Stable Carbenes: Emerging Ligands for Catalysis

稳定的卡宾：新兴的催化配体

• 批准号: 6969665
• 负责人: GUY BERTRAND
• 金额: $ 22.18万
• 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/6969665
• 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）：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都依赖于催化剂的可用性。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，由于使用了体积大、富电子的膦和环状二氨基卡宾（NHC），催化领域，特别是钯交叉偶联反应方面取得了重大进展。拟议的研究计划以我们在稳定卡宾合成方面的长期经验为基础，其目标是合成环状卡宾，以提高表征膦和 NHC 配体的电子和/或空间参数尺度，特别关注配体家族为此，可以精确调整立体声电子参数。迫切需要生产纯对映体形式的治疗药物的技术。对于配体的不对称版本，将制备在卡宾的α位具有手性中心的卡宾，以及具有C2手性和两个截然不同的供体的双齿配体；这应该会导致高手性诱导效应。我们将重点关注芳基氯的钯催化偶联反应（Suzuki-Miyaura 和 Negishi 工艺）以及醛/亚胺的 α-芳基化。由于这种几乎未知的反应，并且由于吲哚在生物系统中发挥的突出作用，我们将开发一种由亚胺和邻二卤代芳烃一锅合成各种吲哚的新型方法。为了加速我们的配体的广泛实施，我们已经正式确定了两项合作，并期待进一步的合作。这项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，这将有助于开发实用的催化剂，这些催化剂将在工业界和学术界用于选择性合成生物学上重要的化合物。