Glycosylations by Nucleophilic Substitution at the Aglycone Carbon

SCHEME 4.53 Glycoside synthesis by nueleophilic substitution at the aglycone earbon. 

Generally, the products derived from the open-chain form are insignificant in the reaction mixture and stereocontrol between the anomeric forms can be achieved. It was observed that the anomeric oxygen in the equatorial alkoxide 276 has enhanced nucleophilicity compared with the axial [284]. Often referred to as the kinetic anomeric effect, this phenomenon can govern the diastereoselective formations of the equatorial glycosides [579]. The anomeric effect, however, favors the formation of the thermodynamically more stable axial glycosides and chelation control can also play a role in determining anomeric stereoselectivity. 

SCHEME 4.56 Regioselective glycoside synthesis by anomeric O-alkylation. 

The difference in stereoselectivity was explained by the formation of differing intramolecular metal complexes (273 and 277). 

Most glycosylations by anomeric O-alkylations were performed on triflates of primary alcohols. Nevertheless, reactions with secondary aUcyl triflates, including carbohydrates, were also described [581]. These reactions afford inverted configurations in the aglycone. 

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