This work implements a catalytic S_N2 glycosylation by employing an amide-functionalized 1-naphthoate platform as a latent glycosyl leaving group. Upon gold-catalyzed activation, the amide group enables the S_N2 process by directing the attack of the glycosyl acceptor via H-bonding interaction, which results in stereoinversion at the anomeric center. Unique in this approach is that the amide group also enables a novel safeguarding mechanism by trapping oxocarbenium intermediates and, hence, minimizing stereorandom S_N1 processes. The strategy is applicable to the synthesis of a broad range of glycosides with high to excellent levels of stereoinversion from anomerically pure/enriched glycosyl donors. These reactions are generally high-yielding, and their applications in the synthesis of challenging 1,2-cis-linkage-rich oligosaccharides are demonstrated.

The stereoselective construction of 1,2-cis furanosidic linkage is synthetically challenging. A strategy that applies to all furanose types remains elusive. In this work, a solution is developed based on gold catalysis and the deployment of the directing-group-on-leaving-group strategy, where a basic oxazole group in the gold-activated leaving group facilitates the stereoinvertive attack by glycosyl acceptors. In addition to exhibiting good to excellent 1,2-cis selectivities, these furanosylation reactions are high-yielding and mostly complete in 30 min to 2 h. A broad range of 1,2-cis-furanosides is prepared. Although some are uncommon, the ease of access enabled by this approach presents new opportunities to study their applications in medicine and materials research.

Generally applicable and stereoselective formation of 1,2-cis-glycopyranosidic linkage remains a long sought after yet unmet goal in carbohydrate chemistry. This work advances a strategy to this challenge via stereoinversion at the anomeric position of 1,2-trans glycosyl ester donors. This S_N2 glycosylation is enabled under gold catalysis by an oxazole-based directing group optimally tethered to a leaving group and achieved under mild catalytic conditions, in mostly excellent yields, and with good to outstanding selectivities. The strategy is also applied to the synthesis of oligosaccharides.