Arene difunctionalization through an acyl-inserting Smiles rearrangement enabled by N-heterocyclic carbene catalysis.

Arene difunctionalization offers a powerful strategy for the simultaneous installation of two functional groups in a single step. Despite recent advances, ipso/para-selective arene transformations remain underdeveloped. Herein, we report an N-heterocyclic carbene (NHC)-catalyzed radical protocol that addresses this challenge. The process features a unique generation of acyl-inserting Smiles rearrangement, wherein radical Meisenheimer intermediates are intercepted by NHC-bound radicals prior to rearomatization. Subsequent ketone deprotonation regenerates ionic Meisenheimer intermediates, thereby completing the rearrangement and affording 1,4-difunctionalized arenes. This organocatalytic protocol exhibits broad substrate scope, tolerates diverse functional groups, and delivers acylated aniline derivatives in excellent yields (96 examples, up to 98% yield). The synthetic potential is further showcased by a ring-expansion strategy to benzo[b]azepines and by late-stage functionalization of drug-like molecules. Mechanistic insights from combined experimental and computational studies shed light on the unique reactivity and the observed excellent site-selectivity.