A Silver-catalyzed enantioselective[3+2]cycloaddition of azomethine ylides with activated alkenes by using a P-stereogenic ligand Ganphos is reported.The method provides an efficient strategy for the effective synthes...A Silver-catalyzed enantioselective[3+2]cycloaddition of azomethine ylides with activated alkenes by using a P-stereogenic ligand Ganphos is reported.The method provides an efficient strategy for the effective synthesis of spirocyclic scaffolds containing a pyrroline motif.Notable features of this approach include good yields,remarkable enantioselectivity,as well as a broad substrate scope and significant step efficiency.展开更多
Pyrazolidinones,as significant analogs ofβ-lactam antibiotics,have garnered substantial interest for their enantioselective synthesis.Azomethine imines,recognized as valuable building blocks for the construction of t...Pyrazolidinones,as significant analogs ofβ-lactam antibiotics,have garnered substantial interest for their enantioselective synthesis.Azomethine imines,recognized as valuable building blocks for the construction of these nitrogen-containing compounds,underscore the continuous pursuit of novel building blocks and reaction methodologies within the chemical community.In this paper,we present a cascade cyclization between alkenyl azomethine imines and furan-2(5H)-one to generate chiral coronal polyheterocyclic compounds with high yields and enantioselectivities,catalyzed by dipeptide-derived phosphonium salts.In-vitro biological activity assays highlight the potential of these chiral compounds in drug discovery.Additionally,density functional theory(DFT)calculations elucidate the pivotal role of phosphonium salts,demonstrating their cooperative activations via hydrogen bonding and ion-pairing interactions.展开更多
A cascade carbonylative ring expansion and [2+2]/[4+2] cycloaddition of strained 1-iminylphosphirane complexes with aryl allenes were reported.The carbonylative ring expansion of 1-iminylphosphirane complexes provides...A cascade carbonylative ring expansion and [2+2]/[4+2] cycloaddition of strained 1-iminylphosphirane complexes with aryl allenes were reported.The carbonylative ring expansion of 1-iminylphosphirane complexes provides an azaphosphacyclohexone complex intermediate with a C=P double bond.The following [2+2] or dearomatic [4+2] cycloaddition of this intermediate with allenes is modulated by the aryl substituents on the imino carbon.The regioselective [2+2] cycloaddition with 1,1-diarylallene provides an entry to bicyclo[4.2.0]octan-4-one skeletons featuring a four-membered phosphacyclobutane moiety.While dearomatic [4+2] cycloaddition was preferred with less aromatic naphthalene and yielded octahydrochrysene skeleton containing heteroatoms.展开更多
The first example of stereoconvergent 1,3-dipolar cycloaddition of nitrile oxides and nitrile imines with E/Z isomeric mixture of electron-deficient olefins is reported,delivering isoxazolines and pyrazolines bearing ...The first example of stereoconvergent 1,3-dipolar cycloaddition of nitrile oxides and nitrile imines with E/Z isomeric mixture of electron-deficient olefins is reported,delivering isoxazolines and pyrazolines bearing two vicinal stereogenic tertiary and trifluoromethylated quaternary carbon centers with perfect regioand diastereoselectivities.The possibility of concerted cycloaddition/epimerization sequence under basic condition to form the thermodynamically stable diastereomers is excluded through some control experiments and DFT calculations,and a stepwise mechanism is proposed.展开更多
Furans bearing epoxy enolsilane units via a tether that incorporates a nitrogen heteroatom,undergo intramolecular(4+3)cycloadditions to generate bis-heteroatomic polycyclic adducts having piperidine moieties in their ...Furans bearing epoxy enolsilane units via a tether that incorporates a nitrogen heteroatom,undergo intramolecular(4+3)cycloadditions to generate bis-heteroatomic polycyclic adducts having piperidine moieties in their frameworks.The cycloadducts,ultimately derived from furfural,a renewal chemical feedstock,are obtained with up to 4:1 dr and with ee retained from the epoxide.展开更多
Tetracyclic coumarins are a class of important compounds with diverse and superior pharmacolog‐ical activities.However,a direct stereoselective method from simple and readily‐made coumarins derivatives remains chall...Tetracyclic coumarins are a class of important compounds with diverse and superior pharmacolog‐ical activities.However,a direct stereoselective method from simple and readily‐made coumarins derivatives remains challenging due to the inertness of coumarins as dienophiles.Herein,we de‐velop a decarboxylative asymmetric[4+2]cycloaddition of 3‐cyanocoumarins with vinyl benzoxa‐zinones,affording the coumarin‐derived condensed rings bearing three continuous stereocenters in high yields with excellent diastereoselectivities(>20/1 d.r.)and enantioselectivities(up to 99%ee).This direct enantioselective reaction was achieved by a Pd(0)/Cu(I)bimetallic catalytic system.The mechanism studies indicated that the synergistic activation effect,in which chiral Cu(I)as an availa‐ble Lewis acid catalyst activates 3‐cyanocoumarin and chiral Pd(0)complex activates benzoxazi‐none by the formation ofπ‐allyl‐palladium intermediate,plays an important role on the stereoselec‐tive control.The current work provides a new activation modes of Cu catalyst in the Pd/Cu bimetal‐lic catalytic system.展开更多
