6796 J. Am. Chem. Soc., Vol. 121, No. 29, 1999
Morimoto et al.
6.7, 4.8, 1.6 Hz), 2.78 (2H, d, J ) 4.8 Hz), 2.62 (2H, d, J ) 5.0 Hz),
2.00-1.72 (4H, m), 1.36 (6H, s); 13C NMR (75 MHz, CDCl3) δ 81.5,
57.0, 52.5, 27.0, 17.3; IR (neat) 2980, 1450, 1350, 1235, 1170, 1060,
995, 965, 900, 845, 805, 715 cm-1; EI-MS m/z (relative intensity) 184
(M+, 5.0), 154 (46), 127 (40), 97 (85), 57 (77), 55 (100); EI-HRMS
calcd for C10H16O3 (M+) 184.1099, found 184.1084.
of trifluoroacetic anhydride and 0.1 mL of acetonitrile, and the solution
was cooled to -45 °C under a nitrogen atmosphere. To the solution
was added diol 3 (56.6 mg, 0.123 mmol) dissolved in 2 mL of
dichloromethane, and the solution was stirred at -45 °C for 8 h. To
the solution was added 5 mL of 1 M aqueous sodium hydroperoxide,
and the mixture was allowed to warm to room temperature. After being
stirred for 30 min, the resulting mixture was filtered through a pad of
Celite. The filtrates were poured into 15 mL of water and extracted
with dichloromethane (15 mL × 3). The extracts were washed with 30
mL of brine, dried over anhydrous magnesium sulfate, and concentrated
in vacuo. The residue was purified by column chromatography (hexane/
ethyl acetate ) 85:15) on 6 g of silica gel to afford diol 3 (2.2 mg,
3.8% yield) as a colorless oil, monocyclized alcohol 9 (8.8 mg, 15.0%
yield) as a colorless oil, and teurilene (1) (17.6 mg, 29.0% yield) as a
white solid.
Neryl Phenyl Sulfide (7). To a solution of nerol (2.29 g, 14.9 mmol)
and diphenyl disulfide (4.54 g, 20.8 mmol) dissolved in 60 mL of
tetrahydrofuran was added dropwise 5.13 mL (20.8 mmol) of tributyl-
phosphine, and the mixture was stirred under a nitrogen atmosphere at
room temperature for 2 h. To the reaction mixture was added 50 mL
of 1 M aqueous sodium hydroxide solution, and the aqueous layer was
extracted with ether (50 mL × 3). The organic layer was washed with
brine, dried over anhydrous magnesium sulfate, and concentrated in
vacuo. The residue was purified by column chromatography (hexane/
ethyl acetate ) 96:4) on 170 g of silica gel to provide sulfide 7 (3.56
g, 97.2% yield) as a colorless oil: Rf ) 0.28 (hexane); 1H NMR (400
MHz, CDCl3) δ 7.35-7.31 (2H, m), 7.29-7.24 (2H, m), 7.16 (1H, tt,
J ) 7.2, 1.5 Hz), 5.32 (1H, dt, J ) 1.3, 7.7 Hz), 5.13-5.06 (1H, m),
3.55 (2H, dd, J ) 7.8, 0.7 Hz), 2.08-1.99 (4H, m), 1.72 (3H, d, J )
1.0 Hz), 1.68 (3H, s), 1.60 (3H, s); 13C NMR (100 MHz, CDCl3) δ
140.0, 137.0, 132.0, 129.4, 128.7, 125.8, 123.9, 119.8, 31.92, 31.87,
26.5, 25.7, 23.4, 17.7; IR (neat) 2990, 2940, 1585, 1480, 1440, 1375,
1220, 1090, 1025, 835, 735, 690 cm-1; EI-MS m/z (relative intensity)
246 (M+, 16), 137 (53), 110 (29), 69 (100); EI-HRMS calcd for
C16H22S (M+) 246.1443, found 246.1432.
(2R*,5S*)-2-[(4Z,1S*)-1-Hydroxy-1,5,9-trimethyl-4,8-decadienyl]-
5-[(4Z,1R*)-1-hydroxy-1,5,9-trimethyl-4,8-decadienyl]tetrahydro-
furan (3). To a solution of bisepoxide 6 (2.06 g, 11.2 mmol), sulfide
7 (8.25 g, 33.5 mmol), and 10 mL (66.3 mmol) of N,N,N′,N′-
tetramethylethylenediamine dissolved in 100 mL of tetrahydrofuran was
added dropwise 27.7 mL (44.7 mmol) of butyllithium (1.6 M in hexane)
under a nitrogen atmosphere at -78 °C, and the mixture was stirred at
the same temperature for 1 h. To the reaction mixture was added 100
mL of water, and the aqueous layer was extracted with ether (100 mL
× 3). The organic layer was washed with brine, dried over anhydrous
magnesium sulfate, and concentrated under reduced pressure. The
residue was subjected to column chromatography (hexane/ethyl acetate
) 85:15) on 180 g of silica gel to yield bissulfide 8 (6.60 g, 87.2%
yield) as a mixture of diastereomeric sulfides.
