ORGANIC
LETTERS
2012
Vol. 14, No. 1
26–29
CuO-Promoted Construction of N-2-Aryl-
Substituted-1,2,3-Triazoles via
Azide-Chalcone Oxidative Cycloaddition
and Post-Triazole Arylation
Yuanqing Zhang, Xiaolong Li, Jihui Li, Jinying Chen, Xu Meng, Mingming Zhao, and
Baohua Chen*
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Gansu
Lanzhou 730000, P. R. China, and Key Laboratory of Nonferrous Metal Chemistry and
Resources Utilization of Gansu Province, Lanzhou, 730000, P. R. China
Received October 11, 2011
ABSTRACT
An efficient one-pot three-component stepwise approach for the synthesis of N-2-aryl-substituted-1,2,3-triazoles has been developed. By using
this azide-chalcone oxidative cycloaddition and post-triazole arylation, a series of N-2-aryl-substituted-1,2,3-triazoles are readily prepared under
mild conditions in excellent yields and high regioselectivity. Both the catalyst and substrates are readily available.
Since the remarkable discovery of Cu-catalyzed-
azide-alkyne-cycloaddition (CuAAC, also referred as
“click-chemistry”), 1,2,3-triazoles have attracted signifi-
cant attention as one of the most important heterocycles.1
Within the past few years, applications of this building
block have been extended widely into various research
fields,2 such as chemical biology, material science, and
medicinal chemistry. Recently described methods for the
catalytic direct functionalization of triazole and its deriva-
tives have also been proven attractive but are mainly
limited to the N-1 position,3 although few methodolo-
gies have been reported for the direct functionalization
of triazoles at the N-2 position.4 Traditional routes to
prepare 1,2,3-triazoles often suffered from poor regios-
electivity, a rather tedious reaction procedure, and a
significant amount of expensive and difficult-to-pre-
pare catalysts. 1-Substituted triazoles and the parent
unsubstituted compounds can be synthesized by the
reaction of organic azides, metal azides, or hydrazoic acid
with alkynes respectively. The reaction with alkenes can
(1) (a) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int.
Ed. 2001, 40, 2004. (b) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.;
Sharpless, K. B. Angew. Chem., Int. Ed. 2002, 41, 2596. (c) Wu, P.;
Fokin, V. V. Aldrichimica Acta 2007, 40, 7. (d) Cohrt, A. E.; Jensen, J. F.;
Nielsen, T. E. Org. Lett. 2011, 12, 5414.
(2) (a) Maliakal, A.; Lem, G.; Turro, N. J.; Ravichandran, R.;
Suhadolnik, J. C.; DeBellis, A. D.; Wood, M. G.; Lau, J. J. Phys. Chem.
A 2002, 106, 7680. (b) Kolb, H. C.; Sharpless, K. B. Drug Discovery
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ꢀ
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K. B.; Fokin, V. V. Angew. Chem., Int. Ed. 2004, 43, 3928. (d) Agard,
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T. S. J. Am. Chem. Soc. 2009, 131, 4174.
(3) Selective methods of synthesizing N-1 substituted 1,2,3-triazoles:
(a) Tornøe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67,
3057. (b) Aucagne, V.; Leigh, D. A. Org. Lett. 2006, 8, 4505.
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D.; Fu, N.; Liu, Z.; Li, Y.; Chen, B. Synlett 2007, 278. (e) Sreedhar, B.;
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Waldo, J. P.; Chen, Y.; Larock, R. C. Org. Lett. 2008, 10, 2409. (g) Qian,
W.; Winternheimer, D.; Allen, J. Org. Lett. 2011, 13, 1682.
(4) Methods of regioselectively synthesizing N-2 substituted 1,2,3-
triazoles: (a) Kamijo, S.; Jin, T.; Huo, Z.; Yamamoto, Y. J. Am. Chem.
Soc. 2002, 125, 7786. (b) Chen, Y.; Liu, Y.; Petersena, J. L.; Shi, X.
Chem. Commun. 2008, 3254. (c) Kalisiak, J.; Sharpless, K. B.; Fokin,
V. V. Org. Lett. 2008, 10, 3171. (d) Liu, Y.; Yan, W.; Chen, Y.; Petersen,
J. L.; Shi, X. Org. Lett. 2008, 10, 5389. (e) Wang, X.; Zhang, L.; Lee, H.;
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r
10.1021/ol202718d
Published on Web 12/01/2011
2011 American Chemical Society