May 2009
In Situ Vinylpyrrole Synthesis. Diels-Alder Reactions with Maleimides
to Give Tetrahydroindoles
531
8
.4 Hz, 2H, Ph), 6.23 (d, J ¼ 2.4 Hz, 1H, 3maj-H), 5.77 (d,
(4 mL), and then a diethyl ether wash (10 mL) gave 103
(1270 mg, 60%) as a cream-colored solid, a mixture of two
0
J ¼ 2.7 Hz, 1H, 3min-H), 3.97 (AA d, J ¼ 15.9 Hz, 1H, Bn
0
0
ꢃ
1
maj), 3.96 (AA d, J ¼ 16.2 Hz, 1H, Bn min), 3.90 (AA d, J ¼
isomers (maj:min ¼ 1.8:1.0): mp 234–235 C; H NMR
0
1
3
5
6
6.2 Hz, 1H, Bn maj), 3.89 (AA d, J ¼ 15.9 Hz, 1H, Bn maj),
(300 MHz, CDCl , d) 8.27 (bs, 1H, 1maj-H), 7.58 (bs, 1H,
3
.81 (s, 3H, OCH ), 3.69 (dd, 1H, 3ba-H), 3.21 (dd, J ¼ 8.4,
1min-H), 7.37–7.51 (m, 3H, Ph), 7.24–7.32 (m, 2H, Ph), 7.16–
7.21 (m, 2H, Ph), 6.85–6.90 (m, 2H, Ph), 6.27 (d, J ¼ 2.4 Hz,
3
.7 Hz, 1H, 6aamin-H), 3.16 (dd, J ¼ 8.7, 5.7 Hz, 1H,
0
aamaj-H), 3.00–3.06 (m, 1H, 10aamaj-H), 2.93 (s, 6H,
1H, 3min-H), 5.81 (J ¼ 2.4 Hz, 1H, 3maj-H), 3.99 (AA d, J ¼
N(CH
ba-H), 1.05–2.22 (m, 8H, cyclohex.); C NMR (75 MHz,
DMSO-d , d) 177.6, 177.5, 176.7, 159.1, 158.0, 133.4, 131.0,
3
)
2
), 2.91–2.92 (m, 1H, 10abmin-H), 2.44–2.52 (m, 1H,
17.1 Hz, 1H, Bn maj), 3.971 (dd, J ¼ 8.6, 2.0 Hz, 1H, 3ba-
1
3
0
0
6
H), 3.968 (AA d, J ¼ 15.9 Hz, 1H, Bn min), 3.91 (AA d, J ¼
15.9 Hz, 1H, Bn maj), 3.81 (s, 3H, OCH ), 3.46 (dd, J ¼ 8.7,
6
3
1
30.0, 129.9, 127.3, 114.1, 108.8, 105.4, 55.5, 44.3, 44.0, 43.8,
8.2, 36.7, 33.2, 33.1, 32.9, 27.6, 25.6, 23.0, 21.4; IR (thin
5.7 Hz, 1H, 6aamaj-H), 3.39 (dd, J ¼ 8.6, 5.3 Hz, 1H,
6aamin-H), 3.08–3.14 (m, 1H, 10aamin-H), 3.02–3.07 (m, 1H,
10abmaj-H), 2.50–2.58 (m, 1H, 6ba-H), 2.04–2.25 (m, 1H,
3
film, cm ) 3371(bs), 2924(m), 2852(m), 1770(w), 1703(s),
ꢂ1
1
1
515(m), 1444(m), 1360(w), 1252(m), 1193(m); HRMS m/z
cyclohex.), 1.18–1.76 (m, 7H, cyclohex.); H NMR (300 MHz,
þ
(
M þ Na ) calcd for C H N O : 430.2102, found 430.2087.
