Copper-Catalyzed Radical Reactions Of ?-carbonyl Imines/Ketones:From Alkylation-Peroxidation To Asymmetric C(sp~3)-H Functionalization

Vicinal difunctionalization of unsaturated bonds has emerged as a powerful synthetic strategy in organic synthesis due to its ability to introduce two functional groups in a single chemical transformation.They have been developed rapidly in recent decades,however,such reactions normally need harsh reaction conditions,and are difficult to control the regioselectivity and stereoselectivity.Moreover,difunctionalization of imines and ketones provide a new efficient strategy for synthesis of structurally diversed molecules,however,have been much less reported incomparison to that of alkenes and alkynes.Thereby,it is of great value and in high demand to develop effective difunctionalization reactions of imines and ketones.In the first part of this work,a radical-mediated C(sp3)-H functionalization of a-ether and alkylation-peroxidation of ?-carbonyl imines or ketones has been accessed by a copper salt under mild conditions,providing a-amino or a-alkyloxyl peroxide products in good yields.Peroxides are commonly used to treat malaria which are typically derived from plants.The product a-amino peroxide is also a substructure of verruculogen.This method may provide an effective strategy to develop new bioactive molecules.In addition,the direct functionalization of hydrocarbon bond can make full use of hydrocarbon resources and provide tremendous impetus for the development of chemistry,chemical industry,medicine,agriculture and materials.Therefore,C-H activation has been praised as the Holy Grail of chemistry.C(sp3)-H is one of the most luxuriant inert C-H bonds in organic molecules.However,direct activation of C(Ssp3)-H is a extremely challenging project because of C(sp3)-H's high bond dissociation energy(BDE).In the second part of this paper,asymmetric C(sp3)-H functionalization of toluene and its derivatives and asymmetric alkylation of a-carbonyl imines were realized by means of an efficient catalytic platform employing a synergistic combination of an HAT organophotocatalyst and a chiral bisoxazoline catalyst of non-precious transition metalThe first chapter summarizes the progress and current situation of this research field,and discusses the purpose and significance of this paperIn the second chapter,copper-catalyzed alkylation and peroxidation of?-carbonyl imines/ketones were studied.We have developed a direct alkylation-peroxidation difunctionalization of ?-carbonyl imines or ketones by a simple copper salt under very mild reaction conditions.The peroxy and alkyl groups were site-specifically introduced into the C=N or C=O double bond,which produced a series of structurally novel and stable ?-amino/?-alkyloxyl peroxidesIn the third chapter,we have developed selective C(sp3)-H functionalization of hydrocarbons by means of an efficient catalytic platform employing a synergistic combination of an HAT organophotocatalyst and a chiral bisoxazoline catalyst of non-precious transition metal.The benzylic C(sp3)-H bonds can be functionalized with good to excellent regioselectivity and stereoselectivity.The method provides a rapid and economic access to direct introduction of stereocenters to more complicated medicinal agents like celebrex and skelaxinThe fourth chapter is a summary and prospect.