Work

Aryl Acid-Alcohol Cross-Coupling: C(sp 3 )–C(sp 2 ) Bond Formation from Nontraditional Precursors

Year: 2025

Type: article

Abstract: Alcohols and aryl carboxylic acids are among the most commercially abundant, synthetically versatile, and operationally convenient building blocks in organic chemistry. Despite their widespread availability, the direct formation of C(sp 3 )–C(sp 2 ) bonds from these functional groups remains a challenge. Recently, our group developed robust protocols to harness alcohols as alkyl radical precursors, but the activation of aryl acids remains relatively unexplored. Herein, we describe the merger of N-heterocyclic carbene (NHC)-mediated deoxygenation and nickel-mediated decarbonylation of aryl acids toward C(sp 3 )–C(sp 2 ) bond formation. The utility of this method is demonstrated through the synthesis of a diverse range of aryl–alkyl cross-coupled products and the late-stage functionalization of complex molecules, including drugs, natural products, and biomolecules.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.4c15827