PAPER
Catalyzed N-Arylations of Nitrogen-Containing Heterocycles
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13C NMR (100 MHz, CDCl3): d = 139.7, 135.7, 129.6, 129.2, 127.9,
126.4, 124.3, 122.3, 121.1, 120.3, 110.5, 103.5.
References
(1) For selected recent examples, see: (a) Zhong, C.; He, J.;
Xue, C.; Li, Y. Bioorg. Med. Chem. 2004, 12, 4009.
(b) Dyck, B.; Goodfellow, V. S.; Phillips, T.; Grey, J.;
Haddach, M.; Rowbottom, M.; Naeve, G. S.; Brown, B.;
Saunders, J. Bioorg. Med. Chem. Lett. 2004, 14, 1151.
(c) Smallheer, J. M.; Alexander, R. S.; Wang, J.; Wang, S.;
Nakajima, S.; Rossi, K. A.; Smallwood, A.; Barbera, F.;
Burdick, D.; Luettgen, J. M.; Knabb, R. M.; Wexler, R. R.;
Jadhav, P. K. Bioorg. Med. Chem. Lett. 2004, 14, 5263.
(d) Qiao, J. X.; Cheng, X.; Modi, D. P.; Rossi, K. A.;
Luettgen, J. M.; Knabb, R. M.; Jadhav, P. K.; Wexler, R. R.
Bioorg. Med. Chem. Lett. 2005, 15, 29. (e) Mano, T.;
Okumura, Y.; Sakakibara, M.; Okumura, T.; Tamura, T.;
Miyamoto, K.; Stevens, R. W. J. Med. Chem. 2004, 47, 720.
(f) Roppe, J.; Smith, N. D.; Huang, D.; Tehrani, L.; Wang,
B.; Anderson, J.; Brodkin, J.; Chung, J.; Jiang, X.; King, C.;
Munoz, B.; Varney, M. A.; Prasit, P.; Cosford, N. D. P. J.
Med. Chem. 2004, 47, 4645. (g) Venkatesan, A. M.; Gu, Y.;
Santos, O. D.; Abe, T.; Agarwal, A.; Yang, Y.; Petersen, P.
J.; Weiss, W. J.; Mansour, T. S.; Nukaga, M.; Hujer, A. M.;
Bonomo, R. A.; Knox, J. R. J. Med. Chem. 2004, 47, 6556.
(h) Lange, J. H. M.; van Stuivenberg, H. H.; Coolen, H. K.
A. C.; Adolfs, T. J. P.; McCreary, A. C.; Keizer, H. G.; Wals,
H. C.; Veerman, W.; Borst, A. J. M.; de Looff, W.; Verveer,
P. C.; Kruse, C. G. J. Med. Chem. 2005, 48, 1823. (i) Quan,
M. L.; Lam, P. Y. S.; Han, Q.; Pinto, D. J. P.; He, M. Y.; Li,
R.; Ellis, C. D.; Clark, C. G.; Teleha, C. A.; Sun, J.-H.;
Alexander, R. S.; Bai, S.; Luettgen, J. M.; Knabb, R. M.;
Wong, P. C.; Wexler, R. R. J. Med. Chem. 2005, 48, 1729.
(j) Barchéchath, S. D.; Tawatao, R. I.; Corr, M.; Carson, D.
A.; Cottam, H. B. J. Med. Chem. 2005, 48, 6409. (k) Voets,
M.; Antes, I.; Scherer, C.; Müller-Vieira, U.; Biemel, K.;
Barassin, C.; Marchais-Oberwinkler, S.; Hartmann, R. W.
J. Med. Chem. 2005, 48, 6632. (l) Wiglenda, T.; Ott, I.;
Kircher, B.; Schumacher, P.; Schuster, D.; Langer, T.; Gust,
R. J. Med. Chem. 2005, 48, 6516. (m) Jiang, W.; Guan, J.;
Macielag, M. J.; Zhang, S.; Qiu, Y.; Kraft, P.; Bhattacharjee,
S.; John, T. M.; Haynes-Johnson, D.; Lundeen, S.; Sui, Z. J.
Med. Chem. 2005, 48, 2126. (n) Mahboobi, S.; Sellmer, A.;
Hocher, H.; Eichhorn, E.; Bar, T.; Schmidt, M.; Maier, T.;
Stadlwieser, J. F.; Beckers, T. L. J. Med. Chem. 2006, 49,
5769.
LRMS (EI, 70 eV): m/z (%) = 193 (M+, 100).
1-(4-Methoxyphenyl)-1H-indole (32)18a
1H NMR (500 MHz, CDCl3): d = 7.72 (d, J = 7.0 Hz, 1 H), 7.49 (d,
J = 5.6 Hz, 1 H), 7.44 (d, J = 7.2 Hz, 2 H), 7.32–7.18 (m, 3 H), 7.07
(d, J = 7.2 Hz, 2 H), 6.69 (s, 1 H), 3.92 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 158.3, 136.4, 132.9, 129.0, 128.3,
126.0, 122.2, 121.0, 120.1, 114.8, 110.4, 102.9, 55.6.
