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
Chiral organosulfur compounds are not only widely distributed in bioactive natural products and pharmaceuticals,but also play a significant role in chiral ligands/catalysts.Throughout the history of synthetic organic ...Chiral organosulfur compounds are not only widely distributed in bioactive natural products and pharmaceuticals,but also play a significant role in chiral ligands/catalysts.Throughout the history of synthetic organic chemistry,chemists have been absorbed in the construction of centrally chiral organosulfur compounds.Nevertheless,there are relatively few reports on installing sulfur functional groups into axially chiral compounds.Atropisomerism is one of the fundamental phenomena in nature,which ubiquitously exists in natural products.After more than a century of development,atropisomers have been designed and extensively applied to pharmaceuticals,functional materials and chiral ligands/catalysts.Due to the importance of chiral sulfurcontaining atropisomers,there is an increasing demand for enantioselective synthesis of them.Recently,a diversity of approaches by C-S bond formations have been established for the construction of enantioenriched sulfur-containing atropisomers,however,there is no comprehensive review to summarize this great progress.In this mini-review,we summarize recent progress in catalytic asymmetric synthesis of sulfur-containing atropisomers by C-S bond formations,which includes sulfur nucleophilic reactions,sulfur electrophilic reactions and sulfur radical reactions.Furthermore,the reaction mechanisms are also discussed.We hope that this mini-review will enable more researchers to further explore this field.展开更多
Atropisomeric C-N compounds belong to an important class of axially chiral compounds.However,whereas the asymmetric synthesis of biaryl atropisomers have been well established,general and efficient strategies to acces...Atropisomeric C-N compounds belong to an important class of axially chiral compounds.However,whereas the asymmetric synthesis of biaryl atropisomers have been well established,general and efficient strategies to access single enantiomers of C-N atropisomers are still rare.Until recently,innovative methods have been developed,providing new opportunities for the highly stereoselective synthesis of this vital class of atropisomers.Herein,we comprehensively summarize the development in this emerging field and give some insights into future advance.Emphasis is placed on the synthetic strategies.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
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
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
Recent developments in chirality chemistry have revealed remarkable instances of atropisomers featuring multiple chiral elements.Despite significant progress in the synthesis and application of atropisomers,developing...Recent developments in chirality chemistry have revealed remarkable instances of atropisomers featuring multiple chiral elements.Despite significant progress in the synthesis and application of atropisomers,developing a synthetic protocol for the simultaneous introduction of axial and point chirality is still a fascinating challenge.In this context,we present a convenient and versatile method for synthesizing novel atropisomers with axial and point chirality.This approach,based on a new reaction mechanism with nickel-controlled Si–C bond activation,facilitates the controllable migratory insertion of aldehydes into the Ni–C bond.We utilize multidimensional strategies of desymmetrization,kinetic resolution and dynamic kinetic resolution to complete enantioselective nickel-catalyzed ring expansion of benzosilacyclobutenes with aldehydes.The design of multidimensional kinetic resolution,desymmetrization,and dynamic resolution,features a straightforward catalytic system,mild reaction conditions,and broad functional group tolerances.Various axially chiral biaryl oxasilacycles bearing carbon-or siliconstereogenic centers are obtained with excellent diastereo-and enantio-selectivities(up to>20:1 dr and>99.9%ee)through the use of a chiral Ni complex with a large cavity-type 1,1,4,4-tetra-aryl-2,3-O-isopropylidene-L-threitol(TADDOL)-derived phosphoramidite ligand.展开更多
Transition metal-catalyzed asymmetric reductive coupling of two electrophiles has emerged as a powerful tool for carbon–carbon bond formation;however,the enantioselective reductive cross-coupling of two aryl halides ...Transition metal-catalyzed asymmetric reductive coupling of two electrophiles has emerged as a powerful tool for carbon–carbon bond formation;however,the enantioselective reductive cross-coupling of two aryl halides has not been developed and remains a challenge.Herein,we demonstrated the enantioselective reductive cross-coupling of two aryl halides by combining cobalt catalysis with electrochemistry to afford axially chiral biaryls with good chemoselectivities(cross-coupling:homo-coupling>20:1)and enantioselectivities(up to 94%ee).This strategy could be extended to the asymmetric crosscouplings of aryl and vinyl halides to provide axially chiral non-C2-symmetric compounds with excellent chemoselectivities(cross-coupling:homo-coupling>20:1)and enantioselectivities(up to 99%ee).Density functional theory calculations and control experiments suggested that high chemo-and enantioselectivities could be realized by selective cathodic reduction of an aryl cobalt(III)species from the first oxidative addition owing to the different redox potentials.展开更多
Asymmetric direct hydrogenation(ADH)is a straightforward and atom-economic methodology to achieve optically active compounds.The synthesis of chiral compounds bearing stereogenic centers has been well established.In c...Asymmetric direct hydrogenation(ADH)is a straightforward and atom-economic methodology to achieve optically active compounds.The synthesis of chiral compounds bearing stereogenic centers has been well established.In contrast,the construction of atropisomers,especially atropisomers bearing multiple chiral elements,has sporadically been explored.Herein,we report an innovative atroposelective iridium-catalyzed hydrogenation of N-arylindole ketones and heterobiaryl ketones via dynamic kinetic resolution(DKR)based on a Lewis acid-base interaction between the nitrogen atom and the carbonyl group of ketones,providing C-N and C-C atropisomers bearing multiple chiral elements with excellent enantioselectivities,diastereoselectivities and yields.The lynchpin of the DKR-ADH process stands in the newly developed planar-chiral tridentate PNO ligand,which ensures the excellent control of enantioselectivity and diastereoselectivity simultaneously.The synthetic utilization of this protocol is proved through stereospecific transformation to a tridentate PNN ligand bearing axial and central chirality,which shows promising potential in iridium-catalyzed asymmetric hydrogenation of simple ketones.展开更多
Herein,the de novo synthesis of atropisomeric benzofurans through the Cu/spirocyclic-pyrrolidine-oxazoline(SPDO)complex catalyze asymmetric formal[3+2]cycloaddition between quinones and ynamides is explored,producing ...Herein,the de novo synthesis of atropisomeric benzofurans through the Cu/spirocyclic-pyrrolidine-oxazoline(SPDO)complex catalyze asymmetric formal[3+2]cycloaddition between quinones and ynamides is explored,producing a range of structurally diverse axially chiral benzofurans in satisfactory yields with good to excellent enantioselectivities.Furthermore,density functional theory calculations were applied to explain the possible reaction mechanism.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
Catalytic enantioselective preparation of axially chiral molecules has gained considerable interest over the past decades, due to their numerous applications in bioactive molecules, natural products, pharmaceuticals, ...Catalytic enantioselective preparation of axially chiral molecules has gained considerable interest over the past decades, due to their numerous applications in bioactive molecules, natural products, pharmaceuticals, materials, ligands, and catalysts. Compared with the well-established synthetic approaches for six-membered axially chiral skeletons, methodologies directed towards five-membered axially chiral compounds are relatively rare. Among these, axially chiral arylpyrroles are especially important structural motifs with wide utility, and the atroposelective synthesis of them is highly desirable. In recent years, novel strategies have been developed based on transition-metal catalysis and organocatalysis. This review summarizes the recent achievements in atroposelective preparation of arylpyrroles, by emphasizing the synthetic methods for each axially chiral framework, reaction mechanisms, and applications.展开更多
The chemistry of axially chiral compounds has emerged as a subject of increasing interest due to their widespread presence in natural products,bioactive molecules,advanced materials,and chiral ligands/catalysts.On the...The chemistry of axially chiral compounds has emerged as a subject of increasing interest due to their widespread presence in natural products,bioactive molecules,advanced materials,and chiral ligands/catalysts.On the other hand,catalytic asymmetric radical-based transformations provide a complementary platform for the construction of enantiomerically enriched molecules that are in growing demand in the chemical and pharmaceutical in-dustries.In recent years,considerable research efforts have been devoted to the development of catalytic asymmetric radical reactions for the construction of axially chiral compounds based on the unique reactivity modes of diverse radicals.In this review,we critically illustrate these recent achievements according to different radical precursors and catalytic activation modes.Wherever possible,special emphasis is also placed on the discussion of mechanistic features underlying these works and substrate scopes.This review should be of great interest to the experts in this area,but also serve as a helpful starting point for new researchers in this field.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 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 (22071149,21871178)the Natural Science Foundation of Shanghai (23ZR1428200)the Program for Professor of Special Appointment (Eastern Scholar)at Shanghai Institutions of Higher Learning。
文摘Chiral organosulfur compounds are not only widely distributed in bioactive natural products and pharmaceuticals,but also play a significant role in chiral ligands/catalysts.Throughout the history of synthetic organic chemistry,chemists have been absorbed in the construction of centrally chiral organosulfur compounds.Nevertheless,there are relatively few reports on installing sulfur functional groups into axially chiral compounds.Atropisomerism is one of the fundamental phenomena in nature,which ubiquitously exists in natural products.After more than a century of development,atropisomers have been designed and extensively applied to pharmaceuticals,functional materials and chiral ligands/catalysts.Due to the importance of chiral sulfurcontaining atropisomers,there is an increasing demand for enantioselective synthesis of them.Recently,a diversity of approaches by C-S bond formations have been established for the construction of enantioenriched sulfur-containing atropisomers,however,there is no comprehensive review to summarize this great progress.In this mini-review,we summarize recent progress in catalytic asymmetric synthesis of sulfur-containing atropisomers by C-S bond formations,which includes sulfur nucleophilic reactions,sulfur electrophilic reactions and sulfur radical reactions.Furthermore,the reaction mechanisms are also discussed.We hope that this mini-review will enable more researchers to further explore this field.
基金Financial support from the National Natural Science Foundation of China(Nos.21925109 and 21772170)the Open Research Fund of School Chemistry and Chemical Engineering,Henan Normal University and the Center of Chemistry for Frontier Technologies of Zhejiang University is gratefully acknowledged.
文摘Atropisomeric C-N compounds belong to an important class of axially chiral compounds.However,whereas the asymmetric synthesis of biaryl atropisomers have been well established,general and efficient strategies to access single enantiomers of C-N atropisomers are still rare.Until recently,innovative methods have been developed,providing new opportunities for the highly stereoselective synthesis of this vital class of atropisomers.Herein,we comprehensively summarize the development in this emerging field and give some insights into future advance.Emphasis is placed on the synthetic strategies.
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.
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 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supported by the National Natural Science Foundation of China(22072035,22361162606,22371060)the Zhejiang Provincial Natural Science Foundation of China(LZ23B020002,LY22B020006,LR22B020002)+1 种基金the Special Support Program for High-level Talents of Zhejiang Province(2021R51005)the Hangzhou Science and Technology Bureau(TD2020015)。
文摘Recent developments in chirality chemistry have revealed remarkable instances of atropisomers featuring multiple chiral elements.Despite significant progress in the synthesis and application of atropisomers,developing a synthetic protocol for the simultaneous introduction of axial and point chirality is still a fascinating challenge.In this context,we present a convenient and versatile method for synthesizing novel atropisomers with axial and point chirality.This approach,based on a new reaction mechanism with nickel-controlled Si–C bond activation,facilitates the controllable migratory insertion of aldehydes into the Ni–C bond.We utilize multidimensional strategies of desymmetrization,kinetic resolution and dynamic kinetic resolution to complete enantioselective nickel-catalyzed ring expansion of benzosilacyclobutenes with aldehydes.The design of multidimensional kinetic resolution,desymmetrization,and dynamic resolution,features a straightforward catalytic system,mild reaction conditions,and broad functional group tolerances.Various axially chiral biaryl oxasilacycles bearing carbon-or siliconstereogenic centers are obtained with excellent diastereo-and enantio-selectivities(up to>20:1 dr and>99.9%ee)through the use of a chiral Ni complex with a large cavity-type 1,1,4,4-tetra-aryl-2,3-O-isopropylidene-L-threitol(TADDOL)-derived phosphoramidite ligand.
基金supported by the National Key R&D Program of China(grant no.2021YFA1500100)the Strategic Priority Research Program of the Chinese Academy of Sciences(grant no.XDB0610000)+1 种基金the NSF of China(grant nos.21821002 and 22361142834)Natural Science Foundation of Ningbo(grant no.2023J035).
文摘Transition metal-catalyzed asymmetric reductive coupling of two electrophiles has emerged as a powerful tool for carbon–carbon bond formation;however,the enantioselective reductive cross-coupling of two aryl halides has not been developed and remains a challenge.Herein,we demonstrated the enantioselective reductive cross-coupling of two aryl halides by combining cobalt catalysis with electrochemistry to afford axially chiral biaryls with good chemoselectivities(cross-coupling:homo-coupling>20:1)and enantioselectivities(up to 94%ee).This strategy could be extended to the asymmetric crosscouplings of aryl and vinyl halides to provide axially chiral non-C2-symmetric compounds with excellent chemoselectivities(cross-coupling:homo-coupling>20:1)and enantioselectivities(up to 99%ee).Density functional theory calculations and control experiments suggested that high chemo-and enantioselectivities could be realized by selective cathodic reduction of an aryl cobalt(III)species from the first oxidative addition owing to the different redox potentials.
