Radical Amination Strategies for the Synthesis of Nitrogen Heterocycles

可见光光氧化还原催化最近成为一种构建多种分子阵列的强大方法。该策略利用可见光能量产生可参与一系列成键反应的活性自由基。温和的反应条件和低催化剂负载提供了更可持续的替代更传统的合成方法。胺基序普遍存在于广泛的社会重要分子中，从药物和农用化学品到支持最新技术的材料。尽管如此，胺的合成方法仍然依赖于完善的合成程序，通常需要使用化学计量金属、有毒试剂或不易获得的起始材料。最近，已经证明在温和条件下光催化生成的氮中心自由基可以添加到容易获得的烯烃中，从而直接获得胺衍生物。该项目旨在探索利用这一战略，以更简洁和可持续的方式获得与制药相关的氮杂环。本项目将分为两个工作包：1。开发生成氮中心自由基的新策略首先将合成具有一系列电子和立体不同取代基的n中心自由基前体库。然后，我们将探索使用这些化合物将胺取代基引入一系列有机分子。特别是，我们将探索开发易于获得的前体（如烯烃）功能化的方法。开发含氮杂环的新途径在项目的第二阶段，我们将探索在含胺片段和杂环合成中使用自由基胺化方法。特别是，我们将开发级联过程，使结构复杂的分子从易于获取的前体快速有效地构建。将展示化学在合成生物活性分子和药物相关支架中的应用

Visible light photoredox catalysis has recently emerged as a powerful method for the construction of a diverse array of molecules. The strategy uses visible light energy to generate reactive radical species that can participate in a range of bond forming reactions. The mild reaction conditions and low catalyst loadings offer more sustainable alternatives to more conventional synthetic methodologies.The amine motif is prevalent in a broad range of societally important molecules ranging from pharmaceuticals and agrochemicals, to materials to support the latest technologies. Despite this, methods for the synthesis of amines are still reliant on well-established synthetic procedures that often require the use of stoichiometric metals, toxic reagents, or starting materials that aren't readily available. Recently, it has been demonstrated that nitrogen centred radicals, generated photocatalytically under mild conditions, can add to readily available olefins providing direct access to amine derivatives. This project aims to explore the use of this strategy to enable access to pharmaceutically-relevant nitrogen heterocycles in a more concise and sustainable manner.This project will be split into two work packages: 1. Development of new strategies for the generation of nitrogen-centred radicalsA library of N-centred radical precursors bearing a range of electronically and sterically different substituents will initially be synthesised. We will then explore the use of these compounds for the introduction of amine substituents into a range of organic molecules. In particular, we will explore the development of methods for the functionalisation of readily available precursors such as olefins.2. Development of new routes to nitrogen-containing heterocycles In the second phase of the project we will explore the use of the radical amination methodology in the synthesis of amine-containing fragments and heterocycles. In particular, we will develop cascade processes that enable the rapid and efficient construction of structurally complex molecules from readily accessed precursors. Applications of the chemistry in the synthesis of bioactive molecules and pharmaceutically-relevant scaffolds will be demonstrated