ORGANIC
LETTERS
2011
Vol. 13, No. 16
4196–4199
Palladium-/Copper-Catalyzed
Regioselective Amination and
Chloroamination of Indoles
Xue-Yuan Liu,*,† Pin Gao,† Yong-Wen Shen,‡ and Yong-Min Liang†
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou
730000, P.R. China, and College of Chemistry and Chemical Engineering, Lanzhou
University, Lanzhou 730000, P.R. China
Received June 7, 2011
ABSTRACT
A palladium-/copper-catalyzed intermolecular CꢀH amination reaction of indoles has been developed. This reaction proceeds in good to excellent
yields to produce a variety of 2-amino-substituted indoles and exhibits excellent regioselectivity at room temperature. Furthermore,
chloroamination of indoles provides a simple method for the construction of CꢀN and CꢀCl bonds in one step.
As a complementary methodology of BuchwaldꢀHartwig
coupling, transition-metal-catalyzed direct CꢀH functio-
nalization/amination provides a new synthetic strategy for
CꢀN bond formation and has recently received much
attention. Although intramolecular oxidative amination
of arenes has been reported in the past few years,1 direct
intermolecular CꢀH amination of both arenes and
heteroarenes has just been investigated recently.2ꢀ5 Two
major advances in this challenging transformation have
been made via transition-metal-catalyzed strategies
(Scheme 1): (1) direct amination of aromatic CꢀH bonds
(eq 1);2ꢀ4 and (2) direct CꢀH amination of azoles (eq 2).5
However, intermolecular CꢀH amination still remains a
challenge because most of the existing examples suffer
from a relatively limited substrate scope. This has led us
to explore a broader substrate scope for catalytic amina-
tion reactions under mild conditions. CꢀH arylation of
† State Key Laboratory of Applied Organic Chemistry.
‡ College of Chemistry and Chemical Engineering.
(1) For intramolecular amidation of CꢀH bonds, see: (a) Tsang,
W. C. P.; Zheng, N.; Buchwald, S. L. J. Am. Chem. Soc. 2005, 127,
14560. (b) Inamoto, K.; Saito, T.; Katsuno, M.; Sakamoto, T.; Hiroya,
K. Org. Lett. 2007, 9, 2931. (c) Yamamoto, M.; Matsubara, S. Chem.
Lett. 2007, 36, 172. (d) Wasa, M.; Yu, J.-Q. J. Am. Chem. Soc. 2008, 130,
14058. (e) Jordan-Hore, J. A.; Johansson, C. C. C.; Gulias, M.; Beck,
E. M.; Gaunt, M. J. J. Am. Chem. Soc. 2008, 130, 16184. (f) Mei, T.-S.;
Wang, X.; Yu, J.-Q. J. Am. Chem. Soc. 2009, 131, 10806. (g) Neumann,
(4) For examples of Cu(II)-catalyzed CꢀH amination reactions with
amides and anilides, see: (a) Chen, X.; Hao, X.-S.; Goodhue, C. E.; Yu,
J.-Q. J. Am. Chem. Soc. 2006, 128, 6790. (b) Uemura, T.; Imoto, S.;
Chatani, N. Chem. Lett. 2006, 35, 842. (c) Brasche, G.; Buchwald, S. L.
Angew. Chem., Int. Ed. 2008, 47, 1932. (d) John, A.; Nicholas, K. M.
J. Org. Chem. 2011, 76, 4158.
(5) For CꢀH amination of azoles, see: (a) Monguchi, D.; Fujiwara,
T.; Furukawa, H.; Mori, A. Org. Lett. 2009, 11, 1607. (b) Wang, Q.;
Schreiber, S. L. Org. Lett. 2009, 11, 5178. (c) Cho, S. H.; Kim, J. Y.; Lee,
S. Y.; Chang, S. Angew. Chem., Int. Ed. 2009, 48, 9127. (d) Armstrong,
A.; Collins, J. C. Angew. Chem., Int. Ed. 2010, 49, 2282. (e) Shimasaki,
T.; Tobisu, M.; Chatani, N. Angew. Chem., Int. Ed. 2010, 49, 2929.
(f) Kawano, T.; Hirano, K.; Satoh, T.; Miura, M. J. Am. Chem. Soc.
2010, 132, 6900. (g) Gu, L.; Neo, B. S.; Zhang, Y. Org. Lett. 2011, 13,
1872. (h) Miyasaka, M.; Hirano, K.; Satoh, T.; Kowalczyk, R.; Bolm,
C.; Miura, M. Org. Lett. 2011, 13, 359. (i) Guo, S.; Qian, B.; Xie, Y.; Xia,
C.; Huang, H. Org. Lett. 2011, 13, 522. (j) Matsuda, N.; Hirano, K.;
Satoh, T.; Miura, M. Org. Lett. 2011, 13, 2860. (k) For a cobalt-
catalyzed CꢀH amination of azoles via acid-promoted nucleophilic
attack, see: Kim, J. Y.; Cho, S. H.; Joseph, J.; Chang, S. Angew. Chem.,
Int. Ed. 2010, 49, 9899.
€
J.; Rakshit, S.; Droge, T.; Glorius, F. Angew. Chem., Int. Ed. 2009, 48,
6892. (h) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147.
(i) Tan, Y.; Hartwig, J. F. J. Am. Chem. Soc. 2010, 132, 3676. (j) Kumar,
R. K.; Ali, Md. A.; Punniyamurthy, T. Org. Lett. 2011, 13, 2102.
(k) Bonnamour, J.; Bolm, C. Org. Lett. 2011, 13, 2012. (l) Cho, S. H.;
Yoon, J.; Chang, S. J. Am. Chem. Soc. 2011, 133, 5996.
(2) For intermolecular amination of C(aryl)ꢀH bonds, see: (a) Thu,
H.-Y.; Yu, W.-Y.; Che, C.-M. J. Am. Chem. Soc. 2006, 128, 9048. (b) Ng,
K.-H.; Chan, A. S. C.; Yu, W.-Y. J. Am. Chem. Soc. 2010, 132, 12862.
(c) Xiao, B.; Gong, T.-J.; Xu, J.; Liu, Z.-J.; Liu, L. J. Am. Chem. Soc.
2011, 133, 1466. (d) Sun, K.; Li, Y.; Xiong, T.; Zhang, J.; Zhang, Q.
J. Am. Chem. Soc. 2011, 133, 1694.
(3) For Pd-catalyzed intermolecular CꢀH amination with alkyla-
mines, see: Yoo, E. J.; Ma, S.; Mei, T.-S.; Chan, K. S. L.; Yu, J.-Q. J. Am.
Chem. Soc. 2011, 133, 7652.
r
10.1021/ol201457y
Published on Web 07/13/2011
2011 American Chemical Society