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（确定问题及其重要性和与可持续性的相关性）有机氟分子是一类重要的化合物，由于其难以置信的强度和C-F键的高极性，它有几种不同的应用。C-F键存在于药品、pet显像剂、农用化学品、聚合物、光电和许多其他高性能分子中。氟化是在有机分子中加入氟原子的过程，在整个20世纪，由于使用有毒和危险的HF和单质氟试剂，这是一项极其不安全且具有挑战性的壮举。这些方法往往选择性差，导致过氟化。因此，在过去二十年中，开发了一系列安全且易于操作的试剂，能够对药物靶点进行后期氟化。然而，这些发展优先考虑了选择性和控制，而不是能源和可持续性问题。这些试剂通常以极低的原子效率进行反应，通常需要过量的试剂，并且需要大量的能量来生产。此外，尽管这类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，目前的估计表明，无机氟化物将维持该工业不到100年。建议的解决方案和方法该行业需要转向使用更环保和更可持续的氟化方法，同时使用更便宜、可获得和对环境影响较小的氟化原料。近年来，多氟化合物和全氟化合物已成为一种有用的原料，因为它们很容易通过既定的工业工艺获得。这些化合物的C-F功能化可以获得部分氟化的构建块，否则很难生产。目前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。过渡金属催化的路线主要是亲氟还原剂，如硅烷和硼烷，因为形成了很强的Si-F和B-F键，导致氟从体系中损失。该项目旨在深入了解过渡金属催化的转移氟化反应，努力实现更循环的氟经济。在该反应中，氟从不需要的过氟化底物中去除，并通过过渡金属催化剂引入到需要的地方，同时产生两种有价值的产品。转移官能化反应是一种新兴的、强大的转化类型，因为它们具有高原子经济性，产生的废物最少。利用现有的氟源设计一种高效和原子经济的氟转移反应，将在单一过程中减轻目前氟化和除氟方法所涉及的问题。