Asymmetric Synthesis Of Spirooxindoles And Fused Heterocyclic Compounds Catalyzed By N-heterocylic Carbenes

N-Heterocyclic carbenes?NHCs?play an important role in asymmetric catalysis.At first,they were mainly applied to umpolung transformations.So far,N-heterocyclic carbenes have been used not only in the umpolung reactions,but also in cyclization reaction,free radical reaction,CO₂ fixation reaction,cooperative catalytic reaction and tandem reaction.The indole structure unit is the core skeleton of many natural products and biologically active molecules,and the indole skeleton with chiral centers is the key component of many drugs.Therefore,it is extremely important to develop simple and efficient method for synthesis of chiral indole skeletons.This article mainly focuses on the asymmetric synthesis of spirooxindole and fused heterocyclic compounds with indole skeleton catalyzed by N-heterocyclic carbene.Chapter 1 This section mainly summarizes some reactions involving acyl anion,homoenolate,azolium enolate,acyl azolium,?,?-unsaturated acyl azolium and azolium dienolate derived from carbonyl compounds in the presence of N-heterocyclic carbenes.Chapter 2 N-Heterocyclic carbene-catalyzed asymmetric formal[3+2]annulation of isatin N-Boc ketimines and 3-bromoenals was developed to construct spirooxindole skeleton with one quaternary chiral center.The disired spiro[indoline-3,2'-pyrrole]derivatives were obtained in good yields?up to 81%yield?with excellent enantio-selectivities?up to 99%ee?.The deprotection reaction was carried out and the target molecule was affored in high yield with maintaining enantioselectivity.This is the first example of the direct synthesis of spiro[indoline-3,2'-pyrrole]-2,5'?1'H?-diones with a chiral center catalyzed by N-heterocyclic carbene.Chapter 3 The N-heterocyclic carbene-catalyzed asymmetric N-alkylation of indole 2-formaldehydes has been achieved.Twenty functionalized cyclic N,O-aminal indole derivatives were obtained in good yields?up to 98%yield?and excellent enantioselectivities?up to 98%ee?using isatin derivatives as electrophiles.In addition,the asymmetric reaction of indole 2-formaldehyde and pyrazolone could occur smooth-ly.The methodology involves a new way to generate nucleophilic nitrogen atom inter-mediate by oxidation and deprotonation,which provides a new entry for the cons-truction of C–N bonds.Chapter 4 The asymmetric formal[2+2]annulation of 2-formylcyclopropanes and isatin derivatives to construct spiro[indoline-3,2'-oxetane]-2,4'-diones with two chiral centers catalyzed by N-heterocyclic carbenes was developed.A series of functionalized3-hydroxy-3-substituted 2-oxindole derivatives were afforded with good to excellent yields?up to 94%yield?and excellent diastereo-?>20:1 dr?and enantioselectivities?up to 95%ee?after ring-opening with benzylamine.In addition,the control experiment proved that the relative configuration of the 2-formylcyclopropane had no effect on the reaction.This reaction has the advantages of simple operation,mild reaction conditions,wide scope of substrates,and high atom economy.Chapter 5 An efficiently stereoselective[4+2]cycloaddition of?-diazoketones and 3-alkylenyloxindoles through sequential visible-light photo activation and N-heterocyclic carbene catalysis was achieved.A series of tetrahydropyrano[2,3-b]indoles with all-carbon quaternary stereocenter was obtained in good yields?up to 96%yield?,excellent diastereo-?>20:1 dr?and enantioselectivities?up to 98%ee?under optimal conditions and the reaction can be well scaled up.This reaction is the first successful case of co-catalysis of visible-light and N-heterocyclic carbene without photosensitizer participation,which is of great significance to the[2+n]cycloaddition reaction catalyzed by N-heterocyclic carbene.