A rhodium-catalyzed desymmetrization reaction for enantioselective methyl C-H arylation is achieved by utilizing an in situ arylating reagent via nucleophilic cyclization of o-aminoaryl alkyne.The reaction results in ...A rhodium-catalyzed desymmetrization reaction for enantioselective methyl C-H arylation is achieved by utilizing an in situ arylating reagent via nucleophilic cyclization of o-aminoaryl alkyne.The reaction results in chiral indoles containing all-carbon quaternary stereocenters under atmospheric conditions,with a wide range of substrates exhibiting good enantioselectivity(44 examples).Mechnism and DFT studies show that the stereocontrol is reasonably achieved through the collaborative control of a large silicon substituted chiral ligand and C-H···π,LP···πinteractions between aryl rings of the carboxylate group and the substrate.Control experiments demonstrate that Rh-aryl bond formation via in situ nucleophilic cyclization is more critical for reaction efficiency than via C-H activation of the nucleophilic cyclization byproduct.展开更多
Phosphorus stereocenter,a ubiquitous central chiral element,plays a crucial role in pharmaceuticals,materials science and asymmetric catalysis.As such,stereoselective construction of phosphorus stereocenters has becom...Phosphorus stereocenter,a ubiquitous central chiral element,plays a crucial role in pharmaceuticals,materials science and asymmetric catalysis.As such,stereoselective construction of phosphorus stereocenters has become important in the field of organic synthesis.Herein we report a general and modular method for the construction of P-stereogenic centers via palladium/chiral norbornene cooperative catalysis-enabled desymmetrization/kinetic resolution process.It is a two-component annulation reaction that involves widely available aryl iodides and prochiral or racemic phosphinamides as the reactants.A wide variety of substrates bearing an assortment of functional groups(50 examples)are compatible with this method.Other features include a distinct enantiodiscrimination mechanism,excellent stereoselectivities,and scalability.The obtained chiral P-stereogenic products bear a common C–Br bond,which can be elaborated for the synthesis of new P-stereogenic compounds with diverse structural features.In addition,preliminary studies uncover the promising chiroptical properties of these P-stereogenic cyclic phosphinamides.Density functional theory calculations are performed to reveal that the noncovalent hydrogen bonding interaction is the origin of enantiodiscrimination during the desymmetrization process.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
The asymmetric cycloaddition reactions of 1,3-fused cyclic azomethine ylides have been extensively studied,but the non-cyclicα-functionalization of these compounds remains unexplored.Herein,an efficient combination o...The asymmetric cycloaddition reactions of 1,3-fused cyclic azomethine ylides have been extensively studied,but the non-cyclicα-functionalization of these compounds remains unexplored.Herein,an efficient combination of the catalytic enantioselective non-cyclicα-functionalization of 1,3-fused cyclic azomethine ylides and the remote-controlled asymmetric desymmetrization of N-arylmaleimides and cyclopentene-1,3-diones has been achieved with a catalyst system consisting of a chiral P,N-ferrocene ligand and AgNO2.This reaction allowed for the synthesis of a series of enantioenriched 3,4-dihydroisoquinoline derivatives bearing multiple stereogenic elements/centers with good yields and stereoselectivities.The practicality of this method was demonstrated by gram-scale synthesis and derivatizations of the products.展开更多
Material advances over the past decades in the recapitulation of natural photosystems have given rise to a series of functional covalent organic frameworks(COFs)for accelerating charge or mass transport.However,there ...Material advances over the past decades in the recapitulation of natural photosystems have given rise to a series of functional covalent organic frameworks(COFs)for accelerating charge or mass transport.However,there has been a paucity of research addressing the functional zoning and cooperation of charge and mass transport in one COF structure.Here,we demonstrate a desymmetrization strategy that separates electron transfer,proton transport,and CO_(2)binding regions in one crystalline COF to collaboratively execute artificial photosynthesis.Owing to its unique functional regionalization,the target COF with symmetry-breaking porphyrin moiety(NiSN3Por-PDAN-COF)exhibits an exceptional CO production rate of∼22.7 mmol g^(−1) h^(−1),which is ca.65 times higher than that of the symmetric counterpart(NiN_(4)Por-PDAN-COF).As unveiled by advanced spectroscopies and theoretical analysis,in NiSN_(3)Por-PDAN-COF,the thiophene component facilitates electron transport,metal site binds CO_(2),and the pyrrole moiety serves as a proton hopping site,“divide and conquer”,to synergistically elevate the conversion efficiency of artificial photosynthesis.展开更多
Enantioselective radical desymmetrization is a highly effective approach for rapidly creating enantioenriched molecules,introducing dramatically increased structural complexity from readily available prochiral or meso...Enantioselective radical desymmetrization is a highly effective approach for rapidly creating enantioenriched molecules,introducing dramatically increased structural complexity from readily available prochiral or meso compound feedstocks.Two strategic modes have been developed for these reactions,which differ in the nature of the stereo-determining steps.The first category deals primarily with the stereoselective desymmetrization of closed-shell radical precursors or functional reagents,whereas the second category achieves desymmetrization by stereoselectively functionalizing open-shell radical species.This mini-review explores the research progress in this growing field,aiming to elucidate mechanistic scenarios related to stereochemical control.Additionally,it offers insights into the challenges and opportunities that lie ahead for further development.展开更多
