Site-Divergent Delivery of Terminal Propargyls to Carbohydrates by Synergistic Catalysis

Carbohydrate-containing molecules are ubiquitous in nature and essential to sustaining lives. Selective modification of carbohydrates provides tremendous opportunities to interrogate the biological roles of this fundamental class of molecules. However, to functionalize a specific hydroxyl group out of numerous others in a carbohydrate scaffold has been a historical challenge. Here, we report a strategy that allows for the site-selective and site-divergent delivery of terminal propargyls to various monosaccharides, the basic units of carbohydrates. This strategy is based on synergistic catalysis that combines copper and borinic acid catalysis. With a pair of antipodal ligands, this method can be tuned to propargylate either the equatorial or the axial hydroxyl with high selectivities. The generality of this transformation is manifest in the direct propargylation of complex, unprotected glycosylated natural products. Equipped with terminal alkyne groups, the products obtained by this method are primed for further manipulations, including copper-catalyzed azide-alkyne coupling chemistry.