Catalytic Enantioselective Olefin Metathesis Reactions

催化对映选择性烯烃复分解反应

基本信息

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
项目类别：
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

项目摘要

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）：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，这些方法提供的产品可用于合成生物活性分子，并且无法通过任何现有协议轻松获得。设计和开发用于有机合成的新型催化剂和催化不对称方案是令人瞩目的目标。有机化学中最重要且快速新兴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，被转化为各种环状或无环化合物。不对称烯烃复分解提供了获得分子的途径，这些分子在非手性催化剂存在下无法通过对映体纯底物的反应轻松制备，部分原因是制备所需的对映体富集底物的方法尚不存在。我们将设计和开发新型钼基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且有效的方法从易于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，引入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烯烃复分解中新型、独特的催化非对映选择性和对映选择性方法。催化不对称反应将被设计为提供合成多功能产品，例如环胺和酰胺，否则很难获得这些产品；大多数产品都含有全碳四元立构中心，这是一个重要且众所周知难以获得的部分，存在于各种具有特殊生物活性的分子中。因此，生物活性生物碱克布拉查明（肾上腺素能阻滞剂）和Rhazinilam（抗癌）的对映选择性全合成将通过本项目中开发的新型手性催化剂和催化不对称方法实现的独特路线来完成。高效、实用和高度立体选择性的手性有机分子制备方法对于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方案是令人瞩目的目标。易于制备且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途径是该项目的目标，并且在医学研究中具有显着的意义。