1,5-Asymmetric induction in reactions between aldehydes and (4S)-5-(tert-butyldimethylsilyloxy)-4-hydroxypent-2-enyl(tributyl)-stannane promoted by tin(IV) chloride

摘要

J. CHEM. SOC. PERKIN TRANS. 1 1995 1,5=Asymmetric induction in reactions between aldehydes and (4s)-54tevt=butyldimethylsilyloxy)=4-hydroxypent-2=enyl(tributy1)-stannane promoted by tin(1v) chloride Robert J. Maguire and Eric J. Thomas * Department of Chemistry, University of Manchester, Manchester M13 9PL, UK (457-5-(tert-Butyldimethylsilyloxy)-4-hydroxypent-2-enyl(tributyl)stannane 18 has been prepared from di- 0-isopropylidene-D-mannitol8. Oxidative cleavage of the mannitol derivative followed by condensation with triethyl phosphonoacetate and reduction gave the alcohol 10 which was converted into the xanthate 11. Deprotection gave the dihydroxy xanthate 12 which was protected as its bis-tert-butyldimethylsilyl ether 13. This rearranged on heating in toluene to give the dithiocarbonate 15 which reacted with tributyltin hydride under free radical conditions to give the (4S)-4,5-bis(tert-butyldimethylsilyloxy)pent-2-enyl(tributyl)stan-nane 16 as an approximately 9 :1 mixture of E-and 2-isomers.Deprotection and selective protection of the primary hydroxy group provided the (4~-5-(tert-butyldimethylsilyloxy)-4-hydroxypent-2-enylstannane 18. As a shorter route, the primary hydroxy group of the dihydroxy xanthate 12 was protected as its tert- butyldimethylsilyl ether 14 which underwent clean rearrangement into the dithiocarbonate 19 when heated in toluene. Reaction with tributyltin hydride under free radical conditions then gave the (5-tert-butyldimethylsilyloxy-4-hydroxypent-2-enyl)stannane18. Treatment of this 4,5-disubstituted pentenylstan- nane with tin(1v) chloride generated an allyltin trichloride which reacted with aldehydes with excellent 1,5-asymmetric induction to give 1,5-syn-products, e.g.20,29-31 and 41. The stereoselectivity of these reactions would appear to be controlled by the 4-hydroxy substituent rather than by the 5-tert-butyldimethylsilyl group. Aspects of the chemistry of these products, in particular their conversion into 2,ti-disubstituted 5,6-dihydro-2H-pyrans, was investigated. Useful levels of remote asymmetric induction have been observed in tin@) chloride promoted reactions of aldehydes and alkoxyalk-2-enyl(trialkyl)stannanes. -6 For example, treatment of the (S)-4-benzyloxypen t -2-enyl( t ributy1)stan- nane 1 with tin(rv) chloride, followed by addition of an OH 397 : s3 aldehyde, gives rise to the formation of 1-substituted syn-5-benzyloxyhex-3-enols 2 containing less than 3 of their 1,5- anti-epimers.Stereoselective transmetallation of the allylstan- nane to generate an allyltin trichloride in which the electron deficient tin atom is coordinated to the heteroatom of the substituent, is believed to be involved.2 During studies associated with the synthesis of a complex natural product, we wished to synthesize cis-2,6-disubstituted 5,6-dihydro-2H-pyrans 3. An approach to these compounds u n 6 7 was envisaged which would involve isomerisation of the unsaturated hydroxy epoxides 47 which in turn would be prepared from the syn-alk-3-ene-2,6-diols 5.By analogy with the stereoselective formation of the 1-substituted 5-benzyloxyhex-3-en- 1-01s 2 from tin(1v) chloride promoted reactions between aldehydes and the (4-benzyloxypent-2-eny1)-stannane 1,3 the diols 5 would be available stereoselectively from reactions between the 5-substituted 4-hydroxypent-2- enylstannane 7and aldehydes 6, if the stereoselectivity of these reactions is controlled by the 4-hydroxy substituent rather than by the 5-substituent. We now report the synthesis of (4S)-5- tert-butyldimethylsilyloxy-4-hydroxypent-2-enyl(tributyl)stan-nane 18 and the stereoselectivity of its reactions with aldehydes. This bifunctionalised stannane was chosen since it was expected that the 4-hydroxy substituent would be more likely to control the stereochemistry of the transmetallation step than the hindered 5-tert-butyldimethylsilyloxy substituent and establish the required configuration in the product formed during the reaction with an aldehyde. Attempts are also described to convert the syn alk-3-ene-2,6-diols so obtained into 5,6-dihydro-2H-pyrans 3.In the accompanying paper, stereo-selective syntheses of cis-2,6-disubstituted 5,6-dihydro-2H- pyrans 3 and their 2,6-trans-stereoisomers based on this chemistry are described. * Results and discussion (4S')-5-tert-Butyldimethylsilyloxy-4-hydroxypent-2-enyl(tri-buty1)stannane 18 was prepared from 1,2:5,6-di-0-isopropylidene-D-mannitol8as outlined in Scheme 1. Oxidative cleavage of the mannitol derivative using sodium periodate and trapping the aldehyde so obtained in situ by triethyl phosphonoacetate and potassium carbonate gave the unsatu- rated ester 9 (87 yield from 8).' Reduction using diisobutylaluminium hydride then gave the alcohol 10, which i, ii1 10R=H8 11 R = MeSC(S) v -viii 0 S OP 15 12 R' = $= H 13 euro;3' = R2P SiMe2Bd 14 R' = H, R2 = SiMe2Bd Bu@-OP OP 16 viii Bu3SnTOH OH 17 viiI Bu3Sn*OP ix MeSKS-OH 18 19 amp;I P = SiMe2Bd Scheme 1 Reagents and conditions: i, sodium periodate, sodium hydrogen carbonate; ii, (EtO),P(O)CH,CO,Et, potassium carbonate (87 from 8);iii, diisobutylaluminium hydride (lW/,); iv, NaH, carbon disulfide, methyl iodide (100); v, aq.hydrogen chloride, tetrahydro- furan (88); vi, terr-butyldimethylsilyl trifluoromethanesulfonate, 2,6-lutidine (95); vii, tert-butyldimethylsilyl chloride, triethylamine, 4-dimethylaminopyridine (14, 69; 18, 80 from 17); viii, toluene, heat under reflux, 18 h (15,99); ix, tributyltin hydride, azoisobutyronitrile (16, 90; 18, 81 from 14); x, tetrabutylammonium fluoride, tetrahydrofuran (66) was converted into its xanthate 11 using sodium hydride, carbon disulfide and methyl iodide." Hydrolysis of the acetonide under acidic conditions '' gave the dihydroxy xanthate 12 which was protected as its bis-tert-butyldimethyl- silyl ether 13. l2 This was rearranged into the dithiocarbonate 15 by heating in toluene under reflux, and treatment with tributyltin hydride under free radical conditions gave the bis(tert-butyldimethylsilyloxy)pent-2-enylstannane 16 as a 9: 1 mixture of E-and Z-double-bond isomers.'3 Deprotection of the bis-protected stannane 16 with an excess of tetrabutylammonium fluoride l4 gave the (4,5-dihydroxypent- 2-eny1)stannane 