A novel class of chiral spiro-fused bisoxazoline ligands possessing a deep chiral pocket was prepared.The developed ligands have been employed in the nickel-catalyzed highly enantioselective Michael-type Friedel-Craft...A novel class of chiral spiro-fused bisoxazoline ligands possessing a deep chiral pocket was prepared.The developed ligands have been employed in the nickel-catalyzed highly enantioselective Michael-type Friedel-Crafts reaction, affording the products bearing a trifluoromethylated all-carbon quaternary stereocenter with moderate to excellent yields(up to 99%) and good to excellent enantioselectivies(up to> 99.9% ee). Moreover, a proposed model of chiral pocket revealed that the attack of indole from the Re-face of β-CF_(3)-β-disubstituted nitroalkene was favorable.展开更多
The AC bicyclic skeleton of daphniyunnine B with the required 3 stereocenters(C4,C5 and C8)was accomplished in a concise route which featured two Claisen-type rearrangement reactions to construct the required vicinal ...The AC bicyclic skeleton of daphniyunnine B with the required 3 stereocenters(C4,C5 and C8)was accomplished in a concise route which featured two Claisen-type rearrangement reactions to construct the required vicinal all carbon quaternary stereocenters(C5 and C8)and an intramolecular iodocyclization reaction to assemble the cis-confused bicyclic lactam.展开更多
Multiple contiguous quaternary carbon stereocenters(CQS) are highly challenging, yet important structural motifs in organic synthesis. Here, we describe a visible light induced catalytic [2 + 2] cycloaddition approach...Multiple contiguous quaternary carbon stereocenters(CQS) are highly challenging, yet important structural motifs in organic synthesis. Here, we describe a visible light induced catalytic [2 + 2] cycloaddition approach that constructed up to four CQS in a pentacyclic fused ring system diastereoselectively, from the readily accessible dienamides with pendent heteroaryls. Variously substituted dienamides have been cyclized with heteroaryls to provide a range of novel CQS-containing scaffolds(26 examples, up to 96%yield and >20:1 dr ratio). Mechanistic studies revealed that it may proceed through an uncommon β-C radical initiated 7-endo cyclization from the biradical intermediate.展开更多
A bifunctional squaramide-catalyzed asymmetric synthesis of chiral tricyclic chromans featuring three contiguous stereocenters has been successfully developed.This innovative strategy relies on the synergistic activat...A bifunctional squaramide-catalyzed asymmetric synthesis of chiral tricyclic chromans featuring three contiguous stereocenters has been successfully developed.This innovative strategy relies on the synergistic activation of 3-aminophenol derivatives and 4-benzylidenepyrrolidine-2,3-diones by the chiral catalyst,enabling an efficient asymmetric oxa-[3+3]-annulation reaction.The protocol exhibits a broad substrate scope with 34 diverse examples,delivering moderate-to-good yields ranging from 64%to 81%,excellent enantioselectivity(up to 99%ee),and tunable diastereoselectivity(dr up to 15:1).Notably,halogen substitution plays a pivotal role in dramatically enhancing stereocontrol,further optimizing the diastereoselectivity of the target products.To validate its practical utility,gram-scale synthesis was successfully conducted without compromising yield or stereoselectivity,and subsequent derivatization reactions confirmed the versatility of the obtained chiral tricyclic chromans.This metal-free,mild reaction system not only enriches the synthetic toolbox for constructing complex chroman architectures,but also provides a versatile platform for the asymmetric synthesis of bioactive molecules containing the chiral tricyclic chroman skeleton,highlighting the significance of enantioselectivity and diastereoselectivity in accessing functionalized heterocyclic compounds.展开更多
Chirality is a universal characteristic of life and the material world,with irreplaceable value in drug development and green synthesis[1].At present,enantioselective transformations primarily rely on two methods,whic...Chirality is a universal characteristic of life and the material world,with irreplaceable value in drug development and green synthesis[1].At present,enantioselective transformations primarily rely on two methods,which are asymmetric synthesis using chiral catalysts or reagents and kinetic resolution depending on enantiomer recognition ability.展开更多
