Chemists have discovered a simple iron catalyst that can turn common household bleach into a highly efficient reagent for making epoxides (J. Am. Chem. Soc. 2026, DOI: 10.1021/jacs.6c06785). The catalyst works under mild conditions at room temperature and is effective in trace amounts.
Epoxides are important building blocks used in pharmaceuticals, materials, and fine chemicals. Organic chemists routinely use peroxyacids such as meta-Chloroperoxybenzoic acid (mCPBA) to make epoxides from alkenes despite long-standing problems with safety, scalability, and heterocycle compatibility.
“I honestly never imagined pursuing development of a catalytic epoxidation reaction,” comments Shannon Stahl, professor of chemistry at University of Wisconsin–Madison. “In fact, if you would have asked me 2 years ago . . . I would’ve said ‘this is a solved problem.’ ”
In the flask, a compound undergoes the new epoxidation reaction, which can be done at room temperature under mild conditions. Credit:
Doohyun Baek
The discovery came while the group was seeking a scalable epoxidation method based on bleach or hydrogen peroxide. “When comparing the new catalyst system with a portfolio of relevant alkenes, we found that this method is even better than mCPBA, which is widely viewed as the most useful general epoxidation reagent,” Stahl says.
The reported reaction uses an iron-porphyrin-based catalyst with sodium hypochlorite (NaOCl) as the oxidant. Sudip Maiti, now a postdoctoral fellow at Lawrence Berkeley National Lab who was a postdoc in Stahl’s lab at the time the research was conducted, says that earlier iron-based epoxidation systems often suffered from poor reactivity and stability. The new reaction tolerates substrates that often react poorly with standard peroxides such as mCPBA; these substrates include heterocycle-containing molecules, glycals, polyenes, and both aromatic and aliphatic alkenes. The catalyst also remained effective at loadings as low as 0.05 mol%, indicating unusual stability.
Maiti explains that the reaction proceeds through a biphasic process in which hypochlorite is slowly transferred into the organic phase and captured by the iron catalyst. However, Stahl notes the source of the catalyst’s unusual selectivity remains unclear. “What is still a mystery to me,” he says, “is why there is such high reactivity for alkenes relative to aromatic heterocycles.”
Using the iron catalyst, researchers were able to expoxidize 100 g of tri-O-acetyl-D-glucal in 15 min. This transformation is particularly significant because glycal epoxides are valuable intermediates for the stereospecific synthesis of β-linked oligosaccharides, yet glycals are notoriously challenging to epoxidize and often decompose under standard conditions such as treatment with mCPBA.
“It outperforms several existing industrial and academic approaches in terms of substrate scope, efficiency, and functional group compatibility,” says Thierry Ollevier at the Université Laval, who was not involved in the current study.
However, Ollevier says that industrial adoption would require tight control of reaction conditions and a reliable supply of sodium hypochlorite. Large-scale use would also require engineering safeguards to manage heat generation, mixing, and side reactions.
The work suggests that inexpensive iron catalysts and commodity oxidants may provide a practical alternative to peroxide-heavy oxidation. “Our work demonstrates that, with the right combination of conditions and catalyst design, these long-standing challenges can be addressed effectively,” Maiti concludes.
