IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-48175-7.html
   My bibliography  Save this article

Enantioselective synthesis of chiral α,α-dialkyl indoles and related azoles by cobalt-catalyzed hydroalkylation and regioselectivity switch

Author

Listed:
  • Jiangtao Ren

    (Yunnan University
    Southwest United Graduate School)

  • Zheng Sun

    (Yunnan University)

  • Shuang Zhao

    (Yunnan University
    Yunnan University)

  • Jinyuan Huang

    (Yunnan University
    Yunnan University)

  • Yukun Wang

    (Yunnan University)

  • Cheng Zhang

    (Yunnan University
    Yunnan University)

  • Jinhai Huang

    (Yunnan University)

  • Chenhao Zhang

    (Yunnan University)

  • Ruipu Zhang

    (Yunnan University
    Yunnan University)

  • Zhihan Zhang

    (Central China Normal University)

  • Xu Ji

    (Yunnan University
    Yunnan University)

  • Zhihui Shao

    (Yunnan University
    Southwest United Graduate School)

Abstract

General, catalytic and enantioselective construction of chiral α,α-dialkyl indoles represents an important yet challenging objective to be developed. Herein we describe a cobalt catalyzed enantioselective anti-Markovnikov alkene hydroalkylation via the remote stereocontrol for the synthesis of α,α-dialkyl indoles and other N-heterocycles. This asymmetric C(sp3)−C(sp3) coupling features high flexibility in introducing a diverse set of alkyl groups at the α-position of chiral N-heterocycles. The utility of this methodology has been demonstrated by late-stage functionalization of drug molecules, asymmetric synthesis of bioactive molecules, natural products and functional materials, and identification of a class of molecules exhibiting anti-apoptosis activities in UVB-irradiated HaCaT cells. Ligands play a vital role in controlling the reaction regioselectivity. Changing the ligand from bi-dentate L6 to tridentate L12 enables CoH-catalyzed Markovnikov hydroalkylation. Mechanistic studies disclose that the anti-Markovnikov hydroalkylation involves a migratory insertion process while the Markovnikov hydroalkylation involves a MHAT process.

