Transformation of cyclic alpha;-phenylthio aldehydes by stereoselective aldol reactions and phenylthio migration into spirocyclic lactones and ethers, andE-allylic alcohols with 1,4-related chiral centres

摘要

J. CHEM. SOC. PERKIN TRANS. 1 1991 45 1 Transformation of Cyclic a-Phenylthio Aldehydes by Stereoselective Aldol Reactions and Phenylthio Migration into Spirocyclic Lactones and Ethers, and E-Allylic Alcohols with 1,4-Related Chiral Centres Varinder K. Aggarwal, lain Coldham, Sara Mclntyre and Stuart Warren * University Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW syn- and anti-Selective aldol reactions between enolates of propionate esters and three a-phenyl- thio cycloalkanecarbaldehydes give single diastereoisomers of phenylthio alcohols which rearrange in acid with 5-hydroxy or 5-C02H participation to give spirocyclic ethers or lactones. In the absence of internal nucleophiles, allylic sulphides are formed which are used to make allylic alcohols with an euro;double bond exo to the ring and two stereochemically defined 1,4-related chiral centres.Acid-catalysed dehydration of the primary alcohol' 1 or the tertiary alcohol 2 gives the allylic sulphide 4 uia the common intermediate 3. The phenylthio (PhS) migration implies stereo- specific inversion at the migration terminus and we now describe3 rearrangements of analogues of 1, in which the migration terminus is a chiral centre, derived from a-PhS- substituted aldehydes by stereoselective aldol reactions. o('"OH 1 H + ,Ph@ 43CKSPh Three cyclic m-PhS-substituted aldehydes 5-7 were made by sulphenylation of a silyl enol ether or by rearrangement' of the adducts 8 from cyclopentanone, cyclohexanone, and N-methyl- piperidin-3-one with SOC1, and base.Rearrangement of 8c t gave a higher yield of 7 in the absence of base as it is itself a tertiary amine. SPh oL,H* 5 series a 6 series b 7 series c SOClzii, ketone TOMe Et3N * 5,617 SPh 8 We studied aldol reactions of various propionate ester eno- lates on aldehyde 6 (Table 1) and selected the lithium enolate of the 2,6-dimethylphenyl ester 5*6 and the boron enolate of the phenylthioester s*7as the most efficient way to make the anti and syn aldols respectively (Scheme 1). The former method was then applied to the other two aldehydes 5 and 7 to give high yields of anti-l0a and anti-l0c. Aldols are unambiguously defined as syn or anti in the usual way.5 It seems logical to retain this system for the spirocyclic compounds even though the arrangement of the chain in a ring instead of an extended conformation means that anti-13 to anti-12 is an inversion. (CHOH) and Me2 in syn and anti-9 are more reliable * (Table 2).L-H+ WSPh anti -10b syn -1lb anti -12b LiOH1 IPh.14banti -13b Ar = 2, 6-Me2C6H3 Rearrangement of the anti 2,6-dimethylphenyl esters 10 with toluene-p-sulphonic acid (TsOH) in benzene gave a mixture of the allylic sulphides 11 and the lactones 12. In series b, higher yields of lactone 12 were obtained by hydrolysis (LiOH, water, MeOH) and rearrangement of the free acid 13. The intermediate 14 and the product 12 are the same as those of sulphenyl- lactonisation in which y-lactones are the thermodynamic though not the kinetic products.These lactones 12 are formed stereospecifically with inversion at C-3: anti-13b gives anti-l2b, while syn-13b gives syn-12b. The lactones show characteristic ' J2*3-values in the 'H NMR spectrum: 12.2 Hz for anti-12b and 8.9 Hz for syn-12b. The rearrangement of anti-l0c was much slower (3 h in CH,Cl,) and gave pure crystalline 12c in 80 yield without chromatography. The slow loss of HAfrom the intermediate 16 t Compounds derived from aldehyde 5 are numbered a those from 6 are numbered b, and those from 7,c. EtCOX6-base Me2 anti -9b SY~-9b Scheme 1 Aldol stereochemistry was confirmed by NM R spectroscopy. Most syn aldols show a lower J2*3-value than do anti aldols but products from large aldehydes (eg., Bu'CHO) show small J2v3-values for both isomer^.^ The 13C NMR shifts of C-3 452 J. CHEM.SOC. PERKIN TRANS. 1 1991 Table 1 Stereoselective aldol reactions on cyclic r-PhS aldehydes (Scheme 1) Products isolated (So) Aldehyde X Reagents Product unti-syn Ratio anti syn 6 OMe LDA 9b 35 :65 27 50 6 OMe i,LDA 9b ii, cp,ZrCl, " Pr',NEt 6 SPh 9-BBN-OTf 9b 6 OArb LDA llb 5 OArb LDA 1la 7 OArb LDA 1 lc a See ref. 20. Ar = 2,6-dimethylphenyl, see refs. 5 and 6. 30: 70 5:95 95:5 84 96:4 70 95:5 72* 59 76 Table 2 Stereochemistry of aldols (see Scheme 1) CO,Ar anti -lOb anti -20b anti -15 li I Ph Aldol J2y3 (Hz) ii anti-1Oa 4.3 16.6 +OH anti-9b 2.3 16.7 anti3c (X = Ar)" anti-15 (R = Ara)b 2.4 3.0 16.7 16.6 anti -18b 19 anti-15 (R = Me)b anti-9b (X = OMe) syn-9b(X = OMe) syn-9b(X = SPh) syn-lS(R = Me)b 2.0 1.8 5.6 5.4 3.0 17.9 18.0 14.2 15.2 12.8 iii1 ii e SPh0"""" a Ar = 2,6-dimethylphenyl.See refs. 5 and 8. (which reinforces our explanation of the regioselectivity of ally1 sulphide formation in similar compounds) gives time for the efficient capture of the intermediate 17 by the molecule of water anti -21b a,b; R = ButPh2Si C; R=PhCO syn -22b released in the formation of intermediate 16. Ph E -syn -23b 02Ar,,+"-CO2Ar Scheme 2 Reugenrs: i, LiAlH,; ii, TsOH; iii, RCl, base; iv, NaIO,; v, PhS-, MeOH MeN Me?+ H the ethers 20 could not be determined by coupling constants as anti -1Oc eg., the two diastereotopic protons at C-2 in anti-20b are each triplets showing that J,,, = J2'3syn- However, NOEJ2qJanti.studies allowed correlation of one of these protons to the methyl l6 group and then to the proton at C-4, confirming inversion att C-4 in both isomers of 20b. Experiments in open-chain compounds l2 with a chiral migration origin (C-4) show that? both cyclisations occur with inversion at that centre also. water -anti -12c Ally1 sulphide formation occurred in high yield after chemo-H selective protection of the primary alcohol of the diol 18 either 17 as a t-butyldiphenylsilyl ether 21a,b or a benzoate 21c. We now prefer the benzoate as it is less susceptible to cleavage under the Reduction of any aldol from Table 1 with LiAIH, gave rearrangement conditions.Rearrangement of anti-2la-c gave the corresponding diol 18 (Scheme 2) with no loss of stereo-syn-22 in high yield while syn-21bgave anti-22bunder the same chemistry. Rearrangement in acid gave the spirocyclic ethers 20 conditions. The rearrangement of the svn compound is faster stereospecifically in excellent yield. The nearest analogy is and the product (anti-22b)is not susceptible to epimerisation. Williams' cyclisation l1 (without PhS migration) of some Anti-21, however, must be rearranged in the absence of light tertiary alcohols giving tetrahydrofurans by endo attack on an and oxygen (preferably under argon) to avoid epimerisation of episulphonium ion (cf 18b in Scheme 2). The stereochemistry of syn-22,probably by a 1,3PhS shift.13 J.CHEM. SOC. PERKIN TRANS. 1 1991 Removalof PhS from the Rearrangement Products.-We have already shown14 that P-PhS butanolides, such as 12, give butenolides in high yield on oxidation and thermolysis. The only unusual example from lactones 12 was the amino compound 12c and this indeed gave a poor yield of the sulphoxide by direct oxidation. Fortunately, prior conversion into the hydrochloride allowed clean formation of the sulphoxide 24c and hence the butenolide 2. Williams ' has used reductive removal of PhS from tetrahydrofurans and so syn- or anti-20 are precursors for spiro compounds 26. 