New Carbon-based Ligands for Hydroamination and olefin metathesis catalysts

描述（由申请人提供）：有机分子的高效和选择性制备对于治疗药物的合成至关重要。许多最熟练的已知工艺取决于催化剂的可用性。有机金属催化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，由于使用了富电子膦和环二氨基烃类，取得了重大进展。我们已经发现了几个新的稳定碳烯家族，如环（烷基）（氨基）碳烯和二氨基环丙烯，它们的行为甚至更像电子供体。它们已经允许改进已知的钯和钌催化过程，甚至促进新的金属催化反应。将研究含这些碳配体的配合物的充分催化潜力。为了获得更强大和高效的过渡金属催化剂，新型碳基配体将被制备出来，这些配体超越了任何其他配体所施加的给电子性质。特别注意的是配体家族，它将有可能精确地调整空间和电子参数。对于纯对映体形式的治疗药物的技术要求很高，因此我们的新配体的光学活性版本将被制备出来。这些研究将集中在催化过程上，这方面仍然存在真正的困难，以及化学转化，这方面尚未实现，但对构建复杂分子的骨架至关重要。级联反应涉及多个反应物，但只有一个催化剂，并导致生物相关的杂环和重要的合成子将被开发。为了加速我们的配体的广泛应用，我们已经与加州理工学院的Robert Grubbs正式建立了合作关系，我们期待着进一步的合作关系。这项研究工作的最终目标是找到真正实用的催化剂和催化反应，这将在工业和学术界中找到应用，用于选择性合成重要的生物化合物。公共卫生相关性：均相催化的成功在很大程度上可归因于各种配体框架的发展，这些配体框架已被用于调整各种催化剂的行为。为了获得稳定高效的过渡金属催化剂，我们希望开发新型的碳基配体。这项研究工作的最终目标是找到真正实用的催化剂和催化反应，这将在工业和学术界中找到应用，用于选择性合成重要的生物化合物。

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.