While oxygen is all around us, it is sometimes surprisingly difficult to use it for selective oxidation reactions. The old definition of oxidation reaction is the gain of oxygen or the loss of hydrogen. Although rarely used now, this definition does point out two major oxidation reactions in organic chemistry: hydroxylation and dehydrogenation.<br/>Hydroxylation of aryl C-H bonds with transition metal catalysts has proven challenging when oxygen is used as the oxidant. we are reporting a palladium complex bearing a bidentate pyridine/pyridone ligand that efficiently catalyzes this reaction at the ortho-positions of carboxylic acids. Infrared, x-ray, and computational analysis support a possible role of ligand tautomerization from mono-anionic (L,X) to neutral (L,L) coordination in the catalytic cycle of aerobic C-H 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.<br/>Dehydrogenation reactions, on the other hand, is another important transformation in both the bulk chemical industry and fine chemical synthesis. When free carboxylic acids are used as substrates, the resulting alpha,beta-unsaturated acids could enable a wide range of downstream transformations. Using similar ligand design principle, we report two divergent dehydrogenation reactions via Pd-catalyzed beta-methylene C-H activation of carboxylic acids, leading to the direct syntheses of alpha,beta-unsaturated carboxylic acids or gamma-alkylidene butenolides. The directed nature of this pair of reactions allows chemoselective dehydrogenation of carboxylic acids in the presence of other enolizable functionalities such as ketones, providing chemoselectivity that is inaccessible with existing carbonyl desaturation protocols.

C–H oxidation reactions for carboxylic acids enabled by novel pyridone ligands

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.