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Functionalized olefin cross-coupling to construct carbon–carbon bonds

Nature volume 516, pages 343–348 (2014)Cite this article

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Abstract

Carbon–carbon (C–C) bonds form the backbone of many important molecules, including polymers, dyes and pharmaceutical agents. The development of new methods to create these essential connections in a rapid and practical fashion has been the focus of numerous organic chemists. This endeavour relies heavily on the ability to form C–C bonds in the presence of sensitive functional groups and congested structural environments. Here we report a chemical transformation that allows the facile construction of highly substituted and uniquely functionalized C–C bonds. Using a simple iron catalyst, an inexpensive silane and a benign solvent under ambient atmosphere, heteroatom-substituted olefins are easily reacted with electron-deficient olefins to create molecular architectures that were previously difficult or impossible to access. More than 60 examples are presented with a wide array of substrates, demonstrating the chemoselectivity and mildness of this simple reaction.

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Figure 1: Functionalized olefin cross-coupling as a strategy for convergent chemical synthesis.
Figure 2: Functionalized olefin cross-coupling optimization studies.
Figure 3: Adducts synthesized by functionalized olefin cross-coupling.
Figure 4: Additional functionalized olefin cross-coupling studies.
Figure 5: Functionalized olefin cross-coupling reverses conventional reactivity expectations.

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Acknowledgements

Financial support for this work was provided by NIH/NIGMS (GM-097444). The National Science Foundation supported a predoctoral fellowship for J.C.L.; the Shanghai Institute of Organic Chemistry, Zhejiang Medicine Co. and Pharmaron supported a postdoctoral fellowship for J.G.; and the Japan Society for the Promotion of Science supported a postdoctoral fellowship for Y.Y. We are grateful to D.-H. Huang and L. Pasternack (TSRI) for assistance with NMR spectroscopy, and A. L. Rheingold and C. E. Moore (UCSD) for X-ray crystallographic analysis. We thank R. A. Shenvi (TSRI) and Y. Ji (TSRI) for discussions.

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  1. Julian C. Lo and Jinghan Gui: These authors contributed equally to this work.

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  1. Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA,

    Julian C. Lo, Jinghan Gui, Yuki Yabe, Chung-Mao Pan & Phil S. Baran

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Contributions

J.C.L. and P.S.B. conceived the work; J.C.L. conducted initial feasibility studies; J.C.L., J.G., Y.Y., C.-M.P. and P.S.B. designed the experiments and analysed the data; J.C.L., J.G., Y.Y. and C.-M.P. performed the experiments; and J.C.L. and P.S.B. wrote the manuscript.

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Correspondence to Phil S. Baran.

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The authors declare no competing financial interests.

Additional information

Crystallographic data for the structure of Fe(dibm)3 (5) is available free of charge from the Cambridge Crystallographic Data Centre under deposition number CCDC 1022625.

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This file contains Supplementary Text and Data, Supplementary Tables 1-2, Supplementary Figures 1-30 and Supplementary References. (PDF 16782 kb)

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Lo, J., Gui, J., Yabe, Y. et al. Functionalized olefin cross-coupling to construct carbon–carbon bonds. Nature 516, 343–348 (2014). https://doi.org/10.1038/nature14006

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