基金supported by the National Key Research and Development Program of China(2023YFA1507500)the National Natural Science Foundation of China(22171260,92356302)+1 种基金the Natural Science Foundation of Liaoning Province(2023-MS-009)the Dalian Institute of Chemical Physics(DICP I202442)。
文摘Asymmetric direct hydrogenation(ADH)is a straightforward and atom-economic methodology to achieve optically active compounds.The synthesis of chiral compounds bearing stereogenic centers has been well established.In contrast,the construction of atropisomers,especially atropisomers bearing multiple chiral elements,has sporadically been explored.Herein,we report an innovative atroposelective iridium-catalyzed hydrogenation of N-arylindole ketones and heterobiaryl ketones via dynamic kinetic resolution(DKR)based on a Lewis acid-base interaction between the nitrogen atom and the carbonyl group of ketones,providing C-N and C-C atropisomers bearing multiple chiral elements with excellent enantioselectivities,diastereoselectivities and yields.The lynchpin of the DKR-ADH process stands in the newly developed planar-chiral tridentate PNO ligand,which ensures the excellent control of enantioselectivity and diastereoselectivity simultaneously.The synthetic utilization of this protocol is proved through stereospecific transformation to a tridentate PNN ligand bearing axial and central chirality,which shows promising potential in iridium-catalyzed asymmetric hydrogenation of simple ketones.
基金supported by the National Natural Science Foundation of China(22278200,21971095,21502080,21772019,21772076,21871117,91956203)the National Key R&D Program of China(2023YFA1506400)+3 种基金the Science and Technology Major Program of Gansu Province of China(22ZD6FA006,23ZDFA015)the“111”Program of Ministry of Education of Chinathe Major Project of the Ministry of Science and Technology of China(2018ZX09711001-005-002)the Science and Technology Commission of Shanghai Municipality(19JC1430100)。
文摘Herein,the de novo synthesis of atropisomeric benzofurans through the Cu/spirocyclic-pyrrolidine-oxazoline(SPDO)complex catalyze asymmetric formal[3+2]cycloaddition between quinones and ynamides is explored,producing a range of structurally diverse axially chiral benzofurans in satisfactory yields with good to excellent enantioselectivities.Furthermore,density functional theory calculations were applied to explain the possible reaction mechanism.
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supported by the National Natural Science Foundation of China (22125108, 92056104)the Fundamental Research Funds for the Central Universities (20720210002, 20720230003)the National Science Fund for Fostering Talents in Basic Science (J1310024)。
文摘Catalytic enantioselective preparation of axially chiral molecules has gained considerable interest over the past decades, due to their numerous applications in bioactive molecules, natural products, pharmaceuticals, materials, ligands, and catalysts. Compared with the well-established synthetic approaches for six-membered axially chiral skeletons, methodologies directed towards five-membered axially chiral compounds are relatively rare. Among these, axially chiral arylpyrroles are especially important structural motifs with wide utility, and the atroposelective synthesis of them is highly desirable. In recent years, novel strategies have been developed based on transition-metal catalysis and organocatalysis. This review summarizes the recent achievements in atroposelective preparation of arylpyrroles, by emphasizing the synthetic methods for each axially chiral framework, reaction mechanisms, and applications.
基金the NationalNatural Science Foundation of China(Nos.21820102003,91956201,21901081,22171099)the Open Research Fund of the School of Chemistry and Chemical Engineering,the Henan Normal University(No.2021YB02)+1 种基金the Program of Introducing Talents of Discipline to Universities of China(No.B17019)the Excellent Doctoral DissertationCultivation Grant to D.L.from Central China Normal University(CCNU).
文摘The chemistry of axially chiral compounds has emerged as a subject of increasing interest due to their widespread presence in natural products,bioactive molecules,advanced materials,and chiral ligands/catalysts.On the other hand,catalytic asymmetric radical-based transformations provide a complementary platform for the construction of enantiomerically enriched molecules that are in growing demand in the chemical and pharmaceutical in-dustries.In recent years,considerable research efforts have been devoted to the development of catalytic asymmetric radical reactions for the construction of axially chiral compounds based on the unique reactivity modes of diverse radicals.In this review,we critically illustrate these recent achievements according to different radical precursors and catalytic activation modes.Wherever possible,special emphasis is also placed on the discussion of mechanistic features underlying these works and substrate scopes.This review should be of great interest to the experts in this area,but also serve as a helpful starting point for new researchers in this field.
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.
