Catalytic Enantioselective Olefin Metathesis Reactions

描述(申请人提供)：烯烃歧化反应以清洁和有效的方式将相对简单的烯烃底物转化为复杂的不对称化合物，并已被证明消除了目标有机分子合成中的许多步骤。因此，烯烃歧化反应在合成具有医学和生物意义的分子方面具有相当大的兴趣。有了更有效和更有选择性的反应和催化剂，可以更容易和更具成本效益的方式向公众提供治疗候选药物。 该计划的主要目标是设计、合成、表征和探索各种新型的不对称钼和钨基烯烃歧化催化剂。此外，这些新型手性催化剂将被用于进行独特的不对称C-C键形成反应，这是合成有机化学家非常感兴趣的。将特别强调那些导致产物的形成的反应，而这些产物不能通过任何现有的催化或酶路线轻易制备。感兴趣的反应包括不对称闭环反应、开环反应和交叉易位反应。在许多情况下，新开发的反应的实用性将通过应用于制备具有生物学意义的分子来展示。 从拟议的研究中产生的催化剂、方法和概念将使化学家能够更有效、更可靠地以高度对映体选择性的方式获得更广泛的生物感兴趣的分子。

DESCRIPTION (provided by applicant): Olefin metathesis converts relatively simple olefinic substrates to complex asymmetric compounds in a clean and efficient manner, and has been shown to eliminate many steps in a synthesis of a target organic molecule. Olefin metathesis is thus of considerable interest in the synthesis of medicinally and biologically significant molecules. With more efficient and selective reactions and catalysts available, therapeutic candidates can be made available to the public more readily and in a more cost effective manner. The main objectives of this program involve the design, synthesis, characterization, and mechanistic exploration of a wide variety of new asymmetric molybdenum- and tungsten-based olefin metathesis catalysts. In addition, these novel chiral catalysts will be used to carry out unique enantioselective C-C bond forming reactions of significant interest to synthetic organic chemists. Particular emphasis will be placed on reactions that lead to the formation of products that cannot be prepared easily through any of the available catalytic or enzymatic routes. Among the reactions of interest will be asymmetric ring-closing, ring-opening, and cross metathesis reactions. In a number of cases the utility of the newly developed reactions will be demonstrated through application to the preparation of biologically significant molecules. The catalysts, methods and concepts that emerge from the proposed studies will allow chemists to access a wider range of molecules of biological interest more efficiently, reliably, and in a highly enantioselective fashion.