The accompanied forge of C(sp^(3))–S and C(sp^(3))–C(sp^(3))bonds across alkene frameworks serves as a potent strategy to construct biologically important compounds.Here,we report a metal-free,photochemically mediat...The accompanied forge of C(sp^(3))–S and C(sp^(3))–C(sp^(3))bonds across alkene frameworks serves as a potent strategy to construct biologically important compounds.Here,we report a metal-free,photochemically mediated fluoroalkyl-mono/disulfuration of unactivated alkenes with high efficiency and high selectivity.A wide range of terminal and internal alkenes are good coupling partners,affording the expected products in moderate to good yields(>90 examples).The exceedingly mild reaction conditions,exceptional functional group tolerance,broad substrate scope,and the potential for late-stage modifications of pharmaceutical molecules highlight the utility of this method in the preparation of privileged motifs from readily available disulfides,tetrasulfides,and diselenides.Mechanistic studies suggest that a secondary alkyl radical intermediate undergoes efficient homolytic substitution with disulfides,facilitating the modular synthesis of a diverse array of unsymmetrical thioethers.展开更多
Mechanistic studies of the cleavage and transformation of unactivated C_(sp3)-H bonds are a significant field of chemistry.Overcoming the inherent low acidity of C-H bonds to activate the inert substrates is challenge...Mechanistic studies of the cleavage and transformation of unactivated C_(sp3)-H bonds are a significant field of chemistry.Overcoming the inherent low acidity of C-H bonds to activate the inert substrates is challenge under mild conditions.And their complex multi-step transformations may also hinder mechanistic understanding.Herein,we perform theoretical calculations and experimental studies to explore the C_(sp3)-H bonds activation and acylation mechanisms of toluene/thioether using the relatively weak base LDA.A synergistic"main and auxiliary"model was revealed involving dual lithium metal by LDA dimers,and the aryl dilithium species as an intermediate base can facilitate C_(sp3)-H activation.This model not only aids in understanding the acidity of unactivated C_(sp3)-H bonds and the nucleophilicity of their conjugate bases for their kinetic control through cooperative interactions,but also predicts unusual kinetic isotope effects(KIE)for newly designed 2-(methylthio)naphthalene that are experimentally validated.This research is expected to provide a crucial scenario for the cleavage and transformation of unactivated C_(sp3)-H bonds and the development of new functionalities for alkali metal reagents.展开更多
The carboxylation of readily available organo halides with CO_(2)represents a practical strategy to afford valuable carboxylic acids.However,efficient carboxylation of inexpensive unactivated alkyl chlorides is still ...The carboxylation of readily available organo halides with CO_(2)represents a practical strategy to afford valuable carboxylic acids.However,efficient carboxylation of inexpensive unactivated alkyl chlorides is still underdeveloped.Herein,we report the electro-reductive carboxylation of C–Cl bonds in unactivated chlorides and polyvinyl chloride with CO_(2).A variety of alkyl carboxylic acids are obtained in moderate to good yields under mild conditions with high chemoselectivity.Importantly,the utility of this electroreductive carboxylation is demonstrated with great potential in polyvinyl chloride(PVC)upgrading,which could convert discarded PVC from hydrophobic to hydrophilic functional products.Mechanistic experiments support the successive single electron reduction of unactivated chlorides to generate alkyl anion species and following nucleophilic attack on CO_(2)to give desired products.展开更多
A nickel-catalyzed direct hydromonofluoromethylation of unactivated olefins with industrial raw fluoroiodomethane is developed,furnishing various primary alkyl fluorides in a step-economic manner.The key factor to suc...A nickel-catalyzed direct hydromonofluoromethylation of unactivated olefins with industrial raw fluoroiodomethane is developed,furnishing various primary alkyl fluorides in a step-economic manner.The key factor to success is the use of pyridine-oxazoline as ligand and(MeO)_(2)MeSiH as the hydrogen source.This transformation demonstrates high efficiency,mild conditions,good functional-group compatibility and great potential in the drug discovery.展开更多
We report a Pd-catalyzed halocyclization of unactivated 1,6-diynes with N-bromosuccinimide(NBS).This approach produces stereo-defined dibromo substituted dihydropyrans,tetrahydropyridines,and 3-methylene cyclohexenes ...We report a Pd-catalyzed halocyclization of unactivated 1,6-diynes with N-bromosuccinimide(NBS).This approach produces stereo-defined dibromo substituted dihydropyrans,tetrahydropyridines,and 3-methylene cyclohexenes with exocyclic double bond appendages in mostly good yields.Copper salt was found to be a useful Lewis acid in this reaction.Mechanistically,a formal anti-carbopalladation and a bromide radical promoted PdⅡ-PdⅢ-PdⅠ-PdⅡcatalytic cycles were proposed to be involved in the formation of the dibromo-substituted products.Further functionalization of the dihydropyran derivatives underwent B(C6F5)3-catalyzed ring opening,and reduction afforded dibrominated 1,3-dienes with excellent stereoselectivity.展开更多
