Synthesis of nitrogen-tethered 1,6-enynes through CuI/TFA catalysis

Abstract

A novel method for the concise and effective construction of nitrogen-tethered 1,6-enynes in moderate to good yields was developed. This transformation involves a TFA-promoted Pictet–Spengler reaction/iminium formation, copper-catalyzed alkyne–iminium ene reaction/alkynylation of a 2-arylethan-1-amine, formaldehyde solution, and a terminal alkyne. The process features exclusive chemoselectivity, simple operation, and high atom economy. Preliminary experimental studies suggest that the alkyne–iminium ene reaction involving an intermolecular hydride transfer is the key step in the current methodology.