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*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

6 Citaten (Scopus)
28 Downloads (Pure)

Samenvatting

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.

Originele taal-2English
Pagina's (van-tot)632-636
Aantal pagina's5
TijdschriftEuropean Journal of Organic Chemistry
Volume2021
Nummer van het tijdschrift4
DOI's
StatusPublished - 26-jan-2021

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