Greener Conditions for Asymmetric Coupling of Terminal Alkynes

Asymmetric 1,3-diynes are a common structure motif but remain challenging to prepare from terminal alkynes using Glaser-Hay reactions. Alternative approaches rely on halogenated alkynes, expensive catalysts, or large excess of one reagent to overcome these challenges. We report greener options to prepare asymmetric diynes using a Glaser-Hay type reaction with mixed copper catalysts. Oxygen is employed as a sustainable oxidant to avoid the need for stoichiometric copper. We also show halogenated and toxic solvents can be completely replaced with the sustainable solvent ethyl acetate. The choice of base plays an important role in the reaction as it serves to both deprotonate alkynes and as a ligand for copper.