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，并由两者平等提供适当的资金。在氢酰化过程中，醛化合物上的羰基C-H键通过氧化加成作用在催化金属中心断裂，并与烯烃或烯烃底物形成新的C-C键。这对合成化学家特别感兴趣，因为该反应本质上是原子高效的，并且是形成C-C键的有用途径。过渡金属催化氢酰化反应的例子很多，但目前最多的是铑催化。铑催化的分子间氢酰化反应只与链状醛发生。目前，对乙炔底物的支化到线性选择性的控制是有限的。如果能够调整反应条件(即催化剂)，使反应具有高度的选择性，能够在工业规模上使用(条件温和，催化剂负载量低，废物最少)，并且能够灵活地使用许多不同的底物和醛来形成广泛的有机产品，那么氢酰化将在合成化学中特别有用。为了实现这些目标，或者至少对这些目标做出贡献，我将通过改变催化剂上的配体以及研究引入选择性的机理来修改催化剂本身。这将涉及完全合成新的配体，最有可能是双膦配体，或者应用已知的但在以前未被探索的催化系统中的配体。这背后的逻辑是鼓励C-H氧化加成(已被证明是速率限制步骤)，同时还通过对Rh金属中心施加空间效应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置。这些新催化剂的设计还将考虑到脱碳途径，这些途径已被证明通过形成稳定的铑-羰基络合物来杀死分子间氢酰化反应中的催化剂。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研究拨款的投资已经进行的广泛研究。这个项目结合了合成有机化学(目前EPSRC的投资为2710万GB)、催化(3830万GB)和合成配位化学(1410万GB)，这就是为什么我要由牛津大学这些化学学科中一些最负盛名和最具活力的研究人员共同监督的原因。该项目的进展将是创新的，并有助于走在合成化学的前沿。除了Weller Group和Willis Group之间的合作外，目前还没有公司或合作者参与这个项目。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.