Enantioconvergent Chan-Lam Coupling: Synthesis of Chiral Benzylic Amides via Cu-Catalyzed Deborylative Amidation.

The Chan-Lam coupling represents one of the most effective methods for constructing C-N bonds due to its mild reaction conditions and broad functional group compatibility. However, asymmetric versions of this transformation to forge C(sp3)-N bonds have remained elusive due to the need for a general mechanistic framework to engage alkylboron reagents. Herein, we demonstrate the first enantioconvergent Chan-Lam C(sp3)-N coupling using synthetically modular alkylboronic pinacol esters. The reported transformation imparts a high degree of enantioselectivity and tolerates a wide range of functional groups, heterocycles, and pharmaceutically relevant frameworks. The reaction mechanism was investigated through Hammett analysis, radical clock tests, and radical trapping experiments. Density functional theory (DFT) calculations support a radical relay pathway: oxidative homolysis of the C-B bond generates prochiral alkyl radicals, which are functionalized by in situ generated Cu(II) intermediate through an inner-sphere mechanism.