Using a previously advanced mechanistic hypothesis, a conformationally rigid, [2.2.2]-bicyclooctane-based, selector intended to differentiate between the enantiomers of underivatized profens, an important group of non-steroidal anti-inflammatory drugs, was designed, synthesized, resolved, and immobilized on silica. The resulting chiral stationary phase effectively discriminates between the enantiomers of the various profens. The discriminating ability of this selector is ascribed to a preorganized cleft which provides an active site in which but one enantiomer of a profen can undergo simultaneous hydrogen bonding, π-π face-to-face stacking, and π-π face-to-edge interaction while in a relatively low energy conformation. The multi-step synthesis of the racemic selector is relatively efficient and employs inexpensive starting materials. The racemic selector is easily resolved on a preparative chiral column derived from the diallyl amide of (S)-naproxen.