The catalytic production of chiral amides from readily available unactivated internal alkenes remains a significant challenge in synthetic chemistry.In this work,we developed a highly enantioselective hydroaminocarbon...The catalytic production of chiral amides from readily available unactivated internal alkenes remains a significant challenge in synthetic chemistry.In this work,we developed a highly enantioselective hydroaminocarbonylation procedure for nonactivated internal alkenes and a wide range ofα-chiral amides were produced effectively with exceptional enantioselectivities using copper as the catalyst.This method is compatible with both symmetric and asymmetric internal alkenes,as well as various hydroxylamine electrophiles,demonstrating wide substrate scope and broad functional group tolerance.The established catalytic system showcases remarkable enantioselective performance in the asymmetric hydroaminocarbonylation of challenging substrates,such as the methyl-ethylα-chiral amide synthesis from trans-2-butene,despite the minimal steric difference between the methyl and ethyl group.This work represents important progress in the field of asymmetric hydroaminocarbonylation and offers a useful tool for the production of valuableα-chiral amide compounds from readily available internal alkenes.展开更多
α-Olefins as aliphatic terminal alkenes could be obtained easily from numerous contemporary synthetic reactions as well as petro-chemical industry,and also found in natural products.Compared to the alkenes attaching ...α-Olefins as aliphatic terminal alkenes could be obtained easily from numerous contemporary synthetic reactions as well as petro-chemical industry,and also found in natural products.Compared to the alkenes attaching the directing groups or activating group,the catalytic asymmetric reaction of unactivated terminal alkenes presents great challenges due to the weak electron effect and small steric hindrance effect.This review mainly summarizes the latest progress of the asymmetric reaction of unactivated terminal olefins since 2016.展开更多
Photocatalyzed alkylsulfonylation of unactivated alkenes using DABCO.(SO_(2))_(2) and thianthrenium salts via a distal heteroaryl migration process has been developed,which provides a new means of synthesizing a varie...Photocatalyzed alkylsulfonylation of unactivated alkenes using DABCO.(SO_(2))_(2) and thianthrenium salts via a distal heteroaryl migration process has been developed,which provides a new means of synthesizing a variety of valuable alkylsulfonyl-substituted compounds.These alkylsulfonyl radicals couple with unactivated alkenes to undergo efficient intermolecular reactions,followed by distal heteroaryl migration.This mild catalytic method is tolerant of functional groups and affords medicinally relevant alkylsulfonylated heterocycles.展开更多
Palladium-catalyzed regioselective amination of unactivated alkene remains a challenge and is of great interest.Herein,a three-component coupling of unactivated alkene,sulfonamide,and N-halo compounds accessing vicina...Palladium-catalyzed regioselective amination of unactivated alkene remains a challenge and is of great interest.Herein,a three-component coupling of unactivated alkene,sulfonamide,and N-halo compounds accessing vicinal haloamine has been conceived.This aminohalogenation represents a modular and regioselective strategy.The electrophilic halogenating agent enables regioselective anti-Markovnikov aminopalladation and facilitates subsequent halogenation events.And this protocol is characterized by gram-scale syntheses and late-stage functionalizations.Of note,the recovered byproduct phthalimide allows for reusing by conversion to the starting material.展开更多
Catalytic four-component radical carbonylation of unactivated alkenes has recently been recognized as a robust protocol for rapid construction of various structurally diverse carbonyl compounds.Given the significance ...Catalytic four-component radical carbonylation of unactivated alkenes has recently been recognized as a robust protocol for rapid construction of various structurally diverse carbonyl compounds.Given the significance of fluorine-containing groups,this reaction class has been extensively applied to assembly of a variety of perfluoroalkyl carboxylic acid derivatives by transition metal catalysis.Herein,we report a visible-light-driven radical relay 1,2-perfluoroalkylation aminocarbonylation of unactivated alkenes using CO gas as carbonyl source and 4CzIPN as organic photocatalyst.A wide range of alkenes and amines were well tolerated,providing the valuableβ-perfluoroalkylated amides with generally good yields and high chemoselectivity.展开更多
Alkynes are versatile synthons in organic synthesis,as well as important structural moieties in bioactive molecules.Recently,transition metal-catalyzed hydroalkynylation of alkenes has been developed with reactive alk...Alkynes are versatile synthons in organic synthesis,as well as important structural moieties in bioactive molecules.Recently,transition metal-catalyzed hydroalkynylation of alkenes has been developed with reactive alkenes and alkenes bearing directing groups.However,the regioselective hydroalkynylation of simple alkenes is still challenging.Herein,we have developed a palladium-catalyzed Markovnikov hydroalkynylation of unactivated terminal alkenes,which provides an efficient approach for the synthesis of branched alkynyl compounds under mild conditions.This reaction features excellent functional group tolerance,good reaction yields and excellent regioselectivity.Moreover,the asymmetric hydroalkynylation reaction has also been achieved with moderate enantioselectivity by introducing a sterically bulky chiral Pyox ligand.展开更多
