Research On Enantioselective Desymmetrization Of Aminodialkenes Through Hydroamination Of Alkenes

Organic nitrogen-containing compounds are widely found in nature,they have extremely wide applications in the synthesis of pesticides,cosmetics,and medical supplies.Hydroamination is an important method for the synthesis of organic nitrogencontaining compounds and the use of desymmetrization strategy to achieve high enantioselective and diastereoselective hydroamination reactions plays an important role.This thesis focuses on developing a simple and efficient method for the construction of chiral pyrrolidines.The first chapter of the thesis briefly introduces the research background and importance of this topic.Then,based on the different reaction types,the related research progress is analyzed from three aspects: hydroamination reaction,desymmetrization and organic catalysis.Then through designing the substrate,screening the reaction parameters,we obtained the optimal reaction conditions for the enantioselective desymmetric hydroamination reaction.It is concluded that the synthesis of pyrrolidines by asymmetric small-symmetry hydroamination has not been reported and remains to be explored.Then,through reasonable substrate design,the aminodialkenes compound was selected as the model substrate,and the chiral phosphonic acid was used as the organic catalyst by screening.The screening and optimization of the reaction conditions were carried out,and the optimal reaction conditions were obtained.The catalytic system shows excellent compatibility in the development of the reaction substrate.This method can be used for the construction of the core skeleton of natural products.Finally,the mechanism of the reaction was discussed,and the transition state of the reaction was proposed.The absolute configuration of the product was determined by single crystal structure.In this paper,an aminodialkenes compound with a thiourea group on the amino group is used as a reaction substrate.Under the catalysis of chiral Bronsted acid,intramolecular desymmetrization reaction occurs,in a one-step,a pyrrolidine compound which have two chiral centers is formed with high diastereoselectivity and high enantioselectivity.