过渡金属η6-配位催化的亲核芳香取代反应研究

亲核芳香取代反应是修饰芳香化合物的重要方法，在药物合成领域应用广泛。然而该方法面临着巨大的化学挑战：反应底物局限于高度缺电性的芳香环。化学家们利用过渡金属的拉电子效应，通过与芳香环π键的η6-配位作用来活化惰性的底物，能够克服底物局限性。但是该策略难以实现催化循环，通常依赖于使用当量的过渡金属η6-配合物，因而需要大量的昂贵金属以及额外的反应步骤。针对上述科学问题，本项目将以催化的亲核芳香取代反应为研究对象，拟通过研究催化剂配体-金属-芳香环在不同配位模式下三者的相互作用关系，辅助理论计算，在分子水平上认识η6-配位催化的本质规律，由此发展新型过渡金属催化剂，实现高效、普适性的亲核芳香取代催化反应。本项目的核心是开发新型配体，拟采用的设计思路是在传统的催化剂配体上引入功能性辅基，辅基在催化循环中通过与底物或金属“暂时”的相互作用来影响反应的历程。

Nucleophilic aromatic substitution (SNAr), an important method for modifying aromatics, has been widely used in pharmaceutical synthesis. Hitherto, there is still a fundamental challenge in this field: reaction substrates are limited to highly deficient aromatic rings. To overcome such challenge, chemists utilized transition-metals (TMs) to activate inert arenes through an interaction with the π-orbitals of aromatics. Due to the electron-withdrawing effect, SNAr reaction is promoted by TMs via such η6-coordination. However, this strategy, in general, relies on using a stoichiometric amount of TM η6-complexes, wasting a lot of costly metals. Moreover, additional steps are required to form the complex and remove the metal after the substitution. This project that focus on catalytic SNAr reactions is going to reveal interactions between ligands, TMs, and aromatic rings in different coordination modes. Assisted by theoretical calculations, we will try to disclose natures of η6-coordination catalysis, and develop new TM-catalysts to achieve highly efficient, catalytic SNAr reactions. The main part of this project is the development of new ligands, which feature a functional group on the skeleton of traditional catalysts. The catalytic cycle could be facilitated by a temporary interaction between such group and substrate or metal.