Koenigs–Knorr reactions. Part 3. Mechanistic study of mercury(II) cyanide promoted reactions of 2-O-acetyl-3,4,6-tri-O-methyl-α-D-glucopyranosyl bromide with cyclohexanol in benzene–nitromethane

Abstract

The kinetics and products of reactions of 2-O-acetyl-3,4,6-tri-O-methyl-α-D-glucopyranosyl bromide(I) with cyclohexanol in the presence of Hg(CN)₂ in nitromethane–benzene (1 : 1 v/v) at 10–25 °C were investigated by polarimetry, g.l.c., and ¹H n.m.r. The reactions exhibited a first-order kinetic dependence on the glucosyl bromide and Hg(CN)₂ concentrations, but the reaction rates were independent of the cyclohexanol concentration. Cyclohexyl 2-O-acetyl-3,4,6-tri-O-methyl-β-D-glucopyranoside (IV) was the major final product (>90%) in reactions. The initial reaction is believed to involve rate-determining, Hg(CN)₂-assisted heterolysis of the carbon–bromine bond to form the glucopyranosyl carboxonium ion. Glucoside formation then results from reaction of the alcohol with the carboxonium ion as the ion pair, the dissociated carboxonium ion, or an intermediate orthoester, 1,2-O-(1-cyclohexyloxyethylidene)-3,4,6-tri-O-methyl-α-D-glucopyranose (III). The orthoester (III) was shown to selectively form the β-glucoside (IV) under the reaction conditions used. The mole fraction of orthoester (III) in the initial reaction products was always substantially greater than that of cyclohexyl 2-O-acetyl-3,4,6-tri-O-methyl-α-D-glucopyranoside (V) and increased as the alcohol concentration decreased. Stereoselective formation of the β-glucoside (IV) in the overall reaction of the glucosyl bromide (I) is due to the fact that in those reactions of (I) which do not yield (IV) directly, α-glucoside (V) formation is minimized by preferential formation of the orthoester (III) which selectively forms the β-glucoside (IV).