Graduate School of Pharmaceutical Sciences, Kyushu University, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
J Am Chem Soc. 2020 Mar 4;142(9):4517-4524. doi: 10.1021/jacs.0c00727. Epub 2020 Feb 24.
We developed a chemoselective catalytic activation of carboxylic acid for a 1e radical process. α-Oxidation of a variety of carboxylic acids, which preferentially undergo undesired decarboxylation under radical conditions, proceeded efficiently under the optimized conditions. Chemoselective enolization of carboxylic acid was also achieved even in the presence of more acidic carbonyls. Extensive mechanistic studies revealed that the cooperative actions of iron species and alkali metal ions derived from 4 Å molecular sieves substantially facilitated the enolization. For the first time, catalytic enolization of unprotected carboxylic acid was achieved without external addition of stoichiometric amounts of Brønsted base. The formed redox-active heterobimetallic enediolate efficiently coupled with free radical TEMPO, providing synthetically useful α-hydroxy and keto acid derivatives.
我们开发了一种羧酸的选择性催化活化方法，用于 1e 自由基过程。在优化条件下，各种羧酸的α-氧化反应能够高效进行，而这些羧酸在自由基条件下优先发生不希望的脱羧反应。即使存在更酸性的羰基化合物，羧酸的选择性烯醇化也能实现。广泛的机理研究表明，铁物种和 4 Å 分子筛衍生的碱金属离子的协同作用极大地促进了烯醇化。首次实现了无需外加化学计量的布朗斯台德碱即可催化未保护羧酸的烯醇化。形成的氧化还原活性杂双金属烯二酮与自由基 TEMPO 有效偶联，提供了具有合成用途的α-羟基和酮酸衍生物。
