Alcohols, ethers and phenols C. S. HAU, ASHLEY N. JARVIS and JOSEPH B. SWEENEYS School of Chemistiy, University of Bristol, Cantock's Close, Bristol BS8 1 TS, UK *Present address: Department of Chemistry, University of Reading, Reviewing the literature published between August 1993 and February 1995 Continuing the coverage in Contemporary Organic Synthesis 1994, 1, 243 1 1.1 1.1.1 1.1.2 1.2 1.3 1.4 1.5 2 3 Preparation of alcohols From carbonyl compounds Via carbon-carbon bond-forming reactions Alcohol synthesis by reductive addition to carbonyl compounds Oxidative methods for alcohol synthesis Alcohol synthesis from epoxides Alcohol synthesis via biotransformations Miscellaneous methods for alcohol synthesis Preparation of ethers and phenols References 1 Preparation of alcohols 1.1 From carbonyl compounds Evans, Dart and Duffy have examined the origins of 1,3-asymmetric induction in two well-known and much-utilised reactions of carbonyl compounds: hydride addition' and Mukaiyama-type aldol reactions2 As a result of these authors' experiments analysing the effects of acyl substituents (RAC), P-substituents (R,) and the steric demand of reducing agent, they have concluded that a revision of the original 'polar Cram model'3 is necessary to account for syn-selectivity in non chelation- controlled reactions. Transition states (TS) A and B are proposed as those responsible for the observed stereoinductive effects, with A generally favoured in hydride reduction except when R, is sterically demanding, in which case B may be preferred.In the case of Mukaiyama aldol reactions, TS B is generally preferred, because there is no acyl substituent (i.e.RAC = H) and TS B minimises the non-bonded interaction shown in Scheme 1. PO Box 224, whiteknights, Reading RG6 2AD, UK 1.1.1 Via carbon-carbon bond-forming reactions 3-Zircona-1 -cyclopentenes and zirconacyclopentanes react with aldehydes to give oxazirconocycles 1 which may be protiolysed to (E)-pent-l-en-5-ols 2 or converted via reaction with elemental iodine to the corresponding 1-iodo analogues 3 (Scheme 2).4 In a similar vein, Whitby and co-workers' contributions to organozirconium chemistry continue: zircona- cyclopentanes 4 undergo sequential insertion reaction with a-lithioallychloride (to give $-ally complex 5 ) and aldehydes or ketones to give (after protonation) (E)-5-cyclopentylpent-3-en-l-q 01s 6 in good yield (Scheme 3).5 Where stereoisomers are produced, diastereoselectivities are low.C6H13 HO '3" Ph I bh 1 1 l2 w H13 Ph 3 65% yield 'Ph Scheme 1 Scheme 2 Hau, Jawis and Sweeney: Alcohols, ethers and phenols 65H*- % 75% yield E :Z = >98:2 4 5 I 0 'OH 6 R' R2 YieM of 6 ("lo) H Ph 90 H 2,4-di-M&Ph 60 H P i 90 H P f 95 M e Me 54 Ph Ph 57 --(CH2)5- 56 Scheme 3 Hydrozirconat ion of 1,l -dimet hylpropa- 1,2-diene gives chlorodicyclopentadienylprenylzirconium 7 which allylates aldehydes and ketones in good yield with high anti:syn selectivity and with allylic rearrangement (Scheme 4).6 The reaction may be applied to a range of other allenes. Enol(oxysilacyc1obutanes) 8, prepared from dichlorosilacyclobutanes7 undergo highly diastereoselective and uncatalysed aldol addition reactions with aldehydes' (Scheme 5).However, only predominantly (E)-enols undergo diastereoselective aldol reaction. The reaction is proposed to proceed via the ubiquitous six- membered transition state. A new catalyst for asymmetric Mukaiyama aldol reactions has been reported.' Thus, catalyst 9'' effects highly enantioselective acetate aldol addition reactions (Scheme 6). The aldol reactions of the lithium enolates of chiral NJV-dialkyl-a-aminomethylketones 10 are enantioselective," due (it is proposed) to the boat- like chelate formed by the neighbouring amine (Scheme 7). This proposal is necessary because methylketone-derived lithium enolates usually react with poor enantioselectivity.Ph 7 OH R Yield (%) anti :syn C5H11 79 96:4 C3H7 82 9o:lO Ph 95 955 77 99:l 88 99:l Scheme 4 Bu'O.7 Zi RCH0,ZO"C * M e O v R + M e O v R >= HFrrHF Me0 8 E:Z in8 R Solvent Yield (Yo) syn :anti 0:lOO Ph CDC13 80 4258 95:5 Ph CDCl3 94 955 93:7 89:11 phd CDC13 95 89:ll C5Hll CDCl3 91 93:7 89: 1 1 CGH11 CDC13 85 >99:1 Scheme 5 The Baylis-Hillman-like aldol condensation of a-allenic esters with aldehydes allows (inter aka) direct preparation of enynes (Scheme 8).12 Microwave irradiation is reported to accelerate the rate of the Baylis-Hillman reaction of aldehydes and a$-unsaturated esters and nitriles in the presence of DABC0.13 At room temperature, these reactions can be notoriously sluggish, sometimes requiring 14 days for complete reaction. Using microwaves, the reactions are complete within 40 minutes.Tetraallyltin is a chemoselective allylator of aldehydes; reaction of these components in aqueous HCl/THF mixtures gives an excellent yield of homoallylic alcohol (Scheme 9),14 This contrasts very favourably with the less selective behaviour of many 66 Contemporary Organic SynthesisBut 9 -But 0 TMSO R2 s-H + /)-OR' -1 0 "c. 9 (2-5 mol% ) Etg, 4 h TBAF, THF 1 1 OH 0 R 2 d O R l R2 ee (%) R' = Et R1 = Me P h w ' 93 97 C6H11 94 95 Ph 93 96 Scheme 6 via: H R' R2 Yield (%) de(%) Me Ph 84 60 Me P i 95 64 Me But 91 76 BU p i 81 78 Bu But 78 80 Bu Ph 76 85 P i Ph 90 >96 P i Pr' 64 >96 P i Bu' 88 >96 Scheme 7 carbonyl allylators. Dials may react to give lactols (Scheme 10). Titanocene monochloride facilitates a Prins-type reaction of cycloheptatriene with aldehydes (Scheme ll).I5 Yields are moderate and diastereoselectivities mediocre.The combination of trichlorosilane and a catalytic amount of Pd(PPh3)4 effects another high- l l a l l b R' R2 Base Ymld of l l a (%) Yield of l l b (%) H H H H H Me Me Me El El El Hex Ph Pr Bu Hex Hex CeH,B- DABCO BuLi DABCO BuLi BuLi BuLi BuLi BuLi BuLi 41 58 54 56 66 0 0 0 64 0 0 0 0 0 73 61 59 0 Scheme 8 tetraallyltin. HCI (aq.), THF; OH 98% yield Scheme 9 H LJH Scheme 10 tetraallyltin, HCI (aq.). THF high dilution _I___) 78% yield yielding Prins-type reaction of 1,3-dienes with aldehydes (Scheme 12). Under these conditions, however, the reactions are highly diastereoselective, in favour ofsyn isomer.I6 Allylic sulfones may be used as equivalents of allylic anions (Scheme 13) and used to prepare homoallylic alcohols.17 Ytterbium triflate catalytically promotes allylation of aldehydes by allyltributyltin, in contrast to most other promoters which must be present in stoichiometric amounts." Germanium iodide promotes allylation of aldehydes by allylic bromides" in the presence of diiodomethane.Zinc mediates allylation of aldehydes and ketones with cinnamyl chloride in an aqueous medium (Scheme 14).*' The enhanced thermal stability of fluorinated propenylzinc reagents compared to the Hau, Jawis and Sweeney: Alcohols, ethers and phenols 67Pd(PPh& (5 ITIOW~); A S O p P h 0 ZnEt,. RCHO I via: R 28-91 % yield ckmo RCHO 6 Scheme 13 \ Scheme 11 OH Cl$W, Pd(PPh3)j; e RCHO. DMF R1& + R ’ L p h R’ dnnamyl chloride k o - R2 Zn.NH&I.THF R2 ’* Ph I Scheme 14 major minor Diene Aldehyde Product Yield (YO) Stereoselectivity s RCHO WCUcl (cat.) DMF.pyridine. vBr - \*OH 70-95% yield CF3 0 PhCHO d p h 91 >91%syn OH roomtern. + 50 “c h PhCHO Y P h 94% syn h OHC-Ph +Ph 92% syn h OHC+ Ph +p,, / 92 92% syn H PhCHO g P h 92 - 0 R’ CI bC1 + $-R2 Li, DTBB (5 ml%) THF, 0 “c, 1 h; ~~~ ~ Me Me 72 1.3:l Et Et 60 1.6:l Scheme 12 corresponding lithium2’ and magnesium species2* allows high-yielding preparation of 2 (trifluoromethy1)allylic alcohols via a Barbier-type reaction of 2-bromo-3,3,3-trifluoropropene with aldehydes (Scheme 15).23 The use of 1,3-dichloropropene as a source of 1,3-dilithiopropene has been reported in full.24 Reaction of 1,3-dichloropropene with lithium metal in the presqnce of a catalytic amount of 4,4’-di-tert- butylbiphenyl (DTBB) and two equivalents of non- enolisable ketones and aldehydes gives substituted pent-3-ene-1,5-diols in moderate to good yield (Scheme 16).The reactions are believed to proceed Scheme 16 by sequential metal-halogen exchange/carbonyl addition processes. 