A NEW APPROACH TO THE SYNTHESIS OF GLYCOSIDES

An new approach towards glycosides, which obviates the use of promoters and depends upon the acidity of the glycosyl acceptor is proposed to achieve regioselective glycosidation. Glycosylidene carbenes, generated under thermal or photolytic conditions from O-benzylated or O-acylated I-azi-glycoses, or from glycono-1,5- (or 1,4)-lactone tosylhydrazones react with hydroxy compounds to yield glycosides. The preparation of these precursors, their structure, their thermal stability, and their products of thermolysis are discussed. A mechanism is proposed to explain and predict the reaction of 1-azi-glycoses with mono-, di-, and triols. Protonation of the carbene in the sigma-plane leads to an ion-pair, which cannot immediately form glycosides. The fate of this ion pair depends upon the pK of the glycosyl acceptor, inter- and intramolecular hydrogen bonds, the direction of H-bonds, the presence of a neighbouring group at C(2), the configuration of the glycosyl acceptor, the solvent, and the temperature. Strongly acidic hydroxy compounds give glycosides in high yields and stereoselectively. Successful regio- and stereoselective glycosidation of diols and triols depends strongly upon intra- (and inter)molecular hydrogen bonds, both between the hydroxy groups of the acceptor and between functional groups of the donor and hydroxy groups of the acceptor. This is illustrated by a number of significant cases. For some of them, regioselectivity is complementary to the one observed in glycosidations of the Koenigs-Knorr-type, for others it is not. Reasons for this are discussed. Other cases present the preferential glycosylation of secondary hydroxy groups in the presence of a primary one, and the selective formation of alpha-D-glycosides of AllNAc and GlcNAc. Intramolecular reactions of alkoxyalkyl carbenes are illustrated by a new method for the formation of benzylidene acetals under basic conditions, and by a new synthesis of homobenzofurans. New reactions, leading to the formation of C,C bonds at the anomeric centre are presented: the synthesis of spiro-oxiranes, of dialkoxy-spiro-cyclopropanes, and of the first glycosylated, enantiomerically pure derivatives of C60-buckminsterfullerene.