A novel approach to α-fluoroamides bearing a C-F quaternary stereocenter is reported herein.With sulfone installed as the activating group;an alkyl group as well as afluorine atom was introduced successively under mi...A novel approach to α-fluoroamides bearing a C-F quaternary stereocenter is reported herein.With sulfone installed as the activating group;an alkyl group as well as afluorine atom was introduced successively under mild conditions.Subsequently;heterolyticfission of the C-S bond occurred smoothly under photoredox conditions to afford a tertiary radical;which then engaged in varied intramolecular cyclizations depending on substrate structure and condition applied;rendering sulfone an overall traceless activating group.展开更多
Vicinal all-carbon quaternary stereocenters are widely present in natural products and bioactive molecules.However,the construction of such motif in one step from readily available starting materials remains a signifi...Vicinal all-carbon quaternary stereocenters are widely present in natural products and bioactive molecules.However,the construction of such motif in one step from readily available starting materials remains a significant challenge.Herein,we report a phosphine-catalyzed divergent γ,γ-and ε,γ-umpolung domino addition of bisoxindoles with allenoates.This method serves as a practical tool for the concise synthesis of a series of bisoxindole derivatives bearing sterically hindered vicinal all-carbon quaternary stereocenters under mild reaction conditions.The applicability of this novel method was demonstrated with the gram-scale synthesis of three known advanced intermediates for the total syntheses of calycanthine,chimonanthine and folicanthine.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
Structure units containing all-carbon quaternary stereogenic center are found in many bioactive natural products. However, enantioselective construction of this type of structure units has been a formidable challenge ...Structure units containing all-carbon quaternary stereogenic center are found in many bioactive natural products. However, enantioselective construction of this type of structure units has been a formidable challenge for synthetic community due to the steric hindrance enforced by all-carbon quatemary stereocenters. In this review, we present the achievements made by Chinese scientists in the area of asymmetric synthesis of all-carbon quaternary stereocenters in natural products during the past two years.展开更多
Chiral phosphoric acid catalyzed the regio-and enantioselective N-H functionalization of N-alkylaniline with pyrazolones derived ketimines as electrophiles,providing a variety of chiral pyrazolones containing a tetras...Chiral phosphoric acid catalyzed the regio-and enantioselective N-H functionalization of N-alkylaniline with pyrazolones derived ketimines as electrophiles,providing a variety of chiral pyrazolones containing a tetrasubstituted stereocenter bearing a new N,N'-acetal motif in excellent yields and high enantioselectivities.This strategy was featured by low catalyst loading,mild conditions,and high efficiency and selectivity.展开更多
While drug chirality remains one of the most important themes in medicinal chemistry and fluorine-containing drugs have comprised large portion of global pharmaceutical market,the synthesis of fluorine-containing comp...While drug chirality remains one of the most important themes in medicinal chemistry and fluorine-containing drugs have comprised large portion of global pharmaceutical market,the synthesis of fluorine-containing compounds featuring a trifluoromethylated stereogenic carbon center is still underdeveloped.Recent strategy of enantioconvergent cross-coupling of trifluoromethylated alkyl halide has significantly updated previous toolbox that is dependent on additional functional group to achieve desired bond formation and highly enantioselective control.However,evident limitations were present in specific coupling candidate(sp?carbon)and/or prerequisite heteroatom in trifluoroalkyl source for inducing effective stereoconvergent differentiation.Leveraging novel design of sterically hindered bisoxazoline ligand and drastic increase of molecular complexity of in situ generated sp3 coupling partner via metal-hydride atom transfer,herein,we report a nickel-catalyzed,highly enantioselective hydrotrifluoroalkylation of unactivated alkenes for diverse synthesis of enantioenriched aliphatic alkanes featuring trifluoromehylated stereogenic carbon.Excellent stereochemical control(mostly>95:5 er),high catalytic reactivity,mild conditions,and broad substrate scope(40+examples),enable convenient late-stage asymmetric trifluoroalkylation of various biologically active complexmolecules.展开更多
