Asymmetric Diversity-oriented [3 + 2] Cyclization Of Trifluoromethyl Oxindole Dipoles

Oxindole and its derivatives are a kind of very important nitrogen-containing heterocyclic compounds,which widely exist in many drugs and natural products,and have a variety of biological activities,such as anti-tumor,antibacterial and so on,so oxindole alkaloids with various significant biological activities are more and more used in drug research field.Trifluoromethyl is a kind of important chemical group in the field of pharmaceutical chemistry,which plays an important role in improving pharmacokinetics and pharmacodynamics.Therefore,it has certain importance and practicability to construct a kind of drug like compound with both oxindole skeleton and trifluoromethyl group.In this paper,we focus on the study of the asymmetric diversity-oriented [3 + 2] cyclization of trifluoromethyl oxindole dipoles.The specific work is as follows:1.Tertiary amines catalyzed the asymmetric [3 + 2] cycloaddition of oxindole dipoles and configuration transformation of the products.This work is use chiral tertiary amine catalyzed the asymmetric [3 + 2] cycloaddition reaction of trifluoromethyl oxindole dipoles and thiazolidone compounds,obtained a series of spirooxindole products 4 with high yield and high stereoselectivity.And these products 4undergoes configuration transformation reaction under acid condition,which could be further transformed into a series of diastereomer 5,which structure same as the compounds 4but different absolute configuration.The reaction is operated simplely,mild conditions,and raw materials is accessible,low in price and good in substrate adaptability.2.Bifunctional catalyst for the asymmetric [3 + 2] cycloaddition of trifluoromethyl oxindole dipoles.In this part,we try to use chiral bifunctional catalyst to catalyze the asymmetric [3 + 2]cycloaddition of oxindole dipoles and thiazolidone compounds,obtained a series of spirooxindole products 6 with high yield and high stereoselectivity,and the structure of this reaction products 6 is same as the above two products(4,5),but the absolute configuration is different,the three products are diastereomer each other.However,it was found that the enantioselectivity of the product obtained by the catalytic reaction of chiral bifunctional catalyst was poor,and the enantioselectivity could not be improved after the screening of conditions.Therefore,we finally chose the achiral bifunctional catalyst to catalyze the asymmetric [3 + 2] cycloaddition reaction to obtained racemic product 6.This reaction is operated simplely,mild conditions,and raw materials is accessible,low in price and good in substrate adaptability.