New Carbon-based Ligands for Hydroamination and olefin metathesis catalysts

描述(由申请人提供)：高效和选择性地制备有机分子对于治疗药物的合成至关重要。许多已知的最熟练的工艺依赖于催化剂的可用性。金属有机催化剂的优点之一是能够通过修饰金属中心周围的配体来调节活性和选择性。最近，由于富含电子的膦和环二氨基卡宾的使用，已经取得了重大进展。我们发现了几个新的稳定的卡宾家族，如环(烷基)(氨基)卡宾和二氨基环丙烯，它们的行为甚至更像是给电子的配体。它们已经允许改进已知的钯和钚催化的过程，甚至促进新的金属催化的反应。含这些卡宾配体的络合物的全部催化潜力将被研究。为了获得更坚固和高效的过渡金属催化剂，人们将制备新型的碳基配体，其给电子性能超过任何其他配体所强加的性能。将特别注意能够精确调节其空间和电子参数的配体家族。对以纯对映体形式生产治疗药物的技术的需求很高，因此将制备我们的新配体的光学活性版本。研究的重点将是仍然存在实际困难的催化过程，以及尚未实现但对构建复杂分子骨架至关重要的化学转化。涉及几种反应物但只有一种催化剂的级联反应将被开发，这些反应导致生物相关的杂环和重要的合成子。为了加快我们的Ligands的广泛实施，我们已经与加州理工大学的罗伯特·格拉布斯正式达成了合作，我们期待着进一步的合作伙伴关系。这项研究的最终目标是找到真正实用的催化剂和催化反应，这将在工业和学术中应用于选择性合成具有生物重要性的化合物。公共卫生相关性：均相催化的成功在很大程度上可以归功于一系列不同的配体框架的发展，这些框架已被用于调整各种催化剂的行为。为了获得坚固高效的过渡金属催化剂，我们希望开发新型的碳基配体。这项研究的最终目标是找到真正实用的催化剂和催化反应，这将在工业和学术中应用于选择性合成具有生物重要性的化合物。

DESCRIPTION (provided by applicant): Efficient and selective preparation of organic molecules is critical for the synthesis of therapeutics. Many of the most proficient known processes depend on the availability of catalysts. One of the advantages of organometallic catalysis is the ability to tune the activity and selectivity through modification of the ligands around the metal center. Recently, major advances have been reported thanks to the use of electron-rich phosphines and cyclic diaminocarbenes. We have uncovered several novel families of stable carbenes, such as the cyclic (alkyl)(amino)carbenes and the diaminocyclopropenylidenes, which behave as even more electron-donating ligands. They have already allowed for improving known palladium and ruthenium catalyzed processes, and even for promoting new metal catalyzed reactions. The full catalytic potential of complexes bearing these carbene ligands will be investigated. In order to obtain even more robust and efficient transition-metal catalysts, novel types of carbon-based ligands, which surpass the electron donating properties imposed by any other ligands, will be prepared. Special attention will be drawn on families of ligands for which it will be possible to precisely tune the steric and electronic parameters. There is a high demand for technology to produce therapeutics in a pure enantiomeric form, thus optically active versions of our new ligands will be prepared. The studies will be focused on catalytic processes for which real difficulties remain, and on chemical transformations, which have not yet been achieved, but are of critical importance for building the skeleton of complex molecules. Cascade reactions that involves several reactants, yet a single catalyst, and which lead to biologically relevant heterocycles and to important synthons will be developed. To accelerate the widespread implementation of our ligands, we have already formalized a collaboration with Robert Grubbs at Caltech, and we are looking forward to further partnerships. The ultimate goal of this research effort is to find truly practical catalysts, and catalytic reactions, which will find applications in both industry and academia for the selective synthesis of biologically important compounds. PUBLIC HEALTH RELEVANCE: The success of homogeneous catalysis can largely be attributed to the development of a diverse range of ligand frameworks that have been used to tune the behavior of the various catalysts. In order to obtain robust and efficient transition-metal catalysts, we wish to develop novel types of carbon-based ligands. The ultimate goal of this research effort is to find truly practical catalysts, and catalytic reactions, which will find applications in both industry and academia for the selective synthesis of biologically important compounds.