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E- and Z-, di- and tri-substituted alkenyl nitriles through catalytic cross-metathesis

Nature Chemistryvolume 11pages478487 (2019) | Download Citation

Abstract

Nitriles are found in many bioactive compounds, and are among the most versatile functional groups in organic chemistry. Despite many notable recent advances, however, there are no approaches that may be used for the preparation of di- or tri-substituted alkenyl nitriles. Related approaches that are broad in scope and can deliver the desired products in high stereoisomeric purity are especially scarce. Here, we describe the development of several efficient catalytic cross-metathesis strategies, which provide direct access to a considerable range of Z- or E-di-substituted cyano-substituted alkenes or their corresponding tri-substituted variants. Depending on the reaction type, a molybdenum-based monoaryloxide pyrrolide or chloride (MAC) complex may be the optimal choice. The utility of the approach, enhanced by an easy to apply protocol for utilization of substrates bearing an alcohol or a carboxylic acid moiety, is highlighted in the context of applications to the synthesis of biologically active compounds.

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Data availability

X-ray crystallographic data for compound 9a, are freely available from the Cambridge Crystallographic Data Centre (CCDC 1861573). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/. All other data in support of the findings of this study are available within the Article and its Supplementary Information or from the corresponding author upon reasonable request.

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Acknowledgements

This research was supported by a grant from the National Institutes of Health (GM-59426). T.T.N. was supported as a John LaMattina Graduate Fellow in Chemical Synthesis. The authors thank S. Torker for helpful discussions.

Author information

Affiliations

  1. Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, MA, USA

    • Yucheng Mu
    • , Thach T. Nguyen
    • , Ming Joo Koh
    •  & Amir H. Hoveyda
  2. Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA

    • Richard R. Schrock

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Contributions

Y.M., T.T.N. and M.J.K. identified the optimal catalyst and conditions, developed the method and performed the experiments to demonstrate utility. The Mo complexes used in this study were designed and developed as part of a long-standing collaboration between the research groups of R.R.S. and A.H.H. A.H.H. directed the investigations and composed the manuscript with revisions provided by the other authors.

Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to Amir H. Hoveyda.

Supplementary information

  1. Supplementary Information

    All experimental and analytical data for the compounds used and generated in the study.

  2. Crystallographic data

    CIF for compound 9a; CCDC reference: 1861573

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https://doi.org/10.1038/s41557-019-0233-x