NEW LIGANDS FOR ASYMMETRIC SYNTHESIS AND CATALYSIS

用于不对称合成和催化的新配体

• 批准号: 3304763
• 负责人: WILLIAM Dean WULFF
• 金额: $ 15.16万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 1996-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3304763
• 关键词: Diels Alder reaction; carbene; catalyst; chemical addition; chemical synthesis; cycloalkene; ligands; organometallic compounds; stereoisomer

A plan is presented to develop a class of chiral Iigands for use in transition metal and Lewis acid mediated asymmetric reactions of value in organic synthesis. Specifically, these are the ligands 13, 14, 86, 87,101 - 106, 111 and 116. All of these ligands are either 2,2'-binaphthyls or 3,3'-biphenanthryl derivatives. None of these ligands have been made before, and in the preliminary results section methods are described which have been developed for the synthesis of 13 and 14. Proposed syntheses of the other ligands are presented. Two general methods are presented for the preparation of these ligands. The oxidative coupling method has been shown to be viable for 13 and 14 and some preliminary evidence is presented to suggest that approaches involving the benzannulation reaction of chromium carbene complexes may have potential. The greatest aspect of this potential is that carbene complexes may provide a route for the asymmetric synthesis of these ligands which would obviate the normally tedious resolution procedures that are required. In a preliminary evaluation of these ligands as chiral controllers it was found that a chloroaluminum complex of ligand 14 gives high asymmetric induction in the Diels-Alder reaction of methacrolein and cyclopentadiene (98 % ee) and in addition will produce 200 turnovers (0.5 mole % catalyst) in 4 h at -78 degrees C. Possible sources of the particular facial selectivity observed for the catalysts derived from these ligands are discussed. Several experiments involving the construction of new ligands are described which are designed to probe the source of the asymmetric induction. In addition to the Diels-AIder reaction, it is proposed that these ligands be evaluated with regard to their utility in asymmetric heteroatom Diels-Alder reactions, aldol reactions, Claisen rearrangements, carbonyl additions, reductive cyclizations, and carbometallation reactions. In addition it is noted that these ligands bear some structural relationship to gossypol, a naturally occurring 2,2'-binaphthol which occurs in cotton seeds and other natural sources. Given the known biological properties of gossypol, it is suggested that some of these ligands and the intermediates in their syntheses be tested for antiviral and anticancer activity.

提出了开发一类手性配体的计划，用于 过渡金属和路易斯酸介导的不对称反应的价值 有机合成。具体来说，这些是配体 13、14、86、87,101 - 106、111和116。所有这些配体都是2,2'-联萘或 3,3'-联菲衍生物。 这些配体均未制备 之前和在初步结果部分中描述了方法 已开发用于合成 13 和 14。 提议的合成 提出了其他配体。 提出了两种通用方法 这些配体的制备。 氧化偶联法 已证明对于 13 和 14 是可行的，并且一些初步证据是 提出建议涉及苯并环化反应的方法 铬卡宾配合物可能具有潜力。 最大的一个方面是 这种潜力在于卡宾配合物可以为 这些配体的不对称合成可以避免通常的合成 所需的繁琐的解决程序。 在对这些配体作为手性控制器的初步评估中， 发现配体 14 的氯铝配合物具有高不对称性 甲基丙烯醛和环戊二烯的狄尔斯-阿尔德反应中的诱导 (98 % ee) 并且此外将产生 200 次周转 (0.5 摩尔 % 催化剂) -78 摄氏度下 4 小时内。特定面部的可能来源 由这些配体衍生的催化剂观察到的选择性是 讨论过。 涉及构建新配体的多项实验 描述了旨在探测不对称源的 就职。 除了 Diels-AIder 反应外，还提出： 评估这些配体在不对称中的效用 杂原子狄尔斯-阿尔德反应、羟醛反应、克莱森重排、 羰基加成、还原环化和碳金属化 反应。此外，值得注意的是，这些配体带有一些结构 与棉酚的关系，棉酚是一种天然存在的 2,2'-联萘酚， 存在于棉籽和其他天然来源中。 鉴于已知 棉酚的生物学特性，建议其中一些 配体及其合成中的中间体进行抗病毒测试 和抗癌活性。