Organic electrosynthesis is an old and rich discipline. By exploiting the cheapest and greenest source of electrons, electricity itself, electrolysis has been shown to be a powerful method to perform redox reactions under mild, safe and green conditions. The field is in the midst of a renaissance and there is little doubt that it will become one of the classic methods to activate small organic molecules in the very near future. Nevertheless, electrosynthesis can be rather daunting for a beginner. In this Review, we will guide synthetic chemists through their first organic and organometallic electrosyntheses by reviewing the essential aspects of the field and by sharing practical tips. We will also cover the fundamentals of electroanalytical techniques, such as cyclic voltammetry, since they are powerful methods to investigate mechanisms. Finally, these concepts will be examined in practice through three case studies.
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Faraday, M. Experimental researches in electricity. Philos. Trans. R. Soc. Lond. 122, 125–162 (1832).
Kolbe, H. Untersuchungen über die Elektrolyse organischer Verbindungen. Justus Liebigs Ann. Chem. 69, 257–294 (1849).
Yan, M., Kawamata, Y. & Baran, P. S. Synthetic organic electrochemical methods since 2000: on the verge of a renaissance. Chem. Rev. 117, 13230–13319 (2017).
Hammerich, O. & Speiser, B. Organic Electrochemistry: Revised and Expanded (CRC Press, 2015).
Bard, A. J. & Faulkner, L. R. Electrochemical Methods: Fundamentals and Applications (Wiley, 2000).
Elgrishi, N. et al. A practical beginner’s guide to cyclic voltammetry. J. Chem. Educ. 95, 197–206 (2018).
Sawyer, D. T., Sobkowiak, A. & Roberts, J. L. Electrochemistry for Chemists (Wiley, 1995).
Kissinger, P. & Heineman, W. R. Laboratory Techniques in Electroanalytical Chemistry, Revised and Expanded 2nd edn (Taylor & Francis, 1996).
Paddon, C. A., Silvester, D. S., Bhatti, F. L., Donohoe, T. J. & Compton, R. G. Coulometry on the voltammetric timescale: Microdisk potential-step chronoamperometry in aprotic solvents reliably measures the number of electrons transferred in an electrode process simultaneously with the diffusion coefficients of the electroactive spec. Electroanalysis 19, 11–22 (2007).
Amatore, C. et al. Absolute determination of electron consumption in transient or steady state electrochemical techniques. J. Electroanal. Chem. 288, 45–63 (1990).
Nicholson, R. S. & Shain, I. Theory of stationary electrode polarography: single scan and cyclic methods applied to reversible, irreversible, and kinetic systems. Anal. Chem. 36, 706–723 (1964).
Britz, D. & Strutwolf, J. Digital Simulation in Electrochemistry (Springer, 2018).
Leech, M. C., Garcia, A. D., Petti, A., Dobbs, A. P. & Lam, K. Organic electrosynthesis: from academia to industry. React. Chem. Eng. 5, 977–990 (2020).
Heard, D. M. & Lennox, A. J. J. Electrode materials in modern organic electrochemistry. Angew. Chem. Int. Ed. 59, 18866–18884 (2020).
Pletcher, D. & Walsh, F. C. Industrial Electrochemistry (Springer, 1993).
Colomer, I., Chamberlain, A. E. R., Haughey, M. B. & Donohoe, T. J. Hexafluoroisopropanol as a highly versatile solvent. Nat. Rev. Chem. 1, 0088 (2017).
McKee, R. H. & Gerapostolou, B. G. Electrolytic reduction of nitro compounds in concentrated aqueous salt solutions. Trans. Electrochem. Soc. 68, 329 (1935).
McKee, R. H. & Brockman, C. J. A new method for electro-organic reductions. Trans. Electrochem. Soc. 62, 203 (1932).
Eberson, L. & Helgée, B. Studies on electrolytic substitution reactions. IX. Anodic cyanation of aromatic ethers and amines in emulsions with the aid of phase transfer agents. Acta Chem. Scand. B 29, 451–456 (1975).
Eberson, L. & Helgée, B. Studies on eectrolytic substitution reactions. XII. Synthesis of 4-alkoxy-4′-cyanobiphenyls — a class of liquid crystals — via anodic cyanation of 4,4′-dialkoxybiphenyls in emulsion systems. Acta Chem. Scand. B 31, 813–817 (1977).
Eberson, L. & Helgée, B. Studies on electrolytic substitution reactions. XIII. Anodic acyloxylation of aromatic substrates in emulsion systems with the aid of phase transfer agents. Acta Chem. Scand. B 32, 157–161 (1978).
Teherani, T., Itaya, K. & Bard, A. J. An electrochemical study of solvated electrons in liquid ammonia. Nouv. J. Chim. 2, 481–487 (1978).
Liu, T. et al. New insights into the effect of pH on the mechanism of ofloxacin electrochemical detection in aqueous solution. Phys. Chem. Chem. Phys. 21, 16282–16287 (2019).
