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.