Nikolaos V. Tzouras

Development of sustainable catalytic systems for the KA² coupling: Towards the expedient assembly of tetrasubstituted propargylamines

Propargylamines are a unique class of compounds, serving as versatile synthons for a variety of organic transformations and possessing intrinsic value due to the bioactive nature of certain members of their diverse family. Consequently, their synthesis has been a topic of intense research, which has given rise to a multitude of catalytic reaction systems proceeding through the C-H activation of terminal alkynes and notably involving the use of sustainable metals. Recently, the KA² coupling reaction (Ketone-Amine-Alkyne) emerged, providing facile access to tetrasubstituted propargylamines. In this regard, our research group has undertaken the development of novel, sustainable catalytic systems for the KA² coupling, based on zinc, manganese or copper catalysis. As demonstrated by the results shown in the scheme below, our zinc-based protocol has a wide substrate scope, leading to the functionalization of challenging molecular scaffolds. Related studies on extensions and modifications of this system as well as the development of related systems are underway, with so far promising results. Importantly, all protocols have been designed to adhere strongly to the principles of Green Chemistry.

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