配体促进的 Pd(II)催化游离脂肪族酸的β-亚甲基 C(sp)-H 芳基化反应。
Ligand-Enabled Pd(II)-Catalyzed β-Methylene C(sp)-H Arylation of Free Aliphatic Acids.
机构信息
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
出版信息
J Am Chem Soc. 2022 Nov 16;144(45):20550-20553. doi: 10.1021/jacs.2c09205. Epub 2022 Nov 7.
Abstract
Ligand development has enabled rapid advances in Pd(II)-catalyzed β-methyl C(sp)-H activation of free carboxylic acids. However, there are only a handful of reports of free-acid-directed β-methylene C(sp)-H activation, all of which are limited to intramolecular reactions. Herein, we report the first Pd(II)-catalyzed intermolecular β-methylene C(sp)-H arylation of free aliphatic acids, which is enabled by bidentate pyridine-pyridone ligands. The bite angle of this ligand has been discovered to play a key role in promoting β-methylene C-H activation of free carboxylic acid. This new transformation provides a disconnection for alkylation of arenes with simple aliphatic acids. A variety of free aliphatic acids, including the antiasthmatic drug seratrodast, were compatible with the reported protocol.
摘要
配体的发展使得钯（II）催化的游离羧酸的β-甲基 C(sp)-H 活化取得了快速进展。然而，只有少数关于游离酸导向的β-亚甲基 C(sp)-H 活化的报道，所有这些都仅限于分子内反应。在此，我们报告了首例钯（II）催化的游离脂肪族羧酸的分子间β-亚甲基 C(sp)-H 芳基化反应，该反应是由双齿吡啶-吡啶酮配体实现的。我们发现该配体的咬合角度在促进游离羧酸的β-亚甲基 C-H 活化方面起着关键作用。这种新的转化为芳烃与简单脂肪族酸的烷基化提供了一种断开键。各种游离脂肪酸，包括抗哮喘药物色甘酸钠，都与报道的方案兼容。
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