Chiral Phosphoric Acid Catalyzed Enantioselective Ring Expansion Reaction of 1,3-Dithiane Derivatives: Case Study of the Nature of Ion-Pairing Interaction

Chiral counterion
controlled asymmetric catalysis via an ion-pairing
interaction has attracted immense attention in recent years. Despite
a number of successful studies, the mechanistic elucidation of the
stereocontrolling element in the ion-pairing interaction is rarely
conducted and hence its nature is still far from being well understood.
Herein we report an in-depth mechanistic case study of a newly developed
enantioselective ring expansion reaction of 1,3-dithiane derivatives
catalyzed by chiral phosphoric acid (CPA). An unprecedented enantioselective
1,2-sulfur rearrangement/stereospecific nucleophilic addition sequence
was proven to be the stereoselective pathway. More importantly, by
thorough investigation of the intrinsic nature of the stereospecific
nucleophilic addition to the cationic thionium intermediate, we discovered
that the key interaction in this process is the nonclassical C–H···O
hydrogen bonds formed between the conjugate base of the CPA catalyst
and the cationic intermediate. These C–H···O
hydrogen bonds not only bind the catalyst to the substrates to form
energetically favored states throughout the overall processes but
also firmly maintain the relative positions of these fragments as
the “fixed” contact ion pair to sustain the chiral information
generated at the initial sulfur rearrangement step. This mechanistic
case study provides a very clear understanding of the nature of the
ion-pairing interaction in organocatalysis. The conclusion encourages
the further development of the research field with the focus to design
new organocatalysts and cultivate novel organocatalytic transformations.