α-C(sp^(3))-H arylation is an important type of C-H functionalization.Various biologically significant natural products,chemi-cal intermediates,and drugs have been effectively prepared via C-H functionalization.Cycli...α-C(sp^(3))-H arylation is an important type of C-H functionalization.Various biologically significant natural products,chemi-cal intermediates,and drugs have been effectively prepared via C-H functionalization.Cyclic carbonyl compounds comprise of cyclic ketones,enones,lactones,and lactams.Theα-C(sp^(3))-H arylation of these compounds have been exhibited high efficiency in forming C(sp^(3))-C(sp^(2))bonds,played a crucial role in organic synthesis,and attracted majority of interests from organic and medicinal communities.This review focused on the most significant advances including methods,mechanism,and applications in total synthesis of natural products in the field ofα-C(sp^(3))-H arylations of cyclic carbonyl compounds in recent years.展开更多
A rhodium-catalyzed desymmetrization reaction for enantioselective methyl C-H arylation is achieved by utilizing an in situ arylating reagent via nucleophilic cyclization of o-aminoaryl alkyne.The reaction results in ...A rhodium-catalyzed desymmetrization reaction for enantioselective methyl C-H arylation is achieved by utilizing an in situ arylating reagent via nucleophilic cyclization of o-aminoaryl alkyne.The reaction results in chiral indoles containing all-carbon quaternary stereocenters under atmospheric conditions,with a wide range of substrates exhibiting good enantioselectivity(44 examples).Mechnism and DFT studies show that the stereocontrol is reasonably achieved through the collaborative control of a large silicon substituted chiral ligand and C-H···π,LP···πinteractions between aryl rings of the carboxylate group and the substrate.Control experiments demonstrate that Rh-aryl bond formation via in situ nucleophilic cyclization is more critical for reaction efficiency than via C-H activation of the nucleophilic cyclization byproduct.展开更多
Catalytic C-H borylation is of prime topical importance,since easily available feedstock chemicals can thereby be transformed into valuable transient functional groups in the absence of directing groups.Herein,we disc...Catalytic C-H borylation is of prime topical importance,since easily available feedstock chemicals can thereby be transformed into valuable transient functional groups in the absence of directing groups.Herein,we disclose an iron-catalyzed C(sp^(3))-H borylation of simple,non-prefunctionalized alkanes,providing access to value-added products in a single step by means of photoelectrochemistry.The power of merging photo-and electrochemistry was mirrored by ample scope and exceedingly mild reaction conditions.Moreover,an outstanding position-selectivity in favor of primary C(sp^(3))-H proved viable within the photoelectrochemical borylation through a chemo-selective anodic overoxidation manifold.The ferro-photoelectrochemistry strategy avoids toxic precious transition metals,enabling C(sp^(3))-H borylations in a site-selective fashion.展开更多
An efficient and scalable electrochemical asymmetric protocol with metal-free catalysts and even without additional oxidants for the cross-dehydrogenative coupling reaction(CDC)of two C(sp^(3))-H bonds is reported.A s...An efficient and scalable electrochemical asymmetric protocol with metal-free catalysts and even without additional oxidants for the cross-dehydrogenative coupling reaction(CDC)of two C(sp^(3))-H bonds is reported.A series of aldehydes including natural products and various substrates containing C(sp^(3))-H bonds including xanthenes,acridines,cycloheptatrienes and even diarylmethane have been shown to undergo asymmetric CDC to afford a series of carbon-carbon bond coupling products with up to 94%yield and 98%ee.Mechanistic studies such as radical clock experiment suggest that the reaction proceeds via nucleophilic attack by enamine under electrochemical conditions.展开更多
An acetic acid-promoted C(sp^(3))-H functionalization of 2-methyl quinoline,enaminoesters and elemental sulfur for the synthesis of 3,4,5-trisubstituted isothiazoles under metal-free conditions has been developed.This...An acetic acid-promoted C(sp^(3))-H functionalization of 2-methyl quinoline,enaminoesters and elemental sulfur for the synthesis of 3,4,5-trisubstituted isothiazoles under metal-free conditions has been developed.This approach provides viable access to various 5-(quinolin-2-yl)isothiazoles in moderate to good yields with good functional group tolerance.Moreover,the success of the gram-scale reaction gives this reaction a great potential application.展开更多
