Interrupted C(sp2) Ritter Reaction Enabled by a Stable Nitrilium Surrogate

Abstract The Ritter reaction is a classic named-reaction for amide synthesis that converts alkenes or tertiary alcohols into N-alkyl amides via carbocation and nitrilium intermediates under strongly acidic conditions. Despite nearly eight decades of development, the synthetic scope remains limited by the inability to control the reactivity of the nitrilium-ion and avoid its rapid hydrolysis to amides. Here, we report a strategy to overcome this long-standing limitation by stabilizing the nitrilium intermediate as an imidoyl fluoride. β-Fluorovinyl iodonium salts, readily prepared from alkynes, undergo a stereoselective C(sp2) Ritter reaction with nitriles in the presence of silver fluoride. Mechanistic studies revealed the nitrilium surrogate to be sufficiently persistent that it could be exploited synthetically by trapping by oxygen-, sulfur-, nitrogen-, and carbon-centered nucleophiles to provide fluorovinyl enamides, imides, imidates, amidines, tetrazoles, enamines, and imines. This work establishes a rare C(sp2) Ritter reaction and demonstrates that nitrilium-ion reactivity can be controlled and diverted from hydrolysis toward productive intermolecular bond-forming processes, opening a new direction for Ritter chemistry.