Diol 3. Rf ) 0.58 (hexane/ethyl acetate ) 70:30). Characterization
data have already been described above.
Monocyclized Alcohol 9. Rf ) 0.45 (hexane/ethyl acetate ) 70:
1
30); H NMR (400 MHz, CDCl3) δ 5.16-5.06 (3H, m), 3.97-3.90
(1H, m), 3.87-3.75 (2H, m), 2.15-1.75 (18H, m), 1.68 (9H, s), 1.61
(6H, s), 1.55-1.43 (2H, m), 1.38-1.20 (2H, m), 1.30 (3H, s), 1.25
(3H, s), 1.22 (3H, s); 13C NMR (100 MHz, CDCl3) δ 135.2, 131.6,
131.5, 125.3, 124.5, 124.3, 87.4, 85.5, 85.2, 84.9, 73.6, 72.0, 38.5, 37.4,
34.3, 31.9, 26.8, 26.6, 25.71, 25.70, 25.66, 25.4, 25.3, 24.5, 24.3, 23.4,
22.2, 22.1, 17.63, 17.60; IR (neat) 3470, 2995, 2950, 2890, 1450, 1375,
1077 cm-1; EI-MS m/z (relative intensity) 476 (M+, 1.9), 458 (8.0),
440 (6.0), 211 (100), 193 (68), 175 (54), 135 (74), 69 (94); EI-HRMS
calcd for C30H52O4 (M+) 476.3866, found 476.3883.
Synthetic Teurilene (1). Rf ) 0.33 (hexane/ethyl acetate ) 70:30);
mp 83.5-85 °C (recrystallized from diisopropyl ether); [R]21D +0.2 (c
0.24, CHCl3);17 1H NMR (400 MHz, CDCl3) δ 5.11 (2H, br t, J ) 6.9
Hz), 3.87 (2H, br t, J ) 5.1 Hz), 3.83 (2H, dd, J ) 9.8, 5.9 Hz), 2.17-
1.55 (18H, m), 1.68 (6H, s), 1.61 (6H, s), 1.49 (2H, ddd, J ) 13.5,
11.6, 5.0 Hz), 1.33 (2H, ddd, J ) 13.4, 11.6, 5.3 Hz), 1.20 (6H, s),
1.18 (6H, s); 13C NMR (100 MHz, CDCl3) δ 131.5, 124.6, 86.7, 85.3,
84.5, 72.2, 37.4, 33.5, 27.3, 25.8, 25.7, 24.5, 24.2, 22.2, 17.6; IR
(CHCl3) 3550, 2980, 2940, 2870, 1450, 1370, 1070 cm-1; EI-MS m/z
(relative intensity) 492 (M+, 1.1), 474 (7.8), 459 (9.6), 405 (11), 392
(12), 347 (33), 211 (100), 193 (54), 69 (49); EI-HRMS calcd for
C30H52O5 (M+) 492.3814, found 492.3832.
