Ferrier Rearrangement Intermediates Featuring Aliphatic Acyl Protecting Groups
- 1Institute of Chemistry and Biochemistry, Freie Universität Berlin, Altensteinstraße 23a, Berlin, Germany, 14195
- 2Department of Molecular Physics, Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 4–6, Berlin, Germany, 14195
- 3Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, Potsdam, Germany, 14476
Abstract
The Ferrier rearrangement of 1,2-unsaturated monosaccharides (glycals) to 2,3-unsatured glycosides, is important for the synthesis of pharmaceuticals and natural products. Mechanistically, the nucleophilic substitution proceeds via a cationic intermediate, the “Ferrier cation”, whose structure is difficult to capture with conventional analytical techniques. Here, we characterize the Ferrier cations of glucal and galactal building blocks involving aliphatic acyl protecting groups (pivaloyl-, levulinoyl- and chloroacetyl esters) using cryogenic gas-phase infrared spectroscopy. Comparing experimental and computed spectra of candidate structures, we established that all intermediates are stabilized by interactions of the C4 acyl protecting group with the C3 carbon of the pyranose ring (neighboring participation), potentially steering the stereochemical outcome of the Ferrier rearrangement. The resulting C4-C3-dioxolenium ion structure appears to be general to aliphatic acyl protecting groups, contributing to our fundamental understanding of Ferrier rearrangement reactions.
Related
- Aliphatic C–H bond methylation enabled by hydrogen atom transfer
- Direct photochemical activation of aliphatic carboxylic acids toward phosphinylation via polarity-reversed Arbuzov process
- Redox-Active Leaving Group Enables the Deoxygenative Arylation of Unactivated Aliphatic Alcohols by Thermal, Homogeneous Iron(I)-Catalyzed Cross-Coupling
- Oxidative functionalization of aliphatic and aromatic amino acid derivatives with H 2 O 2 catalyzed by a nonheme imine based iron complex
- Protecting Groups as Catalysts: Direct Synthesis of Primary Amines from Ammonia under Carbonyl Catalysis
BibTeX
@misc{geue2026ferrier,
title = {{Ferrier Rearrangement Intermediates Featuring Aliphatic Acyl Protecting Groups}},
author = {Niklas Geue and Kim Greis and Sabrina Omoregbee-Leichnitz and Carla Kirschbaum and Julinton Sianturi and Shenchuang Wang and Gert von Helden and Peter H. Seeberger and Kevin Pagel},
howpublished = {ChemRxiv},
year = {2026},
month = sep,
doi = {10.26434/chemrxiv.15009377/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009377/v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Ferrier Rearrangement Intermediates Featuring Aliphatic Acyl Protecting Groups
AU - Niklas Geue
AU - Kim Greis
AU - Sabrina Omoregbee-Leichnitz
AU - Carla Kirschbaum
AU - Julinton Sianturi
AU - Shenchuang Wang
AU - Gert von Helden
AU - Peter H. Seeberger
AU - Kevin Pagel
PY - 2026
DA - 2026/09/23
PB - ChemRxiv
DO - 10.26434/chemrxiv.15009377/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009377/v1
AB - The Ferrier rearrangement of 1,2-unsaturated monosaccharides (glycals) to 2,3-unsatured glycosides, is important for the synthesis of pharmaceuticals and natural products. Mechanistically, the nucleophilic substitution proceeds via a cationic intermediate, the “Ferrier cation”, whose structure is difficult to capture with conventional analytical techniques. Here, we characterize the Ferrier cations of glucal and galactal building blocks involving aliphatic acyl protecting groups (pivaloyl-, levulinoyl- and chloroacetyl esters) using cryogenic gas-phase infrared spectroscopy. Comparing experimental and computed spectra of candidate structures, we established that all intermediates are stabilized by interactions of the C4 acyl protecting group with the C3 carbon of the pyranose ring (neighboring participation), potentially steering the stereochemical outcome of the Ferrier rearrangement. The resulting C4-C3-dioxolenium ion structure appears to be general to aliphatic acyl protecting groups, contributing to our fundamental understanding of Ferrier rearrangement reactions.
ER -