Research Report Of Asymmetric Friedel-Crafts Reaction Of Indoles And Isatins Catalysted By Organocatalysts

Indoles are found in many natural products with biological activity or medicinal value.Therefore,more and more attention has been paid to the asymmetric synthesis and modification of indoles derivatives.Asymmetric catalytic Friedel-Crafts alkylation is one of the important ways for the synthesis of indoles.The asymmetric Friedel-Crafts reaction catalyzed by organic small molecule has the characteristics of environmental friendliness,mild reaction conditions,low toxicity and not easy residue.However,the asymmetric Friedel-Crafts reaction catalyzed by organic small molecules also has some problems to be improved,such as too long reaction time,large amount of catalyst,few kinds of catalysts,poor universality and other problems.Therefore,this paper hopes to improve and solve these problems by studying the organic catalytic asymmetric Friedel-Crafts reaction,expand the types of catalysts,expand the range of substrates,and improve the universality.This article hopes to cinchona alkaloid and thiourea derivatives catalyst used in indole and isatin asymmetric Friedel-Crafts reaction and hydroxy indole and isatin asymmetric Friedel Crafts reaction,the catalytic performance of catalysts,and types of solvent,temperature,amount of catalyst on the reaction of stereoselectivity,in order to screen out the best reaction conditions and universality,probe into its scope of substrates.1)In the study of asymmetric Friedel-Crafts reaction of indoles and indigored catalyzed by quinine derivatives,the optimal reaction conditions were selected as follows:10 mol%catalyst le,tetrahydrofuran as solvent,reaction at room temperature.The asymmetric Friedel-Crafts reaction of indoles with 5 different substituents and indirubin with 8 different substituents yielded excellent yield(87-95%)and stereoselectivity(84-99%ee).2)In the study of asymmetric Friedel-Crafts reaction of hydroxyl indoles and indigored catalyzed by quinine derivatives,the optimal reaction conditions were selected as follows:5 mol%catalyst 1g,tetrahydrofuran as solvent,0℃ reaction.The asymmetric Friedel-Crafts reaction of 4 kinds of hydroxyl indoles with different substituents and 12 kinds of indirubin with different substituents yielded excellent yield(68-91%)and stereoselectivity(up to 97%ee).3)In the study of asymmetric Friedel-Crafts reaction between hydroxyindoles and indirubin catalyzed by thiurea derivatives,the optimal reaction conditions were selected as follows:10 mol%catalyst 5b,ethyl ether as solvent,0℃ reaction.The asymmetric Friedel-Crafts reaction was applied to 4 kinds of hydroxyl indoles and 11 kinds of indirubin with different substituents,and the excellent yield(68-92%)and stereoselectivity(up to 94%ee)were obtained.The results show that the designed chiral catalyst derived from cincinar can catalyze the asymmetric Friedel-Crafts reaction in a high efficiency and high enantioselectivity way.Thiourea derivatives were first used in asymmetric Friedel-Crafts reaction between organic catalyzed hydroxyl group and indirubin.This subject provides a practical and new catalytic system for the development of asymmetric Friedel-Crafts reaction and has a broad application prospect.