A series of 6-O-benzoyl- β-cyclodextrins (CDs) with methyl, methoxy, methoxycarbonyl, and bromo
substituent(s) at the ortho-, meta-, and/or para-position(s) were synthesized as chiral sensitizing hosts for the use in supramolecular enantiodifferentiating photoisomerization of (Z)-cyclooctene (1Z) to its chiral(E)-isomer (1E). The complex stability constants (Ks) of the modified β-CDs with 1Z in aqueous methanol solutions were highly sensitive to the substituent(s) introduced to the benzoate moiety, and the log KS values decreased linearly with slightly different slopes with increasing methanol content. The enantiomeric excess (ee) of 1E obtained upon photosensitization with these hosts was a critical function of the size and position of the substituent, varying from almost zero to 46% ee. This indicates that even an apparently small structural difference between methyl and methoxy can critically affect the enantiodifferentiating photoisomerization of a guest included in the chiral cavity, probably through manipulation of both the orientation of ground-state 1Z and the subsequent rotational relaxation of excited 1Z inside the chiral cavity.