Based On Alcoholic Oxonium Ylide Capture Catalytic Asymmetric Multicomponent And Divergent Tandem Reaction On Efficient Construction Of Chiral Heterocyclic Compounds

Generally, compared to traditional two component reaction, besides the multicomponent reaction showed incomparable synthesis efficiency and product diversity, the tandem reaction without any isolation between two operation steps showed much more consice. If these two methods are combined in the catalytic asymmetric aspect, we believe, which will bring the traditional synthesis with new connotation and significance.In recent years, a series of multicomponent reactions arise from diazo chemistry such as the capture of oxygen, nitrogen ylide and amphoteric ion has greatly developed. This paper mainly studies the alcoholic oxonium ylide fields and begins with finding and confirming the catalytic system which has a good tolerance of substrates. Subsequently, exploring and establishing compatibility conditions for the tandem reaction between each functional group on product. Finally, we have achieved the one pot asymmetric synthesis of a series of heterocyclic compounds while realized the tandem procedure between three component reaction and various types of other reactions. All the above have proved the feasibility and advantage of the catalytic asymmetric multicomponent reaction combining with the tandem concept.Thanks for the catalytic system only recognizes several special groups such as hydroxl, diazo group and aldehyde or imine, we only need to change the non reaction functional group in reaction module for finishing the design synthesis. In our mind, a modular synthesis system has achieved its initial forming, which also pushed the significance of asymmetric catalytic multicomponent reactions based on the capture of alcohol alcoholic oxonium ylide to a new hight.Chapter 1 is an overview, mainly introduced:a) the characteristics of diazo participated multicomponent reactions based on the capture of reactive intermediates. b) The feasibility and significance of the combination with tandem reaction, c) Briefly introduces the research foundation and the design ideas of this paper.In charpter 2, we studied mainly around to find and establish a catalytic system suitable for different types of alcohols. Used phenyl diazo ester, benzyl alcohol and imine as the template reaction substrates, we studied and discussed the control of stereochemistry with different catalytic system, and finally found a chiral zirconium(IV) and Rh2(OAc)4 co-catalyst system with a excellent control performance on the template reaction. After analysis and comparison, we discussed the reason why catalyst in which with different ratio of ligands vs zirconium and different feeding order of substrates are all have impact on this reaction. Then the optimal reaction conditions were established and repeatedly validated by a series reaction of different alcohols which proved that this co-catalyst system is widely applicable for most alcohols.The charpter 3 mainly discussed the asymmetric catalytic three component reactions with diazo ester, alcohol and imine and its tandem reactions. With the successful condition in hand, after some adjustment derived from different substituent alcohol with different tandem reaction conditions, finally, we have synthesized three kinds of substituted chiral morpholine derivatives. And with the new discovery that the catalyst system also has better adaptability for different kinds of diazo ester compounds, after changing the aryl diazo to alkyl diazo and a specific alcohol, a chiral pyrrole derivatives has also been synthesized with good results in one step.The charpter 4 mainly discussed the asymmetric catalytic three component reactions with diazo ester, alcohol and aldehyde and its tandem reactions. Compared our previous work, we firstly confirmed the feasibility of the reaction of diazo ester, alcohol and aldehyde by the modified catalyst system. Then, we compared the fundamentally different and absolute advantage uses of zirconium(IV) and rhodium(II) co-catalyst system with former from the aspects of operation and mechanism. Finally, by choosing specific alcohol, aldehyde and corresponding tandem reaction methods, the asymmetric synthesis of a class of multi substituted pyran derivatives, a kind of multi substitutedl,4-dioxane derivatives and a class of polycyclic compounds with six to eight chiral centers have been achieved in one pot successfully.