Organic Electrochemistry


In electroorganic synthesis, electrons are applied for oxidation or reduction of organic compounds instead of expensive conventionally used reagents.[1] Electrochemical transformations avoid reagent waste leading to a high atom economy and outstanding sustainability, when electricity, generated from renewable energies, is applied.[2] Additionally, remarkable selectivity and reactivity can be observed in electrochemical conversions.[3,4] All these aspects ensure that electrosynthesis is a highly desired technique in modern organic processes.

Nevertheless, organic electrosynthesis often requires challenging optimization of reaction conditions. Therefore, our efforts usually start with screening cell array on a microscale and continue with optimization on the preparative level. For highly relevant targets we already optimized reaction conditions onto molar scales. Among many other parameters, appropriate cell geometry, electrolyte, and electrodes are the key to success. Hence, we are involved in the development and establishment of innovative electrode materials and cell designs.[5,6] Novel additives, mediators and supporting electrolytes allow further advancement. In-house electroanalytical characterization (cyclic voltammetry, ion chromatography, and conductivity measurements) allows early evaluation and mechanistic rationale.

[1] S. R. Waldvogel, Beilstein J. Org. Chem. 2015, 11, 949–950. [DOI: 10.3762/bjoc.11.105] [2] S. R. Waldvogel, B. Janza, Angew. Chem. Int. Ed. 2014, 53, 7122–7123. [DOI: 10.1002/anie.201405082] [3] S. R. Waldvogel, S. Möhle, Angew. Chem. Int. Ed. 2015, 54, 6398–6399. [DOI: 10.1002/anie.201502638] [4] S. R. Waldvogel, M. Selt, Angew. Chem. Int. Ed. 2016, 55, 12578–12580. [DOI: 10.1002/anie.201606727] [5] C. Gütz, B. Klöckner, S. R. Waldvogel, Org. Process Res. Dev. 2016, 20, 26–32. [DOI: 10.1021/acs.oprd.5b00377] [6] C. Gütz, A. Stenglein, S. R. Waldvogel, Org. Process Res. Dev. 2017, published online.


Some examples of novel electroorganic transformations

  • Metal- and reagent-free oxidative coupling of phenols and arenes

Selective formation of carbon-carbon bonds among two distinct substrates is of high interest in modern organic chemistry. Therefore, C,C cross-coupling reactions are essential chemical transformations in a large variety of disciplines like biochemistry, material and pharmaceutical sciences. Especially, biaryls play a highly important role in natural products and modern catalytic systems. The direct C,H arylation for the construction of such molecules represents a modern pathway to these substances. Particularly electrochemical C,H arylation offers the possibility to short cut multiple synthetic steps, avoid harsh reaction conditions, excess of stoichiometric oxidizers and transition metal catalysts. Therefore, the anodic cross-coupling represents a green and atom economic alternative to conventional cross-coupling reactions.[7]

We developed an innovative protocol for the direct electrochemical cross-coupling using carbon based electrodes like boron-doped diamond (BDD), glassy carbon and graphite. In particluar, BDD is a very appealing and innovative electrode material that opens up novel synthetic pathways.[8] Key to this successful transformation is the use of non-nucleophilic fluorinated alcohols such as 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP). Solvation by this unique solvent and therefore stabilization of reactive intermediates and the coupling partners offers the possibility to carry out aryl-aryl cross-coupling reactions in a selective manner and high yields.[9] We were able to develop efficient protocols for the direct synthesis of non-symmetric biphenols,[10] partially protected non-symmetric biphenols,[11]m-terphenyl-2,2’’-diols[12] and non-symmetric 2,2’-diaminobiaryls.[13]

[7] B. Elsler, D. Schollmeyer, K. M. Dyballa, R. Franke, S. R. Waldvogel, Angew. Chem. Int. Ed.2014, 53, 5210–5213. [DOI: 10.1002/anie.201400627] [8] A. Kirste, B. Elsler, G. Schnakenburg, S. R. Waldvogel, J. Am. Chem. Soc.2012, 134, 3571–3576. [DOI: 10.1021/ja211005g] [9] B. Elsler, A. Wiebe, D. Schollmeyer, K. M. Dyballa, R. Franke, S. R. Waldvogel, Chem. Eur. J.2015, 21, 12321–12325. [DOI: 10.1002/chem.201501604] [10] B. Riehl, K. Dyballa, R. Franke, S. Waldvogel, Synthesis2016, 49, 252–259. [DOI: 10.1055/s-0036-1588610] [11] A. Wiebe, D. Schollmeyer, K. M. Dyballa, R. Franke, S. R. Waldvogel, Angew. Chem. Int. Ed.2016, 55, 11801–11805. [DOI: 10.1002/anie.20160432] [12] S. Lips, A. Wiebe, B. Elsler, D. Schollmeyer, K. M. Dyballa, R. Franke, S. R. Waldvogel, Angew. Chem. Int. Ed.2016, 55, 10872–10876. [DOI: 10.1002/anie.201605865] [13] L. Schulz, M. Enders, B. Elsler, D. Schollmeyer, K. M. Dyballa, R. Franke, S. R. Waldvogel, Angew. Chem. Int. Ed.2017, 56, 4877–4881. [DOI: 10.1002/anie.201612613]


