Stable Secondary N-(Per)fluoroalkylamides from 1,2,3-Triazoles via Ketenimines

Stable secondary N-trifluoromethylamides have been prepared and isolated for the first time from N-fluoroalkyl-1,2,3-triazoles via thermally generated ketenimines. This transformation overcomes the long-standing instability of N-trifluoromethyl amine precursors and provides a direct, scalable route to bench-stable secondary N-(per)fluoroalkylamides. Mild hydration of the ketenimines affords amides in high yields, tolerating diverse functional groups and structural motifs. Detailed experimental and computational studies reveal their high thermal stability, good hydrolytic stability, significantly higher acidity, and enhanced lipophilicity and hydrogen bond donor strength compared to conventional secondary amides. The new class of compounds expands the chemical space of fluorinated amides and introduces N-(per)fluoroalkyl secondary amides as easy to handle molecules with potential applications in medicinal and material chemistry.