From A3/KA2 to AYA/KYA multicomponent coupling reactions with terminal ynamides as alkyne surrogates - a direct, green route to γ-amino-ynamides

A copper-catalysed three-component coupling reaction between a carbonyl derivative, a terminal ynamide and an amine has been developed for the one-pot green construction of gamma-amino-ynamides from simple starting materials and with a broad functional group tolerance.The copper-zeolite-catalysed three-component coupling reaction between an aldehyde or a ketone, a terminal ynamide and an amine is reported. The so-elaborated methods, dubbed AYA (i.e. Aldehyde-Ynamide-Amine) and KYA (i.e. Ketone-Ynamide-Amine), enable the straightforward one-pot synthesis of gamma-amino-ynamides from simple starting materials and with a broad functional group tolerance. Moreover, AYA/KYA processes are performed at room temperature under solvent-free conditions or in ethyl acetate as green solvent in the presence of a copper-based easy-to-recover/-remove catalyst, at low loading (3 mol%), making these synthetic methods fully green.

Automated summary

A copper-catalysed three-component coupling reaction has been developed for the efficient synthesis of gamma-amino-ynamides. This method allows the use of simple starting materials and shows a broad functional group tolerance, making it a green and sustainable synthetic approach.