Photocatalytic strategies for the activation of organic chlorides


Driven by the continuous demand for sustainable organic synthesis, the field of photocatalysis has emerged as a powerful manifold for direct modification of various chemical compounds. Organic chlorides have not been typically considered as attractive synthetic precursors for these reactions due to their chemical inertness, however, this situation is now rapidly changing. The past five years have witnessed a growing interest in exploring organic chlorides as cheap, readily available and bench-stable substrates for photocatalytic transformations and a number of protocols have already been reported. This Review Article summarises the conceptual ideas behind the developed methods and presents them in the form of synthetic strategies based on how light energy is accumulated in the catalytic system or the way bond energy in the substrate is reduced. The synthetic application of each strategy is also discussed.

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Fig. 1: Photocatalytic activation of organic chlorides.
Fig. 2: Direct SET strategy using visible light.
Fig. 3: Direct SET strategy using high-energy light.
Fig. 4: conPET strategy.
Fig. 5: SenI-ET and electrophotocatalysis strategies.
Fig. 6: Solvated electron and triplet–triplet annihilation strategies.
Fig. 7: Substitution/oxidative addition strategies.
Fig. 8: Strong-base-assistance strategies.


  1. 1.

    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).

    CAS  PubMed  Google Scholar 

  2. 2.

    Clayden, J., Greeves, N. & Warren, S. Organic Chemistry. (Oxford Univ. Press, 2012).

  3. 3.

    Pandey, D. K., Ankade, S. B., Ali, A., Prabhakaran, V. & Punji, B. Nickel-catalyzed C–H alkylation of indoles with unactivated alkyl chlorides: evidence of Ni(I)/Ni(III) pathway. Chem. Sci. 10, 9493–9500 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Chen, B. Z. et al. Synthesis of alkyl indium reagents by using unactivated alkyl chlorides and their applications in palladium-catalyzed cross-coupling reactions with aryl halides. Org. Lett. 20, 1902–1905 (2018).

    CAS  PubMed  Google Scholar 

  5. 5.

    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).

    CAS  Google Scholar 

  6. 6.

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

    CAS  PubMed  Google Scholar 

  7. 7.

    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).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Tucker, J. W. & Stephenson, C. R. J. Shining light on photoredox catalysis: theory and synthetic applications. J. Org. Chem. 77, 1617–1622 (2012).

    CAS  PubMed  Google Scholar 

  9. 9.

    Strieth-Kalthoff, F., James, M. J., Teders, M., Pitzer, L. & Glorius, F. Energy transfer catalysis mediated by visible light: principles, applications, directions. Chem. Soc. Rev. 47, 7190–7202 (2018).

    CAS  PubMed  Google Scholar 

  10. 10.

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

    CAS  Google Scholar 

  11. 11.

    Lekkala, R., Lekkala, R., Moku, B., Rakesh, K. P. & Qin, H.-L. Recent developments in radical-mediated transformations of organohalides. Eur. J. Org. Chem. 2019, 2769–2806 (2019).

    CAS  Google Scholar 

  12. 12.

    Martin, E. T., McGuire, C. M., Mubarak, M. S. & Peters, D. G. Electroreductive remediation of halogenated environmental pollutants. Chem. Rev. 116, 15198–15234 (2016).

    CAS  PubMed  Google Scholar 

  13. 13.

    Rudolph, A. & Lautens, M. Secondary alkyl halides in transition-metal-catalyzed cross-coupling reactions. Angew. Chem. Int. Ed. 48, 2656–2670 (2009).

    CAS  Google Scholar 

  14. 14.

    Ye, S., Xiang, T., Li, X. & Wu, J. Metal-catalyzed radical-type transformation of unactivated alkyl halides with C–C bond formation under photoinduced conditions. Org. Chem. Front. 6, 2183–2199 (2019).

    CAS  Google Scholar 

  15. 15.

    Connell, T. U. et al. The tandem photoredox catalysis mechanism of [Ir(ppy)2(dtbbpy)]+ enabling access to energy demanding organic substrates. J. Am. Chem. Soc. 141, 17646–17658 (2019).

    CAS  PubMed  Google Scholar 

  16. 16.

    Yin, H., Carroll, P. J., Anna, J. M. & Schelter, E. J. Luminescent Ce(iii) complexes as stoichiometric and catalytic photoreductants for halogen atom abstraction reactions. J. Am. Chem. Soc. 137, 9234–9237 (2015).

