Palladium/Photoredox‐Catalyzed Three‐Component Coupling for Glycoconjugation

ABSTRACT Glycoconjugation—the installation of sugar moieties onto molecular targets—represents a powerful strategy for modulating biological functions, yet the intrinsic structural intricacy of both carbohydrate donors and aglycone acceptors has long rendered this endeavor a formidable synthetic hurdle. Although the Pd‐catalyzed allylic substitution is widely exploited to build complex frameworks, its use in glycoconjugation remains scarce. Here we disclose a visible‐light‐driven, Pd(0)‐catalyzed, three‐component coupling that assembles elaborate glycoconjugates. The protocol employs readily accessible, bench‐stable ortho‐iodobiphenyl S ‐glycosides as glycosyl donors, and proceeds through glycosyl radical intermediates. The Pd(0) catalyst serves dual roles: it liberates glycosyl radicals from the S ‐glycosides and converts these radicals, together with 1,3‐butadiene, into closed‐shell allyl‐Pd electrophiles. Capture of these allyl‐Pd complexes by diverse nucleophiles delivers the corresponding glycoconjugates. The transformation, showcasing a strategy to deploy the Pd‐catalyzed allylic substitution in glycoconjugation, exhibits broad functional‐group compatibility and enables late‐stage modification of oligopeptides and bioactive small molecules. Experimental studies provide insights into the reaction mechanism and elucidate the origin of glycosyl radicals.