Computational Investigation of Selectivity in Suzuki–Miyaura Coupling of Secondary Alkyl Boranes

The Suzuki–Miyaura cross-coupling reaction is an important route to forming carbon–carbon bonds. Suzuki coupling of secondary alkyls containing β-hydrogens is challenging, due in part to a competing and undesired β-hydride elimination. We perform density functional electronic structure calculations on model compounds to study the selectivity of Suzuki coupling of secondary alkyl boranes. Results indicate that the rate and selectivity of the desired reductive elimination are strongly influenced by how the reactants and ligand interact with a coordinatively unsaturated Pd II intermediate. Agostic interactions between Pd II and reactant β-hydrogens provide facile routes to β-hydride elimination, while coordination of electron-donating reactant groups to Pd II slows the reductive elimination. The bulky ligands used in typical Suzuki couplings, such as the SPhos dialkylbiarylphosphine, appear to block both types of undesired interaction while stabilizing the reductive elimination transition state.