A radical decarboxylative C(sp^(3))–C(sp^(3))cross-coupling of NHPI esters and cyclopropanols was developed by combining photocatalysis and copper catalysis,which presents the efficient access toβ-benzyl ketones in ...A radical decarboxylative C(sp^(3))–C(sp^(3))cross-coupling of NHPI esters and cyclopropanols was developed by combining photocatalysis and copper catalysis,which presents the efficient access toβ-benzyl ketones in excellent yields.Terpyridin-4′-one used as the ligand is vital for the reaction,which could facilitate the capture of benzylic radicals by alkyl-copper species generated from copper-catalyzed ring-opening of cyclopropanols.The reaction exhibited broad substrate scope and wide functional group compatibility,providing an alternative approach for C(sp^(3))–C(sp^(3))bond formation.展开更多
The isoindolinone and biaryl scaffolds are prevalent in natural products and drug molecules,which have showed broad and interesting biological activities.The efficient construction of such hybridized molecules and bio...The isoindolinone and biaryl scaffolds are prevalent in natural products and drug molecules,which have showed broad and interesting biological activities.The efficient construction of such hybridized molecules and biological evaluation are of great interest to medicinal chemistry community.In this communication,we report an efficient BrΦnsted acid-promoted C(sp^3)-H functionalization approach that enables the rapid construction of biologically important isoindolinone/[1,2,4]triazolo[1,5-a]pyrimidine hybrids from 5-methyl-7-(2,4,6-trimethoxyphenyl)-[1,2,4]triazolo[1,5-a]pyrimidine,2-formylbenzoic acid and various anilines.The title compounds were generated in high to excellent yields(up to 96%)regardless of the electronic nature and steric effects of the substituents.In this reaction,an isoindolinone scaffold,one C-C single bond,and two C-N bonds were formed simultaneously with high atom economy.In this work,we have envisioned that the methyl group linked to the electron-deficient Nheterocycles could be used as a new synthetic handle for late-state diversification and may have broad applications in the field of organic and medicinal chemistry.Besides,the title compounds have exhibited promising activity against the SKP2-CKS1 interaction.展开更多
Thioether skeletons are widely present in drugs,natural products,functional materials,and life science.In the past decade,the selective C–H functionalization of thioethers has been extensively studied to construct no...Thioether skeletons are widely present in drugs,natural products,functional materials,and life science.In the past decade,the selective C–H functionalization of thioethers has been extensively studied to construct novel thioether derivatives.This mini-review systematically introduces the recent advances in the field of the directα-C(sp^(3))-H functionalization of thioethers.展开更多
Photoredox catalysis can be induced to activate organic substrates or to modulate the oxidation state of transition-metal catalysts via unique singleelectron transfer processes,so as to achieve challenging C(sp^(3))-H...Photoredox catalysis can be induced to activate organic substrates or to modulate the oxidation state of transition-metal catalysts via unique singleelectron transfer processes,so as to achieve challenging C(sp^(3))-H functionalization under mild conditions.However,the specific reaction mechanism and relevant electron transfer process still need to be clarified.Here,a highly regioselective Ir^(Ⅲ)/Ni^(Ⅱ)-metallaphotoredox-catalyzed hydroalkylation of asymmetrical internal alkyne with an etherα-hetero C(sp^(3))-H bond has been investigated by density functional theory(DFT)calculations.A novel radical mechanism was predicted to merge oxidative quenching(Ir^(Ⅲ)-*Ir^(Ⅲ)-Ir^(Ⅳ)-Ir^(Ⅲ))and nickel catalytic cycles(NiⅡ-NiⅢ-NiI-NiⅢ-NiⅡ)for this C(sp^(3))-H functionalization to construct C(sp^(3))-C(sp^(2))bonds.It consists of seven major steps:the single-electron transfer involved in the photoredox cycle for generating active Ni(Ⅰ)-chloride complexes,proton-coupled electron transfer process to provide α-carbon-centered tetrahydrofuran(THF)radicals,radical capture by Ni(Ⅱ),reductive elimination to obtain 2-chlorotetrahydrofuran,alkyne oxidative hydrometallation,innersphere electron transfer,and σ-bond metathesis to yield the desired alkyne hydroalkylation product.Importantly,both the thermodynamic performance for redox potentials and the kinetic exploration for energy barriers and electron-transfer rates have also been evaluated for the corresponding electron transfer processes.In addition,the steric effects play a major role in determining the regioselectivity of alkyne oxidative hydrometallation.展开更多
