The synthesis of fluorinated carbohydrates

Abstract

Three types of reaction are of particular value in the synthesis of fluoro sugars, namely, nucleophilic displacements with fluoride salts, epoxide cleavage reactions, and glycal addition reactions. These reactions have been developed to the point where effective syntheses of a wide range of fluoro sugars can be planned on a rational basis. Nucleophilic displacement usually involves the treatment of sulphonates with fluoride salts. Reagents of the type tetrabutylammonium fluoride -dipolar aprotic solvent are particularly effective for the displacement of secondary sulphonates. An understanding of the stcric and polar factors which can adversely influence the displacement of carbohydrate secondary sulphonates and of competing reaction pathways usually allows the evaluation of this route in designing effective syntheses of fluoro sugars. Selection of ring size (furanosc, pyranose, septanosc derivatives) is an important parameter in synthesis design. The cleavage of carbohydrate epoxides to give /wrv-fluorohydrins can be effected with reagents such as HF or KHF2. The reactions usually occur stereospecifically and predictably if the epoxide ring is part of a rigid molecular system such as l,6-anhydrohexopyranosc. The reagent CF3OF, which is an effective source of electrophilic fluorine, readily adds to O-acetylated glycals to give 2-deoxy-2-f1uoro derivatives. 2-Deoxy-2-fluoro-D-glucose can be converted into 3,4,6-tri-O-acctyl-2-fluoro-D-glucal and thence by treatment with CF,OF. into “2,2-difluoro-D-glucose. © 1973, Walter de Gruyter. All rights reserved.