SN2-Type Glycosylation with Unprotected Pyranoses

An SN2 mechanism was proposed for highly stereoselective glycosylation of benzoic acid with unprotected α-D-glucose under Mitsunobu conditions in dioxane, while an SN1 mechanism seems to be responsible for non-stereoselective glycosylation in DMF. The SN2-type glycosylation can be applicable to various unprotected pyranoses as glycosyl donors and a wide range of carboxylic acids, phenols, and imides as glycosyl acceptors, retaining its high stereoselectivity (34 examples). Glycosylation of a carboxylic acid with unprotected α-D-mannose proceeded also in an SN2 manner to directly afford a usually less accessible 1,2-cis-mannoside. An extremely short-step total synthesis of a middle molecule (1874 Da) natural glycoside with antitumor activity, coriariin A, was achieved via a double SN2 glycosylation strategy with two molecules of unprotected α-D-glucose.