(+)-Dihydrocuscohygrine and Cuscohygrine
carrier gas. Optical rotations were determined on a polarimeter
as solutions in a 10 cm unit cell at 589 nm. Rf values indicated
refer to TLC on 0.2 mm analytical plates coated with silica
gel. MTBE ) methyl tert-butyl ether. Chemicals were pur-
chased and used without further purification.
) -12° (c 0.34, CHCl3). Anal. Calcd for C22H34N2O6SSi: C,
54.77; H, 7.05; N, 5.81. Found: C, 54.36; H, 7.12; N, 6.01.
Ch lor id e 11. To a solution of alcohol 10 (4.25 g, 8.82 mmol)
in pyridine (25 mL) was added mesyl chloride (1.81 g, 15.9
mmol) dropwise under cooling (ice bath) and stirring. After
stirring at room temperature for 18 h, the solvents were
distilled off, and the residue was suspended in ethyl acetate
(100 mL) and filtered through silica. The filtrate was concen-
trated in vacuo. 11 was obtained as a light yellow oil (3.75 g,
p-Nosyla m id e 7. To a solution of acetate 64 (3.5 g, 11.7
mmol), allyl-p-nosylamide10 (4.23 g, 17.5 mmol), and PPh3 (9.17
g, 35.1 mmol) in THF (100 mL) was added diisopropylazodi-
carboxylate (4.71 g, 23.4 mmol) dropwise at 0 °C. After stirring
for 18 h at room temperature, the solution was concentrated
in vacuo and the residue was purified by flash chromatography
(silica, cyclohexane/MTBE 3:1) to give 7 as light yellow oil (5.01
g, 82% yield). Rf ) 0.50 (cyclohexane/MTBE 1:1). 1H NMR (200
MHz): δ 8.28-8.38 (m, 2H), 7.94-8.06 (m, 2H), 5.60-5.91 (m,
2H), 5.09-5.40 (m, 4H), 4.84-4.96 (m, 1H), 4.12-4.28 (m, 1H),
3.90-4.05 (m, 1H), 3.62-3.78 (m, 1H), 1.70-2.25 (m, 4H), 2.03
(s, 3H), 0.85 (s, 9H), 0.03 (s, 6H). 13C NMR (125 MHz): δ
170.00, 149.71, 146.87, 135.01, 134.58, 132.77, 128.25, 124.20,
118.41, 69.95, 64.37, 53.41, 47.66, 42.21, 41.78, 25.60, 21.06,
17.84, - 4.96, - 4.90. IR: ν 3105, 3082, 3035, 1739, 1531, 1350,
1240, 837, 777 cm-1. MS m/z (%) 509 (1), 467 (40), 117 (100),
75 (97). HR-MS calcd for C23H33N2O7SSi 509.1778 [M - CH3]+,
1
85% yield). Rf ) 0.53 (cyclohexane/MTBE 1:1). H NMR (500
MHz): δ 8.30-8.38 (m, 2H), 7.95-8.05 (m, 2H), 5.75-5.86 (m,
2H), 5.40-5.46 (m, 1H), 5.19-5.27 (m, 1H), 5.10-5.18 (m, 1H),
4.97-5.04 (m, 1H), 4.82-4.87 (m, 1H), 4.18-4.27 (m, 1H),
3.93-4.00 (m, 1H), 3.69-3.76 (m, 1H), 2.03-2.20 (m, 3H),
1.85-1.94 (m, 1H), 0.92 (s, 9H), 0.03 (s, 6H). 13C NMR (125
MHz): δ 149.97, 146.86, 135.26, 134.68, 133.98, 128.46, 124.39,
118.65, 66.87, 53.73, 53.63, 48.22, 43.96, 42.05, 25.83, 18.11,
-4.85, -4.79. IR: ν 3106, 3084, 1531, 1350, 1166, 837, 734
cm-1. MS m/z (%) 485 (<1), 443 (100), 299 (24), 69 (39). HR-
MS calcd for C21H30N2O5ClSSi 485.1333 [M - CH3]+, obsd
485.1331. [R]20 ) +71° (c 0.23, CHCl3). Anal. Calcd for
D
C
22H33N2O5ClSSi: C, 52.75; H, 6.59; N, 5.59. Found: C, 52.84;
obsd 509.1775. [R]20 ) -77° (c 0.28, CHCl3). Anal. Calcd for
H, 6.34; N, 5.66.
