CESAm-HAT · Carbonyl-catalyzed EnantioSelective synthesis of primary Amines via Hydrogen-Atom Transfer activation

Chiral primary amines are fundamental building blocks in pharmaceuticals, agrochemicals, and advanced materials. Because their optical purity critically influences biological activity, the asymmetric synthesis of these privileged scaffolds has become a central goal in modern chemistry. Diverse asymmetric catalytic methods have been developed, such as hydrogenation and nucleophilic addition to imines, reductive amination of carbonyls, and direct C-H amination. Among these, carbonyl catalysis stands out as a transition-metal-free strategy for the enantioselective construction of chiral primary amines via formation of azaallyl anion intermediate. Yet, current strategies require stoichiometric amounts of strong Brønsted base, which hampers broader synthetic applications.CESAm-HAT will develop a multicatalytic system for enantioselective functionalization of unactivated primary amines, combining chiral carbonyl and photoinduced Hydrogen-Atom Transfer (HAT) catalysis. This platform will enable the mild and selective generation of chiral azaallyl radicals via HAT activation of transiently formed imine intermediates, thereby avoiding the need for stoichiometric Brønsted bases. The ensuing stereocontrolled bond formation from these open-shell catalytic species will provide access to structurally diverse, enantioenriched primary amines.To achieve this goal, CESAm-HAT will target two synthetic applications. First, the asymmetric α-C–H alkylation of unprotected primary amines, providing one-step access to enantioenriched α-tertiary primary amines under a ternary catalytic system. Second, the dynamic kinetic resolution (DKR) of α-secondary unprotected primary amines promoted by a quaternary catalytic system.Overall, CESAm-HAT is expected to advance sustainable synthetic chemistry and expand the frontiers of enantioselective radical catalysis. More broadly, it will contribute to industry and society by fostering the development of more sustainable and efficient transformations