Catalytic Enantioselective Olefin Metathesis Reactions

催化对映选择性烯烃复分解反应

• 批准号: 8026844
• 负责人: AMIR H HOVEYDA
• 金额: $ 52.46万
• 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 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8026844
• 关键词: Acids; Adrenergic Antagonists; Alkaloids; Alkenes; Amides; Biological; Carbon; Complex; Development; Ethers; Foundations; Goals; In Situ; Investigation; Ligands; Malignant Neoplasms; Metals; Methods; Organic Chemistry; Organic Synthesis; Preparation; Protocols documentation; Reaction; Research; Route; Staging; Therapeutic Agents; base; catalyst; cyclic amine; design; enol; frontier; programs; propadiene; quebrachamine; rhazinilam

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.

描述（由申请人提供）：本项目的目标是设计和开发新的催化剂，有效地促进对映选择性烯烃复分解反应。调查将集中在催化不对称方法，提供可用于合成生物活性分子的产品，不能很容易地通过任何现有的协议。设计和开发新的催化剂和催化不对称的有机合成方案是迫切的目标。有机化学中最重要且迅速出现的一类转化是催化烯烃复分解。容易获得的不饱和化合物通过闭环、开环或交叉复分解反应被转化成各种环状或非环状化合物。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体纯底物的反应不能容易地制备的分子的途径，部分原因是还不存在用于制备必需的对映体富集的底物的方法。我们将设计和开发新型的钼和钨基手性烯烃复分解催化剂，这些催化剂可以通过新的实用和有效的方法从容易获得的前体原位制备。我们将利用在本计划以前的研究中获得的机理理解，引入具有以下一个或多个独特属性的催化剂：立体金属中心，阳离子金属中心，单齿手性配体。在这个计划中开发的催化剂将用于开发新的和独特的催化烯烃复分解的非对映体和对映体选择性方法。催化不对称反应将被设计为提供合成通用的产品，如环胺和酰胺，这是否则难以获得;大多数产品含有一个全碳季立体中心，一个重要的和众所周知的难以获得的部分，发现在各种特殊的生物活性的分子。因此，生物活性生物碱quebrachamine（肾上腺素能阻滞剂）和rhazinilam（抗癌）的对映选择性全合成将通过独特的路线实现可行的新的手性催化剂和催化不对称方法在这个程序中开发。高效、实用和高度立体选择性的手性有机分子的制备方法是获得治疗药物的关键。设计和开发新的催化剂和催化不对称的有机合成方案是迫切的目标。易于制备和高活性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路线是该计划的目标，在医学研究中具有显着的意义。