A Radical Amination Approach to Aliphatic Amines

新分子的合成支撑着对英国经济至关重要的不同学术领域和行业。胺，尤其是贝塔功能胺，普遍存在于日常生活中必不可少的分子中，从普瑞巴林和Januvia等药物，到用于保障全球粮食供应的芬普莫夫等农用化学品。尽管它们很重要，但目前的胺合成方法通常依赖于有毒的试剂(烷基卤化物)、不稳定的前体(醛)或化学计量比的有机金属试剂。因此，对温和而有效的含胺分子的方法有很大的需求。最近，报道了在合成胺中使用以氮为中心的自由基，为传统的合成方法提供了一种温和的替代方法。然而，尽管它们的潜力，自由基氨化反应还没有得到全面的研究，这种方法的真正潜力仍有待实现。在这个项目中，我们将研究在单电子转移过程中还原生成的以氮为中心的自由基在合成具有合成价值的β-芳基胺中的使用。在烯烃中加入以氮为中心的基团，将生成一种多功能的烷基中间体，该中间体可以通过不同的途径进行功能化。拟议的氨基芳基化过程将使人们能够快速获得一系列的胺构建块。这种模块化的胺合成方法，一步构建了两个新的键(C-N和C-C)，将开辟以前未被探索的化学空间，促进新药物、农用化学品和材料的开发。我们将把化学应用于生物活性天然产物和药物类似物的合成，以突出这一研究在学术界和工业界的潜在应用。

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.