8690 J . Org. Chem., Vol. 61, No. 24, 1996
Notes
90%) as colorless needles, which was used in the next step
without purification.
mg, 0.014 mmol), and triethyl orthoacetate (4.0 mL, 28 mmol)
was heated at 160 °C for 3 h on a Dean-Stark apparatus. After
removal of the solvent, the residue was chromatographed.
Elution with a 20:1 mixture of hexane-EtOAc provided the ethyl
ester 10 (87.4 mg, 78%) as a colorless oil: [R]28D +48.22 (c 1.766,
A suspension of the above selenoxide (651 mg, 1.66 mmol) in
THF (15 mL) was refluxed for 0.5 h. After removal of the
solvent, the residue was chromatographed. Elution with a 20:7
mixture of hexane-EtOAc furnished the allylic alcohol 8 (320
mg, 88%) as a colorless oil; [R]24D -5.68 (c 1.09, CHCl3); IR 3400,
CHCl3); IR (CHCl3) 1730 cm-1 1H NMR δ 1.52-1.62 (1H, m),
;
1.24 (3H, t, J ) 6.9), 1.67-1.85 (2H, m), 1.94-2.08 (2H, m), 2.24
(1H, dd, J ) 13.8 and 7.2), 2.41-2.58 (2H, m), 3.40 (1H, dd, J )
9.9, 6.9), 3.48 (1H, dd, J ) 9.9, 5.4), 4.12 (2H, q, J ) 7.5), 4.50
(2H, dd, J ) 17.1, 12.0), 5.52 (1H, dd, J ) 9.9, 2.4), 5.71 (1H, br
d, J ) 9.9), 7.25-7.38 (5H, br s); MS (EI) 288 (M+). Anal. Calcd
for C18H24O3: C, 74.97; H, 8.39. Found: C, 75.22; H, 8.39.
(1′S ,6′S )-2-[6′-(B e n z y lo x y m e t h y l)-2 ′-c y c lo h e x y l]-
eth a n ol (11). To a suspension of LAH (250 mg, 6.58 mmol) in
THF (30 mL) was added dropwise a solution of the ester 10 (1.04
g, 3.61 mmol) in THF (3 mL) at 0 °C, whereupon it was allowed
to stir at rt for 2 h. The solution was then cooled to 0 °C, and
H2O (0.3 mL) was cautiously added followed by 15% aqueous
NaOH (0.3 mL) and then H2O (0.9 mL). After 20 min, hexane
and MgSO4 were added, whereupon the resulting suspension
was filtered through Celite. The filtered solids were washed
with Et2O several times, and then the combined filtrates were
concentrated to yield an oil, which was chromatographed.
Elution with a 2:1 mixture of hexane-EtOAc gave rise to the
1630 cm-1 1H NMR δ 1.47-1.81 (4H, m), 2.31-2.44 (1H, m),
;
3.33-3.44 (2H, m), 4.11-4.20 (1H, br s), 4.51 (2H, s), 5.76-5.89
(2H, m), 7.22-7.40 (5H, m); 13C NMR δ 21.1, 29.7, 35.9, 64.2,
72.9, 73.5, 127.4, 128.2, 130.4, 131.3 and 138.1; MS(EI) m/e 218
(M+). Anal. Calcd for C14H18O2: C, 77.03; H, 8.31. Found: C,
76.93; H, 8.27.
(1S,4R)-4-(Ben zyloxym et h yl)-2-cycloh exen -1-ol
(9).
Meth od A. To a stirred solution of 8 (54 mg, 0.25 mmol) in
THF (5 mL) were added HMPA (0.1 mL, 0.54 mmol), PPh3 (103
mg, 0.40 mmol), and acetic acid (13.6 µL, 0.40 mmol) at 0 °C.
After 10 min, diethyl azodicarboxylate (62 µL, 0.40 mmol) was
added at 0 °C, whereupon the resulting mixture was allowed to
stir at the same temperature for 0.5 h. The mixture was diluted
with 10% HCl solution, and then the resulting mixture was
extracted with Et2O (×3). The combined ethereal layers were
washed with saturated NaCl solution, dried, and evaporated to
afford an oil, which was chromatographed. Elution with a 10:3
mixture of hexane-EtOAc gave the acetate (52 mg, 81%) as a
alcohol 11 (805.3 mg, 91%) as a colorless oil: [R]22 +67.11 (c
D
0.36, CHCl3); IR (CHCl3) 3450 cm-1; 1H NMR δ 1.44-2.19 (8H,
m), 3.41 (1H, dd, J ) 9.3, 6.3), 3.48 (1H, dd, J ) 9.3, 5.4), 3.67-
3.77 (2H, m), 4.51 (2H, dd, J ) 16.5, 12.0), 5.57 (1H, br d, J )
9.9), 5.69 (1H, br d, J ) 9.9), 7.25-7.35 (5H, m); HRMS(EI) calcd
for C16H22O2 (M+) 246.1620, found 246.1605.