17, which was monosilylated to give the (4S)- 5-(tert-butyldimethylsilyloxy)-4-hydroxypent-2-enylstannane 18." As an alternative route to this stannane, the dihydroxy xanthate 12 was converted into its mono-tert-butyldimethylsilyl ether 14 which was rearranged to the dithiocarbonate 19 by heating in toluene under reflux.Treatment with tributyltin J. CHEM. soc. PERKIN TRANS. I 1995 hydride under free radical conditions then gave the 5-(te1-t-butyldimethylsilyloxy)-4-hydroxypent-2-enylstannane18, ratio E:Z = 4: 1 ('HNMR).Reactions between the 5-ter~-butyldimethylsilyloxy-4-hydroxypen-2-enylstannane18and aldehydes were carried out by adding tin(1v) chloride to the stannane at -78 "C, followed by the aldehyde. From benzaldehyde, a mixture of two diols identified as the 1,5-syn-diolU) and its 1,5-anti-isomer 21, ratio 97 :3 (HPLC, 'H NMR), yield 86, was obtained (Scheme 2). The configuration of the major product at C-1 was shown to be S by acetylation of the mixture of products followed by ozonolysis and reduction. This gave the laevorotatory 1-phenylpropane-1,3-diol, a -57.4 (1it.,l6 -63.8), which is known to correspond to the S-enantiomer 23.3*16The double- bond of the major product 20 was assigned the Z configuration by 'H NMR, since its 3,4-coupling constant was found to be 11 Hz, and NOE difference spectra showed significant enhance- ment of 2-H2 on irradiation of 5-H,and vice uersa.To establish the structure of the minor component to confirm that the 1,5-syn- and 1,5-mti-diastereoisomers were being distinguished, the 1,5-syn-product u)was converted into its 1,5-anti-isomer 21 by deprotection and selective acetonide formation, ' followed by inversion of configuration using a Mitsunobu reaction and saponification. Hydrolysis and selective silylation of the primary hydroxy group gave the 1,5- anti-isomer 21 which was distinctly different from its syn- epimer by 'H NMR spectroscopy and HPLC.The 4-hydroxypent-2-enylstannane 18 was treated with acrolein, propanal and ethyl glyoxylate; these aldehydes being chosen so that the products could be used to evaluate the proposed synthesis of the 5,6-dihydro-2H-pyrans 3. With acrolein, a good yield of the syn-diol29 containing ca. 4 of a minor product, believed to be its anti-isomer, was obtained. Propanal gave rise to the formation of a mixture of three products in a ratio of 89: 8: 3, with the major product being identified as the syn-diol 30.Ethyl glyoxylate reacted slightly less stereoselectively giving a mixture of two products, ratio 86: 14, identified as the syn-diol31 together with its anti-isomer. The structures of these products were assigned by analogy with the selective formation of the syn-diol 20 from the reaction of the stannane 18with benzaldehyde, and were consistent with their spectroscopic data.It would appear that the 4-hydroxy-S- (sily1oxy)alkenylstannane18 reacts with aldehydes with useful levels of 1,5-~tereoselectivity induced by the Chydroxy substituent, the 5-silyloxy group not playing a significant part in influencing the stereochemical outcome of these reactions. Conversion of the syn-1,Sdiols 29-31 into cis-2,6-disubsti- tuted 5,6-dihydro-2H-pyrans was briefly investigated. Depro- tection of the product 29 obtained from the reaction of the stannane 18with acrolein gave the triol 32. However, attempts to convert this into the epoxide 4 (R= CH2SH) by selective toluene-p-sulfonylation of the primary hydroxy group and cyclisation, or by a Mitsunobu cyclisation of the triol, gave mixtures of polymeric products which could not be characterised. Perhaps these reactions are unsuccessful because the allylic epoxide group is unstable in the presence of the free hydroxy group leading to polymerisation.As an alternative approach to 5,6-dihydro-2H-pyrans, the product 30from the reaction of the stannane 18with propanal, was desilylated to give the triol 33 which was protected as its acetonide 34.Methanesulfonylation followed by hydrolysis and selective silylation of the primary hydroxy group gave the methanesulfonate 37. However, attempts to cyclise this into the 5,6-dihydro-2H-pyran38using basic conditions were unsuccess- ful, unchanged starting material being obtained.It may be that the displacement of the secondary methane sulfonate by a secondary alcohol is inefficient because of steric hindrance. A third approach to 5,6-dihydro-2H-pyrans was investigated J. CHEM. soc. PERKIN TRANS. I 1995 Scheme 2 Reagents and conditions: i, tin(1v) chloride, -78 OC, 5 min, benzaldehyde, -78 "C, 1 h (86); ii, acetic anhydride, pyridine (93); iii, ozone, dimethyl sulfide, then lithium aluminium hydride (77); iv, tetrabutylammonium fluoride, tetrahydrofuran (96); v, 2,2-dimethoxypropane, pyridinium toluene-p-sulfonate (73); vi, diisopropyl diazodicarboxylate, triphenylphosphine, 4nitrobenzoic acid (79); vii, sodium hydroxide, methanol, water (73); viii, dilute aqueous hydrogen chloride (94); ix, tert-butyldimethylsilyl chloride, triethylamine, 4-dimethylaminopyridine (67) 31 31 I 0ulSnTOP OP 1 J/=y OH OH OH 30 OH 18 39 4 (R = CHpCH) 30I (P = SiMesBu') the polar nature of the product, but gave the triol 39 in reasonable yield.The triol was converted into the cyclic stannoxane 40 which was treated with toluene-p-sulfonyl chloride in situ in the presence of triethylamine to give the toluene-p-sulfonate 41.l9 An alternative synthesis of this compound was developed starting with solketal 43. This was converted into the 2,3-dihydroxypropyl toluene-p-sulfonate 45 by tosylation followed by hydrolysis, and cleavage of the diol using sodium periodate gave the geminal diol 46 (Scheme 3).20*21This was dehydrated using molecular sieves to give the hygroscopic aldehyde 47 which was treated with the pentenylstannane 18 under the usual conditions to give the toluene-p-sulfonate 41 together with its anti-epimer.However, attempts to convert the toluene-p-sulfonate 41 into the epoxide using the syn-diol31 obtained from the reaction of the stannane 42 by treatment with potassium carbonate in methanol gave rise 18 with ethyl glyoxylate. Reduction of the ester group using to the formation of mixtures of products which may have diisobutylaluminium hydride was a little capricious because of contained an epoxide, but which could not be separated. It OH 47 46 Scheme 3 Reagents: i, 4-dirnethylaminopyridine, toluene-p-sulfonyl chloride, pyridine; ii, aqueous HCI, tetrahydrofuran (99 from 43); iii, sodium periodate; iv, 4 8, molecular sieves (77) appeared that both the 2-and 6-hydroxy groups were participating in displacement of the toluene-p-sulfonyloxy group leading to the formation of mixtures of isomeric products.It appears that the use of products prepared from the 4- hydroxypentenylstannane 18 for the synthesis of 5,6-dihydro- 2H-pyrans is not straightforward because the free hydroxy group derived from the stannane can lead to the formation of mixtures of products. Although these investigations could have been pursued, they were discontinued when a parallel study using a derivative of the 4-hydroxypentenylstannane18 resulted in the successful stereoselective synthesis of 2,6-disubstituted 5,6-dihydro-2H-pyrans.This work is described in the accompanying paper.