Ascough David M H, Duarte Fernanda, Paton Robert S
Chemistry Research Laboratory , University of Oxford , 12 Mansfield Road , Oxford OX1 3TA , United Kingdom.
Department of Chemistry , Colorado State University , Fort Collins , Colorado 80523 , United States.
J Am Chem Soc. 2018 Dec 5;140(48):16740-16748. doi: 10.1021/jacs.8b09874. Epub 2018 Nov 21.
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 over that previously proposed. Most importantly, this is also consistent with stereospecificity since reprotonation occurs rapidly on the same π-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···π interaction which ensures that this species has an appreciable lifetime even in polar solvents such as DMSO and MeOH.
芳基茚醇的碱催化重排是[1,3]-氢原子迁移同面迁移的一个罕见例子。其机理被认为是通过连续的[1,5]-σ迁移进行的，这种迁移具有选择性，且避免了非手性中间体的产生。一项使用量子化学的计算分析对这些观点提出了严重质疑：这些途径具有巨大的活化能垒，并且与实验观察结果相反，它们绝大多数情况下更倾向于生成外消旋产物。相反，我们提出同面[1,3]-质子迁移在两步去质子化/再质子化序列中发生。该机理比之前提出的机理更有利，优势为15千卡/摩尔。最重要的是，这也与立体专一性相符，因为再质子化在同一π面上快速发生。我们使用了显式溶剂化分子动力学研究来研究该反应中形成的中间体离子对的持久性和凝聚相动力学。手性转移是由一个特别稳定的接触离子对导致的，该离子对通过静电引力和关键的N-H···π相互作用结合在一起，这确保了即使在二甲基亚砜和甲醇等极性溶剂中，该物种也有可观的寿命。
