Scopus Publications
- Palladium-Catalyzed Benzylation/Semipinacol Rearrangement for the Construction of 3-Quaternary Carbon 2-Spiroindoline
Xin Chang, Kun-Shan Xue, Hai-Yan Tao, Chun-Jiang Wang
Journal of Organic Chemistry, 2025
The 3-quaternary carbon 2-spiroindoline scaffold occupies a significant position in both medicinal and synthetic chemistry. While the dearomatization of indoles represents the most direct and efficient route to such structural units, considerable limitations persist. Herein, utilizing 2-cyclobutanol-3-substituted indoles and benzyl phosphates as model substrates, we developed a novel Pd/BEt3 synergistic catalyzed tandem benzylation/semipinacol rearrangement. This strategy efficiently constructs a series of 3-quaternary carbon 2-spiroindolines in high yields with excellent chemoselectivity and diastereoselectivity. Furthermore, this catalytic cascade reaction proceeds efficiently in a one-pot manner, as the thermally driven semipinacol rearrangement circumvents the need for intermediate isolation. - Dual Cu/Ir Catalyzed Asymmetric Allylation and Pictet-Spengler Cyclization: Stereodivergent Access to Chiral Indole Fused 9-Azabicyclo[4.2.1]nonanes†
Xin‐Lian Liu, Lu Xiao, Yi Liu, Yan Li, Zuo‐Fei Wang, Xin Chang, Xiu‐Qin Dong, Chun‐Jiang Wang
Chinese Journal of Chemistry, 2025
Comprehensive SummaryNitrogen‐containing bridged‐heterocycles and indoles are key subunits of many natural products and pharmacologically active molecules. We herein present a bimetallic Cu/Ir catalyzed asymmetric allylation of ketimine esters and (E)‐4‐indolyl allyl carbonates followed by acid‐promoted Pictet‐Spengler cyclization sequences, enabling stereodivergent synthesis of chiral indole fused 9‐azabicyclo[4.2.1]nonanes containing an eight‐membered ring with one tertiary and two quaternary stereogenic centers. This one‐pot sequential protocol features step economy, good substrate tolerance, and excellent stereoselective control. - Cooperative Catalysis-Enabled Cascade Allylation/aza-Prins Cyclization to Chiral Spiroindolylpiperidine-γButyrolactones
Lu Xiao, Qi Xiong, Hui Xu, Zuofei Wang, Xin Chang, Yanfeng Dang, Xiu-Qin Dong, Chun-Jiang Wang
Ccs Chemistry, 2025 - Asymmetric Relay Catalysis Enables Unreactive Allylic Alcohols to Participate in 1,3-Dipolar Cycloaddition of Azomethine Ylides
Xiang Cheng, Cong Fu, Bo-Bin Chen, Xin Chang, Xiu-Qin Dong, Chun-Jiang Wang
Journal of the American Chemical Society, 2025
Current synthetic transformations occur readily with starting materials that possess both innate reactivity and steric accessibility or functional-group-oriented reactivity. However, achieving reactions with inactive feedstock substrates remains significantly challenging and normally requires cumbersome prior functional group manipulations. Herein, we report an unprecedented example of catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides with nonactivated alkenes enabled by copper/ruthenium relay catalysis. Key to the success is the temporary activation strategy initiated by oxidative dehydrogenation of inert allylic alcohols into electron-demanding reversed highly reactive enones, which triggers the ensuing Cu-catalyzed asymmetric 1,3-dipolar cycloaddition followed by reductive hydrogenation to deliver highly functionalized chiral pyrrolidines with the construction of two C-C bonds and four well-defined stereogenic centers in an atom-/step-economical and redox-neutral manner. This method features mild reaction conditions, operational simplicity, and broad substrate scope and is also characterized by formal dynamic kinetic resolution. Mechanistic studies and control experiments supported a typical borrowing-hydrogen cascade orthogonally merged with 1,3-dipolar cycloaddition and revealed that the superiority and reliability of relay catalysis are enabled by the controlled release of highly reactive but unstable enones to impede the undesired polymerization. It should be noted that up to four stereoisomers of the challenging and otherwise inaccessible pyrrolidines and cyclobutanes could be readily prepared through concise late-stage elaborations. - Stereodivergent assembly of δ-valerolactones with an azaarene-containing quaternary stereocenter enabled by Cu/Ru relay catalysis
Kui Tian, Zhuan Jin, Xin-Lian Liu, Ling He, Hong-Fu Liu, Pin-Ke Yu, Xin Chang, Xiu-Qin Dong, Chun-Jiang Wang
Chemical Science, 2025
Stereodivergent synthesis of chiral δ-valerolactones bearing a unique azaarene-containing α-quaternary and a tertiary stereocenter was enabled by Cu/Ru relay catalysis via cascade borrowing hydrogen/Michael addition/lactonization protocol. - Modular access to chiral bridged piperidine-γ-butyrolactones via catalytic asymmetric allylation/aza-Prins cyclization/lactonization sequences
Cong Fu, Ling He, Hui Xu, Zongpeng Zhang, Xin Chang, et al.