D
C
24H36N2O7SSi: C, 54.96; H, 6.87; N, 5.34. Found: C, 54.96;
Dia m in e 12. Chloride 11 (3.60 g, 7.19 mmol), allylamine
(2.05 g, 36 mmol), and K2CO3 (1.49 g, 10.8 mmol) were stirred
in acetonitrile (25 mL) at 70 °C for 18 h. Then brine (100 mL)
was added and the solution was extracted with MTBE (3 ×
50 mL). The combined organic phases were washed with brine
(20 mL), dried over MgSO4, and concentrated in vacuo, and
the residue was purified by flash-chromatography (silica,
cyclohexane/MTBE 1:1 (2% Et2NH)), giving 12 as a pale yellow
oil (3.23 g, 86% yield). Rf ) 0.50 (cyclohexane/MTBE/Et2NH
10:10:1). 1H NMR (200 MHz): δ 8.28-8.36 (m, 2H), 7.96-8.05
(m, 2H), 5.68-6.02 (m, 3H), 5.08-5.39 (m, 5H), 4.83-4.97 (m,
1H), 4.08-4.24 (m, 1H), 3.87-4.03 (m, 1H), 3.62-3.77 (m, 1H),
3.24-3.40 (m, 3H), 2.00-2.20 (m, 2H), 1.64-1.92 (m, 1H), 0.90
(s, 9H), 0.04 (s, 6H). 13C NMR (125 MHz): δ 149.87, 147.20,
138.06, 136.47, 134.98, 132.06, 128.44, 124.33, 118.34, 116.30,
66.54, 54.13, 52.19, 49.52, 47.85, 42.47, 42.07, 25.85, 18.05,
-4.75, - 4.65. IR: ν 3335, 3104, 3081, 1723, 1531, 1349, 1255,
1165, 836, 735 cm-1. MS m/z (%) 522 (16), 407 (16), 203 (52),
73 (100). HR-MS calcd for C25H40N3O5SSi 522.2458 [MH]+,
H, 7.13; N, 5.56.
Tosyla m id e 8. To a mixture of acetate 6 (610 mg, 2.03
mmol), N-allyl-N-tosylamide11 (500 mg, 2.37 mmol), and NaH
(90 mg 60% suspension in mineral oil, 2.25 mmol) was added
dry THF (15 mL). DMF (4-5 mL) was then added to the
suspension until the solution became clear. Under N2 atmo-
sphere [Pd2(dba)3]dCHCl3 (52 mg, 0.051 mmol, 2.5 mol %) and
dppb (90 mg, 0.21 mmol, 10 mol %) were added as solids. The
solution was stirred for 30 min at 50 °C. After addition of water
(50 mL), the solution was extracted with MTBE (3 × 20 mL).
The combined organic phases were washed with brine (20 mL),
dried over MgSO4, and concentrated in vacuo. The residue was
purified by flash chromatography (silica, cyclohexane/MTBE
3:1), affording 8 (755 mg, 82%) as yellow oil. Rf ) 0.27
(cyclohexane/MTBE 3:1). 1H NMR (200 MHz): δ 7.64-7.72 (m,
2H), 7.21-7.31 (m, 2H), 5.89-6.10 (m, 1H), 5.57-5.70 (m, 1H),
5.38-5.50 (m, 1H), 5.24-5.36 (m, 1H), 5.08-5.17 (m, 1H),
4.74-4.80 (m, 1H), 4.02-4.22 (m, 4H), 3.90-4.02 (m, 1H),
2.20-2.60 (m, 3H), 2.40 (s, 3H), 1.70-1.84 (m, 1H), 0.84 (s,
9H), 0.05 (s, 6H). 13C NMR (125 MHz): δ 143.00, 137.72,
136.27, 131.45, 129.45, 127.98, 126.20, 116.51, 72.55, 67.88,
62.29, 47.67, 41.52, 34.73, 25.59, 21.43, 17.78, - 5.21, - 5.33.
IR: ν 3488, 3081, 3035, 1598, 1338, 1255, 1159, 1091, 1025,
837, 712 cm-1. MS m/z (%) 433 (2) [M+ - OH], 394 (21), 183
obsd 522.2455. [R]20 ) -41° (c 0.60, CHCl3). Anal. Calcd for
D
C
25H39N3O5SSi: C, 57.58; H, 7.49; N, 8.06. Found: C, 58.56;
H, 7.08; N, 7.56.
Dica r ba m a te 13. Diamine 12 (2.20 g, 4.22 mmol) and K2-
CO3 (2.91 g, 21.1 mmol) were suspended in DMF (15 mL).
