Electrocatalyzed Molecular Rearrangements

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Molecular rearrangements consisting of a dislocation of an aromatic ring via intramolecular nucleophilic ipso substitution allow for the replacement of readily-formed Ar-Het bonds with connections that would be more difficult to realize in an intermolecular fashion. The Smiles and the Newman-Kwart rearrangements are typical congeners of this class of reactions and are frequently used in the construction of organic molecules in order to avoid tedious synthetic detours. One of the major challenges, however, is that these rearrangements proceed via energy-rich zwitterionic transition states, which leads to a demand for harsh conditions, i. e. temperatures up to 300 °C and/or alkaline reaction media. A further disadvantage is the restriction of the scope to activated substrates having electron withdrawing moieties on the aromatic ring. The research accounts for these issues and aims at the development of a mild electrochemical alternative, which allows for operation at room temperature and broadens the scope with respect to the aromatic substitution.The research concept is based on our recently developed electrochemical approach toward rearrangement of O-aryl thiocarbamates to the corresponding S-aryl thiocarbamates (electrocatalytic Newman-Kwart rearrangement, NKR). The protocol requires only catalytic amounts of electric charge and simplest equipment, i. e. an undivided cell and galvanostatic conditions. While the thermally induced NKR only works at temperatures between 200 and 300 °C, our electrocatalytic version proceeds smoothly at room temperature. Another interesting feature of our approach is that the reactivity improves with increasingly electron-rich arenes, whereas the trend is inverted for the conventional NKR. Furthermore, we have demonstrated that when the electrolysis is performed in a microflow reactor, almost quantitative yields can be achieved on the decagram scale without using supporting electrolyte.Based on these promising results, we propose a further exploration of electrocatalyzed molecular rearrangements. As a first step, we aim at a better understanding of the electrochemical NKR including the participating intermediates and transition states, as well as the preconditions for a successful rearrangement. We therefore plan a thorough mechanistic study using cyclic voltammetry, control experiments and quantum chemical calculations with the ultimate goal of being able to predict the reactivity for specific substrates. Following the mechanistic work, we plan to expand the electrochemical concept to other transformations such as the Smiles and the Chapman rearrangement, whereby both the development of efficient protocols and the investigation of the mechanisms are in the focus. We expect that our research will lay a foundation for the development of a variety of analogous electrocatalyzed rearrangements and will provide useful insights with relevance to electrochemistry, organic synthesis, and industrial chemistry.