Expanding the scope and utility of DalPhos-based catalyst systems

现代化学合成利用催化剂来促进化学转化，否则将被证明具有挑战性或不可能。在温和的实验条件下，基于过渡金属的催化剂在将简单的底物分子转化为更复杂的增值产品（例如药品）方面已被证明特别有效，并且在某些情况下不会形成废物副产物。事实上，过渡金属催化在工业和学术环境中广泛应用于C-C， C-N和相关键的构建，并且对建立越来越有效的成键反应催化剂有很大的兴趣。虽然过渡金属催化剂的行为主要归因于所使用的金属，但金属的辅助配体的配位为调整金属的反应性提供了强有力的控制因素，从而提供了高水平的选择性和效率的催化过程。在这种情况下，新的过渡金属催化剂的设计越来越具有挑战性的底物转化在很大程度上依赖于新的辅助配体的设计。我的研究小组已经开发了一系列辅助配体（命名为“DalPhos”- DALhousie PHOSphine），已被证明在与晚期过渡金属结合以构建C-C和C-N键时特别有效。例如，我们已经证明Mor-DalPhos/Pd混合物能够促进涉及氨和肼的前所未有的交叉偶联反应，这是制药工业和学术界合成化学家广泛感兴趣的。在获得DalPhos配体家族的专利保护后，为了加速这项有前途的技术的发展以促进商业化，本提案旨在开展关键的研发工作，使我们能够：(a)扩大我们关于物质组成的专利要求；(b)扩展DalPhos配体文库，优化配体合成；(c)扩大dalphos基催化剂的范围；(d)评估DalPhos配体/催化剂在常见实验室条件下的稳定性。

Modern chemical synthesis makes use of catalysts to promote chemical transformations that would otherwise prove challenging or impossible. Catalysts based on transition metals have proven to be particularly effective in enabling the transformation of simple substrate molecules into more complex, value-added products (e.g. pharmaceuticals) under mild experimental conditions, and in some cases without the formation of waste by-products. Indeed, transition metal catalysis is employed broadly in both industrial and academic settings for the construction of C-C, C-N and related bonds, and there is significant interest in the establishment of increasingly effective catalysts for such bond-forming reactions. While the behavior of transition metal catalysts can be attributed primarily to the metal employed, the coordination of ancillary ligands to the metal provides a powerful control element in tuning the reactivity profile of the metal, thereby affording catalytic processes with high levels of selectivity and efficiency. In this vein, the design of new transition metal catalysts for increasingly challenging substrate transformations relies heavily on the design of new ancillary ligands. My research group has developed a family of ancillary ligands (named "DalPhos" - DALhousie PHOSphine) that have proven to be particularly effective in combination with late transition metals for the construction of C-C and C-N bonds. For example, we have demonstrated that Mor-DalPhos/Pd mixtures are capable of promoting unprecedented cross-coupling reactions involving ammonia and hydrazine, which are of widespread interest to synthetic chemists in the pharmaceutical industry as well as in academia. Having secured patent protection for this DalPhos ligand family, and in an effort to accelerate the development of this promising technology in order to promote commercialization, this proposal seeks to carry out key R&D work that will allow us to: (a) broaden our patent claims regarding composition of matter; (b) expand the DalPhos ligand library and optimize the ligand synthesis; (c) expand the scope of DalPhos-based catalysts; and (d) evaluate the stability of DalPhos ligands/catalysts under commonly encountered laboratory conditions.