Even though α-arylation of ketones is attractive for direct C-H functionalization of organic substrates, the method largely relies on phosphine-ligated palladium complexes. Only recently, efforts have focused on developing nitrogen-based ligands as a more sustainable alternative to phosphines, with pyridine-functionalized pyridinium amidate (pyr-PYA) N,N'-bidentate ligands displaying good selectivity and activity. Here, we report on a second generation set of catalyst precursors that feature a 5-membered N-heterocycle instead of a pyridine as chelating unit of the PYA ligand to provide less steric congestion for the rate-limiting transmetalation of the enolate. To this end, new heterocycle-functionalized PYA palladium(ii) complexes containing an oxazole (5b), N-phenyl-triazole (5c), N-methyl pyrazole (5d), N-phenyl-pyrazole, (5e), N-xylyl-pyrazole (5f), and N-isopropyl-pyrazole (5g) were synthesized compared to the parent pyr-PYA complex 5a. Less packing of the palladium coordination sphere was evidenced from solid state X-ray diffraction analysis. While the catalytic activity of the oxazole system was lower, all other complexes showed higher activity. In particular, complex 5g comprised of an electron-donating and sterically demanding iPr-pyrazole chelating PYA ligand is remarkably stable towards air and moisture and shows outstanding catalytic activity with complete selectivity (>99% yield) and turnover frequencies up to 1200 h-1, surpassing that of parent 5a by one order of magnitude and rivalling the most active phosphine-based palladium systems. Kinetic studies demonstrate a first order rate-dependence on palladium and the substrate. Some deviation of linearity together with poisoning experiments suggest a mixed homogeneous/heterogeneous pathway, though the reproducible kinetics of in situ catalyst recycling experiments strongly point to a molecularly defined active species, demonstrating the high potential of PYA-based ligands.
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