2 : E ratios approach unity. of sulfonium ylid leads to an efficient vinylation reaction to give allylic alcohols (Scheme 17). The reaction involves nucleophilic addition to give a p-sulfonium alkoxide from which dimethyl sulfide is eliminatively removed by the excess lid.^' involving organostannanes have continued to be of Treatment of carbonyl compounds with an excess Asymmetric carbonyl alkylation reactions 68 Contemporary Organic SynthesisTi(OPi), Scheme 17 m S n B u 3 / R RCHo 1 3 ~ 1 4 R Yield (%) ee (%) Catalyst R Yield (YO) ee (configuration) (YO) Ph 88 95 13 C7H15 83 C5H11 75 97.4 ( R ) 98.4 ( R ) 92.6 (S) 88.8 (S) 82.0 ( S ) 80.2 ( S ) 95 92 14 14 89 P h A .77 (y 75 P h d # 98 96 14 89 96 13 73 96 13 Scheme 18 Scheme 19 interest. Chiral binaphthyl titanates catalyse asymmetric allylation of aldehydes by allyltributyl tin, as has been described by several groups during the period covered by this review. (S)-Binaphthol- derived dichlorotitanate 12 asymmetrically catalyses the allylation of aromatic and aliphatic aldehydes with good to excellent enantioselectivity (Scheme 18).26 The presence of molecular sieves is vital to the success of the reaction. In a similar study, Keck et al.report that reaction of titanium tetra- isopropoxide with either one or two equivalents of enantiomerically-pure BINOL gives catalysts 13 or 14 which exhibit good to excellent enantiocontrol in the allylation of a range of aryl, aliphatic and heteroaromatic aldehydes (Scheme 19).27 BINOL with either a full or one half equivalent of Ti(OPri)4 asymmetrically mediate the reaction of aryl and aliphatic aldehydes with allenyltributyl- stannane (Scheme 20).28 Allenyl alcohols 15 rather than homoprop-2-ynylic alcohol 16 dominate the reaction mixtures; extensive conjugation in the carbonyl component leads to only allenic product, perhaps due to the concomitant rigidity of such systems. Although the reactions require stoichiometric amounts of catalyst and are not uniformly high-yielding, the enantioexcesses obtained are of useful levels (3 82% ee, often (290% ee).The Lewis acids derived from the reaction of (R)- ?H OH RCHO (R)-BINOL, Ti(OPr')d * R b R 15 16 ~~~~ ~ ee R Ti(OPi), (mop/,) Yield (%) 15 (%) 15:16 50 100 50 100 50 100 50 100 50 100 48 58 50 52 25 27 76 80 64 82 >99 95 94 94 82 82 95 92 89 89 14:l 7 1 >95:5 ("traces of B') >955 ("traces of B') 1oo:o 100:o 23:l 11:l 4: 1 4: 1 Scheme 20 69 Hau, Jarvis and Sweeney: Alcohols, ethers and phenolsStoichiometric asymmetric allylation reactions have also been reported. The double asymmetric induction in the reaction of mannose-derived homochiral allylstannane 17 with homochiral aldehydes is pronounced; 17, it is suggested, has a preference for si-face attack, but this preference is inherently weak, as shown in its reaction with achiral aldehydes.A mechanistic rationale, based on a Felkin-Ahn transition state, is proposed, to explain the underlying motives for matched and mismatched bond formation (Scheme 21).29 induction in reaction of &amino and b-hydroxy- allyl~tannanes’~ with aldehydes has been extra- polated to allow an efficient 1,7-asymmetric induction. Thus, homochiral 6-hydroxyallylstannanes 18 react with aryl and aliphatic aldehydes in the presence of tin( IV) bromide to give predominantly syn-(Z)-hept-4-ene-l,7-diols in moderate to good yield (Scheme 22).” A review has appeared concerning the utility of such homochiral &oxygenated allylstannanes in the asymmetric allylation of aldehydes.’* The demonstrated utility of remote asymmetric I-, 17 L-Quebrachitol has been employed as a chiral auxiliary in the asymmetric [3 + 21-cycloaddition reaction of allylsilanes with a-ketoesters.Diastereocontrol and enantiocontrol in the reaction is impressive (Scheme 23).” Acylsilanes may be enantioselectively allylated using B-ally1 diisopinocampheylborane. Enantio- excesses are moderate to low (Scheme 24).’4 Soai has described the asymmetric alkenylation of prochiral enals using diastereoface-selective delivery of vinylzinc reagents (Scheme 25).’5 Using proline- derived chiral chaperones, the yields and enantio- excesses of the reaction were moderate. The chemo- and enantioselective alkylative addition reactions of ketoaldehydes with diethylzinc in the presence of ( - )-A( N-dibutyl norephedrine [ ( - )-DBNE] has been described in full by the same group (Scheme 26).’6 Enantioexcesses were moderate ( x 80%) while chemoselectivity was excellent.Grignard reagent in the presence of tetrapropyl titanate or tributyl vanadate is known to give a-alkylcyclopropanols.37 Corey has found that use of The reaction of esters with a double equivalent of 0 0 TBDMso-2 I 7 1 1.2 : 1 1 1.5 RO r3 0 - TBDMSO BF3aEi2 18:l (matched) 70% yield OH : OR BF@Ei, 16:l (mismatched) 80% yield 1.5 0 0.2 Scheme 21 70 Contemporary Organic SynthesisR 18 anti OH R Yield ("A) syn :anti Ph 4-CI-CeH4 4-MeCeH4 2-Naphthyl Pi Me Et But BU' 72 71 47 65 63 36 61 58 38 92:8 92:8 89:ll 93:7 89:ll 9 o : l O 91 :9 85:15 95:5 Scheme 22 R' = TBDMS SiR23 Yield ("A) de(%) ee(%) ~~ ~ ~ Me3Si 72 >98 95 PhMe,Si 78 >98 >98 Bu'Me2Si 83 >98 96 Bu'Ph2Si 85 >98 98 Scheme 23 catalytic amounts of chloro(triisopropy1oxy)- titanium(1v) in place of the full alkoxide and use of an excess of magnesium allows a diastereoselective synthesis of cis-1 ,Zdisubstituted cyclopropanols from esters (Scheme 27).38 The reaction is not R' SiR23 Yield (%) 88 (910) 2-thienyl SiepPh 81 17 4-CH346H4 SiMe2Ph 65 26 c-C5Hg SiMe2Ph 70 42 4-CF3-C6H4 SiMe2Ph 81 36 plenyl TMS 72 89 Scheme 24 R' R2 R3 Yield(%) eerh) Ph H Bu 59 77 Ph Me Bu 56 75 Ph Me (CH2),2CH3 39 73 Scheme 25 0 0 Et2Zn (-)-DBNE OH Ph-"- 0 ph+NB~2 OH (-)-DBNE Scheme 26 applicable to benzoates and a-branched esters.When TADDOL catalysis was applied, moderate enantioselectivity was obtained ( - 70% ee). Takeda et al.have found that a 3-exo-trig reaction of a Brook rearrangement derived a-silyloxy anion 19 allows preparation of 1,2-dihydroxycyclopropanes 20-22 in good yields (Scheme 28).'9 Anion 19 is generated by reaction of an acyl silane with a lithium enolate of a methyl ketone. cis-Isomers predominate, but in these isomers the silyl group is scrambled between both hydroxy groups. When silylvinyl ketones are employed in the reaction, yields are lower because of competing Michael addition, but no migration of silicon is observed and only trans-diastereoisomers are obtained (Scheme 29). The same authors also reported a similar Brook rearrangement at the heart of a novel Hau, Jawis and Sweeney: Alcohols, ethers and phenols 71l W ! cis R Hex Hex PM=%CH2 PhCH2CH2 H H Me Me Et Et Hex Et Me Hex Ph Me Ph 79 81 80 79 03 72 80 80 83 Scheme 27 ox OTMS P h - - - f # Y + Ph--f@ R OH 20, X = TMS, Y = H 21, X=H,Y=TMS 22 LiO P h T R 0 TMSO ____) Ph? R 0 19 Yield (%) R 20 21 22 Et 64 21 0 PP 59 21 0 p i 9 0 7 0 But 75 0 9 3 T B D M S LIO I kR Scheme 29 I R I 23 O A R 24 Yield (%) R 23 24 Et 3 5 5 3 P f 30 51 But 36 21 P i 4 0 5 0 via: 0- 25 26 27 28 Scheme 28 Yield (%) R 25 26 27 28 Pr’ 55 19 17 19 Et 70 5 70 83 od 71 8 66 73 PP 74 7 n a7 [3 + 21-cyclopentene annulation reaction between 3-heterosubstituted a$-unsaturated acyl silanes and ketone enolates (Scheme 30).40 The reaction was utilised in a synthesis of clavulone I1 (Scheme 31).by 4-em-trig cyclisation of 0-acyl benzylic anions (Schemes 32 and 33).4’ The recent popularity for oxazaborolidine- mediated asymmetric reactions has led to a concomitant demand for homochiral 2,Zdialkylated amino alcohols.Luche et al. have reported a simple racemisation-free method for preparation of such dialkylated aminols from L-valine (Scheme 34).42 Benzocyclobuten-1-01 derivatives may be prepared Scheme 30 1,l -Dichloro-2- hydroxynitroalkanes may be prepared efficiently via a Reformatsky-like version of the Nef reaction. Thus trichloronitromethane reacts with aryl and aliphatic aldehydes in the presence of tin(1r) chloride to give the coupled 72 Contemporaly Organic Synthesiscbvubne Il Scheme 31 Me0 Me0 V C O P h OMe LDA, THF. -78 "C TMSCI. -78 d I Me0 COPh OMe + 65% LDA, THF. -78 'c TMSCI. -78 'C 1 Ph Me0 OM8 Scheme 32 Ph Me0 OMe 1 w/o LDA, THF, -78 "c; 'q R COBu' NH&l(w.) OMe R = H, 76% R = OMe, 59% Scheme 33 1.1.2 Alcohol synthesis by reductive addition to carbonyl compounds Homochiral a-amino aldehydes may be pinacol- coupled using the well-documented low-valent metal reagents of Pedersen (Scheme 36).Thus, a slight excess of an aliphatic aldehyde reacts with such R' YieM ("A) Me 84 Bun 71 ClOH21 48 Bu' 87 Ph 78 mo45H11 10 Scheme 34 SnCl& Et&. 