First-Principles Molecular Dynamics Analysis of Ligand-Free Suzuki–Miyaura Cross-Coupling in Water Solvent: Oxidative Addition Step

We investigated the oxidative addition of PhX (X = Cl, Br) to a single Pd(0) atom or a PdX– complex in water using first-principles molecular dynamics simulations, with solvent H2O molecules explicitly included in the calculation models, to clarify the origin of the extremely high reactivity of a ligand-free Pd catalyst in an aqueous solution for the Suzuki–Miyaura reaction. The free-energy profiles are estimated using blue moon ensemble sampling to include the entropy effect in chemical reactions in a water solvent. The free-energy barrier of the oxidative addition step is quite low for PhBr, whereas the barrier for PhCl is sizable, indicating that the reaction can proceed at room temperature with a high rate for PhBr but a rather low rate for PhCl. We also investigated the effect of the additional halogen anion on the Pd catalyst as a “supporting ligand”. The activation barrier of the oxidative addition step is not affected by the supporting halogen ligand, but the final state is significantly destabili...