A breakthrough in the chemistry of practically important peroxide cycles was made by scientists of ZIOC

Organic peroxides are receiving a lot of attention from chemists and pharmacologists. This is primarily due to the presence of high antiparasitic, anticancer, fungicidal, and growth-regulatory activity in cyclic peroxides. However, the efficient synthesis of cyclic peroxides from carbonyl compounds and hydrogen peroxide is a very difficult task due to the low selectivity of these transformations, especially in the case of the presence of more than one carbonyl group in the starting compound.

The research carried out in laboratory № 13 of the Zelinsky Institute of Organic Chemistry RAS under the guidance of Prof. Dr. Sci. A.O. Terent’ev in a group led by Dr. I.A. Yaremenko in collaboration with colleagues from group №24 of ZIOC and Florida State University was published in the highly rated international journal Journal of the American Chemical Society. The research focuses on solving the complex problem of constructing complex pharmaceutically important molecules using hydrogen peroxide and carbonyl compounds as building blocks. The team of authors succeeded in solving a very complex conundrum of controlling the reaction between hydrogen peroxide and a tricarbonyl compound (branched β, γ'-triketone). As a result, access to complex conformationally stable tricyclic molecules containing one or two oxygen-oxygen fragments has been opened. By combining experimental and computational methods, the rules for the assembly of cyclic peroxides from branched β, γ'-triketones and hydrogen peroxide were determined. The factors influencing the stability of peroxides, as well as the factors determining the unusual thermodynamic landscape of the reaction, are found, and the reasons that prevent the formation of the most expected peroxide with three O – O fragments are established.

Source:

Ivan A. Yaremenko, Peter S. Radulov, Michael G. Medvedev, Nikolai V. Krivoshchapov, Yulia Yu. Belyakova, Alexander A. Korlyukov, Alexey I. Ilovaisky, Alexander O. Terent′ev, and Igor V. Alabugin. How to Build Rigid Oxygen-Rich Tricyclic Heterocycles from Triketones and Hydrogen Peroxide: Control of Dynamic Covalent Chemistry with Inverse α-Effect. J. Am. Chem. Soc., 2020, 142 (34), 14588-14607. DOI: 10.1021/jacs.0c06294