Desymmetrization of prochiral 3-substituted glutaronitriles offers a new approach to access （S）-Pregabalin and （R）-Baclofen. A number of nitrilases from diverse sources were screened with 3-isobutylglutaronitriles...Desymmetrization of prochiral 3-substituted glutaronitriles offers a new approach to access （S）-Pregabalin and （R）-Baclofen. A number of nitrilases from diverse sources were screened with 3-isobutylglutaronitriles （1a） or 3-（4＇-chlorophenyl）glutaronitriles （1b） as the substrate. Some nitrilases were found to catalyze the desymmetric hydrolysis of la and lb to form optically active 3-（cyanomethyl）-5-methylhexanoic acid （2a） and 3-（4＇-chlorophenyl）-4-cyanobutanoic acid （2b） with high enantiomeric excesse （ee）, respectively. This cannot be achieved using traditional chemical hydrolysis. Among them, AtNIT3 generated （R）-2b whereas BjNIT6402 and HsN1T produced the opposite （S）-enantiomer with high conversions and ee values. Not only the nitrilases showed different activities and stereoselectivities toward these 3-substituted glutaronitriles, the 3-substitueut of the substrates also exerted great effect on the enzyme activity and stereoselectivity. （S）-2a and （S）-2b were prepared with high yields and ee values using BjNIT6402 and HsNIT as the biocatalysts, respectively. A straightforward Curtius rearrangement of （S）-2a and （S）-2b, followed by the acidic hydrolysis, afforded （S）-Pregabalin and （R）-Baclofen. This offers a new platform methodology for the synthesis of optically active β-substituted T-amino acids of pharmaceutical importance.展开更多
A Ru-catalyzed hydrogenative desymmetrization of 2,2,5-trisubstituted cyclohexane-1,3-diones was developed for construction of three stereocenters including two coherent and discontiguous chiral centers and a chiral q...A Ru-catalyzed hydrogenative desymmetrization of 2,2,5-trisubstituted cyclohexane-1,3-diones was developed for construction of three stereocenters including two coherent and discontiguous chiral centers and a chiral quaternary carbon with excellent enantio-and diastereoselectivities.Stereodivergent synthesis of four stereoisomers could be conducted with high enantioselectivities.The desymmetrization could be achieved at gram scale without loss of reactivity and optical purity,and a formal synthesis of bioactive molecule(-)-isocelorbicol was completed.展开更多
N-heterocyclic carbene-catalyzed enantioselective kinetic resolutions,dynamic kinetic resolutions,and desymmetrization reactions are systematically reviewed.The content is organized according to the activation modes i...N-heterocyclic carbene-catalyzed enantioselective kinetic resolutions,dynamic kinetic resolutions,and desymmetrization reactions are systematically reviewed.The content is organized according to the activation modes involved in these transformations.Future advances within this highly active research field are discussed from our perspectives on the topic.展开更多
For the metal-catalyzed asymmetric hydrogenation of α-substituted ketones,cis reductive products are generally obtained due to steric hindrance of substituents.Herein,an unprecedented trans reductive products were ob...For the metal-catalyzed asymmetric hydrogenation of α-substituted ketones,cis reductive products are generally obtained due to steric hindrance of substituents.Herein,an unprecedented trans reductive products were observed in palladium-catalyzed hydrogenative desymmetrization of cyclic and acyclic 1,3-diketones,providing the chiral trans β-hydroxy ketones with two adjacent stereocenters including one α-tertiary or quaternary stereocenter with high enantioselectivity and diastereoselectivity.Mechanistic studies and DFT calculations suggested that the rarely observed diastereoselectivity reversal is ascribed to the charge-charge interaction between the palladium and aromatic ring of the substrate,which could not only result in the reversal of the diastereoselectivity,but also improve the reactivity.展开更多
Chiral silyl ethers and silanols are important synthetic intermediates and bioactive compounds.In this work,we developed a onepot remote desymmetrization/Peterson-olefination of silacyclopentene oxides with benzoic ac...Chiral silyl ethers and silanols are important synthetic intermediates and bioactive compounds.In this work,we developed a onepot remote desymmetrization/Peterson-olefination of silacyclopentene oxides with benzoic acids in the presence of Martin’s sulfurane.This new methodology not only realizes the atom-economy of Peterson olefination,but also represents a catalytic method for synthesis of silicon-stereogenic silyl ethers.Using a bulky chiral phosphoric acid 4i as organocatalyst,the reactions proceeded efficiently to afford various olefin-functionalized organosilyl ethers in excellent diastereoelectivities(up to 25/1 d.r.)and high enantioselectivities(up to 94%ee).展开更多
