First-Principles Molecular Dynamics Analysis of Ligand-Free Suzuki–Miyaura Cross-Coupling in Water: Transmetalation and Reductive Elimination

Abstract

We investigated the transmetalation step of the Suzuki–Miyaura cross coupling reaction (SMR) catalyzed by ligand-free Pd atom or Pd-X– (X = Cl or Br) using first-principles molecular dynamics simulations with an explicit solvent model. When starting from the single Pd atom, the halogen anion bound to the Pd was not replaced by organoboronate species and instead remained bound to the Pd throughout the transmetalation step. However, when starting from the Pd-X– catalyst, one of the two halogen anions was released from the first coordination sphere of the Pd during transmetalation. Therefore, the products after the transmetalation starting with either the single Pd atom or the Pd-X– were the same. We concluded that Pd-X– is the active species of the ligand-free Pd catalyst for the SMR. The overall activation free energies for transmetalation and reductive elimination were relatively low, estimated to be at most, 8.1 kcal/mol for X = Br and 8.4 kcal/mol for X = Cl, respectively, leading to the efficient turno...