S _H 2 Decarboxylative Monofluoromethylation of Aliphatic Carboxylic Acids Enabled by Nickel/Photoredox Dual Catalysis

Abstract

Abstract Catalytic construction of alkyl fluorides through C─C bond‐forming transformations represents a formidable challenge in modern organofluorine chemistry. In this work, we present a decarboxylative monofluoromethylation protocol enabled by synergistic nickel/photoredox dual catalysis for aliphatic carboxylic acid derivatives. A structurally diverse array of tertiary, secondary, and primary N ‐hydroxyphthalimide (NHP) esters underwent efficient conversion to their corresponding fluoromethylated products with excellent functional group tolerance (68 examples, up to 91% yield). The methodology's versatility was highlighted through late‐stage monofluoromethylation of pharmaceutically relevant molecules. Mechanistic investigations reveal the involvement of a radical rebound pathway mediated by nickel (III) intermediate, with the homolytic substitution (S H 2) process at sterically congested center representing a critical mechanistic distinction from conventional cross‐coupling paradigms.