Glycosyl o-[1-(p-MeO-Phenyl)vinyl]benzoates (PMPVB) as Easily Accessible, Stable, and Reactive Glycosyl Donors for O-, S-, and C-Glycosylations under Brønsted Acid Catalysis.

Abstract

Methods suitable for the synthesis of both O- and S-glycosylations are relatively rare because commonly used promoters like halonium sources or gold catalysts are incompatible with thiols as nucleophiles. Here, we present (p-MeO)phenylvinylbenzoates (PMPVB) as easily accessible, stable, and reactive alkene-based glycosyl donors that can be activated with catalytic amounts of a Brønsted acid. This activation protocol not only allows us to synthesize O-glycosides but also can successfully provide S- and C-linked glycosides. The armed and disarmed donors lead to product formation in 5 min, showcasing the high reactivity of the donors. Competitive experiments show that the PMPVB donors are much more reactive than the corresponding PVB donors even under NIS/TMSOTf conditions, whereas PVB donors are not reactive enough to be efficiently activated under Brønsted acid conditions. The potential of the catalytic glycosylation protocol has also been showcased by synthesizing trisaccharides. The Brønsted acid activation of PMPVB donors also allows access to C-glycosides in a stereoselective fashion. The easy accessibility of the donor aglycon on a multigram scale in just two steps makes the PMPVB donors highly attractive alternatives.