In this article we report on the successful synthesis and isolation of cyclometalated Ir complexes having three different nonsymmetric ligands based on ligand-selective electrophilic reactions via interligand HOMO (highest occupied molecular orbital) hopping phenomena. It was hypothesized that the electrophilic substitution reactions of bis-heteroleptic Jr complexes having 8-benzenesulfonamidoquinoline as an ancillary ligand, 5a and 7, would proceed at the 5 position of the quinoline ring of these Jr complexes to afford 18 and 19, because their HOMOs are localized on the quinoline rings, as predicted by density,functional theory (DFT) calculations. In these products, the HOMO is transferred to one of two ppy ligands, in which the phenyl group is trans to the Ir N (1 position of quinoline) bond, and hence, the iodination or formylation of 18 and 19 occurs at the 5' position of the ppy ligand to provide 20a, 23, and 24. Furthermore, we carried out the functionalization of 20a using cross-coupling reactions to obtain tris-heteroleptic Jr complexes containing three different ligands in good yields with negligible diastereomer formation. Photochemical properties, especially dual emission, and response to pH change, of new dual emissive tris-heteroleptic cyclometalated Ir complexes, 21-24, are also reported.