Through-Space Activation Can Override Substituent Effects in Electrophilic Aromatic Substitution
Through-Space Activation Can Override Substituent Effects in Electrophilic Aromatic Substitution
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DOI：
10.1021/jacs.7b09792
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发表时间：
2017-10-25
影响因子：
15
通讯作者：
Lectka, Thomas
中科院分区：
文献类型：
--
作者：
Guan, Liangyu;Holl, Maxwell Gargiulo;Lectka, Thomas
亲电芳香族取代反应是化学中最重要的一类反应。EAS的“铁律”之一是富电子的芳香环与合适的亲电体的反应速度比贫电子的环更快。在这份报告中，我们提出了独特的例子，缺乏电子的芳烃，而不是进行优先取代分子内竞争与更多的电子丰富的环。这些结果是通过利用迄今未知的氢键OH-芳烃相互作用的倾向来切换到替代的Ho-芳烃相互作用以提供活化而实现的。在极端情况下，这种穿过空间的环芳烃活化被证明克服了三氟甲基取代基的失活效应，使另外一个高度缺电子的环成为竞争实验中排他性反应的位置。此外，Ho-芳烃的活化促进了在未活化的“对照”环经历单溴化前日益缺乏电子的芳烃的四溴化反应。我们希望这些结果将有助于阐明生物相互作用，并为芳环的亲电取代提供新的策略。
Electrophilic aromatic substitution (EAS) represents one of the most important classes of reactions in all of chemistry. One of the "iron laws" of EAS is that an electron-rich aromatic ring will react more rapidly than an electron-poor ring with suitable electrophiles. In this report, we present unique examples of electron-deficient arenes instead undergoing preferential substitution in intramolecular competition with more electron-rich rings. These results were made possible by exploiting the heretofore unknown propensity of a hydrogen-bonding OH-arene interaction to switch to the alternative HO-arene interaction in order to provide activation. In an extreme case, this through-space HO-arene activation is demonstrated to overcome the deactivating effect of a trifluoromethyl substituent, making an otherwise highly electron-deficient ring the site of exclusive reactivity in competition experiments. Additionally, the HO-arene activation promotes tetrabromination of an increasingly more electron-deficient arene before the unactivated "control" ring undergoes monobromination. It is our hope that these results will shed light on biological interactions as well as provide new strategies for the electrophilic substitution of aromatic rings.