Rh(I)-Catalyzed Asymmetric Addition Of Ketones And Asymmetric C-H Functionalization Of Arenes

This dissertation consists of two parts: the first part focuses on the design,synthesis of novel chiral sulfonamide-olefin ligands and their applications in Rh-catalyzed asymmetric addition of arylboronic acids to prochiral ketones,affording a series of chiral tertiary alcohols bearing a tetrasubstituted stereocenter in high yields with excellent enantiomeric excesses.The second one mainly describes Rh(I)/dienes complex catalyzed asymmetric C-H insertion of styryldiazoacetate to electron-rich aromatic rings,which realizes the asymmetric C-H functionalization of indoles and aniline derivatives to access enantiomerically enriched γ,γ-diarylsubstituted α,β-unsaturated ester.1.The design,synthesis of novel chiral sulfonamide-olefin ligands and their applications in asymmetric addition of ketonesAs the development of organic fluorine chemistry,it becomes an important strategy to introduce fluorine to drug molecules for beneficial biological activities.Owing to its superior electronegativity and its size equal to hydrogen atom,the introduction of fluorine can lead to minimal steric alterations but dramatic changes in the physic-chemical and biological properties of those molecules.Chiral tertiary alcohols are one type of intriguing building blocks present in numerous biologically active pharmaceuticals and nature products.Moreover,fluorine-containing chiral tertiary alcohols have attracted considerable attention over the years for their distinctive biological properties.However,the preparation of these molecules is difficult due to the high electronegativity of fluorine.Therefore,it is meaningful to develop efficient asymmetric methods to construct enantioenriched fluorine-containing tertiary alcohols.In the past few years,our group have been devoted to the study of transition-metal-catalyzed asymmetric transformations and reported a class of simple and readily available chiral sulfur-based olefin ligands,which were successfully employed in Rh-catalyzed asymmetric addition reactions.Based on our previous work and as part of our ongoing interest,we developed novel chiral sulfur-based trisubstituted-olefin ligands and utilized them in Rh-catalyzed asymmetric addition of arylboronic acids to fluorine-containing acetophenones,furnishing a series of chiral fluorine-containing tertiary alcohols in highly enantioselective manner under mild conditions.Moreover,these ligands also exhibited excellent catalytic activity in the addition of arylboronic acids to simple acetophenones to achieve the desired products in high yields with excellent ee values.In addition,we have developed a highly enantioselective rhodium-catalyzed intramolecular addition of arylboronic acids to unactivated ketones with the use of chiral sulfur-based branched olefin as the ligand,affording a series of chiral tetrasubstituted carbon stereocenter-containing 3-hydroxy-2,3-dihydrobenzofurans in good yields with high enantioselectivities under mild conditions.The reaction provides a practical approach for the synthsis of pharmaceutics containing this skeleton.Fruthermore,the addition product could be easily converted to spirocyclic compounds contained 2,3-dihydrobenzofuran skeleton and 1,3-dihydroisobenzofuran unit which would be otherwise hard-to-access.2.Rh(I)-catalyzed asymmetric C-H insertion of arenesCarbon-carbon bond is the basis for the formation of organic compounds and its construction is an essential subject in organic chemistry.Transition-metal-catalyzed asymmetric C-H insertion of carbenoids has emerged as a direct and efficient approach to construct carbon-carbon bond and has attracted considerable attention of chemists over the years.Although significant progress has been made in asymmetric C(sp3)-H insertion reactions,to the best of our knowledge,the results of asymmetric C(sp2)-H insertion is far less satisfactory.Recently,our group has developed a series of C1-symmetrical chiral dienes based on biocyclo [2.2.2]octadiene framework and successfully used them in rhodium-catalyzed asymmetric B-H and Si-H bonds insertion of carbenoids,providing a series of organoboranes and organsilanes in good yields with high enantioselectivities.On the basis of this work and as a part of our continual interest,we have extended this catalytic system to rhodium(I)-catalyzed asymmetric C-H insertion of indoles at C3 by using styryldiazoacetate,which provides an attractive approach to construct chiral γ-indolyl-γ-arylsubstituted α,β-unsaturated esters with excellent enantioselectivities at room temperature.Additionally,this catalytic system was also effective to C-H functionalization of aniline derivatives,furnishing a series of γ,γ-diarylsubstituted α,β-unsaturated ester with various substituents on phenyl ring through highly enantioselective C-H insertion(up to 95% ee).The dialkylamino substituents on the benzene ring of the products can be removed by Birch reduction,generating a commom chiral gem-diaryl skeleton.Moreover,through Friedel–Crafts reaction,Mitsunobu reaction,Buchwald coupling and insertion after Oxa-Michael addition,the products of the C-H insertion can be transformed to diverse optically active compounds which may find application in related biological activity investigation and offer new opportunities for drug discovery projects.