0 anti -12c 24c 25c The allyiic sulphides 22 are more interesting, as the corre- sponding sulphoxides give 2,3 sigmatropic rearrangements ' which are stereospecifically suprafacial: syn-22 gives syn-23 and anti-22b gives anti-23b, both with 1,4-related chiral centres.They are also stereoselective: both diastereoisomers are formed with an E double bond. Stork has used similar sulphoxide rearrangements in prostaglandin synthesis,16 and Heathcock '' has used 3,3 sigmatropic rearrangements to translate aldol stereochemistry into 1,4- and 1,5-related chiral centres. We have now extended our work to open-chain compounds.12 The syn and anti products 23b (R = Bu'Ph,Si) are almost identical by 'H and I3C NMR spectroscopy (which at least confirms the E-stereochemistry). The free diols 23b (R = H), made either by desilylation of compound 23b with fluoride or by reduction of the ester llb to the alcohol 22b (R = H) and 2,3 rearrangement, had slightly different 'H NMR spectra, but the 3,5-dinitrobenzoates 27 established conclusively that each isomer was free from the other as, e.g., ~(Bu') = 0.94 (anti) and 1.03 (syn).MeN@ 26c 0 E -syn 27 Experimental 1-Trimethylsiloxycyclohexy1idenemethane.-The silyl enol ether was prepared from cyclohexanecarbaldehyde (10 g, 89 mmol) by the method of Stang et a1.,18and gave the silyl enol ether (14.41 g, 88) as an oil, b.p. 86--87"C/18 mmHg (1it.,l8 453 b.p. 75-76"C/12 mmHg); GH(CDC13) 5.89 (1 H, br s, C==CHOSiMe,), 2.08 (2 H, t, J 5.4 Hz, CH,C=C), 1.84 (2 H, t, J 5.4 Hz, CH,C=C), 1.41-1.30 (6 H, m, CH,,) and 0.06 (9 H, s, SiMe,); v,,,(liquid film) 1680 cm-' (C=C).1-Phenylthiocyclohexanecarbaldehyde 6.-Benzenesulphenyl chloride (21.5 cm', 2.0 mol dm-, in CH,Cl,; 43 mmol) was added slowly to a solution of the above silyl enol ether (8 g, 43 mmol) in dry CH,Cl, (10 cm3) under nitrogen at -78 "C. The mixture was allowed to warm to room temperature and solvent was removed under reduced pressure. Theresidue was distilled to give the aldehyde (9.50 g, 98) as an oil, b.p. 131-132 "(70.2 mmHg; G,(CDCl,) 9.24 (1 H, s, CHO), 7.51-7.24 (5 H, m, SPh) and 1.89-1.25 (10 H, m, CH,Is) lit.," GH(CDC1,) 9.28 (1 H, s, CHO). 4-Methoxy( pheny1thio)methyll- 1 -methylpiperidin-4-01 8c.-Butyllithium (34.7 cm3 of a 1.55 mol dm-, solution in hexane, 53.7 mmol) was slowly added to a solution of methoxymethyl phenyl sulphide4 (7.5 cm3, 51.3 mmol) in dry tetrahydrofuran (THF) (80 cm3) under argon at -30 "C.After 40 min, a solution of 1-methyl-4-piperidone (6.0 cm3, 48.8 mmol) in dry THF (65 cm3) was added.After a further 20 min at -30 "C, the solution was poured into saturated aq. ammonium chloride (100 cm3), basified (NaOH), and extracted with CH,CI, (3 x 120 cm3). The combined extracts were dried (MgSO,) and evaporated. The residue was recrystallised from CH,Cl,-light petroleum (b.p. 60-80 "C) to give the amino alcohol 8c (10.5 g) as needles, m.p. 9697 "C; R, ethyl acetate-methanol-triethylamine (66:33: l) 0.20;v,,,(CHC13)/cm-' 3570 (OH) and 1580 (SPh); GH(CDC13) 7.51-7.47 (2 H, m, Ph), 7.31-7.20 (8 H, m, Ph), 4.46 (1 H, s, CHSPh), 3.41 (3 H, s, OMe), 2.68-2.63 (2 H, m, NCH,), 2.42 (1 H, br s, OH), 2.36-2.24 (2 H, m, NCH,), 2.28 (3 H, s, NMe), 1.99 (1 H, dt, J 13.2 and 4.5 Hz, NCH2CHHaX), 1.92 (1 H, dt, J/Hz: 13.2 and 4.5, NCH,CHH""), 1.70 (1 H, dd, J/Hz: 13.4 and 2.6, NCH2CHHeq) and 1.59 (1 H, dd, J/Hz: 13 and 2.6, NCH,CHHeq); Gc(CDC13) 135.83, 132.76, 129.07, 127.34, 102.89, 72.10, 57.61, 51.21, 50.98, 46.09, 33.23 and 33.06; m/z 267 (14, M'), 252 (55, M -Me), 158 (80, M -SPh), and 70 (100, C,H,N) (Found: C, 62.6; H, 7.85; N, 5.1; S, 12.3; M', 267-1294. C14HZ1N02S requires C, 62.9; H, 7.9; N, 5.2; S, 12.0; M, 267-1294).1-Methyl-4-phenylthiopiperidine-4-carbaldehyde7.-Thionyl chloride (2.5 cm3, 34 mmol) was added to a solution of the alcohol amp; (3.0 g, 11.2 mmol) in CH,CI, (20 cm3) under argon at 0 OC.The solution was stirred for 60 min, poured into water (50 cm3), basified (NaOH), and extracted with CH,Cl, (4 x 50 cm3). The combined extracts were dried (MgSO,), evaporated, and purified by column chromatography on silica gel (250 g), eluting with ethyl acetate-methanol-triethylamine (94: 5: I), to give the aldehyde (2.43 g, 92) as an oil, R,ethyl acetate-methanol-triethylamine (94:5 :1) 0.30; v,,,(CDC14)/cm-' 1710 (GO) and 1580 (SPh); GH(CDC1,) 9.23 (1 H, s, CHO), 7.38-7.24 (5 H, m, Ph), 2.75-2.66 (2 H, m, NCH,eq), 2.24 (3 H, s, NMe), 2.15-2.06 (2 H, m, NCH,ax) and 1.99-1.79 (4 H, m, NCH,CH,); G,(CDCI,) 193.88, 137.00, 129.57, 128.91, 128.56, 57.44, 52.23, 45.93 and 30.14 (Found: Mf -CO, 207.1071.C,,H,,NS requires M -CO, 207.1082); m/z 207 (3, M -SPh) and 83 (100, C,H,N). (2RS,3SR)-2,6-Dimethylphenyl 3-Hydroxj,-2-methyl-3-1-(phenylthio)cyclohexylpropionate, anti-l0b.-A solution of 2,6-dimethylphenyl propionate (0.935 g, 5.25 mmol) in THF (10 cm3) was added dropwise to a solution of lithium diisopropylamide (LDA) (5.5 mmol) in THF (30 cm3) during 15 min at -78 "C under argon. After 10 min the aldehyde 6 (1.1 g, 5 mmol) was added and the mixture was stirred for 5 min 454 before the reaction was quenched with saturated aq. ammonium chloride (2 cm3) at -78 "C. After the mixture had warmed to room temperature, saturated aq. ammonium chloride (100 cm3) was added, the organic phase was separated, and the aqueous layer was extracted with diethyl ether (2 x 50 cm').The combined organic fractions were washed with brine (50 cm3), dried (MgSO,), and evaporated under reduced pressure. The residue was recrystallised from diethyl ether-hexane to give the hydroxy ester 10b (1.68 g, 84) as prisms, m.p. 101-102deg;C; R,(CH2C12) 0.37; v,,,(Nujol)/cm-' 3450 (sharp, OH) and 1705 (GO); GH(CDC1,) 7.53-7.31 (5 H, m, SPh), 7.06 (3 H, s, OAr), 4.32 (1 H, d, J8.3 Hz, CHOH), 3.81 (1 H, dq, J/Hz 7.4 and 2.3, CHMe), 3.38 (1 H, dd, J/Hz 8.3 and 2.3, CHOH), 2.19 (6 H, s, ArMe,), 1.99-1.52 (10 H, m, C6H10) and 1.58 (3 H, d, J7.4 Hz, Me); G,-(CDCl,) 175.06, 147.78, 137.09, 130.86, 130.26, 128.93, 128.80, 126.01, 79.33, 60.10, 38.15, 30.70, 25.83, 21.83, 21.76, 18.82 and 16.70 (Found: M+ -PhS, 289.1802. C18H2503 requires M -C6H,S, 289.1798 ;m/z 289 (3, M+ -PhS), 149 (35, Me2C6H3CO2), and 121 (100, Me,C6H,CO) (Found: C, 72.6; H, 7.5; S, 8.0.C24H3003S requires C, 72.4; H, 7.5; S, 8.0). (2RSY3SR)-2,6-Dimethylphenyl 3-Hydroxy-2-methyl-3- 1- (phenylthio)cyclopentylpropionate, anti-1Oa.