CATALYTIC ENANTIOSELECTIVE OLEFIN METATHESIS REACTIONS

催化对映选择性烯烃复分解反应

• 批准号: 6697235
• 负责人: RICHARD R SCHROCK
• 金额: $ 4.56万
• 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/6697235
• 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著加快重要治疗剂的大规模生产和可用性。 该提案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选择性地影响不对称复分解反应。 这里开发的催化剂在促进不对称复分解的能力方面是独特的。 此外，这些催化剂将被用于开发新的反应技术，这些技术提供了通过任何其他金属催化或酶促过程无法获得的产物。 具体目标如下：新型手性光学纯钼基复分解催化剂的合成与开发。 我们已经发现，几个手性钼配合物可以影响高度对映选择性的复分解反应。 这些手性配合物容易使它们自身进行空间和电子修饰。 我们还证明了某些对映选择性反应最好使用手性催化剂的特定变体，而其他转化则使用相关类似物提供最佳结果。 我们将设计，合成和充分表征钼基手性配合物，可以影响更广泛的化合物的对映选择性合成。 这样的多功能性将使我们能够找到一个“最佳匹配”的特定底物，显着扩大的范围和效用的催化不对称复分解，并提高我们的理解的钼催化复分解的机制。二.通过催化闭环置换的对映选择性合成。 我们将利用新的钼基手性配合物，从容易获得的非手性起始原料合成手性分子。 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，其中许多具有季碳立体中心（如上所示的一个例子）。我们将探讨第一部分的新手性钼催化剂的效用，同时仔细研究的有效性的机制模型。 三.催化开环复分解反应的对映选择性合成。 手性钼催化剂作为一种新型的、独特的催化对映体选择性反应，将被用于不对称开环复分解反应的研究。 最近的初步数据清楚地表明，我们的手性钼基配合物能够影响AROM与特殊的对映体选择性。 无论是AROM后的RCM，和AROM后的分子间交叉复分解，将被开发为催化不对称选择性合成的有效方法。