Catalytic Behavior of Mono-N-Protected Amino-Acid Ligands in Ligand-Accelerated C-H Activation by Palladium(II)

Mono-N-protected amino acids (MPAAs) are increasingly common ligands in Pd-catalyzed C-H functionalization reactions. Previous studies have shown how these ligands accelerate catalytic turnover by facilitating the C-H activation step. Here, it is shown that MPAA ligands exhibit a second property commonly associated with ligand-accelerated catalysis: the ability to support catalytic turnover at substoichiometric ligand-to-metal ratios. This catalytic role of the MPAA ligand is characterized in stoichiometric C-H activation and catalytic C-H functionalization reactions. Palladacycle formation with substrates bearing carboxylate and pyridine directing groups exhibit a 50-100-fold increase in rate when only 0.05 equivalents of MPAA are present relative to Pd^II . These and other mechanistic data indicate that facile exchange between MPAAs and anionic ligands coordinated to Pd^II enables a single MPAA to support C-H activation at multiple Pd^II centers.