Glycosyl fluorides remain popular for a variety of synthetic and experimental applications largely because they are much more stable than other glycosyl halides. This stability results from the high energy of the glycosidic C-F bond relative to its brominated or chlorinated counterparts [1], and permits a wide variety of uses. For example, glycosyl fluorides have been shown to be useful intermediates in the synthesis of oligosaccharides and glycoconjugates [2], and have been used as probes in studies of enzyme specificity and mechanism [3]. We have recently become intrigued with the possibility of using acetylated glycosyl fluorides as the final analytes in investigations of difficult-to-analyze carbohydrate polymers in environmental samples [4], and so wished to study the conversion of methyl glycosides into acetylated glycosyl fluorides as an analog to reaction termination in solvolysis experiments [5].
We report here an efficient micro-scale procedure for converting methyl glycosides into glycosyl fluoride per-O-acetates. The conversion is effected by treatment of the methyl glycosides with liquid anhyd HF followed by direct reaction with acetic anhydride. The procedure is a variation on the classical method of synthesis published by Brauns over seventy years ago [6]. In that study glucose and xylose peracetates were treated with anhyd liquid HF in sealed platinum vessels to form the 1-fluorinated counterparts. The reaction scheme is also similar to that presented by Wiesner [7] wherein per-O-acylated sugars were treated with a mixture of acetic anhydride and HF.