Alkyl chlorides are abundant and easily accessible starting materials.However,due to the high reduction potentials associated with unactivated alkyl chlorides,achieving their single electron reduction remains a persis...Alkyl chlorides are abundant and easily accessible starting materials.However,due to the high reduction potentials associated with unactivated alkyl chlorides,achieving their single electron reduction remains a persistent challenge.This challenge has spurred the exploration of efficient activation methods to overcome this issue.In recent years,photocatalysis has emerged as a mild and potent tool for the single electron reduction of unactivated alkyl chlorides,opening up new possibilities in this field.Considering the rapid advancements in this area,a comprehensive review that provides a conceptual understanding of this emerging field,with a specific focus on reaction design and catalytic mechanisms,would be timely and highly valuable.Hence,we present an overview of various synthetic techniques for photoinduced single electron reduction of unactivated alkyl chlorides.Furthermore,we also discuss the limitations of the present methods and future directions that lie ahead in this field.展开更多
An amide-substituted quinuclidine-borane has been identified as a more efficient hydridic hydrogen atom transfer(HAT)catalyst for the hydroalkylation of unactivated olefins under visible-light irradiation.^(1)H NMR ti...An amide-substituted quinuclidine-borane has been identified as a more efficient hydridic hydrogen atom transfer(HAT)catalyst for the hydroalkylation of unactivated olefins under visible-light irradiation.^(1)H NMR titration experiments reveal that the amide moiety of the quinuclidine-borane catalyst forms stronger hydrogen bonds with the carbonyl substrates,thereby improving the reaction yields.Furthermore,it was found that the reaction yields correlate well with the association constant between the quinuclidine-borane catalyst and the carbonyl substrate.A scale-up reaction using a continuous-flow photoreactor has also been demonstrated.展开更多
Herein,we developed the first example of copper-catalyzed silicon radical-initiated 1,4-silylcyanation of unactivated 1,3-enynes,which provided an efficient method to access CN-bearing tri-and tetrasubstituted homoall...Herein,we developed the first example of copper-catalyzed silicon radical-initiated 1,4-silylcyanation of unactivated 1,3-enynes,which provided an efficient method to access CN-bearing tri-and tetrasubstituted homoallenylsilane derivatives in high yields with excellent regioselectivities.This protocol featured good functional group compatibility and broad substrate scopes,enabling the formation of C-Si bond under cheap copper catalyst with a low loading.Furthermore,this means showed potential application value in the late-stage functionalization of natural products.展开更多
Herein,we present a copper-catalyzed carbonylative cross-coupling of unactivated alkyl bromides with aryl boronates under CO atmosphere which enabling the efficient synthesis of C(sp3)-C(sp2)ketones with extensive fun...Herein,we present a copper-catalyzed carbonylative cross-coupling of unactivated alkyl bromides with aryl boronates under CO atmosphere which enabling the efficient synthesis of C(sp3)-C(sp2)ketones with extensive functional group compatibility.This strategy represents a significant advance in copper-catalyzed carbonylation involving alkyl bromides and C(sp2)-nucleophiles.The protocol addresses key challenges commonly encountered in the coupling of C(sp3)-alkyl halides with aryl boron reagents,such as sluggish oxidative addition of alkyl halides,competing Suzuki-Miyaura cross-coupling,undesired dehalogenation and so on.Distinguished by its broad substrate scope and high functional group tolerance,this approach offers a robust and versatile platform for the streamlined synthesis of alkyl aryl ketones.展开更多
Transition metal-catalyzed carbonylation reactions represent a direct and atom-economical approach to synthesize carbonyl compounds or their derivatives by using CO as a cheap and readily available C1 feedstock.While ...Transition metal-catalyzed carbonylation reactions represent a direct and atom-economical approach to synthesize carbonyl compounds or their derivatives by using CO as a cheap and readily available C1 feedstock.While carbonylation of C(sp^(2))-hybridized electrophiles (e.g.,aryl halides) is well developed,carbonylation of less reactive unactivated alkyl electrophiles remains challenging.Recently,the use of earth-abundant base metals including Cu,Co,Mn,Fe,Ni as catalysts has enabled advances in carbonylative coupling of alkyl electrophiles for approaching diverse carbonyl compounds or their derivatives,notably,some of which are of synthetic importance but difficult to be synthesized through previous reported methods.Herein,we have summarized and discussed these recent achievements in base-metal-catalyzed carbonylative C—C,C—N,C—O,C—X coupling and other carbonylation reactions of unactivated alkyl electrophiles using CO as C1 source.展开更多
