N-Hydroxyimides as Efficient Ligands for the
Copper-Catalyzed N-Arylation of Pyrrole,
Imidazole, and Indole
Heng-Chang Ma and Xuan-Zhen Jiang*
Department of Chemistry, Zhejiang UniVersity,
Hangzhou, 310027, China
ReceiVed July 23, 2007
FIGURE 1. Effect of various ligands on the efficiency of the aryl
amidation reaction. The reaction of 1a + 2a was performed with 5
mol % of CuI, 10 mol % of ligand. 1.0 equiv of 1a and 2a, and 1.5
equiv of CH3ONa in DMSO at 90 °C for 12 h. The reaction of 1b +
2b was performed with 10 mol % of CuI, 20 mol % of ligand, 1.0
equiv of 1b and 2b, and 1.5 equiv of CH3ONa in DMSO at 110 °C for
40 h.
However, the harsh reaction conditions such as high tempera-
tures (125-220 °C), the requirement of a stoichiometric amount
of copper catalyst, and the low to moderate yields have
undoubtedly prevented these reactions from being employed to
their full potential. Thus, the development of a mild as well as
highly efficient method for constructing N-arylazole units has
been received increasing interest. Recently, several Pd-catalyzed
C-N formation methods have been discovered for the cross-
coupling of aryl halides with N-H heterocycles by using some
sterically hindered phosphine ligands under relatively mild
conditions.3 Notably, the economic attractiveness of copper has
led to a resurgence of interest in the Ullmann-type coupling
reaction since Buchwald discovered the copper-catalyzed N-
arylation of heterocycles with aryl halides in the presence of
diamine ligands.4 Indeed, some efficient ligands have been
disclosed in these coupling reactions, including amino acids,5
diamines,4 diimines,6 aminoarenethiolate,7 phosphine ligands,8
An experimentally simple, efficient, and inexpensive catalyst
system was developed for the N-arylation of pyrroles, in-
doles, and imidazole with aryl and heteroaryl iodides, bro-
mides, and chlorides by applying CuI as catalyst, N-hydroxy-
succinimide (L1), N-hydroxymaleimide (L2), or N-hydroxy-
phthalimide (L3) as ligand, CH3ONa as base, and DMSO as
solvent. A variety of functional groups are tolerated in the
reaction, including those that are not compatible with Pd-
catalyzed amidation methodology.
Nitrogen-containing heterocycles such as N-arylpyrroles,
N-arylindoles, and N-arylimidazoles are an important class of
compounds that are ubiquitous in numerous natural products
and biologically active pharmaceuticals.1 The copper-catalyzed
Ullmann-Goldberg coupling is a traditional method for the
introduction of amine functionality with use of aromatic halides.2
(3) (a) Wolfe, J. P.; Wagaw, S.; Marcoux, J.-F.; Buchwald, S. L. Acc.
Chem. Res. 1998, 31, 805. (b) Hartwing, J. F. Angew. Chem., Int. Ed. 1998,
37, 2046. (c) Jiang, L.; Buchwald, S. L. Palladium-Catalyzed Aromatic
Carbon-Nitrogen Bond Formation. In Metal-catalyzed Cross-Coupling
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10.1021/jo7015983 CCC: $37.00 © 2007 American Chemical Society
Published on Web 10/13/2007
J. Org. Chem. 2007, 72, 8943-8946
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