Technology-Driven C-H Bond Functionalisations for Amine Synthesis

脂肪族胺普遍存在于药物、农用化学品和其他精细化学品中，并且大多数小分子药物都包含这些基序。在2019年销量最高的25种小分子药物中，有4种含有伯烷基胺官能团，84%的药物含有N-烷基键（其中超过50%是脂肪族N-杂环）。制备脂肪胺的合成化学已经彻底改变了药物的发现，并延伸到人类的健康和繁荣。该项目将探索雄心勃勃和高度冒险的脂肪胺官能化概念，特别关注使能技术。我们的目标是使用机器学习和连续流化学的工具，发明和优化新的反应，用于构建有价值的胺产品作为单一对映异构体，基于我们最近的光氧化还原催化的伯胺的α-C-H键官能化的概念。我们还将探索这些转换的“无光催化剂”电化学变体，使用商业或自制的叉指电极。这里的目的是将我们的光氧化还原化学转化为成对的电化学过程，无论是批量还是流量设置。这可能对绿色化学和环境可持续的药物制造产生重大影响。

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.