Bicyclo[2.1.1]hexanes(BCHs) are structurally unique C(sp^(3))-rich bicyclic hydrocarbons that are gaining prominence in the field of medicinal chemistry as bioisosteres of benzenoids.The nitrile is an important functi...Bicyclo[2.1.1]hexanes(BCHs) are structurally unique C(sp^(3))-rich bicyclic hydrocarbons that are gaining prominence in the field of medicinal chemistry as bioisosteres of benzenoids.The nitrile is an important functionality in drug development due to its ability to improve physicochemical and pharmacokinetic properties and facilitate potential noncovalent interactions with drug targets.Consequently,cyanoarene motifs are commonly found in drug development.The introduction of cyano-BCHs as potential bioisosteres of cyano-arenes shows great promise;however,there are currently no catalytic methods available for their synthesis.Herein,we report a palladium-catalyzed enantioselective [2σ+2π] cycloadditions of bicyclo[1.1.0]butanes with arylidenemalononitriles for the preparation of chiral cyano-BCHs.This method accommodated a wide range of substrates and tolerated various functional groups.The cyano-BCH products could be transformed to molecules with diverse functionality.Control experiments suggest that the reaction proceeds via a zwitterionic intermediate generated by palladium-mediated ring opening of vinyl-carbonyl bicyclo[1.1.0]butanes followed by stereoselective 1,2-addition and intramolecular allylic substitution reactions.展开更多
Allenes,characterized by their cumulated carbon–carbon double bonds,have emerged as indispensable synthons in the construction of complex natural products.Their unique reactivity and stereochemical properties render ...Allenes,characterized by their cumulated carbon–carbon double bonds,have emerged as indispensable synthons in the construction of complex natural products.Their unique reactivity and stereochemical properties render allenes a powerful tool for the efficient and streamlined total synthesis of structurally intricate natural products.This review comprehensively summarizes the total syntheses of complex natural products involving allene cycloaddition reactions reported over the past decade(2014—2024).Among the nearly 20 total syntheses reviewed,the[2+1],[2+2],[3+2],[4+2],[4+3],[5+1]and[2+2+1]cycloaddition reactions of allenes are the most important transformations to construct the key skeleton.This is because of their ability to form multiple bonds in a single step with high atom economy,stereoselectivity,and regioselectivity,often under mild conditions.The strategic application of these reactions in forming key carbon-carbon bonds and controlling stereochemistry makes them practical for the efficient assembly of complex molecular frameworks.With the ongoing exploration of methods for allene generation,particularly the enantioselective approaches,and the continued discovery of novel cyclization reactions of allenes,allene chemistry will maintain its crucial and indispensable role in the total synthesis of natural products.展开更多
Subject Code:B02 With the support by the National Natural Science Foundation of China,a collaborative study by the research groups led by Prof.Chen Yingchun(陈应春)from Sichuan University and Dr.Ouyang Qin(欧阳勤)from...Subject Code:B02 With the support by the National Natural Science Foundation of China,a collaborative study by the research groups led by Prof.Chen Yingchun(陈应春)from Sichuan University and Dr.Ouyang Qin(欧阳勤)from the Third Military Medical University demonstrates switchable regioselective[6+2]。展开更多
A highly efficient and mild method for[3 t 2]cycloaddition ofβ-sulfonyl-α,β-unsaturated ketones with terminal allenoates was well-explored and developed.The reactions were successfully performed by applying multifu...A highly efficient and mild method for[3 t 2]cycloaddition ofβ-sulfonyl-α,β-unsaturated ketones with terminal allenoates was well-explored and developed.The reactions were successfully performed by applying multifunctional chiral phosphine P6 which was screened from eight chiral phosphorus reagents to finally result in a variety of enantioenriched sulfone-substituted cyclopentenes with two chiral centers(up to 81%yield with 94%ee).Moreover,2.5 mol%catalytic equivalents were proved to be feasible when this reaction was performed on a 10 mmol scale.展开更多
The[8+4]cycloaddition of indene-2-carbaldehydes with indole-2,3-quinodimethanes and pyrrolidone-3,4-dienes is described,affording indole and pyrrolidone annulated bicyclo[4.2.1]nonanes in a highly peri-,diastereo-,and...The[8+4]cycloaddition of indene-2-carbaldehydes with indole-2,3-quinodimethanes and pyrrolidone-3,4-dienes is described,affording indole and pyrrolidone annulated bicyclo[4.2.1]nonanes in a highly peri-,diastereo-,and enantioselective fashion in the presence of a secondary amine catalyst.This reaction,which proceeds through catalytically generated isobenzofulvenes,represents the first asymmetric version of high-order[8+4]cycloaddition.展开更多
