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Cleaving arene rings for acyclic alkenylnitrile synthesis

Nature volume 597, pages 64–69 (2021)Cite this article

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Abstract

Synthetic chemistry is built around the formation of carbon–carbon bonds. However, the development of methods for selective carbon–carbon bond cleavage is a largely unmet challenge1,2,3,4,5,6. Such methods will have promising applications in synthesis, coal liquefaction, petroleum cracking, polymer degradation and biomass conversion. For example, aromatic rings are ubiquitous skeletal features in inert chemical feedstocks, but are inert to many reaction conditions owing to their aromaticity and low polarity. Over the past century, only a few methods under harsh conditions have achieved direct arene-ring modifications involving the cleavage of inert aromatic carbon–carbon bonds7,8, and arene-ring-cleavage reactions using stoichiometric transition-metal complexes or enzymes in bacteria are still limited9,10,11. Here we report a copper-catalysed selective arene-ring-opening reaction strategy. Our aerobic oxidative copper catalyst converts anilines, arylboronic acids, aryl azides, aryl halides, aryl triflates, aryl trimethylsiloxanes, aryl hydroxamic acids and aryl diazonium salts into alkenyl nitriles through selective carbon–carbon bond cleavage of arene rings. This chemistry was applied to the modification of polycyclic aromatics and the preparation of industrially important hexamethylenediamine and adipic acid derivatives. Several examples of the late-stage modification of complex molecules and fused ring compounds further support the potential broad utility of this methodology.

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Fig. 1: Cleaving arene rings.
Fig. 2: Scope of polycyclic aromatic compounds and transformations to ortho(cis-cyanovinyl) arylnitriles.
Fig. 3: The cleavage of anilines and phenylboronic acids and downstream transformations.
Fig. 4: Mechanism studies.

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Data availability

The data that support the findings of this study are available from the corresponding authors upon reasonable request.

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Acknowledgements

We acknowledge the NSFC (grant numbers 21632001, 21772002, 81821004, 21933004), the National Key Research and Development Project (grant number 2019YFC1708902), and the US National Science Foundation (CHE-1764328) for financial support of this research.

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Author notes

  1. These authors contributed equally: Xu Qiu, Yueqian Sang, Hao Wu

Authors and Affiliations

  1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China

    Xu Qiu, Hao Wu, Zixi Yan, Yachong Wang, Zengrui Cheng, Xiaoyang Wang, Hui Tan, Song Song, Xiaohui Zhang & Ning Jiao

  2. Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, USA

    Xiao-Song Xue & K. N. Houk

  3. State Key Laboratory of Elemento-organic Chemistry, College of Chemistry, Nankai University, Tianjin, China

    Yueqian Sang & Xiao-Song Xue

  4. Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, China

    Hao Wu & Guisheng Zhang

  5. State Key Laboratory of Organometallic Chemistry, Chinese Academy of Sciences, Shanghai, China

    Ning Jiao

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Contributions

N.J. conceived the project and directed the research. K.N.H. and X.-S.X. supervised the mechanistic study. X.Q., Y.S., X.-S.X., K.N.H. and N.J. wrote the paper. X.Q., H.W., Z.Y., Y.W., Z.C. and X.W. performed the experiments. Y.S. performed the DFT calculations. H.T, S.S., G.Z. and X.Z. discussed the results.

Corresponding authors

Correspondence to K. N. Houk or Ning Jiao.

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Extended data figures and tables

Extended Data Fig. 1 Downstream transformations and mechanism studies.

a, Downstream transformations of alkenyl nitriles. b, The excluded intermediates. c, HOMO(α) and HOMO-1(β) of the triplet copper bis-nitrene intermediate. *See Supplementary Information for experimental details.

Supplementary information

Supplementary Information

This file contains Supplementary Information (see Table of Contents in PDF for full description).

Supplementary Data

This file contains the crystal structure of 48 in Fig 3.

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Qiu, X., Sang, Y., Wu, H. et al. Cleaving arene rings for acyclic alkenylnitrile synthesis. Nature 597, 64–69 (2021). https://doi.org/10.1038/s41586-021-03801-y

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