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Seminar: "Catalytic Glycosylation and the Interplay between Confirmation and Reactivity" (Lecture)

Friday 23 February 2018Add to my calendar
from 11:00
prof. C.M. Pedersen (Univ. Kopenhagen, Denmark)

Glycosylation using the trichloroacetimidate donor has been one of the key-methods for oligosaccharide synthesis since it was developed by Schmidt in the early eighties.[1] The reaction has been studied in detail over the years and many modification have been made, but the classic conditions remain the most frequently used. These conditions involve catalysis by either the Lewis acid BF3∙OEt2 or a Brønsted acid such as a sulfonic acid; most often TMSOTf, which forms TfOH in situ. Recently we have reinvestigated the activation of trichloroacetimidates.

Figure 1. Stereospecific catalytic O-glycosylation.

From low temperature NMR studies [2] insight into the activation using the most commonly used catalysts, i.e. BF3∙OEt2 and TMSOTf, two different reaction pathways were observed. With BF3∙OEt2 a pre-complexation was observed followed by decomposition to give the glycosyl fluorides.[3] Using TMSOTf as the catalyst resulted in the formation of the corresponding glycosyl triflate. Changing to acids with less nucleophilic counter-ions, such as TMSNTf2 or Tf2NH, gave a stable intermediate containing the activated trichloroacetimidate. Preparative glycosylations [4] based on the findings from the NMR study revealed that this new mode of activation gave glycosides with high stereospecificity. The scopes and limitations were studied by challenging the method in rhamnosylations.[5] As a second part our work on reactivity tuning by changing the conformation of the pyranoside ring will be discussed.

[1] Schmidt R.R.; Michel J., Facile Synthesis of α- and β-O-Glycosyl Imidates; Preparation of Glycosides and Disaccharides. Angew. Chem. Int. Ed. 1980, 19, 731-732.
[2] Qiao Y.; Ge W.; Jia, L.; Hou, X.; Wang, Y.; Pedersen, C. M., Glycosylation intermediates studied using low temperature 1H- and 19F-DOSY NMR: new insight into the activation of trichloroacetimidates. Chem. Commun. 2016, 52, 11418-11421.
[3] Nielsen M.M.; Stougaard B.A.; Bols, M.; Glibstrup, E.; Pedersen, C.M., Glycosyl Fluorides as Intermediates in the BF3∙OEt2 Promoted Glycosylation with Trichloroacetimidates. Eur. JOC 2017, 1281-1284
[4] Kowalska, K.; Pedersen, C. M., Catalytic stereospecific O-glycosylation. Chem. Commun. 2017, 53, 2040-2043.
[5] Elferink. H, Pedersen, C.M., L-Rhamnosylation: The Solvent is the Solution. Eur. JOC 2017, 53-59

Thomas Boltje