Intermolecular Enantioselective Nickel‐Catalyzed Arylation of Un‐Activated C(sp ³ )─H Bond

Abstract

Abstract We report the first example of an intermolecular, enantioselective Ni(II)‐catalyzed C(sp 3 )─H arylation, providing direct access to challenging all‐carbon quaternary stereogenic centers. Key to this success is the use of a specially designed BINOL‐derived ligand, which enables efficient desymmetrization of gem‐dimethyl groups through a rate‐ and enantio‐determining C─H activation step. This catalytic system demonstrates remarkable functional group tolerance, affording a wide variety of arylated products in high yields (up to 85%) and with excellent enantioselectivities (up to 95:5 e.r.). Mechanistic studies, combining kinetic isotope effect measurements, deuterium labeling, and DFT calculations, reveal that the Ni–BINOL complex promotes a unique concerted metalation–deprotonation pathway assisted by ligand coordination and π–π interactions. This work establishes nickel as a powerful and sustainable alternative to precious metals for asymmetric C─H activation, opening new perspectives for the construction of enantioenriched quaternary carbon centers of high relevance in drug discovery and materials science.