New-to-Nature Transformation for the Z-Selective Synthesis of Unsaturated Acids via Acyl Azolium Intermediates
- 1Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, Bern, Switzerland, 3012
Abstract
Organocatalytic methods operating via α,β-unsaturated acyl azolium intermediates are extensively studied in organic chemistry and typically proceed through E-configured intermediates that dictate the stereochemical outcome of the final product. To date, the use of this species within enzymatic systems is restricted to a single natural biosynthetic pathway. Herein, we report an example of a versatile new-to-nature biocatalytic transformation that harnesses an α,β-unsaturated acyl azolium intermediate within the active site of a thiaminedependent enzyme. Remarkably, this enzymatic environment favors the formation of the less accessible Z-acyl azolium, enabling the highly selective synthesis of Z-α,β-unsaturated acids via redox hydrolysis of α-bromoenals. The protocol features a broad substrate scope spanning aromatic and aliphatic substrates, all while maintaining excellent Z/E ratios.
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BibTeX
@misc{kqiku2026newtonature,
title = {{New-to-Nature Transformation for the Z-Selective Synthesis of Unsaturated Acids via Acyl Azolium Intermediates}},
author = {Laura Kqiku and Joel Zobrist and Francesca Paradisi},
howpublished = {ChemRxiv},
year = {2026},
month = sep,
doi = {10.26434/chemrxiv.15008234/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008234/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - New-to-Nature Transformation for the Z-Selective Synthesis of Unsaturated Acids via Acyl Azolium Intermediates
AU - Laura Kqiku
AU - Joel Zobrist
AU - Francesca Paradisi
PY - 2026
DA - 2026/09/03
PB - ChemRxiv
DO - 10.26434/chemrxiv.15008234/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008234/v1
AB - Organocatalytic methods operating via α,β-unsaturated acyl azolium intermediates are extensively studied in organic chemistry and typically proceed through E-configured intermediates that dictate the stereochemical outcome of the final product. To date, the use of this species within enzymatic systems is restricted to a single natural biosynthetic pathway. Herein, we report an example of a versatile new-to-nature biocatalytic transformation that harnesses an α,β-unsaturated acyl azolium intermediate within the active site of a thiaminedependent enzyme. Remarkably, this enzymatic environment favors the formation of the less accessible Z-acyl azolium, enabling the highly selective synthesis of Z-α,β-unsaturated acids via redox hydrolysis of α-bromoenals. The protocol features a broad substrate scope spanning aromatic and aliphatic substrates, all while maintaining excellent Z/E ratios.
ER -