A new class of m-hydroxybenzyl alcohols has been designed as competent three-carbon building blocks and achieved their applica-tion in 2-indolylmethanol-involved regioselective(3+3)cycloadditions under the catalysis o...A new class of m-hydroxybenzyl alcohols has been designed as competent three-carbon building blocks and achieved their applica-tion in 2-indolylmethanol-involved regioselective(3+3)cycloadditions under the catalysis of Br?nsted acids.By this appoach,a series of indole-fused six-membered cycloadducts have been synthesized in overall good yields(up to 98%)with excellent regioselectivity(all>95:5 rr),thus affording a powerful method for the construction of indole-fused six-membered rings.Moreover,a catalytic asymmetric version of this(3+3)cycloaddition has been preliminarily investigated,which revealed the potential of the reaction for constructing chiral indole-fused six-membered rings in an enantioselective manner.This work not only has accomplished the first design of m-hydroxybenzyl alcohols as competent reactants,but also represents the first application of m-hydroxybenzyl alcohols as three-carbon building blocks in cycloadditions.In addition,this work provides a good example for regioselective and C3-nucleophilic(3+3)cycloadditions of 2-indolylmethanols,which will substantially enrich the chemistry of 2-indolylmethanols.展开更多
Comprehensive Summary Metallacyclopentadienes play a vital role in transition-metal mediated and catalyzed cycloaddition reactions of alkynes.Though versatile reactions of metallacyclopentadienes with alkynes have bee...Comprehensive Summary Metallacyclopentadienes play a vital role in transition-metal mediated and catalyzed cycloaddition reactions of alkynes.Though versatile reactions of metallacyclopentadienes with alkynes have been disclosed,[2+1]cycloadditions of metallacyclopentadienes and alkynes have never been discovered.In present work,we report the formal[2+1]cycloadditions of a metallacyclopentadiene unit with a broad scope of commercial alkynes,providing a facile strategy to construct tetracyclic conjugated compounds.The deuterated experiment indicates a metal vinylidene intermediate has been involved in[2+1]cycloaddition.Moreover,the electrophilic substitution reaction of the tetracyclic conjugated compound with the aid of density functional theory(DFT)calculated Fukui functions is investigated.展开更多
Understanding and controlling supramolecular template effect assembly via a photochemical reaction in different solid and solution phases is one of the main topics in photochemistry. Here, an interesting case of phase...Understanding and controlling supramolecular template effect assembly via a photochemical reaction in different solid and solution phases is one of the main topics in photochemistry. Here, an interesting case of phase-mediated controllable intramolecular/intermolecular photochemical [2+2] cycloadditions assisted by supramolecular templates was demonstrated. Direct irradiation of the complexes in solution yields intramolecular photoproducts exclusively, whereas exposure of the solid powder sample under the same conditions yields intermolecular dinuclear species quantitatively. The nature of the phase and supramolecular interaction affects the geometrical arrangements of the metallacycles, leading to different cycloaddition products under photoirradiation. The crystal structures of different products were investigated by single-crystal X-ray diffraction, nuclear magnetic resonance(NMR) spectrometry, and electrospray ionization mass spectrometry(ESI-MS).展开更多
A [3＋3] formal cycloaddition reaction between in situ formed azaoxyallyl cations and nitrones from isatins has been developed, furnishing a spectrum of spiro[1,2,4-oxadiazinan-5-one]oxindoles in good to excellent yie...A [3＋3] formal cycloaddition reaction between in situ formed azaoxyallyl cations and nitrones from isatins has been developed, furnishing a spectrum of spiro[1,2,4-oxadiazinan-5-one]oxindoles in good to excellent yields with excellent diastereoselectivity. This method provides direct and efficient access to potentially bioactive spirooxin- doles incorporating a six-membered heterocyclic scaffold.展开更多
