Photocatalytic C–H Amination of Arenes with Saccharin

ABSTRACT

We report an unprecedented, highly general organic photocatalytic strategy for direct C(sp ² )–H amination of arenes using easily accessible saccharin as a nitrogen source. In sharp contrast to conventional radical amination protocols requiring transient arene radical cation intermediates, our system operates via an initial preferential single‐electron transfer (SET) oxidation of the in situ–generated saccharinate anion. This mechanistic pivot successfully bypasses longstanding electronic limitations, enabling an exceptionally broad substrate scope. The protocol tolerates a full spectrum of aromatic systems, including unactivated benzene (using only 2.0 equiv), haloarenes, polycyclic networks, highly electron‐deficient arenes bearing strong electron‐withdrawing groups (ester, nitrile, or trifluoromethyl substituents), and complex pharmaceutical frameworks, delivering the corresponding N ‐aryl saccharins in up to 99% yield (98% for benzene) with predictable regioselectivity. Density functional theory (DFT) calculations quantitatively corroborate the electrophilic radical kinetics (Δ G ^‡ = 2.3–14.4 kcal/mol for arene addition) and TEMPO‐mediated rearomatization cascade. Furthermore, the N ‐aryl saccharin adducts function as robust, programmable modified Gabriel reagents, smoothly delivering diverse primary and secondary aryl amine hydrochloride salts in up to 99% yield under remarkably mild conditions.