A Cu/Cd-cocatalysed cascade reaction for constructing nitrogen-tethered 1,6-enynes enabled by 1,5-hydride transfer

Abstract

The development of sustainable and novel strategies for the construction of valuable and complex compounds is of great interest to the chemical community. Nitrogen-tethered 1,6-enynes are well-known for their functionalization behaviour, which has been widely exploited for their cyclization to access nitrogen-containing heterocycles. Herein, we present the discovery and development of the first synergistic Cu/Cd dual catalytic system for the sequential A³-coupling/α-alkynylation reaction between secondary amines with formaldehyde and terminal alkynes for the synthesis of nitrogen-tethered 1,6-enynes enabled by 1,5-hydride transfer. This method is characterized by its excellent chemo- and site-selectivity, high functional group tolerance, readily accessible substrates and good yields. The synthetic utility of this multicomponent reaction is demonstrated by the large-scale reaction, late-stage functionalization and conversion of the product.