Electrocatalyzed Molecular Rearrangements

电催化分子重排

• 批准号: 427463148
• 负责人: Professor Dr. Robert Francke
• 金额: --
• 依托单位: Bereich Elektrochemie & Katalyse
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/427463148?language=en
• 关键词: Electrocatalyzed; Molecular; Rearrangements

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.

分子重排包括通过分子内亲核原位取代使芳环错位，从而可以用分子间方式更难以实现的连接取代容易形成的 Ar-Het 键。微笑重排和纽曼-夸特重排是此类反应的典型同类反应，经常用于有机分子的构建，以避免繁琐的合成弯路。然而，主要挑战之一是这些重排是通过富含能量的两性离子过渡态进行的，这导致了对恶劣条件的需求，即。 e.温度高达 300 °C 和/或碱性反应介质。另一个缺点是范围仅限于在芳环上具有吸电子部分的活化底物。该研究解决了这些问题，旨在开发一种温和的电化学替代方案，允许在室温下操作并扩大芳香族取代的范围。该研究概念基于我们最近开发的电化学方法，用于将 O-芳基硫代氨基甲酸酯重排为相应的 S-芳基硫代氨基甲酸酯（电催化纽曼-夸特重排，NKR）。该协议仅需要催化量的电荷和最简单的设备，即。 e.未分割的电池和恒电流条件。虽然热诱导 NKR 只能在 200 至 300 °C 的温度下工作，但我们的电催化版本可以在室温下顺利进行。我们的方法的另一个有趣的特点是，反应活性随着芳烃中电子含量的增加而提高，而传统 NKR 的趋势则相反。此外，我们已经证明，当在微流反应器中进行电解时，无需使用支持电解质即可在十克规模上实现几乎定量的产率。基于这些有希望的结果，我们建议进一步探索电催化分子重排。作为第一步，我们的目标是更好地了解电化学 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理研究，最终目标是能够预测特定底物的反应性。在完成机械工作之后，我们计划将电化学概念扩展到其他转化，例如微笑和查普曼重排，其中有效协议的开发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的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。