Stereospecific 1,3‑H Transfer of Indenols Proceeds via Persistent Ion-Pairs Anchored by NH···π Interactions

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 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.