CATALYTIC ENANTIOSELECTIVE OLEFIN METATHESIS REACTIONS

对映选择性化学反应是可靠的、催化的、选择性的（高区域和立体选择性），可以显著加快重要治疗药物的大规模生产和可用性。本提案概述了将导致设计、开发和表征各种新型催化剂的实验，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方面具有独特的能力。此外，这些催化剂将被用于开发新的反应技术，以提供其他任何金属催化或酶促过程无法获得的产物。本研究的主要目标是：1 .新型手性光学纯钼基复分解催化剂的合成与开发。我们已经确定了几种手性Mo配合物可以影响高度对映选择性的复合反应。这些手性配合物很容易进行立体和电子修饰。我们还证明了某些对映选择性反应在特定的手性催化剂上运行得最好，而其他转化在相关的类似物上提供了最佳结果。我们将设计、合成并充分表征钼基手性配合物，这些配合物可以影响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的范围和效用，增强我们对钼催化复分解机理的理解。2。催化合环复分解的对映选择性合成。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，其中许多具有季碳立体中心（如上图所示）。我们将从第一部分开始探索新的手性Mo催化剂的效用，同时仔细检查机理模型的有效性。3。开环复分解催化对映选择性合成。手性钼催化剂作为一种新的、独特的对映选择性催化反应，将用于不对称开环复合反应的发展。最近的初步数据清楚地表明，我们的手性mo基配合物能够通过特殊的对映体选择来影响AROM。AROM - RCM法和AROM -分子间交叉复分解法都将成为催化对映选择性合成的有效方法。

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.