A dearomatization strategy using dicetolic acid(6)as the starting material to synthesize the core intermediate(10R,13S,14S)-10,13-dimethyl-7,10,11,12,13,14,15,16-octahydro-3H-cyclopenta[a]phenanthrene-3,17(6H)-dione(2...A dearomatization strategy using dicetolic acid(6)as the starting material to synthesize the core intermediate(10R,13S,14S)-10,13-dimethyl-7,10,11,12,13,14,15,16-octahydro-3H-cyclopenta[a]phenanthrene-3,17(6H)-dione(20)for the formal synthesis of dydrogesterone is presented,achieving a total yield of 21%over nine steps.This approach features an environmentally friendly carbonyl protection strategy and efficient Heck coupling,while avoiding harsh conditions and hazardous reagents throughout the entire process.展开更多
Linear alkyl benzenes （LABs） are the main materials for detergent production. The presence of aromatic compounds in this material can decrease the quality of the final product and enhance the deactivation rate of ca...Linear alkyl benzenes （LABs） are the main materials for detergent production. The presence of aromatic compounds in this material can decrease the quality of the final product and enhance the deactivation rate of catalysts. In this research we used zeolite NaX for de-aromatization of the recycled paraffin from the alkylation unit of an LAB production complex. The effect of different parameters on the removal efficiency of adsorbent was studied and optimized. To study the re-usability of the adsorbent, the breakthrough curves were obtained by using a fixed bed column filled with the adsorbent. The results indicated that the adsorbent capacity remained unchanged after three regeneration cycles. The Langmuir and Freundlich adsorption models were applied to describe the equilibrium isotherms. It was concluded that the Langmuir model agreed well with the experimental data. The calculated thermodynamic parameters of the adsorption showed that the adsorption process was spontaneous and exothermic. The reaction rate was estimated by the pseudo-second order kinetic model.展开更多
We report herein a palladium-catalyzed diarylative dearomatization of indole by employing thioester and arylboronic acid as the aryl electrophiles.The reaction involved a decarbonylation/migratory insertion/terminal S...We report herein a palladium-catalyzed diarylative dearomatization of indole by employing thioester and arylboronic acid as the aryl electrophiles.The reaction involved a decarbonylation/migratory insertion/terminal Suzuki coupling procedure.Substrates bearing various functional groups are well tolerated in the reaction,affording the diarylated indoline skeletons in moderate to good yields.展开更多
A straightforward and efficient protocol for dearomatizing indoles is described.The reaction,catalyzed by an inexpensive Co(III)/Zn(II)catalyst,starts from easily accessible N‐pyrimidinyl indoles and ene‐yne ketones...A straightforward and efficient protocol for dearomatizing indoles is described.The reaction,catalyzed by an inexpensive Co(III)/Zn(II)catalyst,starts from easily accessible N‐pyrimidinyl indoles and ene‐yne ketones.Mild reaction conditions,high diastereoselectivity,a broad substrate scope,effective functional group tolerance,and reasonable to remarkable yields were observed.展开更多
A catalytic asymmetric hydroxylative dearomatization reaction has been disclosed,and the products can smoothly transform into spiroannulation adducts by simply treated with a base under mild conditions.Novel in-situ g...A catalytic asymmetric hydroxylative dearomatization reaction has been disclosed,and the products can smoothly transform into spiroannulation adducts by simply treated with a base under mild conditions.Novel in-situ generated magnesium catalytic methods are developed by application of combinational ligands.Related concise transformaitons of the spiroannulation adducts have been carried out.展开更多
Photo‐catalyzed tandem dearomatization/carboxylation of benzyl o‐halogenated aryl ether with CO_(2) was achieved,which affords spirocyclic carboxylic acids under mild conditions.The reaction has good functional grou...Photo‐catalyzed tandem dearomatization/carboxylation of benzyl o‐halogenated aryl ether with CO_(2) was achieved,which affords spirocyclic carboxylic acids under mild conditions.The reaction has good functional group tolerance with high yields.Mechanism studies indicate that the transformation was realized via intramolecular radical addition and nucleophilic addition.展开更多
