Bench-stable azidodifluoromethyl imidazolium reagents unlock the synthetic potential of carbonimidic difluorides.

Abstract

N-fluoroalkyl compounds are highly valuable in medicinal chemistry. While carbonimidic difluorides have been recognized as valuable intermediates for N-CF₃ compounds synthesis, their broader synthetic potential remains largely unexplored due to the limitations of current methodologies, particularly in expanding the scope of N-fluoroalkyl derivatives. Herein, we report the design and synthesis of azidodifluoromethyl imidazolium reagents that enable the in situ generation of carbonimidic difluorides. These intermediates undergo a series of controlled transformations, including chlorination, fluorination, monodefluorination, didefluorination, and subsequent derivatization of N-chlorodifluoromethyl compounds, providing an efficient strategy for the synthesis of structurally diverse N-fluoroalkane and amine derivatives.