Rhodium-catalysed intermolecular hydroacylation

我的项目将集中在铑催化的氢酰化反应中的催化剂和催化循环。该项目位于有机化学和无机化学之间的边界，由两者平等地提供适当的资金。在加氢酰化过程中，醛类化合物的羰基C-H键通过氧化加成到催化金属中心而断裂，与烯烃或炔底物形成新的C-C键。合成化学家对此特别感兴趣，因为该反应本身具有原子效率，是形成C-C键的有用途径。过渡金属催化氢酰化的例子很多，但铑催化是目前最多产的。铑催化的分子间氢化作用只在栓系醛中实现。目前，只有有限的控制支链到线性选择性与炔烃底物。如果反应条件（即催化剂）可以调整，使反应具有高度选择性，可以在工业规模上使用（温和的条件，低催化剂负荷和最小的废物），并且具有使用许多不同底物和醛形成广泛有机产品的灵活性，那么氢化作用将在合成化学中特别有用。为了实现这些目标，或者至少为实现这些目标做出贡献，我将通过改变催化剂上的配体来修饰催化剂本身，并研究引入选择性的机制。这将涉及合成新的配体，最有可能是二膦配体，或应用已知的配体，但在以前未开发的催化体系。这背后的逻辑是鼓励C-H氧化加成（这已被证明是限速步骤），同时也通过对铑金属中心施加空间和潜在的电子效应来影响选择性，从而以特定的方式操纵结合位点。这些新催化剂的设计还将考虑脱碳途径，这些途径已被证明可以通过形成稳定的铑羰基络合物在分子间氢化作用中杀死催化剂。该项目属于EPSRC物理科学研究领域。该项目中的基础合成化学研究将有助于通过EPSRC研究资助投资进行的广泛研究。这个项目是合成有机化学（目前EPSRC投资2710万英镑），催化（3830万英镑）和合成配位化学（1410万英镑）的结合，这就是为什么我与牛津大学这些化学学科中最负盛名和最具活力的研究人员共同监督。这个项目的进展将是创新的，并为合成化学的前沿做出贡献。除了威勒集团和威利斯集团之间的合作外，目前没有公司或合作者参与该项目。然而，如果工业支持者有适当的兴趣，那么这将受到鼓励。

My project will concentrate on the catalyst and catalytic cycle in the rhodium-catalysed hydroacylation reaction. This project sits on the boundary between organic and inorganic chemistry and is suitably funded equally by both. During the process of hydroacylation, the carbonyl C-H bond on an aldehyde compound is broken via oxidative addition onto a catalytic metal centre and a new C-C bond with alkene or alkyne substrate is formed. This is particularly interesting to synthetic chemists as the reaction is inherently atom efficient and a useful pathway to C-C bond formation. There are many examples of transition metal catalysed hydroacylation but rhodium catalysis is currently the most prolific. Rhodium-catalysed intermolecular hydroacylation has only been achieved with tethered aldehydes. Currently, there is only limited control of branched to linear selectivity with alkyne substrates. Hydroacylation would be exceptionally useful in synthetic chemistry if the reaction conditions (i.e. catalyst) could be adapted so that the reaction was highly selective, could be used on an industrial scale (mild conditions, low catalyst loading and minimal waste) and has the flexibility to use many different substrates and aldehydes to form a wide range of organic products. In attempts to achieve these goals, or at least contribute towards them, I will modify the catalyst itself by changing the ligands on the catalyst as well as investigating the mechanism by which the selectivity is introduced. This will involve synthesising new ligands altogether, most likely to be diphosphine ligands, or applying known ligands but in previously unexplored catalytic systems. The logic behind this is to encourage C-H oxidative addition (which has been shown to be the rate limiting step) whilst also influencing the selectivity by applying steric and potentially electronic effects to the rhodium metal centre so to manipulate the binding site in a specific fashion. These new catalysts will also be designed in consideration of decarbonylation pathways that have been shown to kill the catalyst in intermolecular hydroacylation through the formation of stable rhodium-carbonyl complexes. This project falls within the EPSRC Physical Sciences research area. The fundamental synthetic chemistry research within this project will contribute towards the extensive research already conducted via investment from EPSRC research grants. This project is a combination of synthetic organic chemistry (the current EPSRC investment is £27.1 million), catalysis (£38.3 million) and synthetic coordination chemistry (£14.1 million) and is why I am co-supervised by some of the most prestigious and dynamic researchers in these disciplines of chemistry at the University of Oxford. The progress within this project will be both innovative and contribute towards the forefront of synthetic chemistry. Other than collaborating between the Weller Group and Willis Group there are currently no companies or collaborators in this project. However, if there is suitable interest from industrial backers then that will be encouraged.