Izutsu, K. Electrochemistry in Nonaqueous Solutions (Wiley, 2011).
Kathiresan, M. & Velayutham, D. Ionic liquids as an electrolyte for the electro synthesis of organic compounds. Chem. Commun. 51, 17499–17516 (2015).
Torriero, A. A. J. Electrochemistry in Ionic Liquids (Springer, 2015).
Comminges, C., Barhdadi, R., Laurent, M. & Troupel, M. Determination of viscosity, ionic conductivity, and diffusion coefficients in some binary systems: ionic liquids + molecular solvents. J. Chem. Eng. Data 51, 680–685 (2006).
Schäfer, H. J. Recent contributions of Kolbe electrolysis to organic synthesis. Top. Curr. Chem. 152, 91–151 (1990).
Tanaka, H., Kuroboshi, M. & Torii, S. in Organic Electrochemistry 5th edn 1267–1307 (CRC Press, 2015).
Moeller, K. D. Synthetic applications of anodic electrochemistry. Tetrahedron 56, 9527–9554 (2000).
Schäfer, H. J. Recent synthetic applications of the Kolbe electrolysis. Chem. Phys. Lipids 24, 321–333 (1979).
Wiebe, A. et al. Electrifying organic synthesis. Angew. Chem. Int. Ed. 57, 5594–5619 (2018).
Hayrapetyan, D., Shkepu, V., Seilkhanov, O. T., Zhanabil, Z. & Lam, K. Electrochemical synthesis of phthalides via anodic activation of aromatic carboxylic acids. Chem. Commun. 53, 8451–8454 (2017).
Dickinson, T. & Wynne-Jones, W. F. K. Mechanism of Kolbe’s electrosynthesis. Part 3. — Theoretical discussion. Trans. Faraday Soc. 58, 400–404 (1962).
Schäfer, H. J. Anodic and cathodic CC-bond formation. Angew. Chem. Int. Ed. Engl. 20, 911–934 (1981).
Nuding, G., Vögtle, F., Danielmeier, K. & Steckhan, E. Rodlike molecules by Kolbe electrolysis. Synthesis 1996, 71–76 (1996).
Seebach, D. & Renaud, P. Chirale Synthesebausteine durch Kolbe-Elektrolyse enantiomerenreiner β-Hydroxy-carbonsäurederivate. (R)- und (S)-Methyl-sowie (R)-Trifluormethyl-γ-butyrolactone und -δ-valerolactone. Helv. Chim. Acta 68, 2342–2349 (1985).
Stang, C. & Harnisch, F. The dilemma of supporting electrolytes for electroorganic synthesis: a case study on Kolbe electrolysis. ChemSusChem 9, 50–60 (2016).
Matzeit, A. et al. Radical tandem cyclizations by anodic decarboxylation of carboxylic acids. Synthesis 11, 1432–1444 (1995).
Bestmann, H. J. et al. Pheromone, 57. Synthese Methylen-unterbrochener Lepidopteren-Polyenpheromone und Strukturanaloger. Acetylensynthese, Wittig-Reaktion und Kolbe-Elektrolyse. Liebigs Ann. Chem. 1987, 417–422 (1987).
Rossi, R., Carpita, A. & Chini, M. Synthesis of the two enantiomers of the sex pheromone of Diabrotica Undecimpunct at a Howardi and of chiral precursors of other pheromones starting from enantiomerically pure methyl hydrogen (R)-3-methylglutarate. Tetrahedron 41, 627–633 (1985).
Jensen-Korte, U. & Schäfer, H. -J. Pheromone, 7. Kolbe-Synthese von 29-tert-Butyldimethylsilyloxy-3,11-dimethyl-1-nonacosen, einer Schlüsselverbindung zur Darstellung eines optisch aktiven Sexuallockstoffes der Deutschen Hausschabe. Liebigs Ann. Chem. 1982, 1532–1542 (1982).
Seebach, D. Preparation of enantiomerically pure compounds employing anodic oxidations of carboxylic acids – A late review of research done in the 1980ies. Helv. Chim. Acta 102, e1900072 (2019).
Brecht-forster, A., Fitremann, J. & Renaud, P. Synthesis of (±)-nephromopsinic, (−)-phaseolinic, and (−)-dihydropertusaric acids. Helv. Chim. Acta 85, 3965–3974 (2002).
Becking, L. & Schäfer, H. J. Pyrrolidines by intramolecular addition of Kolbe radicals generated from β-allylaminoalkanoates. Tetrahedron Lett. 29, 2797–2800 (1988).
Lebreux, F., Buzzo, F. & Marko, I. E. Studies in the oxidation of carboxylic acids: new twists for an old reaction. Synthesis of various cyclic systems and substituted orthoesters. ECS Trans. 13, 1 (2008).
