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Visible-light excitation of iminium ions enables the enantioselective catalytic β-alkylation of enals


Chiral iminium ions—generated upon condensation of α,β-unsaturated aldehydes and amine catalysts—are used extensively by chemists to make chiral molecules in enantioenriched form. In contrast, their potential to absorb light and promote stereocontrolled photochemical processes remains unexplored. This is despite the fact that visible-light absorption by iminium ions is a naturally occurring event that triggers the mechanism of vision in higher organisms. Herein we demonstrate that the direct excitation of chiral iminium ions can unlock unconventional reaction pathways, enabling enantioselective catalytic photochemical β-alkylations of enals that cannot be realized via thermal activation. The chemistry uses readily available alkyl silanes, which are recalcitrant to classical conjugate additions, and occurs under illumination by visible-light-emitting diodes. Crucial to success was the design of a chiral amine catalyst with well-tailored electronic properties that can generate a photo-active iminium ion while providing the source of stereochemical induction. This strategy is expected to offer new opportunities for reaction design in the field of enantioselective catalytic photochemistry.

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Figure 1: Reactivities of iminium ions in biological systems and enantioselective catalytic synthesis.
Figure 2: Design plan and mechanistic proposal: exploiting the direct photoexcitation of transiently generated chiral iminium ions I to enable stereocontrolled photochemical processes.
Figure 3: Photophysical and structural characterization of iminium ions and mechanistic investigations.


  1. 1

    Dalko, P. I. (ed.) Comprehensive Enantioselective Organocatalysis: Catalysts, Reactions, and Applications (Wiley-VCH, 2013).

    Book  Google Scholar 

  2. 2

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

    CAS  Article  Google Scholar 

  3. 3

    Lelais, G. & MacMillan, D. W. C. Modern strategies in organic catalysis: the advent and development of iminium activation. Aldrichim. Acta 39, 79–87 (2006).

    CAS  Google Scholar 

  4. 4

    Córdova, A. (ed.) Catalytic Asymmetric Conjugate Reactions (Wiley-VCH, 2010).

    Book  Google Scholar 

  5. 5

    Wald, G. Molecular basis of visual excitation. Science 162, 230–239 (1968).

    CAS  Article  Google Scholar 

  6. 6

    Ernst, O. P. et al. Microbial and animal rhodopsins: structures, functions, and molecular mechanisms. Chem. Rev. 114, 126−163 (2014).

    CAS  Article  Google Scholar 

  7. 7

    Nathans, J., Thomas, D. & Hogness, D. S. Molecular genetics of human color vision: the genes encoding blue, green, and red pigments. Science 232, 193–202 (1986).

    CAS  Article  Google Scholar 

  8. 8

    Mariano, P. S. The photochemistry of iminium salts and related heteroaromatic systems. Tetrahedron 39, 3845–3879 (1983).

    CAS  Article  Google Scholar 

  9. 9

    Borg, R. M., Heuckeroth, R. O., Lan, A. J. Y., Quillen, S. L. & Mariano, P. S. Arene-iminium salt electron-transfer photochemistry. Mechanistically interesting photoaddition processes. J. Am. Chem. Soc. 109, 2728–2737 (1987).

    CAS  Article  Google Scholar 

  10. 10

    Chen, C., Chang, V., Cai, X., Duesler, E. & Mariano, P. S. A general strategy for absolute stereochemical control in enone-olefin [2 + 2] photocycloaddition reactions. J. Am. Chem. Soc. 123, 6433–6434 (2001).

    CAS  Article  Google Scholar 

  11. 11

    Mariano, P. S. Electron-transfer mechanisms in photochemical transformations of iminium salts. Acc. Chem. Res. 16, 130–144 (1983).

    CAS  Article  Google Scholar 

  12. 12

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

    Article  Google Scholar 

  13. 13

    Brimioulle, R., Lenhart, D., Maturi, M. M. & Bach, T. Enantioselective catalysis of photochemical reactions. Angew. Chem. Int. Ed. 54, 3872–3890 (2015).