We report the first highly diastereo-and enantioselective C-C bond-forming reaction of racemic α-branched ketones to construct tertiary alcohols with adjacent stereocenters.Accordingly,a highly stereoselective cyanos...We report the first highly diastereo-and enantioselective C-C bond-forming reaction of racemic α-branched ketones to construct tertiary alcohols with adjacent stereocenters.Accordingly,a highly stereoselective cyanosilylation of racemic ketones is developed using our bifunctional cyanating reagent,Me_(2)(CH_(2)Cl)SiCN,giving C^(α)-tetrasubstituted silyl cyanohydrins withtwovicinal stereocenters inupto>20:1 diastereomeric ratio(dr)and 90-98% enantiomeric excess(ee)values,which can undergo various diversification reactions bymanipulating the chloromethyl group.A highly selective kinetic resolution of acyclicα-branched ketones is also developed that allows facile access to acyclic α-alkyl,allyl,and propargyl ketones with good recovery and excellent ee values.The synthetic value of this protocol is further demonstrated by the formal synthesis of the anti-obesity agent,taranabant(MK-0364).The activation of Jacobsen’s privileged catalyst(salen)AlCl by a suitable phosphorane plays a crucial role in the reaction.X-ray crystallographic analysis of single crystals of phosphorane-(salen)AlCl complexes and theoretical calculations help provide a working model.The present transformation opens a new path for the catalytic stereoselective synthesis of stereochemically complex tertiary alcohols featuring two stereocenters(adjacent or not)from racemic ketones.展开更多
An efficiently catalytic method toward the synthesis of indolin-2-ones featuring an allylic derived C_(3)-quaternary stereocenter via an intramolecular Heck cyclization/Suzuki coupling of N-substituted-N-(2-bromopheny...An efficiently catalytic method toward the synthesis of indolin-2-ones featuring an allylic derived C_(3)-quaternary stereocenter via an intramolecular Heck cyclization/Suzuki coupling of N-substituted-N-(2-bromophenyl)acrylamides and organoboron reagents was successfully developed by using a 1,3-bis(2,6-diisopropylphenyl)acenaphthoimidazol-2-ylidene(AnIPr)-ligated oxazoline palladacycle.It enabled a very broad substrate scope tolerating different functional groups,electronic properties and steric bulkiness.Notably,it revealed a great potential to build diverse heterocycle-fused indoline alkaloids via the same intermediate 3-allyl-1,3-dimethylindolin-2-one.展开更多
The construction of acyclic quaternary carbon stereocenters,which are ubiquitous in many bioactive compounds,pharmaceuticals and natural products,has been a long persuit in synthetic organic chemistry.Among numerous m...The construction of acyclic quaternary carbon stereocenters,which are ubiquitous in many bioactive compounds,pharmaceuticals and natural products,has been a long persuit in synthetic organic chemistry.Among numerous methods,enantioselective nickel-catalysis has attracted incremental attention in recent years.This review summarizes the recent development in the asymmetric strategies,research progress,mechanistic investigations for the generation of acyclic quaternary carbon stereocenters via enantioselective nickel catalysis.展开更多
A novel,efficient and pragmatic method to prepare gem-diboron products with vicinal tertiary/quaternary stereocenters using LiTMP-mediated 1,6-conjugate addition of gem-diborylalkanes to para-quinone methides was desc...A novel,efficient and pragmatic method to prepare gem-diboron products with vicinal tertiary/quaternary stereocenters using LiTMP-mediated 1,6-conjugate addition of gem-diborylalkanes to para-quinone methides was described for the first time.The results showed that various gem-diboron products with vicinal tertiary and quaternary stereocenters could be formed within 15 min at ambient temperature.This simple protocol has also been applied for the efficient synthesis of the analogue of Bedaquiline.展开更多
We designed thenickel-catalyzed enantioselective C(sp^(3))–H arylation of ketones with phenol-derived aryl pyrimidyl ethers via selective cleavage of the C(aryl)–O bond to construct all-carbon quaternary stereocente...We designed thenickel-catalyzed enantioselective C(sp^(3))–H arylation of ketones with phenol-derived aryl pyrimidyl ethers via selective cleavage of the C(aryl)–O bond to construct all-carbon quaternary stereocenters.This method exhibits good functional group compatibility and broad substrate scope.Drug molecule donepezil can directly transform into corresponding highly optically pure derivatives with this developedmethodology.Mechanistic studies reveal that C(aryl)–O cleavage of aryl pyrimidyl ether probably proceeded by means of an anionic organo-Ni(0)intermediate.展开更多
