Nickel-Catalyzed Cascade Reaction Of Chloroarenes:Synthesis Of Indoles

Purpose:Indole exists widely in nature,most of indole and its derivatives have certain pharmacological activity,and are used in many fields such as chemical industry,fragrance and biology The Mizoroki-Heck and Amination reactions catalyzed by transition metals are powerful tools for the construction of C-C and C-N bonds,and are important methods in the synthesis of drug molecules,organic materials or natural products.Nickel is abundant in the earth’s crust,and aryl chlorides are the most widely sourced aryl halides.Therefore,nickel-catalyzed cascade reactions of aryl chlorides to construct indole derivatives have the advantages of mild conditions,low cost,and economic efficiency.Methods:Chapter 1: Nickel-catalyzed Mizoroki-Heck/Amination cascade reaction of odihaloarenes with allylamine to synthesize N-aryl-3-methylindole derivatives.The practicality of this reaction was explored through derivatization experiments.A reasonable reaction mechanism is proposed.Chapter 2: Nickel-catalyzed cascade reaction of 2-alkenylchlorobenzene and aromatic amines to synthesize 1,3-diarylindole derivatives.The practicability of the reaction was explored through derivatization experiments,and a reasonable reaction mechanism was proposed through controlled experiments.Results:Chapter 1: Nickel-catalyzed Mizoroki-Heck/Amination cascade reaction of odihaloarenes with allylamine to obtain more than 30 indoles with good functional group compatibility in moderate to high yields.Mechanistic studies showed that the intermolecular Mizoroki-Heck reaction occurs firstly and then the intramolecular amination reaction occurs.Chapter 2: Nickel-catalyzed cascade reaction of 2-alkenyl chlorobenzene and aromatic amine to obtain more than 30 kinds of 1,3-diarylindole compounds with high yields,and an active molecular was successfully synthesized.Through the study of the reaction mechanism,it is found that the cascade reaction is that 2-alkenyl chlorobenzene and aromatic amine undergo intermolecular amination firstly and then occur intramolecular dehydrogenative amination.Conclusion:Nickel-catalyzed Mizoroki-Heck/Amination cascade reaction of o-haloarenes and allylamine to synthesize N-aryl indole derivatives.The synthesis reaction has the characteristics of wide source of raw materials,simple operation and cheap catalysts,which is the most suitable for the synthesis of N-aryl indole derivatives.Nickelcatalyzed cascade reaction of 2-alkenylchlorobenzene with aromatic amine to synthesize 1,3-diarylindole derivatives.The reaction route has mild reaction conditions,inexpensive catalysts,simple and easily available substrates and a wide range of substrate adaptations.This reaction is an economical and efficient method for synthesizing 1,3-diarylindole derivatives,which is of significance for the development of new drugs and the discovery of new active biomolecules.