Mechanistic Insights into Formation of All-Carbon Quaternary Centers via Scandium-Catalyzed C–H Alkylation of Imidazoles with 1,1-Disubstituted Alkenes

This density functional theory (DFT) study reveals a detailed plausible mechanism for the Sc-catalyzed C–H cycloaddition of imidazoles to 1,1-disubstituted alkenes to form all-carbon quaternary stereocenters. The Sc complex binds the imidazole substrate to enable deprotonative C2–H bond activation by the Sc-bound α-carbon to afford the active species. This complex undergoes intramolecular cyclization (C═C into Sc–imidazolyl insertion) with exo-selectivity, generating a β-all-carbon-substituted quaternary center in the polycyclic imidazole derivative. The Sc-bound α-carbon deprotonates the imidazole C2–H bond to deliver the product and regenerate the active catalyst, which is the rate-determining step. Calculations illuminate the electronic effect of the ancillary Cp ligand on the catalyst activity and reveal the steric bias caused by using a chiral catalyst that induce the enantioselectivity. The insights can have implications for advancing rare-earth metal-catalyzed C–H functionalization of imidazoles.