Notes
J . Org. Chem., Vol. 62, No. 6, 1997 1889
Ta ble 2
14trans
entry
R1
R2
yield %
1′trans
yield %
60
a
c
d
Me
H
CH2
Me
Et
CH2
14a trans
14ctrans
14d trans
70
62
60
1a ′trans
-(CH2)3-
Isop r op yl Keton e 8b. This compound was prepared, ac-
cording to the typical procedure described above, from the keto
alcohol 4a exo (0.336 g, 2.0 mmol), methyltriphenylphosphonium
iodide (1.620 g, 4.0 mmol), and dimsylsodium (4.0 mmol). After
24 h of reaction at room temperature, the usual workup, and
purification on SiO2 (pentane, Rf 0.25), 0.200 g (60%) of 8b was
obtained as a colorless oil: 1H NMR δ 1.09 (d, 3 H, J ) 6.8 Hz),
1.10 (s, 3 H), 1.12 (d, 3 H, J ) 7.3 Hz), 1.21 (s, 3 H), 1.90 (d, 1
H (major diast), J ) 5.9 Hz), 2.02 (d, 1 H (minor diast), J ) 8.3
Hz), 2.20 (dd, 1 H, J ) 8.3, 5.4 Hz), 2.69 (qq, 1 H), 5.08 (m, 2 H),
5.58 (m, 1 H (major diast)), 6,20 (m, 1H (minor diast)); 13C NMR
δ 17.51, 17.62, 18.02, 19.74, 21.90, 29.63, 29.91, 31.88, 37.22,
37.53, 38.45, 40.72, 42.14, 42.75, 115.59, 116.01, 133.44, 135.52,
210.89, 211.58; IR (film) νCdO 1689 cm-1; MS (EI) m/ e 95, 71.
Isop r op yl Keton e 8c. This compound was prepared, ac-
cording to the typical procedure described above, from the keto
alcohol 4a exo (0.841 g, 5.0 mmol), n-propyltriphenylphosphonium
iodide (4.539 g, 10.5 mmol), and dimsylsodium (10.5 mmol). After
3.25 h of reaction at room temperature, the usual workup and
purification on SiO2 (pentane/ether 95/5, Rf 0.57) gave 0.527 g
(54%) of 8c as a colorless oil: 1H NMR δ 0.97 (t, 6 H, J ) 2.75
Hz), 1.10 (m, 9 H), 1.20 (s, 3 H), 1.79 (d, J ) 5 Hz, 1 H major
diast)), 1.83 (d, J ) 5 Hz, 1 H (minor diast)), 2.07 (m, 2 H (minor
diast)), 2.14 (m, 2 H (major diast)), 2.30 (dd, 1 H, J ) 8.5, 5 Hz),
2.68 (qq, 1 H, J ) 2.75 Hz), 5.10 (dd, 1 H, J ) 10.3, 8.5 Hz (major
diast)), 5.19 (dd, 1 H, J ) 15.1, 6.8 Hz (minor diast)), 5,48 (dt,
1 H, J ) 10.3, 7.3 Hz (major diast)), 5,61 (dt, 1 H, J ) 15.1, 6.4
Hz (minor diast)); 13C NMR δ 14.12, 17.57, 18.06, 19.79, 21.10,
22.18, 31.86, 32.20, 42.06, 42.14, 125.85, 134.42, 211.21; IR (film)
νCdO 1691 cm-1; MS (EI) m/ e 123, 95, 71. Anal. Calcd for
1691 cm-1; MS (EI) m/ e 196 (M), 124. Anal. Calcd for
13H20D2O: C, 79.53; (H + D/2), 11.29. Found: C, 79.48; H,
11.31.
Isop r op yl Keton e 8a ′ fr om Isop r op yl Keton e 8a .
C
A
solution of dimsylsodium was prepared under argon from sodium
hydride (0.046 g, 1.53 mmol) and dimethyl-d6 sulfoxide (1.3 mL).
A solution of the isopropyl ketone 8a (0.248 g, 1.28 mmol) in
dimethyl sulfoxide (1.3 mL) was then added dropwise to the
mixture, which slowly turned pale brown. After it was stirred
at room temperature for 7 h, the reaction mixture was hydro-
lyzed with a saturated aqueous solution of NH4Cl and extracted
with Et2O (3 × 5 mL). The organic layers were combined,
washed with water (2 × 5 mL), and then dried over magnesium
sulfate. Filtration and concentration under reduced pressure
gave 0.136 g (55%) of pure isopropyl ketone 8a ′ as a colorless
oil.
