O-Glycosyl Trichloroacetimidates as Glycosyl Donors and Platinum(IV) Chloride as a Dual Catalyst Permitting Stereo- and Regioselective Glycosidations

Abstract

Stereo- and regioselective glycosidation is still a great challenge in carbohydrate chemistry. Among the tremendous endeavors in this area, acid–base catalysis, available to O-glycosyl trichloroacetimidate activation, is of particular interest. It features an alternative glycosidation pathway initiated by the sequential binding between the catalyst and the glycosyl acceptor and then with the glycosyl donor. Through the formation of a catalyst–acceptor adduct, increased proton acidity and oxygen nucleophilicity are reached, thus enforcing donor activation and concomitant acceptor transfer. As the reaction takes place via an SN2-type transition state, essentially stereoselectivity is granted. Platinum(IV) chloride is an ideal catalyst in this regard; it is a weak Lewis acid, yet it possesses high affinity to the glycosyl acceptor hydroxy group due to its ligand-binding capacity, thus affording from the α-configurated glycosyl donor the glycosidation product predominantly in β-configuration. In addition, the capacity of platinum(IV) chloride to bidentate ligation is another advantage, as it enhances nucleophilicity differences between hydroxy groups, thus permitting regioselective glycosidation, as observed for various 1,2-cis-, 1,3-, and 1,2-trans-diol and 1,2,3-triol moieties present in carbohydrate acceptors. This observation found application in an efficient saponin natural product synthesis.