Synthesis of Acyclic All-Carbon Quaternary Stereocenters through Nickel-Catalyzed Enantioselective C(sp 3 )–H Amination

The catalytic enantioselective construction of acyclic all-carbon quaternary stereocenters via C(sp 3 )–H functionalization represents a fundamental challenge in synthetic chemistry primarily due to the steric congestion and enhanced conformational mobility of these motifs. While noble metals have demonstrated efficacy in such desymmetrizations, the development of sustainable catalytic systems based on earth-abundant 3d metals remains rare. Herein, we report a nickel-catalyzed asymmetric C(sp 3 )–H amination using a commercially available, air-stable Ni(II) catalyst and a sterically tuned chiral BINOL-derived ligand. The reaction enables the direct desymmetrization of prochiral gem -dimethyl groups, providing access to a wide range of enantioenriched β-amino acid derivatives bearing all-carbon quaternary stereocenters in high yields and with excellent enantioselectivity (up to >99% ee). The utility of this transformation is highlighted by the late-stage functionalization of pharmaceutical scaffolds and versatile downstream elaboration of the resulting quaternary stereocenters, establishing a robust platform for sustainable synthesis of these valuable structural motifs.