* Nevertheless, the work described in this paper shows that the useful 1,5-asymrnetric induction observed during reactions between 5-alkoxypentenylstannanes and aldehydes is also found in the analogous reactions of the 43- disubstituted pent-2-enylstannane 18 and extends the use of this chemistry for stereoselective synthesis. Experimenta1 All non-aqueous reactions were carried out under an atmosphere of dry nitrogen or argon. 'H and ',C NMR spectra were recorded on Bruker AC 300, Varian XL 300 and Varian Gemini 200 spectrometers in 2Hchloroform unless otherwise stated. J Values are in Hz. IR spectra were measured on a Perkin-Elmer 1 71OFT spectrometer as evaporated films unless otherwise stated.Mass spectra were recorded on Kratos MS25, Kratos Concept and Fisons VG Trio 2000 mass spectrometers using electron impact (EI) or chemical ionisation (CI) modes. Chromatography refers to flash column chromatography on Merck silica 60 H (40-60pm, 230-300 mesh) or Sorbsil C60 silica gel. Analytical HPLC was performed using a C 18 Novapak cartridge (8 mm x 100 mm) with a Perkin-Elmer diode array system for detection at 254 nm. All solvents were dried by standard procedures and distilled before use. Light petroleum refers to the fraction which distils at 40-60 "C. Ether refers to diethyl ether. aID Values are given in units of lo-' deg cm2 g-'. Ethyl (4S,2E)-4,5-isopropylidenedioxypent-2-enoate9 was prepared and reduced to (4S,2E)-4,5-isopropylidenedioxypent-2-en01 10 as described in the literat~re.~ (4S,2E)-O-4,5-Isopropylidenedioxypent-2-enylS-methyl dithiocarbonate 11 A solution of alcohol 10 (64.1 g, 0.41 mol) in toluene (640 cm3) was added to a suspension of sodium hydride (60 dispersion in oil; 16.2 g) in toluene (1250 cm3) at 0 "C.The solution was allowed to warm to ambient temperature and stirred for 90 min before being cooled to 0 "C. Carbon disulfide (98.8 cm3, 1.64 mol) was added dropwise to it and then the reaction J. CHEM. SOC. PERKIN TRANS. 1 1995 mixture was allowed to warm to ambient temperature. The mixture was stirred for 4 h, cooled to Odeg;C and then iodomethane (100 cm3, 1.61 mol) was added dropwise to it.The mixture was then allowed to warm to ambient temperature and was stirred for 18 h. The mixture was filtered through Celite and the precipitate washed with CH,Cl,. The organic extracts were concentrated under reduced pressure to afford the title compound 11 (99.5 g, 100). This was used without purification, but a small portion was chromatographed on silica gel using light petroleum-ether (10: 1) as eluent for +characterisation (Found: M + NH,, 266.0877. C,,H,,-NO3amp; requires M, 266.0885); a;' +22.3 (c 2.6, CHCl,); v,,,/cm-' 1648, 1213, 1156, 1062 and 863; 6, 1.43 and 1.47(each3H,s,CH,CCH,),2.61(3H,s,SCH3),3.66(1H,t,J 8, 5-H),4.16(1 H,dd, J8, 6, 5-H'),4.59(1 H, 9, J7,4-H),5.14 (2 H, d, J6, 1-H2), 5.88 (1 H, dd, J 15,7,3-H) and 6.04(1 H, dt, J 15, 7, 2-H); 6c 19.1, 25.8, 26.7, 69.3, 72.7, 76.0, 109.6, 126.4, 133.3 and 215.5; m/z (CI) 266 (M' + NH,, loo), 249 (M+ + H, 51), 208 (18) and 191 (63).(4S,2E)-0-4,5-Dihydroxypent-2-enylS-methyl dithiocarbonate 12 Dilute hydrochloric acid (1 mol drn-,; 400 an3)was added dropwise to a solution of xanthate 11 (99 g, 0.4 mol) in tetrahydrofuran (1200 cm3) at 0 "C. The solution was allowed to warm to ambient temperature and stirred for 18 h then cooled to 0deg;C and saturated aqueous NaHCO, was added dropwise to it until effervescence ceased. The aqueous phase was extracted with ethyl acetate and the combined organic extracts washed with brine, dried (Na,SO,) and concentrated under reduced pressure to give a viscous oil which was triturated with pentane to afford the title compound 12 as an amorphous yellow solid (73.1 g, 88).A portion was purified for characterisation by chromatography on silica gel using light petroleum-ethyl acetate (1:2) as eluent (Found: Mf + NH,, 226.0571. C,H,,NO,S, requires M, 226.0572); ah2 +3.4 (c 2.3, CHCl,); v,,,/cm-' 3362, 1644, 1422, 1219, 1060, 969 and 872;6,2.53 (3 H,s, SCH,), 2.96 and 3.23 (each 1 H,br s,OH), 3.48 and 3.67 (each 1 H, m, 5-H), 4.28 (1 H, m, 4-H), 5.09 (2 H, d, J6, 1-H2), 5.83 (1 H, dd, J 16,5,3-H) and 5.98 (I H, dtd, J 16, 7, 1.5,2-H);dc 19.3,66.1,72.2,73.0, 125.1, 134.0and215.3;mlz (CI) 226 (M' + NH,, loo), 209 (Mf + H. 8), 195 (9) and 178 (68). (4S,2E)-0-4,5-Bis(tevt-b~tyldimethylsilyloxy)pent-2-enyl S-methyl dithiocarbonate 13 tert-Butyldirnethylsilyl trifluoromethanesulfonate (1.45 cm3, 8.28 mmol) was added to a solution of dioll2 (0.6 g, 2.88 mmol) and 2,6-lutidine (2,6-dimethylpyridine) (1.65 cm3, 14.1 mmol) in dichloromethane (10 cm3) at 0 "C.The mixture was stirred at 0deg;C for 5 min and then allowed to warm to ambient temperature and stirred for 30 min.The mixture was cooled to OOC, and saturated aqueous NaHCO, (5 cm3) was added dropwise to it. The mixture was extracted with ethyl acetate and the-organic extracts were washed with water and brine, dried (MgSO,) and concentrated under reduced pressure. Chromatog- raphy on silica gel using light petroleum-ethyl acetate (20: 1) as eluent gave the title compound 13 as a pale yellow oil (I .20 g, 95) (Found: M+ + NH,, 454.2297.Cl,H,,NO,S,Si, requires M, 454.2301); ah2 -7.7 (c 1.6, CHC1,); v,,,/cm^' 2857, 1472, 1255, 1218, 1062, 836 and 777; S, 0.09 6 H, S, Si(CH,),, 0.11 and 0.12 (each 3 H, s, SiCH,), 0.94 and 0.95 each 9 H, s, SiC(CH,),, 2.60 (3 H, s, SCH,), 3.49 and 3.61 (each 1 H, dd, J 10,6, 5-H), 4.28 (1 H, m, 4-H), 5.14 (2 H, m, 1- H2)and5.97(2H,m,2-Hand3-H);6, -5.3, -5.2, -4.7, 18.3, 18.4, 19.0, 25.9, 26.0, 67.7, 73.2, 73.6, 123.2, 137.1 and 215.5; m/z (CI) 454 (M' + NH,, 89), 329 (94), 305 (81) and 214 (100). J. CHEM. SOC. PERKIN TRANS. 