β‐Aminosulfonyl Fluorides via Water‐Accelerated N‐Heterocyclic Carbene Catalysis

Abstract

Herein, a water-accelerated, N-heterocyclic carbene (NHC)-catalyzed aza-Michael addition reaction was reported to access β-aminosulfonyl fluorides, which are key hubs of the sulfur(VI) fluoride exchange (SuFEx) reaction. As a crucial reaction medium, water considerably enhanced the reaction rate with excellent chemo- and site-selectivity (up to >99 : 1) compared to conventional solvents. In addition, the late-stage ligation of bioactive molecules with the aliphatic β-amino SuFEx hub was demonstrated. Mechanistic studies on experimental, analytical, and computational approaches support noncovalent activation over NHC catalysis "on-water".