First-row Transition Metal Catalysed Synthesis of Organophosphorus Compounds

有机磷化合物由于在医药、农用化学品、阻燃剂和配体等方面的广泛应用而具有相当重要的意义使用热、光或自由基引发剂合成这些化合物的经典合成方法受到化学计量添加剂的使用、保护基团的使用、官能团耐受性差以及有机磷产品形成区域化学混合物的严重影响由于需要一种更少浪费和更具区域选择性和立体选择性的有机磷合成方法，因此促进了使用金属催化剂形成P-C键；通过在不饱和碳碳双键上加成P-H单元这种方法是理想的，因为它呈现出100%原子经济过程的潜力，符合绿色化学的12个原则之一。然而，在这些反应中通常使用的金属催化剂的很大一部分是贵金属催化剂，主要是钯，以及较小程度的早期镧系元素此外，由于缺乏能够耐受杂原子官能的合适催化剂，最近的大多数文献都集中在使用仲膦对非官能化烯烃和炔烃进行P-H加成反应。这是有问题的，因为所使用的二次膦最初来源于PCl3，根据欧盟指令67/548/EEC， PCl3被归类为剧毒和腐蚀性很强。为了避免这些问题，需要更环保的磷前体和地球上丰富的稳健过渡金属催化剂，使这种方法更具可持续性。Kays小组先前的研究表明，低配位铁配合物可以催化P-H加入到杂原子功能化的底物上，如异氰酸酯（R-N=C=O）。值得注意的是，这些配合物也被证明可以催化这种反应的新的插入途径，这种途径非常罕见，通常难以控制（例如方案1）。在这项工作的基础上，该项目将利用低坐标的第一行过渡金属配合物催化一系列P-H和P(O)-H衍生物添加到含有C=X （X = O， N， S）键的杂分子烯中，从而有效地将杂原子功能引入具有与制药和农用化学工业相关的新型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，与典型的氢磷化反应相比，将使用更广泛的pKa范围和更多的官能团，这将对催化提出更大的挑战。将反应性扩展到其他添加物将使我们能够探索第一排过渡金属预催化剂的适用性。反应机制将通过详细的动力学实验进行研究，并将有助于未来在克尺度上与绿色溶剂的反应发展。

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.