Application Of Chiral Organic Catalysts In Asymmetric Mannich Reaction And Michael Addition Reaction Of Benzofuranones

The asymmetric synthesis of chiral benzofuran compounds has attracted much attention due to their anticancer,anti-tumor,antibacterial,antioxidant,and antiviral activities.In this thesis,we have used quinine derived bifunctional chiral catalysts for the asymmetric Mannich reaction of 3-substituted benzofuranones and N-Boc aminosulfones.On this base,we also developed the asymmetric Michael addition reaction of 3-substituted benzofuranones with benzofuran derived azadienes catalyzed by L-tert-Leucine derived squaramide.The specific research work is as follows:1.The quinine derived bifunctional phase transfer catalysts were used to catalyze the asymmetric Mannich reaction between 3-substituted benzofuranones and N-Boc aminosulfones.Through the optimization of catalyst,solvent,base,temperature,additive and substrate equivalent,the optimal reaction conditions were finally determined as follows:10 mol%of catalyst 3h,fluorobenzene as the solvent,K₂CO₃ as the base,-25℃of reaction temperature.Under the optimal reaction conditions,a series of benzofuranones and N-Boc aminosulfones were used in the asymmetric catalytic reaction to synthesize a series ofβ-aminobenzofuranone derivatives containing a chiral furanone structure.The reaction showed up to 96%yield and good enantiomeric and diastereomeric selectivity（up to 98%ee and>99:1dr）.The applicability of this reaction was demonstrated by gram-level reaction and derivatization experiments.At the same time,the possible transition state model is proposed according to the configuration of the reaction products.2.The L-tert-Leucine derived squaramide catalysts were used to catalyze the asymmetric Michael addition reaction between 3-substituted benzofuranones and benzofuran derived azadienes.Through the screening of solvent,temperature,catalyst and its loading,the optimal reaction conditions were determined as at room temperature,toluene as solvent and 1 mol%catalyst loading.Under optimal reaction conditions,a series of 3-aminobenzofuran derivatives containing chiral benzofuranone fragment structures were synthesized with up to 98%yield and good stereoselectivities（up to 97%ee and 97:3 dr）.The practicality of the reaction was demonstrated through gram-scale reaction and derivatization experiments.At the same time,the possible transition state model is proposed according to the configuration of the reaction products.