The bissulfide 8 (6.60 g, 9.75 mmol) was dissolved in a mixture of
tetrahydrofuran (100 mL) and 2-propanol (50 mL) under a nitrogen
atmosphere. Metallic sodium (5.0 g, 0.217 mol) was added to the boiling
solution under reflux, and the resulting mixture was stirred under reflux
for 12 h. After the mixture was cooled to room temperature, 150 mL
of water was added to the solution and the mixture was extracted with
ether (150 mL × 3). The organic layer was washed with brine, dried
over anhydrous magnesium sulfate, and concentrated in vacuo. The
residue was purified by column chromatography (hexane/ethyl acetate
) 85:15) on 180 g of silica gel to give crude product. Further
purification of the crude product was carried out by column chroma-
tography (benzene/ethyl acetate ) 70:30) on 180 g of 10% silver nitrate-
coated silica gel to provide diol 3 (3.27 g, 75.1% yield) as a colorless
oil: Rf ) 0.33 (benzene/ethyl acetate ) 70:30 on 10% silver nitrate-
coated TLC); 1H NMR (400 MHz, CDCl3) δ 5.15-5.07 (4H, m), 3.77
(2H, br t, J ) 5.0 Hz), 2.25-1.75 (18H, m), 1.68 (12H, s), 1.61 (6H,
s), 1.49 (2H, ddd, J ) 13.7, 10.9, 5.7 Hz), 1.37 (2H, ddd, J ) 13.4,
11.0, 5.7 Hz), 1.27 (6H, s); 13C NMR (100 MHz, CDCl3) δ 135.6,
131.6, 125.1, 124.2, 85.1, 73.8, 38.6, 31.9, 26.5, 25.7, 24.1, 23.4, 22.0,
17.6; IR (neat) 3400, 2980, 2940, 1450, 1370, 1235, 1135, 1080, 985,
825 cm-1; EI-MS m/z (relative intensity) 460 (M+, 1.0), 442 (7.0), 425
(2.1), 378 (10), 292 (24), 195 (27), 177 (44), 136 (50), 109 (63), 69
(100); EI-HRMS calcd for C30H52O3 (M+) 460.3917, found 460.3914.
Teurilene (1). To a solution of rhenium(VII) oxide (357 mg, 0.738
mmol) dissolved in 4 mL of acetonitrile was added dropwise 0.104
mL (0.738 mmol) of trifluoroacetic anhydride, and the solution was
stirred under a nitrogen atmosphere at room temperature for 30 min.
The solution was cooled to 0 °C and concentrated in vacuo to give
trifluoroacetyl perrhenate as a solid.
Monoacetate 11. To a solution of meso diol 3 (503 mg, 1.09 mmol)
and 4-(dimethylamino)pyridine (40 mg, 0.328 mmol) dissolved in 5
mL of dichloromethane were successively added pyridine (0.53 mL,
6.55 mmol) and acetic anhydride (0.41 mL, 4.73 mmol), and the mixture
was stirred under a nitrogen atmosphere at room temperature for 3 days.
To the reaction mixture was added 30 mL of 1 M aqueous hydrochloric
acid, and the aqueous layer was extracted with dichloromethane (20
mL × 3). The organic layer was washed with saturated aqueous sodium
hydrogen carbonate and brine, dried over anhydrous magnesium sulfate,
and concentrated in vacuo. The residue was purified by column
chromatography (hexane/ethyl acetate ) 90:10) on 30 g of silica gel
to afford monoacetate 11 (277 mg, 50.6% yield) as a colorless oil: Rf
) 0.48 (hexane/ethyl acetate ) 80:20); 1H NMR (400 MHz, CDCl3) δ
5.17-5.04 (4H, m), 4.15-4.08 (1H, m), 3.76-3.67 (1H, m), 2.30-
1.20 (20H, m), 1.98 (3H, s), 1.69 (9H, s), 1.67 (3H, s), 1.61 (6H, s),
1.50 (3H, s), 1.23 (3H, s); 13C NMR (100 MHz, CDCl3) δ 170.1, 135.5,
135.3, 131.51, 131.50, 125.2, 124.5, 124.3, 124.2, 85.2, 85.1, 82.1,
73.0, 38.1, 36.2, 31.89, 31.87, 26.54, 26.51, 26.0, 25.7, 25.3, 24.2, 23.34,
23.30, 22.3, 22.2, 21.9, 20.1, 17.6; IR (neat) 3540, 2970, 2925, 1727,
1436, 1361, 1238, 1065, 1010, 820 cm-1; EI-MS m/z (relative intensity)
502 (M+, 4.0), 442 (19), 424 (6.0), 373 (6.0), 305 (20), 292 (25), 177
(25), 142 (36), 109 (40), 81 (43), 69 (100); EI-HRMS calcd for
C32H54O4 (M+) 502.4022, found 502.4018.
Oxidative Cyclization of Monoacetate 11. To a solution of
rhenium(VII) oxide (130 mg, 0.268 mmol) dissolved in 3 mL of
acetonitrile was added dropwise 0.04 mL (0.268 mmol) of trifluoroacetic
anhydride, and the solution was stirred under a nitrogen atmosphere at
room temperature for 30 min. The solution was cooled to 0 °C and
concentrated in vacuo to give trifluoroacetyl perrhenate as a solid.
To a solution of the above trifluoroacetyl perrhenate dissolved in 4
mL of dichloromethane was added 0.09 mL (0.671 mmol) of tri-
To a solution of the above trifluoroacetyl perrhenate dissolved in 3
mL of dichloromethane were sequentially added 0.262 mL (1.85 mmol)