Lang et al.
JOCArticle
(m, 1H), 2.36 (m, 1H), 2.42 (m, 1H), 2.60 (d, 1H, J=8.8 Hz), 2.72
(m, 1H), 2.86 (m, 1H), 3.04 (d, 1H, J=4.4 Hz), 3.40 (dd, 1H, J=
18.1, 7.0 Hz), 3.44 (s, 3H), 3.86 (d, 1H, J=8.2 Hz), 4.16 (dd, 1H,
J=8.2, 3.2 Hz), 5.61 (dd, 1H, J=18.4, 8.8 Hz), 5.74 (d, 1H, J=
18.4 Hz), 6.56 (m, 1H). 13C NMR (75 MHz, CDCl3) δ -1.2,
18.4, 19.3, 27.8, 38.4, 37.2, 43.6, 47.4, 51.6, 52.5, 60.6, 74.2,
100.6, 126.0, 127.9, 130.5, 133.9, 142.6, 145.3, 197.2, 205.9.
HRMS (EI) m/z required for C22H27O4Si (M-CH3) 383.1679,
found 383.1686. Two byproducts, 1R-trimethylsilyl-5aβ-meth-
oxy-11bβ-methyl-1,3aβ,4,5a,6,7,8,9,11b,11c-decahydrocyclo-
penta[7,8]phenanthro[10,1-bc]furan-6,9-dione (24) (19 mg, 5%
yield) and the hydroperoxide-bridged adduct (25) (72 mg,
8.3% yield), were isolated in this reaction. Both of them were
recrystallized from EtOAc/pentane. NMR data for 24: 1H
NMR (300 MHz, CDCl3) δ -0.41 (s, 9H), 1.69 (s, 3H),
2.67-2.74 (m, 3H), 3.10 (m, 3H), 3.25 (s, 3H), 3.7-3.8 (m.
1H), 3.83-3.87 (dd, 1H, J=8.0, 1.5 Hz), 4.13 (t, 1H, J=7.4,
8.0 Hz), 5.65 (m, 1H), 5.85 (m, 1H), 7.56 (d, 1H, J=8 Hz), 7.90
(d, 1H, J=8 Hz). HRMS (EI) m/z required for C23H28O4Si
396.1757, found 396.1752. See the SI for X-ray crystal structure
data. NMR data for 25: 1H NMR (500 MHz, CDCl3) δ -0.08
(s, 9H), 1.49 (s, 3H), 1.87 (m, 1H), 2.04 (m, 1H), 2.38 (m, 3H),
2.57 (m, 1H), 3.14 (d, 1H, J=3.9 Hz), 3.54 (s, 3H), 3.73 (d, 1H,
J=7.8 Hz), 3.91 (m, 1H), 4.09 (dd, 1H, J=7.8, 2.5 Hz), 5.64 (d,
1H, J=18.4 Hz), 5.93 (dd, 1H, J=18.4, 9.5 Hz), 6.47 (d, 1H, J=
5.9 Hz), 6.53 (m, 1H), 7.78 (s, 1H). 13C NMR (75 MHz, CDCl3)
δ -1.5, 19.9, 21.1, 36.3, 41.6, 44.8, 38.4, 49.8, 50.6, 56.5, 74.0,
81.7, 103.4, 121.2, 123.9, 133.4, 138.4, 141.0, 144.5, 200.8,
205.2. See the SI for X-ray crystal structure data.
give the epoxide (5 mg, 24% yield) as a colorless solid. 1H
NMR (300 MHz, CDCl3) δ -0.49 (s, 9H), 1.77 (s, 3H), 2.16 (d,
1H, J=5.3 Hz), 2.72 (m, 2H), 3.29 (m, 1H), 3.77 (m, 1H),4.11
(m, 1H), 4.26 (m, 1H), 4.50 (t, 1H, J=9 Hz), 5.61 (dd, 1H, J=
10.2, 3.45 Hz), 5.81 (m, 1H), 7.50 (d, 1H, J=8.1 Hz), 7.92 (d,
1H, J=8.1 Hz).
(3,8-trans)-7a-Methoxy-4-methyl-8-(20-trimethylsilyl)-(E)-eth-
enyl-2,3,3a,6,7,7a- hexahydro-3,6-methanobenzofuran-7-one (26).
