CATALYTIC ENANTIOSELECTIVE OLEFIN METATHESIS REACTIONS

催化对映选择性烯烃复分解反应

• 批准号: 6045208
• 负责人: RICHARD R SCHROCK
• 金额: $ 37.45万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-01 至 2004-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6045208
• 关键词: alkenes; catalyst; chemical synthesis; cyclization; molecular rearrangement; molybdenum; stereochemistry

Enantioselective chemical reactions that are reliable, catalytic, selective (high regio- and stereoselectivity) can significantly expedite the large scale production and availability of important therapeutics. This proposal outlines experiments that will lead to the design, development and characterization of a various new catalysts that can effect asymmetric metathesis reactions with high efficiency and enantioselectivity. The catalysts developed here are unique in their ability to promote asymmetric metathesis. Furthermore, these catalysts will be utilize to develop new reaction technologies which afford products that are not otherwise accessible by any other metal-catalyzed or enzymatic process. The following specific goals will be pursued: I. Synthesis and Development of New Chiral, Optically Pure Mo-based Metathesis Catalysts. We have already identified that several chiral Mo complexes can effect highly enantioselective metathesis reactions. These chiral complexes easily lend themselves to steric and electronic modifications. We have also demonstrated that certain enantioselective reactions operate best with a specific variant of the chiral catalyst, whereas other transformations afford optimal results with a related analog. We will design, synthesize and fully characterize Mo-based chiral complexes that can effect enantioselective synthesis of a wider range of compounds. Such versatility will allow us to find a "best match" for a particular substrate, significantly expand the scope and utility of catalytic asymmetric metathesis and enhance our understanding of the mechanism of Mo-catalyzed metathesis. II. Enantioselective Synthesis through Catalytic Ring-Closing Metathesis. We will utilize the new Mo-based chiral complexes to synthesize chiral molecules from readily available achiral starting materials. We will develop reliable, catalytic and asymmetric methods for the synthesis of various carbo- and heterocycles, many of which bear quaternary carbon stereogenic centers (an example shown above). We will probe the utility of the new chiral Mo catalysts from part I, while carefully examining the validity of mechanistic models. III. Enantioselective Synthesis through Catalytic Ring-Opening Metathesis. Chiral Mo catalysts will be used in the development of asymmetric ring-opening metatheses as a new and unique catalytic enantioselective process. Recent preliminary data clearly indicate that our chiral Mo-based complexes are capable of effecting AROM with exceptional enantioselection. Both AROM followed by RCM, and AROM followed by intermolecular cross- metathesis, will be developed as efficient methods for catalytic enantioselective synthesis.

可靠的、催化的、选择性的(高区域和立体选择性)对映体选择性化学反应可以大大加快大规模生产和重要治疗药物的可获得性。这项建议概述了将导致各种新催化剂的设计、开发和表征的实验，这些催化剂可以高效和对映体选择性地实现不对称歧化反应。这里开发的催化剂在促进不对称歧化反应方面是独一无二的。此外，这些催化剂将被用于开发新的反应技术，提供任何其他金属催化或酶过程无法获得的产品。具体目标如下：一、新型手性、光学纯的钼基复分解催化剂的合成与开发。我们已经确定了几个手性钼配合物可以进行高对映选择性的歧化反应。这些手性络合物很容易进行空间和电子修饰。我们还证明了某些对映体选择性反应在特定的手性催化剂变种下操作效果最好，而其他转化则在相关类似物的情况下提供了最佳结果。我们将设计、合成和充分表征钼基手性化合物，以实现更广泛的化合物的对映选择性合成。这种多功能性将使我们能够找到特定底物的最佳匹配，显著扩大催化不对称复分解反应的范围和用途，并加深我们对钼催化复分解反应机理的理解。催化关环歧化反应的对映选择性合成。我们将利用新的钼基手性配合物，从现成的非手性起始材料合成手性分子。我们将开发可靠的、催化的和不对称的方法来合成各种碳环和杂环，其中许多都带有四元碳立体中心(如上图所示)。我们将从第一部分开始探索新型手性钼催化剂的用途，同时仔细检查机理模型的有效性。催化开环歧化反应的对映选择性合成手性钼催化剂将作为一种新的、独特的催化对映体选择性方法应用于不对称开环异构体的开发。最近的初步数据清楚地表明，我们的手性钼基络合物能够实现具有特殊对映体选择性的芳香族化合物。芳香族有机化合物和芳香族有机化合物以及分子间交叉复分解反应都将成为催化对映体选择性合成的有效方法。