Skip to main content
SpringerLink
Log in

Synthesis of Organofluorine Compounds

  • Chapter
  • First Online:
Springer Handbook of Inorganic Photochemistry

Part of the book series: Springer Handbooks ((SHB))

  • 4602 Accesses

Abstract

This chapter describes representative examples of the photocatalytic fluorination and di- and trifluoromethylation of organic compounds mediated by metal complexes or metal oxides. These photocatalytic methods are useful for the synthesis of organofluorine compounds. The fundamental reaction design in each of the transformations is discussed, and general experimental procedures are included. Synthetic methodologies that involve defluorination processes or the incorporation of other fluorinated motifs are not considered in this chapter.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 309.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Ojima, I. (ed.): Fluorine in Medicinal Chemistry and Chemical Biology. Wiley-Blackwell, Chichester (2009)

    Google Scholar 

  2. Liang, T., Neumann, C.N., Ritter, T.: Introduction of fluorine and fluorine-containing functional groups. Angew. Chem. Int. Ed. 52, 8214–8264 (2013)

    Article  CAS  Google Scholar 

  3. Yerien, D.E., Bonesi, S., Postigo, A.: Fluorination methods in drug discovery. Org. Biomol. Chem. 14, 8398–8427 (2016)

    Article  CAS  PubMed  Google Scholar 

  4. 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  PubMed  Google Scholar 

  5. 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  PubMed  PubMed Central  Google Scholar 

  6. 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  PubMed  PubMed Central  CAS  Google Scholar 

  7. Koike, T., Akita, M.: Visible-light radical reaction designed by Ru- and Ir-based photoredox catalysis. Inorg. Chem. Front. 1, 562–576 (2014)

    Article  CAS  Google Scholar 

  8. Skubi, K.L., Blum, T.R., Yoon, T.P.: Dual catalysis strategies in photochemical synthesis. Chem. Rev. 116, 10035–10074 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Romero, N.A., Nicewicz, D.A.: Organic photoredox catalysis. Chem. Rev. 116, 10075–10166 (2016)

    Article  CAS  PubMed  Google Scholar 

  10. Marzo, L., Pagire, S.K., Reiser, O., König, B.: Visible-light photocatalysis: does it make a difference in organic synthesis? Angew. Chem. Int. Ed. 57, 10034–10072 (2018)

    Article  CAS  Google Scholar 

  11. Ravelli, D., Protti, S., Fagnoni, M.: Decatungstate anion for photocatalyzed “window ledge” reactions. Acc. Chem. Res. 49, 2232–2242 (2016)

    Article  CAS  PubMed  Google Scholar 

  12. Capaldo, L., Ravelli, D.: Hydrogen atom transfer (HAT): a versatile strategy for substrate activation in photocatalyzed organic synthesis. Eur. J. Org. Chem. 2017, 2056–2071 (2017)

    Article  CAS  Google Scholar 

  13. Suzuki, K., Mizuno, N., Yamaguchi, K.: Polyoxometalate photocatalysis for liquid-phase selective organic functional group transformations. ACS Catal. 8, 10809–10825 (2018)

    Article  CAS  Google Scholar 

  14. Koike, T., Akita, M.: Trifluoromethylation by visible-light-driven photoredox catalysis. Top. Catal. 57, 967–974 (2014)

    Article  CAS  Google Scholar 

  15. Barata-Vallejo, S., Bonesi, S.M., Postigo, A.: Photocatalytic fluoroalkylation reactions of organic compounds. Org. Biomol. Chem. 13, 11153–11183 (2015)

    Article  CAS  PubMed  Google Scholar 

  16. Koike, T., Akita, M.: Fine design of photoredox systems for catalytic fluoromethylation of carbon–carbon multiple bonds. Acc. Chem. Res. 49, 1937–1945 (2016)

    Article  CAS  PubMed  Google Scholar 

  17. Chatterjee, T., Iqbal, N., You, Y., Cho, E.J.: Controlled fluoroalkylation reactions by visible-light photoredox catalysis. Acc. Chem. Res. 49, 2284–2294 (2016)

