3950 J . Org. Chem., Vol. 63, No. 12, 1998
Green et al.
Con ju ga t e Ad d it ion of Tr im et h ylst a n n yllit h iu m t o
5-Isop r op yl-2-cycloh exen on e: P r ep a r a tion of Keton es
28 a n d 29. Trimethylstannyl chloride (1.0 M in THF 34.88
mL, 0.142 mol) was added to a mixture of anhydrous tetrahy-
drofuran (50 mL) and excess lithium metal (10 g) under
nitrogen and left stirring overnight. After removal of excess
lithium, the reaction mixture was treated with 5-isopropyl-2-
cyclohexenone (3.169 g, 0.023 mol), which was added dropwise.
After the mixture was stirred for 7 h, water (150 mL) and the
mixture were left to stir for 15 min. The resulting mixture
was extracted with ether (3 × 75 mL) and the ether solution
dried (MgSO4) and then evaporated under reduced pressure
to give a mixture of cis-5- (29) and trans-5-isopropyl-3-
(trimethylstannyl)cyclohexanone (28) in an approximate ratio
of 1:4 respectively (6.25 g, 90%). 28: 13C NMR δ -10.69, 19.79,
brine (3 × 50 mL), dried (MgSO4), and evaporated under
reduced pressure to give 25 as a colorless oil (2.904 g, 58%),
which was contaminated by a small amount (ca. 10%) of
3-(pentamethyldisilanyl)-3-methylcyclohexanone (26). Puri-
fication by silica gel column chromatography gave 25 as a
colorless oil: 1H NMR (CDCl3) δ 2.32 (1H, d, J ) 12.6 Hz,
H2ax), 2.28-2.24 (2H, m, H6ax,eq), 2.06-1.92 (3H, m, H2eq,
H5ax,eq), 1.74 (1H, ddd, J ) 14.2, 12.6, 4.7 Hz, H4ax), 1.52-
1.44 (1H, m, H4eq), 0.89 (3H, s), -0.05 (9H, s); 13C NMR
(CDCl3) δ 212.58 (C1), 47.88 (C2), 41.32 (C6), 30.50 (C4), 25.55
(C3), 22.79 (C5), 18.58 (Me), -4.99 (SiMe’s). Anal. Calcd for
C
10H20OSi: C, 65.15; H, 10.93. Found: C, 64.95; H, 10.84.
3-Meth yl-3-(tr im eth ylsta n n yl)cycloh exa n on e (27).
A
solution of trimethylstannyl chloride (0.014 mol in THF 23.5
mL) was treated with lithium metal (0.09 mol) and sonicated
for 3 h. The excess lithium was removed, and the resulting
cloudy green solution was cooled to 0 °C, treated with a
solution of 3-methyl-2-cyclohexanone (1 g, 0.009 mol, in THF
5 mL), and stirred at room temperature for 12 h. The resulting
mixture was diluted with water (50 mL) and extracted with
ether (5 × 30 mL). The combined ether extracts were washed
with water (3 × 100 mL), dried (MgSO4), and evaporated under
reduced pressure to give 27 as an oil (2.4 g, 90%) that was
pure by 13C NMR. An analytically pure sample was prepared
by Kugelrohr distillation (90° C, 0.4 mmHg): 1H NMR (CDCl3)
δ 2.53 (1H, d, J ) 15.2 Hz, H2ax), 2.38-2.2 (2H, m, H6ax,eq),
2.16 (1H, dd, J ) 15.2, 2.6 Hz, H2eq), 2.07 (1H, m, H5), 1.97
(1H, m, H4eq), 1.74 (1H, m, H5), 1.57 (1H, ddd, J ) 16.0, 10.0,
5.0 Hz, H4ax), 1.15, (3H, s), 0.02, (9H, s); 13C NMR (CDCl3) δ
211.5 (C1), 53.73 (C2), 41.30 (C6), 37.04 (C5), 31.32 (C3), 26.37
(Me), 24.73 (C4), -11.03; MS M+ 276.0526 (calcd for C10H20OSn
20.03, 21.66, 31.01, 31.88, 45.20, 45.30, 45.61, 212.00. 29: 13
C
NMR δ -11.74, 19.07, 19.62, 23.53, 32.75, 45.25, 50.16, 212.00.