1 1995 (4S,2E)-0-5-( tert-Butyldimethylsilyloxy)-4-hydroxypent-2-enyl S-meth y 1 di thiocar bonat e 14 tert-Butyldimethylsilyl chloride (58.0 g, 0.385 mol) in dichloromethane (500 cm3) was added dropwise to a solution of diol 12 (72.1 g, 0.347 mol), triethylamine (53 cm3, 0.380 mol), and 4-dimethylaminopyridine (2.1 g, 0.01 7 mo1)in dichlorometh- ane (600 cm3) at 0 "C over 2 h.The solution was allowed to warm to ambient temperature and stirred for 18 h before being cooled to 0 OC after which brine (200 cm3) was added dropwise to it. The aqueous phase was extracted with ethyl acetate and the organic extracts were dried (Na,SO,) and concentrated under reduced pressure. Chromatography on silica gel using gradient elution with pentane-ether (30: 1 to 5: 1) as eluent, gave the title compound 14as a yellow oil (76.8 g, 69) (Found: M + + NH,, 340.1432. C,,H30N0,S,Si requires M, 340.1436); Cali2 -4.1 (c 2.1, CHCI,); vmax/cm-' 3460, 2858, 1740, 1649, 1257, 11 17 and 837; 6, 0.1 6 H, s, Si(CH,),, 0.93 9 H, S, SiC(CH,),, 2.54 (3 H, s, SCH,), 2.62 (1 H, d, J 3.5, OH), 3.44 (1 H, dd.J 10, 7.5, 5-H), 3.66 (1 H, dd, J 10,4, 5-H), 4.22 (1 H, m, 4-H), 5.08 (2 H, d, J6, 1-H2), 5.81 (1 H, dd, J 16, 5.5, 3-H) and 5.99 (1 H, dtd, J 16, 6, 1.5, 2-H);dc -5.2, 18.4, 19.2, 25.9, 66.7, 71.8, 73.2, 124.7, 134.1 and 215.2; m/z (CI) 340 (M' + NH,, 94), 323 (M' + H, 16), 293 (18) and 292 (100). (4S)-4,5-Bis(tevt-butyldimeth ylsil ylox y)pen t-2enylI- (tributy1)stannane 16 A solution of xanthate 13 (1.20 g, 2.75 mmol) in toluene (10 cm3) was heated under reflux for 18 h. The solution was cooled and the solvent removed under reduced pressure to give the dithiocarbonate 15 as a mixture of epimers (1.19 g, 99); v,,,/cm-' 2858,1649, 1256, 1118,864,835 and 777;6,0.04 (9 H, br s, 3 x SiCH,), 0.11 (3 H, s, SiCH,), 0.88 l8 H, m, 2 x SiC(CH,),J, 2.38 (1 H, s, SCH,), 2.39 (2 H, s, SCH,), 3.45 (2H,m, 5-H,), 3.88(1 H,m,4-H),4.55(1 H,m, 3-H), 5.11 (0.33 H, m, 1-H), 5.16 (0.66 H, m, 1-H), 5.31 (I H, m, 1-H') and 5.87 (1 H, m, 2-H).The dithiocarbonate 15 (I. 19 g, 2.73 mmol) was dissolved in benzene (14 cm3) and the solution degassed with nitrogen for 90 min at ambient temperature. Tributyltin hydride (0.902 cm3, 3.35 mmol) and azoisobutyronitrile (AIBN) (cat.) were added, and the solution was heated under reflux for 4 h. The mixture was cooled and concentrated under reduced pressure.Chromatography on silica gel using light petroleum-ether ( 100: 1, 1 triethylamine) as eluent, gave the titfe compound 16 (1.53 g, 90), as an approximately 4: 1 mixture of E-and 2-isomers (Found: M+ -C,H,, 563.2758. C,,H,,O,Si, "'Sn requires M, 563.2763); v,,,/cm-l 2857, 1464, 1254, 1125, 1077, 836 and 777;dH 0.09 and 0.10 each 6 H, s, Si(CH,),, 0.93 33 H, m, 2 x SiC(CH,), and (CH,CH,CH,CH,),Sn, 1.20-1.90 14 H, m, (CH,CH,CH,CH,),Sn and l-H2, 3.45 (1 H, dd, J 10,5.5, 248 1 1.34 6 H, m, (CH3CH2CH,CH,),Sn, 1.51 6 H, m, (CH,CH,CH,CH,),Sn, 1.79 (2 H, d, J9, 1-H,), 1.96 and 2.06 (each 1 H, br s, OH), 3.51 and 3.62 (each 1 H, m, 5-H), 4.19 (1 H, m, 4-H), 5.27 (1 H, dd, J 15,7.5,3-H) and 5.96 (1 H, dt, J 15, 6.5, 2-H); dc 9.3, 13.7, 14.7, 27.3, 29.0, 67.0, 73.8, 123.2 and 134.8;m/z (EI) 361 (56), 359 (62), 335 (M' -C,H9, 49), 317 (40), 291 (95) and 235 (100).(4S)-5-(tert-ButyMimethylsilyloxy)4hydroxypent-2-enyl (tributy1)stan~ane 18 From xanthate 14. A solution of xanthate 14 (1 0.27 g, 3 1.9 mmol) in toluene (170 cm3) was heated under reflux for 18 h. The solution was cooled and an aliquot removed and concentrated under reduced pressure to give the dithiocarbonate 19as a pale yellow oil; vmax/cm-l 3407, 2858, 1730, 1648, 1256, 1116 and 869; dH 0.01 6 H, s, Si(CH3)2, 0.83 9 H, s, SiC(CH,),, 2.35 (3 H, s, SCH,), 3.56 (2 H, m, 5-H,), 3.75 and 3.82(each0.5H,m,4-H),4.31(1H,m,3-H),5.13(1H,m,I-H), 5.28 (1 H, m, 1-H') and 5.83 (1 H, m, 2-H).The remainder of the solution was degassed with nitrogen for 1 h and tributyltin hydride (16 cm3, 59.5 mmol) and AIBN (cat.) were added to it. The mixture was heated under reflux for 4 h and cooled, filtered and then concentrated under reduced pressure. Chromatography on silica gel using light petroleum- ether (20 :1, 1 triethylamine) as eluent, gave the title compound 18 as a colourless oil (12.92 g, 81) (Found: M' -Bu, 449.1892. Cl,H,,0,Si'20Sn requires M, 449.1897); vma,/cm-' 3464, 1656, 1463, 1254, 1106, 838 and 779; dH 0.12 6 H, s, Si(CH3),, 0.94 24 H, m, SiC(CH,), and (CH,CH,CH,- CH2),Sn, 1.20-1.90 I4 H, m, (CH,CH,CH,CH,),Sn and 1-H,,2.54(1 H,d, J2.5,OH), 3.42(1 H,dd, JlO,7,5-H),3.61 (1 H,dd, Jl0,3.5,5-H),4.11 (0.8H,m,4-H),4.49(0.2H,m,4-H), 5.06(0.2H,m,3-H), 5.22(0.8H,dd, J15,7.5,3-H), 5.80(0.2H, q, J 9.5, 2-H) and 5.93 (0.8 H, dt, J 15, 7, 2-H); m/z (EI) 453 (M' -C4H9, 1.4), 449 (M' -C4H9, 6), 445 (3), 291 (56) and 235 (80).From dihydroxystannane 17. tert-Butyldimethylsilyl chloride (0.11 g, 0.76 mmol) was added to a solution of the dihydroxystannane 17 (0.27 g, 0.69 mmol), triethylamine (0.11 cm3, 0.76 mmol) and 4-dimethylaminopyridine (cat.) in dichloromethane (1.5 cm3) at 0 "C. The solution was allowed to warm to ambient temperature and stirred for 18 h. Brine (1.5 cm3) was added to the mixture, and the aqueous phase extracted with ethyl acetate. The organic extracts were dried (MgSO,) and then concentrated under reduced pressure. Chromatography on silica gel using light petroleum-ether (20: 1, 1 triethylamine) as eluent, afforded the title compound as a colourless oil (0.28 g, 80).General procedure for the reactions of stannane 18 with 5-H),3.53(1H,dd,J10,7,5-H'),4.14(1H,m,4-H),5.25(1H,dd,aldehydes J 15, 6.5, 3-H) and 5.81 (1 H, dt, J 15, 8, 2-H); m/z (EI) 563 (M+ -Bu, 473, 365 (38), 363 (35) and 291 (100). (2S)-4,5-Dihydroxypent-2-enyl(tributy1)stannane 17 Tetrabutylammonium fluoride (1.1 mol dmP3 in tetrahydro- furan; 6.2 cm3) was added dropwise to a solution of stannane 16 (1.28 g, 3.27 mmol) in tetrahydrofuran (22 cm3) at 0 "C. The solution was allowed to warm to ambient temperature and stirred for 7 h. Brine (5 cm3) was added to it and the mixture stirred for 30 min before being extracted with ethyl acetate.The combined organic extracts were dried (MgSO,) and then concentrated under reduced pressure. Chromatography on silica gel using light petroleum-ethyl acetate (2: 1, 1 triethylamine) as eluent gave the titfe compound 