Helvetica Chimica Acta – Vol. 91(2008)
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CDCl3): 3.72 (d, J ¼ 0.8, 2 H); 3.93 (s, 3 H); 3.94 (s, 3 H); 3.96 (s, 3 H); 6.85 (d, J ¼ 8.6, 1H); 6.87 ( s,
1H); 7.21( d, J ¼ 8.6, 1H). 13C-NMR (100 MHz, CDCl3): 31.1; 35.5; 57.7; 62.0; 106.1; 108.5; 114.1; 125.4;
129.2; 130.6; 136.1; 148.3; 177.6.
Methyl 3-(3-{[(tert-Butoxy)carbonyl]methyl}-1-[2-(6,7-dimethoxy-1-methyl-1H-indol-3-yl)acetyl]-2-
oxopiperidin-3-yl)-2-diazo-3-oxopropanoate (16). A 0.9-g (3.4 mmol) sample of 33 was dissolved in
CH2Cl2 (40 ml), and 1.5 g (12 mmol) of oxalyl chloride was added dropwise. The soln. was stirred
overnight, concentrated under reduced pressure, and the remaining solid was taken up in benzene and
then immediately added to a vigorously stirred mixture containing 1.1 g (3.4 mmol) of 22 and 8 g of 4-
molecular sieves in benzene (30 ml). After stirring for 8 h, the mixture was filtered through a pad of
Celite and concentrated under reduced pressure. The crude material was purified by FC to give 1.8 g
(92%) of 16. Colorless oil: IR (neat): 2144, 1718, 1686, 1331, 1154. 1H-NMR (400 MHz, CDCl3): 1.46 (s,
9 H); 1.65 – 1.77 (m, 1H); 1.82 – 1.92 ( m, 1H); 2.14 – 2.30 ( m, 1 H); 2.19 (d, J ¼ 15.8, 1 H); 2.48 (d, J ¼
15.8, 1 H); 2.62 – 2.72 (m, 1H); 3.72 ( dt, J ¼ 12.4, 4.4, 1 H); 3.78 (s, 3 H); 3.92 (s, 3 H); 3.93 (s, 3 H); 3.95
(s, 3 H); 4.03 – 4.10 (m, 1H); 4.05 ( d, J ¼ 16.8, 1 H); 4.38 (d, J ¼ 16.8, 1 H); 6.78 (s, 1H); 6.80 ( d, J ¼ 8.8,
1H); 7.14 ( d, J ¼ 8.8, 1H). 13C-NMR (100 MHz, CDCl3): 19.5; 26.8; 28.2; 35.4; 36.1; 37.2; 44.7; 52.6; 57.6;
60.6; 61.9; 81.1; 107.5; 108.3; 114.0; 125.9; 129.9; 130.4; 136.1; 148.1; 161.7; 169.9; 173.0; 176.9; 189.9.
Methyl 3a-{[(tert-Butoxy)carbonyl]methyl}-5,12b-epoxy-2,3,3a,4,5,5a,6,11,12,12b-decahydro-7,8-di-
methoxy-6-methyl-4,12-dioxo-1H-6,12a-diazaindeno[7,1-cd]fluorene-5-carboxylate (17).
A 1.2-g
(2.2 mmol) sample of 16 was stirred with Rh(OAc)2 (7.5 mg) and 8 g of 4- molecular sieves in
benzene (100 ml), and the mixture was heated at reflux for 2 h. Then, the mixture was allowed to cool to
r.t. and was filtered through a pad of Celite. The solvent was removed under reduced pressure to give 1.2 g
(97%) of 17. Colorless oil: IR (neat): 1778, 1733, 1613, 1474, 1342, 1262, 1156. 1H-NMR (400 MHz,
CDCl3): 1.13 (d, J ¼ 14.6, 1 H); 1.27 (s, 9 H); 1.60 (d, J ¼ 14.6, 1 H); 1.70 – 1.79 (m, 2 H); 1.91 – 2.01 (m,
1 H); 2.11 – 2.18 (m, 1H); 2.70 ( d, J ¼ 17.2, 1 H); 2.95 (d, J ¼ 17.2, 1 H); 3.04 – 3.12 (m, 1H); 3.11( s,
3 H); 3.60 (s, 3 H); 3.74 (s, 3 H); 3.80 – 3.86 (m, 1H); 3.82 ( s, 3 H); 4.27 (s, 1H); 6.23 ( d, J ¼ 8.6, 1H);
6.51( d, J ¼ 8.6, 1H). 13C-NMR (100 MHz, CDCl3): 18.3; 26.6; 28.0; 28.2; 32.9; 38.2; 39.3; 45.3; 50.4;
53.5; 56.4; 59.0; 60.3; 81.2; 82.4; 92.1; 104.0; 104.1; 118.8; 122.0; 128.5; 135.5; 145.7; 155.3; 166.3; 169.1;
176.9; 202.4. HR-MS: 543.2339 ([C28H34N2O9 þ H]þ; calc. 543.2337).
