Three-Component Route for the Regioselective Construction of N-Arylbenzimidazoles

Key words

benzimidazoles - o-chloroaryl sulfonates - o-chloroaryl halides - anilines - amides - palladium catalysis

Significance

Reported is a regiocontrolled synthesis of N-arylbenzimidazoles 3 and 4 via a three-component reaction using a palladium catalyst. In this reaction, the 2-chloroarenes 1 and 2 show different reactivities in combining with anilines and amides in sequential intermolecular amination and amidation reactions and cyclizations to regioselectively afford two types of N-arylbenzimidazoles, 3 and 4, in moderate to good yields. The reaction scope and limitations for the 2-chloroarenes 2 were not well investigated.

Comment

Benzimidazoles are often found in nature and in drugs displaying broad spectrum pharmaceutical activities (see Review below). Poor ­regiocontrolled benzimidazole arylations to give mixtures of isomeric products have been previously reported (e.g., D. Yang et al. J. Org. Chem. 2008, 73, 7841). The present method not only ­assembles the substituted benzimidazoles in a straightforward way from readily available starting materials, but also offers a high regiocontrol in the construction of single isomer products.

Review

F. Fei, Z. Zhuo Expert Opin. Ther. Patents 2013, 23, 1157–1179.