Photocatalytic Decarboxylative Coupling of Aliphatic N-hydroxyphthalimide Esters with Polyfluoroaryl Nucleophiles

Polyfluoroarenes are an important class of compounds in medical and material chemistry. The synthesis of alkylated polyfluoroarenes remains challenging. Here we describe a decarboxylative coupling reaction of N-hydroxyphthalimide esters of aliphatic carboxylic acids with polyfluoroaryl zinc reagents (Zn-Ar-F) via synergetic photoredox and copper catalysis. This method readily converts primary and secondary alkyl carboxylic acids into the corresponding polyfluoroaryl compounds, which could have a wide range of F-content (2F-5F) and variable F-substitution patterns on the aryl groups. Broad scope and good functional group compatibility were achieved, including on substrates derived from natural products and pharmaceuticals. Mechanistic study revealed that a [Cu-(Ar-F)(2)] species could be responsible for the transfer of polyfluoroaryl groups to the alkyl radicals.

Automated summary

The study presents a decarboxylative coupling reaction using photoredox and copper catalysis to convert alkyl carboxylic acids into polyfluoroaryl compounds. The method demonstrates broad scope and good functional group compatibility, with the potential to achieve a wide range of F-substitution patterns on the aryl groups. Mechanistic study suggests a [Cu-(Ar-F)(2)] species may be responsible for the transfer of polyfluoroaryl groups to alkyl radicals.