Study On Nickel-catalyzed Ullmann-type Reductive Coupling Synthesis Of Dibenzo[c,e]azepine And Its Derivatives

Benzazepines have broad application prospects in production an d life,and such skeletons are often found in the core structural units of many pharmaceutical molecules,biologically active substances and natural products.In addition,due to the rapid development of catalytic chemistry,its framework is included in bo th the auxiliary ligands and organocatalysts of transition metal catalysts.Based on this,developing strategies for efficient synthesis of benzazepines is one of the important research contents in the field of organic chemistry.In recent years,great progress has been made in the research on how to construct benzazepines,which provides reference s for the synthesis of many biologically active molecules and natural products.In this paper,the application of benzazepines compounds is briefly introduced,an d the synthetic strategies of dibenzazepines compounds are analyzed and reviewed.On the basis of literature research,in this paper,taking the dibromoaniline/dibromonaphthylamine compound as the research object,a method was developed to construct seven-member nitrogen heterocyclic compounds with biaryl framework by using a nickel-catalyzed Ullmann type reduction coupling strategy.This article mainly contains two parts:1.A strategy was developed for the construction of dibenzo[ c,e]azepine compounds through Ullmann-type reductive coupling reactions.In the reaction,dibromoaniline compound is used as raw material,nickel catalyst,ligand,additive and reductant are added,Ullmann reaction occurs,and the target product is synthesized.This strategy has the advantages of high synthetic yield,wide substrate adaptability,ability to scale up the synthesis of drug molecules at the gram scale,and simple operation.Based on the results reported in the literature,the mechanism of the reaction was studied,and the reaction process was preliminarily deduced.2.A method for reductive coupling synthesis of binaphthyl secondary amine compounds was developed by nickel-catalyzed Ullmann-type reaction.Using dibromonaphthylamine compound as raw material,under the jo int catalysis of nickel bromide and nitrogen ligand,an intramolecular cyclization reaction takes place.The optimal conditions of the reaction were confirmed,and the substrate range was explored,and 21 target products were synthesized in good to excelle nt yields.The chirality application of this reaction was preliminarily explored,and the conditions of the template reaction were screened and applied to the obtained products.This method has the advantages of simple operation and mild reaction condition s.