    Article  CAS  PubMed  Google Scholar 

  18. Pan, X., Xia, H., Wu, J.: Recent advances in photoinduced trifluoromethylation and difluoroalkylation. Org. Chem. Front. 3, 1163–1185 (2016)

    Article  CAS  Google Scholar 

  19. Koike, T., Akita, M.: New horizons of photocatalytic fluoromethylative difunctionalization of alkenes. Chem. 4, 409–437 (2018)

    Article  CAS  Google Scholar 

  20. Hazeldine, R.N.: The reactions of fluorocarbon radicals. Part I. The reaction of iodotrifluoromethane with ethylane and tetrafluoroethylene. J. Chem. Soc., 2856–2861 (1949)

    Google Scholar 

  21. Studer, A.: A “renaissance” in radical trifluoromethylation. Angew. Chem. Int. Ed. 51, 8950–8958 (2012)

    Article  CAS  Google Scholar 

  22. Kamigata, N., Fukushima, T., Yoshida, M.: Reaction of trifluoromethanesulphonyl chloride with alkenes catalyzed by a ruthenium(ii) complex. J. Chem. Soc. Chem. Commun., 1559–1560 (1989)

    Google Scholar 

  23. Umemoto, T.: Electrophilic perfluoroalkylating agents. Chem. Rev. 96, 1757–1777 (1996)

    Article  CAS  PubMed  Google Scholar 

  24. Umemoto, T., Ishihara, S.: Power-variable electrophilic trifluoromethylating agents. S-, Se-, and Te-(Trifluoromethyl)dibenzothio-, −seleno-, and -tellurophenium salt system. J. Am. Chem. Soc. 115, 2156–2164 (1993)

    Article  CAS  Google Scholar 

  25. Charpentier, J., Früh, N., Togni, A.: Electrophilic trifluoromethylation by use of hypervalent iodine reagents. Chem. Rev. 115, 650–682 (2015)

    Article  CAS  PubMed  Google Scholar 

  26. Beatty, J.W., Douglas, J.J., Cole, K.P., Stephenson, C.R.J.: A scalable and operationally simple radical trifluoromethylation. Nat. Commun. 6, 7919 (2015)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Umemomto, T., Zhang, B., Zhu, T., Zhou, X., Zhang, P., Hu, S., Li, Y.: Powerful, thermally stable, one-pot-preparable, and recyclable electrophilic trifluoromethylating agents: 2,8-difluoro- and 2,3,7,8-tetrafluoro-S-(trifluoromethyl)dibenzothiophenium salts. J. Org. Chem. 82, 7708–7719 (2017)

    Article  CAS  Google Scholar 

  28. Langlois, B.R., Laurent, E., Roidot, N.: Trifluoromethylation of aromatic compounds with sodium trifluoromethanesulfinate under oxidative conditions. Tetrahedron Lett. 32, 7525–7528 (1991)

    Article  CAS  Google Scholar 

  29. Wallentin, C.-J., Nguyen, J.D., Finkbeiner, P., Stephenson, C.R.J.: Visible light-mediated atom transfer radical addition via oxidative and reductive quenching of photocatalysts. J. Am. Chem. Soc. 134, 8875–8884 (2012)

    Article  CAS  PubMed  Google Scholar 

  30. Yasu, Y., Koike, T., Akita, M.: Three-component oxytrifluoromethylation of alkenes: highly efficient and regioselective difunctionalization of C=C bonds mediated by photoredox catalysis. Angew. Chem. Int. Ed. 51, 9567–9571 (2012)

    Article  CAS  Google Scholar 

  31. Yasu, Y., Koike, T., Akita, M.: Intermolecular aminotrifluoromethylation of alkenes by visible-light-driven photoredox catalysis. Org. Lett. 15, 2136–2139 (2013)

    Article  CAS  PubMed  Google Scholar 

  32. Tomita, R., Yasu, Y., Koike, T., Akita, M.: Combining photoredox-catalyzed trifluoromethylation and oxidation with DMSO: facile synthesis of α-trifluoromethylated ketones from aromatic alkenes. Angew. Chem. Int. Ed. 53, 7144–7148 (2014)

