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（问题的识别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 C-F 键具有令人难以置信的强度和高极性，因此具有多种不同的应用。 C-F 键存在于药物、PET 成像剂、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添加氟原子的过程，由于使用有毒有害的 HF 和元素氟试剂，整个 20 世纪这是一项极其不安全且具有挑战性的壮举。这些方法通常选择性较差并导致过度氟化。因此，在过去的二十年中，开发了一系列安全且易于操作的试剂，能够对药物靶标进行后期氟化。然而，这些发展优先考虑了能源和可持续性问题的选择性和控制。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，尽管这一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，目前的估计表明该行业的生存时间不会超过 100 年。 建议的解决方案和方法 该行业需要转向使用更环保、更可持续的氟化方法，同时使用更便宜、易获得且对环境影响更小的氟化原料。近年来，多氟化物和全氟化物已成为有用的原料，因为它们可以通过现有的工业流程轻松获得。这些化合物的 C-F 官能化可以得到部分氟化的结构单元，否则这些结构单元的生产具有挑战性。已经开发了几种过渡金属催化、无金属催化、光催化和电催化路线。过渡金属催化路线主要以亲氟还原剂为主，例如硅烷和硼烷，因为形成了强的Si-F和B-F键，这导致氟从系统中损失。该项目旨在深入了解过渡金属催化的转移氟化反应，努力实现更加循环的氟经济。在该反应中，氟从不需要的过度氟化基质中去除，并通过过渡金属催化剂引入到需要的位置，同时产生两种有价值的产物。转移官能化反应是一类新兴且强大的转化，因为它们以高原子经济性进行并产生最少的废物。使用可用的氟源设计高效且原子经济的氟转移反应将减轻与单一工艺中当前氟化和脱氟方法相关的问题。