0 "C; CI3CN02 - RCHO; H30+ 5 2 - 9 s yield Scheme 35 OH NHC02R3 R1 R2 OH 30 R' R2 R4 R5 Yield(%) de PS Pr' H But 70 >20:1 PhCH,CH, PhW2 H But 67 >20:1 Bu' PhCH2 H But 67 >20:1 c-C6Hl1 ZNH(CH2)4 H Bn 75 >20:1 C,,HS BnOCH, H Bn 54 .20:1 Scheme 36 aldehydes in the presence of low-valent vanadium reagent 29 to give 1,2-syn-2,3-syn-2-amino- 1,2-diols of general formula 30, in good yield."4 Allylic alcohols may be clectrochemically-coupled with ketones to give 1,4-diols (Scheme 37).45 Full details of what is claimed to be the first efficient asymmetric hydrosilylation protocol for reduction of aryl ketones has been unveiled by S .L. Buchwald et al. (Scheme 38).46 Thus chiral catalyst 31 mediates hydrosilylation of aryl alkyl ketones by polymethylsiloxane according to the previously proposed mechanistic pathway (Scheme 39).47 Enantioselectivities arc generally high ( 3 90% ee). Polymethylsiloxanc (PHMS) also reduces carboxylic Huu, Jawis und Sweeney: Alcohols, ethers and phenols 736H via: &face attack Scheme 37 31 4.5 moPh BuLi (2 eq.); Me3Si0 2'- iMe3 (5 eq.); I:+ ArCOR; TBAF or HCI (aq.) H ° F R Ar Configuration Ar R of product Yield (%) ee (%) Ph Me S 73 97 2-Naphthyl Me S 84 95 2-CCC,H4 Me S 78 90 4-Me-C6H4 Me S a4 96 4-F&-C& Me S 66 65 Scheme 30 via: rather than: Scheme 39 esters to give silylated primary alcohols in the presence of titanates and zirconates (Scheme 40).48 Alcohols are liberated from the silyl ethers by alkaline hydrolysis.Carboxylic acids are also reduced to primary alcohols (6340% yield). a$-Epoxyketones may be reduced to the appropriate alcohol by trimethoxysilane in the presence of lithium methoxide catalyst (Scheme 41). R'C4Me R'-OSiR2, Equivalents Equivalents Yiild of silyl R d PHMS d M(OR2), ether ("A) Ph 0.1 1 86 Bn 0.1 1 76 0.1 1 65 0.1 1 82 Ph # Scheme 40 R1&R4 $ 0 (Me0)3SiH (1.2 eq.) solvent LOMe (4 mi%) 1 R' R2 R3 R4 Solvent Yeld(%) syn:anti H H H P h H H Me Ph Me H H Ph Me Me H Ph H H H B u H H Me Bu H H H P h H H Me Ph Me H H Ph Me Me H Ph H H H B u H H Me Bu Et20 Et2O Et20 Et20 Et20 E t20 HMPA HMPA HMPA HMPA HMPA HMPA 100 91 99 88 78 84 98 91 99 100 88 90 8:92 34% 9:91 0: 100 11:89 11:89 9o:lO 72:28 93:7 60:40 81:19 44:s Scheme 41 The diastereoselectivity of the process is solvent- dependent, allowing for choice of chelation- controlled or Felkin-Ahn-type transition states.At best, exclusive anti or very predominantly syn products may be obtained. Yields are generally A pronounced 177-asymmetric induction is seen when boronate-containing P-y-unsaturated ketones 74 Contemporary Organic Synthesis(prepared by 1,4-addition of boronomethylzinc reagents to enones) are reduced using borane complexes (Scheme 42).” Thus, ketoborinates are reduced with high enantioselectivity by achiral borane-dimethylsulfide.The authors propose a pseudo-axial attack of hydride on a half-chair chelated conformer to rationalise the results (Scheme 43). Evans and co-workers have described the results of their studies into asymmetric catalysis of the Meerwein-Ponndorf-Verley reduction of prochiral ketone^.^' The authors replaced the aluminium isopropoxide of the classical reaction by samarium( iv) species 32, readily prepared from benzylamine and commercially available @)-styrene oxide. This complex catalyses a highly enantioselective reduction of aryl alkyl ketones (Scheme 44). L LJ-J - ‘r R BH3*SMe2, 0 “C; NaOH.Hf12 ! major minor R ee (Oh) Yield (“1’) Me Pent Hex Ph CI(CH2)3 WCH2)lO n O L Me02C(C H2)4 85 42 >98 97 93 97 98 >96 83 87 85 95 97 81 a9 95 Scheme 42 highenergy I H- low energy k Substrate Yield of alcohol ee (“A) (“A) 96 74 95 31 77 78 63 82 95 97 96 96 92 94 68 73 96 97 Scheme 44 Oxazaborolidines derived from (S)-indoline- 2-carboxylic acid asymmetrically catalyse the reduction of prochiral ketones. Whilst in itself not entirely without precedent, the ability to prepare from a common precursor chiral controllers which provide either enantiomer of an alcohol is of interest (Scheme 45).’2 Noroyi et al. have reported the reduction of carbonyl compounds using a simple metal hydride H A HO - c h2 THF BH3 A + BH, R’ R’R~CO (R kconfiguration BOYo ee HO )_R2 THF BH3 B +BH3 R’R~CO R’ (S )-configuration 290% ee Scheme 43 Scheme 45 Hau, Jawis and Sweeney: Alcohols, ethers and phenols 75(Scheme 46).53 The authors found that the combination of commercial LiH and TMSCl in the presence of a catalytic amount of metallic zinc or a zinc(ir) salt would reduce aldehydes and ketones to the corresponding TMS ethers in good yield.Silica gel enhances remarkably the carbonyl- reducing activity of B u , S ~ H . ~ ~ Aryl and aliphatic ketones and aldehydes undergo reduction, but the reduction is chemoselective, with the carbonyl of greater electrophilicity reacting preferentially (Scheme 47). R' FP Catalyst Yiild of siiyl ether (%) Scheme 46 OMe 0 & Me H ?Me HO H 78% yield OMe + & 0 CH, Bu3SnH. SiO2 C H & , 24 h ?Me + 0 y-6 Me CH3 90% yield Scheme 47 Prop-2-ynylic cyclic carbonates may be reduced to either (2)-homoallylic alcohols or homoprop- 2-ynylic alcohols by catalytic hydrogenolysis using Pd( acac)2 (Scheme 48).55 The former are obtained by carrying the reaction out at the boiling point of toluene, whilst the latter result from reduction at ambient temperature.In a related reaction, alkynyl cyclic carbonates are reduced to either homoprop- 2-ynylic alcohols or a-allenyl alcohols by a ligand- tuneable catalytic hydrogenolysis using Pd(dba)* (Scheme 49).56 Simple monodentate phosphine ligands favour formation of alkynes, while biphosphines favour allenes. 