Electrocatalyzed Molecular Rearrangements

分子重排是由芳环的位错组成的，通过分子内亲核的ipso取代，可以用更难以在分子间实现的连接取代容易形成的Ar-Het键。smile和Newman-Kwart重排是这类反应的典型同系物，经常用于构建有机分子，以避免繁琐的合成弯路。然而，主要的挑战之一是，这些重排是通过能量丰富的两性离子过渡态进行的，这导致对苛刻条件的需求，即高达300°C的温度和/或碱性反应介质。另一个缺点是范围局限于在芳环上具有吸电子基团的活化底物。该研究考虑了这些问题，旨在开发一种温和的电化学替代品，它允许在室温下操作，并扩大了芳香取代的范围。研究概念是基于我们最近开发的电化学方法，将o -芳基硫氨基甲酸酯重排到相应的s -芳基硫氨基甲酸酯（电催化纽曼-克瓦特重排，NKR）。该方案只需要催化量的电荷和最简单的设备，即未分裂的电池和恒流条件。虽然热诱导的NKR只能在200到300°C的温度下工作，但我们的电催化版本在室温下可以顺利进行。我们的方法的另一个有趣的特点是，反应性随着富电子芳烃的增加而提高，而传统NKR的趋势则相反。此外，我们已经证明，当电解在微流反应器中进行时，几乎可以在十元尺度上实现定量产率，而无需使用辅助电解质。基于这些有希望的结果，我们提出了电催化分子重排的进一步探索。作为第一步，我们的目标是更好地理解电化学NKR，包括参与的中间体和过渡态，以及成功重排的先决条件。因此，我们计划使用循环伏安法，控制实验和量子化学计算进行彻底的机制研究，最终目标是能够预测特定底物的反应性。在机制工作之后，我们计划将电化学概念扩展到其他转换，如Smiles和Chapman重排，从而开发有效的协议和机制的研究都是重点。我们期望我们的研究将为各种类似电催化重排的发展奠定基础，并将提供与电化学，有机合成和工业化学相关的有用见解。

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.