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

Abstract

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.