Isop r op yl Keton e 8a ′′. A solution of isopropyl ketone 8a
(0.388 g, 2.0 mmol) in THF (4 mL) was added dropwise at 0 °C
under argon to a stirred solution of LDA prepared from n-
butyllithium (2.27 mL, 1.50 M, 3.4 mmol) and diisopropylamine
(0.51 mL, 0.367 g, 3.6 mmol) in THF (4 mL). The resulting
brown solution was stirred at room temperature for an additional
0.3 h and then was quenched with D2O (1 mL). The colorless
solution was immediately extracted with ether (3 × 10 mL). The
organic layers were combined, washed with water (2 × 5 mL),
and then dried over magnesium sulfate. Filtration and concen-
tration under reduced pressure gave 0.386 g (99%) of pure 8a ′′
as a colorless oil: 1H NMR δ 1.07 (s, 3 H), 1.10 (s, 3 H), 1.11 (s,
3 H), 1.19 (s, 3 H), 1.68 (s, 3 H), 1.71 (s, 3 H), 1.73 (d, 1 H, J )
5.86 Hz), 2.22 (dd, 1 H, J ) 7.8, 5.86 Hz), 4.92 (d, 1 H, J ) 7.8
Hz); IR (film) νCdO 1691 cm-1; MS (EI) m/ e 195 (M + 1), 123.
Keton e 11. Trimethylsilyl chloride (0.42 mL, 0.360 g, 3.3
mmol) and then triethylamine (0.46 mL, 0.334 g, 3.3 mmol) were
added, at room temperature, to a solution of the keto alcohol
4a exo (0.505 g, 3.0 mmol) in dichloromethane (3 mL). The
reaction mixture was stirred at that temperature for 1 h before
adding sequentially ether (15 mL) and a saturated aqueous
solution of NaHCO3. The ether phase was separated, and the
aqueous layer was extracted with Et2O (2 × 10 mL). The organic
layers were combined, washed with water (1 mL), and then dried
over magnesium sulfate. Filtration and concentration under
reduced pressure gave 0.697 g (97%) of pure ketone 11 as a
colorless oil: 1H NMR δ 0.16 (s, 9 H), 0.96 (s, 3 H), 1.00 (s, 3 H),
1.01 (s, 3 H), 1.13 (s, 3 H), 1.61 (d, 1 H, J ) 5.6 Hz), 1.86 (d, 1
H, J ) 5.6 Hz), 3.79 (s, 1 H); IR (film) νCdO 1724 cm-1; MS (EI)
m/ e 240 (M). Anal. Calcd for C13H24O2Si: C, 64.95; H, 10.08.
Found: C, 64.80; H, 10.19.
C
13H22O: C, 80.35; H, 11.44. Found: C, 80.23; H, 11.43.
Isop r op yl Keton e 8d . This compound was prepared, ac-
cording to the typical procedure described above, from the keto
alcohol 4a exo (0.841 g, 5.0 mmol), cyclohexyltriphenylphospho-
nium bromide (4.466 g, 10.5 mmol), and dimsylsodium (10.5
mmol). After the mixture was stirred for 15 h at 60 °C, the
workup procedure and purification on SiO2 (pentane/ether 95/
5, Rf 0.44) gave 0.461 g (40%) of 8d as a colorless oil: 1H NMR
δ 1.08 (d, 3 H, J ) 6.8 Hz), 1.10 (s, 3 H), 1.11 (d, 3 H, J ) 6.8
Hz), 1.18 (s, 3 H), 1.50 (m, 6 H), 1.72 (d, 1 H, J ) 5.4 Hz), 2.06
(m, 2 H), 2.18 (t, 2 H, J ) 5.5 Hz), 2.24 (dd, 1 H, J ) 7.7, 5.6
Hz), 2,67 (qq, 1 H, J ) 6.8 Hz), 4.86 (d, 1 H, J ) 7.7 Hz); 13C
NMR δ 17.40, 17.87, 19.58, 22.06, 26.52, 27.42, 28.35, 29.16,
31.77, 32.19, 32.23, 36.58, 41.83, 117.82, 142.98, 211.20; IR (film)
νCdO 1690 cm-1; MS (EI) m/ e 163. Anal. Calcd for C16H26O:
C, 81.98; H, 11.20. Found: C, 81.99; H, 11.39.
