Multicomponent reactions for a greener synthesis of pyrroles and propargylamines

Abstract

Pyrroles and propargylamines are important precursors to biologically-active substances and are found in the backbone of a number of important pharmaceuticals. Multicomponent reactions for the synthesis of pyrroles and propargylamines were carried out using a series of novel catalysts and conditions, in order to improve their green protocol and overall efficiency. Following a screening of potential catalysts, the synthesis of pyrro les from amines, aldehydes and nitroalkanes showed evidence of success, albeit with significant complications due to the instability of the products. The synthesis of propargylamines, involving amines, aldehydes and alkynes, dubbed A3-Coupling, gave very positive results following a process of optimisation. The novel copper (I)-based polymer-supported catalyst used furnished products in good to excellent yields (70-98%) in solvent-free conditions and relatively short reaction times. The heterogeneous catalyst was also recycled for at least five consecutive cycles without demonstrating any significant loss in activity. The products obtained were characterised through 1H, 13C NMR and IR spectroscopy and, where novel compounds were isolated, gas chromatography-mass spectrometry (GC-MS). The developed A3-Coupling protocol is viable for a green and efficient formation of a variety of propargylamines without the requirement of solvent, with the catalyst displaying high catalytic activity and considerable reusability.