Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Asymmetric photoredox transition-metal catalysis activated by visible light

Abstract

Asymmetric catalysis is seen as one of the most economical strategies to satisfy the growing demand for enantiomerically pure small molecules in the fine chemical and pharmaceutical industries1. And visible light has been recognized as an environmentally friendly and sustainable form of energy for triggering chemical transformations and catalytic chemical processes2,3,4,5. For these reasons, visible-light-driven catalytic asymmetric chemistry is a subject of enormous current interest2,3,4,5. Photoredox catalysis provides the opportunity to generate highly reactive radical ion intermediates with often unusual or unconventional reactivities under surprisingly mild reaction conditions6. In such systems, photoactivated sensitizers initiate a single electron transfer from (or to) a closed-shell organic molecule to produce radical cations or radical anions whose reactivities are then exploited for interesting or unusual chemical transformations. However, the high reactivity of photoexcited substrates, intermediate radical ions or radicals, and the low activation barriers for follow-up reactions provide significant hurdles for the development of efficient catalytic photochemical processes that work under stereochemical control and provide chiral molecules in an asymmetric fashion7. Here we report a highly efficient asymmetric catalyst that uses visible light for the necessary molecular activation, thereby combining asymmetric catalysis and photocatalysis. We show that a chiral iridium complex can serve as a sensitizer for photoredox catalysis and at the same time provide very effective asymmetric induction for the enantioselective alkylation of 2-acyl imidazoles. This new asymmetric photoredox catalyst, in which the metal centre simultaneously serves as the exclusive source of chirality, the catalytically active Lewis acid centre, and the photoredox centre, offers new opportunities for the ‘green’ synthesis of non-racemic chiral molecules.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Chiral iridium complexes for asymmetric photoredox catalysis.
Figure 2: Substrate scope of the photoinduced enantioselective alkylation of 2-acyl imidazoles with acceptor substituted benzyl bromides and phenacyl bromides.
Figure 3: Plausible mechanism for a combined photoredox and asymmetric catalysis.
Figure 4: Mechanistic investigations.

Similar content being viewed by others

References

  1. Walsh, P. J. & Kozlowski, M. C. Fundamentals of Asymmetric Catalysis (University Science Books, 2009)

    Google Scholar 

  2. Zeitler, K. Photoredox catalysis with visible light. Angew. Chem. Int. Edn 48, 9785–9789 (2009)

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  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)

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  6. Schmittel, M. & Burghart, A. Understanding reactivity patterns of radical cations. Angew. Chem. Int. Edn Engl. 36, 2550–2589 (1997)

    Article  Google Scholar 

  7. Curran, D. P., Porter, N. A. & Giese, B. Stereochemistry of Radical Reactions: Concepts, Guidelines, and Synthetic Applications (VCH, 1996)

    Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  10. Shih, H.-W., Vander Wal, M. N., Grange, R. L. & MacMillan, D. W. C. Enantioselective α-benzylation of aldehydes via photoredox organocatalysis. J. Am. Chem. Soc. 132, 13600–13603 (2010)

    Article  CAS  Google Scholar 

  11. Neumann, M., Füldner, S., König, B. & Zeitler, K. Metal-free, cooperative asymmetric organophotoredox catalysis with visible light. Angew. Chem. Int. Edn 50, 951–954 (2011)

    Article  CAS  Google Scholar 

  12. Cherevatskaya, M. et al. Visible-light-promoted stereoselective alkylation by combining heterogeneous photocatalysis with organocatalysis. Angew. Chem. Int. Edn 51, 4062–4066 (2012)

    Article  CAS  Google Scholar 

  13. Nagib, D. A., Scott, M. E. & MacMillan, D. W. C. Enantioselective α-trifluoromethylation of aldehydes via photoredox organocatalysis. J. Am. Chem. Soc. 131, 10875–10877 (2009)

    Article  CAS  Google Scholar 

  14. DiRocco, D. A. & Rovis, T. Catalytic asymmetric α-acylation of tertiary amines mediated by a dual catalysis mode: N-heterocyclic carbene and photoredox catalysis. J. Am. Chem. Soc. 134, 8094–8097 (2012)

    Article  CAS  Google Scholar 

  15. Tarantino, K. T., Liu, P. & Knowles, R. R. Catalytic ketyl-olefin cyclizations enabled by proton-coupled electron transfer. J. Am. Chem. Soc. 135, 10022–10025 (2013)

    Article  CAS  Google Scholar 

  16. Du, J., Skubi, K. L., Schultz, D. M. & Yoon, T. P. A dual-catalysis approach to enantioselective [2 + 2] photocycloadditions using visible light. Science 344, 392–396 (2014)

    Article  ADS  CAS  Google Scholar 

  17. Bergonzini, G., Schindler, C. S., Wallentin, C.-J., Jacobsen, E. N. & Stephenson, C. R. J. Photoredox activation and anion binding catalysis in the dual catalytic enantioselective synthesis of β-amino esters. Chem. Sci. 5, 112–116 (2013)

