More is Different: Theoretical Investigation on the Origin of Ligand Loading-Dependent Switching Regioselectivity in Ir-Catalyzed C–H Borylation

The ligand loading-dependent <i>ortho</i>/<i>meta</i> switching regioselectivity in an Ir-catalyzed C-H borylation of an aromatic ester has been experimentally achieved recently, while the origin of switching regioselectivity still remains unclear. In this work, we performed density functional theory (DFT) calculations to reveal the reaction mechanism and the principle of the switching regioselectivity. Results show that two active species, namely, (N, B)₂Ir^III(Bpin) and (N, B)Ir^III(Bpin)₂, are generated in situ, and their concentrations are dependent on the ligand loading. When the loading of the ligand is sufficient, the concentration of (N, B)₂Ir^III(Bpin) is higher, which catalyzes the C(sp²)-H bond activation via an unusual N, B bidentate ligand-assisted mechanism. The unexpected <i>meta</i>-selective C(sp²)-H borylation is achieved because the interplay between (N, B)₂Ir^III(Bpin) and the aromatic ester leads to special steric effects and noncovalent interactions. When the ligand is insufficient, the concentration of tetra-coordinated (N, B)Ir^III(Bpin)₂ becomes higher. <i>Ortho</i>-selective C(sp²)-H borylation is achieved via coordination directing because the coordination of the carbonyl group stabilizes tetra-coordinated active species with two vacant sites and leads the <i>ortho</i> C-H bonds approaching the active center. These findings are expected to aid the development of innovative strategies for precise control of the regioselectivity in Ir-catalyzed C-H borylation.