This article reports the synthesis of the two enantiomers of a water‐soluble cryptophane 3 enabling cesium and thallium complexation at neutral or basic pH. The two enantiomers of 3 were obtained in a two steps synthesis from cryptophane 4 , a molecule decorated with three phenol groups and three other phenol groups protected by benzyl units. The two enantiomers of 4 were isolated from liquid chromatography using chiral stationary phase. The absolute configuration of the two enantiomers of 3 was determined by vibrational circular dichroism combined with theoretical calculations. Contrary to cryptophane 1 that present large spectroscopic changes upon cesium and thallium complexation, the electronic circular dichroism spectra of compound 3 exhibit moderate spectral changes suggesting that this compound cannot change the conformation of its linkers as easily as cryptophane 1 .