5 Aliphatic Compounds Part (ii) Other Aliphatic Compounds By B. V. SMITH Department of Chemistry King's College London Strand London WC2 2/23 1 Alcohols and Ethers As an alternative to the traditional reagents the use of sodium percarbonate for oxidation of organoboranes to alcohols has been recommended.' The reagent is inexpensive easy to handle and gives yields comparable with those of the usual methods. Catalytic asymmetric hydroboration of styrenes by the catecholborane (1) in the presence of [Rh(cod),]BF and (+)-BNAP in THF is notable for reversal of regiochemistry and selectivity; thus 4-MeC6H4CH=CH2 in DME at -78 "C gave 77% of the 1-01 (94% e.e.) of R-configuration.2 Very low yields of the 2-01 were detected. An efficient chiral reagent for enantioselective synthesis of secondary and deuterated primary alcohols is (3) prepared from (2) with BH,; thus Bu'COMe QpH 0' &:;Nap NH H BI (1) (2) (3) gave an alcohol of -91% e.e.and PhCOMe afforded an alcohol of -98% e.e.3 Chiral organosilicon compounds afford an entry into the arylcarbinol series via an efficient and selective route shown in Scheme l.4 Oxygenation of simple alkenes [O,-PhSiH,-Co(acac),] constitutes a simple route to secondary alcohols; some ketone is also formed. In a similar way the system Co[ (CF3C0),CH2] with 0,-Et,SiH was regioselective for syntheses of secondary alcohols (a little ketone also being f~rmed).~ Mukaiyama has also reported that under slightly different conditions the alcohols are smoothly oxidized in good yield in the presence of these complexes.6 Allylic alcohols are obtained from chemoselec- tive hydrogen transfer from a simple alcohol to a,P-unsaturated ketones catalysed I G.W. Kabalka P. P. Wadgaonkar and T. M. Shoup Tetrahedron Lett. 1989 30 5103. ' T. Hayashi Y. Matsumotu and Y. Ito J. Am. Chem. SOC.,1989 111 3426. E. J. Corey and J. 0. Link Tetrahedron Lett. 1989 30 6275. T. H. Chan and A. Pellou J. Am. Chem. SOC.,1989 111 8737. S. Isayama and T. Mukaiyama Chem. Lett. 1989 1071. S. Isayama and T. Mukaiyama Chem. Letr. 1989 569; T. Mukaiyama and T. Yamada ibid. p. 519 103 104 B. V. Smith HO Ph Reagents i OMe ; ii Bu'Li-THF; iii RX; iv H,O,-KF-KHCO \ H Scheme 1 by MgO. In this way hex-5-en-2-one gave 90% of alcohols (with only 4% of the P,y-isomer).' The reaction of ally1 bromide with a carbonyl compound in the presence of zinc and chloramine using C,,-coated silica as a solid organic co-solvent was compared with the selectivity of the corresponding Grignard reaction.Yields were variable but the method did provide some useful compounds.8 Acetoxy- selenylation of alkenes was used as a route to vinylic and allylic acetates; 1,2-disub- stituted and terminal alkenes reacted smoothly. In this way C5H,,CH=CH2 gave C5Hl IC( OAc)=CH2 (7 1%).9 Chiral organosilicon compounds have been used in enantioselective syntheses of homoallylic alcohols; pyrrolidinylmethylallylsilanes (4;R = C02Me) gave with 2 equivalents of Lewis acid and an aldehyde good yields of product but with only modest e.e.(50'/0).'~ A regio-reversed addition of allylic stannanes to aldehydes in the presence of CoC12 at the a-position has been used to generate linear homoallylic alcohols." A chemoenzymatic approach to synthesis of the enantiomers of sulcatol ' J. Kaspar A. Trovarelli M. Lenarda and M. Graziani Tetrahedron Lett. 1989 30 2705. ' S. R. Wilson and M. E. Guazzaroni J. Org. Chem. 1989 54,3087. L. Engman J. Org. Chem. 1989 54,884. lo T. H. Chan and D. Wang Tetrahedron Lett. 1989 30 3041. J. lqbal and S. P. Joseph Tetrahedron Lett. 1989 30 2421. Aliphatic Compounds- Part (ii) Other Aliphatic Compounds (5) an insect pheromone has been reported.I2 An efficient coupling/allylic substitu- tion by a terminal alkyne (6)with a halide has been achieved e.g.(7) gave (8) (88%).13 The diastereoselective synthesis of a-allenic alcohols from propargylic epoxides and Grignard reagents has been studied as a function of catalysis by Cu’; optimized conditions were defined for ‘anti’ and ‘syn’ routes (see Scheme 2).14 (E)-Bis(tributylstanny1)ethylene and dilithio methyl(thieny1)cyanocuprate were reacted Hex Hex syn ‘OH anri + *do H H Ill Hex H H Reagents i Pent-MgCI-Et20; ii Pent-MgBr 5% CuBr 2PBu,-Et20 Scheme 2 to form an ‘in situ’ cuprate which afforded a geometrically pure p-hydroxyvinylstan- nane (9).15 Hydrostannylation catalysed by Pd’ of alkynes occurred smoothly to Busn&; (9) give vinylstannanes in high yield. In this way the symmetrical alkyne AcOCH2C~CCH20Ac gave 93%yield; unsymmetrical alkynes gave the syn-adduct as the major product.16 Samarium-catalysed electrochemical coupling of simple carbonyls is a good route to 1,2 diols.” A convenient catalytic two-phase method for dihydroxylation of alkenes has been described; a quaternary salt of a tungsten heteropolyacid mediates the reaction in a C6H,-H20 system.Yields ranged between 71 and 88%.’* A most useful summary paper on the scope of asymmetric dihydroxylation has appeared; I* C. M. Alonso M. T. Barros L. Godhino and C. D. Maycock Tetruhedron Lett 1989 30 2707. l3 T. Jeffery Tetrahedron Lett. 1989 30 2225. 14 A. Alexakis 1. Marek P. Mangeny and J. F. Normant Tetrahedron Lett. 1989 30,2387. l5 J. R. Behling J. S. Ng K. A. Babiak A. L. Campbell E.Elsworth and B. H. Lipshutz Tetrahedron Lett. 1989 30 27. 16 H. Miyake and K. Yamamura Chem. Lett. 1989 981. E. Leonard E. Dunach and J. Perichon J. Chem. Soc. Chem. Commun. 1989 289. 18 C. Venturello and M. Gambaro Synthesis 1989 295. 106 B. V. Smith over 20 examples are given and emphasis is placed on the role of Cinchona alkaloids as chiral ligands.'' Two papers highlight the interest and scope of the Os0,-mediated dihydroxylation of alkenes. Corey and co-workers have developed a method notable for achieving three desirable objectives (i) high and predictable enantio- and diastereoselectivity (ii) clarification of mechanism and (iii) recovery and recycling of osmium.20 The chiral ligand (10) (from the diamine and 2,4,6-Me,C,H2CHO) followed by reduc- PhhPh MesCH,HN NHCH2Mes (10) tion forms a 1 1 complex with OsO which reacts cleanly at -90 "C to give the desired diol; e.g.PhCH=CHC02Me gave 83% of the (2R,3S)-diol (92% e.e.) and MeCH=CH(CH,),OTBDPS gave the (2S,3S)-diol (95% e.e.). The interpretation of this remarkable selectivity centres on the formation of a bidentate octahedral complex of (10) which favours a [3 + 21 cycloaddition at the si,si-face; the model proposed accommodates the lower selectivity observed with 2-alkenes and trisub- stituted types. Replacement of the mesityl group of (10) by benzyl gave lower optical yields presumably because of greater rotational flexibility. Significantly the antipode of (10) gave opposite selectivity. This method offers considerable scope for exploita- tion in diol synthesis.High levels of asymmetric induction have been realized with the chiral ligand (1 1) and OsO,; thus (E)-hept-2-ene with (S,S)-(1 1)-OsO afforded 93% diol (98% e.e.).,' I I R R (11) a-Chloroboronic esters ( 12) of high diastereomeric excess (98-99%) were con- verted into a-tributylstannylboronic esters (13) and then into (aR)-a-tributylstannyl alcohols (14); the derived (aR)-a-lithioethers (19 on coupling with (12) gave BuSn (12) (13) (14) (15) (16). Treatment with H202 followed by hydrolysis of the intermediate gave the known (17) (96% d.e.).22 This method introduces the novel concept of coupling a chiral carbocation equivalent and a chiral carbanion equivalent in a stereospecific ly B.S. Lohray 'T. H. Kalantar B. H. Kim C. Y. Park T. Shibata J. S. M. Wai and K. B. Sharpless Tetrahedron Lett. 1989 30,2041. 20 E. J. Corey P. D. Jardine S. Virgil P.-W. Yuen and R. D. Connell J. Am. Chem. Soc. 1989 111,9243. " T. Oishi and M. Hirama J. Org. Chem. 1989 54 5834. 22 D. S. Matteson P. B. Tripathy A. Sarkar and K. H. Sadhu J. Am. Chem. SOC. 1989 111 4399. Aliphatic Compounds- Part ( ii) Other Aliphatic Compounds way. The role of DIPED is crucial in directing reaction and the potential of the process is seen in assembling (18) which has four chiral centres. BUn40CH20Me (16) (17) (18) A stereoselective synthesis of optically active anti-1,3-polyols relies on the coup- ling of (19) and (20); the resultant (21) after treatment with MeI-CaCO and a diastereoselective reduction with LiAlH(OBu')3 gave (22).23 Starting with a y-(21) (22) menthyloxy-2[ 5HI-furanone a practicable route to optically active butanediols and y-lactones has been developed as shown in Scheme 3; the first asymmetric synthesis of (23) has thus been recorded.24 An enzymatic hydrolysis of a prochiral diacetate RZ R' (M eS1 X (M eS 13C H (R' = R2 = H) (R' = Me,R2 = H) iil Me Me Me (23) Reagents i LiC(SMe), THF -90 "C; ii Ni-Al MeOH-THF then LAH; iii MeI -90 to 45 "C Scheme 3 23 Y.Mori and M. Suzuki Tetrahedron Lett. 1989 30 4383. 