Study On The Asymmetric 1,3-dipolar Cycloaddition Reaction Of Benzoisothiazole Derivatives And Azomethine Ylides

1,3-Dipolar cycloaddition reaction is a common method for synthesizing five-membered heterocyclic compounds due to its high stereoselectivity and mild reaction conditions.In the early 1960 s,Huisgen firstly proposed the concept of 1,3-dipolar cycloaddition,and the research on the mechanism of cycloaddition reaction and its application has been a hotspot in the field of chemistry.With the developing of the research,the use of chiral metal complex as a catalyst for the synthesis of optically active products by 1,3-dipolar cycloaddition reaction has aroused a wide range of attention from experts.Based on the synthesis of natural spirooxindoles and their biological activity,it is proposed that novel spiro benzoisothiazole dioxide derivatives that can be produced with benzoisothiazole-2,2-dioxide-3-ylidene derivatives as dipolarophiles and the azomethine ylides as dipoles through the cycloaddition reaction.At the same time,the 1,3-dipolar cycloaddition reaction of the benzoisothiazole derivatives was studied in depth,and the enantioselectivity of the reaction under chiral catalytic conditions were investigated.The method for the construction of compounds with similar structures was provided and lay an important foundation for further study of asymmetric 1,3-dipolar cycloaddition reactions.The main work that we have accomplished is as follows:(1)1-methyl-1,3-dihydro-benzoisothiazole-2,2-oxides was obtained with o-bromoaniline as raw material.Benzoisothiazole-2,2-dioxide-3-ylidene derivatives were obtained by Knoevenagel condensation of aliphatic aldehydes and aromatic aldehydes with 1-methyl-1,3-dihydro-benzoisothiazole-2,2-oxides.(2)glycine methyl ester hydrochloride or glycine tert-butyl ester was used as the substrate,different kinds of imines were prepared by condensation reaction with aromatic aldehydes containing different substituents and aldehydes with heterocyclic structures.The effects of different substituents on the yield of the reaction were explored and analyzed.(3)with benzoisothiazole-2,2-dioxide-3-ylidene derivatives as the dipolarophiles and azomethine ylides as dipoles,novel spiro benzoisothiazole dioxide derivatives were synthesized under a chiral condition,in which copper trifluoromethanesulfonate/ DM-Segphos catalyzed system was used as the chiral catalyst.The effects of different kinds of ligands,alkali,solvent,temperature and reaction time on the reaction were discussed,and the optimum reaction conditions were determined.A method for the preparation of spiro benzoisothiazole dioxide derivatives that containing four chiral centers of three tertiary carbon atoms and one spiro carbon atom by one step reaction is obtained with high diastereoselectivity and enantioselectivity.The absolute configuration of the product was unambiguously determined by X-ray single crystal diffraction.The catalytic mechanism of copper(II)/ DM-Segphos catalyst system for asymmetric reaction was proposed.