-In the same way, 2,6-dimethylphenyl propionate (1.0 g) and the aldehyde 5 (1.11 g) gave a 96:4 mixture of diasteroisomers, crystallised from hexane to give the ester 10a (1.46 g, 70) as cubes, m.p. 112-1 14 "C; R,CH,Cl,-hexane (9 :l) 0.5 1; v,,,(Nujol)/cm-' 3650-3350 (OH) and 1720 (C=O); amp;(CDCl,) 7.59-755 (2 H, dd, ArH, o to S), 7.37-7.30 (3 H, m, ArH), 7.06 (3 H, s, ArH), 3.80-3.72 (1 H, br, OH), 3.75 (1 H, m, CHCO,Ar), 3.68 (1 H, d, J 4.3 Hz, CHOH), 2.20 (6 H, s, ArMe), 2.00-1.70 (8 H, m, CH,,) and 1.51 (3 H, d, J7.2 Hz, Me); Gc(CDC13) 174.5, 147.8, 136.7, 132.4, 130.3, 128.8, 128.7, 125.9, 79.5,66.7,41.4, 35.4, 34.7, 24.0, 23.9, 17.8 and 16.6 (Found: M+, 384.1747.C23H2803S requires M, 384.1759); m/z 384 (4, M+), 263 (100, M -Me,C,H,O), 177 (48, Me2C6H3Co2CHMe), 122 (45, Me2C6H,0H) and 97 (52, CSH8CHO). (2RS,3SR)-2,6-Dimethylphenyl 3-Hydroxy-2-methyl-3-4'-(1 '-methyl-4'-( phenylthio)piperidyl)propionate, anti-lOc-In the same way, 2,6-dimethylphenyl propionate (2.0 g, 11.2 mmol) and the aldehyde 7 (2.5 g, 10.6 mmol) gave the ester (3.16 g, 72), purified by column chromatography on silica gel (200 g) eluting with ethyl acetate-methanol-triethylamine (94:5: l), as cubes, m.p.115-1 16 "C; amp;ethyl acetate-methanol- triethylamine (94: 5 :l) 0.21; v,,,(CHC1,)/cm-' 3460 (OH), 1725 (C-) and 1580 (SPh); GH(CDC13) 7.53-7.50 (5 H, m, Ph), 7.05(3 H,s,OAr),4.28 (1 H,d, J8.1 Hz,OH),3.78 (1 H,dq, J/Hz 7.3 and 2.6, CHMe), 3.48-3.45 (1 H, dd, J/Hz 7.8 and 2.4, CHOH), 2.73-2.59 (4 H, m, NCH,), 2.34 (3 H, s, NMe) and 2.31-2.04 (2H,m,NCH,CH,);Gc(CDC1,) 174.61,147.75,137.24, 130.21, 129.10, 128.91, 128.74, 125.99, 79.13, 57.33, 51.28, 51.20, 46.20, 38.45, 30.29, 18.73 and 16.69 (Found: M+ -PhS, 304.1890. C18H26NO3 requires M -C,H,S, 304.1913); m/Z 304 (loo, M -PhS and Me,C6H30H) and 122 (61, Me,C6H30H) (Found: C, 69.9; H, 7.8; N, 3.4; S, 8.0. C2,H3,N03S requires C, 69.7; H, 7.55; N, 3.4; S, 7.75).Methyl 3-Hydroxy-2-methyl-3- 1-(phenylthio)cyclohexyl-propionate 9b (X = Me).-A solution of methyl propionate (1.58 g, 18 mmol) in THF (20 cm3) was added dropwise to a solution of LDA (16.5 mmol) in THF (50 cm3) at -78 OC under argon. After 20 min, a solution of the aldehyde 6 (3.3 g, 15 mmol) in THF (2 cm3) was added, and the mixture was stirred for 2 h at -78 "C and then quenched with aq. ammonium chloride (10 cm3) at -78 "C. Water (10 cm3) was added, the organic layer was separated, and the aqueous layer was extracted with diethyl J. CHEM. SOC. PERKIN TRANS. 1 1991 ether (2 x 50 cm3). The combined organic extracts were dried (MgSO,), evaporated under reduced pressure, and purified by column chromatography eluting with CH2C12 to give the aldol syn-9b (X = OMe) (1.87 g, 50) as an oil, R,(CH,Cl,) 0.2; v,,,(film)/cm-' 3450 (OH), 1710 (C=O) and 1580 (SPh); G,(CDC13) 7.53-7.25 (5 H, m, SPh), 3.77 (1 H, dd, J344.3, J32 5.6 Hz, CH30H), 3.61 (3 H, s, OMe), 2.99 (1 H, dq, J7.0, J23 5.6 Hz, CH2Me), 2.92 (1 H, d, J4,4.2 Hz, CH30H), 1.91-1.21 (10 H, m, C6H10) and 1.27 (3 H, d, J 7.0 Hz, CH2Me); GC(CDCl3) 176.79, 137.09, 130.49, 129.01, 128.83, 74.74, 61.41, 51.73, 40.58, 31.35, 30.74, 25.93, 21.96 and 14.15 (Found: M+, 308.1469. C1,H2,0,S requires M, 308.1445); m/z 308 (50/,, M'), 221 (14, M -C3H702), 199 (13, M -PhS), 191 (64, M -CsH,03), 111 (73), 110 (55, PhSH), and 81 (100); and the (2RS,3SR)-aldol anti-9b (X = OMe) (1.02 g, 27) as plates, m.p. 57-59 OC (from diethyl ether-hexane); R,(CH2C12) 0.28; v,,,(film)/cm-' 3450 (OH), 1710 (C=O) and 1580 (SPh); GH(CDC13) 7.48-7.25 (5 H, m, SPh), 4.24 (1 H, d, J438.7, CH20H), 3.71 (3 H, s, OMe), 3.50 (1 H, dq, J,, 1.8, J 7.3 Hz, CH,Me), 3.27 (1 H, dd, J32 1.8, J348.7 Hz, CH30H), 2.10-1.55 (10 H, m, C6HlO) and 1.33 (3 H, d, J 73.Hz, CH2Me); GC(CDCl3) 178.06, 137.05, 131.16, 128.77, 128.70, 79.67, 59.55, 51.89, 37.38, 31.18, 30.22, 25.79, 22.00, 21.80 and 17.97 (Found: M+, 308.1461. C17H2,03S requires M, 308.1446); m/z 308 (4, M+), 191 (100, M -C,H,O3), 111 (58), 110 (77, PhSH) and 81 (68). (2RS,3RS)-3- Hydroxy-2-methyl-3- 1 -(pheny1thio)cyclo-hexylpropionic Acid, syn-l3b.-Lithium hydroxide mono-hydrate (200 mg, 4.2 mmol) was added to a solution of the ester syn-9b (X = OMe) (170 mg, 0.55 mmol) in methanol (3 cm3)- water (1 cm3) and the mixture was stirred for 24 h.Aq. sodium carbonate (3 cm3), aq. sodium hydroxide (1 cm3), and water (10 cm3) were added and the solution was extracted with chloroform (5 cm3). The aqueous layer was acidified with hydrochloric acid and ice and extracted with chloroform (3 x 5 cm3), dried (MgSO,), and evaporated under reduced pressure. The residue was recrystallised from chloroform-hexane to give the acid 13b (152 mg, 94) as needles, m.p. 147-148deg;C; R,MeOH-CH,Cl, (1 :9) 0.27; v,,,(Nujol)/cm-' 3350 (OH, sharp), 3000 (C0,H) and 1695 (C=O); GH(CDCl3) 7.53-7.27 (5 H, m, Ph), 3.80 (1 H, d, J 4.8 Hz, CHOH), 3.02 (1 H, dq, J/Hz 4.8 and 7.2 CHMe), 1.95-1.20 (10 H, m, C6H10) and 1.32 (3 H, d, J 7.2 Hz, CHMe) (Found: M+, 294.1267.C16H2,03S requires M, 294.1284); m/z 294 (5, M+), 191 (45, C6HI0SPh), 185 (4, M -SPh), 110 (75, PhSH) and 81 (100, C6H,). Rearrangement of (2RS,3SR)-2,6-Dimethylphenyl3-Hydroxy-2-methyl-3-l-(phenylthio)cyclohexylpropionate, anti-1Ob.-The ester anti-lob (398 mg, 1.0 mmol) was refluxed in benzene in a foil-wrapped flask (5 cm3) under argon, a refluxing solution (2 cm3) of TsOH in dry benzene (100 mg in 10 cm3) was added, and the mixture was refluxed for a further 10 min. The solution was cooled in ice, passed through a short silica column with CH,C12 as eluant, and the solvents were removed under reduced pressure. Purification by column chromatography on silica gel and elution with CH,C12 gave (2RS,3SR)-2,6-dimethylphenyl 3-(cyclohex- 1 -enyl)-2-methyl-3-( pheny1thio)- propionate, syn-llb (242 mg, 63) as an oil, R,(CH,Cl,) 0.70; v,,,(film)/cm-' 1750 (C=O), 1650 (C=C) and 1580 (SPh); G,(CDCl,) 7.42-7.24 (5 H, m, SPh), 7.03 (3 H, s, OAr), 5.28 (1 H, br s, CH=C), 3.77 (1 H, d, J 11.1 Hz, CHSPh), 3.10 (1 H, dq, J/Hz 11.1 and 6.9, CHMe), 2.27-2.24 (4 H, m), 2.12 (6 H, s, ArMe,), 1.861.46 (4 H, m, CH2CH2), and 1.66 (3 H, d, J 6.9 Hz, CHMe) (Found: M+, 380.1793.C24H2802S requires M, 380.1803); m/z 380 (0.6, M+), 271 (2.5, M -PhS), and 121 (100, C6H ,Me20); and (3RS,4SR)-3-methyl-4-phenylthio-1-oxaspiro3,4decan-2-one,anti-1 2b (90 mg, 32) as needles, J. CHEM. SOC. PERKIN TRANS. 1 1991 m.p.105-106 "C (from diethyl ether-hexane); Rf(CH,C1,) 0.38; vmax(Nujol)/cm-' 1770 (W)and 1580 (SPh); G,(CDCI,) 7.51-7.25 (5 H, m, SPh), 3.11 (1 H, d, J 12.2 Hz, CHSPh), 2.68 (1 H, dq, J/Hz 12.2 and 7.0, CHMe), 1.91-1.14 (10 H, m, CsHlo), and 1.28(3 H, d, J7.0 Hz, CHMe); Sc(CDC13) 176.16,134.17, 132.83, 129.33, 128.11, 86.67, 62.23, 41.55, 36.27, 31.73, 25.11, 22.42, 21.49 and 13.82 (Found: M+, 276.1 193. C16H,002S requires M, 276.1179); m/z 276 (5, M+), 150 (100, M -C~H~OCO~),135 (50),110 (20, HSPh) and 69 (52). (3RS,4RS)-3-Methyl-4-phenylthio-1 -oxaspiro4.5decan-2- one, syn-l2b.--In the same way, the acid syn-13b (42 mg, 0.14 mmol) with catalytic TsOH (5 mg) gave the lactone 12b (34 mg, 86) as an oil, Rf(CH,C12) 0.5; v,,,(film)/cm-' 1760 (lactone) and 1580 (SPh); S,(CDCI,) 7.50-7.19 (5 H, m, SPh), 3.80 (1 H, d, J8.9 Hz, CHSPh), 3.10 (1 H, dq, J/Hz 8.9 and 7.6, CHMe), 1.93-1.20 (10 H, m, C6HI0) and 1.38 (3 H, d, J 7.6 Hz, CHMe); Gc(CDC13) 177.31, 135.34, 130.77, 130.66, 127.14, 87.10, 57.95, 39.36, 36.89, 34.23, 24.89, 22.69, 22.03 and 13.69 (Found: M+, 276.1 180.C, 6H2002S requires M, 276.1 184); m/z 276 (25, M+)and 150 (100, M -C6HlOCO2). (3RS,4SR)-3-Methyl-4-(phenylthio)-1 -oxaspiro4.4nonan-2- one, anti-l2a.--Aq. sodium hydroxide (30; 0.4 cm3) was added to a solution of the ester anti-l0a (205 mg) in methanol (6 cm3) and the solution was stirred at room temperature for 2.25 h, then poured into brine (25 cm3), acidified with sulphuric acid (1.5 mol dm-3), and extracted with ethyl acetate (3 x 15 cm3).The combined extracts were dried (MgS04), and evaporated under reduced pressure. The residue was dissolved in benzene (1 cm3) and TsOH (10 mg) was added. The solution was heated under reflux for 5 min, allowed to cool to room temperature, and filtered through silica gel (elution with CH,CI,). The filtrate was evaporated under reduced pressure to give the lactone 12a (15 mg, 13) as an oil, R,hexane-diethyl ether (2: l) 0.37; v,,,(film)/cm-' 1765 (C=O); S,(CDCl,) 7.50-7.45 (5 H, m, Ph), 3.42 (1 H, d, J 12.2 Hz, CHSPh), 2.63 (1 H, dq, J/Hz 12.2 and 7.0, CHCO,R), 2.27-1.53 (8 H, m, CH,I4) and 1.28 (3 H, d, J 7.0 Hz, Me) (Found: M+, 262.1031. C1,Hl80,S requires M, 262.1028); m/z 262 (22, M+) and 150 (100, PhSCHCHMe).