Max-Planck-Institut für Kohlenforschung, Mülheim an der Ruhr, Germany.
University of Tartu, Institute of Chemistry, Tartu, Estonia.
Nat Chem. 2018 Aug;10(8):888-894. doi: 10.1038/s41557-018-0065-0. Epub 2018 Jul 9.
The chemical synthesis of organic molecules involves, at its very essence, the creation of carbon-carbon bonds. In this context, the aldol reaction is among the most important synthetic methods, and a wide variety of catalytic and stereoselective versions have been reported. However, aldolizations yielding tertiary aldols, which result from the reaction of an enolate with a ketone, are challenging and only a few catalytic asymmetric Mukaiyama aldol reactions with ketones as electrophiles have been described. These methods typically require relatively high catalyst loadings, deliver substandard enantioselectivity or need special reagents or additives. We now report extremely potent catalysts that readily enable the reaction of silyl ketene acetals with a diverse set of ketones to furnish the corresponding tertiary aldol products in excellent yields and enantioselectivities. Parts per million (ppm) levels of catalyst loadings can be routinely used and provide fast and quantitative product formation in high enantiopurity. In situ spectroscopic studies and acidity measurements suggest a silylium ion based, asymmetric counteranion-directed Lewis acid catalysis mechanism.
有机分子的化学合成从本质上涉及碳-碳键的形成。在这种情况下，羟醛缩合反应是最重要的合成方法之一，已经报道了许多催化和立体选择性的版本。然而，由烯醇化物与酮反应生成的三级羟醛缩合反应具有挑战性，只有少数催化不对称 Mukaiyama 羟醛反应用酮作为亲电试剂被描述。这些方法通常需要相对较高的催化剂负载量，提供的对映选择性较差，或者需要特殊的试剂或添加剂。我们现在报告了非常有效的催化剂，这些催化剂可以使硅基烯酮缩醛与各种酮反应，以优异的收率和对映选择性得到相应的三级羟醛缩合产物。ppm 级别的催化剂负载量可以常规使用，并在高对映纯度下快速定量形成产物。原位光谱研究和酸度测量表明，这是一种基于硅鎓离子的、不对称抗衡阴离子导向的路易斯酸催化机制。
