Radical Cyclization of the Methoxy Group
52.7, 60.5, 63.8, 81.8, 117.7, 121.7, 129.8, 151.9, 155.4, 156.4,
166.3, 168.3; MS (EI) m/z (%) 324 (M+, 6), 277 (100); HRMS
(EI) calcd for C16H20O7 (M+) 324.1224, found 324.1209.
13C NMR (75 MHz, CDCl3) δ 22.2, 23.2, 39.3, 46.6, 52.3, 52.6,
58.1, 78.9, 118.9, 124.0, 127.1, 144.0, 172.1; MS (EI) m/z (%)
238 (M+, 3), 121 (100); HRMS (FAB) calcd for C13H19O4 (MH+)
239.1283, found 239.1273.
Dim eth yl (3a R*,8a S*)-3a -Hyd r oxy-5,7-d im eth oxy-1,2,3,
3a ,8,8a -h exa h yd r ocyclop en t a [a ]in d en e-4,6-d ica r b oxy-
la te (30) (Ta ble 2, en tr y 5). By a procedure identical with
that described for the synthesis of 27, ketone 26 (47.5 mg,
0.131 mmol) was converted into 30 (27.5 mg, 63% yield) and
recovered ketone 26 (5.0 mg, 11%): colorless oil; IR (KBr) 3487
(br, OH), 1736 cm-1 (CdO); 1H NMR (300 MHz, CDCl3) δ 1.17-
1.29 (m, 1H), 1.53-1.67 (m, 1H), 1.75-1.88 (m, 2H), 2.01-
2.17 (m, 2H), 2.55 (dd, J ) 16.2, 3.6 Hz, 1H, 8-CHH), 2.71 (m,
1H), 3.28 (dd, J ) 16.2, 8.7 Hz, 1H, 8-CHH), 3.76 (s, 3H, OMe),
3.85 (s, 3H, OMe), 3.89 (s, 3H, OMe), 3.94 (s, 3H, OMe), 4.41
(br s, 1H, OH); 13C NMR (75.5 MHz, CDCl3) δ 26.2, 34.1, 34.3,
41.2, 51.1, 52.6, 52.8, 60.2, 63.7, 93.2, 116.9, 121.9, 130.6, 152.3,
155.9, 157.2, 166.3, 168.7; MS (EI) m/z (%) 350 (M+, 21), 289
(100); HRMS (EI) calcd for C18H22O7 (M+) 350.1365, found
350.1365.
Met h yl (4a R*,5S*)-5-H yd r oxy-1-m et h oxy-5-m et h yl-
2,4a ,5,6,7,8-h exa h yd r on a p h th a len e-2-ca r boxyla tes (42a
a n d 42b) (Ta ble 4, en tr y 2). By a procedure identical with
that described for the synthesis of 42, ketone 35 (51.3 mg,
0.217 mmol) was converted into 42a (17.1 mg, 33% yield) and
42b (17.1 mg, 33% yield).
Com p ou n d 42a : colorless oil; IR (KBr) 3446 (OH), 1736
1
cm-1 (CdO); H NMR (300 MHz, CDCl3) δ 1.02 (s, 3H, CMe),
1.29-1.37 (m, 1H, 7-CHH), 1.42 (br s, 1H, OH), 1.52-1.69 (m,
2H, 6-CHH and 8-CHH), 1.72-1.82 (m, 2H, 6-CHH and
7-CHH), 2.82-2.85 (m, 1H, 4a-H), 2.91 (ddd, J ) 13.7, 1.8,
1.8 Hz, 1H, 8-CHH), 3.52 (s, 3H, OMe), 3.70 (s, 3H, OMe),
3.93-3.98 (m, 1H, 2-H), 5.74 (ddd, J ) 10.1, 3.3, 1.8 Hz, 1H,
4-H), 6.01 (ddd, J ) 10.1, 2.4, 2.4 Hz, 1H, 3-H); 13C NMR (75
MHz, CDCl3) δ 21.5, 23.5, 25.0, 41.8, 44.0, 50.3, 52.5, 58.7,
74.3, 121.6, 122.7, 127.2, 143.7, 172.0; MS (FAB) m/z (%) 253
(MH+, 74), 235 (100); HRMS (FAB) calcd for C14H21O4 (MH+)
253.1440, found 253.1446.
