Nickel-Catalyzed Enantioselective C(sp3)–H Amination toward Acyclic All-Carbon Quaternary Stereocenters

Abstract Despite the efficacy of noble metals in the enantioselective desymmetrization via C(sp3)−H functionalization for constructing acyclic all-carbon quaternary stereocenters, the development of sustainable catalytic systems based on earth-abundant 3d metals remains largely underdeveloped. Herein, we present a nickel-catalyzed asymmetric C(sp3)−H amination reaction that facilitates the direct desymmetrization of prochiral gem-dimethyl groups. This approach utilizes a commercially available, air-stable Ni(II) salt in combination with a sterically tailored, chiral BINOL-derived ligand, offering an efficient method to access a diverse range of enantioenriched β-amino acid derivatives featuring acyclic all-carbon quaternary stereocenters. We further demonstrated the practicality and synthetic utility of this reaction through gram-scale synthesis and a series of subsequent transformations.