International Collaboration in Chemistry: Catalytic Atom-Economical Aromatic Substitution via Radicals

本项目将以质子耦合电子转移(PCET)为基础，开发一种新的催化和原子经济的芳烃均解取代反应，作为芳构化和催化剂再生的关键步骤。PCET是许多生物催化体系和能量转换的关键步骤，但在催化有机合成中的应用还很少。我们希望挖掘这一巨大的潜力，以单电子步骤进行催化过程，而不是经典的方法以两个电子步骤进行。合成组(Gansäuer、有机合成和催化剂合成)和机械组(Flowers、计算和动力学研究)之间的密切合作将使我们能够确定对整个过程的效率至关重要的因素。这样，通过计算、动力学和合成研究之间的反馈循环，就可以合理地设计高效和稳定的催化剂的性质。这一反应对于合成许多具有潜在高生物活性的化合物具有重要意义，例如α-芳基丙酸和具有电子缺陷芳烃的化合物，这些化合物不容易通过经典的亲电取代反应获得。

In this project, a new catalytic and atom economical homolytic aromatic substitution reaction will be developed that is based on proton coupled electron transfer (PCET) as the key step for rearomatization and catalyst regeneration. PCET is a key-step in many biological catalytic systems and energy conversion but has only rarely been employed in catalytic organic synthesis. We wish to tap this large potential for catalysis proceeding in single electron steps rather than classical methods proceeding in two electron steps. The close collaboration between the synthetic (Gansäuer, organic synthesis and catalyst synthesis) and mechanistic group (Flowers, computational and kinetic studies) will allow an identification of the factors critical for the efficiency of the overall process. In this manner, the properties of an efficient and stable catalyst can be rationally designed through a feed-back loop between computational, kinetic, and synthetic investigations. The reaction to be developed is of relevance for the preparation of a number of compounds with potentially high biological activity, such as α-aryl propionic acids and compounds with electron deficient arenes that are not readily obtained via classical electrophilic aromatic substitutions.