By employing a readily available CuCI/DDQ catalyst system,we herein report a direct C(sp^(3))-H sulfonylation of xanthene derivates with odorless sodium sulfinates.Various 9H-xanthenes,thioxanthenes,and 9,10-dihydroac...By employing a readily available CuCI/DDQ catalyst system,we herein report a direct C(sp^(3))-H sulfonylation of xanthene derivates with odorless sodium sulfinates.Various 9H-xanthenes,thioxanthenes,and 9,10-dihydroacridines are efficiently transformed into the desired benzylic sulfonyl products via a radical/radical cross-coupling process,proceeding with the merits of broad substrate scope,operational simplicity,good functional group compatibility,and mild reaction conditions.展开更多
Hydrogen atom transfer(HAT)is an elementary mechanistic step in organic synthesis.The photoredox-catalyzed HAT has transformed organic synthesis by enabling the activation and subsequent cross-coupling of traditionall...Hydrogen atom transfer(HAT)is an elementary mechanistic step in organic synthesis.The photoredox-catalyzed HAT has transformed organic synthesis by enabling the activation and subsequent cross-coupling of traditionally inert yet ubiquitous C(sp^(3))-H bonds.展开更多
基金We gratefully acknowledge financial support from the National Science of Foundation of China(81960631)the Yunnan Fundamental Research Project(202001AS070038)+1 种基金the Top Young Talent of Ten Thousand Talents Program of Yunnan Province(R.Zhan and L.-D Shao)the Start-up Fund of Yunnan University of Chinese Medicine(2019YZG03).
文摘α-C(sp^(3))-H arylation is an important type of C-H functionalization.Various biologically significant natural products,chemi-cal intermediates,and drugs have been effectively prepared via C-H functionalization.Cyclic carbonyl compounds comprise of cyclic ketones,enones,lactones,and lactams.Theα-C(sp^(3))-H arylation of these compounds have been exhibited high efficiency in forming C(sp^(3))-C(sp^(2))bonds,played a crucial role in organic synthesis,and attracted majority of interests from organic and medicinal communities.This review focused on the most significant advances including methods,mechanism,and applications in total synthesis of natural products in the field ofα-C(sp^(3))-H arylations of cyclic carbonyl compounds in recent years.
基金financial support for this work from the National Key R&D Program of China(No.2021YFC0864700)the National Natural Science Foundation of China(Nos.21801066,U1804283 and 82130103)+2 种基金the Central Plains Scholars and Scientists Studio Fund(No.2018002)the project funded by the Natural Science Foundation of Henan(Nos.222300420056,222300420204)the China Postdoctoral Science Foundation(Nos.2020M682307,2021T140183)。
文摘A rhodium-catalyzed desymmetrization reaction for enantioselective methyl C-H arylation is achieved by utilizing an in situ arylating reagent via nucleophilic cyclization of o-aminoaryl alkyne.The reaction results in chiral indoles containing all-carbon quaternary stereocenters under atmospheric conditions,with a wide range of substrates exhibiting good enantioselectivity(44 examples).Mechnism and DFT studies show that the stereocontrol is reasonably achieved through the collaborative control of a large silicon substituted chiral ligand and C-H···π,LP···πinteractions between aryl rings of the carboxylate group and the substrate.Control experiments demonstrate that Rh-aryl bond formation via in situ nucleophilic cyclization is more critical for reaction efficiency than via C-H activation of the nucleophilic cyclization byproduct.
基金the European Research Council(ERC Advanced Grantno.101021358)+2 种基金the Deutsche Forschungsgemeinschaft(DFG,Gottfried Wilhelm Leibniz award to L.A.)the Fonds der Chemischen Industrie(FCI,Kekulé-Fellowship to T.v.M.)the China Scholarship Council(CSC grant no.201906280067 to W.W.).
