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

金属基催化剂在促进化学反应中起着核心作用，这些化学反应产生了我们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，开发新型催化剂，将廉价而丰富的试剂分子转化为有价值的增值产品，是现代学术和工业研究中一个重要而持续的挑战。特别令人感兴趣的是催化剂的鉴定，这些催化剂能够实现目前任何其他方法都无法实现的有用的化学转化。该提案的目标是合理开发新型金属基催化剂，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，直接应用于制备药物和下一代发电设备。正在研究的金属基催化剂建立在申请人研究小组开发的现已商业化的“DalPhos”（DALhousie PHOSphine）配体基础上；这些催化剂表现出显著的催化行为，与大多数其他已知的催化剂类型不同，但我们对这种行为的理解非常有限。作为回应，我们将寻求利用和增强DalPhos金属催化剂的独特行为，通过战略性地多样化/优化DalPhos配体结构，然后进行催化剂筛选，以获得我们可以详细研究其作用模式的优化结构。优化后的DalPhos催化剂将用于解决上述具有挑战性的反应性类型。提出的合成、结构、机制和催化研究将扩大我们对金属催化反应中结扎效应的概念理解，并为新药物和功能材料的开发提供实际的途径。

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.