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Enhancing the potential of enantioselective organocatalysis with light

Nature volume 554, pages 41–49 (2018)Cite this article

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Abstract

Organocatalysis—catalysis mediated by small chiral organic molecules—is a powerful technology for enantioselective synthesis, and has extensive applications in traditional ionic, two-electron-pair reactivity domains. Recently, organocatalysis has been successfully combined with photochemical reactivity to unlock previously inaccessible reaction pathways, thereby creating new synthetic opportunities. Here we describe the historical context, scientific reasoning and landmark discoveries that were essential in expanding the functions of organocatalysis to include one-electron-mediated chemistry and excited-state reactivity.

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Figure 1: Merging photoredox and enamine catalysis.
Figure 2: Merging photoredox and covalent organocatalysis.
Figure 3: Merging photoredox and non-covalent organocatalysis.
Figure 4: Excited-state reactivity of chiral organocatalytic intermediates.
Figure 5: Non-covalent interactions in enantioselective photochemistry.

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References

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

  2. Ojima, I. (ed.) Catalytic Asymmetric Synthesis (John Wiley & Sons, 2010)

  3. Eder, U., Sauer, G. & Wiechert, R. New type of asymmetric cyclization to optically active steroid CD partial structures. Angew. Chem. Int. Ed. Engl. 10, 496–497 (1971)

    Article  CAS  Google Scholar 

  4. Hajos, Z. G. & Parrish, D. R. Asymmetric synthesis of bicyclic intermediates of natural product chemistry. J. Org. Chem. 39, 1615–1621 (1974)

    Article  CAS  Google Scholar 

  5. Hiemstra, H. & Wynberg, H. Addition of aromatic thiols to conjugated cycloalkenones, catalyzed by chiral β-hydroxy amines. A mechanistic study of homogeneous catalytic asymmetric synthesis. J. Am. Chem. Soc. 103, 417–430 (1981)

    Article  CAS  Google Scholar 

  6. Dolling, U. H., Davis, P. & Grabowski, E. J. J. Efficient catalytic asymmetric alkylations. 1. Enantioselective synthesis of (+)-indacrinone via chiral phase-transfer catalysis. J. Am. Chem. Soc. 106, 446–447 (1984)

    Article  CAS  Google Scholar 

  7. List, B., Lerner, R. A. & Barbas, C. F., III . Proline-catalyzed direct asymmetric aldol reactions. J. Am. Chem. Soc. 122, 2395–2396 (2000)

    Article  CAS  Google Scholar 

  8. Ahrendt, K. A ., Borths, C. J . & MacMillan, D. W. C. New strategies for organic synthesis: the first highly enantioselective organocatalytic Diels-Alder reaction. J. Am. Chem. Soc. 122, 4243–4244 (2000). Refs 7 and 8 document the seminal studies on enamine- and iminium-ion-mediated catalysis, respectively, which established the field of modern organocatalysis

    Article  CAS  Google Scholar 

  9. MacMillan, D. W. C. The advent and development of organocatalysis. Nature 455, 304–308 (2008). Thought-provoking discussion on the reasons behind the sudden growth in the field of modern organocatalysis

    Article  ADS  CAS  PubMed  Google Scholar 

  10. Grondal, C., Jeanty, M. & Enders, D. Organocatalytic cascade reactions as a new tool in total synthesis. Nat. Chem. 2, 167–178 (2010)

    Article  CAS  PubMed  Google Scholar 

  11. Jones, S. B., Simmons, B., Mastracchio, A. & MacMillan, D. W. C. Collective synthesis of natural products by means of organocascade catalysis. Nature 475, 183–188 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Chatgilialoglu, C. & Studer, A. (eds) Encyclopedia of Radicals in Chemistry, Biology and Materials (Wiley-VCH, 2014)

  15. Brimioulle, R., Lenhart, D., Maturi, M. M. & Bach, T. Enantioselective catalysis of photochemical reactions. Angew. Chem. Int. Ed. 54, 3872–3890 (2015). Insightful review of the general strategies and concepts underlying the implementation of photochemical homogenous catalytic enantioselective processes

    Article  CAS  Google Scholar 

  16. Sibi, M. P., Manyem, S. & Zimmerman, J. Enantioselective radical processes. Chem. Rev. 103, 3263–3296 (2003)

    Article  CAS  PubMed  Google Scholar 

  17. Shaw, M. H., Twilton, J. & MacMillan, D. W. C. Photoredox catalysis in organic chemistry. J. Org. Chem. 81, 6898–6926 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  Google Scholar 

