Repurposing a Donor 2-OH Group for Catalyst-Controlled Stereodivergent Glycosylation

Abstract The free C2-OH group of glycosyl donors is generally viewed as a liability in glycosylation because it can act as a competing nucleophile and compromise stereocontrol. Here, we show that this functionality can instead be harnessed as a programmable stereochemical element in a catalyst-controlled stereodivergent glycosylation. A single β-configured 2-hydroxy glycosyl 8-alkynyl-1-naphthoate donor was found to deliver either β- or α-glycosides simply by changing the gold(I) catalyst system. Triflate-based catalysts promoted highly β-selective glycosylation, whereas bistriflimide-based conditions enabled complementary α-selective glycosylation from the same donor. The method is applicable to a range of carbohydrate and noncarbohydrate acceptors and enables the programmable assembly of glucooligosaccharides bearing β-(1→6), α-(1→6), and alternating α/β-(1→6) linkages from a common donor platform. Mechanistic studies, including intermediate characterization, variable-temperature NMR experiments, computational analysis, and control glycosylations with the corresponding 2-O-Bn donor, reveal distinct roles of the donor 2-OH group in the two stereochemical manifolds.