A Decade of Electrochemical Dehydrogenative C,C-Coupling of Aryls

CONSPECTUS: The importance of sustainable and green synthetic protocols for the synthesis of fine chemicals has rapidly increased during the last decades in an effort to reduce the use of fossil fuels and other finite resources. The replacement of common reagents by electricity provides a cost- and atom-efficient, environmentally friendly, and inherently safe access to novel synthetic routes. The selective formation of carbon carbon bonds between two distinct substrates is a crucial tool in organic chemistry. This fundamental transformation enables access to a broad variety of complex molecular architectures. In particular, the aryl-aryl bond formation has high significance for the preparation of organic materials, drugs, and natural products. Besides well-known and well-established reductive- and oxidative-reagent-mediated or transition-metal-catalyzed coupling reactions, novel synthetic protocols have arisen, which require fewer steps than conventional synthetic approaches. Electroorganic conversions can be categorized according to the nature of the electron transfer processes occurring. Direct transformations at inert electrode materials are environmentally benign and cost-effective, whereas catalytic processes at active electrodes and mediated electrosynthesis using an additional soluble reagent can have beneficial properties in terms of selectivity and reactivity. In general, these conversions require challenging optimization of the reaction parameters and the appropriate cell design. Galvanostatic reactions enable fast conversions with a rather simple setup, whereas potentiostatic electrolysis may enhance selectivity. This Account discusses the development of seminal carbon-carbon bond formations over the past two decades, focusing on phenols leading to precursors for ligands in, e.g., hydroformylation reaction. A key element in the success of these electrochemical transformations is the application of electrochemically inert, non-nucleophilic, highly fluorinated alcohols such as 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), which exhibit a large potential window for transformations and enable selective cross-coupling reactions. This selectivity is based on the capability of HFIP to stabilize organic radicals. Inert, carbon-based and metal-free electrode materials like graphite or boron-doped diamond (BDD) open up novel electroorganic pathways. Furthermore, novel active electrode materials have been developed to enable intra- and intermolecular dehydrogenative coupling reactions of electron-rich aryls. The application of 2,2'-biphenol derivatives as ligand components for catalysts requires reactions to be carried out on larger scale. In order to achieve this, continuous flow transformations have been established to overcome the drawbacks of heat transfer, overconversion, and conductivity. Modular cell designs enable the transfer of a broad variety of electroorganic conversions into continuous processes. Recent results demonstrate the application of organic electrochemistry to natural product synthesis of the pharmaceutically relevant opiate alkaloids (-)-the baine or (-)-oxycodone.