Stereoselective 1,2-<i>cis</i> Furanosylations Catalyzed by Phenanthroline

Abstract

Stereoselective formation of the 1,2-<i>cis</i> furanosidic linkage, a motif of many biologically relevant oligosaccharides and polysaccharides, remains an important synthetic challenge. We herein report a new stereoselective 1,2-<i>cis</i> furanosylation method promoted by phenanthroline catalysts under mild and operationally simple conditions. NMR experiments and density functional theory calculations support an associative mechanism in which the rate-determining step occurs from an inverted displacement of the faster-reacting phenanthrolinium ion intermediate with an alcohol nucleophile. The phenanthroline catalysis system is applicable to a number of furanosyl bromide donors to provide the challenging 1,2-<i>cis</i> substitution products in good yield with high anomeric selectivities. While arabinofuranosyl bromide provides β-1,2-<i>cis</i> products, xylo- and ribofuranosyl bromides favor α-1,2-<i>cis</i> products.