Tunable stereoselectivity during sialylation using an N-acetyl-5-N,4-O-oxazolidinone-protected p-toluene 2-thio-sialoside donor with Tf2O/Ph2SO/TTBPy Original Research Article

An N-acetyl-5-N,4-O-oxazolidinone-protected p-toluene 2-thio-sialoside donor, promoted by Ph2SO/Tf2O/TTBPy, was thoroughly investigated in the coupling to various acceptors. The stereoselectivity of the sialylation was found to be dependent on the various reaction conditions, such as pre-activation time, reaction time, the amount of Ph2SO, and TTBPy. A detailed Ph2SO/Tf2O-promoted glycosylation mechanism was proposed, which contained three crucial reactive species: an oxacarbenium ion, C2-sialyloxosulfonium salts, and oxosulfonium supramers. Our research results indicate that it is possible to tune the stereoselectivity of the sialylation by carefully changing the reaction conditions. For instance, Ph2SO (2.0–3.0 equiv)/TTBPy (0–1.0 equiv) promotion gives higher α-selective sialylation in dichloromethane, while Ph2SO (4–5 equiv)/TTBPy (0 equiv) or Ph2SO (2.0 equiv)/TTBPy (2.0 equiv) affords lower stereoselectivity.