The VLAO method can be applied not only monodentate but also multidentate phosphine ligands. As a proof-of-concept study, we focused on the reductive elimination of trifluorotoluene from a palladium(II) diphosphine complex 5 (Figure ). In general, this reaction is very challenging, and diphosphine ligands with a large bite angle, such as Xantphos, had been thought to be necessary to promote the desired reductive elimination. Therefore, 1,2-bis(diphenylphosphino)ethane and its analogues (dppe-type ligands), which have relatively small bite angles, had been thought to be unsuitable for this reaction. However, upon a sophisticated ligand engineering based on quantum chemical calculations, Schoenebeck and coworkers have reported that the desired reductive elimination can be effectively accelerated by the dfmpe ligand, which is a dppe-type ligand with CF3 substituents. Indeed, the activation energy for the reaction using dfmpe ligand was calculated to be 25.4 kcal/mol (at the ωB97XD/Def2-SVP level), which is much smaller than that calculated using dppe (35.4 kcal/mol). The key principles of their ligand design were 1) the low steric demand of substituents on the phosphorous atoms, 2) large repulsion of the ligand with the Ph and CF3 groups on the Pd(II) center, and 3) highly electron-withdrawing property of the ligand. The second and third principles are in line with the generally accepted trends for reductive elimination, whereas the first criterion is less intuitive because bulky ligands were considered to accelerate reductive elimination. Also, it should be noted that the first and second criteria generally contradict each other because the first criterion requires small substituents while the second one does large substituents. Schoenebeck and coworkers elegantly met both requirements by introducing a small but highly polarized CF3 group into the ligand.