Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
Angew Chem Int Ed Engl. 2022 Sep 5;61(36):e202208089. doi: 10.1002/anie.202208089. Epub 2022 Jul 25.
The direct C-H trifluoromethylation of arenes via a radical pathway has attracted considerable attention recently. However, a major challenge of C-H trifluoromethylation is the lack of site-selectivity on the phenyl ring especially para-selectivity. Herein we show a new strategy for para-selective C-H trifluoromethylation of benzamide derivatives using iminium activation. The reaction undergoes a radical-type nucleophilic substitution instead of a radical-type electrophilic substitution owing to iminium activation as a result of lowering the LUMO (lowest unoccupied molecular orbital). A wide range of substrates are compatible with this method giving almost exclusive para-trifluoromethylated products.
最近，通过自由基途径直接对芳烃进行三氟甲基化引起了相当大的关注。然而，C-H 三氟甲基化的一个主要挑战是苯环上缺乏位点选择性，特别是对位选择性。在此，我们展示了一种使用亚胺活化对苯甲酰胺衍生物进行对位选择性 C-H 三氟甲基化的新策略。由于亚胺活化降低了最低未占分子轨道 (LUMO)，反应通过自由基型亲核取代而不是自由基型亲电取代进行。由于亚胺活化，该方法适用于广泛的底物，几乎只得到对位三氟甲基化产物。