24 J. F. G. A. Jansen and B. L. Feringa Tetrahedron Lett. 1989 30 5481. 108 B. V. Smith fOR2 O-O-Ph I 0~3 SiPh2Bu' (24) (25) did not lead to an 'asymmetrized tris' (24) which is a chiral building block but an alternative approach (Scheme 4) yielded the protected derivative (25) in 52%yield.25 OAc li I OAc I OSiBu'Ph2 Iv I - /O\/OVPhI I vi,vii H O q Ho+ OSiBu'Ph OSiBu' Ph2 Reagents i Porcine lipase; ii ClSi BU'Ph, imidazole DMF; iii KOH-MeOH; iv CICH20CH2Ph Pr2NEt; v 03,2Me2S 3 NaBH,; vi TsCI Et,N DMAP; vii NaBH, DMSO Scheme 4 The identity of this sample with one derived from (S)-(+)-methyl 3-hydroxy-2- methylpropanoate was proved.The diethylisopropylsilyl protecting group is capable of attachment at primary secondary and tertiary alcoholic OH groups and offers some scope for discrimina- tion in deprotection steps. In AcOH-H,O-THF primary DEIPS ethers are distin- guishable from TBDMS- TES- and THP-protected primary alcohols.At secondary sites DEIPS ethers are easily distinguished from THP ethers and fairly well from TBDMS and TEP protection.26 Selective deprotection of the Me,SiBu' group in the presence of Ph,SiBut has been achieved in high yield by using PPTS; selectivity as high as 96.5% was noted.27 A new oxidatively removable protection strategy uses the p-anisyloxymethyl group; an alcohol is easily derivatized by base-promoted reaction and deprotection is 25 G. Guanti L. Banfi and E. Narisano Tetrahedron Lett. 1989 30 2697. 26 K. Toshima S. Mukaiyama M. Kinoshita and K. Tatsuta Tetrahedron Lett. 1989 30 6413. 21 C. Prakash S. Saleh and I. A. Blair Tetrahedron Lett. 1989 30 19. Aliphatic Compounds- Part (ii) Other Aliphatic Compounds 109 smoothly achieved by CAN in aqueous MeCN.Protected alcohols are stable to base but labile in acid.*’ A very interesting account of kinetic resolution of rac-alcohols (or rac-acyl halides) by esterification in the presence of a chiral base has been published.29 1 mol of achiral RCOCl and 2 mols of rac-ROH in the presence of various t-amines gave esters and alcohols with optical purities up to 60-70%. It was found that the alcohol-derived portion of the ester and the unchanged alcohol were of opposite configuration. Analogously 2 equivalents of rac-acyl halide and 1 equivalent of rac- ROH gave a high degree of optical induction; opposite configurations were again noted for the ester and the acid.Selective oxidation of allylic benzylic and saturated secondary alcohols is brought about by BaMn04-A1203-CuS04 even in the presence of primary OH groups.30 In this system the diol PhCH=CH(OH)(CH,),OH gave 80% of PhCH=CHCO(CH2),0H. Metallic nitrates supported on silica gel are useful oxidants and effect oxidative cleavage of ethers.31 Good-to-excellent yields of enones were formed from the corresponding alcohols with NiS04-K2S208. In competition between PhCH=CHCH20H and 3-phenylpropan-1-01 97% of the latter was recovered and 91% of cinammaldehyde was isolated.32 In a similar way primary allylic alcohols were shown to react faster than secondary analogues. A facile one-pot conversion of ROH into RNH2 is shown in Scheme 5; for R = C5Hll 61% of the amine was isolated.33 Palladium-catalysed allylation of OH ..... RCH,OH -RCH,X -RCH,N=P(OEt) -RCH2NH2 Reagents i Ph3P CBrCI, C6H,; ii NaN, DMF; iii P(OEt),; iv HCI; V NaOH Scheme 5 groups with allyl ethyl carbonate is a useful method particularly in the carbohydrate series; the anomeric OH is selectively ethe~-ified.~~ A new synthesis of benzyl ethers (and N-benzylamines) employs the HBF4-catalysed reaction of PhCHN2 and the alcohol (or amir~e).~~ The synthesis of both enantiomers of benzyl glycidyl ether has been reported; allyl alcohol via Sharpless oxidation tosylation and benzylation gave the intermediate (26) easily transformed into the desired product. For (27) the measured optical purity is the highest ever recorded. The enantiomer was prepared in the same way (95%e.e.).36 A synthesis of (27) from 0-benzylserine uia a multistep route has been a~hieved.~’ The enantiomer was obtained from the same starting material using a Mitsunobu inversion at a key stage.A chemoenzymatic 28 Y. Masaki I. Inata 1. Mukai H. Oda and H. Nagashima Chem. Lett. 1989 659. 29 P. J. Weidert E. Geyer and L. Homer Liebigs Ann. Chem. 1989 533. 30 K. S. Kim S. Chung I. H. Cho and C. S. Hahn Tetrahedron Left. 1989 30 2559. 3’ T. Nishiguchi and F. Asano J. Org. Chem. 1989 54 1531. 32 S. Yamazaki and Y. Yamazaki Chem. Lett. 1989 1361. 33 A. Koziara J. Chem. Res.(S) 1989 296. 34 P. Lakhmiri P. Lhoste and D. Sinou Tetrahedron Lett. 1989 30 4669. 35 L. J. Liotta and B. Ganem Tetrahedron Lett. 1989 30 4759.36 H.4. Byun and R. Bittmann Tetrahedron Lett. 1989 30 2751. 37 P. De Witt D. Misiti and G. Zappa Tetrahedron Lett. 1989 30 5505. 110 B. V. Smith (26) (27) route to give epoxides in high optical purity has been described.38 Attempted acylation of a P-hydroxytosylate [lipase-MeCO,C( Me) =CH,] was extremely slow; better results were obtained with enantioselective cleavage of RCH( OCOPr)CH,OTs in the presence of butanol separation of products and ring closure to the desired compound. Enantioselective lipase-mediated hydrolysis of esters of epoxy secondary alcohols is seen as an alternative to standard Sharpless methodology and in some cases the enantiomeric excess is very high. In one specific example however the e.e. was disappointingly As another alternative to Sharpless methodology photo- oxygenation of alkenes in the presence of titanium alkoxides has been shown to be a general process; selectivity is high in some cases but shows dependence on the titanium species.40 MCPBA epoxidation of liquid alkenes takes place in deionized water at pH 8.3 in good yield.41 Enantiodivergent ring opening of styrene oxide with Me3SiN3-Ti(OPri)4 was solvent dependent; the major product (28) had S-configuration in hexane (72% e.e.) or in DME-0.1% H,O (74% e.e.) but in dry DME the R-isomer (83% e.e.) pred~minated.~,It was suggested that an intramolecular pathway uia an intermediate such as (29) could account for this unexpected reversal.Ph Ph h h N3 OSiMe3 Me3Si0 N3 (28) (29) Titanium-mediated opening of 2,3-epoxy-l-ols at the 3-position uses R2NH2+C1-as the source of halide ions.43 By this route (30) was converted into a mixture of (31) and (32) (X = C1 78% 78:22; X = Br 87% 90 10).(30) (31) (32) a-Methylene cyclic carbonates have been prepared by reaction of alk-2-yn-1-01s with C02 under pressure in the presence of a phosphine catalyst.& [2,3]-Wittig rearrangements of the lithio anions of ally1 propargyl ethers show considerable 38 C.-S. Chen and Y.-C. Liu Tetrahedron Lett. 1989 30 7165. 39 B. A. Marples and M. Rogers-Evans Tetrahedron Lett. 1989 30 261. 40 W. Adam M. Braun A. Griesbeck V. Lucchini E. Staab and B. Will J. Am. Chem. Soc. 1989,111,203. 41 F. Fringnelli R. Germani F. Pizzo and G. Savelli Tetrahedron Lett.1989 111 1427. 42 K. Sutowardoyo M. Emziane and D. Sinou Tetrahedron Lett. 1989 111 4673. 43 L. Gao and A. Murai Chem. Lett. 1989 357. 44 J. Fournier C. Bruneau and P. H. Dixneuf Tetrahedron Lett. 1989 30,3981. 111 Aliphatic Compounds- Part (ii) Other Aliphatic Compounds diastereoselectivity and afford a route to unsaturated alcohols with three contiguous chiral centres. By this route ether (33) gave (34); the cis-ether gave 87% of product as a single isomer. Rearrangement of (35) to (36) was completely ~tereospecific.~’ d SiMel d I ow+’ - +O OH In the presence of KOBu‘ primary alkyl groups migrate to the y-position in Wittig rearrangements thus forming (2) -silyl enol ethers which are easily hydrolysed to aldehydes.46 2 Alkyl Halides Boron tribromide or stannic chloride are effective reagents for conversion of alcohols into the respective alkyl halide.47 Direct transformation of THP ethers into alkyl bromides uses PPh,-CBr4-CH2C12 and is effective for saturated and unsaturated types; it is noteworthy that a tertiary ether (37) gave 62% of the corresponding bromide (with 1525% eliminati~n).~~ A catalytic method for producing RX (X =Br or I) from RCl employs HX-FeX,.The process had wide sc0pe.4~ Tetramethyl-a- halogenoenamines act as halogenating agents for alcohols under neutral conditions. Under mild conditions high yields (>95%) of RX (X =C1 Br I) were ob~erved.~’ Although secondary alcohols were reactive competition showed that primary groups reacted much more readily.From a mixture of butan-1-01 and octan-2-01 with Me2C=C(C1)NPri only BuCl was produced. Light-initiated halogenative decar- boxylation of thiohydroxamic acids gave high yields of RX (X =C1 Br I) from primary secondary and tertiary substituted carboxylic acids.51 Ph& OTHP (37) In a series of papers on vinylic boranes Brown has developed specific methods for (2)-A wide range of (2)-1-iodoalkenes is and (E)-l-halogenoalk-l-ene~.~~ 45 R. Bruckner Chem Ber. 1989 122 193. 