0 II Pd(acac)&uoP NHCOgH4 (1 q.) R I O a R 2 R'O 8, room temp. A 2 286% yield Pd(aca+-Bu3P reflux NHCOfiH4 (4 q.) - R2 1 ?H R'O- 274% yield Scheme 48 0 Pd(dba)* BUJP 4 HCO&I Et3N = R Rk*=L HO Scheme 49 1.2 Oxidative methods for alcohol synthesis Full details have appeared concerning the utility of (R)- 1 -[ (S)-2-( diphenylp hosp hino)ferrocenyl]- ethyldicyclohexylphosphine 33, better and more comfortably christened (R)-(S)-josiphos (after the technician involved in its preparation).This catalyst allows highly enantioselective hydroboration of alkenes to give, after usual peroxidative work-up, enantiomerically enriched alcohols. Yields of the process are good and enantioselectivities are moderate to high (Scheme The catalyst also mediates asymmetric reduction of P-ketoesters, but the ee's of the P-hydroxyesters produced are not as high as Noroyi's Ru-BINAP system (84-97% versus ~ 9 9 % ee). Samarium( 111) iodide catalyses the hydroboration of alkenes by catechol borane (Scheme 51).58 The samarium species is present in one-tenth stoichiometry and was selected as the best catalyst from a range of lanthanide complexes. The reactions do not proceed to completion in several cases and high selectivity is not ubiquitous.of cyclohexenones may be selectively hydroxylated The usually less reactive conjugated double bond 76 Contemporary Organic Synthesisto either cis- or anti-1,3-diols by a two-step reduction-oxidation process (Scheme 52).59 Thus, reaction of pulegone with a higher-order phenyl- dimethylsilyl cuprate gives the chromatographically- separable 1,4-addition products which may be selectively reduced: dissolving metal reduction of the addition products followed by peroxidative 9 #Q (R)-(S )-josiphos 33 [Rh(NDP)@F4 (1 md%) ( R )-( S )-josiphB, -78 "C VH 65%yield i\ 91.5%- Ph ph* catechol borane, DME; * NaOH, 25 "c 65% yield 91.5% 88 (Rh(NDP)#F, (1 MI%) (R)-(S)-josipho~, -78 "C catechol borane, DME; NaOH, H@a 25 "C OH Scheme 50 ph+Ph O P h 0, Ph? 79(98) 5O:l (primary:secondary) 47(59) 5:l (primary:secondary) 81 (91) >99:1 (primary:tertiary) 2:l (syn :anti) W99) Scheme 51 A A t Li, NH3, THF-EtOH, -78 "C; TBAF, THF, 25 "c; 30% H@a KHC03, MeOH.25 "c I 1 1 I (PhMe,,Si)&uCNLi, P h M e 2 S i v + P h M e 2 S i u * oo THF, -23 "C, 85% yield A I I A 5 : l A Scheme 52 Hau, Jarvis and Sweeney: Alcohols, ethers and phenols 77desilylative hydroxylation gives anti-diols exclusively, whereas use of L-SelectrideTM as reducing agent gives the syn-isomer.The Schenk reaction has been employed to good effect in a concise synthesis of homochiral a-methylene lactones. Thus, homochiral 3-tributyl- stannyl ally1 alcohols react with singlet oxygen in a highly diastereoselective fashion to give (after reductive work-up) mainly trans-diols (Scheme 53). The major product of the reaction was converted in a two-step process to a-methylene lactones, including dihydromanubanolide B 34.60 OH ''4 + H O E + "$ \ R Bu3Sn R 7% 5% Bu,Sn Bu3Sn 8148% NI(C0)2(PPh3)* THF I 0 Scheme 53 Interest in asymmetric dihdroxylation (AD) of alkenes has continued unabated, as expected. A review of the area has appeared:' along with a review of the general ligand-accelerated catalysis,62 the cornerstone of the AD reaction. What is surprising is an example of AD which apparently violates the predictive mnemonic of Sharpless.Hale and co-workers have reported that l,1-disubstituted alkenes in which one of the substituents is a silyloqmet hyl moiety undergo AD with opposite enantioinduction to that expected (Scheme 54).63 In most cases, enantioexcesses are low, perhaps indicating that these inverted preferences are to do with steric inhibition. YTBS HO" T <OH Scheme 54 Methanesulfonamide-accelerated AD was also used in the synthesis of a conditurol. Thus, the benzylidine acetal of ck-l,2-dihydroxycyclohexa- 3,s-diene underwent diastereo- and enantio- selective dihydroxylation, and deprotection of the resulting diol gave (+)-conduritol E (Scheme 55).64 The same group further reports that acetonide diol 35 may be subjected to a Mitsunobu reaction to give (after deprotection) ( + )-conditurol-F (Scheme 5Q6' 9" >8!% ee >loo% de 1 bn efxc;ge Ho..&; (t)-conduritol E Scheme 55 Scheme 56 78 Contemporary Organic SynthesisSeveral other interesting reports have emerged from the Scripps Institute: firstly, an improved method for the asymmetric dihydroxylation of tetrasubstituted alkenes.66 The use of the 'methane- sulfonamide addition effect' 67 leads to good yields of cis-diols: enantioselectivities are, however, variable (20-97% ee).Terminal alkenes undergo dihydroxylation with improved enantioexcess using cinchona alkaloids bonded to pyrimidines and phthalizines (36 and 37 respectively) (Scheme 57)." (DHQD),-PYR 36 Scheme 57 VDHQD ODHQD (DHQD)p-PH AL 37 WoMe DHQD An improvement to the reaction of cis-allylic and homoallylic alcohols has been reported.69 This paper reports the results of the study into the suitability of the various AD-mixes with such substrates: these data are summarised diagrammatically in Scheme 58.The enantioselectivity of the reaction is AD-mix, 0 "C OH ee ("h) (absolute configuration) Substrate (DHDQ),-PHAL (DHQ),-PHAL DHQD-IND 57 31 73 72 (2R, 3 s ) (2S,3R) (2R, 35) (25,3R) (2R, 35) (2S, 3R) 64 51 Scheme 58 moderate, but the authors point out that, in the homoallylic example, the near symmetry of the alkene makes any selectivity surprising. The authors suggestion of an hydrogen-bonding r61e for the OH group is reinforced by the poor ee shown in dihydroxylation of the corresponding methyl ethers (Scheme 59).(DHW)z-PHAL R' AD-mix OH R' R2 ee (%) Me0 CH20Bu 23 MeO Ph 13 H Ph 35 MeOCH, Et 0 Scheme 59 Homochiral 2,3-epoxyalcohols may be prepared from allylic halides in a two-step sequence involving asymmetric dihydroxylation followed by ring-closure (Scheme 60).70 Yields and enantioexcesses are moderate to excellent. OH 12-98% ee 50-89% yield (DHQD),-PHAL; R -Hal - NaOH R Scheme 60 Sharpless and Wong have joined forces to devise a chemoenzymatic synthesis of carbohydrate^.^' When the products of the AD reactions of a$-unsaturated aldehydes (or equivalents) are subjected to reaction with hydroxy acetone monophosphate in the presence of aldolase enzymes, ketotetrols are obtained in high enantioexcess (Scheme 61).reported: the reaction is chemoselective in the presence of sulfides, dithianes and di~ulfides.~~ Sharpless has reported at length on the mechanistic studies underway to elucidate the exact species involved in the AD rea~tion.~' Full details have appeared concerning the highly diastereo- and enantio-selective asymmetric dihydroxylation reaction of polyenes using phthalazine-modified AD An impressive example of the ease of use of the Sharpless AD reaction has been reported to allow a 'solid-to-solid' asymmetric synthesis of hydrobenzoin on a kilogram scale (Scheme 62).75 Bu'OH lowers the solubility of stilbene, thereby approximating the optimal 'slow addition' protocol required for high enantioexcess. Furthermore, hydrobenzoin is also poorly soluble in the solvent.Thus, the reaction is marked by the slow disappearance of solid substrate The AD of olefins containing sulfur has been Hau, Jarvis and Sweeney: Alcohols, ethers and phenols 790 I -Q R' .. R'R2NH, LiBF, I c8H'7B CH,CN,80"C * OH R-0' R' R2 Yield(%) But H 95 Et Et 88 PS PS 92 Ph H 98 rn 86 W 0 R OH OH Pd(OH)% H,, MeOH 1 Pd(0H)a H2, MeOH I Scheme 63 occurs at the carbon atom of lesser substitution (Scheme 63). been demonstrated to be effective in the regioselective ring opening of epoxides (Scheme 64). These complexes (previously used in ROMP processes79) are highly soluble in organic solvents, have ligand-tuneable Lewis acidity and a high tolerance of spectator functionality. Metal ions examined were Cr(v), Cr(vi), Mo(vr) and W(vr) and this order reflects the order of electrophilicity." Organoimido complexes of transition metals have R&CHO R R = Me, H, >95% 178% 88 68 R = Ph, >95% w R q C H O 1 OH I Rha aldolase; acid phosphatase Rha aldolase; acid phosphatase ,+OH OH OH OH OH R &Nu= R E O H nucleophile, catalyst, * H30* + Scheme 61 A B Yield of Yield of Reaction R Nucleophile Nu Catalyst A(%) B(%) time(h) 0.25 mop/.ligand 0.2 ml% K20s0,(OH)4 NMO (60% in H20) BU'OH. room temp. * P h q p h Ph/\\/ Ph OH 1 kg 1.04 kg 99% ee Ph Ph Ph Ph Bun Bun Ph Ph Ph Ph TMSN3 TMstJ3 NSN3 TMSN3 NSN3 TMSN3 BU'NHTMS BU~HTMS Et2NHTMS Et2NHTMS N3 N3 N3 N3 N3 N3 BuhH BU'NH Et2NH Et2NH 1 2 3 4 1 4 1 2 1 2 31 0 0 0 26 0 27 7 15 8 64 95 45 95 39 80 33 68 25 23 3 12 48 120 72 120 120 240 120 240 Scheme 62 and the concomitant appearance of solid enantio- merically pure product.This is probably as close as research chemists will get to Cornforth's idea of a process chemist's ideal reaction (a one-armed man pouring reagents into a bath and collecting pure product from the drain pipe)! Catalysts: 1. Cr(NBu')C13(dme) 2. Cr(NBu'),CI, 3. Mo(NB~')~Ck(drne) 4. W(N Bu'),(NHBu'), Scheme 64 1.3 Alcohol synthesis Crotti's work on selectivity and efficacy of epoxide heterolysis continues unabated. Lanthanide( 111) trifluoromethanesulfonates have been unveiled as the latest catalyst for such reactions, in particular for aminolysis of monosubstituted epoxides and cycloalkene A similar reaction using cuprate reagents has been published details of the LiBF4-promoted aminolysis of ~ x e t a n e s .