The Asymmetric Knoevenagel Condensation Catalyzed By Amino Acid Derivatives

Knoevenagel condensation is an important reaction in organic synthesis to form new C-C bond,which can be utilized in many chemical synthesis.This reaction can be catalyzed to form a new product containing an unsaturated double bonds between carbonyl-containing compounds such as aldehydes or ketones with compounds having an active methylene group.Knoevenagel reaction has a wide range of research background and wide application value,but asymmetric Knoevenagel reaction catalyzed by amino acid derivatives is rarely reported.In this paper,a variety of chiral amino acids derivatives were prepared to catalyze the asymmetric Knoevenagel reaction use L-amino acids as raw materials.The application of these catalysts in this reaction was studied and discussed.Details as follows:The synthesis method of chairl amino acid derivatives: Nitrogen in L-amino acids was protected at first,then acylate,deprotecte,N-alkylated and reduction(or reduction before N-alkylated),the chiral amino acid catalysts were obtaied efficiently.The structures of the products were determined by MS and 1H-NMR.The substrates of asymmetric Knoevenagel condensation reaction 2-phenylbutanal and its derivatives were prepared through by two simple and efficient methods: Darzen condensation and Corey epoxidation.These two methods both used Phenylacetone and its derivatives as starting materials.Appropriate reaction time and high yield of products was screened through single factor experiments.The structure of the products was characterized by 1H-NMR.The asymmetric Knoevenagel reaction was investigated by using 2-phenylbutanal and diethyl malonate as reaction template.The optimal conditions of the reaction include catalyst,reaction temperature,solvent were determined by single factor experiments..Under this optimal conditions,the asymmetric Knoevenagel condensation was carried out and a variety of condensed products were synthesized.The desired products were characterized by MS and 1H-NMR,the e.e.value was determined by chiral HPLC.