(3RS,4SR)-3,8-Dimethyl-4-phenylthio-8-aza-1 -oxaspiro4.5- decan-2-one, anti-l2c.-The ester anti-l0c (0.2 g, 0.48 mmol) and TsOH (0.65 g, 3.4 mmol) were heated in CH,C12 (1.5 cm3) under reflux under argon for 3 h. CH2Cl, (10 cm3) and water (10 cm3) were added, and the solution was basified (NaOH) and extracted with CH2C12 (3 x 15 cm3). The combined extracts were dried (Na2S04) and evaporated. The residue was re-crystallised from CH2C1,-hexane to give the spirolactone 12c (0.113 g, 80) as needles, m.p. 116-118 OC; R,ethyl acetate-methanol-triethylamine (74 :25 :l) 0.36; v,,,(CHCIJ)/cm-' 1760 (C=O) and 1580 (SPh); G,(CDCl,) 7.5 1-7.47 (2 H, m, Ph), 7.36-7.28 (3 H, m, Ph), 3.14 (1 H, d, J 12.4 Hz, CHSPh), 2.82- 2.59 (3 H, m, CHMe and NCH,), 2.41-2.32 (3 H, m, NCH, and NCH,CH), 2.30 (3 H, s, NMe), 1.96 (1 H, dt, J/Hz 13.2 and 5.0, NCH,CHHax), 1.64 (1 H, m, NCH2CHHeq), 1.50 (1 H, dd, J/Hz 13.8 and 2.6, NCH2CHHeq) and 1.33 (3 H, d, J 7.0 Hz, CHMe); G,(CDC13) 175.85, 133.78, 129.37, 128.19, 84.22, 61.30, 51.61, 50.77, 46.05, 41.18, 35.51, 31.36 and 13.62; m/z 291 (56, M), 181 (40, M -PhS), and 70 (100, C4H8N) (Found: C, 66.2; H, 7.3; N, 4.95; S, 10.9; M+, 291.1284.C,,H21NO,S requires C, 65.95; H, 7.25; N, 4.8; S, 11.0; My 291.1293). (1 RS,2RS)-2-Methyl- 1 -1-(phenylthio)cyclohexylpropane-1,3-diol, anti-lsb.-Lithium aluminium hydride (304 mg, 8.0 mmol) was added to a solution of the ester anti-lob (1.707 g, * Revealed after D,O shake.455 4.27 mmol) in dry diethyl ether (30 cm3) at 0 "C. After 4 h, the mixture was quenched with ice, diluted with aq. sodium hydroxide (20 cm3) and aq. sodium potassium tartrate (200 cm3), and extracted with diethyl ether (3 x 100 cm3). The combined extracts were dried (MgS04), evaporated under reduced pressure, and purified by column chromatography, eluting with methanol-CH,Cl, (1 :25). Recrystallisation from ethyl acetate gave the diol 18b (1.064 g, 89) as needles, m.p. 120.5-121 "C; R,methanol-CH,Cl, (1 :25) 0.4; v,,,(Nujol)/ cm-' 3360 (sharp, OH) and 3300 br (OH); G,(CDCl,) 7.5C7.25 (5 H, m, SPh), 3.68 * (1 H, dd, JAB 11.2,JAX 3.9 Hz, CHAHBOH), 3.63* (1 H, dd, JBA 11.2, JBx 6.3 Hz, CHAHBOH), 3.21 * (1 H, d, J 4.8 Hz, CHOH), 2.041.17 (1 1 H, m, C6HIo and CHxMe), and 0.87 (3 H, d, J 7.0 Hz, CHxMe); G,(CDC13) 137.09, 129.13, 128.90,79.35,66.59,63.05,34.71,30.38,29.21,26.20, 21.96,21.69 and 18.45 (Found: M+ -C4Hg02,191.0883.C,2Hl,S requires M -C4Hg02, 191.0894); m/z 191 57, M -CH(0H)CH-(Me)CH20H, 110 (67, PhSH) and 82 (100). (2RS,3RS)-2-Methyl- 1 -1-(phenylthio)cyclohexyl propane- 1,3-diol, syn-l8b.-In the same way, the esster syn-9b (X = OMe) (1.15 g, 3.7 mmol) and LiAlH4 (0.19 g, 4.9 mmol) gave, after recrystallisation from diethyl ether-hexane, the diol 18b (0.864 g, 83) as needles, m.p. 79.5-80 "C; R,methanol- CH,C1, (1 :20) 0.27; v,,,(Nujol)/cm-' 3400br (OH) and 1580 (SPh); GH(CDC1,) 7.51-7.25 (5 H, m, SPh), 3.60 (1 H, dd, JAB 10.4, JAX 4.6 Hz, CHAHBOH), 3.55 (1 H, d, J 5.4 Hz, CHOH), 3.53 (1 H, dd, JBA 10.4,JBX 5.4 Hz, CHAHBOH), 2.1-1.19 (1 1 H, m, C6H10 and CHxMe) and 1.05 (3 H, d, J 7.0 Hz, CHxMe); Gc(CDC1,) 137.09, 130.49, 128.96, 128.81, 75.33, 69.33, 62.28, 35.26,31.11,30.94,26.10,22.08,21.89and 11.79 (Found: M+ -C4H902, 191.0890. C12HlSS requires M -C4H902, 191.0894); m/z 191 (45, M -C4Hg02, 191.0890. 191.0894); m/z 191 (45, M -C,Hg02), 171 (20, M -SPh), 125 (26), 110 (74, PhSH) and 8 1 (100, C6H9).(1 RS,2RS)-2-Methyl- 1 -1-(phenylthio)cyclopentylpropane-1,3-diol anti-l8a.-In the same way, the ester anti-l0a (694 mg) gave a pale yellow solid (473 mg). Crystallisation from hexane- diethyl ether gave the alcohol 18a (320 mg, 85) as needles, m.p. 6668 "C (Found: C, 67.4; H, 8.5.CI5H2,O2S requires C, 67.6; H, 8.3); R,CH2C1,-MeOH (95 :5) 0.39; v,,,(Nujol)/cm-' 3400 (OH); S,(CDC13) 7.52-7.29 (5 H, m, Ph), 3.79-3.63 (2 H, ABXsystem, J/Hz 11.1, 3.5 and 6.4,CH20H), 3.49 (1 H,d, J5.5 Hz, CHOH), 3.18-3.15 (1 H, br, OH), 2.09-1.55 (9 H, m, CH,I4 and CHMe) and 0.90 (3 H, d, J 7.0 Hz, Me). (1 RS,2RS)-ZMethyl- 1 -1 -methyl-4-( pheny1thio)piperidin-4- ylpropane-1,3-diol, anti-lamp;.-In the same way, the ester anti-l0c (4.1 g, 10 mmol) and lithium aluminium hydride (0.78 g, 20.5 mmol) gave the diol 18c (2.49 g, 85), recrystallised from ethyl acetate as cubes, m.p. 133-135 OC; R,ethyl acetate-methanol-triethylamine (75 :25 :l) 0.20; v,,,(CDCl,)/cm-' 3420 (OH) and 1580 (SPh); 6,(CDC13) 7.Xk7.45 (2 H, m, Ph), 7.40-7.25 (3 H, m, Ph), 3.98 (1 H, br s, OH), 3.76 (1 H, dd, J/Hz 11.0 and 3.4, CHAHBOH), 3.62 (1 H, dd, J/Hz 11.1 and 6.1, CHAHBOH), 3.30 (1 H, d, J 4.6 Hz, CHOH), 2.742.61 (3 H, m, NCH2eq and NCHaX), 2.53 (1 H, dt, J/Hz 2.8 and 11.6, NCHaX), 2.32 (3 H, s, NMe), 2.162.02 (2 H, m, NCH,CH,""), 1.87-1.75 (1 H, m, CHMe), 1.61 (1 H, dd, J/Hz 14.5 and 2.6, NCH2CHeq), 1.33 (1 H, dd, J/Hz 14.2 and 2.6, NCH2CHeq) and 0.92 (3 H, d, J 7.1 Hz, CHMe); Sc(CDCI3) 137.33, 129.42, 129.30, 129.01, 79.33, 66.37, 59.78, 51.46, 51.14, 46.25, 34.49, 29.65, 29.09 and 18.45 (Found: M+ -C3H,0, 236.1117.Cl3HI8NOS requires M -C3H70, 236.1110); m/z 236 (l, M+ -C3H70), 186 (100, M -PhS), and 96 (50, C,H,oN) (Found: C, 64.7; H, 8.65; N, 4.7; S, 10.7. CI6H2,NO,S requires C, 65.0; H, 8.55; N, 4.7; S, 10.85).456 (3RS,4SR)-3-Methyf-4-phenyfthio-1 -oxaspiro4. Sldecane, anti-20b.-The diol anti-18b (71 mg, 0.25 mmol) was refluxed in dry benzene (2 cm3) and TsOH (5 mg, 0.3 mmol) was added. After 5 min, the solution was cooled in ice, passed through a short silica column, eluting with CH,Cl,, and the eluate was evaporated under reduced pressure to give the title tetra-hydrofuran 20b (65 mg, 98) as an oil, Rf(CH2C1,) 0.4; v,,,(film)/cm-' 2950-2850 (C-H); 6,(CDC13) 7.47-7.18 (5 H, m, SPh), 3.97 (1 H, t, J8.3 Hz, CHAHBOR), 3.35 (1 H, t, J8.3 Hz, CHAHBOR), 2.79 (1 H, d, J 10.4 Hz, CHSPh), 2.29 (1 H, sym m, CHMe), 1.65-1.41 (10 H, m, C6H10) and 1.09 (3 H, d, J 6.6 Hz, CHMe); GC(CDCl3) 136.39, 131.68, 128.91, 126.84, 84.01, 71.12, 64.99,40.78, 36.57, 31.60, 25.66, 23.00, 21.87 and 16.70 (Found: M+, 262.1373.C16H2,0S requires M, 262.1386); m/z 262 (lo, M'), 164 (100, M -C6HlOO), 149 (28), 110(64, PhSH) and 55 (73). (3 R S,4R S)- 3-Methy f-4-pheny fthio-1-oxaspiro4.51decane, syn-20b.--In the same way, the diol syn-18b (54 mg, 0.20 mmol) gave the (3RS,4RS)-tetrahydrofuran20b (47 mg, 92) as an oil, R,(CH,Cl,) 0.55; v,,,(film)/cm-' 1530 (SPh); G,(CDCl,) 7.38-7.13 (5 H, m, Ph), 4.0 (1 H, dd, JAX 7.1, JAB 8.8 Hz, CHAHBOR), 3.51 (1 H, dd, JBX 6.2, JBA 8.8 Hz, CHAHBOR), 3.44 (1 H, d, J8.2 Hz, CHSPh), 2.67 (1 H, sym m, CHxMe), 1.76-1.15 (10 H, m, C6H10) and 1.10 (3 H, d, J7.2 Hz, CH,Me); Gc(CDC13) 137.41, 129.69, 128.94, 126.00, 83.87, 71.78, 60.67, 37.18, 37.11, 32.76, 25.44,23.31,22.32 and 15.63 (Found: M', 262.1400.C16H,,0S requires M, 262.1391); mjz 262 (6, M+), 164 (58, M -C6H100), 149 (15), 110 (40, PtSH) and 55 (100). (3RS,4SR)-3-Methyf-4-phenyfthio-1 -oxaspiro4,4nonane, anti-20a.