46 M. Schiosser and S. Strunk Tetrahedron 1989 45 2649. 47 A. Amrollah-Madjdabadi T. N. Pham and E. G. Ashby Synrhesis 1989,614. 48 A. Wagner M.-P. Weitz and C. Mioskowski Tetrahedron Lett. 1989 30 557. 49 K. B. Yoon and J. K. Kochi J.Org. Chem. 1989 54 3028. 50 F. Munyemana A.-M. Frisque-Hesbain A. Devos and L. Ghosez Tetrahedron Left. 1989 30 3077. 51 W. G. Dauben B. A. Kowalczyk and D. P. Bridon Tetrahedron Lett. 1989 30,2461. 52 H. C. Brown et al. J. Org. Chem. 1989 54 6064 6068 6075 6079 6085. 112 B. V. Smith accessible via the Wittig reaction of iodomethylenetriphenylphosphoranesand an aldehyde. Some di-iodo compounds were produced as by-product^.^^ Addition of secondary and tertiary iodoalkanes to alkynes under the influence of triethylboron gave iodoalkenes with a variable stereoselectivity except for Me,SiC=CH (EtI 84% E:Z = 0:lOO) and Et0,CCECH (Bu‘I 81% E:Z = 92:s). An intramolecular example was achieved (94%) with (38).54 Allylic alcohols with R NBF-Et3N.3HF gave vic-fluorobromohydrins which with base formed epifluorohy- drin~.~~ Alkenes with PhSeBr- AgF in CH2C12 under ultrasonication formed adducts derived from fluoroselenylation and bis-~elenylation.~~ Griller’s ‘Green Reagent’ [(Me3Si)$iH] smoothly dehalogenates alkyl halides and is considered superior to the more traditional Bu,SnH especially in view of the toxicity of tin compo~nds.~’ By using NaBH to regenerate the reagent the silane can be used in catalytic amount; irradiation of the reaction mixture at 254 nm with added anisoyl peroxide causes rapid reaction under such conditions.A reinvesti- gation of the Pd-catalysed cross-coupling of an iodoalkane and a Grignard reagent has been published and the findings were held to be contrary to the original proposals.58 Ab initio calculations on the Finkelstein S,2 reaction in the gas phase showed that for R = Me Et and Pr’ there was a good agreement in the observed trends in E compared with the solution-phase reaction.59 3 Aldehydes and Ketones Carbonyl compounds seem to sustain a high level of activity in both synthesis and reactivity; consequently this section of the Report is once again the longest.One-electron oxidants cause an isomerization of epoxides to ketones.60 The reaction may proceed via a radical cation chain mechanism. The preparation of isomerically pure alkylboranes derived from 9-BBN has been used to advantage in syntheses of homologated ketones (and esters and nitriles) in very high e.e.61 Enantioselective hydrolysis of enol esters by a yeast (Pichia rniso) produced some remarkable results; in each case the enantiomeric excess was >8O%.The face selectivity was attributed to formation of a complex such as (39); (40) gave highest selectivity (goo/ e.e.).62 Similar work with Bacillus coagulans gave variable optical 53 H. J. Bestrnann H. C. Rippel and R. Dostalek Tetrahedron Lett. 1989 30 5261. 54 Y. Ichinose S. Matsunaga K. Fugami K. Oshima and K. Utimoto Tetrahedron Lett. 1989 30 3155. 55 I. Chehidi M. M. Chaabouni and A. Baklouti Tetrahedron Lett. 1989 30 3167. 56 S. Tomoda and Y. Usuki Chem. Lett. 1989 1235. 57 M. Lesage C. Chatgilialoglu and D. Griller Tetrahedron Lett. 1989 30,2733. 58 K. Yuan and W. J. Scott Tetrahedron Lett. 1989 30 4779; cf P.L. Castle and D.A. Widdowson ibid. 1986 27 6013. 59 K. Hirao and P. Kebarle Can. J. Chern. 1989 67 1261. 60 L. Lopez and L. Troisi Tetrahedron Lett. 1989 30 3097. 61 H. C. Brown N. N. Joshi C. Pyun and B. Singaram J. Am. Chem. Soc. 1989 111 1754. 62 K. Matsumoto and H. Ohta Chem. Lett. 1989 1589. Aliphatic Compounds- Part ( ii) Other Aliphatic Compounds (39) (40) yields in some instances; it is clear that this approach is capable of extension and gives promise of extension to a valuable series of compounds not always easily accessible by the more conventional methods.63 A route to a-alkoxy- a-allyloxy- and a-benzyloxy-aldehydes and -ketones has been reported; the key step is substitu- tion of the sulphinyl group in for example (41) by ROH in the presence of Me1 or PPTS.64 Enantioselective synthesis of P-hydroxyketones depends upon the forma- tion and desulphurization of 2-( 2-methyl- l ,3-dithiolan-2-yl)ethanolintermediates.In this way (42) was prepared in 83% yield (70% e.e.).65 R’ A new protocol for the synthesis of various a-fluorinated ketones (and alcohols) relies on acylation of lithium derivatives of enantiomerically pure sulphoxides and later desulphurization.66 Oxidation of 2,2-difluoroalkenylboranes by H,O,-NaOMe (to suppress protonolysis) is a practicable route to difluoromethylketones in good yield.67 Ethyl 4,4,4,-trifluoroacetate reacts with an allylic alcohol in the presence of distannoxane affording an allylic ester which suffers Pd-catalysed decarboxyallyla- tion to form a trifluoromethylketone.68In this way (43) was prepared in 79% yield.CF3LPh (43) Epoxysilylethers with the reagent (44) are transformed into P-siloxyaldehydes with a rigorous chirality transfer; e.g. (45) gave (46) only (87Y0).~~ Methyl s-alkyl ketones have been shown to undergo ‘double a-hydroxylation’ by peracid oxidation of their enol silyl ethers.” Monoacetals of malonaldehyde have been obtained uia a selective hydrolysis or transacetalization of 1,1,3,3-tetramethoxypropane as a general method.’l 63 K. Matsumoto and H. Ohta Chem. Lett. 1989 1109. 64 P. Pflieger C. Mioskowski J. P. Salaun D. Weissbart and F. Durst Tetrahedron Lett. 1989 30 2791. 65 I. Stahl F. Wrabletz and J. Gosselek Chem. Ber. 1989 122 371. 66 P. Bravo E.Piovosi and G. Resnati J. Chem. Res.(S) 1989 134. 67 J. Ichikawa T. Sonoda and H. Kobayashi Tetrahedron Lett. 1989 30 5437. 1. Shimizu H. Ishii and A. Tasaka Chem. Lett. 1989 1127. 69 K. Maruoka T. Ooi and H. Yamamoto J. Am. Chem. SOC.,1989 111 6431. 70 Y. Horiguchi E. Nakamura and I. Kuwajima Tetrahedron Lett. 1989 30,3323. 71 P. Shi-Qi and E. Winterfeldt Liebigs Ann. Chem. 1989 1045. 114 B. V. Smith (44) (45) (46) A divergent synthesis of 1,3-and 1,4-diketones from P-methoxy-y-phenylthioketones is a novel and valuable route to such compounds (from the same starting material).'* As shown in Scheme 6 the 1,3-dione can be considered to arise I Reagents i BuLi,; ii AcCl or MsCI; iii R2CH=C(OSiMe3)R3; iv MCPBA; v A NaHC03; vi H30f; vii BU'OK Analysis of reaction pathways RCH + -C+ + yR' I1 -1,3-diketone 0 0 RCHO MeOCHzSPh OSiMe -YR1 +FO ?CH2 -+ 1,Cdiketone R 0 Scheme 6 from coupling between a carbocation and a carbonyl 1,l-dipole and an enolate; the 1,4-compound is derived from a methylene dipole equivalent coupling with an enolate and an acyl cation.Unsymmetrical 1,4-diketones have been obtained from T. Sato M. Inoue S. Kobara J. Otera and H. Nozaki Tetrahedron Lett. 1989 30,91. Aliphatic Compounds- Part ( ii) Other Aliphatic Compounds 115 Ce'"-mediated cross-coupling of a mono- and a 1,2-disubstituted trimethylsilyl enol ether.73 A new synthesis of a$-unsaturated aldehydes proceeds from a carbonyl com- pound and the new reagent (47) [N-methoxy-N-methyldiethylphosphonoacetamide 0 II (EtO),PCH CO N(0Me)M e (47) prepared from C1CH2COC1 and MeNHOMe then P(OEt)3].74 Typically PhCHO gave 84% yield E :2 = 95 :5.2-Ynols were isomerized to (2E) -enals by a ruthenium complex [RuC~~(P~~P)~] in the presence of a trialkylph~sphine.~' Efficient silylformylation of an alkyne occurred with co-Rh4(co) 12-C6H6-Et3N under pressure; for example Pr'CECH gave (48) (93% 2:E = 90 Pr H OHC SiR (48) A facile stereospecific synthesis of (244 E )-dienals has been disclosed by addition of an organometallic reagent to a pyrylium salt followed by ring opening of the formed 2H-pyran. Selectivity was high (>95%) although there was some depen- dence upon reagent Propargylic alcohols are rearranged by an iridium pentahydride complex to furnish (~,P-enones.'~ Inthis way (49) gave a mixture of (50) and (51) [81 19 respectively; (51) can be arranged to (50)].The same catalytic system will isomerize an cY,P-ynone OH (49) (50) (51) to an a,P :y,S-dienone in high yield.79 In syntheses of divinT1 ketones in a one-pot sequence (52) [from R'CHO and Ph,P=CHC( =NPh)CH2PPh3 Br-] was reacted sequentially with BuLi R2CH0 and H30+ to yield (53) (88%) presumed to arise NHPh 13 E. Baciococchi A. Caw and R. Ruzziconi Tetrahedron Lett. 1989 30 3707. 14 J.-M. Nuzillard A. Boumendjel and G. Massiot Tetrahedron Left. 1989 30 3779. 75 D. Ma and X. Lu J. Chem. SOC.,Chem. Commun. 1989 890. 76 I. Matsuda I. Ogiso S. Sato and Y. Izumi J.Am. Chem. SOC.,1989 111 2332. 77 M. Furber J. M. Herbert and R. J. K. Taylor J. Chem. SOC.,Perkin Trans. I 1989 683. 18 D. Ma and X. Lu Tetrahedron Lett. 1989 30 2109. 19 D. Ma Y. Lu and X. Lu J. Org. Chem. 1989 54 1105. 