Selectivity and Enantiomeric Resolution in Inclusion Chemistry: A Systematic Study of Chiral Discrimination through Crystallization

The mechanism of enantiomeric resolution of 2-butylamine has been elucidated by employing a chiral host which enclathrated (R)- and (S)-2-butylamine in different proportions. We first measured the selectivity curve for a mixture of pyridine and morpholine, whose proportions in the crystals were determined by the refinement of single crystal X-ray structure determination and independently by 1H NMR spectroscopy and showed that X-ray diffraction is a robust and accurate method for determining the composition of mixed guests. We then measured the enantiomeric selectivity of this host for 2-butylamine and found correlation between selectivity, the torsional flexibility of the phenyl moieties of the host, and the concomitant remaining volume that accommodates the guest. This mechanism was confirmed by repeating the competition experiments with a related chiral host.