Triazolium Salt Organocatalysis: Mechanistic Evaluation of Unusual Ortho-Substituent Effects on Deprotonation
Triazolium Salt Organocatalysis: Mechanistic Evaluation of Unusual Ortho-Substituent Effects on Deprotonation
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DOI：
10.3390/catal11091055
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发表时间：
2021-08
期刊：
影响因子：
3.9
通讯作者：
P. Quinn;Matthew S. Smith;Jiayun Zhu;David R. W. Hodgson;A. O’Donoghue
中科院分区：
文献类型：
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作者：
P. Quinn;Matthew S. Smith;Jiayun Zhu;David R. W. Hodgson;A. O’Donoghue
氮杂环卡宾的有机催化反应通常是通过前体唑鎓离子的去质子化形成活性亲核物种而引发的。取代基对去质子化的影响对催化效率有影响，并通过常用的唑鎓体系提供对一般催化机理的洞察。利用NMR动力学方法分析了三种邻位取代的N-芳基三唑盐的C（3）-H/D交换反应，测定了它们的log kex-pD曲线，从而详细分析了邻位取代基对去质子化的影响。这包括N-5-甲氧基吡啶-2-基三唑鎓盐7和二-邻-甲氧基和二-邻-异丙氧基苯基三唑鎓盐8和9，并且我们获得了额外的动力学数据以补充我们先前公开的N-吡啶-2-基三唑鎓盐6的分析。对于2-吡啶基三唑6和7，在酸性条件下观察到C（3）-H/D交换的新的酸催化。这些动力学数据进行了补充DFT分析的构象偏好6后N-质子化。C（3）去质子化机制涉及分子内一般碱去质子化的N（1）-氘代双阳离子三唑鎓盐的吡啶基氮是最符合数据。我们还报告kDO值（protofugalities）的氘代催化交换6-9。8和9的离原性是迄今为止N-芳基三唑系列中最低的值。
Organocatalysis by N-heterocyclic carbenes is normally initiated by the deprotonation of precursor azolium ions to form active nucleophilic species. Substituent effects on deprotonation have an impact on catalytic efficiency and provide insight into general catalytic mechanisms by commonly used azolium systems. Using an NMR kinetic method for the analysis of C(3)-H/D exchange, we determined log kex–pD profiles for three ortho-substituted N-aryl triazolium salts, which enables a detailed analysis of ortho-substituent effects on deprotonation. This includes N-5-methoxypyrid-2-yl triazolium salt 7 and di-ortho-methoxy and di-ortho-isopropoxyphenyl triazolium salts 8 and 9, and we acquired additional kinetic data to supplement our previously published analysis of N-pyrid-2-yl triazolium salt 6. For 2-pyridyl triazoliums 6 and 7, novel acid catalysis of C(3)-H/D exchange is observed under acidic conditions. These kinetic data were supplemented by DFT analyses of the conformational preferences of 6 upon N-protonation. A C(3) deprotonation mechanism involving intramolecular general base deprotonation by the pyridyl nitrogen of the N(1)-deuterated dicationic triazolium salt is most consistent with the data. We also report kDO values (protofugalities) for deuteroxide-catalyzed exchange for 6–9. The protofugalities for 8 and 9 are the lowest values to date in the N-aryl triazolium series.