Base-Free SuFEx Reaction Promoted by Silica Gel for the Synthesis of β-Sultams

β-Sultams are recognized as potential antibacterial agents and crucial building blocks in chemical synthesis. Herein, a “SuFEx on silica gel” approach has been developed for one-step synthesis of β-sultams utilizing readily available amines and ethenesulfonyl fluoride (ESF). This process involves a sequential Michael addition of amines to ESF, followed by an intramolecular SuFEx reaction promoted by silica gel. Silica gel facilitates the activation of sulfonyl fluoride through hydrogen bonding between S^VI–F and the surface hydroxyl groups on the silica gel and eliminates HF formed during the reaction. Notably, the use of a base, which is typically required in nearly all known SuFEx reactions, was rendered unnecessary. The β-sultam moiety was successfully incorporated into 26 tested primary amines, including pharmaceuticals and natural products, in high yields, showcasing the broad potential applications of this method.