Laboratory of Organic Chemistry ETH Zürich, Vladimir-Prelog-Weg 3, 8093, Zürich, Switzerland.
Chemistry. 2021 Dec 15;27(70):17559-17564. doi: 10.1002/chem.202103197. Epub 2021 Oct 13.
The combination of a peptide catalyst and a gold catalyst is presented for enantioselective addition reactions between branched aldehydes and allenamides. The two catalysts act in concert to provide γ,δ-enamide aldehydes bearing a fully substituted, benzylic stereogenic center - a structural motif common in many natural products and therapeutically active compounds - with good yields and enantioselectivities. The reaction tolerates a variety of alkyl and alkoxy substituted aldehydes and the products can be elaborated into several chiral building blocks bearing either 1,4- or 1,5- functional group relationships. Mechanistic studies showed that the conformational features of the peptide are important for both the catalytic efficiency and stereochemistry, while a balance of acid/base additives is key for ensuring formation of the desired product over undesired side reactions.
本文介绍了一种肽催化剂和金催化剂的组合，用于支链醛和烯酰胺之间的对映选择性加成反应。这两种催化剂协同作用，提供了具有完全取代的苄基立体中心的γ,δ-烯酰胺醛 - 这是许多天然产物和治疗活性化合物中常见的结构基序 - 具有良好的收率和对映选择性。该反应可耐受各种烷基和烷氧基取代的醛，并且产物可以被修饰成几个具有 1,4-或 1,5-官能团关系的手性构建块。机理研究表明，肽的构象特征对催化效率和立体化学都很重要，而酸碱添加剂的平衡对于确保形成所需产物而不是不希望的副反应是关键。