    Article  Google Scholar 

  18. Bauer, A., Westkämper, F., Grimme, S. & Bach, T. Catalytic enantioselective reactions driven by photoinduced electron transfer. Nature 436, 1139–1140 (2005)

    Article  ADS  CAS  Google Scholar 

  19. Müller, C., Bauer, A. & Bach, T. Light-driven enantioselective organocatalysis. Angew. Chem. Int. Edn 48, 6640–6642 (2009)

    Article  Google Scholar 

  20. Brimioulle, R. & Bach, T. Enantioselective Lewis acid catalysis of intramolecular enone [2+2] photocycloaddition reactions. Science 342, 840–843 (2013)

    Article  ADS  CAS  Google Scholar 

  21. Alonso, R. & Bach, T. A chiral thioxanthone as an organocatalyst for enantioselective [2+2] photocycloaddition reactions induced by visible light. Angew. Chem. Int. Edn 53, 4368–4371 (2014)

    Article  CAS  Google Scholar 

  22. Arceo, E., Jurberg, I. D., Álvarez-Fernández, A. & Melchiorre, P. Photochemical activity of a key donor–acceptor complex can drive stereoselective catalytic α-alkylation of aldehydes. Nature Chem. 5, 750–756 (2013)

    Article  ADS  CAS  Google Scholar 

  23. Huo, H., Fu, C., Harms, K. & Meggers, E. Asymmetric catalysis with substitutionally labile yet stereochemically stable chiral-at-metal iridium(III) complex. J. Am. Chem. Soc. 136, 2990–2993 (2014)

    Article  CAS  Google Scholar 

  24. Fontecave, M., Hamelin, O. & Ménage, S. Chiral-at-metal complexes as asymmetric catalysts. Top. Organomet. Chem. 15, 271–288 (2005)

    Article  CAS  Google Scholar 

  25. Bauer, E. B. Chiral-at-metal complexes and their catalytic applications in organic synthesis. Chem. Soc. Rev. 41, 3153–3167 (2012)

    Article  CAS  Google Scholar 

  26. Evans, D. A., Downey, C. W. & Hubbs, J. L. Ni(II) bis(oxazoline)-catalyzed enantioselective syn aldol reactions of N-propionylthiazolidinethiones in the presence of silyl triflates. J. Am. Chem. Soc. 125, 8706–8707 (2003)

    Article  CAS  Google Scholar 

  27. Sato, H. & Yamagishi, A. Application of the ΔΛ isomerism of octahedral metal complexes as a chiral source in photochemistry. J. Photochem. Photobiol. C 8, 67–84 (2007)

    Article  CAS  Google Scholar 

  28. Herrmann, A. T., Smith, L. L. & Zakarian, A. A simple method for asymmetric trifluoromethylation of N-acyl oxazolidinones via Ru-catalyzed radical addition to zirconium enolates. J. Am. Chem. Soc. 134, 6976–6979 (2012)

    Article  CAS  Google Scholar 

  29. Studer, A. & Curran, D. P. The electron is a catalyst. Nature Chem. 6, 765–773 (2014)

    Article  ADS  CAS  Google Scholar 

  30. Andrieux, C. P., Le Gorande, A. & Savéant, J. M. Electron transfer and bond breaking. Examples of passage from a sequential to a concerted mechanism in the electrochemical reductive cleavage of arylmethyl halides. J. Am. Chem. Soc. 114, 6892–6904 (1992)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We acknowledge funding from the German Research Foundation (ME 1805/4-1). H.H. thanks the China Scholarship Council for a stipend.

Author information

Authors and Affiliations

Authors

Contributions

E.M. conceived and coordinated the project and wrote the Letter. E.M. and H.H. designed the experiments. H.H. carried out the majority of the experiments. X.S. synthesized the new catalyst Λ-Ir2. C.W. contributed to the synthesis of substrates. L.Z. contributed to the synthesis and crystallization of iridium complexes. L.-A.C. provided insights into iridium enolate chemistry. P.R. performed and analysed the cyclic voltammetry under supervision of G.H. The X-ray crystallographic studies were performed by K.H. and M.M.

Corresponding author

Correspondence to Eric Meggers.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Additional information

The X-ray crystallographic coordinates for structures of the iridium complex Λ-Ir2, substrate coordinated iridium complex I and the iridium enolate complex II have been deposited at the Cambridge Crystallographic Data Centre (CCDC) under deposition numbers CCDC 1014509, 1014510 and 1014876, respectively.

Supplementary information

Supplementary Information

This file contains Supplementary Figures 1-7, Supplementary Table 1, Supplementary Methods and Supplementary References. (PDF 4767 kb)

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Huo, H., Shen, X., Wang, C. et al. Asymmetric photoredox transition-metal catalysis activated by visible light. Nature 515, 100–103 (2014). https://doi.org/10.1038/nature13892

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature13892

This article is cited by

Comments

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.

Search

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