LRMS (EI, 70 eV): m/z (%) = 223 (M+, 100).
1-Pyridin-2-yl-1H-indole (33)29
1H NMR (400 MHz, CDCl3): d = 8.54 (d, J = 8.0 Hz, 1 H), 8.20 (d,
J = 8.4 Hz, 1 H), 7.75 (t, J = 8.0 Hz, 1 H), 7.70 (d, J = 3.6 Hz, 1 H),
7.66 (d, J = 8.0 Hz, 1 H), 7.44 (d, J = 8.4 Hz, 1 H), 7.29 (t, J = 8.8
Hz, 1 H), 7.20 (t, J = 8.0 Hz, 1 H), 7.13–7.10 (m, 1 H), 6.70 (d, J =
3.6 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 152.3, 148.4, 138.4, 134.9, 130.3,
125.9, 123.0, 121.2, 121.0, 120.0, 114.5, 112.8, 105.4.
LRMS (EI, 70 eV): m/z (%) = 194 (M+, 100).
1-Pyrimidin-2-yl-1H-indole (34)29
1H NMR (400 MHz, CDCl3): d = 8.82 (d, J = 8.4 Hz, 1 H), 8.71 (d,
J = 4.8 Hz, 2 H), 8.28 (d, J = 3.6 Hz, 1 H), 7.63 (d, J = 8.0 Hz, 1 H),
7.40 (t, J = 8.0 Hz, 1 H), 7.37–7.33 (m, 2 H), 7.05 (t, J = 5.6 Hz, 1
H), 6.71 (d, J = 3.6 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 158.2, 157.8, 135.4, 131.3, 125.8,
123.7, 122.1, 120.8, 116.3, 116.2, 107.0.
LRMS (EI, 70 eV): m/z (%) = 195 (M+, 100).
1-Thiophen-2-yl-1H-indole (35)
1H NMR (400 MHz, CDCl3): d = 7.66 (d, J = 7.6 Hz, 1 H), 7.59 (d,
J = 8.0 Hz, 1 H), 7.29–7.16 (m, 4 H), 7.07–7.05 (m, 2 H), 6.66 (d,
J = 4.0 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 141.5, 136.9, 129.2, 128.9, 126.0,
122.7, 121.5, 121.0, 120.8, 120.3, 110.6, 104.1.
LRMS (EI, 70 eV): m/z (%) = 199 (M+, 100).
HRMS (EI): m/z calcd for C12H9NS: 199.0456; found: 199.2715.
1-(4-Methoxyphenyl)-2-methyl-1H-indole (36)8
1H NMR (400 MHz, CDCl3): d = 7.56 (d, J = 8.4 Hz, 1 H), 7.28–
7.25 (m, 2 H), 7.11–7.03 (m, 5 H), 6.38 (s, 1 H), 3.90 (s, 3 H), 2.28
(s, 3 H).
13C NMR (100 MHz, CDCl3): d = 159.1, 138.6, 137.4, 130.7, 129.2,
128.1, 120.9, 119.9, 119.5, 114.5, 110.0, 100.8, 55.6.
(2) For selected papers on palladium-catalyzed N-arylations of
imidazoles, see: (a) Hartwig, J. F. In Handbook of
Organopalladium Chemistry for Organic Synthesis;
Negishi, E., Ed.; Wiley Interscience: New York, 2002,
1051. (b) Jiang, L.; Buchwald, S. L. In Metal-Catalyzed
Cross-Coupling Reactions; de Meijere, A.; Diederich, F.,
Eds.; Wiley-VCH: Weinheim, 2004, 699. (c) Bellina, F.;
Cauteruccio, S.; Mannina, L.; Rossi, R.; Viel, S. J. Org.
Chem. 2005, 70, 3997.
LRMS (EI, 70 eV): m/z (%) = 237 (M+, 100).
(3) For selected reviews on the use of copper as the catalyst,
see: (a) Beletskaya, I. P.; Cheprakov, A. V. Coord. Chem.
Rev. 2004, 248, 2337. (b) Ley, S. V.; Thomas, A. W. Angew.
Chem. Int. Ed. 2003, 42, 5400.
(4) For a paper on N-arylations of imidazoles with aryl halides
mediated by stoichiometric copper, see: Lindley, J.
Tetrahedron 1984, 40, 1433.
Acknowledgment
The authors thank the National Natural Science Foundation of
China (No. 20572020), the Fok Ying Tung Education Foundation
(No. 101012), and the Program for New Century Excellent Talents
in University (No. NCET-06-0711) for financial support.
(5) (a) Kiyomori, A.; Marcoux, J. F.; Buchwald, S. L.
Tetrahedron Lett. 1999, 40, 2657. (b) Kuil, M.; Bekedam,
E. K.; Visser, G. M.; van den Hoogenband, A.; Terpstra, J.
Synthesis 2008, No. 11, 1707–1716 © Thieme Stuttgart · New York