A regiospecific synthesis of N-aryl and N-alkyl benzimidazoles

ORGN 935

Nan Zheng, nzheng@mit.edu, Kevin W. Anderson, Xiaohua Huang, Hanh Nho Nguyen, and Stephen L. Buchwald, sbuchwal@mit.edu. Department of Chemistry, Massachusetts Institute of Technology, 18-325, 77 Massachusetts Avenue, Cambridge, MA 02139
Two complementary catalytic methods are described for the preparation of N- aryl and alkyl benzimidazoles in regiochemical pure forms starting from ortho-halo anilides or anilines. The first method employing Pd2(dba)3 and XPhos or RuPhos permits efficient synthesis of N-aryl benzimidazoles and tolerates a wide range of functional groups. The second method utilizing CuI and trans-N, N'-dimethyl-1,2-cyclohexanediamine allows for the preparation of N-alkyl benzimidazoles in good to excellent yields. Additionally, the substrate scope was expanded for the synthesis of N-aryl benzimidazoles by performing sequential amidation and amination on difunctionalized arenes bearing two ortho-disposed halides or tosylates.