CATALYTIC ENANTIOSELECTIVE OLEFIN METATHESIS REACTIONS

催化对映选择性烯烃复分解反应

• 批准号: 6520036
• 负责人: RICHARD R SCHROCK
• 金额: $ 43.58万
• 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/6520036
• 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、催化、选择性（高区域和立体选择性）的对映选择性化学反应可以显着加快重要治疗药物的大规模生产和可用性。 该提案概述了各种实验，这些实验将导致各种新型催化剂的设计、开发和表征，这些催化剂可以高效和对映选择性地实现不对称复分解反应。 这里开发的催化剂具有独特的促进不对称复分解的能力。 此外，这些催化剂将用于开发新的反应技术，提供任何其他金属催化或酶促过程无法获得的产品。 将追求以下具体目标： I.新型手性、光学纯钼基复分解催化剂的合成和开发。 我们已经发现几种手性钼配合物可以实现高度对映选择性的复分解反应。 这些手性配合物很容易进行空间和电子修饰。 我们还证明，某些对映选择性反应在手性催化剂的特定变体下效果最佳，而其他转化则在相关类似物下提供最佳结果。 我们将设计、合成并全面表征钼基手性配合物，这些配合物可以实现更广泛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”，显着扩大催化不对称复分解的范围和效用，并增强我们对钼催化复分解机制的理解。二.通过催化闭环复分解进行对映选择性合成。 我们将利用新型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和不对称方法来合成各种碳环和杂环，其中许多带有季碳立体中心（如上所示的示例）。我们将探讨第一部分中新型手性钼催化剂的实用性，同时仔细检查机械模型的有效性。 三．通过催化开环复分解进行对映选择性合成。 手性Mo催化剂将用于开发不对称开环复分解作为一种新的、独特的催化对映选择性过程。 最近的初步数据清楚地表明，我们的手性钼基配合物能够以优异的对映选择影响 AROM。 AROM 后 RCM 和 AROM 后分子间交叉复分解都将被开发为催化对映选择性合成的有效方法。