synthesis and catalytic functionalization of biologically active indoles

Zn-Catalyzed Hydroamination of Terminal Alkynes
1597, 1519, 1501, 1466, 1377, 1291, 1273, 1184, 1155, 1106, 996,
830, 753, 724, 694, 662 cm 1 .
4-Chloro-N-(1-phenylethyl)aniline [17]
(3l): 95% yield, pale yellow
solid, m.p.: 55–57 8C. 1 H NMR (300 MHz, CDCl3): d = 7.34–7.20 (m,
5 H), 7.02 (d, 2 H, 3 J = 9.0 Hz), 6.41 (d, 2H, 3 J=9.0 H), 4.43 (q, 1 H,
3 3 13
J = 7.2 Hz), 4.04 (br s, 1 H), 1.50 ppm (d, 3H, J = 6.9 Hz). C NMR
(75 MHz, CDCl3): d = 146.0, 144.9, 129.1, 128.9, 127.3, 126.0, 122.0,
114.6, 53.8, 25.1 ppm. MS (EI, 70 eV): m/z (rel. int.): 231 (34) [M + ],
216 (50), 127 (37), 105 (100), 90 (8), 77 (21), 63 (4), 51 (6). HRMS
(EI): m/z calcd for C14H14NCl: 231.0809; found: 231.0812. FTIR (ATR):
3404, 3028, 2974, 2953, 2916, 2888, 2862, 1853, 1598, 1496, 1445,
1371, 1356, 1312, 1291, 1278, 1253, 1208, 1176, 1142, 1093, 1006,
947, 913, 809, 759, 703 cm 1 .
4-Isopropyl-N-(1-phenylethyl)aniline (3m): 97% yield, yellow oil.
1 H NMR (300 MHz, CDCl3): d=7.39–7.28 (m, 4H), 7.24–7.19 (m, 1H),
6.95 (d, 2H, 3 J =8.3 Hz), 6.45 (d, 2 H, 3 J=8.5 Hz), 4.43 (q, 1H, 3 J =
6.7 Hz), 2.76–2.72 (m, 1H), 1.49 (d, 3 H, 3 J=6.7 Hz), 1.16 ppm (d,
6H, 3 J = 6.9 Hz). 13 C NMR (75 MHz, CDCl 3): d = 145.7, 145.6, 137.9,
128.8, 127.2, 127.0, 126.1, 113.4, 54.0, 33.3, 25.3, 24.4 ppm. MS (EI,
70 eV): m/z (rel. int.): 239 (51) [M + ], 224 (100), 208 (7), 162 (4), 135
(5), 120 (59), 105 (49), 91 (7), 77 (16), 65 (3), 51 (3), 39 (2). HRMS
(EI): m/z calcd for C 17H 21N: 239.1669; found: 239.1674. FTIR (ATR):
3408, 3059, 3022, 2956, 2924, 2866, 1614, 1515, 1448, 1408, 1371,
1315, 1288, 1253, 1186, 1140, 1053, 1016, 942, 817, 759, 698 cm 1 .
4-Methoxy-N-(1-phenylethyl)aniline [18] (3n): 91 % yield, pale yellow
solid, m.p.: 54–56 8C. 1 H NMR (300 MHz, CDCl 3): d = 7.38–7.28 (m,
4 H), 7.23–7.18 (m, 1H), 6.68 (d, 2 H, 3 J =9.0 Hz), 6.46 (d, 2H, 3 J =
9.0 H), 4.40 (q, 1 H, 3 J = 6.6 Hz), 3.68 (s, 3H), 1.49 ppm (d, 3 H, 3 J =
6.6 Hz). 13 C NMR (75 MHz, CDCl 3): d = 152.1, 145.6, 141.7, 128.8,
127.0, 126.1, 114.9, 114.8, 55.9, 54.5, 25.3 ppm. MS (EI, 70 eV): m/z
(rel. int.): 227 (89) [M + ], 212 (100), 168 (7), 123 (51), 105 (82), 95 (5),
77 (25), 63 (5), 51 (7). HRMS (EI): m/z calcd for C 15H 17NO: 227.1305;
found: 227.1307. FTIR (ATR): 3376, 3005, 2982, 2962, 2920, 2861,
2836, 1617, 1504, 1451, 1368, 1353, 1302, 1269, 1231, 1178, 1142,
1108, 1081, 1030, 944, 852, 814, 750, 697, 655 cm 1 .
4-(1-Phenylethylamino)benzonitrile [19] (3o): 93% yield, pale yellow
solid, m.p.: 98–101 8C. 1 H NMR (300 MHz, CDCl 3): d = 7.37–7.23 (m,
7 H), 6.46 (d, 2 H, 3 J =8.9 Hz), 4.61 (br s, 1 H), 4.54–4.50 (m, 1 H),
1.55 ppm (d, 3 H, 3 J = 6.7 Hz). 13 C NMR (75 MHz, CDCl 3): d=150.5,
143.8, 133.8, 129.1, 127.6, 125.8, 120.6, 113.1, 99.0, 53.3, 24.9 ppm.