~ ~ Ring-opening nucleophilic attack Crotti has also The impressive work of the Jacobsen group concerning asymmetric processes involving epoxides continues. The most recent report of their studies concerns asymmetric ring cleavage of meso-epoxides by TMSN3 (Scheme 65).8' Furthermore, the process may also be used to allow a kinetic resolution of racemic mixtures of monosubstituted epoxides (Scheme 66). The reaction may be performed with the utmost 'atom economy': for instance, no solvent 80 Contemporary Organic Synthesisdiethylamine. The (R)-enantiomer reacts more slowly than the (S)-antipode, so that the ring- opened product has primarily the (S)-configuration, but ee's of the products (both epoxide and amino alcohol) are mediocre.is strongly catalysed by tetrabutylammonium fluoride. The isomer 39 formed via nucleophilic attack at the carbon atom of lesser substitution, is usually observed (Schemes 68 and 69)." Regioselective ring opening of epoxides by thiols 36 (2 mow.), Et20 R AR TMSN3 CSA, MeOH R R > Bu NEt2 Et2NH, catalyst BU BU" OH (R,R)-36 M = CCl ~~ ~~ ~~ 88 ee Catalyst Conversion (%) epoxide (%) amino alcohol (%) Epoxide Yield (%) ee ("h) Ti(OPS),@INOL 45 22 27 Et2ACVBINOL 48 48 24 EtACI@INOL 47 52 58 Et&BINOL 59 75 91 88 94 94 98 98 0 Fmoc 95 95 0 0 p c F 3 PhSH, TBAF (5 mol%) Rl&R2 + R ' Y R 2 R3 SPh SPh 39 40 B 95 95 Yield ("h) R' R2 R3 39:40 72 81 PhOCH2 H MeOCH, H H 'p' H Ph C6H13 H Ph H cis -Ph Ph trans-Ph Ph -(CH*)4- -(c H2)4- H H H 1oo:o 1oo:o 1oo:o 65" 82 isolated as the TMS ether H 94:6 Scheme 65 H H H H H Ph 99: 1 64:34 100.0 1000 1oo:o 64:23 38 (2 mow.), Et20 "4 TMSN,, 78% cower& ''do 98% ee conf g urat ion unspecified 0 38 (2 m~l%), Et20 P h A TMSN3, 80% convesn Scheme 68 0 ?H Scheme 66 - Pho+ PhSH, TBAF (5 moW.) 25-100 "C SR PhO is necessary and, when the product of the reaction is distilled from the neat mixture, the catalyst may be recycled four times, performing sequential asymmetrical ring-openings of different epoxides without any loss of enantioselectivity.BINOL-derived Lewis acids effect a kinetic resolution of racemic chiral epoxides via nucleo- philic ring cleavage by secondary amines (Scheme 67).82 Thus, mixtures of aluminium and titanium Lewis acids and (R)-( +)-binaphthol mediate the ring opening of simple monosubstituted epoxides by R Yield ("h) PhCH2 96 98 88 HO Scheme 69 81 Hau, Jawis and Sweeney: Alcohols, ethers and phenolsLow-valent titanium radicals promote reductive ring cleavage of epoxides to give alcohols arising from (overall) proteolysis at the most hindered carbon atom (Scheme 70).84 When the epoxide contains a remote alkenic functionality, intra- molecular cyclisations are observed.Epoxide Product Yield (%) L P h 41 (R = Ts) 94 (cis :trans = 1:l) Scheme 70 The direct conversion of epoxides to a-hydroxy- acids is accomplished by a copper-mediated hydrolytic oxidative ring opening (Scheme 71).85 The reaction is only synthetically useful when the substrates are perfluorinated. HO R =- )-C02H HN03. Cu metal R ~ ~~~ R Reaction conditions Yield (Yo) i.LDA or LHMDS ii. Et$CI c R' R'CH,CO,Bu' 1246% yield syn:anti = 955 to 56:44 Scheme 72 14% ee Scheme 73 NaOH f Ky ~ nucleophile 85% yield F3C Nucleophile Y Yield (%) ee ("A) NaN3 N3 65 96 NaCN CN 65 96 LiAIH4 H 70 96 C5H1 ,M!m C5Hll 75 96 PhH, AICIs Ph 72 96 Scheme 74 84 Tetracyanoethylene (TCNE) catalyses the F3C Me 12% HN03 (5 eq.), Cu (3%), 80 "C 15 C 6 H ~ 37% HN03 (5 eq.), Cu (3%), room temp. 2 60% HN03 (5 eq.), Cu (a0/,)), 80 "C alcoholysis of trisubstituted epoxides (Scheme 75).R8 The reaction is highly regioselective, with nucleo- philic attack occurring at the more substituted carbon atom, and yields of ring-opened products are high for attack by primary alcohols. Disubstituted F,C6 35% HN03 (5 eq.), Cu (3%), 80 "C 93 Scheme 71 Lithium enolates react with epoxides in the presence of Lewis acid to give b-hydroxy esters in moderate yield (Scheme 72 and 73).*' The reaction exhibits only moderate stereoselectivity (and, in the cases of the menthyl esters, virtually no diastereoselectivity), but these data represent the first stereoselective epoxide opening by ester enolates.(S)-Trifluoromethyloxirane may be prepared in 96% ee via (-)-DIP chloride mediated reduction of trifluoromethyl bromomethyl ketone. The ring opening reactions of trifluoromethyloxirane have been studied in detail by the same workers (Scheme 74)? R TCNE eq. Yield (%) Me 0.1 ally1 0.1 prop-2-ynyl 0.1 Pr' 0.2 Bn 0.2 97 95 91 61 71 Scheme 75 82 Contemporary Organic Synthesisand terminal epoxides do not undergo selective alcoholysis under the conditions.The mechanism of the process is unproven, but is postulated to involve SET. The reactions of 2,3-epoxytosylates have caused some controversy during the period covered by this review. The ring opening of 2,3-epoxytosylates by halide ions in acetonitrile in the presence of Amberlyst 15 resin is highly regio- and diastereo- selective (Scheme 76).x9 No epoxide was obtained despite what might be expected. These authors reported that it is not possible to reduce 2,3-epoxytosylates to alcohols as the former are easily over-reduced; but Chong and Johannsen have clearly shown that this is not the case by exposing such epoxytosylates to up to eight equivalents of DIBAL to give (after work-up) 2-hydroxytosylates in excellent yield (Scheme 77).90 The nature of the solvent employed in the reaction was important: only in dichloromethane and ether was the reaction feasible.Use of THF gave only starting materials (returned in greater than 95% yield) and hexane solvents induced over-reduction to 2-alkanols. I Lii, MeCN Arnberlyst 15 - ' yoTs 99% yield OH OTs ?Ts 98% yield Lit, MeCN 00 Arnberlyst15 * Scheme 76 DIBAL (3 eq.) CHzCIz,-40"C * @ OH R2 R' R2 Yield (%) C10H21 H H H H Me Me C6H13 H H Ph Cl OH21 C6H13 c-C6H11 96 96 94 96 98 96 03 91 Scheme 77 A variant of the Wharton rearrangement allows for a highly stereoselective alkylative elimination of tosylhydrazones derived from homochiral a,P-epoxy aldehydes (Scheme 78). Thus, hydrazones 41 react with Grignard reagents to give diazo anions 42 as intermediates. These species lose diatomic nitrogen Rl&\N,#Ts 0 R2hAgBr (3 eq.) 0 "C, Et20, 30 mn 41 Epoxyhydrazone R2 Yield of allylic alcohol ("A) 68 66 58 0 Bu 65 Et 67 BnO Ph 70 H *? \ NTs N' Bu Et BU Bu Ph H 65 62 71 62 60 Scheme 78 with concomitant epoxide ring cleavage to give (E)- allylic alcohols in acceptable yields." Imines 43 derived from a,p-epoxyaldehydes and N-amino-1-phenylaziridine undergo thermal fragmentation to give x-hydroxy methylene carbenes 44, which insert into a C-H bond five atoms distant to give cyclopent-s-enols in moderate to good yield (Scheme 79).92 The authors demonstrated that the 43 I 45 Scheme 79 OH 44 1 OH 68% yield OH Ph 44% yield Hau, Jarvis and Sweeney: Alcohols, ethers and phenols 83C-H insertion process is not homolytic by examining the reaction of stannylepoxide 45.Had the insertion been homolytic, one would (the authors suggest) have expected to see a preferential C-Sn insertion: this reaction was not observed. 