colorless oil: [R]26 -101.90 (c 0.63, CHCl3); IR (CHCl3) 1730
D
cm-1
;
1H NMR δ 1.38-1.68 (2H, m), 1.92-2.14 (2H, m), 2.07
(3H, s), 2.42-2.58 (1H, m), 3.27-3.39 (2H, m), 4.51 (2H, s), 5.22-
5.32 (1H, m), 5.70 (1H, br d, J ) 10.2), 5.85 (1H, br d, J ) 10.2),
7.22-7.40 (5H, m); MS(EI) m/e 260 (M+). Anal. Calcd for
C
16H20O3: C, 73.89; H, 7.74. Found: C, 73.70; H, 7.72.
(1′S,6′S)-2-[6′-(Ben zyloxym et h yl)-2′-cycloh exyl]b r om o-
eth a n e (12). To a stirred solution of the alcohol 11 (1.53 g, 6.22
mmol) in CH2Cl2 (20 mL) were added CBr4 (2.75 g, 8.29 mmol)
and PPh3 (2.39 g, 9.10 mmol) at 0 °C, whereupon it was allowed
to stir at rt for 12 h. After removal of the solvent, the residue
was chromatographed. Elution with a 20:1 mixture of hexane-
EtOAc provided the bromide 12 (1.64 g, 86%) as a colorless oil:
To a suspension of LAH (2.16 g, 63.6 mmol) in THF (100 mL)
was added dropwise a THF solution (40 mL) of the acetate (4.25
g, 16.4 mmol) at 0 °C, whereupon it was allowed to stir at the
same temperature for 1 h. H2O (2 mL) was cautiously added
followed by 15% aqueous NaOH solution (2 mL) and then H2O
(6 mL). After the mixture was stirred at rt for 20 min, hexane
and MgSO4 were added, whereupon the resulting suspension
was filtered through Celite. The filtered solids were washed
with Et2O several times, then the combined filtrates were
concentrated to provide an oil, which was chromatographed.
Elution with a 1:1 mixture of hexane-EtOAc gave rise to the
[R]26 +89.90 (c 0.400, CHCl3); 1H NMR δ 1.48-2.21 (8H, m),
D
3.36-3.53 (4H, m), 4.52 (2H, dd, J ) 19.8, 12.0), 5.54 (1H, br d,
J ) 10.3), 7.22-7.48 (5H, m). Anal. Calcd for C16H21BrO: C,
62.14; H, 6.84; Br, 25.88. Found: C, 61.93; H, 6.78; Br, 25.96.
(1′S,6′S)-4-[6′-(Ben zyloxym et h yl)-2′-cycloh exyl]-1-(t r i-
m eth ylsilyl)bu tyn e (13). To a stirred solution of (trimethyl-
silyl)acetylene (1.40 mL, 9.9 mmol) in THF (20 mL) was added
dropwise butyllithium (15% hexane solution, 5.8 mL, 8.7 mmol)
at -78 °C, whereupon it was allowed to warm to 0 °C. After 15
min, the mixture was recooled to -78 °C, and then a THF
solution (2 mL) of the bromide 12 (1.70 g, 5.50 mmol) was added
at -78 °C. After addition of HMPA (1.7 mL, 8.7 mmol), the
resulting mixture was allowed to warm to rt over a period of
0.5 h. After 5 h of stirring, the mixture was quenched with
saturated NH4Cl solution, and then the resulting mixture was
extracted with Et2O. The ethereal layer was dried and evapo-
rated to give an oil, which was chromatographed. Elution with
a 20:1 mixture of hexane-EtOAc afforded the TMS-acetylene
13 (1.58 g, 87%) as a colorless oil: [R]22D + 86.34 (c 0.508, CHCl3);
allylic alcohol 9 (2.93 g, 82%) as a colorless oil: [R]27 -82.83 (c
D
1.536, CHCl3); IR (CHCl3) 3450 cm-1; 1H NMR δ 1.28-1.54 (3H,
m), 1.84-1.96 (1H, m), 2.02-2.14 (1H, m), 2.40-2.52 (1H, m),
3.28-3.40 (2H, m), 4.08-4.32 (1H, m), 4.53 (2H, s), 5.79 (2H,
s), 7.22-7.40 (5H, m); MS(EI) m/e 218 (M+). Anal. Calcd for
C
14H18O2: C, 77.03; H, 8.31. Found: C, 76.86; H, 8.39.
