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

有机分子的甲硅烷基化仍然是合成化学领域的一个巨大挑战，仍然需要漫长的合成途径，包括浪费的密集阶段。尽管含甲硅烷基的分子与体内受体蛋白具有独特的相互作用，与碳类似物相比引起不同的药物化学活性，但这个问题仍然是其应用的根本障碍。此外，用于甲硅烷基化反应的催化剂在历史上一直由铂族金属为中心的络合物如基于铱和铑的那些占主导地位。这些金属明显更昂贵，而且通常比地球上更丰富的对应物更具毒性。目前，许多其他问题困扰着甲硅烷基化化学。将氢清除剂如烯烃以超化学计量的量加入到反应混合物中以推动反应的热力学平衡向前。导向基团通常是甲硅烷基化反应进行所需的，并且可能对所使用的硅烷敏感，其生产使用浪费的有毒试剂。最后，为了形成活性催化物质，需要化学计量或甚至超化学计量的氧化剂来产生活性催化剂。因此，继续开发新的催化剂和条件集，以解决这些问题，并允许获得不同的底物是至关重要的。我们的目标将是开发铁和锰的配合物与-接受配体和测试其作为均相催化剂的苯甲醚的甲硅烷基化作为一个标准，以优化催化剂的功效。一旦针对这种芳香族化合物优化了催化剂，我们将研究官能团耐受性和选择性，并将该方法扩展到不同的底物，包括杂芳香族化合物（吡啶、吡咯、呋喃、噻吩和吲哚），同时还测试具有较弱定向基团的芳香族化合物，例如乙酰基苯，目的是最终向具有较弱或没有定向基团的芳香族化合物发展。从那里，可以进行硅烷如何影响反应的研究，例如是伯硅烷、仲硅烷还是叔硅烷。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，然后可以进行DFT理论水平的计算以计算活化势垒并提供进一步的机理见解。

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.