Lewis Acid-Catalyzed Ring Opening of Cycloadduct 17. A 1.2 g (2.2 mmol) sample of 17 was
dissolved in CH2Cl2 (100 ml) and cooled to 08. To this mixture was added 1.5 g (12 mmol) of BF3 · OEt2 in
CH2Cl2 (10 ml). The mixture was allowed to warm to r.t. overnight. The soln. was then added to a sat. aq.
soln. of NaHCO3 (200 ml), the org. layer was separated, and the aq. layer was extracted three times with
CH2Cl2. The soln. was dried (MgSO4) and concentrated under reduced pressure. The product was
recrystallized from Et2O to give 0.72 g (70%) of 34. White solid. M.p. 223 – 2258. IR (neat): 1798, 1727,
1608, 1493, 1262, 1064. 1H-NMR (400 MHz, CDCl3): 1.54 – 1.70 (m, 3 H); 2.29 (d, J ¼ 17.2, 1 H); 2.38 (d,
J ¼ 17.2, 1 H); 2.45 – 2.55 (m, 1H); 2.85 – 2.95 ( m, 1H); 3.04 ( d, J ¼ 18.0, 1 H); 3.13 (d, J ¼ 18.0, 1 H);
3.16 (s, 3 H); 3.67 (s, 3 H); 3.76 (s, 3 H); 3.81( s, 3 H); 3.88 – 3.96 (m, 1H); 4.26 ( s, 1H); 4.80 ( s, 1H); 6.50
(d, J ¼ 8.4, 1H); 6.86 ( d, J ¼ 8.4, 1H). 13C-NMR (100 MHz, CDCl3): 18.5; 33.4; 36.6; 41.9; 43.3; 45.5;
51.6; 53.0; 53.7; 56.2; 60.1; 77.8; 82.9; 97.8; 105.5; 121.3; 123.3; 135.5; 146.7; 155.3; 166.6; 170.0; 173.7;
204.3. Anal. calc. for C24H26N2O9: C 59.25, H 5.39, N 5.76; found: C 59.19, H 5.51, N 5.56.
MgI2 Demethoxycarbonylation of 34. To 0.9 g (1.9 mmol) of 34 in MeCN (150 ml) was added 1.1 g
(4 mmol) of MgI2, and the soln. was heated at reflux for 4 h. The soln. was allowed to cool to r.t.,
concentrated under reduced pressure, and the residue was taken up in CH2Cl2 (50 ml) and H2O (50 ml).
This soln. was added to a sat. aq. soln. of NaHCO3 (200 ml). The org. layer was separated, and the aq.
layer was extracted twice with CH2Cl2, dried (MgSO4), and concentrated under reduced pressure to give
0.6 g (75%) of 35. White solid. M.p. 210 – 2128. IR (neat): 1794, 1720, 1609, 1494, 1263, 1193. 1H-NMR
(400 MHz, CDCl3): 1.30 – 1.45 (m, 1H); 1.58 – 1.81( m, 2 H); 2.27 (d, J ¼ 17.4, 1 H); 2.34 (d, J ¼ 17.4,
1H); 2.35 – 2.42 ( m, 1H); 2.80 ( d, J ¼ 18.0, 1 H); 2.93 (dt, J ¼ 14.0, 6.7, 1 H); 3.14 (s, 3 H); 3.27 (dd, J ¼
18.0, 0.8, 1 H); 3.68 (d, J ¼ 3.6, 1H); 3.69 ( s, 3 H); 3.83 (s, 3 H); 3.85 (d, J ¼ 3.6, 1H); 4.21– 4.30 ( m,
1H); 4.84 ( t, J ¼ 3.6, 1H); 6.48 ( d, J ¼ 8.6, 1H); 6.89 ( d, J ¼ 8.6, 1H). 13C-NMR (100 MHz, CDCl3):
20.4; 34.1; 37.3; 40.0; 41.4; 44.7; 51.7; 53.4; 56.2; 60.4; 78.0; 98.0; 105.1; 120.4; 122.9; 135.3; 146.5; 155.5;
170.4; 172.5; 207.8. Anal. calc. for C22H24N2O7: C 61.67, H 5.65, N 6.54; found: C 61.18, H 6.21, N 5.94.