A convenient route to higher sugars by two-carbon chain elongation using Wittig/dihydroxylation reactions

The combination of a Wittig olefination and a dihydroxylation reaction cons titutes a facile synthetic protocol for the transformation of unprotected c arbohydrates into higher sugars. The Wittig reaction is carried out with te rt-butyl or diphenylmethyl ester stabilized phosphoranes to give (E)-config ured alpha,beta -unsaturated esters as the only products in most cases. The se are dihydroxylated in a diastereoselective fashion using OsO4/NMO. The s tereochemical outcome in the dihydroxylation follows Kishi's empirical rule and gives high diastereoselectivity (5:1-8:1) when starting from sugars wi th the 2,3-threo configuration. When starting from sugars with the 2,3-eryt hro configuration, the diastereoselectivity in the dihydroxylation is low ( 2:1-2.5:1). As a result, the Wittig/dihydroxylation protocol is most effect ive for producing higher sugars with the galacto configuration at the reduc ing end. The two steps can either be carried out individually or, more effi ciently, as a one-pot procedure.