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

Abstract

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.

Photocatalytic Decarboxylative Coupling of Aliphatic N‐Hydroxyphthalimide Esters with Bromopolyfluorobenzene

“…(Scheme 1c). However, in this novel work, Zn‐Ar F was prepared from pentafluoroiodobenzene with the aid of Li n Bu through multistep reactions [12] . As bromopolyfluorobenzenes are commercially available raw materials, [13] they are one of the most frequently used reagents for incorporating polyfluoroaryls into organic molecules.…”