Morpholines are widespread in many biologically and catalytically active agents,thus being an important aim of pharmaceutical and synthetic chemists.However,efficient strategies for the catalytic asymmetric synthesis ...Morpholines are widespread in many biologically and catalytically active agents,thus being an important aim of pharmaceutical and synthetic chemists.However,efficient strategies for the catalytic asymmetric synthesis of chiral morpholines bearing crowded stereogenic centers still remain elusive.Herein,we disclose a Cu-catalyzed asymmetric propargylic amination/desymmetrization strategy to help resolve this challenge.As a result,two kinds of structurally various chiral morpholines bearing rich functional groups and N-a-quaternary stereocenters were produced with high efficiency and selectivity(42 examples,up to91%yield,97:3 er and>19:1 dr).In addition,a series of transformations were performed to demonstrate the synthetic utility of this methodology.In particular,a hit compound for new antitumor drugs was identified through cellular evaluation.Furthermore,mechanistic investigations reveal that,hydrogen bonding in the key copper-allenylidene intermediate together withπ-πstacking aids remote enantioinduction.展开更多
Atropisomeric phosphines are crucial for asymmetric catalysis but remain synthetically challenging.Herein,an N-heterocyclic carbene(NHC)catalyzed esterification reaction of dialdehydes with arylboronic acids was devel...Atropisomeric phosphines are crucial for asymmetric catalysis but remain synthetically challenging.Herein,an N-heterocyclic carbene(NHC)catalyzed esterification reaction of dialdehydes with arylboronic acids was developed,successfully constructing the framework of axially chiral phosphorus compounds.Mechanistic studies have revealed that the reaction initially undergoes a desymmetrization process,followed by a kinetic resolution pathway,affording a series of axially chiral phosphorus compounds with high enantioselectivity(up to 92%ee).展开更多
Highly efficient synthesis of the entitled compound was achieved from a readily availablemyo-inositol derivative. The key step involved a desymmetrization with (+)-camphor dimethylketal to give two diastereomers. The ...Highly efficient synthesis of the entitled compound was achieved from a readily availablemyo-inositol derivative. The key step involved a desymmetrization with (+)-camphor dimethylketal to give two diastereomers. The two diastereomers could be used to synthesize the samecompound by changing the orders to introduce the protective groups.展开更多
Desymmetrization reactions provide a powerful approach for the construction of complex molecules. Various methods have been developed for the selective monoprotection of symmetrical diols;however, their application to...Desymmetrization reactions provide a powerful approach for the construction of complex molecules. Various methods have been developed for the selective monoprotection of symmetrical diols;however, their application to large-scale operations is limited. In this study, the monotetrahydropyranylation of symmetrical diols in a flow reactor has been developed, whereby the length of the flow reactor tube and the amount of acid were optimized. A higher selectivity for the monoprotected derivative was observed when the reaction was performed in a flow reactor compared with that observed in a conventional batch experiment. The efficient flow method developed herein can be applied to large-scale synthesis by numbering up the flow reactor without affecting the selectivity and yield. Since monoprotection can be achieved without using a large excess of diol, our developed flow method is effective when expensive diol must be used.展开更多
Organosilanes are not found in nature but play a crucial role in the sustainable development of modern society.Si-chiral organosilanes represent a type of novel chemical space that is highly desirable for research ori...Organosilanes are not found in nature but play a crucial role in the sustainable development of modern society.Si-chiral organosilanes represent a type of novel chemical space that is highly desirable for research oriented in terms of their properties,including synthetic chemistry,drug discovery,and materials and life sciences.While much effort has been given to the catalytic enantioselective construction of Si-chirality,the facile synthesis of multifunctional Si-chiral silanes remains undeveloped.Here,we report an unprecedented highly enantioselective copper-catalyzed desymmetric sulfonylation or acylation of prochiral 1,3-siladiols for the expedient synthesis of multifunctional Si-chiral silanes with both a hydroxymethyl group and an ester group as synthetic handles.A one-pot tandem desymmetric sulfonylation/substitution sequence,internally reusing waste chloride or bromide formed from the upstream sulfonylation step as the reagent for a substitution step,is also exploited for the atom-efficient synthesis of Si-chiral silylmethanols featuring a chloromethyl or bromomethyl group.A newly developed sterically confined pyridine-bis(oxazoline)(PYBOX)ligand with a bulky C4 amide-containing shielding group is crucial for achieving excellent reactivity and enantioselectivity.The scale-up synthesis and various diversifying elaborations of multifunctional Si-chiral silylmethanols further highlight the synthetic practicability of this protocol.展开更多
