Construction of the Bicyclo[5.3.0]decenone Skeleton
1H), 3.57-3.48 (m, 1H), 3.21 (t, 2H, J ) 7.3 Hz), 2.81 (tt, 2H,
J ) 7.3, 2.0 Hz), 1.88-1.46 (m, 6H); 13C NMR δ 96.55, 84.73,
77.83, 61.89, 54.25, 30.12, 25.23, 23.97, 18.98, 1.24; MS m/z
294 (M+, 5.8); HRMS calcd for C10H15IO2 294.0117, found
bromide in THF (0.50 M, 57.0 mL, 28.5 mmol) at -20 °C. The
reaction mixture was stirred at the same temperature for 2.5
h; the reaction was quenched by addition of saturated aqueous
NH4Cl, and the mixture was extracted with Et2O. The extract
was washed with water and brine, dried, and concentrated to
dryness. The residue was passed through a short pad of silica
gel with 6:1 hexane-AcOEt to afford the crude alcohol. The
alcohol was taken up in DMF (20 mL), to which imidazole (3.42
g, 50.3 mmol) and TBDMSCl (3.81 g, 25.2 mmol) were added
at room temperature. The reaction mixture was stirred at room
temperature for 12 h; the reaction was quenched by addition
of water, and the mixture was extracted with Et2O. The extract
was washed with water and brine, dried, and concentrated to
dryness. The residual oil was chromatographed with 40:1
hexane-AcOEt to afford 29 (3.04 g, 45%) as a colorless oil:
IR 3306, 2172 cm-1; 1H NMR δ 4.39 (td, 1H, J ) 6.3, 2.0 Hz),
2.38 (d, 1H, J ) 2.0 Hz), 2.27 (t, 2H, J ) 6.9 Hz) 1.89-1.60
(m, 4H), 0.91 (s, 9H), 0.14 (s, 9H), 0.12 (s, 6H); 13C NMR δ
106.90, 85.19, 84.73, 72.20, 62.32, 37.36, 25.75, 24.08, 19.46,
18.17, 0.13, -4.60, -5.08; MS m/z 308 (M+, 0.7); HRMS calcd
for C17H32OSi2 308.1992, found 308.1979.
6-(ter t-Bu tyldim eth ylsiloxy)-1-(tr im eth ylsilyl)-1,7-n on a-
d iyn -9-ol (30a ). To a solution of 29 (871 mg, 2.82 mmol) in
dry THF (28 mL) was added n-BuLi in hexane (1.36 M, 2.49
mL, 3.39 mmol) at -78 °C. After the mixture was stirred for
40 min, (HCHO)n (425 mg, 14.1 mmol) was added, and the
reaction mixture was stirred at room temperature for 6 h. The
reaction was quenched by addition of aqueous saturated
NH4Cl, and the mixture was extracted with Et2O. The extract
was washed with water and brine, dried, and concentrated to
dryness. The residual oil was chromatographed with 6:1
hexane-AcOEt to afford 30a (699 mg, 73%) as a colorless oil:
IR 3609, 3422, 2170 cm-1; 1H NMR δ 4.43 (tt, 1H, J ) 6.3, 2.0
Hz), 4.29 (dd, 2H, J ) 6.4, 2.0 Hz), 2.26 (t, 2H, J ) 6.8 Hz),
1.81-1.62 (m, 4H), 1.50-1.45 (m, 1H), 0.91 (s, 9H), 0.15 (s,
9H), 0.13 (s, 3H), 0.11 (s, 3H); 13C NMR δ 107.00, 87.26, 84.70,
82.29, 62.53, 51.18, 37.42, 25.79, 24.20, 19.51, 18.22, 0.14,
-4.49; MS m/z 338 (M+, 0.3); HRMS calcd for C18H34O2Si2
338.2097, found 338.2086.
294.0111. Anal. Calcd for
Found: C, 40.76; H, 5.25.
C10H15IO2: C, 40.83; H, 5.14.
