Fast copper-, ligand- and solvent-free Sonogashira coupling in a ball mill

A solvent-free method for the Sonogashira coupling reaction was established under ball milling conditions without the use of copper or additional ligands. Pd(OAc)2 or Pd(PPh3)4 in combination with 1,4-diazabicyclo[2.2.2]octane (DABCO) were chosen as catalysts and base, respectively. The reaction was investigated using a variety of aryl halides and acetylenes and with different amounts of the Pd-catalyst and DABCO. Results indicated that the employment of Pd(OAc)2 in combination with SiO2 as a grinding auxiliary preferentially induces the transformation of aryl iodides to the corresponding Sonogashira coupling products. In contrast, both the substitution of SiO2 by Al2O3 or replacement of Pd(OAc)2 with Pd(PPh3)4 enable the reaction of aryl bromides with phenylacetylenes. The selective reaction of bis-ethynyl compounds to double-coupled products and the influence of further common bases on the reaction was also scrutinized, confirming the high reactivity of DABCO as a base for solvent-free transformations.