DMSO-d , d) 10.65 (d, J ¼ 2.1 Hz, 1H, 1maj-H), 10.38 (d,
2
4
29
3
3
6
5-Dimethylamino-8-ethyl-2-(4-methoxybenzyl)-3b,6a,6b,7,8,
,10,10a-octahydro-1H,5H-benzo[g]pyrrolo[3,4-e]indole-4,6-dione
101). Method A gave 101 (287 mg, 22%) as a cream-colored
J ¼ 1.8 Hz, 1H, 1min-H), 7.38–7.54 (m, 3H, Ph), 7.12–7.26
(m, 4H, Ph), 6.81–6.87 (m, 2H, Ph), 5.80 (d, J ¼ 2.4 Hz, 1H,
3min-H), 5.56 (d, J ¼ 2.4 Hz, 1H, 3maj-H), 4.18 (dd, J ¼ 8.4,
1.8 Hz, 1H, 3bamaj-H), 4.02 (dd, J ¼ 8.4, 1.8 Hz, 1H,
9
(
solid, a mixture of three isomers (maj:min ¼ 4.0:1.0:0.2): mp
ꢃ
1
79–180 C; H NMR (300 MHz, CDCl
1
1
6
3
, d) 8.22 (bs 1H,
3
3bamin-H), 3.80 (s, 2H, Bn), 3.71 (s, 3H, OCH ), 3.37 (dd,
min-H), 7.55 (bs, 1H, 1maj-H), 7.16 (d, J ¼ 8.7 Hz, 2H, Ph),
J ¼ 8.4, 5.1 Hz, 1H, 6aamaj-H), 3.34 (dd, J ¼ 8.4, 5.4 Hz,
.86 (d, J ¼ 8.7 Hz, 2H, Ph), 6.22 (d, J ¼ 2.4 Hz, 1H, 3maj-
1H, 6aamin-H), 3.01–3.07 (m, 1H, 10aamin-H), 2.90–2.95 (m,
H), 5.78 (d, J ¼ 2.7 Hz, 1H, 3min-H), 5.74 (d, J ¼ 2.1 Hz,
1H, 10abmaj-H), 2.03–2.42 (m, 2H, cyclohex., 6b-H), 1.03–
0
13
1
(
H, 3min-H), 3.97 (AA d, J ¼ 16.2 Hz, 1H, Bn maj), 3.96
1.64 (m, 7H, cyclohex.); C NMR (75 MHz, DMSO-d , d)
6
0
0
AA d, J ¼ 16.2 Hz, 1H, Bn min), 3.89 (AA d, J ¼ 16.2 Hz, 1H,
178.4, 178.2, 177.4, 176.3, 158.0, 133.4, 138.3, 133.0, 131.1,
130.0, 129.9, 129.6, 129.5, 128.9, 128.8, 127.4, 119.1, 117.3,
114.1, 108.9, 105.6, 102.7, 55.5, 46.2, 45.9, 38.7, 38.5, 38.4,
38.2, 33.2, 33.1, 29.3, 27.6, 26.1, 25.7, 23.5, 22.9, 21.5, 20.9;
0
Bn maj), 3.88 (AA d, J ¼ 16.2 Hz, 1H, Bn min), 3.81 (s, 3H,
OCH
9
3
), 3.69 (dd, J ¼ 8.4, 1.8 Hz, 1H, 3ba-H), 3.24 (dd, J ¼ 5.4,
.6 Hz, 1H, 6aamin-H), 3.20 (dd, J ¼ 8.7, 5.7 Hz, 1H, 6aamin-
ꢂ1
H), 3.19 (dd, J ¼ 8.7, 5.6 Hz, 1H, 6aamin-H), 3.16 (dd, J ¼ 8.6,
IR (thin film, cm ) 3372, 2920, 1697, 1515; HRMS m/z (M
þ Na ) calcd 463.1993, found 463.2009. Anal. Calcd for
þ
5
2
1
.6 Hz, 1H, 6aamaj-H), 2.91–2.94 (m, 7H, 10a-H, N(CH
.58–2.67 (m, 1H, 6bamaj-H), 2.46–2.55 (m, 1H, 6bmin-H),
.00–2.07 (m, 9H, cyclohex., CH CH
), 0.84 (t, J ¼ 7.4 Hz, 3H,
3
)
2
),
28 28 2 3
C H N O : C, 76.34; H, 6.41; N, 6.36. Found: C, 76.26; H,
2
3
6.59; N, 6.35.
13
CH CH maj), 0.76 (t, J ¼ 7.2 Hz, 3H, CH CH maj); C NMR
8-Ethyl-2-(4-methoxybenzyl)-5-phenyl-3b,6a,6b,7,8,9,10,10a-
octahydro-1H,5H-benzo[g]pyrrolo[3,4-e]indole-4,6-dione (104).
Method A gave 104 (450 mg, 32%) as a cream-colored solid, a
mixture of four isomers (maj:min:min:min ¼ 1.1:1.0:0.3:0.3):
2
3
2
3
(
75 MHz, DMSO-d , d) 177.6, 177.4, 176.7, 176.6, 158.0,
6
1
1
4
33.3, 131.0, 130.0, 129.9, 129.8, 127.2, 127.15, 127.1, 117.3,
14.1, 114.0, 108.9, 108.8, 105.4, 105.0, 102.8, 55.5, 43.9, 43.8,
3.6, 36.7, 33.9, 33.0–33.2 (multiple peaks), 32.6, 29.9; IR (thin
ꢂ1
ꢃ
1
mp 214–215 C; H NMR (300 MHz, CDCl , d) 8.25 (bs, 1H,
3
film, cm ) 3378(bs), 2928(m), 2358(w), 1773(w), 1709(s),
þ
1maj-H), 7.58 (bs, 1H, 1min-H), 7.56 (bs, 1H, 1min-H), 7.37–
7.51 (m, 3H, Ph), 7.28–7.32 (m, 2H, Ph), 7.15–7.20 (m, 2H,
Ph), 6.85–6.90 (m, 2H, Ph), 6.26 (d, J ¼ 2.7 Hz, 1H, 3maj-H),
5.82 (d, J ¼ 2.4 Hz, 1H, 3min-H), 5.79 (d, J ¼ 3.0 Hz, 1H,
1
510(m), 1246(m); HRMS m/z (M
þ
Na ) calcd for
C
26
H
33
N
3
O
3
: 458.2415, found 458.2422.