To a solution of 4-methylguaiacol (0.414 g, 3 mmol) and silyl
dienol 20 (2.1 g, 12 mmol) in THF was added BHT (3 crystals),
NaHCO3 (2.4 g, 28.6 mmol), and BTIB (1.3 g, 3 mmol) as a
solid in portions at 0 °C. The mixture was stirred for 0.5 h
followed by addition of NaHCO3 (2.4 g, 28.6 mmol). The
resulting mixture was allowed to warm to room temperature
and was stirred overnight. Solvent was evaporated and the
residue was diluted with ether and washed with water and
brine. The organic layer was dried over Na2SO4 and evapo-
rated. The excess dienol 20 was removed by Kugelrohr dis-
tillation (0.01 Torr, 37 °C). The residue was purified by column
chromatography to give 26 as a white solid. 1H NMR
(300 MHz, CDCl3) δ 0.02 (s, 9H), 1.91 (s, 3H), 2.33 (m, 1H),
2.68 (d, 1H, J=7.3 Hz), 3.06 (dd, 1H, J=3.0, 6.7 Hz), 3.12 (dd,
1H, J=4.1, 2.1 Hz), 3.50 (s, 3H), 3.82 (d, 1H, J=8.1 Hz), 4.12
(dd, 1H, J = 8.1, 3.3 Hz), 5.70 (m, 3H). HRMS (EI) m/z
required for C15H21O3Si (M - CH3) 277.1260, found 277.1267.
1r-Trimethylsilyl-2β,3β-dihydroxy-11bβ-methyl-1,2,3,6,7,
8,9,11b-octahydrocyclopenta[7,8] phenanthro[10,1-bc]furan-6,
9-dione (32). To a solution of 5 (72 mg, 0.2 mmol) and DMAP
(27 mg, 0.22 mmol) in THF/CH2Cl2(10 mL) was added solid
OsO4 (58 mg, 0.23 mmol). The resulting mixture was stirred at
room temperature for 4 days followed by addition of 10% aq
NaHSO3 (10 mL). After 4 h of stirring, the layers were
separated and the aqueous layer was extracted with EtOAc
(3ꢀ2 mL). The combined organic layer was dried over MgSO4
and evaporated. The residue was purified by column chroma-
tography (EtOAc/hexane, 7:3) to give diol 32 (52 mg, 66%
yield) as a white solid, recrystallization of which from EtOAc/
pentane provided colorless crystals. 1H NMR (300 MHz,
CDCl3) δ -0.46 (s, 9H), 1.82 (s, 3H), 2.48 (d, 1H, J = 2.11
Hz), 2.74 (t, 2H, J=5.8 Hz), 3.78 (dt, 2H, J=4.75, 5.37 Hz),
4.61 (br d, 1H, J=5.5 Hz), 4.97 (m, 1H), 7.57 (d, 1H, J=8 Hz),
7.85 (s, 1H), 7.92 (d, 1H, J=8 Hz). 13C NMR (75 MHz, CDCl3)
δ 0.0, 28.5, 36.4, 39.2, 39.9, 40.9, 62.0, 70.9, 123.3, 129.7, 136.8,
126.5, 127.5, 144.3, 145.5, 147.6, 158.2, 158.7, 173.4, 206.9.
HRMS (EI) m/z required for C22H24O5Si 396.1393, found
396.1398. See the SI for X-ray crystallographic data.
1r-Trimethylsilyl-2β,3β-dioxolonyl-11bβ-methyl-1,2,3,6,7,8,
9,11b-octahydrocyclopenta[7, 8]phenanthro[10,1-bc]furan-
6,9-dione. A solution of triphosgene (134 mg, 0.45 mmol) in
dry CH2Cl2 (10 mL) was added dropwise to a mixture of
DMAP (329 mg, 2.7 mmol) and the diol 32 (180 mg, 0.45
mmol) in CH2Cl2 (10 mL) at -78 °C. The reaction was stirred
for 15 min and then was allowed to warm to room temperature.
The resulting solution was quenched with saturated NH4Cl
and the aqueous layer was separated and extracted with
CH2Cl2. The organic extract was washed with water, dried
(over MgSO4), filtered, and evaporated under vacuum to give
the carbonate (138 mg, 72% yield) as a yellow solid. 1H NMR
(300 MHz, CDCl3) δ -0.51 (s, 9H), 1.67 (s, 3H), 2.67 (s, 1H),
2.76 (t, 2H, J=5.5 Hz), 3.78 (t, 2H, J=5.5 Hz), 5.49 (d, 1H, J=
8.8 Hz), 5.88 (d, 1H, J=8.8 Hz), 7.60 (d, 1H, J=8.0 Hz), 7.98
(d, 2H). 13C NMR (75 MHz, CDCl3) δ -0.59, 28.4, 29.6, 36.3,
36.5, 38.2, 67.3, 78.9, 117.3, 126.9, 127.2, 129.6, 137.4, 142.4,
144.6, 148.4, 153.4, 156.3, 158.7, 172.8, 206.1. HRMS (EI) m/z
required for C23H22O6Si 422.1186, found 422.1185.
