Effect of the <i>ortho</i>-hydroxy group of salicylaldehyde in the A³ coupling reaction: A metal-catalyst-free synthesis of propargylamine

Abstract

The synthesis of propargylamines via A³ coupling mostly under metal-catalyzed procedures is well known. This work invented an unprecedented effect of salicylaldehyde, one of the A³ coupling partners, which could lead to the formation of propargylamine, an important pharmaceutical building block, in the absence of any metal catalyst and under mild conditions. The role of the hydroxy group in <i>ortho</i> position of salicylaldehyde has been explored, which presumably activates the C_sp-H bond of the terminal alkyne leading to the formation of propargylamines in good to excellent yields, thus negating the function of the metal catalyst. This observation is hitherto unknown, tested for a variety of salicylaldehyde, amine and acetylene, established as a general protocol, and is believed to be of interest for synthetic chemists from green chemistry.