Asperfilasin A(1),featuring a unique 5/5 cyclopenta[c]pyrrol-one bicyclic core,represents a newly discovered skeletal cytochalasan isolated from Aspergillus flavipes.The enantioselective total synthesis was efficientl...Asperfilasin A(1),featuring a unique 5/5 cyclopenta[c]pyrrol-one bicyclic core,represents a newly discovered skeletal cytochalasan isolated from Aspergillus flavipes.The enantioselective total synthesis was efficiently accomplished from the key intermediate(S)-6 with three contiguous stereocenters in 5 steps and the synthetic 1 induced G2/M-phase cell cycle arrest of HT29 cells and apoptosis of HL60 and NB4 cells by activation of caspase-3 and degradation of PARP.(S)-6,bearing three contiguous chiral centers,was efficiently constructed by a novel Nazarov cyclization reaction containing basic nitrogen,which was less developed,primarily due to the incompatibility of basic nitrogen under acidic reaction conditions.This reaction allows a wide range of pentadienone substrates containing basic nitrogen to undergo Nazarov cyclization in a single regioselective and diastereoselective manner and is capable of generating three stereocenters simultaneously.Furthermore,the mechanism of the Nazarov cyclization and the origin of the regio-and diastereoselectivity were elucidated by DFT calculations and deuteration experiments,providing valuable insights into the reaction and serving as a guide for future applications involving substrates containing basic nitrogen.展开更多
（3S,4R）-Bengamide E（2） was synthesized starting from D-glucono-δ-lactone（3） and the key deoxygenation step from 13 to 15 was achieved by the application of NaBH_3CN and ZnI_2.Compared with natural bengamide E（...（3S,4R）-Bengamide E（2） was synthesized starting from D-glucono-δ-lactone（3） and the key deoxygenation step from 13 to 15 was achieved by the application of NaBH_3CN and ZnI_2.Compared with natural bengamide E（1）,the synthetic compound（35,4R）-bengamide E（2） was inactive against the cell growth of HUVEC and cancer cells.These data represent the significance of the stereochemistry at C-3 and C-4 of bengamides for structural recognition and binding with the target（s）.展开更多
The asymmetric construction of polycyclic spiroindolines featuring one or more quaternary stereocenters remains a significant challenge in synthetic chemistry.We report a highly chemoselective and stereoselective casc...The asymmetric construction of polycyclic spiroindolines featuring one or more quaternary stereocenters remains a significant challenge in synthetic chemistry.We report a highly chemoselective and stereoselective cascade cycloadditions of newly designed oxazepino indolones with 5-methylene-1,3-dioxanones,employing an iridium catalyst in combination with the Carreira ligand for the divergent synthesis of chiral polycyclic spiroindolines.This strategy enables the construction of a series of pentacyclic spiroindolines featuring two chiral quaternary stereocenters and one tertiary stereocenter in good yields with excellent chemoselectivity and stereocontrol(30 examples,up to 81%yield,>20:1 dr,99%ee).The process was scalable,and synthetic transformations of the products were performed to demonstrate their practical utility.展开更多
Asymmetric cascade Heck/C–H functionalization has emerged as an appealing strategy for activating inert C–H bonds and conveniently synthesizing heterocycles with quaternary centers,owing to the domino sequence of ca...Asymmetric cascade Heck/C–H functionalization has emerged as an appealing strategy for activating inert C–H bonds and conveniently synthesizing heterocycles with quaternary centers,owing to the domino sequence of carbopalladation followed by C–H functionalization enabling efficient construction of multiple bonds in one pot.Herein,a palladium-catalyzed enantioselective cascade Heck/intermolecular direct heteroarylation reaction of unactivated alkenes with heteroarenes is developed,providing a facile access to diverse bis-heterocycles of great practicality bearing an all-carbon quaternary stereocenter with excellent levels of yields and enantioselectivities under mild conditions.Moreover,the synthetic utility of this strategy is further demonstrated by the versatile transformations of product.展开更多
基金support from the National Natural Science Foundation of China(No.21871067)the Natural Science Foundation of Guangdong Province(Nos.2018A030313038 and 2021A1515010190)+3 种基金the Shenzhen Fundamental Research Projects(No.JCYJ20180306171838187)the Harbin Institute of Technology(Shenzhen)(Talent Development Starting Fund from Shenzhen Government)the Open Project Program of State Key Laboratory of Elemento-Organic Chemistry(No.202009)the Guangdong Provincial Key Laboratory of Catalysis(No.2020B121201002)。
文摘A novel class of chiral spiro-fused bisoxazoline ligands possessing a deep chiral pocket was prepared.The developed ligands have been employed in the nickel-catalyzed highly enantioselective Michael-type Friedel-Crafts reaction, affording the products bearing a trifluoromethylated all-carbon quaternary stereocenter with moderate to excellent yields(up to 99%) and good to excellent enantioselectivies(up to> 99.9% ee). Moreover, a proposed model of chiral pocket revealed that the attack of indole from the Re-face of β-CF_(3)-β-disubstituted nitroalkene was favorable.
