Catalytic Enantioselective Olefin Metathesis Reactions

描述（申请人提供）：该项目的目标是设计和开发有效促进对映选择性烯烃复分解反应的新型催化剂。研究将集中在催化不对称方法上，这种方法提供的产物可用于合成生物活性分子，并且不容易通过任何现有方案获得。设计和开发新的催化剂和催化不对称协议有机合成是迫切的目标。有机化学中最重要和迅速出现的转化类型之一是催化烯烃复分解。容易得到的不饱和化合物，通过合环、开环或交叉复合反应，转化为各种环或无环化合物。不对称烯烃复分解提供了在非手性催化剂存在下，通过对映异构纯底物的反应无法轻易制备分子的途径，部分原因是制备必要的对映异构富集底物的方法尚不存在。我们将设计和开发新型的Mo基和w基手性烯烃分解催化剂，这些催化剂可以用新的实用和有效的方法从容易获得的前体中原位制备。我们将利用在本项目之前的研究中获得的机理理解，介绍具有以下一种或多种独特属性的催化剂：立体金属中心，阳离子金属中心，单齿手性配体。本项目开发的催化剂将用于开发新的独特的非映对和对映选择性烯烃复分解方法。催化不对称反应将被设计成合成多用途产品，如环胺和酰胺，否则难以获得；大多数产物含有一个全碳的四元立体中心，这是一个重要的，众所周知的难以接近的部分，存在于各种具有特殊生物活性的分子中。因此，本项目开发的新型手性催化剂和催化不对称方法将通过独特的途径实现生物活性生物碱喹克拉明（肾上腺素能阻滞剂）和拉昔尼兰（抗癌药物）的对映选择性全合成。制备手性有机分子的高效、实用和高度立体选择性的方法对治疗药物的可用性至关重要。设计和开发新的催化剂和催化不对称协议有机合成是迫切的目标。制备简单、活性高的手性烯烃复分解催化剂，为含杂原子化合物的合成提供独特的途径，是本项目的目标，在医药研究中具有重要意义。

DESCRIPTION (provided by applicant): The goal of this project is the design and development of new catalysts that efficiently promote enantioselective olefins metathesis reactions. Investigations will be focused on catalytic asymmetric methods that deliver products that can be used in the synthesis of biologically active molecules and cannot be easily accessed by any existing protocols. Design and development of new catalysts and catalytic asymmetric protocols for organic synthesis are compelling objectives. One of the most important and rapidly emerging classes of transformations in organic chemistry is catalytic olefin metathesis. Readily available unsaturated compounds, through ring-closing, ring-opening or cross-metathesis reactions, are converted into a wide range of cyclic or acyclic compounds. Asymmetric olefin metathesis provides access to molecules that cannot be easily prepared by reactions of enantiomerically pure substrates in the presence of achiral catalysts, partly because methods for preparation of the requisite enantiomerically enriched substrates do not yet exist. We will design and develop new classes of Mo- and W-based chiral olefin metathesis catalysts that can be prepared in situ by new practical and efficient methods from easily accessible precursors. We will utilize the mechanistic understanding, obtained during previous studies in this program, to introduce catalysts with one or more of the following unique attributes: stereogenic metal center, cationic metal center, monodentate chiral ligand. The catalysts developed in this program will be utilized in the development of new and unique catalytic diastereo- and enantioselective methods in olefin metathesis. Catalytic asymmetric reactions will be designed that deliver synthetically versatile products, such as cyclic amines and amides, which are otherwise difficult to access; the majority of products contain an all-carbon quaternary stereogenic center, an important and notoriously difficult-to-access moiety that is found in a variety of molecules of exceptional biological activity. Enantioselective total synthesis of biologically active alkaloids quebrachamine (adrenergic blocker) and rhazinilam (anti-cancer) will thus be accomplished through unique routes rendered feasible by the new chiral catalysts and catalytic asymmetric methods developed in this program. Efficient, practical and highly stereoselective methods for preparation of chiral organic molecules are critical to the availability of therapeutic agents. Design and development of new catalysts and catalytic asymmetric protocols for organic synthesis are compelling objectives. Easily prepared and highly active chiral olefin metathesis catalysts that furnish unique routes for the synthesis of heteroatom-containing compounds are the goals of this program and of notable significance in medicinal research.