Design, Synthesis And Application Of Novel Multifunctional Chiral Phosphine Catalyst

Over the past decades,asymmetric phosphine catalysis has been intensely investigated as a powerful tool for the preparation of structurally divergent chiral molecules.Based on the diverse chiral phosphine catalyst,lots of new phosphine catalyzed reactions have been developed for the asymmetric formation of carbon-carbon bond,carbon-hetero bond and different cycloaddition reaction.In this paper,we focus on the design and synthesis of new chiral multifunctional phosphine catalyst and attempt to combine phosphine catalysis with umpolung addition of ketimines,leading to the asymmetric synthesis of chiral?-quaternary amines.The whole dissertation divides into five parts:1.IntroductionThe introduction owns two parts,first of all,we have done a brief introduction of chiral phosphine catalyzed zwitterion intermediate and the newest research development.Secondly,we try to introduce some classic synthetic route of the chiral phosphine catalyst.2.Design,synthesis of Peng-PhosThe ortho aryl substituted benzyl aldimine were obtained quickly through condensation of commercially available chiral tert-butylsulfinamide with ortho aryl substituted benzyl aldehyde.The ortho aryl substituted benzyl aldimine could be nucleophilic attacked by Ph₂PCH₂Li to obtain a series of chiral multifunctional phosphine catalyst.Besides,after bearing a simply transformation of these chiral phosphine catalyst with tert-butylsulfinamide,we can get a set of chiral?–amino phosphine.Through further derivative of these?–amino phosphine,we could gain new chiral phosphine catalyst with diverse type of hydrogen bond.3.Peng-Phos catalyzed asymmetric umpolung allylic-substituted reaction of trifluoromethyl ketimines and MBH adduct for the preparation of?-quaternary chiral trifluoromethyl amineUmpolung addition of trifluoromethyl ketimine with electrophilic regent have emerged as a powerful strategy for the preparation of?-quaternary chiral trifluoromethyl amines.Under the catalysis of chiral phosphine,umpolung allylic substituted of trifluoromethyl ketimine with MBH adduct lead to chiral?-quaternary trifluoromethyl amines.The salient features of this reaction include general substrate scope,mild reaction conditions,high yields,high enantioselectivity,ease of scale-up to gram scale,and further transformations of the products.4.Peng-Phos catalyzed asymmetric umpolung?-addition reaction of trifluoromethyl ketimines and allenoates for the preparation of?-quaternary chiral trifluoromethyl amines and chiral?,?-disubstituted?-amino acid derivativesWe further develop umpolung addition reaction from trifluoromethyl ketimines to electron deficient ketamine.Under the catalysis of chiral phosphine,umpolung?-addition of trifluoromethyl ketimines with allenoates lead to chiral?-quaternary trifluoromethyl amines and chiral??11??-disubstituted?-amino acid derivatives.The reaction still has salient features include mild reaction conditions,high yields,high enantioselectivity,ease of scale-up to gram scale,and further transformations of the products.5.Phosphine-catalyzed enantioselective[4+2]annulation of electron-deficient conjugated dienes and vinyl ketonesA highly efficient phosphine-catalyzed[4+2]annulation of electron-deficient diene and alkyl vinyl ketone was developed for the first time,which provides an easy access to functionalized cyclohexenes.This method has the advantages of mild reaction conditions,widely functional group tolerance,high yields and transition metal free.Chiral cyclohexene compound could also be obtained in 77%yield with 60%ee under the treatment of chiral phosphine catalyst.