Catalytic Enantioselective Olefin Metathesis Reactions

催化对映选择性烯烃复分解反应

• 批准号: 7576752
• 负责人: AMIR H HOVEYDA
• 金额: $ 53.06万
• 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 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7576752
• 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(申请人提供)：该项目的目标是设计和开发能够有效促进对映选择性烯烃歧化反应的新型催化剂。研究将集中在催化不对称方法上，这种方法提供的产品可以用于合成生物活性分子，而现有的任何协议都不容易获得这些产品。设计和开发用于有机合成的新型催化剂和催化不对称协议是迫切需要实现的目标。催化烯烃歧化反应是有机化学中最重要、最迅速出现的一类转化反应。容易获得的不饱和化合物通过开环、开环或交叉歧化反应转化为多种环状或非环状化合物。不对称烯烃歧化反应提供了一种在非手性催化剂存在下不容易通过对映体纯底物反应制备分子的途径，部分原因是尚不存在制备所需的富含对映体底物的方法。我们将设计和开发新型的钼和钨基手性烯烃歧化催化剂，这些催化剂可以通过新的实用和高效的方法从容易获得的前体中原位制备。我们将利用在本计划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。该项目开发的催化剂将用于开发新的和独特的催化非对映和对映体选择性的烯烃歧化方法。催化不对称反应将被设计成合成多种产品，如环胺和酰胺，否则很难获得这些产品；大多数产品包含一个全碳四元立体中心，这是一种重要的、众所周知的难以获得的部分，存在于各种具有特殊生物活性的分子中。因此，本项目中开发的新型手性催化剂和催化不对称方法将通过独特的路线实现生物活性生物碱奎布拉明(肾上腺素受体阻滞剂)和雷克西兰(抗癌药物)的对映选择性全合成。高效、实用和高立体选择性的手性有机分子的制备方法对治疗药物的可用性至关重要。设计和开发用于有机合成的新型催化剂和催化不对称协议是迫切需要实现的目标。易于制备和高活性的手性烯烃歧化催化剂为合成含杂原子化合物提供了独特的路线，这是该计划的目标，在医学研究中具有重要意义。