PhSH (930 mg, 8.22 mmol) was added and the suspension was
stirred at 70 °C for 30 min. The mixture was then cooled to 0
°C and ethylchloroformate (1.37 g, 12.6 mmol) was added
dropwise under stirring over 25 min. The mixture was stirred
for 30 min at 0 °C and then for 2 h at room temperature. The
mixture was poured into water (150 mL) and extracted with
MTBE (50 mL). The aqueous phase was saturated with NaCl
and extracted with MTBE (2 × 50 mL). The combined organic
phases were washed with brine (50 mL), dried over MgSO4,
and concentrated in vacuo. Purification of the residue by flash
chromatography (silica, cyclohexane/MTBE 5:1 to 3:1) yielded
dicarbamate 13 as light yellow oil (1.66 g, 82% yield). Rf )
0.32 (cyclohexane/MTBE 3:1). 1H NMR (200 MHz): (rotameric
mixture) δ 5.64-5.88 (m, 2H), 5.38-5.62 (m, 2H), 4.94-5.18
(m, 4H), 4.28-4.84 (m, 2H), 3.96-4.20 (m, 5H), 3.51-3.92 (m,
4H), 2.08-2.40 (m, 1H), 1.82-2.02 (m, 2H), 1.64-1.80 (m, 1H),
1.19 (t, J ) 7 Hz, 3H), 1.18 (t, J ) 7 Hz, 3H), 0.80 (s, 9H),
-0.04 (s, 6H). 13C NMR (50 MHz): (rotameric mixture) δ
155.61, 135.91, 135.27, 134.85, 133.27, 115.94, 116.18, 66.18,
61.09, 60.93, 51.85, 51.08, 48.00, 46.12, 42.07, 25.53, 17.74,
14.42, -5.08, -4.93. IR: ν 3081, 1699, 1411, 1250, 837, 774
cm-1. MS m/z (%) 480 (5), 423 (85), 294 (44), 186 (100). HR-
(100), 91 (88). HR-MS calcd for C23H35NO3SSi [M+ OH):
-
433.2107, obsd 433.2101. [R]D20 ) -103° (c 0.47, CHCl3). Anal.
Calcd for C23H37NO4SSi: C, 61.20; H, 8.20; N, 3.14; Found:
C, 61.28; H, 8.00; N, 3.11.
Alcoh ol 10. p-Nosylamide 7 (4.95 g, 9.45 mmol) and KCN
(20 mg, 0.3 mmol) were dissolved in MeOH (50 mL) and stirred
for 18 h at room temperature. The solution was concentrated
in vacuo. Purification of the residue by flash chromatography
(silica, cyclohexane/MTBE 1:1) afforded 10 as pale yellow oil
(4.33 g, 95% yield). Rf ) 0.20 (cyclohexane/MTBE/MeOH 5:5:
1
1). H NMR (200 MHz): δ 8.30-8.37 (m, 2H), 7.96-8.05 (m,
2H), 5.68-5.93 (m, 2H), 4.98-5.32 (m, 4H), 4.18-4.37 (m, 2H),
3.91-4.04 (m, 1H), 3.60-3.76 (m, 1H), 2.20-2.60 (br s, 1H),
1.85-2.14 (m, 4H), 0.93 (s, 9H), 0.10 (s, 6H). 13C NMR (125
MHz): δ 149.95, 146.91, 136.76, 134.99, 132.65, 128.45, 124.40,
118.40, 67.46, 67.02, 54.22, 48.06, 42.58, 42.27, 25.83, 18.06,
- 4.97, - 4.81. IR: ν 3540, 3427, 3105, 3082, 3026, 1531, 1350,
832, 736 cm-1. MS m/z (%) 425 (100), 333 (77). HR-MS calcd
for C18H25N2O6SSi 425.1203 [M - C4H9]+, obsd 425.1210. [R]20
D
(10) Prepared according to Beckwith, A. L. J .; Meijs, G. F. J . Org.
Chem. 1987, 52, 1922.
(11) Prepared according to Lee, C.-W.; Oh, K. S.; Kim, K. S.; Ahn,
K. H. Org. Lett. 2000, 2, 1213.
MS calcd for C25H44N2O5Si 480.3020, obsd 480.3023. [R]20
)
D
-56.3° (c 0.70, CHCl3). Anal. Calcd for C25H44N2O5Si: C, 62.50;
H, 9.17; N, 5.83. Found: C, 62.54; H, 9.18; N, 5.95.
J . Org. Chem, Vol. 67, No. 18, 2002 6459