Stereospecific 1,3-H Transfer of Indenols Proceeds via Persistent Ion-Pairs Anchored by NH•••π Interactions
Stereospecific 1,3-H Transfer of Indenols Proceeds via Persistent Ion-Pairs Anchored by NH•••π Interactions
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DOI：
10.1021/jacs.8b09874
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发表时间：
2018-12-05
影响因子：
15
通讯作者：
Paton, Robert S.
中科院分区：
文献类型：
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作者：
Ascough, David M. H.;Duarte, Fernanda;Paton, Robert S.
碱催化的芳基茚醇重排反应是一种罕见的[1，3]-氢原子转移的例子。该机制已被提出通过连续的[1，5]-sigmatropic位移进行，这发生在选择性意义上，避免了非手性中间体。使用量子化学的计算分析对这些建议提出了严重的质疑：这些途径具有巨大的激活障碍，并且与实验观察到的结果相反，它们压倒性地有利于外消旋产物。相反，我们建议，一个超面[1，3]-prototopic转变发生在一个两步的去质子化/reprotonation序列。15 kcal mol（-1）比以前提出的更有利于该机理。最重要的是，这也与立体声特异性相一致，因为重调在同一个π面上迅速发生。我们已经使用明确的溶剂化分子动力学研究的持久性和凝聚相动力学的中间离子对在这个反应中形成的。手性转移是特别有弹性的接触离子对的结果，通过静电吸引和临界NH中心点π相互作用保持在一起，这确保该物质即使在极性溶剂如DMSO和MeOH中也具有可观的寿命。
The base-catalyzed rearrangement of arylindenols is a rare example of a suprafacial [1,3]-hydrogen atom transfer. The mechanism has been proposed to proceed via sequential [1,5]-sigmatropic shifts, which occur in a selective sense and avoid an achiral intermediate. A computational analysis using quantum chemistry casts serious doubt on these suggestions: These pathways have enormous activation barriers, and in constrast to what is observed experimentally, they overwhelmingly favor a racemic product. Instead we propose that a suprafacial [1,3]-prototopic shift occurs in a two-step deprotonation/reprotonation sequence. This mechanism is favored by 15 kcal mol(-1) over that previously proposed. Most importantly, this is also consistent with stereo specificity since reprotonation occurs rapidly on the same pi-face. We have used explicitly solvated molecular dynamics studies to study the persistence and condensed-phase dynamics of the intermediate ion-pair formed in this reaction. Chirality transfer is the result of a particularly resilient contact ion-pair, held together by electrostatic attraction and a critical NH center dot center dot center dot pi interaction which ensures that this species has an appreciable lifetime even in polar solvents such as DMSO and MeOH.