Carbene-Catalyzed Nitrogen to Carbon Aryl Migration via a Radical-Neutral Crossover Process

Aryl migrations represent one of the most potent strategies for preparing aromatic compounds via an intramolecular aryl redistribution between different atoms, and significant advancements have been achieved. However, examples of N-to-C aryl migration are rare due to the formidable challenge of cleaving the strong C–N bond induced by the p–π conjugating effect. Although the evolution of shifting the reaction mechanism from the classic anionic pathway to emerging radical or radical-crossover pathways has partially solved the challenge, the relevant transformations are still in their infancy and suffer from various limitations. Herein, we disclose a carbene-catalyzed effective N-to-C aryl migration by innovating the reaction mechanism with a radical-neutral crossover process. Key steps involve the site-selective trapping of the dearomatized spirocyclic radical species by NHC-bound persistent radicals to form neutral spirocyclic 1,4-cyclohexadienes. The facile and irreversible C–N bond cleavage in the neutral species facilitates the N-to-C aryl migration. Multisubstituted aryl groups, whose migration may be influenced by their inherent electronic nature and steric effect, migrate smoothly under our conditions, enabling effective preparation of multisubstituted arenes. The highly robust reactions can even occur under open-to-air conditions, yielding various benzenepropanamide derivatives in good to high yields. Preliminary antibacterial activity studies revealed that some products exhibit impressive antibacterial activity, superior to or comparable to those of the commercial bactericides bismerthiazol and thiodiazole copper.