A Chiral Bifunctional NHC Ligand Promoted Ni/Al-Catalyzed Regio- and Enantioselective C ₆ –H Alkylation of Pyrimidines

Achieving site- and enantioselective C–H functionalization has long been a formidable challenge in organic synthesis. We report herein a rare enantioselective C–H functionalization of pyrimidines via C–H activation, enabled by a Ni/Al bimetallic catalytic system assisted by a newly designed bifunctional N-heterocyclic carbene (NHC) ligand. This transformation exhibits high reactivity, regioselectivity (up to >20:1), and enantioselectivity (up to 94% ee), while also demonstrating the ability to activate C–H bonds with higher bond dissociation energies. The synthetic utility of this protocol is demonstrated by preparing an iridium complex that is employed in light-emitting devices. Mechanistic investigations reveal that the aluminum cocatalyst plays a crucial role in the dual activation of the pyrimidine substrate. Furthermore, kinetic studies provide insights into the reaction pathway and propose a potential catalyst resting state.