Synthesis Of Multi-nitrogen Heterocyclic Compounds Based On [3+2] Cycloaddition Reaction

Pyrrolidine compounds are a class of compounds containing multiple heterocyclic nitrogen heterocycles,which are found in many natural products.Such compounds have significant biological activities in anti-cancer,anti-bacterial,anti-viral,and anti-oxidant aspects.For example,the alkaloid crispine A extracted from Carduus crispus L has significant anti-cancer activity;the Lamellarins extracted from marine invertebrates have a certain effect in preventing human cancer and anti-virus（HIV-1）.It is precisely because pyrrolidine compounds contain a unique heterocyclic structure and significant pharmacological activity that they have attracted widespread attention from scientific researchers.In the process of studying the synthetic methods of polybasic nitrogen heterocyclic compounds,new types of reactions used to synthesize such compounds are constantly discovered.Among them,the most extensive and in-depth research is the contraction method.As one of the condensation methods,the 1,3-dipolar Cycloadditions cycloaddition reaction has a profound impact on the synthesis of pyrrolidine compounds.The cycloaddition reaction is usually a multi-component reaction,which has many advantages of a multi-component reaction.Therefore,when designing the reaction route,the[3+2]cycloaddition reaction was introduced to synthesize nitrogen-containing compounds with complex structures,and good results were achieved.The research content of this paper is as follows:（1）The[3+2]cycloaddition reaction involving aromatic aldehyde compounds,amino acid esters and 1,4-naphthoquinone was studied.Aromatic aldehyde compounds first undergo a condensation reaction with amino acid esters to form intermediates,and then undergo cycloaddition reactions with active olefins in the deconstruction of benzoquinone to obtain pyrrolidine products,finally undergo further oxidation to obtain aromatization products.In this section,the reaction conditions were screened and optimized,and 11 aromatized products were obtained.The structures were confirmed by ¹H NMR,¹³C NMR and HR-MS（ESI）.（2）The synthesis of pyrrolo[2,1-a]isoquinoline compounds through N-allylation reaction and intramolecular Heck reaction with[3+2]cycloaddition product as starting material was studied.In this chapter,we focus on optimizing the conditions of N-allylation reaction and intramolecular Heck reaction.Use LC-MS to monitor the intramolecular Heck reaction process,understand the intermediates formed in the reaction process,and infer the reaction mechanism.This paper mainly investigates various factors that affect the reaction and optimizes the conditions.The structure of all final products has been characterized by ¹H NMR,¹³C NMR and HR-MS（ESI）.In this paper,a series of nitrogen-containing heterocyclic compounds were synthesized based on the[3+2]cycloaddition reaction.When exploring the conditions of the cycloaddition reaction involving 1,4-naphthoquinone,oxygen is used as the oxidant,and the reaction yield is high and pollution is less.When studying the synthesis method of pyrrolo[2,1-a]isoquinoline compounds,the intramolecular Heck reaction was used to efficiently synthesize the target product.The route is simple to operate,has a wide range of applications,and has a good reaction effect.