4,4-Bis(m eth oxyca r bon yl)-1,7-n on a d iyn -9-ol (25a ). To
a solution of dimethyl malonate (0.20 mL, 1.80 mmol) in dry
DMF (10 mL) was added NaH (60% in mineral oil, 81.0 mg,
2.03 mmol) at 0 °C. After the mixture was stirred for 30 min,
a DMF solution (2.0 mL) of 24 (541 mg, 1.84 mmol) was added,
and the reaction mixture was stirred for 6 h at room temper-
ature. The reaction was quenched by addition of saturated
aqueous NH4Cl, and the mixture was extracted with AcOEt.
The extract was washed with water and brine, dried, and
concentrated to dryness. To a solution of the crude product in
dry THF (10 mL) was added NaH (60% in mineral oil, 81.0
mg, 2.03 mmol) at 0 °C. After the mixture was stirred for 30
min, propargyl bromide (0.14 mL, 1.90 mmol) was added, and
the reaction mixture was stirred at room temperature for 3 h.
The reaction was quenched by addition of saturated aqueous
NH4Cl, and the mixture was extracted with AcOEt. The
extract was washed with water and brine, dried, and concen-
trated to dryness. To a solution of the crude product in MeOH
(10 mL) was added p-TsOH (34.2 mg, 0.18 mmol) at room
temperature. After the mixture was stirred for 12 h, MeOH
was evaporated off, and the residue was extracted with AcOEt.
The extract was washed with water and brine, dried, and
concentrated to dryness. The residue was chromatographed
with 3:1 hexane-AcOEt to afford 25a (249 mg, 56%) as a
colorless oil: IR 3528, 3308, 1734 cm-1; 1H NMR δ 4.24-4.17
(m, 2H), 3.77 (s, 6H), 2.85 (d, 2H, J ) 2.6 Hz), 2.37-2.18 (m,
4H), 2.02 (t, 1H, J ) 2.6 Hz), 1.94 (br s, 1H); 13C NMR δ 170.21,
84.33, 79.28, 78.31, 71.75, 56.14, 52.87, 51.09, 30.82, 22.82,
14.09; MS m/z 252 (M+, 1.0); HRMS calcd for C13H16O5
252.0998, found 252.0998. Anal. Calcd for C13H16O5: C, 61.90;
H, 6.39. Found: C, 61.52; H, 6.48.
6,6-Bis(m eth oxycar bon yl)-3-(ph en ylsu lfon yl)-1,2-n on a-
d ien -8-yn e (26a ). According to the procedure described for
preparation of 12a , 26a (289 mg, 77%) was obtained from 25a
(252 mg, 1.00 mmol) as colorless needles: mp 94-95 °C
(hexane-AcOEt); IR 3308, 1971, 1936, 1734 cm-1; 1H NMR δ
7.91-7.82 (m, 2H), 7.66-7.47 (m, 3H), 5.41 (t, 2H, J ) 3.0
Hz), 3.69 (s, 6H), 2.77 (d, 2H, J ) 3.0 Hz), 2.26-2.08 (m, 4H),
1.95 (t, 1H, J ) 2.6 Hz); 13C NMR δ 207.51, 169.97, 139.95,
133.50, 129.04, 128.03, 112.53, 85.27, 78.10, 71.72, 56.25,
52.87, 30.30, 23.09, 21.75; MS m/z 376 (M+, 8.6); HRMS calcd
for C19H20O6S 376.0981, found 376.0985. Anal. Calcd for
4-(ter t-Bu tyld im eth ylsiloxy)-3-(p h en ylsu lfon yl)-9-(tr i-
m eth ylsilyl)-1,2-n on a d ien -8-yn e (31a ). According to the
procedure described for preparation of 12a , 31a (237 mg, 94%)
was obtained from 30a (184 mg, 0.54 mmol) as a colorless oil:
IR 2172, 1971, 1931 cm-1; 1H NMR δ 7.93-7.87 (m, 2H), 7.65-
7.50 (m, 3H), 5.43-5.33 (m, 2H), 4.49-4.44 (m, 1H), 2.20-
2.15 (m, 2H), 1.91-1.68 (m, 2H), 1.56-1.48 (m, 2H), 0.79 (s,
9H), 0.14 (s, 9H), -0.06 (s, 3H), -0.18 (s, 3H); 13C NMR δ
208.80, 140.88, 133.50, 129.02, 128.10, 117.34, 106.96, 85.21,
84.71, 68.45, 37.07, 25.63, 23.96, 19.55, 18.01, 0.13, -5.17,
-5.34; FABMS m/z 463 (M+ + 1, 2.8); FABHRMS calcd for
C
19H20O6S: C, 60.62; H, 5.36. Found: C, 60.44; H, 5.54.
