Mechanisms And Stereoselectivity Study For The Asymmetric Organic Reactions Catalyzed By Chiral Bisthiourea And Bioxazoline

The highly efficient synthesis of chiral organic compounds with special properties and functions can be achieved by chiral hydrogen-bond catalyzed stereospecific reaction,but deep insights towards mechanisms and stereoselectivity of hydrogen bond catalyzed reactions are still insufficient.The main content of the thesis is to investigate and discuss the detailed mechanisms of both chiral bisthiourea catalyzed asymmetric Diels-Alder reaction and chiral bioxazoline catalyzed asymmetric decarboxylative aldol reaction,with the use of theories such as M06-2X,quantum theory of atoms in molecules(QTAIM),distortion/interaction analysis,etc.This thesis is divided into four parts:Chapter 1: Research background.In this chapter,the author briefly introduced the significance of asymmetric synthesis,the advantages of organic catalyst,the activation to substrate by hydrogen bond.This chapter includes four sections: introduction,hydrogen bond donor activation and hydrogen bond acceptor activation,research progress of(thio)urea catalyzed Diels-Alder reaction,research progress of decarboxylative aldol reaction.Chapter 2: Theoretical basis and computational methods.This chapter contains introductions of developing progress of quantum mechanics,density functional theory,solvation effect model theory,methods to investigate distortion and interaction energies of molecules,basic knowledge of stereochemistry,and fukui function.Chapter 3: Mechanism research of chiral bisthiourea catalyzed asymmetric Diels-Alder reaction.In this chapter,the Diels-Alder reactions between 3-vinylindole and methyleneindolinone with catalyst-free and with chiral bisthiourea catalyst were investigated in detail.We choose M06-2X density functional theory and 6-31G(d,p)basis set and IEFPCM solvation model to optimize all structures,and single-point energies were calculated in Def2-TZVP basis set.The catalyst-free reactions proceeded concerted but asynchronous mechanism,and the origin of stereoselectivity was found out with the help of distortion/interaction energy method,AIM analysis and NCI analysis,that is,smaller total distortion energy and larger interaction energy will improve the preference of reaction.Chiral bisthiourea catalyst combinedwith 3-vinylindole and methyleneindolinone through weak intermolecular interactions.The intermolecular interactions can activate substrates;Moreover,the intermolecular interactions can stabilize transition state to lower its energy;In addition,chiral bisthiourea catalyst can provide a chiral environment to make substrates form tertiary complex in a certain way,and the relative stability of tertiary complex is the origin of stereoselectivity.Chapter 4: Mechanism research of chiral bioxazoline catalyzed asymmetric decarboxylative aldol reaction.In this chapter,the pyridine and chiral bioxazoline catalyzed decarboxylative aldol reactions between ?-carbonyl acid and trifluoroacetaldehyde were investigated.We choose M06-2X density functional theory and 6-311G(d,p)basis set and IEFPCM solvation model to optimize all structures,and single-point energies were calculated in Def2-TZVPP basis set.With computational research,we investigated the decomposition and interconversion of S and R conformations of trifluoroacetaldehyde hemiacetals,the reaction process of styryl alcohol tautomerizing to acetophenone,and the electrophilicity comparison between trifluoroacetaldehyde and the corresponding hemiacetal.After computational investigation we drew conclusions that:When pyridine serves as catalyst,styryl alcohol is nucleophile while trifluoroacetaldehyde is electrophile,the decarboxylation reaction occured on ?-carbonyl acid to form styryl alcohol,further nucleophilic attack took place with trifluoroacetaldehyde;When chiral bioxazoline serves as catalyst,?-carbonyl acid is nucleophile while trifluoroacetaldehyde is electrophile,the nucleophilic addition firstly occured,then decarboxylation reaction took place;In nucleophilic reaction,the chiral bioxazoline catalyst provided a chiral environment for the trifluoroacetaldehyde formed in situ,the Re-face of trifluoroacetaldehyde is blocked,then the stereoselectivity of product can be achieved.By investigating the mechanisms of both chiral bisthiourea catalyzed asymmetric Diels-Alder reaction and chiral bioxazoline catalyzed asymmetric decarboxylative aldol reaction,this thesis provided a better understanding of organocatalyzed asymmetric reaction,and shed light on design of new catalysts and new organic reactions.