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

现代光氧化还原催化的目的是利用比传统合成化学更温和的反应条件和产生更少的废物来实现迄今为止不可能实现的化学转化。它通过使用可见光（通常是蓝光）和少量催化剂（通常含有过渡金属）来进行传统上可能需要使用大量化学试剂并可能产生大量废物和不需要的副产品的反应。这种转向更清洁的合成方法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）将大大降低对环境的影响，而环境是当今环境的一个关键问题。本项目旨在开发一种合成-内酰胺的新方法。-内酰胺通常存在于药物分子中，包括青霉素衍生物（penams）在内的一整类抗生素都含有这种结构。这些类型的结构通常是功能化的（它们包含一些其他类型的结构与它们化学键合），这就产生了分子内的手性。大多数反应不能区分产物的一种形式（对映体）或另一种形式。当只需要一种对映体时，这是一个关键问题，因为分离对映体的成本很高，而且收率受到人为限制。在这个项目中，我们希望开发一种方法，可以区分不同的对映异构体，并只产生所需的一种，从而最大限度地提高效率和减少浪费。将其与有效的光催化相结合，可以更多地改善反应，并且可以使用少量催化剂，从而进一步减少浪费。虽然文献中有不对称光催化的先例，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。存在一些不需要使用共催化剂的手性光催化剂的例子，但它们已用于不同的目的，而不是用于与药物化学和药物直接相关的化学结构。因此，该项目将尝试建立在开发手性光催化剂领域其他人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。该项目属于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.