Meth yl 3-Hyd r oxy-3-m eth yl-2,3-d ih yd r o-1H-in d en e-4-
ca r boxyla te (36c) (Ta ble 3, en tr y 4). By a procedure
identical with that described for the synthesis of 27, ketone
32c (49.0 mg, 0.207 mmol) was converted into 36c (21.4 mg,
50% yield) and recovered ketone 32c (16.2 mg, 33%): colorless
Com p ou n d 42b: colorless oil; IR (KBr) 3498 (OH), 1738
1
cm-1 (CdO); H NMR (300 MHz, CDCl3) δ 1.08 (s, 3H, CMe),
1
oil; IR (KBr) 3456 (br, OH), 1700 cm-1 (CdO); H NMR (500
1.35-1.64 (m, 4H, 6-CHH, 7-CH2, and OH), 1.70-1.83 (m, 2H,
6-CHH and 8-CHH), 2.74-2.77 (m, 1H, 8-CHH), 2.90-2.96 (m,
1H, 4a-H), 3.50 (s, 3H, OMe), 3.69 (s, 3H, OMe), 3.96 (ddd, J
) 8.9, 4.0, 2.1 Hz, 1H, 2-H), 5.75 (ddd, J ) 10.1, 4.0, 2.1 Hz,
1H, 4-H), 5.99 (ddd, J ) 10.1, 3.7, 2.1 Hz, 1H, 3-H); 13C NMR
(75 MHz, CDCl3) δ 22.1, 23.4, 25.1, 41.9, 44.1, 50.8, 52.3, 58.0,
74.7, 121.5, 122.8, 127.2, 143.3, 171.9; MS (EI) m/z (%) 252
(M+, 12), 85 (100); HRMS (FAB) calcd for C14H21O4 (MH+)
253.1440, found 253.1446.
MHz, CDCl3) δ 1.54 (s, 3H, CMe), 2.22 (ddd, J ) 12.5, 8.0, 1.8
Hz, 1H, 2-CHH), 2.26-2.32 (m, 1H, 2-CHH), 2.79-2.86 (m,
1H, 1-CHH), 2.95 (ddd, J ) 16.5, 9.2, 1.8 Hz, 1H, 1-CHH), 3.93
(s, 3H, OMe), 5.81 (s, 1H, OH), 7.26 (dd, J ) 7.9, 7.3 Hz, 1H,
Ar), 7.38 (dd, J ) 7.3 Hz, 1H, Ar), 7.88 (d, J ) 7.9 Hz, 1H,
Ar); 13C NMR (75.5 MHz, CDCl3) δ 26.9, 29.4, 41.4, 52.1, 81.8,
125.3, 127.6, 129.8, 130.3, 143.9, 151.3, 168.8; MS (EI) m/z (%)
207 (MH+, 10), 191 (100); HRMS (FAB) calcd for C12H15O3
(MH+) 207.1022, found 207.1017.
Meth yl (4R*,4a S*)-4-Hyd r oxy-8-m eth oxy-4-m eth yl-3,4,
4a,7-tetr ah ydr o-1H-2-ben zopyr an -7-car boxylates (43a an d
43b) (Ta ble 4, en tr y 3). By a procedure identical with that
described for the synthesis of 41, ketone 38 (48.2 mg, 0.217
mmol) was converted into an inseparable diastereomixture of
43a and 43b (15.8 mg, 33% yield, 2:1): colorless oil; IR (KBr)
3521 (OH), 1738 cm-1 (CdO); 1H NMR (300 MHz, CDCl3)
major isomer δ 1.07 (s, 3H, CMe), 1.54 (br s, 1H, OH), 2.96 (d,
J ) 6.7 Hz, 1H, CH), 3.29 (br s, 1H, CH), 3.51 (s, 3H, OMe),
3.55 (d, J ) 6.7 Hz, 1H, CH), 3.66 (s, 3H, OMe), 3.93-3.98
(m, 1H, CH), 4.78 (d, J ) 12.8 Hz, 1H, CH), 5.74-5.78 (m,
1H, CHdCH), 5.90-5.97 (m, 1H, CHdCH), minor isomer δ
1.15 (s, 3H, CMe), 1.54 (br s, 1H, OH), 2.88 (d, J ) 7.0 Hz,
1H, CH), 3.25 (br s, 1H, CH), 3.46 (s, 3H, OMe), 3.57 (d, J )
7.0 Hz, 1H, CH), 3.66 (s, 3H, OMe), 3.93-3.98 (m, 1H, CH),
4.80 (d, J ) 12.8 Hz, 1H, CH), 5.71-5.76 (m, 1H, CHdCH),
5.90-5.97 (m, 1H, CHdCH); 13C NMR (75 MHz, CDCl3) major
isomer δ 20.9, 43.3, 47.8, 52.6, 58.0, 64.4, 71.3, 77.7, 116.3,
122.9, 126.0, 144.9, 171.4, minor isomer δ 21.3, 43.9, 48.5, 52.5,
58.3, 64.3, 72.0, 77.4, 116.3, 123.2, 125.7, 144.9, 171.3; MS (EI)
m/z (%) 266 (M+, 8), 121 (100); HRMS (FAB) calcd for C13H19O5
(MH+) 255.1233, found 255.1242.