    CAS  PubMed  Google Scholar 

  17. 17.

    Shon, J.-H., Sittel, S. & Teets, T. S. Synthesis and characterization of strong cyclometalated iridium photoreductants for application in photocatalytic aryl bromide hydrodebromination. ACS Catal. 9, 8646–8658 (2019).

    CAS  Google Scholar 

  18. 18.

    Lambert, F. L. & Ingall, G. B. Voltammetry of organic halogen compounds. IV. The reduction of organic chlorides at the vitreous (glassy) carbon electrode. Tetrahedron Lett. 15, 3231–3234 (1974).

    Google Scholar 

  19. 19.

    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). This article describes visible-light-induced dehalogenation of activated α-chlorophenylacetate esters and amides with high selectivity and broad functional groups tolerance.

    CAS  PubMed  Google Scholar 

  20. 20.

    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).

    CAS  Google Scholar 

  21. 21.

    Maji, T., Karmakar, A. & Reiser, O. Visible-light photoredox catalysis: dehalogenation of vicinal dibromo-, α-halo-, and α,α-dibromocarbonyl compounds. J. Org. Chem. 76, 736–739 (2011).

    CAS  PubMed  Google Scholar 

  22. 22.

    Pirtsch, M., Paria, S., Matsuno, T., Isobe, H. & Reiser, O. [Cu(dap)2Cl] as an efficient visible-light-driven photoredox catalyst in carbon-carbon bond-forming reactions. Chem. Eur. J. 18, 7336–7340 (2012).

    CAS  PubMed  Google Scholar 

  23. 23.

    Zhou, W.-J. et al. Visible-light-driven palladium-catalyzed radical alkylation of C−H bonds with unactivated alkyl bromides. Angew. Chem. Int. Ed. 56, 15683–15687 (2017).

    CAS  Google Scholar 

  24. 24.

    Hou, M. et al. Enantioselective photoredox dehalogenative protonation. Chem. Sci. 10, 6629–6634 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Zeng, G., Li, Y., Qiao, B., Zhao, X. & Jiang, Z. Photoredox asymmetric catalytic enantioconvergent substitution of 3-chlorooxindoles. Chem. Commun. 55, 11362–11365 (2019).

    CAS  Google Scholar 

  26. 26.

    Föll, T., Rehbein, J. & Reiser, O. Ir(ppy)3-catalyzed, visible-light-mediated reaction of α-chloro cinnamates with enol acetates: an apparent halogen paradox. Org. Lett. 20, 5794–5798 (2018).

    PubMed  Google Scholar 

  27. 27.

    Jiang, M., Li, H., Yang, H. & Fu, H. Room-temperature arylation of thiols: breakthrough with aryl chlorides. Angew. Chem. Int. Ed. 56, 874–879 (2017).

    CAS  Google Scholar 

  28. 28.

    Senaweera, S. & Weaver, J. D. Dual C–F, C–H functionalization via photocatalysis: access to multifluorinated biaryls. J. Am. Chem. Soc. 138, 2520–2523 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Schmalzbauer, M., Ghosh, I. & König, B. Utilising excited state organic anions for photoredox catalysis: activation of (hetero)aryl chlorides by visible light-absorbing 9-anthrolate anions. Faraday Discuss. 215, 364–378 (2019).

    CAS  PubMed  Google Scholar 

  30. 30.

    Liang, K. et al. Redox-neutral photochemical Heck-type arylation of vinylphenols activated by visible light. Chem. Sci. 11, 2130–2135 (2020).

    CAS  Google Scholar 

  31. 31.

    Ou, W., Zou, R., Han, M., Yu, L. & Su, C. Tailorable carbazolyl cyanobenzene-based photocatalysts for visible light-induced reduction of aryl halides. Chin. Chem. Lett. 2, 10–13 (2019).

    Google Scholar 

  32. 32.

    Petroff, J. T. et al. Enhanced photocatalytic dehalogenation of aryl halides by combined poly-p-phenylene (PPP) and TiO2 photocatalysts. J. Photochem. Photobiol. A Chem. 335, 149–154 (2017).

    Google Scholar 

  33. 33.

    Michelet, B., Deldaele, C., Kajouj, S., Moucheron, C. & Evano, G. A general copper catalyst for photoredox transformations of organic halides. Org. Lett. 19, 3576–3579 (2017).