基金financial support from the National Natural Science Foundation of China (Nos. 21102062, 21472079)
文摘The AC bicyclic skeleton of daphniyunnine B with the required 3 stereocenters(C4,C5 and C8)was accomplished in a concise route which featured two Claisen-type rearrangement reactions to construct the required vicinal all carbon quaternary stereocenters(C5 and C8)and an intramolecular iodocyclization reaction to assemble the cis-confused bicyclic lactam.
基金supported by the National Natural Science Foundation of China(Nos.82122063,81991522 and 81973232)Shandong Science Fund for Distinguished Young Scholars(No.ZR2020JQ32)the Fundamental Research Funds for the Central Universities(No.202041003)。
文摘Multiple contiguous quaternary carbon stereocenters(CQS) are highly challenging, yet important structural motifs in organic synthesis. Here, we describe a visible light induced catalytic [2 + 2] cycloaddition approach that constructed up to four CQS in a pentacyclic fused ring system diastereoselectively, from the readily accessible dienamides with pendent heteroaryls. Variously substituted dienamides have been cyclized with heteroaryls to provide a range of novel CQS-containing scaffolds(26 examples, up to 96%yield and >20:1 dr ratio). Mechanistic studies revealed that it may proceed through an uncommon β-C radical initiated 7-endo cyclization from the biradical intermediate.
基金support from National Natural Science Foundation of China(22371265,22201266)Natural Science Foundation of Henan Province(232301420047)the project of State Key Laboratory of Green Pesticide,Guizhou Medical University(GPLKF202507).
文摘A bifunctional squaramide-catalyzed asymmetric synthesis of chiral tricyclic chromans featuring three contiguous stereocenters has been successfully developed.This innovative strategy relies on the synergistic activation of 3-aminophenol derivatives and 4-benzylidenepyrrolidine-2,3-diones by the chiral catalyst,enabling an efficient asymmetric oxa-[3+3]-annulation reaction.The protocol exhibits a broad substrate scope with 34 diverse examples,delivering moderate-to-good yields ranging from 64%to 81%,excellent enantioselectivity(up to 99%ee),and tunable diastereoselectivity(dr up to 15:1).Notably,halogen substitution plays a pivotal role in dramatically enhancing stereocontrol,further optimizing the diastereoselectivity of the target products.To validate its practical utility,gram-scale synthesis was successfully conducted without compromising yield or stereoselectivity,and subsequent derivatization reactions confirmed the versatility of the obtained chiral tricyclic chromans.This metal-free,mild reaction system not only enriches the synthetic toolbox for constructing complex chroman architectures,but also provides a versatile platform for the asymmetric synthesis of bioactive molecules containing the chiral tricyclic chroman skeleton,highlighting the significance of enantioselectivity and diastereoselectivity in accessing functionalized heterocyclic compounds.
基金supported by the National Natural Science Foundation of China(22271227 and 22471205)Guangdong Basic and Applied Basic Research Foundation(2024A1515011322)+2 种基金the China Postdoctoral Science Foundation(2024M752457)the Postdoctoral Fellowship Program(Grade B)of China Postdoctoral Science Foundation(GZB20240566)Wuhan University and Hubei University for their support of this research.
文摘Chirality is a universal characteristic of life and the material world,with irreplaceable value in drug development and green synthesis[1].At present,enantioselective transformations primarily rely on two methods,which are asymmetric synthesis using chiral catalysts or reagents and kinetic resolution depending on enantiomer recognition ability.
基金support of the Na-tional Natural Science Foundation of China(Nos.22271151,22301133)the Distinguished Youth Foundation of Jiangsu Province(No.BK20211534)the Natural Science Foundation of Jiangsu Province(No.BK20220327).
