Transition metal-catalyzed functionalization of unsymmetrical internal alkynes remains challenging because of the difficulty in controlling regioselectivity of migratory insertion of alkynes into the C–metal bonds. M...Transition metal-catalyzed functionalization of unsymmetrical internal alkynes remains challenging because of the difficulty in controlling regioselectivity of migratory insertion of alkynes into the C–metal bonds. Moreover, the synthesis of C–N atropisomers has received significantly less attention compared to that of C–C atropisomers and there have been only a few isolated examples reported for the construction of chiral diaxes through C–H functionalization. Herein, we report that cobalt can catalyze the C–H annulations of aminoquinoline amides with directing group-tethered internal alkynes or 1-indolylalkynes for the synthesis of chiral diaxes. A variety of vicinal C–N and C–C chiral diaxes and distal double C–N chiral diaxes were synthesized with excellent regio, diastereo, and enantioselectivity under mild reaction conditions. The ready availability of aminoquinoline amides, alkynes, and Salox ligands and the simplicity and good functional group tolerance of this protocol make it highly attractive.展开更多
Axially chiral binaphthol have achieved great success in asymmetric catalysis.Compared toα-binaphthol,axially chiral aryl-β-naphthol are far less reported.Here,we report a method of asymmetric catalysis to construct...Axially chiral binaphthol have achieved great success in asymmetric catalysis.Compared toα-binaphthol,axially chiral aryl-β-naphthol are far less reported.Here,we report a method of asymmetric catalysis to constructβ-naphthol with up to 99%yield,95.5:4.5 enantiomeric ratio,using alkynyl esters as precursors and chiral phosphonic acid(CPA)/Lewis acid as catalysts.Key steps involve oxygen transfer and de novo arene formation to set up the chiral axis.Moreover,this methodology provides a versatile platform for structurally divergent synthesis of atroposelectiveβ-naphthol analogs,which are widely found in bioactive molecules and asymmetric catalysts.展开更多
Planar chiral cyclophanes are a type of structurally intriguing organic molecules,which have found increasingly applications in the field of biologically active compounds,asymmetric catalysis,and optically pure materi...Planar chiral cyclophanes are a type of structurally intriguing organic molecules,which have found increasingly applications in the field of biologically active compounds,asymmetric catalysis,and optically pure materials.As such,significant efforts in the development of new methods to build up enantioenriched cyclophanes in a precise manner have attracted increased attention in recent years.Among the plethora of reported synthetic strategies,catalytic enantioselective method has emerged as one of the most straightforward and efficient ways to deliver optically pure planar chiral cyclophanes.In this review,the recent progress in catalytic enantioselective reactions for the synthesis of planar chiral cyclophanes will be discussed,which would stimulate the research interest of chemists for the discovery of novel asymmetric strategies for the preparation of valuable and previously difficult-to-access chiral molecules.展开更多
Four ＂picket fence＂ porphyrin atropisomers were respectively synthesized from the four corresponding atropisomers of meso-tetra（o-aminophenyl）porphyrin that had been chromatographed on a column eluted with petrole...Four ＂picket fence＂ porphyrin atropisomers were respectively synthesized from the four corresponding atropisomers of meso-tetra（o-aminophenyl）porphyrin that had been chromatographed on a column eluted with petroleum ether and ethyl acetate. Results show that each atropisomer could be successfully synthesized by controlling the acylation temperature at 0 ℃. They were characterized by 1H NMR, HRMS, IR, UV-Vis and Langmuir-Blodgett（LB） film analyses. Although the results of HRMS, IR, UV-Vis analyses indicate there is no remarkable difference among the atropisomers, the results of the 1H NMR and the mean molecular areas obtained by LB film technique imply that the atropisomers are significantly discrepant. The former shows that the chemical shifts of the methyl and amide protons of each atropisomer are distinct, while the later presents that the different atropisomer molecules can occupy the different surface areas at the air/water interface.展开更多
In the pharmaceutical industry, the analysis of atropisomers is of considerable interest from both scientific and regulatory perspectives. The compound of interest contains two stereogenic axes due to the hindered rot...In the pharmaceutical industry, the analysis of atropisomers is of considerable interest from both scientific and regulatory perspectives. The compound of interest contains two stereogenic axes due to the hindered rotation around the single bonds connecting the aryl groups, which results in four potential configurational isomers(atropisomers). The separation of the four atropisomers was achieved on a derivatized β-cyclodextrin bonded stationary phase. Further investigation showed that low temperature conditions, including sample preparation(-70 °C), sample storage(-70 °C), and chromatographic separation(6 °C), were critical to preventing interconversion. LC-UV-laser polarimetric analysis identified peaks 1 and 2 as a pair of enantiomers and peaks3 and 4 as another. Thermodynamic analysis of the retention data indicated that the separation of the pairs of enantiomers is primarily enthalpy controlled as indicated by the positive slope of the van't Huff plot. The difference in absolute Δ(Δ H), ranged from 2.20 k J/mol to 2.42 k J/mol.展开更多
