C–N and C–O Bond Formation in Copper-Catalyzed/Mediated sp³ C–H Activation: Mechanistic Studies from Experimental and Computational Aspects

Mechanistic studies on Cu-catalyzed/mediated sp³ C–H amidation and acetoxylation are investigated from experimental and computational aspects. The concerted metalation–deprotonation (CMD) mechanism rather than a radical-involved pathway is proved to occur in amidation and acetoxylation reactions, and this is the rare example of the CMD mechanism involved in the more challenging sp³ C–H activations. Theoretical calculations demonstrated that CMD is the rate-determining step either for methylic or benzylic positions in amidation and acetoxylation reactions, and intermolecular nucleophilic addition of acetate anions is more favorable than the ring opening of β-lactams and intramolecular acetoxylation. These mechanistic studies on the divergent and condition-dependent product formation are critical for developing Cu-promoted C–H functionalization via the CMD mechanism.