Substituent Effects on Oxidation-Induced Formation of Quinone Methides from Arylboronic Ester Precursors
Substituent Effects on Oxidation-Induced Formation of Quinone Methides from Arylboronic Ester Precursors
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DOI：
10.1002/chem.201300539
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发表时间：
2013-07-01
影响因子：
4.3
通讯作者：
Peng, Xiaohua
中科院分区：
文献类型：
--
作者：
Cao, Sheng;Christiansen, Robin;Peng, Xiaohua
合成了一系列含有不同芳香取代基和不同苄基离去基团（Br或N+ Me 3Br-）的芳基硼酸酯。研究了取代基对它们与H_2O_2反应及醌甲基化反应的影响。NMR光谱和乙基乙烯基醚（EVE）捕获实验，分别用于确定反应机理和QM的形成。在硼酸酯的氧化裂解过程中不产生QM，而是在生理条件下通过随后的苯酚产物转化产生QM。氧化脱硼是促进吸电子取代基，如芳香族F，NO2，或苄基N+ Me 3Br-，而电子给取代基或更好的离去基团有利于QM的生成。含有芳香族CH 3或OMe基团或良好离去基团（Br）的化合物在生理条件下有效地产生QM。最后，通过Hammett作图建立了芳基硼酸酯的结构与活性之间的定量关系。芳基硼酸/酯的反应性和QM形成的抑制或促进现在可以可预测地调节。这种调整很重要，因为某些应用程序可能会受益，而其他应用程序可能会受到QM生成的限制。
A series of arylboronic esters containing different aromatic substituents and various benzylic leaving groups (Br or N+Me3Br-) have been synthesized. The substituent effects on their reactivity with H2O2 and formation of quinone methide (QM) have been investigated. NMR spectroscopy and ethyl vinyl ether (EVE) trapping experiments were used to determine the reaction mechanism and QM formation, respectively. QMs were not generated during oxidative cleavage of the boronic esters but by subsequent transformation of the phenol products under physiological conditions. The oxidative deboronation is facilitated by electron-withdrawing substituents, such as aromatic F, NO2, or benzylic N+Me3Br-, whereas electron-donating substituents or a better leaving group favor QM generation. Compounds containing an aromatic CH3 or OMe group, or a good leaving group (Br), efficiently generate QMs under physiological conditions. Finally, a quantitative relationship between the structure and activity has been established for the arylboronic esters by using a Hammett plot. The reactivity of the arylboronic acids/esters and the inhibition or facilitation of QM formation can now be predictably adjusted. This adjustment is important as some applications may benefit and others may be limited by QM generation.