Exploring transition metal-catalysed fluorine transfer reactions

项目背景(问题的识别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键令人难以置信的强度和高极性，它具有多种不同的应用。C-F键存在于药物、PET显像剂、农用化学品、聚合物、光电子学和许多其他高性能分子中。氟化是将氟原子添加到有机分子中的过程，在整个20世纪，由于使用有毒和危险的HF和元素氟试剂，这是一项极其不安全和具有挑战性的壮举。这些方法往往选择性较差，导致过量氟化。因此，在过去的二十年里，已经开发了一系列安全和易于操作的试剂，能够对药物靶标进行后期氟化。然而，这些事态发展优先考虑选择性和控制性，而不是能源和可持续性问题。这些试剂的反应原子效率往往低得令人难以置信，往往需要过多的量，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。氟是一种有限的资源，几乎全部来自无机氟，目前的估计表明，无机氟将使该行业维持不到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方法进行氟化，同时使用更便宜、更容易获得并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现有的工业工艺获得。这些化合物的C-F功能化使其能够获得部分氟化的积木，否则生产起来很困难。目前已开发出几种过渡金属催化、无金属催化、光催化和电催化的方法。过渡金属催化的途径主要是亲氟还原剂，如硅烷和硼烷，因为形成了强烈的Si-F和B-F键，导致氟从体系中损失。这个项目的目的是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。在这个反应中，氟从不需要的过度氟化的底物中去除，并通过过渡金属催化剂引入到需要的地方，同时产生两个有价值的产品。转移官能化反应是一类新兴而强大的转化，因为它们以高原子经济性进行，并产生最少的废物。利用现有的氟源设计一种高效和原子经济的氟转移反应，将缓解目前单一工艺的氟化和除氟方法所带来的问题。

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.