Practical Synthesis of Unsymmetrical Diarylacetylenes from Propiolic Acid and Two Different Aryl Bromides

A palladium catalyst that mediates the one-pot sequential Sonogashira and decarboxylative coupling of propiolic acid with two different aryl bromides has been developed. Selective coupling of the first aryl bromide was achieved in the presence of a copper-free, monometallic catalyst generated in situ from allylpalladium chloride dimer and SPhos with tetra-n-butylammonium fluoride as the base in an N-methyl-2-pyrrolidone/water solvent mixture. Upon addition of another aryl bromide and raising the temperature from 50 to 80 °C, the intermediate arylpropiolic acid underwent de-carboxylative coupling to give the corresponding diarylacetylene. Thus, the new system permits a one-pot threecomponent synthesis of unsymmetrical diarylacetylenes from widely available aryl bromides, rather than expensive aryl iodides, and propiolic acid, rather than (trimethylsilyl)acetylene, as an inexpensive and easy-to-handle acetylene synthon. The process is highly selective, modular, and gives access to a wide range of unsymmetrical diarylacetylenes in good yields.