  19. Ireland, R. E. Organic Synthesis (Prentice-Hall, 1969)

  20. Evans, D. A. in Asymmetric Synthesis Vol. 3, Part B (ed. Morrison, J. D.) Ch. 1, 1–110 (Academic, 1983)

    Google Scholar 

  21. Doyle, A. G. & Jacobsen, E. N. Enantioselective alkylations of tributyltin enolates catalyzed by Cr(salen)Cl: access to enantiomerically enriched all-carbon quaternary centers. J. Am. Chem. Soc. 127, 62–63 (2005)

    Article  CAS  PubMed  Google Scholar 

  22. Dai, X., Strotman, N. A. & Fu, G. C. Catalytic asymmetric Hiyama cross-couplings of racemic α-bromo esters. J. Am. Chem. Soc. 130, 3302–3303 (2008)

    Article  CAS  PubMed  Google Scholar 

  23. Stork, G., Brizzolara, A., Landesman, H., Szmuszkovicz, J. & Terrell, R. The enamine alkylation and acylation of carbonyl compounds. J. Am. Chem. Soc. 85, 207–222 (1963)

    Article  CAS  Google Scholar 

  24. List, B. et al. The catalytic asymmetric α-benzylation of aldehydes. Angew. Chem. Int. Ed. 53, 282–285 (2014)

    Article  CAS  Google Scholar 

  25. Nicewicz, D. A. & MacMillan, D. W. C. Merging photoredox catalysis with organocatalysis: the direct asymmetric alkylation of aldehydes. Science 322, 77–80 (2008). Besides providing a solution for the longstanding problem of the direct catalytic asymmetric α-alkylation of aldehydes, this seminal study demonstrated the great potential of combining photoredox and organocatalysis

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  26. Giese, B. Radicals in Organic Synthesis: Formation of Carbon–Carbon Bonds (Pergamon, 1986)

  27. Juris, A. et al. Ru(ii) polypyridine complexes: photophysics, photochemistry, electrochemistry, and chemiluminescence. Coord. Chem. Rev. 84, 85–277 (1988)

    Article  CAS  Google Scholar 

  28. van Bergen, T. J., Hedstrand, D. M., Kruizinga, W. H. & Kellogg, R. M. Chemistry of dihydropyridine. 9. Hydride transfer from 1,4-dihydropyridine to sp3-hybridized carbon in sulfonium salts and activated halides. Studies with NAD(P)H models. J. Org. Chem. 44, 4953–4962 (1979)

    CAS  Google Scholar 

  29. Cismesia, M. A. & Yoon, T. P. Characterizing chain processes in visible light photoredox catalysis. Chem. Sci. 6, 5426–5434 (2015); erratum 6, 6019 (2015). Early demonstration of the importance of applying classical experimental techniques, most relevant to photophysical investigations, for elucidating the mechanism of photoredox organocatalytic processes

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  Google Scholar 

  31. Gualandi, A. et al. Organocatalytic enantioselective alkylation of aldehydes with [Fe(bpy)3]Br2 catalyst and visible light. ACS Catal. 5, 5927–5931 (2015)

    Article  CAS  Google Scholar 

  32. 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  PubMed  PubMed Central  Google Scholar 

  33. 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  PubMed  PubMed Central  Google Scholar 

  34. Welin, E. R., Warkentin, A. A., Conrad, J. C. & MacMillan, D. W. C. Enantioselective α-alkylation of aldehydes by photoredox organocatalysis: rapid access to pharmacophore fragments from β-cyanoaldehydes. Angew. Chem. Int. Ed. 54, 9668–9672 (2015)

    Article  CAS  Google Scholar 

  35. Zhu, Y., Zhang, L. & Luo, S. Asymmetric α-photoalkylation of β-ketocarbonyls by primary amine catalysis: facile access to acyclic all-carbon quaternary stereocenters. J. Am. Chem. Soc. 136, 14642–14645 (2014)

    Article  CAS  PubMed  Google Scholar 

  36. 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)

    Article  CAS  PubMed  Google Scholar 

  37. 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)

    Article  CAS  PubMed  Google Scholar 

  38. Twilton, J., Le, C., Zhang, P., Shaw, M. H., Evans, R. W. & MacMillan, D. W. C. The merger of transition metal and photocatalysis. Nat. Rev. Chem. 1, 0052 (2017)

    Article  CAS  Google Scholar 

  39. Yoon, T. P. Photochemical stereocontrol using tandem photoredox–chiral Lewis acid catalysis. Acc. Chem. Res. 49, 2307–2315 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Beeson, T. D., Mastracchio, A., Hong, J.-B., Ashton, K. & Macmillan, D. W. C. Enantioselective organocatalysis using SOMO activation. Science 316, 582–585 (2007). Early use of organocatalysis in enantioselective radical chemistry, before the advent of photoredox catalysis