-In the same way, the alcohol anti-17a (55 mg) gave the tetrahydrofuran 20a (49 mg, 96) as an oil, R,hexane- diethyl ether (2: l) 0.50; 6,(CDCI,) 7.5G7.20 (5 H, m, Ph), 3.95 (1 H, dd, J/Hz 8.4 and 8.4, CHAHBO, trans to Me), 3.36 (1 H, dd, J/Hz 8.4 and 8.4, CHAHB, cis to Me), 3.09 (1 H, d, J 10.1 Hz, CHSPh), 2.32-2.19 (1 H, m, CHMe), 1.95-1.82 (8 H, m, CH,,) and 1.1 1 (3 H, d, J 6.6 Hz, Me); NOE irradiation at 6 3.95 (enhancement at 6 3.36 and 2.25), 3.36 (3.95, 2.25 and 1.11), 3.09 (7.5amp;7.20), and 2.25 (3.36 and 1.11) (Found: M', 248.1230.C15HzoOS requires M, 248.1235); m/z248 (32, M+), 164 (100, M -C,H,O) and 110 (50,PhSH). (3RS74SR)-3,8-Dimethyl-4-phenyfthio-l-azu-l-oxaspiro4,5-decane, anti-2Oc.-TsOH (2 g, 10mmol) was added to a solution of the diol anti-18c (1.0 g, 3.4 mmol) in benzene (5 cm3) in a foil-wrapped flask under argon. The solution was refluxed for 20 min, CH,Cl, (30 cm3) and water (20 cm3) were added, the solution was basified (NaOH), and the organic layer was separated. The aqueous layer was extracted with CH,Cl, (3 x 40 ml). The combined organic phases were dried (Na,SO,), evaporated, and purified by column chromato-graphy on silica gel (95 g), eluting with CH,Cl,-methanol- triethylamine (92: 7 : 1) to give the tetrahydrofuran 20c (0.8 g, 85) as an oil, R,CH,Cl,-methanol-triethylamine (89: 10: l) 0.37; v,,,(CHC13)/cm-1 1580 (phS); 6,(CDC13) 7.467.41 (2 H, m, Ph), 7.29-7.16 (3 H, m, Ph), 3.98 (1 H, t, J 8.3 Hz, CHAHBO, trans to Me), 3.36 (1 H, t, J 8.7 Hz, CHAHBO, cis to Me), 2.82 (1 H, d, J 10.6 Hz, CHSPh), 2.73-2.59 (2 H, m, NCH,), 2.3G2.16 (3 H, m, NCH, and CHMe), 2.25 (3 H, s, NMe), 1.99 (1 H, dt, J/Hz 4.3 and 13.0, NCH,CH""), 1.79 (1 H, dt, J/Hz: 4.7 and 13.0, NCH,CH""), 1.53 (1 H, ddd, J/Hz 2.7, 5.4 and 13.3, NCH2CHeq), 1.40 (1 H, ddd, J/Hz 2.7, 5.4 and 13.3, NCH2CHeq) and 1.14 (3 H, d, J 6.6 Hz, CHMe); G,(CDCl,) 135.93, 131.76, 128.97, 126.96, 81.48, 71.00, 64.11, 52.30, 51.43, 46.16, 40.31, 35.71, 31.31, 29.66 and 16.39 (Found: M', 277.1419.C16H,3NOS requires M, 277.1500); m/z 277 (18, M'), 168 (88, M+ -PhS) and 70 (100, C,H,N). J. CHEM. SOC. PERKIN TRANS. 1 1991 (1RS,2RS)-3-(t-Butyfdiphenyfsifoxy)-2-methyf-1-1-(phenyf-thio)cycfohexyfpropan-1-01, anti-21b (R = Bu'Ph,Si).-t-Butyldiphenylsilyl chloride (837 mg, 3.04 mmol) was added to a solution of the diol anti-18b (775 mg, 2.77 mmol) and imidazole (414 mg, 6.09 mmol) in dry dimethylformamide (15 cm3) under nitrogen at room temperature. After 24 h, DMF was evaporated under reduced pressure, the residue was taken up in CH,Cl, (50 cm3), and the solution was washed with water (100 cm3). The aqueous layer was extracted with CH,Cl, (2 x 30 cm3) and the combined organic phases were dried (MgSO,), evaporated under reduced pressure, and purified by column chromatography on silica gel, eluting with CH,Cl, to give the sifyf ether (1.42 g, 99) as prisms, m.p.9G91 "C (from hexane) (Found: C, 73.9; H, 8.0; S, 6.4. C3,H,,02SSi requires C, 74.1; H, 8.1; S, 6.2); R,(CH,C12) 0.52; v,,,,(Nujol)/cm-' 3450 (OH); G,(CDCl,) 7.76-7.25 (1 5 H, m, Ph), 3.92 (1 H, dd, JAB 10.2, JAX 5.4 HZ, CHAHBOSi), 3.77 (1 H, dd, JBA 10.2, JBX 4.1 Hz, CHAHBOSi), 3.34 (I H, d, J 3.3 HZ, CHOH), 2.0 (1 H, sym m, CHxMe), 1.87-1.16 (10 H, m, C6Hlo), 1.11 (3 H, d, J 7.1 Hz, CHxMe) and 1.05 (9 H, s, But); 6,(CDC13) 136.92,135.61,135.57, 133.26, 131.10, 129.62, 129.60, 128.48, 127.58, 79.34,67.11,61.39, 35.50, 30.72, 26.87, 25.85, 21.91, 28.82, 12.12 and 18.91 Found: M+ -(PhSH + But), 351.1778.C2,H2,02Si requires M -C10H15S, 351.17741; m/z 351 25, M -(PhSH + But), 199 (100, Ph,SiOH), 135 (52) and 110 (32, PhSH). (1RS,2SR)-3-(t-Butyfdiphenyfsilo.xy)-2-methyl-1-1-(phenyf-thio)cycfohexyfpropan-1-of,syn-2lb.-In the same way, the (1RS72SR)-diol syn-l8b (0.8 g, 2.86 mmol) gave the (1RS,2SR)-sifyf ether 21b (1.39 g, 94) as an oil, Rf(CH,C12) 0.71; v,,,(fi~m)/cm-' 3450 (OH) and 1580 (SPh); 6,(CDCl,) 7.63-7.25 (15 H, m, Ph), 3.68 (1 H, br s, OH), 3.48 (1 H, dd, J,amp;B 10.8, JAX 7.2 HZ, CHAHBOSi), 3.51 (1 H, dd, JBA 10.8, JBX 5.2 HZ, CHAHBOSi), 3.1 1 (I H, d, J 2.4 Hi!, CHOH), 2.21-1.1 (I 1 H, m, C6HIo and CHMe), 1.00 (3 H, d, J 6.9 Hz, CHxMe) and 0.94 (9 H, s, But); GC(CDCl3) 137.08, 135.60, 135.50, 133.65, 133.47, 130.58, 129.59, 129.55, 128.76, 127.61, 73.38, 69.10, 62.48, 35.52, 31.08, 30.82, 26.81, 26.13, 22.07, 21.97, 19.1 1 and 11.99 Found: M+ -(But + PhSH), 351.1784.Cz2H2,O2Si requires M -ClOHl,S, 351.17801; m/z 351 loo/,, M -(Bu' + PhSH), 199 (100, Ph,SiOH), 125 (64) and 110 (48, PhSH). (1 RS72RS)-3-(1-Butyldiphenyfsifo.xy)-2-methl,f-1-1 -(phenyf-thio)cycfopentylpropan-1-of,anti-2la.--In the same way, the diol anti-18a (210 mg) gave the sifyfether (332 mg, 83) as an oil, R,CH,Cl,-hexane (1 : l) 0.45; v,,,(film)/cm-' 3475 (OH); GH(CDCl3) 7.69-7.25 (15 H, m, Ph), 3.97 (1 H, dd, J/Hz 4.0 and 10.3, CHAH,OSi), 3.72 (1 H, dd, J/Hz 4.6 and 10.3, CHAHBOSi), 3.57 (1 H, t, J 2 HZ, CHOH), 2.58-2.42 (1 H, m, CHMe), 1.87-1.55 (8 H, m, CH,,), 1.09 (3 H, d, J 7.2 Hz, Me) and 1.06 (9 H, s, Bu') (Found: M -But, 447.1801.C2,H3,0SSi requires m/z,447.1814); mi; 447 (5, M -Bu'), 227 100, C,H,CH(OH)CHMeCH,OSiPh, and 249 (38, M -Ph,Bu'SiO). ( 1RS,2RS)-3-(t-Butyfdiphenyfsifo.xy)-2-methyf-1-(1-methyl-4-phenyfthiopiperidin-4-yl)propan-l-ol,anti-2lc (R = SiPh,Bu'). -In the same way, the diol anti-18c gave the sifyf ether (74 mg, 82), recrystallised from CH,CI,-light petroleum (b.p. 60- 80 "C), as needles, m.p. 91-93 "C; amp;ethyl acetate-methanol-triethylamine (74: 25: l) 0.3 1; v,,,(CDCl,)/cm-' 3430 (OH) and 1580 (SPh); G,(CDCI,) 7.7s7.65 (4 H, m, Ph), 7.54-7.20 (2 H, m, Ph), 7.43-7.25 (9 H, m, Ph), 4.02 (1 H, d, J 4.7 Hz, OH), 3.96 (1 H, dd, J/Hz 10.3 and 4.5, CHAHBOSi), 3.44 (1 H, t, J 4.1 Hz, CHOH), 2.62-2.57 (4 H, m, NCH2), 2.38-2.35 (1 H, m, NCH2CHHaX),2.32 (3 H, s, NMe), 2.1 8-1.95 (2 H, m, CHMe and NCH2CHaX), 1.10(3 H,d, J7.1 1.57-1.48 (2 H, m, NCH2CHZeq), Hz, CHMe) and 1.05 (9 H, s, CMe,); Gc(CDC13) 137.20, 135.72, J.CHEM. SOC. PERKIN TRANS. 1 1991 135.66, 132.92, 132.87, 130.73, 129.77, 128.70, 127.71, 80.04, 67.48, 58.04, 51.49, 51.36,46.27, 35.16, 30.62, 30.43, 26.86, 19.16 and 18.77 (Found: M' -C3H9, 476.2103. C28H34N02SSi requires M -C4H9, 476.2079); m/z 476 (14, M+ -C4H9), 424 (100, M+ -PhS) and 366 33, M+ -(PhSH + C,H,) (Found: C, 71.7; H, 8.25; N, 2.7; S, 6.1. C32H43N02SSi requires C, 72.0; H, 8.1; N, 2.6; S, 6.0). (2RS,3RS)-3- Hydroxy-2-methyl-3- 1 '-methyl-4'-(phenyl- thio)-piperidin-4'-ylpropylBenzoate, anti-2lc.-A solution of the diol anti-18c (30 mg, 0.1 mmol) and benzoic anhydride (50 mg, 0.22 mmol) in CH,CI, (1.0 cm3) was stirred at room temperature under argon for four days.Water (10 cm3) and CH2Cl, (15 cm3) were added, and the solution was neutralised with NaOH (3 cm3; 0.1 mol dm-3) and extracted with CH,CI, (3 x 20 cm3). The combined extracts were dried (Na,SO,), evaporated, and purified by column chromatography on silica gel (5 g), eluting with CH,Cl,-methanol-triethylamine (90:9: 1) to give the ester 21c (39 mg, 96) as an oil, R,CH,C12- methanol-triethylamine (87 : 12: l) 0.39, v,,,(CHCl,)/cm-' 3300 (OH), 1700 (C=O), 1600 (Ph) and 1580 (Ph); GH(CDC13) 8.04-8.00 (2 H, m, Ph), 7.55-7.29 (8 H, m, Ph), 4.63 (1 H, dd, J/Hz 11.1 and 4.0, CHAHBO), 4.29 (1 H, dd, J/Hz 11.1 and 7.9, CHAHBO), 3.37 (1 H, d, J 3.6 Hz, CHOH), 2.87-2.78 (4 H, m, NCH2eq and NCH,aX), 2.47 (3 H, s, NMe), 2.39-2.32 (1 H, m, CHMe),2.24-2.10(1 H,m,NCH""), 1.961.82(1 H,m,NCH""), 1.75 (1 H, dd, J/Hz 14.8 and 2.4, NCH2CHeq), 1.50 (1 H, dd, J/Hz 14.5 and 2.4, NCH2CHeq) and 1.14 (3 H, d, J 6.9 Hz, CHMe); G,(CDCl,) 166.60, 137.21, 132.76, 130.46, 129.29, 129.03, 128.28, 77.89, 67.55, 59.32, 51.34, 51.13, 45.90, 33.25, 29.77, 29.58 and 19.06 (Found: M+ -PhS, 290.1735.C17- H24NO3 requires M -C6H,S, 290.1757); m/z 290 (24, M+ -PhS), 168 (89, M -PhS -PhC0,H) and 105 (100, PhCO). (1 'RS,2'SR)- 1-3'-(t-Butyldiphenylsiloxy)-2'-methyl-1'-(phenylthio)propylcyclohexene,syn-22b.