Unified Copper-Catalyzed Stereoselective Addition: Construction of Vicinal F/CF x -Containing Stereocenters

Abstract Herein, we report a copper-catalyzed asymmetric Michael addition of α-fluoro aza-heteroarenyl acetates to β-fluoroalkyl enones. This transformation provides efficient access to enantioenriched acyclic vicinal F/CFx-containing (vicinal F and CF3, F and CHF2, F and CH2F) stereocenters with exceptional stereocontrol (up to >20:1 dr and 98% ee). Its synthetic utility is underscored by scale-up synthesis and diverse downstream functionalizations. Detailed mechanistic investigations and density functional theory calculations elucidate the catalytic cycle process and the origin of enantioselectivity.