8 Aliphatic Compounds Part (ii) Other Aliphatic Compounds By B. V. SMITH Department of Chemistry Chelsea College Manresa Road London SW3 6LX 1 Alcohols and Ethers The formation of alkanes by deoxygenation of an alkyl tosylate with Bu,SnH-NaI or by pyrolysis/photolysis of an alcohol proceeds efficiently.' Appropriately sub- stituted systems underwent ring closure in a process believed to involve free-radical intermediates (Scheme 1). Chemoselective reduction of an acid group by NaBH,- N,N-dimethylchloromethyleneiminiumchloride is possible in the presence of func- tional groups e.g. Hal C02R CN and alkene; cyano- and nitro-groups in ketones and esters were not reduced by LAH-silica gel whereas the carbonyl groups were reduced in fairly good yield.' Horse liver alcohol dehydrogenase brought about rapid exchange of the pro-1-R-hydrogen in octan- 1-01.The pro-I -S-hydrogen exchanged slowly under these conditions ; both processes required the enzyme. Interestingly yeast dehydrogenase was specific for the pro-1-R-hydr~gen.~ Oxidation of alcohols by solid potassium permanganate was shown to be facilitated by sonica- tion and barium manganate was found to oxidize a wide range of alcohols (and other compounds) efficiently. Methylation of long-chain alcohols (at C-2) showed good selectivity in the presence of Ni-Pd cataly~is.~ Trialkylsilylation of a range of alcohols (and phenols and acids) was effected by Nafion-H,6 a polymeric perfluori- nated resin sulphonic acid. R (la) R = H,X = NTs; (2) (lb) R = Ph,X = 0.Reagents i Bu,SnH-Nal-AIBN-DME 80 "C Scheme 1 Y. Ueno C. Tanaka and M. Okawara Chem. Lett. 1983,795; W. Hartwig Tetrahedron 1983,39,2609. ' T. Fujisawa T. Mori and T. Sato Chem. Lett. 1983 835 Y. Kamitori M. Hojo R. Masuda T. Inoue and T. Izumi Tetrahedron Lett. 1983 24 2575. S. Shapiro T. Arunachalam and E. Caspi J. Am. Chem. SOC. 1983 105 1642. J. Yamawaki S. Sumi T. Ando and T. Hanafusa Chem. Lett. 1983 379; H. Firouzabadi and Z. Mostafavipoor Bull. Chem. SOC.Jpn. 1983 56 914. ' J. Sabadie and G. Descotes Bull. SOC.Chim. Fr. II 1983 253. G. A. Olah A. Husain and B. P. Singh Svnrhesir 1983 892. 165 166 B. V. Smith Structural and chemical evidence was advanced to confirm the identity of an unusually stable enol (3) prepared from (4).7 Several routes to unsaturated alcohols have been reported.Metallic manganese reacts with allylic bromides and the allyl group undergoes Barbier-type addition to a carbonyi group; with an a,P -enone 1,2-addition was noted and with PhCH(Me)CHO and allyl bromide the erythro threo ratio in the product was 3 1.8 Oxidation (H202 or Bu‘OOH) of zirconium-diene (isoprene) complex gave a mixture of products in which the yield of alcohol could be optimized by use of H202;diols were obtained from cyclic precursors.’ Reduction (LAH-Et20) of acetylenic alcohol (5) was 99% cis-selective [to form (6)]only when a clear solution of reagent was used since slurries gave lower selectivity. Solvent dependence in these processes has been explored.” PhC(OMe)=C(OH)Ph PhCN,COPh (3) (4) Me,Si-CH(OH)Me Me,SiCECCH(OH)Me HAH (5) (6) Enantioselective reaction of optically active diallylbis-( 2-phenylbuty1)tin and an aldehyde led to homoallyl alcohols in 2O-8O% optical yield which was independent of solvent but did vary with R.For R = C8HI7 the product (S)-homoallyl alcohol was formed in 84% yield (82% e.e.) in a process considered to involve addition of the allyl group to the re-face of the aldehyde.” a-Substituted allyl boronates with aldehydes gave homoallyl alcohols by y-attack [RCH(OH)CH,CH=CH..-X; X = C1 Br OR or SR] with surprisingly high 2 :E ratio (e.g. R = Me X = C1 2:E = 93 :7).12 Isomerization of triple bonds in alkynols has been brought about by metal salts of amines; e.g. dec-2-yn-1-01 gave dec-9-yn-1-01 (95% 0.5 h).I3 Alkynols e.g.(lo) have been prepared from (7) (see Scheme 2); in the intermediate (8) the d.s. ratio varied from 86 14 to 97 :3 and e.e. in (10) was 70-92% .I4 Addition of silylated alkyne (I 1) to a carbonyl compound was promoted by a trace of fluoride ion and led to PhCECC(OH)R1R2 in good yield.” Advances in stereochemical control in 1,2-and 1,3-diols have been summarized and optical enrichment of asymmetric diols via stannoxanes recommended.16 A useful reversal of the erythro threo ratio in reduction of a-hydroxy-ketones has ’ J. F. McGarrity W. Cretton A. A. Pinkerton D. Schwarzenbach and H. I). Flack Angew. Chem. Int. Ed. Engb 1983 22 405. T. Hiyama M. Sawahata and M. Oboyoshi Chem. Lett. 1983 1237. H. Yasuda K.Nagasuna K. Asami and A. Nakamura Chem. Letf. 1983 955. lo M. L. Mancini and J. F. Honek Tetrahedron Lett. 1983 24,4295; J. W. Blunt M. P. Hartshorn M. H. G. Munro T. S. Lee R. S. Thompson P. R. Trebilco R. W. Vannoort and J. Vaughan Ausf. J. Chem. 1983 35 581 1387. ‘I J. Otera Y. Kawasaki H. Mizuno and Y. Shimizu Chem. Left. 1983 1529. l2 R. W. Hoffmann and B. Landmann Tetrahedron Lett. 1983 24 3209. l3 S. R. Abrams D. D. Nucciarone and W. F. Steck Can. J. Chem. 1983 61 1073. l4 W. S. Johnson R. Elliott and J. D. Elliott J. Am. Chem. Soc. 1983 105 2904. l5 1. Kuwajima E. Nakamura and K. Hashimoto Tetrahedron 1983 39 975. S. Masamune and W. Choy Aldrichim. Acm 1982 15 47; A. Shanzer J. Libman and H. E. Gottlieb J. Org. Chem. 1983. 48 4612. 167 Aliphatic Compounds -Part (ii) Other Aliphatic Compounds SiMe, I c I -1 + Ill Me-*Me CI HO*Me (7) R' (8) R = alkyl R'= Me I ii HO-kCZCR' iii +--R 2Me PhC=CSiMe (11) (10) (9) Reagents i TiCI4-CH2Cl2 -78 "C; ii PCC; iii KOH-MeOH Scheme 2 been reported ;zinc borohydride reduction (0 "C) favours erythro-glycol formation whereas with NaAlH2(0R) [R = MeO(CH2)20CH20-] and the t-butyldiphenyl- silyl ether (-78 "C) the threo-isomer predominates." Regioselective cyclodehydra- tion of chiral diols by (EtO),PPh, has been studied ;(S)-(+)-propane- 1,2-diol gave methyloxirane with 82% retention of configuration.A lower figure (50%) was found for the reaction of (S)-(+)-phenylethane-l,2-diol,which was rationalized in terms of decomposition of the betaine intermediates presumed to be formed." Chirality inversion in the butane-1,3-diol system has been explored and a stereoselective synthesis of a 1,3-diol derivative used as an approach to the ansa-bridge in rifamy- cin.I9 Ally1 alcohol under conditions of the water gas reaction and with a catalyst based on [a,( CO),J,gave butane- 1,4-diol in good yield.20 Derivatization of chiral alcohols (and ketones) and their separation by high-resolution gas chromatography of metal salts have been reported.21 Among several recorded preparative methods for ethers are the use of (Me0)2CH2-Me,SiI the synthesis of alkoxyalkanones preparation of (2S)-2-O-(protected)-2- hydroxypropanals from methyl L-lactate and formation of homoallylic ethers.22 Preparative methods for oxiranes include phase-transfer reaction mediated by dilute H2O2-H3O+-W02-HP0:-(in good yields) the use of (S)-malic acid as a chiral " T.Nakata T. Takana and T. Oishi Tetrahedron Lett. 1983 24 2653. P. L. Robinson C. N. Barry S. W. Boss S. E. Jarvis and S. A. Evans jun. J. Org. Chem. 1983,48,5396. '' S. Takano C. Kasahara and K. Ogawara Chem. Lett. 1983 175; W. C. Still and J. C. Barrish J. Am. Chem. SOC.,1983 105 2487. '' K. Kaneda T. Imanaka and S. Teranishi Chem. Lett. 1983 1465. 21 V. Schurig and R. Weber Angew. Chem. Suppl 1983 1130. 22 G. A. Olah A. Husain and S. C. Narang Synthesis 1983 896; J. Koshimo T. Sugawara T. Yogo and A. Suzuki Chem. Lett. 1983,933; S. K. Massad L. D. Hawkins and D. C. Baker J. Org. Chem.1983 48 5180; H. Sakurai Y. Sakata and A. Hosomi Chem. Lett. 1983 409. 168 B. V. Smith building block a regio- and stereo-specific formation and ring closure of iodohydrins reaction of p-peroxy-substituted free radicals and epoxidation mediated by iron- porphyrin complexes with oxygen transfer from PhI0.23 In this latter report cis trans selectivity for cis-and trans-but-2-ene was -6 1 ; surprisingly trans-stilbene failed to react under conditions in which the cis-isomer gave 77% yield. With prochiral substrates and chiral complexes e.e. varied from 0% (1 -methyl- cyclohexene) to 5 1'/o (4-chlorostyrene). Palladium-catalysed reaction between a halogenocarbonyl compound and a keto- or allyl-tin gave good yields of cyclic ethers and+a small e.e.