文摘Catalytic C-H borylation is of prime topical importance,since easily available feedstock chemicals can thereby be transformed into valuable transient functional groups in the absence of directing groups.Herein,we disclose an iron-catalyzed C(sp^(3))-H borylation of simple,non-prefunctionalized alkanes,providing access to value-added products in a single step by means of photoelectrochemistry.The power of merging photo-and electrochemistry was mirrored by ample scope and exceedingly mild reaction conditions.Moreover,an outstanding position-selectivity in favor of primary C(sp^(3))-H proved viable within the photoelectrochemical borylation through a chemo-selective anodic overoxidation manifold.The ferro-photoelectrochemistry strategy avoids toxic precious transition metals,enabling C(sp^(3))-H borylations in a site-selective fashion.
基金National Natural Science Foundation of China(Nos.22161008,22061003)Guangxi Science and Technology Base and Talent Project(High Level Innovative Talents and Team Training)(Guike No.AD23026094)Guangxi Natural Science Foundation of China(No.2021GXNSFFA220005)for financial support。
文摘An efficient and scalable electrochemical asymmetric protocol with metal-free catalysts and even without additional oxidants for the cross-dehydrogenative coupling reaction(CDC)of two C(sp^(3))-H bonds is reported.A series of aldehydes including natural products and various substrates containing C(sp^(3))-H bonds including xanthenes,acridines,cycloheptatrienes and even diarylmethane have been shown to undergo asymmetric CDC to afford a series of carbon-carbon bond coupling products with up to 94%yield and 98%ee.Mechanistic studies such as radical clock experiment suggest that the reaction proceeds via nucleophilic attack by enamine under electrochemical conditions.
基金Support by the National Natural Science Foundation of China(Nos.22271244,21871226 and 21572194)Postgraduate Scientific Research Innovation Project of Hunan Province(No.CX20200631)the Open Research Fund of the School of Chemistry and Chemical Engineering of Henan Normal University(No.2022C02)is gratefully acknowledged.
文摘An acetic acid-promoted C(sp^(3))-H functionalization of 2-methyl quinoline,enaminoesters and elemental sulfur for the synthesis of 3,4,5-trisubstituted isothiazoles under metal-free conditions has been developed.This approach provides viable access to various 5-(quinolin-2-yl)isothiazoles in moderate to good yields with good functional group tolerance.Moreover,the success of the gram-scale reaction gives this reaction a great potential application.
基金supported by the National Key R&D Program of China(2021YFA1500100)the National Natural Science Foundation of China(91956202,92256301,21821002,21971255)+1 种基金the Science and Technology Commission of Shanghai Municipality(20JC1417000,21520780100)the International Partnership Program(121731KYSB20190016)of the Chinese Academy of Sciences。
文摘A radical decarboxylative C(sp^(3))–C(sp^(3))cross-coupling of NHPI esters and cyclopropanols was developed by combining photocatalysis and copper catalysis,which presents the efficient access toβ-benzyl ketones in excellent yields.Terpyridin-4′-one used as the ligand is vital for the reaction,which could facilitate the capture of benzylic radicals by alkyl-copper species generated from copper-catalyzed ring-opening of cyclopropanols.The reaction exhibited broad substrate scope and wide functional group compatibility,providing an alternative approach for C(sp^(3))–C(sp^(3))bond formation.
基金supported by the National Natural Science Foundation of China(Nos.81773562 and 81703326)China Postdoctoral Science Foundation(Nos.2018M630840 and 2019T120641)Scientific Program of Henan Province(No.182102310123)。
文摘The isoindolinone and biaryl scaffolds are prevalent in natural products and drug molecules,which have showed broad and interesting biological activities.The efficient construction of such hybridized molecules and biological evaluation are of great interest to medicinal chemistry community.In this communication,we report an efficient BrΦnsted acid-promoted C(sp^3)-H functionalization approach that enables the rapid construction of biologically important isoindolinone/[1,2,4]triazolo[1,5-a]pyrimidine hybrids from 5-methyl-7-(2,4,6-trimethoxyphenyl)-[1,2,4]triazolo[1,5-a]pyrimidine,2-formylbenzoic acid and various anilines.The title compounds were generated in high to excellent yields(up to 96%)regardless of the electronic nature and steric effects of the substituents.In this reaction,an isoindolinone scaffold,one C-C single bond,and two C-N bonds were formed simultaneously with high atom economy.In this work,we have envisioned that the methyl group linked to the electron-deficient Nheterocycles could be used as a new synthetic handle for late-state diversification and may have broad applications in the field of organic and medicinal chemistry.Besides,the title compounds have exhibited promising activity against the SKP2-CKS1 interaction.
