Theoretical Insights into the Ir-Catalyzed C(sp ² )–H Borylation Mechanism: Origin of Ligand-Controlled Regioselectivity and Identification of a Potentially Active Species

Comprehensive computational studies were carried out to elucidate the mechanistic basis and the origin of ligand-controlled regioselectivity in Ir-catalyzed C(sp²)-H borylation. Both the N,C(anionic)-type ligand L1 and the neutral bipyridine ligand L2 operate via a classical Ir(III)/Ir(V) catalytic cycle, with regioselectivity determined at the C-H oxidative addition step. In the L1 system, the pronounced trans effect of the anionic carbon atom plays a decisive role in dictating the coordination geometry and reactivity. Therefore, during the regeneration of the active catalyst, the trans position relative to the anionic carbon center must be occupied by a substrate molecule. Additionally, computations identified an L1-chelated Ir(III)BpinH species as a plausible catalytically competent intermediate, capable of mediating C-H borylation using HBpin as the sole boron source. Critically, ligand-controlled regioselectivity originates from fundamental differences in the electronic nature of the C-N and N-N ligands, which leads to divergent coordinative unsaturation in the key Ir(III) intermediates: the four-coordinate L1-Ir(III)Bpin₂ complex affords three accessible sites, allowing the acyl group to function as a directing chelator and thereby enabling selective ortho-C-H activation, whereas the five-coordinate L2-Ir(III)Bpin₃ complex possesses only two vacant coordination sites. This constrained coordination environment prevents effective chelation by the acyl group, causing it instead to behave as a steric hindrance and inducing a destabilizing lone-pair-π repulsion between the acyl carbonyl oxygen and the L2 ligand during ortho-selective C-H activation, thereby leading to predominant meta- and para-selectivity. Collectively, these insights establish a coherent mechanistic framework that provides guidance for the rational design of transition-metal-catalyzed C-H functionalization reactions with improved regiocontrol and enhanced synthetic efficiency.