1. Department of Chemistry, University of Wisconsin-Madison, Madison, WI, 53706 USA;2. Department of Chemistry, University of Chicago, Chicago, IL, 60637 USA;3. Department of Chemistry, Indiana University, Bloomington, IN, 47405 USA
Abstract:
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 PdII. These and other mechanistic data indicate that facile exchange between MPAAs and anionic ligands coordinated to PdII enables a single MPAA to support C−H activation at multiple PdII centers.