Technology-Driven C-H Bond Functionalisations for Amine Synthesis

脂肪族胺在药品、农用化学品和其他精细化学品中无处不在，大多数小分子药物都含有这些基序。在2019年销量最高的25种小分子药物中，有4种含有伯烷基胺功能，84%具有n -烷基键（其中50%是脂肪族n -杂环）。合成化学制备脂肪族胺已经彻底改变了药物的发现，进而促进了人类的健康和繁荣。该项目将探索脂肪胺功能化的雄心勃勃和高度冒险的概念，特别关注使能技术。我们的目标是利用机器学习和连续流化学的工具来发明和优化新的反应，以构建有价值的胺产品作为单一对映体，基于我们最近的光氧化催化-c - h键功能化伯胺的概念。我们还将探索这些转化的“无光催化剂”电化学变体，使用商业或自制造的交叉电极。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，无论是批处理还是流动设置。这可能对绿色化学和环境可持续的药品生产产生重大影响。

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.