    CAS  PubMed  Google Scholar 

  34. 34.

    Li, C.-G., Xu, G.-Q. & Xu, P.-F. Synthesis of fused pyran derivatives via visible-light-induced cascade cyclization of 1,7-enynes with acyl chlorides. Org. Lett. 19, 512–515 (2017).

    CAS  PubMed  Google Scholar 

  35. 35.

    Wei, Y.-L., Chen, J.-Q., Sun, B. & Xu, P.-F. Synthesis of indolo[2,1-a]isoquinoline derivatives via visible-light-induced radical cascade cyclization reactions. Chem. Commun. 55, 5922–5925 (2019).

    CAS  Google Scholar 

  36. 36.

    Liu, Y. et al. Visible light-catalyzed cascade radical cyclization of N-propargylindoles with acyl chlorides for the synthesis of 2-acyl-9H-pyrrolo[1,2-a]indoles. J. Org. Chem. 85, 2385–2394 (2020).

    CAS  PubMed  Google Scholar 

  37. 37.

    He, X., Cai, B., Yang, Q., Wang, L. & Xuan, J. Visible‐light‐promoted cascade radical cyclization: synthesis of 1,4‐diketones containing chroman‐4‐one skeletons. Chem. Asian J. 14, 3269–3273 (2019).

    CAS  PubMed  Google Scholar 

  38. 38.

    Zhao, Q., Xu, G.-Q., Liang, H., Wang, Z. & Xu, P. Aroylchlorination of 1,6-dienes via a photoredox catalytic atom-transfer radical cyclization process. Org. Lett. 21, 8615–8619 (2019).

    CAS  PubMed  Google Scholar 

  39. 39.

    Chang, R. et al. Visible light-mediated direct C–H aroylation and alkylation of heteroarenes. ACS Omega 4, 14021–14031 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Wang, C.-M. et al. Visible-light-promoted synthesis of 1,4-dicarbonyl compounds via conjugate addition of aroyl chlorides. Chem. Asian J. 13, 271–274 (2018).

    CAS  PubMed  Google Scholar 

  41. 41.

    Sarkar, S., Banerjee, A., Yao, W., Patterson, E. V. & Ngai, M. Photocatalytic radical aroylation of unactivated alkenes: pathway to β-functionalized 1,4-, 1,6-, and 1,7-diketones. ACS Catal. 9, 10358–10364 (2019).

    CAS  Google Scholar 

  42. 42.

    Lei, Z. et al. β‐Selective aroylation of activated alkenes by photoredox catalysis. Angew. Chem. 131, 7396–7401 (2019).

    Google Scholar 

  43. 43.

    Patil, D. V., Kim, H. Y. & Oh, K. Visible light-promoted Friedel-Crafts-type chloroacylation of alkenes to β-chloroketones. Org. Lett. 22, 3018–3022 (2020).

    CAS  PubMed  Google Scholar 

  44. 44.

    Qiu, G., Li, Y. & Wu, J. Recent developments for the photoinduced Ar–X bond dissociation reaction. Org. Chem. Front. 3, 1011–1027 (2016).

    CAS  Google Scholar 

  45. 45.

    Li, D., Che, C.-M., Kwong, H.-L. & Yam, V. W.-W. Photoinduced C–C bond formation from alkyl halides catalysed by luminescent dinuclear gold(I) and copper(I) complexes. J. Chem. Soc. Dalt. Trans. 23, 3325–3329 (1992).

    Google Scholar 

  46. 46.

    Discekici, E. H. et al. A highly reducing metal-free photoredox catalyst: design and application in radical dehalogenations. Chem. Commun. 51, 11705–11708 (2015).

    CAS  Google Scholar 

  47. 47.

    Steiner, A. et al. Implementing hydrogen atom transfer (HAT) catalysis for rapid and selective reductive photoredox transformations in continuous flow. Eur. J. Org. Chem. 2019, 5807–5811 (2019).

    CAS  Google Scholar 

  48. 48.

    Matsubara, R. et al. UVA- and visible-light-mediated generation of carbon radicals from organochlorides using nonmetal photocatalyst. J. Org. Chem. 83, 9381–9390 (2018).

    CAS  PubMed  Google Scholar 

  49. 49.

