Stable Carbenes: Emerging Ligands for Catalysis

稳定的卡宾：新兴的催化配体

• 批准号: 7098817
• 负责人: GUY BERTRAND
• 金额: $ 20.51万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7098817
• 关键词: carbene; catalyst; chemical stability; chemical structure function; chemical synthesis; electrochemistry; imines; indoles; ligands; stereochemistry; stereoisomer

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 in catalysis, especially in Pd-cross-coupling reactions, have been reported thanks to the use of bulky, electron-rich phosphines and cyclic diaminocarbenes (NHCs). The proposed research program, built on our long standing experience in stable carbene synthesis, has as its objective the synthesis of cyclic carbenes that push upward the electronic and/or steric parameter scales characterizing both phosphine and NHC ligands, with special attention on families of ligands for which it will be possible to precisely tune the stereo-electronic parameters. There is a demanding need for technology to produce therapeutics in a pure enantiomeric form. For the asymmetric versions of the ligands, carbenes with a chirality center in a position alpha to the carbene, and bidentate ligands featuring C2 chirality and two very different donors will be prepared; this should result in high chiral induction effects. We will focus on palladium-catalyzed coupling reactions of aryl chlorides (Suzuki-Miyaura and Negishi processes) and on the alpha-arylation of aldehydes/imines. Thanks to this virtually unknown reaction, and because of the prominent role played by indoles in biological systems, we will develop a novel one-pot synthesis of a variety of indoles from imines and ortho-dihaloarenes. To accelerate the widespread implementation of our ligands, we have already formalized two collaborations and we are looking forward to further partnerships. The ultimate goal of this proposed research effort is to provide the catalytic community with new, readily available ligands, which will allow for the development of practical catalysts that will find applications in both industry and academia for the selective synthesis of biologically important compounds.

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，由于大量的富含电子的膦和环二氨基卡宾(NHCS)的使用，在催化方面取得了重大进展，特别是在钯交叉偶联反应中。拟议的研究计划建立在我们在稳定的卡宾合成方面的长期经验的基础上，其目标是合成环卡宾，这些环卡宾的合成推动了膦配体和NHC配体的电子和/或空间参数标度的上升，并特别关注能够精确调节其立体电子参数的配体家族。人们迫切需要技术来生产纯对映体形式的治疗药物。对于不对称形式的配体，将制备手性中心位于卡宾的α位置的卡宾，以及具有C2手性的双齿配体和两个非常不同的给体；这将导致高手性诱导效应。我们将集中于钯催化的芳基氯化物的偶联反应(Suzuki-Miyaura和Negishi过程)和醛/亚胺的α-芳基化反应。由于这种几乎未知的反应，以及吲哚在生物系统中的重要作用，我们将开发一种新的一锅法从亚胺和邻位二卤代芳烃合成各种吲哚。为了加快我们的配体的广泛实施，我们已经正式确定了两项合作，我们期待着进一步的合作伙伴关系。这项拟议研究工作的最终目标是为催化界提供新的、容易获得的配体，这将允许开发实用的催化剂，这些催化剂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。