(19'/0) was reported in the most favourable case. Telluronium ylides (R,TeCHCH=CH,) with aldehydes gave oxiranes with reasonable Z-selec- tivity; e.g. C7HI4Oafforded a 68 32% Z/ E mixture.24 The adverse role of water in the Sharpless epoxidation has been stressed and a comprehensive summary of synthetic applications with an evaluation of the mechanism of tartrate-mediated reactions presented. A general review of preparative/synthetic applications has also appeared.25 Ring-opening of trans-I ,2-epoxy-3-methyl- 1,3-diphenyIbutane by BF,OEt,-C,H has been studied by stereochemical and isotopic methods ; a cautionary note was that in some cases the course of reaction depended on the batch of complex used.26 Organocuprate-mediated ring-opening of racemic and chiral oxirane precursors has been applied to the synthesis of (E)-9-hydroxydec-2-enoic acid a swarm-settling pheromone of the queen honey bee.Trialkylaluminiums with 2,3-epoxy-alcohols gave (12) and (13) as major and minor products respectively; periodate oxidation of the product of ring-opening of 2,3-epoxyoctadecan-l-ol by Me3Al gave (14) in high yield (-95%) and with 92% e.e.27 Regiospecific ring-opening by organotin reagents gave alkoxytins capable of further elaboration.28 Rearrangement of unsatur- ated epoxides e.g. (1 5) + (16) has been realized by use of SnCl,-CH,Cl,; a possible intermediate is (17).29 The direction of reaction given by an acetylenic epoxide e.g. (18) and LiNEt is a function of solvent polarity; in ether-hexane a cyclopropane alcohol was formed whereas in HMPT an enynol was produced by p-elimination and rearrangement.30 SiMe, RLOH Me ClA1 Me OH (12) (13) (14) (15) 23 C.Venturello E. Alveri and M. Ricci J. Org. Chem. 1983,48 3831; D. A. Howes M. H. Brookes D. Coates B. T. Golding and A. T. Hudson J. Chem. Res.(S) 1983 9; R. Antonioletti M. D'Auria A. De Mico G. Piancatelli and A. Scettri Tetrahedron 1983 39 1765; E. J. Corey G. Schmidt and K. Shimoji Tetrahedron Lett. 1983 24 3169; J. T. Groves et al. J. Am. Chem. Soc. 1983 105 5786 5791. 24 I. Pri-Bar P. S. Pearlman and J. K. Stille J. Org. Chem. 1983 48 4629 A. Osuka and H. Suzuki Tetrahedron Lett. 1983 24 5109. 25 J. G. Hill B. E. Rossiter and K. B. Sharpless J. Org. Chem. 1983,48 3607; K. B. Sharpless et al.Pure Appl. Chem. 1983 55 589 1823; Aldrichim. Acta 1983 16,(3); A. S.Rao S. K. Paknikar and J. G. Kirtane Tetrahedron 1983 39,2323. 26 J. W.Blunt J. M. Coxon C.-E. Lim and H. A. Schuyt Aust. J. Chem. 1983 36,97. 27 A. A. Kandil and K. N. Slessor Can. J. Chem. 1983 61 1166; W. R. Roush M. A. Adam and S. M. Peseckis Tetrahedron Lett. 1983 24 1377. 28 M. Fiorenza A. Ricci M. Taddei and D. Tassi Synthesis 1983 640. 29 I. Cutting and P. J. Parsons J. Chem. SOC. Chem. Commun. 1983 1435. 30 M. Apparu and M. Barrelle Bull. SOC.Chim. Fr. 11 1983 83. Aliphatic Compounds -Part ( ii) Other Aliphatic Compounds (16) (17) (18) (S)-(+)-and (R)-(-)-3-hydroxytetrahydrofurans have been prepared in high e.e. from chiral malate esters and 2-substituted tetrahydrofurans were obtained by chirality transfer from acyclic chiral half esters in the presence of [Pd(PPh3),]-MeCN-Et3N.31 The role of actylenic diethers as an entry to derivatives of oxocarbons C,O,"- and general routes to cleavage of ethers have been ~urveyed.~' 2 Alkyl Halides Decomposition of optically active a-phenylneopentyl chloroformate gave (R)-(+)-1-chloro-1-phenyl-2,2-dimethylpropanewith optical purity greater than that of the product from treatment of the alcohol with thionyl chloride.The stereochemistry of substitution by Ph,CHLi in THF led to 20% retention of optical activity in the product (S)-(+)-P~,CHCH(P~)BU'.~~ An alternative to the Hunsdiecker reaction has been explored ;esters from N-hydroxypyridine-2-thionewere shown to decom- pose via a radical chain mechanism in the presence of CC14 BrCCl, or CHI3 to form noralkyl halides in high yield.34 Alcohols with sodium iodide in the presence of trimethylsilyl polyphosphate (PPSE) gave alkyl iodides in good yields but in some cases the reaction failed.35 Solid-solid interaction of RBr and MeCO,K catalysed by alkylammonium salts gave alkyl acetates in excellent yield and at room temperat~re.~~ Reductive dehaloge- nation of alkyl halides (LiAlH,) has been studied; a radical intermediate was proposed and trapped in the case of 6-iodohept-1-ene.Tertiary and benzylic halides with Zn(BH,) in ether were smoothly dehalogenated ; complementary studies established the usefulness and high reactivity of LiEt3BH.37 In the last case LiEt,BD is the reagent of choice for site-specific deuteriation.Tertiary halides react with Me3SiCN under the influence of SnC1,. High chemoselectivity was noted; a primary chlorine in a dihalide was not affected. Two possibilities were considered for the mechanism (Scheme 3) of this interesting reaction which affords an entry into tertiary alkanoic acids. On balance evidence from n.m.r. studies supported formation of isocyanides as intermediate^.^^ A higher degree of asymmetric induction was found in addition of (+)-2-methyl- butylmagnesium bromide to PhCHO when (+)-1-methoxy-2-methylbutane was 3' V. K. Tandon A. M. van Leusen and H. Wynberg J. Org. Chem. 1983,48 2767; G. Stork and J. M. Poirier J. Am. Chem. Soc. 1983 105 1073. 32 F.Serratosa Acc. Chem. Res. 1983 16 170; M. V. Bhatt and S. V. Kulkami Synthesis 1983 249. 33 D. A. Bright D. E. Mathisen and H. E. Zieger J. Org. Chem. 1982,47 3521. 34 D. H. R. Burton D. Crich and W. B. Motherwell Tetrahedron Lett. 1983 24 4979. 35 T. Imamoto T. Matsumoto T. Kusumoto and M. Yokoyama Synthesis 1983 460. 36 J. Barry G. Bram G. Decodts A. Loupy P. Pigeon and J. Sansoulet Tetrahedron 1983 39 2673. 37 E. C. Ashby R. N. De Priest and T. N. Pham Tetrahedron Lett. 1983 24 2825; S. Kim C. Y. Hong and S. Yang Angew. Chem. Int. Ed. Engl. 1983 22 562; S. Brandange 0. Dahlman and J. Olund Acta Chem. Scand. (B) 1983 37 141. 38 M. T. Reetz I. Chatziiosifidis H. Kiinzer and H. Miiller-Starke Tetrahedron 1983 39 961. 170 B.V. Smith R3CC1 + Me,SiCN 4R,CCN + Me,SiCI Reagents i SnCI4-CH,CI2 r.t. Either R,CCI + SnCl,sR,C' +SnCIs-~Me,SiN~CCR3SnC15- 11 Me,SiCI + NECCR + SnCI Or Me,SiCN ++ R,C+ SnC1,-=R,C-N~CSiMe,SnCls- R,C-NECCR,=R,CN=C + + SnCl + Me,SiCI li 11 R,C+ + R3CCN Scheme 3 replaced by (-)-1-isopropyl-2-methoxy-4-methylcyclohexane as solvent.39 Coupling of a chiral 1-methylheptyl halide and a-dimethylaminophenylacetonitrile,in liquid ammonia led to partially inverted product. Racemization of reagent was dependent on structure and electron transfer in the alkylati~n.~' Lithio-isobutyrophenone and (S)-(+)-2-iodo-octane reacted with inversion of configuration; some of the halide was racemized under these conditions. Inversion was found for the system Ph3SiLi- (R)-2-chloro-4-phenylbutane in THF (0 OC)."' Alkyl bromides and chlorides were found to couple with R2CuCNLi2 (thus making the use of iodides unnecessary) at -50°C in THF; thus Br(CH2)3C1 afforded BuS(CH2),C1 (89%) with R = Bus.The presence of an alkene was not a drawback as CH,=CHCH(Me)(CH,),Br gave (R = Ph) 91% of product by regioselective reaction at the terminal halide.42 An attempt was made to improve asymmetric induction in the PhX-Bu'MgX system by using nickel complexes containing chiral phosphines; up to 50% e.e. was found and the reaction was dependent on the halide Substitution of RHal by aqueous thiocyanate in a two-phase system and ion-exchanged zeolite-mediated alcoholysis have been reported.@ Alkylation (at C and 0)of MeCOCH,CO,Et by C,H,,CH(I)Me has been studied over a range of conditions and enantiomeric purities of products have been measured.45 1,2-Dibromides (and monobromides) are formed in the reaction of tosylhydrazonzs with bromine.46 Ring closure of a,@-di-iodides by Bu'Li-Et20 gave three- four- and five-membered rings in excellent yield although it failed for I(CH2)21.47 39 L.Jalander and R. Strandberg Acra Chem. Scand. (B) 1983 37 15. 40 J. Chauffaille E. Hebert and Z. Welvart J. Chem. SOC.,Perkin Trans. 2 1982 1645. 4' L. M. Jackman and B. C. Lange J. Org. Chem. 1983,48,4789; T. Hayashi Y. Okamoto and M. Kumada J. Chem. SOC.,Chem. Commun. 