    Qiao, Y., Yang, Q. & Schelter, E. J. Photoinduced miyaura borylation by a rare-earth-metal photoreductant: the hexachlorocerate(iii) anion. Angew. Chem. Int. Ed. 57, 10999–11003 (2018). The presented method uses cerium-based photocatalysts that enable simple and scalable photoinduced borylation of aryl bromides and chlorides with broad functional-group tolerance.

    CAS  Google Scholar 

  50. 50.

    Uyeda, C., Tan, Y., Fu, G. C. & Peters, J. C. A new family of nucleophiles for photoinduced, copper-catalyzed cross-couplings via single-electron transfer: reactions of thiols with aryl halides under mild conditions (0 °C). J. Am. Chem. Soc. 135, 9548–9552 (2013).

    CAS  PubMed  Google Scholar 

  51. 51.

    Ratani, T. S., Bachman, S., Fu, G. C. & Peters, J. C. Photoinduced, copper-catalyzed carbon–carbon bond formation with alkyl electrophiles: cyanation of unactivated secondary alkyl chlorides at room temperature. J. Am. Chem. Soc. 137, 13902–13907 (2015). This article describes a cheap and effective method for the synthesis of various nitriles from secondary alkyl chlorides under UVC light irradiation.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. 52.

    Zhang, X. et al. Synergistic photo-copper-catalyzed hydroxylation of (hetero)aryl halides with molecular oxygen. Org. Lett. 20, 708–711 (2018).

    CAS  PubMed  Google Scholar 

  53. 53.

    Tyagi, A., Yamamoto, A. & Yoshida, H. Photocatalytic Ullmann coupling of aryl halides by a novel blended catalyst consisting of a TiO2 photocatalyst and an Al2O3 supported Pd–Au bimetallic catalyst. Catal. Sci. Technol. 8, 6196–6203 (2018).

    CAS  Google Scholar 

  54. 54.

    Ghosh, I., Ghosh, T., Bardagi, J. I. & Konig, B. Reduction of aryl halides by consecutive visible light-induced electron transfer processes. Science 346, 725–728 (2014). Demonstrates the way to overcome the energetic limitation in visible light photoredox catalysis by using conPET.

    CAS  PubMed  Google Scholar 

  55. 55.

    Glaser, F., Kerzig, C. & Wenger, O. S. Multi-photon excitation in photoredox catalysis: concepts, applications, methods. Angew. Chem. Int. Ed. 59, 10266–10284 (2020).

    CAS  Google Scholar 

  56. 56.

    Ghosh, I. Excited radical anions and excited anions in visible light photoredox catalysis. Phys. Sci. Rev. 4, 20170185 (2019).

    Google Scholar 

  57. 57.

    He, J. et al. Photoactive metal–organic framework for the reduction of aryl halides by the synergistic effect of consecutive photoinduced electron-transfer and hydrogen-atom-transfer processes. ACS Appl. Mater. Interfaces 12, 2199–2206 (2020).

    CAS  PubMed  Google Scholar 

  58. 58.

    Graml, A., Ghosh, I. & König, B. Synthesis of arylated nucleobases by visible light photoredox catalysis. J. Org. Chem. 82, 3552–3560 (2017).

    CAS  PubMed  Google Scholar 

  59. 59.

    Tang, Z. et al. Cercosporin-bioinspired photoreductive activation of aryl halides under mild conditions. J. Catal. 380, 1–8 (2019).

    CAS  Google Scholar 

  60. 60.

    Meyer, A. U., Slanina, T., Heckel, A. & König, B. Lanthanide ions coupled with photoinduced electron transfer generate strong reduction potentials from visible light. Chem. Eur. J. 23, 7900–7904 (2017).

    CAS  PubMed  Google Scholar 

  61. 61.

    Giedyk, M. et al. Photocatalytic activation of alkyl chlorides by assembly-promoted single electron transfer in microheterogeneous solutions. Nat. Catal. 3, 40–47 (2019).

    Google Scholar 

  62. 62.

    Kerzig, C. & Goez, M. Combining energy and electron transfer in a supramolecular environment for the “green” generation and utilization of hydrated electrons through photoredox catalysis. Chem. Sci. 7, 3862–3868 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. 63.

