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Molybdenum chloride catalysts for Z-selective olefin metathesis reactions

Nature volume 542, pages 80–85 (2017)Cite this article

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Abstract

The development of catalyst-controlled stereoselective olefin metathesis processes1 has been a pivotal recent advance in chemistry. The incorporation of appropriate ligands within complexes based on molybdenum2, tungsten3 and ruthenium4 has led to reactivity and selectivity levels that were previously inaccessible. Here we show that molybdenum monoaryloxide chloride complexes furnish higher-energy (Z) isomers of trifluoromethyl-substituted alkenes through cross-metathesis reactions with the commercially available, inexpensive and typically inert Z-1,1,1,4,4,4-hexafluoro-2-butene. Furthermore, otherwise inefficient and non-stereoselective transformations with Z-1,2-dichloroethene and 1,2-dibromoethene can be effected with substantially improved efficiency and Z selectivity. The use of such molybdenum monoaryloxide chloride complexes enables the synthesis of representative biologically active molecules and trifluoromethyl analogues of medicinally relevant compounds. The origins of the activity and selectivity levels observed, which contradict previously proposed principles5, are elucidated with the aid of density functional theory calculations.

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Figure 1: Initial findings and synthesis of Z-alkenyl halides.
Figure 2: Mo MAC complexes engage a typically inert trifluoromethyl-substituted alkene.
Figure 3: Utility and functional group compatibility.
Figure 4: Computational and mechanistic studies.

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Acknowledgements

This research was supported by the United States National Institutes of Health, Institute of General Medical Sciences (GM-59426). M.J.K. acknowledges support through LaMattina and Bristol-Myers Squibb Graduate Fellowships. We thank P. Müller for helping to obtain various X-ray structures and X. Shen for advice and experimental assistance. We are grateful to XiMo, AG for gifts of paraffin tablets.

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Authors and Affiliations

  1. Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, 02467, Massachusetts, USA

    Ming Joo Koh, Thach T. Nguyen, Sebastian Torker & Amir H. Hoveyda

  2. Department of Chemistry, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    Jonathan K. Lam, Jakub Hyvl & Richard R. Schrock

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Contributions

M.J.K. and T.T.N. were involved in the discovery, design and development of the new Z-selective cross-metathesis strategies and their applications. J.K.L., J.H. and R.R.S. were involved in the synthesis and characterization of Mo MAC complexes. S.T. designed and performed the computational investigations, developed the models for the observed levels and patterns in reactivity and stereoselectivity. A.H.H. directed the investigation and wrote the manuscript with suggestions from M.J.K., T.T.N., J.K.L., S.T. and R.R.S.

Corresponding author

Correspondence to Amir H. Hoveyda.

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Competing interests

The catalysts and applications are licensed to a company (XiMo, AG) founded by A.H.H. and R.R.S.

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Supplementary Information

This file contains Supplementary Text and Data, Supplementary Tables 1-4 and additional references (see Contents for details). (PDF 25285 kb)

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Koh, M., Nguyen, T., Lam, J. et al. Molybdenum chloride catalysts for Z-selective olefin metathesis reactions. Nature 542, 80–85 (2017). https://doi.org/10.1038/nature21043

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