Synthesis of Imidazoles by Pd- and Cu-Catalyzed C-N Bond Formation

Significance

An inter- and intramolecular Pd- and Cu-catalyzed reaction sequence for the one-pot synthesis of dihydro[1,2-a:2′,3′-d]imidazole and its analogues is reported. Chemoselective Buchwald-Hartwig Pd-catalyzed amination of 2,3-dibromopyridine 1 with benzo-2-aminopyridines and -diazines 2 leads to products 3 which were subjected to Cu-catalyzed cyclization giving dipyridoimidazoles and their benzo and aza analogues 4 in up to 88% yield. Interestingly, the conversion of 3 to 4 also proceeds under copper-free conditions using Pd₂(dba)₃ catalysis and Xantphos as ligand at higher temperature in a sealed tube, whereas, under reflux conditions, only the amination product 3 is obtained.