The development of novel synthons and efficient methods to synthesize chiral polycyclic indoles has been a hot topic in organic synthesis and medicinal chemistry owing to their broad applications in medicines,pesticid...The development of novel synthons and efficient methods to synthesize chiral polycyclic indoles has been a hot topic in organic synthesis and medicinal chemistry owing to their broad applications in medicines,pesticides,and other functional molecules.Here,we disclosed novel indolyl substituted metal-allyl zwitterionic intermediates through the decarboxylation of conveniently available vinyl indoloxazolidones,which could be regarded as two types of dipolar species through the anionic delocalization.The palladium-π-allyl species tended to serve as an all-carbon 1,3-dipole in the asymmetric[3+2]cycloaddition with electrondeficient alkenes,which furnished polysubstituted cyclopenta[b]indoles with high regio-and stereoselectivities.Meanwhile,the iridium-π-allyl species was recognized as an aza-1,3-dipole in asymmetric[3+2]cycloaddition with in situ generated C1 ammonium enolates,affording pyrrolo[1,2-α]indoles with high diastereo-and enantioselectivities.In addition,the dipolar cycloadditions could be easily scaled-up and several synthetic transformations of the cycloadducts were demonstrated for the rapid synthesis of diverse chiral polycyclic indoles.展开更多
Chiral seven-membered ring systems such as seven-membered carbocycles and heterocycles are widely found in natural products and pharmaceuticals.Therefore,the catalytic enantioselective construction of such frameworks ...Chiral seven-membered ring systems such as seven-membered carbocycles and heterocycles are widely found in natural products and pharmaceuticals.Therefore,the catalytic enantioselective construction of such frameworks has evoked considerable interest in the field of chemistry.Among the various approaches,organocatalytic asymmetric(4+3)cycloadditions are highly effective for the enantioselective construction of seven-membered rings.Over the past two decades,substantial efforts have been devoted to this field and chemists have developed various organocatalytic asymmetric(4+3)cycloadditions.This review summarizes the progress in organocatalytic asymmetric(4+3)cycloadditions from 2003 to early 2022 and provides insights into challenging issues faced in this research field,enabling the future development of this field.展开更多
Three-membered unsaturated rings have been widely utilized in organic synthesis due to their inherent highly strained structures.Although much research has been applied to ring-expansion reactions of such strained rin...Three-membered unsaturated rings have been widely utilized in organic synthesis due to their inherent highly strained structures.Although much research has been applied to ring-expansion reactions of such strained ring systems,pathways other than[3+2]cycloadditions have rarely been observed in their reactions with alkynes,and to date,no[3+1]cycloadditions of isolated three-membered unsaturated rings with alkynes have been reported.Here we demonstrate an unprecedented[3+1]cycloaddition in which a fused metalla-azirine is used as a template to generate a series of planar CCCCX-type(X=N,O,S)pentadentate carbolong complexes 3–6.A series of substituted alkynes was tested for further exploration of the scope and mechanism for the[3+1]cycloaddition reactions.Complexes 3–6 represent rare examples of planar pentadentate complexes that assemble fourπ-conjugated fused rings by one bridgehead atom.These novel complexes are thermally stable in air and absorb ultraviolet,visible,and near-infrared light,and thus are potentially applicable in photoelectric devices and pharmaceuticals.展开更多
Regiodivergent asymmetric cycloadditions from the same set of starting materials offer interesting opportunities for rapid construction of optically active cyclic molecules with structural diversity.However,this remai...Regiodivergent asymmetric cycloadditions from the same set of starting materials offer interesting opportunities for rapid construction of optically active cyclic molecules with structural diversity.However,this remains a challenging task due to the difficulty of simultaneously controlling the regio-,diastereo-,and enantioselectivity in the ring formation processes.To address this long-standing problem.展开更多
Comprehensive Summary,The Pd-catalyzed dipolar cycloaddition represents a significant synthetic strategy for the construction of useful heterocyclic compounds.This study developed the dipolar[4+2]and[6+2]cycloaddition...Comprehensive Summary,The Pd-catalyzed dipolar cycloaddition represents a significant synthetic strategy for the construction of useful heterocyclic compounds.This study developed the dipolar[4+2]and[6+2]cycloaddition reactions of benzo[d]isothiazole 1,1-dioxides(BDs)leading to the synthesis of BD-fused 1,3-oxazinane and 1,3-oxazocane derivatives,respectively.In particular,the synthesis of BD-fused 1,3-oxazinanes demonstrated regio-and enantioselective characteristics,resulting in products with good yields,enantioselectivity and regioselectivity(if applicable).Furthermore,the[6+2]cycloaddition reaction developed in this work represented the first strategy for the synthesis of medium-sized ring compounds based on BDs.展开更多
文摘A Silver-catalyzed enantioselective[3+2]cycloaddition of azomethine ylides with activated alkenes by using a P-stereogenic ligand Ganphos is reported.The method provides an efficient strategy for the effective synthesis of spirocyclic scaffolds containing a pyrroline motif.Notable features of this approach include good yields,remarkable enantioselectivity,as well as a broad substrate scope and significant step efficiency.
