Anomeric Triflates versus Dioxanium Ions: Different Product-Forming Intermediates from 3-Acyl Benzylidene Mannosyl and Glucosyl Donors

The Journal of Organic Chemistry, vol. 89, pp. 1618–1625

Abstract

High Resolution Image Download MS PowerPoint Slide Minimal structural differences in the structure of glycosyl donors can have a tremendous impact on their reactivity and the stereochemical outcome of their glycosylation reactions. Here, we used a combination of systematic glycosylation reactions, the characterization of potential reactive intermediates, and in-depth computational studies to study the disparate behavior of glycosylation systems involving benzylidene glucosyl and mannosyl donors. While these systems have been studied extensively, no satisfactory explanations are available for the differences observed between the 3- O -benzyl/benzoyl mannose and glucose donor systems. The potential energy surfaces of the different reaction pathways available for these donors provide an explanation for the contrasting behavior of seemingly very similar systems. Evidence has been provided for the intermediacy of benzylidene mannosyl 1,3-dioxanium ions, while the formation of the analogous 1,3-glucosyl dioxanium ions is thwarted by a prohibitively strong flagpole interaction of the C-2-O-benzyl group with the C-5 proton in moving toward the transition state, in which the glucose ring adopts a B 2,5 -conformation. This study provides an explanation for the intermediacy of 1,3-dioxanium ions in the mannosyl system and an answer to why these do not form from analogous glucosyl donors.

Authors 11

1. Wouter A. Remmerswaal Aachen

   Leiden University

   Affiliation as printed

   Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden 2300 RA, The Netherlands

2. Hidde Elferink

   Radboud University Nijmegen

   Affiliation as printed

   Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, Nijmegen 6525 AJ, The Netherlands

3. Kas J. Houthuijs

   Radboud University Nijmegen · HFML-FELIX

   Affiliation as printed

   Institute for Molecules and Materials, FELIX Laboratory, Radboud University, Toernooiveld 7, Nijmegen 6525 ED, The Netherlands

4. Floor ter Braak

   Radboud University Nijmegen

   Affiliation as printed

   Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, Nijmegen 6525 AJ, The Netherlands

5. Giel Berden

   Radboud University Nijmegen · HFML-FELIX

   Affiliation as printed

   Institute for Molecules and Materials, FELIX Laboratory, Radboud University, Toernooiveld 7, Nijmegen 6525 ED, The Netherlands

6. Stefan van der Vorm Aachen

   Leiden University

   Affiliation as printed

   Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden 2300 RA, The Netherlands

7. Jonathan K. Martens

   Radboud University Nijmegen · HFML-FELIX

   Affiliation as printed

   Institute for Molecules and Materials, FELIX Laboratory, Radboud University, Toernooiveld 7, Nijmegen 6525 ED, The Netherlands

8. Jos Oomens

   Radboud University Nijmegen · HFML-FELIX

   Affiliation as printed

   Institute for Molecules and Materials, FELIX Laboratory, Radboud University, Toernooiveld 7, Nijmegen 6525 ED, The Netherlands

9. Gijsbert A. van der Marel Aachen

   Leiden University

   Affiliation as printed

   Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden 2300 RA, The Netherlands

10. Thomas Jan Boltje

    Radboud University Nijmegen

    Affiliation as printed

    Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, Nijmegen 6525 AJ, The Netherlands

11. Jeroen D. C. Codée corresponding Aachen

    Leiden University

    Affiliation as printed

    Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden 2300 RA, The Netherlands