Catalytic Silylation of Aryl C-H Bonds with Earth Abundant Metal Catalysts

有机分子的硅基化在合成化学领域仍然是一个强有力的挑战，仍然需要漫长的合成路线，包括浪费的、密集的阶段。尽管含有硅基的分子与体内的受体蛋白具有独特的相互作用，导致与碳类似物不同的药物化学活性，但这一问题仍然是其应用的根本障碍。此外，用于硅烷化反应的催化剂历史上一直由铂族金属中心络合物主导，如基于Ir和Rh的催化剂。这些金属明显比富含稀土的金属贵得多，毒性也普遍更强。目前，还有一些其他问题困扰着硅烷化化学。在反应混合物中加入超化学计量比的氢清除剂，如烯烃，以推动反应的热力学平衡向前推进。硅烷化反应通常需要导向基团来进行，并且可能对所使用的硅烷很敏感，因为硅烷的生产使用了浪费的有毒试剂。最后，为了形成活性催化剂物种，需要化学计量比甚至超化学计量比的氧化剂来生成活性催化剂。因此，继续开发新的催化剂和条件集来解决这些问题并允许获得不同的底物是至关重要的。其目的将是开发含铁和锰的接受配体的配合物，并测试它们作为均相催化剂用于苯甲醚硅烷化的效率，作为优化催化剂的标准。一旦为这种芳香族化合物优化了催化剂，我们将研究官能团的耐受性和选择性，并将该方法扩展到不同的底物，从杂芳烃(吡啶、吡咯、呋喃、噻吩和吲哚)，同时也测试具有较弱导向基团的芳烃，如乙基苯，目的是最终向具有较弱导向基团或没有导向基团的芳烃推进。从那里可以研究硅烷是如何影响反应的，例如硅烷是初级、二级还是三级反应。在整个过程中，将进行动力学和机理研究，以阐明反应的机理途径。基于这些结果，然后可以在DFT理论水平上进行计算，以计算激活势垒，并提供进一步的机械性见解。

Silylation of organic molecules remains a potent challenge in the field of synthetic chemistry, still requiring lengthy synthetic pathways involving wasteful, intensive stages. Despite silyl-containing molecules having unique interactions with receptor proteins in the body, causing different pharmacochemical activities compared to a carbon analogue, this issue remains a fundamental roadblock in their application. In addition, catalysts for silylation reactions have historically been dominated by platinum-group metal-centred complexes such as those based on iridium and rhodium. These metals are significantly more expensive and also generally more toxic than their more earth abundant counterparts. A number of other issues plague silylation chemistry currently. Hydrogen scavengers, such as alkenes are added to reaction mixtures in super stoichiometric quantities to drive the thermodynamic equilibrium of the reaction forwards. Directing groups are often needed for silylation reactions to progress and can be sensitive to the silane being used, the production of which uses wasteful, toxic reagents. Finally, to form the active catalytic species, stoichiometric or even super stoichiometric oxidants are needed to generate the active catalyst. As a result, the continued development of new catalysts and condition sets which combat these issues and allow access to different substrates is of paramount importance. The aim will be to develop iron and manganese containing complexes with -accepting ligands and test their efficacy as homogeneous catalysts for the silylation of anisole as a standard to optimise the catalysts. Once the catalysts have been optimised for this aromatic, we will investigate functional group tolerance and selectivity, and will extend the methodology to different substrates, ranging from heteroaromatics (pyridine, pyrrole, furan, thiophene and indole) whilst also testing aromatics with weaker directing groups such as acetylbenzene with the aim of advancing eventually towards aromatics with weaker or no directing groups. From there, investigation on how the silane affects the reaction, such as whether is primary, secondary, or tertiary can be conducted. Throughout, kinetics and mechanistic studies will be conducted to elucidate mechanistic pathways of reaction. Based on these outcomes, calculations at a DFT level of theory may then be undertaken to compute activation barriers and provide further mechanistic insight.