116 B. V. Smith uia a 2-vinyl aza-l,3-diene intermediate.80 Regioselective 1,4-acylation/alkylation of 1,3-dienes via q3-1 -acetonylallylic Fe(CO),NO complexes has been developed as a practicable method." Bu3SnH-HMPA is an effective reducing agent for aldehydes in the presence of other reducible groups (including ketone and nitro); reductive alkylation was also observed in which R'CHO and R2CH0 formed R1CH20CH2R2.82 A useful summary of the relative reactivity of carbonyl compounds towards reduction by NaBH has been published.83 Reduction by NaBH in the solid state produces surprisingly high yields of alcohols from ketones; with an enone some reduction of the double bond was noted and there was some selectivity with cyclic ~ysterns.'~ Improved selectivity in the reduction of prochiral aliphatic ketones has followed from the introduction of new chiral b~ranes.~~ t-Butylchloroborane gave an adduct with nopol benzyl ether which effectively (but slowly) reduced 3-methylbutan-2-one; the lowering in the rate of reaction was attributed to 0 + B co-ordination in the adduct.It was noted that (54) showed greater reactivity. Chiral reducing agents from SnCl, optically active (54) piperazines and diisobutylaluminium hydride have been shown to reduce prochiral ketones; yields and enantiomeric excesses were variable however.86 The stereochemistry of reduction of ketones by optically active alkyl metals has been thoroughly re~iewed.~' A novel carbonyl-protecting group is the 1,5-dihydro-3 H-2,4-benzodioxepine cleaved by catalytic hydrogenolysis.Yields are generally good (70-98%). 7-bromoheptanone gave the 0-protected derivative (70%) which reacted with (55) to afford (56); this was then desulphurized by Raney nickel to give undecan-Cone (96?'0).~~The synthesis and consecutive double a1 kylation of (2-siloxyallyl)silanes no J. Barluenga I. Merino and F. Palacios Tetrahedron Lett. 1989 30 5493. 81 K. Itoh S. Nakanishi and Y. Otsuji Chem. Lett. 1989 615. 82 I. Shibata T. Yoshida A. Baba and H. Matsuda Chem. Lett.1989 619. 83 D. E. Ward and C. K. Rhee Can. J. Chem. 1989 67 1206. 84 F. Todo K. Kiyoshige and M. Yagi Angew. Chem.,Int. Ed. Engl. 1989 28 320. H. C. Brown and P. V. Ramachandran J. Org. Chem. 1989 54,4504. 86 M. Falorni L. Lardicci G. Giacomelli and M. Marchetti Tetrahedron Lett. 1989 30 3551. 87 M. Falorni L. Lardicci and G. Giacomelli J. Org. Chem. 1989 54 2383. 88 N. Machinaga and C. Kibayashi Tetrahedron Lett. 1989 30 4165. Aliphatic Compounds- Part (ii) Other Aliphatic Compounds 117 has been noted; such a reagent functions as the synthetic equivalent of the acetone ~,a'-dianion.*~ In a typical example (57) with Me2CHCH2(0Me)2 gave 88% of the dialkylation product. o SiR3 SiR3 (57) An interesting conversion of an aldehyde into a ketone via the boron-Wittig reaction has been reported.A suggested pathway is shown in Scheme7. Several examples were given; yields were low in some cases and excellent in others." Mes2BCH-R' Li' 2Mes2BCHR' &Mes,B--CHR' CF3 -CFSCHO H-C-R~ 0-C-H CO-0 I b'nIn I I I O-Li+ R2 COCF I OBMes2 Mes2BCHR' 111 R' CH2C0R2 -I -I R'CH=CR~ O=C-R2 R'CH=CR~ I &Y OCOCF3 Reagents i R'CHO; ii TFAA; iii H,O+ Scheme 7 Stereospecific E-olefination of an aldehyde was claimed for reaction of a bisbenzy- lic arsonium ylide anion in HMPA as exemplified by (58) and CSH,,CHO which Ph Ph at -78°C gave 91% of product (E:Z =>99 l).91 High E-selectivity was also claimed for the Bu,As-catalysed olefination of aldehydes in the presence of (Ph,PO)P-K,CO,; thus BuCHO and PhCOCH,Br gave the product in 80% yield with E :Z =>98 :2.92 89 A.Hosomi H. Hayashida and Y. Tominaga J. Org. Chem. 1989 54 3254. 90 A. Pelter K. Smith S. Elgendy and M. Rowlands Tetrahedron Lett. 1989 30,5643. 91 B. Boubia C. Mioskowski and F. Bellamy Tetrahedron Lett. 1989 30 5263. 92 L. Shi W. Wang Y. Wang and Y.-Z. Huang J. Org. Chem. 1989 54 2027. 118 B. V. Smith Bis-silyloxydienes have been prepared from 1,2- and 1,3-diketones by reaction with Me,SiCl-LiBr in dry THF.93 Deprotonation of ketones by M+ (SiMe3)2N- is regio- and stereoselective and shows considerable differences from that induced by LDA.94 With PhCH,COMe LDA gave typically a mixture of enolates after equilibration but NaH( SiMe3)2 furnished a single product (formulated as the 22-isomer) after 20 h.With 4-methyl- pent-3-en-2-one a similar clean reaction was claimed; the initial product after standing (24 h) contained (59) (95%). (59) The first observation of non-chelate controlled addition to a carbonyl group has been noted for 1-bromo-1-lithioalk-1-enes and 0-protected la~taldehydes.’~ In this way (60) gave (61) (85% d.e.) and then (62) (corresponding to formal addition of-CH20H). A chiral carbenoid gave higher d.e. (95% raised to >98% by further manipulation). OMEM MeIEM I CHO Me Br M e y o H MEM$Me OH OH (60) (61) (62) a-Chlorocrotylboronates were used to obtain a-phenoxy- and a-methoxyboron- ates capable of entering into aldol reactions with aldehyde^.^^ The E-and 2-pentenylboronates react to give aldol products with good-to-excellent diastereoselec- tion; thus (E)-(63) with EtCHO afforded (64) and (65) (81% 35 :65 re~pectively).~’ OH OH (63) (64) (65) Total stereoselectivity was observed in reaction of (S,S,S,)-(66)with PhCHO (aldol product 99%enantiomeric p~rity).~’ Variation in the leaving group in the conversion of ketones into E-or 2-enolborinates has been used to advantage since it is easier to handle dialkylboron chlorides than the analogous triflate~.~~ The choice of R and X in R2BX and the choice of amine (Et3N us.PriNEt) are therefore important and 93 L. Hansson and R. Carlson Acta Chem. Scand. 1989 43 304. 94 M. Gaudemar and M. Bellassoued Tetrahedron Lett.1989 30 2779. 95 M Braun and H. Mahler Angew. Chem. Znt. Ed. Engl. 1989 28 896. 96 R. W. Hoffman and S. Dresely Chem. Ber. 1989 122 903. 97 M. W. Andersen B. Hildebrandt G. Koster and R. W. Hoffman Chem. Ber. 1989 122 1777. 98 R. W. Hoffman K. Ditrich G. Koster and R. Sturmer Chem. Ber. 1989 122 1783. 99 H. C. Brown R. K. Dhar R. K. Bakshi P. K. Pandiarajan and B. Singaram J. Am. Chem. Soc. 1989 111 3441. Aliphatic Compounds- Part (ii) Other Aliphatic Compounds 119 R Me Me (66) modify the E/Z ratio. Brown and co-workers showed that with PhCOEt Et3N and Chx2BC1 (Chx = cyclohexyl) the product (67) was >99% E [with PhCHO furnish- ing 95% anti-aldol (68)] whereas 9-BBN-BCl and Pr';NEt gave (69) [with PhCHO forming 98% syn-aldol (70)].0B-9 -BBN OBChxz / PhGPh \ Ph @ & phg (67) (68) (69) (70) An important diastereoselective aldol reaction has been achieved via the inter- mediacy of acylsilanes.'OO Thus Pr'CHO with EtCOSiBu'Me gave (71) and (72) (>20 l) but the overall yield was rather low. If a chiral aldehyde was used e.g. (73) the percentage yield was improved but the syn:anti ratio was not. a#-(71) (72) (73) Unsaturated aldehydes uia umpolung with Me3SiCN have been reacted with chiral aldehydes and ketones; modest selectivity was observed and good chiral induction was dependent on the presence of an a-phenyl group in the carbonyl component."' Examples have been given of the use of Me,SiCN-umpolung with saturated com- pounds.'02 Aldol+rea;ctions of silyl enol ethers with aldehydes/acetals in the presence of the salt [Ph3POPPh,][triflateI2 furnish adducts in good yield.Ether (74) and OSiMe3 PhCHO afford the expected product (98% syn :anti 71 :29).'03 Michael addition with enones was noted. An interesting and facile reaction of Me,SiCN with orthoesters or acetals derived from a,P-unsaturated carbonyls led to a-cyano deriva- tives in excellent yields; catalytic quantities of NiC12 CoCl2 or PdC12 were nece~sary.'~~ LOO D. Schinzer Synthesis 1989 179. 101 S. Hunig C. Marschner K. Peters and H. G. von Schnering Chem. Ber. 1989 122 2131 102 S. Hiinig and C. Marschner Chem. Ber. 1989 122 1329. 103 T. Mukaiyama S. Matsui and K. Kashiwagi Chem. Lett. 1989 993. 104 T. Mukaiyama T.Soga and H. Takenoshita Chem. Lett. 1989 997. 120 B. V. Smith Fresh experiments have been quoted in a reinterpretation of the pathway involved in addition of allyltributylstannane to a1deh~des.l'~ Keck et al. have shown by *19SnNMR that (75) and SnCl form a tight bidentate chelate and therefrom the (75) product; hence it is not necessary to invoke a transmetallation product (allyltri- chlorostannane). The same is true of 2:l complexes of (75) for example which are also formed at low temperature and in the absence of free SnCl,. No 'burst' of Bu3SnC1 which Denmark's mechanism requires was observed. The reason for the discrepancy between the two sets of experiments is not clear. The BF3.0Et2-mediated rearrangement of an (S)-a-alkoxyallylstannane gives rise to a y-alkoxystannane which enters into clean aldol addition with aldehydes to afford syn-1,2-diols in high yield and in excellent enantiomeric excess.1o6 Virtually complete chirality transfer was observed with for example (76) and C6H13CH0 which gave syn :anti (77) in the ratio 87 13; syn-(77) had e.e.