Suggested Citation

  • Jiangtao Ren & Zheng Sun & Shuang Zhao & Jinyuan Huang & Yukun Wang & Cheng Zhang & Jinhai Huang & Chenhao Zhang & Ruipu Zhang & Zhihan Zhang & Xu Ji & Zhihui Shao, 2024. "Enantioselective synthesis of chiral α,α-dialkyl indoles and related azoles by cobalt-catalyzed hydroalkylation and regioselectivity switch," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48175-7
    DOI: 10.1038/s41467-024-48175-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-48175-7
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-48175-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Lun Li & Jiangtao Ren & Jingjie Zhou & Xiaomei Wu & Zhihui Shao & Xiaodong Yang & Deyun Qian, 2022. "Enantioselective synthesis of N-alkylindoles enabled by nickel-catalyzed C-C coupling," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    2. Michael T. McCabe & Heidi M. Ott & Gopinath Ganji & Susan Korenchuk & Christine Thompson & Glenn S. Van Aller & Yan Liu & Alan P. Graves & Anthony Della Pietra III & Elsie Diaz & Louis V. LaFrance & M, 2012. "EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations," Nature, Nature, vol. 492(7427), pages 108-112, December.
    3. Lei Wang & Chuiyi Lin & Qinglei Chong & Zhihan Zhang & Fanke Meng, 2023. "Photoredox cobalt-catalyzed regio-, diastereo- and enantioselective propargylation of aldehydes via propargyl radicals," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    4. Jia-Wang Wang & Yan Li & Wan Nie & Zhe Chang & Zi-An Yu & Yi-Fan Zhao & Xi Lu & Yao Fu, 2021. "Catalytic asymmetric reductive hydroalkylation of enamides and enecarbamates to chiral aliphatic amines," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    5. Kun Xu & Thomas Gilles & Bernhard Breit, 2015. "Asymmetric synthesis of N-allylic indoles via regio- and enantioselective allylation of aryl hydrazines," Nature Communications, Nature, vol. 6(1), pages 1-7, November.
    6. Yingcheng Wang & Sheng Wang & Wenyu Shan & Zhihui Shao, 2020. "Direct asymmetric N-propargylation of indoles and carbazoles catalyzed by lithium SPINOL phosphate," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    7. Zhaobin Wang & Haolin Yin & Gregory C. Fu, 2018. "Catalytic enantioconvergent coupling of secondary and tertiary electrophiles with olefins," Nature, Nature, vol. 563(7731), pages 379-383, November.
    8. Shan Wang & Jian-Xin Zhang & Tian-Yi Zhang & Huan Meng & Bi-Hong Chen & Wei Shu, 2021. "Enantioselective access to chiral aliphatic amines and alcohols via Ni-catalyzed hydroalkylations," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Xiao-Xu Wang & Yuan-Tai Xu & Zhi-Lin Zhang & Xi Lu & Yao Fu, 2022. "NiH-catalysed proximal-selective hydroalkylation of unactivated alkenes and the ligand effects on regioselectivity," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    2. Qian Gao & Wei-Cheng Xu & Xuan Nie & Kang-Jie Bian & Hong-Rui Yuan & Wen Zhang & Bing-Bing Wu & Xi-Sheng Wang, 2024. "Regio‐ and enantioselective nickel-alkyl catalyzed hydroalkylation of alkynes," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
    3. Yao Zhang & Deyong Qiao & Mei Duan & You Wang & Shaolin Zhu, 2022. "Enantioselective synthesis of α-aminoboronates by NiH-catalysed asymmetric hydroamidation of alkenyl boronates," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    4. Xiaotao Zhu & Wujun Jian & Meirong Huang & Daliang Li & Yajun Li & Xinhao Zhang & Hongli Bao, 2021. "Asymmetric radical carboesterification of dienes," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    5. Xiao Chen & Yinglu Li & Fang Zhu & Xinjing Xu & Brian Estrella & Manuel A. Pazos & John T. McGuire & Dimitris Karagiannis & Varun Sahu & Mustafo Mustafokulov & Claudio Scuoppo & Francisco J. Sánchez-R, 2023. "Context-defined cancer co-dependency mapping identifies a functional interplay between PRC2 and MLL-MEN1 complex in lymphoma," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    6. Varadha Balaji Venkadakrishnan & Adam G. Presser & Richa Singh & Matthew A. Booker & Nicole A. Traphagen & Kenny Weng & Nathaniel C. E. Voss & Navin R. Mahadevan & Kei Mizuno & Loredana Puca & Osasena, 2024. "Lineage-specific canonical and non-canonical activity of EZH2 in advanced prostate cancer subtypes," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    7. Lin Zhang & Jingkun Qu & Yutao Qi & Yimin Duan & Yu-Wen Huang & Zhifen Zhou & Ping Li & Jun Yao & Beibei Huang & Shuxing Zhang & Dihua Yu, 2022. "EZH2 engages TGFβ signaling to promote breast cancer bone metastasis via integrin β1-FAK activation," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    8. Wen Hao Neo & Yiran Meng & Alba Rodriguez-Meira & Muhammad Z. H. Fadlullah & Christopher A. G. Booth & Emanuele Azzoni & Supat Thongjuea & Marella F. T. R. Bruijn & Sten Eirik W. Jacobsen & Adam J. Me, 2021. "Ezh2 is essential for the generation of functional yolk sac derived erythro-myeloid progenitors," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    9. Carolina Gracia-Diaz & Yijing Zhou & Qian Yang & Reza Maroofian & Paula Espana-Bonilla & Chul-Hwan Lee & Shuo Zhang & Natàlia Padilla & Raquel Fueyo & Elisa A. Waxman & Sunyimeng Lei & Garrett Otrimsk, 2023. "Gain and loss of function variants in EZH1 disrupt neurogenesis and cause dominant and recessive neurodevelopmental disorders," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    10. Wen-Tao Zhao & Jian-Xin Zhang & Bi-Hong Chen & Wei Shu, 2023. "Ligand-enabled Ni-catalysed enantioconvergent intermolecular Alkyl-Alkyl cross-coupling between distinct Alkyl halides," Nature Communications, Nature, vol. 14(1), pages 1-7, December.
    11. Yue Wang & Suping Zhang & Ke Zeng & Pengli Zhang & Xiaorong Song & Tie-Gen Chen & Guoqin Xia, 2024. "Deoxygenative radical cross-coupling of C(sp3)−O/C(sp3)−H bonds promoted by hydrogen-bond interaction," Nature Communications, Nature, vol. 15(1), pages 1-8, December.
    12. Pauliina M. Munne & Lahja Martikainen & Iiris Räty & Kia Bertula & Nonappa & Janika Ruuska & Hanna Ala-Hongisto & Aino Peura & Babette Hollmann & Lilya Euro & Kerim Yavuz & Linda Patrikainen & Maria S, 2021. "Compressive stress-mediated p38 activation required for ERα + phenotype in breast cancer," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    13. Daning Zeng & Zihao Liu & Guoce Huang & You Wang & Shaolin Zhu, 2024. "Regio-, stereo-, and enantioselective ipso- and migratory defluorinative olefin cross-coupling to access highly functionalized monofluoroalkenes," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
    14. Ayushi Verma & Akhilesh Singh & Manish Pratap Singh & Mushtaq Ahmad Nengroo & Krishan Kumar Saini & Saumya Ranjan Satrusal & Muqtada Ali Khan & Priyank Chaturvedi & Abhipsa Sinha & Sanjeev Meena & Anu, 2022. "EZH2-H3K27me3 mediated KRT14 upregulation promotes TNBC peritoneal metastasis," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    15. Xiaoyang Li & Yufei Cao & Kai Luo & Lin Zhang & Yunxiu Bai & Jiarong Xiong & Richard N. Zare & Jun Ge, 2022. "Cooperative catalysis by a single-atom enzyme-metal complex," Nature Communications, Nature, vol. 13(1), pages 1-8, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48175-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.