Study On The Synthesis Of Imidazopyridine-based Fused Heterocycles

Imidazopyridines not only exist widely in nature,but also find numerous applications in medicament,pesticide,and dye industry.Therefore,the search for more convenient and effective methods for their preparation is an important task in both synthetic and medicinal chemistry.Meanwhile,transition metal-catalyzed reactions are emerging as an effective tool in organic synthesis due to their simple operation procedure,mild reaction conditions and high efficiency.Inspired by the above facts,this thesis aims to develop effective synthetic approaches toward imidazopyridine-based fused heterocycles by taking advantages of transition metal-catalyzed reactions.The content of this thesis includes the following two parts:Firstly,a novel synthetic approach toward pyrido[2',1':2,3]imidazo[4,5-c]quinoline and 5,6-dihydropyrido[2',1':2,3]imidazo[4,5-c]quinoline via a one-pot cascade procedure featured with a coppercatalyzed amination has been developed.It was found that amination of 2-(2-bromophenyl)imidazo-[1,2-a]pyridine,in situ formed via condensation of 2-bromo-1-(2-bromophenyl)ethan-1-one with 2-aminopyridine,under the catalysis of copper salt by using aqueous ammonia as the nitrogen source afforded 2-(2-aminophenyl)imidazo[1,2-a]pyridine.Condensation of the in situ fomed 2-(2-aminophenyl)imidazo-[1,2-a]pyridine with aldehyde followed by an intramolecular cyclization afforded pyrido[2',1':2,3]imidazo-[4,5-c]quinoline in good yield.Further studies demonstrated that when ketone was used to replace aldehyde,the corresponding reaction efficiently generated 5,6-dihydropyrido[2',1':2,3]imidazo[4,5-c]quinoline.Compared with literature methods,this new protocol shows advantages such as easily obtainable starting materials,mild reaction conditions and high atom-economy.Secondly,an efficient synthetic strategy toward 11H-indene[1',2':4,5]imidazole[1,2-a]pyridin-11-one and 6H-benzopyran[4',3':4,5]imidazole[1,2-a]pyridin-6-one through Pd-catalyzed C-H bond activation and carbonylation has been developed.To be specific,2-(2-bromophenyl)imidazo[1,2-a]pyridine was found to be able to undergo an efficient conbonylation with carbon monoxide under the catalysis of palladium to afford 11H-indene[1',2':4,5]imidazole[1,2-a]pyridin-11-one.Intriguingly,under similar conditions but in the presence of Cu(OAc)2,the reaction selectively afforded 6H-chromeno-[4',3':4,5]-imidazo[1,2-a] pyridin-6-one via a cascade process including hydroxylation,C-H bond activation and carbonylation.Compared with literature methods,this new method shows advantages such as easily obtainable starting materials,excellent selectivity and simple operation procedures.In summary,some efficient methodologies for the preparation of imidazopyridine-based fused heterocycles have been developed through metal-catalyzed one-pot multi-step cascade reactions.With advantages such as easily obtainable starting materials,mild reaction conditions,high efficiency,excellent selectivity and broad substrate scope,these methods are expected to be widely used in related areas.