The Synthesis Of N-Heterocyclic Axially Chiral Compounds & The Investigations For The Chirality Transfer Of BINOLs

Axially chiral compounds have received much attention since their widespread appearance in natural products,physiological active compounds and the significant role in the field of chiral catalysts and chiral ligands in asymmetric catalysis.Given the promising value of axially chiral skeletons,the enantioselective synthesis of axially chiral compounds has become a fundamental hotspot in organic chemistry.In the context,this dissertation has two parts which can be divided into three chapters:The first part mainly focused on the development of quinolizones,which contained the decoration of the skeleton and the atroposelective synthesis of quinlizone-based axially chiral compounds.The second part mainly studied the synthesis of spiro-compounds bearing the quaternary stereocenter via the axial-to-central chirality transfer of enantioenriched BINOLs.The second chapter:This chapter investigated the synthesis of 1-amino-2H-quinolizin-2-one scaffolds by tandem cycloisomerization-amination reaction catalyzed by silver salts.Having di-tert-butyl azodicarboxylate as the amination reagent and AgNO₃ as catalyst,the cycloisomerization-amination reaction proceeded smoothly under mild conditions,delivering 1-amino-2H-quinolizin-2-one scaffolds.The reaction has the broad substrate scope and excellent yields of products were obtained.Control experiments indicated that two competitive reactions may occur during the reaction process.In addition,this reaction could be extended to an asymmetric version,affording quinolizone-based axially chiral anilides,albeit with moderate enantioselectivite excess.The third chapter:This chapter investigated the Br?nsted acid-enhanced copper-catalyzed atroposelective cycloisomerization to access axially chiral arylquinolizones.With CuCl as catalyst and Br?nsted acid as additive,the dearomatization of pyridine could proceed smoothly,which allows for the formation of the axially chiral arylquinolizones in excellent yields and enantioselectivities.With the modification of axially chiral arylquinolizones,a series of quinolizone-based functional molecules could be generated.The asymmetric Michael addition of thiophenol and cyclohenenone could be catalyzed by quinolizone-based bifunctional organocatalyst,which afforded addition adduct in moderate yield and enantioselectivity.Mechanistic studies demonstrated that:（1）Br?nsted acid plays a significant role in promoting the reactivity of the reaction by changing the ratio of enol and keto isomers of the substrates but won’t affect the enantioselectivities;（2）The analysis of linear free energy relationships indicated that the steric hindrance and electronic effects of aryl substituents in substrate play a role in controlling the stereoselectivity simultaneously.The fourth chapter:This chapter investigated the axial-to-central chirality transfer for construction of quaternary stereocenters via dearomatization of enantioenriched BINOLs.When Pd₂（dba）₃ was used as the catalyst and Johnphos was used as the ligand,the chirality transfer of（S）-BINOLs were proceeded smoothly at room temperature,affording almost enantiopured spiro-compounds in high yields.In addition,late-stage modifications of natural products were conducted.As a result,the diaromatic products were obtained in excellent yields without the erosion of diastereoselectivities.At last,the strategy was extended to the kinetic resolution of rac-BINOLs.With the optimization of catalysts,ligands and solvents,the s value could be improved to 9.4.