    Article  CAS  Google Scholar 

  33. Mizuta, S., Verhoog, S., Engle, K.M., Khotavivattana, T., O’Duill, M., Wheelhouse, K., Rassias, G., Médebielle, M., Gouverneur, V.: Catalytic hydrotrifluoromethylation of unactivated alkenes. J. Am. Chem. Soc. 135, 2505–2508 (2013)

    Article  CAS  PubMed  Google Scholar 

  34. Wilger, D.J., Gesmundo, N.J., Nicewicz, D.A.: Catalytic hydrotrifluoromethylation of styrenes and unactivated aliphatic alkenes via an organic photoredox system. Chem. Sci. 4, 3160–3165 (2013)

    Article  CAS  Google Scholar 

  35. Straathof, N.J.W., Cramer, S.E., Hessel, V., Noël, T.: Practical photocatalytic trifluoromethylation and hydrotrifluoromethylation of styrenes in batch and flow. Angew. Chem. Int. Ed. 55, 15549–15553 (2016)

    Article  CAS  Google Scholar 

  36. Zhu, L., Wang, L.-S., Li, B., Fu, B., Zhang, C.-P., Li, W.: Operationally simple hydrotrifluoromethylation of alkenes with sodium triflinate enabled by Ir photoredox catalysis. Chem. Commun. 52, 6371–6374 (2016)

    Article  CAS  Google Scholar 

  37. Lefebvre, Q., Hoffmann, N., Rueping, M.: Photoorganocatalysed and visible light photoredox catalysed trifluoromethylation of olefins and (hetero)aromatics in batch and continuous flow. Chem. Commun. 52, 2493–2496 (2016)

    Article  CAS  Google Scholar 

  38. Nagib, D.A., Scott, M.E., MacMillan, D.W.C.: Enantioselective a-trifluoromethylation of aldehyde via photoredox organocatalysis. J. Am. Chem. Soc. 131, 10875–10877 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Shimizu, M., Hiyama, T.: Modern synthetic methods for fluorine-substituted target molecules. Angew. Chem. Int. Ed. 44, 214–231 (2005)

    Article  CAS  Google Scholar 

  40. Rivkin, A., Chou, T.-C., Danishefsky, S.J.: On the remarkable antitumor properties of fludelone: how we got there. Angew. Chem. Int. Ed. 44, 2838–2850 (2005)

    Article  CAS  Google Scholar 

  41. Shimizu, M., Takeda, Y., Higashi, M., Hiyama, T.: 1,4-bis(alkenyl)-2,5-dipiperidinobenzenes: minimal fluorophores exhibiting highly efficient emission in the solid state. Angew. Chem. Int. Ed. 48, 3653–3656 (2009)

    Article  CAS  Google Scholar 

  42. Iqbal, N., Jung, J., Park, S., Cho, E.J.: Controlled trifluoromethylation reactions of alkynes through visible-light photoredox catalysis. Angew. Chem. Int. Ed. 53, 539–542 (2014)

    Article  CAS  Google Scholar 

  43. Han, H.S., Lee, Y.J., Jung, Y.-S., Han, S.B.: Stereoselective photoredox-caalyzed chlorotrifluoromethylation of alkynes: synthesis of tetrasubstituted alkenes. Org. Lett. 19, 1962–1965 (2017)

    Article  CAS  PubMed  Google Scholar 

  44. Tomita, R., Koike, T., Akita, M.: Photoredox-catalyzed stereoselective conversion of alkynes into tetrasubstituted trifluoromethylated alkenes. Angew. Chem. Int. Ed. 54, 12923–12927 (2015)

    Article  CAS  Google Scholar 

  45. Tong, K., Zheng, T., Zhang, Y., Yu, S.: Synthesis of ortho-(fluoro)alkylated pyridines via visible light-promoted radical isocyanide insertion. Adv. Synth. Catal. 357, 3681–3686 (2015)

    Article  CAS  Google Scholar 

  46. Cheng, Y., Yuan, X., Jiang, H., Wang, R., Ma, J., Zhang, Y., Yu, S.: Regiospecific synthesis of 1-trifluoromethylisoquinolines enabled by photoredox somophilic vinyl isocyanide insertion. Adv. Synth. Catal. 356, 2859–2866 (2014)

