Applications Of Supramolecular Iminium Catalysis In Vinylogous Michael Addition And Kinetic Resolution

Recently,the development of organocatalysis has been limited by several disadvantages such as long reaction time,high catalyst loading et al.Under this background,the concept of supramolecular iminium catalysis has been developed.In supramolecular iminium catalysis,non-convalent catalyst was added to activate the in situ generated iminium so that the concentration and activity of iminium were increased.Many reactions which are difficult to realize under general iminium catalysis can be achieved using supramolecular iminium strategy.Furthermore,the reaction rate can be improved while reducing the catalyst loading.This thesis mainly concerns on the application of supramolecular iminium catalysis in the asymmetric vinylogous Michael addition and kinetic resolution of ? aryl substituted aldehyde.In chapter 1,the organocatalyzed vinylogous Michael reactions was briefly reviewed based on the substrate structures and the activation modes,many challenges vinylogous Michael were facing have been summarized such as the low activity of vinylogous substrates,difficulty to control regio-and stereoselectivity.Meanwhile,opportunaties were also presented since the chiral 1,7-dioxo products obtained from asymmetric vinylogous Michael reaction were important synthons for the synthesis of natural products and pharmaceuticals.In chapter 2,the vinylogous Michael reaction of 3-alkylidene oxindoles to ?,? unsaturated aldehyde via supramolecular iminium catalysis was introduced.Indoles are probably the most privileged molecular scaffolds in natural products and many of which have a wide spectrum of biological activities.Compared with ?-butyrolactams or ?-butenolides,the exocyclic oxindole was much less explored as Michael donors because of its inherently low reactivity.By supramolecular iminium catalysis,in which the in situ generated iminium ion can be activated by thiourea and the nucleophilic dienol intermediate can also be activated and stabilized by anion-bonding interaction as well,good yields and high eanatioselectivities were obtained.After the direct vinylogous Michael addition realized,we next consider how to use this Michael reaction in the construction of structurally diverse molecules.In chapter 3,we designed a vinylogous Michael and Stetter relay sequence to construct HajosParrish Ketone skeletons.Hajos-Parrish Ketone carbon ring motifs are privileged skeletons since they have been widely found in many bioactive natural products and pharmaceuticals.However,in some synthetic examples,a series of linear steps are necessary to achieve the functional group interconversions or transpositions of the Hajos-Parrish Ketone.As a consequence,Hajos-Parrish-type ketones bearing other functional groups or transposed carbonyl groups are also attractive and highly desirable.The combination of organocatalytic vinylogous Michael and Stetter reaction would significantly expand the scopes of these two reactions for the construction of structurally diverse molecules,which has scarcely been reported yet.Our work has made a good complement.In chapter 4,we first described the recent advances in the organocatalyzed kinetic resolution.Kinetic resolution is one of the most reliable and widely used methods in both academia and industry,however,kinetic resolution of ?-aryl substituted aldehyde through enamine and iminium catalysis has never been reported,probably due to the steric hindrance of ?-substituent which presented extra challenge for the catalyst to interact with the substrate.By employing a rationally designed supramolecular catalysis system,an efficient kinetic resolution of ?-aryl substituted aldehydes with ?,?-unsaturated aldehydes was developed to achieve a dual purpose of the synthesis of densely functionalized cyclohexanes as well as the enantioenrichment of the ?-aryl aldehyde.The unique feature of this kinetic resolution is the implementation of a multiactivation system that activates both the substrates and the reactive intermediates in order to drive the reaction.This novel catalysis system opens a new field wherein non-covalent interactions between ion pairs give rise to both the modulated reactivity and selectivity.