Atom-and step-economy in IBX assisted diversity-oriented synthesis is achieved with a versatile AQ auxiliary α-amino acid analogs offering rapid access to polycyclic spiro-quinolines featuring a quaternary stereocent...Atom-and step-economy in IBX assisted diversity-oriented synthesis is achieved with a versatile AQ auxiliary α-amino acid analogs offering rapid access to polycyclic spiro-quinolines featuring a quaternary stereocenter in 20%–91% yields under mild conditions via 7,8-dearomatization of quinolines. Free of a preinstalled activation group is highlight of this intramolecular oxidation spiroannulation tandem reaction. This type of N-heterospirocycles, traditionally difficult to access, may open the door to a potentially interest scaffold for synthetic and medicinal chemistry.展开更多
The copper-catalyzed directed dearomatization of indoles with the assistance of directing groups has been developed for the synthesis of 2,3-diazido indolines with good yields and excellent diastereoselectivities in a...The copper-catalyzed directed dearomatization of indoles with the assistance of directing groups has been developed for the synthesis of 2,3-diazido indolines with good yields and excellent diastereoselectivities in aqueous solution.The resultant 2,3-diazides can be smoothly converted to other functional groups,including vicinal diamines,triazoles and benzotriazoles,in a single step.展开更多
Catalytic asymmetric dearomatization of indoles and alkynes has received much attention in the past decade because this strategy offers an attractive and alternative way for the efficient synthesis of valuable chiral ...Catalytic asymmetric dearomatization of indoles and alkynes has received much attention in the past decade because this strategy offers an attractive and alternative way for the efficient synthesis of valuable chiral polycyclic indolines. However, these reactions have been mostly limited to transition-metal catalysts, and the related chiral Br■nsted acid catalysis has been scarcely reported. Herein, we disclose a chiral phosphoric acid-catalyzed asymmetric dearomatization of indolyl ynamides by direct activation of alkynes. This metal-free method enables the practical and atom-economical construction of an array of valuable chiral polycyclic indolines in moderate to good yields with high enantioselectivities.展开更多
A catalytic asymmetric brominative dearomatization reaction of benzofuran derivatives was achieved by using hydroquinidine 1,4-phthalazinediyl diether [（DHQ）_2PHAL] as the catalyst and N-bromoacetamide（NBAc） as th...A catalytic asymmetric brominative dearomatization reaction of benzofuran derivatives was achieved by using hydroquinidine 1,4-phthalazinediyl diether [（DHQ）_2PHAL] as the catalyst and N-bromoacetamide（NBAc） as the brominating reagent. A series of brominated spiro[benzofuran-2,5＇-oxazoles] bearing two contiguous stereogenic centers were obtained in high yields（up to 99%） with excellent enantioselectivity（up to 97% ee）.展开更多
1,7-Hydride transfer-involved dearomatization of quinolines toward C3-spiro hydroquinoline derivatives has been developed.This method offers a protocol to achieve the dearomatization of electron-deficient arenes via t...1,7-Hydride transfer-involved dearomatization of quinolines toward C3-spiro hydroquinoline derivatives has been developed.This method offers a protocol to achieve the dearomatization of electron-deficient arenes via the redox-neutral hydride transfer process.A series of C3-spiro hydroquinolines can be provided in moderate to excellent yields(up to 98%)with good diastereoselectivities.Significant advantages such as high step-and atomeconomy,as well as redox-neutral and mild conditions,make it an appealing alternative to achieve the dearomatization of quinolines.展开更多
The dearomatization of indole derivatives bearing amide functionalities presents a significant challenge due to the inherent stability of the amide carbonyl group,resulting from nitrogen lone-pair delocalization that ...The dearomatization of indole derivatives bearing amide functionalities presents a significant challenge due to the inherent stability of the amide carbonyl group,resulting from nitrogen lone-pair delocalization that imparts increased resonance stabilization.In this study,we report a visible-light photocatalytic intramolecular dearomatization of indole derivatives with amide groups,achieving the synthesis of spiroindolines via energy transfer.This method enables the efficient formation of a range of hydroxyl-substituted spiroindolines in moderate to high yields,with excellent diastereoselectivity(>20:1)under mild reaction conditions.Control experiments confirmed the involvement of an energy transfer pathway in the reaction mechanism.Density Functional Theory(DFT)calculations further revealed r-stacking interactions between the indole core and pyridine ring,along with the strengthening of hydrogen bonding between the pyridine nitrogen and hexafluoroisopropanol(HFiP)in the excited state.These interactions facilitated the energy transfer-mediated triplet excited state intermolecular proton transfer(T-ESPT),crucial for activating the otherwise amide functionality.This protocol represents a rare example of harnessing the reactivity of amide groups for dearomative transformations.展开更多
