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Synthesis of β‐Glucosides with 3‐ O ‐Picoloyl‐Protected Glycosyl Donors in the Presence of Excess Triflic Acid: Defining the Scope
Author(s) -
Mannino Michael P.,
Demchenko Alexei V.
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201905278
Subject(s) - stereoselectivity , chemistry , glycosylation , trifluoromethanesulfonate , protonation , pyridine , stereochemistry , glycosyl , glycosyl donor , medicinal chemistry , nucleophile , combinatorial chemistry , organic chemistry , ion , catalysis , biochemistry
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.