Anti-Markovnikov hydroazidation of unactivated alkenes using ABX–N3 as an initiator has been developed at room temperature,wherein hydrogen azide(HN3)acts as both hydrogen and azidating agent.Notably,the HN3 reagent ...Anti-Markovnikov hydroazidation of unactivated alkenes using ABX–N3 as an initiator has been developed at room temperature,wherein hydrogen azide(HN3)acts as both hydrogen and azidating agent.Notably,the HN3 reagent was generated from azidotrimethylsilane(TMSN3)and acetic acid in situ.The reaction itself displays broad substrate scope,good yields and excellent regioselectivities.展开更多
While drug chirality remains one of the most important themes in medicinal chemistry and fluorine-containing drugs have comprised large portion of global pharmaceutical market,the synthesis of fluorine-containing comp...While drug chirality remains one of the most important themes in medicinal chemistry and fluorine-containing drugs have comprised large portion of global pharmaceutical market,the synthesis of fluorine-containing compounds featuring a trifluoromethylated stereogenic carbon center is still underdeveloped.Recent strategy of enantioconvergent cross-coupling of trifluoromethylated alkyl halide has significantly updated previous toolbox that is dependent on additional functional group to achieve desired bond formation and highly enantioselective control.However,evident limitations were present in specific coupling candidate(sp?carbon)and/or prerequisite heteroatom in trifluoroalkyl source for inducing effective stereoconvergent differentiation.Leveraging novel design of sterically hindered bisoxazoline ligand and drastic increase of molecular complexity of in situ generated sp3 coupling partner via metal-hydride atom transfer,herein,we report a nickel-catalyzed,highly enantioselective hydrotrifluoroalkylation of unactivated alkenes for diverse synthesis of enantioenriched aliphatic alkanes featuring trifluoromehylated stereogenic carbon.Excellent stereochemical control(mostly>95:5 er),high catalytic reactivity,mild conditions,and broad substrate scope(40+examples),enable convenient late-stage asymmetric trifluoroalkylation of various biologically active complexmolecules.展开更多
The deprotonative functionalization of toluenes,for their weak acidity,generally needs strong bases,thus leading to the requirement of harsh conditions and the generation of by-products.Direct nucleophilic acyl substi...The deprotonative functionalization of toluenes,for their weak acidity,generally needs strong bases,thus leading to the requirement of harsh conditions and the generation of by-products.Direct nucleophilic acyl substitution reaction of amides with organometallic reagents could provide an ideal solution for ketone synthesis.However,the inert amides and highly reactive organometallic reagents bring great challenges for an efficient and selective synthetic approach.Herein,we reported an lithium diisopropylamide(LDA)-promoted benzylic aroylation of toluenes with unactivated tertiary benzamides,providing a direct and efficient synthesis of various aryl benzyl ketones.This process features a kinetic deprotonative functionalization of toluenes with a readily available base LDA.Mechanism studies revealed that the directed ortho-lithiation of the tertiary benzamide with LDA promoted the benzylic kinetic deprotonation of toluene and triggered the nucleophilic acyl substitution reaction with the amide.展开更多
Herein,we describe an iron-catalyzed borylation and silylation of unactivated alkyl chlorides,delivering the tertiary,secondary,and primary alkylboronic esters,and secondary,primary alkylsilanes with high efficiency.T...Herein,we describe an iron-catalyzed borylation and silylation of unactivated alkyl chlorides,delivering the tertiary,secondary,and primary alkylboronic esters,and secondary,primary alkylsilanes with high efficiency.This protocol exhibits broad substrate scope and good functional group compatibility,allowing the efficient late-stage borylation of biorelevant compounds,thus offering an excellent platform in drug discovery and development.Preliminary mechanistic studies suggest that an alkyl radical was involved in this catalytic system.展开更多
文摘The accompanied forge of C(sp^(3))–S and C(sp^(3))–C(sp^(3))bonds across alkene frameworks serves as a potent strategy to construct biologically important compounds.Here,we report a metal-free,photochemically mediated fluoroalkyl-mono/disulfuration of unactivated alkenes with high efficiency and high selectivity.A wide range of terminal and internal alkenes are good coupling partners,affording the expected products in moderate to good yields(>90 examples).The exceedingly mild reaction conditions,exceptional functional group tolerance,broad substrate scope,and the potential for late-stage modifications of pharmaceutical molecules highlight the utility of this method in the preparation of privileged motifs from readily available disulfides,tetrasulfides,and diselenides.Mechanistic studies suggest that a secondary alkyl radical intermediate undergoes efficient homolytic substitution with disulfides,facilitating the modular synthesis of a diverse array of unsymmetrical thioethers.
