Synthesis Of Pyrrolo[2,1-a] Isoquinolines Derivatives By [3+2] Cyclization Of Tetrahydroisoquinoline With Unsaturated Carbonyl Compounds

Pyrroloisoquinoline is an important nitrogen-containing heterocyclic skeleton,which widely exists in natural products,alkaloids,and drug molecules.These compounds have a va-riety of boilogical activities,such as anticancer,antiviral,antibacterial and so on.There are two strategies for obtaining pyrroloisoquinoline derivatives:one is to construct isoquinoline moieties by using pyrrole derivatives,and the other is to construct pyrrole rings from the functionalized isoquinoline derivatives.Many methods have been developed for the synthesis of pyrrolo[2,1-a]isoquinolines.However,these methods still have some drawbacks,such as the conditions are not gentle,the environment is not friendly,the operation is not simple,the atomic economy is not high and so on.Considering the excellent pharmacological potential of pyrrolo[2,1-a]isoquinolines,the synthesis of these compounds has attracted wide attention of chemists in recent years.There-fore,the development of simple,green and high atom-economy methods for the synthesis of pyrrolo[2,1-a]isoquinoline derivatives is of great significance for their application reaearch.[3+2]reaction has become one of the most common and effective methods for the syn-thesis of five-membered nitrogen-containing heterocycles.In this thesis,a new method for the synthesis of pyrroloisoquinoline derivatives from the tetrahydroisoquinoline and unsaturated carbonyl compounds is developed.This method provide an efficient protocol for constructing pyrrole ring in a single operation.This is part of ourcontinuous studies on the development of effective method to synthesis of nitrogen-containing heterocycles.In the experimental part,the reaction conditions are screened by using tetrahydroiso-quinoline and α-methyl cinnamaldehyde as template substrates,and the optimum conditions are obtained as follows:Fe(Ts)3(20 mol%)as catalyst,toluene as solvent,and reaction tem-perature is 110℃.Under these optimal conditions,the target product is obtained in 79%yield after 4 hours.Subsequently,the limitation and scopes of this reaction is studied,and 38 new compounds were obtained by using substituted cinnamaldehydes and chalcones as the staring materials.In addition,the yields are good to excellent.The structure of the products is char-acterized by NMR,HRMS and single crystal X-ray analysis.Our method has some ad-vantages such as easily available starting materials,simple reaction conditions,and high at-om-economy,etc.The method not only provides a new entry for the diversity synthesis of pyrrolo[2,1-a]isoquinoline compounds,but also lay a foundation for studying the application of these compounds.