Department of Chemistry, Sogang University, 35 Baekbeomro Mapogu, Seoul 04107, Korea.
Org Biomol Chem. 2021 May 19;19(19):4320-4326. doi: 10.1039/d1ob00129a.
α-Ketoamides are an important key functional group and have been used as versatile and valuable intermediates and synthons in a variety of functional group transformations. Synthetic methods for making aryl α-ketoamides as drug candidates have been greatly improved through metal-catalyzed aerobic oxidative amidations. However, the preparation of alkyl α-ketoamides through metal-catalyzed aerobic oxidative amidations has not been reported because generating α-ketoamides from aliphatic ketones with two α-carbons theoretically provides two distinct α-ketoamides. Our strategy is to activate the α-carbon by introducing an N-substituent at one of the two α-positions. The key to this strategy is how heterocyclic compounds such as triazoles and imidazoles affect the selectivity of the synthesis of the alkyl α-ketoamides. From this basic concept, and by optimizing the reaction and elucidating the mechanism of the synthesis of aryl α-ketoamides via a copper-catalyzed aerobic oxidative amidation, we prepared fourteen aliphatic α-ketoamides in high yields (48-84%).
α-酮酰胺是一个重要的关键官能团，已被用作各种官能团转化中的多功能且有价值的中间体和合成子。通过金属催化的有氧氧化酰胺化，已经极大地改进了用于制备芳基α-酮酰胺作为药物候选物的合成方法。然而，通过金属催化的有氧氧化酰胺化制备烷基α-酮酰胺尚未被报道，因为从具有两个α-碳的脂肪族酮生成α-酮酰胺理论上提供了两种不同的α-酮酰胺。我们的策略是通过在两个α-位之一引入 N-取代基来激活α-碳。该策略的关键在于杂环化合物（如三唑和咪唑）如何影响烷基α-酮酰胺合成的选择性。基于这一基本概念，并通过优化反应和阐明铜催化的有氧氧化酰胺化合成芳基α-酮酰胺的机理，我们以高收率（48-84%）制备了十四种脂肪族α-酮酰胺。
