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，否则这些转化将被证明是具有挑战性的或不可能的。基于过渡金属的催化剂已被证明能够在温和的实验条件下将简单的底物分子转化为更复杂的增值产品(如药品)，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被广泛用于构建C-C、C-N和相关的键，人们对建立越来越有效的催化剂来进行这种成键反应非常感兴趣。虽然过渡金属催化剂的行为主要归因于所使用的金属，但辅助配体与金属的配位在调节金属的反应性方面提供了强大的控制因素，从而提供了高水平的选择性和效率的催化过程。在这一点上，设计新的过渡金属催化剂以应对日益严峻的底物转化，在很大程度上依赖于新辅助配体的设计。我的研究小组开发了一系列辅助配体(名为“DalPhos”-Dalhousie膦)，事实证明，它们与晚过渡金属结合在一起，特别有效地构建了C-C和C-N键。例如，我们已经证明了MOR-DalPhos/Pd混合物能够促进涉及氨和联氨的前所未有的交叉偶联反应，这引起了制药行业和学术界合成化学家的广泛兴趣。在确保了DalPhos配体家族的专利保护，并努力加快这一前景光明的技术的发展以促进商业化的努力下，这项建议寻求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权利要求；(B)扩大DalPhos配体文库并优化配体合成；(C)扩大基于DalPhos的催化剂的范围；以及(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.