基金the National Key Research and Development Program of China(No.2021YFA1500100)the National Natural Science Foundation of China(Nos.92156017 and 21890722)+1 种基金“Frontiers Science Center for New Organic Matter”,Nankai University(No.63181206)Haihe Laboratory of Sustainable Chemical Transformation of Tianjin(No.24HHWCSS00019)for generous financial support。
文摘Mechanistic studies of the cleavage and transformation of unactivated C_(sp3)-H bonds are a significant field of chemistry.Overcoming the inherent low acidity of C-H bonds to activate the inert substrates is challenge under mild conditions.And their complex multi-step transformations may also hinder mechanistic understanding.Herein,we perform theoretical calculations and experimental studies to explore the C_(sp3)-H bonds activation and acylation mechanisms of toluene/thioether using the relatively weak base LDA.A synergistic"main and auxiliary"model was revealed involving dual lithium metal by LDA dimers,and the aryl dilithium species as an intermediate base can facilitate C_(sp3)-H activation.This model not only aids in understanding the acidity of unactivated C_(sp3)-H bonds and the nucleophilicity of their conjugate bases for their kinetic control through cooperative interactions,but also predicts unusual kinetic isotope effects(KIE)for newly designed 2-(methylthio)naphthalene that are experimentally validated.This research is expected to provide a crucial scenario for the cleavage and transformation of unactivated C_(sp3)-H bonds and the development of new functionalities for alkali metal reagents.
基金provided by the National Natural Science Foundation of China(Nos.22225106,22201027)Fundamental Research Funds for the Central Universities。
文摘The carboxylation of readily available organo halides with CO_(2)represents a practical strategy to afford valuable carboxylic acids.However,efficient carboxylation of inexpensive unactivated alkyl chlorides is still underdeveloped.Herein,we report the electro-reductive carboxylation of C–Cl bonds in unactivated chlorides and polyvinyl chloride with CO_(2).A variety of alkyl carboxylic acids are obtained in moderate to good yields under mild conditions with high chemoselectivity.Importantly,the utility of this electroreductive carboxylation is demonstrated with great potential in polyvinyl chloride(PVC)upgrading,which could convert discarded PVC from hydrophobic to hydrophilic functional products.Mechanistic experiments support the successive single electron reduction of unactivated chlorides to generate alkyl anion species and following nucleophilic attack on CO_(2)to give desired products.
基金National Natural Science Foundation of China(No.21971228)for financial support。
文摘A nickel-catalyzed direct hydromonofluoromethylation of unactivated olefins with industrial raw fluoroiodomethane is developed,furnishing various primary alkyl fluorides in a step-economic manner.The key factor to success is the use of pyridine-oxazoline as ligand and(MeO)_(2)MeSiH as the hydrogen source.This transformation demonstrates high efficiency,mild conditions,good functional-group compatibility and great potential in the drug discovery.
基金National Natural Science Foundation of China(No.21961015)the Natural Science Foundation of Jiangxi Province(No.20202ACBL203005)for financial supportthe Open Project Program of Polymer Engineering Research Center,Jiangxi Science&Technology Normal University(No.KFGJ18014)。
文摘We report a Pd-catalyzed halocyclization of unactivated 1,6-diynes with N-bromosuccinimide(NBS).This approach produces stereo-defined dibromo substituted dihydropyrans,tetrahydropyridines,and 3-methylene cyclohexenes with exocyclic double bond appendages in mostly good yields.Copper salt was found to be a useful Lewis acid in this reaction.Mechanistically,a formal anti-carbopalladation and a bromide radical promoted PdⅡ-PdⅢ-PdⅠ-PdⅡcatalytic cycles were proposed to be involved in the formation of the dibromo-substituted products.Further functionalization of the dihydropyran derivatives underwent B(C6F5)3-catalyzed ring opening,and reduction afforded dibrominated 1,3-dienes with excellent stereoselectivity.
基金support provided by the National Key R&D Program of China(grant no.2023YFA1507500)the National Natural Science Foundation of China(grant no.22302198)the International Partnership Program of Chinese Academy of Sciences(grant no.028GJHZ2023045FN).
