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

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.