New strategies for Bi-mediated C-C bond formation

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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.