C-N Coupling And Construction Of Polysubstituted Quinolines Involved By Anthranils

Anthranils are an important class of organic synthons with rich availability and wide applications,which shows great synthetic potential in transition metal-catalyzed process.At present,the research on anthranils mainly includes transition metal-catalysed C-N coupling reaction,C-H amination reaction and cycloaddition reaction.However,there are still many problems in the above reaction involving anthranils,such as:highly active arylzinc reagent needs to be used in C-N coupling reaction;In the amination reaction of C-H bonds,it is necessary to use directing groups that are difficult to remove.Based on the above studies,this thesis further studied the Cu-catalyzed C-N coupling reaction of readily available arylboronic acids with anthranils;Ni H-catalyzed the hydroamination/cascade cyclization of alkynes and anthranils;And Cu-catalyzed three component cascade cyclization of terminal alkynes,anthranils and amines.These new strategies can effectively avoid the use of highly active raw materials and the dependence on directing groups,enhance the application scope of anthranils in organic synthesis,and provide a new and efficient synthetic method for polysubstituted quinolines with biological activity.In addition,in order to provide an efficient route to acquire the anthranils,an efficient C3functionalization reaction of anthranils was developed in this thesis.The specific research contents and results include:1.Chapter 2.Tf₂O promotes the C3 functionalization reaction of anthranils:in this chapter,Tf₂O was employed to activate anthranils to enhance its C3electrophilicity,followed by electrophilic substitution with aromatics,olefins,carbonyl compounds and heteroatomic nucleophiles,and finally rearomatisation to obtain 3-substituted anthranils.This protocol possesses broad substrate scope and functional group tolerance,and can be used for the late-stage modification of complex molecules and bioactive molecules.Further,a series of drugs and material molecules were synthesized by using 3-substituted anthranils as the starting material.2.Chapter 3.Cu-catalyzed C-N coupling reaction of arylboric acid with anthranils:in this chapter,we developed the Cu-catalyzed C-N coupling reaction of arylboric acid with anthranils to efficiently synthesize N-aryl-2-aminophenones.This transformation is achieved under mild reaction conditions without any ligand;as an electrophilic amination reagent,anthranils can undergo C-N coupling reaction with arylboric acid under redox-neutral conditions to obtain the target N-aryl-2-aminophenones compounds in medium to good yields.Moreover,Ir-catalyzed hydrocarbon boration and Cu-catalyzed electrophilic amination protocol has also been developed to transform simple arenes to the valuable N-aryl-2-aminophenones compounds in one pot.In addition,the target product can be used for the synthesis of OLED molecules and drug molecules.3.Chapter 4.Ni H-catalyzed the hydroamination/cascade cyclization of alkynes and anthranils:in this chapter,we developed the Ni H-catalyzed hydroamination/cascade cyclization of alkynes and anthranils to efficiently construct multi substituted quinoline compounds.In this protocol,alkynes were employed to generate highly active alkenylnickel intermediate under the catalysis of Ni H,which further undergoes C-N coupling with anthranils to form enamines,and then 2,3-disubstituted quinolones was obtained by intramolecular condensation.This mild,operationally simple protocol is amen able to a wide array of alkynes including terminal and internal,aryl and alk yl,electron-deficient and electron-rich ones.This protocol is employed for the late-stage functionalization of several natural products and in the concise synthesis of several bioactive molecules.4.Chapter 5.Cu-catalyzed three component cascade cyclization of terminal alkynes,anthranils and amines:in this chapter,anthranils was also employed as an electrophilic amination reagent,realized the copper catalyzed sp C-H bond aromatic amination of terminal alkyne to form a highly active N-arylalkynylamine intermediate.The intermediate further reacted with aliphatic amine via nucleophilic addition,and finally obtained 2-aminoquinoline product via intramolecular cyclization.The preliminary substrate expansion showed that the protocol features good functional group tolerance and broad substrate scope,and both alkyl and aryl terminal alkynes could participate in th is reaction;In addition to the primary amine,the secondary amine with certain steric hindrance can also be compatible.