Very Short Synthesis of Steroids
J . Org. Chem., Vol. 66, No. 1, 2001 119
(
d), 117.1 (t), 116.4 (t), 93.0 (s), 56.5 (q), 55.5 (s), 52.0 (d), 51.7
16.7 Hz), 5.11 (1H, d, J ) 10.6 Hz), 3.75 (3H, s), 3.71 (3H, s),
3.04 (1H, d, J ) 11.0 Hz), 2.83 (1H, br. q, J ) 8.2 Hz), 2.74
(1H, td, J ) 8.3, 3.0 Hz), 2.70 (1H, d, J ) 12.4 Hz), 2.47 (1H,
br. dt, J ) 11.8, 7.4 Hz), 2.22 (1H, d, J ) 12.3 Hz), 2.04 (1H,
quint., J ) 6.0 Hz), 1.90 (2H, m), 1.88 (1H, dd, J ) 12.9, 7.4
Hz), 1.65 (1H, qd, J ) 12.2, 5.4 Hz), 1.54 (1H, qm, J ) 10.8
(d), 45.7 (d), 32.6 (t), 29.5 (t), 27.4 (t); MS (EI) m/z (relative
intensity) 352 (4), 324 (13), 221(78), 103 (100); HRMS calcd
52.1674, found 352.1689. Anal. Calcd for C22 : C, 74.98;
H, 6.86. Found: C, 75.03; H, 6.75.
-(4-Meth oxyben zocyclobu ten -1-yl)-3-m eth oxyca r bo-
n yl-6,9-d ivin yl-1-oxa sp ir o[4.4]n on a n -2-on e (5b). Yellow
3
24 4
H O
3
Hz), 1.22 (1H, qd, J ) 11.0, 7.5 Hz), 0.94 (1H, qd, J ) 12.1,
1
13
oil, H NMR (CDCl
J ) 8.2, 2.2 Hz), 6.63 (1H, d, J ) 2.2 Hz), 5.68 (1H, ddd, J )
7.8, 9.5, 8.9 Hz), 5.18 (1H, ddd, J ) 17.0, 10.0, 9.4 Hz), 5.03
4H, m), 4.71 (1H, dd, J ) 10.2, 1.7 Hz), 4.21 (1H, dq, J )
3
) δ 6.90 (1H, d, J ) 8.2 Hz), 6.73 (1H, dd,
5.5 Hz); C NMR (CDCl
3
) δ 175.6 (s), 170.5 (s), 157.8 (s), 139.3
(s), 135.0 (d), 134.3 (s), 121.9 (d), 117.2 (t), 114.6 (d), 110.4 (d),
93.2 (s), 55.2 (s), 55.2 (q), 53.2 (q), 52.7 (d), 50.8 (d), 43.4 (d),
42.3 (d), 35.6 (t), 31.8 (t), 30.7 (t), 27.7 (t), 26.0 (t); HRMS calcd
1
(
1
(
7.0, 0.8 Hz), 4.06 (1H, dd, J ) 5.1, 2.1 Hz), 3.74 (3H, s), 3.71
26 5
for C23H O , 382.1780, found, 382.1761.
1
1
3H, s), 3.22 (1H, /
2
AB, d, J ) 14.9, 5.2 Hz), 2.82 (1H, /
2
AB,
AB,
(()-(8â,9r,14r)-11r,13r-γ-Ca r bola cton e-2,3-d im eth oxy-
1
d, J ) 14.9, 2.4 Hz), 2.31 (1H, q, J ) 9.0 Hz), 2.25 (1H, /
2
11â-m eth oxyca r bon yl-17r-vin ylgon a -1,3,5(10)-tr ien e (6c).
