Conformationally constrained glycosyl fluoride donors enable chemoselective glycosylation.

Tuning the relative reactivity of glycosyl donors provides a key approach in the development of iterative glycosylations and convergent oligosaccharide assembly methods. While the sugar identity plays an important role in governing reactivity, strategies that activate or deactivate a donor play a key role in effective approaches. This work focuses on the use of constrained glycosides with cyclic protecting groups to alter the reactivity of glycosyl fluoride donors. Boron-catalyzed glycosylations of glycosyl fluoride donors with silyl ether acceptors can be sequenced by using the constrained glycoside effect to deactivate donors that possess this structural feature. The approach allows constrained glycosyl fluorides to be carried through synthetic steps involving similar donors that lack cyclic protecting groups. Additionally, one pot methods can be designed with sequential additions made possible by the constrained deactivation effect. NMR studies provide a simple mechanistic tool for quickly assessing the magnitude of reactivity changes imparted by a given substrate modification.