Study On The Catalytic Cyclization Reaction Of Aminoquinoline Directed Arylformamide With α-Ots Aryl Ethyl Ketone

Isoquinolinone compounds are important nitrogen-containing heterocyclic molecular frameworks in natural alkaloids.Most of the compounds containing this framework have unique biological activities,such as anti-tumor,anti-immune activity,inhibition of human lung adenocarcinoma cell proliferation,etc.,and have important application value in the field of biomedicine.Therefore,in recent years,people have been committed to establishing effective methods to achieve the synthesis of isoquinolinone compounds.On the other hand,the construction of new C-N/C-C bonds based on transition metal-catalyzed C-H bond activation has received great attention because this method eliminates the step of pre-activating the substrate with the assistance of the guiding group.In addition,specific sites of the reaction can be selectively activated to improve the selectivity of the reaction.Based on the above reasons,with 8-aminoquinolinyl as the guide group,under the catalysis of transition metal palladium,this paper mainly studied the cyclization reaction between N-（8-quinolinyl）aryl carboxamides and 1-aryl-2-tosyloxy ethanones（α-OTs aryl ethyl ketone）,and prepared a series of 3-aryl-2-（8-quinolinyl）isoquinoline-1（2H）-ketone compounds.The method uses C（sp³）synthonα-OTs aryl ethyl ketone as the equivalent of oxyalkynes,has simple operation,good yield,free ligand and high substrate tolerance,and provides a new way for the synthesis of isoquinolinone compounds.The specific research content is as follows:1.The synthesis of two substrates is introduced::（i）A series of N-（8-quinolinyl）aryl carboxamides were synthesized by condensation reaction with cheap and easily available arylacyl chloride and 8-aminoquinoline.（ii）A series ofα-OTs aryl ethyl ketone were synthesized from acetophenone and hydroxytoluene sulfonyl iodobenzene.2.N-（8-quinolinyl）aryl carboxamides andα-OTs aryl ethyl ketone are used as substrates to explore the optimal reaction conditions for the cyclization reaction.Through the exploration of the reaction conditions such as the catalyst,base,solvent,reaction temperature,time,oxidant,etc.,the optimal conditions for the reaction were finally obtained.3.Under the optimal reaction conditions,30 isoquinolin-1（2H）-one products were successfully prepared.All the target products were characterized by nuclear magnetic resonance spectrometry(¹H NMR and ¹³C NMR),mass spectrometry（MS）,high resolution mass spectrometry（HRMS）,infrared spectra（IR）etc..The author also puts forward a possible reaction mechanism through controlled experiments and combined with previous work.