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Amide-directed photoredox-catalysed C–C bond formation at unactivated sp3 C–H bonds

Nature volume 539, pages 272–275 (2016)Cite this article

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Abstract

Carbon–carbon (C–C) bond formation is paramount in the synthesis of biologically relevant molecules, modern synthetic materials and commodity chemicals such as fuels and lubricants. Traditionally, the presence of a functional group is required at the site of C–C bond formation. Strategies that allow C–C bond formation at inert carbon–hydrogen (C–H) bonds enable access to molecules that would otherwise be inaccessible and the development of more efficient syntheses of complex molecules1,2. Here we report a method for the formation of C–C bonds by directed cleavage of traditionally non-reactive C–H bonds and their subsequent coupling with readily available alkenes. Our methodology allows for amide-directed selective C–C bond formation at unactivated sp3 C–H bonds in molecules that contain many such bonds that are seemingly indistinguishable. Selectivity arises through a relayed photoredox-catalysed oxidation of a nitrogen–hydrogen bond. We anticipate that our findings will serve as a starting point for functionalization at inert C–H bonds through a strategy involving hydrogen-atom transfer.

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Figure 1: Selectivity issues with C–H bond functionalization.
Figure 2: Photoredox-catalysed C–C bond formation at unactivated sp3 C–H bonds.
Figure 3: Regioselective functionalization of sp3 C–H bonds.

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Acknowledgements

We thank NIGMS (GM80442) for support. J.C.K.C. thanks the Croucher Foundation (Hong Kong) for support. We thank M. Burns (CSU) for technical assistance. We thank R. R. Knowles (Princeton University) for sharing results before publication.

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Authors and Affiliations

  1. Department of Chemistry, Colorado State University, Fort Collins, 80523, Colorado, USA

    John C. K. Chu & Tomislav Rovis

  2. Department of Chemistry, Columbia University, New York, 10027, New York, USA

    Tomislav Rovis

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  1. John C. K. Chu
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  2. Tomislav Rovis
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Contributions

T.R. and J.C.K.C. conceived the concept and prepared the manuscript. T.R. directed the investigation. J.C.K.C. developed and studied the reaction.

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Correspondence to Tomislav Rovis.

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The authors declare no competing financial interests.

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Nature thanks A. Studer and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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Chu, J., Rovis, T. Amide-directed photoredox-catalysed C–C bond formation at unactivated sp3 C–H bonds. Nature 539, 272–275 (2016). https://doi.org/10.1038/nature19810

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