A Radical Amination Approach to Aliphatic Amines

新型分子的合成支撑着对英国经济至关重要的各种学术领域和行业。胺，特别是β-官能化胺，普遍存在于日常生活所必需的分子中，从Pregabalin和Januvia等药物到用于保护全球粮食供应的农用化学品，如Fenpropimorph。尽管它们的重要性，目前的胺合成方法通常依赖于有毒试剂（烷基卤化物），不稳定的前体（醛），或化学计量的有机金属试剂。因此，有显着的需求温和和有效的方法，含胺molecular.Recently，使用氮中心的自由基在胺的合成已被报道，提供了一个温和的替代传统的合成方法。然而，尽管他们的潜力，自由基氨基官能化反应还没有得到全面的研究，这种方法的真正潜力仍然有待实现。在这个项目中，我们将研究使用氮为中心的自由基，还原产生的一个单一的电子转移过程中，在合成有价值的β-芳基胺。将氮中心自由基加成到烯烃上将产生多功能的烷基自由基中间体，其可以通过多种途径官能化。所提出的氨基芳基化方法将能够快速获得一系列胺结构单元。这种在一步中构建两个新键（C-N和C-C）的胺合成模块化方法将开辟以前未探索的化学空间领域，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，以突出该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.