A Radical Amination Approach to Aliphatic Amines

脂肪胺的自由基胺化方法

基本信息

批准号：
EP/V050176/1
负责人：
James Cuthbertson
金额：
$ 51.83万
依托单位：
University of Nottingham
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2022
资助国家：
英国
起止时间：
2022 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FV050176%2F1
关键词：
Radical Amination Approach Aliphatic Amines

项目摘要

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.

新型分子的合成为英国经济至关重要的各种学术领域和行业。胺，尤其是β官能化胺在日常生活中普遍存在的分子，从诸如Pregabalin和Januvia等药物的日常生活中，到用于保护全球粮食供应的芬植物（例如Fenpropimorph）等农业化学物质。尽管它们的重要性，但当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）或化学计量计的有机金属测量试剂。因此，已经报道了对含胺的分子的轻度和有效方法的显着需求。实际上，已经报道了以氮为中心的自由基在合成胺中的使用，为常规合成方法提供了温和的替代方法。然而，尽管具有潜力，但尚未对自由基的氨基官能化反应进行全面研究，这种方法的真正潜力仍有待实现。在该项目中，我们将研究以氮为中心的自由基的使用，在单个电子传递过程中还原性产生，在合成有价值的β-雄胺合成中。添加以烯烃为中心的氮将产生一种多功能烷基自由基中间体，该中间体可以通过各种途径进行功能化。拟议的氨基酸化过程将使快速进入一系列胺构件。这种模块化的胺合成方法，其中两个新键（C-N和C-C）单步构建，将打开先前未开发的化学空间领域，促进新药，农业化学物质和材料的开发。我们将适用化学对生物活性天然产物和药物类似物的合成的化学，并将其用于介绍的研究。