Investigating the formation of beta-lactams via asymmetric photochemical Staudinger reactions

现代光氧化还原催化的目的是实现化学转化，这是迄今为止不可能使用更温和的反应条件和产生更少的废物比传统的合成化学。它通过使用可见光（通常是蓝色），沿着少量催化剂（通常含有过渡金属）来进行反应，这些反应传统上可能需要使用大量化学试剂，并且可能产生大量废物和不需要的副产物。这种向更清洁的合成方法的转变的影响是显而易见的-大规模生产必要的化学品（药品、农用化学品等）。对环境的影响要小得多，这是当今环境的一个关键问题。该项目的具体目标是开发一种合成β-内酰胺的新方法。β-内酰胺通常存在于药物分子中，包括青霉素衍生物（penams）在内的一类抗生素都含有这种结构。这些类型的结构通常是官能化的（它们含有一些其他类型的结构化学键合到它们），这在分子内产生手性。大多数反应不能区分形成产物的一种形式（对映异构体）或另一种形式。当仅需要一种对映异构体时，这是一个关键问题，因为对映异构体的分离是昂贵的并且产率是人为限制的。通过这个项目，我们希望开发一种方法，可以区分不同的对映体，并只产生所需的一个，从而最大限度地提高效率和减少浪费。将其与高效的催化剂偶联可以进一步改善反应，并且可以使用少量的催化剂，从而进一步减少浪费。虽然不对称催化剂在文献中已有先例，但其中许多使用两种不同类型的催化剂，增加了需要使用的催化剂的总量。存在许多不需要使用助催化剂的手性光催化剂的实例，但是这些手性光催化剂已经用于不同的目的，而不是用于与药物化学和制药直接相关的化学结构。因此，该项目将尝试建立在该领域其他人在开发手性光催化剂方面所做的工作的基础上，并旨在将其应用于与现代化学面临的挑战直接相关的反应和反应性。该项目福尔斯EPSRC合成有机化学研究领域。

Modern photoredox catalysis aims to achieve chemical transformations which were hitherto impossible using milder reaction conditions and producing less waste than traditional synthetic chemistry. It does this by using visible light (usually blue), along with a small amount of catalyst (usually containing a transition metal), to perform reactions which may have traditionally necessitated the use of large amounts of chemical reagents, and which may have produced large amounts of waste and unwanted byproducts. The impact of this shift to cleaner methods of synthesis is clear - large scale production of necessary chemicals (pharmaceuticals, agrichemicals, etc.) will have a much lower impact on the environment, a key concern in today's environment.This project specifically aims to develop a new method of synthesising beta-lactams. Beta-lactams are commonly found in drug molecules and a whole class of antibiotics including penicillin derivatives (penams) contains this type of structure. These types of structure are usually functionalised (they contain some other types of structure chemically bonded to them) and this gives rise to chirality within the molecule. Most reactions cannot discriminate between forming one form (enantiomer) of a product or another. This is a key issue when only one enantiomer is desired as separation of enantiomers is costly and yields are artificially limited. With this project we wish to develop a method which can discriminate between different enantiomers and produce only the desired one, thereby maximising efficiency and minimising waste. Coupling this with efficient photocatalysis improves the reaction even more and small amounts of catalyst can be used which further minimises waste.While asymmetric photocatalysis is precedented in the literature, many of these make use of two different types of catalyst, increasing the overall amount of catalyst which needs to be used. A number of examples chiral photocatalysts which do not require the use of co-catalysts exist, but these have been used for different purposes and not for chemical structures which are directly relevant to medicinal chemistry and pharmaceuticals. The project will therefore attempt to build on the work done by others in the field on developing chiral photocatalysts and aim to apply it to reactions and reactivity which are directly relevant to challenges faced in modern chemistry.This project falls within the EPSRC Synthetic Organic Chemistry research area.