Asymmetric Activation Of 10-C(sp~3)-H Of 5H-benzo[a]pyrroline-3-carbaldehyde Catalyzed By Nitrogen Heterocyclic Carben

N-Heterocyclic Carbene(NHC),as an important tools of organic small molecule catalysts,has been widely used in the field of organic small molecule catalysis.Its main feature is the nucleophilic addition with aldehydes to form the Breslow intermediates,which changes the carbonyl group from the traditional electrophilic to nucleophilic,achieving the polarity reversal of the carbonyl functional group.Compared with conventional catalysts,the high efficiency and sensitivity of NHC-catalyzed reactions can control the selective distribution of complex reaction products,also can achieve the efficient and highly selective construction of many heterocyclic compounds.The catalytic synthesis of organic small molecules using azacyclic carbenes can greatly save energy and avoid raw materials wasting and improve the production efficiency of organic chemical agents.It is well known that indole and its derivatives are widely found in medicinal plants,and they are mainly found in natural flower oils,such as jasmine,daffodil and vanilla,which are the most varieties as well as the most widely distributed heterocyclic natural products.With the rise of human life sciences and the advancement of technology,the exploration of a series of indole derivatives synthesized using organic synthesis and other methods has never stopped discovering by researchers that most of them have important biological activities.Morpholines are endemic structures in many commercial drugs and natural products due to their unique physicochemical properties and potential biological activities.For example,pollen glycosides A and pollen glycosides B containing pyrrolizomorpholine groups are natural products isolated from rape pollen collected by honeybees or herbal medicines,and they are used to treat central nervous system disorders,prostatitis and diabetic nephropathy et al.Therefore,it is important to develop new synthetic methods for the concise,rapid and efficient construction of morpholine-based indole derivatives containing complex polycyclic structures.In this paper,Breslow intermediates were formed by selective activation of aldehyde groups using NHC,and the acyl azolium intermediates formed in the presence of oxidants reacted with N-benzyl-substituted isatin to produce structurally complex biologically active indole derivatives.We performed asymmetric activation of 5Hbenzo[a]pyrroline-3-carbaldehyde remote carbon using NHC,and conducted extensive screening of the reaction system for the type of catalyst,reaction solvent,type of base,base equivalent,reaction concentration,additive,reaction temperature and other conditions,the reaction gave a better result with 3a isolated in 79% yield,> 20:1 dr,and 91:9 er.Based on the optimal conditions,we conducted a substrate generalization study for the model reactions,and the final products could be obtained with high yields and er.In addition,the NHC asymmetric catalytic reaction we developed was scaled up10-fold and was able to obtain the target product in 86% yield and 91:9 er.The results of the antimicrobial activity tests showed that some compounds showed superior biological activity to the commercially available Bismerthiazol(BT)and Thiamethoxam Copper(TC).