文摘A novel approach to α-fluoroamides bearing a C-F quaternary stereocenter is reported herein.With sulfone installed as the activating group;an alkyl group as well as afluorine atom was introduced successively under mild conditions.Subsequently;heterolyticfission of the C-S bond occurred smoothly under photoredox conditions to afford a tertiary radical;which then engaged in varied intramolecular cyclizations depending on substrate structure and condition applied;rendering sulfone an overall traceless activating group.
基金the financial support provided by the National Natural Science Foundation of China(22207063),111 Project(D20015)the Natural Science Research Project of Yichang City(A23-2-002)the Opening Funding of Hubei Key Laboratory of Natural Products Research and Development,China Three Gorges University(2024NPRD03,2024NPRD04,2024NPRD05).
文摘Vicinal all-carbon quaternary stereocenters are widely present in natural products and bioactive molecules.However,the construction of such motif in one step from readily available starting materials remains a significant challenge.Herein,we report a phosphine-catalyzed divergent γ,γ-and ε,γ-umpolung domino addition of bisoxindoles with allenoates.This method serves as a practical tool for the concise synthesis of a series of bisoxindole derivatives bearing sterically hindered vicinal all-carbon quaternary stereocenters under mild reaction conditions.The applicability of this novel method was demonstrated with the gram-scale synthesis of three known advanced intermediates for the total syntheses of calycanthine,chimonanthine and folicanthine.
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 Program for Changjiang Scholars and Innovative Research Team in University (IRT13095)Natural Science Foundation of China (20925205, 21332007)
文摘Structure units containing all-carbon quaternary stereogenic center are found in many bioactive natural products. However, enantioselective construction of this type of structure units has been a formidable challenge for synthetic community due to the steric hindrance enforced by all-carbon quatemary stereocenters. In this review, we present the achievements made by Chinese scientists in the area of asymmetric synthesis of all-carbon quaternary stereocenters in natural products during the past two years.
基金This work was supported by the Innovation Fund(2019A005)the NSFC(22071147 and 81872418)+1 种基金the Shanghai Scientific and Technological Innovation Action Plan(21s11902000)the Transforming Medicine Cross Research Fund of Shanghai Jiao Tong University(ZH2018QNA44).
文摘Chiral phosphoric acid catalyzed the regio-and enantioselective N-H functionalization of N-alkylaniline with pyrazolones derived ketimines as electrophiles,providing a variety of chiral pyrazolones containing a tetrasubstituted stereocenter bearing a new N,N'-acetal motif in excellent yields and high enantioselectivities.This strategy was featured by low catalyst loading,mild conditions,and high efficiency and selectivity.
基金Financial support for this work was provided by the National Key R&D Program of China(2021YFF0701700)the National Natural Science Foundation of China(21971228).
文摘While drug chirality remains one of the most important themes in medicinal chemistry and fluorine-containing drugs have comprised large portion of global pharmaceutical market,the synthesis of fluorine-containing compounds featuring a trifluoromethylated stereogenic carbon center is still underdeveloped.Recent strategy of enantioconvergent cross-coupling of trifluoromethylated alkyl halide has significantly updated previous toolbox that is dependent on additional functional group to achieve desired bond formation and highly enantioselective control.However,evident limitations were present in specific coupling candidate(sp?carbon)and/or prerequisite heteroatom in trifluoroalkyl source for inducing effective stereoconvergent differentiation.Leveraging novel design of sterically hindered bisoxazoline ligand and drastic increase of molecular complexity of in situ generated sp3 coupling partner via metal-hydride atom transfer,herein,we report a nickel-catalyzed,highly enantioselective hydrotrifluoroalkylation of unactivated alkenes for diverse synthesis of enantioenriched aliphatic alkanes featuring trifluoromehylated stereogenic carbon.Excellent stereochemical control(mostly>95:5 er),high catalytic reactivity,mild conditions,and broad substrate scope(40+examples),enable convenient late-stage asymmetric trifluoroalkylation of various biologically active complexmolecules.
基金supported by the National Natural Science Foundation of China(grant no.21725203)the Ministry of Education(PCSIRT)The Fundamental Research Funds for the Central Universities is highly appreciated.
