€
S.M.A. Rahman and B.C.G. Soderberg
Tetrahedron 94 (2021) 132331
7.17 (tt, J ¼ 6.8, 1.2 Hz, 1H), 7.10 (tt, J ¼ 8.0, 1.2 Hz, 1H), 2.84 (t,
J ¼ 7.2 Hz, 2H), 1.73 (sextet, J ¼ 7.6 Hz, 2H), 0.97 (t, J ¼ 7.2 Hz, 3H);
(101 MHz, DMSO-d6)
d
147.2, 143.4, 141.0, 137.5, 131.2, 127.5, 126.2,
121.8, 121.0, 120.3, 119.8, 119.0, 117.9, 112.6, 31.0, 21.5; HRMS (ESI,
negative mode) m/z [M ꢁ H]- calcd for C16H12N: 218.0975; found:
218.0971.
13C{1H} NMR (101 MHz, CDCl3)
d 135.9, 135.4, 135.2, 129.6, 128.4,
127.9, 125.9, 121.5, 119.8, 118.9, 114.5, 110.3, 28.4, 23.1, 13.9.
3-(4-Methoxyphenyl)-2-methyl-1H-indole (58) [43]. Following
Procedure A, styrene 41 (73 mg, 0.27 mmol) was treated with CO
(pCO ¼ 6 atm) in the presence of Pd(OAc)2 (6.1 mg, 0.027 mmol),
dppp (22 mg, 0.053 mmol), phen (4.9 mg, 0.028 mmol) in DMF
(3 mL) at 120 ꢀC for 72 h. The crude product was purified by
chromatography (hexanes/EtOAc 8:2, Rf ¼ 0.58) to give 58 (49 mg,
0.21 mmol, 78%) as a pale yellow solid. mp ¼ 123e124 ꢀC; IR (ATR)
3347, 3054, 3007, 2910, 2835, 1563, 1509, 1457, 1283, 1236, 1173,
1106 1022, 986, 829, 815, 746, 671 cmꢁ1; 1H NMR (400 MHz, CDCl3)
3-(3-Pyridinyl)-1H-indole (61) [45]. Following procedure A,
styrene 44 (90 mg, 0.40 mmol) was treated with CO (pCO ¼ 6 atm)
in the presence of Pd(OAc)2 (8.9 mg, 0.04 mmol), dppp (33 mg,
0.04 mmol), phen (7.2 mg, 0.04 mmol) in DMF (3 mL) at 120 ꢀC for
72 h. The crude product was purified by chromatography (hexanes/
EtOAc 3:7, Rf ¼ 0.23) to give 61 (76 mg, 0.39 mmol, 98%) as a yellow
gum. IR (ATR) 3400, 3038, 2972, 2922. 1565, 1539, 1456, 1408, 1338,
1308, 1242, 1125, 962, 800, 738, 707 cmꢁ1
CDCl3)
;
1H NMR (400 MHz,
d
8.94 (dd, J ¼ 2.4, 0.8 Hz,1H), 8.57 (br s,1H), 8.53 (dd, J ¼ 3.6,
d
7.93 (br s, 1H), 7.62 (d, J ¼ 8.0 Hz, 1H), 7.43 (d, J ¼ 8.8 Hz, 2H), 7.33
1.6 Hz, 1H), 7.98 (ddd, J ¼ 8.0, 2.3, 1.7 Hz, 1H), 7.90 (ddt, J ¼ 7.8, 1.4,
0.8 Hz, 1H), 7.47 (td, J ¼ 8.0, 0.8 Hz, 1H), 7.44 (d, J ¼ 2.8 Hz, 1H), 7.37
(ddd, J ¼ 8.0, 4.8, 0.8 Hz, 1H), 7.29 (td, J ¼ 7.2, 0.8 Hz, 1H), 7.23 (td,
(d, J ¼ 8.0 Hz,1H), 7.16 (td, J ¼ 8.4, 0.8 Hz,1H), 7.10 (td, J ¼ 6.8,1.2 Hz,
1H), 7.02 (d, J ¼ 8.8 Hz, 2H) 3.87 (s, 3H), 2.49 (s, 3H); 13C{1H} NMR
(101 MHz, CDCl3)
d
157.8, 135.1, 131.0, 130.4, 128.0, 127.8, 121.4,
J ¼ 8.4, 1.6 Hz, 1H); 13C{1H} NMR (101 MHz, CDCl3)
d 148.1, 146.6,
119.8, 118.7, 114.0, 114.0, 110.2, 55.3, 12.4.
136.8, 134.5, 131.9, 125.4, 123.7, 122.6, 122.5, 120.6, 119.2, 114.1, 111.7.