17 as a colourless oil (0.54 g, 66) (Found: M+ -Bu, 335.1036. C, ,H2,OZ1 "Sn requires M, 335.1033); vmax/cm-' 3373, 1655, 1463,1073 and 873; dH0.93 15 H, m, (CH3CH2CH2CHz),Sn, Tin@) chloride (1 mol dm-, in dichloromethane) was added dropwise to a solution of the stannane 18 (0.145 mol drn-,; 1 mol equiv.) in dichloromethane at -78 "C. The solution was stirred at -78 "C for 5 min before the aldehyde (1-2 mol equiv.) in dichloromethane was added to it. The solution was stirred at -78 "C for 1 h, then saturated aqueous NaHCO, was added to it, and the mixture allowed to warm to ambient temperature and then extracted with ethyl acetate.The combined organic extracts were washed with water and brine, dried (MgSO,) and then concentrated under reduced pressure. Chromatography on silica gel, using light petroleum-ethyl acetate (1 triethylamine) as eluent, afforded the products as colourless oils. The following compounds were prepared using this procedure. (1S,5S,3Z)-6-(tert-Butyldi1nethylsilyloxy)-1 -amp;en ylhex-kne- 1,5-dioi 20. (0.26 g, 86) (Found: M+ + NH,, 340.2293. C18H34N03Si requires M, 340.2308); Calk2 -28.2 (c 2.5, CHCI,); vmax/cm-' 3361,2857, 1471, 1255, 11 13, 1055,837,779 2482 and 700; 6, 0.1 6 H, s, Si(CH,),, 0.95 9 H, s, SiC(CH,),, 2.50 (1 H, m, 2-H), 2.72 (1 H, dt, J 14,8.5,2-H'), 3.05 and 3.21 (each 1 H, br s, OH), 3.46 (1 H, dd, J 10,8,6-H), 3.53 (1 H, dd, J 10,4.5,6-H), 4.45 (1 H, td, J8,4.5, 5-H), 4.72 (1 H, dd, J8,4.5, l-H),5.59(1H,dd,Jll,8,4-H),5.72(1H,m,3-H)and7.38(5 H, m, ArH); 6, -5.3, -5.2, 18.4, 25.9, 38.4, 66.6, 67.8, 73.0, 125.8,127.5, 128.4, 130.3, 131.2 and 144.3; m/z (CI) 340(M+ + NH,, 58) and 322 (M+, 100). (2S,6S,3Z)-1-(tert-Butyldimethylsilyloxy)octa-3,7diene-2,6-diol 29.(2.39 g, 87) (Found: M+ + NH,, 290.2151. C1,H,,NO3Si requires M, 290.2151); ah2 +31.5 (c 2.9, CHC1,); v,,x/cm-l 3362, 2858, 1471, 1255, 1118, 1060, 837 and 778; BH 0.10 6 H, s, Si(CH,),, 0.94 9 H, s, SiC(CH,),, 2.33 (1 H, dt, J 13, 6, 5-H), 2.47 (1 H, dt, J 14, 8, 5-H), 2.97 and 3.10 (each 1 H, brs,OH), 3.54(1 H,dd, JlO,7, 1-H),3.62(1 H,dd, J 10,4, I -H'), 4.15 and 4.46 (each 1 H, m, 2-H and 6-H), 5.14 (1 J.CHEM. SOC. PERKIN TRANS. 1 1995 A stream of ozone in oxygen was bubbled through a solution of the acetate 22 (0.097 g, 0.24 mmol) in dichloromethane (5 cm3) at -78 "C for 20 min until a blue coloration persisted. A stream of oxygen was then bubbled through the solution for 5 min until the blue coloration was discharged. Methyl sulfide (0.5 cm3, 6.81 mmol) was added to the mixture dropwise at -78 "C and the mixture was then allowed to warm to ambient temperature. Concentration under reduced pressure gave a residue which was dissolved in dry ether (2 cm3) and the solution added dropwise to a suspension of lithium aluminium hydride (0.073 g, 1.92 mmol) in ether (2 cm3) at 0 "C.The mixture was allowed to warm to ambient temperature and stirred for 18 h, then cooled to 0 OC, and aqueous hydrogen chloride (2 cm3) added dropwise to it. The mixture was extracted with ethyl acetate and the combined organic extracts were washed with brine, dried (MgSO,) and then concentrated H,d,J10.5,8-H),5.28(1H,d,J17,8-H'),5.57(1H,dd,J11,8,under reduced pressure. Chromatography on silica gel, using ethyl acetatedichloromethane (2 :3) as eluent, afforded (S)-1- phenylpropane-1,3-diol23(28 mg, 77) (Found: M+ + NH,, 170.1179. C,H16N02 requires M, 170.1181); a;, -57.4 (c 0.6, CHCl,) (1it.,l6 -63.8); v,,,/cmP' 3342, 1494, 1453, 1050, 760 and 701; 6, 2.05 (2 H, m, 2-H2), 2.54 and 2.98 (each 1 H, br s, OH), 3.90 (2 H, t, J6,3-H2), 5.00 (1 H, dd, J8.5,4, 1-H) and 7.35 (5 H, m, ArH); m/z (CI) 170 (M' + NH,, 68) and 152 (Mf, 100).(2S,6S,32)-6-Phenylhex-3-ene-1,2,6-triol24 Tetrabutylammonium fluoride (1 mol dm in tetrahydrofuran; 1 cm3) was added dropwise to a solution of the silyl ether 20(0.21 7.5,4,2-H),5.58(1H,dd,J11.5,8,3-H)and5.72(1H,m,4-H);mg, 0.65 mmol) in tetrahydrofuran (5cm3) at 0 "C. The solution Sc -5.4, -5.3,10.0,18.3,25.9,30.1,35.5,66.7,67.8,71.9,130.8was allowed to warm to ambient temperature and stirred for 18 and 130.9; m/z (CI) 292 (M+ + NH,, 52), 274 (M', 50)and 3-H), 5.67 (1 H, m, 4-H) and 5.91 (1 H, ddd, J 17, 10.5, 5.5, 7- H); 6c -5.4, -5.3, 18.3, 25.9, 35.9, 66.7, 67.9, 71.6, 114.8, 130.0, 131.1 and 140.5; m/z (CT) 290 (Mf + NH,, 24), 272 (M+,29) and 255 (100).(2S,6R,3Z)-l-(tert-Butyldimethylsilyloxy)oct-3-ene-2,6diol 30.(0.4g, 75) (Found: Mf + NH,, 292.2313. C,,H,,NO,Si requires M, 292.2308); a;, + 38.0 (c 1.4, CHCl,); v,,,/cm-' 3365, 2858, 1464, 1256, 1116, 838 and 779; 6, 0.09 6 H, S, Si(CH,),, 0.93 9 H, s, SiC(CH,),, 0.99 (3 H, t, J 7.5, 8-H3), 1.56 (2 H, m, 7-H,), 2.27 (1 H, m, 5-H), 2.38 (1 H, dt, J 14,9,5-H'), 2.52 and 3.02 (1 H, br s, OH), 3.53 (1 H, dd, J 10, 8, 1-H), 3.55 (1 H, m, 6-H), 3.64 (1 H, dd, J 10,4, 1-H), 4.47 (1 H, td, J 257( 100). Ethyl (2S,6S,4Z)-7-(tevt-butyldimethylsilyloxy)-2,6dihydr-oxyhept4enoate 31. (0.2 g, 78) (Found: M+ + NH,, 336.2226.C,,H,,NO,Si requires M, 336.2206); vmax/m-'3410, 2858, 1736, 1255, 1207, 1112, 838 and 779; 6, 0.12 6 H, S, Si(CH,),, 0.94 9 H, s, SiC(CH,),, 1.34 (3 H, t, J 7, OCHZCH,), 2.64 (2 H, t, J 6,3-H,), 3.52 (1 H, dd, J 10,8,7-H), 3.66 (1 H, dd, J 10,4,7-H'), 4.35 (3 H, m, OCH,CH, and 2-H), 4.48 (1 H, td, J8,4,6-H), 5.61 (1 H, dd, J 11,6.5,5-H) and 5.67 (1 H, dt, J 11, 6.5, 4-H);Sc -5.4, -5.3, 14.2, 18.3, 25.9, 32.8, 61.9, 66.6, 68.1, 69.6, 127.7, 132.1 and 174.3; m/z (CI) 336 (M' + NH,, 65), 318 (M', 70), 301 (56), 290 (91) and 169 (100). (1S,6S,3Z)-1,5-Diacetoxy-6-(tert-butyldimethylsilyloxy)-1-phenylhex-Sene22 Acetic anhydride (0.266 cm3, 2.82 mmol) was added dropwise to a solution of the diol 20 (0.083 g, 0.26 mmol) in pyridine (1 cm3) and 4-dimethylaminopyridine (cat.) at 0 "C.The mixture was allowed to warm to ambient temperature and was stirred for 3 h. The solution was cooled to 0 "C and saturated aqueous NaHCO, (1 cm3) was added to it. The mixture was extracted with ethyl acetate and the organic extracts were washed with saturated aqueous CuSO,, water and brine, dried (MgSO,) and then concentrated under reduced pressure. Chromatography on silica gel using light petroleum-ethyl acetate (8 : 1) as eluent gave the title compound22(0.097 g, 93) (Found: M+ + NH,, 424.2518. C,,H,,NO,Si requires M, 424.2519); a;, +43.7 (c 0.8, CHCl,); v,,,/cm-' 2858, 1740, 1371, 1236, 1026 and 838; 6, 0.01 6 H, s, Si(CH,),, 0.86 9 H, s, SiC(CH,),, 2.01 and 2.05 (each 3 H, s, CH,CO), 2.68 and 2.81 (each 1 H, m, 2-H), 3.37 (1 h.Methanol (2 cm3) and water (0.1 cm3) were added to it and the mixture was stirred for a further 30 min. The solution was dis- solved in ethyl acetate, washed with brine, dried (MgSO,) and then concentrated under reduced pressure. Chromatography on silica gel, using ethyl acetate as eluent afforded the titlecompound 24(0.130 g, 96) (Found: Mf + NH,, 226.1445. Cl,H,,NO, requires M, 226.1443); a;, -80.4 (c 2.3, CHCl,); vmax/cm-l 3347,1453, 1028,872 and 760;6,2.41 (1 H, dt, J 14,4,5-H), 2.70 (1 H,dt, J14,9,5-H),3.40(1 H, brs,OH), 3.50(2H,m, l-H2), 4.00(2H,brs,2 x OH),4.50(1H,m,2-H),4.69(1H,dd,J13.5, 3.5,6-H), 5.65 (2 H, m, 3-H and 4-H) and 7.38 (5 H, m, ArH); 6, 37.9,65.9,67.8,72.9,125.7,127.7,128.8,130.2, 131.5 and 144.0; m/z (CI) 226 (M' + NH,, 11) and 208 (M', 100).