基金Financial support from National Natural Science Foundation of China(Nos.21871282,22377113,22301309)Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB0590000)+6 种基金National Key Research and Development Program of China(No.2023YFA0914502)Taishan Scholar Program of Shandong Province(No.tsqn202306103,tsqn202306026)Postdoctoral Fellowship Program of CPSF(No.GZC20232509)Distinguished Young Scholars of Shandong Province(Overseas)(No.2022HWYQ-004)Shandong Postdoctoral Science Foundation(No.SDBX2023044)Qingdao Postdoctoral Science Foundation(No.QDBSH20230202048)the Fundamental Research Funds for the Central Universities(Ocean University of China)。
文摘Pyrazolidinones,as significant analogs ofβ-lactam antibiotics,have garnered substantial interest for their enantioselective synthesis.Azomethine imines,recognized as valuable building blocks for the construction of these nitrogen-containing compounds,underscore the continuous pursuit of novel building blocks and reaction methodologies within the chemical community.In this paper,we present a cascade cyclization between alkenyl azomethine imines and furan-2(5H)-one to generate chiral coronal polyheterocyclic compounds with high yields and enantioselectivities,catalyzed by dipeptide-derived phosphonium salts.In-vitro biological activity assays highlight the potential of these chiral compounds in drug discovery.Additionally,density functional theory(DFT)calculations elucidate the pivotal role of phosphonium salts,demonstrating their cooperative activations via hydrogen bonding and ion-pairing interactions.
基金supported by the National Natural Science Foundation of China(Nos.21302174,21672193 and 21272218)China Post-doctoral Science Foundation(No.2017M622362)+1 种基金Ministry of Industry and Information Technology of the People's Republic of China(No.Z135060009002)Key Research Projects of Universities in Henan Province(No.20A150040)。
文摘A cascade carbonylative ring expansion and [2+2]/[4+2] cycloaddition of strained 1-iminylphosphirane complexes with aryl allenes were reported.The carbonylative ring expansion of 1-iminylphosphirane complexes provides an azaphosphacyclohexone complex intermediate with a C=P double bond.The following [2+2] or dearomatic [4+2] cycloaddition of this intermediate with allenes is modulated by the aryl substituents on the imino carbon.The regioselective [2+2] cycloaddition with 1,1-diarylallene provides an entry to bicyclo[4.2.0]octan-4-one skeletons featuring a four-membered phosphacyclobutane moiety.While dearomatic [4+2] cycloaddition was preferred with less aromatic naphthalene and yielded octahydrochrysene skeleton containing heteroatoms.
基金the financial support for this investigation from the National Natural Science Foundation of China(Nos.21772151,22072111)the Fundamental Research Funds for Central Universities(No.WUT:2021IVA121).
文摘The first example of stereoconvergent 1,3-dipolar cycloaddition of nitrile oxides and nitrile imines with E/Z isomeric mixture of electron-deficient olefins is reported,delivering isoxazolines and pyrazolines bearing two vicinal stereogenic tertiary and trifluoromethylated quaternary carbon centers with perfect regioand diastereoselectivities.The possibility of concerted cycloaddition/epimerization sequence under basic condition to form the thermodynamically stable diastereomers is excluded through some control experiments and DFT calculations,and a stepwise mechanism is proposed.
基金supported by the Research Grants Council General Research Fund (No. 17301314)
文摘Furans bearing epoxy enolsilane units via a tether that incorporates a nitrogen heteroatom,undergo intramolecular(4+3)cycloadditions to generate bis-heteroatomic polycyclic adducts having piperidine moieties in their frameworks.The cycloadducts,ultimately derived from furfural,a renewal chemical feedstock,are obtained with up to 4:1 dr and with ee retained from the epoxide.
文摘Tetracyclic coumarins are a class of important compounds with diverse and superior pharmacolog‐ical activities.However,a direct stereoselective method from simple and readily‐made coumarins derivatives remains challenging due to the inertness of coumarins as dienophiles.Herein,we de‐velop a decarboxylative asymmetric[4+2]cycloaddition of 3‐cyanocoumarins with vinyl benzoxa‐zinones,affording the coumarin‐derived condensed rings bearing three continuous stereocenters in high yields with excellent diastereoselectivities(>20/1 d.r.)and enantioselectivities(up to 99%ee).This direct enantioselective reaction was achieved by a Pd(0)/Cu(I)bimetallic catalytic system.The mechanism studies indicated that the synergistic activation effect,in which chiral Cu(I)as an availa‐ble Lewis acid catalyst activates 3‐cyanocoumarin and chiral Pd(0)complex activates benzoxazi‐none by the formation ofπ‐allyl‐palladium intermediate,plays an important role on the stereoselec‐tive control.The current work provides a new activation modes of Cu catalyst in the Pd/Cu bimetal‐lic catalytic system.
