Dinuclear Zinc Cooperative C Atalysts In Asymmetric[3+2]Annulation Reaction Of Trifluoromethylated Azomethine Ylides And Methyleneindolinones

The chiral spirooxindoles structure is common in many alkaloids,especially when the spiro ring is located at the 3-position,it is often regarded as a characteristic structure of biologically active drugs.It has received extensive attention from domestic and foreign scholars as high efficiency and good selectivity.For example,SAR405838 has made outstanding contributions to the treatment of advanced cancer;and NITD609 is a new and effective antimalarial drug.Although there have been many reports on the synthesis of chiral spirooxindoles,the trifluorobispirooxindoles is still a big challenge in organic synthesis because of its special structure,which contains two adjacent spiro quaternary chiral centers and a highly crowded complex structure.In this thesis,chiral bispirooxindoles skeletons were constructed bythe[3+2]annulation reaction of N-2,2,2-trifluoroethylisatinimine and methylene indolinone catalyzed by dinuclear zinc synergistic catalyst for the first time.Optimizing of reaction conditions,such as ligands,solvents,reaction time,temperatures,catalyst loadings,etc,showed the best reaction conditions were as follow:10 mol%catalystloading,4A MS as additive,in anhydrous toluene for 12 hours at 25 ?.Subsequent expansion of the substrates under the optical conditions,gave the corresponding productswith excellent yields(up to 99%),excellernt enantioselectivities(>99%)and diastereoselectivities(>20:1).To verify the practicability and applicability of the reation,gram-scale experiments and derivative experiments were also carried out.The configuration of the product was determined by X-ray single crystal diffraction,and a reasonable reaction mechanism was proposed based on theabsolute configuration of the product and therelated literature reports.