文摘We report the first highly diastereo-and enantioselective C-C bond-forming reaction of racemic α-branched ketones to construct tertiary alcohols with adjacent stereocenters.Accordingly,a highly stereoselective cyanosilylation of racemic ketones is developed using our bifunctional cyanating reagent,Me_(2)(CH_(2)Cl)SiCN,giving C^(α)-tetrasubstituted silyl cyanohydrins withtwovicinal stereocenters inupto>20:1 diastereomeric ratio(dr)and 90-98% enantiomeric excess(ee)values,which can undergo various diversification reactions bymanipulating the chloromethyl group.A highly selective kinetic resolution of acyclicα-branched ketones is also developed that allows facile access to acyclic α-alkyl,allyl,and propargyl ketones with good recovery and excellent ee values.The synthetic value of this protocol is further demonstrated by the formal synthesis of the anti-obesity agent,taranabant(MK-0364).The activation of Jacobsen’s privileged catalyst(salen)AlCl by a suitable phosphorane plays a crucial role in the reaction.X-ray crystallographic analysis of single crystals of phosphorane-(salen)AlCl complexes and theoretical calculations help provide a working model.The present transformation opens a new path for the catalytic stereoselective synthesis of stereochemically complex tertiary alcohols featuring two stereocenters(adjacent or not)from racemic ketones.
基金National Natural Science Foundation of China(No.22101133)Natural Science Foundation of Jiangsu Province(No.BK20200768)and Nanjing Forestry University are greatly acknowledged.
文摘An efficiently catalytic method toward the synthesis of indolin-2-ones featuring an allylic derived C_(3)-quaternary stereocenter via an intramolecular Heck cyclization/Suzuki coupling of N-substituted-N-(2-bromophenyl)acrylamides and organoboron reagents was successfully developed by using a 1,3-bis(2,6-diisopropylphenyl)acenaphthoimidazol-2-ylidene(AnIPr)-ligated oxazoline palladacycle.It enabled a very broad substrate scope tolerating different functional groups,electronic properties and steric bulkiness.Notably,it revealed a great potential to build diverse heterocycle-fused indoline alkaloids via the same intermediate 3-allyl-1,3-dimethylindolin-2-one.
基金National Natural Science Foundation of China(Nos.22278265,U22B20137)Zhejiang Provincial Natural Science Foundation of China(No.LR24B020002)+4 种基金the start-up funding from Hangzhou Normal University(No.4095C50222204165)support.J.S.thanks the Natural Science Foundation of Hunan Province(2024JJ6485)support.J.L.thanks the National Natural Science Foundation of China(22302063)China Postdoctoral Science Foundation(2022M721086)the Natural Science Foundation of Hunan Province(2023JJ40124)for financial support.
文摘The construction of acyclic quaternary carbon stereocenters,which are ubiquitous in many bioactive compounds,pharmaceuticals and natural products,has been a long persuit in synthetic organic chemistry.Among numerous methods,enantioselective nickel-catalysis has attracted incremental attention in recent years.This review summarizes the recent development in the asymmetric strategies,research progress,mechanistic investigations for the generation of acyclic quaternary carbon stereocenters via enantioselective nickel catalysis.
基金The authors are grateful for the financial support provided by the National Natural Science Foundation of China(No.22001203)the startup funds from Xi'an Jiaotong University.The authors thank Dr.Lu Bai and Ms.Chao Feng from the Instrument Analysis Center of Xi'an Jiaotong University for their assistance with HRMS and NMR analysis.
文摘A novel,efficient and pragmatic method to prepare gem-diboron products with vicinal tertiary/quaternary stereocenters using LiTMP-mediated 1,6-conjugate addition of gem-diborylalkanes to para-quinone methides was described for the first time.The results showed that various gem-diboron products with vicinal tertiary and quaternary stereocenters could be formed within 15 min at ambient temperature.This simple protocol has also been applied for the efficient synthesis of the analogue of Bedaquiline.
基金the National Natural Science Foundation of China(no.NSFC 21902072)and the Guangdong Innovative Program(no.2019BT02Y335)for their financial support.
文摘We designed thenickel-catalyzed enantioselective C(sp^(3))–H arylation of ketones with phenol-derived aryl pyrimidyl ethers via selective cleavage of the C(aryl)–O bond to construct all-carbon quaternary stereocenters.This method exhibits good functional group compatibility and broad substrate scope.Drug molecule donepezil can directly transform into corresponding highly optically pure derivatives with this developedmethodology.Mechanistic studies reveal that C(aryl)–O cleavage of aryl pyrimidyl ether probably proceeded by means of an anionic organo-Ni(0)intermediate.
