Switching on elusive organometallic mechanisms with photoredox catalysis


Transition-metal-catalysed cross-coupling reactions have become one of the most used carboncarbon and carbonheteroatom bond-forming reactions in chemical synthesis. Recently, nickel catalysis has been shown to participate in a wide variety of C−C bond-forming reactions, most notably Negishi, SuzukiMiyaura, Stille, Kumada and Hiyama couplings1,2. Despite the tremendous advances in C−C fragment couplings, the ability to forge C−O bonds in a general fashion via nickel catalysis has been largely unsuccessful. The challenge for nickel-mediated alcohol couplings has been the mechanistic requirement for the critical C–O bond-forming step (formally known as the reductive elimination step) to occur via a Ni(iii) alkoxide intermediate. Here we demonstrate that visible-light-excited photoredox catalysts can modulate the preferred oxidation states of nickel alkoxides in an operative catalytic cycle, thereby providing transient access to Ni(iii) species that readily participate in reductive elimination. Using this synergistic merger of photoredox and nickel catalysis, we have developed a highly efficient and general carbonoxygen coupling reaction using abundant alcohols and aryl bromides. More notably, we have developed a general strategy to ‘switch on’ important yet elusive organometallic mechanisms via oxidation state modulations using only weak light and single-electron-transfer catalysts.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Modulating oxidation states of nickel enables challenging carbon–heteroatom coupling.
Figure 2: Proposed mechanism by which photoredox catalysis switches on challenging nickel-catalysed C–O coupling.
Figure 3: Alcohol and aryl halide scope in the photoredox-nickel-catalysed C–O coupling reaction.
Figure 4: Mechanistic studies support the intermediacy of transient Ni(iii) complex to enable C–O reductive elimination.


  1. 1

    Tasker, S. Z., Standley, E. A. & Jamison, T. F. Recent advances in homogeneous nickel catalysis. Nature 509, 299–309 (2014)

    CAS  ADS  Article  Google Scholar 

  2. 2

    Netherton, M. R. & Fu, G. C. Nickel-catalyzed cross-couplings of unactivated alkyl halides and pseudohalides with organometallic compounds. Adv. Synth. Catal. 346, 1525–1532 (2004)

    CAS  Article  Google Scholar 

  3. 3

    Narayanam, J. M. R. & Stephenson, C. R. J. Visible light photoredox catalysis: applications in organic synthesis. Chem. Soc. Rev. 40, 102–113 (2011)

    CAS  Article  Google Scholar 

  4. 4

    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 

  5. 5

    Schultz, D. M. & Yoon, T. P. Solar synthesis: prospects in visible light photocatalysis. Science 343, 1239176 (2014)

    Article  Google Scholar 

  6. 6

    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 

  7. 7

    Ischay, M. A., Anzovino, M. E., Du, J. & Yoon, T. P. Efficient visible light photocatalysis of [2+2] enone cycloadditions. J. Am. Chem. Soc. 130, 12886–12887 (2008)

    CAS  Article  Google Scholar 

  8. 8

    Narayanam, J. M. R., Tucker, J. W. & Stephenson, C. R. J. Electron-transfer photoredox catalysis: development of a tin-free reductive dehalogenation reaction. J. Am. Chem. Soc. 131, 8756–8757 (2009)

    CAS  Article  Google Scholar 

  9. 9

    Pirnot, M. T., Rankic, D. A., Martin, D. B. C. & MacMillan, D. W. C. Photoredox activation for the direct β-arylation of ketones and aldehydes. Science 339, 1593–1596 (2013)

    CAS  ADS  Article  Google Scholar 

  10. 10

    Hopkinson, M. N., Sahoo, B., Li, J.-L. & Glorius, F. Dual catalysis sees the light: combining photoredox with organo-, acid, and transition-metal catalysis. Chemistry 20, 3874–3886 (2014)

    CAS  Article  Google Scholar 

  11. 11

    Osawa, M., Nagai, H. & Akita, M. Photo-activation of Pd-catalyzed Sonogashira coupling using a Ru/bipyridine complex as energy transfer agent. Dalton Trans.827–829 (2007)

  12. 12

    Kalyani, D., McMurtrey, K. B., Neufeldt, S. R. & Sanford, M. S. Room-temperature C–H arylation: merger of Pd-catalyzed C–H functionalization and visible-light photocatalysis. J. Am. Chem. Soc. 133, 18566–18569 (2011)

    CAS  Article  Google Scholar 

  13. 13

    Ye, Y. & Sanford, M. S. Merging visible-light photocatalysis and transition-metal catalysis in the copper-catalyzed trifluoromethylation of boronic acids with CF3I. J. Am. Chem. Soc. 134, 9034–9037 (2012)

    CAS  Article  Google Scholar 

  14. 14

    Sahoo, B., Hopkinson, M. N. & Glorius, F. Combining gold and photoredox catalysis: visible light-mediated oxy- and aminoarylation of alkenes. J. Am. Chem. Soc. 135, 5505–5508 (2013)

    CAS  Article  Google Scholar 

  15. 15

    Tellis, J. C., Primer, D. N. & Molander, G. A. Single-electron transmetalation in organoboron cross-coupling by photoredox/nickel dual catalysis. Science 345, 433–436 (2014)

    CAS  ADS  Article  Google Scholar 

  16. 16

    Zuo, Z. et al. Merging photoredox with nickel catalysis: coupling of α-carboxyl sp3-carbons with aryl halides. Science 345, 437–440 (2014)

