Technology-Driven C-H Bond Functionalisations for Amine Synthesis

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Aliphatic amines are ubiquitous in pharmaceuticals, agrochemicals, and other fine chemicals, and a majority of small-molecule drugs incorporate these motifs. Of the top 25 highest-selling, small-molecule drugs in 2019, four contained primary alkyl amine functionality, and 84% featured N-alkyl linkages (of which >50% were aliphatic N-heterocycles). Synthetic chemistry to prepare aliphatic amines has revolutionised drug discovery, and by extension human health and prosperity. This project will explore ambitious and highly adventurous concepts for aliphatic amine functionalisation, with a particular focus on enabling technologies. We aim to use the tools of machine learning and continuous flow chemistry to invent and optimise new reactions for the construction of valuable amine products as single enantiomers, based on our recent concept of photoredox-catalysed alpha-C-H bond functionalisation of primary amines. We will also explore "photocatalyst-free" electrochemical variants of these transformations, using commercial or self-fabricated interdigitated electrodes. The aim here is to 'translate' our photoredox chemistry into paired electrochemical processes, in either batch or flow settings. This could have significant implications for green chemistry and the environmentally-sustainable manufacture of pharmaceuticals.