Catalytic Asymmetric Mannich Reaction Of Isatin Ketimines With ?-substituted Aldehydes

Mannich reaction is a kind of important organic reaction,it forms carbon-nitrogen bond while forming carbon-carbon bond,it is an important means of synthesizing ?-aminocarbonyl compounds,because Mannich reaction is synthesizing drug,Natural products and multi-purpose intermediates are widely used,so in recent years,asymmetric catalytic reports of aldehydes and aldimines are common.Although there are numerous reports on asymmetric catalytic Mannich reactions of aldehydes and aldimines,the stereoselectivity in asymmetric catalysis of aldehydes and keto-imines has proved to be challenging.In this paper,the asymmetric Mannich reaction of indirubinone imine with ?-substituted aldehydes catalyzed by different chiral amine catalysts was reviewed,and the different stereoselectivity of the products was demonstrated and analyzed.In the first part of this thesis,the Mannich reaction is introduced and the progress of asymmetric catalytic Mannich reaction between imines and aldehydes is discussed.The second part of this thesis is divided into two modules.The first module describes the asymmetric Mannich reaction of N-Boc protected indirubinone imine and its derivatives with ?-substituted aldehydes catalyzed by chiral primary amines.We used THF as a solvent of 20 mol% chiral primary amines.The reaction at room temperature for 36-178 h resulted in a yield of up to 88%,more than 20:1 dr,92% ee and a high universality in the substrate range.In the second module,the asymmetric Mannich reaction of N-Cbz protected indirubinone imine and its derivatives with?-substituted aldehydes catalyzed by proline silyl ether(secondary amine)catalyst was described.We also used THF as solvent,20 mol% proline silyl ether catalyst for 15-96 h reaction at-30°C to obtain a product with a yield of up to 82%,> 10: 1dr and 99% ee.The universality of the same substrate range is high.Then we explore the mechanism of different product configurations in the former reaction.In conclusion,we studied the asymmetric reaction of indigo imine with?-substituted aldehydes catalyzed by different chiral amines.A highly selective and highly active catalytic method for asymmetric Mannich reaction of ketone imines andaldehydes was obtained.It is worth mentioning that we have obtained different stereoselectivity products through the selection of catalysts,which can be said to be a relatively successful exploration.