Radical Amination Strategies for the Synthesis of Nitrogen Heterocycles

可见光光氧化还原催化是近年来发展起来的一种合成多种分子的有效方法。该策略使用可见光能量来产生可以参与一系列键形成反应的活性自由基物质。温和的反应条件和较低的催化剂负载量为传统的合成方法提供了更可持续的替代方案。胺基序在从药物和农用化学品到支持最新技术的材料等广泛的社会重要分子中普遍存在。尽管如此，胺的合成方法仍然依赖于成熟的合成程序，这些程序通常需要使用化学计量的金属、有毒试剂或不容易获得的起始材料。最近，已经证明在温和条件下光催化产生的氮中心自由基可以添加到容易获得的烯烃中，从而提供直接获得胺衍生物的途径。该项目旨在探索使用这一策略，以更简洁和可持续的方式获得与药物相关的氮杂环化合物。发展新的战略，为产生氮为中心的radicalsA库的N为中心的自由基前体轴承的电子和空间上不同的取代基的范围将首先合成。然后，我们将探索使用这些化合物的胺取代基引入到一系列的有机分子。特别是，我们将探索开发用于容易获得的前体（如烯烃）的官能化方法。2.开发合成含氮杂环化合物的新路线在项目的第二阶段，我们将探索自由基胺化方法在合成含胺片段和杂环化合物中的应用。特别是，我们将开发级联过程，使结构复杂的分子从容易获得的前体的快速和有效的建设。将展示化学在生物活性分子和药物相关支架合成中的应用

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