[structure: see text] The stereomutations in nonsymmetrical salophen ligands 1-4 were studied by means of dynamic NMR and HPLC methods. DNMR experiments showed that in DMSO-d(6) hindered ligands 2-4 exist in two chiral conformations, depending on whether the imine carbon atoms are in a cis or trans disposition with respect to the plane of the central o-phenylenediamine ring, the latter being more stable by 1.0 kcal mol(-1). Owing to its higher dipole moment, in the apolar solvent C(6)D(6) the cis conformer is destabilized with respect to the trans one, in agreement with the results of ab initio calculations. In DMSO-d(6) solution the two conformers are in equilibrium through the less hindered rotation about the C6-N7 bond aligned to the a(6,7) axis, and the interconversion barriers range from 18.4 to 19.3 kcal mol(-1). The enantiomerization process is a two step-process that implies sequential rotations around the C6-N7 and the C1-N8 bonds, so that the rate determining step is the slower rotation around the more hindered C1-N8 bond aligned to the a(1,8) axis, and the energy barriers range from 21.4 to 21.9 kcal mol(-1). These values compare well with those determined by chromatography on an enantioselective HPLC column at low temperature, thus confirming that DNMR and DHPLC can be conveniently employed as complementary techniques.