  • N,N-bond formation for preparation of pyrazolidine-3,5-diones

The electrochemical oxidation of malonic acid dianilides to pyrazolidines-3,5-diones is an elegant and sustainable way to build up N,N-bonds. In classic organic synthesis, N,N-moieties are installed by condensation using hydrazine building blocks. However, most of such N,N’-diaryl hydrazines are toxic and require an upstream preparation due to their low availability. In contrast, with our electrochemical approach, the use of readily accessible dianilides as precursors circumvents this problem and led to the desired pyrozolidine-3,5-dions, which are applied as active agent for rheumatism treatment.[14] If no N,N-bond formation is possible this method can be used for benzoxazole synthesis.[15]

[14] T. Gieshoff, D. Schollmeyer, S. R. Waldvogel, Angew. Chem. Int. Ed. 2016, 55, 9437–9440. [DOI: 10.1002/anie.201603899] [15] T. Gieshoff, A. Kehl, D. Schollmeyer, K. D. Moeller, S. R. Waldvogel, Chem. Commun. 2017, 53, 2974–2977. [DOI: 10.1039/C7CC00927E]


  • Domino-oxidation-reduction sequence for nitrile synthesis

Nitriles are important building blocks in organic synthesis, because of their ability to be transferred in many other functional groups. A common strategy for their preparation is the dehydration of benzaldoximes by applying e.g. P4O10 or thionyl chloride under harsh reaction conditions. A significantly milder possibility is the electrochemical oxidation of oximes to nitrile-N-oxides at the anode followed directly by a reduction to the desired nitrile at the cathode in an undivided cell.[16] This method tolerates a wide range of functional groups, provides the nitrile in good yield and avoids large amounts of reagent waste.

[16] M. F. Hartmer, S. R. Waldvogel, Chem. Commun. 2015, 51, 16346–16348. [DOI: 10.1039/C5CC06437F]


Establishment of novel electrode material

For some transformations, cathode electrode materials possess major drawbacks making electrosynthesis as an alternative approach unattractive. In the case of the twofold dehalogenation of 1,1-dibromo-cyclopropanes to synthesize pharmaceutically relevant building blocks, cathodic corrosion occurs. Common lead electrodes were not stable under applied reaction conditions leading to contamination of the product with large amounts of lead. To avoid such problems, we established leaded bronze as novel electrode material for electro-organic transformations.[17] This material combines the outstanding reactivity of lead electrodes with a significantly increased chemical and mechanical stability.[18] Thereby, the twofold dehalogenation of a variety of substrates could be realized without contamination of the product with lead, copper or tin.

[17] C. Gütz, M. Selt, M. Bänziger, C. Bucher, C. Römelt, N. Hecken, F. Gallou, T. R. Galvão, S. R. Waldvogel, Chem. Eur. J. 2015, 21, 13878–13882. [DOI: 10.1002/chem.201502064] [18] V. Grimaudo, P. Moreno-Garcia, A. Riedo, S. Meyer, M. Tulej, M. B. Neuland, M. Mohos, C. Gütz, S. R. Waldvogel, P. Wurz, P. Broekmann, Anal. Chem. 2017, 89, 1632–1641. [DOI: 10.1021/acs.analchem.6b03738]


Electrosynthesis in Flow

For large scale electrosynthesis, batch cells are less attractive since heat transfer, over-conversion, conductivity and the amount of supporting electrolyte become problematic. To avoid these issues and to realize electrochemical transformations on a technical scale, application of flow systems is advantageous. In particular, for establishing electrosynthesis in R&D and the chemical industry, the development of technically applicable flow processes are highly important. Recently, we developed a highly modular flow cell system for the transfer of nearly all electrochemical processes into continuous methods and to identify all relevant process parameters time efficiently. To save starting material during optimization the size is limited to mg-g scale per cell per hour. Nevertheless, a straightforward scale-up is possible to produce multi-molar amount of product. First, examples of application of our flow cell are dehalogenation,[19] domino-oxidation-reduction sequences and the synthesis of isoxazoles via electrochemical generated nitrile-N-oxides.[20]

[19] C. Gütz, M. Bänziger, C. Bucher, T. R. Galvão, S. R. Waldvogel, Org. Process Res. Dev. 2015, 19, 1428–1433. [DOI: 10.1021/acs.oprd.5b00272] [20] C. Gütz, A. Stenglein, S. R. Waldvogel, Org. Process Res. Dev. 2017, in revision.


Novel electrolyte system for electrochemical double layer capacitors

The storable energy in electrochemical double layer capacitors (supercaps) depends aside from the capacity on the voltage attainable on charge, which is limited by the decomposition voltage of the electrolyte. As the energy increases with the square of the charging voltage, the development of this energy storage system is focused on an enhancement of the potential window of the supporting electrolyte, which makes stable solvents and conducting salts necessary.

A novel electrolyte system based on borates bearing biphenoxy ligands evolved in our lab was applied in supercap test cells.[21,22] A clear trend towards higher anodic stability was shown by introduction of a chelating bridge as well as by installation of fluorine moieties in the ligand sphere, which was shown by cyclic voltammetry. While the biphenoxyborate salts meet the current electrochemical standard for energy storage applications, their chemical and thermal stability is superior to the standard electrolytes, which is particularly important for safety reasons.

[21] S.R. Waldvogel, I.M. Malkowsky, U. Griesbach, H. Pütter, A. Fischer, M. Hahn, R. Kötz, Electrochem. Commun. 2009, 11, 1237–1241. [DOI: 10.1016/j.elecom.2009.04.009] [22] R. Francke, D. Cericola, R. Kötz, G. Schnakenburg, S. R. Waldvogel, Chem. Eur. J. 2011, 17, 3082–3085. [DOI: 10.1016/j.electacta.2011.12.050]