-The hydroxy sul-phide anti-(tlb)(628 mg, 1.21 mmol) and TsOH (20 mg, 0.10 mmol) were refluxed in dry benzene for four min.After cooling, the solution was passed through a short silica column, eluting with CH,Cl,, and the solvents were evaporated off under reduced pressure to give the allyl sulphide syn-22b (605 mg, 98) as needles, m.p. 85.5-86.5 "C (from diethyl ether-methanol); Rf(CH2CI2) 0.85; vmax(Nujol) 1660 cm-' (CS); GH(CDCI3) 7.69-7.19 (15 H, m, Ph), 5.29 (1 H, br s, CH=C), 3.68 (1 H, d, J 9.5 Hz, CHSPh), 3.62 (1 H, dd, JAB 9.90, JAX 4.3 Hz, CHAHBOSi), 3.50 (1 H, d, JBA 9.9, Jnx 5.7 HZ, CHAHBOSi), 2.2s1.37 (9 H, m), 1.28 (3 H, d, J 6.7 Hz, CHxMe) and 1.06 (9 H, s, Bu'); G,(CDC13) 136.34, 135.62, 135.57, 135.19, 133.86, 133.68, 132.71, 129.49, 128.29, 127.57, 126.47, 125.82, 66.66, 60.87, 37.76, 26.87, 25.16, 24.45, 22.71, 22.43, 19.29 and 15.59 (Found: Mf -Bu', 443.1892. C,,H,,OSSi requires M -C,H9,443.1865);m/z443(l0,M-Bu'),333(48,M -But -PhSH) and 199 (100, Ph,SiOH).( 1'RS,2'RS)-1-3'-( t-Butyldiphenylsiloxy)-2'-methyl-1'-(phenylthio)propylcyclohexene,anti-22b.-In the same way, the hydroxy sulphide syn-21b (790 mg, 1.53 mmol) gave the ally1 sulphide-22b (766 mg, 98) as an oil, R,(CH,CI,) 0.83; v,,,(film)cm-' 1660 (CS); amp;(CDC13) 7.27-7.17 (15 H, m, Ph), 5.22 (1 H, m, CH=C), 3.90 (1 H, dd, JAB 9.9, JAX 5.1 Hz, CHAHBOSi), 3.80 (1 H, dd, JBA 9.9, JBX 3.6 Hz, CHAHnOSi), 3.67 (1 H, d, J9.9 Hz, CHSPh), 2.35-1.45 (9 H, m, C,H8 and CHxMe), 1.06 (9 H, s, Bu') and 0.99 (3 H, d, J6.8 Hz, CH,Me); G,(CDC13) 135.70, 135.05, 133.94, 132.88, 129.52, 129.48, 128.30, 127.58, 126.55, 126.10, 66.52, 59.86, 37.80, 26.95, 25.23, 24.26, 22.55, 19.42 and 15.95 (Found: M+ -C16H18, 290.1181.C,,H,,OSSi requires M -C16H18, 290.1 161); mjz 290 (28, M -C16H,8), 181 (73), 149 (74), 121 (100) and 93 (85). (l'RS,2'SR)-l-3'-(t-Butyldiphenylsilo.x~v)-2'-methyl-1'-(phenylthio)propylcyclopentene,syn-22a.-In the same way, the alcohol anti-21a (77 mg) gave the ally1 sulphide syn-22a (75 mg, 100) as an oil, R,CH,CI,-hexane (1:1) 0.71; v,,,(film)/cm-' 3055 and 3045 (C=C; GH(CDC13) 7.64-7.18 (15 H, m, Ph), 5.33 (5 H, br s, CH=C), 4.03 (1 H, d, J7.8 Hz, CHSPh), 3.65 (1 H, dd, J/Hz 5.4 and 9.9, CHAHBOSi), 3.48 (1 H, dd, J/Hz 5.6 and 9.9, CHAHBOSi), 2.44-2.31 (1 H, m, CHMe), 2.15-1.58 (6 H, m, CH,I3), 1.15 (3 H, d, J 6.9 Hz, Me) and 1.02 (9 H, s, But) (Found: M -Bu', 429.1722.C2,H,,0SSi requires m/z 429.1708); m/z 429 (l, M') and 199 (100, Ph,SiO H). (2RS,3SR)-2-Methyl-3-( 1-methylpiperid- 1,2,3,6-tetrahydro- pyridin-4-yl)-3-phenylthiopropylBenzoate, syn-22c.-The ester 21c (17 mg, 0.043 mmol) and TsOH (24 mg, 0.19 mmol) were refluxed in benzene (1.0 cm3) under argon for 15 min. Water (10 cm3) and CH2CI, (20 cm3) were added, and the solution was basified with NaOH (6 cm3; 0.1 mol dm-3) and extracted with CH,Cl, (3 x 20 cm3). The combined extracts were dried (Na,SO,), evaporated, and purified by column chromato- graphy on silica gel (3 g), elution with CH,Cl,-methanol- triethylamine (94:5: l), to give the ester syn-22c (14 mg, 86) as an oil, R,CH,Cl,-methanol-triethylamine (94:5 :l) 0.36; v,,,(CDC13)/cm-' 1705 (C=O), 1600 (Ph) and 1580 (Ph); 6,(CDC13) 8.01-7.97 (2 H, m, Ph), 7.54-7.18 (8 H, m, Ph), 5.32 (1 H, br s, CH=C), 4.38 (1 H, dd, J/Hz 11.0 and 4.8, CHAHBO), 4.14 (1 H, dd, J/Hz 11.0 and 6.8, CHAHBO), 3.59 (1 H, d, J 8.8 Hz, CHSPh), 2.962.86 (2 H, m, NCH,C=C), 2.7C2.56 (2 H, m, NCH,CH,), 2.54-2.42 (1 H, m, NCH,CH), 2.38-2.12 (2 H, m, NCH2CH and CHMe), 2.27 (3 H, s, NMe) and 1.25 (3 H, d, J 6.7 Hz, CHMe); G,(CDCl,) 166.33, 135.33, 133.35, 132.90, 130.23, 129.50, 128.61, 128.36, 127.07, 123.62, 67.81, 60.16, 54.14, 51.79, 45.35, 34.92, 25.40 and 15.52 (Found: M+ -PhS, 272.1630.C17H2,N02 requires M -C,H,S, 272.1651); mjz 272 (loo, M+ -PhS), 150 (91, M -PhS -PhC0,H) and 105 (82, PhCO). 1RS,2'SR-( E)-2-3'-( t-Butyldiphenylsilox~u?.)-2'-methyl-propylidenecyclohexanol, (E)-syn-23b.-A solution of m-chloroperoxybenzoic acid (MCPBA) (1 5 1 mg, 0.66 mmol) in diethyl ether (5 cm3) was added to a solution of the allyl sulphide (E)-syn-22b (300 mg, 0.6 mmol) in dry diethyl ether (10 cm3) at 0deg;C under nitrogen. After 0.5 h, the mixture was diluted with diethyl ether (100 cm3) and washed successively with aq. sodium thiosulphate (2 x 15 cm')), aq. sodium hydrogen carbonate (3 x 15 cm3), and brine (15 cm3), dried (MgSO,) and evaporated under reduced pressure. Purification by column chromatography on silica gel, eluting with ethyl acetate-CH,Cl, (1 :20) gave a 3 :1 mixture of allyl sulphoxides (272 mg, 88).A solution of sodium benzenethiolate from sodium hydroxide (130 mg, 3.3 mmol) and thiophenol (230 mg, 2.1 mmol) in methanol (12 cm3) was added to the mixture of allyl sulphoxides and the resulting mixture was refluxed for 20 min, then cooled. Methanol was evaporated off under reduced pressure, sodium hydroxide (30 cm3 of a 5:~ solution) was added, and the solution was extracted with diethyl ether (3 x 20 cm3). The combined extracts were dried (MgSO,), and evaporated under reduced pressure. Purification by column chromatography on silica gel, eluting with ethyl acetate-CH,Cl, (1 :50) gave the allylic alcohol 23b as an oil (1 70 mg, 79), amp;ethyl acetate-CH,Cl, (1 :20) 0.44; v,,,(film)/cm-' 3350 (OH) and 1655 (C=C); G,(CDCI,) 7.69-7.25 (10 H, m, Ph), 5.09 (1 H, d, J 9.3 Hz, CH=C), 4.05 (1 H, m, CHOH), 3.47 (2 H, m, CH,OSi), 2.65 (1 H, sym m, CHMe), 2.34 (1 H, m, CHCH=C), 1.9G1.18 (7 H, m), 1.06 (9 H, s, But) and 1.01 (3 H, d, J 6.7 Hz, CHMe); Gc(CDC13) 141.52, 135.64, 134.80, 134.09, 129.61, 129.50, 127.69, 127.55, 124.02, 73.61, 68.84, 36.09, 34.27, 27.41, 27.07, 26.91, 26.57, 26.40, 22.88, 19.29 and 17.77 (Found: Mf -But, 351.1749.C2,H2,O2Si requires M -C,H,, 351.1774); m/z 351 (6, M -Bulsquo;), 273 (15, M -But -PhH), 199 (100, Ph,SiOH) and 125 (58). (1 RS,2rsquo;RS)-2-3rsquo;-( t-Butyldiphenylsiloxy)-2rsquo;-methylpropyl-idenecyclohexanol, (E)-anti-23b.-Oxidation and rearrange- ment of the allyl sulphide (E)-anti-22b (650 mg, 1.3 mmol) by the same method gave the intermediate allyl sulphoxide (0.595 g, 89) and then the allylic alcohol (360 mg, 88, 77 over the two steps) as an oil, R,(CH,Cl,) 0.3; v,,,(film)/cm-rsquo; 3400 (OH); GH(CDC1,) 7.70-7.25 (10 H, m, Ph), 5.10 (1 H, d, J 9.3 Hz, CH=C), 4.05 (1 H, m, CHOH), 3.48 (2 H, m, CH,OSi), 2.65 (1 H, sym m, CHMe), 2.32 (1 H, m, CHCH=C), 1.87-1.41 (7 H, m, C6H7), 1.06 (9 H, s, Bursquo;) and 1.01 (3 H, d, J 6.7 Hz, CHMe); Gc(CDCl,) 141.64, 135.65, 134.12, 134.07, 129.53, 127.58, 123.79, 73.62, 68.90, 36.25, 34.31, 27.40, 26.94, 26.50, 23.02, 19.33 and 17.76 (Found: M+ -But, 351.1802.C2,HZ202Si requires M -C,H9, 351.1780); m/z 351 (7, M -Bulsquo;), 227 (24), 199 (100, Ph,SiOH) and 135 (93).