Nature Communications, 2024
Chiral functionalized piperidine and lactone heterocycles are widely spread in natural products and drug candidates with promising pharmacological properties. However, there remains no general asymmetric methodologies that enable rapid assemble both critical biologically important units into one three-dimensional chiral molecule. Herein, we describe a straightforward relay strategy for the construction of enantioenriched bridged piperidine-γ-butyrolactone skeletons incorporating three skipped stereocenters via asymmetric allylic alkylation and aza -Prins cyclization/lactonization sequences. The excellent enantioselectivity control in asymmetric allylation with the simplest allylic precursor is enabled by the synergistic Cu/Ir-catalyzed protocol; the success of aza -Prins cyclization/lactonization can be attributed to the pivotal role of the ester substituent, which acts as a preferential intramolecular nucleophile to terminate the aza -Prins intermediacy of piperid-4-yl cation species. The resulting chiral piperidine-γ-butyrolactone bridged-heterocyclic products show impressive preliminary biological activities against a panel of cancer cell lines. - Rational Design and Stereodivergent Construction of Enantioenriched Tetrahydro-β-Carbolines Containing Multistereogenic Centers
Taotao Chen, Qi Xiong, Hui Xu, Lu Xiao, Zuo-Fei Wang, Xin Chang, Yanfeng Dang, Xiu-Qin Dong, Chun-Jiang Wang
Journal of the American Chemical Society, 2024
Chiral tetrahydro-β-carbolines, as one of the most intriguing subtypes of indole alkaloids, have emerged as the privileged units in plenty of natural products and biologically active molecules with an impressive range of bioactive properties. However, the stereodivergent construction of these valuable skeletons containing multistereogenic centers from readily available starting materials remains very challenging, especially, in view of the introduction of an axial chirality. Herein, we developed an efficient method toward enantioenriched tetrahydro-β-carbolines with readily available tryptophan-derived aldimine esters and allylic carbonates under mild reaction conditions. The reaction proceeds in a sequential fashion involving synergistic Cu/Ir-catalyzed stereodivergent allylation and the Brønsted acid-promoted stereospecific Pictet-Spengler reaction, affording a wide range of chiral tetrahydro-β-carbolines bearing up to four stereogenic centers in good yields with excellent stereoselectivity control. When N-aryl-substituted tryptophan-derived aldimine esters were utilized, notably, a unique C-N heterobiaryl axis could be simultaneously constructed with the formation of the third point stereogenic center in the last cyclization step through dynamic kinetic resolution (DKR). Computational mechanistic studies established a plausible synergistic mechanism for dual Cu/Ir-catalyzed asymmetric allylation and the succeeding protonation-assisted Pictet-Spengler cyclization to complete the annulation. Structure-activity relationship analyses unveil the origins of stereochemistry for the building of one axis and three point stereogenic centers. - Iridium-Catalyzed Asymmetric Cascade Allylation/[1,4]-Phospha-Brook Rearrangement Reaction
Zhi-Yuan Yi, Hui Xu, Xin Chang, Yanfeng Dang, Xiu-Qin Dong, Chun-Jiang Wang
ACS Catalysis, 2024
