Abstract: The pyranoside-into-furanoside (PIF) rearrangement is an uncommon but important process in carbohydrate chemistry. The quantum chemical investigation of the driving force of the recently discovered TfOH-catalyzed ring contraction revealed that it stemmed from the π–π interactions of the phenyl rings in benzoyl-protecting groups. In this study, we focused on the kinetic aspects, which included preliminary 2-O-benzoyl group rotation followed by the protonation of the endo-cyclic O5 atom. Using a combination of DFT and DLPNO-CCSDT methods, we found that in some cases, DFT may not produce adequate energies at the rate-limiting stage of the pyranoside ring opening, presumably due to inadequate modeling of Van der Waals interactions. Predicted rate constants for the PIF rearrangement of the β-O-methyl and β-S-ethyl galactosides were in agreement with NMR kinetic experiments, as the latter reacts significantly slower. The estimated constant for the β-O-phenyl galactoside supports its inability to undergo ring contraction and suggests temperatures of over 400 K for such transformation. The proposed mechanism was additionally confirmed by substituting the triflic acid with the much weaker trifluoroacetic one, which led to a drastic decrease of the reaction rate both in computations and in the experiment.

Cite: Gerbst A.G. , Argunov D.A. , Krylov V.B. , Nifantiev N.E.
The Computational Study of the Mechanism of the Acid-Promoted Pyranoside-into-Furanoside Rearrangement
Molecules. 2026. V.31. N18. 3145 . DOI: 10.3390/molecules31183145 WOS Scopus OpenAlex

Dates:

Submitted:	Aug 11, 2026
Published online:	Sep 8, 2026

Identifiers:

≡ Web of science:	WOS:001891374800001
≡ Scopus:	2-s2.0-105051823088
≡ OpenAlex:	W7211932890

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