Studies On Direct Arylation Of Indoles And Cyclohexanones With Metal-free Systems

Indoles containing heterocyclic nitrogen are widely found in natural products and pharmaceutical molecules.Because of their unique biological pharmacological activities,they have important applications in medicine,pesticides,functional materials and so on.Therefore,the development of environmentally friendly indoles functionalization reaction to synthesize indoles derivatives is one of the research hotspots in organic synthesis.Cyclohexanone is a major organic product and has important applications in organic synthesis and functional material preparation.In addition,cyclohexanone can be used as aryl source by catalytic dehydrogenation of transition metal catalysts in recent years.However,the use of transition metals not only increases the reaction products,but also brings pressure to environmental pollution.Therefore,it is of great significance to develop cyclohexanone dehydroaromatization reactions without transition metal catalysts.In this paper,indoles arylation without transition metal was studied,and the selective functionalization of indoles with cyclohexanone as aryl source was realized.The specific research contents are as follows:1.Two methods of arylation of indoles C-3 under metal-free were developed.In the catalytic system of boron trifluoride ethyl ether,elemental sulfur and 1,1-diphenylethylene,we used N-methyl indole compounds and cyclohexanone derivatives as raw materials to obtain single 3-arylated products,which has good yields and can be prepared in gram scale,providing a simple way for the synthesis of 3-arylindole.A series of 2,3-diarylindole compounds were obtained from 2-phenylindole and cyclohexanone derivatives using iodine bromide,1,1-diphenylethylene as catalysis system,this method has good substrate suitability and excellent reaction yield,and can also be prepared on a gram scale.Both of these methods have the advantages of simple conditions and high yield.In comparison,the yield of iodine bromide system is better.2.A new method for the synthesis of benzothiophene [2,3-b] indoles without metal catalysis was developed.In this method,We take N-methyl indoles,elemental sulfur and cyclohexanone derivatives as raw materials,in which cyclohexanone plays the role of aryl source,the simple inorganic sulfur is inserted between the indoles C-2 position and aryl group using iodine as the catalyst,and the construction of one C-C and two C-S without transition metal is successfully achieved,and then the ring addition of indoles is realized.