Studies On The Catalytic Asymmetric Construction Of Spirocyclic Indoles

Spirocyclic indoles are widely occurred in natural products,pharmaceuticals and bioactive compounds.Therefore,the development of highly efficient strategies for their synthesis is of significance.This thesis mainly focused on the catalytic asymmetric construction of C2-spiro indolines and C3-spirooxidoles,these research works are detailed as follows:In the first part,we developed a chiral tertiary amine catalyzed asymmetric cascade annulation reactions of 2-alkynyl-3,3-difluoro-3H-indoles with 2-mercaptoimidazoles,and the desired chiral gem-difluorinated C2-spiro indolines were obtained in moderate to good yields(37-92%)and enantioselectivities(39-86% ee).Noticeably,this is the first catalytic enantioselective tandem annulation raction that utizating 2-alkynyl-3,3-difluoro-3H-indoles as the biselectrophiles and 2-mercaptoimidazoles as the bisnucleophilies.In the second part,we developed a triethylenediamine(DABCO)catalyzed divergent reaction between isatin-derived MBH carbonates and 3-formylchromones.Depending on the reaction conditions,three types of scaffolds could be obtained.For example,the benzopyrone fused spirocyclopentene oxindoles were obtained in moderate to good yields(55-95%)when using dichloromethane as the solvent;whereas spirocyclopentadiene 2-oxindole incorporating a 2-hydroxybenzoyl moiety were formed in moderate to good yields(65-88%)in the presence of tetrahydrofuran.Interestingly,a series of bisoxindoles were produced in moderate yields(47-75%)in the absence of 3-formylchromones.In addition,the catalytic enantioselecitive variants of these reactions were achieved by using β-isocupreidine derivative as the chiral catalyst.Under the optimal reaction conditions,the spirocyclopentene oxindoles,spirocyclopentadiene 2-oxindoles and bisoxindoles could be afforded in moderate to good yields and good enantioselectivities.