(1S,5S,3Z)-5,6-Isopropylidenedioxy-l-phenylhex-3-enol25 A catalytic amount of pyridinium toluene-p-sulfonate was added to a solution of trio1 24 (95 mg, 0.46 mmol) in 2,2- dimethoxypropane (1 cm3) and dry N,N-dimethylformamide (0.5 cm3) and the solution was stirred for 18 h at ambient temperature. The mixture was dissolved in ethyl acetate (1 5 cm3) and washed with brine, dried (MgSO,) and then concentrated under reduced pressure. Chromatography on silica gel, using light petroleum-ethyl acetate (3 : 1) as eluent, afforded the title compound 25 (82 mg, 73) (Found: M++ PH,, 266.1752. C, ,H,,NO, requires M, 226.1756); a;, -70.0 (c 2.3, CHCl,); vmax/cm-' 3439, 1372, 1215, 1156, 1057 and 860;6,1.41 and 1.44 (each 3 H, s, CH,CCH,), 2.58 (2 H, m, 2-H and OH), 2.68 (1 H, dt, J 14, 6.5, 2-H'), 3.42 (1 H, t, J 8, 6-H), 3.84 (1 H, dd, J 8 and 6,6-H'), 4.73 (2 H, m, 1-H and 5-H), 5.58(1H,dd,J11,8,4-H),5.70(1H,dt,Jll,7.5,5-H)and7.38 (5 H, m, ArH);6, 25.9,26.7, 38.1,69.2, 71.7, 73.5, 109.2, 125.9, + NH,,127.7, 128.5, 130.3, 130.4 and 143.9; m/z (CI) 266 (M' H,dd,Jll,4,6-H),3.47(1H,dd,Jll,7,6-H),5.38(1H,m,3-H), 5.43-5.58 (2 H, m, 4-H and 5-H), 5.76 (1 H, t, J 7, 1-H) and 7.31 (5 H, m, ArH);6, -5.2, 18.4, 21.3, 25.9, 35.2, 64.5, 70.9, 75.0, 126.5, 127.5, 127.9, 128.3, 129.4, 139.7, 169.9 and 170.0; m/z (CI) 424 (M' + NH,, loo), 347 (18), 288 (26) and 287 (92).21), 248 (M+, 14), 231 (100) and 208 (83) (1R,SS,3Z)-5,6-Isopropylidenedioxy-l-phenylhex-3-enyl4-nitrobenzoate 26 Diisopropyl diazodicarboxylate (1.8 cm3, 8.85 mmol) was J. CHEM. SOC. PERKIN TRANS. 1 1995 added dropwise to a solution of the alcohol 25 (0.44 g, 1.77 mmol), triphenylphosphine (2.33 g, 8.85 mmol) and 4-nitrobenzoic acid (1.30 g, 7.79 mmol) in toluene (25 cm3) at -30 OC. The mixture was allowed to warm slowly to ambient temperature and stirred for 18 h. The solution was filtered through a silica plug, the plug was washed with ethyl acetate, and then the filtrate was concentrated under reduced pressure. The residue was adsorbed onto silica, and chromatography using light petroleum-ethyl acetate (10: 1) as eluent, gave the title compound 26 (0.6 g, 79); a;, -28.3 (c 1.6.CHCl,); v,,,/cm ' 1726, 1607, 1529, 1272, 1102, 1059 and 848; BH 1.41 and 1.44 (each 3 H, s, CH,CCH,), 2.91 (2 H, m, 2-H,), 3.43 (1 H, t, J8,6-H), 3.91 (1 H,dd, J8,6,6-H),4.77(1 H, 9, J7,5-H), 5.59(1 H,dd, J11,7,4-H),5.67(1 H,dt, J11,7,3-H),6.11 (1 H, t,J6.5, l-H),7.42(5H,m,ArH)and8.27and8.34(each2H,d, J 9.5, ArH); BC 25.9, 26.7, 34.6, 69.2, 71.8, 76.8, 109.3, 123.6, 126.4, 128.1, 128.5, 128.7, 130.8, 131.0, 135.6, 139.0, 150.7 and 163.8;m/z (CI) 415 (M' + NH,, 38) and 340 (100). (I R,5S,3Z)-5,6-lsopropylidenedioxy-l-phenylhex-3-enol27 Sodium hydroxide (0.2 mol dm-, in methanol; 10 cm3) was added to a solution of nitrobenzoate 26 (0.54 g, 1.36 mmol) in dry methanol (2 cm3) at ambient temperature and the mixture stirred for 18 h before being diluted with ethyl acetate, and washed with water and brine, dried (MgSO,) and then concentrated under reduced pressure.Chromatography on silica gel using light petroleum-ethyl acetate (3 : 1) as eluent, afforded the title compound 27 as a colourless oil (0.25 g, 73) (Found: M ' + NH,, 266.1750. C,,H,,NO, requires M, 266.1756); Cali2 +48.9 (c 2.3, CHCl,); v,,,/cm ' 3448, 1216, 1156, 1057 and 860; 6, 1.41 and 1.44 (each 3 H, s, CH,CCH,), 2.50 (1 H, br s, OH), 2.63 (2 H, m, 2-H,), 3.50 and 3.98 (each 1 H,m,6-H),4.75(2H,m, l-Hand5-H), 5.60(1 H,m,4-H), 5.73 2483 organic extracts were washed with water and brine, dried (MgSOJ and then concentrated under reduced pressure.Chromatography on silica gel using light petroleum-ethyl acetate (3 : 1) as eluent, afforded the title compound 21 (94 mg, 67) (Found: M+ + H, 323.2038. C,,H,,O,Si requires M, 323.2042); Calk2 +86.3 (c 1.6, CHCl,); vmax/cm ' 3385, 2858, 1256, 1110, 1053 and 837; dH0.12 6 H, s, Si(CH,),, 0.86 9 H, s, SiC(CH,),, 2.69 (4 H, m, 2-H, and 2 x OH), 3.49 (1 H, dd, J 10, 8, 6-H), 3.61 (1 H, dd, J 10, 4, 6-H'), 4.47 (1 H, td, J 8, 4, 5-H), 4.84 (1 H, dd, J 6.5, 4.5, 1-H), 5.56 (1 H, dd, J 11, 8, 4-H), 5.66 (1 H, dt, J 11, 8, 3-H) and 7.35 (5 H, m, ArH);S, -5.3, -5.2, 18.4, 25.9, 37.7, 66.7, 68.2, 73.0, 125.8, 127.5, 128.4, 129.5, 131.2 and 144.0; m/z (CI) 340 (M+ + NH,, 12), 323 (M+ + H, 68), 322 (M', 57) and 305 (100). (2S,6S,3Z)-Octa-3,7-diene-1,2,6-triol32 Tetrabutylammonium fluoride (1 mol dm in tetrahydrofuran; 4 cm3) was added dropwise to a solution of diol29 (0.87 g, 3.2 mmol) in tetrahydrofuran (20 cm3) at 0 "C and the solution allowed to warm to ambient temperature and stirred for 18 h.Methanol (5 cm3) and water (ca. 0.5 cm3) were added to it and the mixture was stirred for 1 h before being concentrated under reduced pressure. Chromatography on silica gel using ethyl acetate as eluent, gave the title compound 32 (0.50 g, 99) (Found: M+ + NH,, 176.1288. CsH,,NO, requires M, 176.1287); a;' + 13.5 (c 2.8, CHCl,); v,,,/cm-' 3381, 3016, 1645, 1426, 1075, 1026and734;SH2.30(1 H,dt, J14,4.5, 5-H), 2.49 (1 H, dt, J 14, 8, 5-H'), 3.58 (4 H, m, 1-H, and 2 x OH), 4.19(2H,m),4.55(1H,m,2-H),5.17(1 H,d,J10.5,8-H),5.30 (1 H, d, J 17, 8-H'), 5.66 (2 H, m, 3-H and 4-H) and 5.93 (1 H, ddd, J 17, 10.5, 6, 7-H); 6, 35.6, 66.0, 67.6, 71.6, 115.1, 130.0, 131.6 and 140.3; m/z (CI) 176 (M+ + NH,, 98), 159 (M' + H, 53) and 158 (M', 100).