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，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疗法的大规模生产和可用性。 该建议概述了实验，这些实验将导致各种新催化剂的设计，开发和表征，这些新催化剂可以以高效率和对映选择性影响不对称的分解反应。 这里开发的催化剂在促进不对称的分离的能力方面是独一无二的。 此外，这些催化剂将被用来开发新的反应技术，这些技术提供了其他任何其他金属催化或酶促过程无法使用的产品。 将实现以下特定目标：I。新手性，光学纯Mo的元理解催化剂的合成和开发。 我们已经确定，几种手性mo络合物可以影响高度对映选择性的分解反应。 这些手性配合物很容易将自己带入空间和电子修饰。 我们还证明，某些对映选择性反应与手性催化剂的特定变体一起起作用，而其他转换则具有相关类似物的最佳结果。 我们将设计，合成和完全表征基于MO的手性配合物，这些配合物可以影响更广泛的化合物范围的对映选择性合成。 这种多功能性将使我们能够为特定的底物找到“最佳匹配”，从而显着扩大催化不对称元的范围和实用性，并增强我们对Mo催化元理解机制的理解。 ii。通过催化环的归化来合成对映选择性合成。 我们将利用新的基于MO的手性配合物来合成随时可用的Athiral起始材料的手性分子。 我们将开发可靠，催化和不对称方法，用于合成各种碳和异环的合成，其中许多都带有第四纪碳立体中心（上面显示的示例）。我们将从第I部分探测新的手性MO催化剂的实用性，同时仔细检查机械模型的有效性。 iii。通过催化环的元件促成合成的对映选择性合成。 手性mo催化剂将用于开发不对称环的元素作为一种新的且独特的催化对映选择过程。 最近的初步数据清楚地表明，我们的基于手性的MO络合物能够通过特殊的对映选择来影响芳香。 芳香含量为rCM，芳香和分子间跨隔离，将开发为有效的催化对映选择性合成的方法。