8a -Meth yl-6,7,8,8a -tetr a h yd r on a p h th o[1,8-bc]fu r a n -2-
on e (37) (Ta ble 3, en tr y 7). By a procedure identical with
that described for the synthesis of 27, ketone 35 (48.6 mg,
0.194 mmol) was converted into 37 (30.6 mg, 84% yield):
1
colorless oil; IR (KBr) 1763 cm-1 (CdO); H NMR (300 MHz,
CDCl3) δ 1.47-1.55 (m, 1H, 8-CHH), 1.59 (s, 3H, CMe), 2.01-
2.12 (m, 2H, 7-CH2), 2.32 (ddd, J ) 12.2, 5.8, 3.7 Hz, 1H,
8-CHH), 2.78 (ddd, J ) 17.4, 8.2, 6.1 Hz, 1H, 6-CHH), 2.98
(ddd, J ) 17.4, 7.6, 6.4 Hz, 1H, 6-CHH), 7.35 (d, J ) 7.3 Hz,
1H, Ar), 7.41 (t, J ) 7.3 Hz, 1H, Ar), 7.63 (d, J ) 7.3 Hz, 1H,
Ar); 13C NMR (75.5 MHz, CDCl3) δ 18.5, 23.3, 24.6, 32.2, 83.5,
123.0, 123.9, 129.6, 132.0, 134.0, 153.4, 170.0; MS (EI) m/z (%)
188 (M+, 10), 173 (100); HRMS (EI) calcd for C12H12O2 (M+)
188.0837, found 188.0837.
Gen er a l P r oced u r e for t h e Sa m a r iu m (II) Iod id e-
Med ia ted Cycliza tion in th e P r esen ce of HMP A: Syn -
t h esis of Met h yl (1R*,7a R*)-1-H yd r oxy-4-m et h oxy-1-
m eth yl-2,3,5,7a -tetr a h yd r o-1H-in d en e-5-ca r boxyla te (41)
(Ta ble 4, en tr y 1). Samarium (182.4 mg, 1.20 mmol) and 1,2-
diiodoethane (307.8 mg, 1.09 mmol) were mixed in freshly
distilled THF (6.54 mL) under argon and stirred for 1.5 h at
room temperature. To the resulting dark-blue solution was
added HMPA (0.684 mL, 3.91 mmol) and the mixture was
stirred for 10 min at room temperature. To the stirred mixture
was added a solution of ketone 32c (51.2 mg, 0.217 mmol) and
i-PrOH (33 µL, 0.434 mmol) in THF (5.0 mL) over 30 min at
room temperature. After the mixture was stirred for 2 h,
saturated NH4Cl (2.0 mL) and SiO2 (2.0 g) were added to the
mixture. The whole was concentrated under reduced pressure,
and the residue was purified by column chromatography over
silica gel with n-hexane-EtOAc (2:1) to give 41 (38.7 mg, 75%
yield) as a 8:1 diastereomixture: colorless oil; IR (KBr) 3479
(OH), 1736 cm-1 (CdO); 1H NMR (300 MHz, CDCl3) δ 0.99 (s,
3H, CMe), 1.78-1.90 (m, 3H, 2-CH2 and OH), 2.37 (ddd, J )
17.1, 9.2, 9.2 Hz, 1H, 3-CHH), 2.58 (ddd, J ) 17.1, 10.4, 1.8
Hz, 1H, 3-CHH), 3.13-3.15 (m, 1H, 7a-H), 3.68 (s, 3H, OMe),
3.71 (s, 3H, OMe), 3.82-3.83 (m, 1H, 5-H), 5.82 (ddd, J ) 9.2,
4.3, 2.4 Hz, 1H, 7-H), 5.94 (ddd, J ) 9.2, 1.8, 1.8 Hz, 1H, 6-H);
Met h yl (4a R*,5S*)-5-H yd r oxy-1-m et h oxy-5-m et h yl-
4a ,5,6,7,8,9-h exa h yd r o-2H-ben zocycloh ep ten e-2-ca r box-
yla te (44) (Ta ble 4, en tr y 4). By a procedure identical with
that described for the synthesis of 41, ketone 39 (50.0 mg,
0.189 mmol) was converted into 44 (29.0 mg, 58% yield):
1
colorless oil; IR (KBr) 3489 (OH), 1738 cm-1 (CdO); H NMR
(300 MHz, CDCl3) δ 1.08 (s, 3H, CMe), 1.36-1.46 (m, 2H),
1.58-1.81 (m, 5H), 2.12-2.22 (m, 1H, 9-CHH), 2.67 (ddd, J )
15.9, 8.7, 5.1 Hz, 1H, 9-CHH), 3.06 (dd, J ) 4.5, 4.2 Hz, 1H,
4a-H), 3.55 (s, 3H, OMe), 3.70 (s, 3H, OMe), 3.98-4.02 (m,
1H, 2-H), 5.83 (ddd, J ) 9.9, 4.5, 0.9 Hz, 1H, CHdCH), 6.01
(ddd, J ) 9.9, 4.2, 1.5 Hz, 1H, CHdCH); 13C NMR (75 MHz,
CDCl3) δ 22.4, 23.9, 24.4, 27.8, 43.5, 44.2, 51.2, 52.2, 56.9, 76.9,
120.7, 122.5, 129.8, 145.6, 171.7; MS (EI) m/z (%) 266 (M+, 8),
121 (100); HRMS (FAB) calcd for C15H22O4Na (MNa+) 289.1416,
found 289.1413.
J . Org. Chem, Vol. 68, No. 15, 2003 5915