(1 H,dt,Jl0,8,3-H)and7.38(5H,m,ArH);Sc25.9,26.8,37.5, 69.3, 71.9, 73.3, 109.2, 125.7, 127.6, 128.5, 130.1, 130.2 and 143.9; m,':(CI) 266 (M' + NH,, 28), 248 (M', 14), 231 (88) and 208 (100). (2S,6R,32)-6-Phenylhex-3-ene-l,2,6-trioI28 Aqueous HCl (1 mol dm-,; cm3) was added dropwise to a solution of acetonide 27 (0.196 g, 0.79 mmol) in tetrahydro- furan (3 cm3) at 0deg;C. The solution was allowed to warm to ambient temperature and stirred for 18 h. Ethyl acetate (10 cm3) was added to the mixture, the solution cooled to 0 "C and saturated aqueous NaHCO, (5 cm3) added dropwise to it.The aqueous layer was extracted with ethyl acetate and the organic extracts were washed with brine, dried (MgSO,) and then concentrated under reduced pressure to give the title compound 28 (0.I55 g. 94) which was used without further purification (Found: M' + NH,, 226.1448. C,,H,,NO, requires M, 226.1443); cxA2 +99.6 (c 2.3, CHCl,); v,,,/cm 3347, 1494, 1028, 871 and 701; 6, 2.65 (2 H, m, 5-H,), 2.85 (3 H, br s, 3 x OH), 3.57 (2 H, m, 1-H2), 4.49 (1 H, m, 2-H), 4.84 (1 H, t, J 6, 6-H), 5.60 (2 H, m, 3-H and 4-H) and 7.35 (5 H, m, ArH); b', 37.4. 66.1. 68.2, 73.0, 125.8, 127.7, 128.4, 129.3, 131.7 and 143.6;m/z (CI) 226 (M' + NH,, 13), 208 (M+,100) and 173 (45).(1R,5S,3Z)-6-( tevt-Butyldimethylsilyloxy)-l-phenylhex-3-ene-1,5diol21 tert-Butyldimethylsilyl chloride (70 mg, 0.46 mmol) was added dropwise to a solution of triol 28 (91 mg, 0.44 mmol), triethylamine (0.070 cm3, 0.48 mmol) and a catalytic quantity of 4-dimethylaminopyridine in dichloromethane (2 cm3) at 0 "C. The mixture was allowed to warm slowly to ambient temperature and stirred for 18 h, then partitioned between ethyl acetate (10 cm3) and saturated aqueous NaHCO, (10 cm3), and the aqueous phase extracted with ethyl acetate. The combined (2S,6R,3Z)-Oct-3-ene-l,2,6-triol33 Following the procedure outlined for the synthesis of 32, the diol 30 (90 mg, 0.33 mmol) gave the title compound 33 (45 mg, 86) (Found: M+ + NH,, 178.1447.C8H,,N03 requires M, 178.1443); Calk2 +28.3 (c 1.0, CHCl,); vman/cm ' 3346, 1659, 1461, 1076, 1022 and 869; 6,0.99 (3 H, t, J 7,8-H,), 1.55 (2 H, m, 7-H,), 2.22 (1 H, m, 5-H), 2.38 (1 H, dt, J 14,9, 5-H'), 3.60 (5 H, m, 1-H,, 6-H and 2 x OH), 4.39 (1 H, br s, OH), 4.53 (I H, m,2-H)and5.66(2H,m,3-Hand4-H);6,10.1,30.2,35.3,66.1, 67.7, 72.0, 130.8 and 131.2; m/s (CI) 178 (M+ + NH,, 19) and 160(M+, 100) (3R,7S,52)-7,8-1sopropylidenedioxyoct-5-en-3-ol34 Following the procedure outlined above for the synthesis of 25,the triol 33 (0.081 g, 0.51 mmol) gave, after chromatogra- phy on silica gel using light petroleum-ethyl acetate (4: 1) as eluent, the title compound 34 (0.076 g, 75) (Found: M+ + NH,, 218.1754. C,,H,,NO, requires M, 218.1756); Cali2 + 6.1 (c 1.5, CHCI,); vmax/cm-' 3432, 1457, 1372, 1216, 1157, 1059 and 860; BH 1.00 (3 H, t, J 7.5, 1-H,), 1.41 and 1.44 (each 3 H, s, CH,CCH,), 1.55 (2 H, m, 2-H,), 1.90 (1 H, br s, OH), 2.33 (2 H, m, 4-H2), 3.60 (2 H, m, 3-H and 8-H), 4.12 (1 H, dd, J8, 6, 8-H'), 4.88 (1 H, q, J7, 7-H), 5.64 (1 H, dd, J 11, 8, 6-H) and 5.76 (1 H, dt, J 11, 8, 5-H); 6, 10.0, 25.9, 26.8, 29.8, 35.4, 69.4, 71.8, 72.3, 109.2, 130.1 and 131.2; m/z (CI) 218 (M' + NH,, 4373, 201 (M+ + H, 10) and 160 (100).(3R,7S,5Z)-7,8-1sopropylidenedioxyoct-5-en-3-y1 methanesulfonate 35 Methanesulfonyl chloride (0.1 1 cm3, 1.43 mmol) was added dropwise to a solution of acetonide 34 (96 mg, 0.48 mmol) and triethylamine (0.2 cm3, 1.43 mmol) in dichloromethane (2 cm3) at 0 "C.The mixture was stirred at 0 "C for 1 h, then saturated 2484 aqueous NaHCO, (2 cm3) was added to it, and the mixture allowed to warm to ambient temperature before being partitioned between ethyl acetate (10 cm3) and water (10 cm3). The aqueous phase was extracted with ethyl acetate and the organic extracts were washed with brine, dried (MgSO,) and then concentrated under reduced pressure to afford the title compound 35 (0.130 g, 97) which was used without further purification (Found: M+ + NH,, 279.1259. C12H2,05S requires M, 279.1266); ah2 +33.9 (c 1.5, CHCI,); vmax/cm-l 1350, 1216, 1174, 1059, 911 and 859; 6, 1.00 (3 H, t, J 7.5, 1-H,), 1.38 and 1.41 (each 3 H, s, CH,CCH,), 1.73 (2 H, m, 2- H,), 2.54 (2 H, m, 4-H,), 3.01 (3 H, s, CH,S03), 3.53 (1 H, t, J 8, 8-H), 4.09 (1 H, dd, J 8, 6, 8-H), 4.66 (1 H, quintet, J 6, 3-H), 4.80 (1 H, q, J 7, 7-H), 5.59 (1 H, dd, J 11, 7, 6-H) and 5.66 (1 H, dt, J 11, 6, 5-H); 6, 9.5, 25.9, 26.8, 27.3, 32.4, 38.6, 69.3, 71.8, 83.7, 109.3, 127.9 and 131.2; m/z (CI) 296 (M+ + NH,, lo), 279 (M+ + H, 7) and 238 (100).(2S,6R,3Z)-6-Methylsulfonyloxyoct-3-ene-1,2-diol36 Following the procedure used to prepare 28, the acetonide 35 (0.089 g, 0.32 mmol) was hydrolysed to give the title compound 36 (0.053 g, 70); ah2 +45.4 (c 1.5, CHCl,); v,,,/cm-' 3385, 1335, 1172, 1076,976and911;6,1.04(3H,t,J7,8-H3), 1.79(2 H, quintet, J 7,7-H,), 2.46 (1 H, dt, J 15,5.5,5-H), 2.66 (1 H, dt, J 15, 7, 5-H'), 3.05 (3 H, s, CH,SO,), 3.30-3.80 (4 H, m, 1-H, and 2 x OH), 4.59 (1 H, m, 2-H), 4.70 (1 H, m, 6-H) and 5.63 (2 H, m, 3-H and 4-H); dC 9.6, 27.6, 32.7, 38.8, 66.0, 68.3, 84.6, 127.4and 132.3; m/z (CI) 256 (M' + NH,, 5379,238 (M', 15) and 160 (100).(2S,6amp;3z)-l-( tert-Butyldimethylsilyloxy)-6-methylsulfonyl-oxyoct-3-en-2-ol37 Following the procedure outlined for the synthesis of 21, the diol 36 (0.156 g, 0.66 mmol) gave, after chromatography on silica gel using light petroleum-ethyl acetate (4: 1) as eluent, the title compound 37 (0.168 g, 73); +51.6 (c 0.9, CHCI,); vmax/cmp' 3446, 2858, 1338, 1174, 913 and 838; 6,0.12 6 H, s, Si(CH,),, 0.95 9 H, s, SiC(CH,),, 1.04 (3 H, t, J 7, 8-H3), 1.79(2 H, quintet, J7,7-H2), 2.49 (1 H, dt, J 14, 5, 5-H), 2.66 (2 H, m, 5-H' and OH), 3.05 (3 H, s, CH,SO,), 3.49 (1 H, dd, J 10, 8, 1-H), 3.63 (1 H, dd, J 10,4, 1-H'), 4.49 (1 H, m, 2-H), 4.72 (1 H, quintet, J 7, 6-H) and 5.62 (2 H, m, 3-H and 4-H); 6, -5.4, -5.3,9.5, 18.3,25.9,27.5,32.7,38.8,66.6,68.3,84.1, 127.4and 131.9; m/z (CT) 370 (M' + NH,, 40), 335 (21), 274 (100) and 257 (70).(2S,6S,4z)-7-(tert-Butyldimethylsilyloxy)hept4ene-1,2,6-triol 39 Diisobutylaluminium hydride (1 mol dmP3 in hexane; 2.44 cm3) was added dropwise to a solution of the hydroxy ester 31 (0.176 g, 0.55 mmol) in dichloromethane (5 cm3) at -78 "C. The solution was stirred for 1 h at -78 "C and then allowed to warm slowly to ambient temperature and stirred for 2 h. After cooling to -78 OC, methanol (2 cm3) was added dropwise to it and the mixture allowed to warm to 0deg;C.Saturated aqueous NH,Cl (6 cm3) was added to the mixture and the suspension was stirred for 18 h and then filtered through Celite. The filter cake was washed with ethyl acetate, and the filtrate was washed with 5 aqueous NaSO,, dried (MgS04) and then concentrated under reduced pressure. Chromatography on silica gel using ethyl acetate as eluent, gave the title compound 39 (0.089 g, 65) (Found: M+ + NH,, 294.2098. C,,H,,NO,Si requires M, 294.2101); v,,,/cm-' 3362, 2858, 1255, 1100, 837 and 778; BH 0.12 6 H, s, Si(CH,),, 0.94 9 H, s, SiC(CH,),, 2.24 (1 H, m, 3-H), 2.48 (1 H, m, 3-H'), 3.40 (3 H, br s, 3 x OH), 3.56 (2 H, m), 3.66 (2 H, m), 3.77 (1 H, m, 2-H), 4.77 (1 H, td, J7, 4, 6-H), 5.59 (1 H, dd, J 11, 8, 5-H) and 5.74 (1 H, m, 4-H); dC -5.4, J. CHEM.SOC. PERKIN TRANS. 