Pd-Catalyzed Heteroannulative Synthesis of Benzimidazoles and Imidazopyridines

Significance

Reported is the preparation of N-substituted benzimidazoles 6, 8 and imidazo­pyridines 7 from 2-halonitroarenes 1-3 and amides 4-5 via a C-N cross-coupling amidation and subsequent reductive aminocyclization route. After screening of ligands and palladium sources concerning the amidation reaction, Pd(TFA)₂/(R)-BINAP was found to be the most effective combination. For the subsequent reductive aminocycli-zation, iron in acetic acid was identified as the most effective and reliable reagent (A. Trazza and co-workers J. Chem. Soc., Perkin Trans. 2 1991, 1019). A broad spectrum of 2-halonitroarenes (X = I, Br, Cl) and amides were employed. EWGs and EDGs in various positions of the 2-halonitro­arene substrates were shown to be tolerated. ­Cyclic as well as aliphatic alkyl, aryl, and hetero­aryl amides were converted into benzimidazoles in good yields. Various functional groups, such as cyano, ester, chloro, and pyridyl substituents are compatible with the reaction conditions.