Dydrogesterone as an agonist of the progesterone receptor is an important and selective synthetic progesterone used for the treatment of a variety of conditions associated with progesterone deficiency including menstr...Dydrogesterone as an agonist of the progesterone receptor is an important and selective synthetic progesterone used for the treatment of a variety of conditions associated with progesterone deficiency including menstrual cycle regulation,infertility,and prevention of miscarriage.Its manufacturing process employing photochemical reactions remains a significant challenge.Herein we report the first total synthesis of dydrogesterone via a key 10α-substitution-selective dearomative cyclizationfree of photochemical protocols starting from Hajos-Parrish ketone.A gram-scale synthesis is also accomplished from readily available 9-hydroxy-4-androstene-3,17-dione through a novel aromatization-dearomatization strategy of ring A in steroid chemistry.Key synthetic features include a facile chemical aromatization of 9-hydroxy-4-androstene-3,17-dione,efficient ligand-controlled asymmetric dearomative cyclization to install the 10α-Me group,and an effective hydroxyl-directed hydrogenation of sterically congested tetrasubstituted olefin to establish the 8β-H,9β-H stereochemistry.展开更多
Chiral[2.2]paracyclophane(PCP)is an intriguing prevalent scaffold widely utilized inπ-stacked polymers,luminescent materials,and asymmetric catalysis.However,current synthetic methods to access chiral PCP derivatives...Chiral[2.2]paracyclophane(PCP)is an intriguing prevalent scaffold widely utilized inπ-stacked polymers,luminescent materials,and asymmetric catalysis.However,current synthetic methods to access chiral PCP derivatives are still limited to physical separation and chemical or kinetic resolution.The direct desymmetric functionalization of nonsubstituted PCP has been a challenge since its discovery 70 years ago.Herein,we present a catalytic desymmetric dearomatization cyclopropanation reaction of PCP,providing rapid access to enantioenriched PCP cyclopropyl carboxylates with continuous tertiary/quaternary/quaternary chiral centers.The application of the chiral PCPs obtained has also been demonstrated by transformation to structurally novel C_(2) symmetric dirhodium catalysts.Of equal importance,detailed density functional theory calculations have been carried out to reveal the mechanism of this reaction.The key to this success is a structurally symmetric bulky C_(4) dirhodium catalyst:noncovalent interactions exist between substrates and catalysts,which form a cavity to host substrates,and mainly affect the regio-and enantioselectivity.展开更多
An asymmetric fluorinative dearomatization reaction of tryptophol derivatives was developed via chiral anion phase-transfer catalysis. Vari- ous fluorinated furoindolines were obtained in moderate to excellent yields ...An asymmetric fluorinative dearomatization reaction of tryptophol derivatives was developed via chiral anion phase-transfer catalysis. Vari- ous fluorinated furoindolines were obtained in moderate to excellent yields and enantioselectivity in the presence of Selectfluor. The preliminary mecha- nistic studies suggested the existence of an in situ formed tryptophol boronic ester plays a critical role in determining the enantioselectivity. This method features the facile introduction of a fluorine atom in a highly enantioselective manner and construction of two contiguous quaternary stereogenic cen- ters.展开更多
Copper-catalyzed intermolecular oxidative-etherification type dearomatization reaction of 2-naphthols was developed.With air as the terminal oxidant,the reaction proceeded in excellent yields under mild conditions.In ...Copper-catalyzed intermolecular oxidative-etherification type dearomatization reaction of 2-naphthols was developed.With air as the terminal oxidant,the reaction proceeded in excellent yields under mild conditions.In addition,the reaction between two different naphthol substrates occurred smoothly.A series of multifunctionalized β-naphthalenones,important scaffold existed widely in natural products and biologically active molecules,were synthesized efficiently.展开更多