1982 1072. 42 B. H. Lipschutz D. Parker J. A. Kozlowski and R.D. Miller J. Org. Chem. 1983 48 3334.43 G. Consiglio F. Morandini and 0. Piccolo Tetrahedron 1983 39 2699. 44 W. P. Reeves and J. V. McClusky Tetrahedron Lett. 1983,24 1585; M. Onaki M. Kawai and Y.Izumi Chem. Lett. 1983 1001. 45 G. Bram D. Cabaret E. D'lncan N. Maigrot and Z. Welvart J. Chem. Res.(S) 1982 86. 46 G. Palmieri Tetrahedron 1983 39 4097. 47 W. F. Bailey and R. P. Gagnier Tetrahedron Lett. 1982 23. 5123. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 171 An improved procedure for vinyl iodides has appeared.48 B-Bromo- or B-iodo-9- BBN reacts readily with alkynes chemoselectively at terminal sites ; protolysis of the products gave 2-bromo- or 2-iodo-alk-1-ene~.~~ A range of saturated and unsatur- ated alkyl bromides was smoothly dehydrohalogenated by KF-A1203 in various solvents.50 Prenylation catalysed by Lewis acids of alkenes and furans has been rep~rted.~' Rearrangement of allylic structures during oxidative hydrolysis has been interpreted as involving formation of an iodoso-intermediate which undergoes [2,3]sigmatropic rearrangement (Scheme 4).52 Vinyl bromides with organozincs (from sec-alkyl Grig- nard reagents) underwent coupling in the presence of chiral Pd" catalysts with e.e.UP to 86'/0.~~ 1ii I Reagents i ii [O]; iii OH- \o Scheme 4 Highly crowded compounds such as (19) and (20) have been prepared from Bu',SiCHBr and unusual bond lengths and angles recorded. Olah's reagent (HF- C5H5N ratio 10 1) reacted smoothly with amino-alcohols ;erythro-diastereoisomers gave a product in which threo-fluoramine pred~minated.~~ Bu',SiCH =CHSiBu' [Bu',SiCHBr] (19) (20) 3 Aldehydes and Ketones Interest in the chemistry of these systems continues unabated.Principal features of published work are reported here but it is almost impossible to do justice to the skill and ingenuity of many syntheses. Preparative routes to ketones include the use of alkyl-tins to transfer one group to an acyl chloride nickel-mediated metathesis of ArCH2X and an acyl chloride clean reduction of cy -halogenocarbonyls by NaTeH reaction of cuprates and pyridyl esters and the route shown in Scheme 5 which was applied to synthesis of the 411 D. H. R. Barton G. Bashiardes and J.-L. Fourrey Tetrahedron Lett. 1983 24 1605. 49 S. Hara H. Dojo S. Takinarni and A.Suzuki Tetrahedron Lett. 1983 24 731; Synthesis 1983 1005. so J. Yamawaki T. Kawate T. Ando and T. Hanafusa Bull. Chem. SOC.Jpn. 1983 56 1885. " H. Klein A. Erbe and H. Mayr Angew. Chem. Znt. Ed. EngL 1982 21 82; Z. M. Isrnail and H. M. R. Hoffrnann Angew. Chem. Suppl. 1983 985. 52 S. Yarnarnoto H. Itami T. Tsuji and W. Nogata J. Am. Chem. SOC.,1983 105 2909. 53 T. Hayashi T. Hagihara Y. Katsuro and M. Kurnada Bull. Chem. SOC.Jpn. 1983 56 363. 54 M. Weidenbruch and H. Flott Angew. Chem. Int. Ed. Engl. 1982 21 368; G. Alvernhe S. Lacombe A. Laurent and C. Rousset J. Chem. Res. (S) 1983 246. 172 B. V. Smith RYSMe i,ii '\ iiii R\/c=o RCH,Ts -* R'/CHTS ~ R" 'Ts R' Reagents i Bu"Li -20 "C; ii R'X -78 T;iii (MeS), -78 "C; iv CuC12-SiOz r.t.Scheme 5 Douglas fir tussock moth pher~mone.~~ 7'rimethylsilyl ethers have been used as an approach to aliphatic (and alicyclic) ketones carrying t-butyl Some success was claimed for ozonation as a route to carbonyl corn pound^.^^ Several routes have been developed to a$-unsaturated carbonyl compounds. Direct dehydrogenation of saturated aldehydes has been achieved by the use of [PdC12( PhCN),]-AgOSO,CF in the presence of N-rnethylm~rpholine.~~ Yields were good. In the same paper a one-pot route uia Sn" enolates is reported. Stereodefined reaction of alkenyl-lithium cuprate with an acyl halide at low tem- perature gave an enone with >96% Z-isomer in the most favourable case.59 Alkenyl halides were coupled to Zn salts of enol ether anions in the presence of Pd" catalyst with regiospecificity retention of alkenyl stereochemistry and in good yield; a related method used silyl enol ethers of saturated carbonyl compounds and ally1 carbonate with a palladium-phosphine catalyst in (preferably) a nitrile as solvent.Ally1 ketones were prepared by a similar method ; with stannic chloride enol silyl ethers gave stannylated ketones.60 Other routes reported are acylation (by RCOC1) of an alkene in presence of Zn compounds stereoselective ring-opening of chlorosiloxycyclopropanes formylation or acylation of isoprene (as the Cp,Zr complex) a retro-Diels-Alder reaction and oxidation (by Ce'") of alkylfurans.6' Approaches to acetylenic ketones have been made by a borane-oxidation sequence the use of lithiated 2-alkynyl- 1,3-dioxanes (as oxygenated acyl anion equivalents) and through alkynyl transfer from an alkynyl boron.62 The hydroboration route has been applied to the preparation of hydroxy-ketones (and of dihydrojasmone from the appropriate precursor); a-alkoxyalkyl carbonyls have been obtained through zinc-mediated reaction of functionalized carbonyl compounds and a -chloro-a -aceto~y-ethers.~~ This latter method was elaborated 55 J.W. Labadie D. Tueting and J. K. Stille J. Org. Chem. 1983 48 4634; S.-I. fnaba and R. D. Rieke Tetrahedron Lett. 1983 24 2451; A. Osuka and H. Suzuki Chem. Lett. 1983 119; S. Kim and J. 1. Lee J. Org. Chem. 1983 48 2608; Y. Murata K. Inomata H. Kinoshita and H. Kotake Bull. Chem. Soc. Jpn. 1983 56 2539.56 C. Lion and J.-E. Dubois Bull. Soc. Chim. Fr. 11 1983 375. 57 E. Niki Y. Yamamoto T. Saito K. Nagano S. Yokoi and Y. Kamiya Bull. Chem. Soc. Jpn. 1983 56 223. 5H T. Mukaiyama M. Ohshima and T. Nakatsuka Chem. Lett. 1983 1207. 59 N. Jabri A. Alexakis and J. F. Normant Tetrnhedron Lett. 1983 24 5081. 60 C. E. Russell and L. S. Hegedus J. Am. Chem. Soc. 1983 105,943; J. Tsuki I. Minami and I. Shimizu Terrahedron Lett. 1983 24 5635 5639; Chem. Lett. 1983 1325; E. Nakamura and I. Kuwajima ibid. p. 59. 61 T. Shono I. Nishiguchi M. Sasaki H. Ikeda and M. Kurita J. Org Chem. 1983,48 2503; J.-M. Conia and L. Blanco Noun J. Chim.,1983,7,399; M. Akita H. Yasuda and A. Nakamura Chem. Lett. 1983 217; R. Bloch Tetrnhedron 1983 39 639; L.Lepage and Y. Lepage Synthesis 1983 1018. 62 H. C. Brown N. G. Bhat and D. Basaviah Synthesis 1983 885; K. J. H. Kruithoff R. F. Schmitz and G. W. Klumpp Tetrahedron 1983,39,3073;M. Yamaguchi T. Waseda and I. Hirao Chem. Lett. 1983 35. 63 H. C. Brown D. Basaviah and U. S. Racherla Synthesis 1983 886; M. T. Reetz and H. Muller-Starke Liebigs Ann. Chem.. 1983 1726. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 173 toward synthesis of glycosides. The chemistries of 1,2- and 1,4-dicarbonyl transposi- tion have been explored and a 3-ketobutyl synthon [1-(2-methyl)- 1,3-dioxolan-2-y1-2- nitroethane] has been used to generate 1,4-diket0nes.~~ Aldehydes (not ketones) were reduced by Bu,N+ BH(OAc),- in refluxing benzene except in the case of PhCOCMe,CHO where intramolecular hydride delivery was suspected.Zn(BH,), as a stable complex with DMF reduced ketones with a speed which depended on structure.65 Borane complexed with (S)-valinol gave 65-73'/0 selectivity in reduction of a prochiral ketone and high asymmetric induction (>go%) was found in reduction of keto-esters derived from (-)-8-phenylmenthol with KB( Pr'O),H. Reactivity factors and the stereochemistry of metal borohydride and aluminohydride reduction have been surveyed.66 Prochiral a -halogeno-ketones gave with 9-BBN halohydrins in good e.e. ;these were transformed into chiral epoxides or alcohols. Yeast-mediated reactions were applied to a range of halogenated ketones (and keto-esters); high yields and optical purities were noted.67 An alternative to Wolff-Kishner reactions is the use of LiAlH4-P214 in refluxing benzene; yields were variable but excellent in some cases.68 Efficient procedures for a -deuteration or a -tritiation of ketones have appeared.69 a -Bromo-ketones can be obtained by treatment of an alkene with sodium br~mite.