Quantification and Theoretical Analysis of the Electrophilicities of Michael Acceptors
Quantification and Theoretical Analysis of the Electrophilicities of Michael Acceptors
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DOI：
10.1021/jacs.7b05106
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发表时间：
2017-09-27
影响因子：
15
通讯作者：
Mayr, Herbert
中科院分区：
文献类型：
--
作者：
Allgaeuer, Dominik S.;Jangra, Harish;Mayr, Herbert
为了量化常见迈克尔受体的亲电反应性，我们测量了单受体取代的乙烯 (H2C=CH-Acc, 1) 和苯乙烯 (PhCH=CH-Acc, 2) 与吡啶叶立德 3、锍叶立德 4 和磺酰基取代的氯甲基阴离子 5 的反应动力学。 57 的取代 将测量的二阶速率常数 (log k) 和之前报道的 3-5 的亲核试剂特异性参数 N 和 s(N) 转换为相关性 log k = s(N)(E + N) 使我们能够计算迈克尔受体 1 和 2 的 15 个新的经验亲电性参数 E。对这些不同类型的反应使用相同的参数 s(N)、N 和 E 表明所有反应都通过共同的速率决定进行 步骤，3-5对迈克尔受体的亲核攻击，形成无环中间体，随后环化分别得到四氢中氮茚（与3逐步1,3-偶极环加成）和环丙烷（与4和5）。由此确定的亲电性参数E可用于计算迈克尔受体1和2与已知N和s(N)的任何亲核试剂的反应速率。进行 DFT 计算以确认所建议的反应机制并阐明亲电反应性的起源。虽然亲电性 E 与 LUMO 能量和帕尔亲电指数 omega 相关性较差，但在实验观察到的 44 个迈克尔受体的亲电反应性与其计算的甲基阴离子亲和力之间发现了良好的相关性，特别是当通过应用 SMD 连续溶剂化模型考虑二甲亚砜的溶剂化时。由于考虑到这些相关性的迈克尔受体的结构多种多样，覆盖了 17 个数量级的反应性范围，因此我们认为甲基阴离子亲和力的计算是快速估计亲电反应性的首选方法。
In order to quantify the electrophilic reactivities of common Michael acceptors, we measured the kinetics of the reactions of monoacceptor-substituted ethylenes (H2C=CH-Acc, 1) and styrenes (PhCH=CH-Acc, 2) with pyridinium ylides 3, sulfonium ylide 4, and sulfonyl-substituted chloromethyl anion 5. Substitution of the 57 measured second-order rate constants (log k) and the previously reported nucleophile-specific parameters N and s(N) for 3-5 into the correlation log k = s(N)(E + N) allowed us to calculate 15 new empirical electrophilicity parameters E for Michael acceptors 1 and 2. The use of the same parameters s(N), N, and E for these different types of reactions shows that all reactions proceed via a common rate-determining step, the nudeophilic attack of 3-5 at the Michael acceptors with formation of acyclic intermediates, which subsequently cyclize to give tetrahydroindolizines (stepwise 1,3 -dipolar cycloadditions with 3) and cyclopropanes (with 4 and 5), respectively. The electrophilicity parameters E thus determined can be used to calculate the rates of the reactions of Michael acceptors 1 and 2 with any nucleophile of known N and s(N). DFT calculations were performed to confirm the suggested reaction mechanisms and to elucidate the origin of the electrophilic reactivities. While electrophilicities E correlate poorly with the LUMO energies and with Parr's electrophilicity index omega, good correlations were found between the experimentally observed electrophilic reactivities of 44 Michael acceptors and their calculated methyl anion affinities, particularly when solvation by dimethyl sulfoxide was taken into account by applying the SMD continuum solvation model. Because of the large structural variety of Michael acceptors considered for these correlations, which cover a reactivity range of 17 orders of magnitude, we consider the calculation of methyl anion affinities to be the method of choice for a rapid estimate of electrophilic reactivities.