Construction Of Indoline Or Tetrahydroindole Deriatives Via Metal-Free Catalytic Annulation Of Ynamides

Metal-free catalytic organic reactions have attracted more and more attention in recent years.Metal-free catalysis possesses advantages of green,mild conditions and insensitive of air.However,compared with transition-metal catalysis,metal-free catalysis was developed later,especially the reaction involving alkynes.Most reports of metal-free catalytic reactions of alkynes focus on the last decade and are relatively limited.Indolines and tetrahydroindoles are important skeletons for bioactive and medicinal molecules.Chemists have developed various strategies for the synthesis of these compounds.However,most of these strategies are transition-metal catalysis,and metal-free catalysis,which is in the minority,focuses on racemic reactions.Based on the ynamide chemistry established by our group,this thesis focuses on the investigation of metal-free catalytic reactions of ynamides to construct N-heterocycle-containing compounds by utilizing the nature and the nitrogen atom of ynamides,and expects to synthesize indolines and tetrahydroindoles.There are mainly four parts in this thesis:In part one,we carried out the investigation of the references and made an introduction of the research background,including reported synthetic methods for indolines and tetrahydroindoles,and metal-free catalytic reactions involving ynamides developed in recent years.We proposed the research ideas through the summary of the background.In part two,we constructed chiral bridged indoline compounds through CPA-catalyzed asymmetric dearomatization and cyclization cascade of indoles and ynamides.This reaction achieved the metal-free CADA reaction of indoles and ynamides.This reaction can not only give high enantioselectivities,but also control the Z/E configuration of products well.Moreover,the simple derivatization of the product indicated the potential applications of this reaction.Finally,mechanistic experiments show the importance of functional groups in substrate,and we proposed the mechanism of this reaction.In part three,we realized the metal-free catalytic[4+2]cycloaddition of ynamides and siloxy dienes,furnishing 2,3,3a,6-tetrahydroindoles in excellent yields.The mechanistic studies indicated that this reaction might undergo a catalyst-free Diels-Alder reaction.This reaction provided a new method for the efficient synthesis of tetrahydroindoles and indicated ynamides could undergo cycloaddition with electron-rich dienes.In part four,on the basis of part three,we constructed new axially chiral indoline compounds via chiral secondary amine catalyzed[4+2]cycloaddition of ynamides and enals.Most of the products could be obtained with excellent enantioselectivities.The synthesized axially chiral products were expected to be transformed into axially chiral ligands and organocatalysts through the derivatization of products.We speculated that this reaction experienced a dienamine intermediate,and underwent a[4+2]cycloaddition with ynamide.The mechanism was similar to part three.