Nickel‐Catalyzed Highly Selective Radical C‐C Coupling from Carboxylic Acids with Photoredox Catalysis

Abstract

The selective coupling of two different radicals is a long‐standing challenge due to the process occurring statistically. Generally, the cross‐coupling selectivity is achieved by the persistent radical effect (PRE), resulting in limited radical precursors. In this paper, a highly selective cross‐coupling of alkyl radicals with acyl radicals to construct C(sp2)‐C(sp3) bonds, or with alkyl radicals to construct C(sp3)‐C(sp3) bonds have been achieved with the readily available carboxylic acids and their derivatives (NHPI ester) as coupling partners. The success originates from the use of tridentate ligand (L1) to enable radical cross‐coupling process to Ni‐mediated organometallic mechanism. This protocol offers a facile and flexible access to structurally diverse ketones (up to 90% yield), and also a new solution for the challenging double decarboxylative C(sp3)‐C(sp3) coupling. The broad utility and functional group tolerance are further illustrated by the late‐stage functionalization of natural‐occurring carboxylic acids and drugs.