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）：有机分子的有效和选择性制备对于治疗剂的合成至关重要。许多最熟练的已知方法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。近年来，由于大体积、富电子的膦和环状二氨基卡宾（NHC）的使用，催化反应，特别是Pd-交叉偶联反应取得了重大进展。建议的研究计划，建立在我们长期的稳定的卡宾合成的经验，其目标是环状卡宾的合成，推动了电子和/或空间参数尺度表征膦和NHC配体，特别注意配体的家庭，它将有可能精确地调整立体电子参数。迫切需要生产纯对映体形式的治疗剂的技术。对于配体的不对称版本，将制备在卡宾的α位置具有手性中心的卡宾和具有C2手性和两个非常不同的供体的双齿配体;这将导致高手性诱导效应。我们将集中在钯催化偶联反应的芳基氯（铃木宫浦和根岸过程）和醛/亚胺的α-芳基化。由于这个几乎未知的反应，并由于吲哚在生物系统中发挥的突出作用，我们将开发一种新的一锅法合成各种吲哚从亚胺和邻二卤代芳烃。为了加速配体的广泛应用，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界应用于生物重要化合物的选择性合成。