1.4 Alcohol synthesis via biotransformations An oxidoreductase from Geotrichum candidum effects highly diastereo- and enantio-selective reduction of ethyl 2-methyl ketobutyrate (Scheme solution) was incubated with substrate in the Thus, the isolated enzyme (as a 10% glycerol The previously known” enantioselective hydrolysis of cyclohexene oxide by Corynosporium cassiicola has been re-investigated in depth.96 The authors found that racemic diol46 and meso-diol47 could be converted into the same single enantiomer 48 of trans-cyclohexane-l,2-diol with very high enantiomeric purity.This, along with similar findings using other diols, suggests that C. cassiicola contains two or more dehydrogenase enzymes which operate a tandem oxidation-reduction transformation (Scheme 82). presence of glucose, using GDH to regenerate NADPH. anti-Ethyl-(2S,3S)-2-methyl-3-hydroxy- 5 days butanoate was isolated in 69% yield with >99% de OH 50% yield and 94% ee after 48 h. (i)-46 48, >99%ee 47 0 0 OH 0 69% yield * y o E t >99%de >94% 88 oxidoreductase, GDH Scheme 80 Two features of Geotrichum candidum-mediated reductions of carbonyl compounds have been exploited to allow for improvement to the enantioselectivity of such biotransformations (Scheme 81).94 Thus, immobilisation of the microorganism upon a water-absorbent polymeric support and addition of alcohols to the reaction mixture leads to high levels of enantioselection in reductions of arylmethyl ketones.The r6le of the alcoholic component is to improve recycling of NAD’ by inducing activity of the glycerol dehydrogenase present in the cell. immobilized Geofdrhum candidum Ho Ar k hexan-2-oVhexane * Ar Absolute Ar Additive Yield (%) ee (“A) configuration none 52 propan-2-01 29 cyclopentanol 58 hexan-2-d 73 hexan-2-d 38 hexan-2-d 81 hexan-2-d 99 hexan-2-d 81 hexan-2-d 41 hexan-2-d 59 hexan-2-01 60 hexan-2-d 40 28 >99 >99 >99 >99 89 >99 92 >99 >99 99 9a R S S S S S S S S S S S Scheme 81 dehydrogenase 2 reduction l a::::: dehydrogenase 1 oxidation of (R)-OH dehydrogenase 2 reduction 1 a:: Scheme 82 A one-pot sequence of three sequential asymmetric aldol reactions involving three equivalents of a chiral aldehyde component is carried out by the enzyme 2-deolryribose- 5-phosphate aldolase (DERA).The general reaction is shown in Scheme When three equivalents of acetaldehyde and one equivalent of a substituted acetaldehyde are employed in the reaction, substitute pyranosides may be obtained from the reaction (Scheme 84). The products of these reactions are useful synthons for analogues of HMG-CoA reductase inhibitors. Since DERA has been overexpressed in E. coli, large quantities of this enzyme are available, thereby making the transformation of considerable synthetic utility. The interest in bacterial hydroxylation reactions has continued unabated. The reaction of 1,4-disubstituted aromatics in the presence of strains 84 Contemporary Organic Synthesisx] CHsCHO;DERA_ OH OH - H I CHGHO; E R A 20% yield I I kH I VoH Scheme 03 ‘)-H + 3 eq.Scheme 84 H 20 OH <3 OMe 65 CI 70 Br - N3 23 OH R Yield (“A) off? Putida is tuneable, with different strains having different substrate preferences, thus allowing preparation of both enantiomers of benzenoid cis- 1,2-diols (Scheme 85). para-Dihalobenzenes and para-iodotoluene react in the presence of mutant UV4 to give cis-diols of opposite configuration to those usually obtained from the wild-type oxidation, although the enantioexcesses of these diols is inferior to that normally observed in the ‘natural’ oxidation. Hydrogenolysis of the C-I bond furnishes diols which may then be exposed to wild-type NCIMB8859: this organism selectively oxidises the ‘natural’ cis-diols, thereby leading to an enantiomeric enrichment of the ‘unnatural’ antipode.Other wild-type and mutant strains of P Putida were examined by the authors and found to cis-hydroxylate naphthoquinones, indenes and homologues with variable enantiocontrol (35 to >98% ee).98 An isolated P-ketoester reductase from Baker’s yeast allows introduction of multiple asymmetry, via an enantioselective reduction and a dynamic kinetic res01ution.~~ Thus, when racemic ketoesters 49, in which the ester component contains an a-asymmetric centre, are reacted with reductase L-enzyme-1”) in the presence of NADPH (regenerated using the G6P couple) one diastereoisomer of 49 is reduced to give enantio- merically pure (>99% ee) stereotriad 50.The W4 mutant I X = Me, Br, CI 6H 1548%- OH P. Pulida wild type NClMB 8850 0lH OH 30% yield 98% ee Scheme 85 unreacted diastereoisomers undergo epimerisation at the acidic C-H position under the reaction conditions, but the configuration of the stereocentre of the pendant ester moiety remains intact (Scheme 86). Double reduction of 2-benzylidenecyclohexanone has recently been shown to be highly selective 49 L-Enzyme-1 MOPS0 buffer pH 7.0,30 OC, 18 h I GGPIGGPDH couple 51 50 Yield of 51 (“A) Yield of 50 (“A) R (-) (”/I (ee) (%) de of 50 (%) C6Hll 64 (32) 34 (>99) 66 Ph 9 (68) 48 (>99) 74 4-CI-CGH4 69 (36) 31 (>99) 77 4-Me-C& 56 (58) 44 (>99) 75 4-NOz-C& 9 (35) 41 (>99) 80 2-CCCeH4 64 (39) 36 (>99) 70 Scheme 86 Hau, Jarvis and Sweeney: Alcohols, ethers and phenols 850 LiAIH4 U M F , reflux U 76% yield Scheme 87 (Scheme 87).'" When the same enone is subjected to reductive biotransformation (on a 50 g scale), the reaction exhibits variable levels of stereocontrol (Scheme 88).Io2 Thus, under typical conditions, 1,2- and 1,4-reduced products are obtained in roughly equal amounts. When forcing conditions (twice the amount of yeast) are employed, double reduction is observed but the reaction is poorly diastereoselective.Ph Baker's yeast 85% yield I 1 : 1.5 : trace : trace - E L 1 Baker's yeast : 2 'forcing conditions' 80% yield Scheme 88 Both enantiomers of 3-hydroxypyrrolidin-2-one are accessible via lactate dehydrogenase (LDH) reduction of N-protected 4-amino-2-keto- carboxylates (Scheme 89).lo3 1.5 Miscellaneous methods for alcohol synthesis Capitalising upon the fact that oxazolidinones are good leaving groups, the N-benzoyloxazolidinone 52 derived from tert-leucinol acts as an asymmetric benzoyl transfer reagent upon reaction with secondary alcohols.IM Racemic aryl alkyl carbinols react, in large excess (10 equivalents), with 52 in the presence of methyl magnesium bromide to give (I?)- benzoates.Lack of an aryl group in the alcohol leads to poor enantioexcess. Halophenols are easily exhaustively hydrogenated to the corresponding dehalogenated cyclohexanols upon reaction with Raney nickel-aluminium alloy in saturated barium hydroxide solution. The reduction is independent of the number of halogen atoms Scheme 89 Ph "y 52 H ~ ~~ ~~~ ~ Halophenol Product X R &(OH), (ml) Ni-AI alloy (9) YieM ("A) ~~~~~~~ ~ 3Br H 60 4-Br H 60 2.4-Br H 60 2,4,6-Br3 H 55 3CI-2,4.6-Br3 H 130 2,3,4,6-Br4 H 130 2,4,6-CI, H 50 2,3,4.6-C14 H 50 2,3,4,5,6-C15 H 100 2,4,BCI3 3-Me 20 2,6-C12 4-Me 50 8 54 9 74 10 65 12 42 16.5 62 16.5 52 8.3 65 8.3 62 12.0 91 8.0 30 cis, 45 m s 20.0 45 cis, 49 trans Scheme 90 present, but chlorophenols are reduced more easily than bromophenols (Scheme 90).'05 Lautens and Delanghe have reported in detail their studies on the cyclopropanation of a-allenic alcohols.Io6 Following a thorough screening of a wide range of cyclopropanation protocols, the samarium metal-chloroiodomethane combination was shown to deliver the best diastereoselectivity (Scheme 91).86 Contemporaiy Organic SynthesisRe'@-?