Triplet Energy Transfer-Based Deracemization of Axially Chiral Alkenes Enabled by a Dual Catalyst System

Photochemical deracemization has been recognized as a highly efficient strategy in asymmetric synthesis. Consequently, several pivotal chiral photosensitizers have been developed to participate in energy transfer (EnT)-based mechanisms. Nevertheless, the limited diversity of catalyst types and the pronounced spatial effects of photosensitizer moieties on enantioselectivity present an inherent challenge, thereby significantly restricting the substrate scope. In this context, exploring the feasibility of dual-catalyst systems becomes a critical task due to the flexibility of independently selecting two catalysts. Notably, the intrinsic racemization of enantioenriched products, even in the absence of chiral catalysts, represents a substantial obstacle that considerably impacts the efficiency of enantiomer enrichment. Despite these challenges, we have successfully achieved this objective, providing robust proof-of-concept validation. As a result, under a dual-catalyst system comprising a chiral phosphoric acid (CPA) and 4CzIPN mediated by visible light, a broad range of valuable axially chiral azaarylidene cycloalkanes can be synthesized with exceptional yields and enantioselectivities. The scope of the substrates is remarkably extensive, including a wide range of cyclohexanes, cyclopentanes, and cyclobutanes substituted with various azaarenes and featuring diverse stereocenter configurations. Notably, this encompasses spiro- and all-carbon quaternary stereogenic centers, all of which exhibit exceptional compatibility. More importantly, numerous bioactive molecules, such as a key mGlu5 antagonist, can be directly synthesized with high precision, further highlighting the significance of this work.