ORGANIC
LETTERS
2011
Vol. 13, No. 17
4668–4671
Three-Component Synthesis of
Polysubstituted Pyrroles from r-
Diazoketones, Nitroalkenes, and Amines
Deng Hong, Yuanxun Zhu, Yao Li, Xufeng Lin, Ping Lu,* and Yanguang Wang*
Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China
pinglu@zju.edu.cn; orgwyg@zju.edu.cn
Received July 13, 2011
ABSTRACT
Polysubstituted pyrroles are regiospecifically synthesized via the copper-catalyzed three-component reaction of R-diazoketones, nitroalkenes,
and amines under aerobic conditions. The cascade process involves an NꢀH insertion of carbene, a copper-catalyzed oxidative dehydrogenation
of amine, and a [3 þ 2] cycloaddition of azomethine ylide.
Pyrroles represent an important class of heterocycles in
organic chemistry. They are structural units in many
natural products and pharmaceuticals and are key inter-
mediates for the synthesis of a variety of biologically active
molecules and functional materials.1 As the world’s
leading cholesterol-lowering drug, atorvastatin calcium
(Lipitor) is a prime example.2 The conventional methods
for the construction of a pyrrole ring include the Hantzsch
reaction,3 the PaalꢀKnorr synthesis,4 and various cy-
cloaddition methods.5 A number of metal-catalyzed ap-
proaches were also developed.6 Still, general and efficient
strategies for the synthesis of pyrroles from simple and
readily available precursors are of great value due to the
continuedimportanceof the pyrrolecoreinbothbiological
and chemical fields.
Multicomponent reactions (MCRs) have emerged as
powerful and bond-forming efficient tools in organic,
combinatorial, and medicinal chemistry for their facileness
and efficiency as well as their economy and ecology in
organic synthesis.7 These features make MCRs well suited
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r
10.1021/ol201891r
Published on Web 08/10/2011
2011 American Chemical Society