Study On The Reaction Of Catalytic Electron-deficient Olefins And Aromatic Nitrones By Chiral Inda-BOX Metal

The 1,3-dipolar cycloaddition reaction is a common method for synthesizing a five-membered heterocyclic compound.The five-membered heterocyclic chiral com pound synthesized by the 1,3-dipolar cycloaddition reaction has a wide range of app lications in the field of new drug research.In organic drugs,drugs interact with rece ptor sites in a chiral manner.The two enantiomers of the drug participate in different ways and can lead to different effects.The introduction of a chiral catalyst can grea tly improve the regioselectivity,diastereomerism and enantioselectivity of the cyclo addition reaction.Finding the appropriate chiral metal complex is the focus of stu dying the asymmetric catalyzed 1,3-dipolar cycloaddition reaction.Inda-BOX?L7?is used as a chiral catalyst.In this paper,the reaction of electron-deficient olefins with C,N-diaryl nitrone was studied,and a highly stereoselective cycloaddition product w as obtained.The specific research contents are as follows:1.Inda-BOX synthesis:First,the B-eye were reacted with a HCl/ethanol solu tion to obtain diethyl aminomalonate,and diethylaminomalonate was further reacted with a chiral amine alcohol to obtain a ligand L in a yield of 26%.L5 was reacted wi th methyl iodide to obtain a ligand L6 in a yield of 60%.Reaction of L5 with 1,2-dibromoethane to obtain ligand L7 in a yield of 66%.2.Synthesis of C,N-diaryl nitrone series derivatives:using nitrobenzene as a starting material,phenylhydroxylamine is obtained by reduction reaction,and phen ylhydroxylamine is condensed with benzaldehyde to obtain C,N-diaryl The nitrone is in a yield of 76%.3.Synthesis of electron-deficient olefins:reaction of urea with ethanolamine to obtain 1,3-oxazolidin-2-one,The 1,3-oxazolidin-2-one was reacted with acryloyl chl oride to obtain an N-?,?-unsaturated acyloxazolidinone?1a?with a yield of 91%.The N-?,?-unsaturated acylpyrazole?1b?was obtained by reacting 3,5-dimethylpyrazole with acryloyl chloride in a yield of 90%.4.Cu?OTf?₂-Inda-BOX?L7?was used as chiral metal catalyst.The chiral metal complex catalyzes the reaction of N-?,?-unsaturated acyloxazolidinone?1a?with diph enylnitrone.The paper discusses the effects of stereoselectivity on the reaction by ch anging the metal salt type,catalyst dosage,reaction temperature and nitrone structure.Finally,the optimal reaction conditions were obtained.The results show that Cu?OTf?₂-Inda-BOX?L7?is used as a chiral catalyst at 0°C and 20%catalyst.The regio selectivity of the reaction was increased to 100%,the exo/endo selectivity was incre ased to 84%,and the ee?enantiomeric excess?value of the main product exo-4 was97%.5.Ni?OTf?₂-Inda-BOX?L7?was used as chiral metal catalyst.The chiral metal complex catalyzes the reaction of N-?,?-unsaturated acylpyrazole?1b?with diphenyl nitrone.The paper discusses the effects of stereoselectivity on the reaction by chan ging the metal salt type,catalyst dosage,reaction temperature and nitrone structure.Finally,the optimal reaction conditions were obtained.The results show that Ni?OTf?₂-Inda-BOX?L7?is used as a chiral catalyst at room temperature and 30%cata lyst.The regioselectivity of the reaction was increased to 83%,the endo/exo select ivity was increased to 96%,and the main product endo-4 had an ee value of 98%.