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

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. © the Partner Organisations.