Copper-Catalyzed Enantioselective Synthesis of <i>N</i> -Heterocycle-Substituted Quaternary Carbon Stereogenic Centers

The enantioselective construction of all-carbon quaternary stereogenic centers adjacent to N -heterocycles remains a long-standing challenge in asymmetric catalysis. Herein we report a copper-catalyzed enantioselective hydropyridylation of 1,1-disubstituted allenes with 2-halopyridines that proceeds via a nucleophilic aromatic substitution (S N Ar) pathway. This transformation enables the efficient synthesis of α-quaternary N -heterocyclic compounds with a broad substrate scope in high yields (up to 96%) with excellent enantioselectivities (up to 99% ee ). The methodology is compatible with various functional groups and N -heterocycles and can be extended to copper-catalyzed boropyridylation, affording versatile alkenylboronates. Mechanistic studies, including deuterium labeling, kinetic isotope effect analysis, and DFT calculations, support a 2,3-hydrocupration followed by a stereodetermining S N Ar step. This strategy provides a practical and general approach for constructing structurally diverse azaarene-containing quaternary centers, which are potentially valuable for drug discovery and development.