Carbene-Catalyzed Desymmetrization and Direct Construction of Arenes with All-Carbon Quaternary Chiral Center.

Abstract

Multisubstituted arenes such as indanes with attached all-carbon quaternary centers are unique scaffolds in synthetic functional molecules and sophisticated natural products. A key challenge in preparing such molecules lies in the enantioselective installation of the quaternary carbon centers. Conventional methods in this direction include asymmetric substitution reactions and substrate-controlled cyclization reactions. These reactions lead to poor stereoselectivities and/or require long and tedious synthetic steps. Disclosed here is a one-step organic catalytic strategy for enantioselective access to this class of molecules. The reaction involves an N-heterocyclic carbene catalyzed process for direct benzene construction, indane formation, remote-carbon desymmetrization, and excellent chirality control. This approach will enable the concise synthesis of arene-containing molecules, including those with complex structures and challenging chiral centers.