Sustainable protocol for Cu-catalysed A3-coupling under solvent-free conditions

Org Biomol Chem. 2024 Dec 3. doi: 10.1039/d4ob01728e. Online ahead of print.

Abstract

A Cu-catalyzed three-component cascade reaction has been developed, involving ortho-alkynylaryl aldehydes, terminal alkynes and aliphatic/aromatic amines or diamines. This diversity oriented methodology successfully delivered a rich library of 72 molecules in good to excellent yields (yields up to 99%) through the application of an A3-coupling reaction. This method is green, straightforward to execute, requires a short reaction time (2 min-4 h), does not require solvents or harsh or inert conditions, i.e. can be performed in open air, and utilizes only a small amount of a cheap and readily available catalyst (2.5 to 10 mol% CuI). It proficiently produced a variety of biphenylacetylene tethered propargylamines, alkyne tethered dihydroisoquinolines, and N-fused benzimidazoles with excellent regioselectivity.