(lRS,2RS)-3-(t-Butyldiphenylsiloxy)-l-(cyclopent-l-enyl)-2-methylpropyl Phenyl Su1phoxide.-A solution of MCPBA (80-85; 27 mg) in dichloromethane (1 cm3) was added to a solution of the sulphide syn-22a (50 mg) in dichloromethane (3 cm3) in a foil-wrapped flask at -78 ldquo;C under nitrogen. The solution was stirred for 50 min, then brine (10 cm3) and saturated aq. sodium thiosulphate (10 cm3) were added and the mixture was allowed to warm to room temperature. The solution was extracted with dichloromethane (3 x 10 cm3) and the combined extracts were dried (MgSO,), then evaporated under reduced pressure to give the sulphoxide (56 mg, 100) as a waxy solid, R,CH,Cl,-hexane (1 :l) 0.25; v,,,(Nujol)/cm-rsquo; 3055 and 3045 (W);GH(CDCl,) 8.09-7.29 (15 H, m, Ph), 5.53 and 5.16 (1 H, br t, CH=C, 1:3 ratio of diastereoisomers), 3.56 (2 H, dd, J/Hz 3.4 and 3.4, CH,OSi), 3.14 (1 H, d, J 11.1 Hz, CHSOPh), 2.58-2.22 (1 H, m, CHMe), 2.28-1.87 (6 H, m, CH,l3), 1.54 (3 H, d, J6.6 Hz, Me), and 1.03 and 1.02 (9 H, s and s, Bulsquo;, 1 :3 mixture of diastereoisomers) (Found: M -But, 445.1672. C,,H,,O,SSi requires m/z, 445.1658); m/z 445 (l, M -Bursquo;) and 197 (100, Ph,SiOH). (1 RS,2rsquo;SR)-(E)-2- 3rsquo;-(t-Butyldiphenylsiloxy)-2rsquo;-rnethyl-propylylidenecyclopentanol, (E)-syn-23a.-A solution of the above sulphoxide (82 mg) in methanol (1 cm3) was added to a mixture of sodium hydroxide (1 14 mg) and thiophenol (0.26 cm3) in methanol (2 cm3) in a foil-wrapped flask under nitrogen. The solution was heated under reflux for 10 min, the methanol was evaporated off under reduced pressure, and the residue taken into water (5 cm3)-brine (20 cm3) and extracted with diethyl ether (3 x 15 cm3).The combined extracts were dried (Na,SO,), and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (10 g), eluting with CH,Cl,-propan-2-01 (98 :2) to give the alcohol 23a (30 mg, 66) as an oil, R,CH,CI,-Prlsquo;OH (98:2) 0.24; v,,,(film)/cm-rsquo; 3350 (OH), 3060 and 3050 (C=CH); G,(CDCl,) 7.73-7.33 (10 H, m, Ph), 5.30 (1 H, ddd, J/Hz 9.5, 3.9 and 2.5, CH=C), 4.33 (1 H, br t, CHOH), 3.48 (2 H, d, J6.6 Hz, CH,OSi), 2.6G2.40 (1 H, m, CHMe), 2.40-2.05 (2 H, m, CH,C=C), 1.92- 1.72(2 H, m, CH,CHOH), 1.68-1.47 (3 H, m, CH,CH,CH, and OH), 1.03 (9 H, s, But) and 0.99 (3 H, d, J 6.8 Hz, Me) (Found: M -But, 337.1628.C21H2502Si requires m/z 337.1624); m/z 337 (8, M -But) and 199 (100, Ph,SiOH). (1 RS,2rsquo;SR)-( E)-2- 3rsquo;4 t-Butyldiphenylsiloxy)-2rsquo;-methyl-propylidenecyclohexyl 3,5-Dinitrobenzoate, (E)-syn-27.-The allylic alcohol (E)-syn-23b (145 mg, 0.35 mmol), 3,5-dinitro- benzoyl chloride (90 mg, 0.38 mmol) and 4-(dimethylani1ino)- J. CHEM. SOC. PERKIN TRANS. 1 1991 pyridine (DMAP) (66 mg, 0.38 mmol) were stirred in dry CH,Cl, (1 cm3) under N,. After 20 min, the mixture was purified by column chromatography on silica gel with CH,Cl, as eluant to give the ester syn-26 (189 mg, 89) as an oil, R,(CH,Cl,) 0.66; v,,,(film)/cm-rsquo; 1715 (C=O), 1620 (C=C), 1590, 1580, 1540 (NO,) and 1350 (NO,); G,(CDCI,) 9.21-9.13 3 H, m, Ar(NO,),, 7.67-7.33 (10 H, m, Ph), 5.52 (1 H, m, CHOCO), 5.31 (1 H, d, J8.8 Hz, CH=C), 3.48 (2 H, d, J6.3 Hz, CH,OSi), 2.67 (1 H, sym m, CHMe), 2.24-1.30 (8 H, m, C~HB), 1.03(9 H, S, But) and 1.01 (3 H, d, J6.3 Hz, CHMe) (Found: M+ -C10H15, 467.1255.C,,H,,N,O,Si requires M -CI0Hl5, 457.1275); m/z 467 (4, M -Bulsquo; -PhH), 393 (48), 333 (98, M -Bulsquo; -ArCO,H) and 199 (100, Ph,SiOH). (1 RS,2rsquo;RS)-( E)-2-3rsquo;-(~-Butyldiphenylsiloxy)-2rsquo;-methyl-propylidenecyclohexyl 3,5-Dinitrobenzoate, (E)-anti-27.--In the same way the allylic alcohol anti-22b (268 mg, 0.66 mmol) gave the ester anti-27. (400 mg, 100) as an oil, Rf(CH2C12) 0.75; v,,,(film)/cm-rsquo; 1715 (C=O), 1620 (C=C), 1590, 1580, 1560 (NO,) and 1350 (NO,); GH(CDCI3) 9.18-9.07 3 H, m, Ar(NO,),, 7.63-7.25 (10 H, m, Ph), 5.57 (1 H, m, CHOCOR), 5.30 (1 H, d, J9.2 Hz, CHS), 3.49 (1 H, dd, JAB 9.8, JAX 6.8 Hz, CHAHBOSi), 3.44 (I H, dd, JAB 9.8, JBX 6.6 HZ, CHAHBOSi), 2.67 (1 H, sym m, CHxMe), 2.35-1.3 (8 H, m, C6H8), 0.97 (3 H, d, J, 6.7 Hz, CHxMe) and 0.94 (9 H, s, Bulsquo;); G,(CDCl,) 161.73, 148.65, 135.64, 135.55, 135.00, 133.81, 129.96, 129.54, 129.27, 127.58, 127.55, 122.65, 79.19, 68.37, 34.47, 32.91, 26.81, 26.75, 26.30, 22.30, 19.19 and 17.43 (Found: M+ -C10H15, 467.1259.C23H23N207Sirequires M -C10H15, 467.1274); m/z (0.5, M -PhH -Bulsquo;), 391 (5), 333 (7) and 199 (100, Ph,SiOH). (1 RS,2rsquo;RS)-(E)-2-( 3rsquo;-Hydroxy-2rsquo;-rnethylpropylidene)cyclo-hexanol, (E)-anti-23b (R = H).-Tetrabutylammonium fluoride (0.33 cm3 of a 1 mol dm-, solution in THF) was added to a solution of the silyl ether (E)-anti-23b (125 mg, 0.31 mmol) in THF (5 cm3) and the mixture was stirred for two days.The reaction mixture was quenched with aq. ammonium chloride (20 cm3), the organic layer was separated, and the aqueous layer was extracted with diethyl ether (2 x 5 cm3). The combined organic phases were dried (MgSO,), evaporated under reduced pressure, and purified by column chromatography on silica gel (10 g), eluting with methanol-CH,Cl, (1 :13) to give the diol(51 mg, 96) as prisms, m.p. 8amp;82 ldquo;C (from diethyl ether- hexane); R,methanol-CH,Cl, (1 : 13) 0.14; vm,x(Nujol)/cm-l 3350 (OH) and 1660 (C=C); G,(CDCl,) 5.1 1 (1 H, dd, J/Hz 0.9 and 9.5, CSH), 4.07 (1 H, m, CHOH), 3.49 (1 H, dd, JAB 10.5, JAX 5.6 Hz, CHAHBOH), 3.32 (1 H, dd, JBA 10.5, JBX 8.2 Hz, CHAHBOH), 2.65 (1 H, sym m, CHxMe), 2.42 (1 H, m, RCHHCS), 2.02 (1 H, m, RCHHCS), 1.861.43 (6 H, m, CH,,) and 0.93 (3 H, d, J 6.7 Hz, CHxMe) (Found: M+, 170.1313.C,oH1802 requires M, 170.1307); m/z 170 (8, Mrsquo;), 152 (18, M -HZO), 139 (32, M -CHZOH), 122 (loo), 111 (81) and 55 (76). (1RS,2rsquo;RS)-(E)-2-(3rsquo;-Hydroxy-2rsquo;-rnethylpropylidene)eyclo-pentanol, (E)-syn-23a (R = H).-In the same way, alcohol (E)-syn-23a (20 mg) gave the diol (5.6 mg, 72) as an oil, R,CH2Cl,-MeOH (95 :5) 0.17; v,,,(film)/cm-rsquo; 3300 (OH); GH(CDC13) 5.31 (1 H, ddd, J/Hz 9.5, 4.1 and 2.5, CH=C), 4.40 (1 H, t, J 5.4 Hz, CHOH), 3.51 (1 H, dd, J/Hz 10.5 and 5.9, CHAHBOH), 3.39 (1 H, dd, J/Hz 10.5 and 7.8, CHACHBOH), 2.49-2.39 (2 H, m, CH,CS), 2.28-2.20 (1 H, m, CHMe), 1.89- 1.78 (2 H, m, CH,CHOH), 1.661.52 (4 H, m, CH2CH2CH2 and both OH) and 0.97 (3 H, d, J 6.7 Hz, Me) (Found: M+, 156.1135.CgH1,02 requires M, 156.1150); m/z 156 (3, Mrsquo;), 125 (45, M -CH,OH), 97 (100, C6H90) and 55 (85, C,H,). (2RS,3SR)-3-( Cyclohex- 1 -enyl)-2-methyl-3-phenylthiopropan- J. CHEM. SOC. PERKIN TRANS. 1 1991 1-01, (E)-syn-22b (R = H).-LiAlH, (110 mg, 2.9 mmol) was added to a solution of the ester anti-lob (550 mg, 1.46 mmol) in dry diethyl ether (20 cm3) at 0"C and the mixture was stirred for two hours. Ethyl acetate (1 cm3) was added and the reaction mixture was poured into aq.ammonium chloride (50 cm3). Dil. hydrochloric acid (20 cm3) was added, the organic layer was separated and the aqueous layer was extracted with diethyl ether (2 x 30 cm3). The combined organic phases were washed successively with water (20 cm3) and brine (20 cm3), dried (MgSO,) and evaporated under reduced pressure. Purification by column chromatography, eluting with MeOH-CH,CI, (1 :200) gave the alcohol as an oil (359 mg, 9473, Rf(CH2C12) 0.16; v,,,(film)/cm-' 3450 (OH) and 1580 (SPh); G,(CDCl,) 7.37-7.15 (5 H, m, SPh), 5.32 (1 H, br s, CH=C), 3.60 (1 H, dd, JAX 4.8, JAB 11.0 Hz, CHAHBOH), 3.47 (1 H, dd, JBX 5.6, JBA 11.0 Hz, CHAHBOH), 3.47 (1 H, d, J9.4 Hz, CHSPh), 2.31-1.39 (9 H, m, C6H8 and CHMe) and 1.18 (3 H, d, J 6.7 Hz, CHMe) (Found: M+, 262.1407.C16H,,0S requires M, 262.1391); rn/z 262 (3, M+), 153 (16, M -SPh), 152 (16, M -PhSH), 135 (60), 121 (58), 110 (62, PhSH), 95 (82), 93 (82) and 79 (100). (1RS,2'SR)-( E)-2-( 3'-Hydroxy-2-rnethylpropylidene)cyclo-hexanol, (E)-syn-23b (R = H).