~' Some miscellaneous reactions include an improved route to gem-diacetates (Ac,O- FeCl,) asymmetric Strecker synthesis and selective protection of carbonyl groups using silica-supported Girard's reagent.71 General surveys of alkylation reactions metal enolates homoenolates and homoenolization have appeared.72 Aldol-type reactions continue to occupy prime interest.An efficient one-pot generation and reaction of lithiated ethers ROCH,Li has been used to explore reactivity in addition processes; Bu'OMe is a hydroxymethyl anion equivalent.' The stereochemistry of products formed from enolates of alkyl t-butyl ketones and PhCHO has been explored; syn-aldols e.g.(2I) were preferred Aldehyde t-butylhydrazones via lithiated derivatives reacted with carbonyl compounds or alkyl halides to form C-trapped t-butyl azo-compounds which by isomerization and hydrolysis gave either a -hydroxy-ketones or ketones. These reagents are thus con- 64 V. V. Kane V. Singh A. Martin and D. L. Doyle Tetrahedron 1983,39,345; T. Shono and S. Kashimura J. Org Chem. 1983 48 1939; G. Rosini R. Ballini and P. Sorrenti Tetrahedron 1983 39 4127. 6T C. F. Nutaitis and G. W. Gribble Tetrahedron Lett. 1983 24 4287; B.J. Hussey R. A. W. Johnstone P. Boehm and I. D. Entwistle Tetrahedron 1982 38 3769. 66 S. Itsuno A. Hirao S. Nakahama and N. Yamazaki J. Chem. Soc. Perkin Trans. I 1983 1673; J. K. Whitesell D. Deyo and A. Bhattacharya J. Chem. Soc. Chem. Commun. 1983 802; B. Caro B. Boyer G. Lamaty and G. Jaqueu Bull Soc. Chim. Fr. U 1983 281; H. Haubenstock Top. Sfereochem. 1983 14 23 I. 67 H. C. Brown and G. G. Pai J. Org. Chem. 1983 48 1784; M. Bucciarelli A. Forni I. Moretti and G. Torre Synthesis 1983 897; T. Kitazume and N. Ishikawa Chem. Lett. 1983 237. 68 H. Suzuki R. Mosuda H. Kubota and A. Osuko Chem. Lett. 1983 909. 69 G. Rosini and R. Ballini Synthesis 1983 228; S. Hegade R. M. Coates and C. J. Pearce J. Chem. Soc. Chem. Commun. 1983 1484. 70 T.Kageyamo Y.Tobito A. Katoh Y. Ueno and M. Okawara Chem. Lett. 1983 1481. " K. S. Kochbar B. S. Bal R. P. Deshpande S. N. Rajadhyaksha and H. W. Pinnick J. Org. Chem. 1983 48 1765; D. M. Stout L. A. Black and W. L. Matier ihid. p. 5369; T. Chihara E. Waniguchi T. Wakabayashi and K. Taya Chem. Lerr. 1983 1647. 72 J. K. Whitesell and M. A. Whitesell Synthesrs 1983 517; T. Mukaiyama Pure Appl. Chem. 1983 55 1749; N. H. Werstiuk Tetrahedron 1983 39 205. 7? E. J. Corey and T. M. Eckrich Tetrahedron Lett. 1983 24 3 163 3 165. 74 C. H. Heathcock and J. Lampe J. Org. Chem.. 1983,48. 4330. 174 B. V.Smith venient acyl anion equivalent^.^^ An electron-transfer route has been claimed in reaction between lithiated pinacolone and ethyl p-nitr~benzoate.~~ Synthetic uses of silyl enol ethers and ketene acetals have been reviewed.77 Silicon derivatives have been employed in alkylation of cyanhydrin silyl ethers allylsilane- aldehyde reactions generation of Michael adducts of cis-stereochemical addition preferential erythro-selective (kinetically controlled) aldol reaction of enamino- silanes and aldehydes and stereoselective additions of t-butyldimethyl enolsilanes and aldehydes7* In the most favourable case in this last report MeC0,Bu' and PhCH(Me)CHO gave j3-hydroxy-ester with >97O/0 d.s.The Nazarov reaction (ther- mal ring closure of divinyl ketones) has been 'silicon-directed' in the transformation of (22) and (23) into (24) and ultimately to (25). The reaction affords an interesting annelation procedure and should be capable of elab~ration.~~ Diene (26) with PhCHO-[Eu(hfc),] gave a cyclic adduct transformed into (27); when R = But 38% e.e.was observed and with diene (28) 58% e.e. was noted for (29)." Me0 Me,SiO H 0' H Me Ph (26) R = Me or But (27) (28) (29) A new chiral borane B-allyldi-isopinocampheylborane(30)' gave 83-96% e.e. in production of homoallyl alcohols (from RCHO)." Ally1 boronates a j3-alkoxy- carbanion equivalent formed homoallyl alcohols with high threo erythro ratio ; 75 R. M. Adlington J. E. Baldwin J. C. Bottaro and M. W. D. Perry J. Chem. SOC., Chem. Commun. 1983 1040. 76 E. C. Ashby and W.3. Park Tetrahedron Lett. 1983 24 1667. 77 P. Brownbridge Synthesis 1983 I 85. 78 T. Mukaiyama T.Oriyama and M. Murakami Chem. Lett. 1983,985; S. E. Denmark and E. J. Weber Helu. Chim. Actu 1983 66 1655; I. Crossland and S. 1. Hommeltoft Actu Chem. Scand. (B) 1983 37 21; W. Ando and H. Tsumaki Chem. Lett, 1983 1409; C. H. Heathcock and L. A. Flippin J. Am. Chem. SOC. 1983 105 1667 S. Kiyooka and C. H. Heathcock Tetrahedron Lett. 1983 24 4765; G. Kjeldsen J. S. Knudsen L. S. Ravn-Petersen and K. B. G. Torssell Tetrahedron 1983 39 2237. 79 T. K. Jones and S. E. Denmark Helv. Chim. Acta 1983 66 2377 2397. 80 M. Bednarski C. Maring and S. Danishefsky Tetrahedron Lett. 1983 24 3451. *' H. C. Brown and P. K. Jadhav. J Am. Chem. Soc. 1983 105. 2092. Aliphatic Compounds -Part ( ii) Other Aliphatic Compounds triallylborons with lithiated phenylselenyl ethers generate linear (3 1) or branched (32) homoallyl alcohols in which the key to the product ratio is the fate of (33).82 Divalent tin enolates of achiral aldehydes reacted with 3-acetylthiazolidine-2- thione and a chiral auxiliary to form P-hydroxy-aldehydes in which optical purities of 65-90% had been induced.83 In the presence of a palladium(0) catalyst 1-bromoalk-1-enes couple with tributyltin enolates to form P,y-unsaturated ketones in good yields.84 Enantio- and diastereo-selective syntheses using chiral glyoxylate esters and allylic tin reagents gave high erythro threo ratios; tin(1r) enolates of 1,3-dihydroxypropan-2-0nederivatives reacted with MeCOC0,Me in an anti-crossed aldol process in good yield whereas the corresponding crossed reaction with 2-bromo-2-methylpropanal and RCHO gave acceptable yields of /3 -hydroxy-aldehydes8' Penta-2,4-dienyltrimethylstannane with a,P-unsaturated carbonyls did not give Diels-Alder adducts with Lewis acids but normal (1,2) addition was noted.86 New (a-ethoxyalkeny1)tins have been employed in aldolization e.g.(34) -* (35) (71Y0).'~ General reviews of Ti- and Zr-mediated reactions have appeared. Dicarbonyl (intramolecular) coupling has been used to generate cyclic ketones or alkenes.88 Titanated butynyl carbamates (which as lithiated derivatives are synthetic equivalents of MeC=CHCHO) react with carbonyl compounds regio- and diastereo-selectively in which (36) is believed to represent the transition state.89 (34) (35) (36) ML3 = TiOPr' An interesting evaluation of the role of titanium and the stereochemistry of aldolization led to the conclusions that Lewis acids had a 'stereosteering' role and that increase of pressure could reverse threo erythro ratios observed in normal reactions.A similar re-evaluation of the boat transition state in Ti- and Sn-mediated x2 P. G. M. Wuts P. A. Thompson and G. R. Callen J. Org. Chem. 1983,48,5400; Y. Yamamoto Y. Saito and K. Maruyama ibid. p. 5408. 83 N. Iwasawa and T. Mukaiyama Chem. Lett. 1983 297. x4 M. Kosugi I. Hagiwara and T. Migita Chem. Lett. 1983 839. 85 Y. Yamamoto N. Maeda; and K. Maruyama J. Gem. Soc. Chem. Commun. 1983,774; R. W. Stevens and T. Mukaiyama Chem. Left. 1983 595; J.-I. Kato and T. Mukaiyama ibid. p. 1727. 86 Y. Naruta N.Nagai Y. Arita and K. Maruyama Chem. Lett. 1983 1683. 87 J.-P. Quintard B. Elissondo and M. Pereyre J. Org. Chem. 1983 48 1559. 88 B. Weidmann and D. Seebach Angew. Chem. Int. Ed. Engl. 1983 22 31; J. E. McMurry Acc. Chem. Res. 1983 16 405; J. E. McMurry and D. D. Miller J. Am. Chem. Soc. 1983 105 1660. 89 D. Hoppe and C. Riemenschneider. Angew. Chem. Int. Ed. Eng1 1983 22 54. 176 B. V. Smith reactions has appeared." Reetz has reported on the reaction shown in Scheme 6; high erythro :threo ratios were noted. 100% N-titanation was observed with (37) and for R' = Me X = OPr' R2 = Ph the product ratio was 91 :9.Chiral P-alkoxy- aldehydes gave 1,3-asymmetric induction in Ti-mediated addition to enolsilyl ethers ; zirconium behaved similarly.'' Methenylation of ketones (and nitriles and alkynes) occurs by means of titanocene dichloride-methylenezinc iodide.92 Aldehydes in the presence of TiCl, react with 3-phenyl-3-trimethylsilylprop-1-ene to form homoallylic alcohols which could be converted into P-hydroxy-esters; thus Bu'CHO afforded (R)-Bu'CH(OH)CH,CO,Me with 9 1'/o e.e.93 Zirconocene-induced coupling of a ketone with isoprene showed reversal of regioselectivity ;high threo-selectivity was noted for addition of e.g.