    Article  CAS  Google Scholar 

  47. Wang, R., Jiang, H., Cheng, Y., Kadi, A.A., Fun, H.-K., Zhang, Y., Yu, S.: Somophilic isocyanide insertion: synthesis of 6-arylated and 6-trifluoromethylated phenanthridines. Synthesis. 46, 2711–2726 (2014)

    Article  CAS  Google Scholar 

  48. Nagib, D.A., MacMillan, D.W.C.: Trifluoromethylation of arenes and heteroarenes by means of photoredox catalysis. Nature. 480, 224–228 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Iqbal, N., Choi, S., Ko, E., Cho, E.J.: Trifluoromethylation of heterocycles via visible light photoredox catalysis. Tetrahedron Lett. 53, 2005–2008 (2012)

    Article  CAS  Google Scholar 

  50. Beatty, J.W., Douglas, J.J., Miller, R., McAtee, R.C., Cole, K.P., Stephenson, C.R.J.: Photochemical perfluoroalkylation with pyridine N-oxides: mechanistic insights and performance on a kilogram. Chem. 1, 456–472 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. 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  PubMed  CAS  Google Scholar 

  52. Straathof, N.J.W., Tegelbeckers, B.J.P., Hessel, V., Wang, X., Noël, T.: A mild and fast photocatalytic trifluoromethylation of thiols in batch and continuous-flow. Chem. Sci. 5, 4768–4773 (2014)

    Article  CAS  Google Scholar 

  53. Li, Y., Koike, T., Akita, M.: Photocatalytic trifluoromethylthiolation of aromatic alkenes associated with hydroxylation and akoxylation. Asian J. Org. Chem. 6, 445–448 (2017)

    Article  CAS  Google Scholar 

  54. Honeker, R., Garza-Sanchez, R.A., Hopkinson, M.N., Glorius, F.: Visible-light-promoted trifluoromethylthiolation of styrenes by dual photoredox/halide catalysis. Chem. Eur. J. 22, 4395–4399 (2016)

    Article  CAS  PubMed  Google Scholar 

  55. Dagousset, G., Simon, C., Anselmi, E., Tuccio, B., Billard, T., Magnier, E.: Generation of the SCF3 radical by photoredox catalysis: intra- and intermolecular carbotrifluoromethylthiolation of alkenes. Chem. Eur. J. 23, 4282–4286 (2017)

    Article  CAS  PubMed  Google Scholar 

  56. Zhang, W., Wang, F., Hu, J.: N-Tosyl-S-difluoromethyl-S-phenylsulfoximine: a new difluoromethylation reagent for S-, N-, and C-nucleophiles. Org. Lett. 11, 2109–21112 (2009)

    Article  CAS  PubMed  Google Scholar 

  57. Tang, X.-J., Dolbier Jr., W.R.: Efficient Cu-catalyzed atom transfer radical addition reactions of fluoroalkylsulfonyl chlorides with electron-deficient alkenes induced by visible light. Angew. Chem. Int. Ed. 54, 4246–4249 (2015)

    Article  CAS  Google Scholar 

  58. Rong, J., Deng, L., Tan, P., Ni, C., Gu, Y., Hu, J.: Radical fluoroalkylation of isocyanides with fluorinated sulfones by visible-light photoredox catalysis. Angew. Chem. Int. Ed. 55, 2743–2747 (2016)

    Article  CAS  Google Scholar 

  59. Noto, N., Koike, T., Akita, M.: Metal-free di- and tri-fluoromethylation of alkenes realized by visible-light-induced perylene photoredox catalysis. Chem. Sci. 8, 6375–6379 (2017)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Lin, Q.-Y., Xu, X.-H., Zhang, K., Qing, F.-L.: Visible-light-induced hydrodifluoromethylation of alkenes with a bromodifluoromethylphosphonium bromide. Angew. Chem. Int. Ed. 55, 1479–1483 (2016)

    Article  CAS  Google Scholar 

  61. Yatham, V.R., Shen, Y., Martin, R.: Catalytic intermolecular dicarbofunctionalization of styrenes with CO2 and radical precursors. Angew. Chem. Int. Ed. 56, 10915–10919 (2017)

