The Journal of Organic Chemistry
Article
methyl-5-nitroindole (88 mg, 0.5 mmol), [Ir(OMe)cod]2 (10 mg, 3
mol %), dtbpy (8 mg, 6 mol %), and B2Pin2 (1.5 equiv, 190 mg) in
THF (2.5 mL total) heating to 80 °C in a microwave29 for 2 h.
Purification using 3:2 n-hexane−ethyl acetate gave the title compound
(55.9 mg, 0.185 mmol, 37%) as a crimson oil, νmax (neat)/cm−1 3438,
2981, 1592, 1561, 1520, 1468, 1373, 1312, 1268, 1204, 1185, 1138,
1072, 1009, 986, 963, 893, 851, 791, 752, 707, 691, 673; δH (400 MHz,
CDCl3) 9.15 (1 H, br s, NH), 8.48 (1 H, d, J 2.0, ArH), 8.45 (1 H, d, J
2.4, ArH), 6.34 (1 H, q, J 0.8, ArH), 2.51 (3 H, d, J 0.8, Me), 1.41 (12
H, s, 4 × Me); δC (100 MHz, CDCl3) 144.3 (C), 141.5 (C), 138.8
(C), 127.8 (C), 123.7 (CH), 119.1 (CH), 102.1 (CH), 84.6 (2 × C),
82.9 (C), 25.0 (4 × Me), 14.0 (Me); HRMS [ESI, (M + Na)+] found
325.1324, [C15H19BN2O4 + Na]+ requires 325.1333.
in THF (2.5 mL total) heating to 80 °C in a microwave29 for 2 h.
Purification using 4:1 n-hexane−ethyl acetate gave the title compound
(153 mg, 0.385 mmol, 77%) as a colorless solid, mp 201−204 °C; νmax
(neat)/cm−1 3446, 2978, 2930, 1735, 1688, 1615, 1594, 1492, 1466,
1379, 1347, 1323, 1304, 1259, 1237, 1212, 1144, 1127, 1099, 1045,
1020, 961, 916, 857, 753, 728; δH (400 MHz, CDCl3) 8.80 (1 H, br s,
NH), 7.61−7.58 (2 H, m, 2 × ArH), 7.10 (1 H, t, J 7.6, ArH), 4.68 (2
H, br s, CH2), 3.77 (2 H, br s, CH2), 2.80 (2 H, br s, CH2), 1.50 (9 H,
s, 3 × Me), 1.39 (12 H, s, 4 × Me); δC (100 MHz, CDCl3) 155.2 (C
O), 141.4 (CH), 130.7 + 130.3 (C), 128.9 (C), 125.9 (C), 121.5
(CH), 119.0 (CH), 109.9 (C), 108.7 + 108.2 (C), 83.9 (2 × C), 79.9
(C), 42.7 + 42.4 (CH2), 41.8 + 41.4 (CH2), 28.5 (3 × Me), 25.0 (4 ×
Me), 21.2 + 21.0 (CH2); HRMS [ESI, (M + Na)+] found 421.2255.
[C22H31BN2O4 + Na]+ requires 421.2273.
2-Methyl-5-nitroindol-7-ol (26B). General procedure B1 was
performed using 26A (30 mg, 0.1 mmol) and H2O2 (0.3 mL) in THF
tert-Butyl 8-Hydroxyl-3,4-dihydropyrido[3,4-b]indole-2-car-
boxylate (25B). General procedure B1 was performed using 25A (70
(5 mL). Purification using 1:1 n-hexane−ethyl acetate as eluent gave
the title compound (14 mg, 0.073 mmol, 73%) as an orange solid, mp
183−186 °C; νmax (neat)/cm−1 3377, 3307, 3088, 2922, 2852, 1708,
1639, 1573, 1520, 1471, 1386, 1315, 1271, 1244, 1232, 1146, 1102,
1078, 1067, 980, 950, 885, 868, 847, 817, 778, 737, 647; δH (400 MHz,
DMSO-d6) 11.62 (1 H, br s, NH), 10.49 (1 H, s, OH), 8.00 (1 H, d, J
2.0, ArH), 7.37 (1 H, d, J 2.0, ArH), 6.40 (1 H, m, ArH), 2.44 (3 H, s,
Me); δC (100 MHz, DMSO-d6) 142.6 (C), 140.8 (C), 138.8 (C),
129.6 (C), 128.6 (C), 108.1 (CH), 102.1 (CH), 99.2 (CH), 13.2
(Me); HRMS [ESI, (M + H)+] found 193.0608. [C9H8N2O3 + H]+
requires 193.0608.
mg, 0.176 mmol) and H2O2 (0.3 mL) in THF (5 mL). Flash column
chromatography using 1:1 n-hexane−ethyl acetate as eluent gave the
title compound (44 mg, 0.152 mmol, 87%) as a colorless oil; νmax
(neat)/cm−1 3412, 3340, 2981, 2932, 2849, 1642, 1631, 1582, 1480,
1422, 1386, 1372, 1311, 1280, 1246, 1218, 1198, 1152, 1115, 1069,
1049, 981, 927, 875, 845, 813, 775, 682; δH (400 MHz, DMSO-d6)
10.61 (1 H, br s, NH), 9.41 (1 H, s, OH), 6.84 (1 H, d, J 7.6, ArH),
6.75 (1 H, t, J 7.6, ArH), 6.48 (1 H, dd, J 7.6, 0.8, ArH), 4.53 (2 H, br
s, CH2), 3.66 (2 H, t, J 5.6, CH2), 2.64 (2 H, t, J 5.6, CH2), 1.44 (9 H,
s, 3 × Me); δC (100 MHz, DMSO-d6) 154.3 (CO), 143.2 (C),
130.6 (C), 128.4 (C), 125.6 (C), 119.1 (CH), 108.7 (CH), 107.1 (C),
105.6 (CH), 79.0 (C), 42.3 + 42.1 (CH2), 41.4 + 40.9 (CH2), 28.1 (3
× Me), 21.2 (CH2); HRMS [ESI, (M + Na)+] found 311.1362.
[C16H20N2O3 + Na]+ requires 311.1366.
5-Cyano-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-
indole (27A). General procedure A3 was performed using 5-
cyanoindole (142 mg, 1.0 mmol), triethylamine (152 mg, 1.5
mmol), and dimethylchlorosilane (142 mg, 1.5 mmol) in THF (1
mL) for 6 h followed by addition of [Ir(OMe)cod]2 (1.7 mg, 0.0025
mmol, 0.25 mol %), dtbpy (1.4 mg, 0.005 mmol, 0.5 mol %), and
B2Pin2 (1.05 equiv, 267 mg) in THF (1 mL) and the resulting mixture
heated to 80 °C for 16 h. Desilylation was performed using sodium
hydrogen carbonate for 1 h. Purification using 4:1 petroleum ether−
ethyl acetate as eluent gave the title compound (29 mg, 0.11 mmol,
11%) as a colorless solid, mp 133−138 °C; νmax (neat)/cm−1 3348,
2982, 2223, 1372, 1301, 1207, 1137, 852, 739; δH (400 MHz, CDCl3)
9.44 (1 H, br s, NH), 8.07 (1 H, dd, J 1.4, 0.5, ArH), 7.88 (1 H, d, J
1.6, ArH), 7.37 (1 H, dd, J 3.2, 2.4, ArH), 6.62 (1 H, dd, J 3.3, 2.1,
ArH), 1.41 (12 H, s, 4 × BPin Me); δC (100 MHz, CDCl3) 142.5 (C),
132.3 (CH), 129.0 (CH), 126.9 (C), 126.5 (CH), 120.8 (C), 103.1
(CH), 102.9 (C), 84.7 (2 × C), 25.1 (4 × Me), 1 × C not observed;
HRMS [ESI, (M +Na)+] found 291.1271. [C15H17BN2O2 + Na]+
requires 291.1271.
tert-Butyl 5,8-Dioxo-3,4,8,9-tetrahydropyrido[3,4-b]indole-
2-carboxylate (25C). General procedure C was performed using
25B (22 mg, 0.076 mmol) and salcomine (12 mol %, 3 mg) in
acetonitrile (5 mL). Purification using 1:1 n-hexane−ethyl acetate as
eluent gave the title compound (16 mg, 0.053 mmol, 70%) as an
orange solid, mp 247 °C (decomp); νmax (neat)/cm−1 3209, 2923,
1652, 1586, 1498, 1480, 1462, 1413, 1366, 1279, 1253, 1236, 1164,
1108, 1073, 1032, 976, 933, 874, 847, 785, 770; δH (400 MHz,
DMSO-d6) 12.53 (1 H, br s, NH), 6.60 (1 H, d, J 10.0, ArH), 6.54 (1
H, d, J 10.0, ArH), 4.45 (2 H, br s, CH2), 3.57 (2 H, t, J 5.8, CH2),
2.69 (2 H, t, J 5.8, CH2), 1.43 (9 H, s, 3 × Me); δC (100 MHz,
DMSO-d6) 183.9 (CO), 176.4 (CO), 154.1 (CO), 137.0
(CH), 136.5 (CH), 133.1 (C), 129.5 (C), 121.7 (C), 117.1 (C), 79.4
(C), 40.8 (CH2), 29.0 (CH2), 28.0 (3 × Me), 22.1 (CH2); HRMS
[ESI, (M + Na)+] found 325.1155. [C16H18N2O4 + Na]+ requires
325.1159.
5-Cyanoindol-7-ol (27B). General procedure B2 was performed
using 27A (20 mg, 0.075 mmol), H2O2 (0.08 mL), and NaOH (1 M,
2-Methyl-5-nitro-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
2-yl)indole (26A). General procedure A1 was performed using 2-
0.08 mL) in THF (2.5 mL). Purification using 4:1 n-hexane−ethyl
acetate as eluent gave the title compound (5 mg, 0.032 mmol, 42%) as
a brown solid, mp 173 °C (decomp); νmax (neat)/cm−1 3386, 3209,
2919, 2850, 2222, 1585, 1461, 1331, 1253, 1059, 824, 723; δH (400
MHz, acetone-d6) 10.73 (1 H, br s, NH), 9.36 (1 H, br s, OH), 7.57 (1
H, d, J 0.8, ArH), 7.46 (1 H, d, J 3.2, ArH), 6.81 (1 H, d, J 0.9, ArH),
6.59 (1 H, d, J 3.1, ArH); δC (100 MHz, acetone-d6) 144.8 (C), 130.7
J
J. Org. Chem. XXXX, XXX, XXX−XXX