1,3,4,9-Tetrahydrospiro[2H-carbazole-2,2'-[1,3]dioxolane] (62)
[46]. Following procedure A, styrene 45 (84 mg, 0.32 mmol) was
treated with CO (pCO ¼ 6 atm) in the presence of Pd(OAc)2 (7.3 mg,
0.032 mmol), dppp (27 mg, 0.065 mmol), phen (5.8 mg,
0.032 mmol) in DMF (3 mL) at 120 ꢀC for 72 h. The crude product
was purified by chromatography (hexanes/EtOAc 7:3, Rf ¼ 0.45) to
3-(2,4-Dimethoxyphenyl)-2-methyl-1H-indole
(6)
Following procedure A, styrene 5 (81 mg, 0.27 mmol) was treated
with CO (pCO ¼ 6 atm) in the presence of Pd(OAc)2 (6.1 mg,
0.027 mmol), dppp (22 mg, 0.053 mmol), phen (4.9 mg,
0.027 mmol) in DMF (3 mL) at 120 ꢀC for 72 h. The crude product
was purified by chromatography (hexanes/EtOAc 7:3, Rf ¼ 0.43) to
give 6 (42 mg, 0.16 mmol, 59%) as an off-white solid.
give 62 (60 mg, 0.26 mmol, 81%) as
a pale yellow solid.
Following Procedure B, 2-bromonitrobenzene (16) (100 mg,
0.50 mmol) was treated with hydrazone 4 (269 mg, 0.74 mmol),
PdCl2(PPh3)2 (8.7 mg, 0.012 mmol), lithium tert-butoxide (149 g,
1.86 mmol) in 1,4-dioxane (8 mL) at 100 ꢀC for 8 h, followed by
addition of dppp (41 mg, 0.10 mmol) under CO (pCO ¼ 6 atm,
140 ꢀC, 72 h). The crude product was purified by chromatography
(hexanes/EtOAc 7:3, Rf ¼ 0.43) to give 6 (109 mg, 0.41 mmol, 82%) as
an off-white solid. mp ¼ 198e199 ꢀC; IR (ATR) 3387, 2999, 2958,
2934, 2834, 1612, 1566, 1503, 1459, 1302, 1258, 1209, 1158, 1136,
mp ¼ 89e90 ꢀC; IR (ATR) 3398, 2924, 2893, 2851, 1600, 1467, 1452,
1284, 1236, 1099, 1057, 1011, 946, 840, 740 cmꢁ1
;
1H NMR
(400 MHz, CDCl3)
d
7.68 (br s, 1H), 7.46 (d, J ¼ 7.6 Hz, 1H), 7.27 (d,
J ¼ 6.8 Hz, 1H), 7.14e7.05 (m, 2H), 4.06 (s, 4H), 3.00 (s, 2H), 2.89 (t,
J ¼ 6.4 Hz, 2H), 2.04 (t, J ¼ 6.4 Hz, 2H); 13C{1H} NMR (101 MHz,
CDCl3)
d 136.4, 131.4, 127.1, 121.2, 119.2, 118.0, 110.5, 109.1, 109.0,
64.7, 64.7, 34.3, 32.0, 18.8.
7-Aza-3-phenylindole (63) [25], 1-Hydroxy-4-phenyl-1,8-
naphthyridin (64) [47] and 2-Amino-3-(1-phenyl-1-ethenyl-1-yl)
pyridine (65). Following procedure A, styrene 46 (79 mg,
0.35 mmol) was treated with CO (pCO ¼ 6 atm) in the presence of
Pd(OAc)2 (7.8 mg, 0.035 mmol), dppp (29 mg, 0.07 mmol), phen
(6.3 mg, 0.035 mmol) in DMF (3 mL) at 120 ꢀC for 72 h . The crude
product was purified by chromatography (hexanes/EtOAc 1:1) to
give 63 containing a trace amount of 65 (46 mg, 0.24 mmol, 69%,
63/65e20:1, Rf ¼ 0.30) followed by 64 (14.3 mg, 0.063 mmol, 18%,
Rf ¼ 0.20), both as white solids.
1049, 1032, 826, 797, 747, 599, 584, 543, 519 cmꢁ1
(400 MHz, CDCl3)
;
1H NMR
d
7.93 (br s, 1H), 7.39 (d, J ¼ 8.0 Hz, 1H), 7.32e7.27
(m, 2H), 7.11 (td, J ¼ 6.8, 1.2 Hz, 1H), 7.05 (td, J ¼ 7.2, 0.8 Hz, 1H),
6.62e6.58 (m, 2H), 3.88 (s, 3H), 3.78 (s, 3H), 2.36 (s, 3H); 13C{1H}
NMR (101 MHz, CDCl3)
d 159.7, 158.3, 135.2, 132.5, 132.3, 128.7,
121.0, 119.4, 119.2, 116.5, 110.2, 110.2, 104.3, 99.0, 55.4, 55.4, 12.7.
