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.

  • Article
  • Published:

Photochemical activity of a key donor–acceptor complex can drive stereoselective catalytic α-alkylation of aldehydes

Nature Chemistry volume 5, pages 750–756 (2013)Cite this article

Subjects

Abstract

Asymmetric catalytic variants of sunlight-driven photochemical processes hold extraordinary potential for the sustainable preparation of chiral molecules. However, the involvement of short-lived electronically excited states inherent to any photochemical reaction makes it challenging for a chiral catalyst to dictate the stereochemistry of the products. Here, we report that readily available chiral organic catalysts, with well-known utility in thermal asymmetric processes, can also confer a high level of stereocontrol in synthetically relevant intermolecular carbon–carbon bond-forming reactions driven by visible light. A unique mechanism of catalysis is proposed, wherein the catalyst is involved actively in both the photochemical activation of the substrates (by inducing the transient formation of chiral electron donor–acceptor complexes) and the stereoselectivity-defining event. We use this approach to enable transformations that are extremely difficult under thermal conditions, such as the asymmetric α-alkylation of aldehydes with alkyl halides, the formation of all-carbon quaternary stereocentres and the control of remote stereochemistry.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1: Mechanistic proposal for asymmetric catalytic photochemical processes.
Figure 2: Mechanistic investigations.
Figure 3: Evaluating the scope and the strategy's potential to address synthetically relevant problems.
Figure 4: Two possible reaction mechanisms.
Figure 5: Mechanistic investigations.

Similar content being viewed by others

References

  1. Balzani, V., Credi, A. & Venturi, M. Photochemical conversion of solar energy. ChemSusChem, 1, 26–58 (2008).

    Article  CAS  Google Scholar 

  2. Ciamician, G. The photochemistry of the future. Science 36, 385–394 (1912).

    Article  CAS  Google Scholar 

  3. Albini, A. & Fagnoni, M. Handbook of Synthetic Photochemistry (Wiley-VCH, 2010).

    Google Scholar 

  4. Bach, T. & Hehn, J. P. Photochemical reactions as key steps in natural product synthesis. Angew. Chem. Int. Ed. 50, 1000–1045 (2011).

    Article  CAS  Google Scholar 

  5. Inoue, Y. & Ramamurthy, V. Chiral Photochemistry (Marcel Dekker, 2004).

    Book  Google Scholar 

  6. Müller, C. & Bach, T. Chirality control in photochemical reactions: enantioselective formation of complex photoproducts in solution. Aust. J. Chem. 61, 557–564 (2008).

    Article  Google Scholar 

  7. Ojima, I. Catalytic Asymmetric Synthesis (Wiley, 2010).

    Book  Google Scholar 

  8. Guo, H., Herdtweck, E. & Bach, T. Enantioselective Lewis acid catalysis in intramolecular [2+2] photocycloaddition reactions of coumarins. Angew. Chem. Int. Ed. 49, 7782–7785 (2010).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  11. Knowles, R. R. & Jacobsen, E. N. Attractive noncovalent interactions in asymmetric catalysis: links between enzymes and small molecules catalysts. Proc. Natl Acad. Sci. U.S.A. 107, 20678–20685 (2010).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  13. 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 

  14. Mulliken, R. S. Molecular compounds and their spectra. II. J. Am. Chem. Soc. 74, 811–824 (1952).

    Article  CAS  Google Scholar 

  15. Foster, R. Electron donor–acceptor complexes. J. Phys. Chem. 84, 2135–2141 (1980).

    Article  CAS  Google Scholar 

  16. MacMillan, D. W. C. The advent and development of organocatalysis. Nature 455, 304–308 (2008).

    Article  CAS  Google Scholar 

  17. Mukherjee, S., Yang, J. W., Hoffmann, S. & List, B. Asymmetric enamine catalysis. Chem. Rev. 107, 5471–5569 (2007).

    Article  CAS  Google Scholar 

  18. Cantacuzene, D., Wakselman, C. & Dorme, R. Condensation of perfluoroalkyl iodides with unsaturated nitrogen compounds. J. Chem. Soc. Perkin Trans. 1 1365–1371 (1977).

  19. Russell, G. A. & Wang, K. Electron transfer processes. 53. Homolytic alkylation of enamines by electrophilic radicals. J. Org. Chem. 56, 3475–3479 (1991).

    Article  CAS  Google Scholar 

  20. Singh, J. O., Anunziata, J. D. & Silber, J. J. n–π Electron donor–acceptor complexes. II. Aliphatic amines with dinitrobenzenes. Can. J. Chem. 63, 903–907 (1985).

    Article  CAS  Google Scholar 

  21. Müller, K., Previdoli, F. & Desilvestro, H. Enamines, II. A theoretical and photoelectron spectroscopic study of the molecular and electronic structures of aliphatic enamines. Helv. Chim. Acta 64, 2497–2507 (1981).

    Article  Google Scholar 

  22. Rosokha, S. V. & Kochi, J. K. Fresh look at electron-transfer mechanisms via the donor/acceptor bindings in the critical encounter complex. Acc. Chem. Res. 41, 641–653 (2008).