Meth od B. A mixture of Ph3P (1.11 g, 4.25 mmol), p-
nitrobenzoic acid (709.8 mg, 4.25 mmol), and DEAD (0.668 mL,
4.25 mmol) in THF (10 mL) was stirred at -30 °C for 20 min,
and then to the resulting mixture was added dropwise a THF
solution (2 mL) of the allylic alcohol 8 (712 mg, 3.27 mmol) at
the same temperature. The mixture was allowed to warm to
rt, whereupon it was allowed to stir for 2 h. Saturated NaHCO3
solution was added, and then the resulting mixture was ex-
tracted with Et2O. The organic layer was dried and evaporated
to leave an oil, which was chromatographed. Elution with a 4:1
mixture of hexane-EtOAc provided the benzoate (1.35 g) as a
1
IR (CHCl3) 2150 cm-1; H NMR δ 0.13 (9H, s), 1.44-2.08 (8H,
m), 2.12-2.36 (2H, m), 3.38 (1H, dd, J ) 9.6, 7.5), 3.48 (1H, dd,
J ) 9.6, 5.1), 4.50 (2H, dd, J ) 19.8, 12.0), 5.54 (1H, br d, J )
10.3), 5.69 (1H, br d, J ) 10.3), 7.25-7.40 (5H, m); HRMS(EI)
calcd for C21H20OSi (M+) 326.2066, found 326.2040.
colorless oil containing trace impurities: IR (CHCl3) 1720 cm-1
;
1H NMR δ 1.40-1.52 (1H, m), 1.72-1.84 (1H, m), 1.92-2.08 (1H,
m), 2.14-2.28 (1H, m), 3.33-3.44 (2H, m), 4.54 (2H, s), 5.55-
5.59 (1H, m), 5.72 (1H, br d, J ) 7.8), 5.86 (1H, br d, J ) 9.9),
7.24-7.38 (5H, m); HRMS(EI) calcd for C21H21NO5 (M+) 367.1420,
found 367.1406.
(1′S,6′S)-4-[6′-(Ben zyloxym et h yl)-2′-cycloh exyl]b u t yn e
(14). A mixture of the TMS-acetylene 13 (1.17 g, 3.59 mmol)
and 1 M NaOH-MeOH solution (50 mL) was stirred at rt for 3
h. After removal of the solvent, H2O was added, and then the
solution was extracted with Et2O. The ethereal layer was
washed with saturated NaCl solution, dried, and evaporated to
give rise to an oil, which was chromatographed. Elution with a
20:1 mixture of hexane-EtOAc provided the acetylene 14 (833
To a suspension of LAH (248 mg, 6.53 mmol) in THF (20 mL)
was added dropwise a THF solution (5 mL) of the above benzoate
(1.35 g) at ambient temperature, whereupon it was stirred at rt
for 1 h. The solution was then cooled to 0 °C, and H2O (0.25
mL) was carefully added followed by 15% NaOH solution (0.25
mL) and then H2O (0.75 mL). After 0.5 h, MgSO4 was added,
whereupon the resulting suspension was filtered through Celite.
The filtered solids were washed with Et2O several times, and
then the combined filtrates were concentrated to give an oil,
which was chromatographed. Elution with a 5:2 mixture of
hexane-EtOAc furnished the alcohol 9 (570 mg, 80% form 8).
Eth yl (1′S,6'S)-2-[6′-(Ben zyloxym eth yl)-2′-cycloh exyl]a c-
eta te (10). A mixture of the allylic alcohol 9, o-nitrophenol (5.0
mg, 93%) as a colorless oil: [R]22 +108.29 (c 0.310, CHCl3); IR
D
(CHCl3) 2120 cm-1
;
1H NMR δ 1.44-1.66 (2H, m), 1.67-1.92
(3H, m), 1.94-2.02 (3H, m), 2.02-2.14 (1H, m), 2.14-2.36 (2H,
m), 3.38 (1H, dd, J ) 9.3, 7.5), 3.49 (1H, dd, J ) 9.3, 5.1), 4.50
(2H, dd, J ) 18.0, 12.0), 5.55 (1H, br d, J ) 9.9), 5.71 (1H, br d,
J ) 9.9), 7.25-7.40 (5H, m); HRMS(EI) calcd for C18H22O (M+)
254.1671, found 254.1627.
(3a R,4S,7a R)-4-(Ben zyloxym eth yl)-3a ,4,5,6,7,7a -h exa h y-
d r o-1-in d en e (15). Ra d ica l Cycliza tion . To a stirred solution