Oxidation reactions are of fundamental importance in nature and often proceed in an enantioselective manner.Palladium-catalyzed oxidative cascade carbocyclizations are efficient protocols for C–C bond formation and c...Oxidation reactions are of fundamental importance in nature and often proceed in an enantioselective manner.Palladium-catalyzed oxidative cascade carbocyclizations are efficient protocols for C–C bond formation and cyclic scaffolds construction,thus attracting widespread attention.However,the development of enantioselective versions of these reactions is challenging because commonly used phosphine-based ligands are not tolerated under oxidative conditions.The use of chiral phosphoric acids(CPAs)that provide a chiral counterion to the metal is one solution to this problem.Herein,we report a palladium-catalyzed oxidative enantio-and diastereo-selective carbocyclization-borylation of dienallenes via desymmetrization,enabling the construction of a diverse set of cyclohexenes bearing two nonadjacent stereocenters(up to 99.5:0.5 er and>20:1 dr).The asymmetric induction was obtained by the use of a catalytic amount of chiral diphenyl-3,3'-biphenanthryl-4,4′-diyl phosphate-phosphoric acid(VAPOL-PA)through significant ligand acceleration.Moreover,the reaction could be advanced into aerobic biomimetic oxidation,where molecular oxygen was used as the terminal oxidant.The introduction of a readily modifiable boronate group with a stereogenic center at theβ-position further demonstrated the synthetic utility of this methodology.展开更多
Transition metal-catalyzed[2+2+2]cycloaddition represents a cornerstone methodology in organic synthesis.However,the cobalt-catalyzed asymmetric cycloaddition system remains underexplored despite its synthetic potenti...Transition metal-catalyzed[2+2+2]cycloaddition represents a cornerstone methodology in organic synthesis.However,the cobalt-catalyzed asymmetric cycloaddition system remains underexplored despite its synthetic potential and advantages.This work describes a cobalt-catalyzed atroposelective[2+2+2]cycloaddition/electrocyclic ring-opening cascade between 1,6-diynes and axial pre-chiral biaryl dialdehydes,to generate axially chiral conjugated diene ketones.Notably,aldehydes serve as both oxygen and carbon donors,undergoing formal double bond cleavage to forge new C=O and C=C bonds in a single catalytic cycle.The cascade transformation operates under mild,redox-neutral conditions,achieving exceptional Z/E selectivity,high enantioselectivity,and broad functional group compatibility.Mechanistic investigations combining density functional theory calculations and experimental studies suggest the involvement of a cobaltmediated[2+2+2]cycloaddition and ring-opening step in the cascade process.The deformation energy of the catalyst and substrate steric effects contributed to chiral induction.展开更多
The stereoselective reduction of strained molecules and subsequent synthetic transformations provide an efficient strategy to access multi-substituted carbocycles.These carbocycles are important structural skeletons i...The stereoselective reduction of strained molecules and subsequent synthetic transformations provide an efficient strategy to access multi-substituted carbocycles.These carbocycles are important structural skeletons in natural products and bioactive molecules.We report here a Luche-type enantioselective reduction of cyclobutenones and strained-ring fused cyclic imides.This process utilizes the catalysis of Sc-N,N’-dioxide ligand complex and NaBH_(4) as reductant.Moreover,the developed methodology is applicable to the strained olefins,which are not tolerated under metal hydride conditions.展开更多
Axially chiral phosphines are a class of extremely important ligands in asymmetric catalysis.Herein,an unprecedented copper(Ⅰ)-catalyzed asymmetric SNAr reaction with HP(S)R2is uncovered,which delivers a series of ax...Axially chiral phosphines are a class of extremely important ligands in asymmetric catalysis.Herein,an unprecedented copper(Ⅰ)-catalyzed asymmetric SNAr reaction with HP(S)R2is uncovered,which delivers a series of axially chiral phosphine derivatives in high yields with excellent enantioselectivity.Furthermore,the diastereoselective reaction with the kinetic resolution of racemic HP(S)Ar R proceeds smoothly,providing the products with moderate diastereoselectivity and excellent enantioselectivity.Control experiments indicate that HP(S)Ph2is much more active than HPPh2and HP(O)Ph2as the pronucleophile in the present reaction.It is found that the SNAr reaction(the first SNAr)proceeds in a desymmetric manner,providing the desired chiral products while a continued SNAr reaction(the second SNAr)slightly occurs in a kinetic resolution manner in the present catalytic system,which enhances the ee of the desired chiral products.DFTcalculations support a concerted reaction pathway rather than a step-wise mechanism.Finally,axially chiral olefin-phosphines produced by the present method work as suitable ligands in Pdcatalyzed asymmetric allylic substitution with C-,N-,and O-nucleophiles and Rh-catalyzed asymmetric addition of arylboronic acid to benzil.展开更多
基金financial support for this work from the National Key R&D Program of China(No.2021YFC0864700)the National Natural Science Foundation of China(Nos.21801066,U1804283 and 82130103)+2 种基金the Central Plains Scholars and Scientists Studio Fund(No.2018002)the project funded by the Natural Science Foundation of Henan(Nos.222300420056,222300420204)the China Postdoctoral Science Foundation(Nos.2020M682307,2021T140183)。
文摘A rhodium-catalyzed desymmetrization reaction for enantioselective methyl C-H arylation is achieved by utilizing an in situ arylating reagent via nucleophilic cyclization of o-aminoaryl alkyne.The reaction results in chiral indoles containing all-carbon quaternary stereocenters under atmospheric conditions,with a wide range of substrates exhibiting good enantioselectivity(44 examples).Mechnism and DFT studies show that the stereocontrol is reasonably achieved through the collaborative control of a large silicon substituted chiral ligand and C-H···π,LP···πinteractions between aryl rings of the carboxylate group and the substrate.Control experiments demonstrate that Rh-aryl bond formation via in situ nucleophilic cyclization is more critical for reaction efficiency than via C-H activation of the nucleophilic cyclization byproduct.