>95%.'07 (76) (77) 'Perfect stereochemical control' appears to have been achieved in a synthesis of syn-a-methyl+- hydroxythioesters. The silyl enol ether of (S)-ethyl propanethioate and an aldehyde is directed by a chiral promoter [from a chiral diamine-Sn(OTf),- Bu3SnF] with exceptional selectivity. PhCHO and (78) with (79) as the diamine afforded (80) (86%' 100% syn!). The enantiomeric excess was also high and this (78) (79) (80) process will no doubt be developed as another valuable method in asymmetric synthesis.It was further shown that with Sn(OTf) alone this type of reaction proceeded in 74% yield but the e.e. was zero.lo8 It is considered that activation in a chiral environment is due to a complex such as (81). The same type of chiral promoter has been successfully employed in reaction of achiral aldehydes and achiral ketene silyl acetals; the enantiomeric excess was variable but at -95"C 105 G. E. Keck M. B. Andrus and S. Castellino 1. Am. Chem. SOC.,1989 111 8136; cJ S. E. Denmark T. Wilson and T. M. Willson ibid. 1988 110 984. 106 J. A. Marshall and W. Y. Gung Tetrahedron Lett. 1989 30,2183. '07 T. Mukaiyama H. Uchino and S. Kobayashi Chem. Lett 1989 1001. 108 T.Mukaiyama and S. Kobayashi Chem. Lett. 1989 297. Aliphatic Compounds- Part (ii) Other Aliphatic Compounds I . -.' 0 /sn II Tfo ; 0-S-CF3 FSn---0II (81) 89% e.e. was realized."' The addition of PhCHO to (E)-but-2-en-l-o1 mediated by PdCl,. (PhCN),-SnC1 ,shows a strong solvent-dependence on selection; DMSO gave principally syn-selection but in THF the opposite was seen."' Addition of water to DMSO markedly affected the selection. This behaviour was rationalized on the geometry of different transition state structures (82) and (83) which were held to operate in THF and DMSO respectively. R Diastereoselective aldol addition of a silyl enol ether to a chiral fluorinated aldehyde takes place with moderate-to-excellent diastereomeric excess.In this way (84) and CH2=C(Bu')OSiMe3 formed (85) (83% threo erythro = 78:22)."' The HxOCH2Ph 0 (84) enantioselective allylation of carbonyl compounds by Ti-carbohydrate complexes is a new way to exert control. CpTiC13 and for example 1,2:5,6-diisopropylidene-glucose form CpTi(OR),; this reacts with C3H5MgCl to give CpTi(C3H5)(OR) . Reaction of the latter with for example PrCHO gave an allylation product with 93% e.e."' Very high diastereoselectivity was found for Ti-mediated reactions of silyl ethers; e.g. (86) and aldehydes in the presence of LDA. The extent of selection 0si ButMe v 109 S. Kobayashi T. Sano and T. Mukaiyama Chem. Lett. 1989 1319. 110 Y. Masuyama J. P. Takahara and Y. Kurusu Tetrahedron Lett. 1989 30,3437.111 T. Yamazaki T. Yamamoto and T. Kitazune J. Org. Chem. 1989 54 83. 112 M. Riediker and R. 0.Duthaler Angew. Chem. Znt. Ed. Engl. 1989 28 494. 122 B. V. Smith was dependent on the nature and amount of Ti reagent; Ti(OPr') was nearly as effective as ClTi(OPr') . Addition of 12-crown-4 also had a marked effe~t."~ The levels of asymmetric induction in 'Mukaiyama aldol' reactions of chiral silyl ketene acetals in the presence of a chiral auxiliary (e.g. N-methylephedrine) are attributable to the influence of stereocentre 1 in the aminoalcohol; stereocentre 2 has only a minor r01e.I'~ Electrophilic condensation reactions of silyl ethers derived from homopropargyl alcohols such as (87) and aldehydes mediated by TiC14 proceed to form two possible products (88) and (89); whilst EtCHO gave a mixture (1:9) with (90) it gave only (89).I15 Ketene silyl acetals react smoothly with a,p-enones in the presence (87) (88) (89) (90) of [1,2-benzenediolato- O,O']oxotitanium to form Michael adducts.'16 Cp2ZrC12- CH2Br2-Zn forms a reactive organometallic species which rapidly methylenates aldehydes ketones and enones.No reaction was observed in the absence of the zirconium compound nor with esters or lactones under normal conditions. 1,l- Dibromopentane did not form any alkene; it was surmised that elimination had occurred.' l7 Careful control allows preparation of a Grignard reagent from a P-halogenoacetal which will then react with a carbonyl group regardless of halogen or acetal struc- ture.I18 2-Acyl- 1,3-dithiane 1 -oxides undergo diastereoselective addition of Grignard reagents; the products can be easily desulphurized.' l9 Autoxidation of R2Zn precedes conjugate addition to a$-enones which undergo epoxidation uia alkylperoxospecies.Selectivity was good; thus (91) with BuJn-0,- PhMe at room temperature gave 77% of (92) (erythro:threo = >99 1).120 A chiral OBu OBu Pri 0 (91) erythrol threo- (92) promoter (93) caused selectivity in the addition of organozincs to alkynals; e.g. alcohol (94) had 78% e.e.'*' Double alkylation of a$-unsaturated acetals by I13 C. Siege1 and E. R. Thornton J. Am. Chem. SOC.,1989 111 5722. 114 C. Gennari F. Molinari P.-G. Cozzi and A. Oliva Tetrahedron Lett. 1989 30,5163. T.-H. Chan and P.Arya Tetrahedron Lett. 1989 30,4065. T. Mukaiyama and R. Hara Chem. Lett. 1989 1171. 117 J. M. Tour P. V. Bedworth and R. Wu Tetrahedron Lett. 1989 30 3927. A. Greiner Tetrahedron Lett. 1989 30,3547. 119 P. C. B. Page D. Westwood A. M. Z. Slawin and D. J. Williams J. Chem. SOC.,Perkin Trans. 1 1989 1158. 120 K. Yamamoto and N. Yamamoto Chem. Lett. 1989 1149. 121 K. Soai and S. Niwa Chem. Lett. 1989 481. Aliphatic Compounds- Part ( ii) Other Aliphatic Compounds R'C3 CCH( OH)R2 I Me (93) (94) (i) RZnBr-NiBr,-Bu3P and (ii) Me1 gave modest yields; it was possible to run the reaction in a one-pot system.'22 Allyl-allenyl zinc reagents undergo rearrangement to form allylic bis-metallic species; electrophiles react with high regioselectivity affording a route to functionalized vinylzinc reagents.Selectivity in reaction with carbonyl groups has been exp10red.l~~ One potential advantage of this method is that an ester will react only as far as the ketone stage. A copper-catalysed conjugate addition of an organomanganese reagent to an a$-enone in THF is claimed as superior to cuprate addition; low temperatures are avoided no stabilizing or solubilizing additives are needed MnC1 is cheap and work-up is convenient especially on a large scale.'24 Me2C=CHCOMe obtained by this route with BuMnCl gave 94%adduct. RMnBr has also been used to advantage in such reactions. Acetylenic ketones add halide ion in a conjugate manner uia the agency of CeX,-R,SiCl-NaX/hN+ X-in MeCN; HCECCOC5HIl formed (E)-ICH=CHCOCSH1 (890/,),whereas HCECCONEt gave predominantly the 2-iodo adduct.'*' Coupling of Co complexes of alkynylaldehydes and silyl enol ethers is promoted by a Lewis acid; liberation of the organic product is achieved by CAN.'26 Complex (95) and EtC(OSiMe,)=CHMe produced (96) (79% syn :anti = 32 1).Ph c) 4CO13 (95) (96) l,l-Dichlorobut-2-ene and PhCHO with CrC1 in THF-DMF gave threo-(2) -4-chloro-2-methyl-1-phenylbut-3-en-1-01 (96% threo :erythro = 97 :3 2:E = 97 :3). Other examples showed similar high or very high ~e1ection.l~~ Stereohomogeneous (E)-and (2)-crotyltrifluorosilanes were prepared and gave highly diastereoselective reactions with aldehydes leading to erythro-P-methyl homoallylic alcohols in good- to-very good yields.128 Thus (E)-MeCH=CHCH2SiF3 and C8H17CH0 gave (97) (96% 99% isomerically pure) with CsF-THF.(97) I22 A. Yanagisawa S. Habaue and H. Yamamoto J. Am. Chem. SOC.,1989 111 366. 123 J. F. Normant J. C. Quirion A. Alexakis and Y. Masuda Tetrahedron Lett. 1989 30,3955. 124 G. Cahiez and M. Alami Tetrahedron Lett. 1989 39 3541. 12' T. Fujisawa A. Tanaka and Y. Ukaji Tetrahedron Lett. 1989 30 1255. I26 J. Ju B. R. Reddy M. Khan and K. M. Nicholas J. Org. Chem. 1989 54 5426. I27 K. Takai Y. Kataoka and K. Utimoto Tetrahedron Lett. 1989 30 4389. I28 M. Kira T. Hino and H. Sakurai Tetrahedron Lett. 1989 30 1099. 124 B. V. Smith P-Substituted allylsilanes behave as nucleophiles in the presence of fluoride not as anionic 1,3-dipoles in reaction with RCHO; e.g.CH2=C(SiMe3)CH2SiMe3 and CsF-DMF gave a quantitative yield of (98).'29 nR X OH X = Ph or SiMe (98) 4 Carboxylic Acids Esters and Lactones Alkenes are oxidized to acids by reaction with aqueous H202-H2W04; the yield was low for oct-1-ene (some diol was formed as well) but for 1-methylcyclohexene 72% of 6-oxoheptanoic acid was is01ated.l~' A specific route to chiral deuterated phenyldodecanoic acids (required for study of metabolic pathways of fatty acids) has been described via microbial reduction of the enoic acids.'31 Enantioselective reaction of MeC02Bu' and a Ti-carbohydrate complex led to P-hydroxyesters in good chemical and optical yield (see Scheme 8).'32 A stereospecific route to chiral CI I OLi R'O-Ti-OR' OH 0 A AOBul 0 I 0R' Reagents i LDA Et20 -70°C; ii CPT~CI(OR*)~ -30°C; iii RCHO -70°C; iv TFA (R' = But -+ R = H) Scheme 8 alkyl chloroalkanoates relies on displacement of mesylate derivatives in reaction with AlC13.133 It was suggested that (99) or similar is responsible for selectivity.Perfluoroalkyl iodides undergo carbonylation-hydration in the presence of a Pd Co or Rh catalyst; alcohols gave esters and amines formed arnide~.'