Kazim Muhammad, Feng Zhitao, Vemulapalli Srini, Siegler Maxime A, Chopra Anant, Minh Nguyen Phuong, Gargiulo Holl Maxwell, Guan Liangyu, Dudding Travis, Tantillo Dean J, Lectka Thomas
Department of Chemistry, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218, USA.
Current address: Chemical Biology Laboratory, National Cancer Institute, Frederick, MD 21702, USA.
Chemistry. 2023 Sep 15;29(52):e202301550. doi: 10.1002/chem.202301550. Epub 2023 Aug 13.
We report a detailed experimental and theoretical analysis of through-space arene activation with halogens, tetrazoles and achiral esters and amides. Contrary to previously assumed direct activation through σ-complex stabilization, our results suggest that these reactions proceed by a relay mechanism wherein the lone pair-containing activators form exothermic π-complexes with electrophilic nitronium ion before transferring it to the probe ring through low barrier transition states. Noncovalent interactions (NCI) plots and Quantum Theory of Atoms in Molecules (QTAIM) analyses depict favorable interactions between the Lewis base (LB) and the nitronium ion in the precomplexes and the transition states, suggesting directing group participation throughout the mechanism. The regioselectivity of substitution also comports with a relay mechanism. In all, these data pave the way for an alternate platform of electrophilic aromatic substitution (EAS) reactions.
我们报告了关于通过空间用卤素、四唑以及非手性酯和酰胺对芳烃进行活化的详细实验和理论分析。与之前所认为的通过σ-络合物稳定化实现直接活化相反，我们的结果表明这些反应通过一种接力机制进行，其中含孤对电子的活化剂先与亲电硝鎓离子形成放热的π-络合物，然后通过低势垒过渡态将其转移至探针环上。非共价相互作用（NCI）图和分子中原子的量子理论（QTAIM）分析描绘了预络合物和过渡态中路易斯碱（LB）与硝鎓离子之间的有利相互作用，表明导向基团在整个机制中都有参与。取代反应的区域选择性也与接力机制相符。总之，这些数据为亲电芳香取代（EAS）反应的另一种平台铺平了道路。