基金the National Key Research and Development Program of China(grant no.2022YFA1503703)the National Natural Science Foundation of China(grant no.22325106)the Fundamental Research Funds for the Central Universities(grant no.2042024kf1014),and Wuhan University for financial support.
文摘Phosphorus stereocenter,a ubiquitous central chiral element,plays a crucial role in pharmaceuticals,materials science and asymmetric catalysis.As such,stereoselective construction of phosphorus stereocenters has become important in the field of organic synthesis.Herein we report a general and modular method for the construction of P-stereogenic centers via palladium/chiral norbornene cooperative catalysis-enabled desymmetrization/kinetic resolution process.It is a two-component annulation reaction that involves widely available aryl iodides and prochiral or racemic phosphinamides as the reactants.A wide variety of substrates bearing an assortment of functional groups(50 examples)are compatible with this method.Other features include a distinct enantiodiscrimination mechanism,excellent stereoselectivities,and scalability.The obtained chiral P-stereogenic products bear a common C–Br bond,which can be elaborated for the synthesis of new P-stereogenic compounds with diverse structural features.In addition,preliminary studies uncover the promising chiroptical properties of these P-stereogenic cyclic phosphinamides.Density functional theory calculations are performed to reveal that the noncovalent hydrogen bonding interaction is the origin of enantiodiscrimination during the desymmetrization process.
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the National Natural Science Foundation of China(Nos.22171029,22271027)Natural Science Foundation of Sichuan Province(2024NSFSC1115)Chemical Synthesis and PollutionControl KeyLaboratory of Sichuan Province(CSPC202406)for the financial support.
文摘The asymmetric cycloaddition reactions of 1,3-fused cyclic azomethine ylides have been extensively studied,but the non-cyclicα-functionalization of these compounds remains unexplored.Herein,an efficient combination of the catalytic enantioselective non-cyclicα-functionalization of 1,3-fused cyclic azomethine ylides and the remote-controlled asymmetric desymmetrization of N-arylmaleimides and cyclopentene-1,3-diones has been achieved with a catalyst system consisting of a chiral P,N-ferrocene ligand and AgNO2.This reaction allowed for the synthesis of a series of enantioenriched 3,4-dihydroisoquinoline derivatives bearing multiple stereogenic elements/centers with good yields and stereoselectivities.The practicality of this method was demonstrated by gram-scale synthesis and derivatizations of the products.
基金This research was made possible as a result of a generous grant from Research Grants Council(RGC)Senior Research Fellowship Scheme(grant no.SRFS2021-5S01)the Hong Kong Research Grants Council(PolyU 15307321)+1 种基金Research Institute for Smart Energy(CDAQ),Research Centre for Nanoscience and Nanotechnology(CE2H),Miss Clarea Au for the Endowed Professorship in Energy(847 S),National Key R&D Program of China(grant nos.2022YFA1502903 and 2022YFA0911900)the National Natural Science Foundation of China(grant nos.22309156,22088102 and 21971251),and the New Cornerstone Science Foundation.
文摘Material advances over the past decades in the recapitulation of natural photosystems have given rise to a series of functional covalent organic frameworks(COFs)for accelerating charge or mass transport.However,there has been a paucity of research addressing the functional zoning and cooperation of charge and mass transport in one COF structure.Here,we demonstrate a desymmetrization strategy that separates electron transfer,proton transport,and CO_(2)binding regions in one crystalline COF to collaboratively execute artificial photosynthesis.Owing to its unique functional regionalization,the target COF with symmetry-breaking porphyrin moiety(NiSN3Por-PDAN-COF)exhibits an exceptional CO production rate of∼22.7 mmol g^(−1) h^(−1),which is ca.65 times higher than that of the symmetric counterpart(NiN_(4)Por-PDAN-COF).As unveiled by advanced spectroscopies and theoretical analysis,in NiSN_(3)Por-PDAN-COF,the thiophene component facilitates electron transport,metal site binds CO_(2),and the pyrrole moiety serves as a proton hopping site,“divide and conquer”,to synergistically elevate the conversion efficiency of artificial photosynthesis.
基金Financial support from the National Natural Science Foundation of China (grant nos.22025103,92256301,21831002,22271133,22101122,and 22201127)the National Key R&D Program of China (grant nos.2021YFF0701604 and 2021YFF0701704)+1 种基金New Cornerstone Science Foundation through the XPLORER PRIZE,Shenzhen Science and Technology Program (grant nos.KQTD20210811090112004 and JCYJ20220818100600001)Shenzhen Key Laboratory of Cross-Coupling Reactions (grant no.ZDSYS20220328104200001).
