N-heterocyclic carbene- and organic photoredox-catalysed meta-selective acylation of electron-rich arenes

Abstract

meta-Selective functionalization of electron-rich arenes provides a complementary route to that of traditional organic synthesis. In classical electrophilic aromatic substitution reactions of electron-donating group-pendant arenes, C–H functionalization occurs at the ortho- or para-positions. There have been numerous efforts to overcome this selectivity, and various synthetic methods have been developed, typically using transition metal catalysis. Here we report a combined N-heterocyclic carbene- and organic photoredox-catalysed method for meta-selective acylation of electron-rich arenes, using acyl imidazoles as acylating reagents. This approach proceeds without directing groups or steric factors required in transition metal-catalysed processes, resulting in the opposite regioselectivity to conventional approaches such as Friedel–Crafts acylation. Mechanistic studies reveal the process involves a sequence of single-electron oxidation of an electron-rich arene followed by the radical–radical coupling between a ketyl radical and an arene radical cation. meta-Selective acylation of arenes typically requires directing groups or steric hindrance. Now, a combined N-heterocyclic carbene and organic photoredox catalysed of electron-rich arenes, using acyl imidazoles as acylating agents, is reported. Mechanistic studies reveal the process proceeds through single-electron oxidation and radical–radical coupling steps.