Halogen-Bonding Interaction Stabilizing Cluster-type Diastereomeric Salt Crystals

O-Ethyl 4-chlorophenylphosphonothioic acid (1) was newly synthesized and applied as a chiral selector for the enantioseparation of racemic 1-(4-halophenyl)ethylamines (halo = F, Cl, Br, I; 2a−d) through diastereomeric salt formation. The phosphonothioic acid 1 showed an excellent chirality-recognition ability for the fluorinated and iodinated amines 2a and 2d with the dramatic switch of the absolute configuration of the enantio-enriched isomers in the deposited salts from R for the amine 2a to S for the amine 2d. The X-ray crystallographic analyses of the four pairs of diastereomeric salts revealed that halogen-bonding interaction in the salt crystals plays a very important role for the switch.