2.49 mmol) in THF (3 ml) was added dropwise at Ϫ78 ЊC a 1.61
M solution of BuLi in hexane (1.55 ml, 2.48 mmol). After being
stirred for 20 min, a solution of 13 (362 mg, 2.04 mmol) in THF
(2 ml) was added dropwise and stirring was continued for an
additional 30 min. To the reaction mixture was added a solu-
tion of methyl bromoacetate (1.09 g, 7.14 mmol) and HMPA
(408 mg, 2.48 mmol) in THF (2 ml). The reaction mixture
was stirred for 4 h, during which the reaction temperature rose
slowly to Ϫ40 ЊC, quenched by addition of aqueous NH4Cl,
and extracted with EtOAc. Removal of the solvent followed
by filtration of the residue through a short silica gel column
(hexane–EtOAc, 9:1) gave a mixture of 14a and b as an oil. A
mixture of the oil and K2CO3 (280 mg, 2.0 mmol) in methanol
(5 ml) was stirred at room temperature for 20 h, and concen-
trated. Water was added to the residue, and the product was
extracted into EtOAc. Evaporation of the solvent followed by
purification of the residue with MPLC (hexane–EtOAc, 9:1)
gave the title compound 14a (306 mg, 60%) as an oil, [α]D ϩ3.35
4.90 (1H, d, J 11.0), 5.76 (1H, dd, J 17.3, 11.0); m/z (EI) 206
(Mϩ Ϫ H2O, 25), 191 (12), 175 (18), 161 (30), 93 (100).
To a solution of 17 (2.41 g, 10.7 mmol) and imidazole (2.19 g,
32.2 mmol) in DMF (20 ml) was added a solution of TBDM-
SCl (1.68 g, 11.2 mmol) in DMF (10 ml) with stirring. The
reaction mixture was stirred for 1 h, quenched by addition of
aqueous NaHCO3, and extracted with ether–hexane (1:1).
Concentration of the extract followed by purification of the
residue with chromatography on silica gel (hexane–AcOEt,
12:1) gave the title compound 18 (3.15 g, 87%) as an oil
(Found: C, 70.89; H, 11.48. C20H38O2Si requires C, 70.94; H,
11.31%); [α]D ϩ18.3 (c 0.35, in CHCl3); νmax(neat)/cmϪ1 3510,
1250, 1093, 836; δH(CDCl3) 0.07 (6H, s), 0.90 (9H, s), 1.17 (3H,
s), 1.22–1.27 (2H, m), 1.57–1.87 (5H, m), 1.71 (3H, s), 1.99 (1H,
m), 2.67 (1H, br s, OH), 3.59 and 3.69 (1H, m each), 4.02 (1H,
br s, 1/2H = 8.5‡), 4.62 and 4.81 (1H, s each), 4.87 (1H, d,
J 17.5), 4.90 (1H, d, J 10.5), 5.77 (1H, dd, J 17.5, 10.5).
1
(c 0.34, in CHCl3). The IR and H NMR spectra of 14a were
2-[(1S,3R,4R)-(3-Isopropenyl-4-methyl-4-vinylcyclohexyl)]-
ethanol 21
identical with those of its enantiomer prepared earlier.10
To a stirred solution of 18 (4.55 g, 13.4 mmol) in THF (50 ml)
at Ϫ78 ЊC was added dropwise a 1.54 M solution of BuLi in
hexane (13.0 ml, 20.0 mmol). After being stirred for 30 min, CS2
(1.6 ml, 26.7 mmol) was added, and after being stirred for an
additional 30 min, MeI (1.7 ml, 27.3 mmol) was added drop-
wise. Stirring was continued for an additional 50 min, the reac-
tion mixture was quenched by addition of aqueous NH4Cl, and
the product was extracted with ether. Removal of the solvent
left an oil which was chromatographed on silica gel (hexane–
AcOEt, 50:1) to give 19 (5.70 g, quant.), [α]D Ϫ11.5 (c 0.60, in
CHCl3); νmax(neat)/cmϪ1 1231, 1216, 1050, 835; δH(CDCl3) 0.04
(6H, s), 0.89 (9H, s), 1.06 (3H, s), 1.51–1.63 (5H, m), 1.75 (3H,
s), 1.79–1.95 (2H, m), 2.03–2.11 (2H, m), 2.59 (3H, s), 3.64 (2H,
td, J 6.1, 1.2), 4.67 (1H, s), 4.87 (1H, d, J 17.3), 4.91 (1H, d,
J 10.7), 4.93 (1H, s), 5.78 (1H, dd, J 17.3, 10.7).
To a stirred solution of 19 (6.15 g, 14.3 mmol) in toluene (40
ml) at 90 ЊC was added dropwise a solution of AIBN (449 mg,
2.73 mmol) and tributyltin hydride (11.2 ml, 40.2 mmol) in
toluene (20 ml), and stirring was continued for an additional 30
min. After being cooled at room temperature, the reaction mix-
ture was added to a silica gel column. Toluene and organic tin
compounds were removed by use of hexane as an eluent, then
the product was eluted with hexane–AcOEt (50:1), giving 20
(4.50 g, quant.) as an oil, [α]D ϩ9.30 (c 0.60, in CHCl3);
νmax(neat)/cmϪ1 1254, 1100, 835, 775; δH(CDCl3) 0.05 (6H, s),
0.90 (9H, s), 0.95 (3H, s), 1.02–1.17 (2H, m), 1.70 (3H, s), 1.26–
1.61 (7H, m), 1.96 (1H, dd, J 12.4, 3.0), 3.68 (2H, t, J 7.1), 4.57
(1H, s), 4.85 (1H, s), 4.87 (1H, d, J 10.4), 4.90 (1H, d, J 17.8),
5.81 (1H, dd, J 17.8, 10.4).
