Mechanistic Insights into the Gold(I)-Catalyzed Activation of Glycosyl ortho-Alkynylbenzoates for Glycosidation

Anomerization, which involves cleavage and formation of the anomeric C–O bond, is of fundamental importance in the carbohydrate chemistry. Herein, the unexpected gold­(I)-catalyzed anomerization of glycosyl ortho-alkynylbenzoates has been studied in detail. Especially, crossover experiments in the presence of an exogenous isochromen-4-yl gold­(I) complex confirm that the anomerization proceeds via the exocleavage mechanism, involving (surprisingly) the addition of the isochromen-4-yl gold­(I) complex onto a sugar oxocarbenium (or dioxolenium) and an elimination of LAu+ from the vinyl gold­(I) complex. The inhibitory effect of the exogenous isochromen-4-yl gold­(I) complex when in stoichiometric amount on the anomerization has guided us to disclose an isochromen-4-yl gem-gold­(I) complex, which is inactive in catalysis but in equilibrium with the monogold­(I) complex and the LAu+ catalyst. The proposed key intermediate in the anomerization, a transient glycosyloxypyrylium species, is successfully trapped via a cycloaddition reaction with n-butyl vinyl ether as a dienophile. SN2-like substitution of the initially formed glycosyloxypyrylium intermediate has then been achieved to a large extent via charging with acceptors in an excess amount to lead to the corresponding glycosides in a stereoselective manner.