基金funding support from the National Key R&D Program of China (Nos.2022YFA1503703,2023YFA1506700)the National Natural Science Foundation of China (Nos.22071118,22271162)the Haihe Laboratory of Sustainable Chemical Transformations and the Fundamental Research Funds for the Central Universities for financial support。
文摘Bicyclo[2.1.1]hexanes(BCHs) are structurally unique C(sp^(3))-rich bicyclic hydrocarbons that are gaining prominence in the field of medicinal chemistry as bioisosteres of benzenoids.The nitrile is an important functionality in drug development due to its ability to improve physicochemical and pharmacokinetic properties and facilitate potential noncovalent interactions with drug targets.Consequently,cyanoarene motifs are commonly found in drug development.The introduction of cyano-BCHs as potential bioisosteres of cyano-arenes shows great promise;however,there are currently no catalytic methods available for their synthesis.Herein,we report a palladium-catalyzed enantioselective [2σ+2π] cycloadditions of bicyclo[1.1.0]butanes with arylidenemalononitriles for the preparation of chiral cyano-BCHs.This method accommodated a wide range of substrates and tolerated various functional groups.The cyano-BCH products could be transformed to molecules with diverse functionality.Control experiments suggest that the reaction proceeds via a zwitterionic intermediate generated by palladium-mediated ring opening of vinyl-carbonyl bicyclo[1.1.0]butanes followed by stereoselective 1,2-addition and intramolecular allylic substitution reactions.
基金supported by National Key R&D Program of China(No.2022YFE0205500)Shenzhen Medical Research Fund(D2403012)+4 种基金State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources(Guangxi Normal University,CMEMR2024-B18)the National Natural Science Foundation of China(Grant nos.22225102,22371212)the Guangdong Department of Education(No.2021ZDJS097)the Shenzhen Science and Technology Program(JCYJ20220818100603008)high levelof special funds(G03050K003).
文摘Allenes,characterized by their cumulated carbon–carbon double bonds,have emerged as indispensable synthons in the construction of complex natural products.Their unique reactivity and stereochemical properties render allenes a powerful tool for the efficient and streamlined total synthesis of structurally intricate natural products.This review comprehensively summarizes the total syntheses of complex natural products involving allene cycloaddition reactions reported over the past decade(2014—2024).Among the nearly 20 total syntheses reviewed,the[2+1],[2+2],[3+2],[4+2],[4+3],[5+1]and[2+2+1]cycloaddition reactions of allenes are the most important transformations to construct the key skeleton.This is because of their ability to form multiple bonds in a single step with high atom economy,stereoselectivity,and regioselectivity,often under mild conditions.The strategic application of these reactions in forming key carbon-carbon bonds and controlling stereochemistry makes them practical for the efficient assembly of complex molecular frameworks.With the ongoing exploration of methods for allene generation,particularly the enantioselective approaches,and the continued discovery of novel cyclization reactions of allenes,allene chemistry will maintain its crucial and indispensable role in the total synthesis of natural products.
文摘Subject Code:B02 With the support by the National Natural Science Foundation of China,a collaborative study by the research groups led by Prof.Chen Yingchun(陈应春)from Sichuan University and Dr.Ouyang Qin(欧阳勤)from the Third Military Medical University demonstrates switchable regioselective[6+2]。
基金The authors are grateful to NSFC(Nos.21971066 and 21772042)for financial support.Special thanks to profJunliang Zhang(Fudan University)for his kind suggestion on this[3 t 2]cycloaddition reaction.
文摘A highly efficient and mild method for[3 t 2]cycloaddition ofβ-sulfonyl-α,β-unsaturated ketones with terminal allenoates was well-explored and developed.The reactions were successfully performed by applying multifunctional chiral phosphine P6 which was screened from eight chiral phosphorus reagents to finally result in a variety of enantioenriched sulfone-substituted cyclopentenes with two chiral centers(up to 81%yield with 94%ee).Moreover,2.5 mol%catalytic equivalents were proved to be feasible when this reaction was performed on a 10 mmol scale.
基金This work is supported by the National Natural Science Foundation of China(Nos.21772038 and 21971062)The authors thank the Research Center of Analysis and Test of East China University of Science and Technology for the assistance with the HRMS and NMR analysis.