Herein,we report a novel palladium(Pd)-catalyzed asymmetric domino Heck/carbocyclization/Suzuki reaction of N-(2-bromoaryl)-2-naphthylacrylamides.The reaction involves a novel and enantioselective dearomative 1,2-inse...Herein,we report a novel palladium(Pd)-catalyzed asymmetric domino Heck/carbocyclization/Suzuki reaction of N-(2-bromoaryl)-2-naphthylacrylamides.The reaction involves a novel and enantioselective dearomative 1,2-insertion of the naphthalene group,thus providing a unique dearomatization strategy of nonactivated naphthalenes.A new phosphoramidite ligand L12,which displayed excellent reactivity and enantioselectivity in the reaction,has been developed.展开更多
Spiro compounds are widely prevalent in biological activities and natural products.However,developing new strategies for their efficient synthesis and derivatization remains a challenge.Outstanding progress has been m...Spiro compounds are widely prevalent in biological activities and natural products.However,developing new strategies for their efficient synthesis and derivatization remains a challenge.Outstanding progress has been made in the synthesis of spiro compounds through dearomatization of aromatic compounds,most of them are mediated by the hypervalent iodine reagents.Herein,we report a method of anodic oxidation spiroamination and spirolactonization of anisole derivatives with concomitant cathodic reduction of protons in the absence of hypervalent iodine reagents.A wide variety of spiropyrrolidines and spirolactones with diverse functional groups made useful scaffolds in this transformation,with yields up to 97%.Moreover,hectogram-scale synthesis could supply target product with 83% yield in a flow electrochemical cell using carbon paper as the anode and nickel plate as the cathode,demonstrating the potential application of this method.展开更多
An enantioselective[4+1]spiroannulation ofαbromo-β-naphthols with azoalkenes has been developed for the one-step construction of a new class of pyrazoline-based spirocyclic molecules.Using chiral Cu(II)/Box catalyst...An enantioselective[4+1]spiroannulation ofαbromo-β-naphthols with azoalkenes has been developed for the one-step construction of a new class of pyrazoline-based spirocyclic molecules.Using chiral Cu(II)/Box catalysts,asymmetric induction was achieved with high levels of enantioselectivity[up to 99:1 enantiomeric ratio(er)].Notably,α-chloroandα-iodo-substitutedβ-naphthols were also tolerated by this reaction.Mechanistic studies disclosed that this process was triggered by electrophilefacilitated dearomatization ofα-bromo-β-naphthols and followed by the debromination via SRN 1-subsitution with in situ-formed N-nucleophile.The chiral copper(II)-species,bound with azoalkene moiety,was assumed to control the enantiodiscrimination over the naphthoxy C-radical that was generated from the debromination step.Moreover,the potential utility of this protocol was greatly amplified by the derivatization of spirocyclic products through oxidative dearomatization of the other aromatic ring in the naphthyl fragment,providing a rather attractive route for the rapid generation of synthetically more valuable doubly dearomatized architectures.展开更多
Asymmetric construction of quinuclidine derivatives has been realized by an iridium-catalyzed allylic dearomatization reaction.The catalytic system,derived from[Ir(cod)Cl]2 and the Feringa ligand,tolerates a broad ran...Asymmetric construction of quinuclidine derivatives has been realized by an iridium-catalyzed allylic dearomatization reaction.The catalytic system,derived from[Ir(cod)Cl]2 and the Feringa ligand,tolerates a broad range of substrates.A large array of quinuclidine derivatives can be obtained under mild conditions in good to excellent yields(68%–96%),diastereoselectivity(up to>20/1 dr),and enantioselectivity(up to>99%ee).These pro-ducts feature versatile functional group diversity and can undergo diverse transformations.A model that accounts for the origin of the stereoselectivity has been proposed based on density functional theory(DFT)calculations.展开更多
文摘A dearomatization strategy using dicetolic acid(6)as the starting material to synthesize the core intermediate(10R,13S,14S)-10,13-dimethyl-7,10,11,12,13,14,15,16-octahydro-3H-cyclopenta[a]phenanthrene-3,17(6H)-dione(20)for the formal synthesis of dydrogesterone is presented,achieving a total yield of 21%over nine steps.This approach features an environmentally friendly carbonyl protection strategy and efficient Heck coupling,while avoiding harsh conditions and hazardous reagents throughout the entire process.
