The Construction Of Axially Chiral Naphthoquinones Derivatives By Chiral Phosphoric Acid Catalysis

Axially chiral molecules have received extensive attention from organic chemists and pharmacologists because of their widespread appearance in biologically natural products,ligands and catalysts.The construction of privileged chiral molecular skeletons by readily asymmetric transformations with simple raw materials not only fulfills the requirements of “accelerating the construction of resource-saving and environment-benign societ”,but also one of the goals that organic synthetic chemists are constantly pursuing.Chiral phosphoric acid based organocatalysis has been studied most deeply and are widely used in various asymmetric catalytic reactions.The main research content of this thesis is the synthesis of axially chiral naphthoquinone derivatives with quinones and indoles as reactants in a high enantiocontrolled manner by chiral phosphoric acid catalytic asymmetric Michael-addition.In this thesis,the loading of reactants was firstly screened,and then the chiral phosphoric acids of different skeletons were evaluated.Subsequently,the external oxidant,reaction solvent,reaction temperature and reaction concentration were careful screened.After the determination of the optimal conditions,we next move to explore the universality and limitation of the quinone and indole substrates.The experimental results clearly indicated the good functional-group compatibility of this reaction.Up to 16 atropisomeric naphthoquinones with different substituents were synthesized in the thesis.Most of them gave the desired products in good yields with moderate to good enantioselectivities,with a maximum 77% yield and 93% enantioselectivity.The series of axially chiral compounds synthesized in this thesis contain novel skeletons and are important supplements to existing axially chiral molecules.Quinones and their derivatives have long been important synthetic precursors for the construction of highly functionalized molecules,and their use in asymmetric organic catalysis has been increasing.Therefore,a series of axially chiral quinones synthesized in this thesis have potential value.