Advancing Late Metal Catalysis: DalPhos Ligand Design, Mechanism, and New Reactivity

金属催化剂在促进化学反应方面发挥着核心作用，这些化学反应产生了我们在日常生活中使用的分子和材料(例如燃料、塑料、药品等)。在这方面，开发能够将廉价和丰富的试剂分子转化为感兴趣的增值产品的新型催化剂是现代学术和工业研究中的一个重要和持续的挑战。特别令人感兴趣的是确定能够实现有用的化学转化的催化剂，这是目前任何其他手段都不可能实现的。该提案旨在合理开发新型金属催化剂，以实现极具挑战性的反应，将廉价而丰富的小分子，包括氨、肼和羟胺，以高效和更环保的方式转化为有用的产品，并直接应用于制药和下一代发电设备的制备。正在研究的金属催化剂建立在申请者研究小组开发的现已商业化的“DalPhos”(Dalhousie膦)配体的基础上；这些配体表现出与大多数其他已知催化剂类型不同的非凡催化行为，但我们对这种行为的了解非常有限。作为回应，我们将寻求通过对DalPhos配体结构的战略性多样化/优化以及催化剂筛选来利用和增强基于DalPhos的金属催化剂的独特行为，目的是获得优化的结构，我们可以详细研究其作用模式。然后，优化的DalPhos催化剂将被应用于解决上面列出的具有挑战性的反应类型。拟议的合成、结构、机理和催化研究将扩大我们对金属催化反应中连接效应的概念性理解，并为开发新的药物和功能材料提供实用途径。

Metal-based catalysts play a central role in promoting chemical reactions that give rise to the molecules and materials that we make use of in our everyday lives (e.g. fuels, plastics, medicines, and other). In this regard, the development of new classes of catalysts that allow for the conversion of cheap and abundant reagent molecules into value-added products of interest represents an important and ongoing challenge in modern academic and industrial research. Of particular interest is the identification of catalysts that enable useful chemical transformations that are not currently possible by any other means. This proposal targets the rational development of new classes of metal-based catalysts to enable extremely challenging reactions that convert cheap and abundant small-molecules, including ammonia, hydrazine, and hydroxylamine, into useful products in an efficient and more environmentally friendly manner, with direct applications in the preparation of pharmaceuticals and next-generation power-generating devices. The metal-based catalysts under investigation build upon what are now commercialized “DalPhos” (DALhousie PHOSphine) ligands developed in the applicant’s research group; these exhibit remarkable catalytic behavior that is distinct from most other known catalyst types, but our understanding of this behavior is very limited. In response, we will seek to harness and augment the unique behavior of DalPhos-based metal catalysts via strategic diversification/optimization of the DalPhos ligand structure followed by catalyst screening, with the goal of obtaining optimized structures that we can study in detail regarding their mode of action. Optimized DalPhos catalysts will then be applied toward addressing the challenging reactivity types listed above. The proposed synthetic, structural, mechanistic, and catalytic studies will expand our conceptual understanding of ligation effects in metal-catalyzed reactions, as well as providing practical in-roads to new medicines and functional materials.