    Ghosh, I., Shaikh, R. S. & König, B. Sensitization-initiated electron transfer for photoredox catalysis. Angew. Chem. Int. Ed. 56, 8544–8549 (2017). Twocentre photoredox approach based on Ru(bpy)3Cl2 and polycyclic aromatic hydrocarbons enables the photocatalytic application of arenes that do not absorb visible light.

    CAS  Google Scholar 

  64. 64.

    Ghosh, I., Bardagi, J. I. & König, B. Reply to “Photoredox catalysis: the need to elucidate the photochemical mechanism”. Angew. Chem. Int. Ed. 56, 12822–12824 (2017).

    CAS  Google Scholar 

  65. 65.

    Marchini, M., Bergamini, G., Cozzi, P. G., Ceroni, P. & Balzani, V. Photoredox catalysis: the need to elucidate the photochemical mechanism. Angew. Chem. Int. Ed. 56, 12820–12821 (2017).

    CAS  Google Scholar 

  66. 66.

    Kim, H., Kim, H., Lambert, T. H. & Lin, S. Reductive electrophotocatalysis: merging electricity and light to achieve extreme reduction potentials. J. Am. Chem. Soc. 142, 2087–2092 (2020). Electrophotocatalytically generated excited radical anions activate substrates with very negative reduction potential.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. 67.

    Cowper, N. G. W., Chernowsky, C. P., Williams, O. P. & Wickens, Z. K. Potent reductants via electron-primed photoredox catalysis: unlocking aryl chlorides for radical coupling. J. Am. Chem. Soc. 142, 2093–2099 (2020).

    CAS  PubMed  Google Scholar 

  68. 68.

    Wooster, C. B. & Godfrey, K. L. Mechanism of the reduction of unsaturated compounds with alkali metals and water. J. Am. Chem. Soc. 59, 596–597 (1937).

    CAS  Google Scholar 

  69. 69.

    Ou, H., Tang, C., Chen, X., Zhou, M. & Wang, X. Solvated electrons for photochemistry syntheses using conjugated carbon nitride polymers. ACS Catal. 9, 2949–2955 (2019).

    CAS  Google Scholar 

  70. 70.

    Buxton, G. V., Greenstock, C. L., Helman, W. P. & Ross, A. B. Critical review of rate constants for reactions of hydrated electrons, hydrogen atoms and hydroxyl radicals (OH/O in aqueous solution. J. Phys. Chem. Ref. Data 17, 513–886 (1988).

    CAS  Google Scholar 

  71. 71.

    Goez, M., Kerzig, C. & Naumann, R. An “all-green” catalytic cycle of aqueous photoionization. Angew. Chem. Int. Ed. 53, 9914–9916 (2014).

    CAS  Google Scholar 

  72. 72.

    Naumann, R., Kerzig, C. & Goez, M. Laboratory-scale photoredox catalysis using hydrated electrons sustainably generated with a single green laser. Chem. Sci. 8, 7510–7520 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. 73.

    Naumann, R., Lehmann, F. & Goez, M. Generating Hydrated Electrons for Chemical Syntheses by Using a Green Light-Emitting Diode (LED). Angew. Chem. Int. Ed. 57, 1078–1081 (2018).

    CAS  Google Scholar 

  74. 74.

    Naumann, R. & Goez, M. A green-LED driven source of hydrated electrons characterized from microseconds to hours and applied to cross couplings. Chem. Eur. J. 24, 9833–9840 (2018).

    CAS  PubMed  Google Scholar 

  75. 75.

    Kohlmann, T., Kerzig, C. & Goez, M. Laser‐induced Wurtz‐type syntheses with a metal‐free photoredox catalytic source of hydrated electrons. Chem. Eur. J. 25, 9991–9996 (2019).

    CAS  PubMed  Google Scholar 

  76. 76.

    Naumann, R. & Goez, M. First micelle-free photoredox catalytic access to hydrated electrons for syntheses and remediations with a visible LED or even sunlight. Chem. Eur. J. 24, 17557–17567 (2018).

    CAS  PubMed  Google Scholar 

  77. 77.

    Kerzig, C., Guo, X. & Wenger, O. S. Unexpected hydrated electron source for preparative visible-light driven photoredox catalysis. J. Am. Chem. Soc. 141, 2122–2127 (2019). This article describes the catalytic generation of hydrated electrons under mild conditions and their application in challenging reduction reactions in water.

    CAS  PubMed  Google Scholar 

  78. 78.

