Strain-Release Glycosylation of Thio- and Selenoglycosides Enabled by Activation of Donor–Acceptor Oxiranes with Catalytic TfOH

We have developed a strain-release glycosylation method for thio/selenoglycosides utilizing donor-acceptor oxiranes (DAOs) and triflic acid (2 mol %) via C-C bond cleavage under ambient conditions. This protocol is effective for acid-sensitive and sterically hindered substrates, demonstrating broad applicability. Experimental results and DFT calculations reveal that DAO/TfOH-derived zwitterionic oxocarbenium species activate donors via glycosyl zwitterion intermediates, facilitating glycosidic bond formation and proton transfer. This approach pioneers epoxide-mediated thio/selenoglycosides activation, offering a mild, efficient platform for diverse glycoside synthesis and advancing methodologies in carbohydrate chemistry.