The Construction Of Axially Chiral 1-aryl Isoquinolines Via Rhodium-catalyzed Asymmetric C-H Functionalization

This thesis mainly focuses on rhodium(Ⅲ)-catalyzed atroposelective C-H functionalization reactions for the construction of axially chiral 1-aryl isoquinolines,including the following three parts.(1)The application of hypervalent iodine reagents(HIR)in rhodium(Ⅲ)-catalyzed asymmetric C-H functionalization reactions to form C-C bond.The asymmetric C-H indolylation reaction with indole derived hypervalent iodine reagents and the asymmetric C-H alkynylation reaction with the application of alkyne derived hypervalent iodine reagents were realized,respectively.(2)Rhodium(Ⅲ)-catalyzed asymmetric C-H functionalization reactions to form carbonhetero bond.The asymmetric C-H iodination and selenation reactions were realized.(3)Rhodium(Ⅲ)-catalyzed asymmetric C-H cyanation reaction was realized.In the first part,rhodium(Ⅲ)-catalyzed atroposelective C-H indolylization of1?aryl isoquinolines with 3-indolylphenyliodonium salts was studied.The rhodium(Ⅲ)-catalyzed highly atroposelective C-H indolylization reaction was realized with indole derived hypervalent iodine reagents for the first time.This reaction could be carried out under mild conditions thanks to the high reactivity of 3-indolylphenyliodonium salts,affording the axially chiral indolylized 1-aryl isoquinolines in excellent yields(up to 98%)and enantioselectivity(up to 95% ee).It is noteworthy that pyridine directing group is compatible in this reaction.In the second part,rhodium(Ⅲ)-catalyzed atroposelective C-H alkynylation of1?aryl isoquinolines with alkyne derived hypervalent iodine reagents was studied.The first rhodium(Ⅲ)-catalyzed highly atroposelective C-H alkynylation reaction was realized with alkyne derived hypervalent iodine reagents.This reaction could be carried out under mild conditions in the presence of TIPS-EBX reagent,affording the axially chiral alkynylized 1-aryl isoquinolines in excellent yields(up to 94%)and enantioselectivity(up to 95% ee).The diverse transformations of the product were achieved,such as Sonogashira coupling reaction,silane reduction reaction,click reaction and the synthesis of nitrogen oxides.In the third part,rhodium(Ⅲ)-catalyzed atroposelective C-H iodination of 1?aryl isoquinolines was studied.The first rhodium(Ⅲ)-catalyzed highly atroposelective C-H iodination reaction was realized.This reaction could be carried out under mild conditions,furnishing axially chiral 1-aryl isoquinoline iodides in excellent yields(up to 99%)and enantioselectivity(up to 97% ee).Pyridine directing group was found to be compatible in this reaction.The C-H bromination and chlorination were also compatible.Diverse transformations including the synthesis of N,P and N,N ligands were achieved.The N,P ligand could be applied in asymmetric Buchwald-Hartwig coupling reaction.In the fourth part,rhodium(Ⅲ)-catalyzed atroposelective C-H selenation of 1?aryl isoquinolines was studied.The first rhodium(Ⅲ)-catalyzed highly atroposelective C-H selenation reaction was realized,furnishing the axially chiral 1-aryl isoquinoline selenides in excellent yields(up to 95%)and enantioselectivity(up to 96% ee).This method provides a new way for the synthesis of chiral selenides.The mechanism of the reaction was further disclosed by DFT calculation.In the fifth part,rhodium(Ⅲ)-catalyzed atroposelective C-H cyanation of 1?aryl isoquinolines was explored.The first rhodium(Ⅲ)-catalyzed highly atroposelective CH cyanation reaction was realized,affording a series of axially chiral cyanated 1-aryl isoquinoline nitriles in excellent yields(up to 94%)and enantioselectivity(up to 91%ee).This method provides a novel way for the synthesis of chiral nitrile products.