Copper-Catalyzed Three-Component Synthesis of 2H-Indazoles

Significance

The synthesis of 2H-indazoles is ­reported using a copper-catalyzed three-component reaction of 2-bromobenzaldehydes, primary amines, and sodium azide. CuI as catalyst and TMEDA as ligand were found to be the best combination to afford products in moderate to good yields. Aliphatic and (hetero)aromatic amines were tolerated, although sterically hindered and EWG aromatics gave lower yields. Control experiments were carried out to investigate the effect of copper catalyst. On the basis of these studies, the authors suggested that the reaction occurs first through A, which then undergoes a substitution by the azide in the presence of copper to get B. Activation of the terminal nitrogen of the azide by copper would then allow the attack of the benzylideneaniline nitrogen to form the N-N bond (C).