Synthesis and N.M.R. spectra of methyl 2-deoxy-2-fluoro- and 3-deoxy-3-fluoro-α- and β-d-glucopyranosides

Abstract

Methyl 3-deoxy-3-fluoro-α- and β-D-glucopyranosides and α- and β-D-glucofuranosides were prepared by methanolysis of 3-deoxy-3-fluoro-1,2:5,6-di-O-isopropylidene-α-D-glucofuranose. Crystalline 3,4,6-tri-O-acetyl-2-deoxy-2-fluoro-α-D-glucopyranosyl chloride (2) and the corresponding glycosyl bromide (3) were prepared from 1,3,4,6-tetra-O-acetyl-2-deoxy-2-fluoro-β-D-glucopyranose (1). Reaction of 2 with methanol under the conditions of both silver triflate- and silver perchlorate-catalyzed glycosylation showed remarkable lack of stereoselectivity for the formation of the corresponding methyl α-glycoside, despite the presence at C-2 of the fluorine functionality presumably not capable of neighboring-group participation. Pure methyl 2-deoxy-2-fluoro-α- and β-d-glucopyranosides were obtained by fractional crystallization from the mixture formed by methanolysis of 1. The structure of these substances as well as of several other derivatives of 2-deoxy-2-fluoro- and 3-deoxy-3-fluoro-d-glucose were verified by n.m.r. (1H, 13C, and 19F) spectroscopy.