基金Financial support of the Iran Chemical Industries Investment Company is greatly acknowledged
文摘Linear alkyl benzenes （LABs） are the main materials for detergent production. The presence of aromatic compounds in this material can decrease the quality of the final product and enhance the deactivation rate of catalysts. In this research we used zeolite NaX for de-aromatization of the recycled paraffin from the alkylation unit of an LAB production complex. The effect of different parameters on the removal efficiency of adsorbent was studied and optimized. To study the re-usability of the adsorbent, the breakthrough curves were obtained by using a fixed bed column filled with the adsorbent. The results indicated that the adsorbent capacity remained unchanged after three regeneration cycles. The Langmuir and Freundlich adsorption models were applied to describe the equilibrium isotherms. It was concluded that the Langmuir model agreed well with the experimental data. The calculated thermodynamic parameters of the adsorption showed that the adsorption process was spontaneous and exothermic. The reaction rate was estimated by the pseudo-second order kinetic model.
基金the Shanghai Institute of Materia Medicathe Chinese Academy of Sciences+4 种基金the National Natural Science Foundation of China(Nos.21772211 and 21920102003)the Youth Innovation Promotion Association CAS(Nos.2014229 and 2018293)the Science and Technology Commission of Shanghai Municipality(Nos.17JC1405000 and 18431907100)the Program of Shanghai Academic Research Leader(No.19XD1424600)the National Science&Technology Major Project“Key New Drug Creation and Manufacturing Program”,China(No.2018ZX09711002-006)for financial support。
文摘We report herein a palladium-catalyzed diarylative dearomatization of indole by employing thioester and arylboronic acid as the aryl electrophiles.The reaction involved a decarbonylation/migratory insertion/terminal Suzuki coupling procedure.Substrates bearing various functional groups are well tolerated in the reaction,affording the diarylated indoline skeletons in moderate to good yields.
文摘A straightforward and efficient protocol for dearomatizing indoles is described.The reaction,catalyzed by an inexpensive Co(III)/Zn(II)catalyst,starts from easily accessible N‐pyrimidinyl indoles and ene‐yne ketones.Mild reaction conditions,high diastereoselectivity,a broad substrate scope,effective functional group tolerance,and reasonable to remarkable yields were observed.
基金the financial support from the National Natural Science Foundation of China (Nos. 21901092, 21807053)Innovation Fund for Medical Sciences (No. 2019-12M-5-074)+2 种基金Program for Chang-jiang Scholars and Innovative Research Team in University (PCSIRT) (No. IRT_15R27)the Funds for Fundamental Research Creative Groups of Gansu Province (No. 20JR5RA310)the Fundamental Research Funds for the Central Universities (Nos. lzujbky2020-49, 2021-kb21)
文摘A catalytic asymmetric hydroxylative dearomatization reaction has been disclosed,and the products can smoothly transform into spiroannulation adducts by simply treated with a base under mild conditions.Novel in-situ generated magnesium catalytic methods are developed by application of combinational ligands.Related concise transformaitons of the spiroannulation adducts have been carried out.
文摘Photo‐catalyzed tandem dearomatization/carboxylation of benzyl o‐halogenated aryl ether with CO_(2) was achieved,which affords spirocyclic carboxylic acids under mild conditions.The reaction has good functional group tolerance with high yields.Mechanism studies indicate that the transformation was realized via intramolecular radical addition and nucleophilic addition.
