Chiral Biarylpyridoxal Catalyzed The Asymmetric Michael Addition/cyclization Reaction Of α,β-unsaturated Esters At The α Position Of Glycine Esters

Chiral γ-lactams are a core structure of a variety of bioactive compounds,usually,the synthesis of chiral γ-lactam requires multi-steps.The development of new effecient mothod to access chiralγ-lactams is of great value.Vitamin B6 as a coenzyme can catalyze many reactions in biological system,Such as transamination and aldol reaction of glycine.We developed a series of chiral pyridoxals which based on the structured skeleton of vitamin B6.These chiral pyridoxal can catalyze asymmetric Michael addition of the α-carbon of glycinate to α,β-unsaturated esters.The adducts then underwent intramolecular cyclization to give various.chiralγ-lactams in good yields with excellent enantioselectivity.Thetransformation is characterized with environmental friendliness,simple operation,and mild conditions,representing an intriguing method for synthesis chiral γ-lactamswe envisage simulating an enzyme catalytic system in vivo.A series of chiral catalysts have been developed with vitamin B6 as the core skeleton,which can catalyze glycine tert-butyl ester the Asymmetric Michael addition to the α,β-unsaturated ester,and then product undergoes intramolecular cyclization.The method could be widely used for the aspects synthesis of chiral γ-lactam in one step form commercialy available starting waterial without the protection and deprotection of NH2 This article mainly includes the following three parts:(1)Development of chiral pyridoxal catalysts.(2)Optimization of reaction conditions for Michael addition /cyclization process.(3)Successing substrate scope for Michael addition /cyclization process.