| N-Heterocyclic carbene(NHC)have been widely used as one of important organocatalysts,in the construction of various chemical bonds.Owing to their unique catalytic activation mode through umpolung,they have emerged as efficient and versatile organocatalysts in the rapid construction of traditional functional molecules and novel framework functional molecules which are not easily synthesized through traditional methods.However,novel catalytic activation modes or functional molecules via NHC catalysts are still less studied in terms of applications.Lactones or lactams,especially?-lactone or?-lactam compounds,are widely present in pesticides,pharmaceuticals,and biologically active natural products.Additionally,?-lactones or?-lactams are also important organic synthons for complex natural products.Therefore,a simple and efficient synthetic method to access to?-lactones or?-lactams is highly desirable.Pesticides are a strong guarantee for agricultural safety production.Effects have long been put in the development of new green pesticides in the field of pesticide research.It is extremely important to find compounds with certain biological activities.This thesis mainly focused on the application of NHC catalyst in the construction of chiral?-lactone or?-lactam through one-step reactions.Their biological activities were also tested,aiming at figuring out some small biologically active function molecules.The important points of this thesis work could be individed into four parts.The first part is literature reviews.The discovery history and the state of the art of NHC catalysis were firstly described,and then the catalytic activation modes of carbonyl compounds by NHC catalysts were elaborated.According to the differences in activation sites or reaction modes,these reactions could be divided into five parts:(1)activation of the carbon atom of carbonyl groups;(2)activation of the?-carbon atom of carbonyl compounds;(3)activation of the?-carbon atom of carbonyl compounds;(4)activation of the?-carbon atom and remote carbon atom of carbonyl compounds;(5)radical reactions.Subsequently,the application of new functional molecules in the pesticides was reviewed,which were obtained through NHC catalyzed reactions.We also described the inhibitory activity against X.oryzae pv.oryzae and P.syringae pv.actinidiae in recent years.In the second part,chiral spirocyclic?-lactones was synthesized via?-C-H bond activation of?-chloroaldehydes by the catalysis of NHC catalyst,and then their biological activities were tested.In the field of NHC catalysis,?-chloroaldehydes have been powerful reaction substrates.However,the reactions of?-chloroaldehydes mostly proceeded through an enol intermediate,the reaction site was accordingly limited to?-carbon atoms of the aldehyde group,the transformation through?-carbon activation have not been reported.Owing to its saturated C-C bonds,the?-sp~3-C-H bond of?-chloroaldehydes were less reactive,resulting in the difficulty of activation of?-carbon in most NHC promoted reactions.With the design of the reaction process and careful optimization of reaction conditions,we finally realized the?-C-H bond activation of?-chloroaldehydes.In these transformations,homoenolate intermediate was generated and then reacted with isatins,affording chiral spirocyclic?-lactones efficiently through[3+2]asymmetric cycloaddition reaction.Further investigation showed good substrate compatibility.A various of spirocyclic?-lactones could be obtained in up to 99%yield,up to 20:1 dr value,and up to 98%ee value.We also performed some preliminary investigations of the products'bioactivities.However,these compounds were found to exhibit no inhibitory activity against X.oryzae pv.oryzae or P.syringae pv.actinidiae.The third part focused on the NHC catalyzed?-C-H bond activation of?-chloroaldehydes for the synthesis of chiral spirocyclic?-lactams and their biological activity studies.Chiral spirocyclic?-lactams,especially isatin-derived chiral spirocyclic?-lactams are important structural units in the field of organic synthesis.They are widely found in pharmaceutical molecules and bioactive natural products.In addition,this type of compounds are usually used as important organic synthons for the construction of complex structures.Here in,we employed an NHC catalyst to catalyze the asymmetric[3+2]cycloaddition reaction of?-chloroaldehydes and isatin-derived imines through a highly nucleophilic homoenolate intermediate.A series of chiral spirocyclic?-lactams compounds were constructed in good yields and enantioselectivities.We also performed some preliminary investigations of the products'bioactivities.However,these compounds were found to exhibit no inhibitory activity against X.oryzae pv.oryzae or P.syringae pv.actinidiae.The fourth part is about the NHC-catalyzed asymmetric reaction ofa,?-unsaturated aldehydes for the synthesis of chiral pyrrolidone compounds and its bioactivity studies.Pyrrolidone or?-lactam compounds have attracted great attention due to their unique chemical structures and biological activities.Besides,these compounds are also important intermediate for the construction of biologically active macromolecules.Here in,we achieved an NHC-catalyzed asymmetric[3+2]cycloaddition ofa,?-unsaturated aldehydes and?-amino acid esters via the formation of unsaturated acylazolium intermediate under oxidative conditions.We realized the efficient construction of a wide range of chiral pyrrolidone compounds.Through the inhibition test on the inhibition activity of X.oryzae pv.oryzae.,we found that the compounds 4-3d,4-3e and 4-3g had same inhibitory activities compared with bismerthiazol against X.oryzae pv.oryzae.at a concentration of 200?g/m L.It was also found that these compounds have some inhibitory activity against P.syringae pv.actinidiae.The compounds 4-3g and 4-3l showed the same inhibitory activities inhibition rate compared with bismerthiazol at 200?g/m L. |
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