基金the National Natural Science Foundation of China (Nos. 22101074, 21877206, and 21772032)the 111 Project (No. D17007)+2 种基金Excellent Youth Foundation of Henan Scientific Committee (No. 222300420012)China Postdoctoral Science Foundation (No. 2019M660173)the Natural Science Foundation of Henan Province (No. 202300410233)。
文摘Atom-and step-economy in IBX assisted diversity-oriented synthesis is achieved with a versatile AQ auxiliary α-amino acid analogs offering rapid access to polycyclic spiro-quinolines featuring a quaternary stereocenter in 20%–91% yields under mild conditions via 7,8-dearomatization of quinolines. Free of a preinstalled activation group is highlight of this intramolecular oxidation spiroannulation tandem reaction. This type of N-heterospirocycles, traditionally difficult to access, may open the door to a potentially interest scaffold for synthetic and medicinal chemistry.
基金the National Natural Science Foundation of China(Nos.21472172,21272212)Natural Science Foundation of Zhejiang Province(No.LY17B060009)。
文摘The copper-catalyzed directed dearomatization of indoles with the assistance of directing groups has been developed for the synthesis of 2,3-diazido indolines with good yields and excellent diastereoselectivities in aqueous solution.The resultant 2,3-diazides can be smoothly converted to other functional groups,including vicinal diamines,triazoles and benzotriazoles,in a single step.
基金financial support from the National Natural Science Foundation of China(Nos.22125108,22101238,92056104 and 21772161)the China Postdoctoral Science Foundation(No.2020M680087)+3 种基金the Natural Science Foundation of Fujian Province of China(No.2019J02001)the President Research Funds from Xiamen University(No.20720210002)the Fundamental Research Funds for the Central Universities(No.20720202008)NFFTBS(No.J1310024)。
文摘Catalytic asymmetric dearomatization of indoles and alkynes has received much attention in the past decade because this strategy offers an attractive and alternative way for the efficient synthesis of valuable chiral polycyclic indolines. However, these reactions have been mostly limited to transition-metal catalysts, and the related chiral Br■nsted acid catalysis has been scarcely reported. Herein, we disclose a chiral phosphoric acid-catalyzed asymmetric dearomatization of indolyl ynamides by direct activation of alkynes. This metal-free method enables the practical and atom-economical construction of an array of valuable chiral polycyclic indolines in moderate to good yields with high enantioselectivities.
基金the National Key R&D Program of China (No. 2016YFA0202900)National Basic Research Program of China (No.2015CB856600)+1 种基金the National Natural Science Foundation of China (Nos. 21332009, 21421091)the Chinese Academy of Sciences (Nos. XDB20000000, QYZDY-SSW-SLH012) for generous financial support
文摘A catalytic asymmetric brominative dearomatization reaction of benzofuran derivatives was achieved by using hydroquinidine 1,4-phthalazinediyl diether [（DHQ）_2PHAL] as the catalyst and N-bromoacetamide（NBAc） as the brominating reagent. A series of brominated spiro[benzofuran-2,5＇-oxazoles] bearing two contiguous stereogenic centers were obtained in high yields（up to 99%） with excellent enantioselectivity（up to 97% ee）.
基金support from the Taishan Scholars Construction Projects of Shandong(No.tsqn201909131)the National Natural Science Foundation of China(No.22001144)the Natural Science Foundation of Shandong Province(Nos.ZR2020QB046,ZR2020KB007 and ZR2020QB047).
文摘1,7-Hydride transfer-involved dearomatization of quinolines toward C3-spiro hydroquinoline derivatives has been developed.This method offers a protocol to achieve the dearomatization of electron-deficient arenes via the redox-neutral hydride transfer process.A series of C3-spiro hydroquinolines can be provided in moderate to excellent yields(up to 98%)with good diastereoselectivities.Significant advantages such as high step-and atomeconomy,as well as redox-neutral and mild conditions,make it an appealing alternative to achieve the dearomatization of quinolines.
