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Updated: Jan 30, 2026

A Micropatterning Assay for Measuring Cell Chirality
Published on: March 11, 2022
Hydrogen-Bond-Enabled Dynamic Kinetic Resolution of Axially Chiral Amides Mediated by a Chiral Counterion
Alison J Fugard1, Antti S K Lahdenperä1, Jaqueline S J Tan1
1Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.
Abstract:
Non-biaryl atropisomers are valuable in medicine, materials, and catalysis, but their enantioselective synthesis remains a challenge. Herein, a counterion-mediated O-alkylation method for the generation of atropisomeric amides with an er up to 99:1 is outlined. This dynamic kinetic resolution is enabled by the observation that the rate of racemization of atropisomeric naphthamides is significantly increased by the presence of an intramolecular O-H⋅⋅⋅NCO hydrogen bond. Upon O-alkylation of the H-bond donor, the barrier to rotation is significantly increased. Quantum calculations demonstrate that the intramolecular H-bond reduces the rotational barrier about the aryl-amide bond, stabilizing the planar transition state for racemization by approximately 40 kJ mol-1 , thereby facilitating the observed dynamic kinetic resolution.
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