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

作者：Xiaowen Qin, Heng Li, Shuhui Sun, Siyi Shen, Tiefeng Xu, Xiao‐Feng Wu, Zhiping Yin · 发表于：Organic Letters · 年份：2025 · DOI：10.1021/acs.orglett.5c03937 · 被引用次数：3 · 研究领域：Catalytic C–H Functionalization Methods、Advanced Synthetic Organic Chemistry、Catalytic Cross-Coupling Reactions

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.