Isop r op yl Keton e 8a ′ fr om th e Keto Alcoh ol 4a exo. Iso-
propyltriphenylphosphonium iodide (1.81 g, 4.2 mmol) in di-
methyl-d6 sulfoxide (4 mL) was added dropwise under argon to
a stirred solution of dimsylsodium (from sodium hydride, 0.120
g, 4.0 mmol) in dimethyl-d6 sulfoxide (2 mL) maintained at 0
°C. The reaction mixture instantly became deep red and was
then stirred at room temperature for 0.25 h. A solution of the
keto alcohol 4a exo (0.340 g, 2.0 mmol) in dimethyl-d6 sulfoxide
(2 mL) was then added dropwise to this mixture, which slowly
turned pale brown. After it was stirred at room temperature
for 2 h, the reaction mixture was hydrolyzed with H2O (3 mL),
washed with a saturated aqueous solution of NH4Cl (10 mL) and
then extracted with Et2O (20 mL). The Et2O phase was
separated, and the aqueous layer was extracted with Et2O (3 ×
15 mL). The organic layers were combined, washed with water
(2 × 5 mL), and then dried over magnesium sulfate. Filtration
and concentration under reduced pressure gave a crude reaction
mixture. Addition of pentane, filtration of triphenylphosphine
oxide, concentration under reduced pressure, and purification
of the resulting crude mixture on SiO2 (pentane, Rf 0.36) gave
0.250 g (65%) of 8a ′ as a colorless oil: 1H NMR δ 1.07 (s, 3 H),
1.10 (s, 3 H), 1.11 (s, 3 H), 1.19 (s, 3 H), 1.68 (s, 3 H), 1.71 (s, 3
H), 2.21 (d, 1 H, J ) 8.3 Hz), 4.92 (d, 1 H, J ) 8.3 Hz); 13C NMR
δ 17.56, 18.07, 18.49, 19.88, 22.24, 25.60, 31.93, 33.21, 41.29,
41.55, 41.75, 41.95, 42.17, 121.43, 135.11, 211.65; IR (film) νCdO
Diol 12. n-Butyllithium (3.12 mL, 1.6 M, 5.0 mmol) was
added dropwise with stirring at 0 °C under argon to a suspension
of the keto alcohol 4a en d o (0.168 g, 1.0 mmol) in toluene (5 mL).
The mixture slowly turned pale yellow and was stirred at 0 °C
for 3 h. A saturated aqueous solution of NaHCO3 was then
added to the mixture. The organic phase was separated, and
the aqueous layer was extracted with Et2O (2 × 10 mL). The
organic layers were combined, washed with water (3 × 1 mL),
and then dried over magnesium sulfate. Filtration and concen-
tration under reduced pressure gave 0.207 g of a crude reaction
mixture. Purification on SiO2 (pentane/ether 50/50, Rf 0.74) gave
0.155 g (68%) of 12: 1H NMR δ 0.97 (m, 12 H), 1.20 (d, 1 H, J
) 7.81 Hz), 1.44 (m, 7 H), 1.69 (m, 4 H), 2.19 (bs, 1 H), 3.96 (d,
1 H, J ) 6.35 Hz); 13C NMR δ 14.14, 16.92, 19.17, 23.31, 25.94,
26.36, 32.01, 35.71, 37.64, 41.12, 58.91, 84.10, 85.32; IR (film)
νOH 3416 cm-1; MS (EI) m/ e 193. Anal. Calcd for C14H26O2: C,
74.27; H, 11.60. Found: C, 74.27; H, 11.46.
Hyd r oxy k eton e 14a tr a n s. A solution of isopropyl ketone 8a
(0.170 g, 0.87 mmol) in THF (1.5 mL) was added dropwise at
-78 °C under argon to a stirred solution of LDA prepared at
-78 °C from n-butyllithium (0.67 mL, 1.50 M, 1.0 mmol) and
diisopropylamine (0.14 mL, 0.101 g, 1.00 mmol) in THF (1.5 mL).
After a further 0.2 h the temperature was raised to 0 °C and a
balloon of oxygen was attached to the reaction flask. The