Lebreux, F., Buzzo, F. & Markó, I. E. Synthesis of five- and six-membered-ring compounds by environmentally friendly radical cyclizations using Kolbe electrolysis. Synlett 2008, 2815–2820 (2008).
Hofer, H. & Moest, M. Ueber die Bildung von Alkoholen bei der Elektrolyse fettsaurer Salze. Justus Liebigs Ann. Chem. 323, 284–323 (1902).
Yoshikawa, M., Wang, H. K., Tosirisuk, V. & Kitagawa, I. Chemical modification of oleanene-oligoglycosides by means of anodic oxidation. Chem. Pharm. Bull. 30, 3057–3060 (1982).
Kitagawa, I., Kamigauchi, T., Ohmori, H. & Yoshikawa, M. Saponin and Sapogenol. XXIX. Selective cleavage of the glucuronide linkage in oligoglycosides by anodic oxidation. Chem. Pharm. Bull. 28, 3078–3086 (1980).
Pergola, F., Nucci, L., Pezzatini, G., Wei, H. & Guidelli, R. Direct electro-oxidation of d-gluconic acid to d-arabinose. Electrochim. Acta 39, 1415–1417 (1994).
Thomas, H. G. & Katzer, E. Acylale durch anodische oxydation von α-alkoxy-carbonsäuren. Tetrahedron Lett. 15, 887–888 (1974).
Stapley, J. A. & BeMiller, J. N. The Hofer–Moest decarboxylation of d-glucuronic acid and d-glucuronosides. Carbohydr. Res. 342, 610–613 (2007).
Torii, S., Okamoto, T. & Tanaka, H. Electrolytic decarboxylation reactions. I. Electrosynthesis of γ-substituted butyrolactones and γ-substituted α,β-butenolides from γ-substituted paraconic acids. J. Org. Chem. 39, 2486–2488 (1974).
Shono, T., Hayashi, J., Omoto, H. & Matsumura, Y. The migratory aptitude in the anodic oxidation of β-hydroxycarboxylic acids, and a new synthesis of di-muscone. Tetrahedron Lett. 18, 2667–2670 (1977).
Lin, D. Z. & Huang, J. M. Electrochemical N-formylation of amines via decarboxylation of glyoxylic acid. Org. Lett. 20, 2112–2115 (2018).
Schäfer, H. J., Harenbrock, M., Klocke, E., Plate, M. & Weiper-Idelmann, A. Electrolysis for the benign conversion of renewable feedstocks. Pure Appl. Chem. 79, 2047–2057 (2007).
Dos Santos, T. R., Harnisch, F., Nilges, P. & Schröder, U. Electrochemistry for biofuel generation: transformation of fatty acids and triglycerides to diesel-like olefin/ether mixtures and olefins. ChemSusChem 8, 886–893 (2015).
Meyers, J. et al. Electrochemical conversion of a bio-derivable hydroxy acid to a drop-in oxygenate diesel fuel. Energy Environ. Sci. 12, 2406–2411 (2019).
Holzhäuser, F. J. et al. Electrochemical cross-coupling of biogenic di-acids for sustainable fuel production. Green Chem. 21, 2334–2344 (2019).
Lam, K. & Geiger, W. E. Anodic oxidation of disulfides: detection and reactions of disulfide radical cations. J. Org. Chem. 78, 8020–8027 (2013).
Swarts, J. C., Nafady, A., Roudebush, J. H., Trupia, S. & Geiger, W. E. One-electron oxidation of ruthenocene: reactions of the ruthenocenium ion in gentle electrolyte media. Inorg. Chem. 48, 2156–2165 (2009).
The authors are grateful to the Engineering and Physical Sciences Research Council (grant EP/s017097/1 awarded to K.L. and M.C.L.) and the University of Greenwich for their financial support.
The authors declare no competing interests.
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An electronic instrument that controls the voltage difference between two electrodes.
- Supporting electrolyte
A chemical species that is not electroactive in the range of the applied potentials being studied, which is added to a solvent medium in order to increase its conductivity, ideally without affecting the electrochemical behaviour of the analyte.
The adhesion of a chemical substance (known as the adsorbate) onto a surface.
Alternatively a membrane or frit, a semipermeable material that allows the flow of ions between the anolyte and the catholyte compartments in a divided cell without mixing the two solutions.
The electrolyte in the presence of the cathode in an electrochemical cell.
The electrolyte in the presence of the anode in an electrochemical cell.
- Dielectric constant
A measure of the polarity of an organic solvent and its ability to insulate charge.
- Ohmic drop
Also known as IR drop, a potential drop caused by the inherent resistance of the solvent, which can cause shifts in peak potential, reduce observed currents and increase the separation between anodic and cathodic peaks.
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Leech, M.C., Lam, K. A practical guide to electrosynthesis. Nat Rev Chem 6, 275–286 (2022). https://doi.org/10.1038/s41570-022-00372-y
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