Self‐Promoted N‐Glycosylation: Extended Substrate Scope and Substituent Effects

• Published in: European journal of organic chemistry 2023-04, Vol.26 (16), p.n/a
• Main Authors: Rønne Kristensen, Benedicte, Pedersen, Christian Marcus
• Format: Article
• Language: English
• Subjects: Additives; glycoconjugates; High temperature; mechanism; selectivity; self-promoted glycosylation; Stereoselectivity; substituent effects; Substrates
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.202300213

A self‐promoted glycosylation method for the stereoselective formation of β‐glucosides from a substrate library of glycosyl trichloroacetimidate glycosyl donors and glycosyl acceptors is presented. The simple two‐component reaction takes place at elevated temperatures, without the addition of any additives or catalysts. After a simple basic workup, N‐glycosides were obtained in good yields and with high β‐selectivity and hence this method allows for easy access to glycoconjugates under very mild conditions. The influences of neighboring group participation and substituents, in both the glycosyl donor and acceptor, were studied. Kinetic data were obtained from in situ IR and these were used for a Hammett study. A connection between the pKa of the acceptor and reaction rate was found and new mechanistic insight in self‐promoted glycosylations gained. Amino acid sidechains have been functionalized and glycosylated without the aid of catalysts or additives. Disarmed glycosyl donors were found to react efficiently and excess glycosyl acceptor as well as trichloroacetamide could effectively be removed by aqueous workup. The influence of substituents on the self‐promoted glycosylation was studied by constructing Hammett plots.