shifts of the side-chain C atoms in meta- and para-disubstituted benzenes have also been studied and inter~reted.'~ Further reviews illuminate the reactivity-selectivity debate.150~6 Considerations concerning change of solvent and temperature have been emphasized as has the fact that if substituents influence bond cleavage as well as bond formation a more reactive species can be more selective than a less reactive one in spite of an 'earlier' transition state.An illustrative example is the competition of aniline and 3-chloroaniline for substituted benzenesulphonyl chlorides where selectivity increases with reactivity. This argument is similar to that concerning desolvation of ions in reactions of charged species [see Ann. Reports (B) 1976 73 p. 2031.This latter effect has however been regarded as unimportant. l6 2 Benzene Isomers Oxides and Homobenzenes The photoelectron spectrum of benzvalene has been reported17 and this has led to the suggestion that the unusual U.V.absorption (217nm) may be due to the superimposition of the first member of a low-lying Rydberg series on a valence- shell transition. Full details of the preparation separation and aromatization of meso- and dl-l,l'-dimethyl-3,3'-bicyclopropenyls have now appeared." The aromatization l2 M. Godfrey J.C.S. Perkin IZ,(a)1975 1016; (b) 1977 769. 13 B. M. Lynch Canad.J. Chem. 1977,55,541. l4 N. Inamoto S. Masuda K. Tori and Y. Yoshimura Tetrahedron Letters 1977,737;J. Bromilow R. T. C. Brownlee and D. J. Craik Austral. J. Chem. 1977 30 355. Is (a)B. Giese Angew Chem. Internat. Edn. 1977,16 125; (6)A. Pross Ado. Phys. Org. Chem. 1977 14,69.l6 C. D. Ritchie and M. Sawada J.Amer. Chem. SOC.,1977,99 3754. l7 P. J. Harman J. E. Kent T. H. Gan J. B. Peel and G. D. Willett J. Amer. Chem. Soc. 1977,99,943. Is J. H. Davis K. J. Shea and R. G. Bergman J. Amer. Chem. SOC.,1977,99 1499. R. G. Coombes passes through an intermediate in which the stereochemical distinction between the diastereoisomers has disappeared. The data are most consistent with Scheme 1for gas-phase aromatization and probably for reaction in solution also. 1,4-Hexamethylene-Dewar-benzene is formed slowly and apparently quantitatively on irradiation of a solution of [6 Jparacyclophane in cyclohexane; warming the solution to 50-90 “Cresults in a clean and rapid reversion to the thermodynamic- ally more stable precursor.” A polemical reminder of the limitatiop of the use of correlation diagrams illustrated by that for the ‘allowed’ but not spontaneous thermal aromatization of benzvalene has been given;20 the words ‘allowed’ and ‘forbidden’ are only of use when there is a choice between two stereochemically different modes of reaction.Benzvalene has been shown2* to undergo a degenerate rearrangement catalysed by silver(1) ion in competition with the known catalysed aromatization. Evidence was presented that the reaction of the silver(1) ion with the bicyclobutane moiety is a reversible process involving the intermediacy of (4). Scrambling does not occur with other bicyclobutane derivatives. (4) (5) Ts=p-MeC6H4S02 (6) The synthesis of 3-t-butoxycarbonylbenzeneoxide has been accomplished” and in contrast to the 4-isomer it exists mainly as the benzene oxide valence tautomer.Attempts to effect nucleophilic addition on this molecule failed although the 4-isomer reacts uia its oxide tautomer. Benzene oxide itself is converted into (Z,Z)-hexa-2,4-dienedial on oxidation with pero~y-acids,~~ the oxidative ring opening involving the oxepin tautomer. The reaction of [Rh(C0)2C1]2 with ben- zene oxide and arene oxides at room or lower temperatures in chloroform or methanol leads to both deoxygenation and the formation of phenol by mechanisms involving initial Lewis acid catalysis.24 The equilibrium between the azepine (5) and its bicyclic valence tautomer (6) has been directly observed2’ in the range -70 to +40 “C [AG*,(S)-D (6) =46 kJ mol-’I.l9 S. L. Kammula L. D. Iroff M. Jones jun. J. W. van Straten W. H. de Wolf and F. Bickelhaupt J. Amer. Chem. SOC.,1977.99,5815. 2o J. J. C. Mulder J. Amer. Chem. SOC.,1977 99 5177. 21 U. Burger and F. Mazenod Tetrahedron Letters 1977,1757. 22 B. A. Chiasson and G. A. Berchtold J. Org. Chem. 1977,42 2008. 23 S. G. Davies and G. H. Whitham. J.C.S. Perkin I 1977 1346. ” R. W. Ashworth and G. A. Berchtold Tetrahedron Letters 1977,343. ” H. Prinzbach H. Babsch H. Fritz and P. Hug Tetrahedron Letters 1977 1355. Aromatic Compounds A new synthetic pathway to substituted trans-bishomobenzenes is now avail- able.26 Thermolysis of di bromote tracyclo[ 5,1,0 02*4,03*5]octanes readily available from tricyclo[4,1 ,0,02v7]hept-3-enes gave the species (7) which was readily Reagents i Li-Bu‘OH in THF Scheme 2 dehalogenated (Scheme 2).Studies of the flash pyrolysis (485“C)of 2H1-labelled hexahomobenzene (8) have shown2’ that there is not sufficient interaction energy amongst the three constituent rings to allow for bond shifting a result in agreement with last year’s report concerning trioxahexahomobenzenes [see Ann. Reports (B) 1976,73 p. 2051. 3 Benzene and its Derivatives General.-The second part28 of the review of the organic photochemistry of ben- zene is concerned with photoreactions with other molecules. The photoaddition of methyl phenylpropiolate to benzene has been shown29a to form the tetra-cyclo[3,3,0,02*4,03~6]oct-7-ene (9) as major product in addition to the known 1-methoxycarbonyl-8-phenylcyclo-octatetraene, and in proportions which vary with Ph the wavelength of irradiation.The products are also photochemically intercon- vertible. The presumed precursor to both products at least in the photoaddition reaction is the corresponding bicyclo[4,2,0]octatriene,and species with this struc-ture have now been from the photoaddition of alkynes to hexafluoro- benzene. 26 R. T. Taylor and L. A. Paquette J. Amer. Chern. SOC.,1977,99,5824. ” M.R. Detty and L. A. Paquette Tetrahedron Letters 1977 347. D.Bryce-Smith and A. Gilbert Tetrahedron 1977,33,2459. 29 (a)A. H. A. Tinnemans and D. C. Neckers J. Amer. Chem. SOC.,1977,99,6459;(b)B. Sket and M. Zupan ibid. p. 3504. 220 R. G. Coombes The major product of photocycloaddition of 2,3-dihydropyran to benzene is the endo-1,2-adduct formed in a process of surprising selectivity having a quantum efficiency greater than those previously observed for any mode of addition of an ethene to ben~ene.~'" The 1,3-photocycloadditions of ethyl vinyl ether to toluene and in particular those to anisole are promoted by polar solvents indicating that the 1,3-addition is not the general homopolar process as was previously believed.306 The synthetic utility of the 1,3-addition of alkenes to anisole has been explored as a route to the bicyclo[3,2,1 jocten-8-one sy~tern.~" 1,3-Cycloadducts are the major products of photochemical reactions30d between benzene and both (10) ethene [to give (lo)] and propene in contrast to the behaviour expected from the ionization potentials of these alkenes.28 The authors suggest that electron affinities are more relevant for these alkenes which are electron acceptors relative to benzene.2,2-Dimethyl- 1,3-dioxole undergoes 1,2-photoaddition to benzene as expected from its ionization potential but gives in contrast to normal alkenes the exo- addu~t.~'' Photoreactions of hexafluorobenzene have been the subject of some attenti~n.*~~*~'~-~ The [2 +2 Jcycloaddition of cyclopentene in cyclohexane solution proceeds3'" to give predominantly the exo-adduct (85YO) and reaction with norbornadiene gives predominantly (80%) the exu-~yn-isomer.~~~ It may be that these results reflect the stereochemistry of precursor complexes formed in the absence of irradiation.28 Studies of the photoaddition of aliphatic amines to ben- zene have been reported in An important covers the field of cobalt-catalysed cyclo-oligomeriza- tion of alkynes and full details326 of the formation of benzocycloalkenes using this approach and of their synthetic utility have appeared.The method has also been applied in an elegant synthesis of the steroid nucleus.32c The key step involves the reaction of the precursor (1 1) (Scheme 3) which is available by convergent series of reactions from hexa- 1,5 -diyne and 2-methylcyclopent-2-enone.The overall yield is 28% based on the former. Some attention has been paid to the mechanism(s) of the trimerization. Evidence has been presented33a that there exist at least two distinct mechanisms for the production of aromatic compounds from the reaction of alkynes with metallocyclopentadienes if these are intermediates.One path 30 (a)A. Gilbert and G. Taylor Tetrahedron Letters 1977,469; (b) J.C.S. Chem. Comm. 1977 242; (c) J. A. Ors and R. Srinivasan J. Org. Chem. 1977,42 1321; (d)M. F. Mirbach M. J. Mirbach and A. Saus Tetrahedron Letters 1977 959; (e)H.-D. Scharf and J. Mattay ibid. p. 401. 31 (a)B. Sket and M. Zupan J.C.S. Chem. Comm. 1977,365; (b) Tetrahedron Letters 1977,281 1; (c)M. Zupan B. Sket and B. Pahor ibid. p. 4541; (d)M. Bellas D. Bryce-Smith M. T. Clarke A. Gilbert G. Klunkin S. Krestonosich C. Manning and S. Wilso,i J.C.S. Perkin Z 1977 2571. 32 (a) K. P. C. Vollhardt Accounts Chem. Res. 1977,JO 1; (b) R. L. Hillard tert.and K. P. C. Vollhardt J. Amer. Chem. Soc. 1977 99 4058; (c)R. L. Funk and K. P. C. Vollhardt ibid. p. 5483. 33 (a)D. R. McAlister J. E. Bercaw and R. G. Bergman J. Amer. Chem. SOC.,1977 99 1666; (b)P. Caddy M. Green E. O'Brien L. E. Smart and P. Woodward Angew. Chem. Znternat. Edn. 1977,16 648. Aromatic Compounds Reagents i bis(trimethylsilyl)acetylene-CpCo(C0)2 Scheme 3 involves initial co-ordination of the alkyne and the other direct pathway may involve Diels-Alder addition. Other of 5-indenylrhodium(~) complexes have however suggested the intermediacy of metallocyclopent-2-enes. Ynamines (R'C-CNR;) undergo cyclotrimerization in moderate yields on warming in acetonitrile solution over Ni" or Ni' but not Cu' catalysts and they form the unsymmetrical triaminobenzene (12).34a A useful synthesis of hindered Rtot Rt /NR; NR; (1 2) aromatic amine~~~' also involves ynamines which react with a-pyrone carbon dioxide being lost spontaneously; methyl 2-(NN-diethylamino)-3-methylbenzoate for example is formed in 79% yield from 1-diethylaminoprop-1-yne.Two procedures have been reported for the preparation of metu-bisannelated benzenes (13). The first procedure35a (Scheme 4)utilizes Corey's modified pinacol x= (CH2)rn (13) y= (CH2)n Reagents i Mg(HgkTiCl4; ii POC13-pyridine; iii acrylic acid; iv 1O0/o Pd/C A Scheme 4 reduction and the involves the initial reaction of 2-cyclo-alkenylcycloalkanones with malonodinitrile acid-catalysed cyclization and efficient removal of the nitrile function from the ortho-amino-nitrile.A simpler albeit low-yield preparation of benzo[ 1,2 :3,4]dicyclobutane (13; n = m = 1) has been de~cribed,~~" and the procedure of the earlier Diels-Alder method has been (a)J. Ficini J. d'Angelo and S. Falou Tetrahedron Letters 1977 1645; (6) T. A. Bryson and D. M. Donelson J. Org. Chem. 1977,42 2930. 35 (a)M. E. Isabelle D. H. Lake and R. H. Wightman Canad.J. Chem. 1977,55,3268; (b)J. Sepiol B. Kawalek and J. Mirek Synthesis 1977 701. " (a)E. Giovannini and H. Vuilleumier Helu. Chim. Acta 1977 60 1452; (b)R. P. Thummell and W. Nutakul J. Org. Chem. 1977 42 300. 222 R. G. Coombes applied'6b to a series of meta- and para-bisannelated benzenes involving fused 4-and 5-membered rings. Syntheses of benzocyclobutenes abound.The flash vacuum pyrolysis of tolyl propargyl ethers provides a low-yield source of aromatic-ring-methylated benzo-cyclopropene~.~' Full details of the thermal and electron-impact syntheses of benzocyclobutene itself and examples having oxygenated substituents on the aryl ring have appeared.38" The latter type of compound however can indeed be prepared38b by the ready and efficient cyclization of the corresponding ortho- lithio(2-bromoethy1)benzenes. 3,4-Bis(trimethylsilyl)benzocylobutene has been synthesized for the first time.39 Interestingly the trimethylsilyl group at the 4-position is five-hundred times more susceptible to hydrolysis than that at the 3-position. The reaction of aaaa-tetrabromo-o-xylene with pentacarbonyliron gave4' a facile synthesis of mainly trans- 1,2-dibromobenzocyclobutene.Pyrolysis (600"C; 0.3 s) of 2-methylbenzoyl chlorides gave the corresponding benzocyclobutenones in good yield^.^' Benzocycloalkenones have been synthesized4*" in good yield by treatment of o-bromophenylalkanoic acids with butyl-lithium at low temperatures and the procedure allows for the presence of some functionality in the ring being formed. An extension of the oxidative rear- rangement of styrene derivatives by thallium(II1) nitrate a general method for the ring expansion of benzocycloalkanones of this type. They are first subjected to a Wittig procedure whereby a methylene carbon which may be substituted is inserted selectively between the aromatic ring and the carbonyl group.The reactions of polyfluoro-aromatic compounds with aryl and alkyl radicals have been reviewed.43 Some scavenging reactions of phenyl radicals from the thermal decomposition of p heny lazo trip hen ylme t hane are nearly diffusion-controlled in media of low viscosity and are so controlled in media of high viscosity leading to relative rates approaching unity for pairs of scavenger^.^^ Competition with slower reactions at higher viscosities has given absolute rate constants. The reactions of the phenyl radicals do not show a clear selectivity- reactivity relationship. Correlations for the rate of hydrogen abstraction from substituted toluenes by isopropyl and t-butyl radicals by a Hammett equation have been re~orded.~' The authors suggest that substituent effects on both the structure of the transition state (consideration of polar resonance structures) and of the initial state (bond dissociation energy) are important and that contrary to common practice both should be considered.The ability of aromatic nitro-compounds to increase the yields of biaryls in arylation reactions is now believed46 to involve 37 J. M. Riemann and W. S. Trahanovksy Tetrahedron Letters 1977 1863. (a) R. J. Spangler B. G. Beckmann and J. H. Kim J. Urg. Chem. 1977,42,2989;(6)P. D. Brewster J. Tagat C. A. Hergrueter and P. Helquist Tetrahedron Letters 1977,4573. 39 R. L. Hillard tert. and K. P. C. Vollhardt Angew. Chem. Internat. Edn. 1977 16 399. 40 R. Victor Transition Metal Chem. (Weinheim) 1977 2 2.41 P. Schiess and M. Heitzmann Angew. Chem. Internat. Edn. 1977 16 469. 42 (a) R. J. Boatman B. J. Whitlock and H. W. Whitlock jun. J. Amer. Chem. SOC.,1977,99,4822; (b) E. C. Taylor C.-S. Chiang and A. McKillop Tetrahedron Letters 1977 1827. " L. S. Kobrina Russ. Chem. Rev. 1977 46 348. 44 R. G. Kryger J. P. Lorand N. R. Stevens and N. R. Herron J. Amer. Chem. Soc. 1977,99 7589. 45 W. H. Davis jun. and W. A. Pryor J. Amer. Chem. SOC.,1977,99 6365. 46 R. Henriquez and D. C. Nonhebel J. Chem. Res. (S) 1977,253. Aromatic Compounds 223 oxidation of the intermediate arylcyclohexadienyl radicals by an electron-transfer mechanism examples having electron-withdrawing substituents being more effective. The authors of the original experimental work on the photobromination of dihalogeno-benzenes have reacted4’ to the suggestion that ipso-substitution is involved [see Ann.Reports (B),1976,73 p. 2081 and show that such substitution is neither required nor precluded by their results. A deamination reaction that uses alkyl nitrite and copper(r1) halide has been used in several processes that are of synthetic imp~rtance.~~ The reagent rapidly converts arylamines into aryl chlorides and bromides in high yield,48b and a Meer- wein-type arylation of alkenic substrates giving a-halogeno-P-aryl compounds occurs if the reaction is carried out in acetonitrile or acetone solutions containing the sub~trate.~~‘ Good to excellent yields of phenols are formed from aryl bromides under basic conditions on reaction of the derived Grignard reagent with molybdenum peroxide-pyridine-hexamethylphosphoramide.4g A procedure for the formation of phenols from diazonium ions which avoids the usual highly acidic conditions and is considered to be the method of choice for new cases consists in adding copper(!) oxide to a dilute solution of the arenediazonium salt in the presence of a large excess of copper(I1) nitrate.” Electrophilic Substitution.-Studies of the gas-phase pyrolysis of some 1-arylethyl acetates have leds1 to the conclusion that the Baker-Nathan order of electron release by alkyl groups is a solvation phenomenon and also that hyperconjugation from C-C bonds is greater than that from C-H bonds.These studies also suggest that the solvolysis of aa-dimethylbenzyl chlorides is exceptionally sensitive to steric hindrance to solvation and that this limits the suitability of the derived (++ constants for the description of electrophilic aromatic substitution.The pro- tonations of toluene and ethylbenzene in super-acid media have been rein- vestigateds2 and the presence of the ortho-protonated species has been established; the results are now in agreement with gas-phase studies. Details of the gas-phase reaction of the t-butyl cation with phenol and anisole to give initially predominantly t-butylated oxonium ions have appeared.53a In contrast to the t-butyl cation which exhibits both substrate and positional selec- tivity the isopropyl cation does not show substrate selectivity in its reactions with arene~.~~~ It does however exhibit a measurable degree of positional selectivity and its reactions are complicated by secondary dealkylation and isomerization processes.Chlorobenzene is isopropylated at a rate only half that of toluene and the predominant ortho-substitution is again attributeds3‘ to initial attack at the substituent. The attack of CH5+ and CzH5+ ions on halogeno-benzenes causess4 47 P. Gouverneur and J. P. Soumillion Bull. SOC. chim. belges 1977 86 647. 48 M. P. Doyle J. F. Dellaria jun. B. Siegfried and S. W. Bishop J. Org. Chem. 1977 42 3494; M. P. Doyle B. Siegfried and J. F. Dellaria jun. ibid. p. 2426; M. P. Doyle B. Siegfried R. C. Elliott and J. F. Dellaria jun. ibid. p. 2431. 49 N. J. Lewis S. Y. Gabhe and M. R. DeLaMater J. Org. Chem.1977,42 1479. 50 T. Cohen A. G. Dietz jun. and J. R. Miser J. Org. Chem. 1977,42 2053. 51 E. Glyde and R. Taylor J.C.S. Perkin ZZ 1977 678. ’* D. FgrcaSiu M. T. Melchior and L. Craine Angew. Chem. Znrernat. Edn. 1977,16 315. 53 (a)M. Attins F. Cacace G. Ciranni and P. Giacomello J. Amer. Chem. Soc. 1977,99 4101 5022; (6) ibid. p. 2611; (c)M. Attina and P. Giacomello Tetrahedron Letters 1977 2373. 54 M. Speranza and F. Cacace J. Amer. Chem. Soc. 1977,99 3051. 224 R. G.Coombes extensive dehalogenation by two competitive routes which lead to pro-todehalogenation and methyldehalogenation and are a reflection of the ambident nucleophilic character of the substrates. Mono- and di-substituted benzenes have been brominated by 80Br+ in the gas phase.” The relative rates led to good u+,p+ plots (p’ = -0.9) and the data on toluene agreed with the Brown selectivity rela- tionship.Perrin has asserteds6 that aromatic nitration is not always a conventional elec- trophilic substitution but that for some reactive substrates the mechanism involves the transfer of an electron from the aromatic to the nitronium ion followed by collapse of the radical pair. Experiments quoted in support of this proposal involve the determination of anodic half-wave potentials for nitrogen dioxide and some aromatic compounds and one involving the generation of the naphthalene radical cation in the presence of nitrogen dioxide which gives the normal isomer ratio of nitro-naphthalenes. The author appears to confuse and combine the different approaches of others to encounter pairs and wcomplexes and ignores the possi- bility of catalysis by nitrous acid which must surely affect the results obtained for some substrates which are used to support the proposed mechanism.Catalysis by nitrous acid is evident in the formation of the ipso-Substituted u-complex (14)that is formed on nitration of NN-dimethyl-p-toluidine in 70-77% sulphuric acid.57 It slowly rearranges to the NN-dimethyl-4-methyl-2-nitroaniliniumion. 6MeZ OzN Me Q It seems that the problem of the identity of the electrophile for nitration by nitric acid in acetic anhydride has at last been The observed rates have been shown to be sensitive to the presence of trace impurities at [HN03]< 0.9 mol dmP3 and a comparison of the true rate constant for the reaction of the electrophile and toluene with that for the reaction in acetic acid indicates that reaction indeed involves the nitronium ion.A study of some model compounds has led to a reconsiderati~n~~~ of the nitration of acetanilide and it now seems clear that this molecule is in fact nitrated as the unprotonated species by nitric acid in aqueous sulphuric acid. For anisole in the same mediums9* the ortho :para ratio varies considerably and an explanation has been offered that involves the combined effects of hydrogen bonding and a diffusion-controlled reaction. With 0-and p-methylanisole ipso-substitution at C-Me is of importance and in the latter case this leads to 4-methyl-2-nitrophenol ” E. J. Knust J.Amer. Chem. SOC.,1977,99 3037. s6 C. L. Perrin J. Amer. Chem. Soc. 1977 99,5516. *’ K. Fujiwara J. C. Giffney and J. H. Ridd J.C.S. Chem. Comm. 1977 301. 58 N. C. Marziano R. Passerini J. H. Rees and J. H. Ridd J.C.S. Perkin 11 1977 1361. 59 (a)R. B. Moodie P. N. Thomas and K. Schofield J.C.S.Perkin 11,1977 1693; (b)J. W. Barnett R. B. Moodie K. Schofield J. B. Weston R. G. Coombes J. G. Golding and G.D. Tobin J.C.S. Perkin ZZ 1977.248. Aromatic Compounds as a major product. 4-Methyl-4-nitrocyclohexa-2,5-dienone,a postulated inter- mediate in this reaction has been observed60a as a product from the nitration of p-methylanisole and some other para-substituted toluenes in acetic anhydride. Nitration ips0 to an ethyl group has been observed60b in p-diethylbenzene p-ethyltoluene and almost exclusively in ethylmesitylene.Attempts to activate a biphenyl to nitration ips0 to a phenyl group have however failed. The sensitivity of ipso-nitration to substituent effects has been examined6'" by the competitive study of a series of 5-X-hemimellitene derivatives (X =H F Br OAc OMe and NHAc) and a p+ value (-8>p+ > -12) has been estimated showing a satisfactory agreement with that for nitrodeprotonation. Some synthetic aspects of side-reactions attending aromatic nitration have been reviewed.61 An interesting example of intramolecular trapping of a Wheland intermediate has been observed6*" in the isolation of (15) from the nitration of methyl P-(2,3,4-trimethylphenyl)isovalerate. Another reaction involving initial ipso-substitution is the conversion626 of some p-xylonitrile derivatives into 1-imino- 1,3 -di hydroiso benzofurans [e.g.(1 6) from 2,3,4,6- te trame thy1 benzonitrile]. Solvolytic of the ipso-adducts formed on nitration of hemimellitene have reinforced the view [see Ann. Reports (B) 1976 73,p. 2101 that in >50% sulphuric acid adducts of this type yield the ipso-Wheland intermediate which is then partitioned between trapping by water and rearrangement by in this case sequer.tia1 1,2-shifts of the nitro-group. Full details of the reactions of nitronium salts with pentamethylbenzene have been given,64 confirming that the initially detected species is the l-nitro-l,2,3,4,6-pentamethylbenzenoniumion. The 1,3- dinitro-l,2,4,5,6-pentamethylbenzenonium ion formed from pentamethyl-nitrobenzene undergoes a degenerate rearrangement of a nitro-group from posi- tion 1 to position 5.(15) The mercuric-acetate-catalysed nitration of toluene in acetic acid at 80 "C,which produces 36% 0-,12% m-,and 52% p-nitrotoluenes has been to involve initial mercuration followed by nitrosodemercuration and subsequent oxidation of the nitroso-toluenes. The sulphonations of some polyethyl- and polyisopropyl-benzenes in concen- trated sulphuric acid have been studied.66 The sulphonic acids from 1,2,3,5- and 6o A. H. Clernens M. P. Hartshorn K. E. Richards and G. J. Wright Austral. J. Chem. 1977,30 (a)p. 113; (b)p. 103. 61 H. Suzuki Synthesis 1977 217. 62 (a)M. Shinoda and H. Suzuki J.C.S. Chem.Comm. 1977 479; (6) H. Suzuki M. Koge and T. Hanafusa ibid. p. 341. 63 T. Banwell C. S. Morse P. C. Myhre and A. Vollmar J. Amer. Chem. SOC.,1977,99 3042. 64 A. N. Detsina V. I. Marnatyuk and V. A. Koptyug J. Urg. Chem. (U.S.S.R.),1977,13 122. 65 L. M. Stock and T. L. Wright J. Org. Chem. 1977,42 2875. 66 A. Koeberg-Telder and H. Cerfontain J.C.S. Perkin IZ 1977 717; H. Cerfontain A. Koeberg-Telder and C. Ris ibid. p. 720. 226 R. G. Coombes 1,2,4,5-tetraethylbenzeneare unstable and rearrange into 2,3,4,5-tetraethylben- zenesulphonic acid. With 1,3,5-tri-isopropylbenzene,both rearrangement and dealkylation reactions become of importance. Kinetic and product have shown that the sulphonation of aniline in a large excess of 100-102% sulphuric acid at 25°C proceeds by direct attack of the electrophile (H&O,+) on the aromatic ring of the anilinium ion.Under more aqueous conditions (-97% sulphuric acid) at higher temperatures some reaction occurs by the same mechanism as shown by the formation of rn-aminobenzenesulphonicacid but reaction involving the intermediacy of phenylsulphamic acid may also occur. The latter compound itself at 25 "C,yields67b only u-and p-aminobenzenesulphonic acids by an intermolecular path involving C-sulphonation of the minority 0-protonated species PhNHS03H and subsequent N-desulphonation although at lower acidities solvolysis to the anilinium ion is a competing process.67c The sulphonation of m-aminobenzenesulphonic acid in fuming sulphuric acid has also been studied.68" Studies of methanesulphonanilide (PhNHS0,Me) indicate6*' that sulphonation occurs on the unprotonated species which is in the minority above 84% sulphuric acid.For non-catalytic bromination reactions the process may follow the power-series rate equation and involve a reaction pathway in which more than one molecule of bromine is concerned in the transition state. The suggestion [see Ann. Reports (B) 1975 72 p. 2251 that this will show the same kinetic behaviour as an A-SE2 process in which the rate of the reverse of the first step becomes significant and that the rate expressions for these processes are equivalent is in~orrect.~~" The circumstances under which a distinction may be made have been established and the authors also briefly review the mechanisms available for brominations by molecular bromine.The effect of addition of bromide and perchlorate to the bromination of polymethylbenzenes in 90% aqueous acetic acid shows clearly6" that in this case reaction involves a transition state which includes more than one molecule of bromine. Flow 'H n.m.r. studies have clearly confirmed7' the general- ity of the occurrence of cyclohexadienone intermediates in the bromination of substituted phenols in aqueous acetic acid the lifetime of the intermediates decreasing with the size of alkyl substituents at 2-and 6-positions. 'Free' CT3+cations have been generated from the decay of a radioactive atom in a tritiated methane solution in toluene and ben~ene.~' The attack of the cation on the arene is likely to occur in a much shorter time than is necessary for the formation of an organised solvent sphere.The intermolecular selectivity was indicated by an approximate to1uene:benzene rate ratio of 2.3:1 and a very low but slightly electrophilic intramolecular selectivity was observed The vinylation of some aromatic substrates by a variety of vinyl triflates [e.g. PhC(Me)=C(Ph)OS02CF3] lacking a p C-H bond is possible and it results in " P. K. Maarsen and H. Cerfontain J.C.S. Perkin 11 1977 (a)p. 1008; (b)p. 921; (c) p. 929. (a) P. K. Maarsen R. Bregman and H. Cerfontain J.C.S. Perkin II 1977 1863; (b)P. K.Maarsen and H. Cerfontain ibid. p. 1003. " (a)N. H. Briggs P. B. D. de la Mare and D. HaII J.C.S. Perkin ZZ 1977 106; (6) R.M. Keefer and L. J. Andrews J. Amer. Chem. SOC., 1977,99 5693. 70 C. A. Fyfe and L. Van Veen jun. J. Amer. Chem. SOC., 1977,99 3366. 71 F. Cacace and P. GiacomeIIo J. Amer. Chem. SOC.,2977,99 5477. Aromatic Compounds 227 good yields of styrenes under moderate conditions even in the absence of Friedel-Crafts Nucleophilic Substitution.-Recent developments in the application of linear free- energy relationships between reactivity and physical properties of leaving groups and substrates have been A comparison of some substitution reactions of both neutral and negative nucleophiles in the 2,4-dinitrohalogeno-benzeneswith reactions with organic cations has provided16 further support for the general applicability of the N+ nucleophilicity scale.Selectivity again appears not to be a function of reactivity in these reactions. The photostimulated SRNlreaction between iodobenzene and potassium diethylphosphite in DMSO has been st~died,'~" with particular attention being paid to the initiation and termination stages. The main reaction for the latter is first-order in propagating radical. The initiation however may involve initial absorption by iodobenzene or by a molecular complex of iodobenzene with diethylphosphite. An SRNl reaction in aqueous t-butyl alcohol has been identified746 in the reaction of halogeno-benzenes with phenoxide ion in the presence of sodium amalgam to form benzene and diphenyl ether. A thermally induced SRNl reaction has been in the reaction of bromo- and iodo- benzenes with ketone enolate anions in DMSO at 25°C in the dark and in one example this was well separated from the photostimulated process.Large rate accelerations by added oxygen nitrobenzene and ferric nitrate were however not explained. The reactions of picryl chloride and bromide with the diethylmalonate anion have been studied7' by the stopped-flow technique which enables the stages involving fast formation of a-complexes followed by slower decomposition to the picryl esters to be identified. In the reaction of 2,4,6-trinitroanisol& with n-butylamine to give in the absence of a large excess of the amine N-&-butyl)picramide the 'H n.m.r spectrum of the intermediate u-complex has been recorded using a flow technique.76 The stable intramolecular a-complex (17) formed under basic conditions from N-benzyl-N-(2-hydroxyethyl)picramide cyclizes under the conditions of the Smiles' rearrangement without prior rear- rangement to form 4-benzyl-5,7-dinitro-2,3-dihydrobenzoxazine.77 Kinetic and equilibrium data have been reported7* for the addition of sodium ethoxide to a series of &substituted 2,4-dinitrophenetoles to give a-complexes.The results support the suggestion that interaction with the cation for 1,l -diethoxy-complexes involves the oxygen atoms of the alkoxy-groups attached to C-1 and the ortho-substituents. 72 P. J. Stang and A. G. Anderson Tetrahedron Letters 1977 1485. 73 G. Bartoli and P. E. Todesco Accounts Chem. Res. 1977,10 125; see also G. Bartoli P. E. Todesco and M.Fiorentino J. Amer. Chem. SOC.,1977,99,6874. 74 (a) S. Hoz and J. F. Bunnett J. Amer. Chem. Soc. 1977 99 4690; (b) S. Rajan and P. Sridaran Tetrahedron Letters 1977 2177; (c) R. G. Scamehorn and J. F. Bunnett J. Org. Chem. 1977 42 1449,1457. 75 K. T. Leffek and A. E. Matinopoulous-Scordou Canad. J. Chem. 1977,SS 2656,2664. 76 C. A. Fyfe A. Koll S. W. H. Damji C. D. Malkiewich and P. A. Forte J.C.S. Chem. Comm. 1977 335. 77 V. N. Drozd V. N. Knyazev and V. M. Minov J. Org. Chem. (U.S.S.R.) 1977,13,357. 78 M. R. Crampton J.C.S. Perkin ZI 1977 1442. R. G. Coombes (17) (1 8) (1 9) The formation of the a-complex (18; R = NHPh) from 1,3,5-trinitrobenzene and aniline catalysed by a tertiary amine in DMSO has been shown79a to involve rate-limiting deprotonation by the catalyst of the zwitterionic intermediate (19) and it shows only a small primary kinetic isotope effect.The magnitude of the effect should have relevance to the identification of rate-limiting stages in SNAr reactions (see below). The complex (18; R=NHPh) may also be formed by the reaction of aniline with the complex (18; R = OMe) and the full evidence that in this example a dissociative mechanism involving the intermediacy of tri-nitrobenzene is involved has been given.79b Methoxide ion acts in a similar fashion to the tertiary amine catalyst in the previous reaction but in this case the formation of the intermediate (19) is rate-limiting. It seems that the unreactivity of aromatic as opposed to aliphatic amines towards nitro-aromatic compounds is due to ther- modynamic rather than kinetic factors.Arguments have been presentedsoo that currently available evidence indicates that the specific base-general acid-catalysed mechanism for substitution in activated aromatic compounds by amines involving fast deprotonation and rate- limiting catalysed expulsion of the leaving group is not a significant pathway in protic solvents. Instead the mechanism involves a rate-limiting deprotonation of (20) when the expulsion of the leaving group is relatively fast (e.g.X = OPh) or a rapid equilibrium deprotonation of (20) followed by a rate-limiting non-catalysed H Y (20) expulsion of a very poor leaving group (e.g.on occasions when X = OMe). Catalysis by base in the reaction of piperidine with 2,4-dinitrophenyl4-nitrophenylether in benzene solution has been discussedsob in terms of concerted proton transfer and expulsion of the leaving group the protic base acting as a bifunctional catalyst.Evidence from the uncatalysed reaction of morpholine with 2,4-dinitrophenyl phenyl ether in dipolar aprotic solvents suggests that here also fast deprotonation and slow expulsion of the leaving group does not occur,soc and the authors also 79 (a) E. Buncel W. Eggimann and H. W. Leung J.C.S. Chem. Comm. 1977 55; E. Buncel and W. Eggimann J. Arner. Chem. Soc. 1977 99 5958; (b)E. Buncel J. G. K. Webb and J. F. Wiltshire ibid. p. 4429. (a)C. F. Bernasconi R.H. De Rossi and P.Schmid J. Amer. Chem. SOC.,1977 99 4090; (b) D. Spinelli G.Consiglio and R. Noto J.C.S. Perkin 11 1977 1316; (c) D. Ayediran T. 0.Bamkole J. Hirst and I. Onyido ibid. p. 597. Aromatic Compounds 229 discuss shortcomings of the concerted mechanism for media of low dielectric constant and suggest a modification involving the formation of aggregates within which bond-making and -breaking is not synchronous. Biary1s.-An important modification of the nickel-phosphine-complex-catalysed homo-coupling of aryl halides has been reported,'l and the reaction proceeds catalytically in nickel in the presence of zinc which reduces the Ni" species formed to the active Nio species. The molar ratio PhBr :Zn :PPh3:Ni(PPh3)2CI2 of 1:1:0.3:0.5 in DMF solution at 50°C gave an 89% yield of biphenyl. The presence of iodine greatly accelerated the reaction.Efficient formation of the symmetrical biaryl has been observeds2 when some arylcopper cluster compounds [e.g. (4-MeC6H4)4C~4] react with equimolar quantities of copper triflate. These reactions involve intermediate complexes which may be isolated in some cases Treatment of a variety of aromatic substrates with thallium(rI1) trifluoroacetate in trifluoroacetic acid results in oxidative coupling to giveg3 biaryls in good yield in the absence of powerfully electron-withdrawing substituents probably by a radical cation mechanism; 2,5-dimethylanisole for example is converted into 2,2',5,5'- te trame t hyl-4,4'-dime t hoxybiphen yl. An improved me thods4 has been reported for the conversion of arylmercury (11) chlorides into biaryls using [ClRh(CO),] as a catalyst in the presence of lithium chloride.Thermal decomposition of tetra-aryl-tellurium compounds at 140 "C forms biaryls by a non-radical path~ay.~' The preparation of a wide variety of mixed biaryls in improved yields is possible by the application of phase-transfer catalysis to a Gomberg reaction.86 Potassium acetate in the presence of 18-crown-6 apparently reacts with an arenediazonium ion in non-polar solution to form a diazoanhydride which then decomposes in the presence of various aromatic compounds to form biaryls. The reaction of some arylzinc derivatives with aryl bromides or iodides in the presence of a small amount of a nickel or palladium catalyst [e.g. Ni(PPh,),] provides a general and highly selective route to unsymmetrical biaryl~.'~ Palladium(I1) chloride ( < 0.001 mol equivalent) appears" to be a preferred catalyst in Kharasch-type reactions of aryl Grignard reagents with iodobenzenes in THF.Aromatic nitrogen compounds (nitroso- azo- azoxy- and nitro-benzenes and NN-dialkylaniline N-oxides in addition to aryl-hydroxylamines) are susceptible to nucleophilic attack by benzene to give biphenyls in varying yields under strongly acidic condition^;'^ S-(NN-dimethylamino)-2-methylbiphenyl,for example is formed in 46% yield from NN-dimethyl-p-toluidine N-oxide. A comparison of the rates of solvolysis of some a-(7-X-fluoren-2-yl)benzyl chlorides and cr-(4'-X-biphenyl-4-yl)benzyl halides is consistent with regarding '' M. Zembayashi K. Tamao J.-I. Yoshida and M.Kumada Tetrahedron Letters 1977 4089. '' G. van Koten J. T. B. H. Jastrzebski and J. G. Noltes J.C.S. Chem. Comm. 1977,203; J. Org. Chem. 1977,42,2047. " A. McKillop A. G. Turrell and E. C. Taylor J. Org. Chem. 1977,42 764. 84 R. C. Larock and J. C. Bernhardt J. Org. Chem. 1977,42 1680. 85 D. H. R. Barton S. A. Glover and S. V. Ley J.C.S. Chem. Comm. 1977,266. 86 S. H. Korzeniowski L. Blum and G. W. Gokel Tetrahedron Letters 1977 1871. " E.-I. Negishi. A. 0.King and N. Okukado J. Org. Chem. 1977,42 1821. '' A. Sekiya and N. Ishikawa J. Organometallic Chem. 1977 125 281. 89 T. Ohta K. Shudo and T. Okamoto Tetrahedron tetters 1977 101; K. Shudo T. Ohta Y. Endo and T. Okamoto ibid. p. 105. 230 R. G. Coombes fluorene as a planar biphenyl structure and yields an interplanar angle for biphenyl in accord with other estimates." Both systems respond to substituent effects in a similar way.The overall reactivity to protiodetritiation of 9,lo-dihydrophenanth-rene relative to that of fluorene is consistent with the differences in coplanarity between the and other results confirm that the low reactivity of the a-position of the latter arises from an increase in strain on going to the correspond- ing transition state. The reversible rearrangement of 1-fluoro-9H-fluoren-9-one into the 3-fluoro-isomer in polyphosphoric acid provides the first direct evidence for the complete reversibility of a Friedel-Crafts a~ylation.~~' Quinones and Related Compounds.-A review of photoinitiated reactions of quinones has appeared.92 A convenient synthesis93 of 2-alkyl p-benzoquinones in 65-70°/0 yields involves the oxidation of the p-alkylphenol with thallium(II1) perchlorate in perchloric acid.The reaction of allyl-silanes with various p-benzo- quinones in the presence of titanium tetrachloride gave94 allyl-substituted hydro- quinones whilst 2,fi-disubstituted quinones gave p-allyl-quinols which were presumed also to be intermediates in the former cases. An interesting base- catalysed rearrangement of p-peroxyquinol ethers to give p-quinoxyacetic acid derivatives has been and is shown formally in (21). The suggested mechanism involves initiation by homolysis of the 0-0 bond even at -60 "C. The quinone methide (22) which has a vinyl group in conjugation with the quinone system forms in the solid or in concentrated solution in an aprotic solvent a dimer involving Diels-Alder addition of the terminal double bond of one mole- cule to the side-chain diene system of another molecule.96a The products of nucleophilic addition to (22) have been and with water and methanol both 1,6- and 1,B-adducts are observed.Kinetic studies of the related methylene compound have also appeared.96" Some reactive 1,3-dipoles (R-b=N-X) add to 2,6-di-t-butyl-4-methylenecyclohexa-2,5-dienone to give the 1:1 cycloadducts (23) in high yield providing ready access to the hetero-~pir0[4,5]decatrienone system.96d 90 R. Bolton and R. E. M. Burley J.C.S. Perkin ZZ,1977,426. 91 (a)H. V. Ansell and R. Taylor I.C.S. Perkin ZZ,1977,866;(6)I.Agranat Y. Bentor and Y.4. Shih I. Amer. Chem. SOC.,1977,99,7068. 92 A. V. El'tsov 0.P. Studzinskii and V. M.Grebenkina Rum. Chem. Rev. 1977 46 93. 93 Y. Yamada and K. Hosaka Synthesis 1977 53. 94 A. Hosomi and H. Sakurai Tetrahedron Letters 1977,4041. 95 A. Nishinaga K. Nakamura K. Yoshida and T. Matsuura Chem. Letters 1977 303. 96 (a)J. A. Hemingson Tetrahedron Letters 1977,2967;(b)J.C.S. Perkin ZZ,1977,616; (c)G.Leary I. J. Miller W. Thomas and A. D. Woolhouse ibid. p. 1737; (d) A. D. Woolhouse Austral. J. Chem. 1977,30 1145. Aromatic Compounds 231 An electron-diffraction study of p-xylylene which is widely accepted to have a singlet structure has been made,97a and the conclusion reached that the molecule does not simply contain conjugated double and single bonds.The average C=C bond length is longer than typical values for conjugated double bonds and in good agreement with simple HMO theory. The i.r. and Raman spectra of o-xylylene have been observed for the first time.97b The molecule was generated in the gaseous phase by the reaction of aa'-dibromo-o-xylene with sodium or potassium vapour which had been excited by a microwave discharge and it was then collected in an argon matrix (at 8-30 K). 2,2-Dimethyl-2H-indene (24) shows more than a (24) transient existence.98a It was generated and isolated in a matrix at 77 K but was also generated in a solution at room temperature where it was suficiently stable for its 'H n.m.r. spectra to be recorded. Transient isoindenes have been observed and studied in the flash photolysis of a series of l,l-diaryl-indene~.~~~ Isoindene itself has been im~licated~~' as an intermediate in a photobisdecarbonylation reaction which may be suitable for future matrix-isolation studies.o-Xylylenes have also been observed as transients in the flash photolysis of methylated indan-2-0nes.~~ The intermediacy of the 2H-indenes (26) in the thermal rearrangement of the 1-acyl- 1,3-diphenyl- and -dimethyl-indenes (25) to the corresponding 2-acyl- indenes (27) has been established,'00" and migratory aptitudes have been described. Other studies of the related photochemical rearrangement of 3-substituted 1,l- diphenylindenes have been reported. loob (25) (26) (27) R = Ph or Me; X = e.g. CHO COMe COPh or C02Me Oxidation of 4-aryl-2,6-di-t-butylphenolswith oxygen in the presence of a cobalt(r1) complex followed by decomposition of the intermediate hydroperoxides with toluene-p-sulphonic acid gave the 5-aryl-3-t-butyl-o-benzoquinones in good yield."' Oxidation of a series of o-benzoquinones with lead(1v) acetate in methanol to yield the corresponding dimethyl hexa-2,4-dienedioates in 60-90% 97 (a)P.G. Mahaffy J. D. Wieser and L. K. Montgomery J. Arner. Chem. Soc. 1977,99,4514; (b)K. L. Tseng and J. Michl ibid.,pp. 4840 6154. 98 (a) W. R. Dolbier jun. K. Matsui J. Michl and D. V. Horak J. Amer. Chem. SOC.,1977,99,3876; (b) K. K. de Fonseka C. Manning J. J. McCullough and A. J. Yarwood ibid. p. 8257; (c) R. N. Warrener R. A. Russell and T. S.Lee Tetrahedron Letters 1977,49. 99 K. K. de Fonseka J. J. McCullough and A. J. Yarwood J.C.S. Chem. Comm. 1977,721. loo (a) D. W. Jones and G. Kneen J.C.S. Perkin I 1977 1313; (6)W. A. Pettit and J. W. Wilson J. Amer. Chem. SOC.,1977,99,6372. A. Nishinaga K. Nishizawa H. Tomita and T. Matsuura Synthesis 1977 270. R. G. Coombes yield has been reported."* A pronounced and unexpected solvent effect has been in the reaction of some o-benzoquinones with butadiene; 4-methoxy- 5-methyl-o-benzoquinone for example gave mainly the abnormal spiro-compound (28) in benzene and (29) in methanol. (28) (29) An unusually stable orange-red crystalline o-quinone methide probably (30) has been from the oxidation of 2-cinnamyl-4,5-methylenedioxyphenol with silver oxide and the corresponding methide from 2-(4-methoxybenzyl)-4,5-methylenedioxyphenol rapidly dimerizes in polar solvents.Another stable o-quinone methide (m.pt. 284-5 "C)is (31) prepared'046 by the reaction of 2,4-dimethylphenol with two equivalents of 1,3-benzodithiolylium tetrafluoroborate in (30) (31) acetonitrile and subsequent addition of triethylamine. 6-Acetoxycyclohexa-2,4-dien-1-ones react with Grignard and lithium reagents to give in addition to the expected 1,2-and 1,4-addition an ether which is the product of the formal addition of a carbanion to the carbonyl oxygen.'o5a Ether formation largely supersedes conjugate addition with tertiary and benzylic organometallics. Substituent effects support an electron-transfer mechanism,'056 and further evidencelosc suggests that dialkylmagnesium species are concerned in the case of Grignard reagents.The metallation reaction of electrochemically derived quinone bisacetals [see Ann. Reports (B) 1976 73,p. 2151 has been modified'06 to produce organo- copper-lithium derivatives which will react efficiently with allylic halides to provide a route to some isoprenoid natural products (e.g. cymopol). 4 Cyclophanes A review of the information to be gained concerning steric effects of substituents from conformational studies of cyclophanes has appeared.lo7 [5]Metacyclophane Io2 M. Wiessler Tetrahedron Letters 1977 233. Io3 S. Danishefsky P. F. Schuda and W. Caruthers J. Org. Chem. 1977 42 2179. (a) L. Jurd Tetruhedron 1977 33 163; (b) J. Nakayama K.Yamashita M. Hoshino and T. Takemasa Chem. Letters 1977 789. lo' (a)B. Miller J. Org. Chem. 1977 42 1402; (b) ibid. p. 1408; (c) B. Miller E. R. Matjeka and J. G. Haggerty Tetrahedron Letters 1977 323. '06 P. W. Raynolds M. J. Manning and J. S. Swenton J.C.S. Chem. Comm. 1977 499. lo' H. Forster and F. Vogtle Angew. Chem. Internut. Edn. 1977,16,429. Aromatic Compounds the lowest member of this series to date is a by-product of a synthesis of 3,3'-hexamethylenebicyclopropenyl.'08 Its spectral properties are indicative of unusu-ally high strain and also of high conformational rigidity of the pentamethylene chain. A novel synthesislog of [71-and [8]-paracyclophanes involves flow pyrolysis of the spiroquinodimethanes (32; n =6 and 7) and a simple synthesis"o of some [lO]paracyclophanes [e.g.