~~.'~~ (99) '29 S. Pernez and J. Hamelin Tetrahedron Lett. 1989 30 3419. 130 T. Oguchi T. Ura Y. Ishii and M. Ogawa Chem. Lett 1989 857. 131 G. Gorger W. Boland U. Preiss and H. Simon Helo. Chim. Acta 1989 72 917. 132 R.0. Duthaler P. Herold W. Lottenbach K. Oertle and M. Riediker Angew.Chem. In?. Ed. Engl. 1989 28 495. 133 U. Azzena G. Delogu G. Melloni and 0.Piccolo Tetrahedron Lett. 1989 30,4555. 134 H. Urata 0. Kosukegawa Y.Ishii H. Yugari and T. Fuchikami Tetrahedron Left. 1989 30 4403. 13' H. Urata Y. Ishii and T. Fuchikami Tetrahedron Left. 1989 30 4407. Aliphatic Compounds- Part ( ii) Other Aliphatic Compounds An interesting enantioselective hydrogen transfer to a-methylenesuccinic acid has given high optical yields in the preparation of (100). Formic acid and an amine (which can be chiral) with rhodium and a chiral phosphane gave >85% e.e.; with (S)-PhCH(Me)NH, >97% e.e. was a~hieved.',~ Stereospecific carbonylation of vinyl bromides/chlorides in PTC conditioiis led to a,P-unsaturated acids.'37 A nickel cyanide catalyst was employed and it was suggested that a cyano-tricarbonyl nickelate anion was the effective agent.Ethoxyethyne and B-iodo-9-borabicyclo[3.3.l]nonanes formed a halogenoboration adduct which with an aldehyde gave an (E)-a$-unsaturated ester in good yield and configurational purity.13* Pd-mediated addition of allylic chlorides to carbon nucleophiles gives rise to unsaturated esters. By such means (101) and (102) afforded (103) (62Y0).',~ The fluorosulphone ( 104) reacted with ethyl 3-methylbut-2-enoate with NaOEt-DMF to form ethyl chrysanthemate in modest ~ie1d.I~' a,P-Ynoic esters are isomerized in refluxing toluene with a catalytic amount of Bu3P and 1rH5(Pr\P) to a,P y,S-dienoic ester~.'~' Eleven examples were given. Diallyl a-oxalcarboxylates and HC02H-Pd2( DBA),-PPh,-Et,N furnished a-ketocarboxylates in good yield.If HC02H was omitted decarboxylation-allylation was ~bserved.'~' A new monofunctionalization of malonic acid is based on reaction of Meldrum's acid and silylated amines lactams or alcohols to form silyl esters readily converted into substituted P-ket0a~ids.l~~ The procedure referred to in ref. 138 when applied to an @-enone is a useful route to a 6-ketoester. MeCOCH=CH gave a 93% yield of MeCO(CH,),CO,Et and surprisingly C1(CH2)3COMe gave 95% of product; cyclohex-2-enone was inertla Chiral acetylureas react after deprotonation with an aldehyde to form P-alkyl-P-hydroxypropionyl ureas; separation of isomers and methanolysis gave optically pure methyl P-alkyl-P- hydroxypropionates.By such means PhCH(OH)CH,CO,Me was prepared in 97% yield and with e.e. > 99'/0.'~~ 136 H. Brunner E. Graf W. Leitner and K. Wutz Synthesis 1989 743. 137 H. Alper I. Amer and G. Vasapollo Tetrahedron Lett. 1989 30 2615. 138 Y. Satoh T. Tayano S. Hara and A. Suzuki Tetrahedron Lett. 1989 30 5153. 139 G. Mignani F. Gross M. Aufrand and D. Marel Tetrahedron Lett. 1989 30 2383. 140 M. Hanack A. Auchter C. Wunde and T. Stoll Liebigs Ann. Chem. 1989 853. 141 D. Ma and X. Lu Tetrahedron Lett. 1989 30 843. 142 I. Shimizu T. Makuta and M. Oshima Chem. Lett. 1989 1457. 143 B. Rigo D. Fasseur P. Cauliez and D. Couturier Tetrahedron Lett. 1989 30 3073. I44 F. Kawamura T. Tayano Y. Satoh S. Hara and A. Suzuki Chem.Lett. 1989 1723. 145 K. Kishikawa M. Yamamoto S. Kohmoto and K. Yamada Chem. Lett. 1989 787. 126 B. V. Smith Claisen rearrangement of chiral ally1 thioethers has provided a route to chiral P-branched @-unsaturated thi0e~ters.l~~ Kinetic resolution of (*)-a-arylcarboxylic acids has been achieved by decomposi- tion of the 2-pyridinethiol ester in Pr'OH with a chiral 1,4-diol; PhCH(Et)C02Pri was prepared in 69% yield (91% e.e.).14' A versatile enzymatic resolution of 3-butanoylalkanoates of varying chain length provides a method for obtaining chiral hydroxyalkanoic acids valuable as intermediates in synthesi~.'~' Further upgrading of optical purity was possible by crystallization of dicyclohexylammonium salts. Some useful resolutions of (*)-P y-epoxyesters with porcine liver esterase provide chiral ester and acid; the former e.g.(105) (as a single isomer from the esterase- mediated resolution of the racemic ester) with HC02H was transformed into a y-lactone (106) but (107) of opposite configuration from MeOH-HC1.'49 By conversion of a$-unsaturated (butyl) esters into diols and thence into esters of 2,2-dimethyl-1,3-dioxolane-4-carboxylicacids chiral building blocks can be obtained from lipase-mediated hydrolysis of racemic esters e.g. (1O8).l5O Double diastereoselection occurred in the sulphoxide piperidine and carbonyl (SPAC -an acronym the writer feels has little to commend it) reaction of sulphinyl acetate esters and an a-unsubstituted aldehyde; y-hydroxy-a#-unsaturated esters were produced in good-to-excellent yield and with high ~electivity.'~' Reaction of y-mesyloxy-a-alkyl-a$-enoates and an organocyanocopper with BF3 brings about 1,3-chirality transfer and is a method for construction of chiral quaternary centres.'52 In this way (109) gave (1 10) (99 :1 S :R isomer).OTBS OTBS (109) (110) I46 R. Oehrlein R. Jeschke B. Emst and D. Bellus Tetrahedron Lett. 1989 30 3517. 147 K. Narasaka F. Kanai M. Okudo and N. Miyoshi Chem. Lett. 1989 1187. 148 C. Feichter K. Faber and H. Griengl Tetrahedron Lett. 1989 30 551. 149 P. Mohr L. Rosslein and C. Tamm Tetrahedron Lett. 1989 30 2513. I50 M. Pottie J. Van der Eycken and M. Vandewalle Tetrahedron Lett. 1989 30 5319. 151 K. Burgess.and I. Henderson Tetrahedron Lett.1989 30,4325. I52 T. Ibuka N. Akimoto M. Tanaka S. Nishii and Y. Yamamoto J. Am. Chem. Soc. 1989 111 4864. Aliphatic Compounds- Part ( ii) Other Aliphatic Compounds Enantiomerically and diastereomerically pure threo-3-aryl-2,3-dihy-droxypropanoic acid derivatives have been prepared via a sequence starting with cyanohydrins of aryl aldehydes which are transformed into cyanodiols and then into the products.153 Selective Claisen and Dieckmann ester condensations are promoted by dichlorobis(trifluoromethy1sulphonate)Ti'". MeCH2C02Me and PhCHO did not form a crossed product but gave MeCH,COCH(Me)CO,Me (36%). The best cyclization was achieved with molecular sieves; Me02C(CH2),C02Me at 0 "C gave 80% ketoe~ter.''~ A highly diastereoselective Michael addition was effected by reaction of an enamine and the 2,2-dimethoxyethyl esters of a$-unsaturated acids using TiC1 as an activator.The process was characterized by syn selection (111) gave (112) (82%; syn :anti = 93 :7) probably uia a chair-like transition state (1 13).'" The dienolate of (1 14) -a synthetic equivalent of acetoacetic ester dianion -adds selec- tively to enals and enters into highly selective aldol addition^.''^ (113) (114) Diethyl ketomalonate serves as an equivalent of C02 in Diels- Alder reactions with simple (unactivated) azadienes. This is the first report of such a reaction. Diester (1 19 from appropriate precursors,- gave only (1 16) on hydrolysis; the structure of the latter was confirmed by an independent route.''' (115) (116) Intramolecular asymmetric lactonization of a prochiral bis-acid chloride with a chiral auxiliary has been examined (RJ?)-1,2-diphenylethane-l,2-diamine and acid I53 B.R. Matthews H. Gountzos W. R. Jackson and K. G. Watson Tetrahedron Lert 1989 30,5157. 154 Y. Tanabe Bull. Chem. SOC.Jpn. 1989 62 1917. 155 Y. Hashimoto S. Machida K. Saigo J. Inoue and M. Hasegawa Chem. Lett. 1989 943. 156 D. Seebach U. Misslitz and P. Uhlmann Angew. Chern. Int. Ed. Engl. 1989 28 472. 157 J. Barluenga F. J. Gonzalez and S. Fustero Tetrahedron Left. 1989 30 2685. 128 B. V. Smith chloride (117) gave the bis-amide cleaved and re-cyclized by TFA to (118) (>96% e.e.).15* The synthesis of analogues of mevalonolactone via silylcuprate chemistry has been used to confirm the structure of a rare urinary metab~lite.'~' ClCO( CH,),CH(OAc)(CH,),COCl (1 17) Lipase-mediated hydrolysis of a prochiral diacetate precursor has led to (S)-(-) -paraconic acid (119) and by further steps to the A-factor.16' Carbonylation of 2-bromo-1 -phenylbuta-1,3-diene is a route to a methylene-a-ketolactone and hence by reaction with Si02 ketobutenolide.'61 07c02H 0 5 Amines and Amides Facile reduction of azides occurs with hydrazine in the presence of a Pd catalyst.Reaction is quite rapid and yields are >70%.'62 A convenient one-pot conversion of an azide into a BOC-protected amine gives very good yields and is useful for a range of chiral corn pound^.'^^ Amides when treated with the calculated quantity of PhCH2Me3N+ Br; and alkali are transformed into amine~.'