(E)-C,H,ZrCICp2 to EtCHO at -1 10 "C (92% j.94 Rf\ I' R+ R'CH2CH=NNMe2 c,c\ -".N (37) NMe N-NMe / TIX3 I R' R' erythro threo Reagents i LDA 0°C; ii CITi(OPr') or BrTi(NEt,), -78°C iii R'CHO -78 to -40°C Scheme 6 Regioreversal in the addition of (E)-MeCH=CHCH,MgCl to carbonyl groups occurs in the presence of A1Cl3 to form the a-adduct prefer en ti all^.^^ The reason for this is not clear but two possibilities are shown in Scheme 7.The major product (38) from 3-phenylprop- I -enylmagnesiuln chloride and PhCHO supported the 'open chain rne~hanism'.~~ Chain lengthening (Me,SiCH,MgCl-R'COR2) is a con- venient pro~ess.~' Miscellaneous reactions include addition of ally1 or benzyl halides to aldehydes catalysed by Sm" ring-opening of oxazolidines (from ephedrine) by organocuprates to give aldehydes with modest e.e. alkylation of ketones by alkenes (with Ag2S20R) YO Y. Yamamoto K. Maruyama and K. Matsumoto J. Am. Chem. Soc. 1983 105 6963; E. Nakamura and I. Kuwajima Tetrahedron Lett. 1983 24 3343 3347.91 M. T. Reetz R. Steinbach and K. Kesseler Angew. Chem. Suppl. 1982 1899; M. T. Reetz and A. Jung J. Am. Chem. Soc. 1983 105 4833. 92 J. J. Eisch and A. Piotrowski Tetrahedron Lett. 1983 24 2043. Y3 T. Hayashi M. Konishi and M. Kumada J. Org. Chem. 1983 48 281. 94 G. Erker and U. Dorf Angew. Chem. Int. Ed. Engl. 1983,22 777; K. Mashima H. Yasuda K. Asami and A. Nakamura Chem. Lett. 1983 219. 95 Y. Yamamoto N. Maeda and K. Maruyama J. Chem. SOC.,Chem. Commun. 1983,742; J. Org. Chem. 1983 48 1564. 96 J. M. Coxon G. W. Simpson P. J. Steel and V. C. Trenerry Tetrahedron Lett. 1983 24 1427. 97 C. Burford F. C'ooke G. Roy and P. Magnus Tetrahedron 1983 39 867. Aliphatic Compounds -Part ( ii) Other Aliphatic Compounds 177 t \ I (38) Reagents iii AICI, -78 "C; iv RCHO -78 "C Scheme 7 and addition of Et,Zn to PhCHO catalysed by chiral complexes of Co and Pd.98 Catalytic activity has been noted for Pd complexes (aldolization) Fe carbonyl species (trimerization of aldehydes) and organomolybdenum (Wittig-like reaction) and chiral Rh complexes (cyclization of enal~).~~ Several papers describe Michael and related reactions.Aryl halides with either Li-ZnBr or a Pd catalyst gave products of conjugate addition (of ArH).'" LiMe2Cu gave fast conjugate addition in hydrocarbon solvents when reacting with (E)-PhCH=CHCOMe; in DMF or DMSO no conjugate addition was seen."' The stereocontrol of Michael addition was probed by addition of the p-lactone enolate (39) to (2)-dimethyl butenedioate and discussed in terms of the formation of the major product (40).Addition-cyclization was also discussed in terms of control exercised.Io2 The role of L-ascorbic acid in Michael addition to acrolein was described in stereochemical terms and speculatively proposed as a pathway for detoxifica-tion.Io3 Convenient addition (Et,Nf I-CF3CO2H) to enones formed P-iodo-ketones. lo4 H-(39) (40) YX J. Souppe J. L. Namy and H. B. Kagan Tetrahedron Lett. 1982 23 3497; P. Mangeney A. Alexakis and J. F. Normant ibid. 1983 24 373; A. Citterio F. Ferrario and S. De Bernardinis J. Chem. Res. (S) 1983 310; N. Oguni T. Omi Y. Yamamoto and A. Nakamura Chem. Lett. 1983 841. 99 J. A. Soderquist and W. W.-H. Leung Tetrahedron Lett. 1983 24 2361; J.Tsuji I. Minami and I. Shimizu ibid. p. 1793 1797; K. Ito M. Kamiyama S. Nakanishi and Y. Otsuji Chem. Lett. 1983 657; T. Kauffmann B. Ennen J. Sander and R. Wieschollek Angew. Chem. In?. Ed. Engl. 1983 22 244; B. R. James and C. G. Young J. Chem. SOC.,Chem. Commun. 1983 1215. I00 J.-L. Luche C. Petrier J.-P. Lansard and A E. Greene J. Org. Chem. 1983 48 3837; S. Cacchi and A. Arcadi ibid. p. 4236. 101 G. Hallnemo and C. Ullenius Terrahedron 1983 39 1621. I02 J. Mulzer A. Chucholowski 0. Lommer I. Jibril and G. Huttner J. Chem. SOC., Chem. Commun. 1983 869; G. Stork C. S. Shiner and J. D. Winkler J. Am. Chem. SOC.,1982 104 310. 103 G. Fodor R. Arnold 1. Mohacsi I. Karle and J. Flippen-Andersen Tetrahedron 1983 39 2137. I04 J. N. Mark Terrahedron 1983 39 1529.178 B. V. Smith 4 Carboxylic Acids and Esters Several methods for efficient esterification have been published. Acids with an alkyl chloroformate and Et,N-DMAP gave esters rapidly in high yield as did their reaction with Me,SiCl followed by addition of an alcohol. 1,l'-Dimethylstannocene is effective as a catalyst for acylation of alcohols (and amides) and for esterification of acids including hindered ones. 2-Chlor0-3~5-dinitropyridine catalysed esterifica- tion probably through anhydride formation. Bis(trimethylsily1) peroxide with ketones promoted Baeyer-Villiger-type ester formation in high yield.'05 Acid chlorides have been converted into terminal alkenes by the sequence in Scheme 8; use of LiAlD4 gave deuteriated alkenes.lo6 ... R'COCI ''I' R'COCH,CI -R'R2C(OM)CH2CI 1 R'R2C=CH2 tRiR2C(OM)CH2Li Reagents i CH,N,-Et,O; ii HCI; iii R2MgX (M = Mg); iv LiAIH,-AlCI Scheme 8 Phase-transfer catalysis of acid formation from vinyl halides led to a$ -unsatur-ated acids. lo' Prochiral a,P-unsaturated acids undergo asymmetric hydrogen transfer in achiral or chiral alcohols with chiral Ru phosphine complexes; the observed e.e. was generally low.'o8 Halogenation of a$-unsaturated acids via trimethylsilyl esters is efficient."' y,S-Unsaturated-P-0x0-esters uia dianions are alkylated exclusively at the y-position ; diketene and Grignard reagents with Co" catalyst formed 3-methylenealkanoic acids precursors for terpenoids. lo During Kolbe elec- trolysis (Z)-4-enoic acids are partially isomerized to (E)-isomers probably uia a cyclopropylcarbinyl radical.' I Preparation of optically active derivatives has employed the oxazoline/chiral auxiliary route (giving 2-chloro- or 2-phenyl-alkanoic acids in moderate e.e.) the generation of P-hydroxy-acids by addition of a chiral nitrile oxide to an alkene or by addition of RCHO to the trislithiated derivative of (R)-N-acetyl-a-phenylglycinol with improvement over previous methods."* Pig liver esterase has been used in selective hydrolysis of chiral3-hydroxy-3-methylalkanoic acid esters.' I3 Malate esters and L-serine have served as precursors for chiral building blocks.'14 S.Kim Y. C. Kim and J. I. Lee Tetrahedron Lett. 1983 24 3365; M. A. Brook and T. H. Chan Synthesis 1983,201;T.Mukaiyama J. Ichikawa and M. Asami Chem. Lett. 1983,293,683; S. Takimoto N. Abe Y. Kodera and H. Ohta Bull. Chem. SOC.Jpn. 1983 56 639; S. Matsubara K. Takai and H. Nozaki ibid. p. 2029. 106 J. Bariuenga M. Yus J. M. Concellon and P. Bernad J. Org. Chem. 1983 48 31 16. I07 J.-J. Brunet C. Sidot and P. Caubkre J. Org. Chem. 1983 48,1919. 108 K. Yoshinaga T. Kito and K. Ohkubo Bull. Chem. SOC.Jpn. 1983 56 1786. Io9 M. Beilassoued F. Habbachi and M. Gaudemar Synthesis 1983 745; T. Azuhata and Y. Okamoto ibid. p. 461. 110 J. A. M. van den Goorbergh and A. van der Gen J. R Neth. Chem. Soc. 1983 102 393; T. Fujisawa T. Sato Y. Gotoh M. Kawashima and T. Kawara Bull. Chem. SOC.Jpn. 1982 55 3555. 111 M. Huhtasaari H.-J.Schafer and H. Luftmann Acta Chem. Scund. (B) 1983 37 537. 112 S. Shibata H. Matsushita H. Kaneko M. Noguchi M. Saburi and S. Yoshikawa Bull. Chem. SOC. Jpn. 1982,55 3546; A P. Kozikowski Y. Kitagawa and J. P. Springer J. Chem. SOC. Chem. Commun. 1983 1460; M. Braun and R. Devant Angew. Chem. In?. Ed. Engl. 1983 22 788. 