Photoredox-Catalyzed Nucleophilic Aromatic Substitution of Halophenols with Azoles via Oligomeric Phenylene Oxide Radicals

Nucleophilic aromatic substitution (S_NAr) reactions are widely employed in organic synthesis yet typically require the use of electron-deficient arenes for efficient reactivity. Herein, we report a photocatalytic protocol for formal S_NAr of electron-rich 4-halophenols with azole nucleophiles under mild, redox-neutral conditions. The transformation proceeds via a two-stage mechanism consisting of initial halophenol oligomerization to produce a key oligo(phenylene oxide) intermediate and its subsequent breakdown through S_NAr with the azole enabled by photoredox-catalyzed arene umpolung. Reaction monitoring, stoichiometric control experiments, and luminescence quenching data implicate phenoxyl radicals and Brønsted acid-activated oligo(phenylene oxide) radicals as the reactive species in the oligomerization and the S_NAr stages, respectively. The synthetic utility of this method is demonstrated across 17 (pseudo)halophenols bearing a variety of leaving groups (F, Cl, Br, OMs, and OTs) and 22 azole examples.