文摘The[8+4]cycloaddition of indene-2-carbaldehydes with indole-2,3-quinodimethanes and pyrrolidone-3,4-dienes is described,affording indole and pyrrolidone annulated bicyclo[4.2.1]nonanes in a highly peri-,diastereo-,and enantioselective fashion in the presence of a secondary amine catalyst.This reaction,which proceeds through catalytically generated isobenzofulvenes,represents the first asymmetric version of high-order[8+4]cycloaddition.
基金financial support from the National Natural Science Foundation of China(22125104 and 21831007)the Natural Science Foundation of Jiangsu Province(BK20210916)+1 种基金the High Education Natural Science Foundation of Jiangsu Province(No.21KJB150009)Undergraduate Students Project of Jiangsu Province(No.202110320019Z).
文摘A new class of m-hydroxybenzyl alcohols has been designed as competent three-carbon building blocks and achieved their applica-tion in 2-indolylmethanol-involved regioselective(3+3)cycloadditions under the catalysis of Br?nsted acids.By this appoach,a series of indole-fused six-membered cycloadducts have been synthesized in overall good yields(up to 98%)with excellent regioselectivity(all>95:5 rr),thus affording a powerful method for the construction of indole-fused six-membered rings.Moreover,a catalytic asymmetric version of this(3+3)cycloaddition has been preliminarily investigated,which revealed the potential of the reaction for constructing chiral indole-fused six-membered rings in an enantioselective manner.This work not only has accomplished the first design of m-hydroxybenzyl alcohols as competent reactants,but also represents the first application of m-hydroxybenzyl alcohols as three-carbon building blocks in cycloadditions.In addition,this work provides a good example for regioselective and C3-nucleophilic(3+3)cycloadditions of 2-indolylmethanols,which will substantially enrich the chemistry of 2-indolylmethanols.
基金the National Natural Science Foundation of China(Nos.21931002,22071098,22101115,and 22101123)the Shenzhen Science and Technology Innovation Committee(Nos.JCYJ20200109140812302 and JCYJ20210324105013035)the Guangdong Provincial Key Laboratory of Catalysis(No.2020B121201002)。
文摘Comprehensive Summary Metallacyclopentadienes play a vital role in transition-metal mediated and catalyzed cycloaddition reactions of alkynes.Though versatile reactions of metallacyclopentadienes with alkynes have been disclosed,[2+1]cycloadditions of metallacyclopentadienes and alkynes have never been discovered.In present work,we report the formal[2+1]cycloadditions of a metallacyclopentadiene unit with a broad scope of commercial alkynes,providing a facile strategy to construct tetracyclic conjugated compounds.The deuterated experiment indicates a metal vinylidene intermediate has been involved in[2+1]cycloaddition.Moreover,the electrophilic substitution reaction of the tetracyclic conjugated compound with the aid of density functional theory(DFT)calculated Fukui functions is investigated.
基金supported by the National Natural Science Foundation of China (22025107, 21722105)the National Youth Top-notch Talent Support Program of China+2 种基金the Key Science and Technology Innovation Team of Shaanxi Province (2019TD-007, 2019JLZ-02)Xi’an Key Laboratory of Functional Supramolecular Structure and Materialsthe FM&EM International Joint Laboratory of Northwest University。
文摘Understanding and controlling supramolecular template effect assembly via a photochemical reaction in different solid and solution phases is one of the main topics in photochemistry. Here, an interesting case of phase-mediated controllable intramolecular/intermolecular photochemical [2+2] cycloadditions assisted by supramolecular templates was demonstrated. Direct irradiation of the complexes in solution yields intramolecular photoproducts exclusively, whereas exposure of the solid powder sample under the same conditions yields intermolecular dinuclear species quantitatively. The nature of the phase and supramolecular interaction affects the geometrical arrangements of the metallacycles, leading to different cycloaddition products under photoirradiation. The crystal structures of different products were investigated by single-crystal X-ray diffraction, nuclear magnetic resonance(NMR) spectrometry, and electrospray ionization mass spectrometry(ESI-MS).
文摘A [3＋3] formal cycloaddition reaction between in situ formed azaoxyallyl cations and nitrones from isatins has been developed, furnishing a spectrum of spiro[1,2,4-oxadiazinan-5-one]oxindoles in good to excellent yields with excellent diastereoselectivity. This method provides direct and efficient access to potentially bioactive spirooxin- doles incorporating a six-membered heterocyclic scaffold.