6,7-Dihydro-5H-benzo[c]carbazole (59) [44]. Following Pro-
cedure A, styrene 42 (80 mg, 0.32 mmol) was treated with CO
(pCO ¼ 6 atm) in the presence of Pd(OAc)2 (7.1 mg, 0.032 mmol),
dppp (22 mg, 0.063 mmol), phen (5.7 mg, 0.032 mmol) in DMF
(3 mL) at 120 ꢀC for 72 h. The crude product was purified by
chromatography (hexanes/EtOAc 8:2, Rf ¼ 0.23) to give 59 (50 mg,
0.23 mmol, 72%) as an off-white solid. mp ¼ 103e104 ꢀC; IR (ATR)
3404, 3049, 2930, 2893, 2831, 1601, 1548, 1496, 1447, 1355, 1254,
7-Aza-3-phenylindole (63), 2-Nitro-3-(1-phenyl-1-ethene-1-yl)
pyridine (46) and 2-Amino-3-(1-phenyl-1-ethene-1-yl)pyridine
(65). Following Procedure B, 3-bromo-1-nitropyridine (28)
(100 mg, 0.493 mmol) was treated with acetophenone 4-
methylphenylsulfonylhydrazone (14) [24] (213 mg, 0.74 mmol) in
the presence of PdCl2(PPh3)2 (8.7 mg, 0.012 mmol) and LiOt-Bu
(148 mg, 1.85 mmol) in 1,4-dioxane (8 mL) at 100 ꢀC for 1 h, fol-
lowed by addition of dppp (40.7 mg, 0.10 mmol) under CO
(pCO ¼ 6 atm, 140 ꢀC, 72 h). The crude product was purified by
chromatography (hexanes/EtOAc, 7:3 then 1:1) to give, in order of
elution, 46 (21.9 mg, 0.097 mmol, 20%, Rf ¼ 0.70) as a brown oil and
a mixture of 63 and 65 (69.0 mg, Rf ¼ 0.30). The two compounds
were separated by a second chromatography (hexanes/EtOAc/ace-
tic acid, 7:3:0.1) to give 63 as a mixture with acetic acid. In order to
elute compound 65, the mobile phase was changed (hexanes/
EtOAc, 6:4) and 65 (11.9 mg, 0.061 mmol, 12%) was isolated as a
faint brown solid. Acetic acid was removed from the mixture with
63 by a third chromatography (hexanes/EtOAc, 7:3 then 1:1) to give
pure 63 (57.1 mg, 0.294 mmol, 60%) as a white solid.
1183, 1015, 968, 742, 733, 693 cmꢁ1 1H NMR (400 MHz, CDCl3)
;
d
8.02 (dd, J ¼ 7.2, 1.2 Hz, 1H), 7.97 (br s, 1H), 7.85 (dd, J ¼ 7.2, 1.2 Hz,
1H), 7.38e7.27 (m, 2H), 7.24e7.15 (m, 3H), 7.08 (td, J ¼ 7.2, 1.6 Hz,
1H), 3.06 (t, J ¼ 8.0 Hz, 2H), 2.99e2.91 (m, 3H); 13C{1H} NMR
(101 MHz, CDCl3)
d 137.2, 136.1, 133.8, 133.3, 127.9, 126.9, 124.9,
124.3, 122.2, 121.4, 120.5, 119.4, 111.1, 110.6, 29.4, 22.4.
5,6-Dihydro-3-methylindeno[2,1-b]indole (60). Following Pro-
cedure A, styrene 43 (67 mg, 0.27 mmol) was treated with CO
(pCO ¼ 6 atm) in the presence of Pd(OAc)2 (5.9 mg, 0.027 mmol),
dppp (22 mg, 0.053 mmol), phen (4.8 mg, 0.027 mmol) in DMF
(3 mL) at 120 ꢀC for 72 h. The crude product was purified by
chromatography (hexanes/EtOAc 8:2, Rf ¼ 0.17) to give 60 (26 mg,
0.12 mmol, 44%) as a black solid. mp ¼ 214e215 ꢀC; IR (ATR) 3374,
3056, 2915, 1616, 1574, 1483, 1449, 1385, 1248, 1215, 1168, 1021, 818,
Analytical data for 63: mp ¼ 188e189 ꢀC; IR (ATR) 3082, 3030,
736, 725 cmꢁ1 1H NMR (400 MHz, DMSO-d6)
; d 11.48 (br s, 1H),
2988, 2875, 1533, 1418, 1264, 960, 895, 771, 697, 750 cmꢁ1; 1H NMR
7.82e7.79 (m, 1H), 7.51 (d, J ¼ 7.6 Hz, 1H), 7.44e7.40 (m, 1H), 7.25 (s,
(400 MHz, DMSO-d6)
J ¼ 2.4 Hz, 1H), 7.72 (d, J ¼ 7.2 Hz, 2H), 7.44 (t, J ¼ 8.0 Hz, 2H), 7.26 (t,
d 11.91 (br s, 1H), 8.31e8.26 (m, 2H), 7.87 (d,
1H), 7.12e7.06 (m, 3H), 3.76 (s, 2H), 2.34 (s, 3H); 13C{1H} NMR
13