文摘Enantioselective radical desymmetrization is a highly effective approach for rapidly creating enantioenriched molecules,introducing dramatically increased structural complexity from readily available prochiral or meso compound feedstocks.Two strategic modes have been developed for these reactions,which differ in the nature of the stereo-determining steps.The first category deals primarily with the stereoselective desymmetrization of closed-shell radical precursors or functional reagents,whereas the second category achieves desymmetrization by stereoselectively functionalizing open-shell radical species.This mini-review explores the research progress in this growing field,aiming to elucidate mechanistic scenarios related to stereochemical control.Additionally,it offers insights into the challenges and opportunities that lie ahead for further development.
基金financially supported by the Chinese Academy of Sciences (KSZD-EW-Z-015)the CAS Agenda to Provide S&T Support and Services for the National Strategic Emerging Industries
文摘Desymmetrization of prochiral 3-substituted glutaronitriles offers a new approach to access （S）-Pregabalin and （R）-Baclofen. A number of nitrilases from diverse sources were screened with 3-isobutylglutaronitriles （1a） or 3-（4＇-chlorophenyl）glutaronitriles （1b） as the substrate. Some nitrilases were found to catalyze the desymmetric hydrolysis of la and lb to form optically active 3-（cyanomethyl）-5-methylhexanoic acid （2a） and 3-（4＇-chlorophenyl）-4-cyanobutanoic acid （2b） with high enantiomeric excesse （ee）, respectively. This cannot be achieved using traditional chemical hydrolysis. Among them, AtNIT3 generated （R）-2b whereas BjNIT6402 and HsN1T produced the opposite （S）-enantiomer with high conversions and ee values. Not only the nitrilases showed different activities and stereoselectivities toward these 3-substituted glutaronitriles, the 3-substitueut of the substrates also exerted great effect on the enzyme activity and stereoselectivity. （S）-2a and （S）-2b were prepared with high yields and ee values using BjNIT6402 and HsNIT as the biocatalysts, respectively. A straightforward Curtius rearrangement of （S）-2a and （S）-2b, followed by the acidic hydrolysis, afforded （S）-Pregabalin and （R）-Baclofen. This offers a new platform methodology for the synthesis of optically active β-substituted T-amino acids of pharmaceutical importance.
基金the National Natural Science Foundation of China(21532006,21690074)Chinese Academy of Sciences(XDB17020300,SSW-SLH035)。
文摘A Ru-catalyzed hydrogenative desymmetrization of 2,2,5-trisubstituted cyclohexane-1,3-diones was developed for construction of three stereocenters including two coherent and discontiguous chiral centers and a chiral quaternary carbon with excellent enantio-and diastereoselectivities.Stereodivergent synthesis of four stereoisomers could be conducted with high enantioselectivities.The desymmetrization could be achieved at gram scale without loss of reactivity and optical purity,and a formal synthesis of bioactive molecule(-)-isocelorbicol was completed.
基金supported by the National Natural Science Foundation of China (21961006,32172459,22371057)Science and Technology Department of Guizhou Province (Qiankehejichu-ZK[2021]Key033)+1 种基金Program of Introducing Talents of Discipline to Universities of China (111 Program,D20023) at Guizhou UniversityFrontiers Science Center for Asymmetric Synthesis and Medicinal Molecules,Department of Education,Guizhou Province (Qianjiaohe KY (2020)004),Guizhou University (China)。
文摘N-heterocyclic carbene-catalyzed enantioselective kinetic resolutions,dynamic kinetic resolutions,and desymmetrization reactions are systematically reviewed.The content is organized according to the activation modes involved in these transformations.Future advances within this highly active research field are discussed from our perspectives on the topic.
基金supported by the National Natural Science Foundation of China(21871255,21532006,21873096)Chinese Academy of Sciences(XDB17020300,XDB17010200)
文摘For the metal-catalyzed asymmetric hydrogenation of α-substituted ketones,cis reductive products are generally obtained due to steric hindrance of substituents.Herein,an unprecedented trans reductive products were observed in palladium-catalyzed hydrogenative desymmetrization of cyclic and acyclic 1,3-diketones,providing the chiral trans β-hydroxy ketones with two adjacent stereocenters including one α-tertiary or quaternary stereocenter with high enantioselectivity and diastereoselectivity.Mechanistic studies and DFT calculations suggested that the rarely observed diastereoselectivity reversal is ascribed to the charge-charge interaction between the palladium and aromatic ring of the substrate,which could not only result in the reversal of the diastereoselectivity,but also improve the reactivity.
