Modular Amide Synthesis via Dual C-O and N-O Bond Cleavage: Palladium-Catalyzed Deoxygenative Carbonylation of Benzyl Alcohols with Nitroarenes.

Alcohols and nitroarenes are among the most commercially abundant and synthetically versatile functional groups in organic chemistry. Herein, we developed a palladium-catalyzed deoxygenative carbonylation that directly couples benzyl alcohols with nitroarenes to construct amide bonds in a single operation. This transformation addresses key challenges in amide synthesis by eliminating the need for pre-functionalized coupling partners and stoichiometric activating reagents through a synergistic combination of pentafluoropyridine-mediated C-O activation, carbonyl insertion, and nitro reduction. The reaction demonstrates excellent functional group compatibility, accommodating diverse substituents, including halogens, ketones, and heterocycles, with yields up to 95%, while enabling late-stage modification of complex pharmaceuticals. Mechanistic studies reveal a well-defined catalytic cycle involving benzyloxypyridinium formation and nitrosobenzene capture. This method represents a significant advance in amide synthesis by combining multiple transformations into one efficient process with broad synthetic utility.