Chiral δ-carbonyl phosphates and their derivatives represent important structural units frequently found in natural products and biologically active molecules and have been extensively employed as key intermediates in organic synthesis. Herein, an unprecedented iridium-catalyzed asymmetric cascade allylation/[1,4]-phospha-Brook rearrangement of β-keto phosphonates with vinyl ethylene carbonate was established, offering an efficient synthetic strategy to access highly functionalized chiral δ-carbonyl phosphates that are difficult to access via known methods. This protocol features easily available starting materials, mild reaction conditions, high chemo-/regio-/enantioselectivity, and a wide substrate scope. Notably, this methodology can be extended to various β-functionalized phosphonates. The gram-scale reaction, diverse functional transformations, and stereodivergent synthesis of chiral δ-hydroxyl phosphates containing two nonadjacent stereocenters demonstrated the synthetic potential of this method. The synthetic utility of this cascade reaction was further confirmed in the concise formal synthesis of natural products hormosirene, dictyopterene A, and biologically active (R)-MCPA-CoA. Control experiments and density field theory computational mechanistic studies revealed that this transformation undergoes asymmetric allylation via kinetic resolution followed by a unique [1,4]-phospha-Brook rearrangement. Ligand–substrate interactions were identified to rationalize the kinetic resolution and chiral induction. The stronger σ-bond of P–O than that of O–C makes the [1,4]-phospha-Brook rearrangement kinetically and thermodynamically favorable. - Copper/ruthenium relay catalysis enables 1,6-double chiral inductions with stereodivergence
Hao-Ran Yang, Xiang Cheng, Xin Chang, Zuo-Fei Wang, Xiu-Qin Dong, Chun-Jiang Wang
Chemical Science, 2024
A stereodivergent synthesis of chiral ζ-hydroxy amino esters containing 1,6-stereocenters and a unique β,γ-unsaturation was developed through asymmetric Cu/Ru relay catalysis to conduct the borrowing hydrogenation/1,6-Michael addition protocol. - Visible-light-enabled stereoselective synthesis of functionalized cyclohexylamine derivatives via [4 + 2] cycloadditions
Yi-Nan Lu, Chao Che, Guangjin Zhen, Xin Chang, Xiu-Qin Dong, Chun-Jiang Wang
Chemical Science, 2024
Photocatalyzed [4 + 2] cycloaddition of benzocyclobutylamines with α-substituted vinylketones afforded benzocyclohexylamines in moderate to good yields with excellent diastereoselectivities. An asymmetric version of this was preliminarily investigated. - Copper/Ruthenium Relay Catalysis for Stereodivergent Access to δ-Hydroxy α-Amino Acids and Small Peptides
Cong Fu, Ling He, Xin Chang, Xiang Cheng, Zuo‐Fei Wang, Zongpeng Zhang, Vladimir A. Larionov, Xiu‐Qin Dong, Chun‐Jiang Wang
Angewandte Chemie International Edition, 2024 - Stereodivergent synthesis of α-fluoro α-azaaryl γ-butyrolactones via cooperative copper and iridium catalysis
Kui Tian, Xin Chang, Lu Xiao, Xiu-Qin Dong, Chun-Jiang Wang
Fundamental Research, 2024 - Copper-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides with β-trifluoromethyl-substituted alkenyl heteroarenes
Xiang Cheng, Xin Chang, Yuhong Yang, Zongpeng Zhang, Jing Li, Yipu Li, Wenxiao Zhao, Lung Wa Chung, Huailong Teng, Xiu-Qin Dong, Chun-Jiang Wang
Science China Chemistry, 2023 - Electron-rich benzofulvenes as effective dipolarophiles in copper(i)-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides
Xin Chang, Xue-Tao Liu, Fangfang Li, Yuhong Yang, Lung Wa Chung, Chun-Jiang Wang
Chemical Science, 2023 - Enantio- and diastereodivergent synthesis of fused indolizines enabled by synergistic Cu/Ir catalysis
Bing-Ke Zhu, Hui Xu, Lu Xiao, Xin Chang, Liang Wei, Huailong Teng, Yanfeng Dang, Xiu-Qin Dong, Chun-Jiang Wang
Chemical Science, 2023 - Stereodivergent synthesis of enantioenriched unnatural α-amino acids enabled by synergistic dual metal catalysis
Liang Wei, Xin Chang, Zongpeng Zhang, Zuo-Fei Wang, Chun-Jiang Wang
Kexue Tongbao Chinese Science Bulletin, 2023 - Cooperative Catalyst-Enabled Regio- and Stereodivergent Synthesis of α-Quaternary α-Amino Acids via Asymmetric Allylic Alkylation of Aldimine Esters with Racemic Allylic Alcohols
