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Chapter 13. Synthetic methods

 

作者: G. Pattenden,  

 

期刊: Annual Reports Section "B" (Organic Chemistry)  (RSC Available online 1977)
卷期: Volume 74, issue 1  

页码: 309-342

 

ISSN:0069-3030

 

年代: 1977

 

DOI:10.1039/OC9777400309

 

出版商: RSC

 

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.

 



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