Study on the New Synthetic Methodologies of Indole and Oxindole Derivatives

Author:Li Yin Long

Supervisor:xiong li cha de richard hsungdeng jun


Degree Year:2017





The indole ring system is one of the widely distributed heterocycles in nature.Indole and its derivatives have been referred to as―privileged structures‖since the particularity and diversity of the structures.Meanwhile,The difluorinated oxindoles are important indole derivatives,the incorporation of fluorinated moieties into oxindoles are high value to explore their applications in pharmaceuticals.This thesis focus on the syntheses of indole and difluorinated oxindoles derivatives,four synthetic protocols have been developed:Firstly,a novel metal-free synthesis of indoles from N-Ts-2-alkenylanilines has been described,the reaction involves a N-Iodosuccinimide(NIS)-mediated cascade C-N bond formation/aromatization process.The developed strategy could be conducted under mild conditions without any transition metals or additives.This protocol also possesses a wide substrate scope,more than 30 examples of indole derivatives had been prepared with up to 99%yield.Based on the above research,we also disclosed that 3-iodoindoles could be conveniently prepared from2-alkynylanilines through triphenylphosphine(Ph3P)-catalyzed iodocyclization in the presence of N-iodosuccinimide(NIS).Meanwhile,3-iodobenzo[b]furan derivatives also could be afforded under the standard conditions.Due to the catalytic Ph3P was essential to obtain the product with high efficiency and yield,we proposed that Ph3P could active the iodonium ion intermediate of the reaction.Additionally,in order to enrich the structure diversity of indole derivatives,we also developed a facile method to synthesize difluorinated oxindoles by usingα,α-difluoroarylacetic acids as the difluoro source.In the presence of AgNO3 and K2S2O8,α,α-difluoroarylacetic acids and N-acryamides occured decarboxylation,racial addition/cyclization cascade to afford the difluorinated oxindoles.For the purpose of accessing difluorinated oxindole bearing a chiral quaternary centre,a new synthetic strategy was also established,and the ee values of difluorinated oxindoles were up to 95%.This reaction involved the bifunctional quinine-derivative catalyzed enantioselective decarboxylative aldol reaction ofα,α-difluoro-β-keto acids with isatins,which realized the first asymmetric reaction ofα,α-difluoro-β-keto acids and provided a new protocol for the asymmetric synthesis of difluorinated oxindoles.