The Applications Of Asymmetric Bifunctional Organocatalysis On The Construction Of Complex Molecules

This thesis makes some researches on the asymmetric synthesis of spiro-cyclohexene pyrazolones and enantioselective C-H functionalization of indoles in the carbocyclic ring via bifunctional organocatalysis,which is composed of four parts:Chapter 1: Chiral chemistry has a long and abundant history.Asymmetric catalysis,as an important part of chiral chemistry,has been fully developed since 1960 s with the rise of transition-metal catalysis.Orgnocatalysis has a long history,but was has been extensively exploited since 2000.Firstly,this chapter briefly introduced the developments of chiral chemistry and asymmetric catalysis.Then,the birth and rise of organocatalysis was described through illuminating and comparing different catalytic model.Finally,we emphatically demonstrated the advances of bifunctional organocatalysis through reviewing the history of bifunctional organocatalysts and bifunctional organocatalytic model.Chapter 2: Pyrazole derivatives have been extensively explored due to their widespread applications as potential pharmaceutical agents,synthetic scaffolds,photographic couplers and chelating agents.At the beginning of this chapter,we introduced the recent advances of the asymmetric synthesis of pyrazolone scaffolds.And on this basis,a variety of spirocyclohexene pyrazolones with enormous pharmaceutical potential were synthesized in good yields with excellent stereoselectivities through an asymmetric,intermolecular,quaternary carbon center forming [3+3] cycloaddition reaction catalyzed by a bifunctional catalyst.The vinylogous pyrazolones used as binucleophilic synthons in this reaction exhibited a superior ability for constructing pyrazolone related spirocyclic scaffolds.Chapter 3: Indole frameworks have been extensively exploited because of their enormous potential and widespread applications as pharmaceutical agents,synthetic scaffolds,and chelating agents.However,the majority of attention has been focused on the asymmetric functionalization of indoles in the azole ring.We have developed a practical and efficient approach for asymmetric C-H functionalization of indoles in the carbocyclic ring via organocatalysis,and a series of tetrahydropyranoindoles were obtained in moderate to high yields with excellent stereoselectivities.The cascade reactions also proceeded smoothly on large scale,further proving their synthetic value.The control experiments and thermodynamic calculations demonstrated that C-3 functionalization of this system needed to overcome higher Gibbs-free energy.Particularly,together with previous asymmetric C-3 functionalization of hydroxyindoles,the strategy realized the switchable,regiodivergent modification of indolesChapter 4: Axially chiral compounds have been extensively studied due to their widespread applications as bioactive molecules,natural products and chiral catalysts in asymmetric catalysis.This chapter fistly introduced the synthesis of axially chiral compounds via asymmetric catalysis,and mainly described the advances of constructing axial chirality via organocatalysis.Then,we developed an efficient method to construct axial chirality in the carbocyclic ring of indoles via asymmetric hydrogen-bond donors,and a variety of axially chiral biaryldiols were synthesized in good yields with excellent atroposelectivities.In addition,the new axially chiral compounds were proved to be efficient and practical ligands for asymmetric catalysis.The strategy not only provides a novel method to synthesize axially chiral compounds,but also extends the scope of chiral catalysts.