Late-stage Functionalisation of Heteroarenes and Saturated Heterocycles by Electrochemically-generated Free Radicals

在农业化学研究中，获得具有一系列功能的农业化学构建模块的能力在先导优化阶段非常重要。然而，传统的合成路线不适合于此目的，因为所有的功能通常在多步合成开始时引入，并且必须对每个新化合物重复整个合成顺序。因此，开发能够将功能性引入已经合成的分子（所谓的后期功能化）的方法最近已成为一个重要课题。自由基通常是非常短暂的，许多人认为自由基反应的选择性很差，在合成上不是很有用。然而，事实并非如此。自由基反应通常具有很强的选择性，对一系列官能团具有耐受性，并且在温和的条件下进行。因此，自由基反应非常适合后期官能化，最近有许多成功用于此目的的例子。然而，自由基反应的最大缺点是它们需要高毒性的引发剂（例如，过渡金属离子）或危险的（例如，过氧化物）。该项目的目的是开发一种产生有机自由基的电化学方法，然后将其用于杂芳烃和饱和杂环的后期官能化，这些杂芳烃和饱和杂环是农用化学品中常见的基序。电化学是一种非常干净的引发自由基反应的方法，不涉及任何其他试剂。例如，羧酸根阴离子可以在阳极处还原以形成羧基自由基，羧基自由基迅速失去CO2以产生烷基自由基（柯尔贝反应）。在该项目中，由此形成的烷基将用于官能化一系列杂芳烃和饱和杂环分子。这些反应将通过光谱电化学技术进行监测;所获得的机理信息将有助于我们优化反应条件并研究新反应的范围。在该项目的后期阶段，将探索一系列不同的反应，并将新方法应用于农业化学目标。

In agrochemical research, the ability to access agrochemical building blocks with a range of functionalities is important in the lead optimisation stages. However, traditional synthetic routes are not appropriate for this purpose, as all functionalities are usually introduced at the start of the multistep synthesis, and the whole synthetic sequence must be repeated for each new compound. Developing methods that make it possible to introduce a functionality to the already-synthesised molecule (so-called late-stage functionalisation) has thus recently become an important topic. Free radicals are usually very short-lived and many people assume that radical reactions have poor selectivity and are not very useful synthetically. However, this is not the case. Radical reactions are often quite selective, tolerant to a range of functional groups and proceed under mild conditions. Therefore, radical reactions are well suited for late-stage functionalisation, and there are many recent examples of their successful use for this purpose. The big disadvantage of radical reactions, however, is that they need initiators which are either highly toxic (e.g., transition metal ions) or dangerous (e.g., peroxides). The aim of this project is to develop an electrochemical method for generating organic radicals which will then be used for late-stage functionalisation of heteroarenes and saturated heterocycles, which are common motifs in agrochemicals. Electrochemistry is a very clean method for initiation of radical reactions which does not involve any other reagents. For instance, carboxylate anions can be reduced at the anode to form carboxyl radicals which promptly lose CO2 to yield alkyl radicals (Kolbe reaction). In this project, the alkyl radicals thus formed will be used to functionalise a range of heteroarenes and saturated heterocycles molecules. The reactions will be monitored by spectroelectrochemical techniques; the mechanistic information obtained will help us optimise reaction conditions and investigate the scope of the new reactions. In the later stages of the project, a series of different reactions will be explored, and the new approach will be applied to agrochemical targets.