基金the National Natural Science Foundation of China(21901072)the China Postdoctoral Science Foundation(2019T120310)Shanghai Sailing Program(18YF140560)。
文摘The development of novel synthons and efficient methods to synthesize chiral polycyclic indoles has been a hot topic in organic synthesis and medicinal chemistry owing to their broad applications in medicines,pesticides,and other functional molecules.Here,we disclosed novel indolyl substituted metal-allyl zwitterionic intermediates through the decarboxylation of conveniently available vinyl indoloxazolidones,which could be regarded as two types of dipolar species through the anionic delocalization.The palladium-π-allyl species tended to serve as an all-carbon 1,3-dipole in the asymmetric[3+2]cycloaddition with electrondeficient alkenes,which furnished polysubstituted cyclopenta[b]indoles with high regio-and stereoselectivities.Meanwhile,the iridium-π-allyl species was recognized as an aza-1,3-dipole in asymmetric[3+2]cycloaddition with in situ generated C1 ammonium enolates,affording pyrrolo[1,2-α]indoles with high diastereo-and enantioselectivities.In addition,the dipolar cycloadditions could be easily scaled-up and several synthetic transformations of the cycloadducts were demonstrated for the rapid synthesis of diverse chiral polycyclic indoles.
基金supported by the National Natural Science Foundation of China(22125104,21831007)the Natural Science Foundation of Jiangsu Province(BK20210916)the High Education Natural Science Foundation of Jiangsu Province(21KJB150009)。
文摘Chiral seven-membered ring systems such as seven-membered carbocycles and heterocycles are widely found in natural products and pharmaceuticals.Therefore,the catalytic enantioselective construction of such frameworks has evoked considerable interest in the field of chemistry.Among the various approaches,organocatalytic asymmetric(4+3)cycloadditions are highly effective for the enantioselective construction of seven-membered rings.Over the past two decades,substantial efforts have been devoted to this field and chemists have developed various organocatalytic asymmetric(4+3)cycloadditions.This review summarizes the progress in organocatalytic asymmetric(4+3)cycloadditions from 2003 to early 2022 and provides insights into challenging issues faced in this research field,enabling the future development of this field.
基金supported by the National Natural Science Foundation of China(U1705254,21871225,and 21931002)the Fundamental Research Funds for the Central Universities(20720190042),and the Research Grants Council of Hong Kong(N_HKUST603/15).
文摘Three-membered unsaturated rings have been widely utilized in organic synthesis due to their inherent highly strained structures.Although much research has been applied to ring-expansion reactions of such strained ring systems,pathways other than[3+2]cycloadditions have rarely been observed in their reactions with alkynes,and to date,no[3+1]cycloadditions of isolated three-membered unsaturated rings with alkynes have been reported.Here we demonstrate an unprecedented[3+1]cycloaddition in which a fused metalla-azirine is used as a template to generate a series of planar CCCCX-type(X=N,O,S)pentadentate carbolong complexes 3–6.A series of substituted alkynes was tested for further exploration of the scope and mechanism for the[3+1]cycloaddition reactions.Complexes 3–6 represent rare examples of planar pentadentate complexes that assemble fourπ-conjugated fused rings by one bridgehead atom.These novel complexes are thermally stable in air and absorb ultraviolet,visible,and near-infrared light,and thus are potentially applicable in photoelectric devices and pharmaceuticals.
基金from the National Natural Science Foundation of China(grant nos.22071209 and 22071206)the National Youth Talent Support Program,the Natural Science Foundation of Fujian Province of China(grant no.2017J06006)+1 种基金the Fundamental Research Funds for the Central Universities(grant no.20720190048)Basic Disciplines Training Program for Top-notch Students of the Ministry of Education.
文摘Regiodivergent asymmetric cycloadditions from the same set of starting materials offer interesting opportunities for rapid construction of optically active cyclic molecules with structural diversity.However,this remains a challenging task due to the difficulty of simultaneously controlling the regio-,diastereo-,and enantioselectivity in the ring formation processes.To address this long-standing problem.
基金supported by the NSFC(22071210,22101033,22201023,22271242)the Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology(BM2012110)+1 种基金the Natural Science Foundation of Jiangsu Province(BK20210849)the Innovation&Entrepreneurship Talents Plan of Jiangsu Province(JSSCRC2021536).
文摘Comprehensive Summary,The Pd-catalyzed dipolar cycloaddition represents a significant synthetic strategy for the construction of useful heterocyclic compounds.This study developed the dipolar[4+2]and[6+2]cycloaddition reactions of benzo[d]isothiazole 1,1-dioxides(BDs)leading to the synthesis of BD-fused 1,3-oxazinane and 1,3-oxazocane derivatives,respectively.In particular,the synthesis of BD-fused 1,3-oxazinanes demonstrated regio-and enantioselective characteristics,resulting in products with good yields,enantioselectivity and regioselectivity(if applicable).Furthermore,the[6+2]cycloaddition reaction developed in this work represented the first strategy for the synthesis of medium-sized ring compounds based on BDs.
