Article

Synthesis of E- and Z-trisubstituted alkenes by catalytic cross-metathesis

  • Nature volume 552, pages 347354 (21 December 2017)
  • doi:10.1038/nature25002
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Abstract

Catalytic cross-metathesis is a central transformation in chemistry, yet corresponding methods for the stereoselective generation of acyclic trisubstituted alkenes in either the E or the Z isomeric forms are not known. The key problems are a lack of chemoselectivity—namely, the preponderance of side reactions involving only the less hindered starting alkene, resulting in homo-metathesis by-products—and the formation of short-lived methylidene complexes. By contrast, in catalytic cross-coupling, substrates are more distinct and homocoupling is less of a problem. Here we show that through cross-metathesis reactions involving E- or Z-trisubstituted alkenes, which are easily prepared from commercially available starting materials by cross-coupling reactions, many desirable and otherwise difficult-to-access linear E- or Z-trisubstituted alkenes can be synthesized efficiently and in exceptional stereoisomeric purity (up to 98 per cent E or 95 per cent Z). The utility of the strategy is demonstrated by the concise stereoselective syntheses of biologically active compounds, such as the antifungal indiacen B and the anti-inflammatory coibacin D.

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Acknowledgements

This research was supported by the United States National Institutes of Health, Institute of General Medical Sciences (GM-59426 and, in part, CHE-1362763). M.J.K. and T.J.M. are grateful for support in the form of a Bristol Myers-Squibb Fellowship in Organic Chemistry and a John LaMattina Graduate Fellowship, respectively.

Author information

Author notes

    • Thach T. Nguyen
    •  & Ming Joo Koh

    These authors contributed equally to this work.

Affiliations

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

    • Thach T. Nguyen
    • , Ming Joo Koh
    • , Tyler J. Mann
    •  & Amir H. Hoveyda
  2. Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

    • Richard R. Schrock

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Contributions

T.T.N. and M.J.K. were involved in the discovery, design and development of the cross-metathesis strategies and their applications. T.J.M. carried out the initial exploratory studies with 1,1-disubstituted alkenes. A.H.H. designed and directed the investigations. A.H.H. and R.R.S. conceived the studies that led to the development of molybdenum complexes used in this study. A.H.H. wrote the manuscript with revisions provided by T.T.N., M.J.K. and T.J.M.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Amir H. Hoveyda.

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    Supplementary Information

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