Synthesis, Functionalization, and Reactivity of Vinyl Sulfondiimidamides

Acrylamides are the dominant electrophilic warheads used in bioactive covalent inhibitors. A limitation of acrylamides and related unsaturated sulfonamides is the narrow scope to modulate their electrophilicity, and hence reactivity, through simple structural modification. Here, we show that vinyl sulfondiimidamides are effective electrophilic motifs for reaction with both sulfur- and nitrogen-based biologically relevant nucleophiles. We demonstrate that the electrophilicity of these new reagents can be tuned through variation of the imidic N-substituents. Vinyl sulfondiimidamides are prepared via a short sequence that features a Cope elimination as the key alkene-forming step. A broad range of N-substituents can be installed.