基金support from the National Natural Science Foundation of China(NSFC,No.21702019)and Advanced Catalysis and Green Manufacturing Collaborative Innovation Center,Changzhou UniversityHaibo Ge,Mazen Elsaid and Chong Liu acknowledge NSF(No.CHE-2029932),Robert A.Welch Foundation(No.D-2034-20200401),and the Texas Tech University for financial support.
文摘Thioether skeletons are widely present in drugs,natural products,functional materials,and life science.In the past decade,the selective C–H functionalization of thioethers has been extensively studied to construct novel thioether derivatives.This mini-review systematically introduces the recent advances in the field of the directα-C(sp^(3))-H functionalization of thioethers.
文摘Photoredox catalysis can be induced to activate organic substrates or to modulate the oxidation state of transition-metal catalysts via unique singleelectron transfer processes,so as to achieve challenging C(sp^(3))-H functionalization under mild conditions.However,the specific reaction mechanism and relevant electron transfer process still need to be clarified.Here,a highly regioselective Ir^(Ⅲ)/Ni^(Ⅱ)-metallaphotoredox-catalyzed hydroalkylation of asymmetrical internal alkyne with an etherα-hetero C(sp^(3))-H bond has been investigated by density functional theory(DFT)calculations.A novel radical mechanism was predicted to merge oxidative quenching(Ir^(Ⅲ)-*Ir^(Ⅲ)-Ir^(Ⅳ)-Ir^(Ⅲ))and nickel catalytic cycles(NiⅡ-NiⅢ-NiI-NiⅢ-NiⅡ)for this C(sp^(3))-H functionalization to construct C(sp^(3))-C(sp^(2))bonds.It consists of seven major steps:the single-electron transfer involved in the photoredox cycle for generating active Ni(Ⅰ)-chloride complexes,proton-coupled electron transfer process to provide α-carbon-centered tetrahydrofuran(THF)radicals,radical capture by Ni(Ⅱ),reductive elimination to obtain 2-chlorotetrahydrofuran,alkyne oxidative hydrometallation,innersphere electron transfer,and σ-bond metathesis to yield the desired alkyne hydroalkylation product.Importantly,both the thermodynamic performance for redox potentials and the kinetic exploration for energy barriers and electron-transfer rates have also been evaluated for the corresponding electron transfer processes.In addition,the steric effects play a major role in determining the regioselectivity of alkyne oxidative hydrometallation.
基金the National Natural Science Foundation of China(No.21971071)the Natural Science Foundation of Guangdong Province(No.2021A1515010155)the Fundamental Research Funds for the Central Universities(No.2020ZYGXZR075).
文摘By employing a readily available CuCI/DDQ catalyst system,we herein report a direct C(sp^(3))-H sulfonylation of xanthene derivates with odorless sodium sulfinates.Various 9H-xanthenes,thioxanthenes,and 9,10-dihydroacridines are efficiently transformed into the desired benzylic sulfonyl products via a radical/radical cross-coupling process,proceeding with the merits of broad substrate scope,operational simplicity,good functional group compatibility,and mild reaction conditions.
基金We are grateful for financial support from the National Key R&D Program of China(2021YFA1502500)National Natural Science Foundation of China(22071203)Fundamental Research Funds for the Central Universities(20720210014).
文摘Hydrogen atom transfer(HAT)is an elementary mechanistic step in organic synthesis.The photoredox-catalyzed HAT has transformed organic synthesis by enabling the activation and subsequent cross-coupling of traditionally inert yet ubiquitous C(sp^(3))-H bonds.
