One-pot α-glycosylation pathway via the generation in situ of α-glycopyranosyl imidates in N, N-dimethylformamide

Abstract

Divergent pathways are disclosed in the activation of 2- O-benzyl-1-hydroxy sugars by a reagent combination of CBr 4 and Ph 3P, all of which afford one-pot α-glycosylation methods. When this reagent is used in CH 2Cl 2, the 1-hydroxy sugar is converted to the α-glycosyl bromide in a conventional way and leads to the one-pot α-glycosylation method based on a halide ion-catalytic mechanism. In either DMF or a mixture of DMF and CHCl 3, however, alternative α-glycosyl species are generated. From the 1H and 13C NMR study of the products, as well as the reactions using Vilsmeier reagents [(CH 3) 2N + CHX]X − (X = Br and Cl), these were identified as cationic α-glycopyranosyl imidates having either Br − or Cl − counter ion. The cationic α-glycosyl imidate (Br −), derived specifically in the presence of DMF, is more reactive than the α-glycosyl bromide and thus is responsible for the accelerated one-pot α-glycosylation. The one-pot α-glycosylation methodology performed in DMF was assessed also with different types of acceptor substrates including tertiary alcohols and an anomeric mixture of 1-OH sugars.