Iridium-Catalyzed Asymmetric Aromatic C-H Alkylation Or Alkenylation By Alkenes Or Alkynes

Chiral compounds are widely used in chemical industry,medicine,materials,pesticides and other fields.How to quickly and efficiently construct chiral compounds has long been an important area of concern for synthetic chemists.Asymmetric catalysis is one of the main means to achieve efficient synthesis of chiral compounds.Among them,transition metal-catalyzed asymmetric C-H bond functionalization has been rapidly developed in recent years,and has gradually become an important strategy for the efficient construction of structurally diverse chiral compounds.The use of unsaturated hydrocarbons such as olefins,alkynes and other unsaturated hydrocarbons as functionalization reagents can not only make full use of the advantages of unsaturated hydrocabons as basic chemical raw materials,which are cheap,easy to obtain,and rich in variety,but also has extremely high steps and atomic economy,in line with the concept of green chemistry and sustainable development.Focusing on the development of asymmetric catalytic systems,in this dissertation,iridium(I)-catalyzed asymmetric alkylation or alkenylation of aromatic C-H bonds under neutral redox condition has been developed using olefins or alkynes as functional reagents.The research contents include:1.Iridium(I)-Catalyzed Linear Selective Asymmetric Alkylation of Olefins to2-ArylpyridinesUsing 2-arylpyridine or 1-arylisoquinoline as the substrate,iridium(I)-catalyzed linear selective asymmetric alkylation of olefins to these substrates for efficient construction of alkylated axially chiral heteroaromatic compounds has been developed under the directing of pyridine or isoquinoline groups in the substrate.The reaction uses cationic iridium(I)as a catalyst and(R)-segphos as a chiral ligand,the corresponding axially chiral alkylation products can be obtained with excellent stereoselectivity and mederate to excellent linear selectivity under neutral redox condition.The reaction has the advantages of excellent stereoselectivity,simple catalytic system,mild conditions and high universality of substrates which provide a new way to realize asymmetric C-H functionalization of aromatic rings with unsaturated hydrocarbons.2.Iridium(I)-Catalyzed Asymmetric Alkenylation of Alkynes to 2-ArylpyridinesBased on the monovalent iridium catalytic system developed above,the asymmetric alkenylation of 2-arylpyridine or 1-arylisoquinoline substrate was realized by further using terminal alkynes as functionalization reagent.The atom economic synthesis of the corresponding axially chiral alkenylated heteroaromatic ring compounds was realized.Compared with the oxidative coupling pathway using palladium or rhodium catalysts under oxidation conditions in the literature work,this method is realized under the redox neutral conditions,avoids the use of oxidants,and provides a new idea for further exploring the asymmetric functionalization reaction participated by alkynes.3.Iridium(I)-Catalyzed Branched Selective Asymmetric Alkylation of Olefins to N-arylisoindolinoneBased on the successful use of iridium(I)catalytic system to realize the asymmetric C-H functionalization of heteroaromatic ring construct axial chiral compounds,the asymmetric branched chain selective alkylation of N-arylisoindolinone with olefins was further developed.The alkylation products containing benzyl chiral centers were obtained with excellent branched chain selectivity and good enantioselectivity by means of the chelation assistance of carbonyl oxygen in N-arylisoindolinone substrate.The key to realize the asymmetric control of this reaction is the use of biphephos type chiral ligands,which play an important role in improving the reaction activity and regulating the stereoselectivity.Since substituted N-arylisoindolinones exist in many drugs or bioactive molecules,the construction of such chiral alkylation products is expected to lay a good foundation for the exploration of related bioactivities.