H. Adams et al. / Tetrahedron: Asymmetry 10 (1999) 4129–4142
4137
give the product 13b as a white crystalline solid (5.87 g, 40%); mp 96°C (ethyl acetate/light petroleum);
[α]D −100 (c 0.87, CHCl3); νmax cm−1 (thin film) 3380 (OH), 1065 (S_O); 1H NMR (250 MHz, CDCl3)
δ 4.10 (1H, ddd, J=10, 10 and 4 Hz, CHOH), 3.81 (1H, dt, J=10 and 10 Hz, CHSO), 2.84 (1H, m,
SOCH), 2.74 (1H, ddq, J=10, 8 and 4 Hz, CHCH3), 1.48 (3H, d, J=8 Hz, CHCH3), 1.20 (3H, s, CH3),
1.00 (3H, s, CH3); (found: C, 67.5; H, 9.8; S, 11.5; m/z 285. C16H28O2S1 requires: C, 67.6; H, 9.9; S,
11.3; M+ 285). Followed by the product 14b as a white crystalline solid (5.34 g, 36%); mp 166°C (ethyl
acetate/light petroleum); [α]D +29 (c 0.84, CHCl3); νmax cm−1 (thin film) 3380 (OH), 1065 (S_O); 1H
NMR (250 MHz, CDCl3) δ 4.08 (1H, ddd, J=10, 10 and 4 Hz, CHOH), 3.22 (1H, dt, J=9 and 9 Hz,
CHSO), 2.85 (1H, ddd, J=12, 9 and 4 Hz, CHSO), 2.74 (1H, m, CHCH3), 2.33–1.54 (11H, m, ring
protons), 1.47 (3H, d, J=8 Hz, CHCH3), 1.22 (3H, s, CH3), 0.99 (3H, s, CH3); (found: C, 67.7; H, 9.8;
S, 11.4; m/z 285. C16H28O2S1 requires: C, 67.6; H, 9.9; S, 11.3; M+ 285).
4.7. (1R,2R,10R,20S,30R)-trans-2-(4-Methoxybenzyl)-nopylthiocyclohexanol and (1S,2S,10R,20S,30R)-
trans-2-4-methoxybenzyl)-nopylthiocyclohexanol 12a
4-Methoxybenzylnopan-3(R)-thiol (1 g; 3.12 mmol) was added to a stirred solution of sodium ethoxide
(67 mg, in 20 mL of absolute ethanol), and stirring was continued for 15 min. Cyclohexene oxide (0.32
mL, 3.12 mmol) was added and the reaction mixture was stirred for 2.5 h and refluxed for 0.5 h. The
solution was diluted with ether (20 mL), washed with water (3×10 mL) and dried over MgSO4. Removal
of the solvent under reduced pressure gave the crude product which was chromatographed on silica
eluting with ether/light petroleum (15%) to give a mixture of two diastereoisomeric hydroxy sulfides 12a
as a colourless oil (1.19 g, 91%). High performance liquid chromatography on a small sample gave a 90%
separation of the diastereoisomers; first diastereoisomer: νmax cm−1 (liquid film) 3456 and 2981 (OH),
2860 (OMe), 1610 (aromatic); 1H NMR (250 MHz, CDCl3) δ 7.28 (2H, d, J=9 Hz, Ar), 6.84 (2H, d, J=9
Hz, Ar), 4,42 (2H, s, CH2Ar), 3.90 (3H, s, OCH3), 3.64 (1H, dt, J=10 and 10 Hz, H-3), 3.43 (2H, t, J=7
Hz, OCH2), 3.28 (1H, dt, J=9.5 and 4 Hz, CHS), 3.03 (1H, br s, CHOH), 2.52–1.21 (17H, m, aliphatic),
1.17 (3H, s, CH3), 0.95 (3H, s, CH3); m/z 418 (M+); second diastereoisomer: νmax cm−1 3456 and 2981
(OH), 2860 (OMe), 1610 (aromatic); 1H NMR (250 MHz, CDCl3) δ 7.29 (2H, d, J=9 Hz, Ar), 6.85 (2H,
d, J=9 Hz, Ar), 4.42 (2H, s, CH2Ar), 3.81 (3H, s, OCH3), 3.63 (1H, dt, J=10 and 10 Hz), 3.45 (2H, m,
OCH2), 3.25 (1H, br s, OH), 3.03 (1H, ddd, J=11, 9 and 4 Hz, CHS), 2.49–1.23 (17H, m, aliphatic), 1.21
(3H, s, CH3), 0.94 (3H, s, CH3); m/z 418 (M+).
4.8. (−)-(1R,2R,Ss,10R,20S,30R)-trans-2-(4-Methoxybenzyl)-nopylsulfinylcyclohexanol 13a and (+)-
(1S,2S,Rs,10R,20S,30R)-trans-2-(4-methoxybenzyl)-nopylsulfinylcyclohexanol 14a
meta-Chloroperoxybenzoic acid (451 mg, 2.62 mmol) was added to a stirred solution of sulfides 12a
(1.093 g, 2.62 mmol) in dichloromethane (20 mL) at 0°C. The solution was stirred for 20 min after
which time the reaction was complete. Na2SO3 solution was added, and the organic layer was separated
and washed with saturated NaHCO3 solution (3×30 mL) and dried over MgSO4. The solvent was
removed under reduced pressure and the crude product was chromatographed on silica eluting with ethyl
acetate/light petroleum (40%) to give the product 13a as a colourless viscous oil (388 mg, 34%); [α]D
−95 (c 0.104, CHCl3); νmax cm−1 (liquid film) 3645, 3450 (OH), 1607 (aromatic), 1060 (S_O); 1H NMR
(250 MHz, CDCl3) δ 7.32 (2H, d, J=9 Hz, Ar), 6.88 (2H, d, J=9 Hz, Ar), 5.39 (1H, br s, OH), 4.42 (2H,
s, CH2Ar), 4.05 (1H, m, CHOH), 3.81 (1H, s, OCH3), 3.50 (2H, m, OCH2), 3.21 (1H, dt, J=9 and 9 Hz,
H-3), 1.17 (3H, s, CH3), 1.01 (3H, s, CH3); (found: C, 67.8; H, 8.7; S, 7.2; m/z 424. C25H38SO4·0.5H2O
requires: C, 67.7; H, 8.9; S, 7.2; M+ 424). Further elution with ethyl acetate/light petroleum (70%) gave