In the two examples above, all substituents in a VL were described by common electronic and steric parameters, thereby enabling design of symmetric phosphine ligands such as PR3 and R2PCH2CH2PR2. Because electronic and steric parameters can be set independently for each substituent, the VLAO strategy would also be applicable to engineering of asymmetric phosphine ligands. To prove this, we focused on the Cu-catalyzed asymmetric hydroboration of aliphatic terminal alkenes reported by Ito and coworkers (Figure ). The hydroboration of terminal alkene 6 potentially affords three isomeric products, namely (S)-7, (R)-7 and 8. Ito and coworkers found that, this reaction can be catalyzed with high regio-and enantioselectivity when (S)quinoxt Bu3, a C1-symmetric quinoxaline-based diphosphine ligands, was used. Then, the authors conducted detailed analyses of origin of observed selectivities based on both computational and experimental methods and established a design principle: Whereas the regioselectivity is affected by R 2 and R 4 , the enantioselectivity is determined by R 2 and R 3 (Figure , right). According to this guideline, the authors then designed and synthesized an unprecedented asymmetric ligand, namely (S)-quinoxt OctAd2. Indeed, this ligand enabled the hydroboration of 6 in excellent regio-and enantioselectivity (92 and 99%, respectively).