基金supported by the National Natural Science Foundation of China(Nos.81725021,81903461)the National Key R&D Program of China(No.2022YFA1503200)the Natural Science Foundation of Hubei Province(No.ZRMS2023000340)。
文摘Asperfilasin A(1),featuring a unique 5/5 cyclopenta[c]pyrrol-one bicyclic core,represents a newly discovered skeletal cytochalasan isolated from Aspergillus flavipes.The enantioselective total synthesis was efficiently accomplished from the key intermediate(S)-6 with three contiguous stereocenters in 5 steps and the synthetic 1 induced G2/M-phase cell cycle arrest of HT29 cells and apoptosis of HL60 and NB4 cells by activation of caspase-3 and degradation of PARP.(S)-6,bearing three contiguous chiral centers,was efficiently constructed by a novel Nazarov cyclization reaction containing basic nitrogen,which was less developed,primarily due to the incompatibility of basic nitrogen under acidic reaction conditions.This reaction allows a wide range of pentadienone substrates containing basic nitrogen to undergo Nazarov cyclization in a single regioselective and diastereoselective manner and is capable of generating three stereocenters simultaneously.Furthermore,the mechanism of the Nazarov cyclization and the origin of the regio-and diastereoselectivity were elucidated by DFT calculations and deuteration experiments,providing valuable insights into the reaction and serving as a guide for future applications involving substrates containing basic nitrogen.
基金the financial supports from National Basic Research Program of China(No.2007CB914504)Natural Science Foundation of China(No.30973621)
文摘（3S,4R）-Bengamide E（2） was synthesized starting from D-glucono-δ-lactone（3） and the key deoxygenation step from 13 to 15 was achieved by the application of NaBH_3CN and ZnI_2.Compared with natural bengamide E（1）,the synthetic compound（35,4R）-bengamide E（2） was inactive against the cell growth of HUVEC and cancer cells.These data represent the significance of the stereochemistry at C-3 and C-4 of bengamides for structural recognition and binding with the target（s）.
基金support for this work from the National Natural Science Foundation of China(21901142,22201161)the Natural Science Foundation of Shandong Province(ZR2024MB004,ZR2022QH294)+4 种基金the Medical and Health Science and Technology Development Program of Shandong Province(202102070368)the Fundamental Research Funds of Shandong University(2020QNQT007 and 2020QNQT009)Funded by Basic Research Program of Jiangsu(BK20220097)Open Research Fund Program of Key Laboratory of Marine Drugs,Ministry of Education(Ocean University of China,MDME2308-03)the Open Project of Guangxi Colleges and Universities Key Laboratory of Applied Chemistry Technology and Resource Development(2024GCUKLACTRD003).
文摘The asymmetric construction of polycyclic spiroindolines featuring one or more quaternary stereocenters remains a significant challenge in synthetic chemistry.We report a highly chemoselective and stereoselective cascade cycloadditions of newly designed oxazepino indolones with 5-methylene-1,3-dioxanones,employing an iridium catalyst in combination with the Carreira ligand for the divergent synthesis of chiral polycyclic spiroindolines.This strategy enables the construction of a series of pentacyclic spiroindolines featuring two chiral quaternary stereocenters and one tertiary stereocenter in good yields with excellent chemoselectivity and stereocontrol(30 examples,up to 81%yield,>20:1 dr,99%ee).The process was scalable,and synthetic transformations of the products were performed to demonstrate their practical utility.
基金funding support of the National Key R&D Program of China(No.2021YFF0701600)NSFC(No.22031004)+1 种基金the Shanghai Municipal Education Commission(No.20212308)STCSM(No.23ZR1445600).
文摘Asymmetric cascade Heck/C–H functionalization has emerged as an appealing strategy for activating inert C–H bonds and conveniently synthesizing heterocycles with quaternary centers,owing to the domino sequence of carbopalladation followed by C–H functionalization enabling efficient construction of multiple bonds in one pot.Herein,a palladium-catalyzed enantioselective cascade Heck/intermolecular direct heteroarylation reaction of unactivated alkenes with heteroarenes is developed,providing a facile access to diverse bis-heterocycles of great practicality bearing an all-carbon quaternary stereocenter with excellent levels of yields and enantioselectivities under mild conditions.Moreover,the synthetic utility of this strategy is further demonstrated by the versatile transformations of product.
