ZIOC continues to study the Nazarov reaction

Divinyl ketones are important synthons for the Nazarov reaction and are actively used for the synthesis of biologically active substances and natural compounds. One of the most important tasks of the modern development of this field of chemistry is the development of reactive polarized divinyl ketones and their study in the Nazarov reaction. This strategy allows us to develop convenient methods for obtaining various carbocyclic structures for use in medicinal and materials chemistry.

In the Laboratory of Heterocyclic Compounds of the ZIOC active research has been carried out in the field of the chemistry of divinyl ketones over the past years. Scientists have found that intramolecular cyclization of triaryldivinylketones under acidic conditions proceeds via two possible pathways leading to derivatives of cyclopentenone (Nazarov reaction) and dihydronaphthalene (intramolecular cyclization). In this work, the researchers of the Laboratory, together with American colleagues from the University of Rochester (USA), studied in more detail the possibility of controlling the direction of this reaction using the example of compounds containing a thiophene substituent. It was shown that the chemoselectivity of the process depended on the nature of the acid catalyst used and the steric hindrance of the starting compounds. Quantum-chemical calculations confirmed the obtained experimental data and showed that the formation of cyclopentenones by the Nazarov reaction is controlled thermodynamically, and dihydronaphthalenes — kinetically. The value of this study lies not only in the development of a useful strategy for the synthesis of biologically active analogs of combretastatin A-4, but also in the development of the synthetic potential of aryldivinylketones, which expands the possibilities of the Nazarov reaction.
 

Source:

Anton V. Yadykov, Artem E. Eremchenko, Aleksa Milosavljevic, Alison J. Frontier, Valerii Z. Shirinian Divergent Reactivity of Triaryldivinyl Ketones: Competing 4π and Putative 6π Electrocyclization Pathways // J. Org. Chem. 2022, 87, 13643–13652. DOI: 10.1021/acs.joc.2c01294.