Unveiling Cooperative Effects of Two Bidentate Pyridone-Pyrazole Ligands in the Regioselective C–H Activation: A Theoretical Study

Bidentate pyridone-derived ligands have emerged in metal-catalyzed C-H activation, but the associated cooperative effects remain unclear. Herein, a new mechanism enabled by two bidentate pyridone-pyrazole ligands is proposed for Pd-catalyzed C-H activation, and a unique cooperation of the two bidentate pyridone-pyrazole ligands through the intramolecular hydrogen bond and the π-π stacking interaction is found. The computed energy spans indicate that the new mechanism is more favorable than the traditional mechanism for <i>meta</i> and <i>para</i> products, but the traditional mechanism accounts for the <i>ortho</i> product. The computed energy spans (29.0, 30.3, and 31.4 kcal/mol) are consistent with the experimentally observed regioselectivity for the <i>meta</i>, <i>para</i>, and <i>ortho</i> products. The substrate and ligand deconstruction is carried out, suggesting that the regioselectivity originates from the cooperative effect of the two bidentate pyridone-pyrazole ligands.