Unprecedented salt-promoted direct arylation of acidic sp2 CH bonds under heterogeneous Ni-MOF-74 catalysis: Synthesis of bioactive azole derivatives

Abstract

Herein, nickel-based metal-organic framework, Ni-MOF-74, was synthesized by a solvothermal method and its properties was characterized by a host of techniques. Ni-MOF-74 exhibited exceptional catalytic activity toward the direct arylation of azoles via CH activation while other Ni-MOFs, nickel-based heterogeneous systems, and homogeneous counter parts displayed lower activity. Optimal conditions involved the use of Li₂CO₃ or KCl salts in diglyme solvent in 18 h and no additional ligand is required. This is the first and unprecedented report using KCl salt as promoter for arylation of heterocycles. By avoiding the use of strong bases and oxidants, optimized conditions are compatible with wide range of functional groups and heterocycles. Furthermore, by taking advantage of large aperture size of Ni-MOF-74, we are able to utilize optimized conditions to successfully synthesize several bioactive arylated azole derivatives. Previous studies using heterogeneous catalysts to approach these bioactive compounds are not performed in the literature. Leaching tests indicated that homogeneous catalysis via leached active nickel species is unlikely. Thus, the catalyst was facilely separated from the reaction mixture and reused several times without significant degradation of the catalytic reactivity.