Sod iu m Bor oh yd r id e Red u ction of th e Isop r op yl Ke-
ton e Mixtu r e 28 a n d 29. To an ethanol (100 mL) solution
of the crude isomeric mixture of 28 and 29 (3 g, 0.0099 mol)
was added sodium borohydride (0.5 g, 0.0132 mol) in portions
with stirring at 0 °C. The reaction was left to stir at room
temperature for a further 4 h. The reaction mixture was
quenched cautiously by adding dilute hydrochloric acid (10 mL)
dropwise. Excess water (100 mL) was added, and the mixture
was extracted with ether (3 × 50 mL), the combined organic
extracts were washed with saturated sodium chloride (2 × 50
mL) and dried, and the solvent was removed under reduced
pressure to give an oily residue. In the 13C NMR of this oil,
characteristic signals were discernible at δ -11.06 (equatorial
SnMe3), 67.35 (C-OH) 24-H; -9.48 (axial SnMe3), 70.27 (C-
OH), 30-H; -11.92 (equatorial SnMe3), 71.83 (C-OH) 31-H.
The residue (2.4 g 80%) was dissolved in pyridine (10 mL) and
stirred on ice under an atmosphere of nitrogen. The mixture
was then treated with p-nitrobenzoyl chloride (1.6 g, 1.1 equiv)
and stirred for 3 h. The resulting slurry was then poured into
water (100 mL), and the aqueous suspension was extracted
with ether (3 × 50 mL). The combined extracts washed with
1 M HCl (3 × 50 mL) and aqueous NaaHCO3 (10%, 3 × 50
mL), dried (MgSO4), and evaporated down to a creamy solid
(4 g 90%). The mixture of p-nitrobenzoates 24-P NB, 30-P NB,
and 31-P NB was partially separated by dry flash chromatog-
raphy on silica gel using ether/petroleum ether as eluants.
Partially purified fractions were repeatedly recrystallized from
methanol to afford r-5-isopropyl-t-3-(trimethylstannyl)cyclo-
hexan-t-1-yl p-nitrobenzoate (24-P NB) as yellow needlelike
crystals (300 mg): mp 95-97.5 °C; 1H NMR (CDCl3) δ 8.3 (1H,
d, J ) 9 Hz), 8.3 (1H, d, J ) 9 Hz), 5.05 (1H, m), 2.2-2.0 (2H,
m), 1.95-1.75 (2H, m), 1.5-1.1 (5H, m), 0.9 (3H, d J ) 6 Hz);
13C NMR δ -11.52, 16.74, 21.09, 21.16, 26.86, 31.56, 34.19,
35.79, 42.27, 73.05, 123.36, 130.57, 136.31, 150.36, 164.21.
276.0536); IR νmax (thin film) 1707, 767 cm-1
.
tr a n s-3-Meth yl-3-(tr im eth ylsilyl)cycloh exa n ol (20-H).
A solution of L-Selectride (0.001 mol) in anhydrous THF (10
mL), stirred under nitrogen, was cooled to -78 °C and treated
with a solution of 3-methyl-3-(trimethylsilyl)cyclohexanone
(25) (0.20 g, 0.001 mol). The resulting mixture was stirred at
this temperature for 4 h and then quenched by the addition
of water (3 mL) and allowed to reach room temperature. The
resulting solution was treated with with sodium hydroxide (3
M, 0.24 mL) and 30% H2O2 (dropwise) and stirred for 1 h. The
mixture was extracted with ether (3 × 50 mL), and the
combined extracts were washed with brine (3 × 50 mL), dried
(MgSO4), and evaporated to give 20 as a colorless oil (0.15 g,
73%): 13C NMR (CDCl3) δ 68.11, 44.50, 35.00, 34.96, 26.59,
20.87, 18.98, -2.24; IR νmax (thin film) 3454, 1068 cm-1
.
