Palladium/Photoredox‐Catalyzed Three‐Component Coupling for Glycoconjugation

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.