- OH Sm (low.) CICH21 (10 q.) THF, -78 "C -+ room temp. I &+&' + J - + c 6 H I l OH OH 9 1 82% yield Scheme 91 A highly stereoefficient asymmetric Simmons- Smith cyclopropanation of allylic alcohols using the boronate 53 derived from (+)-N,N,","- tetramethyl tartaric acid diamide has been reported.Thus, at room temperature, allylic alcohols are cyclopropanated in 91-94% ee by Zn(CH21)2 in the presence of stoichiometric amounts of 53 (Scheme 92). lo' 53 (l.leq.), Zn(CH,J), OH Rw CH,CI,,25 "C, 2 h Me,N(O)Ch CONMe, I Bu 53 R Yield (%) ee (%) Ph >98 93 Pr 80 93 (Z)-Et 90 93 (Z)-TBDMSOCH, 80 91 Scheme 92 Dianions derived from (2-hydroxy)ethylphenyl sulfone may be dialkylated efficiently to give cx-disubstituted hydroxy sulfones 54.These products may be cyclised via iodetherification to give substituted iodomethyl tetrahydrofuranyl sulfones 55 which may in turn be converted by double elimination to 2,4-disubstituted furans (Scheme 93).Io* Yields of the overall process are good. Alkylidenephosphoranes undergo an insertion reaction with 1,2-dioxetanes to give phosphorinanes in quantitative yield.'" These species may be converted to the monoethers of 1,2-diols 56 or to 2-oxyvinylalcohols (Scheme 94). An asymmetric Meisenheimer rearrangement allows the asymmetric preparation of allylic alcohols of high ee (Scheme 95).'" Thus, C-2 symmetric pyrrolidine 58 is converted into a range of allylic tertiary amines and oxidised to the N-oxide, which undergoes asymmetric [2,3]-rearrangement to give PhS02 R'Br, THF, PhSO2 LoLi -70 "C + room temp; R2&Br , THF, -40 "C Li OH 54 NaHC03,12 room temp., 1 h THFIH20 (21) 1 BU'OK, THF, o oc t'- A 7589% yield Scheme 93 quantitative NaOH, MeOWHfl; PhCHO 57 56 Scheme 94 hydroxylamines 59 in good yield and mediocre de (62-73%).These compounds were purified by HPLC and converted to allylic alcohols 60 of ~ 9 3 % ee. 2 Preparation of ethers and phenols A review has appeared delineating the use of a-haloethers in preparation of ethers."' Jacobsen and Larrow have observed a kinetic resolution in effect during the authors' previously well-documented Mn-salen catalysed asymmetric epoxidation process (Scheme 96).Il2 The authors observed that the ee of the product of asymmetric epoxidation of 1,2-dihydronaphthalene increased with reaction time, at the expense of yield.Surmising that there was a secondary kinetic resolution process in effect, they exposed racemic 1 -2-dihydronaphthalene oxide to the system utilised in asymmetric epoxidation, whereupon they observed a benzylic oxidation reaction; the enantiomer which reacted slower was that corresponding to the major product from the Hau, Jawis and Sweeney: Alcohols, ethers and phenols 870% OMe I 58 OH HPLC; mCPBA; [2,3]-rearrangement I 60 >93% 88 59 ~~ ~ R ee of 60 (%) Configuration Me 95.2 R Et 91.5 R P f 96.3 R P i 96.0 R But 93.1 S Scheme 95 93 : 7 Ph Ph -'.a- X catalyst62 fast 'I 86% ee 98% ee 53% yield Scheme 97 pseudo-axial hydrogen atom leads to a pseudo-axial hydroxy group. This was confirmed when epoxides having little energetic difference between pseudo- axial and pseudo-equatorial C-Hs were shown to react with poor diastereoselectivity. An umpolung may be exploited to allow the efficient preparation of 2-aryloxyphenols by means of a two-step analogue of the Ullman alkylated in high yield by phenols to give tht: corresponding 2'-formylbiphenylethers which undergo Baeyer-Villiger reaction to give the aforementioned aryloxyphenols (Scheme 98).Thus, 2-fluorobenzaldehyde is CHO I mCPBA, CH2C12 OCHO room temp., 1 h R But' \ But (R,R)-61, X=OMe (R ,R )-a, X = Bu' Scheme 98 Scheme 96 epoxidation of 1,2-dihydronaphthalene, while the enantiomer which is the minor product of epoxidation was rapidly oxidised to syn-epoxy alcohol. Thus the authors devised a one-pot, two- catalyst system to allow rapid epoxidation and subsequent rapid C-H oxidation to take place (Scheme 97).The mechanism does not involve an epoxide-directed C-H insertion reaction, as might naively be expected, but rather a stepwise radical process in which preferential abstraction of a R Yield (%) H 96 CI 89 Br 90 But 87 OMe 79 OPh 85 Radical cyclisation of the 3-hydroxybutyrate- derived oxygen-tethered a$-unsaturated ester 63 gives cis-2,5-disubstituted tetrahydrofuran-3-ones with high syn-selectivity (Scheme 99). Slow addition (syringe pump) is vital, and so the reaction may be less feasible on a large aromatisation of 2-alkylthiocyclohexanones in the presence of molecular bromine (Scheme a,a-Difluoroethers and acetals formally derived from carbonyl difluoride may be prepared by fluorinative desulfonylation of thioesters and 0-Alkylthiophenols may be prepared by 88 Contemporary Organic SynthesisYYo 0 SePh k O & k ___) 63 Reaction conditions syn :anti Yield (%) Ph3SnH.AIBN, A, 3 h 88:12 82 Ph3SnH, EtJ3, air, rt, 96 h 2955 63 Bu3SnH, AIBN, A, 2.5 h 8515 94 Ph3SnH. Et36, air, A, 4 h 94:6 97 Scheme 99 812 - R Yield (%) Scheme 100 R' R2 Yield (%) Me Bu 37 Me 4-biphenyl 74 Et 4-biphenyl 77 Ph El 43 Ph Bn 76 Ph Ph 76 Scheme 101 thiocarbonates respectively (Scheme l O l ) . ' l6 Tetrabutylammonium perfluoride is the reagent which allows these transformations to be realised. Rozen's method' l 7 allows preparation of %,a-difluoroethers from thioesters, but uses the more exotic BrF,. 3 References 1 D. A. Evans, M. J. Dart and J.L. Duffy, Tetrahedron 2 D. A. Evans, M. J. Dart and J. L. Duffy, Tetrahedron Lett., 1994, 35, 8537. Lett., 1994, 35, 8537. 3 T. J. Leitereg and D. J. Cram, J. Am Chem. SOC., 1968,90,4011. 4 C. Copkrat, E. Negishi, Z. Xi and T. Takahashi, Tetrahedron Lett., 1994,35, 695. 5 T. Luker and R. J. Whitby, Tetrahedron Lett., 1994, 35, 785. 6 M. Chiro, T. Matsumoto and K. Suzuki, Synlett, 1994, 359. 7 N. Auner, J. Grobe and R. Damrauer, J. Organomet. Chem., 1980, 188, 25; N. S. Namekin, N. V. Ushakov and M. V. Vdovin, Zh. Obshch. Khim., 1974,44, 1970; P. Jutzi and P. Langer, J. Organornet. Chem., 1977, 132, 45. 8 S. E. Denmark, B. D. Griedel, D. M. Coe and M. E. Schnuti, J. Am. Chem. SOC., 1994, 116, 7026. 9 E. M. Carriera, R. A. Singer and W. Lee, J. Am. Chem. SOC., 1994, 116, 8837.10 H. Nitta, D. Yu, M. Kudo and A. Mori, J. Am. Chem. SOC., 1992, 114, 7969. M. Hayashi, Y. Miyamoto, T. Inoue and N. Ogumi, J. 0%. Chem., 1993,58, 1515. 11 B. R. Lago, H. M. Crane and D. C. Liotta, J. 0%. Chem., 1993, 58,4191. 12 S. Tsuboi, H. Kuroda, S. Takatsuka, T. Fukawa, T. Sakai and M. Utaka, J. 0%. Chem., 1993,58,5952. 13 M. K. Kundu, S. B. Mukherjee, N. Balu, R. Padmakumar and S. V. Bhat, Synlett, 1994,444. 14 A. Yanagisawa, H. Inone, M. Morodome and H. Yamamoto, J. Am. Chem. SOC., 1993, 115, 10 356. 15 J. Synoniak, D. Felix and C. Moi'se, Tetrahedron Lett., 1994,35, 8617. 16 S. Kobayashi and K. Nishio, Synthesis, 1994,457. 17 J. M. Clayden and M. Julia, J. Chem. SOC., Chem. Commun., 1994, 2261. 18 H. C. Aspinall, A. F. Browning, N. Greeves and P.Ravenscroft, Tetrahedron Lett., 1994, 35, 4639. 19 Y. Hashimoto, H. Kagoshima and K. Saigo, Tetrahedron Lett., 1994, 35, 4805. 20 R. Sjoholm, R. Rairama and M. Ahonen, J. Chem. SOC., Chem. Commun., 1994, 1217. 21 J.-F. Normant,J. Organomet. Chem., 1990, 400, 19. 22 R. N. Haszeldine, J. Chem. SOC., 1954, 1273. 23 F. Hong, X. Tang and C. Hu, J. Chem. SOC., Chem. Commun., 1994,289. 24 A. Guijario and M. Yus, Tetrahedron, 1994, 51, 13 269. 25 J. J. Harnett, L. Alcarez, C. Miokowski, J. P. Martel, T. Le Gall, D.-S. Shin and J. R. Falck, Tetrahedron Lett., 1994, 35, 2009. 26 A. L. Costa, M. G. Piazza, E. Tagliavini, C. Trombini and A. Umani-Ronchi, J. Am. Chem. SOC., 1993,115, 7001. Chem. SOC., 1993, 115, 8467. Tetrahedron Lett., 1994,35, 8323. Chem. SOC., 1994, 116, 8536.Commun., 1994, 285. Commun., 1994, 283. 27 G. E. Keck, T. H. Tarbet and L. S. Cieraci, J. Am. 28 G. E. Keck, D. Krishnamurthy and X. Chen, 29 W. R. Roush and M. S. van Nieuwenhze, J. Am. 30 S. J. Stanway and E. J. Thomas, J. Chem. SOC., Chem 31 J. S. Carey and E. J. Thomas, J. Chem. SOC., Chem. 32 A. H. McNeill and E. J. Thomas, Synthesis, 1994, 322, 33 T. Akiyama, T. Yasusa, K. Ishikawa and S. Ozaki, 34 J. D. Buynak, B. Geng, S. Uang and J. B. Strickland, 35 K. Soai and K. Takahashi, J. Chem. SOC., Perkin Trans. 