Uncovering the Unwritten-Rules in Photoredox Catalysis for Late Stage Functionalisation

揭示光氧化还原催化后期功能化的不成文规则

• 批准号: 2278965
• 金额: --
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2278965
• 关键词: Uncovering; Unwritten; Rules; Photoredox; Catalysis

Photoredox catalysis offers new ways to construct bonds to already complex molecules such as drugs and lead-like compounds. This reaction manifold uses visible light and a photocatalyst to generate reactive intermediates under much milder reactions conditions that circumvent the use of strong oxidants and reductants. Such reaction pathways enable broader functional group compatibility, open-up new options for molecular design and accelerate the synthesis of derivatives. Photoredox catalysis therefore has enormous potential to be broadly applied in the drug discovery process as an enabling technology for the discovery of new medicines. Despite its potential, a detailed contemporary understanding of photoredox catalytic processes is limited. Reactions can be notoriously difficult to reproduce owing to the technical nature of this chemistry and the number of variables involved for these light driven reactions. Crucial factors such as the reaction temperature are either rarely reported or poorly controlled, and the combination of variables is unusually large involving: photocatalyst, light source, wavelength, reagent concentration, solvent, reactor design and reactor material. The interplay of many of these variables, effect of wavelength and temperature for example, has not been studied. This project aims to study these multiple factors in batch and continuous flow processes in order to generate a greater understanding of photoredox catalysis and the underpinning reaction conditions. We will begin by investigating CH functionalization reactions of heterocycles - an important challenge both academically and relevant to pharma. By using batch and flow photo-reactors it will be possible to study the reaction conditions in greater detail, to generate much more data on the factors and to map out the 'reaction space' that will lead to successful reactions. Building on work within the Bull group we aim to develop new batch photoreactor that will enable the accurate control of reaction temperatures. Beyond this we will leverage this understanding to generate 'data rich' reactions through the use of a continuous flow droplet based micro reactors. This will enable us to perform large numbers of reactions with precise control and provide much more extensive data than is currently possible. This will allow wide exploration of reaction variables, and also substrates, to map reactivity of different substrates under different conditions and develop clear selectivity guides towards the controlled late stage functionalisation of complex molecules.Keywords: Photoredox catalysis; heterocycle synthesis; flow chemistry; late stage functionalisation.

光氧化还原催化提供了新的方法来构建已经复杂的分子，如药物和铅样化合物的键。该反应歧管使用可见光和光催化剂在温和得多的反应条件下产生活性中间体，从而避免使用强氧化剂和还原剂。这样的反应途径使得更广泛的官能团相容性成为可能，为分子设计开辟了新的选择，并加速了衍生物的合成。因此，光氧化还原催化具有巨大的潜力，可广泛应用于药物发现过程中，作为发现新药的一种使能技术。尽管它的潜力，详细的当代了解光氧化还原催化过程是有限的。由于这种化学的技术性质和这些光驱动反应所涉及的变量的数量，反应可能非常难以重现。关键因素如反应温度要么很少报道，要么控制不好，变量的组合异常大，涉及：光催化剂，光源，波长，试剂浓度，溶剂，反应器设计和反应器材料。许多这些变量的相互作用，例如波长和温度的影响，还没有被研究。该项目旨在研究间歇和连续流过程中的这些多个因素，以便更好地了解光氧化还原催化和基础反应条件。我们将开始调查CH功能化反应的杂环-一个重要的挑战，学术和相关的制药。通过使用间歇式和流动式光反应器，可以更详细地研究反应条件，生成更多关于因素的数据，并绘制出导致成功反应的“反应空间”。在Bull集团工作的基础上，我们的目标是开发新的间歇式光反应器，以实现对反应温度的精确控制。除此之外，我们将利用这种理解，通过使用基于连续流液滴的微反应器来产生“数据丰富”的反应。这将使我们能够在精确控制的情况下进行大量的反应，并提供比目前可能的更广泛的数据。这将允许广泛探索的反应变量，也基板，映射不同的基板在不同条件下的反应性，并制定明确的选择性指南对复杂molecules.Keywords控制后期功能化：光氧化还原催化;杂环合成;流动化学;后期功能化。