Exploring transition metal-catalysed fluorine transfer reactions

探索过渡金属催化的氟转移反应

• 批准号: 2606306
• 金额: --
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2606306
• 关键词: Exploring; transition; metal; catalysed; fluorine

Project background (identification of the problem and its importance and relevance to sustainability) Organofluorine molecules are an important class of compounds which find several diverse applications due to the incredible strength and high polarity of the C-F bond. C-F bonds are found within are found in pharmaceuticals, PET-imaging agents, agrochemicals, polymers, optoelectronics and many other high-performance molecules. Fluorination is the process of adding fluorine atoms to organic molecules, which throughout the 20th century was an extremely unsafe and challenging feat due to the toxic and hazardous HF and elemental fluorine reagents used. These methods often have poor selectivity and lead to over-fluorination. Therefore, over the past two decades, a portfolio of safe and easy-to-handle reagents have been developed, capable of late-stage fluorination of pharmaceutical targets. However, these developments have prioritised selectivity and control over energy and sustainability concerns. These reagents often react with incredibly low atom-efficiencies, are often required in excess quantities and require tremendous amounts of energy to produce. Furthermore, despite the impact this important class of compounds has had on society, our dependence on this raw material is unsustainable. Fluorine is a finite resource derived almost entirely from inorganic fluoride, in which current estimates suggest will sustain the industry for less than 100 years. Proposed solution and methodology The industry requires a shift towards using greener and more sustainable methods for fluorination, whilst utilising fluorinated feedstocks that are cheaper, accessible and have lower environmental impact. Over recent years, poly- and perfluorinated compounds have become a useful feedstock because they are easily accessed via established industrial processes. C-F functionalisation of these compounds gives access to partially fluorinated building blocks, that are otherwise challenging to produce. Several transition metal-catalysed, metal-free catalysed, photocatalytic and electrocatalytic routes have been developed. Transition metal-catalysed routes are dominated by fluorophilic reducing agents, such as silanes and boranes, due to the strong Si-F and B-F bonds formed, which result in the loss of the fluorine from the system. This project aims to develop insight into transition-metal catalysed transfer fluorination reactions, to strive towards a more circular economy for fluorine. In this reaction, fluorine is removed from an over-fluorinated substrate where it is not required and introduced to where it is desired via a transition-metal catalyst, yielding two valuable products simultaneously. Transfer functionalisation reactions are an emerging and powerful class of transformations as they proceed with high atom economies and produce minimal waste. The design of an efficient and atom-economic fluorine transfer reaction, using available sources of fluorine would mitigate the issues associated with current fluorination and defluorination methods in a single process.

项目背景（确定问题及其与可持续性的重要性和相关性）有机氟分子是一类重要的化合物，由于C-F键的强度和高极性，因此发现了几种不同的应用。 C-F键在药品，宠物成像剂，农业化学物质，聚合物，光电子和许多其他高性能分子中发现。氟化是将氟原子添加到有机分子中的过程，在整个20世纪，由于使用了有毒和危险的HF和元素氟试剂，因此在整个20世纪都是极其不安全且具有挑战性的壮举。这些方法通常具有较差的选择性，并导致过度氟化。因此，在过去的二十年中，已经开发了一组安全且易于手柄的试剂组合，能够对药物靶标的后期氟化。但是，这些事态发展优先考虑了对能源和可持续性问题的选择性和控制权。这些试剂通常会以难以置信的低原子效应反应，通常需要过多的数量，并且需要大量的能量才能产生。此外，尽管这种重要的化合物对社会产生了影响，但我们对这种原材料的依赖是不可持续的。氟是一种几乎完全来自无机氟化物的有限资源，当前的估计表明该行业将在不到100年的时间内维持该行业。 拟议的解决方案和方法论，该行业需要转向使用更绿色，更可持续的方法进行荧光，同时利用更便宜，可访问且具有较低环境影响的氟化原料。近年来，多氟化化合物已成为有用的原料，因为它们可以通过既定的工业过程轻松获取。这些化合物的C-F功能化可以访问部分氟化的构件，否则这些构件却具有挑战性。已经开发了几种过渡金属催化，无金属催化，光催化和电催化途径。由于形成强大的Si-F和B-F键，过渡金属催化的途径以荧光还原剂（例如硅烷和硼烷）为主，从而导致系统中流失了氟。该项目旨在发展对过渡金属催化转移氟化反应的见解，以努力为氟的循环经济。在此反应中，从过度氟化的底物中除去氟，并通过过渡金属催化剂将其引入所需的位置，同时产生两种有价值的产品。转移功能反应是一种新兴而有力的转化类别，它们具有高原子经济性并产生最小的废物。使用可用的氟来源的高效和原子经济转移反应的设计将减轻单个过程中与当前氟化和屈光化方法相关的问题。