By using a perylene diimine(PDI)syn-atropisomer as highly preorganized precursor,we successfully constructed a visible-light-active organic macrocycle PDI-M.The formation of macrocyclic structure effectively avoids se...By using a perylene diimine(PDI)syn-atropisomer as highly preorganized precursor,we successfully constructed a visible-light-active organic macrocycle PDI-M.The formation of macrocyclic structure effectively avoids self-aggregation of PDI cores and enhances the absorption in visible region.As a photocatalyst,PDI-M exhibits excellent activity on aerobic selective oxidation of sulfide into sulfoxide under visible light irradiation at room temperature.Mechanism studies show that both superoxide and singlet oxygen act as reactive oxygen species.This work provides a typical case toward the maximum utilization of photosensitive groups under mild conditions.展开更多
Many therapeutic drugs are racemates;i.e. they are chiral molecules consisting of “left”- and “right-handed” enantiomers (stereoisomers that are mirror images of each other, and are non-superimposable). In some ca...Many therapeutic drugs are racemates;i.e. they are chiral molecules consisting of “left”- and “right-handed” enantiomers (stereoisomers that are mirror images of each other, and are non-superimposable). In some cases, both enantiomers of the drug contribute to some extent (or equally) to the therapeutic effect;in other cases they contribute not at all. The same is true for the adverse effects of racemate drugs: the adverse effects of a racemate drug can be greater-than, less-than, or equal to one or the other enantiomer. An unusual situation arises when a drug consists of “atropisomers”, stereoisomers arising because of hindered rotation about a single chemical bond. We summarize the concept of atropisomerism, and give examples.展开更多
Comprehensive Summary.Planar-chiral cyclophanes with carbon-centered chirality are important targets in natural products and pharmaceuticals.However,synthesizing such planar chiral cyclophanes with two stereogenic ele...Comprehensive Summary.Planar-chiral cyclophanes with carbon-centered chirality are important targets in natural products and pharmaceuticals.However,synthesizing such planar chiral cyclophanes with two stereogenic elements via a one-step asymmetric reaction remains a formidable challenge.Herein,we present an efficient kinetic resolution method for synthesizing planar-chiral[n]cyclophanes with carbon-centered chirality.This is achieved through the enantioselective allylation of racemic aldehyde[n]cyclophanes catalyzed by Bi(OAc)3 and chiral phosphoric acid.The reaction delivers planar-chiral[n]cyclophanes and multiple chiral[n]cyclophanes with high yields and excellent enantioselectivities,showcasing remarkable kinetic resolution efficiency(s factor up to 292).The broad substrate scope,scalability,and potential for derivatization highlight the value of this methodology.DFT calculations have also been performed to provide insights into the origin of the experimentally observed diastereo-and enantioselectivity for this reaction.展开更多
Atropisomeric carbazoles are widely used in organic synthesis,medicine,and material science.Although the enantioselective coupling of two aryl units provides a straightforward means to access biaryl atropisomers,this ...Atropisomeric carbazoles are widely used in organic synthesis,medicine,and material science.Although the enantioselective coupling of two aryl units provides a straightforward means to access biaryl atropisomers,this approach has yet to be explored extensively for carbazole-based structures due to their diverse reactive sites.This report presents a chiral phosphoric acidcatalyzed approach to achieve enantioselective synthesis of carbazole-based atropisomers with exceptional chemo-,site-,and stereoselectivities.The key innovation lies in the organocatalytic activation of the heteroaromatic compound,which represents the first example of converting nucleophilic carbazoles into electrophilic species,thereby enriching the field of carbazole chemistry.Hydrazine-decorated carbazoles undergo oxidative homo-coupling to furnish atropisomeric bicarbazoles,while the inclusion of external indole nucleophiles as coupling partners leads to the formation of indole-carbazole atropisomers.A novel chiral phosphine ligand has been synthesized on the homo-coupled bicarbazole skeleton.The distinctive features of this complex reaction system were enabled by the in situ oxidation of both substrates and products,as well as the judicious choice of indoles as nucleophiles to regulate selective coupling.展开更多