    Article  ADS  CAS  PubMed  Google Scholar 

  41. Koike, T. & Akita, M. Photoinduced oxyamination of enamines and aldehydes with TEMPO catalyzed by [Ru(bpy)3]2+. Chem. Lett. 38, 166–167 (2009)

    Article  CAS  Google Scholar 

  42. Capacci, A. G., Malinowski, J. T., McAlpine, N. J., Kuhne, J. & MacMillan, D. W. C. Direct, enantioselective α-alkylation of aldehydes using simple olefins. Nat. Chem. 9, 1073–1077 (2017)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Flamigni, L., Barbieri, A., Sabatini, C., Ventura, B. & Barigelletti, F. in Photochemistry and Photophysics of Coordination Compounds II (eds Balzani, V. & Campagna, S. ) 143–203 (Springer, 2007)

    Book  Google Scholar 

  44. Mayer, J. M. Understanding hydrogen atom transfer: from bond strengths to Marcus theory. Acc. Chem. Res. 44, 36–46 (2011)

    Article  CAS  PubMed  Google Scholar 

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

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  46. Studer, A. The persistent radical effect in organic synthesis. Chem. Eur. J. 7, 1159–1164 (2001)

    Article  CAS  PubMed  Google Scholar 

  47. Curran, D. P., Porter, N. A. & Giese, B. (eds) Stereochemistry of Radical Reactions (VCH Verlag, 1996)

  48. Jakobsen, H. J., Lawesson, S. O., Marshall, J. T. B., Schroll, G. & Williams, D. H. Mass spectrometry. XII. Mass spectra of enamines. J. Chem. Soc. B 940–946 (1966)

  49. 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)

    Article  ADS  CAS  PubMed  Google Scholar 

  50. Bahamonde, A. et al. Studies on the enantioselective iminium ion trapping of radicals triggered by an electron-relay mechanism. J. Am. Chem. Soc. 139, 4559–4567 (2017)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Fischer, H. & Radom, L. Factors controlling the addition of carbon-centered radicals to alkenes—an experimental and theoretical perspective. Angew. Chem. Int. Ed. 40, 1340–1371 (2001)

    Article  CAS  Google Scholar 

  52. Quasdorf, K. W. & Overman, L. E. Catalytic enantioselective synthesis of quaternary carbon stereocentres. Nature 516, 181–191 (2014)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  53. 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  PubMed  PubMed Central  Google Scholar 

  54. 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 (2014)

    Article  CAS  Google Scholar 

  55. Lian, M., Li, Z., Cai, Y., Meng, Q. & Gao, Z. Enantioselective photooxygenation of β-keto esters by chiral phase-transfer catalysis using molecular oxygen. Chem. Asian J. 7, 2019–2023 (2012)

    Article  CAS  PubMed  Google Scholar 

  56. Rono, L. J ., Yayla, H. G ., Wang, D. Y ., Armstrong, M. F. & Knowles, R. R. Enantioselective photoredox catalysis enabled by proton-coupled electron transfer: development of an asymmetric aza-pinacol cyclization. J. Am. Chem. Soc. 135, 17735–17738 (2013). Seminal example demonstrating the possibility of exploiting proton-coupled electron transfer in enantioselective organocatalysis

    Article  CAS  PubMed  Google Scholar 

  57. Miller, D. C., Tarantino, K. T. & Knowles, R. R. Proton-coupled electron transfer in organic synthesis: fundamentals, applications, and opportunities. Top. Curr. Chem. 374, 30 (2016)

    Article  CAS  Google Scholar 

  58. Uraguchi, D., Kinoshita, N., Kizu, T. & Ooi, T. Synergistic catalysis of ionic Brønsted acid and photosensitizer for a redox neutral asymmetric α-coupling of N-arylaminomethanes with aldimines. J. Am. Chem. Soc. 137, 13768–13771 (2015)

    Article  CAS  PubMed  Google Scholar 

  59. Turro, N. J., Ramamurthy, V. & Scaiano, J. C. Modern Molecular Photochemistry of Organic Molecules (University Science Books, 2010)

  60. Balzani, V . Ceroni, P. & Juris, A. Photochemistry and Photophysics (Wiley-VCH, 2014)

  61. Arceo, E ., Jurberg, I. D ., Alvarez-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). First demonstration that enamines—key intermediates in ground-state organocatalysis—can use photochemical mechanisms to activate substrates

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  63. 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 

  64. 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)

    Article  CAS  PubMed  Google Scholar 

  65. 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)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Studer, A. & Curran, D. P. Catalysis of radical reactions: a radical chemistry perspective. Angew. Chem. Int. Ed. 55, 58–102 (2016)

    Article  CAS  Google Scholar 

  67. Cecere, G., König, C. M., Alleva, J. L. & MacMillan, D. W. C. Enantioselective direct α-amination of aldehydes via a photoredox mechanism: a strategy for asymmetric amine fragment coupling. J. Am. Chem. Soc. 135, 11521–11524 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Filippini, G., Silvi, M. & Melchiorre, P. Enantioselective formal α-methylation and α-benzylation of aldehydes by means of photo-organocatalysis. Angew. Chem. Int. Ed. 56, 4447–4451 (2017)

    Article  CAS  Google Scholar 

  69. Arceo, E., Bahamonde, A., Bergonzini, G. & Melchiorre, P. Enantioselective direct α-alkylation of cyclic ketones by means of photo-organocatalysis. Chem. Sci. 5, 2438–2442 (2014)

    Article  CAS  Google Scholar 

  70. Shirakawa, S. & Maruoka, K. Recent developments in asymmetric phase-transfer reactions. Angew. Chem. Int. Ed. 52, 4312–4348 (2013)

    Article  CAS  Google Scholar 

  71. Woz´niak, Ł., Murphy, J. J. & Melchiorre, P. Photo-organocatalytic enantioselective perfluoroalkylation of β-ketoesters. J. Am. Chem. Soc. 137, 5678–5681 (2015)

    Article  CAS  Google Scholar 

  72. Silvi, M., Verrier, C., Rey, Y. P., Buzzetti, L. & Melchiorre, P. Visible-light excitation of iminium ions enables the enantioselective catalytic β-alkylation of enals. Nat. Chem. 9, 868–873 (2017)

    Article  CAS  PubMed  Google Scholar 

  73. Mariano, P. S. Electron-transfer mechanisms in photochemical transformations of iminium salts. Acc. Chem. Res. 16, 130–137 (1983)

    Article  CAS  Google Scholar 

  74. Taylor, M. S. & Jacobsen, E. N. Asymmetric catalysis by chiral hydrogen-bond donors. Angew. Chem. Int. Ed. 45, 1520–1543 (2006)

    Article  CAS  Google Scholar 

  75. Bach, T., Bergmann, H., Grosch, B. & Harms, K. Highly enantioselective intra- and intermolecular [2 + 2] photocycloaddition reactions of 2-quinolones mediated by a chiral lactam host:host–guest interactions, product configuration, and the origin of the stereoselectivity in solution. J. Am. Chem. Soc. 124, 7982–7990 (2002)

    Article  CAS  PubMed  Google Scholar 

  76. Bauer, A., Westkämper, F., Grimme, S. & Bach, T. Catalytic enantioselective reactions driven by photoinduced electron transfer. Nature 436, 1139–1140 (2005). Seminal example of enantioselective organocatalysis of photochemical reactions in the excited state

    Article  ADS  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  PubMed  Google Scholar 

  79. Vallavoju, N., Selvakumar, S., Jockusch, S., Sibi, M. P. & Sivaguru, J. Enantioselective organo-photocatalysis mediated by atropisomeric thiourea derivatives. Angew. Chem. Int. Ed. 53, 5604–5608 (2014)

    Article  CAS  Google Scholar 

  80. Madarász, Á. et al. Thiourea derivatives as Brønsted acid organocatalysts. ACS Catal. 6, 4379–4387 (2016)

    Article  CAS  Google Scholar 

  81. Emmanuel, M. A., Greenberg, N. R., Oblinsky, D. G. & Hyster, T. K. Accessing non-natural reactivity by irradiating nicotinamide-dependent enzymes with light. Nature 540, 414–417 (2016). Landmark demonstration that light excitation of cofactors can alter the natural reactivity of enzymes

    Article  ADS  CAS  PubMed  Google Scholar 

  82. Huisman, G. W., Liang, J. & Krebber, A. Practical chiral alcohol manufacture using ketoreductases. Curr. Opin. Chem. Biol. 14, 122–129 (2010)

    Article  CAS  PubMed  Google Scholar 

  83. Fukuzumi, S., Hironaka, K. & Tanaka, T. Photoreduction of alkyl halides by an NADH model compound. An electron transfer chain mechanism. J. Am. Chem. Soc. 105, 4722–4727 (1983)

    Article  CAS  Google Scholar 

  84. Bornscheuer, U. T. et al. Engineering the third wave of biocatalysis. Nature 485, 185–194 (2012)

    Article  ADS  CAS  PubMed  Google Scholar 

  85. Huo, H. et al. Asymmetric photoredox transition-metal catalysis activated by visible light. Nature 515, 100–103 (2014)

    Article  ADS  CAS  PubMed  Google Scholar 

  86. Cambié, D., Bottecchia, C., Straathof, N. J. W., Hessel, V. & Noël, T. Applications of continuous-flow photochemistry in organic synthesis, material science, and water treatment. Chem. Rev. 116, 10276–10341 (2016)

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    CAS  Google Scholar 

  89. Enders, D., Niemeier, O. & Henseler, A. Organocatalysis by N-heterocyclic carbenes. Chem. Rev. 107, 5606–5655 (2007)

    Article  CAS  PubMed  Google Scholar 

  90. Breslow, R. On the mechanism of thiamine action. IV. Evidence from studies on model systems. J. Am. Chem. Soc. 80, 3719–3726 (1958)

    CAS  Google Scholar 

  91. Sheehan, J. & Hara, T. Asymmetric thiazolium salt catalysis of the benzoin condensation. J. Org. Chem. 39, 1196–1199 (1974)

    Article  CAS  Google Scholar 

  92. Enders, D. & Kallfass, U. An efficient nucleophilic carbene catalyst for the asymmetric benzoin condensation. Angew. Chem. Int. Ed. 41, 1743–1745 (2002)

    Article  CAS  Google Scholar 

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

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  94. Sigman, M. & Jacobsen, E. N. Schiff base catalysts for the asymmetric Strecker reaction identified and optimized from parallel synthetic libraries. J. Am. Chem. Soc. 120, 4901–4902 (1998)

    Article  CAS  Google Scholar 

  95. Reisman, S. E., Doyle, A. G. & Jacobsen, E. N. Enantioselective thiourea-catalyzed additions to oxocarbenium ions. J. Am. Chem. Soc. 130, 7198–7199 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Akiyama, T., Itoh, J., Yokota, K. & Fuchibe, K. Enantioselective Mannich-type reaction catalyzed by a chiral Brønsted acid. Angew. Chem. Int. Ed. 43, 1566–1568 (2004)

    Article  CAS  Google Scholar 

  97. Uraguchi, D. & Terada, M. Chiral Brønsted acid-catalyzed direct Mannich reactions via electrophilic activation. J. Am. Chem. Soc. 126, 5356–5357 (2004)

    Article  CAS  PubMed  Google Scholar 

  98. Parmar, D., Sugiono, E., Raja, S. & Rueping, M. Complete field guide to asymmetric BINOL-phosphate derived Brønsted acid and metal catalysis: history and classification by mode of activation; Brønsted acidity, hydrogen bonding, ion pairing, and metal phosphates. Chem. Rev. 114, 9047–9153 (2014)

    Article  CAS  PubMed  Google Scholar 

  99. Brak, K. & Jacobsen, E. N. Asymmetric ion-pairing catalysis. Angew. Chem. Int. Ed. 52, 534–561 (2013)

    Article  CAS  Google Scholar 

  100. Staveness, D., Bosque, I. & Stephenson, C. R. J. Free radical chemistry enabled by visible light-induced electron transfer. Acc. Chem. Res. 49, 2295–2306 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

P.M. thanks the Generalitat de Catalunya (CERCA Program), Agencia Estatal de Investigación (AEI) (CTQ2016-75520-P), and the European Research Council (ERC 681840-CATA-LUX) for financial support. M.S. thanks the EU for a Horizon 2020 Marie Skłodowska-Curie Fellowship (grant 744242).

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  1. School of Chemistry, University of Bristol, Cantock’s Close, Bristol, BS8 1TS, UK

    Mattia Silvi

  2. ICIQ, Institute of Chemical Research of Catalonia—the Barcelona Institute of Science and Technology, Avenida Països Catalans 16, Tarragona, 43007, Spain

    Paolo Melchiorre

  3. ICREA, Catalan Institution for Research and Advanced Studies, Passeig Lluís Companys 23, Barcelona, 08010, Spain

    Paolo Melchiorre

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P.M. outlined the content of the Review and defined its scope. M.S. and P.M. worked together to prepare and edit the manuscript, figures and references.

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Silvi, M., Melchiorre, P. Enhancing the potential of enantioselective organocatalysis with light. Nature 554, 41–49 (2018). https://doi.org/10.1038/nature25175

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