    Kerzig, C. & Wenger, O. S. Reactivity control of a photocatalytic system by changing the light intensity. Chem. Sci. 10, 11023–11029 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. 79.

    Kerzig, C. & Wenger, O. S. Sensitized triplet–triplet annihilation upconversion in water and its application to photochemical transformations. Chem. Sci. 9, 6670–6678 (2018). Sensitized triplet–triplet annihilation enables the activation of C–Cl bond in a homogeneous aqueous environment.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. 80.

    Shimakoshi, H., Tokunaga, M., Baba, T. & Hisaeda, Y. Photochemical dechlorination of DDT catalyzed by a hydrophobic vitamin B12 and a photosensitizer under irradiation with visible light. Chem. Commun. 16, 1806–1807 (2004).

    Google Scholar 

  81. 81.

    Tahara, K. & Hisaeda, Y. Eco-friendly molecular transformations catalyzed by a vitamin B12 derivative with a visible-light-driven system. Green. Chem. 13, 558–561 (2011).

    CAS  Google Scholar 

  82. 82.

    Tian, H. et al. Photocatalytic function of the B12 complex with the cyclometalated iridium(III) complex as a photosensitizer under visible light irradiation. Dalton Trans. 47, 675–683 (2018).

    CAS  PubMed  Google Scholar 

  83. 83.

    Shimakoshi, H. & Hisaeda, Y. Oxygen-controlled catalysis by vitamin B12-TiO2: formation of esters and amides from trichlorinated organic compounds by photoirradiation. Angew. Chem. Int. Ed. 54, 15439–15443 (2015). Trichlorinated organic compounds can be selectively transformed into fine chemicals thanks to oxygen-switchable B12-TiO2 catalyst.

    CAS  Google Scholar 

  84. 84.

    Tian, H., Shimakoshi, H., Ono, T. & Hisaeda, Y. Visible light‐driven, one‐pot amide synthesis catalyzed by the B12 model complex under aerobic conditions. ChemPlusChem 84, 237–240 (2019).

    CAS  PubMed  Google Scholar 

  85. 85.

    Shichijo, K., Fujitsuka, M., Hisaeda, Y. & Shimakoshi, H. Visible light-driven photocatalytic duet reaction catalyzed by the B12-rhodium-titanium oxide hybrid catalyst. J. Organomet. Chem. 907, 121058 (2020).

    CAS  Google Scholar 

  86. 86.

    Chen, L. et al. Visible light-driven cross-coupling reactions of alkyl halides with phenylacetylene derivatives for C(sp3)–C(sp) bond formation catalyzed by a B12 complex. Chem. Commun. 55, 13070–13073 (2019).

    CAS  Google Scholar 

  87. 87.

    Chen, L., Hisaeda, Y. & Shimakoshi, H. Visible light‐driven, room temperature heck‐type reaction of alkyl halides with styrene derivatives catalyzed by B12 complex. Adv. Synth. Catal. 361, 2877–2884 (2019).

    CAS  Google Scholar 

  88. 88.

    Shields, B. J. & Doyle, A. G. Direct C(sp3)–H cross coupling enabled by catalytic generation of chlorine radicals. J. Am. Chem. Soc. 138, 12719–12722 (2016). This article describes a photocatalytic generation of chlorine radicals and their use in the arylation of C(sp3)–H bonds.

    CAS  PubMed  PubMed Central  Google Scholar 

  89. 89.

    Nielsen, M. K. et al. Mild, redox-neutral formylation of aryl chlorides through the photocatalytic generation of chlorine radicals. Angew. Chem. Int. Ed. 56, 7191–7194 (2017).

    CAS  Google Scholar 

  90. 90.

    Claros, M. et al. Reductive cyclization of unactivated alkyl chlorides with tethered alkenes under visible-light photoredox catalysis. Angew. Chem. Int. Ed. 58, 4869–4874 (2019).

    CAS  Google Scholar 

  91. 91.

    Park, B. Y., Pirnot, M. T. & Buchwald, S. L. Visible light-mediated (hetero)aryl amination using Ni(II) salts and photoredox catalysis in flow: a synthesis of tetracaine. J. Org. Chem. 85, 3234–3244 (2020).

    CAS  PubMed  Google Scholar 

  92. 92.