Chiral BINAM-derived selenide/achiral acid co-catalyzed atroposelective electrophilic sulfenylation of pyrrole derivatives has been realized for the first time.A variety of C-N axially chiral sulfur-containing pyrrole...Chiral BINAM-derived selenide/achiral acid co-catalyzed atroposelective electrophilic sulfenylation of pyrrole derivatives has been realized for the first time.A variety of C-N axially chiral sulfur-containing pyrrole derivatives were readily obtained in moderate to good yields with moderate to excellent enantioselectivities.This catalytic system involves sequential desymmetrization and kinetic resolution.展开更多
We report herein an unprecedented N-heterocyclic carbene-catalyzed formal[3+3]annulation of ynals with N-Ts indolin-3-ones under the oxidation condition affording the functionalized pyrano[3,2-b]indol-2-ones.The alkyn...We report herein an unprecedented N-heterocyclic carbene-catalyzed formal[3+3]annulation of ynals with N-Ts indolin-3-ones under the oxidation condition affording the functionalized pyrano[3,2-b]indol-2-ones.The alkynyl acylazoliums via the combination of a carbene with ynals in the presence of oxidate proved to be the important intermediates for the success of this transformation.This method features a broad substrate scope and mild conditions,including axially chiral skeletons with suitable substitutions.展开更多
Atroposelective synthesis of N-N atropisomers is an emerging area but remains underexplored;in particular,the synthesis of N-N benzimidazole atropisomers is still unprecedented.Herein,the first enantioselective synthe...Atroposelective synthesis of N-N atropisomers is an emerging area but remains underexplored;in particular,the synthesis of N-N benzimidazole atropisomers is still unprecedented.Herein,the first enantioselective synthesis of N-N benzimidazole atropisomers via the palladium-catalyzed de novo construction of benzimidazole skeleton is presented.With readily available palladium catalyst and biphosphine ligand,a broad range of nonbiaryl benzimidazole and indole-benzimidazole atropisomers were conveniently ac-cessed in high yields and with excellent enantioselectivities.Significantly,these N-N benzimidazole atropisomers showed great anti-tumor activity and selectivity to breast cancer MCF-7 cells.The simple catalytic system,broad substrate scope,high enantioselectivi-ty,and good bioactivity make this approach highly attractive.展开更多
Herein,we report an asymmetric two-component alkenyl Catellani reaction for the construction of C—N axial chirality through a palladium/chiral norbornene cooperative catalysis and an axial-to-axial chirality transfer...Herein,we report an asymmetric two-component alkenyl Catellani reaction for the construction of C—N axial chirality through a palladium/chiral norbornene cooperative catalysis and an axial-to-axial chirality transfer process.Various partially aromatic iodinated 2-pyridones,quinolones,coumarin and uracil substrates react with 2,6-disubstituted aryl bromides with a tethered amide group,to afford a wide variety of polycyclic C—N atropisomers(38 examples,up to 97%e.e.).The obtained C—N axial chirality originates from the preformed transient C—C axial chirality with high fidelity.The synthetic utility of this chemistry is demonstrated by facile prepa-ration of complex quinoline and pyridine based C—N atropisomers through a N-deprotection and aromatization sequence.In addi-tion,a remote axial-to-central diastereoinduction process dictated by C—N axial chirality is observed with excellent diastereocontrol.展开更多
Axially chiral biaryls represent the most important class of atropisomers,and they widely exist in natural products and biologically active molecules.They also constitute a unique scaffold for chiral ligands and catal...Axially chiral biaryls represent the most important class of atropisomers,and they widely exist in natural products and biologically active molecules.They also constitute a unique scaffold for chiral ligands and catalysts in organic synthesis.The development of synthetic methods to obtain such chiral compounds has received widespread attention,among which catalytically atroposelective ring-opening of configurationally labile compounds represents one of the most attractive strategies.Various substrates with strained cyclic structures,such as the renowned Bringmann's lactones,can undergo asymmetric transformation into stable atropisomers.Known advancement primarily relies on metal catalyst combined with well-designed chiral ligands,the approaches utilizing organocatalysis as a critical resolution strategy are notably scarce.In this study,we disclosed a N-heterocyclic carbene(NHC)-catalyzed asymmetric ring-opening reaction of biaryl lactams via direct atroposelective nucleophilic activation.The optimized bulky carbene catalyst ensures that the reaction can proceed under mild conditions,affording the desired product with good to excellent yields and atroposelectivity.展开更多