36 M. Watanabe and K. Soai, J. Chem. SOC., Perkin Tetrahedron Lett., 1994, 35, 8401. Tetrahedron Lett., 1994, 35, 985. I , 1994, 1257. Trans. I , 1994, 3125. Hau, Jawis and Sweeney: Alcohols, ethers and phenols 8937 0. G. Kulinkovich, V.L. Sorokin and A. V. Kelin, Zh. 0%. Khim., 1993, 29, 66. 38 K. Takeda, S. A. Rao and M. C. Noe, J. Am. Chem. SOC., 1994, 116, 9345. 39 K. Takeda, J. Nakatani, H. Nakamura, K. Sako, E. Yoshi and K. Yamaguchi, Synlett, 1993, 841. 40 K. Takeda, M. Fujisawa, T. Makino and E. Yoshii, J. Am. Chem. SOC., 1993, 115, 9351. 41 K. Kobayashi, M. Kawakita, T. Mannami and H. Konishi, Tetrahedron Lett., 1995, 36, 733. 42 P. Delair, C. Einhorn, J. Einhorn and J. L. Luche, J. Org. Chem., 1994, 59, 4680. 43 A. S. Demir, C. Tanyeli, A. S. Mahawneh and H. Aksoy, Synthesis, 1994, 155. 44 A. W. Konradi, S. J. Kemp and S. F. Pedersen, J. Am. Chem. SOC., 1994,116, 1317. 45 T. Shono, Y. Morishima, N. Moriyoshi and M. Ishifume, J. 0%. Chem., 1994, 59, 273. 46 M. B. Carter, B. Schifltt, A.GutiCrrez and S. L. Buchwald, J. Am. Chem. SOC., 1994,116, 11 667. 47 J. W. Lauher and R. Hoffman, J. Am. Chem. SOC., 1976,98, 1729. 48 S. W. Breedon and N. J. Lawrence, Synlett, 1994, 833. 49 M. Hojo, A. Fujii, C. Murakami, H. Aihara and A. Hosomi, Tetrahedron Lett., 1995, 36, 571. 50 G. A. Molander and K. L. Bobbitt, J. Am. Chem. SOC., 1993,115, 7517. 51 D. A. Evans, S. G. Nelson, M. R. GagnC and A. R. Muci, J. Am. Chem. SOC., 1993, 115, 9800. 52 Y. H. Kim, D. H. Park and I. S. Bynn, J. 0%. Chem., 1993, 58, 511. 53 T. Ohkuma, S. Hashiguchi and R. Noroyi, J. 0%. Chem., 1994,59,217. 54 B. Figadere, C. Chaboche, X. Franck, J.-F. Peyrat and A. CavC, J. 0%. Chem., 1994,59, 7138. 55 S. K. Kang, D. C. Park, D. G. Cho, J. U. Chung and K. Y. Jung, J. Chem. SOC., Perkin Trans.I , 1994, 237. 56 C. Dariel, S. Bartoch, C. Bruneau and P. H. Dixneuf, Synlett, 1994, 457. 57 A. Togni, C. Breutel, A. Schnyder, F. Spindler, H. Landert and A. Tijani, J. Am. Chem. SOC., 1994, 116, 4062. Chem., 1993,58,5307. Tetrahedron Lett., 1995, 36, 351. 58 D. A. Evans, A. R. Muci and R. Sturmer, J. 0%. 59 D. F. Taber, L. Yet and R. S. Bhamidipati, 60 W. Adam and P. Klug, Synlett, 1994, 567. 61 H. C. Kolb, M. S. van Nieuwenhze and K. B. Sharpless, Chem. Rev., 1994,94, 2483. 62 D. J. Berrisford, C. Bolm and K. B. Sharpless,Angew. Chem., Int. Ed. Engl., 1995, 34, 1059. 63 K. J. Hale, S. Mahaviazar and S. A. Peak, Tetrahedron Lett., 1994, 35,425. 64 S. Takano, T. Yoshimitsu and K. Ogasawara, J. 0%. Chem., 1994,59,54; 1995, 60, 1478. 65 T. Yoshimitou and K.Ogasawara, Synlett, 1995,257. 66 K. Morikawa, J. Park. P. G. Anderson, T. Hashiyana and K. B. Sharpless, J. Am. Chem. SOC., 1993, 115, 8463. 67 K. B. Sharpless, W. Amberg, Y. L. Bennani, G. A. Crispino, J. S. Hartung, K.-S. Jeong, H.-L. Kwong, K. Morikawa, Z.-M. Wang, D. Xu and X.-L. Zhang, J. 0%. Chem., 1992,57,2768. 68 G. A. Crispino, K. S. Jeong, H. C. Kolb, Z. M. Wang, D. Xu and K. B. Sharpless, J. 0%. Chem., 1993,543, 3785. Tetrahedron Lett., 1994, 35, 843. Sharpless, Tetrahedron Lett., 1994, 35, 3469. 69 M. S. van Nieuwenhze and K. B. Sharpless, 70 K. P. M. Vanhessche, Z. M. Wang and K. B. 71 I. Henderson, K. B. Sharpless and C. H. Wong, J. Am. Chem. SOC., 1994,116,559. 72 P. J. Walsh, P. T. King, S. B. King and K. B. Sharpless, Tetrahedron Lett., 1994,35, 5 129.73 H. C. Kolb, P. G. Anderson, Y. L. Bennani, G. A. Crispino, K. S. Jeong, H. L. Kwong and K. B. Sharpless, J. Am. Chem. SOC., 1993, 115, 12 226; T. Gobel and K. B. Sharpless, Angew. Chem., Znt. Ed. Engl., 1993,43, 1329; D. V. McGrath, G. D. Brabson, K. B. Sharpless and L. Andrews, Inoq. Chem., 1993, 32,4164; H. C. Kolb, P. G. Anderson and K. B. Sharpless, J. Am. Chem. SOC., 1994, 116, 1278; P. 0. Norrby, H. C. Kolb and K. B. Sharpless, Organometallics, 1994, 13, 344. 74 H. Becker, M. A. Soler and K. B. Sharpless, Tetrahedron, 1995, 51, 1345. 75 Z.-M. Wang and K. B. Sharpless, J. 0%. Chem., 1994, 59, 8302. 76 M. Chini, P. Crotti, L. Favero, F. Macchia and M. Pineschi, Tetrahedron Lett., 1994,35,433. 77 Y. Yamamoto, N. Asao, M. Meguro, M. Tsukada, H.Nemoto, N. Sayadori, J. G. Wilson and H. Nakamura, J. Chem. SOC., Chem. Commun., 1993, 1201. 78 M. Chini, P. Crotti, L. Favero and F. Macchia, Tetrahedron Lett., 1994, 35, 761. 79 R. R. Schrock, Acc. Chem. Res., 1991,23, 1580. 80 W. H. Leung, E. K. F. Chow, M. C. Wu, P. W. K. Kum and L. L. Yeung, Tetrahedron Lett., 1995, 36,107. 81 L. E. Martinez, J. L. Leighton, D. H. Carsten and E. N. Jacobsen, J. Am. Chem. SOC., 1995, 117,5897. 82 M. Brunner, L. Mussmann and D. Vogt, Synlett, 1994, 69. 83 D. Albanese, D. Landini and M. Penso, Synthesis, 1994, 34. 84 T. V. Rajan Babu and W. A. Nugent, J. Am. Chem. SOC., 1994, 116, 987. 85 T. Katagiri, F. Obara, S. Toda and K. Furahashi, Synlett, 1994, 507. 86 S. K. Taylor, J. A. Fried, Y. N. Grassl, A. E. Marelewski, E. A. Pelton, T.-J. Poel, D. S. Rezanka and M. R. Whittaker, J. 0%. Chem., 1994,59, 7304. 87 P. V. Ramachandran, B. Gong and H. C. Brown, J. 0%. Chem., 1995, 60, 41. 88 Y. Masaki, T. Miura and M. 0. Chiai, Synlett, 1993, 847. 89 C. Bonini, L. Chiammiento and M. Funicello, Tetrahedron Lett., 1994,35, 797. 90 J. M. Chon and J. Johannsen, Tetrahedron Lett., 1994, 35, 7 3 7 . 91 S. Chandrasekhar, M. Takhi and J. S. Yadav, Tetrahedron Lett., 1995, 36, 307. 92 S. Kim and C. M. Cho, Tetrahedron Lett., 1994,35, 8405. 93 Y. Kawai, K. Tananobe, M. Tsujimoto and A. Ohno, Tetrahedron Lett., 1994, 35, 147. 94 K. Nakamura, Y. Inoue and A. Ohno, Tetrahedron Lett., 1995,36, 265. 96 A. J. Carnell, G. Iacazio, S. M. Roberts and A. J. Willetts, Tetrahedron Lett., 1994, 35, 331. 97 H. J. M. Gijsen and C.-H. Wong, J. Am. Chem. SOC., 1994,116, 8422. 98 C. C. R. Allen, D. R. Boyd, H. Dalton, N. D. Sharma, I. Brannigan, N. A. Kerly, G. N. Sheldrake and S. C. Taylor, J. Chem. SOC., Chem. Commun., 1995, 117. Tetrahedron Lett., 1995, 36, 591. 100 K. Nakamura, Y. Kawai, N. Nakajima and A. Ohno, J. 0%. Chem., 1991,56,4778; K. Nakamura, Y. Kawai, T. Miyai, S. Honda, N. Nakajima and A. Ohno, Bull. Chem. SOC. Jpn., 1991, 64, 1467. 99 Y. Kawai, K. Hida, K. Nakamura and A. Ohno, 90 Contemporary Organic Synthesis101 K. Koch and J. H. Smitrovich, Tetrahedron Lett., 1994, 35, 1137. 102 G. Fronza, G. Fogliato, C. Fuganti, S. Lanati, R. Rallo and S. Servi, Tetrahedron Lett., 1995, 36, 123. 103 J. M. Bentley, H. J. Wadsworth and C. L. Willis, J. Chem. SOC., Chem. Commun., 1995,231. 104 D. A. Evans, J. C. Anderson and M. K. Taylor, Tetrahedron Lett., 1993, 34, 5563. 105 T. Tsukinoki, T. Kakinami, Y. Iida, M. Ueno, T. Mashimo, H. Tsuzuki and M. Tashiro, J. Chem. SOC., Chem. Commun., 1995, 209. 106 M. Lautens and P. H. M. Delanghe, J. Am. Chem. SOC., 1994, 116, 8526. J. Org. Chem., 1993, 58, 5037 107 A. B. Charette and H. Juteau, J. Am. Chem. SOC., 1994, 116, 2651. 108 J. H. Jung, J. W. Lee and D. Y. Oh, Tetrahedron Lett., 1995, 36, 923. 109 W. Adam, H. M. Harrer and A. Treiber, J. Am. Chem. SOC., 1994, 116, 7581. 110 D. Enders and H. Kempen, Synlett, 1994, 969. 11 1 T. Benneche, Synthesis, 1995, 1. 112 J. F. Larrow and E. N. Jacobsen, J. Am. Chem. SOC., 113 G. W. Yeager and D. N. Schissel, Synthesis, 1995, 28. 114 P. A. Evans and J. D. Roseman, Tetrahedron Lett., 115 V. V. Samashin and K. V. Kudrayavtser, Tetrahedron 116 M. Kuorboshi and T. Hiyama, Synlett, 1994, 251. 117 S. Rozen and E. Mishani, J. Chem. Soc., Chem. 1994, 16, 12 129. 1995,36, 31. Lett., 1994, 35, 7413. Commun., 1993, 1761. Hau, Jarvis and Sweeney: Alcohols, ethers and phenols 91