User-Friendly Thioglycoside Preactivation via Instant Sulfenyl Chloride Generation

Thioglycoside preactivation enables one-pot oligosaccharide assembly but relies on unstable sulfenyl chloride activators. We report a user-friendly manifold that forms sulfenyl chlorides in seconds from common thiols and <i>N</i>-chlorosuccinimide, with succinimide precipitating and the clear supernatant serving as a drop-in activator solution. The protocol tolerates the substrate scope, accommodating special stereoselective glycosylation reactions and iterative one-pot sequences. A concise synthesis of a human milk tetrasaccharide demonstrates rapid one-pot access to a biologically relevant motif.