1r-Trimethylsilyl-11bβ-methyl-1,6,7,8,9,11b-hexahydrocy-
clopenta[7,8]phenanthro[10,1-bc]furan-6,9-dione (5). The crude
material from the previous IMDA reaction was dissolved in
Cl2CHCHCl2 (10 mL) in a test tube and stirred at 120 °C for 2
days in the dark. The solvent was removed under high vacuum
(0.01 Torr, 40 °C), and the residue was flashed by column
chromatography (EtOAc/hexane, 3:7) to give allyl silane 5 (172
mg, 23.8% yield from 13) as a yellow solid, recrystallization of
1
which from benzene/pentane provided colorless crystals. H
NMR (300 MHz, CDCl3) δ -0.47 (s, 9H), 1.56 (s, 3H), 2.67 (d,
1H, J=6.48 Hz), 2.75 (m, 2H), 3.80 (m, 2H), 6.11 (dd, 1H, J=
9.62, 6.48 Hz), 6.51 (d, 1H, J=9.62 Hz), 7.51 (s, 1H), 7.57 (d,
1H, J =8 Hz), 7.91 (d, 1H, J= 8 Hz). 13C NMR (75 MHz,
CDCl3) δ -0.8, 28.5, 32.8, 36.4, 38.9, 39.1, 114.1, 126.2, 127.9,
133.2, 121.5, 130.8, 137.1, 143.6, 143.7, 156.2, 158.5,
141.0, 173.2, 206.7. HRMS (EI) m/z required for C21H19O3Si
(M - CH3) 347.1103, found 347.1096. See the SI for X-ray
crystallographic data. On some occasions, the formation of 1R-
trimethylsilyl-11bβ-methyl-1,3aβ,4,6,7,8,9,11b-octahydrocy-
clopenta[7,8]phenanthro[10,1-bc]furan-6,9-dione (31) was ob-
served (124 mg, 17% yield from 13). 1H NMR (300 MHz,
CDCl3) δ -0.50 (s, 9H), 1.59 (s, 3H), 2.46 (d, 1H, J=5.1 Hz),
2.72 (m, 2H), 3.65 (dt, 1H, J=5.7, 19.5 Hz), 3.79 (dt, 1H, J=
5.7, 19.5 Hz), 4.18 (m, 2H), 4.92 (t, 1H, J=7.3 Hz), 5.69 (d, 1H,
J=8.1 Hz), 5.87 (dd, 1H, J=9.8, 5.1 Hz), 7.63 (d, 1H, J=8.1
Hz), 7.89 (d, 1H, J=8.1 Hz). 13C NMR (75 MHz, CDCl3) δ -
1.2, 27.1, 28.3, 36.5, 40.5, 41.4, 45.0, 76.5, 121.6, 126.1, 127.8,
130.0, 130.3, 137.0, 139.5, 147.5, 156.4, 157.9, 176.7, 206.7.
HRMS (EI) m/z required for C22H24O3Si 364.1495, found
364.1481.
1r-Trimethylsilyl-11bβ-methyl-5a,11c-epoxy-1,3a,4,5a,6,7,8,
9,11b,11c-decahydrocyclopenta[7,8]phenanthro[10,1-bc]furan-
6,9-dione. The dihydrofuran 31 (20 mg, 0.055 mmol) and m-
CPBA (12.99 mg, 0.08 mmol) were dissolved in CH2Cl2 (2 mL).
The resulting solution was stirred at room temperature for 45 h
and then washed with saturated NaHCO3 (1 mL). The aqueous
layer was extracted with CH2Cl2. The combined organic layer
was dried over MgSO4 and evaporated. The residue was
flashed by column chromatography (EtOAc/hexane, 1:1) to
3β-Hydroxy-11bβ-methyl-3,6,7,8,9,11b-hexahydro[7,8]phe-
nanthro[10,1-bc]furan-6,9-dione (35). Cesium fluoride (70 mg,
0.46 mmol) was vacuum dried at 100 °C (0.5 Torr) for 4 h. The
J. Org. Chem. Vol. 74, No. 15, 2009 5437