Direct Catalytic Asymmetric Aldol Reaction

描述(申请人提供)：Aldol反应历来是合成生物活性分子的最重要的反应之一，但Aldol反应方法的改进仍需开发，以便为这些分子提供更短的合成路线。这项研究的目标是建立一种利用Aldol反应催化形成碳-碳键的新方法。具体地说，目标将是在一个新的催化循环中将羰基化合物的烯醇化与它们与醛的加成结合起来。在这个催化循环中，一个不稳定的硅-氮或硅-氧键将被裂解，以使金属醛酸盐硅化，同时生成可以使羰基化合物去质子化的碱。这种方法应该克服了其他催化羟醛反应的一些缺点，包括需要在单独的步骤中激活羰基化合物，以及这些反应缺乏通用性。这项研究的最终目的是利用这种新的催化反应来诱导产物中的不对称。如果开发成功，这种方法将有助于合成复杂的生物活性化合物。

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.