Construction Of Chiral Skeletons Of Coumarins By Asymmetric Michael Reaction

Chirality is one of the basic attributes of life.Most of the important basic substances that constitute a living body have chirality.Many natural products and drug molecules also contain chiral centers.In recent years,asymmetric reactions catalyzed by small organic molecules have developed rapidly and are widely used in the synthesis of various chiral molecules.Among them,the asymmetric Michael addition reaction is an important part of organic catalysis.The Michael addition reaction is a classic reaction in organic chemistry and one of the most commonly used methods to build carbon-carbon bonds.Therefore,it has always been a research hotspot in the field of organic synthesis.Coumarin compounds are one of the most advantageous scaffold materials in the fields of medicinal chemistry and materials science,and they are widely distributed in a large number of biologically active molecules.This thesis mainly studies the asymmetric Michael addition reaction of coumarins catalyzed by small molecules.This thesis is divided into four chapters.The first chapter briefly summarizes theα-Michael addition reaction of ketones and the advantages of 3-acylcoumarin in the field of chemistry.The second chapter is a brief introduction to the physiological activities and pharmaceutical applications of benzofuran-containing compounds;then a brief literature review of the asymmetric reaction involved in benzofuranimine;finally,we have developed a 3-acylcoumarin group the asymmetric 1,4-addition reaction of coumarin and benzofuranimine provides a novel method for constructing benzofurancoumarin skeletons.A series of benzofuranocoumarin skeletons were obtained with good yield(up to 99%yield)and excellent enantioselectivity(up to 99%ee)under the catalysis of 1 mol%squaraamide catalyst for 4h.And can be prepared on a larger scale.Chapter Three gives a brief introduction to the biological activity,drug application and distribution of chromone compounds;then we give a brief introduction to the research progress of dienchromone compounds in chemical reactions;finally,we develop The asymmetric Michael addition reaction of 3-acylcoumarin and dienchromone provides a quick and easy method for constructing a new type of chromone coumarin skeleton compound.Under the catalysis of 10 mol%squaraamide catalyst for 4h,the reaction has a good yield(up to 96%yield),excellent diastereoselectivity(up to 97:3 dr)and excellent enantioselectivity(up to 99%ee)A chromone coumarin derivative connected by two chiral centers is obtained.The last chapter summarizes the work of this thesis.In summary,we have developed two types of asymmetric Michael addition reactions catalyzed by small molecules,and synthesized a series of benzofuran coumarin compounds and chromone coumarin compounds connected by two chiral centers for follow-up research Provide a foundation with applications.