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Pd-Catalyzed Heteroannulative Synthesis of Benzimidazoles and Imidazopyridines
J. Alonso, N. Halland, M. Nazaré*, O. R’kyek, M. Urmann, A. Lindenschmidt*
Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany
16 February 2011 (online)
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.