Atroposelective construction of axially chiral alkene-heteroaryl scaffolds is highly desired but challenging.In this work,we established an atroposelective construction of axially chiral alkene-indole scaffolds via th...Atroposelective construction of axially chiral alkene-heteroaryl scaffolds is highly desired but challenging.In this work,we established an atroposelective construction of axially chiral alkene-indole scaffolds via the strategy of catalytic enantioselective addition reaction of 3-alkynyl-2-indolylmethanols with bulky nucleophiles.展开更多
A highly efficient kinetic resolution of racemic thioanilide atropisomers via C(sp^(3))-H arylation has been achieved by a hybrid palladium catalyst bearing an anionic chiral Co^(Ⅲ)-complex and a phosphoramidite liga...A highly efficient kinetic resolution of racemic thioanilide atropisomers via C(sp^(3))-H arylation has been achieved by a hybrid palladium catalyst bearing an anionic chiral Co^(Ⅲ)-complex and a phosphoramidite ligand,leading to both enantioenriched atropisomeric arylation thioanilides(up to 99%ee)and N-Me atropisomeric thioanilides(up to 99%ee),simultaneously.The remained enantioenriched substrates can be arylated again by using an achiral anionic ligand to give the enantiomer with the opposite configuration.展开更多
Atropisomeric anilides are one of important C-N axially chiral compounds.Compared with the A/-terminal functionalization to prepare such compounds,C-terminal functionalization strategies have been rarely reported.We d...Atropisomeric anilides are one of important C-N axially chiral compounds.Compared with the A/-terminal functionalization to prepare such compounds,C-terminal functionalization strategies have been rarely reported.We describe herein an efficient synthesis of axially chiral anilides enabled by Pd-catalyzed desymmetric Sonogashira cross-coupling reactions with the use of a newly identified Ming-Phos.Moderate to high yields with high enantioselectivities(up to 98%ee)were obtained.展开更多
The widespread applications of atropisomeric compounds have led to an increasing demand for their synthesis.Rather than synthesizing different functionalized atropisomers individually,an attractive alternative is to i...The widespread applications of atropisomeric compounds have led to an increasing demand for their synthesis.Rather than synthesizing different functionalized atropisomers individually,an attractive alternative is to identify a key intermediate or precursor that can be readily elaborated and functionalized to realize divergent synthesis of this class of compounds.Building on our previous research on asymmetric ring-opening of cyclic diaryliodoniums,in this work we developed a copper-catalyzed enantioselective ring-opening reaction of ortho,ortho’-dibromo substituted cyclic diaryliodonium with lithium iodide.The resulting optically active product 2,2'-dibromo-6,6'-diiodo-1,1'-biphenyl,possessing two C—Br bonds and two C—I bonds,can be selectively advanced to form different functionalities.Remarkably,the utilities of the product were highlighted by successively demonstrating C—I and C—Br metalation,followed by carboxylation,boroylation,oxygenation,allylation,phosphinylation,etc.,all of which provide a new and convenient approach to synthesizing a range of functionalized axially chiral biphenyls.展开更多
A visible light accelerated C-H functionalization reaction in palladium-catalyzed arylation of vinyl arenes with diaryliodonium salts is reported in the absence of additional photosensitizer. The kinetic isotope effe...A visible light accelerated C-H functionalization reaction in palladium-catalyzed arylation of vinyl arenes with diaryliodonium salts is reported in the absence of additional photosensitizer. The kinetic isotope effect （kH/kD） was changed from 3.6 （under darkness） to 1.1 when irradiated by visible light, which indicated that the C-H functionalization step was the rate determining step under darkness and significantly accelerated by the irradia- tion of visible light. Finally the synthesis of ortho tetra-substituted vinylarene atropisomers with high enantiospecificity was realized via this protocol.展开更多
Construction of axially chiral 1-azafluorenes via nickel-catalyzed[2+2+2]cycloaddition of alkynes and(o-alkynyl)benzyl nitriles is described.This strategy enables enantioselective discrimination of two sterically simi...Construction of axially chiral 1-azafluorenes via nickel-catalyzed[2+2+2]cycloaddition of alkynes and(o-alkynyl)benzyl nitriles is described.This strategy enables enantioselective discrimination of two sterically similar ortho substituents,such as H and F,during the construction of tri-ortho-substituted biaryl atropisomers.Mechanistic studies including the stereochemistry model and the stability of the atropenantiomers toward racemization are provided.The unique steric hindrance provided by 1-azafluorene skeleton and the fine chiral cavity of the nickel catalyst are key to achieving high enantioselectivity.展开更多
基金supported by the NSF of China(22071068)the Instrumental Analysis Center of Huaqiao University.
文摘Transition metal-catalyzed functionalization of unsymmetrical internal alkynes remains challenging because of the difficulty in controlling regioselectivity of migratory insertion of alkynes into the C–metal bonds. Moreover, the synthesis of C–N atropisomers has received significantly less attention compared to that of C–C atropisomers and there have been only a few isolated examples reported for the construction of chiral diaxes through C–H functionalization. Herein, we report that cobalt can catalyze the C–H annulations of aminoquinoline amides with directing group-tethered internal alkynes or 1-indolylalkynes for the synthesis of chiral diaxes. A variety of vicinal C–N and C–C chiral diaxes and distal double C–N chiral diaxes were synthesized with excellent regio, diastereo, and enantioselectivity under mild reaction conditions. The ready availability of aminoquinoline amides, alkynes, and Salox ligands and the simplicity and good functional group tolerance of this protocol make it highly attractive.
基金financial support from the National Natural Science Foundation of China(Nos.22071062,22001077 and 22271096)Guangdong Science and Technology Department(Nos.2021A1515012331,2023A1515011001)+1 种基金the Fundamental Research Funds for the Central Universities(No.2022ZYGXZR016)South China University of Technology for start-up funds。
文摘Axially chiral binaphthol have achieved great success in asymmetric catalysis.Compared toα-binaphthol,axially chiral aryl-β-naphthol are far less reported.Here,we report a method of asymmetric catalysis to constructβ-naphthol with up to 99%yield,95.5:4.5 enantiomeric ratio,using alkynyl esters as precursors and chiral phosphonic acid(CPA)/Lewis acid as catalysts.Key steps involve oxygen transfer and de novo arene formation to set up the chiral axis.Moreover,this methodology provides a versatile platform for structurally divergent synthesis of atroposelectiveβ-naphthol analogs,which are widely found in bioactive molecules and asymmetric catalysts.
基金financial support provided by Huanghuai University and Hangzhou Medical College.
文摘Planar chiral cyclophanes are a type of structurally intriguing organic molecules,which have found increasingly applications in the field of biologically active compounds,asymmetric catalysis,and optically pure materials.As such,significant efforts in the development of new methods to build up enantioenriched cyclophanes in a precise manner have attracted increased attention in recent years.Among the plethora of reported synthetic strategies,catalytic enantioselective method has emerged as one of the most straightforward and efficient ways to deliver optically pure planar chiral cyclophanes.In this review,the recent progress in catalytic enantioselective reactions for the synthesis of planar chiral cyclophanes will be discussed,which would stimulate the research interest of chemists for the discovery of novel asymmetric strategies for the preparation of valuable and previously difficult-to-access chiral molecules.
基金Supported by the National Natural Science Foundation of China(No.20806025)
文摘Four ＂picket fence＂ porphyrin atropisomers were respectively synthesized from the four corresponding atropisomers of meso-tetra（o-aminophenyl）porphyrin that had been chromatographed on a column eluted with petroleum ether and ethyl acetate. Results show that each atropisomer could be successfully synthesized by controlling the acylation temperature at 0 ℃. They were characterized by 1H NMR, HRMS, IR, UV-Vis and Langmuir-Blodgett（LB） film analyses. Although the results of HRMS, IR, UV-Vis analyses indicate there is no remarkable difference among the atropisomers, the results of the 1H NMR and the mean molecular areas obtained by LB film technique imply that the atropisomers are significantly discrepant. The former shows that the chemical shifts of the methyl and amide protons of each atropisomer are distinct, while the later presents that the different atropisomer molecules can occupy the different surface areas at the air/water interface.
文摘In the pharmaceutical industry, the analysis of atropisomers is of considerable interest from both scientific and regulatory perspectives. The compound of interest contains two stereogenic axes due to the hindered rotation around the single bonds connecting the aryl groups, which results in four potential configurational isomers(atropisomers). The separation of the four atropisomers was achieved on a derivatized β-cyclodextrin bonded stationary phase. Further investigation showed that low temperature conditions, including sample preparation(-70 °C), sample storage(-70 °C), and chromatographic separation(6 °C), were critical to preventing interconversion. LC-UV-laser polarimetric analysis identified peaks 1 and 2 as a pair of enantiomers and peaks3 and 4 as another. Thermodynamic analysis of the retention data indicated that the separation of the pairs of enantiomers is primarily enthalpy controlled as indicated by the positive slope of the van't Huff plot. The difference in absolute Δ(Δ H), ranged from 2.20 k J/mol to 2.42 k J/mol.
基金supported by the National Natural Science Foundation of China(No.22171021)Yanjing Young Scholar Candidate Program of Capital Normal University,Capacity Building for SciTech Innovation-Fundamental Scientific Research Funds.
文摘By using a perylene diimine(PDI)syn-atropisomer as highly preorganized precursor,we successfully constructed a visible-light-active organic macrocycle PDI-M.The formation of macrocyclic structure effectively avoids self-aggregation of PDI cores and enhances the absorption in visible region.As a photocatalyst,PDI-M exhibits excellent activity on aerobic selective oxidation of sulfide into sulfoxide under visible light irradiation at room temperature.Mechanism studies show that both superoxide and singlet oxygen act as reactive oxygen species.This work provides a typical case toward the maximum utilization of photosensitive groups under mild conditions.
文摘Many therapeutic drugs are racemates;i.e. they are chiral molecules consisting of “left”- and “right-handed” enantiomers (stereoisomers that are mirror images of each other, and are non-superimposable). In some cases, both enantiomers of the drug contribute to some extent (or equally) to the therapeutic effect;in other cases they contribute not at all. The same is true for the adverse effects of racemate drugs: the adverse effects of a racemate drug can be greater-than, less-than, or equal to one or the other enantiomer. An unusual situation arises when a drug consists of “atropisomers”, stereoisomers arising because of hindered rotation about a single chemical bond. We summarize the concept of atropisomerism, and give examples.
基金financial support from the National Natural Science Foundation of China(Grant Nos.22371219,22193011 and 21933008).
文摘Comprehensive Summary.Planar-chiral cyclophanes with carbon-centered chirality are important targets in natural products and pharmaceuticals.However,synthesizing such planar chiral cyclophanes with two stereogenic elements via a one-step asymmetric reaction remains a formidable challenge.Herein,we present an efficient kinetic resolution method for synthesizing planar-chiral[n]cyclophanes with carbon-centered chirality.This is achieved through the enantioselective allylation of racemic aldehyde[n]cyclophanes catalyzed by Bi(OAc)3 and chiral phosphoric acid.The reaction delivers planar-chiral[n]cyclophanes and multiple chiral[n]cyclophanes with high yields and excellent enantioselectivities,showcasing remarkable kinetic resolution efficiency(s factor up to 292).The broad substrate scope,scalability,and potential for derivatization highlight the value of this methodology.DFT calculations have also been performed to provide insights into the origin of the experimentally observed diastereo-and enantioselectivity for this reaction.
基金supported by the National Key R&D Program of China(2022YFA1503703,2021YFF0701604)the National Natural Science Foundation of China(22425011,22231004,22271071)+6 种基金the Guangdong Innovative Program(2019BT02Y335)the Guangdong Basic and Applied Basic Research Foundation(2024B1515020055)the New Cornerstone Science Foundation through the Xplorer PrizeShenzhen Science and Technology Program(KQTD20210811090112004)the High Level of Special Funds(G03050K003)the Natural Science Foundation of Zhejiang Province(LY20B020010)Laboratory of Precise Synthesis of Functional Molecules of Zhejiang Province,Department of Chemistry,School of Science,Westlake University。
文摘Atropisomeric carbazoles are widely used in organic synthesis,medicine,and material science.Although the enantioselective coupling of two aryl units provides a straightforward means to access biaryl atropisomers,this approach has yet to be explored extensively for carbazole-based structures due to their diverse reactive sites.This report presents a chiral phosphoric acidcatalyzed approach to achieve enantioselective synthesis of carbazole-based atropisomers with exceptional chemo-,site-,and stereoselectivities.The key innovation lies in the organocatalytic activation of the heteroaromatic compound,which represents the first example of converting nucleophilic carbazoles into electrophilic species,thereby enriching the field of carbazole chemistry.Hydrazine-decorated carbazoles undergo oxidative homo-coupling to furnish atropisomeric bicarbazoles,while the inclusion of external indole nucleophiles as coupling partners leads to the formation of indole-carbazole atropisomers.A novel chiral phosphine ligand has been synthesized on the homo-coupled bicarbazole skeleton.The distinctive features of this complex reaction system were enabled by the in situ oxidation of both substrates and products,as well as the judicious choice of indoles as nucleophiles to regulate selective coupling.
基金Z.-M.Chen thanks National Natural Science Foundation of China(22071149,21871178)Natural Science Foundation of Shanghai(23ZR1428200)financial support.H.Ke thanks Natural Science Foundation of Jiangxi Province(20202ACBL213005)for financial support.
文摘Chiral BINAM-derived selenide/achiral acid co-catalyzed atroposelective electrophilic sulfenylation of pyrrole derivatives has been realized for the first time.A variety of C-N axially chiral sulfur-containing pyrrole derivatives were readily obtained in moderate to good yields with moderate to excellent enantioselectivities.This catalytic system involves sequential desymmetrization and kinetic resolution.
基金We thank the financial support from the Program for Young Talents of Shaanxi Province(5113200043)the Fundamental Research Funds for the Central Universities.
文摘We report herein an unprecedented N-heterocyclic carbene-catalyzed formal[3+3]annulation of ynals with N-Ts indolin-3-ones under the oxidation condition affording the functionalized pyrano[3,2-b]indol-2-ones.The alkynyl acylazoliums via the combination of a carbene with ynals in the presence of oxidate proved to be the important intermediates for the success of this transformation.This method features a broad substrate scope and mild conditions,including axially chiral skeletons with suitable substitutions.
基金supported by Taishan Scholar Youth Expert Program in Shandong Province (tsqn201909096)National Natural Science Foundation of China (22371152)+1 种基金Shandong Provincial Natural Science Foundation Project (ZR2023JQ006,ZR2022MB021)the startup fund from Qingdao University.
文摘Atroposelective synthesis of N-N atropisomers is an emerging area but remains underexplored;in particular,the synthesis of N-N benzimidazole atropisomers is still unprecedented.Herein,the first enantioselective synthesis of N-N benzimidazole atropisomers via the palladium-catalyzed de novo construction of benzimidazole skeleton is presented.With readily available palladium catalyst and biphosphine ligand,a broad range of nonbiaryl benzimidazole and indole-benzimidazole atropisomers were conveniently ac-cessed in high yields and with excellent enantioselectivities.Significantly,these N-N benzimidazole atropisomers showed great anti-tumor activity and selectivity to breast cancer MCF-7 cells.The simple catalytic system,broad substrate scope,high enantioselectivi-ty,and good bioactivity make this approach highly attractive.
文摘Herein,we report an asymmetric two-component alkenyl Catellani reaction for the construction of C—N axial chirality through a palladium/chiral norbornene cooperative catalysis and an axial-to-axial chirality transfer process.Various partially aromatic iodinated 2-pyridones,quinolones,coumarin and uracil substrates react with 2,6-disubstituted aryl bromides with a tethered amide group,to afford a wide variety of polycyclic C—N atropisomers(38 examples,up to 97%e.e.).The obtained C—N axial chirality originates from the preformed transient C—C axial chirality with high fidelity.The synthetic utility of this chemistry is demonstrated by facile prepa-ration of complex quinoline and pyridine based C—N atropisomers through a N-deprotection and aromatization sequence.In addi-tion,a remote axial-to-central diastereoinduction process dictated by C—N axial chirality is observed with excellent diastereocontrol.
基金the Natural Science Foundation of Jiangsu Province(BK20221309)the National Natural Science Foundation of China(21602105).
文摘Axially chiral biaryls represent the most important class of atropisomers,and they widely exist in natural products and biologically active molecules.They also constitute a unique scaffold for chiral ligands and catalysts in organic synthesis.The development of synthetic methods to obtain such chiral compounds has received widespread attention,among which catalytically atroposelective ring-opening of configurationally labile compounds represents one of the most attractive strategies.Various substrates with strained cyclic structures,such as the renowned Bringmann's lactones,can undergo asymmetric transformation into stable atropisomers.Known advancement primarily relies on metal catalyst combined with well-designed chiral ligands,the approaches utilizing organocatalysis as a critical resolution strategy are notably scarce.In this study,we disclosed a N-heterocyclic carbene(NHC)-catalyzed asymmetric ring-opening reaction of biaryl lactams via direct atroposelective nucleophilic activation.The optimized bulky carbene catalyst ensures that the reaction can proceed under mild conditions,affording the desired product with good to excellent yields and atroposelectivity.
