A tautomeric ligand enables directed C-H hydroxylation with molecular oxygen

Hydroxylation of aryl carbon-hydrogen bonds with transition metal catalysts has proven challenging when oxygen is used as the oxidant. Here, we report a palladium complex bearing a bidentate pyridine/ pyridone ligand that efficiently catalyzes this reaction at ring positions adjacent to carboxylic acids. Infrared, x-ray, and computational analysis support a possible role of ligand tautomerization from monoanionic (L,X) to neutral (L,L) coordination in the catalytic cycle of aerobic carbon-hydrogen hydroxylation reaction. The conventional site selectivity dictated by heterocycles is overturned by this catalyst, thus allowing late-stage modification of compounds of pharmaceutical interest at previously inaccessible sites.

Automated summary

This study reports a palladium complex that efficiently catalyzes hydroxylation of aryl carbon-hydrogen bonds at positions adjacent to carboxylic acids. The catalyst overturns the conventional site selectivity dictated by heterocycles, allowing late-stage modification of pharmaceutical compounds at previously inaccessible sites. Infrared, x-ray, and computational analysis support a potential role of ligand tautomerization in the catalytic cycle of this reaction.