文摘The catalytic production of chiral amides from readily available unactivated internal alkenes remains a significant challenge in synthetic chemistry.In this work,we developed a highly enantioselective hydroaminocarbonylation procedure for nonactivated internal alkenes and a wide range ofα-chiral amides were produced effectively with exceptional enantioselectivities using copper as the catalyst.This method is compatible with both symmetric and asymmetric internal alkenes,as well as various hydroxylamine electrophiles,demonstrating wide substrate scope and broad functional group tolerance.The established catalytic system showcases remarkable enantioselective performance in the asymmetric hydroaminocarbonylation of challenging substrates,such as the methyl-ethylα-chiral amide synthesis from trans-2-butene,despite the minimal steric difference between the methyl and ethyl group.This work represents important progress in the field of asymmetric hydroaminocarbonylation and offers a useful tool for the production of valuableα-chiral amide compounds from readily available internal alkenes.
基金supports were provided by National Key R&D Program of China (2021YFA1500200 and 2021YFF0701600)NSFC (22271249)the Fundamental Research Funds for the Central Universities (226-2022-00224 and 226-2023-00115).
文摘α-Olefins as aliphatic terminal alkenes could be obtained easily from numerous contemporary synthetic reactions as well as petro-chemical industry,and also found in natural products.Compared to the alkenes attaching the directing groups or activating group,the catalytic asymmetric reaction of unactivated terminal alkenes presents great challenges due to the weak electron effect and small steric hindrance effect.This review mainly summarizes the latest progress of the asymmetric reaction of unactivated terminal olefins since 2016.
基金the National Natural Science Foundation of China(Nos.21702103 and 21522604)the Jiangsu Synergetic Innovation Center for Advanced Bio-Manufacture(No.XTD2203)+1 种基金the Natural Science Research Projects of Jiangsu Higher Education(No.19KJB150027)Jiangsu Funding Program for Excellent Postdoctoral Talent(No.2022ZB389).
文摘Photocatalyzed alkylsulfonylation of unactivated alkenes using DABCO.(SO_(2))_(2) and thianthrenium salts via a distal heteroaryl migration process has been developed,which provides a new means of synthesizing a variety of valuable alkylsulfonyl-substituted compounds.These alkylsulfonyl radicals couple with unactivated alkenes to undergo efficient intermolecular reactions,followed by distal heteroaryl migration.This mild catalytic method is tolerant of functional groups and affords medicinally relevant alkylsulfonylated heterocycles.
基金Financial support was provided by the National Natural Science Foundation of China(22231002 and 21871095)the Key-Area Research and Development Program of Guangdong Province(2020B010188001).
文摘Palladium-catalyzed regioselective amination of unactivated alkene remains a challenge and is of great interest.Herein,a three-component coupling of unactivated alkene,sulfonamide,and N-halo compounds accessing vicinal haloamine has been conceived.This aminohalogenation represents a modular and regioselective strategy.The electrophilic halogenating agent enables regioselective anti-Markovnikov aminopalladation and facilitates subsequent halogenation events.And this protocol is characterized by gram-scale syntheses and late-stage functionalizations.Of note,the recovered byproduct phthalimide allows for reusing by conversion to the starting material.
基金the financial support from the National Natural Science Foundation of China(21971081,22171099,21820102003,91956201,22203034,and 92256301)the Double-Thousand Talents Plan of Jiangxi Province(jxsq2023102004)+1 种基金the Open Research Fund of School of Chemistry and Chemical Engineering,Henan Normal University(2021YB02)and the Program of Introducing Talents of Discipline to Universities of China(111 Program,B17019).
文摘Catalytic four-component radical carbonylation of unactivated alkenes has recently been recognized as a robust protocol for rapid construction of various structurally diverse carbonyl compounds.Given the significance of fluorine-containing groups,this reaction class has been extensively applied to assembly of a variety of perfluoroalkyl carboxylic acid derivatives by transition metal catalysis.Herein,we report a visible-light-driven radical relay 1,2-perfluoroalkylation aminocarbonylation of unactivated alkenes using CO gas as carbonyl source and 4CzIPN as organic photocatalyst.A wide range of alkenes and amines were well tolerated,providing the valuableβ-perfluoroalkylated amides with generally good yields and high chemoselectivity.
基金the National Key R&D Program of China(No.2021YFA1500100)the National Nature Science Foundation of China(Nos.22101295,21971255,91956202,92256301 and 21821002)+1 种基金the Science and Technology Commission of Shanghai Municipality(Nos.20JC1417000 and 21520780100)the Youth Innovation Promotion Association,CAS(Y2022074).