基金We are grateful for financial support from the National Natural Science Foundation of China(Nos.21772069 and 21831007)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.KYCX20_2235)the Natural Science Foundation of JSNU(No.19XSRX013)。
文摘Atroposelective construction of axially chiral alkene-heteroaryl scaffolds is highly desired but challenging.In this work,we established an atroposelective construction of axially chiral alkene-indole scaffolds via the strategy of catalytic enantioselective addition reaction of 3-alkynyl-2-indolylmethanols with bulky nucleophiles.
基金We are grateful for the financial support from NSFC(Grant No.21831007).
文摘A highly efficient kinetic resolution of racemic thioanilide atropisomers via C(sp^(3))-H arylation has been achieved by a hybrid palladium catalyst bearing an anionic chiral Co^(Ⅲ)-complex and a phosphoramidite ligand,leading to both enantioenriched atropisomeric arylation thioanilides(up to 99%ee)and N-Me atropisomeric thioanilides(up to 99%ee),simultaneously.The remained enantioenriched substrates can be arylated again by using an achiral anionic ligand to give the enantiomer with the opposite configuration.
基金the funding support of NSFC(Nos.22031004,21921003,21901043)Shanghai Municipal Education Commission(No.20212308).
文摘Atropisomeric anilides are one of important C-N axially chiral compounds.Compared with the A/-terminal functionalization to prepare such compounds,C-terminal functionalization strategies have been rarely reported.We describe herein an efficient synthesis of axially chiral anilides enabled by Pd-catalyzed desymmetric Sonogashira cross-coupling reactions with the use of a newly identified Ming-Phos.Moderate to high yields with high enantioselectivities(up to 98%ee)were obtained.
基金financial supports from National Natural Science Foundation of China(92056102)the Natural Science Foundation of Fujian Province(2023J011395).
文摘The widespread applications of atropisomeric compounds have led to an increasing demand for their synthesis.Rather than synthesizing different functionalized atropisomers individually,an attractive alternative is to identify a key intermediate or precursor that can be readily elaborated and functionalized to realize divergent synthesis of this class of compounds.Building on our previous research on asymmetric ring-opening of cyclic diaryliodoniums,in this work we developed a copper-catalyzed enantioselective ring-opening reaction of ortho,ortho’-dibromo substituted cyclic diaryliodonium with lithium iodide.The resulting optically active product 2,2'-dibromo-6,6'-diiodo-1,1'-biphenyl,possessing two C—Br bonds and two C—I bonds,can be selectively advanced to form different functionalities.Remarkably,the utilities of the product were highlighted by successively demonstrating C—I and C—Br metalation,followed by carboxylation,boroylation,oxygenation,allylation,phosphinylation,etc.,all of which provide a new and convenient approach to synthesizing a range of functionalized axially chiral biphenyls.
文摘A visible light accelerated C-H functionalization reaction in palladium-catalyzed arylation of vinyl arenes with diaryliodonium salts is reported in the absence of additional photosensitizer. The kinetic isotope effect （kH/kD） was changed from 3.6 （under darkness） to 1.1 when irradiated by visible light, which indicated that the C-H functionalization step was the rate determining step under darkness and significantly accelerated by the irradia- tion of visible light. Finally the synthesis of ortho tetra-substituted vinylarene atropisomers with high enantiospecificity was realized via this protocol.
基金supported by the National Key Research and Development Program of China(2022YFA1502902)the National Natural Science Foundation of China(22371215,22222111,21971198)+2 种基金the Guangdong Basic and Applied Basic Research Foundation(2022A1515012614)the Large-scale Instrument and Equipment Sharing Foundation of Wuhan UniversityChina Postdoctoral Science Foundation(2022M722451)for the financial support。
文摘Construction of axially chiral 1-azafluorenes via nickel-catalyzed[2+2+2]cycloaddition of alkynes and(o-alkynyl)benzyl nitriles is described.This strategy enables enantioselective discrimination of two sterically similar ortho substituents,such as H and F,during the construction of tri-ortho-substituted biaryl atropisomers.Mechanistic studies including the stereochemistry model and the stability of the atropenantiomers toward racemization are provided.The unique steric hindrance provided by 1-azafluorene skeleton and the fine chiral cavity of the nickel catalyst are key to achieving high enantioselectivity.
