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On the Origin of Regioselectivity in Palladium‐Catalyzed Oxidation of Glucosides
Author(s) -
Wan Ieng Chim Steven,
Hamlin Trevor A.,
Eisink Niek N. H. M.,
Marinus Nittert,
Boer Casper,
Vis Christopher A.,
Codée Jeroen D. C.,
Witte Martin D.,
Minnaard Adriaan J.,
Bickelhaupt F. Matthias
Publication year - 2021
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202001453
Subject(s) - regioselectivity , chemistry , palladium , ring (chemistry) , catalysis , oxygen , density functional theory , glucoside , medicinal chemistry , photochemistry , computational chemistry , stereochemistry , organic chemistry , medicine , alternative medicine , pathology
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.