Lu Xiao, Xin Chang, Hui Xu, Qi Xiong, Yanfeng Dang, Chun‐Jiang Wang
Angewandte Chemie International Edition, 2022 - Iridium-Catalyzed Asymmetric Cascade Allylation/Retro-Claisen Reaction
Zhi-Yuan Yi, Lu Xiao, Xin Chang, Xiu-Qin Dong, Chun-Jiang Wang
Journal of the American Chemical Society, 2022 - Recent Advances in Catalytic Asymmetric 1,3-Dipolar Cycloaddition Reactions with Kinetic Resolution
Huachao Liu, Chong Shen, Xin Chang, Chunjiang Wang
Chinese Journal of Organic Chemistry, 2022 - Stereodivergent Construction of 1,4-Nonadjacent Stereocenters via Hydroalkylation of Racemic Allylic Alcohols Enabled by Copper/Ruthenium Relay Catalysis
Xin Chang, Xiang Cheng, Xue‐Tao Liu, Cong Fu, Wei‐Yi Wang, Chun‐Jiang Wang
Angewandte Chemie International Edition, 2022 - Stereodivergent Synthesis of Enantioenriched α-Deuterated α-Amino Acids via Cascade Cu(I)-Catalyzed H-D Exchange and Dual Cu- and Ir-Catalyzed Allylation
Cong Fu, Xin Chang, Lu Xiao, Chun-Jiang Wang
Organic Letters, 2022 - Catalytic Asymmetric Benzylation of Azomethine Ylides Enabled by Synergistic Lewis Acid/Palladium Catalysis
Xin Chang, Jing-Di Ran, Xue-Tao Liu, Chun-Jiang Wang
Organic Letters, 2022 - Palladium-Catalyzed Asymmetric Allylic Alkylation/α-Iminol Rearrangement: A Facile Access to 2-Spirocyclic-Indoline Derivatives
Xin Chang, Chao Che, Zuo-Fei Wang, Chun-Jiang Wang
Ccs Chemistry, 2022 - Catalytic asymmetric synthesis of enantioenriched α-deuterated pyrrolidine derivatives
Xin Chang, Xiang Cheng, Chun-Jiang Wang
Chemical Science, 2022 - Cu-catalyzed endo-selective asymmetric 1,3-dipolar cycloaddition of azomethine ylides with ethenesulfonyl fluorides: Efficient access to chiral pyrrolidine-3-sulfonyl fluorides
Yi-Nan Li, Xin Chang, Qi Xiong, Xiu-Qin Dong, Chun-Jiang Wang
Chinese Chemical Letters, 2021 - Palladium catalyzed cascade umpolung allylation/acetalation for the construction of quaternary 3-amino oxindoles
Xi-Shang Sun, Xin Chang, Li-Min Shi, Zuo-Fei Wang, Liang Wei, Chun-Jiang Wang
Chemical Communications, 2021 - β-Substituted Alkenyl Heteroarenes as Dipolarophiles in the Cu(I)-Catalyzed Asymmetric 1,3-Dipolar Cycloaddition of Azomethine Ylides Empowered by a Dual Activation Strategy: Stereoselectivity and Mechanistic Insight
Xin Chang, Yuhong Yang, Chong Shen, Kun-Shan Xue, Zuo-Fei Wang, Hengjiang Cong, Hai-Yan Tao, Lung Wa Chung, Chun-Jiang Wang
Journal of the American Chemical Society, 2021 - Chiral Ugi-type amines: Practical synthesis, ligand development, and asymmetric catalysis
Wu-Wei Dong, Yi-Nan Li, Xin Chang, Chong Shen, Chun-Jiang Wang
ACS Catalysis, 2020 - Catalytic Asymmetric Reactions with N-Metallated Azomethine Ylides
Liang Wei, Xin Chang, Chun-Jiang Wang
Accounts of Chemical Research, 2020 - Copper(I)-Catalyzed Kinetic Resolution of exo-3-Oxodicyclopentadienes and endo-3-Oxodicyclopentadiene
Xin Chang, Xi-Shang Sun, Chao Che, Yuan-Zheng Hu, Hai-Yan Tao, Chun-Jiang Wang
Organic Letters, 2019 - Stereodivergent Synthesis of α,α-Disubstituted α-Amino Acids via Synergistic Cu/Ir Catalysis
Liang Wei, Qiao Zhu, Shi-Ming Xu, Xin Chang, Chun-Jiang Wang
Journal of the American Chemical Society, 2018 - Nickel(II)-Catalyzed Cascade Vinylogous Mukaiyama 1,6-Michael/Michael Addition of 2-Silyloxyfuran with N-Sulfonyl-1-aza-1,3-dienes: Access to Fused Piperidine/Butyrolactone Skeletons
Kang Liu, Xin Chang, Chun-Jiang Wang
Organic Letters, 2016 - Cu(I)-Catalyzed Asymmetric Multicomponent Cascade Inverse Electron-Demand Aza-Diels-Alder/Nucleophilic Addition/Ring-Opening Reaction Involving 2-Methoxyfurans as Efficient Dienophiles
Rong Huang, Xin Chang, Jun Li, Chun-Jiang Wang
Journal of the American Chemical Society, 2016
