Synthesis of Chiral Triarylmethanes via Catalytic Asymmetric Skeletal Editing

Abstract

Abstract Catalytic asymmetric skeletal editing (CASE) has emerged as a powerful strategy for accessing chiral organic molecules through enantioselective modification of parent molecular skeletons. Herein, we report an enantioselective Rh-catalyzed single-carbon insertion into indole rings with diazoesters via either desymmetrization or kinetic resolution, thereby enabling arene-to-arene transmutation and, for the first time, the construction of exocyclic carbon-centered stereocenters. Starting from indole-containing triarylmethanes, a broad range of optically active triarylmethanes bearing diverse arene/heteroarene combinations with distinct aromatic electronic properties were obtained in moderate to good yields and high enantioselectivities (up to 96% ee). The method was further extended to desymmetrizing skeletal editing of alkyl- and alkenyl-substituted bis(indolyl)methanes, indole-containing simple natural products and pharmaceutical motifs. Its potential for structural transmutation was further demonstrated by a 3-fold programmable skeletal editing sequence of an indene-substituted bis(indolyl)methane.