Catalytic Reactions of Arenes via transient arene Ru Complexes

当通过配位与过渡金属结合时，芳香族化合物的反应性显著改变。在配位时，芳香族和苄基C H键变得更加酸性，并且环本身变得更加亲电。因此，配位芳烃在选定的反应中显示出改进的反应性。芳烃金属配合物的亲核芳族取代在20世纪90年代得到了特别好的开发，其中配位的金属片段取代了共价结合的吸电子基团。最近，该领域出现了某种复兴，几个研究小组（包括沃尔顿小组）报告了芳烃配合物的当代反应，包括CH C C和CH C CF 3转化。在这个由先正达部分资助的博士项目中，我们将探索几种新的工业相关的芳烃催化反应，这些反应具有原子效率，并允许芳香族化合物的后期官能化。第一个目标是亲核取代。含氟芳烃在农药和医药工业中是重要的基序。目前的电催化方法通常是亲电的或使用HF，这需要专门的设备。一个有吸引力的选择是使用可以与芳烃进行亲核加成的氟化物源。我们将研究芳烃的亲核取代，通过钌芳烃配合物进行。最终目标是产生在Ru中具有催化作用的反应。然而，该项目可以被分解为在开发完整的催化过程之前首先查看Ru的化学计量比。对于化学计量反应，活化[CpRu]+可以通过光解回收。我们将探索各种条件，包括溶剂效应和亲核氟化物的选择以优化反应。第二个目标将是开发一种原子效率的异喹啉合成。杂环化合物，如异喹啉，是重要的药物靶标。一般来说，目前的合成方法是原子效率低的。使用我们的催化芳烃活化方法，我们将尝试合成异喹啉与100%的原子效率使用催化钌。与上面的钌反应一样，最初我们将在Ru中进行化学计量的反应，并使用光解来释放结合的异喹啉。这个博士项目将培养以下领域的技能：（i）催化反应开发;（ii）使用惰性气氛技术合成和纯化过渡金属络合物（Schlenk线工艺、脱气溶剂、HPLC纯化）;（iii）有机化合物和金属络合物的表征（iv）使用平行合成设备优化反应条件（v）使用ReactIR和动力学分析确定机理;（vi）使用电脑软件进行数据分析（例如Excel求解器功能，以确定反应动力学）和（vii）通过定期小组会议和更新报告的书面和口头陈述技能。

The reactivity of aromatic compounds is significantly altered when bound to transition metals through coordination. Upon coordination, aromatic and benzylic C H bonds become more acidic and the ring itself becomes more electrophilic. As a result, coordinated arenes show improved reactivity in selected reactions. Nucleophilic aromatic substitution of arene metal complexes was particularly well exploited in the 1990s, in which the coordinated metal fragment takes the place of a covalently-bound electron withdrawing group. Recently, there has been somewhat of a renaissance in this field with several research groups (including the Walton group) reporting contemporary reactions of arene complexes, including C H C C and C H C CF3 transformations. In this PhD project, part-funded by Syngenta, we will explore several new industrially-relevant catalytic reactions of arenes, which are atom efficient and would allow for late-stage functionalisation of aromatic compounds.The first aim will be nucleophilic fluorination. Fluorinated arenes are important motifs in the agrochemical and pharmaceutical industries. Current methods of fluorination are generally electrophilic or use HF, which requires specialist equipment. An attractive option would be to use a source of fluoride which could undergo a nucleophilic addition to aromatics. We will investigate a nucleophilic fluorination of aromatics, proceeding via a Ru arene complex. The final target is to produce a reaction that is catalytic in Ru. However, the project can be broken down into first looking at fluorination stoichiometric in Ru, before developing the full catalytic process. For the stoichiometric reaction, the activating [CpRu]+ can be recovered by photolysis. We will explore various conditions, including solvent effects and the choice of nucleophilic fluoride to optimise the reaction. The second aim will be to develop an atom-efficient isoquinoline synthesis. Heterocycles, such as isoquinoline, are important pharmaceutical targets. Generally, current methods of synthesis are atom inefficient. Using our catalytic arene activation methodology we will attempt to synthesise isoquinolines with 100% atom efficiency using catalytic Ru. As with the fluorination reaction above, initially we will develop the reaction stoichiometric in Ru and use photolysis to liberate the bound isoquinoline. Then we will develop the full catalytic cycle.This PhD project will develop skills in the following areas: (i) Catalytic reaction development; (ii) Synthesis and purification of transition metal complexes using inert atmosphere techniques (Schlenk line processes, degassing solvents, HPLC purification); (iii) characterisation of organic compounds and metal complexes (1D an 2D NMR, Mass Spectrometry; (iv) optimisation of reaction conditions using parallel synthesis equipment (v) mechanism determination using ReactIR and kinetic analyses; (vi) data analysis using computer software (e.g. Excel Solver function to determine reaction kinetics) and (vii) written and oral presentation skills through regular group meetings and update reports.