4
W. E. NOLAND ET AL.
ꢀ
ꢀ
ꢂ1
1
1
18–120 C (lit. 113–117 C); R ¼ 0.37; IR (KBr, cm ): 3412, 3053, 2977, 2936, 1490,
f
1
457, 1414, 1371, 1338, 1245, 1100, 1070, 1026, 1011, 742, 702; H NMR (500 MHz,
CD Cl ): d 8.011 (brs, 2H), 7.421–7.397 (m, 2H), 7.361 (d, J ¼ 8.2 Hz, 2H), 7.281–7.253
2
2
(
7
m, 4H), 7.227–7.193 (m, 1H), 7.111 (ddd, J ¼ 8.2, 7.0, 1.1 Hz, 2H), 6.894 (ddd, J ¼ 8.1,
13
.1, 1.1 Hz, 2H), 6.702 (d, J ¼ 2.5 Hz, 2H), 2.350 (s, 3H); C NMR (126 MHz, CD Cl ):
2
2
d 148.7, 137.7, 128.6, 128.3, 127.0, 126.4, 125.0, 123.9, 122.3, 122.0, 119.3, 111.8, 44.2,
2
þ
9.3; HRMS (ESI) m/z: [M þ Na] Calcd for C H N 359.1519; Found 359.1518.
24
20 2
rac-(1R,3S)-1,2,3,4-tetrahydro-3-(1H-indol-3-yl)-1-methyl-1,3-bis(4-methylphenyl)-
H-cyclopent[b]indole (12b) was prepared by Method A from 8b (402 mg) as an
1
1
ꢀ
off-white crystalline solid; 126 mg, 26% (calcd by H NMR); mp 168.5–172 C; R ¼ 0.39;
f
ꢂ1
IR (KBr, cm ): 3411, 3052, 3021, 2960, 2922, 2865, 1622, 1511, 1456, 1414, 1371, 1288,
1
1
243, 1187, 1097, 1068, 818, 743; H NMR (500 MHz, CD Cl ): d 8.125 (brs, 1H), 7.985
2
2
(
7
brs, 1H), 7.393 (d, J ¼ 8.2 Hz, 2H), 7.319 (d, J ¼ 8.1 Hz, 1H), 7.285 (d, J ¼ 8.2 Hz, 2H),
.168–7.043 (m, 8H), 6.966–6.939 (m, 4H), 3.554 (d, J ¼ 13.3 Hz, 1H), 3.434 (d,
13
J ¼ 13.4 Hz, 1H), 2.296 (s, 3H), 2.238 (s, 3H), 1.754 (s, 3H); C NMR (126 MHz,
CD Cl ): d 147.9, 147.6, 144.3, 141.8, 137.9, 136.2 135.6, 129.3, 129.2, 127.8, 126.8,
2
2
1
6
26.7, 125.0, 124.8, 123.3, 123.1, 122.6, 121.7, 121.1, 120.2, 120.0, 119.7, 112.5, 112.0,
þ
5.1, 51.7, 47.6, 30.1, 21.2, 21.1; HRMS (EI) m/z: [M] Calcd for C H N 466.2404;
34
30 2
Found 466.2413.
rac-(1R,3R)-1,2,3,4-tetrahydro-3-(1H-indol-3-yl)-1-methyl-1,3-bis(4-aminophenyl)-
H-cyclopent[b]indole (13c) was prepared according to Method A from 8c (406 mg) as
1
1
ꢀ
a red crystalline solid; 37.5 mg, 7.5% (calcd by H NMR); mp 190–193 C; R ¼ 0.38; IR
f
ꢂ1
(
KBr, cm ): 3411, 3335, 3213, 3052, 2958, 2921, 2862, 1620, 1512, 1449, 1290, 1244,
183, 1103, 1043, 829, 744; H NMR (400 MHz, (CD ) SO): d 10.870 (s, 1H), 10.709 (s,
1
1
1
7
6
3 2
H), 7.321 (d, J ¼ 8.0 Hz, 1H), 7.260 (d, J ¼ 8.1 Hz, 1H), 7.203 (d, J ¼ 7.8 Hz, 1H),
.070–6.896 (m, 8H), 6.733 (ddd, J ¼ 8.0, 1.2, 1.0 Hz, 1H), 6.593 (d, J ¼ 2.5 Hz, 1H),
.497 (d, J ¼ 8.6 Hz, 2H), 6.437 (d, J ¼ 8.5 Hz, 2H), 4.892 (s, 2H), 4.767 (s, 2H), 3.302 (d,
1
3
J ¼ 13.1 Hz, 1H), 3.254 (d, J ¼ 13.1 Hz, 1H), 1.564 (s, 3H); C NMR (126 MHz, CD Cl ):
2
2
d 147.6, 145.5, 144.8, 141.6, 140.9, 138.2, 137.6, 128.8, 127.7, 126.7, 125.3, 124.8, 123.5,
1
4
22.4, 122.2, 121.4, 120.9, 120.1, 119.8, 119.6, 115.32, 115.26, 112.5, 111.9, 66.0, 51.5,
þ
7.1, 29.8; HRMS (ESI) m/z: [M þ Na] Calcd for C H N 491.2206; Found 491.2201.
32
28 4
Results and discussion
Indole 1a (1 Eq.) reacted with eight acetophenones 8a–h (1.5 Eq.) in a solution of
ethanol and hydrochloric acid. A small quantity of naphthalene 10 was added as an
ꢀ
internal NMR standard. The resulting mixtures were stirred at 20 C for 5 days, or
ꢀ
4
0 C for 3 days. The organics were extracted, neutralized, concentrated, and then
separated by column chromatography. Yields of the corresponding 2:1 condensation
products, 3,3-(1-phenylethane-1,1-diyl)bis(1H-indoles) (11a–h), and 2:2 condensation
products, diastereomers of 1,2,3,4-tetrahydro-3-(1H-indol-3-yl)-1-methyl-1,3-diphenylcy-
clopent[b]indoles (12a–h, syn; 13a–h, anti), are listed in Table 1.
þ
Compared to 8a, the ketones with electron-withdrawing groups, 8c (as R ¼ NH ),
3
and 8f–h, gave higher 2:1 and lower 2:2 condensation yields. Conversely, the electron-
rich ketones, 8b, 8d, and 8e favored 2:2 condensation. Increasing the temperature from
ꢀ
2
0 to 40 C gave higher yields of the 2:2 products, and lower 2:1 yields. The reaction