(33)] involves the reaction of methyl propiolate and aluminium chloride with cyclododecene and thermal dehydrogenation of the resul- ting 2 :1 adducts. [3.3]Paracyclophane is now readily available by a route"'a'b involving the surprisingly efficient (94%) pyrolysis of the disulphone of 2,13-di thia[4.4]paracyclop hane. The di thia[4.4]cyclophanes may also yield' ' the [3.3]cyclophanes on photodesulphurization in triethyl phosphite. Another approach to [3.3]paracyclophanes also suitable for higher cyclic oligomers has involved the construction of aliphatic bridges by a reaction between a bromide and a carbanionic species. Charge-transfer interactions in some [3.3]cyclophanes have been studied.'1'b~1'2a Such interactions may be transmitted through intervening rings in multilayered cyclophanes."2b The general usefulness of the sulphone pyrolysis procedure for the synthesis of many-membered hydrocarbon rings has also been illustrated.' l3 Representatives of the highly strained cyclophanes which have two benzene rings held with three or more ethano-bridges have been synthesized.A new approach to [2.2.2](1,2,4)cyclophane involves the formation of the third bridge in a paracy- clophane deri~ative."~ The chiral [2.2.2](1,2,4)(1,3,5)cyclophane has been synthesized,"' and it has a marked tendency to resinify at room temperature. Its skew geometry causes an upfield shift of one aromatic proton to 74.96. [2.2.2.2](1,2,3,5)Cyclophane, the first to have a consecutive arrangement of three lo* J.W. van Straten W. H. de Wolf and F. Bickelhaupt Tetrahedron Letters 1977,4667. 109 J. W. van Straten W. H. de Wolf and F. Bickelhaupt Rec. Trav. chim. 1977,96 88. 'lo B. B. Snider and N. J. Hrib Tetrahedron Letters 1977 1725. '11 (a) D. T. Longone S. H. Kiisefogiu and J. A. Gladysz J. Org. Chem 1977 42 2787; (6) M. W. Haenel A. Flatow V. Taglieber and H. A. Staab Tetrahedron Letters 1977 1733; (c)T. Otsubo M. Kitasawa and S. Misumi Chem. Letters 1977 977; (d)T. Synmyozu K. Kumagae T. Inazu and T. Yoshino ibid. p. 43. (a) T. Shinmyozu T. Inazu and T. Yoshino Chem. Letters 1977 1347; (6)H. A. Staab U. Zapf and A. Gurke Angew. Chem. Internat. Edn. 1977 16 801; see also H. A. Staab and C. P. Herz ibid. p. 392; C.P. Herz and H. A. Staab ibid. p. 394. J. Grutze and F. Vogtle Chem. Ber. 1977,110 1978; L. Rossa and F. Vogtle J. Chem. Res. (S) 1977 264. 114 S. Trampe K. Menke and H. Hopf Chem. Ber. 1977,110,371. 115 M. Nakazaki K. Yamamoto and Y. Miura J.C.S. Chem. Comm. 1977,206. R. G. Coombes ethano-bridges has been synthesized"6a by a procedure analogous to that applied to the (1,2,4,5)-isomer [see Ann. Reports (B) 1975,72 p. 2311; an X-ray structure of the latter has now appeared."6b [2.1.2.1]Paracyclophane has been synthesized in 14% yield by a modified Wurtz reaction under high dilution on 4,4'-dichlorome th yldiphenylme thane. l7 The application of the Wittig procedure to the synthesis of [2.2.2.2]cyclophanetetraenes [see Ann.Reports (B) 1975,72 p. 2311 has been extended,118a but an attempt to form [2.2.2]paracyclophanediene from 4,4'-bibenzyldicarbaldehyde and the bisphosphonium salt of 1,4-di(bromoethyl)benzene failed but gave a small yield of all-ci~-[2~]paracyclophanetetraene, providing an improved route to [26]paracyclophane. The Wittig approach has also led to the synthesis"sb of [2.0.2.0]metacyclophanediene,which on photolysis in the presence of iodine gave bi-4,5-phenanthrylene (34) a non-planar analogue of [8]circulene. The reaction of benzene-l,3,5,-tricarbaldehyde and the bisphosphonium salt of 1,4-di(bromo-methy1)benzene has given1l8' a route to the bicyclophane (35) which should exist as a rapidly equilibrating mixture of enantiomeric conformations. The 'benzene-Stevens' route [see Ann.Reports (B) 1975,72 p. 231 Scheme 21 has been applied"' to the syntheses of both syn-and anti-[2.2](1,4)naphthaleno-phane-1,13-dienes. [2](1,5)Naphthaleno[2]paracyclophane and its 2,6-isomer where the bridging is from one benzene ring of the naphthalene moiety to the other have been synthesized for the first time.120a The naphthaleno-paracyclo- phane (36) has also been prepared'20b for the first time by two routes and in spite 116 (a)W. Gilb K. Menke and H. Hopf Angew. Chem. Internat. Edn. 1977.16 191; @)A.W. Hanson Acta Cryst. 1977 833 2003. 117 S. Sergheraert P. Marcinal and E. Cuingnet Tetrahedron Letters 1977 2879. 118 (a)B. Thulin 0.Wennerstrom I. Somfai and B. Chmielarz Acta Chem. Scand. (B) 1977 31 135; (6) B. Thulin and 0.Wennerstrom Tetrahedron Letters 1977,929; (c)H.E. Hogberg B. Thulin and 0.Wennerstrom ibid. p. 93 1. 119 T. Otsubo and V. Boekelheide J. Org. Chem. 1977,42 1085. 120 (a) M. W. Haenel Tetrahedron Letters 1977 4191; (b) W. Bieber and F. Vogtle Angew. Chem. Internat. Edn. 1977 16 175. Aromatic Compounds of the similarity of its U.V. spectrum to that of a 1,8-diarylnaphthalene the 'Hn.m.r. spectrum shows an enhancement of the anisotropic effect due to the closer approach of the p-phenylene rings. (37) A further synthesis and an X-ray structure of [2.2](2,7)pyrenophane have appeared.lZ1 [2.21 (1,4)tropylio( 1,4)cycloheptatrienop hane (37) te trafluoro borate has been formedlZ2" from [2.2]paracyclophane by a route involving ring expansions using dibromocarbene.In contrast to its normal behaviour the cycloheptatriene ring acts as a good intramolecular charge-transfer donor. New cyclophanes having tropylium rings have been reported.lZZb A new series of compounds which have the combined attributes of helicenes and cyclophanes are the 4,4'"-o-guaterphenylophanes (38; n = 2 and 6) which have been ~ynthesized'~~ by a sulphone-extrusion procedure. Species (38; n = 2) exhi- bits an unexpectedly high conformational flexibility. 5 Molecular Rearrangements The thermal and acid-catalysed Claisen rearrangements of N-allyl-anilines have been invesfigated.lZ4 The rearrangement of N-(l',l'-dimethylallyl)-2,6-dimethyl-aniline into 4-( l',l'-dimethylallyl)-2,6-dimethylaniline cannot be achieved ther- mally but occurs readily in 4moldm-3 sulphuric acid.A new regioselective synthesis of anilides having carbonyl-functionalized alkyl groups in the ortho-position has been ac~omplished'~~" in 40-70% yields by decarboxylative 1-aza-1'-oxa[3.3]~igmatropic'~~~ Claisen rearrangements of enolizable or enolized N-aryl- NO-diacyl-hydroxylamines i.e. (39)-+(40). N-Acyl-N-aryl-azasulphoniumsalts 0 R' R'KNH 121 H. Irngartinger R. G. H. Kirrstetter C. Krieger H. Rodewald and H. A. Staab Terruhedron Letters 1977 1425. 122 (a)J. G. O'Connor and P.M.Keehn Tetrahedron Letters 1977,3711;(b)H. Horita T. Otsubo and S. Misumi Chem. Letters 1977 1309. 123 F.Vogtle M.Atzmiiller W. Wehner and J. Grutze Angew. Chem. Znternat. Edn. 1977,16 325. 124 S.Jolidon and H.-J. Hansen Chimia (Switz.) 1977.31,46;Helv. Chim. Acfu 1977,60 978. 125 (a)R. M.Coates and I. M. Said J Amer. Chem. SOC. 1977 99 2355; (b) F. Vogtle and E. Goldschmidt Chem. Ber. 1976,109,1; (c) P.G.Gassman and R. J. Balchunis Tetrahedron Letters 1977.2235. R. G. Coombes have been prepared for the first time and when treated with base they yield ylides (41) which undergo spontaneous [2,3]sigmatropic rearrangement to produce o-methylthiomethyl-anilides and thus provide another route to ortho-substituted anilide~.'~'' The assumption that the severe conditions necessary for [3,3]sig- matropic rearrangement of 0-aryl or 0-vinyl oximes refer to the preliminary tautomerism stage have been confirmed,126 and some N-aryl-O-vinyl-hydro-xylamines [e.g.(4211 and 0-aryl-N-vinyl-hydroxylaminesundergo spontaneous rearrangement demonstrating the ease of cleavage of N-0 bonds when a Cope rearrangement path is available. It has been by deuterium labelling that 2-vinyl-phenols at 143 "C undergo reversible 1,5-hydrogen shifts to give o-quinone methides and the same process leads to rapid (E,Z)isomerization of for example 2-(prop- 1-eny1)-phenols. X I COMe MeO,( (41) (42) It has been noted that an autoxidation process to form dimethylbenzylamine and benzoic acid occurs during Stevens rearrangement of benzy Idime th yIp henacylam- monium ylide at low temperatures and that this predominates under an atmos- phere of oxygen.'** The solvent hexamethylphosphoramide enables the extension of the application of the Smiles' rearrangement of 2-aryloxy-2-methyl- pro- panamide~'~~~ into N-aryl-2-hydroxy-2-methyl-propanamidesto examples which possess deactivated aromatic This reaction is the basis of a new method for the conversion of phenols into anilines.1296 The kinetic nitrogen isotope effect for the benzidine rearrangement of hydra-zobenzene is kI4/kl5= 1.0203 (*0.0007) demonstrating at last unequivocally that breaking of the N-N bond in this two-proton process is part of the rate- limiting step. This result'30 rules out the recent proposal involving a second pro- tonation at the C-1 atom but cannot distinguish between the traditional mechanism having pre-equilibria at the two nitrogen atoms followed by rate- limiting rearrangement or some concerted process involving N-N bond scission and almost complete second protonation in the rate-limiting stage.The synthetic usefulness of the oxygen analogue of the benzidine rearrangement has been examined.131 The reactions of salts of N-aryl-hydroxamic acids with activated halogeno-benzenes yield 4-amino-4'-hydroxybiphenyls uia intermediate NO-diaryl-hydroxylamines. Biaryls are also formed by a new ~earrangement'~~ of arylhydrazones of aromatic aldehydes and diary1 ketones which is stated to be of 12' T. Sheradsky E. Nov,S. Segal and A. Frank J.C.S. Perkin I 1977 1827. H.-J. Hansen Helv. Chim. Acta 1977,60 2007. lZ8 S. H. Pine and E. Fujita J. Org. Chem. 1977 42 1460. 129 R. Bayles M. C. Johnson R. F. Maisey and R. W. Turner Synthesis 1977 (a)p.31; (6)p. 33. I3O H. J. Shine G. N. Henderson A. Cu and P. Schmid J. Amer. Chem. Soc. 1977,99 3719. 13' T. Sheradsky and E. Nov,J.C.S. Perkin I 1977 1296. '32 F. Fusco and F. Sannicolo Tetrahedron Letters 1977 3163. Aromatic Compounds 237 general applicability and which is exemplified by the formation of 4-amino-3'-formyl-6'-methoxy-3,5-dimethylbiphenyl (35%) on heating the 2,6-dimethyl-phenylhydrazone of anisaldehyde in polyphosphoric acid. The product data from the nitramine rearrangement of N-methyl-N-nitro-m-chloroaniline have been with those from the Claisen rearrangement of ally1 m-chlorophenyl ether and it is claimed that the 'cartwheel' mechanism for the former is not able to accommodate the findings that isomer formation except for a small steric effect and the requirement for ortho,puru-substitution is random.Photochemical rearrangement of the sulphonyl group has been in the conversion of phenyl benzenesulphonate into 0-and p-hydroxyphenyl phenyl sul- phones by U.V. irradiation and a mechanism involving a caged radical pair has been proposed. Further of the Fischer-Hepp rearrangement and concurrent denitrosation have involved methyl-substituted N-methyl-N-nitroso-anilines, with a view to the evaluation of steric effects; in particular those on the enigmatic intramolecular rearrangement step. A steric effect was apparent for the 3,s- dimethyl compound. N-Nitrosodiphenylamine is denitrosated by various nucleo- philes and can also act as a direct ring-nitrosating agent towards aniline~.'~~' 6 Condensed Systems A new route'36 to polymethylated naphthalenes anthracenes and phenanthrenes involves the reaction of 3,4-dichloro-1,2,3,4-tetramethylcyclobutenewith aromatic hydrocarbons in the presence of aluminium tribromide and for example reaction with naphthalene gave 1,2,3,4-tetramethylphenanthrene(60%).The usefulness of photodehydrocyclization reactions of stilbenes and analogues to give phenanth- renes has been increased as reaction occurs much more cleanly137 in the presence of certain 7r-acceptor molecules (e.g. tetracyanoethylene) under anaerobic condi- tions and if necessary at low temperature. The generation of a'-bromo-1,2-naphthoquinodimethane from 1-bromomethyl-2-dibromomethylnaphthaleneis in an improved one-pot synthesis of phenanthrenes.The species then undergoes Diels-Alder reaction with N-phenylmaleimide elimination of hydrogen bromide and fortuitous oxidation to give (43). A new phenanthrene synthesis is NPh 0 (43) (45) a=99" (44) p=138" 133 W. N. White and J. R. Klink J. Org. Chem. 1977 42 166. 134 Y. Ogata K. Takagi and S. Yamada. J.C.S. Perkin II 1977 1629. 13' (a)I. D. Biggs and D. L. H. Williams J.C.S. Perkin II 1977 44; (b)J. T. Thompson and D. L. H. Williams ibid. p. 1932. 136 A. P. Krysin N. V. Bodoev and V. A. Koptyug J. Org. Chem. (U.S.S.R.), 1977,13 1183. 137 J. Bendig M. Beyerrnann and D. Kreysig Tetrahedron Letters 1977 3659. 13' G. W. Gribble E. J. Holubowitch and M. C. Venuti Tetrahedron Letters 1977 2857. 238 R.G. Coombes in the direct conversion of a 2,2'-di(chloromethy1)-substituted biphenyl into the phenanthrene with sodamide in ammonia using an iron catalyst. Vanadium trifluoride oxide has been to convert a variety of 1,2-diaryl-ethene derivatives into phenanthrenes in high yield. Full details of the preparation of 1,l-dichlorocyclopropa[b]naphthalenefrom 1,l,la,7a-tetrachloro-la,2,7,7a-tetrahydro-2,7diphenylcyclopropa[~]naphthalene have appeared.I4* The gem-dibromo-derivative cannot be formed in an analogous way but the reaction of the dichloro-compound with a small excess of ethyl- or phenyl-magnesium bromide leads to halogen exchange the isolable gem-diethyl compound only being formed with a large excess of the Grignard reagent. The unisolable gem-diphenyl compound undergoes ready cleavage of the cyclopropane ring.Acenaphthylene is formed (41% yield) by the elimination of carbon monoxide from 1H-phenalen-1-one on flow pyrolysis at 900°C.141 This method is of more general utility and for example provides the preferred route to indeno[2,1- alindene (dibenzopentalene). Acenaphth[ 1,2-a]acenaphthylene (44) has been synthesi~ed'~~ by a new route and the increasingly strained compounds obtained by introducing ethano-bridges across the peri-positions of (44) have been made for the first time. Spectral effects due to strain were noted and the authors remark on the lack of calculations on these systems. The structure of 1-bromo-lH-cyclo-buta[de ]naphthalene (45) has been determined143a and surprisingly the three rings are essentially coplanar.The strain due to peri-bridging is accommodated by adjustments particularly in bond angles [see (45)] throughout the molecule. The first determination of the crystal structure of a Dewar molecule has been per- formed'43b on 1,3,6,8-tetra-t-butylhemi-Dewar-naphthalene. The molecule has a syn-structure as the substituents cause considerable distortion and the benzo- cyclobutene system is not planar. Decamethylanthracene has been prepared for the first time,'44 utilizing (in part) the removal of a nitrogen bridge in a 1,4-imine by oxidation with peroxide [see Ann. Reports (B) 1976,73 p. 2241. The strain in the structure was illustrated by the ease of photochemical conversion into the 9,lO-Dewar-isomer. A convenient method has been for the introduction of a tertiary carbon carrying an elec- tronegative group into the 9-position of anthracene.The appropriate alkyl radical generated thermally from an azo-compound reacts with anthrone under basic conditions to give the 10-alkyl-anthrone and the alcohol formed on subsequent reduction could be aromatized to the desired 9-substituted anthracene by phos- phorus pentoxide. Dehydrogenation of a series of mono-and di-t-butyldihy- droanthracenes has been in~estigated'~~ as a potential synthetic route to t-butyl- anthracenes. 1-and 2-t-Butylanthracene were prepared in this way although rearrangements complicated other cases. 2,6-Di-t-butylanthracene could be pre- pared in high yield by direct t-butylation of anthracene.13' (a) M. S. Newman and H. M. Dali J. Org. Chem. 1977,42,734; (b)A. J. Liepa and R. E. Summons J.C.S. Chem. Comm. 1977 826. 140 A. R. Browne and B. Halton J.C.S. Perkin I 1977 1177. 14' G. Shaden Angew. Chem. Internat. Edn. 1977,16 50. R. H. Mitchell T. Fyles and L. M. Ralph Canad. J. Chem. 1977 55 1480. 143 (a) M. Gessner P. Card H. Shechter and G. G. Christoph J. Amer. Chem. SOC.,1977,99,2371; (b) R. W. Franck R. Gruska and J. G. White Tetrahedron Letters 1977 509. 14* H. Hart and B. Ruge Tetrahedron Letters 1977 3143. 14' T. Mitsuhashi S. Otsuka and M. bki Tetrahedron Letters 1977 2441. "'P. P. Fu and R. G.Harvey J. Org. Chem. 1977,42 2407. Aromatic Compounds Some unusual structures in the anthracene series have been stabilized.2,4,9-Trichloro- 1,lO-anthraquinone is a stable crystalline solid prepared14' by refluxing 9-chloro-1O-hydroxy- 1,4-anthraquinone with thionyl chloride and triethylamine and some stable 9,lO-quinodimethanes [e.g. (46) m.pt. 105 "C] have been pre- pared148a by the initial reaction of the anthraquinone with methylmagnesium iodide followed by treatment with phosphoryl chloride in pyridine. Related compounds (47) have been formed'48b from the appropriate anthrone. Compounds which had at least two peri-methyl-methyl interactions were formed with the alkylidenedi- hydroanthracene structures shown whereas simpler compounds were formed as the anthracene tautomer. Other examples have been rep~rted'~~.'~*~ of the ease of loss of aromaticity of the central rings of anthracenes caused by double peri interactions.(47)R' R2 R3= Me H Me; Me Me H; H Me Me; or Me Me Me A'3C-labelling experiment has revealed'490 the scrambling of a-and p-(but not angular) carbon atoms in naphthalene at 1035 "C ('automerization') and a reason- able (but unproven) hypothesis involves the intermediacy of azulene. Mass spec- trometric studies indicate'496 that complete scrambling of the carbon atoms of naphthalene occurs in an energy range between the ionization potential and 18.8eV and prior to loss of C2H2. The oxidation of naphthalene with m-chloroperbenzoic acid under carefully controlled conditions has led'5oa to a synthesis of unti-naph-thalene 1,2 :3,4-dioxide which complements that of the syn-isomer reported last year [see Ann.Reports (B) 1976,73 p. 2251. A naphthalene pentaoxide has been from 1,6-epoxy[ 101annulene by two successive sequences of addi- tion of singlet oxygen and thermolysis and it has been shown to have the syn,syn,syn,syn-1,2;3,4;5,6;7,8-unti-9,10-structure. The mechanism proposed for the photocatalysed nitrosation of 2-naphthol appeared ~nlikely'~'" [see Ann. Reports (I?),1975,72 p. 2231 but new evidence for acid-catalytic action of singlet excited 2-naphthol on a ground-state reaction has been presented for the production of acetals from the irradiation of alkanals in Although 1-naphthol in contrast to phenol does not undergo pho- todimerization it has now been reportedlS2 that irradiation of the 1-naphthoxide ion 14' M. V. Gorelik S. P. Titova and V.A. Trdatyan J. Org. Chem. (U.S.S.R.),1977,13 424. (a)B. F. Bowden and D. W. Cameron Tetrahedron Letters 1977,383; (6)J.C.S. Chem. Comm. 1977 78; (c)H. Hart and H. Wachi ibid.,p. 409. 149 (a)L. T. Scott and G. K. Agopian J. Amer. Chem. SOC., 1977,99,4506;(6) H. Budzikiewicz and R. Stoize Monatsh. 1977 108,869. lS0 (a)K. Ishikawa and G. W. Griffin Angew. Chem. Inrernat. Edn. 1977,16 171; see also K. Ishikawa H. C. Charles and G. W. Griffin Tetrahedron Letters 1977 427; (b) E. Vogel A. Brewer C.-D. Sornmerfeld R. E. Davis and L.-K. Liu Angew. Chem. Internat. Edn. 1977 16 169. (a)E. A. Chandross J. Amer. Chem. SOC.,1976 98 1053; (b)M. Hisaoka and K. Tokurnaru Chem. Letters 1977 533. T. Kitamura T. Irnagawa and M. Kawanisi J.C.S. Chem. Comm. 1977 81. 14' R.G. Coombes remarkably gives a dimer (48),probably via a photoinduced nucleophilic addition reaction. In a seemingly unprecedented nucleophilic substitution reaction the formation of 1-piperidhometh yl-4-meth yl-3-nitronap h thalene has been recor-ded’53 from the reaction of 1,4-dimethyl-2,3-dinitronaphthalene with piperidine and the authors suggest redefining the term ‘tele-substitution’ to cover reactions where the entering group occupies a position one or two atoms away from that vacated by the leaving group. (48) Heating potassium 2-naphthoxide in a primary alcohol (benzyl or containing more than three carbon atoms) has been to give a novel route to the 1-alkyl-2-naphthol in good yield. The syntheses of 1-t-butyl- and l-t-pentyl-2- naphthol have been and although these molecules are considerably strained any ketone tautomer present was undetectable.The bulk of the alkyl group does lead however to an extremely rapid autoxidation to the hydro- peroxynaphthalenone (49). It has been that the unreactivity to oxygen of some 1-aryl- and 1-aralkyl-2-naphthols is due to intramolecular hydrogen bonding of the hydroxy-group to the aryl group of the substituent. The first quantitative determination of the reactivity towards electrophiles of anthracene results from studies of pr~tiodetritiation.’~~ The 1-and 2- positions are more reactive than the corresponding positions in naphthalene but are closer in reactivity than are those in naphthalene. Irradiation of 2-~tyrylbenzo[c]phenanthrenein chiral solvents gives”’ the optic- ally active hexahelicene albeit with low optical yields (0.2-2%).3,15-Ethano- and 3,15-(2-oxapropano)-[7]helicenehave been synthe~ized,’~~ and their conformations lS3 G. Guanti S. Thea M. Novi and C. Dell’Erba Tetrahedron Letters 1977 1429. lS4 T. Kit0 and K. Ota J. Org. Chem. 1977,42 2020. 155 (a)J. Carnduff and P. A. Brady J. Chem. Res. (S) 1977 235; (6)P. A. Brady J. Carnduff and F. Monaghan Tetrahedron Letters 1977 3295. 156 H. V. Ansell M. M. Hirschler and R. Taylor J.C.S. Perkin IZ 1977 353. lS7 W. H. Laarhoven and Th. J. H. M. Cuppen J.C.S. Chem. Comm. 1977,47. lS8 M. Joly N. Defay R. H. Martin J. P. Declerq and G. Cermain Helv. Chim. Acta 1977,60 537. Aromatic Compounds 241 and 'H n.m.r.spectra compared with those of [7]helicene and 3,15-dimethyl[7] helicene. Thermolysis of l-formyl[6]helicene tosylhydrazone in benzene in the presence of sodium hydride gavels9 the carbene-insertion product (50),which was resolved using h.p.1.c. [see Ann. Reports (B) 1976,73 p. 2261. 7 Non-benzene Systems Three- and Four-membered Rings.-The 11-methyl-1l-tricyclo[4,4 1,01*6]undecyl cation has been formed,160 below -60 "C and its 13Cn.m.r. spectrum suggests that it has significant 2~-homoaromatic character leading to an unsymmetrical structure (51). The planar l-(2,3-diphenylcycloprop-2-enylidenemethyl)-2,3-diphenylcyclopropenium ion has been synthesized'61 by treatment of bis(2,3-diphenylcycloprop-2-eny1)methane with trityl perchlorate. Spectral measurements indicate a significant contribution of (52) to its structure.Tetra(NN-dialkyl-amino)triafulvalene dications [e.g. (53)] have been synthesized'62 for the first time. PriN-NPr; *______ Me;.i3 Ph*Ph Ph Ph PriN N Pr; (52) (53) (51) The mono- bis- and tris-(p-NN-di-isopropylamino)triphenylcyclopropeniumions have been formed163a by the reaction of NN-di-isopropylaniline with the appro- priate chlorocyclopropenium ion; the fully substituted ion is one of the most stable cyclopropenium ions yet reported. Studies of these ions allow an interesting comparison to be made with analogous triphenylmethyl cations showing for example the reduced importance of the immonium canonical form in the former cases. The reactions of 1,2-bisdialkylarnino-3-halogenocyclopropeniumions and aryl Grignard reagents have been and reactions of an intermediate cyclopropenium Grignard reagent identified.Two electrochemical have yielded values for 'antiaromatic' destabiliza- tion upon the formation of a cyclobutadiene ring. The value for cyclobutenedione upon reduction to the radical anion was at least 59kJm0l-'.'~~~ Dewar has reinforced'65a his suggestion that the cyclobutadiene formed by the matrix-isolation technique is a metastable triplet [see Ann. Reports (B),1975,72 p. 2401 and he has used MIND0/3 theory to calculate (with apparent success) the i.r. 159 J. Jespers N. Defay and R. H. Martin Tetrahedron 1977 33 2141. G. A. Olah G. Liang D. B. Ledlie and M. G. Costopoulos J. Amer. Chem. SOC., 1977,99,4196.161 K. Komatsu K. Masumoto and K. Okamoto J.C.S. Chem. Comm. 1977 232. 162 Z.-I. Yoshida H. Konishi S.-I. Sawada and H. Ogoshi J.C.S.Chem. Comm. 1977 850. (a) K. Komatsu R. West and D. Stanislawski J. Amer. Chem. Sac. 1977,99,6286; (b)Z.-I. Yoshida H. Konishi Y. Miura and H. Ogoshi Tetrahedron Letters 1977 4319. 164 (a) M. Horner and S. Hiinig Angew. Chem. Internat. Edn. 1977 16 410; (6) R. D. Rieke C. K. White L. D. Rhyne M. S. Gordon J. F. W. McOmie and N. P. Hacker J. Amer. Chem. SOC., 1977 99 5387. (a)M. J. S. Dewar and A. Komornicki J. Amer. Chem. Soc. 1977 99 6174; (6) H. Kollmar and V. Staemmler ibid. p. 3583. R. G. Coombes spectrum of such a species. The paper seems however to have been overtaken in publication by the doubts raised concerning the experimental values [see Ann.Reports (B) 1976 73,p. 2281. In contrast to Dewar's calculations and with relevance to his arguments concerning metastability another treatment that even for a square geometry the singlet is lower in energy than the triplet which is in violation of Hund's rule due to spin polarization effects. Both observed and calculated electron densities for a rectangular cyclobutadiene for which the struc- ture is known have shown166n that the density maxima for the four-membered ring lie significantly off the lines joining the carbon atoms indicating that the bonds are 'bent'. The symmetrical and apparently uncomplexed tetrakis(trifluoromethy1)cyclobutadiene has been fully characterized'66h spectrally in solution and matrix at low temperatures.It has a singlet ground state and appears to be rectangular. Tri-t-butylcyclobutadiene for which a rectangular structure is to be assumed has now been shown'66c to undergo reactions typical of a triplet diradical species; for example it undergoes addition with carbon tetrachloride. It was suggested that the two structures may be in rapid equilibrium or that the reaction is initiated by transfer of an electron from the cyclobutadiene within a donor-acceptor complex. Labelling experiment^^^' have confirmed the intermediacy of butalene (54) in the reaction of l-chloro[2,2,0]bicyclohexa-2,5-dienewith lithium dialkylamides to give dialkyl-anilines but this pathway only accounts for about 50% of the product. -SiMe (54) (55) 1,2-Bis(trimethylsilyl)benzocyclobutadienehas been prepared'68 by the vacuum pyrolysis of the &,cis-dienediyne (55) as a thermally stable air-sensitive orange-red oil.The 'H n.m.r. spectrum provides convincing evidence of strong paramagnetic ring-current contributions to the induced ring-current. The pathways of oxidation of benzocyclobutadienes have been ~larified'~~" by the observation that in solution the tetraphenylbenzo[ 1,2 :4,5]dicyclobutadiene (56) is oxidized initially to the oxide (57). In the solid however the stable o-quinone methide (58) is formed. Bu' BU' 166 (a)H. Irngartinger H.-L. Hase K.-W. Schulte and A. Schweig Angew. Chem. Internat. Edn. 1977 16 187; (b)S. Masamune T. Machiguchi and M. Aratani J. Amer. Chem.SOC.,1977,99,3524;(c)G. Maier and W. Sauer Azgew. Chem. Internat. Edn. 1977 16 51. 16' R. Breslow and P. L. Khanna Tetrahedron Letters 1977 3429. K. P. C. Vollhardt and L. S. Yee J. Amer. Chem. Soc. 1977 99 2010. 169 (a)F. Toda N. Dan K. Tanaka and Y. Takehira J. Amer. Chem. SOC.,1977 99,4529; (b)F. Toda and T. Yoshioka Chem. Letters 1977 561. 243 Aromatic Cornpounds Cycloadditions of tetracyanoethylene to substituted analogues of (56) occur in a [2 + 21manner across the bond indicated (1,2) to give highly strained propel lane^.'^^^ Five-and Seven-membered Rings.-A fulvene synthesis has ~esulted’~’ from a study of the reactions of thiobenzophenones with the dicarbonylcyclopentadienyl-iron anion. Yields are improved by the inclusion of para-electron-releasing substituents in the aryl group.The synthesis of fulvenes from the reaction of 1-chloroalkyl acetates and sodium pentadienide followed by base-catalysed eli- mination has been extended171a to some 6-substituted fulvenes and 1,2-benzo- fulvene 1,2,3,4-dibenzofulvene and the corresponding 6-methyl- and 6-phenyl- derivatives have been prepared by an analogous procedurei71* from sodium indenide or sodium fluorenide. 1,2-Benzofulvene has also been formed”* by the flash vacuum pyrolysis of the 11-diphenylmethyleue derivative (59) which was prepared from the benzyne adduct of 6,6-diphenylfulvene by selective hydro- genation. t (59) (40) (61) X = C02Me CHO,or CN A series of 6,6-disubstituted fulvenes has been protonated under super-acid conditions at low temperatures.173 Protonation takes place exclusively at the C-2 position of the fulvene ring in accord with calculated electron densities. The crystalline isolable 1,2,3,4-tetraphenyi- and 1,2 :3,4-dibenzofulvalenes and 2,3- diphenylfulvalene (60) which is only stable in solution have been synthesized. 174 Species (60) readily dimerizes by [4 +2laddition. The scope of the facile pentalene synthesis from 1,3-di-t-butyl-6-dimethylaminofulvene[see Ann. Reports (B) 1976 73,p. 2301 has been by using other alkynes to give the pentalenes (61). These pentalenes are formed as dimers with which the monomers are in rapid equilibrium and which form the monomers in organic solvents. The dimerization reactions and other dimerization products that are formed after longer times have been st~died,”~“ as have the reactivities of the pentalene monomers to acids bases dienophiles and dienes.175b 3-Amino-tropones have been f~rmed”~ by rapid pyrolysis of a corresponding enamine; 3-amino-4-methyltropone,for example being formed from (62). 3-Ethoxy- and 3-phenoxy-tropones have been prepared’77 by the reaction of 3- tosyloxytropone with sodium ethoxide and lithium phenoxide respectively. A 170 H. Alper and H.-N. Paik J.C.S. Chem. Comm. 1977 126. (a)M. Neuenschwander and R. Iseli Helv. Chim. Acra 1977,60 1061; (b)M. Neuenschwander R. VBgeli H.-P. Fahrni H. Lehmann and J.-P. Ruder ibid. p. 1073. 172 R. N. Warrener K. I. Gell and M. N. Paddon-Row Tetrahedron Letters 1977 53. G. A. Olah G. K. S.Prakash and G. Liang J. Org. Chem. 1977,42,661. 174 H. Prinzbach H. Sauter H.-G. Horster H.-H. Limbach and L. Knothe Annalen 1977 869. 17’ hl. Suda and K. Hafner Tetrahedron Letters 1977 (a)p. 2449; (b)p. 2453. 17‘ J. Ficini and A. Durkault Tetrahedron Letters 1977 809. 177 M. Cavazza R. Cabrino and F. Pietra Synthesis 1977 298. R. G. Coombes reported preparation'78a of 3-hydroxytropone derivatives appears however to be incorrect,'786 the products being 2-hydroxyacetophenones. Electrophilic substitution of 5-methyltropolone by arenediazonium ions occurs first at the 3-and then at the 7-position. 179a 5-Arylazotropolones undergo arylazo exchange (61-92%) on reaction with a different arenediazonium ion. 1796 The reaction of 5-nitrosotropolone with cyclopentadiene gives (63) and provides an example of a stable tropolone derivative reacting as a 27~ compound in a [4+ 2]~ycloaddition.*~~' 5-Phenylazotropolone however which is known to react as its diketo-form adds to cyclopentadiene utilizing its N=N-C=C linkage to give (64).179d Further reactions with cyclopropene have established the endo-stereo- chemistry required for the latter reaction.179e An analogous side-chain reaction has also been established'79f as a minor pathway in one case in a homodiene system on reaction of 2-methoxy-6-styryltropone with maleic anhydride. The first benzo[3,4]cyclobuta[ 1,2-c]tropolone7 the 9-chloro-derivative7 has been synthesizedlaO and appears to exist predominantly or exclusively as the tautomer (65).The geometrically isomeric 2,3 :6,7-dioxa-bis-cr-homotropones [e.g. (66)] have been formed18' by the direct oxidation of tropone with alkaline hydrogen peroxide. The unreactivity of the remaining double bond however limits their synthetic utility. A series of methoxy-substituted heptalene-l,8- and -3,8-diones have been formed"*" by oxidation of 8H-cyclohepta[~tropolone.182b In solution in fluorosulphonic acid these compounds are diprotonated and provide the first examples of the lop-heptalenium dication structure [e.g. (67)]. The MIND0/3 method has been applied to the prediction of the rearrangement of benzyl and substituted benzyl cations to tropylium ions and related processes and "I3 (a)J. H. Clark and J. M. Miller Tetrahedron Letters 1977 139; (6)H.Takeshita ibid.,p. 1657. 179 (a)T. Ide K. Imafuku and H. Matsumura Chem. Letters 1977 717; (6) ibid. p. 511; (c)I. Saito K. Sakan. and S. It8 ibid. p. 253; (d)S. It8 and I. Saito Tetrahedron Letters 1977 1203; (e)Y. Fujise M. Sakaino and S. It8 ibid. p. 2663; cf> I. Saito Y. Watanabe and S. It8 ibid. p. 3049. 'I3' M. Sato S. Ebine and J. Tsunetsugu Tetrahedron Letters 1977 855. H. Prinzbach W. Seppelt and H. Fritz Angew. Chem. Znternat. Edn. 1977,16 198. S. Kuroda and T. Asao Tetrahedron Letters 1977 (a)p. 289; (6)p. 285. Aromatic Compounds of the properties of these ions.'83 A pure heptamethyltropylium salt has been prepared'84 for the first time by the use of phosphorus pentachloride as a reagent for hydride abstraction from 1,2,3,4,5,6,7 -heptame t hyltropilidene.The 9,lO-dihydr0-9-10-(1,2-tropylio)anthraceneion (68) has been synthesi~ed,'~~ and the U.V.spectrum is indicative of strong intermolecular charge-transfer interaction despite the small overlap of the orbital systems involved. 8-Phenylheptafulvene has been preparedlg6 by the reaction of the benzyl- tropylium ion with an equivalent of triethylamine in dichloromethane. It is stable for several days in solution at room temperature under nitrogen. U.V. spectroscopy suggests even less r-electron delocalization than in heptafulvene itself and only a small contribution of the dipolar canonical form for this system. 8-Amino- and 8-methoxy-8-(triethylsi1oxy)heptafulvene have also been synthesized; they are hygroscopic and thermolabile.18' A facile synthesis of 8-azaheptafulvenes involves the reaction of tropylium borofluoride with anilines to give 8-aryl-8-azahep- tafulvenium salts which are deprotonated with aqueous sodium carbonate.'88a The cycloaddition reactions of these compounds with inter alia isocyanates and ketens to give (usually) [8+ 2]cycloadducts have also been studied.'88b Two independent report^'^' have been given of an improved route to azulenes by [6+ 4lcycloaddition of 6-NN-dimethylaminofulvenewith thiophen 1,l-dioxides; 3,4-dichlorothiophen for example yielding the hitherto unknown 5,6-dichloroazulene in 60% or 46% 1896 yield. 2,6-Dihydroxyazulene has been preparedlgoa from diethyl 2,6-dihydroxyazulene- 1,3-di~arboxylate'~~~ and undergoes a heavily solvent-dependent keto-enol tautomerism.In chloroform the species exists mainly as 1,3-dihydroazulene-2,6-dione.1,3-Dicarbethoxyazulene-2,6-dione has also been ~ynthesized,'~~' but was isolated only in the form of a dimer. 1-Alkyl-azulenes are converted into 1-acyl-azulenes in 59-98 yields by O/O a novel oxidation using DDQ.I9*' C. Cone M. J. S. Dewar and D. Landman J. Amer. Chem. Soc. 1977,99,372; M. J. S. Dewar and D. Landman ibid. pp. 2446 4633 7439. K.-I. Takeuchi Y. Yokomichi and K. Okamoto Chem. Letters 1977 11 77. T. Nakazawa and I. Murata J. Amer. Chem. SOC.,1977,99 1996. K. Komatsu M. Fujimori and K. Okamoto Tetrahedron 1977 2791. '13' K. M. Rapp and J. Daub Tetrahedron Letters 1977 227. "'(a) K.-I. Sanechika S. Kajigaeshi and S. Kanemasa Synthesis 1977 202; (6) K.Yamamoto S. Kajigaeshi and S. Kanemasa Chem. Letters 1977 85 91. (a)S. E. Reiter L. C. Dunn and K. N. Houk J. Amer. Chem. Soc. 1977,99,4199;(b)D. Copland D. Leaver and W. B. Menzies Tetrahedrm Letters 1977,639. 19* (a)T. Morita H. Kanzawa. and K. Takase Chem. Letters 1977 753; (b)T. Morita and K. Takase ibid. p. 513; (c)T. Amemiya M. Yasunami and K. Takase ibid. p. 587. 246 R. G. Coombes Annulenes.-A series of substituted cyclo-octatetraene dications has now been prepared'" by oxidation of the parent hydrocarbon. Most are stable only at low temperatures but the sym-dibenzocyqlo-octatetraene dication is stable even at 0 "C,and spectral evidence suggests that delocalization of all fourteen .rr-electrons about the sixteen-carbon-atom periphery is occurring.Oxidation of cyclo-octa[deflfluorene by a different method gave'92 the protonated cyclo-octa[deflfluorenone dication (69) a 14~electron aromatic system which is stable at room temperature. The 9,10-diphenylbicyclo[6,2,0]decapentaenes(70) have been ~ynthesized'~~ by a route involving initial photoaddition of diphenylacetylene to bicyclo[4,2,0]octa-3,7-diene,and other stages one of these involving the thermal isomerization of bicyclo[4,2,0]octatriene to cyclo-octatetraene. The preliminary evidence suggests that welectron delocalization in (70; R = H) but not in (70; R = Me) overcomes the strain involved in attaining (near) planarity. R (70) R =H,D or Me PMO theory has demon~trated'~~ that the small variations in the perimeter bond lengths of 1,6-methano[ 101annulene are due mainly to transannular 1,6-homoaromatic interaction.This type of interaction is smaller but still important for the 1,6-methano[ 1l]annulenium cation [cf. Ann. Reports (B) 1976 73,p. 2341. 1,&Methano[ 1Olannulene and some hetero-bridged analogues undergo Diels-Alder addition with 4-substituted-1,2,4-triazoline-3,5-diones, giving both mono- and bis-adducts formed by anti-attack. 195a The methylene bridge also hinders sterically the approach of NNN'N'-tetramethyl-p-phenylenediamineto 2,7-dinitro-1,6-methano[lO]annulene,leading to the formation of only a 1:1 donor-acceptor complex.'95b Unsubstituted 1,5-methano[ lO]annulene has been synthesized and appears to maintain a diamagnetic ring current.'96 In contrast to its 1,&analogue however its electronic spectrum extends into the visible region and it is an orange crystalline solid.Two sets of correlation^'^' have been reported between experimentally deter- mined properties of annulenes and variously calculated values of 'resonance ener- gies per v-electron' (REPE). In the first case197n the correlation involved the rates of formation of some annulenes determined by Sondheimer et al. in connection 19' G. A. Olah J. S. Staral G. Liang L. A. Paquette W. P. Melega and M. J. Carmody J. Amer. Chern. SOC.,1977,99,3349. 19* I. Willner A. L. Gutman and M. Rabinovitz J. Amer. Chem. SOC.,1977,99,4167. M. Oda H. Oikawa N. Fukazawa and Y. Kitahara Tetrahedron Letters 1977 4409. 194 R.C. Haddon J. Org. Chem. 1977 42 2017. lQ5 (a) P. Ashkenazi D. Ginsburg and E. Vogel Tetrahedron 1977 33 1169; (b) J. A. Chudek R. Foster and E. Vogel J.C.S. Perkin ZI 1977 994. S. Masamune and D. W. Brooks Tetrahedron Letters 1977 3239. 19' (a) B. A. Hess jun. and L. J. Schaad J.C.S. Chem. Comm. 1977 243; (b) B. A. Hess jun. L. J. Schaad and M. Nakagawa J. Org. Chem. 1977,42,1669. 19' Aromatic Compounds with their 'reactivity criterion' of aromaticity [see Ann Reports (B) 1976 73,p. 2371. In the second the differences in 'Hn.m.r. chemical shifts of the inner (i) and outer (0)protons of some dehydroannulenes (71 ;rn =p =0 1 2 or 3) gave a good linear correlation with REPE suggesting that chemical-shift data at least if used in this way can give quantitative information concerning aromaticity.(71) n=l or3 Studies of some newly synthesized model compounds have led to the conclusion that the [12lannulene rings in some previously studied di- and tri-benzannelated bisdehydro[ 12lannulenes are paratropic. '98a A necessarily planar benzo-naphtho- analogue was also synthesi~ed,'~'' and the 'H n.m.r. shifts were interpreted in terms of paratropicity of the [12]annulene ring. The 2,3 :6,7 8,9 12,13-tetra- benzo[l3]annulenyl anion (72) the first such ion to contain only formal double and single bonds has been prepared'99a from the corresponding hydrocarbon. *99b The 'H n.m.r. spectrum is indicative of the reduced diatropicity caused by benzan- nelation and in addition of the considerable change in ring conformation from that of the parent hydrocarbon.Full details*"" of the synthesis of 3,7,10,14-tetrasubstituted 1,8-bisdehy-dro[ 14lannulenes by the method involving cyclic dimerization of 2,3-dien-4-yne ketones and the details2"' of the greatly improved synthetic route to bisde- hydrobenzannulenes have appeared. In the latter publication the syntheses of bisdehydrobenz-[141-,-[161- -[181- and -[20]-annulenes as well as of some methyl derivatives are described. It seems that the structural features which allow one to draw equivalent Kekul6 structures for some dehydroannulenes [e.g. (73)] have little effect on their properties.201 Diatropicity differences between (73) and (73) 198 (a)H. A. Staab and P. Gunthert Chem. Ber. 1977,110 619; (b)H.A. Staab and H. J. Shin ibid. p. 631. 199 I. Willner A. Gamliel and M. Rabinovitz (a) Chem. Letters 1977 1273; (6) Synthesis 1977 410. 200 (a)K. Fukui T. Nomoto S. Nakatsuji S. Akiyama and M. Nakagawa Bull. Chem. SOC.Japan 1977 50 2758; (b)N. Darby T. M. Cresp and F. Sondheimer J. Org. Chem. 1977,42 1960. 201 (a)M. Osuka S. Akiyama and M. Nakagawa Tetrahedron Letters 1977 1649; (b)Y. Yoshikawa S. Nakatsuji F. Iwatani S. Akiyama and M. Nakagawa ibid. p. 1737. R. G. Coombes (71);rn = 0,n = 3 p = l) for example appear to be insignificant,201” and similar conclusions were also drawn from studies of a paratropic bisdehydro[ 16lannulene system.z01b It seems that energy differences between non-equivalent canonical forms [e.g. in (71;rn = 1 n = 3 p = l)] are not enough to depress significantly the T-electron delocalization.Benzo[l8]annulene has been synthesized,*02 in low yield by a route involving prototropic isomerization of an intermediate 13,14,15,16-bisdehydro-derivative. Again annelation of the benzene ring reduces the diatropicity of the macrocyclic ring. Two further annulenes have been synthesized203 where extensive benzan- nelation has removed the diatropicity of (4n+2)~-electron macrocyclic rings and for example tribenzo[a,g,rn]-l5,17-bisdehydro[ 18lannulene is atropic. The dimethyldihydrobenzo[e]pyrene (74) sustainszo4 about 55% of the ring-current of the parent non-benzannelated dimethyldihydropyrene. This amount is much greater than the value for other benzannelated [14]annulenes and reflects the greater aromaticity of the rigid dihydropyrene nucleus.All-~is-[2~](2,5)thio-phenophanetetraene (75) has been prepared205 in a one-step reaction from thio- phen-2,5-dicarbaldehyde and the Wittig reagent from 2,5-bis(chloromethyl)thio-phen. The compound shows a small paramagnetic ring current over the 24~-electron periphery; this is enhanced on cooling when planar conformations become of more importance. The presence of the thiophen nuclei does not seem to interfere with the paratropicity of the molecule. The syntheses of the dibenzannulenones (76;n = 1 2 and 3) have been completedzo6“ and the results for (76;n = 1) and (76;n =2) have now been in full The paratropicity exhibited by (76;n = 1) and (76;n = 2) which are however less paratropic than monobenzannelated analogues disap- pears in (76; n = 3) and comparison with an acyclic analogue indicates that the latter is atropic.The first monocyclic large-ring annulenones (77;R =H)and (77; R = Me) have been synthesized.z06‘ The introduction of the additional methyl group (77;R=Me) causes a change in conformation at the other trans double bond. Both species exhibit paratropicity and this is enhanced on dissolution in *02 U. E. Meissner A. Gensler and H. A. Staab Tetrahedron Letters 1977 3. 203 J. Ojima M. Enkaku and C. Uwai Bull. Chem. SOC.Japan 1977,50 933. 204 S. Icli V. J. Nowlan P. M. Rahimi C. Thankachan and T. T. Tidwell Canad. J. Chem. 1977 55 3347. 205 A. Strand B. Thulin and 0.Wennerstrom Actu Chem. Scund. (B), 1977,31 521.206 (a)J. Ojima M. Enkaku and M. Ishiyama J.C.S. Perkin I 1977 1548; (b)J. Ojima Y. Yokoyama and M. Enkaku Bull. Chem. SOC.Jupan 1977,50 1522; J. Ojima M. Ishiyama and A. Kimura ibid. p. 1584; (c)T. M. Cresp J. Ojima and F. Sondheimer J. Org. Chem. 1977 42 2130. Aromatic Compounds 0 0 deuteriotrifluoroacetic acid. syn-4,13;6,11 -Dimethano[ 15lannulenone (78) has been synthesized as an air-stable red crystalline solid and an X-ray crystallographic analysis has been performed. The molecule is protonated in trifluoroacetic acid to give a delocalized annulenium The syntheses of the first bridged [22]annulenes i.e. syn- and anti-(79) have been accomplished,208 in one step by the dimerization of 6,ll -methano[ 1llannu-lenylidene followed by ring closure and loss of hydrogen.'H N.m.r. measurements show no diatropicity and suggest that there is localization of bonds as shown in (79). The first derivative to be formed that is derived from the hitherto unknown nonalene skeleton is the planar delocalized diatropic dibenzo[gh oplnonalenide dianion (80) formed209 from the reaction of 6,14-dihydrodibenzo[gh oplnonalene with butyl-lithium. Further bicyclic compounds containing two fused macrocyclic conjugated 7r-systems have been Octalene (81) has been prepared2'Oa from 1,4,5,8- tetrahydronaphthalene as a lemon-yellow air-sensitive compound. Structures involving a central double bond or aromatic structures were ruled out. Peripheral C=C bond shifting occurs above 80"C.ortho-Fused [14]annuleno-[16]- and -[18]-annulenes analogous to the original [14]annulene [see Ann.Reports (B) 1975,72 p. 2481 have been synthesized.*"' The diatropicity of the 14-membered ring is reduced as the size of the fused annulene is decreased irrespective of whether this latter annulene is (4n +2)-or 4n-membered. Other annuleno-annulenes are (82; rn = 1)210c and (82; m = 2),210dwhich are both strongly diatropic and quite stable in 207 W. Wagemann K. Miillen E. Vogel T. Pilati and M. Simonetta Angew. Chem. Internat. Edn. 1977 16 170. 208 U. H. Brinker R. W. King and W. M. Jones J. Amer. Chem. SOC.,1977,99 3175. *09 I. Willner and M. Rabinovitz J. Amer. Chem. Soc. 1977,99 4507. *lo (a) E. Vogel H.-V. Runzheimer F. Hogrefe B. Baasner and J. Lex Angew. Chem. Internat.Edn. 1977,16,871; J. F. M. Oth K. Miillen H.-V. Runzheimer P. Mues and E. Vogel ibid. p. 872; (b)T. M. Cresp and F. Sondheimer J. Amer. Chem. SOC.,1977,99 194; (c) S. Nakatsuji S. Akiyama and M. Nakagawa Tetrahedron Letters 1977 3723; (d) M. Osuka Y. Yoshikawa S. Akiyama and M. Nakagawa ibid.,p. 37 19. 250 R. G. Coombes (82) (83) contrast to the appropriate [26]-and [30]-annulenes. In the 'H n.m.r. spectra the inner protons of the 14-membered ring appear at a much higher field than those of the 18-membered ring and the latter and all outer protons shift to higher field as the distance from the central bridge increases. Finally the first examples of annulenophanes e.g. (83) have been reported.211 The benzenoid protons of (83) show the expected upfield shift due to the ring current in the [lolannulene ring.The indications are however that in this example transannular interaction of welectrons is small. *" M. Matsumoto T. Otsubo Y. Sakata and S. Misumi Tetrahedron Letters 1977 4425.

ISSN:0069-3030    

DOI:10.1039/OC9777400215

出版商:RSC    

年代:1977

数据来源: RSC

摘要:

11 Heterocyclic Chemistry By A. J. BOULTON School of Chemical Sciences University of East Anglia Norwich NR4 7TJ 1 Heterocycles in Functional Group Transformations Mukaiyama has continued to exploit quaternary salts containing reactive halogen atoms as a means of converting stable organic functions into good leaving groups. The conversions of trialkylammonium dithiocarbamates into isothiocyanates,' of thioureas into carbodi-imides2 (using reagent l) of alcohols into chloride^,^ formamides into is~cyanides,~ and epoxides into 1,2-dichlorides (using Z),5 are briefly reported. More preliminary notes describe the further work of Katritzky's group on the reaction of pyrylium salts (3) with primary amino-functions to give (3) x=o (4) X=NCH*R Me I ' T.Shibanuma M. Shiono and T. Mukaiyama Chem. Letters 1977,573. * T. Shibanuma M. Shiono and T. Mukaiyama Chem. Letters 1977,575. T. Mukaiyama S. Shoda and Y. Watanabe Chem. Letters 1977,383. Y. Echigo Y. Watanabe and T. Mukaiyama Chem. tetters 1977,697. ' Y. Echigo Y. Watanabe and T. Mukaiyama Chem. Lencrs 1977,1013. 25 1 252 A. J. Boulton pyridinium salts (4) which then lead to iodides6 (using 3 A = I) and esters’ (using 3 A = BF4) from primary amines RCH2NH2 and by rearrangement carbodi-imides ArN :C :NAr’ from amidrazones ArNHCAr’ :NNHzs (using 3 A = ClO,). ‘Sac-charin chloride’ the benzisothiazole (5) is suggested as a useful reagent for the production of p -1actams from acids and imines.’ Another condensing technique uses 2-chlorobenzothiazole which activates a primary alcohol as outlined in Scheme 1.The quaternary salt (6) may alkylate another nucleophile (the method works with a wide variety of these) possibly with the pseudobase (7) as an inter- mediate.” 2 General Heterocyclic Synthesis The salt (8)is a versatile reagent for the synthesis of many heterocycles (with five- six- and seven-membered rings) with the structural element (A);” the isomeric arrangement (B) had earlier been shown to be derived similarly from (9).12 Both starting-materials are made from dimethyl phosgenimmonium chloride (Scheme 2). N-Ethoxycarbonylthioamides (10) provide smaller pieces for building into hetero- cycles three-atom and one-atom units are incorporated on reaction (a) with 1,2- and 1,3-binucleophiles and (b) with 1,4- and larger binucleophiles re~pective1y.l~ +-R RN=CCl-NR-CCI=NMe2Cl + -/ RNyyMe2 RN=C=NR (8) + (A) Me2N=CC12 C1 Scheme 2 3 Three-membered Rings Attempts to prepare oxirene by heating epoxy-barrelenes have been unsuccessful.At 300-400 “C cycloheptatriene aldehyde derivatives were obtained from (11) N. F. Eweiss A. R. Katritzky P.L. Nie and C. A. Ramsden Synthesis 1977 634. ’ U. Gruntz A. R. Katritzky D. H. Kenny M. C. Rezende and H. Sheikh J.C.S. Chem. Comm. 1977 701. ’A. R. Katritzky P.L. Nie A. Dondoni and D. Tassi Synthetic Comm. 1977,7 387. M. S. Manhas H. P. S. Chawla S. G. Amin and A. K. Bose Synthesis 1977,407. lo F. A. Souto-Bachiller and S. Masamune Tetrahedron Letters 1977 1881.’‘ A. Elgavi and H. G. Viehe Angew. Chem. Internat. Edn. 1977,16 181. l2 Z. Janousek and H. G. Viehe Angew. Chem. Internat. Edn. 1973 12,74. l3 B. George and E. P. Papadopoulos J. Org. Chem. 1976,41 3233; ibid. 1977,42,441 2530. Heterocy c Zic Chemistry (acidic alumina brought about the same transformation) but at 600-800°C flash thermolysis did produce some ketene the expected rearrangement product of ~xirene.'~ The bridged anthracenes (12; R=H and Me) rearranged on heating rather than eliminating the bridge." Developments in the study of the Wolff rearrangement and the involvement of oxirenes and their interconversion with a-ketocarbenes are treated in Chapter 5 of this Volume. (11) (1 2) (13) Thiirene seems to be slightly less elusive than oxirene its marrix-isolation has been reported along with an i.r.study and data were also obtained on mono- and di-deuterio- and methyl derivatives and on selenirene.16 Benzothiirene appears to be an intermediate in the pyrolytic formation of two isomeric thianthrenes from a monosubstituted 1,2,3-ben~othiadiazole,'~ although this view is challenged by another group." Thiirenium salts appear to be more stable and one of these (13)has been studied by X-ray crystallography. The ring C-S bonds are unusually long (1.82 A; cf. 1.80 8 for the S-Me bond)." Thiirenium salts are prepared by methods analogous to those used for the thiiranium seleniraniurn and selenirenium salts reported earlier.** Oxidation of thioketen monomers e.g.(14) with a pyrroline-l-oxide forms thiiran-2-ones (thiol-a -lactones) e.g (15) the structures of which were established by i.r. CQ. 1800cm-') and the X-ray crystallography of (15).22 0 (14) (15) (16) (17) -Flash photolysis of the cis and trans isomers of a-cyanostilbene oxide (16) forms carbonyl ylids (PhCH=b-CPhCN) which are highly coloured and the rates of their reactions and their interconversion could be studied. Upper and lower limits are suggested for the depths of the energy troughs in which the ylids lie.23Irradia-tion of naphthoquinone oxides in the presence of norbornene and other dipolaro- philes forms bridged benzoxepin cycloadducts derived from the valence tautomer (17).24 l4 E. Lewars and G. Morrison Tetrahedron Letters 1977 501.Is H. Hart J. B. C. Jiang and M. Sasaoka J. Org. Chem. 1977,42 3840. l6 A. Krantz and J. Laureni J. Amer. Chem. Soc. 1977,99,4842. l7 T. Wooldridge and T. D. Roberts Tetrahedron Letters 1977 2643. L. Benati P. C. Montevecchi and G. Zanardi J. Org. Chem. 1977,42 575. l9 R. Destro T. Pilati and M. Simonetta J.C.S. Chem. Comm. 1977 576. 2o G. Capozzi V. Lucchini G. Modena and P. Scrimin Tetrahedron Letters 1977 91 1. cf. Ann. Reports (B),1975,72 253. '* E. Schaumann and U. Behrens Angew. Chem. Internat. Edn. 1977,16 722. 23 R. Huisgen V. Markowski and H. Hermann Heterocycles 1977,7,61. 24 S. Arakawa J. Org. Chem. 1977,42 3800. 254 A. J. Boulton cis-2-Vinyl-3-ethynyloxirane(18) has been shown to rearrange cleanly via two Cope rearrangements to the cyclopropane (19).With the corresponding N-t- butylaziridine (20) however the presumed intermediate (21; X = NBu') is side-tracked by an intramolecular proton shift and the product is 1-t-b~tylazepine.~' (18) x=o (20) X=NBu-t (22) R = H C1 or Me R \ CR=CCI (24) (23) Viehe et ai.26have discovered an interesting analogy to the rearrangement of singlet oxygen-diene adducts (A2-1,4-peroxides) to bis-epoxides the nitroso- olefins (22) with cyclopentadiene form the diene mono-oxide-mono-imines (23) via (4 +2) cycloadducts (24) which are detectable intermediates at -60 "C. The addition of nitronic esters (25) to acetylenes (26) does not form the expected N-alkoxyisoxazolines (27); these are probable intermediates but they immediately rearrange to 2-acyl- 1-alkoxyaziridines.The stereochemistry of this reaction has been studied and it was found that the products (28 29) are formed stereo- specifically only with respect to the relative configurations of the substituents on H YCO H"' R2 + yco-1 N OMe OMe OMe R' =CN or C02Me R2=H or vice verso Y = COPh COMe or C02Me *' N. Ma,nisse and J. Chuche J. Amer. Chern. SOC.,1977,99 1272. 26 H. G. Viehe R. Merenyi E. Francotte M. Van Meerssche G. Germain J. P. Declerq and J. Bodart-Gilmont J. Amer. Chem. Soc. 1977 99 2340. 27 R. Grei and R. Carrii J. Amer. Chem. SOC.,1977,99,6667;J.C.S. Chem. Comm. 1975 112. Heterocyclic Chemistry 255 The automerization rates of perfluorotetramethyl Dewar thiophene (30) and its S-oxide have been compared.28 The former exchanges slowly (AG' 93.8* 0.5 kJ mol-' at 157"C) the latter extremely rapidly (AGS 28*0.5 kJ mol-' at -136 "C),but the authors suggest that the mechanism is probably similar.Me (31) R = subst. phenyl (32) R=NMe2 Dh (33) (34) + H2C=O S S '0- ~i 'Me NMe 0 Me -Me H2C' '6 (35) (36) (39) 1977 saw the publication of a number of papers from the Zurich group on the chemistry of 2H-azirines. The U.V. spectra and also the regiospecificity of cyclo-addition to various dipolarophiles of the benzonitrile isopropylides formed by photochemical ring-opening of the azirines (3l) are in~estigated.~' 3-Dimethyl- amin0-2~2-dirnethylazirine (32) is a fertile source of interesting reactions. With a munchnone (1,3-oxazolium-5-olate) it appears to add to the acylamidoketen valence tautomer (r.t. in MeCN); subsequent rearrangement and recyclization leads to the amino-oxazoline (33).30Azirine (32) forms eight-membered hetero- cycles (34; X = CO SO*)by insertion into the heterocyclic rings of phthalimide and ~accharin.~'The adduct with CS exists as the betaine (35) in the solid phase but mainly as the open-chain structure (36) in non-polar Isothiocyanates form adducts of structure similar to (35) amongst other things.33 With substituents other than methyl at C-2 other types of product are sometimes formed.34 2E C. H. Bushweller J. A. Ross,and D. M. Lemal J. Amer. Gem. Soc. 1977,99,629. 29 U. Gerber H. Heimgartner H. Schrnid and W. Heinzelrnann Helv. Chim.Acta 1977,60,687. 30 J. LukAE J. H. Bieri and H. Heimgartner Helu. Chim. Am 1977,60 1657. 31 S. Chaloupka P. Vittorelli H. Heimgartner H. Schrnid H. Link K. Bernauer and W. E. Oberhansli Helu. Chim. Acta 1977,60 2476. 32 S. Chaloupka H. Heimgartner H. Schmid H. Link P. Schonholzer and K. Bernauer Helv. Chim. Acta 1976 59 2566. 33 E. Schaumann E. Kausch and W. Valter Chem. Ber. 1977,110,820. 34 E. Schaumann S. Grabley K. D. Seidel and E. Kausch Tetrahedron Letters 1977 1351. 256 A. J. Boulton The detection of dioxirane (37) by mass35 and microwave36 spectrometry as a transient intermediate in the gas-phase ozonolysis of ethylene has been claimed. Calculations3’ had earlier suggested that it should compare favourably in stability with the zwitterionic (38) and diradical (39)open-chain forms and that its de- composition might proceed by 0-0 cleavage; some kinetic evidence appears to support this view.38 L’abbk et aL3’ have described the preparation of alkylidenediaziridines (40).They do not isomerize to aziridinimines on heating but rather form methacrylic amidines (41). With phenyl isocyanate the adduct (42)is obtained. The thermal rearrangement of aziridinimines (e.g. 43S 44) has been studied kinetically. UnfortunateIy they also decompose very easily and these reactions compete with the rearrange men^^' T Me Me2C=C=NAr PhCH2NdMe L+ PhCH2NC +MeS02N3 NBu‘ +Me2C=NBut +t -BuNH~ -PhCH2N=CMe2 +t-BuNC (44) Quast’s group have made further contributions to this general theme (‘hetero- trimethylenemethanes’).Phenyl isocyanate adds to a diaziridinimine (45; R1= R2= R3=Pr’) to form a 1,2,4-triazolidinonimine (46); deuterium-labelling [(CD3),CH] demonstrated (a) that the diaziridinimine did not scramble the label between the N atoms and (b),that addition occurred across the exocyclic and one of the ring N atoms as expected.41 The addition of (45) to dimethyl acetyl- enedicarboxylate eventually yields a 1:3 adduct of spiro-construction (47).42 The possibility of thiaziridinimine-diaziridinethione involvement in some reactions of 35 R. I. Martinez R. E. Huie and J. T. Herron Chem. Phys. Letters 1977 51 457. 36 F. J. Lovas and R. D. Suenrarn Chem. Phys. Letters 1977 51,453. 37 W. R. Wadt and W. A. Goddard J. Amer. Chem.SOC.,1975,97 3004. 38 J. T. Herron and R. E. Huie J. Amer. Chem. SOC.,1977,99 5430. 39 G. L’abbC C. C. Yu and S. Toppet Angew. Chem. Internat. Edn. 1977,16,475. 40 H. Quast and P. Schafer Tetrahedron Letters 1977 1057. 41 H. Quast and E. Spiegel Angew. Chem. Internat. Edn. 1977 16 109. 42 H. Quast K. H. Ross,E. Spiegel K. Peters and H. G. von Schnering Angew. Chem. Internat. Edn. 1977,16 177. Hete roc y c1ic Chemistry thiatriazoles and tetrazolinethiones has been raised by L'abbk,43*44 but this seems to be speculative at present. (451 (46) (47) E=C02Me (48)R1= Me,R2= R3= H (49) R' = H,R2R3= C4H4 (50) (51) PhC=C-SiMe2-SiMe3 hl; PhVSiMe Si (52) Me2 (53) The irradiation of 3-oxidopyridazinium betanes (48) and the corresponding phthalazines (49) in acetonitrile forms bicyclic valence isomers (50).These compounds show little or no amide resonance ca. 1750 cm-') and in protic solvents the five-membered ring is opened; recyclization and aromatization pro- duces the rearranged pyridazinones (5l).45 A further development on the silirene front46 is the reported photochemical conversion of the acetylenic disilane (52) into the cyclic isomer (53). In several reactions of (53) which were investigated external groups were inserted into the Si-C(Ph) bond.47 4 Four-membered Rings By a careful choice of temperature wavelength of illumination (270nm) and matrix material it has proved possible to convert the oxazinone (54; R' = R2= H) into its bicyclic valence isomer (55). Shorter wavelengths (254 nm) produced the keten (56); both valence isomerizations were reversed thermally.Substituted oxazinones behaved similarly. Prolonged irradiation of the lactone (55; R'= Me R2=Buf) gave the dimer(s) of the azete (57),when conducted at -70°C in 2-methyltetrahydrofuran but at 7K (Ar matrix) fission products (CO, acetylenes and cyanides) were formed which were consistent with the formation of (57) rather than with cleavage of (55)to a nitrile and ~xetone.~~ (Scheme 3) '' G. L'abbk G. Verhelst and S. Toppet J. Org. Chem. 1977,42 1159. 44 G. L'abbC G. Verhelst and G. Vermeulen Angew. Chem. Internat. Edn. 1977,16 403. 45 Y. Maki M. Kawamura H. Okamoto M. Suzuki and K. Kaji Chem. Letters 1977 1005. O6 Ann. Reports (B) 1976 73 243. 47 H.Sakurai Y. Kamiyama and Y. Nakadaira J. Amer. Chem. SOC.,1977 99 3879. G. Maier and U. Schafer Tetrahedron Letters 1977 1053. cf. also A. Krantz and B. Hoppe J. Amer. Chem. Soc. 1975,97,6590. 258 A. J. Boulton 0 Me AN QR OMe Ph Me O q O M e -PhqOMe "'@TLR PhOMe Me (59) (58) (60) (61) R =Tosyl or C02Me Further examples49 of azetines have been reported. The hl-azetin-3-one acetal (58) is formed by thermal decomposition of the photoadduct (59) of 6-methyl-2-phenyl- 1,3-0xazin-4-one and l,l-dimeth~xyethene,~~ while photolysis of the tetracyclic compounds (60) gave the A2-azetine derivatives (6 l)? Adam et al. have given details for their synthesis of 1,2-dioxetanones (62) by carbodi-imide cyclization of a-hydroperoxy-carboxylic for which a con- venient preparation has been rep~rted.~" An optically active 172-dioxetane has been prepared54 and its crystal structure was determined;55 it was found to emit circularly polarized chemiluminescence when it dec~rnposed.~~ Singlet oxygen adds to the dihydrodioxin (63) at -78 "C to form the (4+2) cycloadduct which rearranges to the dioxetane (64) (silica gel r.t.in xylene); the luminescent de- composition of (64) occurs at 80 0C.57 Benzothiet (65) has been prepared by flash vacuum pyrolysis of benzo[b]thio- phene 1,l-dio~ide.~~ Thiete dioxides (66) on heating form vinyl sulphenes which undergo (4+2) cycloaddition to olefins. Yields are poor however unless conditions are favourable (as for instance when the olefin is ~trained).~~ The remarkable diphosphete (67) is reported by Appel et a1.60as a stable white solid.49 cf.Ann. Reports (B),1975 72 254; ibid. 1976,73 243. so T. H. Koch R. H. Higgins and H. F. Schuster Tetrahedron Letters 1977,431. s1 R. N. Warrener G. Kretschmer and M. N. Paddon-Row J.C.S. Chem. Comm. 1977 806. 52 W. Adam A. Alzerreca J. C.Liu and F. Yany J. Amer. Chem. Soc. 1977 99 5768. " W. Adam and 0.Cueto J. Org. Chem. 1977,42 38. '4 H. Wynberg and H. Numan J. Amer. Chem. SOC.,1977,99,603. s5 H. Numan J. H. Wieringa H. Wynberg J. Hess and A. Vos J.C.S. Chem. Cornm. 1977 591. 56 H. Wynberg H. Numan and H. P. J. M. Dekkers J. Amer. Chem. SOC.,1977,99 3870. 57 A. P. Schaap P. A. Burns and K. A. Zaklika J. Amer. Chem. SOC.,1977,99 1270. W. J. M. van Tilborg and R.Plomp J.C.S. Chem. Comm. 1977 130. s9 D. C. Dittmer J. E. McCaskie J. E. Babiarz and M. V. Ruggeri J. Org. Chem. 1977 42 1910. 6o R. Appel F. Knoll and H. D. Wihler Angew. Chem. Internat. Edn. 1977 16 402. Heterocyclic Chemistry + Ph,P -PPh2 rJ+2c1-Ph,P PPh 5 Five-membered Rings Simple furans can be elaborated into a variety of useful ‘synthons’ according to several research groups. The acid-catalysed rearrangement of 2-furylcarbinols(68) to 5-hydroxycyclopenten-3-oneshas been used in prostaglandin-intermediate synthesis.61 Rather than undergo simple acyloin reduction furoic esters form the OCHR RQC0,Et -B SiMe3 RCOCH2CHI I OH OH I C=CSiMe3 (68) (69) 0 RCH2I C + R‘/ \() \CH I HC \“Me2 (71) dLi 0 I c NMe I Scheme 4 G.Piancatelli A. Scettri and S. Barbadoro Tetrahedron Letters 1976 3555; G. Piancatelli and A. Scettri ibid. 1977 1131. 260 A. J. Boutton acetylenic derivatives (69) by ring cleavage with sodium and trimethylsilyl chloride in tetrahydrofuran followed by acid workup.62 Further synthetic possibilities of this product are explored.63 2,5-Dilithiated furan thiophene and pyrroles have been in~estigated,~~ and the lithiated bromofuran (70) has provided another route to 'rose f~ran'.~~ Glyoxal monohydrazones (e.g. 71) provide a route to 2,3-disubstituted pyrroles and their 1-amino-substituted derivatives as outlined in Scheme 4.66 A convenient synthesis of azulenes is claimed from the (6+4) cycloaddition of B-dialkylamino-fulvenes to thiophene dio~ide.~~,~~ Indoles (72) are formed by intramolecular cyclization of a-lithiated o-tolyl isocyanides (a favourable '5-Endo-Dig' process in Baldwin's scheme6').The lithio derivatives (73; R = H) can be alkylated at -70 "C and the product again metal- lated (PriNLi) to (73; R = alkyl); cyclization occurs on heating to room tempera- ture." HR L -1 H (73) (74) I . R' Et Me J (77) (76) i Et shift and cyclization ii Chloranil(-4H) x-Y c R' (75) Mschanisms of alkyl group migration in the Fischer indolization reaction of the hydrazone (74) have been e~amined.~' The major product (75) is suggested to be e 62 I. Kuwajima K. Atsumi and I. Azegami J.C.S. Chem. Comm. 1977 76. " K. Atsumi and I.Kuwajima Tetrahedron Letters 1977 2001. 64 D. J. Chadwick and C. Willbe J.C.S. Perkin I 1977 887. " N. D. Ly and M. Schlosser Helv. Chim. Acta 1977,60 2085. "T. Severin and H. Poehlmann Chem. Ber. 1977,110,491. 67 D. Copland D. Leaver and W. B. Menzies Tetrahedron Letters 1977 639. S. E. Reiter L. C. Dunn and K. N. Houk J. Amer. Chem. SOC.,1977,99,4199. 69 J. E. Baldwin J.C.S. Chem. Comm. 1976 734. 70 Y. Ito K. Kobayashi and T. Saegusa J. Amer. Chem. SOC. 1977,99,3532. B. Miller and E. R. Matjeka Tetrahedron Letters 1977 131. Heterocyclic Chemistry 261 formed via (76) which arises from two 1,2-alkyl shifts (or a 1,5-shift?) from the primary rearrangement ions (77; R=Me R’=Et and vice versa). In the final migration step the ethyl group moves in preference to the methyl.Minor products are produced by 1,2-alkyl shifts in (77) leading to 1,4-dialky1-5,6,7,8-tetrahydro-carbazoles. Peri-bridged naphthalene systems (78) continue to receive attention. The reac- tions of methyl-lithium followed by methyl iodide on the three congeners (78; X = Y = S Se and Te) contrast in that the dithio-compound forms 1,8-bis(methyl- thio)naphthalene (79; R = R’= SMe) the diseleno- gives a 4:1 mixture of the bis(methylse1eno)naphthalene and the mono-C-alkylated compound (79; R = SeMe R’ =Me) while the ditelluride loses the tellurium altogether giving 1,8-dimeth~lnaphthalene.~~ The synthesis of analogues with mixed group six elements (78; X=S Y=Se and Te and X=Se Y=Te) has been rep~rted.’~ The dithiole 1,l-dioxide (78; X = S,Y = SO,) forms a mixture with the monoxide and trioxide (78; X= SO Y = S and SO2 respectively) when treated with NaOH followed by HC1.74,75 An extensive series of interesting papers describes the work of J.C. Martin’s group on the heterocyclic sulphuranes. The optically active chlorosulphurane (80) was found to racemize slowly,76 and the two isomers of the spiro-compound (81) interconverted also slowly (AG* ca. 125 kJ m~l-l).~~ The mechanism of these reactions is uncertain. The X-ray crystal structure of the asymmetric compound (82) shows that the S-0 bond lengths are significantly different (a 1.955 A b 1.713 A),78a state of affairs reminiscent of that obtaining with the S-S distances found in unsymmetrically substituted thiathiophthenes.R2 Me Me /\ Ph C1 (80) Me (83) (81) R’= Me R2 = Et (82) R’= R2= CF3 Et Et Et R2 R2 eFe [:o EtfiMe c <,o~MeB,l=l ,BMe +m+ * / 1.-, .._. BIN,-,NR’ S B Et Et (84) (86) R/\X (85) (87) 72 J. Meinwald D. Dauplaise F. Wudl and J. J. Hauser J. Amer. Chem. SOC. 1977 99 255. 73 J. Meinwald D. Dauplaise and J. Clardy J. Amer. Chem. Sm. 1977.99 7743. 74 B. I. Stepanov V. Ya. Rodionov M. A. Andreeva V. P. Perevalov and S. E. Voinova Zhur. nbshchei Khim. 1977,47 234. These authors claim the trioxide as a new compound; see however ref. 75. 75 J. L. Kice and H. Margolis J. Org. Chem. 1975,40 3623; M. M. Chau and J. L. Kice J. Org. Chem. 1977,42,3265. 76 J. C. Martin and T. M. Balthazor J. Amer. Chem. SOC.,1977,99 152.77 L. J. Adzirna and J. C. Martin J. Org. Chem. 1977 42 4006. ’‘ L. J. Adzima E. N. Duesler and J. C. Martin J. Org. Chem. 1977 42 4001. 262 A. J. Bouiton Phenylene orthosulphite (83) has been reported as showing an AA'BB' 220 MHz 'H n.m.r. spectrum indicating a four-fold (D2d)symmetry at least when time- averaged. It is very unstable to moist~re.~' The reaction between ethylene and ozone has been studied by i.r. in CO and CC14 matrices at temperatures down to 65 K. The secondary ozonide (1,2,4- trioxolan) was the major product observed but a less volatile minor compound remained after that along with ethylene ozone and COz had been pumped off at -120 "C and this was assumed to be the primary ozonide 1,2,3-trioxolan (84).80 For the gas-phase ozonolysis of ethylene see Section 3.A number of appetizing sandwich compounds containing boron heterocycles including some of the triple-decker type were reported during 1977. Both sides of the 1,3-diborole ring are complexed in (85)," and both sides of a 1,2,5-thiadi- borolene (86) accept cobalt" and manganeseg3 tricarbonyl bonding units. 1,3,2-Diazabarolenium salts (87) are formed by the reaction of a-di-imines with dihalo- borane~.~~ which They can be reduced to the very unstable 1,3,2-dia~aborolenes,~~ may be stabilized in the form of Cr(C0)3 comple~es.~~ Some water-stable iron tricarbonyl compounds of boroles have been prepared.86 4-Oxazolin-2-ones (88; R = H or Ph X = NH or NAc) with dienes form Diels- Alder adducts which can be hydrolysed to provide a synthesis of p-amino-alco-hols in the same way that 1,2-diols can be made using vinylene carbonate (88; R=H X=O).87 Another illustration of the synthetic use of oxazoles is in the heating of 3-sulphoximino-2-oxazolidinones(89); these decompose as indicated to leave an olefin and they have been used in attempts to prepare the (2) (successfully) and (E)isomers of bicyclo[3,3 llnon- 1-ene.88 Potts has extended his work on the mesoionic heterocycles of general structure (90; X Y = 0 S Se or NR').These compounds are conveniently prepared by reaction of a 1,2-bielectrophile RCHBrCOCl (R=Ph or C02Et) with a wide variety of 1,3-bin~cleophiles.~~ 79 G. E. Wilson and B. A. Belkind J. Org. Chem. 1977,42,765. 'O B. Nelander and L.Nord Tetrahedron Letters 1977 2821. " W. Siebert and M. Bochmann Angew. Chem. Internat. Edn. 1977,16 857. 82 W. Siebert and W. Rothermel Angew. Chem. Internat. Edn. 1977 16 373. 83 W. Siebert and K. Kinberger Angew. Chem. Internat. Edn. 1976,15,434. 84 G. Schmid and J. Schulze Chem. Ber. 1977,110 2744. " G. Schmid and J. Schulze Angew. Chem. Infernat. Edn. 1977 16 249. 86 G. E. Herberich J. Hengesbach 0.Kotle and W. Oschmann Angew. Chem. Infernat. Edn. 1977,16 42. J. A. Deyrup and H. L. Gingrich Tetrahedron Letters 1977 31 15. ''M. G. Kim and J. D. White J. Amer. Chem. SOC.,1977,99 1172; cf. Ann. Reports (B),1975,72,312. 89 K. T. Potts S. J. Chen J. Kane and J. L. Marshall J. Org. Chem. 1977,42 1633; K. T. Potts and S. J. Chen ibid. p. 1639; K. T.Potts F. Huang and R. K. Khattak ibid. p. 1644. Heterocyclic Chemistry (91) (92) The structures of Reissert salts have been reformulated as fused 5-amino- oxazolium systems (9 1) rather than the 4H-imino-structures previously assigned." The fused oxazolo[5,4-b]pyridine (92) is formed as a 3 1 addition product of benzoyl isocyanide and dimethyl acetylenedi~arboxylate.~~ The thermal rearrangement of 5-hydrazinoisoxazoles has been studied in some detail.92 The products are 1-and 4-aminopyrazolin-5-ones, and tetrahydro- 1,2,4- triazin-6-ones in varying proportions depending on the solvent and substituents. Another interesting rearrangement product was observed when the photochemistry of a variety of N-alkyl-2,1-benzisoxazoliurnsalts was in~estigated.~~ In protic solvents N-substituted o-amino-phenyl ketones are formed with further substitu- tion in the benzene ring (e.g.93-94); this is perhaps unexceptional but in acetonitrile the 1-adamantyl-3-phenyl compound gives a red salt for which the structure of the cation is suggested to be (95) or (96). The former is supported by Ph I - PhCNO HN-0 (97) PhCN + HNOz Ph (98) 'NOH yo M.J. Cook,A. R. Katritzky and A. D. Page J. Amer. Chern. Soc.,1977,99,165. 91 G. Hofle and B. Lange Angew. Chern. Internat. Edn. 1977,16,262. 92 G. Adembri A. Camparini F. Ponticelli and P. Tedeschi J.C.S. Perkin I 1977 971. 93 N. F. Haley J. Org. Chem. 1977,42 3929. 264 A. J. BouIton 13 C n.m.r. the latter by its i.r. spectrum.Another interesting observation in the isoxazole series is the curious insertion of the PhC element of benzonitrile oxide into some isoxazolin-5-ones (97; substituents unspecified) which forms 1,3-0xazin- 6-ones (98); the route suggested is Benzothiazoles with a nitro-group in the benzene ring react with alkylmagnesium bromides followed by addition of boron trifluoride etherate to the complex to produce alkyl-nitroso-benzothiazoles(e.g. 99+100) in fair to good yields.95796 It remains to be seen what role if any the thiazole ring plays in this rather unexpec- ted reaction. The full paper has appeared from Meth-Cohn’s group on the preparation of benzimidazole- 1,3-dioxides (101) from benzofuroxan and secondary nitroparaffins and of 1-hydroxybenzimidazole-3-oxidessimilarly from primary nitroparaffins.The products undergo some curious and fascinating reactions with a variety of reagents [(NC)2C=C(CN)2 MeO2CC=CCO2Me malononitrile] ; with the acetyl- enic ester the structure (102) is formed.97 2H-Benzimidazoles (e.g. 103) suffer nucleophilic attack by amines and sulphides; the products are oxidized by the starting compounds to the correspondingly substituted derivatives (104).98 (99) 0-(103) X=H (104) X=Nu E (1 02) E = C02Me COR I + ,COR‘ “HN) NN rJ-I I COR COR R (105) (106) (107) 1-Alkyl and 1-arylimidazoles react with acyl chlorides in the presence of tri- ethylamine in polar solvents (e.g. MeCN) to form the 2-acyl derivatives. Possibly the zwitterion (105) is involved in this reaction.99 Imidazole itself gives the dimeric 94 G.Lo Vecchio F. Foti G. Grassi and F. Risitano Tetrahedron Letters 1977 21 19. 95 G. Bartoli and G. Rosini Synthesis 1976 270. % G. Bartoli R. Leardini M. Lelli and G. Rosini J.C.S. Perkin I 1977 884 ’’ D. W. S. Latharn 0.Meth-Cohn H. Suschitzky and J. A. L. Herbert J.C.S. Perkin I 1977 470. 98 A. M. Jefferson and H. Suschitzky J.C.S. Chem. Comm. 1977,189. 99 E. Regel and K. H. Buchel Annulen 1977 145. Heterocyclic Chemistry compound (106),'0° under the same conditions while with isocyanates in hot solution 2-carboxamides are formed."' Benzimidazole suffers a three-pronged attack by 2,2'-dichlorocarbonyldiphenylamine;the structure of the product (107) has been confirmed by X-ray crystallography.lo* Prolonged irradiation of the pyridoindazole (1 08)in tetrahydrofuran forms S -carboline (109) and a spiro-intermediate is proposed (110) being one of many canonical forms by which it can be repre~ented."~ However the thermal rear- rangement of the 3-imidazolyl and 3-pyrazolylanthranils (1 11) and (1 12) leads to a variety of products which are reasonably suggested to arise by rearrangement of spiro-intermediates (113).'04 The Authors argue that in the case of the re-arrangement of the 3-(2-pyridyl)anthranil which cleanly forms pyrido[ 1,241- cinnolin-11-one (1 14),'05 a spiro-2-pyridine intermediate of type (113) is improbable. r=Y Me (1 13) (114) (115) (111) X=N,Y=CH (112) X=CH,Y=N The structure (1 15) of the product of reaction of 2-phenacylisoquinolinium bromide and ammonium acetatelo6 has been confirmed by X-ray crystallo- graphy.lo' Two pyrazole syntheses from azines were noted in the year under review.a'-0x0-aP-unsaturated azines (1 16) for which a variety of synthetic methods are available give pyrazolyl ketones and esters (1 17; R' = alkyl aryl or alkoxy) on heating.'" This is an extension of a reaction reported some ten years ago,'O9 and appears to be efficient and versatile. The other synthesis involves cyclization of simple ketazines with lithium di-isopropylamide in hexamethylphosphoramide and lea E. Regel Annulen 1977 159. lo' E. P. Papadopoulos J. Org. Chem. 1977,42 3925. lo' A. Banerji J. C. Cass and A. R. Katritzky J.C.S. Perkin I 1977 1162. Ifl3J.H. Boyer and C. C. Lai J.C.S. Perkin I 1977 74. lf14R. Y. Ning J. F. Blount P. B. Madan and R. I. Fryer J. Org. Chem. 1977,42 1791. lo' R. Y. Ning W. Y. Chen and L. H. Sternbach J. Heterocyclic Chem. 1974,11 125. If16R. F. Cookson D. P. Nowotnik R. T. Parfitt J. E. Airey and A. S. Kande J.C.S.Perkin I 1976. 201. lo7 H. J. Lindner and B. Kitschke Tetrahedron Letters 1977 2091. lo' T. A. Albright S. Evans C. S. Kim C. S. Labaw A. B. Russiello and E. E. Schweizer. J. Org. Chem. 1977,42,3691. lo' R. L. Stern and J. G. Krause J. Org. Chem. 1968 33 213; J Heterocyclic Chem. 1968 5 263. 266 A. J. Boulton is exemplified by pinacolone azine (118). The product (119) contains an extra carbon atom; this is evidently C-5 of the ring and is derived from the solvent."' The propensity for azines to undergo 'criss-cross' electrocyclic reactions is also illustrated in some work of Burger on what he terms 'dipole metathesis'.The azomethineimine (120) adds to electrophilic olefins and with acetylenes it under- goes a series of somersaulting additions to provide a variety of 1'5-and 1'7-dipolar systems."' Other work from Delaware"* is relevant to this area. R4 R3 RJ R3 rn R5CH ,N -%R5PN N N/ II I I R'C-COR CHR~-COR' MeC-Bu' MeCHBu' (120) (121) R =H or Me (122) 1,4-Dinitropyrazoles (12 1) with secondary amines undergo interesting cine-substitution with departure of the leaving group from the nitrogen. With the isomeric 1,3-dinitro compound (122) the amine simply removes the l-nitro- group.'13 A potentially useful synthesis of 1-substituted pyrazole-2-oxides (123) is the reaction of nitrile oxides with imidoyl-substituted oxosulphonium ylids (124).'14 Freeman's group has published further results in the 4H-series.The chlorination of pyrazoles 1-hydroxypyrazoles and their 2-oxides forms 4-chloro-derivatives;' 15*116 these with methoxide introduce a methoxy substituent into a + OMe Me-SO I R 0-OH (124) (123) (125) (126) methyl group either in the 4- or 3-position probably via diazafulvene derivatives e.g. (125)+(126). Silver acetate converts 4-chloro-4H-pyrazole-1,2-dioxides into the 4-acetoxy-dioxides but the 4-chloromonoxides (127) give 3-acetoxy 'lo Y. Tamaru T. Harada and Z. Yoshida Tetrahedron Letters 1977 4323. 'I' K. Burger H.Schickaneder and C. Zettl Angew. Chem. Internat. Edn. 1977,16 54 55. 'I2 S. Evans R. C. Gearhart L. J. Guggenberger and E. E. Schweizer J. Org. Chem. 1977,42,452. C. L. Habraken and E. K. Poels J. Org. Chem. 1977,42,2893. R. Faragher and T. L. Gilchrist J.C.S. Perkin I 1977 1196. 'I5 J. P. Freeman and E. R. Janiga J. Org. Chem. 1974 39 2663. J. P. Freeman and J. F. Lorenc J. Org. Chem. 1977 42 177. Heterocyclic Chemistry derivatives (128). With silver nitrate the monoxides (127) decompose to acetyl- enes probably through the 3-hydroxy-3H compounds (129) but 3-acetoxy compounds in part revert to 4-hydroxy derivatives besides decomposing to acetyl- enes (not invariably the expected ones carrying the 4-and 5-~ubstituents).'~' 0-0-(127) (128) R = Ac (129) R=H 3H-Pyrazoles readily lose nitrogen on irradiation The sufphur-containing derivatives (130; n = 0 1 and 2) form carbenes (131) which can be intercepted with olefins and cyclopropenes (132) which can be trapped by 1,3-dipolar cyclo- addition of dimethyldiazomethane and in the case of the sulphone (132; n = 2) by (135) X = S 0,CO 1 RZ R2 (136) (137) Diels-Alder addition to furan.The question whether or not an equilibrium exists between the carbenes (131) and the cyclopropenes (l32) was not settled but products of the carbene mode of addition are produced even after the irradiation has ceased.'l8 An account of a careful study of the photodecomposition of spiro- pyrazoles (1 33) using monochromatic radiation has been given.' '' The benzo- cyclopropenes (1 34) which are the first identifiable products undergo further J.P. Freeman E. R. Janiga and J. F. Lorenc J. Org. Chem. 1977,42 3721. M. Franck-Neumann and J. J. Lohmann Angew. Chem. Internat. Edn. 1977,16 323. E.Luddecke. H.Rau H. Durr and H. Schrnitz Terrahedron 1977,33,2677. 268 A. J. Boulton photoreactions which depend on the nature of the substituents and the illumina- tion. Spiropyrazoles (135) on irradiation form spirocyclopropenes (136) and in some cases fused indenes (e.g. 137). It is not yet clear whether (137) is formed via (136).'*' Pyrolysis of 172,3-thiadiazole cleanly forms thioketene which was characterized by its photoelectron spectrum.'*' For the pyrolysis of 172,3-benzo- thiadiazoles see Section 3.The rearrangement of the oxadiazolinethiones (1 38) to thiadiazolinones has been studied for a wide range of alkyl and aryl substituents. The reaction proceeds well photochemically and also thermally when catalysed by copper; without the copper only the 3-aryl compounds give thiadiazolinones. These results are in striking contrast to the very ready thermal rearrangement of open-chain oxime -thiono- carbamates.12* An extension of an old-fashioned rearrangement forms 1,2,4-thiadiazoles (139; X Y = N CH CMe or CPh) from 3-amino-1,2-oxazoles (140). The intermediate thioamides can sometimes be is01ated.l~~ The reaction of an aroyl chloride in pyridine with 5-amino-1,2,3,4-thiatriazole(141) eventually provides the diox- athiadiazapentalene system (142) with loss of Imidoyl chlorides behave similarly to give thiatetra-azapentalenes (143),44 but with acetyl chloride a more profound reorganization produces the thiadiazole (144).124 Further examples (145; X = 0 or S) of the 'extended thiathiophthene' system have been ~repared.'~' NHPh X Y/' VN\NHPh U (1 39) N AcHN(/ ]NHAc S-N (ACCI HzNTN~y ArCXCI S-N N Arf/ x-s-x NyAr (144) (141) (142) X=O (143) X=NAr' R' I2O H. Durr S. Frohlich B. Schley and H. Weisgerber J.C.S. Chem. Comm. 1977 843. H. Bock B. Solonki G. Best and P. Rosmus J. Amer. Chem. SOC.,1977,99 1663. 122 A. Pelter and D. Sumengen Tetrahedron Letters 1977 1945. 123 N. Vivona G. Cusmano and G. Macaluso J.C.S. Perkin I 1977 1616. R. J. S. Beer and I. Hart J.C.S.Chem. Comm.1977. 143. 12' E. G. Frandsen J.C.S. Chem Comm. 1977 851. Heterocyclic Chemistry 269 The addition of a sulphene to the dithiazolinimines (146) is reported to form the rearranged system (147). 126 Addition of benzonitrile oxide to sulphines generally produces 1,4,2-oxathiazole-4-oxides(1 48) but in the case of fluorenethione-S- oxide the isomeric 1,5,2-oxathiazole-5-oxideis also f0~med.l~' A very interesting reaction occurs between 2,5-dimethylfuran and nitrosocar- bonylbenzene PhCONO. The 1,3,4-dioxazole (149) is formed possibly by rear- rangement of the primary Diels-Alder adduct as indicated and it is reversible! The product (149) on heating regenerates the two original Diels-Alder participants.l** Me Ph 11 J 0-0 1,2,4-Dioxazoles (150) are produced by the reaction of singlet oxygen with oxa~oles.~*~ Their decomposition gives a variety of products including diacyl- amines.I3O The reaction of 1,3,4-thiadiazoliurn pseudobases (15 1) with diethyl acetyl- enedicarboxylate in boiling benzene involves an ylid intermediate and an unusual p-nitrophenyl group migration. The products (152) undergo further addition of an a1k~narnine.l~~ (Scheme 5). /C,H,N02 + /C,H,N02 + /C6H,NO, N-N N-N -N-N L -Ark YH OR -Ark. ,!-s S (151) \;102CCGCCO*Et 41.52) Scheme 5 '26 H.W.Linden and J. Goerdeler Tetrahedron Letters 1977 1729. 127 B. F. Bonini G. Maccagnani G. Mazzanti L. Thijs P. M. M. Ambrosius and B. Zwanenburg J.C.S. Perkin I 1977 1468. 12' C. J. B. Dobbin D.Mackay M. R. Penney and L. H. Dao J.C.S. Chem. Comm. 1977,703. '29 M. L. Graziano M. R. Iesce A. Carotenuto and R. Scarpati J. Heterocyclic Chem. 1977 14 261; Synthesis 1977 572. I3O M. L. Graziano A. Carotenuto M. R. Iesce and R. Scarpati Tetrahedron Letters 1977,447. 13' G. Scherowsky K.Dunnbier and G. Hofle Tetrahedron Letters 1977,2095. 270 A. J. Boulton Dehydrodithizone (1 53) and its oxygen analogue (154) both ‘Type B mesoionic compounds’ in the classification of Ollis and Ram~den,’~~ are thermally rearranged to the isomeric ‘Type A’ heterocycles (155).’33 Dehydrodithizone reacts with tetracyclone to give an interesting product (1 56)containing an open-chain azimine grouping rather than the isomeric fused dihydrotetrazole which seems to be an elusive The structure of (156) was proved by X-ray crystallography and the same technique was applied to solve the structure of the reaction product (157) of glyoxal and the bis-azo compound (1~9.l~~ Ph I Ph Ph XYN+ I Ph yh N+ Phn >N’ *NPh N-N .N-N \ \ Ph Ph 0 Ph N (153) X=S (155) (156 (154) X=O Q The 1,2,3,5-dithiadiazolium system (159; R=Bu’ CCI3 or Ph) has been pre- pared by the reaction of the nitriles RCN with trithiazyl chloride S3N3C13.’36 The reactions of this and other thiazyl chlorides with a variety of olefinic substrates have been studied by Barton and B~bb;’~’ isothiazoles and thiadiazoles are among the products observed.(159) An interesting study of thioamide base-pairing through hydrogen bonds has been reported.13* In CCl the tetrahydropyrimidine-2-thione(160) (weakly associated ‘32 D.W. Ollis and C. A. Ramsden Ado. Heterocyclic Chem. 1976,19,1. 133 P. N. Preston and K. Turnbull J.C.S. Perkin Z 1977 1229. 134 G. V. Boyd T. Norris and P. F. Lindley J.C.S. Perkin Z 1976 1673; ibid. 1977 965. 13’ P. Skrabal and M. Hohl-Blumer Helv. Chim. Acta 1976 59 2906; P. Luger J. Malkowski and P. Skrabal ibid. 1977 60 1545. 136 G. G. Alange A. .I.Banister B. Bell and P. W. Millen Znorg. Nuclear Chem. Letters 1977 13 143. 13’ D. H. R. Barton and W. A. Bubb J.C.S. Perkin Z 1977,916. 13* E. Gentric J. Lauransan C. Roussel and J. Metzger Tetrahedron Letters 1977 251. Heterocyclic Chemistry by itself because of the weak hydrogen bonding tendency on the part of its NH group) when mixed with an equal proportion of the benzothiazolinethione (161) (which is fairly strongly dimerized on account of the very acidic NH group and in spite of its weakly basic thione S-atom) forms a hydrogen-bonded dimer pair as shown with an association constant almost twice the value of that for the homo- associated pair (161)*.1.r. spectroscopy was used to determine the equilibrium constants and the results agreed well with the predictions based on calculation. The structures (162; R = alkyl X = S or Se) are assigned on the basis of 13C n.m.r. evidence to the products of alkylation followed by demethylation of 1-aryl-5-methylthio- and -methylseleno-tetrazoles. The same technique is used to distinguish between tautomeric thiol and thione structures and the corresponding selenol-selenones in a series of az01es.l~~ An interesting case of tautomerism arises with the bicyclic phosphorus compound (163).The exchange is sufficiently rapid at room temperature that the n.m.r. spectra indicate overall two-fold symmetry of the molecule; the signals separate at low temperature (-60 "C; 13Cn.m.r. at 22.63 MHz). Compound (163) arises by disproportionation of the diazaphospholane (164) as shown. 140 Several 1977 papers illustrate the propensity for PI1*to expand its valency to P" particularly when the atom is contained in a five-membered ring. Equilibria have been studied for a variety of systems of the type (165)+ (166) (X= 0 or NR) and the results were rationalized using Pearson's HSAB treatment.I4l The P-Hphos-phoranes (166; X = 0)react with aldehydes and ketones to form products (167),'42 which have been studied by i.r.and n.m.r. spectroscopy. 143 Bicyclic phosphoranes 139 J. R. Bartels-Keith M. T. Burgess and J. M. Stevenson J. Org. Chem. 1977,42 3725. Id* H. Sliwa and J. P. Picavet Tetrahedron Letters 1977 1583 and personal communication. 14' A. Munoz Bull. SOC. chim. France 1977 728. 14' H. Gerrna and R. Burgada Buil. SOC. chim. France 1975,2607. 143 H. Germa M. Bon and F. Mathis Bull. SOC. chim. France 1977 508. 272 A. J. Boulton containing nitrogen (e.g. 168) are reversibly formed from the PIrrcompounds (169).144 6 Six-membered Rings The relationship between odd alternant hydrocarbon anions and six-membered mesomeric betaines has been used by Ram~den'~~ to formulate general rules for predicting whether 1,3-dipolar reactivity can be expected.The statement is made that 'neutral heterosystems isoelectronic with irreducible odd alternant hydro- carbon anions cannot be represented by non-polar structures if the lone-pair originates at an unstarred position.' This arises from simple parity arguments. The treatment places for example the pyrazinium derivative (170) into the class of fully conjugated mesomeric betaines entirely distinct from the pyrimidine (17 l) which is a cross-conjugated dipole. In fact the former behaves as a 1,3-dipole the latter as a 1,4-dipole. Sammes's group exploited the 1,4-dipolar reactivity of compounds of type (171) earlier,146 and they have now presented further examples (172+173) in which intramolecular cyclization of olefinic acetylenic or cyano substituents to pyrimidine rings -not necessarily dipolar -leads to useful syntheses of annulated pyridines and pyrimidine^.'^^ I R (172) X = CH or N (171) R = OH Meor Ph Considerable interest is still shown in conformational analysis and several papers have illustrated the great value of the information provided by '3Cn.m.r.Some years ago 1-chloropiperidine was studied by 'H n.m.r. and a barrier to ring inversion of 56.5 kJ mol-' was found.14' This technique gave no information on the N-inversion process except that it had to be faster. The I3C n.m.r. has now shown that at -32 "C the C1-axial form is ca. 4% abundant (AGO ca.6 kJ mol-') with AG* 43 kJ mol-I for the N-inversion process.'49 For such heavily-biased equilibria the dynamic 13Cn.m.r. method is particularly useful as illustrated in the case of the perhydro- 1,2,4-triazines and -1,3,4-thiadiazine~.'~~ The conformations of 1-methylpiperidinium salts in water provided evidence for solvation of the NH' group as a factor in influencing equilibria.''' 144 D. Houlla F. H. Osman M. Sanchez and R. Wolf Tetrahedron Letters 1977 3041. 14' C. A. Ramsden J.C.S. Chem. Comm. 1977 109. Ann. Reports (B),1975 72 312. 147 L. B. Davies P. G. Sammes and R. A. Watt J.C.S. Chem. Comm. 1977,663. 14* J. B. Lambert W. L. Olivers and B. S. Packard J. Amer. Chem. SOC.,1971,93 933. 149 F. A. L. Anet and I. Yavari Tetrahedron Letters 1977 3207.lS0 A. R. Katritzky R. C. Patel and D. M. Read Tetrahedron Letters 1977 3803. E. L. Eliel C. Y. Yen and G. Zuniga Juaristi Tetrahedron Letters 1977 2931. Heterocyclic Chemistry Further use of ion cyclotron resonance to determine gas-phase basicities and hence to obtain estimates of tautomeric equilibrium constants has been made.'52 1H-2- and 4-Pyridinethione structures strongly favoured in polar solvents are of minor importance in the gas phase. 3-Acetyl-2-ethoxy-3,4,5,6-tetrahydropyridine (174a) exists practically completely as such in CDC13 but the similarly constructed furopyridine (175) strongly prefers the NH form (b). It is suggested that a destabil- izing interaction exists between the lone pairs of the heteroatoms in (175a); this is avoided in (174a) by rotation of the ethoxy group.153 CoMe = N N OEt Q;;=0 momo H(1 74b) (175a) H(175b) (1 74a) A number of papers featured the thermal and photochemical destruction of heteroaromatic six-membered rings.The irradiation of [ 1,4-15N2]-1,2,4,5-tetra-zine under a variety of conditions (exciting both singlet and triplet states) produced N2 and HCN but no C2Hz or doubly-labelled N2,suggesting that 1,4-bonding plays no significant role in the photodecomposition of tetra~ine.'~~ The fused 1,2,3- triazine (176) loses nitrogen to form the nitrile (177).15' Py?idine-1-oxide when irradiated at 10 K in an argon mattix forms an unstable isocyanide the anion (178) of which is much more stable being formed if the irradiation is carried out at room temperature in aqueous base.'56 Pyridazine- 1,2-dioxide (179) has been found (after a false start1") to be isomerized to the dihydroisoxazoloisoxazole(180).15* It is tempting to ascribe this to cleavage of (179) to 1,4-dinitrosobutadiene which then undergoes serpentine bicyclization in a manner for which several precedents C.B. Theissling N. M. M. Nibbering M. J. Cook S. El-Abbady and A. R. Katritzky Tetrahedron Letfers 1977 1777. See also M. J. Cook A. R. Katritzky M. Taagepera T. D. Singh and R. W. Taft J. Amer Chem. SOC. 1976,98,6048. H. Sliwa and L. Delaunay Tetrahedron Letters 1977,2793. D. S. King C. T. Denny R. M. Hochstrasser and A. B. Smith J. Amer. Chem. Soc. 1977,99,271. I. Ito N. Oda S. I. Nagai and Y. Kudo Heterocycles 1977,8 319.0.Buchardt J. J. Christensen C. Lohse J. J. Turner and I. R. Dunkin J.C.S. Chem. Comm. 1977 837. H. Arai A. Ohsawa K. Saiki and H. Igeta J.C.S. Chem. Comm. 1977 133. H. Arai A. Ohsawa K. Saiki H. Igeta A. Tsuji T. Akimoto and Y. Iitaka J.C.S. Chem. Comm. 1977,856. 274 A. J. Boulton exist.159 Vacuum pyrolysis of benzo[c]cinnoline derivatives has provided further examples of aza-biphenylenes. 160 An attempted halogen-lithium exchange in the acetal (181) led after hydrolytic work-up to the pyridone (182). The proposed explanation which was consistent with deuterium-labelling experiments involved metallation at the pyridine 3-position indicated followed by cleavage to the nitrile (183) and recyclization. In the reaction of the pyridinium salt (184) with a secondary amine it is the pyridine 2-position which is deprotonated; the ylid cyclizes to the ester group and the pyridine ring is then opened leaving a 4-isoxazolinone (185).16' R2NH; -R,N-(CH=CH), 3 N-0 0 0,CMe,CO,Et (185) (184) The pyrolysis of aryl propargyl ethers provides a goldmine of interesting chem- istry.The two isomeric cyclobutapyridines (186) and (187) (ratio 2 :1 50% overall yield) are formed in a curious reaction (the mechanism of which requires fuller investigation) from 4-propargyloxypyridine at 550 0C.163 Abramovitch et aZ.'64 have reported the preparation and some reactions of 1-aryloxypyridinium salts and 1-aryloxy-2-pyridones. The salts prepared from the N-oxides and diaryliodonium fluoborates are unstable and rearrange usually under the influence of bases.With phosphorus oxychloride the pyridones form pyrido[ 2,3 -b 3benzofurans. see e.g. G. Maier and M. Wiessler Tetrahedron Letters 1969 4987. A recent dihydro-pyrrolopyrrole (R. M. Carr. R. 0.C. Norman and J. M. Vernon J.C.S. Chem. Comm. 1977 854) also conforms to the same structure type and may be formed analogously. 160 S. Kanoktanaporn and J. A. H. MacBride Tetrahedron Letters 1977 1817. G. R. Newkome J. D. Sauer and S. K. Stakes J. Org. Chem. 1977,42 3524. 16* H. Sliwa and A. Tartar Tetrahedron Letters 1977 311. 163 J. M. Riemann and W. S. Trahanovsky Tetrahedron Letters 1977 1867. 164 R. A. Abramovitch and M. N. Inbasekaran Tetrahedron Letters 1977 1109; R. A. Abramovitch G.Alvernhe and M. N. Inbasekaran ibid. p. 1113. Heterocyclic Chemistry 275 The full pape? has appeared on the preparation and reactions of 1,l'-bi-pyridinium salts which have been mentioned in these Reports earlier.'66 The pyridine-N-imine derivatives (188) undergo a variety of thermal and photochemical cyclization reactions an outline of which is presented in Scheme &I6' and/or I-0- N Scheme 6 [1,2,4]-Triazino[ 1,6,5-ji]quinolines (189) can be prepared by N-amination followed by cyclization of 8-acylaminoquinolines (1 90). The red products behave as 1,3-(or 1,ll-) dipoles (189; R =H) giving the cyclazine derivative (191) with dime t hyl acetylene dicarboxylate. RCONH R R R R + p-II NH NH \/ \/ (192) The diazenium salt (192) can be obtained by electrochemical oxidation of 1-amino-1,2,3,4-tetrahydroquinoline.In acid it adds to olefins; in base it forms a 2-tetra~ene.l~~ Cycloaddition reactions also trap the azomethine ylid (193) generated by acetic anhydride-triethylamine dehydration of the N-oxide (194)."' 165 M.P. Sammes H. K. Wah and A. R. Katritzky J.C.S. Perkin I 1977 327. Ann. Reports (B),1975,72,269; ibid. 1976,73,429. A. Kakehi S. Ito K. Uchikama Y. Konno and K. Kondo J. Org. Chem. 1977,42,443. 168 Y. Tamura Y. Miki H. Hayashi Y. Sumida. and M. Ikeda Heterocycles 1977.6 281. 169 G. Cauquis B. Chabaud and Y. Gohee Tetrahedron Letters 1977 2583. 17* M. Ikeda Y. Miki S. Kaita Y. Nishikawa and Y. Tamura J.C.S.Perkin I 1977,44. 276 A. J.Boulton The preparati~n'~' and stability'72 of N-ethoxycarbonyl-1-pyrindine(195) is discussed by Anastassiou et al.They claim that the ethoxycarbonyl grouping robs the heterocyclic system of none of its aromaticity in contrast to what is observed with 1-e thoxycarbonylazonine. Dihydropyridines are featured in a number of noteworthy papers. 1-Carbo-methoxy-1,2-dihydropyridinewas the starting-point for a synthesis of the dihydro- azabarrelene (196) which is a remarkably unstable compound decomposing to benzene in a few hours. 173 Surprisingly organomagnesium and organocadmium reagents attack 1-acylpyridinium salts at the 2-position so quickly that competition from attack at the carbonyl group is not serious. The acid chloride can even be added to a mixture of the organometallic reagent and the pyridine competition from the acid chloride under these conditions is also negligible.174 1,2-Dihy- dropyridines have been used in syntheses of di- and tetra-hydroazocines and-of pyrr~lizidines.'~~ A new technique for preparing Reissert compounds using tri- methylsilyl cyanide and aluminium chloride allows their formation in water-free solvents and so permits use of acid chlorides which are sensitive to hydr01ysis.l~~ Spiro-l,4-dihydropyridines(197) are formed by addition of dimethyl acetyl- enedicarboxylate to a wide variety of heterocyclic imines.177 I C02Et (195) (197) so; X =S or NMe E =C02Me Me (199) Me Chau and Kice have found that the dibenzodithiin trioxide (198) with sulphite ion produces the Bunte salt S-oxide (199) an unusual and unstable type of 171 A.G. Anastassiou S. J. Girgenti R. C. Griffith and E. Reichmanis J. Org. Chem. 1977,42 2651. 172 A. G. Anastassiou and E. Reichmanis J. Amer. Chem. SOC. 1977 99 7392. 173 H. Sliwa and Y. le Bot Tetrahedron Letters 1977,4129. 174 R. E. Lyle J. L. Marshall and D. L. Comins Tetrahedron Letters 1977 1015. 175 P. S. Mariano M. E. Osborn D. Dunaway-Mariano B. C. Gunn and R. C. Pettersen J. Org. Chern. 1977,42,2903. 176 S. Ruchiwarat N. Phadungkul M. Chuankamnerdkarn and C. Thebtaranonth Heterocycles 1977,6 43. 177 H. Quast and E. Spiegel Tetrahedron Letters 1977 2705. Heterocyclic Chemistry ~tructure."~ Interesting sulphur-containing six-membered rings that were noted were the 2,1,3-benzothiadiazinium system (200),17' and the 1,2,4-oxathiazine (201),'80 the latter arising by bromine oxidation of the thiourea (202).The synthetic utility of 2-chloro-1,3-dithian has been investigated.'" The rearrangement of optically active 10-thia-anthracenes (203) occurs with predominant racemization but some retention of optical activity in the product (204).18* H Ar I Ar (203) 0Li+ phnoH As X I I Ar Me (207) (208) R=Ac (210) (211) X = P As Sb (209) R=H (212) X=CMe Research on six-membered rings with more unusual heteroatoms has been the subject of much activity and here too several rearrangements have been dis- covered. The benzyl group migrates on heating from the arsenic atom to the 4-substituent in (205); this has been known for some time in the phosphorin series.'83 Aryl groups undergo 1-2 migration with acid catalysis in (206)Ig4 and (207);18' hydrolysis of the acetoxy-derivative (208) forms the hydroxy-compound (209) which appears to exist as although alkylation of 4-hydroxyarsenin "'M.M. Chau and J. L. Kice J. Org. Chem. 1977,42 3103 3265. 179 W. Kosbahn and H. Schafer Angew. Chem. Internat. Edn. 1977,16 780. lSo S. Solyom P. Sohar L. Toldy A. Kalman and L. Parkanyi Tetrahedron Letters 1977 4245. C. Kruse N. Broekhof A. Wijsrnan and A. van der Gen Tetrahedron Letrers 1977,885; E. C. Taylor and J. L. LaMattina ibid. 1977 2077. '" C. A. Maryanoff. K. S. Hayes and K. Mislow J. Amer. Chem. Soc. 1977,!39 4412. G. Markl and J. B. Rampal Tetrahedron Letters 1977 2569.G. Markl and R. Liebl Angew. Chem. Internat. Edn. 1977,16,637. G. Markl and J. B. Rampal Tetrahedron Letters 1977 3449. 278 A. J. Boulton gives the l-alkyl-4-0ne.'~~ The 'phosphaphenol' (210) too appears to be prefer- red over a ketonic tautomer.'86 Diels-Alder addition and retro-addition of dimethyl acetylenedicarboxylate and methyl propiolate to arsabenzene and its 2-methyl derivative have been studied. Some dimethyl phthalate is produced indicating that 1-arsabarrelene derivatives are not exclusively formed but that also some of the 2-arsa compounds arise; these can lose HC-As to produce the ~htha1ate.l~' Methyl-lithium adds the alkyl group to the heteroatoms of phospha- arsa- and stiba-benzene in contrast to pyridine to give the anions (211).The chemical shifts of the protons on the pentadienyl fragments are very similar to those in (212) suggesting that little or no stabilizing interaction is derived from the presence of the heteroatom in (211).'88 (214) (213) (217) (2 18) (219) X =0,CR2 Irradiation of the 1,4-diphosphorin (213) is reported to form the diphos- phabenzvalene (214) a remarkably stable while with carbon tetra- chloride it reacts in an odd way giving the 1,4-bridged compound (215) and the unstable dichloro-derivative (216) which was not Representatives of &N3P (217)191 and CN2P3 (218)'92 ring systems were noted. With group IV elements the stannins (219) with sp2-hybridization of all the ring carbon atoms were prepared,'93 and a report on the generation of a silabenzene appeared this is mentioned in Chapter 6.7 Seven-membered and Larger Rings Like the thiirenes mentioned earlier so 1-benzothiepins are stabilized appreciably by quaternization at sulphur. The benzothiepinium salt (220) has a half-life of 69 hours at 80"C (CD,N02) while (22 1) is nearly half gone in three hours (80OC CCl,). The sulphoxide (222) is much less stable than either the sulphone (223) much more.'94 G. Markl G. Adolin F. Kees and G. Zander Tetrahedron Letters 1977 3445. "'A. J. Ashe and H. S. Friedman Tetrahedron Letters 1977 1283. A. J. Ashe and T. W. Smith Tetrahedron Letters 1977 407. Y. Kobayashi S. Fujino H. Hamana I. Kumadaki and Y.Hanzawa I. Amer. Chem. Soc. 1977.99 8511. '90 Y. Kobayashi I.Kumadaki H.Hamana and S. Fujino Tetrahedron Letters 1977 3057. 191 P. P. Kornuta N. V. Kolotilo and L. N. Markovskii Zhur. obshch. Khim. 1977,47,342. 19' R. T. Oakley and N. L. Paddock Canad. J. Chem. 1977,55,3651. 193 G. Markl and J. B. Rampal Tetrahedron Letters 1977 2325. H. Hofmann and A. Molnar Tetrahedron Letters 1977 1985. 19' 279 Heterocyclic Chemistry (220) X=iMe (224) (a) R=H (225) (221) x=s (b) R = C02Me (222) x = so (223) X=SOz The equilibrium between 1-tosylazepines (224) and the corresponding benzene N-tosylimines (225) has been investigated by "C and 'H n.m.r. spectroscopy. Although the signals from the imine (225a) were not directly observed line- broadening phenomena of the azepine bands revealed its presence (ca.l0/o) and gave AG' ca. 46 kJ mol-' for the activation barrier. The imine (225b) was more abundant at equilibrium (ca. 10% at -70 "C,in [2H6]-acetone).195 A full paper has appeared on Becker and Gustafsson's work on the action of amines on the 'spiro-benzoxete' oxidation dimers of 2,4-di-t-alkylphenol~.'9~The azepinone product (226) is rapidly oxidized (NaBi03) to the tricyclic compound (227); this forms a tetracyclic photo-isomer which can be oxidized to the spiro-benzofuranone (228).19' Some further work has been reported on the interesting rearrangement of 3,4-diazanorcaradienes to 6H-1,4-diazepines which was mentioned in these Reports last year,I9* and some ambiguities in the details of the various steps have been ~1arified.l~~ Details of the preparation of 1H-and 3H-1,2- benzodiazepines have been published.200 & Me But/ \ \ OH / -B u ' I Bu' o I -6 But IBu' --+ B ~ Bu' ' ~ L 00 ~ Bu' (226) (227) (228) / (230) R=Li (234) (231) R=H (233) R =Me Ph (232) R=Me 19' H.Prinzbach H. Babsch H. Fritz and P. Hug Tetrahedron Letters 1977 1355. '% cf Ann. Reports (B) 1976,73,271. The dimers have recently been shown to possess oxepino[2,3-6]-benzofuran structures H. Meier H. P. Schneider A. Ricker and P. B. Hitchcock Angew. Chem. Internat. Edn. 1978,17 121. o~ 19' 19' H. D. Becker and K. Gustafsson J. Org. Chem. 1977,42,2966. Ann. Reports (B).1976,73 271. 199 G. Reissenweber and J. Sauer Tetrahedron Letters 1977 4389; H. D. Fuhlhuber and J. Sauer ibid. 1977,4393.2oo T. Tsuchiya J. Kurita and V. Snieckus,J. Org. Chem. 1977,42 1856; cfi Ann. Reports (B),1974,71 354. 280 A. J.Boulton A neat procedure for preparing the dizenzo[ f,h][ 1,5]diazonine system is repor- ted,201 in the base-promoted cleavage of a transannular bond in the dihydro- pyrazole derivative (229). The lithium salt (230) can be protonated and alkylated to give the neutral species (23 1) and (232). 1,8-DiIithionaphthalene on reaction with dichlorostannanes gave the peri-naphtho-fused distannocins (233). X-ray crystallography showed the central ring to be strongly distorted from planarity but the molecule (233; R = Me) was con- formationally mobile down to -100 “C the methyl protons appeared as a singlet in the n.m.r. spectrum. The oxadistannepin (234) was also prepared.202 The dimerization of 3-( 1-imidazolyl and 1-benzimidazolyl)quinolines,by e.g.metalation (PriNLi) followed by oxidation yields e.g. interesting fused diazocines (235).203 Other ring assemblies of note include the circulenes and helicenes pro- duced by oligomerization by acid of quinones which have been studied by X-ray crystallography. The ‘closed tetramer’ (236) was found to be planar.2o4 The pre- paration of the ‘phenanthrolinophane’ (237)205 parallels that of the corresponding hexa-aza compound (238) reported earlier.206 (237) X=CH (238) X=N A method for the repetitive ring-expansion of cyclic allylsulphonium allylides is described from two laborat~ries.~~’*~~~ For example (Scheme 7) 2-vinyltetra- s? P+ Scheme 7 201 D.G. Farnum and K. Rasheed J. Org. Chem. 1977 42 573. The ring system (230) is incorrectly named and numbered in this paper. ’02 J. Meinwald S. Knapp. and T. Tatsuoka Tetrahedron Letters 1977 2247. 203 T. Kaufmann D. Tigler and A. Woltermann Tetrahedron Lett& 1977 741. 204 J. E. Bug H. Erdtman H. E. Hogberg B. Karlsson A. M. Pilotti and A. C. Soderholm Tetrahedron Letters 1977 1831. 205 S. Ogawa J.C.S. Perkin I 1977 214. 206 S. Ogawa T. Yamaguchi and N. Gotoh J.C.S.Perkin I 1974,976. *07 R. Schmid and H. Schmid Helv. Chim. Acta 1977,60 1361. 208 E. Vedejs M. J. Mullins J. M. Renga and S. P. Singer Tetrahedron Letters 1978 519. Heterocyclic Chemistry hydrothiophen can be converted into a 2-vinylthiocin (239)’and the process could be repeated to produce 11- 14- and 17-membered monothia-cycloalkenes.Although 1,4-diazabicyclo[ 2,2,2]octane is a well-known compound its homolo- gues with bridges of other lengths are difficult to obtain. Alder et aL209have now described a procedure starting from bridged hydrazines which promises to be quite versatile. The formation of 1,4-diazabicyclo[3,3,3]undecane(240) is shown in Scheme 8. (240) Scheme 8 Polydentate ligands containing oxygen nitrogen and sulphur are an active area of research and the preliminary notes of previous years are being followed by detailed papers. Cram’s series of six2l0 are particularly noteworthy as are Stod- dart’s reports on chiral crown ethers211 and on macro-bicyclic polyethers with bridgehead carbon atoms,212 in which the question of ‘in-out’ isomerism is dis- cussed.An ‘in-out -out-in’ isomerization process has been observed in this type of compound the chiral ‘cryptand’ (241) shows two bridgehead carbon signals at -70 “C,but only one at +112 OC and the achiral homologue (242) also isomerized apparently much more rapidly.’13 (241) n=l (242) n= 2 Ari octa-aza cage compound (243) (for which the trivial name ‘sepulchrate’ was coined in keeping with the somewhat morbid nomenclature for this type of compound) has been assembled by reaction of the tris(ethylenediamine)cobalt(IIi) ion with formaldehyde and ammonia.214 The nitrogen atoms in the bridges preserve their (chiral) octahedral arrangement about the metal atom disinterment of which was not accomplished.’09 R. W. Alder R. B. Sessions J. M. Mellor and M. F. Rawlins J.C.S. Chem. Comm. 1977 747. Part 6 R. C. Helgeson T. L. Tarnowski J. M. Timko,and D. J. Cram J. Amer. Chem. Soc. 1977,99 6411. 211 I. J. Burden A. C. Coxon J. F. Stoddart and C. M. Wheatley J.C.S. Perkin I 1977,220;W.D.Curtis D. A. Laidler J. F. Stoddart and G. H. Jones ibid. p. 1756. ’12 A. C. Coxon and J. F. Stoddart J.C.S. Perkin I 1977 767. ’13 B. H. Gregory A. H. Haines and P. Karntiang J.C.S. Chem. Comm. 1977 918. I. 1. Creaser J. M. Harrowfield A. J. Herlt A. M. Sargeson J. Springborg R. J. Geue and M. R. Snow,J. Amer. Chem. SOC.,1977,99,3181. 282 A. J. Boulton 8 Reviews A two-volume monograph on heterocyclic stereochemistry has been p~blished.~~’ Other aspects of general heterocyclic chemistry which have been reviewed include (2+ 2)-cycloaddition and cycloreversion reactions,216 reactions involving cyclo- elimination of nitr~gen,~” the thermochemistry of the alkylation of tautomeric the gas-phase thermal and photochemical decomposition of heterocycles containing 0 N or S,219 and the rearrangements of N-oxides.220 Macrocycles containing ‘sub heterocyclic rings’ -he terocyclophanes for the most part -have been Among reviews of specific ring systems or groups of systems are two of particular interest to phosphorus chemists ‘Compounds of Two-co-ordinated Phosphorus’222 include the A 3-phosphorins and the diaza- and triaza-phospholes and ‘Polycyclic Carbon-Phosphorus encompass a wide variety of structural types.Other topics reviewed are pyrrolodiazines with bridgehead nitrogen,224 6,8-dioxabicyclo[3,2 llo~tanes,~~~ boraheterocycle~,~~~ the heterocyclic analogues of prostaglandin^,^^^ thiiranium and thiirenium ions,228 tetrazole~,~~~ tellurophenes 230 thieno~yridines,~~~ isoxa~olidines,~~~ and oxazolone~,~~~ 1,2-and dioxetan~,~~~the mesomeric betaine derivatives of heteropentalene~.~~’ Reviews on the electrocyclic ring-opening reactions of ethylene the action of hydroxylamines and hydrazines on y-pyrone derivatives,237 and the photochemistry of 2H-azirine~~~~ deal with special aspects of specific heterocyclic rings. A monograph devoted to pyrroles has appeared.239 Chemical Society pub- lications of particular heterocyclic interest include the regular specialist reports on ’15 W.L. F. Armarego ‘Stereochemistry of Heterocyclic Compounds’ Parts I and XI Wiley-Interscience New York 1977. ’I6 D. N. Reinhoudt Ado. Heterocyclic Chem. 1977 21 253. ’17 H. Meier and K. P. Zeller Angew. Chem. Internat. Edn. 1977 16 835. ’18 P. Beak Accounts Chem. Research 1977,10 186. 219 S. Braslavsky and J. Heicklen Chem. Rev. 1977 77 473. 220 S. Oae and K. Ogino Heterocycles 1977,6 583. ’” G. R. Newkome J. D. Sauer J. M. Roper and D. C. Hager Chem. Rev. 1977,77,513. 222 N. I. Shvetsov-Shilovskii R. G. Bobkova N. P. Ignatova and N. N. Mel’nikov Uspekhi Khim. 1977 46 967; Russ. Chem. Rev. 1977,46 514. 223 S. D. Venkataramu G. D. MacDonell W. R. Purdum M.El-Deek and K.D. Berlin Chem. Rev. 1977,77 121.224 D. E. Kuhla and J. G. Lombardino Adv. Heterocyclic Chem. 1977,21 1. 225 H. C. Brown and E. Negishi Tetrahedron,1977 33 2331. 226 P. P. Mundy K. B. Lipkowitz and G. W. Dirks Heterocycles,1977,6 51. 227 E. I. Levkoeva and L. N. Yakhontov Uspekhi Khirn. 1977,46 1074; Russ. Chem. Rev. 1977,46 565. 228 G. H. Schmid in ‘Topics in Sulfur Chemistry’ ed. A. Senning and P.S. Magee Thieme Stuttgart 1977 vol. 3. 229 R. N. Butler Adv. Heterocyclic Chem. 1977 21 223. 230 F. Fringuelli G. Marino and A. Taticchi Adv. Heterocyclic Chem. 1977 21 119. 231 J. M. Barker Adv. Heterocyclic Chem. 1977 21 65. 232 R. Filler and Y. S. Rao Adv. Heterocyclic Chern. 1977 21 175. 233 Y. Takeuchi and F. Furusaki Adv. Heterocyclic Chem. 1977,21,207. 234 W. Adam Adv.Heterocyclic Chem. 1977 21,437. 235 C. A. Ramsden Tetrahedron,1977,33 3203. 236 R. Huisgen Angew. Chem. Internat. Edn. 1977 16 572. 237 C. Morin and R. Beugelmans Tetrahedron,1977,33,3183. 238 P. Gilgen H. Heimgartner H. Schmid and H. J. Hansen Heterocycles,1977 6 143. 239 R. A. Jones and G. P.Bean ‘The Chemistry of Pyrroles’ (Organic Chemistry monographs) Academic Press Inc. London 1977 vol. 34. Heterocyclic Chemistry 283 aromatic and Group VI and a volume on the 0-lactam which should prove extremely valuable to the many active research workers in this field. ‘The Alkaloids’ ed. M. F. Grundon (Specialist Periodical Reports)The Chemical Society London 1977 vol. 7. 241 6 Aromatic and Heteroaromatic Chemistry’ ed. C. W. Bird and G.W. H. Cheeseman (Specialist Periodical Reports) The Chemical Society London 1977,vol. 5. 242 ‘Organic Compounds of Sulphur Selenium and Tellurium’ ed. D. R. Hogg. (Specialist Periodical Reports) The Chemical Society London 1977,vol. 4. 243 ‘Recent Advances in the Chemistry of 0-Lactam Antibiotics’ ed. J. Elks (Special Publication no. 28) The Chemical Society London 1977.

ISSN:0069-3030    

DOI:10.1039/OC9777400251

出版商:RSC    

年代:1977

数据来源: RSC

摘要:

12 Alicyclic Chemistry By A. COX Department of Chemistry and Molecular Sciences University of Warwick Coventry CV4 7AL 1 Introduction This year has seen the publication of a further volume of 'Organic Syntheses" and a survey of the 1975 literature on mechanisms has appeared.2 Reviews have been published on the chemistry of rings of various sizes,3 intramolecular [4+2] and [3 +21 cycl~additions,~ pericyclic ~ynthesis,~ the Robinson Annelation6 and strained organic rnolec~les.~ Finally further work is reported on the rules for ring closure' and a new mechanistic criterion has appeared for early and late transition ~tates.~ 2 Synthesis Three-and Four-membered Rings.-A high-yield route to cyclopropyl and cyclo- propenyl ethers has appeared" which involves trapping of an alkoxycarbenoid as the key step.For example treatment of a mixture of EtOCH2CI and cyclohexene with lithium 2,2,6$-tetramethylpiperidine (LiTMP) leads to 7-ethoxynorcarane (55%). In a related paper an improved synthesis of cyclopropanols is reported." Use is again made of LiTMP to generate simple alkoxycarbenoids which are then allowed to react with an alkene but in this case they are formed by a-elimination of HCI from P-chloroethyl ethers. The product ethers are subsequently cleaved using n-butyl-lithium; use of acyloxycarbenes generated similarly is also reported. l2 A method has been de~cribed'~ for the conversion of @-unsaturated aldehydes and esters into cyclopropanes. The transformation (Scheme 1)involves conversion of the carbonyl oxygen into a leaving group while the /3-carbon is rendered nucleo- philic by Birch reduction of the thiophenyl moiety.A communication describing an 'Organic Syntheses' ed. G. H. Biichi Wiley New York 1977 Vol. 56. 'Organic Reaction Mechanisms' ed. A. R. Butler and M. J. Perkins Interscience London 1977. 'Alicyclic Chemistry' ed. W. Parker (Specialist Periodical Reports) The Chemical Society London 1977 Vol. 5. W. Oppolzer Angew. Chem. Internat. Edn. 1977,16 10. A. G. Anastassiou Accounts Chem. Res. 1976 9,453. R.E. Gawley Synthesis 1976 777. ' J. F. Liebman and A. Greenberg Chem. Rev. 1976.74 311. J. E. Baldwin and L. I. Kruse J.C.S. Chem. Comm. 1977,233. R. Huisgen and R. Schug J. Amer. Chem. Soc. 1976,98,7819. lo R. A. Olofson K.D. Lotts and G. N. Barber Tetrahedron Letters 1976 3779. G. N. Barber and R. A Olofson Tetrahedron Letters 1976 3783. l2 R. A. Olofson K. D. Lotts and G. N. Barber Tetrahedron Letters 1976 3381. l3 Y.-H. Chang D. E. Campbell and H. W. Pinnick Tetrahedron Letters 1977 3337. 285 286 A. Cox Reagents i PhSH-Na; ii LiAIH4; iii MeSOzCI-py; iv Li-NH3 Scheme 1 efficient and operationally straightforward route to divinylcyclopropanes has appeared.14 Conversion of trans -1-bromo-2-vinylcyclopropane into trans-lithio- vinylcyclopropane is accomplished using t-butyl-lithium in ether-pentane at -78 "C and following addition of 3-ethoxy-2-methylcyclopent-2-enoneand subsequent hydrolysis (Scheme 2) the trans-divinylcylopropane product can be isolated in high yield.Scheme 2 The generation and trapping of the interesting hydrocarbon methylene- cyclopropane has been reported (Scheme 3).15 Reaction of (1) with Bu'OK in Reagents i Bu'OK-MeS-; ii H202-MeC02H; iii Bu'OK-Me2SO Scheme 3 Me2S0 in the presence of MeS- yields (2) together with the sulphide (3). Oxidation of (3) gives (4) which with Bu'OK leads to (2) as the only volatile product Since l4 P. A. Wender and M. P. Filosa J. Ore. Chem. 1976,41 3490. l5 W. E. Billups A. J. Blakeney and W. T.Chamberlain J. Org. Chem. 1976 41 3771. Alic yclic Chemistry sulphones are well known to give alkenes via p-elimination this provides compel- ling evidence for the intermediacy of methylenecyclopropane. Also reported16 is the synthesis of methylenecyclopropenes lacking a stabilizing polar substituent on the exocyclic double bond (Scheme 4).It has been found that treatment of (5) with (5) R' =Hor But (6) R2= But or H Scheme 4 Bu'OK in dry THF at low temperatures leads to (6) a structure observed to be extremely reactive towards water. A synthesis of four-membered rings has appeared" which allows cyclobutane cyclobutene and cyclobutanone to be generated from both saturated and @-unsaturated aldehydes and ketones triu the intermediacy of the adducts of 1-1ithiocyclopropyl phenyl sulphide to the carbonyl partner. In another communication further syntheses of cyclobutanones poten- tially useful in the terpene field are reported." The reaction involves acid rear- rangement of a variety of alcohols having the 1-oxycyclopropyl structure and prepared from CY -alkoxy-@-unsaturated ketones and esters by way of reduction followed by Simmons-Smith reaction of the resultant (Y -alkoxyallyl alcohols.Five- and Six-membered Rings.-A new synthesis of five-membered rings accord- ing to a (C3+Cz) pattern has been anno~nced'~ and provides a unique route to derivatives having the functionality shown in two readily executed steps (Scheme 5). Slow addition of solutions of the lithium enolates of the ketones (7) to a solution R2 K-R'. 'f R2 (9) Scheme 5 l6 W. E. Billups and A. J. Blakeney J. Amer. Chem. SOC.,1976,98,7817. l7 B. M.Trost D. E. Keeley H. C. Arndt and M. J. Bogdanowicz J. Amer. Chem. Soc. 1977,99,3088. E.Wenkert N.F. Golob R.P.Hatch D. Wenkert and R. Pellicciari HeZu. aim. Am 1977,60,1. l9 D.Seebach M.S.Hoekstra and G. Protschuk Angew. Chem. Internut. Edn. 1977,16,321. 288 A. Cox of P-nitropropionyl chloride in THF at -80 "C furnishes the diketone (8). Cycliza-tion can be effected by a buffer solution of pH 8.5 to give hydroxycyclopentenone which rearranged to (9) on prolonged treatment. In another method based on the (C,+C,) pattern and one of considerable generality the very highly reactive dimethoxytetrachlorocyclopentadiene is heated in the presence of olefins.20 This leads to the Diels-Alder adducts which on reaction with sodium in liquid ammonia- ethanol removes all the chlorine atoms. Oxidation of the norbornene-type double bond is accomplished using potassium permanganate in a pH 7 buffer system (Na2HP04,-KH2P04) with t-butyl alcohol as co-solvent.Yields of between 22 and 40% overall have been achieved for the four steps involved. The construction of five-membered rings of potential use in prostaglandin synthesis continues to attract interest and one such example is a newly reported21 ene route to 3-hydroxy- cyclopentanone derivatives. The vinylogous aldol (lo) protected as its t-butyl- dimethylsilyl derivative is submitted to the kinetic aldol reaction with propynal to give (1 1). Reaction of (11) with trimethylsilyl cyanide promotes cyanohydrin formation and simultaneously protects the two free hydroxyls as their trimethylsilyl ethers. By heating in toluene at 250°C thermal cyclization of (12) is readily effected giving (13) (Scheme 6).An interesting report has appeared22 of the H OH I OH application in 11-deoxyprostaglandin El synthesis of thiophenol behaving as a nucleophile in stereospecific ring-opening reactions. The key transformation involves treatment of methyl exo-6-(trans-hept-l-enyl)-2-oxobicyclo[3,1,0] hexane-1-carboxylate (14)with potassium thiophenolate in Bu'OH at room temperature to produce the 2,3-disubstituted cyclopentanone (Scheme 7) in 89% 2o M. E. Jung and J. P. Hudspeth J. Amer. Chem. SOC.,1977,99,5508. 21 G. Stork and G. Kraus J. Amer. Chem. SOC.,1976,98,6747. 22 K. Kondo T. Umemoto Y. Takahatake and D. Tunemoto Tetrahedron Letters 1977 113. Alicyclic Chemistry Scheme 7 yield. The desired 11-deoxyprostaglandin El was then reached in four steps by standard means.A synthesis of PGA2 using the same procedure has also been reported.23 The reaction between some cyclic olefins (C5-Cs inclusive) and diethyl(methy1)silane and CO in the presence of CO~(CO)~ has been In the particular case of cyclopentene a 48% yield of the enol silyl ether of cyclo-hexanone has been achieved and much better yields are reported for the higher homologues. The reaction affords direct access to enol silyl ethers from olefins. A report has appeared2’ of the preparation of a versatile new diene 2-methoxy-3- phenylthiobutadiene which can serve as an annelating agent to introduce a masked @-ketosulphide moiety as an integral part of an annelation; this masking allows structural modification elsewhere.A second point of importance is that the regio- chemistry complements that normally obtained with 2-oxygenated dienes and the ease with which sulphur can be removed from organic molecules suggests this as a possible general approach to reversing the normal orientation of Diels-Alder reactions studied. However although this diene reacts highly successfully with maleic anhydride at room temperature yields of adducts derived from the easily polymerizable methacrylyl dienophiles are low. An investigation of the iodocy- clization of homologous dienes reveals2’ that in the case of hepta-l,&diene introduction of dialkyl substitutents at the 4-position completely changes the reaction path from that of addition to cyclization (Scheme 8).The scope of the iodocyclization of several other dienes has also been investigated. Scheme 8 Seven- and Eight-membered Rings.-A description has been given2* for the con-struction of functionalized cycloheptadienes which is based on the use of 2-vinyl-cyclopropylcopper reagents. For example treatment of the homocuprate (1 5) with 23 D. F. Taber J. Amer. Chem. SOC.,1977,99 3513. 24 Y.Seki A. Hidaka S. Murai and N. Sonoda Angew. Chem. Internat. Edn. 1977.16 174. 25 B. M. Trost and A. J. Bridges J. Amer. Chem. SOC.,1976,98 5017. 2b S. Danishefsky C. F. Yan and P. M. McCurry jun. J. Org. Chem. 1977,42 1819. 27 H. J. Giinther V. Jager and P. S. Skell Tetrahedron Letters 1977 2539. J. P. Marino and L. J. Browne Tetrahedron Letters 1976 3245. 290 A.Cox methyl propiolate at -78 "C gives the trans-divinylcyclopropene(16) (80%) and the rearranged cycloheptadiene (17) (15%) as shown in Scheme 9. Subsequent rearrangement of (16) at 140"C yields (17) quantitatively. A new general route29 to 3-substituted cyclohepta-l,4-dienes involves [4 +21 cycloaddition of the appro-priate 7-substituted cycloheptatriene to 4-phenyl-172,4-triazoline-3,5-dione. CHC0,Me CuLi HCEECCO~M~ d -78 "C d+ (15) (16) ""'"-o // (16) Scheme 9 Following catalytic reduction basic hydrolysis of the heterocyclic ring of these products and Cu2' oxidation of the resulting hydrazo-compounds nitrogen is readily lost to give 3-substituted cyclohepta-1,4-dienes. An improved one-step method for preparing trans-cyclo-octene has been pub-lished3' involving direct photoisomerization of the cis-isomer in pentane.The practical procedure consists of direct irradiation at 185 nm of the 0.12or 0.6 molar solution of cis-cyclo-octene and subsequent extraction of the product with aqueous silver nitrate. The same authors also report3' a detailed investigation of the direct and sensitized cis-trans photoisomerizations of cyclo-octene in the liquid phase along with photosensitization in the vapour phase. A discussion is presented of the effects of spin multiplicity and vibrationa1 activation of the excited states on the photostationary state and potential curves accounting for the results are proposed. A convenient synthesis of some substituted cis,trans-cyclo-octadienes (18) has been which can be either isolated or trapped depending on their reactivity.R' R' R2 (18) R' = C02Me R2=H R' =CN R~= H R' =R2 = C02Me Annu1enes.-The first report has appeared of the 175-methano[lolannulene (bicy-clo[5,3,l]undeca-1,3,5,7,9-pentaene)system" and several of its derivative^.^^ The 29 I. Pikulik and R. F. Childs Canad. J. Chem. 1977 55 251. 30 Y. Inoue S. Takamuku and H. Sakurai Synthesis 1977 111. 31 Y. Inoue S. Takamuku and H. Sakurai J. Phys. Chem. 1977,81,7. 32 H. D. Martin M. Hekman G. Rist H. Sauter and D. BelluH Angew. Chem. Internat. Edn. 1977 16 406. 33 S. Masarnune and D. W. Brooks Tetrahedron Letters 1977 3239. 34 S. Masamune D. W. Brooks K. Morio and R. L. Sobczak J. Amer. Chem. SOC.,1976,98 8277. Alicyclic Chemistry 291 13 C n.m.r.spectrum of (19 R'=R2= H) exhibits only seven signals even at -80 "C and the molecule therefore possesses two-fold symmetry. Induction of a diamag- netic ring current in this monocyclic 10welectron system is suggested by the high-field H signals due to the C-11 protons and the appearance of signals in the aromatic region. In contrast to the 1,6-methano counterpart the U.V. spectrum of R' (19) (19) extends deeply into the visible region. Sondheimer has described3' a new and improved synthesis of derivatives of [14]annuleno[ 14]annulene [14lannu-leno[ 16]annulene and [14]annuleno[ 18lannulene. These vinylogues of naphthalene are the first examples of bicyclic compounds consisting of two fused macrocyclic conjugated v-systems and the effect of one ring upon another has been investigated by 'H n.m.r.spectroscopy. The synthesis and properties of a third example of a fused non-benzenoid aromatic hydrocarbon (20),incorporating two 14~-electron systems has been reported.36 Analysis of the 100MHz 'H n.m.r. spectrum reveals that (20) is strongly diatropic showing the inner proton signals at S -2.85 and those of the outer protons at S 10.16. The electronic spectrum of (20) shows a considerable hypsochromic shift as compared with that of 3,11,14,22-tetra-t-butyl-l,12-bisdehydro[22]annulene. Both of these observations suggest that the bicyclic annulene (20) is a higher analogue of napthalene and may be represented by the delocalized formula (21). The synthesis of the tosylhydrazone sodium salt (22) (20) (21) has been and pyrolysis of the salt in refluxing diglyme gives contrary to anticipation not the [4,4,2]propellane (24) via a carbene+arbene rearrangement but rather only products believed to originate from carbene (or allene) dimers.The probable intermediates (23) are thought to lose hydrogen spontaneously to give the unsaturated hydrocarbon (25) with the double bonds localized as shown in Scheme 10. Polycyclic Systems.-A new reversible formation of bicyclobutanes involving a 1,3-bismethylenecyclobutanehas been described.38 Specifically solutions of (26) in ethanolic lithium perchlorate react rapidly with iodine to give the bicyclobutanes 35 T. M. Cresp and F. Sondheimer J. Amer. Chem. SOC.,1977,99 194. 36 S.Akiyama M. Iyoda and M. Nakagawa J. Amer. Chem. SOC.,1976,98,6410. 37 U. H. Brinker R. W. King and W. M. Jones,J. Arner. Chem. SOC.,1977,99,3175. 38 M. Horner and S. Hiinig J. Amer. Chem. Soc.,1977,99. 6120. 292 A. Cox N-N-Ts (23) syn +anti (25) syn +anti 1 I Scheme 10 (27) in high yield (Scheme 11). It is also observed that the bridging bond in (27) is readily cleaved by reduction e.g. Na-Hg in acetonitrile to regenerate the original (26) R' = H R2 =Me R' = H R2= PhCH2 ~1~ R~= M~ R' =Me R2 = PhCH2 Scheme 11 1,3-bismethylenecyclobutanes.Evidence has been made available3' testifying to the fleeting existence of bicycle[ 1,l,O]but-1(3)-ene a compound suggested by calculations to exist on a local minimum on the C4H4potential energy hypersur- face.It has been observed that reaction of (28) with n-butyl-lithium leads to an 87% yield of l-n-butyltricyclo[4 1,0,02*']heptane in a very rapid reaction. Of the three mechanistic possibilities considered for this conversion elimination of hydrogen chloride from (28) by the organometallic reagent with the formation of a bicyclo[1,l,O]but-l(3)-ene derivative and addition of the organolithium compound to the strained double bond is considered the most likely. The first member has been reported4' of a class of hitherto unknown fused bicylic trans-cycloalkenes in which two rings share a common double bond. This class of chiral olefin is 39 G. Szeimies J. Harnisch and 0.Baumgartel J. Amer. Chern. SOC.,1977,99 5183.40 J. A.Marshall and M. Lewellyn J. Amer. Chem. SOC.,1977 99 3508. Alicyclic Chemistry designated [a,b]betweenanenes (29) and the one reported is [ 10,lolbetweenanene (30). No report is available of the chemical and physical properties which could be bcl L (28) (29) (30) unusual as a consequence of the buried nature of the double bond. Semibenzilic acid ring contraction of 6-halogenotricyclo[3,2,1 ,03*6]octan-7-one (3 1) has been observed to give4' tricyclo[3,1,1 ,03.6]heptane-6-carboxylicacid (32) a compound 0 R (31) X=C1 or Br (32) R=C02H containing a new ring system characterized by three cyclobutane rings fused to a common carbon atom. The structure of this acid was determined unequivocalIy by examination of the 'H and 13Cn.m.r.spectra of the corresponding methyl ester. Studies are reported 42 of the synthesis of the novel bridgehead olefin tri- cyc10[3,3,3,0~.~] undec-2(6)-ene (33). In Wiseman's analysis of bridgehead olefins this compound may be viewed as a bisethano-derivative of trans-cycloheptene and although the olefin carbons in such molecules may be somewhat pyramidalized overlap between the atomic orbitals forming the rr-part of the double bond is principally diminished by torsion. Although (33) has not been isolated decom- position of (34) in refluxing triethyl phosphite containing diphenylisobenzofuran as trapping agent gives the Diels-Alder adduct of (33) in 85% isolated yield Detailed 'S (33) (34) reactivity studies are reported43 of substrates which can serve as precursors to the 'anchored' trishomoaromatic ions (35)-(37).Particular reference is made to gain- ing access to (35) and a number of remarkable interconversions on the (CH), energy surface are described. For example reduction of tri-cyclo[5,4,1 ,04v'2]dodeca-2,5,8 10-tetraene (38) using potassium metal in ammonia gives a mixture of four hydrocarbons of which the major product (39) has been '' S. A. Monti and J. M. Harless J. Amer. Chem. SOC.,1977,99 2690. 42 R.Greenhouse T. Ravindranathan and W. T. Borden J. Amer. Chem Soc. 1976,98,6738. 43 L. A. Paquette M. J. Kukla S. V. Ley and S. G. Traynor J. Amer. Chem. Soc.,1977,99,4756. 294 A. Cox defined spectroscopically. On the basis of these measurements it is not possible to distinguish between direct two-electron reduction of (38) to dianion (35) or a stepwise reduction sequence mediated by a radical anion.In a related paper,44 consideration is given to (37). However all attempts to deprotonate nortriquinacene (40) failed and this lack of acidity is interpreted to mean that the (38) (39) (40) transition state for ex0 -hydrogen abstraction does not experience significant stabil- izing interaction with the proximate double bonds. Metal-reduction studies also failed to provide evidence for formation of a stabilized carbanion. Further studies are reported4’ on attempts to synthesize dodecahedrane (41) and of the successful synthesis of the pentasecododecahedrane derivative (42) the most highly conden- sed precursor of (41) known.Elaboration of dodecahedrane from (42) appears to require development of a dehydrative retro-Baeyer-Villiger sequence which will not trigger transannular reactions and ultimate closure by threefold C-C bond formation. The first synthesis of two vinylidenedicyclopropanesdoubly halogenated in their allylic positions has been together with their intramolecular coupling to give the dispiroheptanes (43) and (44). By cyclopropanation using the Simmons- Smith reagent (43) can be quantitatively transformed into [3]rotane and the higher rotanes (45) can all be prepared by way of (44). In an accompanying paper4’ (45) n =4,5 or 6 4.1 L. A. Paquette H. C. Berk C. R. Degenhardt and G. D. Ewing J. Amer. Chem SOC.,1977,99,4764. *’ L. A. Paquette M.J. Wyvratt 0.Schallner D. F. Schneider W. J. Begley and R. M. Blankenship J. Amer. Chem. SOC.,1976,98,6744. 46 L. Fitjer Angew. Chem. Internat. Edn. 1976 15 762. 47 L. Fitjer Angew. Chem. Internat. Edn. 1976.15 763. Alicyclic Chemistry 295 by the same author a method permitting synthesis of each of the higher rotanes (45) is reported which is based upon a closed homologation sequence and which can in principle be repeated without limit. 3 Stereochemistry The 'Hn.m.r. spectrum of a solution of phenylcyclopropane has been in a CS2 solution and the spin-spin coupling constant between the para-proton of the phenyl group and the a!-proton in the cyclopropyl moiety found to be -0.23 f 0.02Hz. The authors conclude that this indicates a two-fold barrier to internal rotation of 8.4 f1.3kJ mol-' and implies that the low-energy conformation is such that the C-H bond prefers the plane of the phenyl group.This result is consistent with other theoretical and experimental data. Silver-ion assisted methanolysis of the epimeric tricyclic derivatives (46) and (47) has been studied4' in an attempt to provide insight into the stereochemistry of the cyclopropyl cation predicted by calculation to be planar. The results suggest that a planar encumbered ion is not formed and also exclude extensive participation of unsaturation in the transition state during the solvolysis of (47). A study of the effect of increasing pressure on (46) (47) the ring inversion of cyclohexane reports" that pressure rises promote an increase in inversion rate.In qualitative terms this can be explained by assuming that the twist or boat conformations adopted by the molecule during ring inversion have slightly smaller molar volumes than the energetically more favourable chair forms. Results are reported51 of ab initio calculations involving cis- 1,4-di-t-butylcyclo- hexane made in an attempt to decide whether a chair or boat form of this molecule is the more stable. By employing standard single-determinant molecular orbital theory on the STO-3G minimal basis set level the total energies have been calculated and a boat emerges as the most stable conformer. Similar calculations show that in trans- 1,2-di-t-butylcyclohexane both the diaxial chair and diaxial boat are of importance in its ground state.SCF-INDO-FPT calculations have been performed for various geometries of the flat cyclohexa-1,4-diene molecule and the values of 'Jcis/'JR,,,s found'* to remain within the relatively narrow range 1.22- 1.29 Hz. This result is claimed to preclude the need to postulate a rapidly inverting cyclohexa-174-diene ring. Similar on [2,3,4,5,6-2H5,carboxy-'3C]-1,4-dihydrobenzoic acid (48) [2,3,4,5,6,7,8-2H7,carboxy-'3C]-1,4-dihydro-1-48 W. J. E. Parr and T. Schaefer J. Amer. Chem. SOC.,1977,99 1033. 49 D. B. Ledlie W. Barber and F. Switzer Tetrahedron Letters 1977 607. H.-D. Liidemann R. Rauchschwalbe and E. Lang Angew. Chem. Internat. Edn. 1977,16,331. M. Askari D. L. Merrifield and L. Schafer Tetrahedron Letters 1976 3497. 52 P.W. Rabideau J. W. Paschal and J. L. Marshall J.C.S. Perkin ZI 1977 842. 53 J. L. Marshall L. G. Faehl C. R. McDaniel jun. and N. D. Ledford I. Amer. Chem. SOC.,1977 99 321. 296 A. Cox naphthoic acid (49) and [carboxy-13C]-9 10-dihydro-9-anthroic acid (50) show that the ratio Jcq-eq/Jax-eq(for JHH)decreases and the ratio Jax,.ax/Jax-eq (for J,,) increases in the series (48)-(50) indicating that the puckering in (49) is inter-mediate between that of (48) and (50). This leads to the identification of three DmD D D D \ D \ / H' 'D D H' 'D HH (48) (49) (50) categories 'flat' 'flattened boat' and 'true boat'. The results of calculations based on a potential function derived using vibrational datas4 to determine conformations of cycloheptane oxepan and 1,3-dioxepan are compareds5 with n.m.r.results and with rotational Raman spectra. This leads to a consistent picture of the seven- membered rings with twist-chairs as the lowest-energy conformations. The con- formation of 1-dimethylphosphono-1 -hydroxycycloheptane has been determined56 in the solid state by X-ray analysis and it has been found that both the twist-chair and chair conformers occur in the crystal structure. The relative abundances as determined by a refinement of occupancy factor are 0.93 and 0.07. Values of energy barriers associated with conformational ring inversion processes occurring in certain trans -cycloalkenes have been by analysis of their tempera- ture-dependent 13Cn.m.r. spectra. In cis trans-cyclo-octa- 1,5-diene (5 1) and the derived compounds (52) these barriers are estimated to be 146.4 173.6 188.3 (51) (52) X =0,CH2,or NPh and 186.2 kJ mol-' respectively.An investigation of the 251 MHz'H and 63.1 MHzI3C n.m.r. of cis cis-cyclonona-l,5-diene extending over the tempera- ture range -5 to -170 "C has been carried outs8 and the data interpreted in terms of a pair of chiral chair-like conformations with C2symmetry. A I3C n.m.r. study has been reported5' in which the thermodynamic parameters for equilibration of the chair-chair conformational enantimorphs of cis-10-methyldecalin-9-01 and cis-10-methyldecal-1-one have been determined. N.m.r. spectroscopy has also been used to determine the conformational preferences of a number of mobile ring systems including a series of 9-R-9,lO-dihydrophenanthrenes(R =Me CN But COMe C02Me C02Et OH or SiMe3) as well as two related 5,6-dihydro- chrysenes with special regard to the location of substituents in pseudoaxial or " D.F. Bocian and H. L. Strauss J. Amer. Chem. SOC.,1977,99 2866. " D. F. Bocian and H. L. Strauss J. Amer. Chem. SOC.,1977 99 2876. s6 G. I. Birnbaum G. W. Buchanan and F. G. Morin J. Amer. Chem. SOC.,1977 99 6652. 57 S. G. Davies P. F. Newton and G. H. Whitham J.C.S. Perkin 11 1977 1371. 58 F. A. L. Anet and I. Yavari J. Arner. Chem. SOC.,1977,99,6496. 59 J. W. Blunt J. M. Coxon N. B. Lindley and G. A. Lane Austral. J. Chem. 1976 29,967 Alicyclic Chemistry 297 pseudoequatorial positions. With the exception of CN all the substituents are found6' to adopt the pseudoaxial conformation preferentially.Ab initio energies have been reported61 for several minimum-energy conformations using standard single-determinant MO theory with an STO-3G minimal basis set for a number of compounds including trans-decal-2-one lO-methyl-trans-decal-2-one la-methyl-trans-decal-2-one 3a -methyl-trans-decal-2-one and 1,l ,lo-trimethyl- trans -decal-2-one. The calculations predict a significant population of flexible states for the latter two compounds at moderate temperatures. The results of calculations carried out using a 1973 force field on the 25 isomers of dodeca-hydrophenanthrene are presented6* in a report which lists the values of AH; for each conformation together with the values of AH for each compound (con- formational mixture) and the relative entropies.4 Structural Properties and Orbital Interactions In order to account for the fact that substituents on cyclopropane are known to alter the bond lengths in the ring ab initio wavefunctions have been obtained63 for cyclopropane and a number of relevant related molecules. Comparison of orbital composition energies and overlap populations of the parent with substituted molecules has been utilized to ascertain the origin of these substituent and ring- closure effects. The analysis shows that the substituent induced electron with- drawal and charge redistribution in the cyclopropane orbitals so that the adjacent bonds were shortened while the opposite bond was lengthened. Although no cases are known in which simple cyclopropyl cations have been unambiguously demon- strated as intermediates in solvolysis reactions by use of ion cyclotron double- resonance techniques it has been that cyclopropene forms a C3H5+ ion by proton transfer from dimethyloxonium ion.Such experiments suggest that the C3H5+ ion produced has a heat of formation of 996 kJ mol-'. This value is not consistent with the heat of formation of the ally1 cation and suggests that a cyclopropyl cation may have been formed. The surfaces of the ground state and first excited singlet and triplet states for the conversion of cyclopropene into vinylcarbene have been using the MIND0/3 semi-empirical MO method. In general the results appear to be in agreement with the known thermal and photochemical reactivities of cyclopropenes and the results of some ab initio calculations on these species.Generalized valence-bond calculations on cyclo- propene and vinylmethylene have been carried out.66 These predict that (a) the allyl-type .rr-system has a methylene-like triplet but a 1,3-biradical-like singlet state (b) the lowest singlet state of vinylmethylene is of the form of a singlet methylene and (c) the ground state of vinylmethylene should exist in two geometrical forms. These results suggest that the ring opening of cyclopropene proceeds directly to a biradical planar intermediate. The reaction of tri-t-butyl-6o R. G. Harvey P. P. Fu and P. W. Rabideau J. Org. Chem. 1976,41 3722. 61 M. Askari N. S. Ostlund and L. Schafer J. Amer. Chem. SOC.,1977,99 5246.62 H. Honig and N. L. Allinger J. Org. Chem. 1977,42 2330. 63 C. A. Deakyne L. C. Allen and V. W. Laurie J. Amer. Chem. SOC.,1977,99,1343. 64 D. H. Aue W. R. Davidson and M. T. Bowers J. Amer. Chem. SOC.,1976,98,6700. 65 J. A. Pincock and R. J. Boyd Canad. J. Chem. 1977,55 2482. 66 J. H. Davis W. A. Goddard and R.G. Bergman J. Amer. Chem. SOC.,1977,99,2427. 298 A. Cox cyclopropene with photochemically generated t-butoxyl radicals has been moni- t~red~~ using e.s.r. It is found that the magnitude of the 13Ccoupling constants is inconsistent with (53) involving an aromatic .rr-radical and is in agreement with (54) involving equilibrium of energetically equivalent a-radicals. The l-isocyano- R R R R R RboR =RbR eRX R (54) 2,2-diphenylcyclopropyl anion has been found68 to be configurationally stable at -72 "C in contrast to the corresponding 1-cyano-derivative.This stability is not affected by changing the cation from Li to Na to K nor is it affected by change in solvent or by the addition of co-ordinating agents such as crown ethers triglyme or HMPA. A series of 1-methylcyclopropylcarbinyl cations has been prepared and the 'H and 13C n.m.r. spectra inve~tigated~~ under stable-ion conditions. The parent ion has been found to be best represented in terms of a dynamic equilibrium involving significant contributions from both the 1-methylcyclobutyl cation and the set of three equivalent 8-delocalized 1-methylcyclopropyl cations a conclusion supported by ab initio MO calculations at the split-valence-shell 4-3 1G level.Ab initio calculations of the equilibrium structure of cyclobutane have been reported7' in which use is made of a single-determinant restricted Hartree-Fock theory involving an extended basis set of Gaussian orbitals augmented by polariza- tion functions. The molecule is found to be non-planar with a degree of puckering of 0.23 8,and a barrier to planarity of 3.8 kJ mol-'; tilting of the methylene groups proves to be essential for relieving steric strain. Semi-empirical SCFMO cal-culations (CNDO/I CNDO/II and MIND0/3) have been used7' to estimate the contribution of 1,3-carbon-carbon interactions to the strain energy of cyclobutane and perturbation energies are found to lie between 85.4 and 140.2 kJ mol-' depending upon the particular calculation and molecular geometry.The analyses suggest that cognisance of 1,3-carbon*arbon interactions is obligatory in the cyclobutane series. Cyclobutadiene continues to attract interest. The energy rela- tionships between the singlet and triplet states of cyclobutadiene have been dis- cussed'* in terms of MIND0/3 calculation and ab initio 'SCF calculations using the 4-31G basis set; calculations have also been made of molecular vibration frequen- cies. The results support the suggestion that the (CH) species obtained by pho- 6' K. Schriener and A. Berndt Angew. Chem. Internat. Edn. 1976,15 698. "M.P. Periasamy and H. M. Walborsky J. Amer. Chem. Soc.,1977,99,2631. 69 G.A. Olah R. J. Spear P. C. Hiberty and W. J. Hehre J.Amer. Chem. SOC.,1976.98 7470. 'O D. Cremer J. Amer. Chem. SOC.,1977,99 1307. N. L. Bauld and J. Cessac J. Amer. Chem. SOC.,1977,99 942. 72 M. J. S. Dewar and A. Komornicki J. Amer. Chem. SOC.,1977,99 6174. Alicyclic Chemistry tolyses in matrices at low temperatures is a metastable triplet. The fluxional isomerism of cyclobutadiene has been analy~ed~~ at the rr-electronic level in terms of an orbital correspondence analysis in maximum symmetry which shows that the process is allowed under a skew-planar distortion. Analysis of the ground-state eigenvector indicates that the most significant structure is the singlet biradical which is consistent with cycloaddition reactions of 1,3-di-t-butylcyclobutadiene.A full spectral characterization of tetrakis(trifluoromethy1)cyclobutadiene has been The compound has a singlet ground state and if the assignment of the i.r.band at 1700 cm-’ to the C=C stretching vibration proves to be correct then its geometry is not square but rectangular. This study also shows that at low temperature direct irradiation does not lead to the formation of the tetrahedrane system at least as a major course of reaction. In another comm~nication,~~ tri-t-butylcyclobutadiene (59 a molecule for which a rectangular structure is assumed has been shown to undergo reactions typical of a triplet molecule. Thus if (55) prepared by matrix isolation of 2,3,4-tri-t-butylcyclopentadienone,is allowed to react after thawing with an excess of CC14 the product is found to contain no dimer of (55) but exclusively the adduct (56).A possible mechanism for the formation of (56)is shown (Scheme 12). A number of substituted cyclobutadiene dications have Scheme 12 been prepared under stable-ion conditions and st~died’~ by ‘H 19F,and 13Cn.m.r. spectroscopy. The 13C n.m.r. spectra of the phenylated cyclobutadiene dications indicate that the aromatic 277-electron cyclobutenediylium ring interacts mesomerically with phenyl rings and accepts a significant amount of rr-electron density from them. The question as to whether the n.m.r. spectroscopic obser- vations of cyclobutadiene dications correspond to several species in dynamic equil- ibrium or to static non-equilibrating dications has been systematically investigated and unequivocal evidence for the latter presented.The photoelectron spectrum of bicyclo[4,1,1] octa-2,4-diene has been Based upon assignment of the first bands in the spectrum it is concluded that the interaction between the Walsh orbitals of the cyclobutane ring and the olefinic moiety can be described by a resonance integral p = -183 kJ mol-’. The e.s.r. spectra of the radical anions of 1,4-and 1,5-dimethylcyclo-octa- tetraene have been meas~red’~ and it is found that in the former compound the rr-spin density is spread almost equally over the eight ring carbons whereas in the 73 E. A. Halevi F. A. Matsen and T. L. Welsher J. Amer. Chem. SOC.,1976.98,7088. 74 S.Masamune T. Machiguchi and T. Aratani J. Amer. Chem. Soc.,1977,99,3524. 75 G.Maier and W. Sauer Angew. Chem.Zntemat. Edn. 1977,16,51. 76 G. A. OIah and J. S.Staral. J. Amer. Chem. Soc. 1976 98 6290. 77 R.Gleiter P. Bischof W. E. Volz,and L. A. Paquette J. Amer. Gem. Soc. 1977,99,8. 78 J. H. Hammons C. T. Kresge and L. A. Paquette J. Amer. Chcm. Soc. 1976,98 8172. 300 A. Cox latter compound it is localized on the four odd-numbered ring carbons. It is argued that these results provide support for symmetry-orbital models of substituted COT radical anions. The structures of the 1,4-dimethyl- 1,3,5,7-tetramethyl- 1,3,5,7- tetraphenyl- and sym -dibenzo-cyclo-octatetraenedications prepared by oxidation of suitably substituted cyclo-octatetraenes using SbF in S02CIF solution have been in~estigated'~ by 'Hand I3Cn.m.r. spectroscopy. The observations reported indicate that these ions possess those characteristics expected of a C8 67r aromatic system.Calculations using MIND0/3 have been reported*' for a number of potential homoaromatic molecules including (57) and (58) and the homocon- jugate interactions in the cyclobutyl-fused compounds studied were shown to be negligible whereas (57) appears to be homoaromatic. Judging the compounds investigated as a whole the conclusion is drawn that the energetic impact of monohomoaromaticity is only profound for the cyclobutenyl and homotropylium cations. Metallation routes have been announced" to the trilithium salts of the cycloheptatrienyl trianion its n-butyl derivative and its linearly conjugated analogue the heptatrienyl trianion. Among the evidence given is the appearance of the e.s.r.signal expected for cycloheptatrienyl dianion radical dilithium (aH= 3.52 and uLi= 0.83 G) and a singlet in the 'H n.m.r. and also in the I3Cn.m.r. spectra. By use of the newly synthesized bicyclobutanes (27) in which the bridge- head carbons are connected to pyridinium rings and positions 2 and 4 to substi-tuents of different size quantitative data have been provided82 concerning the effect of Ir-substituents and geometry on the LUMO energies in bicyclobutanes. Electrochemical oxidation transforms the 1,3-bisrnethylenecyclobutane(26) into (27) which in turn is reduced back to (26) and the evidence gained from cyclic voltammograms indicates a large decrease in the energy of the LUMO in (27) into which the two electrons are added as compared with that required for reduction of normal bicyclobutanes.The U.V. spectrum of bicyclo[ l,l,O]butane has been examineds3 and the band occurring near 50 000 cm-I assigned to a transition between bonding and antibonding 'T-like' central C-C bond orbitals. The lowest electronic state (A)has been examineds4 with a resolution of 0.3 cm-' permitting the rotational band contours for the vibronic components to be observed. Analysis of the band contours has shown the first excited state to have A2 symmetry. A number of spiroconjugated hydrocarbons have been studieds5 theoretically and by use of a modification within the MIND0 framework an orbital splitting is obtained which is within 5% of experiment in the case of spiro[4,4] nonatetraene. The 79 G.A. Olah J. S. Starel G. Liang L. A. Paquette W. P. Melega and M. J. Carmody J. Amer. Chem. SOC.,1977,99 3349. W. L. Jorgensen J. Amer. Chem. SOC.,1976,98,6784. 81 J. J. Bahl R. B. Bates W. A. Beavers and C. R. Launer J. Amer. Chem. SOC.,1977,99,6126. M. Horner and S. Hiinig J. Amer. Chem. SOC.,1977,99 6122. 83 K. B. Wiberg G. B. Ellison and K. S. Peters J. Amer. Chem. SOC.,1977 99 3941. 84 K. B. Wiberg K. S. Peters G. B. Ellison and F. Alberti J. Amer. Chem. SOC.,1977,99 3946. M. D. Gordon T. Fukunaga and H. E. Simmons J. Amer. Chem. SOC.,1976,98,8401. Alicyclic Chemistry conclusion is also drawn that the MIND0 technique using properly corrected overlap can yield realistic predictions on the magnitude of ‘through space’ inter- actions.The orbital energy differences for a number of spiro-compounds of type (59) and for the analogues in which the spiro-centre is replaced by a four-membered ring (60) have been calculated.86 This shows that the interaction between two mutually perpendicular n-systems linked by a spiro-centre becomes considerably stronger on replacing the spiro-centre by a four-membered ring and this is considered to occur by the Walsh orbitals of the four-membered ring acting as a ‘relay’. 5 Reactions Metal-promoted Reactions.-Methylenecyclopropane has been catalytically tri- merized using Nio compounds modified by trialkylphosphines to give a mixture of three open-chained and three cyclic CI2Hl8isome~s.~’The composition of the mixture depends on the nature of the alkyl groups attached to the phosphorus and a suggested route to one of the products (61) is shown in Scheme 13.Exclusive e- Qlx Scheme 13 [2u+ 27r] cycloaddition of methylenecyclopropane with alkenes has been found” on Pdo catalysts where in contrast to the Nio-catalysed reactions the three- membered ring is opened between C-2 and C-3. The catalytic cycloadditions 86 P. Bischof R.Gleiter and R. Haider Angew. Chem. Zniemaf. Edn. 1977 16 110. 13’ P. Binger A. Brinkmann and J. McMeeking Annalen 1977 1065. P. Binger and U. Schuchardt Angew. Chem. Internal. Edn. 1977 16 249. 302 A. Cox described might proceed via palladacyclobutanes of type (62) and palladacyclo- hexanes of type (63). Vinylcyclopropanes have beeri foundR9 to undergo a novel R" R2 epimerization in the presence of dicarbonylrhodium(1) chloride dimer and this has been shown to be coupled with trans-cis isomerization about the C-C r-bond.In related work kinetic studies involving rearrangement of l,l-dimethyl-2-vinyl-cyclopropane and other compounds provide evidence in support of a mechanism for ring cleavage involving initial co-ordination of the vinyl group with Rh' and stereospecific cis-P-hydride elimination from a subsequent metallocyclic allyl- rhodium(II1) alkyl intermediate. Methylenecyclobutane and its 3-substituted derivatives are reported" to undergo a Pd"-catalysed ring expansion to the cor- responding cyclopentanones in good yield. Analogous but somewhat less efficient reactions are observed for camphene methylenecamphor and methyl-enecyclopentane.The transformation has been found to be solvent sensitive yields being highest in benzene but falling off with increasing solvent polarity. An examination has been made91 of the silver(1) perchlorate-catalysed rearrangement of [l-2H]benzvalene to [2Hl]benzene in which rupture of two diagonally opposed bonds of the bicyclobutane moiety occurs. By following the reaction with the 2H-('H} FTn.m.r. technique it is found that the benzvalene deuterium label is scrambled by a catalysed degenerate rearrangement in competition with the aromatization. Together with labelling studies the observations provide unequivocal evidence that the reaction of the Ag' ion with the cyclobutane moiety is a reversible process involving rupture and then reclosure of a C-C bond.A study has been made92 of the heats of metal-catalysed rearrangements of some small-ring hydrocarbons in an attempt to rectify the lack of experimental ther- mochemical data. In particular the isomerizations of quadricyclane to norbor- nadiene and of tricycle[$ 1,0,02v7]heptaneto 3-methylenecyclohexene have been studied. The synthesis of anti-tetramantane (64) a C22H28 hydrocarbon having the regular topology of the diamondoid lattice has been achieved,93 in which the key step is a ring expansion+yclization reaction of a polycyclic diene (65) in hydrogen in the gas phase on a platinum-silica catalyst. The mode of expansion of the four-membered ring in the [2+2] dimers of adamantane in the gas phase on platinum has also been in~estigated~~ and the results support the view that loss of a single bridgehead hydrogen atom from the alkane is sufficient to initiate rear- rangements.This is to say that essentially covalently bonded alkyl groups rear- 89 R. G. Salomon M. F. Salomon and J. L. C. Kachinski J. Amer. Chem. SOC.,1977,99 1043. 90 P. Boontanonda and R. Grigg J.C.S. Chem. Comm. 1977 583. 91 U. Burger and F. Mazenod Tetrahedron Letters 1977 1757. 92 K. B. Wiberg and H. A. Connon J. Amer. Chem. SOC.,1976,98,5411. 93 W. Burns T. R. B. Mitchell M. A. McKervey J. J. Rooney G. Ferguson and P. Roberts J.C.S. Chem. Comm. 1976,893. 94 W. Burns M. A. McKervey J. J. Rooney N. G. Samman J. Collins P. von R. Schleyer and E. Osawa J.C.S. Chem. Comm. 1977 95. Alicyclic Chemistry (64) (65) range on a platinum surface in a manner commonly observed with carbonium ions.This represents an alternative pathway to the formation and further reaction of aah -triadsorbed intermediate (66) and is presumably followed as the aah Me Me fi -Pt-Pt-(66) mechanism is ruled out on simple geometric grounds. It has been that (diphenylcarbene)pentacarbonyltungsten without added co-catalysts is an effective initiator of metatheses of numerous cis-cycloalkenes converting them into polyalkenamers 90% or more of whose double bonds are cis. Cyclobutene cyclopentene cyclohexene cycloheptene cyclo-octene and norbornene are all transferred in this way. In an accompanying paper,96 (phenylmethoxy- carbene)pentacarbonyltungstenis also reported as being able to bring about meta- theses of cyclobutene and norbornadiene to the corresponding polyalkenamers.The importance of this discovery is that although ways have yet to be found to replace the stabilizing substituents in the metal carbenes such as (phenyl-methoxycarbene)pentacarbonyltungstenin order to transform them into initiators for olefin metathesis it emerges that this carbene is itself an effective catalyst. The photochemical decomposition of a number of substituted metallocyclobutane derivatives of the general form [(75-C5H5)2WCH2CHR2CHR'] have been studied9' and the major olefin formed on decomposition is shown to have one carbon less than the appropriate carbon chain of the initial metallocyclobutane. It is suggested that the initial photochemical reaction causes a q5-C5Hs to-q3-C5Hs ring shift and that this 16-electron intermediate allows the rearrangement of the metallocyclo- butane ring to occur.Equilibria of the type shown in Scheme 14 have been postulated as the central step in the olefin dismutation reaction and these results provide strong support for this mechanism. It has been found98 that l-methyl- trans-cyclo-octene undergoes metathesis to yield a polymer that within the limits of the detection method is perfectly alternating. Thus to the extent that this reaction is a valid measure the selectivity for equation (1)is >50 times that for equation (2) (Scheme 15). The experiments also show the stereochemistry of trisubstituted olefin metathesis (E-olefins yield mainly E-products) and indicate 95 T.J. Katz S. J. Lee and N. Acton Tetrahedron Letters 1976 4247. 96 T. J. Katz and N. Acton Tetrahedron Letters 1976 4251. 97 M. Ephritikhine and M. L. H. Green J.C.S. Chem. Comm. 1976,926. 98 S. J. Lee J. McGinnis and T. J. Katz J. Amer. Chem. SOC.,1976 98 7818. 304 A. Cox 16-electron 18-electron 1 R’ = R2 =R3 = R4 = H; R’ = R3=H R2 = R4 = Me; or R’ =Me R2 = H R3 = Me or H R4 = H or Me Scheme 14 the presence of the metathesis initiator at the ends of the polymer chains. A model has been proposedg9 to account for both the observed metathesis and the cis-trans isomerization as measured by the relative amounts of the various olefins produced at low conversion from the reaction of cis-pent-2-ene on a tungsten catalyst.A stereochemical model is proposed based on the belief that an olefin co-ordinated to a metallo-carbene unit passes through a four-centre transition state to form a new olefin and a new metallo-carbene. 99 J. L. Bilou J. M. Basset R. Mutin and W. F. Graydon J.C.S. Chem. Comm. 1976 970. Alicyclic Chemistry Thermally Induced Reactions.-A laminar flow reactor has been described'" which is useful for gas-phase kinetic measurements on small amounts of compounds; the vinylcyclopropane rearrangement and the retro-Diels-Alder reaction of dicyclobutadiene were the reactions used in test runs to demonstrate the reliability of the results. Light has been cast on the stereochemistry of the cyclo- pentene-forming reaction by reports'01 of a study of the thermal isomerization of (+)-(1S,2S)-trans,trans-2-methyl-l-propenylcyclopropanefor which the figures shown in Scheme 16 have been obtained.It is suggested that there is competition among four concerted processes two allowed and two forbidden with the possible intervention of a planar .rr-vinylcyclopropane intermediate having an orbital struc- ture appropriate for disrotatory ring closure to racemic (67). A study has been made1O2of the pyrolysis of 6-exo-vinylbicyclo[3,1 ,O]hex-2-ene in order to deter- mine whether isomerization to the 6-endo-isomer occurs through a one-centre epimerization at C-1 and C-5. The results show that the one-centre epimerization pathway is followed and for the first time this is demonstrated in a cyclopropane for which the alternative two-centre option is geometrically possible.Investigation of the thermal decomposition of bicyclic divinyl- A'-pyrazolines and divinylcyclo- propanes has that identical product decomposition patterns arise from (68) and (69) (Scheme 17). Comparison of the kinetic parameters for decomp- osition of (68) with those for trans-3,5-dimethyl-A1-pyrazoline and 3-vinyl-A'- pyrazoline suggests a contribution towards a lowering of the activation enthalpy \ Scheme 17 loo L.-U. Meyer and A. de Meijere Chem. Ber. 1977,110 2545. lo' G.D.Andrews and J. E. Baldwin J. Amer. Chem. SOC.,1976,98,6705. J. E.Baldwin and K. E. Gilbert 1.Amer. Chem. SOC.,1976,98,8283. '03 M. P. Schneider and B. Csacsko J.C.S. Chem. Comm.1977,330. 306 A. Cox consistent with formation of a diallylic 1,3-biradical and this is taken as supporting evidence that the thermal rearrangement of trans -divinylcyclopropane proceeds through a biradical intermediate. In order to attempt to define the mechanism for thermal geometrical isomerizations of cyclopropanes the rates have been meas~red"~ for three distinct degenerate processes shown by the cyclopropyl moiety of (Z)-l-methyl-2-deuteriospiro[2,4]hepta-4,6-diene.The results show that even in this favourable case the first cyclopropane constituted to enhance prospects for one-centre epimerization through a planar intermediate epimeriza- tion at C-3 is definitely not prominent and may well be absent. Studies"* of the thermal rearrangement of methylenecyclobutane indicate that electronic factors are least likely to be the cause of the observed sterepspecificity in this reaction and they also reveal a similarity between the reaction of cyclopropane arid cyclobutane with that of methylenecyclobutane in that all pass through a biradical transition state (or intermediate) which is not bound by large rotational barriers.Experi- ments have been reported *06which are claimed to demonstrate unambiguously 'hot molecule' effects at an atmosphere of nitrogen and exclusive operation of the C-1 -C-4 bond-cleavage mechanism in the transformation of bicyclo[2,1,0]pent-2-ene to cydopentadiene. It is suggested that the assumption that collisional de- activation in solution always pre-empts thermal reactions of vibrationally excited molecules can no longer be credited.The first experimental evidence has been reportedlo7 which demonstrates that stabilization of norcaradiene relative to cyclo- heptatriene can be achieved by replacement of hydrogen at C-7 with a wdonor. The equilibria (70)*(71) (Scheme 18) have been established and the time- averaged values of &,.6 in (70a) r,(71b) (4.45) and (70b) r* (71b) (4.88) indicate that in contrast to (71c) (5.74) substantial quantities of the norcaradiene form are present in both mixtures. From n.m.r. data can be obtained KZ5.,[(70a) a(71b)] -0.7 [41%(71a)l and K25aC[(70b)* (7lb)]-0.3 124% (71b)l. This establishes that a piperidino-group stabilizes the norcaradiene form relative to the cycloheptatriene PF Ph Ph Ph (70) a; R = 1-piperidino b; R = cyclohexyl c; R = €I Scheme 18 form slightly more than does the sterically similar cyclohexyl group.It is suggested that HOMO-LUMO interactions between v-electron donors and a cyclopropyl ring whether in a perpendicular or a bisected conformation must cause stabiliza- lo4 K. E. Gilbert and J. E. Baldwin J. Amer. Chem. SOC.,1976,98 1593. lo' W. W. Schoeller J. Amer. Chem. SOC.,1977,99 5919. G. D. Andrews and J. E. Baldwin J. Amer. Chem. SOC.,1977,99,4853. lo' S. W. Staley M. A. Fox and A. Cairncross J. Amer. Chem. SOC.,1977 99 4524. Alicyclic Chemistry tion not destabilization. An investigation has been undertaken"' of the thermal rearrangements of spiro[4,4 Jnonatetraene (72) and the related less unsaturated analogues spiro[4,4]nona- 1,3,6-triene (73) spiro[4,4]nona- 1,3,7-triene (74) and spiro[4,4]nona- 1,3-diene (75).Low activation barriers are observed for (72) and (73) relative to (74) and (75) and a transition state is favoured which implicates the w-system at the migrating carbon for (72) and (73). The transition state (76) for a WQQm (72) (73) (74) (75) simple sigmatropic shift of a carbon unit attached to a cyclopentadiene ring is appropriate for reactions of (74) and (75) but may be modified in the cases of (72) and (73) owing to interactions of a porbital on the migrating carbon (LUMO of an olefin or 1,3-diene unit with the cyclopentadienyl r-system HOMO). This HOMO-LUMO interaction (77) would stabilize the transition states leading to the (76) Orbital interaction during 15 (77) Secondary n-orbital interaction alkyl shift during 1,5-vinyl shift low barriers to rearrangement for (72) and (73) as compared with (74) and (75).Thermal isomerization'Og of cyclopropylallene at 380 "Cusing a contact time of ca. 2 minutes leads to a mixture of five components of which two 1,4-dimethylcyclohexa- 1,3-diene and pxylene cannot be explained without invoking a facile 1,7-hydrogen migration The thermolysis of bicyclo[2,2,0]hex-2-ene has been approached'".by generating a complete list of mechanistic alternatives both plausible and otherwise and then by experiment rigorously excluding as many as possible. By this method there is found no pericyclic alternative to the symmetry-forbidden least-motion mechanism shown in Scheme 19.The kinetic distribution of isomeric xylenes formed on thermal aromatization of dl-and meso-1,l-dimeth~l-3,3'-bicyclopropenyls and Scheme 19 M. F. Semmelhack H. N. Weller and J. S. Foos J. Amer. Chem. SOC.,1977,W. 292. lo9 D. E. Minter and G. J. Fonken Tetrahedron Letters 1977 1717. M.J. Goldstein R. S. Leight and M. S.Lipton J. Amer. Chem. Soc. 1976,98. 5717. 308 A. Cox of l,l'-dimethyl-3,3'-bicyclopropenylhas been determined."' The data are most consistent with a mechanism involving initial cleavage of one of the cyclopropane rings followed by expansion of the other ring closure to a Dewar-benzene and finally opening of the Dewar intermediate to form aromatic products. A report has appeared112of a study of the kinetic and thermochemistry of the valence iso- merization of benzvalene to benzene.The transformation is found to be essentially non-chemiluminescent and the valence isomerization may be viewed as a symmetry- forbidden [,2+,2] process and as such it may be supposed that a biradical mechanism is involved. 'I1 J. H. Davis K. J. Shea and R. G. Bergman J. Amer. Chern. Soc. 1977,99 1499. N.J. Turro C. A. Renner and T.J. Katz TerrahedronLettks 1976,4133.

