化学
均分解
激进的
电泳剂
亲核细胞
光化学
亲核芳香族取代
正在离开组
亲电芳香族取代
放射分析
取代反应
亲核取代
芳基
药物化学
有机化学
催化作用
烷基
作者
Nick Y. Shin,Elaine Tsui,Adam Reinhold,Gregory D. Scholes,Matthew J. Bird,Robert R. Knowles
摘要
While heteroatom-centered radicals are understood to be highly electrophilic, their ability to serve as transient electron-withdrawing groups and facilitate polar reactions at distal sites has not been extensively developed. Here, we report a new strategy for the electronic activation of halophenols, wherein generation of a phenoxyl radical via formal homolysis of the aryl O-H bond enables direct nucleophilic aromatic substitution of the halide with carboxylate nucleophiles under mild conditions. Pulse radiolysis and transient absorption studies reveal that the neutral oxygen radical (O•) is indeed an extraordinarily strong electron-withdrawing group [σp-(O•) = 2.79 vs σp-(NO2) = 1.27]. Additional mechanistic and computational studies indicate that the key phenoxyl intermediate serves as an open-shell electron-withdrawing group in these reactions, lowering the barrier for nucleophilic substitution by more than 20 kcal/mol relative to the closed-shell phenol form of the substrate. By using radicals as transient activating groups, this homolysis-enabled electronic activation strategy provides a powerful platform to expand the scope of nucleophile-electrophile couplings and enable previously challenging transformations.
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