    CAS  ADS  Article  Google Scholar 

  17. 17

    Matsunaga, P. T., Hillhouse, G. L. & Rheingold, A. L. Oxygen-atom transfer from nitrous oxide to a nickel metallacycle. Synthesis, structure, and reactions of [cyclic] (2,2′-bipyridine)Ni(OCH2CH2CH2CH2). J. Am. Chem. Soc. 115, 2075–2077 (1993)

    CAS  Article  Google Scholar 

  18. 18

    Matsunaga, P. T., Mavropoulos, J. C. & Hillhouse, G. L. Oxygen-atom transfer from nitrous oxide (N = N = O) to nickel alkyls. Syntheses and reactions of nickel(II) alkoxides. Polyhedron 14, 175–185 (1995)

    CAS  Article  Google Scholar 

  19. 19

    Han, R. & Hillhouse, G. L. Carbon–oxygen reductive-elimination from nickel(II) oxametallacycles and factors that control formation of ether, aldehyde, alcohol, or ester products. J. Am. Chem. Soc. 119, 8135–8136 (1997)

    CAS  Article  Google Scholar 

  20. 20

    Camasso, N. M. & Sanford, M. S. Design, synthesis, and carbon-heteroatom coupling reactions of organometallic nickel(IV) complexes. Science 347, 1218–1220 (2013)

    ADS  Article  Google Scholar 

  21. 21

    Zhou, W., Schultz, J. W., Rath, N. P. & Mirica, L. M. Aromatic methoxylation and hydroxylation by organometallic high-valent nickel complexes. J. Am. Chem. Soc. 137, 7604–7607 (2015)

    CAS  Article  Google Scholar 

  22. 22

    Macgregor, S. A., Neave, G. W. & Smith, C. Theoretical studies on C–heteroatom bond formation via reductive elimination from group 10 M(PH3)2(CH3)(X) species (X = CH3, NH2, OH, SH) and the determination of metal–X bond strengths using density functional theory. Faraday Discuss. 124, 111–127 (2003)

    CAS  ADS  Article  Google Scholar 

  23. 23

    Torraca, K. E., Huang, X., Parrish, C. A. & Buchwald, S. L. An efficient intermolecular palladium-catalyzed synthesis of aryl ethers. J. Am. Chem. Soc. 123, 10770–10771 (2001)

    CAS  Article  Google Scholar 

  24. 24

    Wolter, M., Nordmann, G., Job, G. E. & Buchwald, S. L. Copper-catalyzed coupling of aryl iodides with aliphatic alcohols. Org. Lett. 4, 973–976 (2002)

    CAS  Article  Google Scholar 

  25. 25

    Kataoka, N., Shelby, Q., Stambuli, J. P. & Hartwig, J. F. Air stable, sterically hindered ferrocenyl dialkylphosphines for palladium-catalyzed C–C, C–N, and C–O bond-forming cross-couplings. J. Org. Chem. 67, 5553–5566 (2002)

    CAS  Article  Google Scholar 

  26. 26

    Mann, G. & Hartwig, J. F. Nickel- vs. palladium-catalyzed synthesis of protected phenols from aryl halides. J. Org. Chem. 62, 5413–5418 (1997)

    CAS  Article  Google Scholar 

  27. 27

    Amatore, C. & Jutand, A. Rates and mechanism of biphenyl synthesis catalyzed by electrogenerated coordinatively unsaturated nickel complexes. Organometallics 7, 2203–2214 (1988)

    CAS  Article  Google Scholar 

  28. 28

    Lowry, M. S. et al. Single-layer electroluminescent devices and photoinduced hydrogen production from an ionic iridium(III) complex. Chem. Mater. 17, 5712–5719 (2005)

    CAS  Article  Google Scholar 

  29. 29

    Klein, A. et al. Halide ligands—more than just σ-donors? A structural and spectroscopic study of homologous organonickel complexes. Inorg. Chem. 47, 11324–11333 (2008)

    CAS  Article  Google Scholar 

  30. 30

    Durandetti, M., Devaud, M. & Perichon, J. Investigation of the reductive coupling of aryl halides and/or ethylchloroacetate electrocatalyzed by the precursor NiX2(bpy) with X = Cl, Br or MeSO3 and bpy = 2,2′-dipyridyl. New J. Chem. 20, 659–667 (1996)

    CAS  Google Scholar 

Download references


Financial support was provided by the National Institute of General Medical Sciences (R01 GM093213-01) and gifts from Merck, AbbVie and Bristol-Myers Squibb. J.A.T. thanks Bristol-Myers Squibb for a Graduate Fellowship. J.D.C. thanks Marie Curie Actions for an International Outgoing Fellowship. The authors thank Eric R. Welin for assistance in preparing Ni(ii) complexes.

Author information




J.A.T., J.D.C. and V.W.S. performed and analysed experiments. J.A.T., J.D.C., V.W.S. and D.W.C.M. designed experiments to develop this reaction and probe its utility, and also prepared this manuscript.

Corresponding author

Correspondence to David W. C. MacMillan.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Text and Data, Supplementary Figures 1–11, NMR spectral data for novel compounds and additional references (see Contents for details). (PDF 9586 kb)

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Terrett, J., Cuthbertson, J., Shurtleff, V. et al. Switching on elusive organometallic mechanisms with photoredox catalysis. Nature 524, 330–334 (2015). https://doi.org/10.1038/nature14875

Download citation

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing