Generating carbyne equivalents with photoredox catalysis


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.


  1. 1

    Trost, B. M. & Fleming, I. Comprehensive Organic Synthesis (Pergamon, 1991)

  2. 2

    Thap, D. M., Gunning, H. E. & Strausz, O. P. Formation and reactions of monovalent carbon intermediates. I. Photolysis of diethyl mercuribisdiazoacetate. J. Am. Chem. Soc. 89, 6785–6787 (1967)

    Article  Google Scholar 

  3. 3

    Strausz, O. P., Thap, D. M. & Font, J. Formation and reactions of monovalent carbon intermediates. II. Further studies on the decomposition of diethyl mercurybisdiazoacetate. J. Am. Chem. Soc. 90, 1930–1931 (1968)

    CAS  Article  Google Scholar 

  4. 4

    Strausz, O. P. et al. Formation and reactions of monovalent carbon intermediates. III. Reaction of carbethoxymethyne with olefins. J. Am. Chem. Soc. 96, 5723–5732 (1974)

    CAS  Article  Google Scholar 

  5. 5

    Patrick, T. B. & Kovitch, G. H. Photolysis of diethyl mercurybisdiazoacetate and ethyl diazoacetate in chloroalkanes. J. Org. Chem. 40, 1527–1528 (1975)

    CAS  Article  Google Scholar 

  6. 6

    Patrick, T. B. & Wu, T.-T. Photodecomposition of diethyl mercurybis(diazoacetate) in several heterocyclic systems. J. Org. Chem. 43, 1506–1509 (1978)

    CAS  Article  Google Scholar 

  7. 7

    Fürstner, A. Alkyne metathesis on the rise. Angew. Chem. Int. Ed. 52, 2794–2819 (2013)

    Article  Google Scholar 

  8. 8

    Bino, A., Ardon, M. & Shirman, E. Formation of a carbon-carbon triple bond by coupling reactions in aqueous solution. Science 308, 234–235 (2005)

    CAS  ADS  Article  Google Scholar 

  9. 9

    Bogoslavsky, B. et al. Do carbyne radicals really exist in aqueous solution? Angew. Chem. Int. Ed. 51, 90–94 (2012)

    CAS  Article  Google Scholar 

  10. 10

    Cernak, T., Dykstra, K. D., Tyagarajan, S., Vachal, P. & Krska, S. W. The medicinal chemist’s toolbox for late stage functionalization of drug-like molecules. Chem. Soc. Rev. 45, 546–576 (2016)

    CAS  Article  Google Scholar 

  11. 11

    Swings, P. & Rosenfeld, L. Considerations regarding interstellar molecules. Astrophys. J. 86, 483–486 (1937)

    CAS  ADS  Article  Google Scholar 

  12. 12

    Rydbeck, O. E. H., Ellder, J. & Irvine, W. M. Radio detection of interstellar CH. Nature 246, 466–468 (1973)

    CAS  ADS  Article  Google Scholar 

  13. 13

    Morris, P. W. et al. Herschel/HIFI spectral mapping of C+, CH+, and CH in Orion BN/KL: the prevailing role of ultraviolet irradiation in CH+ formation. Astrophys. J. 829, 15–46 (2016)

    ADS  Article  Google Scholar 

  14. 14

    Landau, E. Building Blocks of Life’s Building Blocks Come From Starlight. (JPL, 2016)

  15. 15

    Ford, A. et al. Modern organic synthesis with α-diazocarbonyl compounds. Chem. Rev. 115, 9981–10080 (2015)

    CAS  Article  Google Scholar 

  16. 16

    Nicewicz, D. A. & MacMillan, D. W. C. Merging photoredox catalysis with organocatalysis: the direct asymmetric alkylation of aldehydes. Science 322, 77–80 (2008)

    CAS  ADS  Article  Google Scholar 

  17. 17

    Prier, C. K., Rankic, D. A. & MacMillan, D. W. C. Visible light photoredox catalysis with transition metal complexes: applications in organic synthesis. Chem. Rev. 113, 5322–5363 (2013)

    CAS  Article  Google Scholar 

  18. 18

    Yoshimura, A. & Zhdankin, V. V. Advances in synthetic applications of hypervalent iodine compounds. Chem. Rev. 116, 3328–3435 (2016)

    CAS  Article  Google Scholar 

  19. 19

    Wang, L. & Liu, J. Synthetic applications of hypervalent iodine(III) reagents enabled by visible light photoredox catalysis. Eur. J. Org. Chem. 2016, 1813–1824 (2016)

    CAS  Article  Google Scholar 

  20. 20

    Weiss, R., Seubert, J. & Hampel, F. α-Aryliodonio diazo compounds: SN reactions at the α-C atom as a novel reaction type for diazo compounds. Angew. Chem. Int. Ed. Engl. 33, 1952–1953 (1994)

    Article  Google Scholar 

  21. 21

    Schnaars, C., Hennum, M. & Bonge-Hansen, T. Nucleophilic halogenations of diazo compounds, a complementary principle for the synthesis of halodiazo compounds: experimental and theoretical Studies. J. Org. Chem. 78, 7488–7497 (2013)

    CAS  Article  Google Scholar 

  22. 22

    Boursalian, G. B., Ham, W. S., Mazzotti, A. R. & Ritter, T. Charge-transfer-directed radical substitution enables para-selective C–H functionalization. Nat. Chem. 8, 810–815 (2016)

    CAS  Article  Google Scholar 

  23. 23

    Ye, F. et al. Palladium-catalyzed C-H functionalization of acyldiazomethane and tandem cross-coupling reactions. J. Am. Chem. Soc. 137, 4435–4444 (2015)

    CAS  Article  Google Scholar 

  24. 24

    Fu, L., Mighion, J. D., Voight, E. A. & Davies, H. M. L. Synthesis of 2,2,2,-trichloroethyl aryl- and vinyldiazoacetates by palladium-catalyzed cross-coupling. Chem. Eur. J. 23, 3272–3275 (2017)

    CAS  Article  Google Scholar 

  25. 25

    Lovering, F., Bikker, J. & Humblet, C. Escape from flatland: increasing saturation as an approach to improving clinical success. J. Med. Chem. 52, 6752–6756 (2009)

    CAS  Article  Google Scholar 

  26. 26

    Schönherr, H. & Cernak, T. Profound methyl effects in drug discovery and a call for new C-H methylation reactions. Angew. Chem. Int. Ed. 52, 12256–12267 (2013)

    Article  Google Scholar 

  27. 27

    Le, C., Liang, Y., Evans, R. W., Li, X. & Macmillan, D. W. C. Selective sp3 C–H alkylation via polarity-match-based cross-coupling. Nature 547, 79–83 (2017)

    CAS  ADS  Article  Google Scholar 

  28. 28

    Caballero, A. et al. Silver-catalyzed C−C bond formation between methane and ethyldiazoacetate in supercritical CO2 . Science 332, 835–838 (2011)

    CAS  ADS  Article  Google Scholar 

  29. 29

    Panish, R., Selvaraj, R. & Fox, J. M. Rh(II)-catalyzed reactions of diazoesters with organozinc reagents. Org. Lett. 17, 3978–3981 (2015)

    CAS  Article  Google Scholar 

  30. 30

    Qin, T. et al. A general alkyl-alkyl cross-coupling enabled by redox-active esters and alkylzinc reagents. Science 352, 801–805 (2016)

    CAS  ADS  Article  Google Scholar 

  31. 31

    Zhu, Z., Bally, T., Stracener, L. & McMahon, R. J. Reversible interconversion between singlet and triplet 2-naphthyl(carbomethoxy)carbene. J. Am. Chem. Soc. 121, 2863–2874 (1999)

    CAS  Article  Google Scholar 

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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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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.

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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).

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