基金supported by the National Natural Science Foundation of China(22001220)Sichuan Science and Technology Program(2023NSFSC1086)+1 种基金the Collaborative Fund of Luzhou Government and Southwest Medical University(2024LZXNYDJ016)Ningbo Key Scientific and Technological Project(2023ZI58)。
文摘The dearomatization of indole derivatives bearing amide functionalities presents a significant challenge due to the inherent stability of the amide carbonyl group,resulting from nitrogen lone-pair delocalization that imparts increased resonance stabilization.In this study,we report a visible-light photocatalytic intramolecular dearomatization of indole derivatives with amide groups,achieving the synthesis of spiroindolines via energy transfer.This method enables the efficient formation of a range of hydroxyl-substituted spiroindolines in moderate to high yields,with excellent diastereoselectivity(>20:1)under mild reaction conditions.Control experiments confirmed the involvement of an energy transfer pathway in the reaction mechanism.Density Functional Theory(DFT)calculations further revealed r-stacking interactions between the indole core and pyridine ring,along with the strengthening of hydrogen bonding between the pyridine nitrogen and hexafluoroisopropanol(HFiP)in the excited state.These interactions facilitated the energy transfer-mediated triplet excited state intermolecular proton transfer(T-ESPT),crucial for activating the otherwise amide functionality.This protocol represents a rare example of harnessing the reactivity of amide groups for dearomative transformations.
基金supported by the National Key R&D Program of China(Nos.2022YFA1503702 and 2021YFF0701001)NSFC(Nos.81971822,82183101,22071261 and 21725205)G.X.was grateful to the Youth Innovation Promotion Association,CAS.
文摘Dydrogesterone as an agonist of the progesterone receptor is an important and selective synthetic progesterone used for the treatment of a variety of conditions associated with progesterone deficiency including menstrual cycle regulation,infertility,and prevention of miscarriage.Its manufacturing process employing photochemical reactions remains a significant challenge.Herein we report the first total synthesis of dydrogesterone via a key 10α-substitution-selective dearomative cyclizationfree of photochemical protocols starting from Hajos-Parrish ketone.A gram-scale synthesis is also accomplished from readily available 9-hydroxy-4-androstene-3,17-dione through a novel aromatization-dearomatization strategy of ring A in steroid chemistry.Key synthetic features include a facile chemical aromatization of 9-hydroxy-4-androstene-3,17-dione,efficient ligand-controlled asymmetric dearomative cyclization to install the 10α-Me group,and an effective hydroxyl-directed hydrogenation of sterically congested tetrasubstituted olefin to establish the 8β-H,9β-H stereochemistry.
基金support of the Natural Science Foundation of China and Shandong Province(grant nos.21971149,92156007,21933003,ZR2019ZD45,and ZR2020KB005).
文摘Chiral[2.2]paracyclophane(PCP)is an intriguing prevalent scaffold widely utilized inπ-stacked polymers,luminescent materials,and asymmetric catalysis.However,current synthetic methods to access chiral PCP derivatives are still limited to physical separation and chemical or kinetic resolution.The direct desymmetric functionalization of nonsubstituted PCP has been a challenge since its discovery 70 years ago.Herein,we present a catalytic desymmetric dearomatization cyclopropanation reaction of PCP,providing rapid access to enantioenriched PCP cyclopropyl carboxylates with continuous tertiary/quaternary/quaternary chiral centers.The application of the chiral PCPs obtained has also been demonstrated by transformation to structurally novel C_(2) symmetric dirhodium catalysts.Of equal importance,detailed density functional theory calculations have been carried out to reveal the mechanism of this reaction.The key to this success is a structurally symmetric bulky C_(4) dirhodium catalyst:noncovalent interactions exist between substrates and catalysts,which form a cavity to host substrates,and mainly affect the regio-and enantioselectivity.
文摘An asymmetric fluorinative dearomatization reaction of tryptophol derivatives was developed via chiral anion phase-transfer catalysis. Vari- ous fluorinated furoindolines were obtained in moderate to excellent yields and enantioselectivity in the presence of Selectfluor. The preliminary mecha- nistic studies suggested the existence of an in situ formed tryptophol boronic ester plays a critical role in determining the enantioselectivity. This method features the facile introduction of a fluorine atom in a highly enantioselective manner and construction of two contiguous quaternary stereogenic cen- ters.
