Koenigs–Knorr reactions. Part 1. Effects of a 2-O-acetyl substituent, the promoter, and the alcohol concentration on the stereoselectivity of reactions of 1,2-cis-glucopyranosyl bromide

Abstract

Koenigs–Knorr reactions of 2,3,4,6-tetra-O-methyl-α-D-glucopyranosyl bromide and the 2-O-acetyl analogue with cyclohexanol, with various promoters in the customary solvents, were investigated at 23 °C. The promoters employed were silver(I) oxide with iodine in chloroform, mercury(II) oxide with mercury(II) bromide in chloroform, cadmium carbonate in toluene, and mercury(II) cyanide in benzene–nitromethane (1 : 1 v/v). Primary emphasis was on reactions having an alcohol (ROH) to glucosyl halide (RBr) molar ratio of 3 : 1 at a glucosyl halide concentration of ca. 6.5 × 10^–2M. In addition, mercury cyanide-promoted reactions employing 10 : 1 and 30 : 1 molar ratios of ROH to RBr were studied. The 2-O-acetylglucosyl bromide selectively afforded the β-glucoside (95–98% of the glucosidic products) in all the reactions. In contrast, reactions of the 2-O-methylglucosyl bromide were less selective (53–91%β-glucoside), and the selectivity was dependent on the promoter and alcohol concentration. The selectivity for β-glucoside formation was greatest in the silver oxide system and least in the cadmium carbonate system. In the mercury cyanide system, selectivity for β-glucoside formation increased as the alcohol concentration was increased.