Enantioselective Synthesis of Benzimidazole Atropisomers Featuring a N‐N Axis†

Abstract

Comprehensive SummaryAtroposelective synthesis of N‐N atropisomers is an emerging area but remains underexplored; in particular, the synthesis of N‐N benzimidazole atropisomers is still unprecedented. Herein, the first enantioselective synthesis of N‐N benzimidazole atropisomers via the palladium‐catalyzed de novo construction of benzimidazole skeleton is presented. With readily available palladium catalyst and biphosphine ligand, a broad range of nonbiaryl benzimidazole and indole‐benzimidazole atropisomers were conveniently accessed in high yields and with excellent enantioselectivities. Significantly, these N‐N benzimidazole atropisomers showed great antitumor activity and selectivity to breast cancer MCF‐7 cells. The simple catalytic system, broad substrate scope, high enantioselectivity, and good bioactivity make this approach highly attractive.