Study On The Synthesis Of 2-indolones And 3-fluorobisindoles From Indole Oxides Catalyzed By Iron And Nickel

The indole skeleton is an important heterocyclic scaffold,which is widely found in medicine,fine chemicals and natural products.Its derivatives have a variety of unique characteristics.Therefore,it is of great research significance to develop new synthetic methods to realize the conversion of indole to form various biologically active molecules.This paper mainly includes three parts:(1)the iron-catalyzed oxidation of indole compounds;(2)the nickel-catalyzed oxidation of indole compounds;(3)the development of nickel-catalyzed fluorination indole compounds.The main research contents are summarized as follows:1.An iron-catalyzed oxidation of indole compounds to 2-indolinone compounds has been studied.N-methylindole was used as a model substrate to optimize the oxidant,additive,solvent and catalyst respectively,and the optimal conditions were obtained:Fe Cl₂ as the catalyst,H₂O₂ as the oxidant,TMDSO(1,1,3,3-tetramethyldisilazide oxane)as additive,ethanol as solvent,80°C.Under the optimal conditions,the substrate extension of indole can obtain in good or excellent yields,and the reaction mechanism has been studied.2.A method of nickel-catalyzed oxidation of indole compounds to synthesize 2-indolinone compounds was studied.The oxidation of N-methylindole in the air as a model reaction was used to optimize the additives,solvents and catalysts,and the optimal conditions were obtained:Ni Br₂ as the catalyst,atmospheric air as the oxidant,and PMHS(polymethylhydrogen siloxane)as Additive,ethanol as solvent,80°C.Under the optimal conditions,a variety of indoles proceeded smoothly and afforded the desired products in 50%-90%yields.Notably,this protocol is suitable for late-stage oxidation of natural products and pharmaceutically active molecules.The reaction mechanism was also explored.3.A nickel-catalyzed fluorination of indole compounds has developed to synthesize 3-fluorobiindole compounds.N-methylindole was used as a model substrate to optimize the fluorinating agent,additive,solvent and catalyst,and the optimal conditions were obtained:Ni Br₂ as the catalyst,N-fluorobisbenzenesulfonamide as the fluorinating agent,and PMHS(polymethyl Hydrogen siloxane)as an additive,ethanol as a solvent,80°C.Under the optimal conditions,the desired products can be obtained in good yields,and the method was found to have good functional group compatibility,and the reaction mechanism was preliminarily explored.