First-row Transition Metal Catalysed Synthesis of Organophosphorus Compounds

有机磷化合物由于其作为药物、农用化学品、阻燃剂和配体的许多应用而具有相当重要的意义。1使用热、光或自由基引发剂来合成这些化合物的经典合成方法显著地受到使用化学计量添加剂、使用保护基团、差的官能团耐受性和有机磷产品的区域化学混合物的形成。有机磷合成促进了金属催化剂的使用以形成P-C键;通过将P-H单元添加到不饱和碳-碳双键上。3这种方法是理想的，因为它具有成为100%原子经济方法的潜力，符合绿色化学的12个原则之一。4然而，在这些反应中常用的金属催化剂中有很大一部分是贵金属催化剂，主要是钯和少量的早期镧系元素。2另外，最近的大部分文献集中于使用仲膦对未官能化的烯烃和炔进行P-H加成，这是由于缺乏能够耐受杂原子官能团的合适催化剂。这是有问题的，因为所使用的二级膦最初衍生自PCl 3，PCl 3在EU指令67/548/EEC下被归类为非常有毒和腐蚀性的。为了避免这些问题，需要更环保的磷前体和地球丰富的强大的过渡金属催化剂，使这种方法更具可持续性。Kays小组先前的研究表明，低配位铁络合物可以催化P-H加成到杂原子官能化的底物如异氰酸酯（R-N=C=O）上。值得注意的是，这些络合物还显示出催化该反应的新的二插入途径，其非常罕见并且通常难以控制（例如方案1）。在这项工作的基础上，该项目将利用低配位第一行过渡金属配合物催化一系列P-H和P（O）-H衍生物与含有C=X（X = O，N，S）键的杂累积多烯的加成，将杂原子官能团有效地引入具有与制药和农业化学工业相关的新基序的有机磷化合物中。该项目的一个关键部分将是使用更可持续和良性的有机磷衍生物，这可能对催化剂提出更大的挑战，因为与典型的氢膦化反应相比，将使用更宽的pKa范围和更多的官能团。将反应性扩展到其他添加物将使我们能够探索第一行过渡金属预催化剂的适用性。反应机理将使用详细的动力学实验进行研究，并将有助于告知未来的反应发展，在克规模与绿色溶剂。

Organophosphorus compounds are of considerable importance due to their many applications as medicines, agrochemicals, fire retardants and ligands.1 Classical synthetic methodologies to synthesise these compounds using heat, light or radical initiators suffer significantly from the use of stoichiometric additives, the use of protecting groups, poor functional group tolerance and the formation of regiochemical mixtures of organophosphorus products.2 The need for a less wasteful and more regioselective and stereoselective method of organophosphorus synthesis has promoted the use of metal catalysts to form P-C bonds; by addition of a P-H unit to an unsaturated carbon-carbon double bond.3 This methodology is ideal because it presents the potential to be a 100% atom economic process, in line with one of 12 Principles of Green Chemistry.4 However, a significant proportion of the metal catalysts commonly used in these reactions are precious metal catalysts, mainly palladium and to a lesser extent early lanthanides.2 Additionally, the majority of recent literature has focused on P-H addition using secondary phosphines to unfunctionalised alkenes and alkynes, due to a lack of suitable catalysts that can tolerate heteroatom functionality. This is problematic as the secondary phosphines used are originally derived from PCl3, which is classified as very toxic and corrosive under EU Directive 67/548/EEC. To circumvent these issues, more environmentally benign phosphorus precursors and earth-abundant robust transition metal catalysts are needed to make this methodology more sustainable. Previous research by the Kays group has shown that low co-ordinate iron complexes can catalyse P-H addition to heteroatom-functionalised substrates such as isocyanates (R-N=C=O). Significantly these complexes have also been shown to catalyse novel diinsertion pathways for this reaction, which are exceedingly rare and typically difficult to control (e.g. Scheme 1). Building on this work the project will utilise low coordinate first-row transition metal complexes to catalyse the addition of a range of P-H and P(O)-H derivatives to heterocumulenes containing C=X (X = O, N, S) bonds, to introduce a heteroatom functionality efficiently into organophosphorus compounds with novel motifs relevant to pharmaceutical and agrochemical industries. A key part of the project will be to use more sustainable and benign organophosphorus derivatives which can present more challenge to the catalysis as a much broader pKa range and more functional groups compared will be used compared to typical hydrophosphination reactions. Expansion of the reactivity to other additions will allow us to explore the applicability of the first-row transition metal precatalysts. Reaction mechanisms will be investigated using detailed kinetic experiments and will help inform future reaction development at the gram scale with green solvents.