Synthesis Of Benzimidazole-Fused Phenanthridines Via Palladium-Catalyzed C-H Functionalities

Benzimidazole-fused phenanthridines are frequently found in a diverse array of compounds, including a wide range of significant natural products, biologically and therapeutically active compounds.For examples, benzimidazole-fused isoquinoline frameworks are an important class of pharmacophores and many derivatives display a wide range of biological and therapeutical activities, such as anticancer, antimicrobial, anesthetic and insecticide properties. Therefore,molecules containing this motif play an important role in drug discovery. Benzimidazole-fused phenanthridines, as electron-transporting and emission functional units, are prevalent in advanced organic materials. Hence, molecules containing this motif have attracted considerable attention in organic synthesis, medicinal and material chemisty, and much effort has been focused on the synthetic methods of benzimidazole-fused aromatic system.Starting from 2-arylbenzimidazoles and aryl halides, an efficient palladium-based catalytic method for the synthesis of benzimidazole-fused phenanthridines has been developed. This reaction sequence comprises intermolecular C-H arylation and intramolecular aerobic oxidative C-H amination.With Pd(OAc)2 (10 mol%) as the catalyst, Xphos (20 mol%) as the ligand, and K2CO3 as the base,2-arylbenzimidazoles and aryl halides could undergo tandem cross-coupling reaction in DMF at 160℃ for 72 hours to produce the corresponding target in 88% yield.Encouraged by the above result, the scope and generality of the present process was then explored. The result shows that the method has good tolerance of substituents on the 2-arylbenzimidazoles and aryl halides, including electron-withdrawing group and electron-donating group, In addition, the effect of electron-donating groups has a better result.The reactivity of different aryl halides follows the sequence of iodobenzene> bromobenzene> chorobenzene.This thesis has developed a practical, simple and efficient method to synthesize Benzimidazole-fused phenanthridines derivatives. This protocol is not only a valuable addition to the tool box of the synthesis of benzimidazole-fused phenanthridines, but also enriches the contents of palladium-catalyzed cascade cyclizations reactions, which should be of considerable interest of the valuable synthetic building blocks for medicinal and material science.