    Article  CAS  Google Scholar 

  62. Arai, Y., Tomits, R., Ando, G., Koike, T., Akita, M.: Oxydifluoromethylation of alkenes by photoredox catalysis: simple synthesis of CF2H-containing alcohols. Chem. Eur. J. 22, 1262–1265 (2016)

    Article  CAS  PubMed  Google Scholar 

  63. Zhang, Z., Tang, X., Dolbier Jr., W.R.: Photoredox-catalyzed tandem insertion/cyclization reactions of difluoromethyl and 1,1-difluoroalkyl radicals with biphenyl isocyanides. Org. Lett. 17, 4401–4403 (2015)

    Article  CAS  PubMed  Google Scholar 

  64. Halperin, S.D., Fan, H., Chang, S., Martin, R.E., Britton, R.: A convenient photocatalytic fluorination of unactivated C–H bonds. Angew. Chem. Int. Ed. 53, 4690–4693 (2014)

    Article  CAS  Google Scholar 

  65. West, J.G., Bedell, T.A., Sorensen, E.J.: The uranyl cation as a visible-light photocatalyst for C(sp3)–H fluorination. Angew. Chem. Int. Ed. 55, 8923–8927 (2016)

    Article  CAS  Google Scholar 

  66. Ventre, S., Petronijevic, F.R., MacMillan, D.W.C.: Decarboxylative fluorination of aliphatic carboxylic acids via photoredox catalysis. J. Am. Chem. Soc. 137, 5654–5657 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Rueda-Becerril, M., Mahé, O., Drouin, M., Majewski, M.B., West, J.G., Wolf, M.O., Sammis, G.M., Paquin, J.-F.: Direct C–F bond formation using photoredox catalysis. J. Am. Chem. Soc. 136, 2637–2641 (2014)

    Article  CAS  PubMed  Google Scholar 

  68. González-Esguevillas, M., Miró, J., Jeffrey, J.L., MacMillan, D.W.C.: Photoredox-catalyzed deoxyfluorination of activated alcohols with selectfluor. Tetrahedron. 75, 4222–4227 (2019)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Brioche, J.: One-pot synthesis of tertiary alkyl fluorides from methyl oxalates by radical deoxyfluorination under photoredox catalysis. Tetrahedron Lett. 59, 4387–4391 (2018)

    Article  CAS  Google Scholar 

  70. Su, J.Y., Grünenfelder, D.C., Takeuchi, K., Reisman, S.E.: Radical deoxychlorination of cesium oxalates for the synthesis of alkyl chlorides. Org. Lett. 20, 4912–4916 (2018)

    Article  CAS  PubMed  Google Scholar 

  71. Xuan, J., Zhang, Z.-G., Xiao, W.-J.: Visible-light-induced decarboxylative functionalization of carboxylic acids and their derivatives. Angew. Chem. Int. Ed. 54, 15632–15641 (2015)

    Article  CAS  Google Scholar 

  72. Schwarz, J., König, B.: Decarboxylativve reactions with and without light–a comparison. Green Chem. 20, 323–361 (2018)

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Applied Chemistry, Faculty of Fundamental Engineering, Nippon Institute of Technology, Saitama, Japan

    Takashi Koike

Authors
  1. Takashi Koike
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Takashi Koike .

Editor information

Editors and Affiliations

  1. Laboratory “Photoactive Nanocomposite Materials”, Saint-Petersburg State University, Saint-Petersburg, Russia

    Detlef Bahnemann

  2. Laboratory of Photochemistry and Materials Science, Institute of Chemistry, Federal University of Uberlandia, Uberlandia, Brazil

    Antonio Otavio T. Patrocinio

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Koike, T. (2022). Synthesis of Organofluorine Compounds. In: Bahnemann, D., Patrocinio, A.O.T. (eds) Springer Handbook of Inorganic Photochemistry. Springer Handbooks. Springer, Cham. https://doi.org/10.1007/978-3-030-63713-2_53

Download citation

Publish with us

Policies and ethics

Search

Navigation