Metal- and Reagent-Free Anodic Dehydrogenative Coupling Reactions

The dehydrogenative cross-coupling is a hot topic of contemporary organic synthesis. The anodic cross-coupling reaction of aromatic substrates is established without necessity of leaving functionalities or mediating catalyst. Employment of electric current as terminal oxidant is reagent-free and consequently, avoids the generation of reagent waste since only electrons are flowing. The method can be conducted in an undivided cell, is suitable for scale-up and inherently safe. Therefore, it is highly attractive for a sustainable synthesis. The key for this electroorganic synthesis is the use of 1,1,1,3,3,3-hexafluoroisopropanol as electrolyte component. [1] The high hydrogen-bonding donor capability allows a decoupling of oxidation potential from the nucleophilicity. [2] This solvent effect can be controlled by the addition of methanol or water. [3] By this method we were able to make in almost exclusive selectivity ortho -meta coupled 2,3’-biphenols, [4] non-symmetric 2,2-biphenols, [5] and phenol-arene cross-coupling products. [6] References: [1] A. Kirste, M. Nieger, I. M. Malkowsky, F. Stecker, A. Fischer, S. R. Waldvogel, Ortho-selective Phenol coupling reaction by Anodic Treatment on Boron-doped Diamond electrode using Fluorinated Alcohols, Chem. Eur. J. 15 (2009) 2273. [2] B. Elsler, A. Wiebe, D. Schollmeyer, K. M. Dyballa, R. Franke, S. R. Waldvogel, Source of Selectivity in Oxidative Cross-Coupling of Aryls by Solvent Effect of 1,1,1,3,3,3-Hexafluoropropan-2-ol, Chem. – Eur. J. 21 (2015) 12321 [3] A. Kirste, B. Elsler, G. Schnakenburg, S. R. Waldvogel, Efficient anodic and direct phenol-arene C,C cross-coupling – the benign role of water or methanol, J. Am. Chem. Soc. 134 (2012) 3571. [4] A. Kirste, G. Schnakenburg, S. R. Waldvogel, Anodic Coupling of Guaiacol Derivatives on Boron-doped Diamond Electrodes, Org. Lett. 13 (2011) 3126. [5] B. Elsler, D. Schollmeyer, K. M. Dyballa, R. Franke, S. R. Waldvogel, Metal- and Reagent-Free Highly Selective Anodic Cross-Coupling Reaction of Phenols, Angew. Chem. Int. Ed. 53, (2014) 5210. [6] A. Kirste, G. Schnakenburg, F. Stecker, A. Fischer, S. R. Waldvogel, Anodic phenol arene cross-coupling reaction on boron-doped diamond electrodes, Angew. Chem. Int. Ed. 49 (2010) 971. Figure 1