Origin of norbornene-mediated selective meta-C-H arylation of anisole derivatives overcoming the "ortho constraint" in Pd/S,O-ligand catalysis

This study explored the mechanism and origin of norbornene (NBE)-controlled mono- and di-meta-C-H arylation of anisole under Pd/S,O-ligand catalysis with density functional theory (DFT) calculations. The result shows that the meta-C-H activation step determines the selectivity. The bridgehead-modified NBE enables the Ag-NBE coordination due to the steric hindrance between the bridgehead substituent of the NBE and ligands, while the unmodified NBE relies on favorable electrostatic interaction resulting in the coordination of Ag with the ligand. For the Ag-NBE coordination mode, the increase of the steric hindrance of the bridgehead substituent leads to the geometric twisting of the substrate arene skeleton overcoming the "ortho constraint" and ultimately resulting in mono-meta-selectivity. These findings may expand our understanding of the dynamics of the NBE-mediated Catellani-type reaction and will facilitate the design of reactions.