AgOTf-Assisted β-Glucuronidation Enables Convergent Synthesis of β-(1 → 4)-Linked Polyglucuronates up to the 32-Mer.

β-Glucuronides are widespread motifs in biologically important glycoconjugates and oligo/polysaccharides. However, the C-5 carboxylate of glucuronic acid renders glucuronosyl donors poor electrophiles and glucuronosyl acceptors weak nucleophiles, often leading to unproductive glycosylation. We disclose a robust, general gold(I)-catalyzed β-glucuronidation using glucuronosyl 8-alkynyl-1-naphthoate donors with the assistance of AgOTf catalysis. Mechanistic studies reveal the role of AgOTf: it promotes orthoester-to-β-glycoside conversion, likely through trace acid generated from the interaction of Ag+ with adventitious moisture, while HOTf generated in situ from -OTf facilitates regeneration of the active Au(I) catalyst from the resting-state vinyl-digold complex. The method is compatible with diverse substrates and protecting-group patterns, including strongly electron-withdrawing substituents that attenuate the reactivity. Leveraging this platform, we achieve a convergent synthesis of β-(1 → 4)-polyglucuronate (glucuronan) up to a 32-mer, addressing one of the most demanding linkage patterns in anionic polysaccharide construction.