6-(ter t-Bu tyldim eth ylsiloxy)-1-(tr im eth ylsilyl)-1,7-octa-
C
24H39O3SSi2 463.2158, found 463.2160.
d iyn e (29). To a solution of 5-hexyn-1-ol (15) (2.15 g, 21.9
mmol) in dry THF (65 mL) was added n-BuLi in hexane (1.46
M, 36.0 mL, 52.6 mmol) at -78 °C. After the mixture was
stirred for 1 h, TMSCl (14.0 mL, 110 mmol) was added, and
the reaction mixture was stirred at the same temperature for
30 min and then at room temperature for 12 h. Then, 10%
aqueous HCl (18 mL) was added to the reaction mixture, which
was stirred for 1 h, neutralized with saturated aqueous
NaHCO3, and extracted with AcOEt. The extract was washed
with water and brine, dried, and concentrated to dryness. The
residue was passed through a short pad of silica gel with 3:1
hexane-AcOEt to afford the C-silylated hexynol. To a solution
of the hexynol, DMSO (5.00 mL, 70.4 mmol), and Et3N (10.0
mL, 71.7 mmol) in dry CH2Cl2 (100 mL) was added SO3‚
pyridine (10.5 g, 66.0 mmol) at 0 °C. After the mixture was
stirred for 6 h at room temperature, the reaction was quenched
by addition of saturated aqueous NH4Cl, and the mixture was
extracted with CH2Cl2. The extract was washed with water
and brine, dried, and concentrated to dryness. The residue was
passed through a short pad of silica gel with 8:1 hexane-
AcOEt to afford the crude aldehyde. To a solution of the crude
aldehyde in dry THF (100 mL) was added ethynylmagnesium
3-(P h en ylsu lfon yl)-9-(t r im et h ylsilyl)-1,2-n on a d ien -8-
yn -4-ol (32a ). To a solution of 31a (160 mg, 0.35 mmol) in
MeOH (3.4 mL) was added 10% aqueous HCl (0.6 mL) at room
temperature. After the mixture was stirred for 14 h, MeOH
was evaporated off, and the residue was extracted with AcOEt.
The extract was washed with water and brine, dried, and
concentrated to dryness. The residual oil was chromatographed
with 7:3 hexane-AcOEt to afford 32a (92.8 mg, 77%) as a
colorless oil: IR 3551, 2172, 1967, 1929 cm-1; 1H NMR δ 7.94-
7.89 (m, 2H), 7.66-7.52 (m, 3H), 5.45 (d, 2H, J ) 1.5 Hz),
4.49-4.43 (m, 1H), 2.93 (d, 1H, J ) 4.4 Hz), 2.18 (td, 2H, J )
6.8, 3.4 Hz), 1.80-1.41 (m, 4H), 0.12 (s, 9H); 13C NMR δ 207.44,
140.35, 133.76, 129.09, 128.06, 115.86, 106.59, 85.46, 85.04,
67.88, 34.16, 24.48, 19.40, 0.10; MS m/z 348 (M+, 0.4); HRMS
calcd for C18H24O3SSi 348.1216, found 348.1219. Anal. Calcd
for C18H24O3SSi: C, 62.03; H, 6.94. Found: C, 61.78; H, 7.02.
1-(Tr im eth ylsilyl)-1,7-octa d iyn -3-ol (33). To a solution
of 5-hexyn-1-ol (15) (1.96 g, 20.0 mmol), DMSO (6.40 mL, 90.0
mmol), and Et3N (12.5 mL, 90.0 mmol) in dry CH2Cl2 (100 mL)
was added SO3‚pyridine (14.3 g, 90.0 mmol) at 0 °C. After the
mixture was stirred for 1 h, the reaction was quenched by
J . Org. Chem, Vol. 68, No. 4, 2003 1383