-tert-Butyl-5-(dimethylamino)-2-(4-methoxybenzyl)-3b,6a,
8
b,7,8,9,10,10a-octahydro-1H,5H-benzo[g]pyrrolo[3,4-e]indole-
0
0
6
4
3min-H), 3.98 (AA d, J ¼ 15.9 Hz, 1H, Bn min), 3.97 (AA d,
J ¼ 16.2 Hz, 1H, Bn maj), 3.96 (dd, J ¼ 8.6, 2.0 Hz, 1H,
,6-dione (102). Method A gave 102 (292 mg, 21%) as orange
ꢃ
1
0
0
crystals, a single isomer: mp 95–96 C; H NMR (300 MHz,
CDCl
, d) 7.43 (bs, 1H, 1-H), 7.13 (d, J ¼ 8.4 Hz, 2H, Ph),
3ba-H), 3.91 (AA d, J ¼ 16.2 Hz, 1H, Bn min), 3.90 (AA d,
3
3
J ¼ 16.2 Hz, 1H, Bn maj), 3.82 (s, 3H, OCH ), 3.48 (dd, J ¼
6
3
1
1
6
1
1
0
1
1
2
1
.85 (d, J ¼ 8.7 Hz, 2H, Ph), 6.08 (d, J ¼ 2.7 Hz, 1H, 3-H),
9.02, 5.3 Hz, 1H, 6aamin-H), 3.45 (dd, J ¼ 8.1, 5.7 Hz, 1H,
6aamin-H), 3.42 (dd, J ¼ 7.8, 5.4 Hz, 1H, 6aamin-H), 3.39
(dd, J ¼ 8.4, 5.4 Hz, 1H, 6aamaj-H), 2.97–3.08 (m, 1H, 10a-
H), 2.65–2.74 (m, 2H, 6bamaj-H, 6bamin-H), 2.53–2.62
(m, 2H, 6bbmin-H), 1.07–2.30 (m, 7H, cyclohex.), 1.43 (app.
0
0
.92 (AA d, J ¼ 17.1 Hz, 1H, Bn), 3.83 (AA d, J ¼ 17.1 Hz,
H, Bn), 3.81 (s, 3H, OCH ), 3.78 (dd, J ¼ 7.8 Hz, 1.7 Hz,
3
H, 3ba-H), 3.09 (dd, J ¼ 8.0, 5.9 Hz, 1H, 6aa-H), 2.87 (s,
3 2
H, N(CH ) ), 2.61–2.70 (m, 1H, 6ba), 2.50–2.57 (m, 1H,
0aa-H), 1.65–2.06 (m, 4H, cyclohex.), 1.49 (ddd, J ¼ 13.8,
q, J ¼ 7.5 Hz, 2H, CH
2
CH
CH CH maj), 0.79 (t, J ¼ 7.2 Hz, 3H, CH CH min);
3
), 0.85 (t, J ¼ 7.2 Hz, 3H,
13
0.4, 6.8 Hz, 1H, cyclohex.), 1.07–1.30 (m, 2H, cyclohex.),
C
2
3
2 3
1
3
.89 (s, 9H, t-Bu); C NMR (75 MHz, DMSO-d , d) 177.7,
76.4, 158.0, 133.0, 131.3, 130.5, 130.0, 129.9, 114.1, 109.1,
04.2, 55.5, 43.6, 43.55, 43.1, 33.9, 33.3, 33.0, 32.8, 30.4,
NMR (75 MHz, DMSO-d , d) 178.4, 178.2, 177.4, 176.3,
6
6
158.0, 133.4, 133.35, 133.3, 133.0, 132.9, 132.8, 131.1, 131.0,
130.0, 129.9, 129.8, 129.7, 129.6, 129.5, 128.9, 128.7, 127.4,
127.35, 127.3, 119.0, 118.8, 117.4, 114.1, 109.0, 105.5, 105.0,
102.8, 55.5, 45.9, 45.5, 38.9, 38.7, 38.4, 38.2, 38.1, 34.3,
33.9, 32.7–33.3 (multiple peaks), 30.0, 27.4, 23.7, 23.6, 12.6,
ꢂ1
8.0, 27.9; IR (thin film, cm ) 3364(bs), 2955(m), 1774(w),
þ
712(s), 1511(s), 1364(m), 1246(m); HRMS m/z (M þ Na )
37 3 3
calcd for C28H N O : 486.2728, found 486.2720.
ꢂ1
2
-(4-Methoxybenzyl)-5-phenyl-3b,6a,6b,7,8,9,10,10a-octahy-
11.8; IR (thin film, cm ) 3389(bs), 2931(m), 1777(w),
1706(s), 1509(m), 1383(m), 1246(m), 1176(m); HRMS m/z (M
dro-1H,5H-benzo[g]pyrrolo[3,4-e]indole-4,6-dione (103). Method
B with 3c (687 mg, 7.00 mmol), 3.5-h reflux, ethanol wash
þ
þ Na ) calcd 491.2306, found 491.2323. Anal. Calcd for
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet