Direct synthesis of dialkyl ketones from deoxygenative cross-coupling of carboxylic acids and alcohols

Carboxylic acids and alcohols are widely commercially available, structurally diverse, benchtop stable, and ubiquitous in both natural products and pharmaceutical agents, making them ideal coupling partners for organic synthesis. Though various transformations have been developed by enabling the activation and subsequent cross-coupling of carboxylic acids and alcohols in separate contexts, the direct coupling of these two structural motifs to build value-added molecules is rare. Herein, we developed a direct deoxygenative cross-coupling between carboxylic acids and alcohols for dialkyl ketone synthesis via photoredox/nickel dual catalysis. This protocol provides a powerful platform to construct a wide range of structurally diverse ketone scaffolds with broad substrate scope, good functional group tolerance, step-economy and mild reaction conditions, using simple and readily available substrates. Moreover, the large-scale synthesis and late-stage functionalization of biological molecules also demonstrate the potential practicality.