To a stirred solution of 20 (4.50 g) in THF (30 ml) was added
dropwise a 1.0 M solution of Bu4NF in THF (16.1 ml, 16.1
mmol), and stirring was continued for an additional 6 h. The
reaction mixture was quenched by addition of aqueous
NaHCO3, and extracted with ether. Removal of the solvent
followed by chromatography of the residue on silica gel gave the
title compound 21 (2.52 g, 90% from 19) as an oil (Found:
C, 80.39; H, 11.70. C14H24O requires C, 80.71; H, 11.61%);
νmax(neat)/cmϪ1 3332, 1375, 1045, 890; δH(CDCl3) 0.98 (3H, s),
1.12–1.65 (10H, m), 1.70 (3H, s), 1.97 (1H, dd, J 12.4, 2.4), 3.71
(2H, br s), 4.57 and 4.81 (1H, s each), 4.88 (1H, d, J 10.5), 4.89
(1H, d, J 17.8), 5.81 (1H, dd, J 17.8, 10.5); m/z (EI) 208 (Mϩ,
12%), 193 (34), 163 (59), 121 (60), 107 (100).
Method 2. To a stirred mixture of NaH (715 mg, 0.85 mmol)
in THF (20 ml) was added dropwise at 0 ЊC a solution of 15
(3.38 g, 13.5 mmol) in THF (20 ml). After being stirred for 30
min, HMPA (2.5 ml, 13.8 mmol) followed by methyl bromo-
acetate (2.2 ml, 16.7 mmol) was added dropwise, and the
reaction mixture was stirred for 4 h, during which the reaction
temperature rose slowly to room temperature. The reaction
mixture was quenched with aqueous NH4Cl, and extracted
with ether. Concentration of the extract gave an oil which was
filtered through a short silica gel column (hexane–ether, 3:1) to
give diester 16 (4.13 g, 95%) as an oil (Found: C, 66.69; H, 8.17.
C18H26O5 requires C, 67.06; H, 8.13%); νmax(neat)/cmϪ1 3085,
1747, 1739, 1714, 911, 862; δH(CDCl3) 1.05 (3H, s), 1.27 (3H, t,
J 7.0), 1.77 (3H, s), 2.04 (1H, br s), 2.06 (1H, dd, J 13.4, 3.2),
2.22 (1H, d, J 13.4), 2.43 (1H, dd, J 13.4, 3.2), 2.67 (1H, d,
J 13.4), 2.80 (1H, d, J 16.4), 3.09 (1H, d, J 16.4), 3.63 (3H, s),
4.23 (2H, q with fine splitting, J 7.0), 4.76 and 4.96 (1H, s each),
4.94 (1H, d, J 17.8), 5.00 (1H, d, J 10.8), 5.84 (1H, dd, J 17.8,
10.8).
A mixture of 16 (4.10 g, 12.7 mmol), DMSO (20 ml) and
aqueous NaOH (20%, 20 ml) was stirred at 50 ЊC for 12 h. After
cooling at 0 ЊC, the reaction mixture was acidified by addition
of aqueous HCl and saturated with brine. The product was
extracted with EtOAc, and the residue obtained by concen-
tration of the extracts was filtered through a short silica gel
column (EtOAc). Concentration of the eluate left an oil, which
was dissolved in ether (100 ml). The ethereal solution was
treated at 0 ЊC with a diazomethane–ether solution and con-
centrated. An oily residue was chromatographed on silica gel
(hexane–EtOAc, 12:1) to give the title compound 14a (2.73 g,
81% from 15).
(1S,2S,4R,5R)-2-[2-(tert-Butyldimethylsilyloxy)ethyl]-4-iso-
propenyl-5-methyl-5-vinylcyclohexanol 18
To a stirred mixture of lithium aluminium hydride (507 mg,
13.4 mmol) in THF (25 ml) was added dropwise at Ϫ50 ЊC a
solution of 14a (3.37 g, 13.4 mmol) in THF (20 ml). The reac-
tion mixture was stirred for 2 h, quenched carefully by addition
of aqueous NH4Cl, and filtered. The solid was washed with
ether, and the combined filtrates were dried. Evaporation of the
solvent left an oil which was chromatographed on silica gel
(hexane–AcOEt, 1:1) to give diol 17 (2.46 g, 81%) as an oil, [α]D
ϩ41.6 (c 0.03, in CHCl3); νmax(neat)/cmϪ1 3355, 1446, 1006, 891;
δH(CDCl3) 1.17 (3H, s), 1.24–1.32 (2H, m), 1.60–2.04 (8H,
m), 1.72 (3H, s), 3.69 and 3.76 (1H, m each), 4.03 (1H, br s,
1/2H = 8.3‡), 4.62 and 4.82 (1H, s each), 4.90 (1H, d, J 17.3),
Methyl 2-[(1S,3R,4R)-3-isopropenyl-4-methyl-4-vinylcyclo-
hexyl]acetate 11
To a stirred solution of 21 (650 mg, 3.12 mmol) in acetone (10
ml) at 0 ЊC was added Jones reagent dropwise, prepared from
CrO3 (13.4 g), concentrated H2SO4 (12 ml) and water (25 ml),
until the orange colour of the reagent persisted for a few minutes.
‡ 1/2H Refers to the half band width, with values given in Hz.
786
J. Chem. Soc., Perkin Trans. 1, 1999, 783–788