© 2018 American Chemical Society. In this work a photosubstitution strategy is presented that can be used for the isolation of chiral organometallic complexes. A series of five cyclometalated complexes Ru(phbpy)(N-N)(DMSO-κS)](PF 6 ) (PF 6 -PF 6 ) were synthesized and characterized, where Hphbpy = 6′-phenyl-2,2′-bipyridyl, and N-N = bpy (2,2′-bipyridine), phen (1,10-phenanthroline), dpq (pyrazino[2,3-f][1,10]phenanthroline), dppz (dipyrido[3,2-a:2′,3′-c]phenazine, or dppn (benzo[i]dipyrido[3,2-a,2′,3′-c]phenazine), respectively. Due to the asymmetry of the cyclometalated phbpy - ligand, the corresponding [Ru(phbpy)(N-N)(DMSO-κS)] + complexes are chiral. The exceptional thermal inertness of the Ru-S bond made chiral resolution of these complexes by thermal ligand exchange impossible. However, photosubstitution by visible light irradiation in acetonitrile was possible for three of the five complexes (PF 6 -PF 6 ). Further thermal coordination of the chiral sulfoxide (R)-methyl p-tolylsulfoxide to the photoproduct [Ru(phbpy)(phen)(NCMe)]PF 6 , followed by reverse phase HPLC, led to the separation and characterization of the two diastereoisomers of [Ru(phbpy)(phen)(MeSO(C 7 H 7 ))]PF 6 , thus providing a new photochemical approach toward the synthesis of chiral cyclometalated ruthenium(II) complexes. Full photochemical, electrochemical, and frontier orbital characterization of the cyclometalated complexes PF 6 -PF 6 was performed to explain why PF 6 and PF 6 are photochemically inert while PF 6 -PF 6 perform selective photosubstitution.