Direct Catalytic Asymmetric Aldol Reaction

直接催化不对称羟醛反应

• 批准号: 6550584
• 负责人: JED L HUBBS
• 金额: $ 3.66万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-02 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6550584
• 关键词: aldehydes; analytical method; biochemistry; carbon; carbonyl compound; catalyst; chemical bond; chemical reaction; chemical synthesis; method development; molecular asymmetry; nitrogen; organometallic compounds; oxygen; postdoctoral investigator; silicon; stereochemistry

DESCRIPTION (provided by applicant): The aldol reaction has historically been one of the most important reactions for the synthesis of biologically active molecules, yet improvements in aldol reaction methods still need to be developed in order to provide shorter synthetic routes to these molecules. The objective of the proposed research is to establish a new method for catalytically forming carbon-carbon bonds using the aldol reaction. Specifically, the aim will be to couple the enolization of carbonyl compounds with their addition to aldehydes in a novel catalytic cycle. In this catalytic cycle, a labile silicon-nitrogen or silicon-oxygen bond will be cleaved to silylate a metal aldolate and simultaneously generate a base that can deprotonate a carbonyl compound. This method should overcome some of the disadvantages of other catalytic aldol reactions, which include the need to activate the carbonyl compound in a separate step and the lack of generality in these reactions. The ultimate goal of this research is to use this new catalytic reaction to induce asymmetry in the products. If successfully developed, such a method would facilitate the synthesis of complex biologically active compounds.

描述（由申请人提供）：羟醛反应历来是合成生物活性分子的最重要的反应之一，但仍需要开发羟醛反应方法的改进，以便为这些分子提供更短的合成路线。本研究的目的是建立一种利用羟醛反应催化形成碳-碳键的新方法。具体来说，目标是将羰基化合物的烯醇化与醛的加成在新型催化循环中耦合起来。在这个催化循环中，不稳定的硅-氮或硅-氧键将被裂解，使金属醛醇盐甲硅烷基化，同时产生可以使羰基化合物去质子化的碱。该方法应该克服其他催化羟醛反应的一些缺点，包括需要在单独的步骤中活化羰基化合物以及这些反应缺乏通用性。这项研究的最终目标是利用这种新的催化反应来诱导产物的不对称性。如果开发成功，这种方法将有助于复杂的生物活性化合物的合成。