Mechanisms and Origins of Regioselectivity in Rare-Earth-Catalyzed C–H Functionalization of Anisoles and Thioanisoles

The direct catalytic C–H functionalization of aromatic compounds such as anisoles and thioanisoles is of great interest and significance. However, achieving precise regioselectivity remains a major challenge. In this study, we conducted comprehensive density functional theory calculations to explore the mechanisms of rare-earth-catalyzed regioselective C–H alkylation, borylation, and silylation of anisole and thioanisole. The results reveal that in cationic C–H alkylation systems, the alkene insertion step follows a substrate-assisted mechanism, in which an additional substrate molecule acts as a ligand to facilitate the transformation. In neutral C–H borylation and silylation systems, although mononuclear hydride species readily dimerize into binuclear hydride species due to thermodynamic stability, the catalytic process predominantly proceeds via a mononuclear pathway. Furthermore, the origins of regioselectivity were thoroughly elucidated. A detailed analysis of electronic and steric effects in related transition states reveals that, for anisole, regioselectivity is primarily governed by ring strain. Since α-C(sp³)–H activation involves the formation of a highly strained three-membered ring, the reaction preferentially occurs at the ortho-C(sp²)–H site, forming a less strained four-membered ring. In contrast, for thioanisole, electronic effects play a decisive role, driving C–H activation at the more negatively charged α-C(sp³) site due to stronger metal–carbon interactions.