New strategies for Bi-mediated C-C bond formation

项目背景（问题的识别及其重要性和与可持续性的相关性）碳对碳（C-C）键在天然和合成分子中都是丰富而重要的，例如我们体内的氨基酸和药物。形成这类键的方法多种多样，但许多方法使用有毒、稀有和/或非常昂贵的金属，如钯。因此，希望通过使用“绿色”化学品使这些反应更可持续。铋基化合物有可能发挥这样的作用。铋是一种无毒的采矿业废物，使其成为一种廉价和可持续的材料。此外，典型的C-C键形成方法结合了复杂的构建块，其制备需要额外的步骤，从而产生额外的浪费。一个更可持续的过程是完全避免这一步骤。碳氢键官能化使得简单的非官能化的碳碳键能直接形成。整个过程可能比传统的C-C键形成方法（更低的过程质量强度，PMI）浪费更少，因为合成底物所需的步骤更少，偶联反应本身产生的浪费更少。Ball小组先前开发了一种快速且用户友好的方法，用于铋促进碳氢化合物功能化。在该过程的最后，含铋的副产物可以高产量地回收，并在进一步的反应中循环使用。该项目旨在扩展Ball集团现有技术的范围，使其更具可持续性，并适用于更广泛的制药和农用化学有价值的目标分子。该项目的目标是使铋促进的碳氢官能化更具可持续性和更普遍。为此，我们将研究铋基试剂的结构/性质与它们在C-H官能化反应中的效率之间的关系。由此产生的洞察力将允许更有效的铋基试剂和工艺的合理设计。这些新试剂将被应用于广泛的目标分子的制备，这些目标分子受到工业的重视，或者目前难以以对环境负责的方式获得。

Project background (identification of the problem and its importance and relevance to sustainability) Carbon to carbon (C-C) bonds are abundant and important in both natural and synthetic molecules, for example amino acids in our bodies, and medicines. Various methods are available to form these types of bonds, but many use metals such as palladium that are toxic, rare and/or very expensive. Therefore, it is desirable to make these reactions more sustainable by using 'green' chemicals. Bismuth-based compounds could potentially fulfil such a role. Bismuth is a non-toxic waste product of the mining industry, making it an inexpensive and sustainable material. Additionally, typical C-C bond-forming methods combine complex building blocks, the preparation of which requires additional steps that generate additional waste. A more sustainable process is to avoid this step altogether. C-H functionalisation enables direct C-C bond formation between simple, unfunctionalized partners. The overall process is potentially less wasteful than traditional C-C bond forming methods (lower process mass intensity, PMI) as fewer steps are required to synthesise the substrates and less waste is produced in the coupling reaction itself. The Ball group have previously developed a rapid and user-friendly method for C-H functionalisation that is promoted by bismuth. At the end of the process, the bismuth-containing co-product can be recovered in high yields, and recycled for re-use in further reactions. This project seeks to extend the remit of the Ball group's prior art, making it more sustainable and applicable to a wider range of pharmaceutically- and agrochemically-valuable target molecules. Proposed solution and methodology The objective of the project is to make bismuth-promoted C-H functionalisation more sustainable and more general. To do this, we will study the relationship between the structure / properties of the bismuth-based reagents, and their efficiency in C-H functionalisation reactions. The resulting insight will allow rational design of more efficient bismuth-based reagents and processes. The new reagents will be applied to the preparation of a wide range of target molecules that are valued by industry, or that are otherwise currently challenging to access in an environmentally responsible way.