1
1
J ) 14.3 Hz), 2.13 (1H, /
m), 1.84 (1H, dtd, J ) 13.3, 9.0, 4.3 Hz), 1.71 (1H, ddt, J )
7.0, 10.6, 6.6 Hz), 1.43 (1H, dddd, J ) 13.1, 9.4, 6.6, 3.7
2
AB, J ) 14.3 Hz), 2.08-2.05 (1H,
White crystals, mp 137-138 °C; H NMR (CDCl
3
) δ 6.65 (1H,
s), 6.50 (1H, s), 5.88 (1H, ddd, J ) 17.6, 9.6, 8.2 Hz), 5.12 (2H,
m), 3.83 (3H, s), 3.77 (3H, s), 3.68 (3H, s), 3.05 (1H, d, J )
11.2 Hz), 2.80-2.73 (3H, m), 2.62 (1H, d, J ) 12.3 Hz), 2.48
(1H, dt, J ) 11.5, 7.5 Hz), 2.31 (1H, d, J ) 12.3 Hz), 2.05 (1H,
br. q, J ) 5.9 Hz), 1.95-1.87 (4H, m), 1.66 (1H, qd, J ) 12.2,
5.5 Hz), 1.54-1.47 (2H, m), 1.34 (1H, qd, J ) 11.1, 6.7 Hz),
1
1
3
Hz); C NMR (CDCl
(
1
3
) δ 173.7 (s), 170.6 (s), 160.8 (s), 144.8
s), 137.2 (d), 135.4 (d), 134.3 (s), 123.8 (d), 118.1 (t), 117.3 (t),
14.0 (t), 108.7 (t), 94.2 (s), 57.5 (s), 55.5 (d), 53.3 (d or q), 53.0
(
(
d or q), 52.8 (d or q), 45.7 (d), 32.7 (t), 30.2 (t), 28.2 (t), 27.8
t); HRMS calcd for C23 , 382.1780, found 382.1781.
-(4,5-Dim eth oxyben zocyclobu ten -1-yl)-3-m eth oxyca r -
bon yl-6,9-d ivin yl-1-oxa sp ir o[4.4]n on a n -2-on e (5c). Major
H
26
O
5
1.00 (1H, dq, J ) 12.0, 5.7 Hz); 13C NMR (CDCl
) δ 175.2 (s),
3
3
171.0 (s), 147.0 (s), 146.8 (s), 135.1 (d), 133.0 (s), 129.7 (s), 117.2
(t), 112.3 (d), 106.5 (d), 92.7 (s), 56.1 (q), 55.9 (q), 55.1 (s), 52.9
(d or q), 52.6 (d or q), 51.0 (d), 43.4 (d), 43.0 (d), 36.1 (t), 31.8
(t), 30.5 (t), 27.5 (t), 26.5 (t); MS (EI) m/z (relative intensity)
412 (100), 205 (36), 189 (29), 163 (38); HRMS calcd for
1
diastereomer, white crystals, mp 89 °C; H NMR (CDCl
.65 (1H, s), 6.57 (1H, s), 5.70 (1H, dt, J ) 17.8, 9.2 Hz), 5.20
1H, dt, J ) 17.2, 9.6 Hz), 5.05 (2H, m), 4.73 (1H, dd, J ) 10.2,
.4 Hz), 4.29 (1H, d, J ) 17.0 Hz), 4.08 (1H, dd, J ) 4.8, 2.0
Hz), 3.82 (3H, s), 3.78 (3H, s), 3.73 (3H, s), 3.20 (1H, dd, J )
3
) δ
6
(
1
C
24
H
28
O
6
, 412.1885, found, 412.1894.
Gen er a l P r oced u r e for th e Dem eth oxyca r bon yla tion .
1
9
1
4.3, 4.9 Hz), 2.79 (1H, dd, J ) 14.3, 2.0 Hz), 2.35 (1H, q, J )
A mixture of 6 (5 mmol), 40 mL of DMSO, and NaCN (735
mg, 15 mmol) was heated at 90 °C under argon. The progress
of the reaction was followed by TLC analysis. After cooling at
room temperature, the mixture was poured in water and then
1
1
.3 Hz), 2.27 (1H, /
2
AB, J ) 14.3 Hz), 2.16 (1H, / AB, J )
2
4.3 Hz), 2.06 (1H, m), 1.86 (2H, m), 1.71 (1H, m), 1.45 (1H,
1
3
m); C NMR (CDCl
1
3
) δ 174.0 (s), 170.6 (s), 151.0 (s), 150.1 (s),
37.1 (d), 135.5 (d), 135.3 (s), 133.7 (s), 118.2 (t), 117.4 (t), 107.1
2 2
extracted with CH Cl . The organic layer was washed with
(
(
2
d), 106.6 (d), 94.3 (s), 57.6 (s), 56.4 (d or q), 56.3 (d or q), 53.5
d or q), 53.0 (d or q), 52.9 (d or q), 45.9 (d), 32.6 (t), 30.2 (t),
water, filtered, and concentrated under vacuum. The residue
was chromatographed on silica gel and then recrystallized in
diethyl ether to give 7 (1.04 g, 3.55 mmol, 71% for 7a , 1.02 g,
3.14 mmol, 63% for 7b, 1.61 g, 4.55 mmol, 91% for 7c).
(()-(8â,9r,14r)-11r,13r-γ-Ca r bola cton e-17r-vin ylgon a -
8.3 (t), 27.8 (t). Anal. Calcd for C24
28 6
H O : C, 69.89; H, 6.84.
Found: C, 69.92; H, 6.88. Minor diastereomer, white crystals,
mp 110 °C; H NMR (CDCl
(
(
s), 3.79 (3H, s), 3.20 (1H, dd, J ) 14.3, 4.9 Hz), 2.78 (1H, dd,
J ) 14.3, 1.8 Hz), 2.37-1.38 (9H, m); C NMR (CDCl
(
1
(
(
1
3
) δ 6.65 (1H, s), 6.57 (1H, s), 5.70
1H, dt, J ) 17.8, 9.2 Hz), 5.49 (1H, dt, J ) 17.8, 9.2 Hz), 5.06
4H, m), 4.08 (1H, dd, J ) 4.9, 1.8 Hz), 3.73 (3H, s), 3.82 (3H,
1
1,3,5(10)-tr ien e (7a ). White crystals, mp 95 °C; H NMR
(CDCl ) δ 7.30 (1H, d, J ) 6.8 Hz), 7.16 (2H, m), 7.11 (1H, d,
3
J ) 6.9 Hz), 5.91 (1H, ddd, J ) 17.6, 9.6, 8.2 Hz), 5.15-5.07
(2H, m), 3.24 (1H, br. s), 2.90 (2H, m), 2.75 (1H, d, J ) 10.9
Hz), 2.46 (1H, dt, J ) 11.4, 7.5 Hz), 2.14 (1H, quint.m, J ) 4.9
Hz), 2.05 (1H, s), 2.04 (1H, s), 2.01 (1H, m), 1.93 (1H, m), 1.90
(1H, m), 1.66 (1H, qd, J ) 12.1, 5.5 Hz), 1.58-1.49 (2H, m),
1
3
3
) δ 172.8
s), 169.6 (s), 150.4 (s), 149.3 (s), 136.4 (d), 134.7 (d), 134.5 (s),
32.9 (s), 117.2 (t), 116.4 (t), 106.5 (d), 105.8 (d), 93.2 (s), 56.7
s), 55.5 (q), 55.4 (q), 52.7 (q), 52.1 (d), 51.8 (d), 44.9 (d), 31.8
t), 29.4 (t), 27.5 (t), 27.0 (t).
1.09 (1H, qd, J ) 12.1, 5.7 Hz); 13C NMR (CDCl
) δ 180.6 (s),
3
Gen er a l P r oced u r e for th e Th er m olysis of 5. The
138.6 (s), 137.0 (s), 135.8 (d), 129.4 (d), 126.5 (d),125.9 (d), 124.3
(d), 116.5 (t), 94.5 (s), 52.2 (d), 51.5 (d), 41.4 (d), 40.5 (d), 40.2
(d), 33.0 (t), 31.7 (t), 29.9 (t), 29.0 (t), 27.2 (t); MS (EI) m/z
(relative intensity) 294 (100), 265 (36), 249 (15), 222 (38), 156
benzocyclobutenic precursor 5 (1 mmol) was dissolved in 10
mL of 1,2,4-trichlorobenzene and boiled under argon. The
progress of the reaction was followed by TLC analysis. After
cooling at room temperature, the mixture was concentrated
under vacuum. The residue was chromatographed on silica gel
(32), 141 (42), 128 (52); HRMS calcd for C20
H
22
O
2
, 294.1620,
found, 294.1619. Anal. Calcd for C20
Found: C, 81.55; H, 7.59.
22 2
H O : C, 81.60; H, 7.53.
(
6
petroleum ether/diethyl ether) to give the expected compound
in 85-87% yield.
