Catalytic Asymmetric Conjugate Addition And Sulfenylation Of Diarylthiazolidin-2,4-Diones

Compounds made up of elements such as C,H,O,N are closely related to our life,and we know that the most compounds in nature are chiral,and only one of them is effective.Nowadays,more and more chiral materials are widely used in our daily life.Chiral compounds are changing people's lives with the development of the pharmaceutical industry.We know that the synthesis of chiral materials is more difficult.Therefore,how to obtain chiral materials by a simple,green,efficient and feasible method has attracted the attention of chemists.With the continuous efforts of chemists,various methods have been developed to obtain chiral materials.Among them,the asymmetric catalyst based on transition metals has been a great success.However,due to the use of transition metal catalyst will produce a certain amount of heavy metal residues,which restricts its application in many industries,especially in industries related to people closely.The organic asymmetric catalyst with small organic molecules for environmental friendly,catalytic efficiency has rapidly developed in recent years.More and more attention has been paid to the chiral drug of the thiazolidinedione as the core.In the three years of my graduate student,We report the first example of using diarylthiazolidin-2,4-diones as nucleophiles in asymmetric catalysis.Through employing chiral amino acid-based(thio)urea-tertiary amines as catalysts,asymmetric conjugate addition to nitroolefins and sulfenylation to N-(sulfanyl)-succinimides of diarylthiazolidin-2,4-diones have been developed.This paper reads as follows:1.Synthesis of ThiazolidinedionesThiazolidinedione is a very useful reaction substrate,the synthesis of diaryl thiazolidinedione can be traced back to 1901,but its synthesis yield is generally low,and applicability is poor.For electron donations on the aromatic ring,it is not applicable.After a century there are few reports.On this basis,a new,simple,high yield and good applicability method was reported to synthesize this kind of compound.2.Asymmetric Michael addition of thiazolidinediones with nitroolefinsBased on the history research in our group,herein,5H?Oxazol?4?ones was applied again in Michael addition with another substrate nitroolefins.excellent results involving yields and stereoselectivities have been successfully obtained(for Michael products: up to 99% ee,> 99% Dr).Next,under the leadership of my brother,I studied the Michael addition reaction with oxazolidinedione as the substrate and nitroolefin.The use of threonine as the core skeleton of urea as a catalyst to obtain 98% yield,94% ee,> 19: 1 Dr.On the basis of the research of the research group,we proposed the addition of the thiazolidinedione as the reactant with the nitroolefin.We reported for the first time the asymmetric Michael addition reaction with diaryl thiazolidinedione as a nucleophile.5-aryl-5-substituted thiazolidine-2,4-dione(>99% ee,>19:1 Dr)with high enantioselectivity and non-corresponding selectivity was obtained,MTT assay showed satisfactory anticancer activity against three different cancer cell lines.3.Asymmetric Sulfenylation of thiazolidinediones with N-(sulfanyl)-succinimidesFirst,The development of sulfenylation is briefly summarized.Based on the research on the reaction of our group,the Sulfenylation of diaryl thiazolidinedione is carried out.The thiourea derivatives derived from tert-leucine as the core skeleton were used as catalyst to obtain(for Sulfenylation products: up to 98% yield,91% ee).and the product was subjected to simple stepwise oxidation to synthesize a pharmacologically active Compounds.