ISSN:0069-3030    

DOI:10.1039/OC9777400285

出版商:RSC    

年代:1977

数据来源: RSC

摘要:

13 Synthetic Methods By G. PATTENDEN Department of Chemistry The University Nottingham NG7 2RD 1 Introduction The first volume of a new Specialist Periodical Report entitled ‘General and Synthetic Methods’ has been published by the Chemical Society.’ 2 Alkanes A number of useful procedures for the reduction of secondary alcohols based on free-radical intermediates have emerged in the past few years. Billingham efa1.’ have now demonstrated that primary and secondary alcohols are converted into the corresponding hydrocarbon by radical-initiated reduction of their chloroformates using tri-n-propylsilane in the presence of t-butyl peroxide at 140“C (Scheme 1). ROH ROCOCl ‘I*[R-OCO +R]+RH Reagents i COC12; ii Pr3SiH-(But0h Scheme 1 Quantitative yields of hydrocarbons are realized when primary halides are reduced with LiAlH4 in the presence of first-row transition-metal halides (e.g.COC~~,N~C~~).~ The same modified reducing agents also effect reductions of alkenes to alkanes and of disubstituted alkynes to cis-alkenes in high yields. A novel method for the direct substitution of a hydroxy-group in an alcehol by an alkyl group proceeds via aminophosphonium salts [viz. (l)] produced by the reaction of the lithium alkoxyalkylcuprate with NN-methylphenylamino-triphenylphosphonium iodide (Scheme 2).4 ROH R-0-CuBu3Li3 -h [R-O-PPh3] +[Bu3CuNMe2PhLi2]-+ R-Bu (1) + Reagents i MeLi; ii CuI; iii BuLi; iv Ph3PN(Me)Ph I-Scheme 2 ‘General and Synthetic Methods’ ed. G. Pattenden (Specialist Periodical Reports) The Chemical Society London 1978 Vol.1. R. C. Billingham R. A. Jackson and F. Malek J.C.S. Chem. Comm. 1977 344. E. C. Ashby and J. J. Lin Tetrahedron Letters 1977 4481. Y. Tanigawa H. Kanamaru A. Sonoda and S. I. Murahashi J. Amer. Chem. SOC.,1977,9!3,2361. 309 310 G. Pattenden Vedejs and Stolle’ have shown that alkyl-lithium reagents add readily to the C-N linkage in aldehyde hydrazones producing adducts [viz.(2)] which fragment leading to the corresponding hydrocarbon ‘reductive alkylation’ products (Scheme 3). R2 R1%-NHTs i,R1-N-ms i,RIA-fiTs (2) )/;teRIX R2 R’ N=N Reagents i R2Li; ii H20(-N2) Scheme 3 3 Alkenes In no other area of natural product synthesis has the Wittig reaction had such a profound effect as in carotenoid synthesis.It is timely therefore that in an article based on an address delivered on the occasion of Professor Wittig’s 80th birthday H. Pommer should provide an account of the importance of the reaction in industrial practice generally and in the synthesis of carotenoids and Vitamin A in particular.6 Leznoff and his co-workers’ have extended their work on the use of insoluble polymer supports in synthesis and have shown that the approach can be used to synthesize unsymmetrical carotenoids by the Wittig reaction. Thus the reaction between the di-aldehyde (7) and the cross-linked divinylbenzene-styrene copolymer (3) containing vicinal diol groups led to the mono-blocked polymer- bonded aldehyde (4) which was condensed with phosphoranylides to give the polymer-bonded Wittig reaction product (S) as shown in Scheme 4; hydrolysis with acid then led to (6).The synthesis of the strained methylene-bridged bicyclic alkenes (8) (9) and (10) via intramolecular olefinations using phosphoranylides attests further to the synthetic versatility of the Wittig reaction.* The Wadsworth-Emmons modification of the Wittig reaction using phos- phonate carbanions is well known to lead to predominantly (-95%) trans-olefins in condensation reactions with aldehydes. Thus condensation between iso-butyraldehyde and the phosphonate (11)produces a sample of the alkene (12) that contains less than 7% of the cis-isomer (14). Observations of this type are usually rationalized on the basis of reversible formation and interconversion of the erythro and threo ‘betaine’ intermediates producing ultimately the more stable threo-form which then undergoes elimination to the trans-olefin.It is known that phosphorus compounds that have five-membered rings react faster than their acyclic counter- parts and the observation has now been exploited in a synthetically useful E. Vedejs and W. T. Stolle Tetrahedron Letters 1977 135. ‘H. Pommer Angew. Chem. Internat. Edn. 1976 15 161. C. C. Leznoff and W. Symanyk J. Org. Chem. 1977,42,3203. K. B. Becker Helu. Chim. Ada 1977,60,69 81. 311 Synthetic Methods ucoztt (1 3) (14) approach to cis-alkenes by the Wadsworth-Emmons reaction using the cyclic phosphonate (13); this is found to react with isobutyraldehyde for example leading to largely cis-alkene (14) (-70Y0).~ E.Breuer and D. M. Banet Tetrahedron Letters 1977 1141; cf. B. Deschamps J. P. Lamyin F. Mathey and J. Segden-Penne ibid. 1977 1 I37 and I. F. Wilson and J. C. Tebby J. Chern. SOC.,(C) 1972,2713. P 312 G. Pattenden Allyl-tin and allyl-silicon reagents are increasingly used as reagents in synthesis and both reagents are easily synthesized via Wittig reactions involving 0-tri- methylstannyl and P-trimethylsilyl phosphoranylides. lo The scope provided by carbonyl olefination with trimethylsilylmethyl-lithium and its derivatives (i.e. the Peterson reaction) and the importance of the reaction as an alternative to the Wittig reaction has been stressed in earlier Reports [see Ann.Reports (B) 1975 72 p. 311; 1976 73 p. 3041. Now Kauffman et a1.l' have shown that the analogous reaction with triphenylstannylmethyl lithium could offer even more advantages as an alternative olefination sequence. Vinylsilanes are valuable 'starters' for the synthesis of the P-hydroxy-silane intermediates in the Peterson reaction and a number of alternative approaches to these molecules have been developed in the past few years. A new approach starts from a carbonyl compound which is first converted into the corresponding tosylhydrazone; treat- ment with BuLi in tetramethylethylenediamine followed by trimethylsilyl chloride then leads to the required vinylsilane (Scheme 5)'' Reagents i BuLi-MezNCH2CHZNMe2 (TMEDA); ii Me3SiC1 Scheme 5 Details of the conversion of 1,2-diols into alkenes via reductive elimination of cyclic phosphoric amide derivatives with dissolving metals have been presented," and Barton and his co-~orkers'~ have shown that the conversion is just as readily accomplished by treatment of the corresponding bis-dithiocarbonates with BuySnH.In related studies Lythgoe and Waterhousels demonstrate that treat- ment of /3 -hydroxy-sulphides P-hydroxy-sulphones and P-chloro-sulphides with Bu;SnH also provides an expeditious synthesis of alkenes. The decarboxylative dehydration of P-hydroxy-acids can be accomplished lit- erally within seconds at O'C using the adduct of triphenylphosphine and ethyl azodicarboxylate,'6 and in one of the first illustrations of the use of organo-tellurium(1) reagents in synthesis Clive and Menchen have shown that epoxides can be converted into the corresponding alkenes by treatment with 00-diethyl phos- phorotelluroate.l7 The use of di-imide as a reducing agent for the stereospecific hydrogenation of alkynes to cis-alkenes is well documented. In a procedure which seems to have several practical advantages over existing methods Kondo et al. *' have now shown lo D. Seyferth K. R. Wursthorn and R. E. Mammarella J. Org. Chem. 1977 42 3104. T. Kauffman R. Kriegesmann and A. Wothermann Angew. Chem. Internat. Edn. 1977 16 862. l2 R. F. Taylor C. R. Degenhardt W. P. Melega and L. A. Paquette Tetrahedron Letters 1977 159. l3 J. A. Marshall and M. E. Lewellyn J. Org. Chem. 1977,42 131 1. l4 A. G.M. Barrett D.H. R. Barton R. Bielski and S. W. McCombie J.C.S. Chem. Comm. 1977 866. l5 B. Lythgoe and I. Waterhouse Tetrahedron Letters 1977 4223. l6 I.Mulzer and G. Bruntrup Angew. Chem. Internat Edn. 1977.16 255. D. L. J. Clive and S. M. Menchen J.C.S. Chem. Comm. 1977,658. '' K. Kondo S. Murai and N. Sonoda Tetrahedron Letters 1977 3727. Synthetic Methods that elemental selenium provides a useful alternative oxidizing agent for the generation of di-imide from hydrazine. Disubstituted alkynes are also converted into the corresponding cis-alkenes with the organo-copper reagent prepared from CuI and two equivalents of a primary Grignard reagent;” this reaction presumably proceeds via copper hydride species. Vinyl organometallic reagents which are easily available from the corresponding alkynes have featured in several useful routes to functionalized alkenes2L22 and 1,3-diene~~~-~~ published this year (Scheme 6).R ,LCuMgBr2 R’ c1 Reagents 1 Rz2BH; ii Pd(OAch-Et3N; iii EtCuMgBr;?; iv 00; v Cl(H)ZrCpz; vi R3X-Ni(PPh& Scheme 6 The boron-trifluoride-catalysed elimination of borate esters of secondary alco- hols provides a useful synthesis of disubstituted aIkene~,*~ and the combination of nucleophilic addition to vinyl sulphones followed by in situ Ramberg-Backlund rearrangement provides an interesting approach to olefins of type (15).26 05=4+.4S02Ph (15) In a procedure which may have scope for the synthesis of more difficultly accessible terminal alkenes Poulter and his co-workers2’ have shown that this type of alkene is produced by the addition of Grignard reagents to Eschenmoser’s salt (16) followed by oxidation and elimination (Scheme 7).l9 J. K. Crandall and F. Collonges J. Org. Chem. 1977,41,4089. 2o H. Yatagai Y. Yamamoto K. Maruyama A. Sonoda and S. 1. Murahashi J.C.S. Chem. Comm. 1977 852. A. Marfat P. R. McGuirk R. Kramer and P. Helquist J. Amer. Chem. SOC.,1977 99 253. 22 E.-I. Negishi and D. E. Van Horn J. Amer. Chem. SOC.,1977,99 3158. ” M. Yoshifuji M. J. Loots and J. Schwartz Tetrahedron Letters 1977 1303. 24 H. Westmijze H. Kleijn J. Meijer and P. Vermeer Tetrahedron Letters 1977 869. 25 M. P. Doyle S. B. Williams and C. C. McOsker Synthesis 1977 717. 26 T. B. R. A. Chen J. J. Burger and E. R. de Waard Tetrahedron Letters 1977 4527.*’ J. L. Roberts P. S. Borromeo and C. D. Poulter Tetrahedron Letters 1977 1299. 314 G. Pattenden Reagents i H202; ii A 150"C Scheme 7 Although these Reports have commented frequently on the use of the 'ene' reaction in the elaboration of complex ring systems in general the synthetic potential of the reaction is diminished somewhat by the forcing thermal conditions required to make it go. Gill and Wallace2* have now shown that the ene reaction of chloral with olefins is greatly accelerated in the presence of a Lewis acid catalyst and furthermore that these catalysed reactions have high regio- and stereo-specificities [e.g. (17)+( 1s)]. (83'/o ) (100%) (18) In a remarkably short synthesis of the steroid nucleus Funk and Vollhardt" have shown that the pentacyclic ketone (22) is produced when the 1,5-diyne (19) is added to bis(trimethylsily1)acetylene.This synthesis which avoids the isolation of any of the intermediates proceeds through the benzocyclobutane (20) and via intramolecular Diels-Alder reaction of the ottho-xylylene (21). The intermediate (23) which is suitable for pentacyclic triterpene synthesis has also been synthesized by an intramolecular Diels-Alder rea~tion.~' In a novel approach towards the polyene dimethylcrocetin (28) Quinkert et aL31 have demonstrated that the sunlight of Frankfurt is an effective enough 'reagent' for the photochemical cleavage of the cyclohexadienones (24) and (25) affording the seco-isomeric dienyl ketones (26) and (27) respectively which were used subsequently to synthesize (28).4 Alkynes Enynes and Allenes 1,l-Dichloroalkenes are useful intermediates in the synthesis of a wide range of mono- and di-substituted alkynes [see Ann. Reports (B) 1975 72 p. 316). A useful alternative olefination procedure for the preparation of these compounds32 28 G. B. Gill and B. Wallace J.C.S. Chem. Comm. 1977,380 382. 29 R. L. Funk and K. P. C. Vollhardt J. Amer. Chem. Soc. 1977,99,5483. 30 T.Kametani Y.Hirai F. Satoh and K. Fukumoto J.C.S. Chem. Comm. 1977 16. 31 G.Quinkert K. R. Schmieder G. Durner K. Hache A. Stegk and D. H. R. Barton Chem. Ber. 1977,110,3582. 32 P. Coutrot C. Laurenco and J. F. Normant Synthesis 1977 615. Synthetic Methods \ 316 G.Pattenden 0 (24) kv,MeOH MeO& MeO,Cw % Y Y uses the phosphorane (29) prepared from bromotrichloromethane and hexamethylphosphortriamide (Scheme 8).33 (Me2N)3P + (Me2N)3P=CC12 RYc'-% RCECLi --+ + (29) CI BrCC13 Reagents i RCHO; ii BuLi Scheme 8 Brown and Negi~hi~~ have shown that the isomerization of the triple bond in alkynyl-organoboranes can be effected in high yield using the 'acetylene zipper' potassium 3-aminopropylamide (KAPA). The resulting w-alkynyl-organoborane can then be used in typical organoborane reactions (Scheme 9). Full details have lii Reagents 1 RzBH; ii KHN(CH&NH2 (KAPA); iii H202-NaOH Scheme 9 33 W. G. Salmond Tetrahedron Letters 1977 1239. 34 C. A. Brown and E.-I. Negishi. J.C.S.Chem. Cornm. 1977 318. Synthetic Methods 317 appeared of Coke's work on the synthesis of acetylene ketones which uses a variant of the Eschenmoser fragmentation [e.g. (30 -+ (31)].35 (30) (31) The coupling of alkynyl-zinc reagents with (2)-and (E)-alkenyl halides in the presence of a Pd catalyst provides a refreshingly new and efficient method for the regio- and stereo-selective synthesis of conjugated enynes (Scheme Sym-R1-) Br +R2CZECZnCl I* "'7 R2 AI(Me)Bu2'Li R=XR -% RyR Reagents i Pd complex; ii MeLi-Bu'2AlH; iii H+ Scheme 10 metrically substituted trans-enynes are produced by the hydroalumination of con-jugated diynes followed by protonation (Scheme and in their total synthesis of laurencin (32) from marine algae Murai et aZ.used the familiar Wittig reaction approach to introduce the sensitive terminal enyne unit.38 n.,./ -...+ OAc -Br Br 0 H \ i (32) The Wadsworth-Emmons olefination procedure has proved useful in the synthesis of allenic amides of type (34) using the phosphonate amide (33),39and allenic boranes feature in a useful synthesis of substituted allenes of the type (35).40 35 J. L. Coke H. J. Williams and S. Natarajan J. Org. Chem. 1977,42 2380. 36 A. 0.King N. Okukado and E.-I. Negishi J.C.S. Chem. Comm. 1977,683. 37 G. Zweifel R. A. Lynd and R. E. Murray Synthesis 1977 52. 38 A. Murai H. Murase H. Matsue and T. Masamune Tetrahedron Letters 1977 2507 39 P. D. Landor S. R. Landor and 0.Odyek J.C.S. Perkin I 1977,93. 40 M. M. Midland J.Org. Chem. 1977,42 2650. 318 G. Pattenden (35) In a demonstration of the application of 1,4-addition of organocuprates to allenic esters Bertrand et al. have developed a useful synthetic approach to the irregular terpenoid carbon skeleton present in lavandulol(36) (Scheme 1l).41 Reagents i Me3CuLi; ii Me*C=CHCHzBr; iii LiAlH4 Scheme 11 5 Halogeno-compounds A very simple and efficient one-step method for the conversion of primary secon- dary and tertiary alcohols into the corresponding iodides is via treatment with trimethylsilyl iodide.42 Primary alkyl chlorides are quantitatively converted into their corresponding bromides in the presence of ethyl bromide N-methyl-2-pyr- rolidinone and a catalytic amount of metal bromide.43 A new synthetic method for the transformation of alcohols into alkyl chlorides uses 2-chlorobenzoxazolium salts in the presence of tetraethylammonium The tertiary phosphine-carbon tetrachloride reagent has proved extremely use- ful for chlorinations of alcohols.Magid et (11.45 have now shown that the cor- responding ‘reagent’ from hexachloroacetone and PPh3 off ers several practical advantages over CC14-PPh3 particularly for the stereo- and regio-selective con- versions of allyl alcohols into allyl chlorides [e.g. (37) +(38)]. Allylic bromides are produced by the ‘anti-Markovnikov’ addition of phenylselenyl bromide to terminal alkenes followed by oxidation with H202[e.g.(39)+(40)].46 OH CI -RYB~ R--+ RVB~ (39) SePh (40) Vinylic halides feature prominently in a number of useful synthetic trans- formations.Two general approaches to vinyl bromides published this year employ 41 M. Bertrand G. Gil and J. Viala Tetrahedron Letters 1977 1785. 42 M. E. Jung and P. L. Ornstein Tetrahedron Letters 1977 2659. 43 W. E. Willy D. R. McKean and B. A. Garcia Bull. Chem. Soc. Japan 1976,49 1989. T. Mukaiyama S.-I. Shoda and Y. Watanabe Chem. Letters 1977 383. ‘’ R. M. Mazid 0.S. Fruehey and W. L. Johnson Tetrahedron Letters 1977 2999. 46 S. Raucher Tetrahedron Letters 1977 3909. Synthetic Methods ~inyl-silanes~’ and ar@-epoxy-silanes4* as starting materials (Scheme 12) whilst a third method proceeds via vinylcopper reagents (Scheme 13).49 OH Reagents i Clz; ii NaOMe; iii HBr; iv BF3 Scheme 12 Reagents i R’CuMgBrZ; ii NBS Scheme 13 6 Alcohols Posner and his co-workersS0 have reported on the scopes and limitations of the two ‘reagents’ isopropyl alcohol and di-isopropyl alcohol on dried Woelm alumina for the controlled reduction of the carbonyl function to alcohols.These reagents are weaker reducing agents than sodium cyanoborohydride and 9-borabicyclononane (9-BBN) and permit the selective reduction of aldehydes in the presence of ketones and also the selective reductions of cup-unsaturated aldehydes to the corresponding allylic alcohols; other functional groups e.g. nitro ester and nitrile are unaffected by the reagents. Two alternative methods which permit the specific reductions of aldehydes in the presence of ketones use either NaBH4 in the presence of thiol” or organomagnesium iodides.s2 Gibson and Bailey53 have described the preparation of a series of polymer- supported reducing agents containing units of structure (4 l),from anion-exchange @-CH2AMe BH4 +CH,CH I (41) 47 R.B.Miller and G. McGarvey Synth. Comm. 1977,475. 48 P. F. Hudrlik A. M. Hudrlik R. J. Jona R. N. Misra and G. P. Withers J. Amer. Chem. Soc. 1977 99 1993. 49 A. B. Levy P. Talley and J. A. Dunford Tetrahedron Letters 1977 3545. .5’ G. H. Posner A. W. Runquist and M. J. Chapdelaine J. Org. Chem. 1977,42 1202. 51 Y. Maki and K. Kikuchi Tetrahedron Letters 1977 263. 52 G. Cahiez and J. F. Normant Tetrahedron Letters 1977 3383. 53 H. W. Gibson and F. C. Bailey J.C.S. Chem. Comm. 1977 815. 320 G.Pattenden resins of the quaternary ammonium type and aqueous NaBH4. The method clearly offers scope for easy work-up of reduction products by simple filtration or by the use of columns. Lithium ~-isopinocamphenyl-9-borabicyclo[3,3, llnonyl hydride is a newly described reagent for the asymmetric reduction of ketones,54 and Crumbie et aLSs have reported the selective reduction of one enantiomer of racemic ketones by actively fermenting yeast; the latter method yields optically active secondary alco- hols and leaves the ketone in optically pure form. Although selenium dioxide is one of the most useful reagents for the direct introduction of oxygen into activated C-H bonds the method suffers from the drawback that the reduced forms of selenium that are produced concurrently are often exceedingly difficult to remove.Umbreit and Sharple~s~~ have now made the interesting observation that the Se02 can be employed in a catalytic sense in the presence of t-butyl hydroperoxide which rapidly re-oxidizes the selenium species to Se02 as soon as it is consumed in the oxidation. Using this method yields are comparable with those obtained by Se02 alone and the messy work-up operations normally associated with oxidation by Se02 are avoided. 7 Ethers Ethers are produced directly from alcohols and halides in the presence of bis(acety1acetonato)nickel as ~atalyst;~’ by contrast phenols do not give the cor- responding ethers under these conditions. A frequent limitation to the use of alkyl ethers as protecting groups for aliphatic alcohols has been the difficulty associated with their removal.Jung and LysterS8 have now shown that the interesting elec- trophile trimethylsilyl iodide is an exceptionally efficient reagent for this purpose. Olefins undergo smooth expoxidations when one uses benzene-peroxyseleninic acid which is readily generated in situ from benzeneseleninic acid and 50% H202.59Epoxides of the Darzen type [uiz. (42)] can be prepared by oxidation of P-hydroxy-ester dianions with iodine as shown in Scheme 14.60 A feature of this method is that it leads to the formation of the least hindered compound whereas the classical Darzens procedure generally leads to diastereoisomeric mixtures. Reagents i LiCH2C02Et; ii LiNPr’2;iii I2 Scheme 14 S.Krishnamurthy F. Vogel and H. C. Brown J. Org. Chem. 1977.42 2534. ’’ R. L. Crumbie D. D. Ridley and G. W. Simpson J.C.S. Chem. Comm. 1977 315. ” M. A. Umbreit and K. B. Sharpless J. Amer. Chem. SOC.,1977 99 5526. ” M. Yamashita and Y. Takegami Synthesis 1977 803. ’13 M. E. Jung and M. A Lyster J. Org. Chem. 1977,42,3761. 59 P. A. Grieco Y. Yokoyama S. Gilman and M. Nishizawa J. Org. Chem. 1977,42 2034. 6o G. A. Kraus and M. J. Taschner Tetrahedron Letters 1977 4575. Synthetic Methods The antifungal antibiotic 'cerulenin' (45) containing an interesting epoxide moiety has attracted the attentions of the synthetic chemist and two syntheses of the antibiotic have been published during the period covered by this Report. In each synthesis the epoxide moiety was introduced at an early stage in the form of the butanolide (43) and the anhydride (44).61762 (44) Both the Wadsw~rth-Emmons~~ and the variants of the Wittig reaction offer considerable advantages over the Wittig method for the synthesis of vinyl ethers from a-alkoxyalky phosphorus ylides (Scheme 15).0 0 II II (R0)2PCH(OR')R2 -+R3 YOR' +Ph2PCH(OR')R2 R' Scheme 15 8 Amines Phase-transfer catalysis features in a useful synthesis of primary amines from alkyl halides via the corresponding diethoxyphosphine oxide [viz. (46)].65 By the same general procedure secondary amines are produced from primary amines by the alkylation under phase-transfer conditions of the amide (46) followed by treat- ment with gaseous HCI in THF at 25 "C,as shown in Scheme 16.0 II R'Br -&R'NHP(0Et)Z A R'NH2 /(46) \i R2 I R'NH2 NH R' ' Reagents i (EtOhPONHZ; ii HCl iii (EtO),POH iv R21 Scheme 16 61 A. A. Jakabouski F. S. Guzier and M. Tishler Tetrahedron Letters 1977 2399. 62 E. J. Corey and D. R. Williams Tetrahedron Letters 1977 3847. 63 E. Schaumann and F. F. Grabley Annalen 1977 88. 64 C. Earnshaw C. J. Wallis and S. Warren J.C.S. Chem. Comm. 1977 314. A. Zwierzak and J. Brylikowska-Piotrowicz Angew. Chem. Internat. Edn. 1977,16 107; A. Zwierzak and I. Podstawczynska ibid.,p. 702. 322 G.Pattenden The merits of 1,2-diphenylmaleyl as an alternative to phthaloyl as a group for the protection of ainino-functions have been discussed,66 and a new method for the protection of amine functions is based on their conversion into 9-anthrylmethyl carbamates (47).In spite of the fact that carbamates are resistant to the action of OCONHR / I various bases and acids the removal of these protecting groups is achieved simply by treating them with the sodium salt of methanethiol (4 min at 25 0C!).67 9 Aldehydes and Ketones In the general pursuit of more regioselective oxidizing agents for poly-alcohol substrates Jung and Spe1tz6* have shown that secondary alcohols are oxidized selectively in the presence of primary alcohols by treatment of the trimethylsilyl or t-butyl ethers of the alcohols with triphenylcarbonium salts [e.g.(48) +(49)]; these oxidations proceed via initial hydride abstraction followed by loss of the group on oxygen.OH I 0 i MefSiCl ii Ph3C %OH %OH +’ Chromyl chloride adsorbed on silica-alumina is an effective reagent for the oxidation of alcohols to carbonyl compounds when the use of neutral non-aqueous conditions is imp~rtant.~’ The method also offers the manipulative convenience provided by the recently described method based on the use of chromic acid on anion-exchange resins [see Ann. Reports (I?) 1976 73 p. 3201. Yet another oxidizing agent is pyridine oxodiperoxychromium(vI) one of the family of modified chromic acids which is prepared by adding hydrogen peroxide to a mixture of pyridine and Cr03 in water.70 The homogeneous oxidation of secondary alcohols to ketones by molecular oxygen can be effected at ambient temperature in the presence of PdCl2-Na0Ac,’l and the technique of ‘dry ozonization’ has proved particularly useful for the 66 U.Zehavi J. Org. Chem. 1977,42,2819. ” N. Kornblum and A. Scott J. Org. Chem. 1977,42 399. M. E. Jung and L. M. Speltz J. Amer. Chem. Sue. 1976,98,7882. 69 J. S. Filippo and C.-I. Chern J. Org. Chem. 1977 42 2182. ’O G. W. J. Fleet and W. Little Tetrahedron Letters 1977 3749. ” T. F. Blackburn and J. Schwartz J.C.S.Chem. Comm. 1977 157. Synthetic Methods oxidation of cyclopropanes in the a-position leading to cyclopropyl ketones [e.g. (50) -+(51)].72 \ Dv b 03,si02h 0 (50) (51) Shono and his co-worker~~~ have elaborated further on the potential provided by the synthesis of carbonyl compounds by anodic cleavage of glycols and their alkyl ethers (Scheme 17) and Ho and Olah74 have shown that the oxidative cleavage of alkyl methyl ethers to carbonyl compounds can be smoothly accomplished with nitronium tetrafluoroborate.R I RMgBr R-C-CH20Me % R2C0 I OH Reagents i MeOCH2C02Et; ii -e Scheme 17 The reduction of acid chlorides to aldehydes can be effected in excellent yields using the hydridotetracarbonylferrate anion (52) in aprotic solvent^;^' an acyl- hydride complex (53) is implicated in the reaction. An alternative practical RCOCl+ [HFe(C0)4]- + R-C=O + RCHO HFe(C0)4 (52) (53) synthesis of aldehydes from carboxylic acids is via reduction of the corresponding sym-triazolium salts with NaBH4 followed by hydrolysis of the resulting sym -tria~olines.~~ Highly substituted ketones are produced by the acylation of cu-anions of carb- oxylic acid salts with acid chlorides (Scheme 18),77and Pittman and Hanes7' have shown that the polymer-bound bis(tripheny1phosphine)chlorocarbonylrhodium compound (54) is an excellent regeneratable reagent for the synthesis of ketones from acid chlorides and organolithium reagents (Scheme 19).Reagents i LiNPr,'; ii RCOCI; iii A Scheme 18 72 E. Prokseh and A. de Meijere Angew. Chem. Internat. Edn. 1976,15,761. 73 T. Shono H. Harnaguchi Y.Matsumura and K. Yoshida Tetrahedron Letters 1977 3625. 74 T.-L.Ho and G. A. Ohal J. Org. Chem.. 1977,42,3097. 75 T. E. Cole and R. Pettit Tetrahedron Letters 1977 781. 76 G. Doleschall Tetrahedron 1977 32 2549.77 A. P. Krapcho D. S. Kashdan E. G. E. Jahngen and A. J. Lovey J. Org. Chem. 1977,42,1189. C. U. Pittman and R.M. Hanes J. Org. Chem. 1977.42 1194. 324 G. Pattenden RhCl(CO)(PPh3)2 I P PPh&RhCl(CO) ' Jli, (54) iii PPhz)zRh"'(R2CO)R'(CO) R'COR' Reagents i PPh2; ii R'Li; iii R'COCI; iv A Scheme 19 The conversion of nitro-groups into carbonyl groups is well known and of considerable value in synthesis. An extraordinarily simple method for effecting this conversion which is based on the Nef reaction involves oxidation by 'dry oxida- tion' whereby the nitro-compound is simply embedded into activated basic silica gel for 2 days; the carbonyl compound is then simply eluted from the silica t-Butyl hydroperoxide in the presence of [VO(aca~)~] as catalyst can be used in an alternative mild oxidative procedure for the nitro +carbonyl conversion.s0 In what amounts to a unique combination of electrolytic decarboxylation and the Moffatt oxidation Mandell et al." have shown that carboxylic acids can be reduced to the lower homologous aldehyde by simple electrolysis in DMSO solution (Scheme 20).A useful method for the homologation of aldehydes (and ketones) is by direct conversion into the corresponding silyl-epoxide psing a-chloro-a-tri- methylsilyl carbanion followed by hydrolysis (Scheme 2 l).82*83 -2e + RCH2C02H -RCHz +[R-CH OLSMe2 ] -+ RCHO (-C02) DMSo f+ Scheme 20 Acid chlorides are smoothly coupled in the presence of [Fez(C0)9] producing symmetrical ketones,84 and Olah and his co-workers have shown that the simple Friedel-Crafts acylation of tetra-alkyl-silanes provides a useful route to unsym- metrical dialkyl ketones (Scheme 21).85 Organo-tin reagents have featured in a number of synthetically useful trans- formations in the past few years.In a further demonstration of their unique reactivity Stills6 has shown that the ease with which alkyl-stannanes undergo oxidation provides a useful entry to carbonyl compounds of type (55) (Scheme 23). 