()-(8â,9r,14r)-11r,13r-γ-Ca r b ola ct on e-11â-m et h oxy-
ca r bon yl-17r-vin ylgon a -1,3,5(10)-tr ien e (6a ). White crys-
(()-(8â,9r,14r)-11r,13r-γ-Ca r bola cton e-3-m eth oxy-17r-
(
vin ylgon a -1,3,5(10)-tr ien e (7b). White crystals, mp 134 °C;
1
H NMR (CDCl ) δ 7.20 (1H, d, J ) 8.5 Hz), 6.72 (1H, dd, J )
3
1
tals, mp 112 °C; H NMR (CDCl
J ) 6.3 Hz), 5.86 (1H, dt, J ) 17.6, 8.3 Hz), 5.13 (2H, m), 3.71
3H, s), 3.09 (1H, d, J ) 10.9 Hz), 2.82 (2H, m), 2.75 (1H, d, J
12.2 Hz), 2.47 (1H, dt, J ) 11.8, 7.1 Hz), 2.22 (1H, d, J )
2.2 Hz), 1.99 (4H, m), 1.63 (2H, m), 1.23 (1H, m), 0.90 (1H,
3
) δ 7.09 (3H, m), 6.83 (1H, d,
8.5, 2.5 Hz), 6.65 (1H, d, J ) 2.5 Hz), 5.91 (1H, ddd, J ) 16.4,
10.8, 8.4 Hz), 5.08 (1H, d, J ) 16.4 Hz), 5.08 (1H, d, J ) 10.8
Hz), 3.76 (3H, s), 3.17 (1H, s), 2.87 (2H, m), 2.70 (1H, d, J )
11.3), 2.45 (1H, dt, J ) 11.5, 7.4 Hz), 2.15-1.85 (3H, m), 1.65
(
)
1
(1H, qd, J ) 12.0, 6.4 Hz), 1.55-1.45 (2H, m), 1.08 (1H, qd, J
1
3
13
dq, J ) 11.9, 5.5 Hz); C NMR (CDCl
3
) δ 175.3 (s), 170.2 (s),
) 11.9, 5.6 Hz); C NMR (CDCl ) δ 180.6 (s), 158.1 (s), 138.3
3
1
1
4
42.0 (s), 137.6 (s), 134.8 (d), 128.5 (d), 125.9 (d), 125.5 (d),
(s), 135.9 (d), 130.7 (s), 125.6 (d), 116.5 (t), 114.7 (d), 111.3 (d),
94.5 (s), 55.3 (q), 52.1 (d), 51.5 (d), 41.0 (d), 40.8 (d), 40.5 (d),
33.0 (t), 31.7 (t), 29.9 (t), 29.5 (t), 27.3 (t); HRMS calcd for
20.6 (d), 116.9 (t), 93.1 (s), 54.9 (s), 53.1 (q), 52.4 (d), 50.5 (d),
2.9 (d), 42.6 (d), 35.3 (t), 31.6 (t), 30.5 (t), 27.0 (t), 25.8 (t);
MS (EI) m/z (relative intensity) 352 (85), 308 (52), 306 (70),
76 (59), 154 (65), 129 (100), 128 (85); HRMS calcd for
C
21
H
24
O
3
, 324.1725, found 324.1726.
(()-(8â,9r,14r)-11r,13r-γ-Ca r bola cton e-2,3-d im eth oxy-
17r-vin ylgon a -1,3,5(10)-tr ien e (7c). White crystals, mp 196
2
C
C
22
22
(
H
H
24
O
O
4
,
352.1674, found, 352.1674. Anal. Calcd for
1
24
4
: C, 74.98; H, 6.86. Found: C, 74.50; H, 7.02.
°C; H NMR (CDCl ) δ 6.79 (1H, s), 6.59 (1H, s), 5.91 (1H, ddd,
3
()-(8â,9r,14r)-11r,13r-γ-Ca r bola cton e-3-m eth oxy-11â-
J ) 17.6, 9.6, 8.2 Hz), 5.15-5.05 (2H, m), 3.87 (3H, s), 3.83
(3H, s), 3.12 (1H, d, J ) 3.7 Hz), 2.89-2.80 (2H, m), 2.72 (1H,
d, J ) 10.2 Hz), 2.46 (1H, br. dt, J ) 11.2, 7.2 Hz), 2.12 (1H,
m et h oxyca r b on yl-17r-vin ylgon a -1,3,5(10)-t r ien e (6b ).
1
White crystals, mp 98 °C; H NMR (CDCl
.4 Hz), 6.71 (1H, d, J ) 2.6 Hz), 6.61 (1H, dd, J ) 8.4, 2.6
Hz), 5.87 (1H, ddd, J ) 16.7, 10.6, 8.2 Hz), 5.12 (1H, d, J )
3
) δ 6.74 (1H, d, J )
1
1
8
m), 2.08 (1H, /
2
AB, J ) 11.9 Hz), 2.03 (1H, / ABd, J ) 11.9,
2
4.3 Hz), 1.94-1.86 (2H, m), 1.66 (1H, qd, J ) 12.0, 5.4 Hz),