NEW LIGANDS FOR ASYMMETRIC SYNTHESIS AND CATALYSIS

用于不对称合成和催化的新配体

• 批准号: 2183080
• 负责人: WILLIAM Dean WULFF
• 金额: $ 12.41万
• 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/2183080
• 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.

提出了一种开发一类用于手性配体的计划。 过渡金属和Lewis酸催化的价值不对称反应 有机合成。具体地说，这些是配体13、14、86、87、101 -106、111和116。所有这些配体要么是2，2‘-联萘，要么是 3，3‘-联苯基衍生物。这些配体都没有被制造出来 在此之前，以及在初步结果一节中描述的方法 已被开发用于合成13和14。建议的合成 还介绍了其他的配体。给出了两种通用的计算方法 这些配体的制备。氧化偶联的方法已经被 显示在13岁和14岁是可行的，一些初步证据是 提出了涉及苯环化反应的方法 铬卡宾络合物可能具有潜在的应用前景。最伟大的方面 这种可能性是卡宾络合物可能为 这些配体的不对称合成将避免正常的 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的氯铝络合物具有很高的不对称性 甲基丙烯醛与环戊二烯Diels-Alder反应的诱导 (98%ee)，此外还将产生200个周转率(0.5摩尔%催化剂) 在零下78摄氏度的4小时内，特定面部的可能来源 观察到的这些配体衍生的催化剂的选择性为 讨论过。涉及构建新配体的几个实验 描述了被设计用于探测不对称的来源的 归纳法。除了Diels-aider反应外，还提出了 根据它们在不对称反应中的用途对这些配体进行评估 杂原子Diels-Alder反应，Aldol反应，Claisen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，这些配体具有一些结构 与棉酚的关系，棉酚是一种天然存在的2，2‘-联萘酚，它 发生在棉花种子和其他自然来源中。鉴于已知的 关于棉酚的生物学特性，有人建议其中一些 对配体及其合成中间体进行抗病毒检测 和抗癌活性。