Does C2 symmetry improve enantioselectivity?

The suggestion that the enantiomers of compounds having an axis of symmetry tend to be more readily resolved by chromatographic enantioseparation than are the enantiomers of compounds lacking such symmetry is examined in thermodynamic terms. Consideration of a hypothetical situation in which enantiomers with C-2 symmetry interact with a single type of isolated chiral adsorption site in exactly the same way as do otherwise identical enantiomers of C-1 symmetry leads to the conclusion that while the chromatographic retention of C-n compounds will be greater than that of their C-1 counterparts, the separation factors (ct) of the enantiomers will be the same in each case. Compounds which can participate in bridging interactions with multiple chiral selector sites can show either enhanced or diminished enantioselectivity relative to their C-1 analogs. Two similar racemates, one with C-1 and the other with C-2 symmetry, are chromatographed on nine chiral stationary phases (CSPs), the enantioselectivity of the C-2 symmetrical analyte being poorer in most cases. The results emphasize the fact that there is nothing inherent in C-n symmetry which increases enantioselectivity.