79 E. Keinan and Y. Mazur J. Amer. Chem. Soc. 1977 99 3861. P. A. Bartlett F. R. Green tert. and T. R. Webb Tetrahedron Letters 1977 331. " L. Mandell R. F. Daly and R. A. Day I. Org. Chem. 1977 42 1461. 82 C. Burford F. Cooke E. Ehlinger and P.Magnus J. Amer. Chem. Soc. 1977,99 4536. 83 F. Cooke and P. Magnus J.C.S. Chem. Comm. 1977 513. 84 T. C. Flood and A. Sarhangi Tetrahedron Letters 1977 3861. '' G. A. Olah T.-L. Ho G. K. S. Prakash and B. G. B. Gupta Synthesis 1977,677. W. C. Still J. Amer. Chem. Soc. 1977 99 4836. Synthetic Methods 325 0/&SiMe % RCH2CH0 Reagents i Me$iCH(Li)CI; ii H2SOd-MeOH-HZO Scheme 21 RCOCl+ FeZ(C0)9 + RCOR R'COCI + R4*Si *''I3 + R'COR~ Scheme 22 Reagents i Me3SnLi; ii RLi; iii Cr03,2CsHsN Scheme 23 Thioketals en joy widespread use for the protection of carbonyl compounds and are also used as a means of inverting the normal polarity of the =C=O group (i.e. carbony1 umpolung). A useful new method for their formation is by reaction with thiosilanes in the presence of various acid catalyst^.^' Benzeneseleninic anhydride holds promise as a useful alternative to existing reagents for the regeneration of carbonyl compounds from their 1,3-dithiolan derivatives." The same reagent is also useful for the hydrolysis of oximes and semicarbazones to carbonyl corn pound^.'^ A simple alternative to conventional methods for the conversion of thioacetals into the parent carbonyl compound is to irradiate them in the presence of oxygen.9o The interesting electrophilic reagent Me3SiI is also highly recommended for the regeneration of carbonyl compounds from ketals under non-aqueous condition^.^^ Functionalized Aldehydes and Ketones.-Ketone enolates play pivotal roles in a wide range of synthetic transformations yet their regiosezective formation is by no means an easy task.In an excellent review on this subject d'Angelo has sum- marized the methods available for accomplishing this end and also outlined the major uses of the enolates in synthesis.92 Contemporaneously Jackman and Large93 have reviewed the 'Structure and Reactivity of Alkali Metal Enolates' and Rasmu~sen~~ has summarized the recent developments in the preparation and *' D. A. Evans L. K. Truesdale K.G. Grimm and S. L. Nesbitt J. Amer. Chem. SOC.,1977,99 5009. D. H. R. Barton N. J. Cussans and S. V. Ley J.C.S. Chem. Comm. 1977 751. 89 D. H. R. Barton D. J. Lester and S. V. Ley J.C.S. Chem. Comm. 1977,445. 90 T. T. Takahashi C. Y. Nakamura and J. Y. Satoh. J.C.S. Chem. Comm. 1977 680.91 M. E. Jung,W. A. Andrus and P. L. Ornstein Tetrahedron Letters 1977,4175. 92 J. d'Angela Tetrahedron,1976 32 2979. 93 L. M. Jackman and B. C. Lange Tetrahedron,1977,33 2737. 94 J. K.Rasmussen Synthesis 1977 91. 326 G. Pattenden reactions of silyl enol ethers derived from aldehydes and ketones. In the light of these reviews it is interesting that treatment of a-halogeno-ketones with zinc trimethylsilyl chloride and tetramethylethylenediamine (TMEDA) provides a regioselective method for the preparation of silyl enol ethers of the more substituted type [uiz.(56)],95and that the reaction between n-butyl-lithium and THF at 25 "C (56) (R= H) (R =Cl) affords an exceptionally mild method for the preparation of the lithium enolate of acetaldehyde in essentially quantitative yield [(57) -+ (58)].96 Developments in 'methods' for controlling the directionality of the familiar aldol condensation continue.Heathcock and his co-workers9' have observed complete regioselectivity in a number of simple aldol condensations where there is a bulky group R present in the enolate i.e. (2)-enolate (59) leads to the erythro-product while (E)-enolate (60) leads to the threo-product. (E)-(60) Efficient crossed aldol condensations between enol silyl ethers and carbonyl compounds under the influence of a catalytic amount of tetrabutylammonium fluoride,98 or in the presence of TiC14,99 have been described. The interesting boron enolates (61) and (63) feature in directed aldol condensations between two carbonyl compounds the di-n-butyl derivative (61) producing aldol (62) and the 9-BBN derivative (63) leading to the opposite regioselectivity [uiz.(64)].'0° 95 G.M. Rubottom R. C. Mott and D. S. Krueger Synth. Comm. 1977,7 327. 96 M. E. Jung and R. B. Blum Tetrahedron Letters 1977 3791. 97 W. A. Kleschick C. T. Buse and C. H. Heathcock J. Amer. Chem. SOC., 1977,99 247. 98 R. Noyori K. Yokoyama J. Sakata I. Kuwajima E. Nakamura and M. Shimizu J. Amer. Chem. SOC. 1977,99 1265. 99 K. Banno Bull. Chem. SOC.Japan 1976,49,2286. loo I. Inoue T. Uchimaru and T. Mukaiyama Chem. Letters 1977 153. Synthetic Methods 327 7 THR OBBU; RCHob Two apparently useful methods for controlling carbonyl group condensations and which ultimately lead to practical syntheses of a@-unsaturated carbonyl systems have been developed (Scheme 24).In the first of these a keto-ester (65)is employed as a ketone-specific enol equivalent in reactions with aldehydes,"' and in the second method use is made of an enol-silane of an acyl-silane as a specific enol of an aldehyde in condensation with an acetal leading to (66).Io2 0 R2 2 A R' )(& 0 R' L R R' CO,Et L,R1%o&Rl& R3 RZ R3 SiMe R' R' (66) Reagents i NaOEt-(Et02C)z; ii R3CHO; iii KHC03; iv BF3-R2CH(OR3)2; v Bu4& Scheme 24 A number of alternative syntheses of @-unsaturated aldehydes and ketones have been reported during the period covered by this Report and these are collected in Scheme 25.'03-'06 Methods for the synthesis of a@-unsaturated alde- hydes from carbonyl compounds by two- and three-carbon homologation pro- cedures have also been reported (Scheme 26).107,108 lo' G.M. Ksander J. E. McMurry and M. Johnson J. Org. Chem. 1977,42 1180. lo* T. Sato M. Arai and I. Kuwajima J. Amer. Chem. SOC.,1977,99 5827. lo3 K. Yakakoto 0.Nunokawa and J. Tsuji Synthesis 1977 721. '04 A. A. Schegoler W. A. Smit S. A. Khurshudyan V. A. Chertkov and V. F. Kucherov Synthesis 1977,324. lo' V. Reutrakul and W. Kanghae Tetrahedron Letters 1977 1377. E. Friedrich and W. Lutz Angew. Chem. Znternat. Edn. 1977,16,413. lo' T. Nakai T. Mimura and A. Ari-Izumi Tetrahedron Letters 1977 2425. '08 S. F. Martin and P. J. Garrison Tetrahedron Letters 1977 3875. 328 G. Pattenden SiMe + CI,CHOMe A R-o Ref.103 R' + RC-CH +RCO BF4-+ArH + Ref. 104 R Ref. 105 Cyu-+ oosiMe3 iv Cl;roSiMe3 OOH Ref. 106 v'vi* ao Reagents i TiC14; ii PhSOCH2C1; iii A; iv '02; v PPh3; vi MeOH Scheme 25 j" \ SCONMe S II Reagents i MgBr; ii NaH-CICNMe2; hi A; iv LiNPr'2-MeS2Me; v Hg"; +-vi Ph3P / OMe; vii H+ Scheme 26 The Claisen rearrangement of 1-siloxy-3-oxahexa-1,5 -dienes provides a useful new approach to py-unsaturated ketones (Scheme 27),lo9 and Reuter and Salomon"o have shown that tris(tripheny1phosphine)ruthenium is an efficient cata- lyst for the thermal rearrangement of diallyl ethers to y8-unsaturated aldehydes [(67)+(68)]; in the latter sequence the catalyst first effects regiospecific iso-merization to an ally1 vinyl ether which then undergoes the conventional Claisen rearrangement.The acylation of olefins with acetyl hexachloroantimonate at low temperatures in the presence of a hindered tertiary amine also affords an interes- J. L. C. Kachinski and R. G. Salomon Tetrahedron Letters 1977 3235 'lo J. M.Reuter and R. G. Salomon I. Org. Chem. 1977,42 3360. Synthetic Methods 329 +R _iii DoSiMe3 R \ Reagents i RCOCHN2; ii MesSiCl; iii HI04-MeOH Scheme 27 (67) (68) ting approach to py-unsaturated ketones [e.g. (69)-+ (7O)J;'" this sequence pro- bably involves an 'ene' reaction. ag! i. MeCO;. SbCl; ii (-H+)hindered amine (49) (70) The oxidation of a methylene group a-to a ketone function to form an a-diketone is usually effected by reagents like Se02 or alkyl nitrites.Wasserman and Ives112 have now shown that the same transformation can be smoothly accom- plished via reaction between the corresponding enamine of the ketone and singlet oxygen. Aldehydes can be converted into a-diketones via their dithian anions using pentacarbonyliron as a carbonylating agent (Scheme 28).'13 In another Reagents i (HSCH2)2; ii Bu"Li; iii Fe(C0)S; iv R21; v H20 Scheme 28 interesting new approach to a-diketones use is made of tosylmethyl isocyanide as a masked formaldehyde (Scheme 29).lI4 '" H. M. R. Hoffmann and T. Tsue Rima J. Amer. Chem. Sue. 1977,99,6008. ''* H. H. Wasserman and J. L. Ives J. Amer. Chem. Sue. 1976,98,7868. 'I3 M. Yamashita and R. Suemitsu J.C.S. Chem. Comm. 1977,691.D. van Leusen and A. M. van Leusen Tetrahedron Letters 1977 4233. 330 G.Pattenden Reagents 1 BuLi; ii R'COCI; iii H+ Scheme 29 Several new useful syntheses of 1,4-diones have been described. Lithium enolates derived from ketones can be coupled with copper(1) halides or with Cu(OTf)z to give symmetrical 1,4-diones (Scheme 30),115*116 and Cooke and Parlman"' have shown that organo-tetracarbonylferrates undergo Michael addi- tion with enones leading to unsymmetrical 1,4-diones of type (71) (Scheme 30). 0 +[RFe(CO)J hRAy 0 0 (71) Reagents i Cu(0Tf)z or CuCIz; ii H+ Scheme 30 2-Hydroxycyclobutanes feature in an alternative route to 1,4-diones,'l8 and the acylation of butenolides followed by acid work-up provides another attractive route to this functionality (Scheme 31).'l9 Reagents i BuLi; ii DHP-H+; iii Hg"CI; iv RMgX; v HIO,; vi Ac20-MeC(OEt)3; vii AcOH-H20 Scheme 31 Y.Ito T. Konoike T. Harada and T. Saegusa J. Amer. Chem. SOC.,1977,99 1487. Y. Kobayashi T. Taguchi and E. Tokuno Tetrahedron Letters 1977 3741. M. P. Cooke and R. M. Parlman J. Amer. Chem. SOC.,1977,99,5222. A. Murai M. Ono andT. Masamune J.C.S. Chem. Comm. 1977 573. 'I9 M. Asaoka N. Sugimura and H. Takei Chem. Letters 1977 171. Synthetic Methods 331 Grobel and Seebach’” have provided an excellent account of the umpolung of carbonyl reactivity through sulphur-containing reagents. They stress in their review that the term masked functionality should be reserved for those cases in which the normal polarity of a group is inverted and that latent functionality should be used in cases where the reagent exhibits the normal polarity of the hidden (or ‘masked’) group.It is interesting that Dolak and Brysonl2’ have demonstrated that two sulphur atoms as in dithians are not actually necessary for the stabilization of adjacent carbanion centres. These workers have shown that when tertiary-butyl- lithium is used anions from simple alkyl phenyl sulphides can be prepared. In some related studies Fuji et have described the use of 1,3-oxathians as equivalents of acyl anions; since these are cleaved under milder conditions than the corresponding dithians they may ultimately have wider utility as equivalents of acyl anions. Anions derived from cyclic vinyl ethers constitute a useful series of substituted acyl anions [e.g.(72) +(73)],’23 and Magnus and his co-worker~’~~ have outlined (.9 +Q-Qvy-.-+ H+ 0 (72) (73) the use of the ally1 anion derived from allyltrimethylsilane as an effective 0-acylcarbanion equivalent (Scheme 32). ASiMe HO Reagents i BuLi; ii >O ; iii m-CIC6H4C03H; iv H+;v Jones oxidation Scheme 32 N-Nitromethylphthalimide has been employed in synthesis as an equivalent of formyl anion,125 and 2-lithio-3,3-diethoxypropene (74) is a useful a-acrolein carbanion equivalent.’26 In spite of all the current interest in dithian anions as equivalents of carbonyl-group anions the corresponding formyl cation is just as inaccessible as its anion. In I2O B.-T. Grobel and D.Seebach Synthesis 1977,357. 12’ T. M. Dolak and T. A. Bryson Tetrahedron Letters 1977 1961. 12’ K. Fuji M. Ueda and E. Fujita J.C.S. Chem. Comrn. 1977 814. 123 R. K. Boeckman and K. J. Bruza Tetrahedron Letters 1977,4187. D. Ayalon-Chass E. Ehlinger and P. Magnus J.C.S. Chem. Comm. 1977 772. ’” F. G. Cowherd M.-C. Doria E. Galeazzi and J. M. Muchowski Canad. J. Chem. 1977 55,2515. 126 R. K. Boeckman and M. Ramaiah J. Org. Chem. 1977,42,1581. -/SiMe 332 G. Pattenden this case Taylor and La Mattina12' have now shown that the chloride (75) is a useful equivalent. n ( 7) + LC02Et -+ s\/s C' I CI LJ (75) 10 Carboxylic Acids and Anhydrides Trimethylsilyl iodide has emerged as an exceptionally efficient reagent for the cleavage of esters to carboxylic acids under neutral conditions.128*129 Hindered esters undergo hydrolysis at room temperature using so-called 'anhydrous hydroxide' generated via the reaction of two equivalents of potassium t-butoxide with one equivalent of water.13' The monohydroboration of 1-alkynyl-silanes followed by oxidation of the resulting 1-boro-1 -silyl-alkene (76) with H202-NaOH provides an attractive synthesis of carboxylic acids from terminal acetylenes (Scheme 33);13' a feature of R'CrCH -+ R'CGCSiMe3 RIYBR' + RCH2COzH SiMe (76) Reagents i Rz2BH; ii NaOH-Hz02 Scheme 33 the method is that it can be applied to the synthesis of &unsaturated acids starting with conjugated enynes. Optically pure a-hydroxy-acids are produced from 6-keto-acids by reduction with an actively fermenting mutant of Succharumyces cere~isiae.'~~ They are also obtained from ap-unsaturated carboxylic acids via the corresponding amide with S-proline according to Scheme 34.'33 The novel fragmentation of tetramethylsilyl ethers derived from bicyclic cylo- propanols initiated by oxidation with Pb(OAc), has provided an expeditious synthesis of w-unsaturated acids [viz.(77) -+(78)].134o-Unsaturated acids are also produced from the nucleophilic ring opening of lactones with phenylselenide ion followed by elimination of the selenium residue (Scheme 35).'35 12' E. C. Taylor and J. L. La Mattina Tetrahedron Letters 1977 2077. M. E. Jung and M. A. Lyster J. Amer. Chem. SOC., 1977,99,968. 129 T.-L. Ho and G.A. Olah Angew. Chem. Internat. Edn. 1977,15 774. 13' P. G. Gassman and W. N. Schenk J. Org. Chem.. 1977 42 918. 13' G. Zweifel and S. J. Backlund J. Amer. Chem. Soc. 1977 99 3184. 132 B. S. Deol D. D. Ridley and G. W. Simpson Austral. J. Chem. 1976,29 2459. 133 S. Terashima and S.-S. Jew Tetrahedron Letters 1977 1005. 134 G. M. Rubottom R. Marrero D. S. Krueger and J. L. Schreiner Tetrahedron Letters 1977,4013. 135 D. Liotta and H. Santiesteban Tetrahedron Letters 1977,4369. 12' Synthetic Methods CH,R' Reagents i ;ii NBS; iii Bu3SnH; iv Hf a0,, H Scheme 34 Me,SiO 0 u,iii,w (77) (78) Reagents i Pb(OAc)*-HOAc; ii H20; iii PhSe-; iv H202. Scheme 35 Minami and Kuwajima have found that the hindered base (79) can be used to produce the relatively inaccessible enolate anions of saturated anhydrides; the anions can then be used in condensation reactions with aldehydes for example; this provides a useful synthesis of lactones (Scheme 36).136 Nucleophilic addition of Reagents i RCH2CHO; ii NaHC03 Scheme 36 136 N.Minami and I. Kuwajima Tetrahedron Letters 1977 1423. 334 G. Pattenden methoxycarbonylmethylenetriphenylphosphoraneto the unsymmetrical anhydride (80) has led to a facile synthesis of the ylidenetetronic acid derivatives (81) and (82); the former has been isolated from Penicilliurn rnulticolor. 13' Mew 0 -Me02C* + 0 Me0,C 11 Esters and Functionalized Esters Nowhere is the synthetic application of catalysis by crown-ethers better illustrated this year than in the synthesis of esters by the traditional malonic ester synthesis.Hunter and Perry13* have shown that in the presence of 18-crown-6 ether the whole malonic ester synthesis can be performed essentially in 'one pot' where the crown ether (a) accelerates the hydrolysis of the ester in stage one by potassium hydroxide and (6)allows decarboxylation of the potassium carboxylate under mild conditions in stage two (Scheme 37). COzEt KOH / RCH2Br+CH,(C02Et)z -RCH2CH 18-Crown-6 \ CO2Et Stage 1 1 C02K RCH,CH,CO,Et Stage 2 RCHzCH/ Scheme 37 Primary amines can be converted into esters in a two-step process involving reaction with a pyrylium salt followed by pyrolysis of the resulting pyridiniurn salt with the corresponding sodium carboxylate (Scheme 38).139 CH2R' Scheme 38 M.J.Begley D. R.Gedge and G. Pattenden J.C.S. Chem. Comm. 1978 60. 13' D. H. Hunter and R. A. Perry Synthesis 1977 37. 139 U. Gruntz A. R. Katritzky D. H. Kenny M. C. Rezende and H. Sheikh J.C.S. Chem. Comm. 1977 701. 13' Synthetic Methods Two vinylation methods provide useful routes to a@-and py-unsaturated esters. In one method Miyaura et ~21.~~' have found that the reaction between Cu' methyl- trialkylborates and P-bromo-acrylates proceeds in a stereospecific manner leading to (2)-and (E)-aP-unsaturated esters and in the second method Millard and Rathke141 show that py-unsaturated esters are produced by vinylations of lithium ester enolates in the presence of a catalyst produced from the addition of Bu"Li to Ni" bromide (Scheme 39).py-Unsaturated esters are also obtained from P-keto- Scheme 39 esters via the Shapiro reaction involving conversion into the corresponding tosyl- hydrazone metallation alkylation and quenching with ammonium chloride (Scheme 40).14* C0,Et N-NLiTs N-NHTs C0,Et ii iii 0 -+ C02Et Reagents i LiNPr'z; ii MeI; iii H+ Scheme 40 Lactones.-Benzeneperoxyseleninic acid which can be generated in situ from benzeneseleninic acid and hydrogen peroxide holds promise as a useful alternative reagent in the Baeyer-Villiger synthesis of lactones from ring ketones.'43 1,3-Dienes are smoothly transformed into lactones by conversion into the mono-epoxide followed by complexation with [Fe2(CO)S] and oxidation [e.g.(83) -+(84)],'44 and two groups of workers have shown that certain unsaturated carboxylic acids react with benzeneselenyl chloride to afford phenylselenyl lactones [e.g. (85)-+ (86)].'45 x0-y-Jo 4 +php!J --*/A$ \ CO H 0-4 0 0 (83) (84) (85) (86) 140 N. Miyaura N. Sasaki M. Itoh and A. Suzuki Tetrahedron Letters 1977 3369. lA1 A. A. Millard and M. W. Rathke J. Amer. Chem. SOC.,1977,99,4833. 142 C. A. Bunnell and P. L. Fuchs J. Amer. Chem. SOC.,1977,99 5184. 143 P.A. Grieco Y.Yokoyama S.Gilman and Y. Ohfune J.C.S. Chem. Comm. 1977,870. G. D. Annis and S. V. Ley J.C.S. Chem. Comm. 1977,581. 14' K.Nicolaou and Z. Lysenko J.C.S. Chem. Comm. 1977 293; D. L. J. Clive and G. Chittattu ibid. p. 484. 336 G.Pattenden 3-Substituted furanoterpenes occur widely in nature and can be obtained by reduction of the corresponding but-2-enolides with di-isobutylaluminium hydride. Two approaches to substituted but-2-enolides proceed via the corresponding P-ylidenelactone (87),'46 and by direct prenylation of a but-2-enolide (Scheme 41).14' Reagents i EtOH; ii RCHO; iii NaAlEt2H2; iv pMeC6H4S03H; v A1203; vi Bu'zAlH; vii LiNPri2-HMPA; viii RCHzBr Scheme 41 Macro1ides.-Most of the procedures employed in ihe past few years for the synthesis of macrolides from o-hydroxy-carboxylic acids have adopted a strategy whereby the carboxy-group is activated; it is then attacked by the hydroxy-group acting as nucle~phile.~~~-'~~ The 'reverse-activation' technique is best applied using azodicarboxylate-triphenylphosphine and in certain instances this strategy offers considerable advantages over the more conventional method e.g.vermi-culine (89)from (88)151,152 In some related and pyrenophorin (9 1)from (90).152*'53 studies Vorbruggen and Krolikiewi~z'~~ have shown that NN-dimethylformamide di-neopentylacetal functions in the same manner as azodicarboxylate-tri-phenylphosphine. In spite of these developments the carboxyl activation method is much valued in macrolide synthesis and has been used recently; for example in the synthesis of (a) enterobactin (92) a macrolide iron-transporting agent,ls5 (b) brefeldin (93) a fungal metab~lite,'~~"~~ and (c) diploidialide A (94) a steroid- hydroxylation inhibitor.ls8 In an alternative approach to the macrolides Trost and his ~o-workers-'~~ have used anions of sulphones in the presence of 2-6% tetrakis(tripheny1-'46 J.E. McMurry and S. F. Donovan Tetrahedron Letters 1977 2869. 14' D. R. Gedge and G. Pattenden Tetrahedron Letters 1977 4443. "* T. G. Back Tetrahedron 1977 33 3041. 149 K. C. Nicolaou Tetrahedron 1977 33 683. 150 S. Masamune G. S. Bates and J. W. Corcoran Angew. Chem. Internat. Edn. 1977,16 585. 15' Y. Fukuyama C. L. Kinkemo and J. D. White J. Amer. Chem. SOC.,1977,99,646. lS2 D. Seebach B. Seuring H.-0. Kalinowski W. Lubosch and B. Renger Angew. Chem. Internat. Edn. 1977 16 264. lS3 H. Gerlach K. Oertle and A. Thalmann Helu. Chim. Acta 1977,60 2860. lJ4 H. Vorbruggen and K. Krolikiewicz Angew.Chem. Internat. Edn. 1977 16 876. 15' E. J. Corey and S. Bhattacharyya Tetrahedron Letters 1977 3919. 156 E. J. Corey R. H. Wollenberg and D. R. Williams Tetrahedron Letters 1977 2243. 15' R. Baudoug P. Crabb& A. E. Greene. C. Le Drian and A. F. Orr Tetrahedron Letters 1977 2973. 15' T. Ishida and K. Wada J.C.S. Chem. Comm. 1977 337. 159 B. M. Trost and T. R. Verhoeven J. Amer. Chem. SOC.,1977,99 3867. Synthetic Methods n HO OH ro phosphine)palladium as a strategem for the synthesis of the appropriate macro- cycles [e.g. (95) +(96)]. (Ph3P)4Pd C0,Me NaH & LT AcO M e S0,Ph C 0 SOzPh (95) (96) 338 G.Pattenden 12 Nitriles Ziegler and WenderI6' have provided further details of the method of converting carbonyl compounds into nitriles containing an additional carbon atom based on the decomposition of methyl dialkylcyanodiazenecarboxylates(Scheme 42); a modification of this approach uses the corresponding benzenesulphonates.R R R R RAO A RANNHC02h4e R+NHNHCO,Me -RACN CN Reagents i H2NNHC02Me; ii HCN-MeOH; iii NaOMe Scheme 42 Vinyl nitriles are conveniently produced from vinyl halides by treatment with KCN in the presence of a catalytic amount of Pdo complex and crown ethers,162 and the Vilsmeir formylation approach outlined in Scheme 43,provides a useful CHO CN Reagents i POC13-DMF; ii NH20H Scheme 43 synthesis of vinyl nitriles from carbonyl Aldehydes are smoothly converted into vinyl nitriles of the type (97) following cyanoselenylation and oxidative removal of the selenium residue (Scheme 44).'64 Reagents i PhSeCN-Bu3P; ii H202 Scheme 44 13 Alkylation In an extension of their earlier studies Enders and Ei~henauer'~~ have demon- strated that optically pure a-alkyl-substituted aldehydes can be produced by metallation and alkylation of chiral hydrazones.In related studies Whitesell and his co-w~rkers~~~.~~' have observed enantioselective alkylation (optical purities F. E. Ziegler and P.A. Wender J. Org. Chem. 1977,42 2001. D. M. Orere and C. B. Reese J.C.S. Chem. Comm. 1977 280. 162 K. Yamamura and S.-I. Murahashi Tetrahedron Letters 1977,4429. P. C. Traas H. J. Takken and H. Boelens Tetrahedron Letters 1977,2027. 164 P. A. Grieco and Y. Yokoyama J. Amer.Chem. SOC.,1977,99,5210. 16' D. Enders and H. Eichenauer Tetrahedron Letters 1977 191. J. K. Whitesell and S. W. Felman J. Org. Chem. 1977,42 1663. J. Whitesell and M. A. Whitesell J. Org. Chem. 1977 42 377. Synthetic Methods 80-90%) of the cyclohexanone enamine (98) prepared from (+)-truns-2,5-dimethylpyrrolidine and also of the imine (99) containing C-2 0-butyl substitution. (S;83%) n c ..,..LU v (R;81%) (99) A perennial problem that arises with the alkylation of P-dicarbonyl compounds is the concurrent formation of both C-and 0-alkylated products. Clark and have now found that exclusive C-alkylation of P-dicarbonyl compounds can be accomplished using the corresponding H-bonded solvates formed with tetraethyl- ammonium fluoride; the method is a useful alternative to that based on the utilization of thallium(1) enolates.C-2-Substituted cyclohexane-l,3-diones are most conveniently produced from the bis-enol ether (100) according to Scheme 45.169 OMe OMe OMe (100) Me / I Reagents i Na-NH3; ii Bu'Li; iii RX; iv H+ Scheme 45 HBjek and Malek'" have made the interesting observation that alkylation of carbanions of the doubly activated type [uiz. (lol)]with alk-1-enes can be initiated by certain metal oxides and it has been shown that angular allylation of fused cyclic 16* J. H. Clark and J. M. Miller J.C.S. Chem. Comm. 1977,64. E. Piers and J. R. Grierson J. Org. Chem. 1977,42. 3755. "O J. Hajek and J. Malek Synthesis 1977 454. 340 G. Pattenden RlAR2 + fiakyt -dr0RLa,,, (101) R' = R2=C02Et COMe or CN ap-enones can be readily accomplished using allyl-silanes in the presence of TiCI4.l7 Although copper derivatives are well known to add in a conjugate sense to cup-enones most reactive carbon nucleophiles undergo direct attack at the carbonyl group.Cooke and Goswami show that the carbonyl group in the phosphorane (102) has so little reactivity that even alkyl-lithiums add at the conjugate posi- eco2hfe i,ii,BuLi, RX 0 (102) tion.17' In a remarkable demonstration of the directing effect of the phenyl group on the stereochemistry of enolate alkylation it is found that the vicinal bis- alkylation of cyclopentenone with lithium diphenylcuprate followed by alkylation leads to cis-2-alkyl-3-phenylcyclopentanone(103); all other vicinal substitutions have been shown to lead to the corresponding trans-i~omers.'~~ 0 14 Ring Synthesis Further experimental support for some of Baldwin's Rules for ring closure announced last year [see Ann.Reports (B),1976,73,p. 3353 has been obtained by Baldwin and his colleagues. 174,175 They have shown for example that the enolate (104)cyclizes to the enol ether (105) (i.e. 5-endo-trig is disfavoured) whereas the corresponding enolate (106) undergoes ring closure with alkylation on carbon to give the ring ketone (107) (i.e. 6-endo-trig is favoured). The intramolecular coupling of dicarbonyl compounds to cycloalkenes induced by low-valent titanium shows promise as a useful general route to medium- and 17' A.Hosorni and H. Sakurai J. Amer. Chem. SOC.,1977,99 1673. 172 M. P. Cooke and R. Goswami J. Amer. Chem. SOC.,1977,99,642. 173 G. H. Posner and C. M. Lentz Tetrahedron Letters 1977 3215. 174 J. E. Baldwin R. C. Thompson L. I. Kruse and L. Silberman J. Org. Chem. 1977,42 3856. 175 J. E. Baldwin and L. I. Kruse J.C.S. Chem. Comm. 1977 233. Synthetic Methods 341 (106) (107) large-ring carbocycles; McMurry and Kee~'~~ show that the method can be applied in the synthesis of anything between four- and sixteen-membered rings in yields between 70 and 90%. Treatment of propane-1,3-diols under the same conditions leads to cyclopropanes. '" In an interesting synthesis of the tetracyclic sesquiterpene ishwarane (109)Corey and McLaren have applied a 'double insertion' reaction of dibromocarbene into the olefinic and the C-H bond (asterisked) in the cyclohexene (108).'78 (108) (109) Photochemistry has featured in a number of approaches to interesting naturally occurring cyclopentanes published this year.Roberts and his ~o-workers,~~~ for example have shown that photolysis of the bicyclo[2,2,l]heptan-2-one(110)pro-vides a facile entry to the important prostaglandin intermediate (1 1 l) and Barton 0Rz OR' and Hulshof'" have found that photochemical ring contraction of the pyrone (1 12) in the presence of sodium cyanoborohydride leads to the mould metabolite terrein (1 13). Intramolecular [2+2] cycloaddition of dicyclopent-1-enylmethanes(1 14) 0 176 J. E. McMurry and K. L. Kees J. Org.Chem. 1977,42 2655. 177 A. L. Baurnstark C. J. McCloskey T. L. Tolson and G. T. Syriopoulus Tetrahedron Letters 1977 3003. 178 R. M. Cory and F. R. McLaren J.C.S. Chem. Comm. 1977 587. 179 N. M. Crossland S. M. Roberts and R. F. Newton J.C.S. Chem. Comm. 1977 866. 180 D. H. R. Barton and L. A. Hulshof J.C.S. Perkin I 1977 1103. 342 G. Pattenden followed by in situ addition of methanol to the strained three-membered ring in the presumed intermediate has provided a new entry to fused [5,5,5]-ring systems [tlir. (115)Jfound in hirsutic acid and related natural sesquiterpenes.161 (1 14) (1 15) The synthesis of biologically important macrocycles continues to be an active area. Yamamoto and his co-workers'82 have described a stereoselective approach to the humulene molecule which has an eleven-membered ring based on the intramolecular cyclization of the (r-ally1)palladium complex (117) derived from (116) and Kato et avg3have used an intramolecular Friedel-Crafts reaction in a synthesis of several cembrenoid (fourteen-membered) carbon skeletons [e.g.(118)+ (119)l. J. S. H. Kueh M. Mellor and G. Pattenden J.C.S. Chem. Comm. 1978,5. lS2 Y. Kitagawa A. Itoh S. Hashimoto H. Yamamoto and H. Nozaki J. Amer. Chem. Soc. 1977,99 3864. T.Kato M. Suzuki Y. Nakazima K. Shimizu and Y. Kitahara Chem. Letters 1977 705.

