Asymmetric Ugi Four Component Reactions Catalyzed By Anionic Stereogenic-at-cobalt(Ⅲ) Complexes

The Ugi reaction have been proven to be atom and step-efficient strategies for construction of highly valuable peptide-like skeletons heterocycles.However,the creation of structurally diverse range of new chiral catalytic systems and the discovery of new approaches for catalytic stereocontrol of the classical Ugi four-component reactions is still in high demand but challenging.In this thesis,we developed a novel method for asymmetrically catalyzing the Ugi four-component reaction using anionic stereogenic-at-cobalt(Ⅲ)complexes as catalysts.The details are as follows: In view of the difficulty of stereo control of the four-component Ugi reaction,this paper explores the asymmetric Ugi four-component reaction involving carboxylic acid.The conditions for the selective asymmetric Ugi four-component reaction: the anionic stereogenic-atcobalt(Ⅲ)complexes is used as the catalyst,toluene is used as the reaction solvent,and the reaction temperature is-20 oC or-40 ℃.Under these conditions,more than 40 α-acylaminoamide derivatives(up to 98:2 e.r.)with good enantioselectivity were synthesized by asymmetric Ugi reaction involving carboxylic acid,and some α-acylaminoamide derivatives were preliminarily studied.Antifungal activity of acylaminoamides.Through controlled experiments and kinetic experiments,the reaction mechanism was explored and guessed: isocyanide nucleophile attacked the chiral ion pair composed of anionic stereogenic-at-cobalt(Ⅲ)complexes and protonated imine in the reaction,resulting in the key The nitrile onium ion is then captured by the carboxylic acid and undergoes a Mumm rearrangement to form a chiralα-acylaminoamide.The reaction successfully achieved the asymmetric catalysis of the gram-level reaction,providing a new method for the synthesis of chiral aminoamide compounds,which has potential application value;at the same time,this reaction not only provides a new method for the chiral anion-directed catalytic reaction system The idea greatly enriches the research content of asymmetric catalytic Ugi reaction.