1 1995 -5.3, 18.4, 25.9, 32.0, 66.3, 66.6, 67.7, 70.9, 130.5 and 130.8; m/z(CI) 294 (M+ + NH,, 83), 276 (M', 100) and 259 (75). (2S,6S,4Z)-7-(tert-Butyldimethylsilyloxy)-2,6dihydroxyhept-Cenyl toluene-p-sulfonate 41 Dibutyltin oxide (0.060 g, 0.24 mmol) was added to the trio1 39 (0.067 g, 0.24 mmol) in methanol (6 cm3) and the solution heated under reflux for 1 h and then cooled to 0deg;C. Triethylamine (0.102 cm3, 0.73 mmol) and toluene-p-sulfonyl chloride (0.140 g, 0.73 mmol) were added to it and the mixture was allowed to warm to ambient temperature and stirred for 18 h. The mixture was then filtered through Celite, the filter cake washed with ethyl acetate, and the filtrates were concentrated under reduced pressure. Chromatography on silica gel using light petroleum-ethyl acetate as eluent gave the title compound 41 (0.071 g, 68) (Found: M+ + NH,, 448.2186. C20H38- NOsSSi requires M, 448.2189); v,,,/cm-' 3379, 2857, 1361, 1253, 1177, 1098 and 836; 6, 0.12 6 H, s, Si(CH3),, 0.95 9 H, s, SiC(CH,),, 2.40 (2 H, m, 3-H,), 2.48 (3 H, m, ArCH,), 2.70 (2 H, br s, 2 x OH), 3.52 (1 H, dd, J 10,8,7-H), 3.65 (1 H, dd, J 10,4,7-H'), 3.88 (1 H, m, 2-H), 4.02 (2 H, m, 1-H,), 4.42 (1 H, td, J 7, 3.5, 6-H), 5.62 (2 H, m, 4-H and 5-H) and 7.40 and 7.84 (each 2 H, d, J 7, ArH); 6, -5.4, -5.3, 18.3, 21.7, 25.9, 31.9,66.5,67.7,68.0, 128.9,129.5,130.0, 131.4, 132.7and 145.0; m/z (CI) 448 (M+ + NH,, 100) and 430 (M+, 10).Following the standard procedure outlined above, reaction of the aldehyde 47 (0.8 mmol) with stannane 18 which had been treated with tin(1v) chloride gave the toluene-p-sulfonate 41 (0.22 g, 71). 2,3-Dihydroxypropyl toluene-p-sulfonate 45 A catalytic quantity of 4-dimethylaminopyridine and toluene-p- sulfonyl chloride (4.33 g, 22.7 mmol) were added to the 2,3- isopropylidenedioxypropanol43(2.0 g, 15.2 mmol) in pyridine (10 cm3) at 0 "C and the solution was allowed to warm to ambient temperature and stirred for 18 h. The mixture was then decanted into a mixture of ice-water (100cm3)and ethyl acetate (100 cm3), and allowed to warm to ambient temperature. The aqueous layer was extracted with ethyl acetate and the organic extracts were washed with saturated aqueous CuSO,, brine and water, dried (MgSO,) and then concentrated at reduced pressure to afford the toluene-p-sulfonate 44 (4.33 g, 100) which was used without further purification; v,,,/cm 1366, 1177, 1055, 979 and 828; 6, 1.31 and 1.34 (each 3 H, s, CH,CCH,), 2.45 (3 H, s, CH,Ar), 3.76 (1 H, dd, J 9, 5, 3-H), 4.05 (3 H, m, 1-H, and 3-H'), 4.28 (1 H, quintet, J 5, 2-H) and 7.35 and 7.79 (each 2 H, d, J 8, ArH); 6, 22.2, 25.6, 27.1, 66.7, 70.0, 73.4, 110.5, 128.5, 130.4, 133.1 and 145.6; m/z (CI) 304 (M+ + NH,, 100)and287(M+ + H, 18).Aqueous hydrogen chloride (3 mol drn-,; 2 cm3) was added to a solution of the toluene-p-sulfonate 44(1.5 g, 5.2 mmol) in tetrahydrofuran (6 cm3) at ambient temperature and the mixture stirred for 4 h.It was then cooled to 0 "C and saturated aqueous NaHCO, added dropwise to it until effervescence ceased. The mixture was extracted with ethyl acetate and the combined organic extracts were washed with brine, dried (MgSO,) and then concentrated under reduced pressure to give the title compound 45,l (1.28 g, 99) which was used without further purification; v,,,/cm-' 3365, 1356, 1176, 1097, 1052 and 975; 6, 2.41 (3 H, s, CH,Ar), 3.3-3.95 (5 H, m, 3-H,, 2-H and 2 x OH), 4.01 (2 H, m, 1-H,), and 7.32 and 7.76 (each 2 H, d, J 8,ArH);dC22.1,63.3,70.1,71.3,120.5, 130.5, 132.7and 145.7; m/z(CI) 264 (M' + NH,, 100). 2- Oxoe thy1 toluene-p-sul fona te 47 Sodium periodate (6.75 g, 31.5 mmol) in water (60 cm3) was added to a solution of the toluene-p-sulfonate 45 (5.16 g, 22.0 mmol) in dichloromethane (30 cm3) at ambient temperature, J.CHEM. soc. PERKIN TRANS. 1 1995 and the mixture stirred for 18 h. The organic phase was washed with water and brine and then heated under reflux over 4 8, molecular sieves for 3 h. The solution was decanted from the sieves, which were washed with dichloromethane, and the combined organic extracts were concentrated under reduced pressure to afford the title compound 47 (3.62 g, 77); d"2.47 (3 H, s, CH,Ar), 4.51 (2 H, s, 2-H2),7.38 and 7.83 (each 2 H, d, J 8, ArH) and 9.62 (1 H, s, 1-H). This aldehyde was immediately dissolved in dichloromethane (34 cm3) to give a solution of 0.5 mol dm concentration which was used in subsequent reactions.Acknowledgements We thank Rhone Poulenc Rorer for a studentship (to R. J. M.) and Dr C. Smith of Rhone Poulenc Rorer for many helpful discussions. References 1 E. J. Thomas, in Stereocontrolled Organic Synthesis, ed. B. M. Trost, Blackwell, 1994,pp. 235-258. 2 E. J. Thomas, ChemTracts: Org. Chem., 1994, 207. 3 A. H. McNeill and E. J. Thomas, Synthesis, 1994, 322; A. H. McNeill and E. J. Thomas, Tetrahedron Lett., 1990, 31,453. 4 A. H. McNeill and E. J. Thomas, Tetrahedron Lett., 1992,33, 1369; J. S. Carey and E. J. 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Okawara, Tetrahedron Lett., 1980, 21, 1767. 14 E. J. Coreyand A. Venkateswarlu, J. Am. Chem. SOC..1972,94,6190. 15 S. K. Chaudhary and 0.Hernandez, Tetrahedron Lett., 1979,20,99. 16 R. Chgnevert, G. Fortier and R. Be1 Rhlid, Tetruhedron., 1992, 48, 6769. 17 M. Kitamura, M. Isobe, Y. Ichikawa and T. Goto, J. Am. Chem. SOC.,1984,106,3252. 18 S. F. Martin and J. A. Dodge, Tetrahedron Lett, 1991, 32, 3017; 0.Mitsunobu, Synthesis, 1981, 1. 19 D. Wagner, J. P. H. Verheyden and J. G. Moffitt. J. Org. Chem., 1974,39,24;S. David and S. Hanessian, Tetrahedron, 1985,41,643. 20 M.-J. Shiao, C.-Y. Yang, S.-H. Lee and T.-H. Wu. Synth. Commun., 1988, 18, 359. 21 K. C. Nicolson, R. Zipkin and D. Tanner, J. Chem. Soc., C'hem. Commun., 1984,349. Paper 5/018881 Received 24th March 1995 Accepted 26th May 1995