    CAS  Article  Google Scholar 

  14. 14

    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. Nat. Chem. 5, 750−756 (2013).

    CAS  Article  Google Scholar 

  15. 15

    Silvi, M., Arceo, E., Jurberg, I. D., Cassani, C. & Melchiorre, P. Enantioselective organocatalytic alkylation of aldehydes and enals driven by the direct photoexcitation of enamines. J. Am. Chem. Soc. 137, 6120–6123 (2015).

    CAS  Article  Google Scholar 

  16. 16

    Bahamonde, A. & Melchiorre, P. Mechanism of the stereoselective α-alkylation of aldehydes driven by the photochemical activity of enamines. J. Am. Chem. Soc. 138, 8019−8030 (2016).

    CAS  Article  Google Scholar 

  17. 17

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

    CAS  Article  Google Scholar 

  18. 18

    Balzani, V. Ceroni, P. & Juris, A. in Photochemistry and Photophysics 103–123 (Wiley-VCH, 2014).

    Google Scholar 

  19. 19

    Yoshida, J., Kataoka, K., Horcajada, R. & Nagaki, A. Modern strategies in electroorganic synthesis. Chem. Rev. 108, 2265–2299 (2008).

    CAS  Article  Google Scholar 

  20. 20

    Dockery, K. P. et al. Nucleophile-assisted cleavage of benzyltrialkylsilane cation radicals. J. Am. Chem. Soc. 119, 1876–1883 (1997).

    CAS  Article  Google Scholar 

  21. 21

    Yoon, U. C., Mariano, P. S., Givens, R. S. & Atwater, B. W. in Advances in Electron Transfer Chemistry. Vol. 4, 117–206 (JAI, 1994).

    Google Scholar 

  22. 22

    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  Article  Google Scholar 

  23. 23

    Terrett, J. A., Clift, M. D. & MacMillan, D. W. C. Direct β-alkylation of aldehydes via photoredox organocatalysis. J. Am. Chem. Soc. 136, 6858–6861 (2014).

    CAS  Article  Google Scholar 

  24. 24

    Yoshida, J., Murata, T. & Isoe, S. Electrochemical oxidation of organosilicon compounds I. Oxidative cleavage of carbon-silicon bond in allylsilanes and benzylsilanes. Tetrahedron Lett. 27, 3373–3376 (1986).

    CAS  Article  Google Scholar 

  25. 25

    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).

    CAS  Article  Google Scholar 

  26. 26

    Hu, J., Wang, J., Nguyen, T. H. & Zheng, N. The chemistry of amine radical cations produced by visible light photoredox catalysis. Beilstein J. Org. Chem. 9, 1977–2001 (2013).

    Article  Google Scholar 

  27. 27

    Müller, K., Faeh, C. & Diederich, F. Fluorine in pharmaceuticals: looking beyond intuition. Science 317, 1881–1886 (2007).

    Article  Google Scholar 

  28. 28

    Morgenthaler, M. et al. Predicting and tuning physicochemical properties in lead optimization: amine basicities. Chem. Med. Chem. 2, 1100–1115 (2007).

    CAS  Article  Google Scholar 

  29. 29

    Zimmer, L. E., Sparr, C. & Gilmour, R. Fluorine conformational effects in organocatalysis: an emerging strategy for molecular design. Angew. Chem. Int. Ed. 50, 11860–11871 (2011).

    CAS  Article  Google Scholar 

  30. 30

    Kim, S.-H. & Rieke, R. D. Benzylic manganese halides, sulfonates, and phosphates: preparation, coupling reactions, and applications in organic synthesis. J. Org. Chem. 65, 2322–2330 (2000).

    CAS  Article  Google Scholar 

  31. 31

    Van Heerden, P. S., Bezuidenhoudt, B. C. B., Steenkamp, J. A. & Ferreira, D. Conjugate addition of benzyl copper reagents to α,α-enoates and enones. Tetrahedron Lett. 33, 2383–2386 (1992).

