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K. Chen et al. / Steroids 75 (2010) 513–516
Table 1
ꢀ1-Dehydrogenation of AD with DDQ in the presence of chlorosilane agents.a
.
Entry
Solvent
Silylating agent
Reaction time (h)
Conversion
2a/3ab
1
2
3
4
5
6
7
8
9
Benzene
Benzene
CHCl3
(CH3)3SiCl
–
(CH3)3SiCl
(CH3)3SiCl
HCl
24
24
24
24
24
24
30
24
36
24
48
48
81.5
NR
78.4
93.5
NR
75/25
–
70/30
75/25
–
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
(CH3)3SiCl + Et3N
tBu(CH3)2SiCl
Et3SiCl
NR
–
90.4
83.3
90.3
NR
92.7
77.8
94/6
85/15
94/6
–
95/5
95/5
tBuPh2SiCl
BSTFA
10
11
12
tBu(CH3)2SiClc
tBu(CH3)2SiCld
a
Unless otherwise indicated, reactions have been carried out at room temperature in the presence of silylating agents (0.05 equiv.) for 24 h.
b
c
The ratio of 2a/3a was determined by NMR.
DDQ was added at 0 ◦C.
d
TBDMSCl 0.025 equiv.
1.55–1.78 (m, 2H), 1.79–1.92 (m, 3H), 1.93–2.02 (m, 1H), 2.03–2.18
81.4, 124.4, 128.7, 141.7, 158.9, 200.1; MS (EI): m/z 272 (M+, 60%),
133 (100%); Anal. calcd. for C18H24O2: C, 79.37; H, 8.88. Found: C,
79.48; H, 8.80.
(m, 2H), 2.38–2.58 (m, 3H), 6.10 (d, J = 1.0 Hz, 1H), 6.25 (dd, J = 1.5,
10.0 Hz, 1H), 7.05 (d, J = 1.0 Hz, 1H); 13C NMR (CDCl3): ı 13.8, 18.7,
21.9, 22.1, 31.2, 32.3, 32.5, 35.1, 35.6, 43.4, 47.7, 50.4, 52.3, 124.1,
127.7, 155.3, 168.2, 186.2, 219.9; MS (EI): m/z 284 (M+, 12%), 122
(100%); Anal. calcd. for C19H24O2: C, 80.24; H, 8.51. Found: C, 80.14;
H, 8.87.
2.6. Phenol (2e)
Mp. 39.5 ◦C; 1H NMR (CDCl3): ı 4.77 (s, 1H), 6.83 (dd, J = 1.0,
8.0 Hz, 1H), 6.94 (t, J = 8.0 Hz, 1H), 7.54 (dd, J = 2.5, 8.0 Hz, 1H).
2.3. 17ˇ-Hydroxy-17˛-methyl-androsta-1,4-diene-3-one (2b)
2.7. 6-Methylenandrost-1,4-diene-3,17-dione (2f)
Mp. 148.3–150.5 ◦C; [␣]D20 −1.8◦ (c 1.12, CHCl3); 1H NMR
(CDCl3): ı 0.94 (s, 3H), 0.99–1.07 (m, 2H), 1.17–1.22 (m, 1H), 1.19 (s,
3H), 1.25 (s, 3H), 1.24–1.40 (m, 3H), 1.55–1.90 (m, 7H), 1.94–2.00
(m, 1H), 2.34–2.38 (m, 1H), 2.44–2.52 (m, 1H), 6.07 (t, J = 1.5 Hz,
1H), 6.23 (dd, J = 1.5, 10.0 Hz, 1H), 7.07 (d, J = 10.0 Hz, 1H); 13C NMR
(CDCl3): ı 14.0, 18.7, 22.6, 23.4, 25.8, 31.3, 32.8, 33.3, 36.3, 38.7, 43.6,
45.6, 49.8, 52.4, 81.3, 123.8, 127.4, 156.0, 169.3, 186.4; MS (EI): m/z
300 (M+, 8%), 122 (100%); Anal. calcd. for C20H28O2: C, 79.96; H,
9.39; Found: C, 80.12; H, 9.23.
Mp. 196–197 ◦C; [␣]D20 278◦ (c 1.19, CHCl3); 1H NMR (CDCl3):
ı 0.95 (s, 3H), 1.17 (s, 3H), 1.23–1.27 (m, 2H), 1.31–1.40 (m, 3H),
1.58–1.77 (m, 2H), 1.88–1.97 (m, 3H), 1.98–2.03 (m, 1H), 2.08–2.17
(m, 1H), 2.46–2.53 (m, 1H), 2.58–2.67 (m, 1H), 5.00 (d, J = 2.0 Hz,
1H), 5.07 (t, J = 2.0 Hz, 1H), 6.25 (dd, J = 2.0, 10.0 Hz, 1H), 7.07 (d,
J = 10.0 Hz, 1H); 13C NMR (CDCl3): ı 13.8, 19.7, 21.8, 22.0, 31.2, 35.3,
35.6, 39.3, 43.7, 47.6, 50.0, 50.8, 112.5, 122.8, 127.9, 145.3, 154.0,
167.2, 186.3, 219.6; MS (EI): m/z 296 (M+, 11%), 148 (100%); Anal.
calcd. for C20H24O2: C, 81.04; H, 8.16; Found: C, 81.21; H, 8.11.
