Portal Substituent Modulations in Chiral Imido–Pd(II) Cages for the Enhanced Separation of Styrene Oxide Enantiomers

Sensing and separation of enantiomers are crucial for the synthesis of biologically relevant compounds as well as for applications in catalysis and pharmaceutical development. Chiral coordination cages have gained significant attention as effective platforms for enantioselective processes through their well-defined, tunable cavities that facilitate host-guest interactions. In this study, we systematically explored the enantioselective binding and separation properties of two tetrahedral Pd(II) cages, <b>1-R</b> and <b>2-R</b>, with the molecular formula [Pd₃(PO[N(^RCH(CH₃)Ph)₃])₄(C₆O₄X₂)₆] (X = Cl for <b>1-R</b>, and X = F for <b>2-R</b>). Their enantioselective abilities were investigated for small chiral molecules with diverse functional groups. Notably, the <b>2-R</b> cage demonstrated a high enantioselectivity value of 88 for <i>R</i>-styrene oxide. Chiral separation experiments further revealed impressive enantiomeric excess (ee) values of 98% for <i>R</i>-styrene oxide from their racemic mixtures upon desorption from <b>2-R</b>. The enhanced selectivity and separation efficiency were attributed to an optimal guest-to-cavity fit and the presence of multiple interaction sites within the host framework. Remarkably, portal substituent modulation in <b>2-R</b> led to a 16-fold enhancement in enantioselective separation efficiency compared to <b>1-R</b>, primarily due to improved portal dimensions, tighter molecular packing, and increased hydrogen bonding interactions. These findings highlight the potential of neutral chiral coordination cages for various enantioselective applications.