113 W. K. Wilson S. B. Baca Y. J. Barber T. J. Scailen and C. J. Morrow J. Org. Chem. 1983 48 3960. I14 J. D. Aebi M. A. Sutter D. Wasmuth and D. Seebach Liebigs Ann. Chem. 1983 21 14; R. Dumont and H. Pfander Helv. Chim. Acta 1983 66 814. Aliphatic Compounds -Part ( ii) Other Aliphatic Compounds 179 Synthesis and properties of a-keto-acids have been reviewed. Organocadmium reagents with CNC02Et-ZnC12 formed RCOC0,Et in fair yield.' I5 Keto-acids with a quaternary carbon at C-2 have been prepared from gem-dichlorocyclopropanes which act as masked esters; y-keto-acids were prepared by ring-opening of 2-alkoxycyclopropanecarboxylic esters.' l6 Yeast-mediated reduction of ethyl acetoace- tate gave (S)-ethyl-3-hydroxybutyrate in claimed 95-97% e.e.;use of Geotrichum candidurn gave the (R)-ester in -90% e.e.This is the first report of microbiological production of the (R)-isomer. Similar reduction of the y-chloro-ester was studied as a function of the size of the alkyl group in the ester; above C8 the rate diminished. With C1CH2COCH2CO2C8H the (-)-hydroxy-ester was formed with e.e. -96%.' '' These methods hold promise for a range of systems. Selective hydrolysis (pig liver esterase) of dimethyl esters of a range of diacids (symmetrical meso and cis-1,2-cyclic types) produced significant e.e.in the half-ester products. Thus Me02CCH,CH(Me)CH2C02Me formed a half-ester with e.e. of 90% (cJ 14% from chymotrypsin). In discussion of the mechanism it was suggested that binding to the enzyme was regulated so that in the dimethyl ester of 2,4-dimethyl-3- hydroxyglutarate the pro-S-group is hydrolysed."8 Tetraethoxyallene has been prepared and used as the synthetic equivalent of the malonate dianion ,-C(C02Et),. Copper(1)-promoted arylation of ethyl sodiocyanoacetate proceeds cleanly.' l9 5 Lactones Two useful synthetic routes are heterogeneous dehydrobromination of w -bromocar-boxylic acids and treatment of 1,n-diols with sodium bromite (NaBrO,).120 Enol-6-lactones were prepared from the Wittig reagent RO,CC( Me)=PPh and glutaric anhydride derivatives with some selectivity and p -keto-lactones via the dianion from an w -halogeno-P-keto-ester.'21 Asymmetric synthesis of bicyclic lactones was achieved in high yield (and good e.e.) from a chiral imide precursor; transformation of the appropriate lactone precursor was applied to a synthesis of (lR,3S)-cis-chrysanthemic acid (81'/o e.e.). Macrocylic lactones have been piepared from protec- ted hydroxy-aldehydes and the phosphonium ketene Ph,P-C=C=O as starting material ;transformation of the adduct was successfully achieved and exaltolide and ambrettolide were synthesized.'22 I15 A. J. L. Cooper J. Z. Ginos and A. Meister Chem.Rev. 1983,83 321; Y. Akiyama T. Kawasaki and M. Sakamoto Chem. Lett. 1983 1231. I I6 M. G. Banwell J. Chem. SOC.,Chem. Commun. 1983 1453; H. Kunz and M. Lindig Chem. Ber. 1983 116 220. I17 B. Wipf E. Kupfer R. Bertozzi and H. G. W. Leuenberger Helv. Chim. Acta 1983 66 485; B.-N. Zhou A. S. Gopalan F. Van Middlesworth W.-R. Shieh and C.J. Sih J. Am. Chem. SOC.,1983,105,5929. I I8 P. Mohr N. Waespe-SarEevik C. Tamm K. Gawronska and J. K. Gawronski Helv. Chim. Acta 1983 66 2501. II9 R. W. Saalfrank and W. Rost Angew. Chem. SuppL 1983,451; A. Osuka T. Kobayashi and H. Suzuki Synthesis 1983 67. 120 Y. Kimura and S. L. Regen J. Org. Chem. 1983 48 1583; T. Kageyama S. Kawahara K. Kitamura Y. Ueno and M. Okawara Chem. Letf. 1983 1097. 12' S.Tsuboi H. Fukumoto and A. Takeda Chem. Lett. 1983 1219; R. J. Sims S. A. Tischler and L. Weiler Tetrahedron Lett. 1983 24 253. I22 T. Mukaiyama H. Yamashita and M. Asami Chem. Lett. 1983 385; H.-J. Bestmann and R. Schobert Angew-. Chem. lnt. Ed. EngL 1983 22 780. 180 B. V. Smith y-Butyrolactones (as the disilyl enolate) react with a simple aldehyde with com- plete diastereoface selectivity as only one of four possible diastereoisomers was formed.123 Adduct (4 1) was formed with complete threo-selectivity (Scheme 9) and as shown afforded (42) or (43) by appropriate reaction. Control was considered to be due to a bicyclic (44) or acyclic (45) transition state (Scheme 9). OSiMe GOH .* 0 Me3Sio __* Me,% ii i ' H"Q -H% RZ R' R' R' R' R' Reagents i TiCI,RCHO -78 "C; ii BF,-Et,O; iii KN(SiMe& Scheme 9 Several ring-opening reactions noted are regioselective attack of alkylaminostan- nanes the use of 9-BBN to form substituted cyclopropylacetic acids from p-lactones and production of a,o-diesters of long-chain diacids by addition of Grignard reagents (from a,w-dihalides) to P-propiolactone (including synthesis of a precursor for ~ivetone).'~~ Epoxide formation was noted in attack of PhS02CH2Li on (46) which yielded (47); cyclization of (47) gave a mixture in which (48) ~red0minated.l~~ y-Butenolides reacted with KMn0,-crown ether to give principally cis-2,3-dihy- droxy-y-butyrolactone; a bulky substituent in (49) favoured formation of (50) at the expense of the other isomer.An entry into the carbohydrate series was available from such precursors.'26 I23 K.Yamamoto and Y. Tomo Chem. Lett. 1983 531. I24 A. Ricci M. Romanelli M. Taddei G. Seconi and A. Shanzer Synthesis 1983 319; M. Kawashima and T. Fujisawa Chem. Lett. 1983 1273; T. Fujisawa T. Sato T. Kawara and H. Tago Bull. Chem. SOC.Jpn. i983 56 345. I25 S. Batmangherlich A. H. Davidson and G. Procter Tetrahedron Lett. 1983 24 2889. T. Mukaiyama F. Tabusa and K. Suzuki Chem. Lett.. 1983 173. Aliphatic Compounds -Part ( ii) Other Aliphatic Compounds (47)X= PhSO HO’ OH (49) (50) 6 Amines and Amides Amination of alkenes has been reviewed.’” Synthetic routes reported include a reductive Beckmann reaction of oximes which gave good yields of secondary amines formation of functionalized tertiary amines hydroboration-alkylation of propargyl amines to form unsaturated amines a conversion of primary amines into secondary allylamines via a Wittig-type sequence and generation of tertiary propargyl- amines.”* Synthesis of primary allylic amines has been reviewed.lz9 Ally1 boronates with Schiff bases gave secondary homoallylamines.13’ Direct addition of the amino- group to an alkene was possible by use of NH2CN-NBS; trans-but-2-ene formed (*)-2,3-diaminob~tane.’~’ Primary amines have been converted into imines (and other products) by an excess of RLi into ketones (by anodic methoxylation of carbamates) and into imines by reaction with N-chlorosuccinimide followed by elimination from the formed N-chloroamine.32 An asymmetric synthesis of substituted propargylamines (and a-substituted a-amino-acids) employed in the first stage amidine formation from a chiral pyrrolidine (51) and R’R2CHNH2; the amidine (52) was a source of either product according to p -hydroxyamines were resolved kinetically by enan- tioselective N-oxide f~rmation.’~~ o*o II (51) (52) 127 M. B. Gase A. Lattes and J. J. Perie Tetrahedron 1983 39 703. 128 S. Sasatani T. Miyazaki K. Maruoka and Y. Yamamoto Tetrahedron Lett. 1983,24,4711; G. Courtois and P. Miginiac Bull. SOC.Chim. Fr. ZZ 1983 148; J. L. Torregosa M. Baboulene V. Speziale and A. Lattes Tetrahedron 1983,39,3101; R. J. Linderman and A. I. Meyers Tetrahedron Lett. 1983,24,3043; G. Boche M. Bernheim and M. Neissner Angew.Chem. Suppl 1983 34. I29 R.B. Cheikh R. Chaabouni A. Laurent P.Mison and A. Nafti Synthesis 1983 685. I30 R. W. Hoffmann G. Eichler and A. Endesfelder Liebigs Ann. Chem. 1983 2000. 131 H. Kohn and S.-H. Jung J. Am. Chem SOC.,1983 105,4106. 132 H. G. Richey jun. and W. F. Erickson J. Org. Chem. 1983 48 4349; T. Shono Y.Matsumura and S. Kashimura ibid. p. 3338; J.-C. Guillemin and J.-M. Denis Angew. Chem. Suppl. 1982 1515. 133 M. Kolb and J. Barth Liebigs Ann. Chem. 1983 1668. I34 S. Miyano L. D.-L. Lu S. M. Viti and K. B. Sharpless 1.Org. Chem. 1983 48 3608. 182 B. V.Smith Stereoselective preparation of amino-ketones (Scheme 10) gave (53) as a single isomer which afforded the threo-amino-ketone (54).'35Mannich bases have been prepared from iminium salts and silyl enol ethers and an alternative route to Mannich-functionalized amines has been presented.136 Me NHTs Me NHTs IV Me Me N-TS I MenAa iv o/ *Me I Me Me Me (53)\JJ/ (54) Reagents i TsN=S=O PhMe 0 "C ii 5% NaOH r.t.; iii 5% HCI 0 "C;iv Os0,-Na104 Scheme 10 Enamine chemistry has been re~iewed.'~' A one-pot synthesis has been reported optimization of yields has been undertaken and bicyclic enamines have been obtained from 1a~tams.I~~ a-Chloroenamines with R'C02H-R2MgX gave chemoselectively ketones in high yields; CN and OAc groups were unreactive since PhCH(OAc)CO,H gave only PhCH(OAc)COCH2CH2Ph with the appropriate reagent. 139 Very effective asymmetric synthesis was noted for Mi'chael addition of (55) to ArCH=C(CO,Et),; (56)was formed with d.s.95% and e.e. 92% .I4' Metallated enamines have been prepared and studied; nucleophilic attack of an enamine on a chiral allylic molybdenum complex formed alkenes or alkenals in good optical yield and enaminoketones with RLi gave a,@-unsaturatedketones. 