    CAS  Article  Google Scholar 

  32. 32

    Fañanás-Mastral, M. & Feringa, B. L. Copper-catalyzed regio- and enantioselective synthesis of chiral enol acetates and β-substituted aldehydes. J. Am. Chem. Soc. 132, 13152–13153 (2010).

    Article  Google Scholar 

  33. 33

    Dell'Amico, L., Companyó, X., Naicker, T., Bräuer, T. M. & Jørgensen, K. A. Asymmetric organocatalytic benzylation of α,β-unsaturated aldehydes with toluenes. Eur. J. Org. Chem. 2013, 5262–5265 (2013).

    CAS  Article  Google Scholar 

  34. 34

    Li, T. et al. A strategy enabling enantioselective direct conjugate addition of inert aryl methane nucleophiles to enals with a chiral amine catalyst under mild conditions. Chem. Eur. J. 19, 9147–9150 (2013).

    CAS  Article  Google Scholar 

  35. 35

    Walbiner, M., Wu, J. Q. & Fischer, H. Absolute rate constant for the addition of benzyl and cumyl radicals to alkenes in solution. Helvetica Chim. Acta 78, 910–924 (1995).

    CAS  Article  Google Scholar 

  36. 36

    Sibi, M. P., Liu, P., Ji, J., Hajra, S. & Chen, J.-x. Free-radical-mediated conjugate additions. enantioselective synthesis of butyrolactone natural products: (–)-enterolactone, (–)-arctigenin, (–)-isoarctigenin, (–)-nephrosteranic acid, and (–)-roccellaric acid. J. Org. Chem. 67, 1738–1745 (2002).

    CAS  Article  Google Scholar 

  37. 37

    Huo, H., Harms, K. & Meggers, E. Catalytic, enantioselective addition of alkyl radicals to alkenes via visible-light-activated photoredox catalysis with a chiral rhodium complex. J. Am. Chem. Soc. 138, 6936−6939 (2016).

    CAS  Article  Google Scholar 

  38. 38

    Montanaro, S., Ravelli, D., Merli, D., Fagnoni, M. & Albini, A. Decatungstate as photoredox catalyst: benzylation of electron-poor olefins. Org. Lett. 14, 4218–4221 (2012).

    CAS  Article  Google Scholar 

  39. 39

    Murphy, J. J., Bastida, D., Paria, S., Fagnoni, M. & Melchiorre, P. Asymmetric catalytic formation of quaternary carbons by iminium ion trapping of radicals. Nature 532, 218−222 (2016).

    CAS  Article  Google Scholar 

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Financial support was provided by the CERCA Programme (Generalitat de Catalunya), MINECO (Severo Ochoa Excellence Accreditation 2014-2018, SEV-2013-0319), and the European Research Council (ERC-2015-CoG 681840 - CATA-LUX). C.V. thanks the Marie Skłodowska-Curie Actions for a postdoctoral fellowship (H2020-MSCA-IF-2014 658980). L.B. thanks MINECO for a predoctoral fellowship (CTQ2013-45938-P). The authors thank M. Moliterno for helpful discussions. This work is dedicated to V. Balzani on the occasion of his 80th birthday.

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M.S. was involved in the discovery and initial development of the light-driven reactions. C.V. and Y.P.R. designed and synthesized the catalysts. C.V., Y.P.R. and L.B. performed the experiments. All of the authors analysed the data and designed the experiments. P.M directed the project and wrote the manuscript with contributions from all of the authors.

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Correspondence to Paolo Melchiorre.

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The authors declare no competing financial interests.

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Supplementary information (PDF 12610 kb)

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Crystallographic data for compound 1c. (CIF 2371 kb)

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Crystallographic data for compound 5a. (CIF 2802 kb)

Supplementary information

Crystallographic data for compound Ic. (CIF 1815 kb)

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Silvi, M., Verrier, C., Rey, Y. et al. Visible-light excitation of iminium ions enables the enantioselective catalytic β-alkylation of enals. Nature Chem 9, 868–873 (2017).

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