PAPER
Halogenation of Indoles with Copper(II) Halides
1541
1
H NMR (400 MHz, CDCl ): d = 8.28 (d, J = 8.0 Hz, 1 H), 7.44 (d,
(3) For representative papers on the synthesis of 2- or 3-halo-
indoles mediated by N-halosuccinimides, see: (a) Saulnier,
M. G.; Gribble, G. W. J. Org. Chem. 1982, 47, 757.
3
J = 8.0 Hz, 1 H), 7.33–7.25 (m, 2 H), 2.84 (s, 3 H), 2.26 (s, 3 H).
1
3
C NMR (100 MHz, CDCl ): d = 169.8, 137.0, 129.4, 125.2, 123.5,
3
(
b) Saulnier, M. G.; Gribble, G. W. J. Org. Chem. 1983, 48,
1
18.1, 116.1, 107.5, 28.2, 10.5.
2690. (c) Mistry, A. G.; Smith, K.; Bye, M. R. Tetrahedron
+
+
LRMS (EI, 70 eV): m/z (%) = 253 (M + 2, 32), 251 (M , 33), 211
(
Lett. 1986, 27, 1051. (d) Zhang, P.; Liu, R.; Cook, J. M.
Tetrahedron Lett. 1995, 36, 3103. (e) Liu, R.; Zhang, P.;
Gan, T.; Cook, J. M. J. Org. Chem. 1997, 62, 7447.
+
99), 210 (44), 209 (100), 208 (40), 130 (M – 42 – Br, 88).
Methyl 2-Bromo-1-methyl-1H-indole-3-carboxylate (5la)
Slightly yellow solid; mp 90.2–92.0 °C.
(
f) Kobayashi, Y.; Fujimoto, T.; Fukuyama, T. J. Am. Chem.
Soc. 1999, 121, 6501. (g) Katayama, S.; Ae, N.; Nagata, R.
J. Org. Chem. 2001, 66, 3474. (h) Ma, C.; Liu, X. X.; Li, X.
Y.; Anderson, J. F.; Yu, S.; Cook, J. M. J. Org. Chem. 2001,
1
H NMR (400 MHz, CDCl ): d = 8.28 (s, 1 H), 7.74, (s, 1 H), 7.36
3
(
3
d, J = 8.8 Hz, 1 H), 7.19 (d, J = 8.8 Hz, 1 H), 3.91 (s, 3 H), 3.80 (s,
66, 4525. (i) Nicolaou, K. C.; Snyder, S. C.; Huang, X. H.;
H).
Simonsen, K. B.; Koumbis, A. E.; Bigot, A. J. Am. Chem.
Soc. 2004, 126, 10162. (j) de Koning, C. B.; Michael, J. P.;
Pathak, R.; van Otterlo, W. A. L. Tetrahedron Lett. 2004, 45,
1117. (k) Mejia-Oneto, J. M.; Padwa, A. Org. Lett. 2004, 6,
3241.
1
3
C NMR (100 MHz, CDCl ): d = 165.0, 136.5, 135.9, 128.0, 125.7,
3
1
24.2, 115.6, 111.2, 106.4, 51.1, 33.6.
+
+
LRMS (EI, 70 eV): m/z (%) = 269 (M + 2, 84), 267 (M , 86), 238
(
+
98), 236 (100), 157 (M – Br, 12).
HRMS (EI): m/z [M]+ calcd C H BrNO : 266.9895; found:
79
(4) (a) Bocchi, V.; Palla, G. Synthesis 1982, 1096. (b) Martin,
P. Tetrahedron Lett. 1987, 28, 1645. (c) Martin, P. Helv.
Chim. Acta 1988, 71, 344. (d) Timms, G. H.; Tupper, D. E.;
Morgan, S. E. J. Chem. Soc., Perkin Trans. 1 1989, 817.
1
1
10
2
2
66.9893.
(
6
e) Billimoria, A. D.; Cava, M. P. J. Org. Chem. 1994, 59,
777. (f) Katritzky, A. R.; Xie, L. J. Org. Chem. 1995, 60,
Acknowledgment
The authors thank Specialized Research Fund for the Doctoral Pro-
gram of Higher Education (No. 20060542007), the National Natural
Science Foundation of China (No 20572020 and 20472090), Hunan
Provincial Natural Science Foundation of China (No. 05JJ1002),
Fok Ying Tung Education Foundation (No. 101012) and the Key
Project of Chinese Ministry of Education (No. 206102) for financial
support.
3
707. (g) Morales-Rios, M. S.; Santos-Sanchez, N. F.;
Suarez-Castillo, O. R.; Joseph-Nathan, P. J. Org. Chem.
2
003, 68, 305. (h) Ohshita, J.; Lee, K.-H.; Kimura, K.;
Kunai, A. Organometallics 2004, 23, 5622. (i) Brennan, M.
R.; Erickson, K. L.; Szmalc, F. S.; Tansey, M. J.; Thornton,
J. M. Heterocycles 1986, 24, 2879.
(
(
5) (a) Akinori, K.; Tatsuya, N. Synthesis 1980, 365.
(b) Tarzia, G.; Diamantini, G.; Giacomo, B. Di.; Spadoni, G.
J. Med. Chem. 2000, 43, 2449.
References
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(
(
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Synthesis 2007, No. 10, 1535–1541 © Thieme Stuttgart · New York