基金supported by the National Natural Science Foundation of China(22271276,21871254,21702203)the National Key Research and Development Program of China(2022YFC2105900)。
文摘Chiral silyl ethers and silanols are important synthetic intermediates and bioactive compounds.In this work,we developed a onepot remote desymmetrization/Peterson-olefination of silacyclopentene oxides with benzoic acids in the presence of Martin’s sulfurane.This new methodology not only realizes the atom-economy of Peterson olefination,but also represents a catalytic method for synthesis of silicon-stereogenic silyl ethers.Using a bulky chiral phosphoric acid 4i as organocatalyst,the reactions proceeded efficiently to afford various olefin-functionalized organosilyl ethers in excellent diastereoelectivities(up to 25/1 d.r.)and high enantioselectivities(up to 94%ee).
基金supported by the National Key R&D Program of China(2023YFE0110100)the National Natural Science Foundation of China(22271113,92256301,21822103,and 21820102003)。
文摘Morpholines are widespread in many biologically and catalytically active agents,thus being an important aim of pharmaceutical and synthetic chemists.However,efficient strategies for the catalytic asymmetric synthesis of chiral morpholines bearing crowded stereogenic centers still remain elusive.Herein,we disclose a Cu-catalyzed asymmetric propargylic amination/desymmetrization strategy to help resolve this challenge.As a result,two kinds of structurally various chiral morpholines bearing rich functional groups and N-a-quaternary stereocenters were produced with high efficiency and selectivity(42 examples,up to91%yield,97:3 er and>19:1 dr).In addition,a series of transformations were performed to demonstrate the synthetic utility of this methodology.In particular,a hit compound for new antitumor drugs was identified through cellular evaluation.Furthermore,mechanistic investigations reveal that,hydrogen bonding in the key copper-allenylidene intermediate together withπ-πstacking aids remote enantioinduction.
基金Project supported by the Natural Science Foundation of Henan Province(Nos.232300421234,252300421726)the Leading Talents in Scientific and Technological Innovation in Shangqiu(No.SQRC202212004)the Program of Ecological Environmental Protection in the Area of Old Course of Yellow River of Shangqiu Normal University。
文摘Atropisomeric phosphines are crucial for asymmetric catalysis but remain synthetically challenging.Herein,an N-heterocyclic carbene(NHC)catalyzed esterification reaction of dialdehydes with arylboronic acids was developed,successfully constructing the framework of axially chiral phosphorus compounds.Mechanistic studies have revealed that the reaction initially undergoes a desymmetrization process,followed by a kinetic resolution pathway,affording a series of axially chiral phosphorus compounds with high enantioselectivity(up to 92%ee).
文摘Highly efficient synthesis of the entitled compound was achieved from a readily availablemyo-inositol derivative. The key step involved a desymmetrization with (+)-camphor dimethylketal to give two diastereomers. The two diastereomers could be used to synthesize the samecompound by changing the orders to introduce the protective groups.
文摘Desymmetrization reactions provide a powerful approach for the construction of complex molecules. Various methods have been developed for the selective monoprotection of symmetrical diols;however, their application to large-scale operations is limited. In this study, the monotetrahydropyranylation of symmetrical diols in a flow reactor has been developed, whereby the length of the flow reactor tube and the amount of acid were optimized. A higher selectivity for the monoprotected derivative was observed when the reaction was performed in a flow reactor compared with that observed in a conventional batch experiment. The efficient flow method developed herein can be applied to large-scale synthesis by numbering up the flow reactor without affecting the selectivity and yield. Since monoprotection can be achieved without using a large excess of diol, our developed flow method is effective when expensive diol must be used.
基金supported by the National Natural Science Foundation of China(22471073,22171087)the Technology Innovation Project of Shanghai Municipal Agricultural Committee(HNK(T2023302))+2 种基金the Innovation Program of Shanghai Municipal Education Commission(2023ZKZD37)the Ministry of Education(PCSIRT)the Fundamental Research Funds for the Central Universities。
文摘Organosilanes are not found in nature but play a crucial role in the sustainable development of modern society.Si-chiral organosilanes represent a type of novel chemical space that is highly desirable for research oriented in terms of their properties,including synthetic chemistry,drug discovery,and materials and life sciences.While much effort has been given to the catalytic enantioselective construction of Si-chirality,the facile synthesis of multifunctional Si-chiral silanes remains undeveloped.Here,we report an unprecedented highly enantioselective copper-catalyzed desymmetric sulfonylation or acylation of prochiral 1,3-siladiols for the expedient synthesis of multifunctional Si-chiral silanes with both a hydroxymethyl group and an ester group as synthetic handles.A one-pot tandem desymmetric sulfonylation/substitution sequence,internally reusing waste chloride or bromide formed from the upstream sulfonylation step as the reagent for a substitution step,is also exploited for the atom-efficient synthesis of Si-chiral silylmethanols featuring a chloromethyl or bromomethyl group.A newly developed sterically confined pyridine-bis(oxazoline)(PYBOX)ligand with a bulky C4 amide-containing shielding group is crucial for achieving excellent reactivity and enantioselectivity.The scale-up synthesis and various diversifying elaborations of multifunctional Si-chiral silylmethanols further highlight the synthetic practicability of this protocol.