    Patel, N. R., Kelly, C. B., Jouffroy, M. & Molander, G. A. Engaging alkenyl halides with alkylsilicates via photoredox dual catalysis. Org. Lett. 18, 764–767 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. 93.

    Fan, P., Lan, Y., Zhang, C. & Wang, C. Nickel/photo-cocatalyzed asymmetric acyl-carbamoylation of alkenes. J. Am. Chem. Soc. 142, 2180–2186 (2020).

    CAS  PubMed  Google Scholar 

  94. 94.

    Amani, J., Sodagar, E. & Molander, G. A. Visible light photoredox cross-coupling of acyl chlorides with potassium alkoxymethyltrifluoroborates: synthesis of α-alkoxyketones. Org. Lett. 18, 732–735 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. 95.

    Levernier, E. et al. Cross coupling of alkylsilicates with acyl chlorides via photoredox/nickel dual catalysis: a new synthesis method for ketones. Org. Chem. Front. 6, 1378–1382 (2019).

    CAS  Google Scholar 

  96. 96.

    Buzzetti, L., Prieto, A., Roy, S. R. & Melchiorre, P. Radical-based C−C bond-forming processes enabled by the photoexcitation of 4-alkyl-1,4-dihydropyridines. Angew. Chem. Int. Ed. 56, 15039–15043 (2017).

    CAS  Google Scholar 

  97. 97.

    Su, Y., Zhang, L. & Jiao, N. Utilization of natural sunlight and air in the aerobic oxidation of benzyl halides. Org. Lett. 13, 2168–2171 (2011).

    CAS  PubMed  Google Scholar 

  98. 98.

    Mazzarella, D., Magagnano, G., Schweitzer-Chaput, B. & Melchiorre, P. Photochemical organocatalytic borylation of alkyl chlorides, bromides, and sulfonates. ACS Catal. 9, 5876–5880 (2019).

    CAS  Google Scholar 

  99. 99.

    Barham, J. P. et al. KOtBu: A privileged reagent for electron transfer reactions? J. Am. Chem. Soc. 138, 7402–7410 (2016).

    CAS  PubMed  Google Scholar 

  100. 100.

    Emery, K., Young, A., Arokianathar, J., Tuttle, T. & Murphy, J. KOtBu as a single electron donor? revisiting the halogenation of alkanes with CBr4 and CCl4. Molecules 23, 1055 (2018).

    PubMed Central  Google Scholar 

  101. 101.

    Cheng, Y., Gu, X. & Li, P. Visible-light photoredox in homolytic aromatic substitution: direct arylation of arenes with aryl halides. Org. Lett. 15, 2664–2667 (2013).

    CAS  PubMed  Google Scholar 

  102. 102.

    Zhang, L. & Jiao, L. Visible-light-induced organocatalytic borylation of aryl chlorides. J. Am. Chem. Soc. 141, 9124–9128 (2019).

    PubMed  Google Scholar 

  103. 103.

    Xu, Z. et al. Visible light photoredox catalyzed biaryl synthesis using nitrogen heterocycles as promoter. ACS Catal. 5, 45–50 (2015).

    CAS  Google Scholar 

  104. 104.

    Kainz, Q. M. et al. Asymmetric copper-catalyzed C-N cross-couplings induced by visible light. Science 351, 681–684 (2016). The authors describe a visible-light-driven, enantioconvergent C–N bond-forming reaction of tertiary alkyl chlorides catalysed by copper.

    CAS  PubMed  PubMed Central  Google Scholar 

  105. 105.

    Zhou, Z.-Z., Zhao, J.-H., Gou, X.-Y., Chen, X.-M. & Liang, Y.-M. Visible-light-mediated hydrodehalogenation and Br/D exchange of inactivated aryl and alkyl halides with a palladium complex. Org. Chem. Front. 6, 1649–1654 (2019).

    CAS  Google Scholar 

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We gratefully acknowledge funding from the National Science Centre, Poland (SONATA 2018/31/D/ST5/00306).

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M.G. designed the work and had a major contribution to researching data, writing and editing the manuscript. M.C.-C. and J.S. contributed equally to the discussion of content, preparation of figures and writing.

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Correspondence to Maciej Giedyk.

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Cybularczyk-Cecotka, M., Szczepanik, J. & Giedyk, M. Photocatalytic strategies for the activation of organic chlorides. Nat Catal 3, 872–886 (2020).

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