Organocatalytic Asymmetric Friedel–Crafts Reaction-Cyclization-Elimination Cascade for Atroposelective Construction of 3,3′-Biindoles

Abstract Atroposelective indole formation is an efficient method for the preparation of indole-based biaryls. Herein, a protocol for a convenient organocatalytic asymmetric synthesis of 3,3′-biindole derivatives has been developed via an asymmetric Friedel–Crafts reaction-cyclization-elimination cascade employing indole based α-hydroxyl ketone and N-phenyl-2-naphthylamine. This method constitutes a rare central-to-axial chirality conversion (CACC) technique without the requirement of additional reagent. The reaction was catalyzed by chiral phosphoric acid and 3,3′-biindole compounds were effectively produced with high yields and enantioselectivities (up to 93% yield, 97:3 er). With water as the only byproduct, this method offers a convergent synthetic strategy for the enantioselective synthesis of axially chiral 3,3′-biiindole frameworks.