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Design of catalysts for site-selective and enantioselective functionalization of non-activated primary C–H bonds

Nature Chemistryvolume 10pages10481055 (2018) | Download Citation

Abstract

C–H functionalization represents a promising approach for the synthesis of complex molecules. Instead of relying on modifying the functional groups present in a molecule, the synthetic sequence is achieved by carrying out selective reactions on the C–H bonds, which traditionally would have been considered to be the unreactive components of a molecule. A major challenge is to design catalysts to control both the site- and stereoselectivity of the C–H functionalization. We have been developing dirhodium catalysts with different selectivity profiles in C–H functionalization reactions with donor/acceptor carbenes as reactive intermediates. Here we describe a new dirhodium catalyst capable of the functionalization of non-activated primary C–H bonds with high levels of site selectivity and enantioselectivity.

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Acknowledgements

Financial support was provided by the National Science Foundation (NSF) via the CCI Center for Selective C–H Functionalization (CHE-1700982). D.G.M. acknowledges NSF MRI-R2 grant CHE-0958205 and the use of the resources of the Cherry Emerson Center for Scientific Computation. Funds to purchase the NMR and X-ray spectrometers used in these studies were supported by the NSF (CHE 1531620 and CHE 1626172). The authors thank J. Bacsa for the X-ray structure determinations.

Author information

Affiliations

  1. Department of Chemistry, Emory University, Atlanta, GA, USA

    • Kuangbiao Liao
    • , Djamaladdin G. Musaev
    •  & Huw M. L. Davies
  2. Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, USA

    • Yun-Fang Yang
    • , Yingzi Li
    • , Jacob N. Sanders
    •  & K. N. Houk
  3. College of Chemical Engineering, Zhejiang University of Technology, Hangzhou, Zhejiang, P.R. China

    • Yun-Fang Yang
  4. Cherry L. Emerson Center for Scientific Computation, Emory University, Atlanta, GA, USA

    • Djamaladdin G. Musaev

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Contributions

K.L. and H.M.L.D. designed the synthetic experiments, K.L. performed the synthetic experiments, Y.-F.Y., Y.L., J.S., D.G.M. and K.N.H. conducted the computational studies, and K.L., K.N.H and H.M.L.D. prepared the manuscript.

Competing interests

H.M.L.D. is a named inventor on a patent entitled ‘Dirhodium catalyst compositions and synthetic processes related thereto’ (US 8,974,428, issued March 10, 2015). The other authors declare no competing interests.

Corresponding author

Correspondence to Huw M. L. Davies.

Supplementary information

  1. Supplementary information

    Supplementary experimental and computational details

  2. Crystallographic data

    CIF for compound 11; CCDC reference: 1551026

  3. Crystallographic data

    Structure factors for compound 11; CCDC reference 1551026

  4. Crystallographic data

    CIF for catalyst F; CCDC reference: 1552206

  5. Crystallographic data

    Structure factors for catalyst F; CCDC reference 1552206

  6. Computational data

    Calculated C2 symmetric structure for catalyst I

  7. Computational data

    Calculated C4 symmetric structure for catalyst I

  8. Computational data

    Calculated C4a symmetric structure for catalyst I

  9. Computational data

    Calculated D2 symmetric structure for catalyst I

  10. Computational data

    Calculated C2 symmetric carbene structure

  11. Computational data

    Calculated C4 symmetric carbene structure for catalyst

  12. Computational data

    Calculated transition state TS1

  13. Computational data

    Calculated transition state TS2

  14. Computational data

    Calculated transition state TS3

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DOI

https://doi.org/10.1038/s41557-018-0087-7