Dipartimento di Chimica, Università di Torino, via P. Giuria 7, 10125, Torino, Italy.
Dipartimento di Farmacia-Scienze del Farmaco, Università di Bari Aldo Moro, Consorzio CINMPIS, Via E. Orabona 4, 70125, Bari, Italy.
Chemistry. 2021 Feb 5;27(8):2868-2874. doi: 10.1002/chem.202004840. Epub 2021 Jan 14.
We report that the nucleophilic acyl substitution reaction of aliphatic and (hetero)aromatic amides by organolithium reagents proceeds quickly (20 s reaction time), efficiently, and chemoselectively with a broad substrate scope in the environmentally responsible cyclopentyl methyl ether, at ambient temperature and under air, to provide ketones in up to 93 % yield with an effective suppression of the notorious over-addition reaction. Detailed DFT calculations and NMR investigations support the experimental results. The described methodology was proven to be amenable to scale-up and recyclability protocols. Contrasting classical procedures carried out under inert atmospheres, this work lays the foundation for a profound paradigm shift of the reactivity of carboxylic acid amides with organolithiums, with ketones being straightforwardly obtained by simply combining the reagents under aerobic conditions and with no need of using previously modified or pre-activated amides, as recommended.
我们报告说，在环境友好的环戊基甲醚中，在室温下、空气氛围中，通过有机锂试剂进行脂肪族和（杂）芳族酰胺的亲核酰基取代反应，具有快速（20 秒反应时间）、高效和化学选择性，底物适用范围广泛，可以高达 93%的收率得到酮，有效抑制了臭名昭著的过度加成反应。详细的 DFT 计算和 NMR 研究支持实验结果。所描述的方法被证明适用于放大和可回收性方案。与在惰性气氛下进行的经典方法形成对比，这项工作为羧酸酰胺与有机锂的反应性的深刻范式转变奠定了基础，酮可以通过简单地在有氧条件下组合试剂来直接获得，而无需使用以前推荐的改性或预激活的酰胺。
