Stereospecific 1,3-H Transfer of Indenols Proceeds via Persistent Ion-Pairs Anchored By NH···Pi Interactions

07 September 2018, Version 1
This content is an early or alternative research output and has not been peer-reviewed by Cambridge University Press at the time of posting.

Abstract

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 p-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···p interaction which ensures that this species has an appreciable lifetime even in polar solvents such as DMSO and MeOH.

Keywords

computational organic chemistry
molecular dynamics
ion-pairing
chirality transfer
DLPNO-CCSD(T)
mechanism
sigmatropic rearrangement
stereospecific

Supplementary materials

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PATON 13H TRANSFER SI
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