MS (EI, 70 eV): m/z (rel. int.): 222 (22) [M + ], 207 (30), 129 (8), 118
(13), 105 (100), 95 (4), 77 (14), 69 (12), 57 (17), 41 (12). HRMS (EI):
m/z calcd for C 15H 14N 2: 222.1152; found: 222.1148. FTIR (ATR): 3374,
3347, 3032, 2966, 2925, 2868, 2208, 1602, 1524, 1451, 1374, 1342,
1280, 1207, 1171, 1143, 1090, 1027, 944, 906, 826, 812, 756,
696 cm 1 .
3-(2-Phenylethylamino)pyridine (3p): 77 % yield, white solid, m.p.:
105–1068C. 1 H NMR (300 MHz, CDCl 3): d=7.99 (d, 1 H, 4 J=2.7 Hz),
7.88 (dd, 1H, 3 J=4.8 Hz, 4 J = 1.5 Hz), 7.35–7.22 (m, 5 H), 6.95 (dd,
1H, 3 J = 4.8 Hz, 3 J =8.4 Hz), 6.69 (ddd, 1H, 3 J =8.4 Hz, 4 J=2.7 Hz,
4 J = 1.5 Hz), 4.43 (m, 1H), 4.17 (br s, 1 H), 1.53 ppm (d, 3 H, 3 J =
6.6 Hz). 13 C NMR (75 MHz, CDCl 3): d = 144.4, 143.4, 138.8, 136.8,
129.0, 127.4, 125.9, 123.8, 119.2, 53.5, 25.2 ppm. MS (EI, 70 eV): m/z
(rel. int.): 198 (65) [M + ], 183 (83), 121 (7), 105 (100), 94 (50), 77 (18),
67 (3), 51 (8). HRMS (EI): m/z calcd for C 13H 14N 2: 198.1152; found:
198.1155. FTIR (ATR): 3230, 3151, 3094, 3033, 2966, 2922, 2879,
1590, 1528, 1475, 1447, 1413, 1346, 1299, 1245, 1204, 1143, 1108,
1089, 1014, 946, 797, 765, 700 cm 1 .
N-Methyl-N-(1-phenylethyl)aniline (5a): 76% yield, pale yellow oil.
1 H NMR (300 MHz, CDCl3): d=7.33–7.31 (m, 4H), 7.27–7.22 (m, 3H),
6.85–6.82 (m, 2 H), 6.75–6.70 (m, 1 H), 5.13 (q, 1H, 3 J=6.9 Hz),
2.67 ppm (s, 3 H), 1.54 (d, 3 H, 3 J = 6.9 Hz). 13 C NMR (75 MHz, CDCl 3):
d = 150.4, 143.0, 129.4, 128.6, 127.2, 127.1, 116.8, 113.3, 56.7, 32.1,
16.5 ppm. MS (EI, 70 eV): m/z (rel. int.): 211 (41) [M + ], 196 (100),
180 (10), 134 (18), 105 (89), 91 (5), 77 (42), 65 (3), 51 (10), 39 (4).
HRMS (EI): m/z calcd for C 15H 17N: 211.1356; found: 211.1355. FTIR
(ATR): 3059, 3025, 2972, 2933, 2874, 2814, 1595, 1501, 1446, 1370,
1309, 1214, 1156, 1110, 1026, 990, 906, 861, 745, 721, 690 cm 1 .
N-Benzyl-N-(1-phenylethyl)aniline [20]
(5b): 51% yield, pale yellow
oil. 1 H NMR (300 MHz, CDCl3): d = 7.31–7.10 (m, 12H, 6.77–6.66 (m,
3 H), 5.26 (q, 1H, 3 J = 7.0 Hz), 4.47 (dd, 2 H, J = 7.6 Hz), 1.58 ppm (d,
3H, 3 J = 7.0 Hz). 13 C NMR (75 MHz, CDCl3): d = 149.4, 143.0, 140.3,
129.2, 128.7, 128.5, 127.1, 127.1, 126.6, 117.3, 114.3, 57.2, 50.5,
19.0 ppm. MS (EI, 70 eV): m/z (rel. int.): 287 (48) [M + ], 272 (73), 210
(7), 183 (43), 105 (82), 91 (100), 77 (43), 65 (11), 51 (10), 39 (3).
HRMS (EI): m/z calcd for C21H21N: 287.1669; found: 287.1667. FTIR
(ATR): 3057, 3022, 2982, 2924, 2876, 2853, 1594, 1501, 1451, 1389,
1332, 1294, 1254, 1203, 1165, 1074, 1025, 987, 918, 885, 865, 772,
732, 689 cm 1 .
Acknowledgements
This work was funded by the State of Mecklenburg-Western Pomerania,
the Bundesministerium für Bildung und Forschung
(BMBF), the Deutsche Forschungsgemeinschaft (Graduiertenkolleg
1213, and Leibniz Prize), and the Fonds der Chemischen Industrie
(FCI). We thank Dr. W. Baumann, Dr. C. Fischer, S. Buchholz, S.
Schareina, and K. Mevius for their excellent technical and analytical
support.
Keywords: alkynes · amines · homogeneous catalysis ·
hydroamination · zinc
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