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 meta and para products, but the traditional mechanism accounts for the ortho product. The computed energy spans (29.0, 30.3, and 31.4 kcal/mol) are consistent with the experimentally observed regioselectivity for the meta, para, and ortho 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.