AA-STARR: Aromatic Amine Synthesis by Tapping Aminium Radical Reactivity

芳香胺是最重要的化学基元之一，主要存在于着色剂、药物和农用化学品等功能分子中。事实上，现代化学工业的基础在很大程度上是由19世纪50年代以芳香胺为基础的新型染料的发展推动的。尽管芳香胺的重要性很大，但它们的生产方法仍然可能涉及使用有毒废气的浪费的多步骤过程。已经开发了更现代的方法，如所谓的布赫瓦尔德-哈特威格耦合，但这些方法需要使用预先功能化的底物(携带自己的废物库存)和基于稀有贵金属钯的催化剂。在这项工作中，我们将开发使用简单且廉价的试剂结合光源(紫外线和可见光)直接胺化芳香环的方法。这些反应利用了被称为氨基的活性物种。氨基的反应已经知道100多年了，但它们仍然没有得到充分的利用。我们最近开发了利用这些活性物种进行高效芳香族胺化的方法。此外，这种反应性使我们能够获得不同寻常的分子结构，这将在药物发现和荧光材料的制备中得到应用。我们的目标是(I)创造一套条件来实现胺化反应；(Ii)通过创造一系列具有不同结构的新分子来证明这一点；(Iii)开发一种新的变体，其中芳香环在此过程中被‘破坏’，从而允许从相同类型的起始材料中获得非常不同的产品。我们将展示我们工作的非学术影响，方法是(通过项目合作伙伴)提供新的分子‘构建块’可供购买，并创建一个称为片段的独特小分子文库，可用于药物发现中的筛选程序。

Aromatic amines are amongst the most important chemical motifs, featuring in functional molecules such as colourants, pharmaceutical drugs and agrochemicals. Indeed, the foundation of the modern chemical industry was driven in large part by the development of new dyestuffs based on aromatic amines in the 1850s. Despite the significance of aryl amines, methods for their production can still involve wasteful multi-step processes with noxious waste streams. More modern methods have been developed such as the so-called Buchwald-Hartwig coupling, but these require the use of pre-functionalised substrates (which carry their own waste inventory) and catalysts based upon the scarce precious metal palladium. In this work, we will develop methods to directly aminate aromatic rings using simple and cheap reagents in conjunction with light sources (ultra-violet and visible). The reactions exploit active species known as aminium radicals. Reactions of aminium radicals have been known for over 100 years, but they remain underexploited. We have recently developed ways to harness these reactive species to give highly productive amination of aromatics. Further, the reactivity allows us to access unusual molecular structures which will find applications in drug discovery and the preparation of fluorescent materials.Our objectives are to (i) create a suite of conditions to achieve the amination reactions; (ii) to demonstrate this in the creation of a wide range of novel molecules with diverse structures; (iii) develop a new variant in which the aromatic ring is 'destroyed' in the process, allowing access to very different products from the same type of starting materials. We will demonstrate non-academic impact of our work by making novel molecular 'building blocks' available to buy (through a project partner), and by creating a unique library of small molecules known as fragments which can be used for screening programmes in drug discovery.