The presence of stereogenic elements is a common feature in pharmaceutical compounds, and affording optically pure stereoisomers is a frequent issue in drug design. In this context, the study of the chiral molecular recognition mechanism fundamentally supports the understanding and optimization of chromatographic separations with chiral stationary phases. We investigated, with molecular docking, the interactions between the chiral HPLC selector Whelk-O1 and the stereoisomers of two bioactive compounds, the antiviral Nevirapine and the anticonvulsant Oxcarbazepine, both characterized by two stereolabile conformational enantiomers. The presence of fast-exchange enantiomers and the rate of the interconversion process were studied using low temperature enantioselective HPLC and VT-NMR with Whelk-O1 applied as chiral solvating agent. The values of the energetic barriers of interconversion indicate, for the single enantiomers of both compounds, half-lives sufficiently long enough to allow their separation only at critically sub-ambient temperatures. The chiral selector Whelk-O1 performed as a strongly selective discriminating agent both when applied as a chiral stationary phase (CSP) in HPLC and as CSA in NMR spectroscopy.