A Cyclochiral Conformational Motif Constructed Using a Robust Hydrogen-Bonding Network

A novel conformational motif constructed
with a robust intramolecular
hydrogen-bonding (H-bonding) network was discovered. A pyrrolidine
derivative possessing four identical amide substituents at C(2) and
C(5) formed a strong intramolecular H-bonding network consisting of
all the amide groups. This conformation yielded a cyclochiral structure
with a handedness that depended on the directionality of the H-bonding
network. The most stable compound was isolated and applied to the
acylative kinetic resolution of secondary alcohol. The handedness
of the H-bonding network was biased by the presence of chiral substituents,
and the preferred direction could be switched under an external stimulus.
A structural analysis using NMR, X-ray crystallography, and theoretical
calculation techniques indicated that the conformation of the substituents
was highly ordered and depended on the directionality of the H-bonding
network.