文摘Copper-catalyzed intermolecular oxidative-etherification type dearomatization reaction of 2-naphthols was developed.With air as the terminal oxidant,the reaction proceeded in excellent yields under mild conditions.In addition,the reaction between two different naphthol substrates occurred smoothly.A series of multifunctionalized β-naphthalenones,important scaffold existed widely in natural products and biologically active molecules,were synthesized efficiently.
基金supported by generous grants from the National Natural Science Foundation of China(nos.NSFC-21971204,21622203,and 21702161)the Innovation Capability Support Program of Shaanxi Province(no.2020TD-022).
文摘Herein,we report a novel palladium(Pd)-catalyzed asymmetric domino Heck/carbocyclization/Suzuki reaction of N-(2-bromoaryl)-2-naphthylacrylamides.The reaction involves a novel and enantioselective dearomative 1,2-insertion of the naphthalene group,thus providing a unique dearomatization strategy of nonactivated naphthalenes.A new phosphoramidite ligand L12,which displayed excellent reactivity and enantioselectivity in the reaction,has been developed.
基金supported by the National Natural Science Foundation of China(no.22031008)the Science Foundation of Wuhan(no.2020010601012192).
文摘Spiro compounds are widely prevalent in biological activities and natural products.However,developing new strategies for their efficient synthesis and derivatization remains a challenge.Outstanding progress has been made in the synthesis of spiro compounds through dearomatization of aromatic compounds,most of them are mediated by the hypervalent iodine reagents.Herein,we report a method of anodic oxidation spiroamination and spirolactonization of anisole derivatives with concomitant cathodic reduction of protons in the absence of hypervalent iodine reagents.A wide variety of spiropyrrolidines and spirolactones with diverse functional groups made useful scaffolds in this transformation,with yields up to 97%.Moreover,hectogram-scale synthesis could supply target product with 83% yield in a flow electrochemical cell using carbon paper as the anode and nickel plate as the cathode,demonstrating the potential application of this method.
基金supported by the National Natural Science Foundation of China(nos.21925108 and 21901203)the Key Science and Technology Innovation Team of Shaanxi(no.2017KCT-37)+1 种基金the Key Laboratory Project of Xi’an(no.201805058ZD9CG42)the Education Department of Shaanxi Province(nos.18JS108 and 20JK0934).
文摘An enantioselective[4+1]spiroannulation ofαbromo-β-naphthols with azoalkenes has been developed for the one-step construction of a new class of pyrazoline-based spirocyclic molecules.Using chiral Cu(II)/Box catalysts,asymmetric induction was achieved with high levels of enantioselectivity[up to 99:1 enantiomeric ratio(er)].Notably,α-chloroandα-iodo-substitutedβ-naphthols were also tolerated by this reaction.Mechanistic studies disclosed that this process was triggered by electrophilefacilitated dearomatization ofα-bromo-β-naphthols and followed by the debromination via SRN 1-subsitution with in situ-formed N-nucleophile.The chiral copper(II)-species,bound with azoalkene moiety,was assumed to control the enantiodiscrimination over the naphthoxy C-radical that was generated from the debromination step.Moreover,the potential utility of this protocol was greatly amplified by the derivatization of spirocyclic products through oxidative dearomatization of the other aromatic ring in the naphthyl fragment,providing a rather attractive route for the rapid generation of synthetically more valuable doubly dearomatized architectures.
文摘Asymmetric construction of quinuclidine derivatives has been realized by an iridium-catalyzed allylic dearomatization reaction.The catalytic system,derived from[Ir(cod)Cl]2 and the Feringa ligand,tolerates a broad range of substrates.A large array of quinuclidine derivatives can be obtained under mild conditions in good to excellent yields(68%–96%),diastereoselectivity(up to>20/1 dr),and enantioselectivity(up to>99%ee).These pro-ducts feature versatile functional group diversity and can undergo diverse transformations.A model that accounts for the origin of the stereoselectivity has been proposed based on density functional theory(DFT)calculations.
