Development, Scope, and Catalyst Selection in Boron-Catalyzed Iterative Glycosylation

Boron-catalyzed glycosylations provide an effective strategy for the rapid and simple preparation of glycosidic bonds by using glycosyl fluoride donors and silyl ether acceptors. This study examines the utility of this reaction type in iterative glycosylations, where the sequence of formation of glycosidic bonds with silyl ether acceptors is governed by a trialkyl silane structure rather than the inherent reactivity of the hydroxyl precursors. Relative rates and selectivities of glycosylations were studied by ¹⁹F NMR, identifying BF₃·OEt₂ as an excellent catalyst choice for iterative processes. Using this protocol, a number of site-selective and stereoselective iterative glycosylations were demonstrated to produce tri- and tetrasaccharides from monosaccharide precursors, and more complex examples were prepared by related stepwise approaches.