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

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 PdX- 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 turnover of the SMR. We ascribe the origin for the suppression of the catalytic reactivity of the ligand-free SMR for PhCl to the larger activation barrier in the oxidative addition step, which causes the aggregation of Pd catalysts.