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Generating carbyne equivalents with photoredox catalysis

Nature volume 554, pages 86–91 (2018)Cite this article

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Abstract

Carbon has the unique ability to bind four atoms and form stable tetravalent structures that are prevalent in nature. The lack of one or two valences leads to a set of species—carbocations, carbanions, radicals and carbenes—that is fundamental to our understanding of chemical reactivity1. In contrast, the carbyne—a monovalent carbon with three non-bonded electrons—is a relatively unexplored reactive intermediate2,3,4,5,6; the design of reactions involving a carbyne is limited by challenges associated with controlling its extreme reactivity and the lack of efficient sources7,8,9. Given the innate ability of carbynes to form three new covalent bonds sequentially, we anticipated that a catalytic method of generating carbynes or related stabilized species would allow what we term an ‘assembly point’ disconnection approach for the construction of chiral centres. Here we describe a catalytic strategy that generates diazomethyl radicals as direct equivalents of carbyne species using visible-light photoredox catalysis. The ability of these carbyne equivalents to induce site-selective carbon–hydrogen bond cleavage in aromatic rings enables a useful diazomethylation reaction, which underpins sequencing control for the late-stage assembly-point functionalization of medically relevant agents. Our strategy provides an efficient route to libraries of potentially bioactive molecules through the installation of tailored chiral centres at carbon–hydrogen bonds, while complementing current translational late-stage functionalization processes10. Furthermore, we exploit the dual radical and carbene character of the generated carbyne equivalent in the direct transformation of abundant chemical feedstocks into valuable chiral molecules.

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Figure 1: Monovalent carbyne species enable an assembly-point functionalization strategy for chiral centre construction with aryl C–H bonds.
Figure 2: New hypervalent iodine reagents and photoredox catalysis enables a C–H bond diazomethylation reaction.
Figure 3: Arene C–H diazomethylation by means of photoredox catalysis.
Figure 4: Late-stage assembly-point diversification of medically relevant agents.
Figure 5: Catalytic assembly-point functionalization of carbyne equivalents with feedstock chemicals.

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Acknowledgements

This work was funded by the ICIQ Foundation, the CERCA Programme (Generalitat de Catalunya), MINECO (CTQ2016-75311-P, AEI/FEDER-EU; Severo Ochoa Excellence Accreditation 2014–2018, SEV-2013-0319), the CELLEX Foundation through the CELLEX-ICIQ high-throughput experimentation platform. We thank the European Union for a Marie Curie-COFUND post-doctoral fellowship (to Z.W.) and the CELLEX Foundation for pre-doctoral (to A.G.H.) and post-doctoral fellowships (to A.M.d.H.). We thank the ICIQ Research Support Area, and F. Bravo for LC/MS instrumentation. M.G.S. is a Junior Group Leader of the ICIQ Starting Career Programme 2014−2019.

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Authors and Affiliations

  1. Institute of Chemical Research of Catalonia (ICIQ), The Barcelona Institute of Science and Technology, Avinguda Països Catalans 16, Tarragona, 43007, Spain

    Zhaofeng Wang, Ana G. Herraiz, Ana M. del Hoyo & Marcos G. Suero

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  1. Zhaofeng Wang
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  2. Ana G. Herraiz
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  3. Ana M. del Hoyo
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  4. Marcos G. Suero
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Contributions

M.G.S. conceived the idea of developing new hypervalent iodine reagents for the generation of carbynes. Z.W., A.G.H. and A.M.d.H. performed the experiments. M.G.S. wrote the manuscript. All authors contributed to the analysis and interpretation of the data and commented on the final draft of the manuscript.

Corresponding author

Correspondence to Marcos G. Suero.

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Competing interests

M.G.S. and Z.W. have filed a provisional patent application (number EP17382063) through the Fundació Institut Català D’Investigació Química (ICIQ) that is based on the results presented here.

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Reviewer Information Nature thanks I. Larrosa and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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Wang, Z., Herraiz, A., del Hoyo, A. et al. Generating carbyne equivalents with photoredox catalysis. Nature 554, 86–91 (2018). https://doi.org/10.1038/nature25185

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