14' Weak acids with RNH and P214,formed amides in excellent yield; alkylation of RCONH [by R'OH and RuC12(PPh3),]was effective and R'CHO and a secondary amine formed tertiary amides in excellent yield with Pd" cata1~st.l~~ Alkyldiphenyl-sulphonium salts proved efficient 0-alkylating agents for amides and ~reas.'~~ A chiral stationary phase (recognition model) derived from 3,5-dinitrophenyl-glycine has been applied to the resolution of N-acyl-1-amino-1-ary1alkanes.l4 Reduction of amides from MeCOC0,H and chiral amines has been studied; e.e.was low in the products and depended on the conditions used. Improved selectivity was found for reduction [Zn(BH,),] of 2-alkyl-3-oxoamides in which product with a high d.s. ratio was obtained e.g. MeCOCH(Me)CONH gave 13.' R. S. Garigipati J. A. Morton and S. M. Weinreb Tetrahedron Lett. 1983 24 987. I36 R. N. Benaud D. BCrubC and C. J. Stephens Can. J. Chem. 1983,61,1379;G.Courtois and P. Miginiac Bull. Soc. Chim. Fr. II 1982 395; ibid. 1983 p. 21. 137 P. W. Hickmott Tetrahedron 1982 38 3363. 138 R. Knorr P. Low and P. Hassel Synthesis 1983 785; R. Carlsson A. Nilsson and M. Stromquist Acta Chem. Scand. (B) 1983 37 7; J.M. McIntosh L. Z. Pillon S. 0.Acquaah J. R. Green and G. S. White Can. J. Chem. 1983 61 2016. I39 T. Fujisawa T. Mori K. Higuchi and T. Sago Chem. Letf. 1983 1791. 140 S. J. Blarer and D. Seebach Chem. Ber. 1983 116 2250; cf D. Seebach and V. Prelog Angew. Chem. Int. Ed. Engl. 1982 21 567. 141 H. Albrecht Synthesis 1983 56 58 61; J. W. Faller and K.-H. Chao J. Am. Chem. SOC.,1983 105 3893 T. Mukaiyama and T. Oshurni Chem. Left. 1983 875. I42 H. Suzuki J. Tsuji Y. Hiroi N. Sato and A. Osuka Chem. Left. 1983 449; Y. Watanabe T. Ohta and Y. Tsuji Bull. Chem. Soc. Jpn. 1983,56,2647; Y. Tamaru Y. Yarnada and Z. Yoshida Synthesis 1983 474. 143 M. Julia and H. Mestdagh Tetrahedron 1983 39 433. I44 W. H. Pirkle C. J. Welch and M. H. Hyun J.Org Chem. 1938 48 5022. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds (*)-MeCH(OH)CH(Me)CONH (syn :anti = 98:2).'45 High e.e. in the formation of amide (58) and its subsequent hydrolysis to a 2-substituted malate (59) was found; the chiral auxiliary (57) was highly effective here.'46 r---. N Me A I Primary enamides (E)-or (2)-RCH=CHNHAc have been generated by copper- catalysed decarboxylation of the acids RCH=C(CO,H)NHAc; the (2)-or (15)-isomer can be prepared by choice of ~olvent.'~' 7 Other Nitrogen Compounds Efficient conversions of acids and oximes into nitriles by ethyl polyphosphate and trimethylsilyl polyphosphate respectively have been Phase-transfer catalysis has been employed in smooth dehydration of ald~ximes.'~~ An 'acetal template' has been used in the generation of cyanhydrins in high optical yield (Scheme 1 1).I5' Oxidation of sec-alkyl cyanides (MezSO-O2-base) afforded ketones but in variable ~ie1d.l~' Stereocontrolled synthesis of 2-substituted-cu,P-unsaturated nitriles employed TiCl,-promoted condensation of an aldehyde and silylketene- imines.15 Allenic nitriles were prepared from oxime precursors.lS3 Transformation Reagents i Me3SiCN-TiC14 -40 to -20 "C:ii TsOH-dioxane Scheme 11 I45 T. Munegumi and K. Harada Chem. Lett. 1983 1225; Bull. Chem. Soc. Jpn. 1983,56,298 2774; Y. Ito and M. Yamaguchi Tetrahedron Lett. 1983 24 5385. 146 R. W. Stevens and T. Mukaijama Chem. Len. 1983 1799. 147 U. Schmidt and A. Lieberknecht Angew.Chem. In?. Ed. Engl. 1983 22 550. 148 T. Imamoto T. Takaoka and M. Yokoyama Synthesis 1983 142 J. M. Aizpura and C. Palomo Nouv. J. Chim. 1983 7 465. I49 H. Shinozaki M. Imaizumi and M. Tajima Chem. Lett. 1983 929. I 50 J. D. Elliott V. M. F. Choi and W. S. Johnson J. Org. Chem. 1983 48 2294. IS1 S. S. Kulp and M. J. McGee J. Org. Chem. 1983 48 4097. IS2 H. Okada I. Matsuda and Y. Izumi Chem. Lett. 1983 97; Bull. Chem. SOC.Jpn. 1983 56 528. J. Grimaldi and A. Cormons. Bull. Snc. Chim. Fr. 11 1983 49. 184 B. V. Smith of RN=C=O into RN=C has been followed by I3C n.m.r.; Bu'Ph,SiLi was effective and the nature of the intermediates was ~1arified.l~~ Ethoxymethylenemalonitrile served as a building block for some heterocyclic No evidence for a vinyl cation was found when (EtO),C=CH(N,+) was decom- posed in solution.156 Oxidation of R1R2CHN02 [Fe(CN);-] gave dinitro-compounds whereas reductions of unsaturated nitro-compounds afforded ketones and oxime~.'~' Convenient nitro-aldol reaction could be effected by use of alumina at room temperat~re."~ The preparation and reactions of diazomethane have been surveyed.159 8 Sulphur Compounds Simple preparative routes to and reactions of thioaldehydes have been studied.I6' Terminal alkynes via thiophenyl ethers and their reaction with HgS04-H+ can be transformed into acids. AcSH adds to a$-unsaturated carbonyl compounds in the presence of cinchonine forming adducts with variable e.e.16' Activation of azides by sulphur improved their reactivity toward organometallics ; the adducts (RNHN=NCH,SPh) by acylation and subsequent cleavage with base gave good yields of amides RNHCOR'.162 Two-phase alkylation using sulphonium salts was accelerated by Cu'; prenyl salts gave only tertiary esters in presence of CUB^.'^^ Sodium bromite was effective and selective for conversion of dialkyl sulphides into sulph~xides.'~~ The facile production of an a,p-enone from a P-oxosulphide trans- formation of methyl ketones into a-chlorosulphenyl chlorides efficient generation of chiral sulphinates and a Darzens reaction in the presence of chiral L-menthyl chloromethanesulphonate (with low e.e.in the formed epoxysulphonate) have been noted.165 Chiral (arylsulphinylmethyl) oxazolines serve as chiral enolace- tate equivalents leading to P-hydroxy-acids in moderate e.e.The d.s. ratio in the product from XC6H4CH0 and (*)-MeC6H4SOCH2CH=CH2-LDA was found not to depend significantly on the substituent X. Liquid chromatographic separation of sulphoxides and sulphoximines is possible with a chiral stationary phase [(R)-N-(3,5-dinitrobenzoyl)phenylglycine].166 I54 J. E. Baldwin A. E. Derome and P. D. Riordan Tetrahedron 1983 39 2989. I55 H. W. Schmidt R. Schipfer and H. Junek Liebigs Ann. Chem. 1983 695. I56 I. Szele M. Tencer and H. Zollinger Helu. Chim. Acta 1983 66 1691. 157 N. Kornblum H. K. Singh and W. J. Kelly J. Org. Chem. 1983 48 332; S. Torii H. Tanaka and T. Katoh Chem. Lett. 1983 607. G. Rosini R. Ballini and P. Sorrenti Synthesis 1983 1014. 159 T.H. Black Aldrichim. Acta 1983 16 3. I60 E. Vedejs and D. A. Perry J. Am. Chem. Soc. 1983 105 1683; J. E. Baldwin and R. C. G. Lopez Tetrahedron 1983 39 1487. 161 S. R. Abrams Can.J. Chern. 1983,61,2423;J. K. Gawronski K. Gawronska H. Kolbon and H. Wynberg J. R. Neth. Chem. Soc. 1983 102 479. 162 B. M. Trost and W. H. Pearson J. Am. Chem. SOC. 1983 105 1054. I63 B. Badet M. Julia M. Ramirez-Munoz and C. A. Sarrazin Tetrahedron 1983 39 31 11. I64 T. Kageyama Y. Ueno and M. Okawara Synthesis 1983 815. I65 Y. Ueno L. D. S. Yadav and M. Okawara Chem. Lett. 1983 831; G. Adiwidjaja H. Giinther and J. Voss Liebigs Ann. Chem. 1983 11 16; K. Hiroi R. Kitayama and S. Sato Synthesis 1983 1040; M. H. H. Nkunya and B. Zwanenburg J. R. Neth. Chem.Soc. 1983 102 461. I66 R. Annunziata M. Cinquini and A. Gilardi Synthesis 1983 1016; D. D. Ridley and M. A. Smal Aust. J. Chem. 1983 36 1049; S. Allenmark L. Nielsen and W. H. Pirkle Acta Chem. Scand. (B) 1983,37 325. Aliphatic Compounds -Part ( ii) Other Aliphatic Compounds 185 Alkyl allyl and benzyl sulphones by metallation and subsequent treatment with Me,SiOOSiMe, gave ketones. Ketones with LiMe3SiCHzS02Ph in DME gave a$-unsaturated sulphones chemoselectively. Dianions from P-hydroxy-sulphones reacted with alkyl halides or carbonyls to form furanones; dianions from P-keto- sulphones underwent a -and y-alkylation and by brominative cleavage alkenes were formed.16' In this way was prepared non-6-en-1-01 (fruit fly pheromone). The sulphone dianion is a synthetic equivalent of the dianion C=C.A range of dienes can be conveniently prepared from the monoanion of RCH,CH=CHSOZCH,Br by sequential intramolecular loss of Br- and SO2. Ths bis-sulphone (60) is a synthetic equivalent of the 1,3-dipole +CHzCH2CHz.169 Electrophilic cyclization-fragmentation of allenic sulphones and sulphinates led to (chiral) a,P -unsaturated sultines. Functionalized resins with hydrazinosulphonyl groups bind carbonyl compounds; when heated with alkali the formed sulphonylhy- drazones gave alkenes or in the presence of NaBH,-LiAlH, alkanes or with MeOH-KCN homologated nitriles. Some sensitivity to the steric bulk of groups in the carbonyl compound was discerned. 