A Radical Amination Approach to Aliphatic Amines

The synthesis of novel molecules underpins diverse academic fields and industries vital to the UK economy. Amines, in particular beta-functionalised amines, are prevalent in molecules essential to everyday life ranging from pharmaceuticals such as Pregabalin and Januvia, to agrochemicals, such as Fenpropimorph, which are used to safeguard global food supplies. Despite their importance, current methods for amine synthesis are often reliant upon toxic reagents (alkyl halides), unstable precursors (aldehydes), or stoichiometric organometallic reagents. There is therefore significant demand for mild and efficient approaches to amine-containing molecules.

Recently, the use of nitrogen centred radicals in the synthesis of amines has been reported, providing a mild alternative to conventional synthetic methods. However, despite their potential, radical aminofunctionalisation reactions have not been comprehensively investigated, and the true potential of this approach remains to be realised.

In this project we will investigate the use of nitrogen centred radicals, reductively generated in a single electron transfer process, in the synthesis of synthetically valuable beta-aryl amines. The addition of a nitrogen centred radical to an alkene, will generate a versatile alkyl radical intermediate that can be functionalised through a diverse range of pathways. The proposed aminoarylation processes will enable rapid access to a range of amine building blocks. This modular approach to amine synthesis, in which two new bonds (C-N and C-C) are constructed in a single step, will open up previously unexplored areas of chemical space, facilitating the development of new pharmaceuticals, agrochemicals, and materials.

We will apply the chemistry to the synthesis of bioactive natural products and pharmaceutical analogues to highlight the potential applications of the research in academia and industry.