Lewis Base Catalyzed The Michael Addition Reaction Of ?-aminonitriles And Electron-deficient Olefins

The Michael addition reaction is a classic synthesis method for building carbon-carbon and nitrogen-carbon bonds.The Michael addition catalyzed by Lewis base is one of the most important synthetic methods in the Michael addition reaction.?-Aminonitrile is a common intermediate in synthetic chemistry and is widely used to synthesize multifunctional structures because of its potential to generate molecular diversity.?-amino acid esters and?-lactam compounds are intermediates of many drugs,and they are often found in various natural products and biologically active compounds.These compounds have a very wide range of biological activities,they have great potential for development in the synthesis of organic drugs.In this paper,a method is designed to catalyze the Michael addition of?-amino nitriles and?,?-unsaturated olefins by different Lewis bases,followed by intramolecular cyclization to finally generate?-amino acid esters and?-lactam compounds.Therefore,the research content of this article is divided into the following parts:1.?-amino acid ester compounds have great therapeutic potential.This article studies a method to synthesize?-amino acid ester compounds by using Lewis base(DBU)to catalyze the Michael addition reaction of?-amino nitrile and methyl acrylate.This method uses 1,8-diazabicyclo[5.4.0]undec-7-ene(DBU)to first react with?-aminonitrile,and the resulting carbon anion undergoes a Michael addition reaction with methyl acrylate.The?-amino acid ester is generated,and the regenerated DBU can be recycled in this reaction,the reaction conditions are mild,and the substrate can be applied in a wide range.2.?-lactam compounds are the core structure of a large number of natural and non-natural compounds,and these compounds themselves also have physiological activities.In this paper,a method for the synthesis of?-lactam compounds by the Michael addition of methyl acrylate and?-aminonitrile catalyzed by Lewis base(PBu₃)is studied.The method uses tributyl phosphine(PBu₃)to catalyze the formation of phosphonium-zwitterions from methyl acrylate to protonate?-amino nitrile,and the generated carbon anion undergoes Michael addition reaction with methyl acrylate to form?-lactam.The method can directly synthesize the target product,and has fewer synthesis steps,can also realize intramolecular recycling,and is green and environmentally friendly.3.Based on the research of the above work,the author also tried to use the"one-pot method"to directly synthesize the product,which is also feasible.In addition,replacing methyl acrylate with other?,?-unsaturated olefin compounds can also obtain better yields.