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.

提出了一个计划，以开发一类手性iigands供使用 过渡金属和刘易斯酸介导的价值的不对称反应 有机合成。具体而言，这些是配体13、14、86、87,101 -106、111和116。所有这些配体都是2,2'-二磷酸或 3,3'-双烯烷烯衍生物。 这些配体都没有制成 以前，在“初步结果”部分中描述了哪个方法 已经开发了13和14的合成。提出的合成 提出了其他配体。 提出了两种通用方法 这些配体的准备。 氧化耦合方法已经 证明对13和14是可行的，一些初步证据是 提出表明涉及苯并反应的方法 卡宾铬络合物的含量可能具有潜力。 最大的方面 这种潜力是卡宾综合体可以为 这些配体的不对称合成将避免正常 需要的乏味的解决程序。 在对这些配体作为手性控制器的初步评估中 发现配体14的叶绿体复合物可产生高的不对称 甲状酸烯和环戊二烯的Diels-Alder反应的诱导 （98％EE）及其还将产生200个失误（0.5摩尔％催化剂） 在-78度的4小时内C.特定面部的可能来源 从这些配体得出的催化剂观察到的选择性是 讨论。 涉及新配体的几个实验 描述了旨在探测不对称的来源的设计 就职。 除了Diels-aider反应外，还提出了 这些配体在不对称中的效用评估 杂原子Diels-Alder反应，藻反应，Claisen重排， 羰基添加，还原环化和碳测量值 反应。此外，注意到这些配体带有一些结构 与Gossypol的关系，这是一种天然发生的2,2'binaphthol的关系 发生在棉种子和其他天然来源中。 鉴于已知 Gossypol的生物学特性，建议其中一些 测试抗病毒的配体和中间体 和抗癌活性。