Study On Addition Reaction Of Indole Derivatives To Enamides

Many compounds containing bis-indolyl skeletons are active and can be extracted from marine materials.It is of great significance to study their synthesis methods.At present,The scientists have proposed synthetic methods that provide important guidance for subsequent studies to synthesize bis-indolyl or tri-indolyl compounds.It has been reported in the article that bis-indolyl compounds can be obtained in the Friedel-Crafts reaction of indole and imine.According the literature,a bis-indolyl alkane compound is usually obtained by condensing indole with a carbonyl compound,an amino group,and a terminal alkyne.However,the traditional synthetic methods are not economical and environmental,and need the precious metal to catalytic reactions,or require a higher temperature,toluene and other solvents to better react.Establishing the optimal conditions for the reaction.In the exploration and optimization of experimental conditions in this paper,different Lewis acids were used to catalyze the reaction,and different combinations of solvents,temperatures,and reaction times of the system were studied.Sc(OTf)3)as a catalyst,the reaction temperature is 60 ?,and the combination of conditions in the inert gas environment for 12 hours,the gas chromatography(GC)quantitative analysis can obtain the target standard product with 98%yield.The isolated yield was 92%.Two substrates involved in the reaction were screened under optimal conditions,where 10 enamide compounds were screened and the target product was obtained in 71%-92%yield.It is worth mentioning that the E-enamide and the tri-substituted enamide can be reacted with indole under this condition.The 9 indole derivatives screened can be obtained with yield of 65%-98%.In the mechanistic study,the intermediates were successfully captured by controlling the equivalent ratio and reaction time of the substrate in the experiment,and the target intermediate was obtained with an isolated yield of 53%.After the characterization,the indole and intermediates reacted under standard conditions and gave the target product in isolated yield of 94%.Based on the mechanism research experiments and literature reports,this paper proposes possible reaction paths and mechanisms,and successfully established a mild,efficient,economical and environmentally friendly method for the synthesis of bis-indoyl compounds.The catalytic system is suitable for use in enamides of various alkyl chain lengths and various amide substituents.Trans-enamide and tri-substituted enamides can also react to give a bis-indoyl alkane compound.The position of the fluorene substituent has no significant effect on the yield.The catalytic system is compatible with functional groups including ethers,halides,and acetates,and yields are good.