Nabi Rifat N, Jarquin Kimberly A, Karmakar Anupam, Brunner Kyle E, Kim Daniel K
Department of Chemistry, Temple University, 1901 North 13th Street, Philadelphia, Pennsylvania, 19122, USA.
Chemistry. 2025 Jul 2;31(37):e202501613. doi: 10.1002/chem.202501613. Epub 2025 May 30.
Due to favourable pharmacological properties, the introduction of the fluorine atom into small molecules has become increasingly more common over the past few decades. In particular, the trifluoromethyl ketone group is of great interest due to its role as a carboxylic acid bioisostere. Recently, these fragments have been accessed via acyl radical equivalents. Herein, we disclose an unconventional intramolecular proton-coupled electron transfer activation of α-keto acids by photoredox catalysis to generate ketyl radicals toward accessing functionalizable lactones. These lactones serve as synthons for modular one-pot syntheses of trifluoromethyl ketones in a net dicarbofunctionalization of electron-rich olefins.
由于良好的药理学性质,在过去几十年中,将氟原子引入小分子变得越来越普遍。特别是,三氟甲基酮基团因其作为羧酸生物电子等排体的作用而备受关注。最近,这些片段已通过酰基自由基等价物获得。在此,我们披露了一种通过光氧化还原催化对α-酮酸进行非常规的分子内质子耦合电子转移活化,以生成酮基自由基来制备可官能化内酯的方法。这些内酯可作为合成子,用于在富电子烯烃的净双碳官能化反应中一锅法模块化合成三氟甲基酮。