2.4. 17ˇ-Hydroxyandrosta-1,4-diene-3-one (2c)
2.8. 17-Propionyloxy-androsta-1,4-diene-3-one (2g)
Mp. 166–167 ◦C; [␣]D20 27◦ (c 1.07, CHCl3); 1H NMR (CDCl3): ı
0.83 (s, 3H), 0.93–1.12 (m, 4H), 1.24 (s, 3H), 1.29–1.38 (m, 1H),
1.39–1.50 (m, 2H), 1.60–1.72 (m, 2H), 1.74–1.80 (m, 1H), 1.85–1.97
(m, 2H), 2.03–2.10 (m, 1H), 2.34–2.10 (m, 1H), 2.43–2.50 (dt, J = 4.5,
12.0 Hz, 1H), 3.64 (m, 1H), 6.07 (t, J = 1.5 Hz, 1H), 6.30 (dd, J = 2.0,
10.0 Hz, 1H), 7.06 (d, J = 10.0 Hz, 1H); 13C NMR (CDCl3): ı 11.2, 18.7,
22.5, 23.5, 30.4, 32.8, 33.1, 35.6, 36.3, 43.1, 43.6, 50.1, 52.5, 81.5,
123.9, 127.5, 155.8, 169.1, 186.4; MS (EI): m/z 286 (M+, 2%), 122
(100%); Anal. calcd. for C19H26O2: C, 79.68; H, 9.15; Found: C, 79.55;
H, 9.12.
Mp. 136–137 ◦C; [␣]D20 33◦ (c 0.97, CHCl3); 1H NMR (CDCl3): ı
0.87 (s, 3H), 1.03–1.10 (m, 3H), 1.14 (t, J = 7.5 Hz, 3H), 1.22 (s, 3H),
1.33–1.42 (m, 1H), 1.46–1.54 (m, 1H), 1.61–1.83 (m, 6H), 1.94 (m,
1H), 2.15–2.22 (m, 1H), 2.31 (q, J = 7.5 Hz, 2H), 2.33–2.50 (m, 2H),
4.60 (t, J = 8.0 Hz, 1H), 6.07 (t, J = 1.5 Hz, 1H), 6.21 (dd, J = 2.0, 10.0 Hz,
1H), 7.06 (d, J = 10.0 Hz, 1H); 13C NMR (CDCl3): ı 9.3, 12.1, 18.8, 22.4,
23.7, 27.5, 27.8, 32.7, 33.1, 35.9, 36.6, 43.5, 50.0, 52.2, 82.1, 124.0,
127.6, 155.6, 168.8, 174.4, 186.2; MS (EI): m/z 342 (M+, 3%), 122
(100%); Anal. calcd. for C22
H, 8.84.
H30O3: C, 77.16; H, 8.83. Found: C, 76.92;
2.5. Estra-1,3,5(10)-triene-3,17-diol (2d)
2.9. Pregna-1,4-diene-3,20-dione (2h)
Mp. 166–168 ◦C; [␣]D20 77◦ (c 0.89, CHCl3); 1H NMR (CDCl3): ı
0.83 (s, 3H), 1.09–1.18 (m, 3H), 1.30–1.55 (m, 4H), 1.76–1.90 (m,
3H), 2.07–2.16 (m, 2H), 2.24–2.47 (m, 3H), 2.52 (d, J = 2.0 Hz, 1H),
3.71 (t, J = 8.0 Hz, 1H), 5.78 (s, 1H), 6.18 (s, 2H); 13C NMR (CDCl3):
ı 10.9, 22.8, 25.1, 27.0, 30.3, 36.3, 37.8, 40.9, 41.4, 43.8, 46.1, 48.0,
Mp 149–150 ◦C; [␣]D20 121◦ (c 0.89, CHCl3); 1H NMR (CDCl3):
ı 0.70 (s, 3H), 1.02–1.19 (m, 3H), 1.23 (s, 3H), 1.26–1.30 (m,
1H), 1.40–1.48 (m, 1H), 1.62–1.75 (m, 4H), 1.77–1.82 (m, 1H),
1.94–1.99 (m, 1H), 2.06–2.10 (m, 1H), 2.12 (s, 3H), 2.13–2.22 (m,