Studies On Copper-catalyzed Annulative Synthesis Of Quinoxaline-2（1H）-ones From Ugi Adducts And ZnEt₂/Chiral Amino Alcohols-Induced Asymmetric α-Allylation Of Isocyanacetates

The development of new organic synthesis methods is the basis for the creation of new drugs,pesticides,materials and other fine chemicals,and it is also an important way to green the transformation of traditional chemical production processes.Quoxaline-2（1H）-one and chiralαquaternary carboα-allyl isocyanacetate are two types of intermediates with great application potential in the field of organic synthesis.In this paper,two new and efficient synthesis methods are developed for the synthesis of these two types of intermediates based on readily available reaction raw materials.Ⅰ)First,using the readily available Ugi reaction adduct based on o-iodoaniline as raw material,a mild,efficient,atomically economical Copper-Catalyzed intramolecular ring closing method was developed,and a new method for constructing quinoxaline-2（1H）-ketone heterocyclic skeleton was realized.By selecting the template substrate,the influence of external conditions on the reaction was investigated in detail from the aspects of reaction catalyst,base,solvent,temperature and time,and the optimal reaction conditions of the reaction were obtained.By systematically changing the substituent type of the starting component,the compatibility and limitations of the reaction to various functional groups are investigated in detail.Through the subsequent transformation study of typical products,the practicability of reaction products and the application value of reaction products are preliminarily explored.The results show that the reaction with Cu I as catalyst and Cs₂CO₃ as base,the reaction in acetonitrile at 85^oC for 12 hours can obtain the target quinoxaline-2（1H）-one product with high yield,and the reaction has good tolerance to a variety of different functional groups,and subsequent transformation studies show that the reaction products can be further converted into a variety of useful structures.This part of the research can lay a solid foundation for the synthesis of many molecules containing important bioactive natural products,drugs and other molecules of the skeleton.Ⅱ)By selecting Zn Et₂ and chiral amino alcohols as the catalytic combination,the asymmetric substitution reaction between Boc-protected Baylis-Hillman adduct andα-isocyanacetate was realized.Through the detailed optimization of the dosage,substrate ratio,reaction solvent,temperature and time of catalyst,ligand,Zn Et₂dosage,substrate ratio,reaction solvent,temperature and time in the reaction,the influence of external conditions on the reaction was explored,and the optimal reaction conditions were obtained.By transforming theα-isocyanacetate substituents,the universality of the reaction was preliminarily studied.The results showed that the reaction was induced by Zn Et₂ and chiral amino alcohol under the protection of room temperature nitrogen in1,2-dichloroethane for 12 hours,and the target product could be obtained with a high yield,and the reaction ee value could reach a moderate level（56%）.