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 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 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 mono-saccharide precursors, and more complex examples were possible by related stepwise approaches.