Palladium-catalyzed Carbonylation And Cyclization And Zirconocene-catalyzed Aza-DA Reaction

Heterocyclic are an integral part of many bioactive molecules,and plant alkaloids,alkaloids and glycosides in plants contain heterocyclic structures.In addition,heterocyclic compounds also play a very important role in medicinal chemistry.many currently marketed drugs hold heterocycles as their core structure,and thus the synthesis of heterocyclic compounds has great research value.On the basis of summarizing the traditional palladium catalyzed carbonylation Sonogashira coupling reaction and its research progress as well as taking the construction of the typical structure of flavone,aurone and quinolone heterocyclic as the objective,a more effective and convenient synthesis method has been developed and reported in the thesis through control and change of the key factors affecting the reaction such as base,ligand,carbonyl source.The synthesis reaction of the zirconium Lewis acid catalized three components Aza-Diels-Alder reaction has also been proposed and studied for the construction of isoquinine compounds.The detailed research contents of the thesis include:(1)An efficient strategy for divergent synthesis of flavones and aurones via base-controlled regioselective palladium catalyzed carbonylative cyclization has been developed.Under the mild condition,the selectivity and structure control of the product were successfully realized by changing the key factors of the reacyion.The catalytic experiment results indicated that piperazine preferentially accelerated 6-endo cyclization and triethylamine mediated Pd catalyzed 5-exo cyclization.Under optimal conditions,we have successfully synthesized 22 examples of flavone derivatives with a maximum yield of 95%,and 17 examples of aurones with a maximum yield of 92%and a good regio-selectivity.(2)A CO gas and ligand free method for the synthesis of quinolone derivatives via palladium catalyzed carbonylative Sonogashira coupling has been developed by using Fe(CO)5 as the CO source.Ketone product was afforded when potassium phosphate as the base was used alone,but acetyenic ketone product effectively converted to quinolone cyclization products when piperazine was added to reaction system.Further mechanism research revealed that the addition intermediate of piperazine to ketone is the key to the formation of the ring products.This method has been used to synthesize 18 examples of quinolone compounds,which is suitable for the construction of quinolone compounds containing aromatic groups,alkyl and heterocyclic aromatic hydrocarbons,and has a good tolerance of functional groups.(3)A method for synthesis of isoquinine ring derivatives by zirconium Lewis acid catalyzed three-component Aza-Diels-Alder reaction has been proposed.Under the cooperative effect of o-aminobenzene sulfonic acid and Cp2ZrCl2,this method revealed the high conversion rate and good yield,but ratio of exo:endo could only reach 85:15.