ISSN:0069-3030    

DOI:10.1039/OC9777400309

出版商:RSC    

年代:1977

数据来源: RSC

摘要:

14 Biological Chemistry Part (i) Monosaccharides By P. M. COLLINS Department of Chemistry Birkbeck College Malet Street London WC7 E 7HX 1 Introduction It is four years since monosaccharides were last reviewed in Annual Reports and for a comprehensive survey of the work published during that period the reader is referred to the Specialist Periodical Reports on carbohydrate chemistry the 10th volume of which appears this year. The present report is necessarily highly selec- tive. 2 Glycosides The search for efficient stereospecific syntheses of 0-glycosides continues. Angyal’s have shown that calcium or strontium chloride can affect the outcome of the Fischer glycosidation of sugars in which the two hydroxy-groups adjacent to the anomeric centre have the erythro-configuration.Complex forma- tion occurs with the anomer which has three oxygen atoms in an axial-equatorial- axial sequence on six-membered rings or in a cis-cis sequence on five-membered rings. In this way good yields of methyl aldosides’ and ketosides2 were obtained which are not otherwise readily available. Glycosidations utilizing halide displacements have undergone many refinements over the years and are now used with much success. Lemieux’s group proposed three conditions for the best yields of a-glycosides by halide-ion-catalysed glyco- sidations from glycosyl halides with non-participating groups at C-2. Firstly the concentration of halide ion should be such that anomerization of the glycosyl halide is faster than the displacement of the less reactive a-halide by the alcohol secondly the glycosyl halide should react with the alcohol without assistance from metal ions or highly polar solvents and finally the reaction conditions should minimize the formation of glycosidic products other than the desired a-gly~oside.~ Based upon these considerations several a-linked disaccharides have been synthesized in good yields and in a highly stereoselective manner by the reaction of perbenzylated glycopyranosyl bromides with suitably protected sugar derivatives in the presence of S.J. Angyal C. L. Bodkin,and F. W. Parrish Austral. J. Chem. 1975,28 1541. * S. J. Angyal C. L. Bodkin J. A. Mills and P. M. Pojer Austral. 1.Chem. 1977 30 1259. R. U. Lemieux. K. B. Hendriks R. V. Stick and K.James J. Amer. Chem. SOC..1975,97,4056. 343 344 P. M. Collins tetraethylammonium bromide. The Lea blood-group antigenic determinant 0-(a-L-fucopyranosy1)-(1 -* 4)-[ 0-(P-D-galactopyranosyl)-(l + 3)]-2-acetamido-2-deoxy-D-glucose was synthesized using similar principle^,^ as was 0-(a-L-fuco-pyranosy1)-(1 -+ 2)-[0-(a-D-galactopyranosyl)-(l +3)]-D-galaCtOSe which forms part of the antigenic determinant of blood-group B substance.' One of the key steps in the synthesis of this trisaccharide is the a-D-galactosylation of disaccharide (1) with (2). The D-galactopyranoside derivative (3) is an important intermediate in the synthesis of disaccharide (1) since after fucosylation the 3,4-0-iso-propylidene group was replaced by a 3,4-0-(ethoxyethylidene)group which was regiospecifically opened on partial hydrolysis to give the corresponding axial 4- acetate.P-Glycosides of 0-(a-L-fucopyranosy1)-(1 +4)-[O-(P-D-galacto-pyranosy1)-(1 +3)]-2-acetamido-2-deoxy-~-glucose have also been prepared using either 8-ethoxycarbonyl- or 8-methoxycarbonyl-octanol.6Semisynthetic antigens were then prepared from these esters by conversion into an 8-azidocarbonyfoctyl derivative which reacts with the free amino-groups in bovine serum albumin. Antibodies raised with the trisaccharide antigen precipitated blood-group Lea substance and agglutinated Lea red-blood cells. PhCHl? ,OCH,Ph PhCH,OG4 Br OCH,Ph Me@OCH2Ph PhCH20 CH,Ph (3) The 2-0-benzyl group is the most popular non-participating group in glyco- sylations although others have been used.For example 6-0-acetyl-2-azido-3,4- di-0-benzyl-P-D-glucopyranosyl chloride reacted with benzyl 2-azido-3,4-0- benzyl-0-D-glycopyranosideunder silver-perchlor ate-catalysedconditions to give an a-linked (1+6) disaccharide without participation from the azido-gro~p.~ Syntheses of 1,2-trans -linked disaccharides from glycopyranosyl bromides possessing participating groups at C-2 have been reported' which use silver trifluoromethanesulphonate as the catalyst and 1,1,3,3-tetramethylurea as the pro- ton acceptor. Thus glycosylations at hydroxy-groups situated individually at C-2 C-3 C-4 and C-6 in suitably protected sugar derivatives have been achieved by this method with 2,3,4,6-tetra-O-acetyl-a -D-glucopyranosyl bromide.The result- ing (1-2)- (1+3)- (1-4)- and (1+6)-@-linked disaccharide derivatives were 'R. U. Lemieux and H. Driguez 1.Amer. Chem. Soc. 1975,97,4063. ' R. U. Lemieux and H. Driguez I. Amer. Chem. Soc. 1975,97,4069. 'R. U. Lemieux D. R. Bundle and D. A. Barker J. Amer. Chem. Soc. 1975,97,4076. 'H. Paulsen and W. Stenzel Angew. Chem. Internat. Edn.,1975,14 558. S. Hanessian and J. Banoub Carbohydrate Res. 1977 53 C1-3. Biological Chemistry -Part (i) Monosaccharides 345 respectively formed in a high state of anomeric purity in preparatively significant yields and with much manipulative simplification compared with previously used methods. Glycosylating agents other than glycosyl halides have been studied in the past few years.The well-established orthoester procedure continues to attract attention and it has been shown that the basicity of the alcohol used influences the ratio of a-and @-glycosides formed.' Thus the ethyl derivative (4) gave only the @-glycoside whereas the chloroethyl derivatives (5) (6) and (7) yielded mixtures containing 16 50 and 67% respectively of the corresponding a-glycoside. Disaccharide derivatives are formed when 1-0-aryloxycarbonyl-pyranose derivatives which possess non-participating groups at C-2 are fused with partially blocked sugar derivatives as illustrated for example by the condensation of the 1-0-aryloxycarbonyl mannose derivative (11) with 1,2,3,4-tetra-O-acetyl-p-D-glucopyranose to give the a (1 +6)-linked disaccharide derivative (15)" When participating groups are present at C-2 then the reaction takes a different course and orthoesters are produced in good yields.AcOUO (11) R' =OCOZPh R2 = H Mc (12) R' =OH R2 = H (4) R=OEt (13) R' = C1 R2 = H (5) R = OCH2CEI2C1 (14) R' = H R2=CECH (6) R = OCH2CHC12 CH,O + (7) R = OCHzCC13 (8) R=SEt R'= ACO-(9) R = iEtCPh3 (15) R~=H 0 (10) R= tOCH,-( YOMe OAc oAc Sinay and his co-workers" have introduced what appears to be an excellent Q -glycosylating reagent. They have shown that 2,3,4,6-tetra-O-benzyl-a -D-glycopyranosyl chloride reacts with N-methylacetamide to give 1-0-(N-me thy1)ace timidyl-2,3,4,6 -te tra- 0-benzyl-P -D-glucopyranose in 88Yo yield. This compound readily glucosylates free hydroxy-groups in partially protected sugars [see compound (16)].For example with methyl 2,3,6-tri-O-benzyl-a -D-gluco- pyranoside in anhydrous benzene containing toluene-p-sulphonic acid it gave methyl hepta-0-benzyl-a -D-maltoside in 85% yield which is remarkably good for 'P. J. Garegg and I. Kvarnstrom Acta Chem. Scand. 1976 B30 655. 10 Y. Ishido S. Inaba H. Komura and A. Matsuno J.C.S. Chem. Comm. 1977 90. I' J.-R. Pougny J.-C. Jacquinet M. Nassr D. Duchet M.-L. Milat and P. Sinay J. Amer. Chem. Soc. 1977,99,6762. 346 P. M. Collins ,OCH,Ph the glycosylation of this 4-OH group. Eleven glycosides were prepared in 70-92% yield by this method and it was also extended to include a-L-fucosylation with obvious application in the synthesis of natural products of biological significance.Schuerch12 has extended the use of glycosyl sulphonates to the synthesis of disaccharides. Reactions related to this have been developed in which a free anomeric hydroxy-group in an otherwise fully protected sugar derivative is sulphonated and the product is used in situ to glycosylate the aglycone hydroxy- group. For example Perlin andco- worker^'^activated the anomeric hydroxy-groupof 2,3,4,6-tetra-0-benzyl-D-glucopyranose with trifluoromethanesulphonic anhydride and thence formed an LY-D-(~ -+6)-linked disaccharide in 60% yield by the addition of 1,2,3,4-tetra-O-acetyl-~-D-glucopyrznose. In a different appr~ach'~ to the activation of the anomeric position the hydroxy- group at C-1 in 2,3 5,6-di-O-isopropylidenernannofuranose(12) was treated with dichlorocarbene which was generated from chloroform and aqueous sodium hydroxide in benzene in the presence of the phase-transfer catalyst benzyl- triethylammonium chloride.This gave the a-furanosyl chloride (13) which could be isolated in reasonable yield or treated directly with simple alcohols or partially protected sugars to give glycosides or disaccharides respectively in yields in the range 65-85%. Presumably the dichlorocarbene inserts into the 0-H bond and the dichloromethyl aglycone so formed (or a hydrolysed form of it) undergoes nucleophilic displacement by chloride ion attack at the anomeric centre. Several groups have tried for improvements in glycoside synthesis by activation of the alcohol from which the aglycone is derived.Cyclic amide acetals derived from simple vicinal diols or carbohydrates have been used as a source of aglycones in glycoside and disaccharide syntheses." For example condensation of 1-0-acetyl-2,3,5-tri-O-benzoyl-P -D-ribofuranose with the 3,4-cyclic amide derived from 2-0-mesyl-P -D-arabinopyranoside (17) in the presence of stannic chloride gave the intermediate (18) which after hydrolysis yielded the formyl ester of the disaccharide (19). The elegance of this method stems from the regiospecific open- ing of the cyclic amide ring in which the disaccharide linkage is formed at the equatorially oriented hydroxy-group at C-3. Trialkylstannylation of alcohols increases their nucleophilicity. Therefore a good yield of methyl 2,3,4,6-tetra-0-acetyl-~-D-glucopyranoside was formed when the corresponding a-D-glucosyl bromide was treated with tributylstannyl methiodide l2 R.Eby and C. Schuerch Carbohydrate Res. 1976,50 203. l3 J. Leroux and A. S. Perlin Carbohydrate Res. 1976,41 C8. '4 P. Di Cesare and B. Gross Carbohydrate Res. 1977,58 C1. S. Hanessian and J. Banoub. Tetrahedron Letters 1976 661. 347 Biological Chemistry-Part (i)Monosaccharides OBz OBz + (18) X = =NMe2 C1- (19) X = =O and stannic chloride in dichloromethane. l6 Other glycosides were formed by treatment with the appropriate stannyl alkoxide. Alkoxides derived from primary alcohols gave -glycosides whereas those derived from secondary alcohols gave a-anomers.If the Lewis acid was omitted from the condensation and tetraethyl- ammonium bromide used in its place orthoesters were formed by participation from the 2-0-acetyl group upon the anomerized bromide. In this way several orthoesters were produced in excellent yields. Thus acetobromoglucose gave (10) almost quantitatively when treated with the tributylstannyl alkoxide of methyl 2,3-O-isopropylidene-~-D-ribopyranoside under these reaction conditions. Simple aglycones have been produced” from a variety of dialkyl acetals of dimethylformamide e.g. Me,NCH(OR), in which R = Me CHMe2 PhCH2 CH2CMe3 or cyclohexyl since these have been shown to react with peracetylated sugars in the presence of stannic chloride to give almost quantitative yields of 1,2-trans-gl ycosides.Tritylated sugars have been glycosylated.” For example in the presence of trityl perchlorate the anomeric carbon atom in the orthothioacetate (8) was nucleo- philically attacked by 0-6 of 1,2,3,4-tetra-O-acety1-6-0-tr~tyl-~-D-glucopyranose to give a /3(1 -+ 6)-linked disaccharide derivative. The reaction is thought to occur uia the sulphonium ion intermediate (9). Interest in the solid-phase method for the synthesis of oligosaccharides continues. For example 2,3,4-tri-O-benzyl- 1-thio-P-D-glucopyranose has been attached to a polystyrene support by a thioglycosidic linkage and the free hydroxy- group at C-6 has been gly cosyla ted with 6-0-acet yl-2,3,4-tri-0-benzyl-a-D-glucopyranosyl bromide.” The disaccharide was detached from the resin by sequential methylation and cleavage of the sulphonium salt with benzyl alcohol to give fully benzylated 6’-O-acetyl isomaltoside.The presence of the 6-0-acetyl residue in the resin-attached dimer offers future scope for selective deblocking and thence oligomer formation. The hydrolysis of 0-glycosides remains their most studied reaction and many investigations have been reported. One of interest2’ monitored the hydrolysis of p-nitrophenyl tetrahydropyran-2-yl ether as a model for glycosides with cyclo- hepta-amylose 2- 3- and 6-monophosphoric acids to determine their effectiveness l6 T. Ogawa and M. Matsui Carbohydrate Res. 1976 51 C13. ” S. Hanessian and J. Banoub Tetrahedron Letters 1976 657. N. N. Kochetkov L. V. Backinowsky and Y. E. Tsvetkov Tetrahedron Letters 1977 3681.l9 S.-H. L. Chiu and L. Anderson Carbohydrate Res. 1976 50 227. 2o B. Siegel A. Painter and R. Breslow J. Amer. Chem. Soc. 1977,99 2309. 348 P. M. Collins as general acid catalysts for the hydrolysis of glycosides. Only the 3-phosphoric acid showed any net catalysis. The 2- and 6-phosphoric acids were not able to overcome the catalytic suppressing effect which binding to the p -cyclodextrin causes. The synthesis of C-glycosides continues to attract much attention because of their potential as precursors for C-nucleosides. Buchanan and co-workers21 report that ethynylmagnesium bromide reacts with 2,3 :5,6-di-O-isopropylidene-D-man-nofuranose (12) to give a 65% yield of 1,2-dideoxy-4,5 :7,8-di-O-isopropylidene-D-glycero-D-tab-oct- 1-ynitol (20); this efficiently ring-closed to the p-D-manno- furanosylethyne derivative (14) upon monotosylation via the 3-sulphonate (21).On the other hand sulphonation of the 3-benzoate (22) followed by methoxide- catalysed debenzoylation caused ring closure in the opposite sense yielding the talosylethyne derivative (23). Derivatives of this type are of value because they can be readily modified by cycloadditions to the acetylene residue. For example two group^^^,^^ have pre- pared the ribofuranosyl-pyrazole derivative (25) by diazomethane addition to the ribosylethyne (24) and another group24 prepared the closely related derivative (27) by addition of the reagent to (26). Me,C/O '04 (20) R'=R~=H (21) R'=TS,R~=H (22) R' = Bz R2 = H C0,Me C /"NH C0,Me R30YY ORZ OR' (24) R' = R2= R3=CH2Ph (25) R' = R2 = R3 = CH2Ph (26) R'R2 =CMe2 R3 = CPh3 (27) R'R2 = CMe2 R3=CPh3 Formylaminomethylenation of lactones provides C-glycosyl precursors.the mannonolactone derivative (28) condenses with ethyl isocyanoacetate in the J. G. Buchanan A. D. Dunn and A. R. Edgar J.C.S. Perkin I 1976 68. 22 C. M. Gupta G. H. Jones and J. G. Moffatt J. Org. Chem. 1976,41 3000. 23 J. G. Buchanan A. R. Edar M. J. Power and G. C. Williams Carbohydrate Res. 1977 55 225. 24 F. G. de Las Heras S. Y.-K. Tam R. S. Klein and J. J. Fox J. Org. Chem. 1976,41 84. 25 R. H. Hall K. Bischofberger S. J. Eitelman and A. Jordaan J.C.S. Perkin I 1977,743. Biological Chemistry-Part (i)Monosaccharides 349 presence of potassium hydride to yield the manno-octenoate (29).This can be hydrogenated to give the amino-acid derivative (30) which is related to the nucleoside amino-acids found in the polyoxin complex of antifungal agents. If in the condensation the potassium hydride is omitted and 1,5-diazabicyclo-[4,3,0]non-5-ene is used in its place then the oxazole (31) is produced.26 Both condensation products are formed from the oxazolide anion (32) which rearranges either by route (a)to give after protonation (29) or by route (b) to give (31). (28) R=O= (30) Et02C \ (29) R= C= / OHCNH C0,Et 3 Unsaturated Sugars 2,3-Unsaturated hexopyranose derivatives are of value as synthetic intermediates and there is active interest in their synthesis.Fraser-Reid's group2' has recom- mended a high-yielding route to ethyl 2,3,6-trideoxy-a-D-erythro-hex-2-enopy-ranoside (34) in which the 6-deoxy position was formed after the introduction of the double bond. Thus ethyl a-D-erythro-hex-2-enopyranoside(33) was deoxy- genated at C-6 via its primary tosylate which was nucleophilically displaced with sodium iodide in ethyl methyl ketone containing pyridine; the product was reduced to (34) with Raney nickel without detriment to the double bond. Pyridine was essential during the iodide displacement since in its absence the product rearranged to 2-(2-iodo-l-hydroxyethyl)furan.The enone (35) could be readily prepared from (34) but when it was the compound of interest it proved more economical to oxidize the allylic hydroxy-group in (33) iodinate the enone so formed directly at C-6 with triphenoxyphosphonium methodide and follow this by selective hydro- genolysis.A new method which augurs well for the preparation of this class of compounds has recently been introduced by Barton's group.28 They showed that vicinal diol " R. H. Hall K. Bischofberger S. J. Eitelman and A. Jordaan J.C.S. Perkin I 1977,2236. 27 M. B. Yunker S. Y.-K.Tam D. R. Hicks and B. Fraser-Reid Cunud.J. Chem. 1976,54,2411. 28 A. G. M. Barrett D. H. R. Barton R. Bielski and S. W. McCombie J.C.S. Chem. Comm. 1977,866. 350 P.M. Collins Me Me (33) (34) (35) bisdithiocarbonates reacted with tributylstannane in refluxing toluene to give olefins.Thus the glycopyranoside derivative (36) gave in 59% yield the hex-2- enoside derivative (37). The corresponding mannoside also gave (37) in 79% yield. The reaction which appears to be of general applicability occurs by the free- radical mechanism outlined in (36). Nucleosides containing a 2-enopyranosyl unit occur in antibiotics such as blasti-cidin S and they also serve as potential synthetic intermediates for amicetin and plicacetin. Consequently the preparation of the 2,3-dideoxyglyc-2- enopyranosylthymine derivative (40)from the 2,3-di-O-mesylthymine derivative (38) is of interest. The best overall yield of 56% was obtained when the 2,2'- anhydride (39) prepared from the dimesylate (38) by the action of sodium benzo- ate in DMF was isolated and heated with sodium iodide in DMF.Treatment of either (39) or (38) under the more usual Tipson-Cohen conditions (e.g. with added zinc) gave (40) in lower yield. 0 ,Me 0 Ph OMS (38) (39) (40) Methods based upon the Diels-Alder addition of n-butyl glyoxylate (Bu02CCHO) to dienes have been reported for the preparation of 2,3-unsaturated uronate derivative^.^"^' If mono-buta-l,3-dienyl ethers derived from sugars are used as dienes in this reaction then disaccharide derivatives containing a uronate are formed. By reducing the ester group and functionalizing the double bond in 29 T. Yamazaki K. Matsuda H. Sugiyama S. Seto and N. Yam'aoka J.C.S. Perkin I 1977,1654. 30 R.R. Schmidt and R. Angerbauer Angew. Chem. Infernat.Edn. 1977,10,783. 31 S.David A.Lubineau and J.-M. Vatkle J.C.S. Perkin I 1976 1831. Biological Chemistry -Part (i) Monosaccharides 351 these adducts David et aL3’ have developed this reaction into a route to unusual disaccharides. Furanoid glycal derivatives are not easily produced by zinc reduction of furanosyl halides. Therefore the reported3’ conversion of 2,3 :5,6-di-O-isopropylidene-a -D-mannofuranosyl bromide into the unsaturated disaccharide derivative (42) in 59% yield by sodium in tetrahydrofuran could prove of value. The anion (41) which would be formed from the mannosyl halide by bromine atom abstraction presumably rearranges with elimination of acetone to an 0-3 alkoxide derivative which attacks another mannosyl bromide molecule. An unusual reaction which leads to 172-unsaturated pyranoid derivatives has been observed33 to occur between phenyl tetra-O-benzoyl- l-thio-P-D-gluco- pyranoside (43) and an excess of N-bromosuccinimide in refluxing carbon tetra- chloride under visible light; it gives phenyl 2,4,6-tri-O-benzoyl-l-thio-D-erythro-hex- l-enopyranosid-3-ulose (47) in 76% yield.The galacto-isomer of (43) gave the threo-epimer of (47) in 83% yield when similarly treated. The reaction is thought to occur uia a halide intermediate (45) which is reasonable since free-radical bromination at C-1 would be facilitated by the enhanced radical-stabilizing character of sulphur. Elimination of hydrogen bromide from (45) to give the lY2-unsaturated derivative (46) followed by its allylic bromination gives after loss of acyl bromide from C-3 the enone (47).The a-anomer of the glucoside (43) also gave enone (47) but a ten-fold increase in reaction time was required. The orientation of the anomeric hydrogen atoms in the thioglucosides is responsible for this rate difference since radical attack on axial anomeric hydrogen atoms is stereoelectronically favoured. The tetra-O-acetylated analogue (44) gave the corresponding enone (48) in lower yield accompanied by the 2-bromoacetyl derivative (49). &Ti””’ {3SPh R2((-ph RO OR OBr OBz 0 OR ’ (47) R’= R2= Bz (43) R = Bz (45) (46) (48)R’ = R2 = Ac (44)R=Ac (49) R’ = COCH’Br R2 = Ac 4 Dicarbonyl Sugars A mild photochemical method for the preparation of keto- and aldehydo-dicar- bony1 sugars from pyruvate esters of secondary or primary hydroxy-groups of ’2 S.3. Eitelman and A. Jordaan J.C.S.Chem. Comm. 1977 552. 33 R.J. Ferrier and R. H. Furneaux J.C.S. Perkin I 1977,1993. 352 P. M. Collins suitably blocked sugars has been For example 1,2 :5,6-di-O-iso-propylidene-a-D-glucofuranose was esterified with pyruvoyl chloride in benzene containing pyridine and the product irradiated in benzene with U.V. light either directly or after isolation which gave the furanos-3-ulose derivative in 71% yield. Several other isopropylidenated sugars have been similarly oxidized as have suitably blocked sugar acetates. Thus 1,3,4,6-tetra-O-acetyl-a-D-glucopyranose 2-pyruvate (50) gave upon irradiation the very unstable fully acetylated pyranos- 2-ulose derivative (51) which readily rearranged with loss of acetic acid to kojic acid diacetate (52).Thus this oxidation method appears to be one of the few mild enough to oxidize hydroxy-groups in partially acylated sugars. The method has also been applied with success to nucleosides the 5’-O-trityl and 5’-O-benzoyl deriva- tives of 3’-O-pyruvoylthymidine being converted in good yields into the cor-responding 3’-ulose derivatives. These ulose derivatives were also unstable since in pyridine or on silica gel the heterocyclic base was eliminated and a 1-ene-3-one formed. The oxidation reaction appears to be an example of the Norish Type I1 reaction as shown in (50). Microbiological oxidation of methyl a-D-xylopyranoside to the pentopyranosid- 4-ulose (53) has been to occur with Acetobacter suboxydans during four days in 76% yield.The p-anomer on the other hand was 28% oxidized during 30 days. Other pentosides were oxidized only to a small extent and hexopyranosides showed little oxidation. 6 Ac@tOAc OAc Ac0 6:) OAc .xb 0 0 0 OAc OH MeNo (5 1) (52) (53) (50) A base-catalysed degradation of the 3-ulose derivative (54) has been developed3’ into a useful synthesis of the rare deoxyketose derivative (56). A two-phase system of diethyl ether and water containing lithium hydroxide was found to bring the conversion about in 55% yield. The transformation is thought to occur by initial opening of the pyranose ring uia (57) rather than by elimination of methanol and hence via methyl 4,6-O-benzylidene-a-~-erythro-hex-l-en-3-ulose.34 R. W. Binkley J. Org. Chem. 1977. 42 1216. ’’ R. W. Binkley D. G. Hehemann and W. W. Binkley Carbohydrate Res. 1977,58 C10. 36 W. A. Szarek and G. W. Schnarr Carbohydrate Res. 1977,55 C5. 37 J.-C. Fischner D. Horton and W. Weckerle Canad. J. Chem. 1977,55,4078. Biological Chemistry-Part (i) Monosaccharides 353 Several groups have investigated the chemistry of a!-keto-oxirans. Methyl 3,4-anhydro-6-deoxy-a -~-lyxo -hexopyranosid-2-ulose was found to give the chloro-enone (58)when treated with lithium chloride in tetrahydr~furan~~ or with hydrochloric acid in acetone.39 Catalytic hydrogenation over palladium on char- coal selectively opened the an hydro-ring yieIding methyl 3,6-dideoxy-a-~-threo -' hexopyranosid-2-ulose.The sequential oxidation-reduction of partially protected sugars has been adop- ted as a standard procedure for epimerization. However a recent report4' indicates that the reduction step is not always straightforward as illustrated by methyl 2-0-acetyl-4,6-0-benzylidene-c~-~-ribo-hexopyranosid-3-ulose (55) which with sodium borodeuteride in moist methanol or propan-2-01 gave the expected alloside derivative (59) labelled with deuterium at C-3 whereas borodeu- teride reduction in dry propan-2-01 gave a 1 1 mixture of (59) and the [2- 2H]glucopyranoside(60). The formation of (60) may involve an unusual nucleo- philic attack upon C-2 of a 2,3-enediol intermediate. (59) (60) Deoxygenation of hexosulose derivatives by the Wolff-Kishner reaction has been examined again.41 1,5-Anhydro-4,6-0-benzylidene-2-deoxy-~-eryth~o-hex-3-ulose was smoothly converted into 1,5-anhydr0-4,6-0-benzylidene-2,3-dideoxy-erythro-hexitol in 69*/? yield.However the reaction was less satisfactory with glycosidulose derivatives since extensive degradation occurred. Deoxygenation of sugar ketones has also been achieved by reduction of their gem -dithio and related derivatives which are formed by the action of phosphorus pentasulphide in pyridine upon protected keto-s~gars.~' Based upon these findings 1,6-anhydro-3,4-0-isopropylidene-~-~-lyxo-hexopyranosulose gave the bridged derivative (61) whereas 1,2 5,6-di-O-isopropylidene-a -D-ribo-hexofuranos-3-ulose gave the disulphide (62). Reductive desulphurization of these products gave respectively the 2-deoxy derivative corresponding to (61) and 3-deoxy-l,2 5,6-di-0-isopropylidene-a!-D-xylo-hexofuranose. An overall inversion of configuration at C-4 occurred in the transformation of the 3-ulose to the 3-deoxy-derivative ..(41) 38 H. Paulsen and K. Eberstein Chem. Ber. 1976,109 3907. 39 G. S. Hajivarnava W. G. Overend and N. R. Williams Carbohydrate Res. 1976 49 93. 40 D. C. Baker J. Defaye A. Gadelle. and D. Horton J. Org. Chem. 1976,41 3834. 41 D. Horton W. Weckerle L. Odier and R. J. Sorenson J.C.S. Perkin I 1977 1564. 42 P.Koll R.-W. Rennecke and K. Heyns Chem. Ber. 1976,109 2537. 354 P. M. Collins presumably because hydrogen added to the double bond in (62) from its least hindered face.5 Esters Acylations which do not occur readily in pyridine have been to proceed' efficiently in tetrahydrofuran containing tetra-n-butylammonium fluoride. Thus when 5'-0-p-methoxytritylthymidinewas treated with pivalic anhydride in pyri- dine the 3'-pivalate was formed in only 9% yield whereas 95% of the ester was produced from a reaction carried out under the recommended conditions. Improved selectivity in tosylations of diols under phase-transfer conditions has been achieved,44 as shown by methyl 4,6-0-benzylidene-a-D-glucopyranoside which gave the 2-tosylate derivative in 78% yield when treated with tosyl chloride in a mixture of dichloromethane and aqueous sodium hydroxide containing tetra- butylammonium hydrogen sulphate.The mannose derivative exhibited even greater selectivity yielding the 2-tosylate in 95% yield. The use of di-n-butyltin oxide first introduced by Moffa~t~~ in nucleoside chem- istry has been used to selectively esterify pyranosides and their derivative^.^^ With this reagent in methanol methyl a-D-glucopyranoside gave a quantitative yield of the 2,3-0-dibutylstannylene derivative (63) which was converted into methyl 2-0-benzoyl-a-D-glucopyranoside in 80-90% yield by subsequent treatment with benzoyl chloride. Similarly (63) and myristoyl chloride or tosyl chloride gave the corresponding 2-esters. In contrast the P-glucoside was esterified only at its primary hydroxy-group. The method also gave 2-esters with the methyl 4,6-0- benzylidene pyranosides of a -D-gluCoSe a-D-galactose and a-D-allose.It failed with the corresponding derivatives of P -D-glucose and a-D-mannose. This has led to the proposal that the success of this reaction depends in part upon a stabilizing interaction between the tin atom and a suitably positioned methoxy-group as shown in (63). In a related process further selective acylations of secondary positions in hexo- pyranosides have been achieved through the regioselective enhanced nucleophili- city of one hydroxy-group by trialkyl~tannylation.~' In this way methyl a-D-glucopyranoside gave after sequential treatment with bis(tributylstanny1) oxide and benzoyl chloride its 2,6-dibenzoate in 82% yield. The selectivity is thought to arise because stannylation occurred preferentially at an equatorial hydroxy-group which has an alkoxy- (or hydroxy-) group cis to it.Stabilization of the type depicted in (64) is thought to accrue from such an arrangement. The methyl pyranosides of a-D-mannose and P-D-galactose give after similar treatment excellent yields of their 3,6-dibenzoates. The 2,3-and 3-4-cis-hydroxy-groups in these pyranosides would be respectively involved in the formation of the stannyl derivative. It is however not yet clear why the equatorially disposed 3-hydroxy-group should be esterified from both arrangements. 43 S. L. Beaucage and K. K. Ogilvie TetrehedronLetters 1977 1691. 44 P. J. Garegg T. Iversen and S. Oscarson Carbohydrate Res. 1977 53 C5. " D. Wagner J. P. H. Verheyden and J. G. Moffatt J. Org.Chem. 1974,39 24. "R. M. Munavu and H. H. Szmant J. Org. Chem. 1976,41 1832. 47 T. Ogawa and M. Matsui Carbohydrate Res. 1977 56 C1. Biological Chemistry -Part (i) Monosaccharides ,OH HO 0 ,OMe \ ,' Bu/\ Bu,Sn Bu (64) The order of reactivity of hydroxy-groups in carbohydrate derivatives towards acylation continues to attract attention. It has been that the hydroxy- groups in methyl p-lactoside react with benzoyl chloride in pyridine in the order 6'>3' > 6> 2 >2',4'> 3. Nucleophilic displacement remains a major interest in carbohydrate chemistry. Accordingly there have been several studies using trifluoromethanesulphonates (triflates) as good leaving group^.^^.^^ It was found for example that the 3-triflate (65) underwent ready nucleophilic displacement with sodium benzenethiolate at 5 "C with inversion of configuration.Reduction of the 3-phenylthioalloside (66)so formed gave the 3-deoxy-sugar derivative (67). C0,CH :Ph (65) R' = OSO;CF, R2 = H (66) R' = H R2 = SPh (67) R'=R~=H A series of ap-unsaturated esters have been prepared51 as temporary blocking groups for the 5'-position in nucleosides which can be removed by treatment with hydrazine under mild conditions. Deblocking occurs via a hydrazino addition product which cyclizes to a pyrazolidin-3-one with release of the deblocked nucleoside. Carbohydrate ester derivatives provide excellent models for examining the importance of stereochemistry in acyloxonium ion chemistry.Paulsen and his co-workers5* have reported examples of five-membered acetoxonium ions fused trans to conformationally locked pyranose rings. For example treatment of 2,3,4- tri-O-acetyl-1,6-anhydro-~-D-idopyranose with trifluoromethanesulphonic acid gave two such ions fused at the 2,3- and 3,4-positions. The same group have showns3 that 1,3-rearrangernent processes of acetoxonium ions compete with the more common 1,2-rearrangements. They found this by *' R. E. Bhatt L. Hough and A. C. Richardson 1.C.S.Perkin I 1977 2001. 49 L. D. Hall and D. C. Miller Carbohydrate Res. 1976,47 299. so T. H. Haskell P. W. K. Woo and D. R. Watson J. Org. Chem. 1977 42 1302. 51 R. Arentzen and C. B. Reese J.C.S. Chem. Comm. 1977 270. '* H. Paulsen H. Hohne and P.L. Durette Chem. Ber. 1976,109 597. 53 H. Paulsen and 0.Brauer Chem. Ber. 1977 110 331. 356 P.M. Collins observing the racemization of 2,3,4- tri- 0-acety1-1,5-an hydro-D-arabini to1 in hydrogen fluoride containing trifluoromethanesulphonic acid. Racemization can only occur uia the two 1,3-rearrangements shown in Scheme 1. 6 Ethers and Acetals New methods are being applied to carry out traditional carbohydrate etherifications. methyl at ion^^^*^^ and benzylationsss of partially protected sugars have been achieved with methyl and benzyl trifluoromethanesulphonate using the sterically hindered weak base 2,6-di-t-butylpyridine. The former reaction was carried out in refluxing dichloromethane whereas the latter was accomplished at -7O"C the benzyl triflate being prepared in situ from benzyl alcohol and the sulphonic acid anhydride.Sugars have been built into macrocyclic ethers as a source of asymmetry. Several chiral asymmetric 18-crown-6 macrocycles incorporating D-glucose and D-galac- tose residues have been prepareds6 by the condensation of disodio derivatives of the methyl 4,6-0-benzylidene-2,3-di-O-(2-hydroxyethyl)-~-~-hexopyranosides with triethylene glycol bis(tosy1ate). The ability of these crowns to form dia- stereoisomeric complexes with primary and secondary alkylammonium cations in solution has been st~died.~' One unexpected observation was that the galacto-crowns which have one face more sterically hindered on account of the cis-ring junction at C-4 and C-5 formed stronger complexes than the corresponding gluco-crowns.The reason for this is that in for example the diastereoisomeric complex (68) the 0-4 can participate with the macrocyclic ether oxygen atoms in hydrogen bonding and/or electrostatic stabilization of the quaternary ammonium hydrogens. (68) '' J. Arnarp L. Kenne B. Lindberg and J. Lonngren Carbohydrate Res. 1975,44 C5. '' J. M. Berry and L. D. Hall Carbohydrate Res. 1976,47 307. s6 D. A. Laidler and J. F. Stoddart Carbohydrate Res. 1977 55 C1. '' D. A. Laidler and J. F. Stoddart J.C.S. Chem. Comm. 1977,481. Biological Chemistry -Part (i) Monosaccharides The role of acetals in carbohydrate chemistry has been changing during the past decade because synthetically useful reactions have been introduced which open cyclic acetals to give partially blocked sugars.Developments in this area have continued. For example Klemer and her co-workersS8 have extended their studies of the reaction of butyl-lithium on 0-benzylidene-sugar derivatives to various mono- and di- 0-isopropylidene derivatives. Their general findings are illustrated by the conversion of 1,2:3,4-di-O-isopropylidene-6-O-methyl-a -D-galacto-pyranose into the (E)-and (2)-isomers of the unsaturated polyol(72). Abstraction of the anomeric proton is thought to initiate this transformation and the anion (69) so formed subsequently rearranges with loss of acetone to (70) which then eli- minates another acetone molecule to give after protonation at 0-4 the unsaturated lactone (71). Further attack on (71) gives the isomeric products (72) in low yield.rOMe rOMe rOMe HO{ OH CH20Me (72) The synthetic value of this reaction has been studieds9 with methyl 2,3-0-benzylidene-a -L-rhamnopyranoside (73) and its 4-0-methyl derivative (74). Butyl-lithium smoothly converted (74) at -30 "C into the 3-ulose derivative (75) whereas the unmethylated compound (73) reacted only at 0 "C to give a mixture of elimination products. The vigorous reaction conditions needed to abstract a carbon-bonded proton from the 0-4 oxyanion of (73) were thought to be respon- sible for the difference in this case. Me 0 Ox0H (75) Ph (73) R=H (74) R=Me 58 G. Rodemeyer and A. Klemer Chern. Ber. 1976,109,1708. 59 D.M. Clode D. Horton. and W.Weckerle Carbohydrate Res. 1976,49,305. 358 P M. Collins Liptak's studies with the lithium aluminium hydride-aluminium trichloride reducing agent have revealed that the regiospecificity observed in the hydro- genolytic ring cleavage of 2,3-60 and 3,4-0-benzylidene6' derivatives is dependent upon the stereochemistry at the acetal centre. Accordingly the exo-isomer of (73) afforded methyl 3-0-benzyl-a -L-rhamnopyranoside whereas the endo-isomer of (73) gave the 2-0-benzyl derivative. The high degree of stereoselectivity does not appear to arise from steric interaction with the phenyl group in the endo-isomer of (73) since the spin-lattice relaxation times for all carbon atoms in endo- and exo- (73) were found6* to be similar which indicates that rotation of the phenyl groups occurs to the same extent in both isomers.By use of this reagent 0-benzylidene residues have been employed as temporary blocking groups in oligosaccharide ~yntheses.~~ Cleavage of the 1,3-dioxan ring in 4,6-O-benzylidene derivatives with this reagent is less predictable.60 This was also unfortunately found to be the case vith photogenerated ketyl radicals.64 Thus U.V. irradiation of acetophenone for exam- ple in an oxygenated solution of 1,2,3-tri-O-acetyl-4,6-0-benzylidene-@-~-glucopyranose gave a mixture of the 4-0-benzoyl and 6-0-benzoyl derivatives of 1,2,3-tri-O-acetyl-P-D-glucopyranose, plus an adduct formed by ketyl radical addition to the benzylidene acetal carbon atom 7 Halo-and Thio-sugars and other Inorganic Sugar Derivatives Two new to the synthesis of halo-sugars have been introduced which are particularly satisfactory for primary iodo- and chloro-derivatives.The precursors for the iodo-compounds are the readily available cyclic thiocarbonates which have been found to undergo opening of the thiocarbonate ring when treated with methyl Hence the 4,6-thiocarbonate (76) when treated with methyl iodide gave a high yield of 6-deoxy-6-iodo-4-0-methylthiocarbonyl glucoside (78).66 The ring opening occurred via the intermediate (77) which underwent regiospecific attack by iodide at the least hindered primary position. As would be expected from this mechanism methyl 4,6-O-benzylidene-a-~-gluco-pyranoside 2,3-thiocarbonate opened non-regio~pecifically~~ to give a mixture of the 2-and 3-iodo-glucoside derivatives with presumed rnanno- and allo-configura- tions respectively.6o A. Liptik P. Fugedi and P. Ninasi Carbohydrate Res.. 1976 51,C19. 61 A. Liptlk Tetrahedron Letters 1976 355 1. 62 A. NeszmClyi A. Liptlk and P. Nlnisi Carbohydrate Res. 1977,58 C7. 63 A Liptik and P.Nlnisi Tetrahedron Letters 1977 921. 64 M. Suzuki T. Inai and R. Matsushima Bull. Chem. SOC.Japan 1976,49 1585. 65 D. H. R. Barton and R. Subramanian J.C.S. Perkin I 1977 1718. 66 D. H. R. Barton and R. V. Stick J.C.S.Perkin I 1975 1773. 359 Biological Chemistry -Part (i) Monosaccharides The chloro-sugars were prepared6' by treating partially protected sugar deriva- tives possessing an unblocked I ,2- or 1,3-diol structural unit with NN-dimethyl- + a-chlorobenzylideneammonium chloride [Ph(Cl)C=NMe2 C1-1.In this way the pair of hydroxy-groups at C-5 and C-6 in 1,2-0-isopropylidene-3-0-methyl-a-D-glucofuranose react with this reagent to give in almost quantita- tive yield 5-0-benzoyl-6-chloro-6-deoxy-l,2-0-isopropylidene-3-O-methyl-a-D-glucofuranose. The reaction occurs via the cyclic intermediate (79) with ring opening taking place by chloride ion attack at C-6. Chloro-derivatives were not obtained from methyl 4,6-0-benzylidene-a -D-glucopyranoside and this reagent. 6-Bromo-6-deoxy-sugars are often prepared by opening dioxan rings in 4,6-0- benzylidene-pyranosides with N-bromosuccinimide but there are fewer cases of this reagent being used to cleave dioxolan rings in 0-benzylidene-sugar derivatives.However two recent report^^**^^ showed the reaction to be regiospecific since methyl 2,3-0-benzylidene-4-O-methyl-a -L-rhamnoside (74) gave68 a 3-bromo-3- deoxy 2-benzoate and methyl 3,4-0-benzylidene-P-D-fucopyranosidegave69 a 3-bromo-3-deoxy 4-benzoate. The biological properties of fluorinated saccharides have led to continued inter- est in this class of compounds and new fluorinating reagents are frequently applied to sugar derivatives. One such compound diethylaminosulphur trifluoride con- verted the primary hydroxy-group in 1,2,3,4-tetra-O-acetyl-P-D-glucopyranose into a 6-deoxy-6-fluoro-group in high yield." Free keto- or aldehydo-carbonyl groups in otherwise fully blocked sugars are converted" into gem-difluorides by this reagent as shown by methyl 2,3-0-isopropylidene-~-D-eryfhro-pentopy-ranosid-4-ulose which gave the 4-deoxy-4,4-difluoro-derivative(80)'l when so treated.Ferrier and Furneaux7* have reported radical bromination at C-5 in some methyl hexopyranuronates which yield glycopyranosyl bromides of unusual structure. Thus methyl glycopyranuronate (81) and its 2,6-anhydro analogue (83) gave upon treatment with N-bromosuccinimide in refluxing carbon tetrachloride under bright light the monobromo-derivatives (82) and (84) respectively. Acetolysis of (84) followed by deacylation and subsequent treatment with hydrogen chloride gave L-ascorbic acid. C0,Me F FGMe0' AcO OAc OAc (81) R'=OAC,R2 = H (82) R' =OAc R2 = Br (83) R' =R2 = H (84)R' =H R2 = Br 67 T.G. Black D. H. R. Barton andB. L. Rao J.C.S. PerkinI 1977 1715. 68 C. Monneret J.-C. Florent N. Gladieux and Q. Khuong-Huu Carbohydrate Res. 1976 50 35. 69 K. Eklind P. J. Garegg and B. Gotthammer Actu Chem. Scund. 1975 B29,633. 70 M. Sharma and W. Korytnyk Tetrahedron Letters 1977 573. " R. A. Sharma I. Kavai Y. L. Fu and M. Bobek Tetrahedron Letters 1977 3433. 72 R. J. Ferrier and R. H. Furneaux J.C.S. Perkin I 1977 1996. 360 P. M. Collins N.m.r. of relevance to glycopyranosyl chlorides have been carried out on chloromethyl methyl ether. At -182°C the methylene protons give rise to a distinct symmetrical doublet consistent with a gauche conformation about the carbon-xygen bond. Line-shape calculations on the coalescing methylene proton resonance at -180 “C suggested that two chiral gauche forms were exchanging with a rate constant of 250 s-l from which a value of 2-3 kcal mol-’ for the anomeric effect in a-chloro-ethers was calculated.1-Thioglycosides are usually produced by the action of thiols on 1,2-trans-glycosyl acetates but dithioacetals formed by opening of the glycosidic ring often contaminate the products. It has been that formation of dithioacetal derivatives can be suppressed by the use of tributylstannyl sulphide (TBSS). Based upon this finding 2,3,4,6-tetra-O-acetyl- 1-thio-P-D-glycopyranosidewas formed in good yield when the corresponding a -D-glucosyl 1-bromide was treated with this reagent. Unfortunately only 45% of the bromo-derivative reacted under the usual reaction conditions because the nucleophilicity of the sulphur in TBSS is attenuated.However upon addition of stannic chloride to the reaction a quan- titative yield of an anomeric mixture of the thioglucoside derivatives was produced. The isomers were formed by the stannic-chloride-catalysed anomerization of the &isomer. The propensity of sulphur to participate in displacement reactions and in ring closures is well known and interest in both continues. For example 5-thio-D- ribose and 5-thio-D-xylose both gave upon acid-catalysed acetonation 1,2 :3,4-di-0-isopropylidene-pyran~ses.~’ Furanose products (oxygen in the ring) were not detected thus demonstrating the strong preference for those diacetals with a six-membered sulphur-containing ring despite the strain engendered by a cyclic acetal derived from a vicinal trans-diol in the xylopyranose compound and by a cis-syn-cis-arrangement of cyclic acetal rings in the ribopyranose derivative.Neighbouring group participation by a thioether residue has been ~tilized’~ in the key step in the conversion of tubercidin (85) into 2’-deoxytubercidin (87). Thus when the 3’-S-benzyl 2’-mesylate (88) which was obtained from 2‘,3’-anhy-drotubercidin was heated with sodium benzoate in DMF the thiobenzyl group migrated to the 2’-position to give after deblocking (86). Reductive desul- phurization of this product gave (87). NH, I HNBz I OH R‘ OMS (85) R’ =OH R2= H (86) R’= H R2= SCHzPh (88) (87)R’=R~=H 73 F.A. L. Anet and I. Yauari J. Amer. Chem. SOC.1977,99,6752. 74 T. Ogawa and M..Matsui Carbohydrate Res. 1977 54 C17. 75 N. A. Hughes and C. J. Wood Carbohydrate Res. 1976,49 225. 76 M. J. Robins and W. H. Muhs J.C.S. Chem. Comm. 1976 269. Biological Chemistry -Part (i) Monosaccharides Reports of sugar rings containing phosphorus have appeared. Inokawa's group" have for example synthesized 5-ethylphosphinyl-5-deoxy-D-xylopyranose (89) the phosphorus being introduced by displacement at C-5 in 3-0-acetyl-S-deoxy-S- iodo- 1,2- 0-isopropylidene-a-D-xy lofuranose with 00-trie thylphosphorite. Compound (go) containing both phosphorus and oxygen in the six-membered ring was obtained when 2,3 :5,6-di-O-isopropylidene-D-mannofuranose was sub- jected to the Abramov reaction with dimethyl ph~sphite.~' (89) (90) Application of tin-containing reagents to carbohydrates has now become quite common so it was inevitable that stannane carbohydrate derivatives would even- tually appear.This new class of sugar derivative containing a carbon-tin bond has been prepared79 by triphenyltin lithium displacements in sugar tosylates or opening of oxiran rings in sugar epoxides. For example with methyl 2,3-anhydro-4,6-0- benzylidene-a -D-allopyranoside this reagent gave (methyl 4,6-0 -benzylidene-a -D-altropyranosid-2-y1)triphenylstannanein 75% yield. 8 Deoxy-sugars and Branched-chain Sugars Several new methods for preparing deoxy-sugars have recently been reported. Primary and secondary iodo-sugar derivatives have been in high yields by the Cr*+-thiol procedure.For example the 6-deoxy-6-iodo-glucoside derivative (78) was reduced with chromium(I1) acetate in DMF containing butane- l-thiol to give after de-esterification methyl 6-deoxy-2,3-di-O-methyl-a-D-glucopyranoside in excellent yield. A mild method for deoxygenation of secondary alcohols has been successfully applied to sugars.*' In this method NN-dimethyl-a -chlorobenzylideneammonium chloride reacts with one free hydroxy-group in an otherwise fully blocked sugar derivative to give an intermediate which is converted into a thionobenzoate by hydrogen sulphide. Reduction of the thiono-ester with tributylstannane gives the corresponding deoxy-sugar in high yield. In addition to preparing iodo-sugars from cyclic thiocarbonates Barton and co-w~rkers~~ have reductively ring-cleaved them.Thus the 5,6-thiocarbonate (91) 07 ,I 0-C (91) Me* 77 F. Seo and S. Inokawa Bull. Chem. SOC.Japan 1975,48,1237. ''J. Thiem M. Gunther H. Paulsen and J. Kopf Chem. Ber. 1977 110,3190. 79 L. D. Hall D. C. Miller and P. R. Steiner Carbohydrate Res. 1976 52 C1. D. H.R. Barton and S. W. McCornbie. J.C.S. Perkin I 1975 1574. 362 P. M. Collins upon refluxing with tributylstannane in toluene containing aa'-azoisobutyronitrile gave after alkaline hydrolysis the corresponding derivative of the 5-deoxy-hexose in 67% yield as the only deoxy-sugar product. The regiospecificity arises because the radical-initiated ring cleavage leads to the secondary radical at C-5,as shown in (91).The 4,tj-thiocarbonate (76) similarly gave the corresponding derivative of the 4-deoxy-hexose. Specificity was absent in the reaction of methyl 4,6-0-ben- zylidene-a-D-glucopyranoside 2,3-thiocarbonate with the tin hydride since this gave 3-deoxy- and 2-deoxy-glycoside derivatives in 60 and 30% yields respec- tively. Common primary and secondary esters of sugars have been photochemically reduced in aqueous hexamethylphosphortriamide(HMPT). Accordingly 1,2 :5,6-di-0-isopropylidene-a-D-glucofuranose3-a~etate~~*~* or 3-~ivalate,'~ upon U.V. irradiation in aqueous HMPT gave the corresponding 3-deoxy-hexose derivative in 70% yield. Di- and tri-deoxy-sugars were obtained from the corresponding di- and tri-esters in one step and in this way the readily available 2,3,6-tri-0-acetyl-a- D-glucopyranoside was converted into methyl LY -Damicetoside in reasonable yield.82 The branched-chain sugar L-dendroketose (96) has been synthesized using the well-established aldol-condensation procedure to generate the branch points3 from the u2dehydo-arabinose derivative (92) and formaldehyde.The branched alditol derivative (93) so formed was deblocked and oxidized by Acetobacter suboxyduns at the C-2 position as expected from the Bertrand-Hudson rule to give (96). Acetonation of (96) gave 1,2:3,4-and 2,3 :4,4'-di-O-isopropylidene-~-dendroketose derivatives which were used in 13C n.m.r. spectroscopic studies to assign the configuration at C-4.'" CH,OH M I A X A-R20 c=o LMC2 Me .-"$ '0 CH,0R3 Ez+CH20H CHO CH20R3 CH,OH (93) R'R2 = CMe2 R3= H (96) (94) R' = R3= Bz,R2 = H (95) R'= CPh3 R2= H R3= CHzPh In an earlier attempts5 to prepare dendroketose compound (94) was oxidized with a chromium trioxide-pyridine complex to give the fully protected branched- chain sugar.However base-catalysed debenzoylation of this material was accom- panied by isomerization at C-3. This problem has been overcomes6 by use of compound (95) which upon oxidation yielded a dendroketose derivative from which the blocking groups could be removed without recourse to base. J.-P. Pete C. Portelk C. Monneret J.-C. Florent and Q. Khuong-Huu Synthesis 1977 774. P. M. Collins and V. R. N. Munasinghe J.C.S. Chem. Comm. 1977 927. 83 W. A. Szarek G.W. Schnarr H. C. Jarrell and K. J. N.Jones Carbohydrate Res. 1977 53 101. 84 D. M. Vyas H. C. Jarrell and W. A. Szarek Cunad. J. Chem. 1975 53 2748. " H. C. Jarrell W. A. Szarek J. K. N. Jones A. Dmytraczenko and E. B. Rathbone Carbohydrate Res. 1975,45 151. E. B. Rathbone and G. R. Woolard Carbohydrate Res. 1976,46 183. 363 Biological Chemistry -Part (i) Monosaccharides A new route to branched-chain sugar derivatives has been reported87 which involves the condensation shown in (97) between 2,3-O-isopropylidene-D-gly-ceraldehyde and 4,5-dimethyldioxaphospholento give the corresponding dioxo- phospholan. The addition is remarkable because the two new chiral centres are generated stereospecifically. Hydrolysis of the dioxophospholan followed by Fischer glycosidation gave a methyl pyranoside and furanoside of 1-deoxy-3-C-methyl+ -D-ribo -hexulose in 20% and 30% yields respectively.(97) Anions derived from 1,3-dithians are frequently added to ulose derivatives as the key step in syntheses of branched-chain sugars The monobenzoyl derivative of pillarose (99) has been prepared in this way.nn Thus the dianion of 1,3-dithian-2-methanol reacted with methyl 2,3,6-trideoxy-a -~-glycero-hexopyranosid-4-ulose to give the addition product (98) which was monobenzoylated at the primary hydroxy-group and deblocked at the carbonyl group to give the pillarose derivative (99) in overall 10'/0 yield. Although additions to ulose derivatives remain one of the most common routes to branched-chain sugars 1,4-additions to carbohydrate enones are beginning to attract attention.One such example is the addition of lithium dimethylcuprate to the hex-2-enopyranosid-4-ulose(100) to give (in 84% yield) the 2-C-methyl derivative (102).89 The addition occurred to the least hindered side of the pyranose ring trans to the aglycone. Lithium dimethylcuprate vinylmagnesium bromide and 2-lithio-2-ethoxycar- bonyl- 1,3-dithiolan have been similarly added" to methyl hex-2-enopyranosid-4- ulose (101) to give the 2-C-branched derivatives shown in (104). <>>Rt o{E$ 0 R4 R2 OEt (100) R'=R4=H,R2=OEt (102) R=Me (98) R= R3= CH20CPh3 (103) R = CHzOH (101) R' = OMe R2 = R3 = H, R4= Me (99) R = BzOCH~CO 87 Ltpine G. Aranda and G. Vass J.C.S. Chem. Comm. 1976 747.S. David M.-C. 88 H. Paulsen K. Roden V. Sinnewell and W. Koebernick Chem. Ber. 1977,110,2146. 89 M. B. Yunker D. E. Plaumann and B. Fraser-Reid Canad. J. Chem. 1977,5S 4002. H. padsen W. Koebernick and H. Koebernick Tetrahedron Letters 1976 2297. 364 P. M. Collins R (104) R = Me or CH2=CH Photochemically induced conjugate additions of simple a~etals,~~ and aldehydes to this class of carbohydrate derivative have been achieved. Thus U.V. irradiation of benzophenone in methanol containing the enone (100) gave (103) presumably by the 1,4-addition of photogenerated hydroxymethyl radicals. The addition was stereospecific and the configuration at C-2 in (103) was verified by ready formation of a 2,3-cyclopropane derivative with the D-lyxo-structure.Photoexcited 1,2 :4,6-diacetalated hexopyranosid-3-uloses have been found93 to react with methanol to give isomeric mixtures of the corresponding derivatives of 3-C-hydroxymethyl branched-chain sugars the configurations of which were determined by 13Cn.m.r. spectroscopy. A photochemical synthesis of DL-apiose (108) has been achieved94 by appli- cation of the Patterno-Buchii reaction to 1,3-dihydroxy-2-propanonediacetate (105) and 1,3-dioxolen-2-one (106) which gave the oxetan (107) and upon subsequent a1 kaline hydrolysis DL-apiose. OAc CHO 9 Amino-sugars The occurrence of amino-sugars that possess unusual structures in antibiotics has been responsible for the continuing interest in the synthesis of this class of compounds.Two synthetic to the aminodeoxy-octose lincosamine which is a constituent of lincomycin have been reported. One highly stereoselec- tive route9' commences with the unsaturated nitro-sugar (109) epoxidation of which gave the key intermediate (110). This was opened with benzylamine to give (1 11) and subsequently reduced and converted into the N-acetyl derivative of lincosamine (112). The other route96 to (112) which uses the diazoketone deriva- tive (1 13) as the starting material contained steps that were not stereospecific. 91 B. Fraser-Reid N. L. Holder D. R. Hicks and D. L. Walker Canad. J. Chem. 1977,55 3978. 92 B. Fraser-Reid R.C. Anderson D. R. Hicks and D. L. Walker Canad. J. Chem. 1977 55 3986. 93 P.M. Collins V. R. N. Munasinghe and N. N.Operaeche J.C.S. Perkin I 1977 2423. 94 Y. Araki J. Nagasawa and Y. Ishido Carbohydrate Res. 1977,58 C4. 9s G. R. Woolard E. B. Rathbone W. A. Szarek and J. K. N. Jones J.C.S. Perkin I 1976,950. 96 S. M. David and J.-C. Fischer Carbohydrate Res. 1976 50 239. Biological Chemistry-Part (i) Monosaccharides PhCHZHN A reaction which could be of value for selectively reducing an azido-group in an unsaturated nucleoside has been rep~rted.~' The unsaturated azide is treated with hydrogen sulphide in aqueous pyridine at room temperature for 3 h. The sulphur is filtered off and the unsaturated amino-nucleoside isolated. A method of synthesis of amino-sugar derivatives which has attracted the atten- tion of three is the addition of the Sharpless reagent'" to unsaturated sugars.Thus chloramine T (TsNClNa) in the presence of osmium tetroxide was added99 to the diacetylated derivative of the pseudo-glucal(33) to give in moderate yield a mixture of the 2-and 3-tosylamino-mannosides (1 14) and (1 15). A higher yield of the products (116) and (117) was from the corresponding methyl hexenopyranoside after acetylation of the hydroxy-groups in the initially formed adducts. Attempts have been made to improve the potency and antibacterial spectra particularly against resistant organisms of aminoglycoside antibiotics by chemically modifying their structures. For example gentamicin X2(1 18) which is produced only as a minor component by Micromonospora purpurea has been prepared"' semi-synthetically. The key step in the synthesis is the a-glycosylation of the 1,3,3'-tris-N-benzoyloxycarbonylderivatives of the semi-synthetic pseudodisac- charide garamine (1 19)'** by the Lemieux-Nagabhushan reaction using the nitrosyl chloride adduct of triacetyl glucal.The total syntheses of streptomycin and its 3"-deoxydihydro analogue have been reported by Umezawa's gro~p.'~~.'~~ Labelling studies that have revealed the biosynthetic pathways by which D-glucose is converted into the amino-cyclitol components of streptomycin and spec- tinomycin have been reviewed.'05 97 I. Adachi Y. Yamada and I. Inoue Synthesis 1977,45. 98 K. Heyns and J. Feldmann Tetrahedron Letters 1977 2789. 99 I. Dyong Q. Lam-Chi G. Schulte B. Fraser-Reid and J. L. Primeau Angew. Chem.Internat. Edn. 1977,16 553. 100 K. B. Sharpless A. 0.Chong and K. Oshima J. Org. Chem. 1976,41,177. 101 M. Kugelman A. K. Mallams H. F. Vernay D. F. Crowe G. Detre M. Tanabe and D. M. Yasuda J.C.S. Perkin I 1976 1097. 102 M. Kugelman A. K. Mallmas H. F. Vernay D. F. Crowe and M. Tanabe J.C.S.Perkin I 1976 1088. 103 S. Umezawa Y. Takahashi T. Usui and T. Tsuchiya J. Antibiotics 1974,27,997. 104 H. Sano T. Tsuchiya S. Kobayashi M. Hamada S. Umezawa and H. Umezawa J. Antibiotics 1976 29 978. 10s K. L. Rinehart jun. and R. M. Stroshane J. Antibiotics 1976 319. 366 P.M. Collins AcO [:iR, (1 14) R' = Et R2 = NHTs R3 = OH (115) R'=Et R2=OH R3=NHTs (116) R' =Me R2 =NHTs R3 = OH (117) R' = Me R2 =OH R3 =NHTs (118) R= HO-p-+ Meoq>R CH,OH HO NH R2 (119) R=H (120) R'=H R2=N02 (121) R' =Me R2= AcNH The branched-chain nitro-sugar evernitrose has been shown to possess the L-ambino-configuration (1 20) from an X-ray crystallographic analysis of the 3-acetamidopyranoside (121) which was prepared from it in three steps.lo6 Thus the complete structure of the octasaccharide antibiotic everninomicin D with its uncommon orthoester linkages is now known.'" 10 Synthesis of Non-carbohydrate Compounds There is increasing use of carbohydrate derivatives as precursors for the synthesis of optically active non-carbohydrate compounds.Some examples of this approach that have been applied to the synthesis of natural products this year include the preparation of the antifungal metabolite (-)-isoavenaciolide from hiacetone-D-glucose'os and the conversion of 1,6-anhydro-P-D-glucose into the growth factor (+)-biotin'" in a biomimetic synthesis which involved a stereospecific ring closure to the tetrahydrothiophen.Prostaglandin and related substances have also been prepared from carbohydrate sources. Thus prostaglandin PGEl has been prepared from D-glyceraldehyde"' and thromboxane B2 has been synthesized by two from methyl a-D-glucopyranoside. A. K. Ganguly 0.Z. Sarre A. T. McPhail and K. D. Onan J.C.S. Chem. Comm. 1977,313. lo' A. K. Ganguly 0.Z. Sarre D. Greeves and J. Morton J. Amer. Chem. SOC.,1975 97,1982. lo* R. C. Anderson and B. Fraser-Reid Tetrahedron Letters 1977 2865. lo9 T. Ogawa T. kawano and M. Matsui Carbohydrate Pes.1977,57 C31. 'lo G. Stork and T. Takahashi J. Amer. Chem. Soc. 1977,99 1275. S. Hanessian and P. Lavallee Canad. J. Chem. 1977.55 562. E. J. Corey M. Shibasaki and J. Knolle Tetrahedron Letters 1977 1625.

ISSN:0069-3030    

DOI:10.1039/OC9777400343

出版商:RSC    

年代:1977

数据来源: RSC