17* Triflates have been reviewed and their chemistry in acylation has been e~plored.'~' 9 Phosphorus Compounds Preparation and uses of chiral [160,'70,180]phosphateesters has been reviewed.17* Stable alkylidenephosphenes have been reported; the reduction of bis-arylphos- phenes gave a mixture of (*)-and me~ophosphanes.'~~ Attack by ethoxy-radicals at trivalent phosphorus occurred with net inver~i0n.I~~ Diphosphorus tetraiodide is useful for deoxygenation of benzylic alcohols and hydroxymethyl groups attached to Pv.175 A considerable volume of work on Wittig-type reactions has appeared.Wadsworth-Emmons processes have been revisited and synthetic applications sum-mari~ed.'~~ Novel and interesting reactions include the first stereoselective synthesis of 2-cqp-unsaturated esters by the Horner-Emmons reaction (Scheme 12) the successful use of heterogeneous conditions and weak bases in HzO to obtain I67 J.R. Hwu J. Org. Chem. 1983,48,4432; S. V. Ley and N. S. Simpkins J. Chem. SOC.,Chem. Commun. 1983 1281 K. Tanaka K. Ootake K. Imai N. Tanaka and A. Kaji Chem. Lett. 1983,633; D. Scholz Liebigs Ann. Chem. 1983 98. 168 E. Block et al. J. Am. Chem. SOC. 1983 105 6164 6165. I69 B. M. Trost J. Cossy and J. Burks J. Am. Chem. SOC.,1983 105 1052. I70 S. Brouerman and Y. Duar J. Am. Chem. SOC.,1061; H. Kamogawa A. Kanzawa M. Kadoya T. Naito and M. Nanasawa Bull. Chem. SOC.Jpn. 1983 56 762. 171 P. J. Stang and M. R. White Aldrichim. Acta 1983 16 15; F. Effenberger G. Epple J. K. Eberhard U. Buhler and E. Sohn Chem. Ber. 1983 116 1183. I72 G.Lowe Acc. Chem. Res. 1983 16 244. 173 M. Yoshifuji K. Toyota K. Shibayama and N. Imamoto Chem. Lett. 1983 1653; M. Yoshifuji K. Shibayama and N. Imamoto ibid. p. 585. I74 W. G. Bentrude M. Moriyama H.-D. Mueller and A. E. Sopchik J. Am. Chem. SOC.,1983 105 6053. I75 H. Suzuki H. Sani H. Kobuta N. Sato J. Tsuji and A. Osuka Chem. Lett. 1983 247; M. Yamashita K. Tsunekawa M. Sugiura T. Oshikawa and S. Ionokawa ibid. p. 1673. I76 W. J. Stec Acc. Chem. Rex 1983 16 41 I. 186 B. V. Smith a,P -unsaturated ketones and esters reaction of P -hydroxy-carboxylic acids with the phosphorane from diethyl azodicarboxylate to form alkenes+( with ste+reocontrol in some cases) and the preparation and decomposition of R3P-CF-PR3 which afforded a route to a 1,2-difl~oroalkene."~ A one-pot process leading to a conjugated diene used the palladium-promoted coupling of an aldehyde and allylic alcohol in the presence of Ph,P; penta-2,4-dienylphosphineoxide with carbonyl compounds gave conjugated trienes.'?* The rate of reaction of stabilized ylides and yield of E-alkene were increased at a pressure of 10 kbar.'79 0 R I1 (CF,CH20),PCH(R)C0,Me 2 ~1 CO,Me Reagents i R'CHO KN(SiMe3),-THF-18-crown-6, -78 "C Scheme 12 Wittig reactions have also been applied to the preparation of enamines and enol ethers of aldehydes and the stereoselective synthesis of cyclopropanes and bicyclic lactones.'" Phosphonium ylides via acylation and decomposition of the acyl ylide gave 1,2-diketones transformable into dialkylacetylenes.Ph3PC12 with lithium car- boxylates formed an acyloxyphosphonium salt ; treatment of this with Grignard reagent afforded ketones in good or very good yield.18' A boron analogue of the Wittig reaction is shown in Scheme I3 ; decomposition of the diastereoisomeric Li' Mes2BCR1R2 R'R2C-CR3R4 II Mes,B OLi Scheme 13 adducts from PhCHO and n-C8H17BMes2 gave PhCH=CHC7H, with >99.9% E-isomer. Yields were generally better at low temperatures. Mixed dior-ganoborinanes formed from a phosphonium ylide and borane undergo addition to an alkene (Scheme 14) in a scheme which can be expressed as in the equation R'CH2X + CI,CHOMe + R2CH,X + R3COR4 + R'CH2COCH(R2)CHR3R4 177 W. C. Still and C. Gennari Tetrahedron Lett. 1983 24,4405; J.Villitras and M. Rambaud C. R. Hebd. Seances Acud. Sci. 11 1983 1175; Synthesis 1983,300; J. Mulzer and 0.Lammer Angew. Chem. Suppl. 1983 887; D. J. Burton and D. G. Cox J. Am. Chem. Soc. 1983 105 650. 178 M. Moreno-Manas and A. Trins Bull. Chem. Soc. Jpn. 1983 56 2154; C. C. Santini and F. Mathey Can. J. Chem. 1983 61 21. 179 A. Nonnenmacher R. Mayer and H. Plieninger Liebigs Ann. Chem. 1983 2135. IBo J. C. Gilbert and U. Weerasooriya J. Org. Chem. 1983 48 448; A. Moupert J. Martelli R. Gree and R. Carrit Nouv. J. Chim. 1983 7 345; R. W. Saalfrank P. Schierling and P. Schatzlein Chem. Ber. 1983 116 1463. 181 H.-J. Bestmann K. Kumar and L. Kisielowski Chem. Ber. 1983 116 2378; T. Fujisawa S. Iida H. Uehara and T. Sato Chem. Lett. 1983.1267. Aliphatic Compounds -Part ( ii) Other Aliphatic Compounds RICH-GPh rRiCH-6PhS] A R'CH2BH2PPh iii 1-AH3 1 1 X R3 X / R'CH,COCHR2 -R'CH2!5CH(R2)CH' R1CH2B .PPh I CH \R4 \H R3/ \R4 Reagents i BH3-THF; ii A; iii HX; iv R2CH=CR3R4; v R'I; vi C1,CHOMe; vii LiOCEt3; viii H,O,-NaOH Scheme 14 The ylide (61) has been used to add to carbonyl groups in a Horner-type process generating E/Z-a,P-unsaturated esters in which the E-isomer predominated.'82 R,feC HC0,Et (61) It proved possible to isolate a ketophosphonium halide from a phosphorus(m) ester and an a -halogenocarbony1 compound. Decomposition via an Arbuzov reac- tion was the only observed reaction forming (RO),P(0)CH2COR1. lg3 The synthetic usefulness of Homer-Wittig reactions based on Ph2P(0)CH2R1 is well illustrated by Scheme 15 in which stereospecific elimination from (62) led to (62) Reagents i HO-H,O; ii BuLi then R'CHO then separate isomers iii NaH-DMF Scheme 15 2-alkene in good yield ;stereoselective reduction of ketone (63) gave a rhreo-product (64) which also underwent stereospecific elimination to an E-alkene.In a variation on this theme trisubstituted alkenes were prepared from the appropriate starting material.184By protecting the carbonyl group (as a dioxolane) sequences to P,y-and y,S-unsaturated ketones have been successfully employed. Full regio- and stereo-chemical control in formation of E-and 2-allylamides from /3-(acy1amino)alkylphosphine oxides was achieved. A lack of stereospecificity in elimi- nation from (63) was attributed to a fragmentation and recombination; it proved possible to use a trap (3-ClC6H4CHO) to detect formed PhCHO and isolate E-and 2-chlorostil bene~.'~~ I xz A.Pelter B. Singaram and J. W. Wilson Tetrahedron Lett. 1983,24,635; H.-J. Bestmann and T. Roder Angew. Chem. Int. Ed. EngL 1983 22 782; A. Osuka Y. Mori H. Shimizu and H. Suzuki Tetrahedron Ler?. 1983 24 2599. 183 1. Petnehazy G. Szakai and L. Toke Tetrahedron 1983 39 4229. I84 A. D. Buss and S. Warren Tetrahedron Lett. 1983 24 3931 5293 11 I; C. Earnshaw R. S. Torr and S. Warren J. Chem. Soc. Perkin Trans. 1 1983 2879 2893. ins C. A. Cornish and S. Warren Tetrahedron Lett. 1983 24 2603; D. Cavalla and S. Warren ibid. p. 295; A. D. Buss S. Warren J.S. Leake and G. H. Whitham J. Chem. SOC.,Perkin Trans. I 1983 2215. 188 B. V. Smith Diastereoisomerically pure phosphinates have been generated from an Arbuzov reaction of (2S,4S)-4-methyl-2-phenyl-I ,3,2-dioxaphosphorinane and used to pre- pare chiral phosphine oxides in high (76-1 00%) optical yield.'" p-Hydroxyalkylphosphonates underwent smooth fluoride ion-catalysed elimination; in a similar reaction scheme a-trimethylsilylalkylphosphonates gave alkenes by reaction with carbonyl compounds in the presence of CsF (the best ~atalyst).'~' By this latter approach PhCOMe afforded Ph(Me)C=CHMe with an E :2 ratio of 1 :3. Epoxidation of a$-and &?-unsaturated phosphonates has been achieved by H,02-Na2W0 or Bu~~~H-Mo(C~)~.'~~ 10 Miscellaneous A review of applications of alkali-metal fluorides in organic synthesis has appeared.lg9 IX6 M.Segi Y. Nakamura T. Nakajima and S. Suga Chem. Lett. 1983 913. I87 T. Kawashima T. Ishii and N. Imamoto Chem. Lett. 1983 1375; Tetrahedron Lett. 1983 24 739. G. Sturtz and A Pondaven-Raphalen Bull. SOC.Chim. Fr. II 1983 125. I X9 G. G. Yakobsoii and N. W. Akhmetova Synthesis 1983 169.