tr a n s-3-Meth yl-3-(tr im eth ylsta n n yl)cycloh exa n ol (21-
H). A solution of L-Selectride (0.0018 mol) in anhydrous THF
(10 mL) was cooled to -78 °C and then treated with a solution
of 3-methyl-3-(trimethylstannyl)cyclohexanone (27) in THF (5
mL). The resulting mixture was stirred at this temperature
for 4 h and then diluted with water (3 mL) and allowed to
reach room temperature. Treatment with aqueous sodium
hydroxide (3M, 0.6 mL) was followed by dropwise addition of
30% H2O2 (0.6 mL). The mixture was stirred for a further hour
and then extracted with ether (3 × 50 mL). The combined
extracts were dried (MgSO4) and evaporated under reduced
pressure to give 21 as a colorless oil: 13C (CDCl3) δ 69.21,
49.47, 38.94, 35.46, 31.16, 29.27, 23.86, -9.69; IR νmax (thin
The ester 24-P NB (200 mg) was refluxed in methanol (20
mL) containing potassium hydroxide (2 equiv) for 2 h. The
solution was diluted with water (100 mL) and extracted with
ether (3 × 50 mL), and the combined extracts were dried
(MgSO4) and evaporated under reduced pressure, giving r-5-
isopropyl-t-3-(trimethylstannyl)cyclohexan-t-1-ol (24-H) (120
mg, 90%): 13C NMR (CDCl3) δ -11.06, 17.8, 20.80 (overlapping
i-Pr CH3’s), 27.97, 31.93, 37.65, 38.98, 41.03, 67.35.
film) 3345, 1447 cm-1
.
3-Meth yl-3-(tr im eth ylsilyl)cycloh exa n on e (25). A solu-
tion of HMPA (30 mL) and hexamethyldisilane (8.9 mL, 0.044
mol) was cooled with stirring to 0 °C. The mixture was then
diluted with cold THF (15 mL at -78 °C) and treated
immediately with methyllithium (1.4 mol solution in ether,
25 mL) followed by the addition of cold THF (100 mL, -70
°C). The resulting bright red mixture was cooled to -78 °C
and treated with a solution of 3-methylcyclohexanone (3.01 g,
0.027 mol) in THF (5 mL). The mixture was stirred at -78
°C for a further 15 min, warmed to room temperature, and
stirred for a further hour. The addition of methanol (15 mL)
was followed by extraction with petroleum (3 × 50 mL). The
combined extracts were washed with water (3 × 50 mL) and
cis-3-Meth yl-3-(tr im eth ylsta n n yl)cycloh exa n ol (23-H).
A stirred solution of 3-methyl-3-(trimethylstannyl)cyclohex-
anone (27) (0.51 g, 0.0019 mol) in ethanol (50 mL), was treated
at 0 °C with sodium borohydride (0.14 g, 0.004 mol). The
resulting mixture was stirred at this temperature for 4 h and
then quenched by the addition of 1 M HCl (5 mL). The
resulting mixture was extracted with ether (3 × 50 mL), and
the combined extracts were washed with brine (3 × 50 mL),
dried (MgSO4), and evaporated under reduced pressure to give
21-H and 23-H as a ca. 1:1 mixture (0.42 g, 84%). Separation
by flash chromatography on silica gel with ether/petroleum
eluants gave 21-H and cis-3-methyl-3-(trimethylstannyl)cy-
clohexanol (23-H): 13C NMR (CDCl3) δ 66.00, 45.38, 35.90,
35.70, 25.93, 23.50, 19.69, -11.63; IR νmax (thin film) 3357,
(33) Frank, R. L.; Hall, H. K. J . Am. Chem. Soc. 1950, 72, 1645.
1447, 1048, 762 cm-1
.