    Article  CAS  Google Scholar 

  23. Hilinski, E. F., Masnovi, J. M., Amatore, C., Kochi, J. K. & Rentzepis, P. M. Charge-transfer excitation of electron donor–acceptor complexes. Direct observation of ion pairs by time-resolved (picosecond) spectroscopy. J. Am. Chem. Soc. 105, 6167–6168 (1983).

    Article  CAS  Google Scholar 

  24. Rathore, R. & Kochi, J. K. Donor/acceptor organizations and the electron-transfer paradigm for organic reactivity. Adv. Phys. Org. Chem. 35, 193–318 (2000).

    Google Scholar 

  25. Gotoh, T., Padias, A. B. & Hall, J. H. K. An electron donor–acceptor complex and thermal triplex as intermediates in the cycloaddition reaction of N-vinylcarbazole with dimethyl 2,2-dicyanoethylene-1,1-dicarboxylate. J. Am. Chem. Soc. 113, 1308–1312 (1991).

    Article  CAS  Google Scholar 

  26. Berionni, G., Bertelle, P-A., Marrot, J. & Goumont, R. X-ray structure of a CT complex relevant to Diels–Alder reactivity of anthracenes. J. Am. Chem. Soc. 131, 18224–18225 (2009).

    Article  CAS  Google Scholar 

  27. Melchiorre, P. Light in aminocatalysis: the asymmetric intermolecular α-alkylation of aldehydes. Angew. Chem. Int. Ed. 48, 1360–1363 (2009).

    Article  CAS  Google Scholar 

  28. Jensen, K. L., Dickmeiss, G., Jiang, H., Albrecht, Ł. & Jørgensen, K. A. The diarylprolinol silyl ether system: a general organocatalyst. Acc. Chem. Res. 45, 248–264 (2012).

    Article  CAS  Google Scholar 

  29. Costentin, C., Robert, M. & Savéant, J-M. Electron transfer and bond breaking: recent advances. Chem. Phys. 324, 40–56 (2006).

    Article  CAS  Google Scholar 

  30. Mannschreck, A., Roza, P., Brockmann, H. & Kemmer, T. Demonstration of diastereomeric electron-donor–acceptor complexes by 1H-NMR spectroscopy. Angew. Chem. Int. Ed. Engl. 17, 940–942 (1978).

    Article  Google Scholar 

  31. Kornblum, N. Substitution reactions which proceed via radical anion intermediate. Angew. Chem. Int. Ed. Engl. 14, 734–745 (1975).

    Article  Google Scholar 

  32. Russell, G. A., & Ros, F. Reactions of α-halo ketones with nucleophiles J. Am. Chem. Soc. 107, 2506–2511 (1985).

    Article  CAS  Google Scholar 

  33. Rossi, R. A., Pierini, A. B. & Peñéñory, A. B. Nucleophilic substitution reactions by electron transfer. Chem. Rev. 103, 71–168 (2003).

    Article  CAS  Google Scholar 

  34. Van Humbeck, J. F., Simonovich, S. P., Knowles, R. R. & MacMillan, D. W. C. Concerning the mechanism of the FeCl3-catalyzed α-oxyamination of aldehydes: evidence for a non-SOMO activation pathway. J. Am. Chem. Soc. 132, 10012–10014 (2010).

    Article  CAS  Google Scholar 

  35. Nazareno, M. A. & Rossi, R. A. SRN1 reactions of 7-iodobicyclo[4.1.0]heptane, 1-iodoadamantane, and neopentyl iodide with carbanions induced by FeBr2 in DMSO. J. Org. Chem. 61, 1645–1649 (1996).

    Article  CAS  Google Scholar 

  36. 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 

Download references

Acknowledgements

This work was supported by the Institute of Chemical Research of Catalonia Foundation and by the European Research Council under the European Community's Seventh Framework Program (FP7 2007–2013)/ERC Grant agreement 278541. This work is dedicated to P. G. Cozzi on the occasion of his 50th birthday.

Author information

Author notes

  1. Elena Arceo and Igor D. Jurberg: These authors contributed equally to this work

Authors and Affiliations

  1. Institute of Chemical Research of Catalonia, Avenguda Països Catalans, Tarragona, 16-43007, Spain

    Elena Arceo, Igor D. Jurberg, Ana Álvarez-Fernández & Paolo Melchiorre

  2. Institució Catalana de Recerca i Estudis Avançats, Passeig Lluís Companys, Barcelona, 23-08010, Spain

    Paolo Melchiorre

Authors
  1. Elena Arceo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Igor D. Jurberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ana Álvarez-Fernández
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paolo Melchiorre
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

E.A. and I.D.J. were involved in the discovery and subsequent development of the light-driven alkylation reactions. E.A., I.D.J. and A.Á-F. performed the experiments. E.A., I.D.J., A.Á-F. and P.M. designed and analysed the experiments. P.M. conceived and directed the project and wrote the manuscript with contributions from E.A.

Corresponding author

Correspondence to Paolo Melchiorre.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary information (PDF 6665 kb)

Supplementary information

Crystallographic data for compound 1c (CIF 27 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Arceo, E., Jurberg, I., Álvarez-Fernández, A. et al. Photochemical activity of a key donor–acceptor complex can drive stereoselective catalytic α-alkylation of aldehydes. Nature Chem 5, 750–756 (2013). https://doi.org/10.1038/nchem.1727

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchem.1727

This article is cited by

Search

Advanced 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