文摘Alkynes are versatile synthons in organic synthesis,as well as important structural moieties in bioactive molecules.Recently,transition metal-catalyzed hydroalkynylation of alkenes has been developed with reactive alkenes and alkenes bearing directing groups.However,the regioselective hydroalkynylation of simple alkenes is still challenging.Herein,we have developed a palladium-catalyzed Markovnikov hydroalkynylation of unactivated terminal alkenes,which provides an efficient approach for the synthesis of branched alkynyl compounds under mild conditions.This reaction features excellent functional group tolerance,good reaction yields and excellent regioselectivity.Moreover,the asymmetric hydroalkynylation reaction has also been achieved with moderate enantioselectivity by introducing a sterically bulky chiral Pyox ligand.
基金supported by the National Natural Science Foundation of China (22001248)the Fundamental Research Funds for the Central Universitiesthe University of the Chinese Academy of Sciences。
文摘Alkyl chlorides are abundant and easily accessible starting materials.However,due to the high reduction potentials associated with unactivated alkyl chlorides,achieving their single electron reduction remains a persistent challenge.This challenge has spurred the exploration of efficient activation methods to overcome this issue.In recent years,photocatalysis has emerged as a mild and potent tool for the single electron reduction of unactivated alkyl chlorides,opening up new possibilities in this field.Considering the rapid advancements in this area,a comprehensive review that provides a conceptual understanding of this emerging field,with a specific focus on reaction design and catalytic mechanisms,would be timely and highly valuable.Hence,we present an overview of various synthetic techniques for photoinduced single electron reduction of unactivated alkyl chlorides.Furthermore,we also discuss the limitations of the present methods and future directions that lie ahead in this field.
基金the National Natural Science Foundation of China(grant nos.22371180 and 22001163 to Y.J.and 22361032 to H.Z.)Shanghai Jiao Tong University(SJTU)is acknowledged.Dr.Pandaram Sakthivel(SJTU)is acknowledged for reproducing the results of compounds 6,10,and 21.
文摘An amide-substituted quinuclidine-borane has been identified as a more efficient hydridic hydrogen atom transfer(HAT)catalyst for the hydroalkylation of unactivated olefins under visible-light irradiation.^(1)H NMR titration experiments reveal that the amide moiety of the quinuclidine-borane catalyst forms stronger hydrogen bonds with the carbonyl substrates,thereby improving the reaction yields.Furthermore,it was found that the reaction yields correlate well with the association constant between the quinuclidine-borane catalyst and the carbonyl substrate.A scale-up reaction using a continuous-flow photoreactor has also been demonstrated.
基金support of this work by the funding of the National Natural Science Foundation of China(No.22371269)the State Key Laboratory of Elementoorganic Chemistry Nankai University(No.202001)+1 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB0450301)the Open Project of Key Laboratory of Organosilicon Chemistry,and Material Technology of Ministry of Education,Hangzhou Normal University(No.KFJJ2022013)。
文摘Herein,we developed the first example of copper-catalyzed silicon radical-initiated 1,4-silylcyanation of unactivated 1,3-enynes,which provided an efficient method to access CN-bearing tri-and tetrasubstituted homoallenylsilane derivatives in high yields with excellent regioselectivities.This protocol featured good functional group compatibility and broad substrate scopes,enabling the formation of C-Si bond under cheap copper catalyst with a low loading.Furthermore,this means showed potential application value in the late-stage functionalization of natural products.
文摘Herein,we present a copper-catalyzed carbonylative cross-coupling of unactivated alkyl bromides with aryl boronates under CO atmosphere which enabling the efficient synthesis of C(sp3)-C(sp2)ketones with extensive functional group compatibility.This strategy represents a significant advance in copper-catalyzed carbonylation involving alkyl bromides and C(sp2)-nucleophiles.The protocol addresses key challenges commonly encountered in the coupling of C(sp3)-alkyl halides with aryl boron reagents,such as sluggish oxidative addition of alkyl halides,competing Suzuki-Miyaura cross-coupling,undesired dehalogenation and so on.Distinguished by its broad substrate scope and high functional group tolerance,this approach offers a robust and versatile platform for the streamlined synthesis of alkyl aryl ketones.
基金Fundamental Research Funds for the Central Universities and Natural Science Foundation of Hunan Province(2022JJ30122,2023JJ10003)for financial support.
文摘Transition metal-catalyzed carbonylation reactions represent a direct and atom-economical approach to synthesize carbonyl compounds or their derivatives by using CO as a cheap and readily available C1 feedstock.While carbonylation of C(sp^(2))-hybridized electrophiles (e.g.,aryl halides) is well developed,carbonylation of less reactive unactivated alkyl electrophiles remains challenging.Recently,the use of earth-abundant base metals including Cu,Co,Mn,Fe,Ni as catalysts has enabled advances in carbonylative coupling of alkyl electrophiles for approaching diverse carbonyl compounds or their derivatives,notably,some of which are of synthetic importance but difficult to be synthesized through previous reported methods.Herein,we have summarized and discussed these recent achievements in base-metal-catalyzed carbonylative C—C,C—N,C—O,C—X coupling and other carbonylation reactions of unactivated alkyl electrophiles using CO as C1 source.
基金supported by the National Basic Research Program of China(973-2015CB856600)the National Natural Science Foundation of China(21532009,21821002,21790330,21761142010)+2 种基金the Science and Technology Commission of Shanghai Municipality(17XD1404500,17QA1405200,17JC1401200)the strategic Priority Research Program(XDB20000000)the Key Research Program of Frontier Science(QYZDJSSW-SLH055)of the Chinese Academy of Sciences
文摘Anti-Markovnikov hydroazidation of unactivated alkenes using ABX–N3 as an initiator has been developed at room temperature,wherein hydrogen azide(HN3)acts as both hydrogen and azidating agent.Notably,the HN3 reagent was generated from azidotrimethylsilane(TMSN3)and acetic acid in situ.The reaction itself displays broad substrate scope,good yields and excellent regioselectivities.
基金Financial support for this work was provided by the National Key R&D Program of China(2021YFF0701700)the National Natural Science Foundation of China(21971228).
文摘While drug chirality remains one of the most important themes in medicinal chemistry and fluorine-containing drugs have comprised large portion of global pharmaceutical market,the synthesis of fluorine-containing compounds featuring a trifluoromethylated stereogenic carbon center is still underdeveloped.Recent strategy of enantioconvergent cross-coupling of trifluoromethylated alkyl halide has significantly updated previous toolbox that is dependent on additional functional group to achieve desired bond formation and highly enantioselective control.However,evident limitations were present in specific coupling candidate(sp?carbon)and/or prerequisite heteroatom in trifluoroalkyl source for inducing effective stereoconvergent differentiation.Leveraging novel design of sterically hindered bisoxazoline ligand and drastic increase of molecular complexity of in situ generated sp3 coupling partner via metal-hydride atom transfer,herein,we report a nickel-catalyzed,highly enantioselective hydrotrifluoroalkylation of unactivated alkenes for diverse synthesis of enantioenriched aliphatic alkanes featuring trifluoromehylated stereogenic carbon.Excellent stereochemical control(mostly>95:5 er),high catalytic reactivity,mild conditions,and broad substrate scope(40+examples),enable convenient late-stage asymmetric trifluoroalkylation of various biologically active complexmolecules.
基金This work was supported by the Natural Science Foundation of Tianjin(19JCYBJC20100).
文摘The deprotonative functionalization of toluenes,for their weak acidity,generally needs strong bases,thus leading to the requirement of harsh conditions and the generation of by-products.Direct nucleophilic acyl substitution reaction of amides with organometallic reagents could provide an ideal solution for ketone synthesis.However,the inert amides and highly reactive organometallic reagents bring great challenges for an efficient and selective synthetic approach.Herein,we reported an lithium diisopropylamide(LDA)-promoted benzylic aroylation of toluenes with unactivated tertiary benzamides,providing a direct and efficient synthesis of various aryl benzyl ketones.This process features a kinetic deprotonative functionalization of toluenes with a readily available base LDA.Mechanism studies revealed that the directed ortho-lithiation of the tertiary benzamide with LDA promoted the benzylic kinetic deprotonation of toluene and triggered the nucleophilic acyl substitution reaction with the amide.
基金support from the National Natural Science Foundation of China(no.21801029)the Fundamental Research Funds for the Central Universities(no.2020CDJQY-A043)+4 种基金the Sichuan Key Laboratory of Medical Imaging(North Sichuan Medical College,no.SKLMI201901)the Strategic Cooperation of Science and Technology between Nanchong City and North Sichuan Medical College(nos.19SXHZ0441 and 19SXHZ0227)the Chongqing Postdoctoral Science Foundation(no.cstc2020jcyj-bsh0061)the China Postdoctoral Science Foundation(no.2020M673121)the Natural Science Foundation of Chongqing(no.cstc2019jcyj-msxmX0048).
文摘Herein,we describe an iron-catalyzed borylation and silylation of unactivated alkyl chlorides,delivering the tertiary,secondary,and primary alkylboronic esters,and secondary,primary alkylsilanes with high efficiency.This protocol exhibits broad substrate scope and good functional group compatibility,allowing the efficient late-stage borylation of biorelevant compounds,thus offering an excellent platform in drug discovery and development.Preliminary mechanistic studies suggest that an alkyl radical was involved in this catalytic system.