-Sodium periodate (330 mg, 1.54 mmol) was added to a solution of the allyl sulphide (E)-syn-22b (359 mg, 1.37 mmol) in methanol (10 cm3) and water (-20 drops) was added until a very faint precipitate persisted. After 24 h, methanol was removed under reduced pressure, brine (50 cm3) was added, and the solution was extracted with ethyl acetate (3 x 20 cm3). The combined extracts were dried, and the solvent was removed under reduced pressure to give the crude allyl sulphoxide (400 mg).A solution of sodium benzene- thiolate sodium hydroxide (260 mg, 6.5 mmol) and thiophenol (158 mg, 1.45 mmol) in methanol (12 cm3) was added and the mixture was refluxed for 0.5 h, then cooled, when aq. sodium hydroxide (5; 50 cm3) was added and the solution was extracted with diethyl ether (3 x 20 cm3). The combined extracts were dried (MgSO,) and evaporated under reduced pressure. Purification by column chromatography on silica gel (20 g), eluting with methanokthyl acetate (1:20) gave the allylic alcohol (177 mg, 76 over the two steps) as an oil, R,methanokthyl acetate (1 :20) 0.38; v,,,(film)/cm-' 3300 (OH) and 1660 (C=C); G,(CDCl,) 5.15 (1 H, dd, J/Hz 9.3 and 1.1, C=CH), 4.08 (1 H, m, CHOH), 3.48 (1 H, dd, JAB 10.4, JAX 5.9 Hz, CHAHBOH), 3.34 (1 H, dd, JBA 10.4, JBx 8.1 Hz, CHAHBOH), 2.67 (1 H, sym m, CHMe), 2.48 (1 H, m, RCHHCK), 2.05-1.35 (7 H, m) and 0.95 (3 H, 3 H, d, J6.7 Hz, CHxMe) (Found: M+, 170.1305.CloHl802 requires M, 170.1307); m/z 170 (6, M'), 162 (12, M -H,O), 139 (20, M -CH ,OH), 122 (42), 11 1 (68, M -C3H70), 69 (76) and 55 (100). 3,8-Dimethyl-8-aza-l-oxaspiro4.5dec-3-en-2-one25c.-A solution of MCPBA (0.24 g, 1.1 mmol) in CH,Cl, (8 cm3) was added to a solution of the lactone hydrochloride anti-12c (0.332 g, 1 .O mmol) in CH,CI, (7 cm3) under argon at -78 "C. After 20 min, the solution was allowed to warm to 0 "C and was stirred for one h. CH,Cl, (100 cm3), aq. sodium thiosulphate (60 cm3), and aq. NaHCO, (50 cm3) were added, the organic layer was removed, and the aqueous layer was extracted with CH2C12 (2 x 100 cm3).The combined organic phases were dried (Na,SO,) and evaporated to give the sulphoxide 24c, R,CH,Cl,-methanol-triethylamine (90:9: l) 0.31; v,,,(CHC13)/cm-' 1760 (C=O) and 1048 (S=O), which was heated to 110deg;C in dimethyl sulphoxide (DMSO) (1.0 cm3) under argon. After 2 h, CH,Cl, (30 cm3) and water (30 cm3) were added, the organic layer was removed and the aqueous layer was extracted with CH2Cl, (2 x 30 cm3). The combined organic phases were dried (Na,SO,), evaporated and the 459 residue was purified by column chromatography on silica gel (25 g), eluting with CH,Cl,-thanol-ammonia (120: 8: 1) to give the butenolide 25c (92 mg, 50) as needles, m.p.117- 119 "C; RfCH2C1,-methanol-triethylamine (90: 9: l) 0.29; v,,,(CHC13)/cm-' 1735 (GO) and 1655 ((2s); G,(CDCl,) 7.01 (1 H, d, J 1.6 Hz, HC=C), 3.00 (2 H, br d, J 10.9 Hz, NCHzeq), 2.73 (2 H, br t, J 11.8 Hz, NCH,""), 2.51 (3 H, s, NMe), 2.29 (2 H,br t, J 11.1 Hz, NCH2CH2aX), 1.91 (3 H, d, J 1.6 Hz, C=CMe) and 1.64 (2 H, br d, J 12.0 Hz, NCH,CH,eq); Gc(CDC13) 173.04, 152.35, 129.43, 82.52, 51.53, 45.66, 33.93 and 10.55 (Found: M+, 181.1099. CloH,,NO, requires M, 181.1103); m/z 181 (60, M'), 180 (54, M -H),70 (50, C,H,N) and 57 (100, C3H7N). 3,8-Dirnethyl-8-aza- 1 -oxaspiro4.Sldecane 26c.-Raney nickel (2 g of a 50 slurry in water) was added to a solution of the sulphide anti-20c (319 mg, 1.15 mmol) in ethanol (12 cm3) and the mixture was heated under reflux under nitrogen for 45 min.The suspension was filtered to remove the catalyst, washed with ethanol, and evaporated to give an oil. The acid-washed catalyst was extracted with CH,CI2 (2 x 25 cm3), and the combined layers were dried (Na,SO,) and evaporated. Ethereal HCI (2 cm3) was added to the combined oils, the solvent was evaporated off and the residue was triturated with diethyl ether to give the hydrochloride salt of the amine 26c (44 mg, 19) as needles, m.p. 157-1 59 "C; R,CH2C1,-ethanol-ammonia (75: 8: l) 0.41; v,,,(Nujol)/cm-' 3400 (OH) and 2750-2350 (NH+); GH(CDCl3) 3.92 (1 H, t, J 8.0 Hz, CHAHBO), 3.36 3.28 (1 H, m, CHN) 3.31 (1 H, t, J 8.0 Hz, CHAHBO), 3.08 (2 H, br s, CH,N), 2.73 (3 H, s, NMe), 2.52-2.25 (3 H, m, CHMe and NCH,CH,), 2.02 (1 H, dd, J/Hz 13.0 and 9.5, CffAHBCHMeCH,O), 1.84-1.70 (2 H, m, NCH,CH,), 1.38 (1 H, dd, J/Hz 13.0 and 9.5, CHAffBCHMeCH20) and 1.05 (3 H, d, J/Hz 6.5, CHMe) (Found: M+, 169.1470.CloHlgNO requires M, 169.1467); m/z 169 (23, M'), 110 (32, M+ -C3H70) and 96 (100, M+ -C4HgO) (Found: C, 55.9; H, 10.15; N, 6.5. CloH,,NO~HCl~0.5H20 requires C, 55.9; H, 9.8; N, 6.5). Acknowledgements We thank SERC for grants to (V. K. A., I. C. and S. McI.) and Glaxo Group Research (Ware) for a CASE award (to I. C.). References 1 P. Brownbridge and S. Warren, J. Chem. SOC.,Perkin Trans. I, 1977, 2272. 2 M. Hannaby and S. Warren, Tetrahedron Lett.. 1985, 26, 3133; J. Chem. Soc., Perkin Trans. I, 1989, 303. 3 Preliminary communcation: V. K. Aggarwal and S. Warren, Tetrahedron Lett., 1986,27, 101. 4 A. de Groot and B. J. M. Jansen, Tetrahedron Lett., 1981, 22, 887; Synthesis, 1985,434; J. Otera, Synthesis, 1988,95. 5 C. H. Heathcock in Asymmetric Synthesis, ed. J. D. Morrison, Academic, Orlando, Florida, 1984, vol. 3, p. 11 I. 6 C. H. Heathcock, M. C. Pirrung, S. H. Montgomery and J. Lampe, Tetrahedron, 1981,37,4087. 7 M. Hirama, D. S. Garvey, L. D.-L. Lu and S. Masamune, Tetrahedron Lett., 1979, 3937. 8 C. H. Heathcock, M. C. Pirrung and J. E. Sohn, J. Org. Chem., 1979, 44,4294. 9 K. C. Nicolaou, S. P. Seitz, W. J. Sipio and J. F. Blount, J.Am. Chem. SOC.,1979, 101,3884. 10 D. Savostianoff and M. Pfau, Bull. SOC.Chim.Fr., 1967,4162. 11 D. R. Williams and J. G. Phillips, Tetrahedron, 1986, 42, 3013. 12 V. K. Aggarwal and S. Warren, Tetrahedron Lett., 1987, 28, 1925. 13 P. Brownbridge and S. Warren, J. Chem. SOC.,Perkin Truns. I, 1976, 2125. 14 P. Brownbridge, E. Egert, P. G. Hunt, 0.Kennard and S. Warren, J. Chem. Soc., Perkin Trans. I, 1981, 2751. 460 J. CHEM. SOC. PERKIN TRANS. 1 1991 15 D. A. Evans and G. C. Andrews, Acc. Chem. Rex, 1974,7, 147. 19 P. Groenewegen, H. Kallenberg and A. van der Gen, Tetrahedrori 16 J. G. Miller, W. Kurz, K. G. Untch and G. Stork, J. Am. Chem. SOC., Lett., 1979, 28 17. 1974,96,6774. 20 D. A. Evans and L. R. McGee, Tetrahedron Lett., 1980, 21, 3975; 17 C. H. Heathcock and E. T. Jarvi, Tetrahedron Lett., 1982, 23, 2825; Y. Yamamoto and K. Maruyama, Tetrahedron Lett., 1980,21,4607. C. H. Heathcock, E. T. Jarvi and T. Rosen, Tetrahedron Lett., 1984, 25,243; C. H. Heathcock and B. L. Finkelstein, J. Chem. Soc., Chem. Paper 0/03332D Commun., 1983,919. 18 P. J. Stang, M. G. Mangum, P. D. Fox and P. Haak, J. Am. Chem. Received 23rd Juljv 1990 SOC.,1974,96,4562. Accepted 13th August 1990