On the Origin of Regioselectivity in Palladium-Catalyzed Oxidation of Glucosides

Ieng Chim Wan, Trevor A. Hamlin, Niek N.H.M. Eisink, Nittert Marinus, Casper de Boer, Christopher A. Vis, Jeroen D. C. Codée, Martin D. Witte*, Adriaan J. Minnaard, F. Matthias Bickelhaupt

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

The palladium-catalyzed oxidation of glucopyranosides has been investigated using relativistic density functional theory (DFT) at ZORA-BLYP−D3(BJ)/TZ2P. The complete Gibbs free energy profiles for the oxidation of secondary hydroxy groups at C2, C3, and C4 were computed for methyl β-glucoside and methyl carba-β-glucoside. Both computations and oxidation experiments on carba-glucosides demonstrate the crucial role of the ring oxygen in the C3 regioselectivity observed during the oxidation of glucosides. Analysis of the model systems for oxidized methyl β-glucoside shows that the C3 oxidation product is intrinsically favored in the presence of the ring oxygen. Subsequent energy decomposition analysis (EDA) and Hirschfeld charge analysis reveal the role of the ring oxygen: it positively polarizes C1/C5 by inductive effects and disfavors any subsequent buildup of positive charge at neighboring carbon atoms, rendering C3 the most favored site for the β-hydride elimination.

Original languageEnglish
Pages (from-to)632-636
Number of pages5
JournalEuropean Journal of Organic Chemistry
Volume2021
Issue number4
DOIs
Publication statusPublished - 26-Jan-2021

Keywords

  • Carbohydrates
  • Density functional calculations
  • Energy decomposition analysis
  • Oxidation
  • Regioselectivity

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