Researchers of the Zelinsky Institute published a review on the use of the A³-coupling reaction in the synthesis of N, O, S-heterocyclic compounds

A³-coupling is a fundamental process of great interest in modern organic chemistry. It proceeds as a metal-catalyzed three-component reaction of amines, aldehydes, and terminal alkynes with the formation of propargylamines. Currently, A³-coupling is actively used in polymer chemistry and pharmacology for the synthesis of new materials and libraries of compounds for high-throughput screening of potential drugs. In recent years, more and more interest in the field of A³-coupling processes is their use in cascade transformations proceeding due to the presence of several reaction centers in the propargylamines formed. As a result, it becomes possible to synthesize a large number of various linear and cyclic organic compounds.

A review article published by the researchers of Laboratory № 22 of the Zelinsky Institute is devoted to the use of the A³-coupling reaction in the synthesis of N, O, S-heterocyclic compounds through cascade transformations of propargylamines generated in situ. In the last decade, using this approach, effective methods for the preparation of a number of different classes of heterocycles, including important pharmacophores such as imidazoles, imidazolidines, pyrazoles, pyrroles, indoles, azaindoles, isoindoles, indolizines, oxazolidines, oxazoles, quinolines, dihydroisoquinolines, coumarins, benzazepines, benzodiazepines, were developed. The main advantages of this method are high chemoselectivity and atom-efficiency as well as the possibility of using commercially available copper and iron salts as catalysts.

Source:

Yulia Volkova, Sergey Baranin, Igor Zavarzin A³ Coupling Reaction in the Synthesis of Heterocyclic Compounds Adv. Synth. Catal., 2021, 363, 40-61. DOI: 10.1002/adsc.202000866.