~~ Yields in excess of 70% were obtained.A powerful versatile reducing agent (LiBH,-NaBH4-Me,SiCl) efficiently converts amides nitriles and nitro compounds into arnine~.'~~ The sa2e reagent reduces acids (alcohols) and sulphoxides (sulphides). A new synthon (= CH2NH2) has been utilized by reaction of N-triphenylphosphorylidene-1-(benzotriazol-1-y1)methyl-amine (120) and an alkyllithium or a Grignard reagent and can be illustrated by the preparation of C13H27NH3 Cl-(87?40).'~~ 158 N. Baba A. Sakamoto M. Mimura Y.Yamamoto K. Uchida and J. Oda Chem. Lett. 1989 889. 159 I. Fleming S. K. Armstrong and R. J. Pollitt J. Chem. Res.(S) 1989 19. 160 K. Mori and N. Chiba Liebigs Ann.Chem. 1989 957. H. Alder and G. Vasapollo Tetrahedron Lett. 1989 30 2617. A. A. Malik S. B. Preston T. G. Archibald M. P. Cohen and K. Baum Synthesis 1989 450. 163 S. Saito H. Nakajima M. Inaba and T. Moriwake Tetrahedron Lett. 1989 30 837. 164 S. Kajigaeshi K. Asano S. Fujisaki T. Kakinami and T. Okamoto Chem. Lett. 1989 463. 165 A. Giannis and K. Sandhoff Angew. Chem. Znt. Ed. Engl. 1989 28 218. 166 A. R. Katritzky J. Jiang and L. Urogdi Tetrahedron Lett. 1989 30 3303. Aliphatic Compounds-Part (ii) Other Aliphatic Compounds Direct regio- and stereoselective lithiation of secondary and methyl-allylamines allows the preparation of a new versatile y-aminated organolithium reagent reactive towards electrophilic centres.'67 This method was adapted to produce a$-unsatur- ated butyrolactams.Regio- and chemoselective nucleophilic addition of amines to oxiranes was promoted by Ph4Sb+OTf- and is a good route to P-aminoalcohols.'68 Methoxy- selenation or -bromination of chiral 3-acyl-2-oxazolones with a chiral auxiliary constitutes the basis for a highly stereoselective formation of chiral synthons for P-aminoalcohols; the best results were secured with (121) which gave 96% d.e. (121) (PhSeC1) and 89% d.e. [Br2-MeC(OMe)3].'69 A stereoselective synthesis of threo- and erythro-P-aminoalcohols proceeds via hetero-Diels-Alder addition of an N-protected a-aminoaldehyde to a reactive diene promoted by Eu(hfc) . Reaction proceeds in a manner consistent with chelation control (anti-Cram) with formation of (122) and (123) from the appropriate diene (threo erythro = 80:20); however a reversal was noted for (124) in the presence of Et,AlCl (threo erythro = < 1:99).l7' /J 3 R3 OMe R3 OMe N(CH2PhI2 NR1R2 N R' R~ (122) (123) (124) Ylides CH2=SMe2 and CH2=AsPh3 react with doubly protected a-amino-aldehydes to form aminoalkyl epoxides with high diastereofacial selectivity (in the range 86 14 to >95 5).The configuration of the products was determined by ring opening with Me,CuLi affording N-protected P-aminoalcohols whose configuration was established rigor~usly.'~' Homochiral allylic amines with 9-BBN-catechol- borane and a rhodium catalyst give an entry into syn-3-aminomethyl-substituted alcohols. The best catalytic system appeared to be Rh(cod)C12-4P(OEt),; (125) N(phthaloy1) 167 J.Barluenga F. Foubelo F. J. Fananas and M. Yus J. Chem. Res.(S) 1989 200. 168 M. Fujiwara M. Imada A. Baba and H. Matsuda Tetrahedron Lett. 1989 30 739. 169 T. Ishizuka S. Ishibuchi and T. Kunieda Tetrahedron Lett. 1989 30 3449. 170 M. M. Midland and M. M. Alfonso J. Am. Chem. SOC.,1989 111,4368. M. T. Reetz and J. Binder Tetrahedron Lett. 1989 30,5425. 171 130 B. V. Smith under these conditions showed syn :anti selectivity of 98 :2.'72 An interesting tandem aldolization/ lactonization/dyotropic rearrangement of a-aminoaldehydes has been uncovered by Reetz and co-worker~.'~~ The essential features are shown in Scheme 9. (126) R = Me or Bu Reagents i 4OSiMe3,MgCI, CH2CI,; ii spontaneous OPh Scheme 9 The configuration of (126) was established unequivocally by reaction of (127) (from L-isoleucine] with the silyl ketene acetal.N-Protected a-amino aldehydes are transformed into y-aminoesters in a two-stage process first the aldehyde was converted into an a$-unsaturated ester and thence with R2CuLi-Me,SiC1 into syn/anti-(128) with a 94 6 syn preferen~e.'~~ N( CH2P h)2 syn/ anti-(128 ) Ring-opening of N,N'-bis-protected 2-aminomethylaziridines produced 3-substituted 1,2-diaminopropanes carrying various functionality at C3.17* Alkylation of Ph,C=NCH,CO,R with ally1 bromide in a phase-transfer system and in the presence of a chiral quaternary salt gave only low e.e. (5% with R = CH,Ph). An improvement was noted for the t-butyl ester; the best result of all was from the neopentyl ester and 4-ClC,H4CH,Br which gave after work-up 4-chlorophenylalanine (>99% e.e.).176 Phosphorus ylides and t-butylamino (diphenylmethylene) oxamate react to form 2-aza-1,3-dienes reduced with NaBH3CN to protected a-amin~acids.'~~ The lithium enolate of ethyl [2-(2,2,5,5- tetramethyl-l-aza-2,5-disila)cyclopent-l-yl]acetate underwent slow transmetallation with CpTiCl(OR),; subsequent aldol reaction of aldehydes showed an astonishingly high stereoselectivity in formation of D-threo-P-hydroxy-a-aminoacids.The per- ceived advantages of the method are simplicity use and recovery of reagents and selection. in the example shown in Scheme 10 (R2 = H BOC or CHO) the product had enantiomeric and diastereomeric excesses of 98%.'78 Total stereochemical purity 172 K.Burgess and M. J. Ohlmeyer Tetrahedron Lett. 1989 30,5861. 173 M. T. Reetz A. Schmitz and X. Holdgriin Tetrahedron Lett. 1989 30 5421. I74 M. T. Reetz and D. Rohrig Angew. Chem. Int. Ed. EngL;1989 28 1706. 175 D. S. Jones A. Srinivasan S. Kasina A. R. Fritzberg and D. W. Wilkening J. Org. Chem. 1989,54,1940. 176 M. J. O'Donnell W. D. Bennett and S. Wu J. Am. Chem. SOC.,1989 111 2353. 177 J. P. Bazureau D. Person and M. Le Corre Tetrahedron Lett. 1989 30 3065. 178 G. Bold R. 0. Duthaler and M. Riediker Angew. Chem. Int. Ed. Engl. 1989 28 497. Aliphatic Compounds- Part ( ii) Other Aliphatic Compounds Reagents i LDA -78 "C;ii CpTiCI(OR), THF-U,O; iii R'CHO -78 "C -+ r.t.Scheme 10 was achieved in the synthesis of (129) a component of microbial cell walls. A new synthesis of a-aminoacid-(E)-P,y-enol ethers is an E-selective process; a P-alkoxyaldehyde and (MeO),POCH( NHZ)CO,Me (Z = COPh CHO Ac etc.) with OH NHz (129) KOBu' generate ROCH,CH=C( NHZ)CO,Me in turn isomerized to the P,y-isomer by LDA-THF at -70 0C.179 DEAD and Li dienolates or Sn/Ge masked dienolates furnish either a-or y-aminoacid derivatives; (E)-MeCH=CHCO,Me in HMPA-THF at -78 "C gave principally the y-adduct whereas Bu3SnCH2C(OSiMe3)=CHC02Et showed opposite selectivity with ZnC1 An unusual organometallic-mediated aldol reaction from (2R,4E)-2-methylhex-4-enal and NCCH,CO,Et has given a route to some unusual unsaturated hydroxyaminoacids.'81 Dienic a-aminoacids have been synthesized from the Pd-mediated addition of LiCH(C02Me)N=CPh2 to allenes.'82 -1mines react with+ke$ene silyl acetals under the catalytic influence of the bisphosphonium salt Bu3POPBu3 thereby forming aminoesters in good yield.'83 Facile formation of amides by reaction of an acid and an amine in the presence of molecular sieves has been A one-pot reaction leading to amides (and esters by using alcohols) has been developed; yields were consistently good-to- e~cellent.'~~ An improved method for the Ritter reaction is applicable to primary and secondary substrates rather than the tertiary ones usually employed.Alcohols 179 M. Daumas L. Vo-Quang Y. Vo-Quang and F. Le Goffic Tetrahedron Lett.1989,30 5121. 1x0 Y. Yamamoto S. Hatsuya and J. Yamada Tetrahedron Lett. 1989 30,3445. A. Togni S. D. Pastor and G. Rihs Helv. Chim. Act4 1989,72 1038 1471; cf J. Am. Chem. SOC.,1989 111 1471. 1x2 N. Kopola B. Friess B. Gazes and J. Gore Tetrahedron Lett. 1989 30,3963. 183 T. Mukaiyama K. Kashiwagi and S. Matsui Chem. Lett. 1989 1397. 184 J. Cosy and C. Pale-Grosdemange Tetrahedron Lett. 1989 30,2771. I X5 J. M. Jaszay 1. Petnehazy and L. Toke Svnrhesis 1989 745. 132 B. V. Smith were converted into triflates and thence into amides by carbocation addition to a nitrile.lS6 Yields in the range 50-98% were obtained. Enzymatic syntheses of propargylamides from the esters and arylamines with microbial lipase gave yields >8O% and worked well in organic solvents.'87 Secondary amides with (CF3C0)20-Bu4N+ NO; in CH2C12 underwent N-nitra- tion in good yield; some N-nitrosation was also noted.'" Secondary amines with CO and 10 mol% Se S and an alkylating agent form R'R2NCOSR3; it was presumed that the S-alkylthiocarbamate was produced via a seleno~arbamate.'~~ Two papers describe a detailed exploration of the chemistry of carbamate~.'