基金support from the Swedish Research Council(grant nos.2019-04042 and 2022-03682)the Swedish Foundation for Strategic Environmental Research(Mistra:project Mistra Safe-Chem,2018/11 and 2023/11)the Olle Engkvist Foundation,Stockholm,Sweden.W.K.also thanks the Natural Science Foundation of China(grant no.22201217)for financial support.
文摘Oxidation reactions are of fundamental importance in nature and often proceed in an enantioselective manner.Palladium-catalyzed oxidative cascade carbocyclizations are efficient protocols for C–C bond formation and cyclic scaffolds construction,thus attracting widespread attention.However,the development of enantioselective versions of these reactions is challenging because commonly used phosphine-based ligands are not tolerated under oxidative conditions.The use of chiral phosphoric acids(CPAs)that provide a chiral counterion to the metal is one solution to this problem.Herein,we report a palladium-catalyzed oxidative enantio-and diastereo-selective carbocyclization-borylation of dienallenes via desymmetrization,enabling the construction of a diverse set of cyclohexenes bearing two nonadjacent stereocenters(up to 99.5:0.5 er and>20:1 dr).The asymmetric induction was obtained by the use of a catalytic amount of chiral diphenyl-3,3'-biphenanthryl-4,4′-diyl phosphate-phosphoric acid(VAPOL-PA)through significant ligand acceleration.Moreover,the reaction could be advanced into aerobic biomimetic oxidation,where molecular oxygen was used as the terminal oxidant.The introduction of a readily modifiable boronate group with a stereogenic center at theβ-position further demonstrated the synthetic utility of this methodology.
基金supported by the National Key R&D Program of China(2024YFA1509704)the National Natural Science Foundation of China(22471034,22193012,22201033)+1 种基金the Natural Science Foundation of Jilin Province(20230101047JC,YDZJ202201ZYTS338)the Fundamental Research Funds for the Central Universities。
文摘Transition metal-catalyzed[2+2+2]cycloaddition represents a cornerstone methodology in organic synthesis.However,the cobalt-catalyzed asymmetric cycloaddition system remains underexplored despite its synthetic potential and advantages.This work describes a cobalt-catalyzed atroposelective[2+2+2]cycloaddition/electrocyclic ring-opening cascade between 1,6-diynes and axial pre-chiral biaryl dialdehydes,to generate axially chiral conjugated diene ketones.Notably,aldehydes serve as both oxygen and carbon donors,undergoing formal double bond cleavage to forge new C=O and C=C bonds in a single catalytic cycle.The cascade transformation operates under mild,redox-neutral conditions,achieving exceptional Z/E selectivity,high enantioselectivity,and broad functional group compatibility.Mechanistic investigations combining density functional theory calculations and experimental studies suggest the involvement of a cobaltmediated[2+2+2]cycloaddition and ring-opening step in the cascade process.The deformation energy of the catalyst and substrate steric effects contributed to chiral induction.
基金Financial support from the National Natural Science Foundation of China(grant number 22271052)is acknowledged.
文摘The stereoselective reduction of strained molecules and subsequent synthetic transformations provide an efficient strategy to access multi-substituted carbocycles.These carbocycles are important structural skeletons in natural products and bioactive molecules.We report here a Luche-type enantioselective reduction of cyclobutenones and strained-ring fused cyclic imides.This process utilizes the catalysis of Sc-N,N’-dioxide ligand complex and NaBH_(4) as reductant.Moreover,the developed methodology is applicable to the strained olefins,which are not tolerated under metal hydride conditions.
基金supported by the National Key R&D Program of China(2023YFF0723900)the National Natural Science Foundation of China(22271302,92156017)+2 种基金the Science and Technology Commission of Shanghai Municipality(21XD1424800)the Haihe Laboratory of Sustainable Chemical Transformations(24HHWCSS00019)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB0590000)。
文摘Axially chiral phosphines are a class of extremely important ligands in asymmetric catalysis.Herein,an unprecedented copper(Ⅰ)-catalyzed asymmetric SNAr reaction with HP(S)R2is uncovered,which delivers a series of axially chiral phosphine derivatives in high yields with excellent enantioselectivity.Furthermore,the diastereoselective reaction with the kinetic resolution of racemic HP(S)Ar R proceeds smoothly,providing the products with moderate diastereoselectivity and excellent enantioselectivity.Control experiments indicate that HP(S)Ph2is much more active than HPPh2and HP(O)Ph2as the pronucleophile in the present reaction.It is found that the SNAr reaction(the first SNAr)proceeds in a desymmetric manner,providing the desired chiral products while a continued SNAr reaction(the second SNAr)slightly occurs in a kinetic resolution manner in the present catalytic system,which enhances the ee of the desired chiral products.DFTcalculations support a concerted reaction pathway rather than a step-wise mechanism.Finally,axially chiral olefin-phosphines produced by the present method work as suitable ligands in Pdcatalyzed asymmetric allylic substitution with C-,N-,and O-nucleophiles and Rh-catalyzed asymmetric addition of arylboronic acid to benzil.
