Synthesis of β-Glucosides with 3-O-Picoloyl-Protected Glycosyl Donors in the Presence of Excess Triflic Acid: Defining the Scope

Abstract

Excellent β-stereoselectivity for the glycosylation with glucosyl donors equipped with the 3-O-picoloyl (Pico) group, without the use of participating group, was achieved in the presence of NIS/excess TfOH promoter system. A complete investigation of the scope of this reaction was performed, revealing all important attributes of successful glycosylation. While altering the halogen source was tolerated, substitution of the triflate anion resulted in complete loss of stereoselectivity. Protonation of the Pico group was determined to be crucial in this reaction. The stability or extent of the protonated pyridine ring was also found to be another important key factor in obtaining high stereoselectivity. The nucleophilicity of the acceptor was found to be proportional to the stereoselectivity obtained, suggesting an S_N 2-like mechanism.

Keywords: glycosylation; mechanism; oligosaccharides; stereoselectivity; synthesis.