~~ In the first- electrophilic sulphonylation of allylic carbamates led to 1 -(p-toluenesulphony1)-2-alkenyl carbamates whose achiral Li derivatives reacted with carbonyl groups in the usual way; chiral titanium derivatives added at the y-position affording a new class of homoenolate reagents.Selectivity and reactivity of matched/unmatched pairs was also examined.The nucleophilic alkenoylation of protected chiral a-oxy- and a-aminoaldehydes by lithiated tosylcarbamates showed complete syn-stereoselectivity in production of a,/?-difunctionalized ap-enones. 6 Other Nitrogen Compounds TiC14-SnC12 serves as a mild reagent for cleavage of aldoximes and ketoximes possibly via an imine intermediate.'" Dichloro- and dibromoformaldoximes react with alkenes to form 3-halogenoisoxazolines in a convenient one-pot reaction; the latter may be transformed into P-hydroxynitriles [by Fe(CO),] or /?-hydroxyesters (methoxylation and catalytic reduction). With ally1 alcohols and allylamines a method was devised for butyrolactones and ~~-3-hydroxy-4-aminoacids, respec-tive~~.'~~ Oxidative conversion of aliphatic nitro compounds by sodium chlorite (NaC102) forms carbonyl compounds in good yields; primary nitro groups give aldehydes and secondary compounds form ketones [e.g.MeCH( N02)CH2CH2COMe gave the 1,4-diketone (78Y0)].'~~ Other functional groups were compatible. Asymmetric reduc- tion of nitroalkenes by baker's yeast gives significant enantiomeric excess in the formed nitroalkanes; for example (E)-(130) gave (131) (58% yield 83% e.e.).194 The 2-isomer of (130) gave lower e.e. (66%). Alkyl nitronates and aldehydes with 186 A. G. Martinez R. M. Alvarez E. E. Vilar A. G. Fraile M. Hanack and R. Subramanian Tetrahedron Lett. 1989 30 581. 187 F. Rebolledo R. Brieva and V. Gotar Tetrahedron Lett. 1989 30,5345. I88 E. Carvalho J. Hey F. Norberto and E.Rosa J. Chem. Res.(S) 1989 260. 189 N. Sonoda T. Mizuno S. Murakame K. Kondo A. Ogawa I. Ryu and N. Kambe Angew. Chem. In&. Ed. Engl. 1989 28 452. 190 M. Reggelin P. Tebben and D. Hoppe Tetrahedron Lett. 1989 30 2915 2919. 19' R. Balicki L. Kaczmarek and M. Malinowski Liebigs Ann. Chern. 1989 1139. 192 K. Halling I. Thomsen and J. B. G. Torssell Liebigs Ann. Chem. 1989 985. 193 R. Ballini and M. Petrini Tetrahedron Lett. 1989 30,5329. 194 H.Ohta N. Kobayashi and K. Ozaki J. Org. Chem. 1989 54 1802. Aliphatic Compounds- Part (ii) Other Aliphatic Compounds Pr'OTiCl formed satisfactory yields of erythro-@-nitroalcohols.'9s The a-nitro group of nitroketones is smoothly replaced on reaction with Na2S204-Et3SiH in HMPA-H,O (or D20).These reagents are preferred to any containing Sn'V.'96 Very high yields of nitriles have been prepared in a one-pot reaction of an aldehyde and NH,Cl-Cu powder-0 in pyridine.The method is applicable to tertiary struc- tures e.g. t-C,H,CHO gave 90% of the 11itri1e.l~~ a,@-Unsaturation was not a drawback but the method failed with enolizable compounds. Similar methodology was used to convert primary amines into nitriles in excellent ~ie1ds.I~' Asymmetric hydrocyanation of aldehydes with chiral titanium reagents gave very high selectivity in formation of cyanohydrins (e.e. > 90'/0).'~~ An intriguing C-ethylation during yeast-mediated reduction of MeCOCH2CN [which formed synlanti-MeCH(OH)CH(Et)CN] has been reported. MeCOCH(Et)CN was isolated after shorter reaction time and is the logical inter- mediate.', @-Phenylthio- and P-methylthioacetoxynitriles were good substrates for kinetic recognition by lipase and were transformed into @-hydroxynitriles in excel- lent optical yield.200 Steric control in addition of cyanide ion to Schiff bases was secured by use of a modified haemin co-polymer; the formed a-aminoacids had much enhanced e.e.(~O-~~YO).~O' 7 Phosphorus and Sulphur Compounds This section does not attempt to give comprehensive coverage of pertinent literature scanned being limited by reason of space. The fate of the oxaphosphetanes formed from Bu'CHO and Bu,P=CHPr has been carefully studied; at the beginning of reaction at -55 "C the cis :trans ratio is 40 60. By measurement of the 3'P NMR signal it was shown that the concentration of the trans-isomer increased at the expense of the cis-compound and before product formation this change was essentially complete.The E :2 isomer ratio of the formed alkenes was 96 :4.,02 Kinetic factors were dominant in Wittig reactions of conjugated ylides and reversal of oxaphosphetane formation was insignificant (<5%).,03 Only oxaphosphetanes are needed to describe overall alkene formation. Exceptional E-selectivity was observed with dibenzophosphole (132) which gave E :2 ratios (132) 195 A. G. M. Barrett C. Robyr and C. D. Spilling J. Org. Chem. 1989 54 1233. 196 A. Kamimura K. Kurata and N. Ono Tetrahedron Lett. 1989 30,4819. 197 P. Capdevielle A. Lavigne and M. Maumy Synthesis 1989 451 453.198 H. Minamikawa S. Hayakawa T. Yamada N. Iwasawa and K. Narasaka Bull. Chem. SOC.Jpn. 1989 61 4379. 199 T. Itoh Y. Takagi and T. Fujisawa Tetrahedron Lett. 1989 30,3811. 200 T. Itoh and Y. Takagi Chem. Lett. 1989 1505. 201 K. Saito and K. Harada Tetrahedron Lett. 1989 30,4535. 202 B. E. Maryanoff A. B. Reitz D. W. Graden and H. R. Almond jun. Tetrahedron Lett. 1989 30,1361. 203 E. Vedejs and T. J. Fleck J. Am. Chern. SOC.,1989 111 5861. 134 B. V. Smith as high as 99 1. Phosphorane ylides react with succinic anhydrides to generate enol lactones; reaction takes place preferentially at the less hindered carbonyl except when an adjacent methoxy group directs attack via an intramolecular complex.2o4 In this way (133) gave (134) as a single isomer.0 0 (133) (134) Mesityl(prop-2-eny1)phosphine is rearranged by heating at 100 "C to the isopro- pylidene analogue (80-90% yield).205Phosphinomethylenetriphenylphosphoranes and BF etherate form 2-phosphonio-1 -phosphaalkenes.206 Photorearrangement of ally1 diphenyl phosphate may occur via a Norrish type I1 reaction and proceed uia phosphoranyl 1,3-biradi~als.~~' The isolated product was (135). Preparation of (E)-1 -alkenyl phenyl sulphides from vinylic bromides with high selectivity has been recorded.208 An efficient route to chiral t-butyl sulphoxides uses the method shown in Scheme 11 .209 Optical purity of the final product was dependent Reagents i SOClz NEt,; ii R'M; iii R2M Scheme 11 204 M. M. Kayser and L.Brean Can. J. Chem. 1989 67 1401. *05 F. Mercier C. Hugel-Le Goff and F. Mathey Tetrahedron Lett. 1989 30 2397 '06 H. Griitzmacher and H. Pritzkow Angew. Chem. Int. Ed. EngL 1989 28 740. 207 D. R. Anderson and C. N. Eley Tetrahedron Lett. 1989 30 4059. 208 A. Carpita R. Rossi and B. Scamuzzi Tetrahedron Lett. 1989 30,2699. 209 F. Rebiere and H. B. Kagan Tetrahedron Lett. 1989 30,3659. Aliphatic Compounds- Part (ii) Other Aliphatic Compounds upon choice of R2M but for three examples (PhLi BuLi vinylMgC1) 100% e.e. was attained. An approach to homochiral sulphoxides relied on lipase-mediated cleavage of racemic esters R(SO)CH2C02Me (R = aryl alkyl or cyclic).21o Direct asymmetric oxidation of acetylated or silylated S-methyl+- hydroxysulphides fol- lowed by deprotection gave S-methyl-P- hydroxysulphoxides in reasonable optical purity and which could be further upgraded by crystallization.211 The oxidant used was Bu'OOH-Ti(OPr'),-DET.Active methylene compounds react with Corey-Kim reagent (136) to form stable S-ylides.212 a,P-Epoxysulphides and LiMe2Cu generate an enolate which is reactive towards aldehydes with high regio~electivity.~~~ Claisen rearrangement of allylic ethers is markedly accelerated by an arylsulphon- methide group at C2. This reaction offers a method for construction of vicinal chiral quaternary A general account of the structure of lithium derivatives of compounds containing sulphur (sulphones sulphoxides thioethers) and nitrogen (nitriles nitro derivatives and hydrazones) has been published.215 8 Miscellaneous A multiauthor review entitled 'Emerging Organic Reactions' has ca.80% of its material in the area of interest of this Recent advances in the field of Reformatsky reactions have been surveyed.217 A very wide-ranging review of allylic 1,3-strain as a controlling factor in stereoselective transformations has been published by R. W. Hoffman.218 The usefulness of acylsilanes in synthesis has been reviewed.219 A massive review of the Wittig reaction and its modifications has been compiled by Maryanoff and Reitz."' 210 K. Burgess and I. Henderson Tetrahedron Lett. 1989 30 3633. 211 V. Conte F. DiFuria G. Licini and G. Modena Tetrahedron Lett. 1989 30 4859. 212 S. Katayama T. Watanabe and M.Yamauchi Chem. Lett. 1989 973. 213 T. Satoh A. Sugimoto M. Itoh and K. Yamakawa Bull. Chem. Soc. Jpn. 1989 62 2942. 214 S. E. Denmark M. A. Harmata and K. S. White J. Am. Chem. Soc. 1989 111 8878. 21s G. Boche Angew. Chem. Znt. Ed. Engl. 1989 28 297. 216 See Issue No. 7 Chem. Rev. 1989 89 1411-1617. 217 A. Furstner Synthesis 1989 571. 218 R. W. Hoffmann Chem. Rev. 1989 89 1841. 219 A. Ricci and A. D'Innocenti Synthesis 1989 647. 220 B. E. Maryanoff and A. B. Reitz Chem. Rev. 1989 89 863.