Palladium-Catalyzed Double C-H Arylation Reaction:Synthesis Of Heteroarenes From Imidazo[1,2-a]Pyridine And O-Dihaloarenes

In the past decades, considerable attention has been devoted to the development of novel aromatic heteropolycyclics as organic fluorophores for application in materials science and medicine. Of these fluorophores, the isoindole or indolizine-fused polycyclic frameworks have attracted significant interest as organic electronic and optical materials. In medicine, the imidazopyridine derivatives show a high potential medicinal value, and they have properties of anti-viral, anti-ulcer, anti-bacterial, anti-fungal, anti-cancer, anti-inflammatory and analgesic, so various types of drugs based on these characteristics have been developed to cure insomnia, diabetes, schizophrenia and Alzheimer’s and other diseases.A palladium-catalyzed direct arylation of 2-aryl imidazo[1,2-a]pyridines with o-diha-loarenes via double C-H activation has been described. The process comprises intermolecular C3-arylation of 2-aryl imidazo[1,2-a]pyridines followed by an intramolecular C5-arylation in a highly regioselective fashion, affording benzo[a]imidazo[5,1,2-cd]indolizine derivatives in moderate to good yields. Recent studies reveal that 2-phenylimidazo[1,2-a]pyridine and o-dibromobenzene were selected as the coupling partners for a Pd-catalyzed tandem twofold C-H activation/arylation sequence. Extensive experiments were conducted in the presence of different ligands for the Pd catalyst, bases, solvents, and temperature, and some relevant results the experiment was examined in DMF at 160 ℃ for 24 h using Pd(OAc)2 (10 mol%) as the catalyst, Xphos (20 mol%) as the ligand, K2CO3 (3 equiv) as the base, and the yield was 77%. Encouraged by the above result, the scope and generality of the present process was then explored. Our research shows that the targethas good tolerance of substituents on the o-dihaloarens and imidazopyridine derivatives, including electron-withdrawing group (F and Cl) and electron-donating group (Me and OMe). In addition, due to reactive halogen atom is chloro> bromo> iodo, it could have a high regioselectivity with different halogen atoms in the ortho-halogenation of benzene. On the basis of the above results, the step involved an electrophilic attack by the aryl-palladium halide species and the mechanism of intramolecular metallization-deprotonation reaction.In summary, we have developed a palladium-catalyzed protocol for the tandem synthesis of benzo[a]imidazo[5,1,2-cd]indolizines from 2-arylimidazo[1,2-a]pyridines and 1,2-dihalo-arenes. The process is based on highly regiocontrolled intermolecular C3-arylation and subsequent intramolecular C5-arylation to form the desired products in moderate to good yields. This Pd-catalyzed double-arylation reaction will provide a useful tool for the discovery of fluorescent materials.