Why do many C2-symmetric bisphosphine ligands fail in asymmetric hydroformylation?: Theory in front of experiment

Supported by a pure QM and MM treatment, stereoselectivities of rhodium systems containing the C-2-symmetric ligands CHIRAPHOS (2,3-bis(diphenylphosphino)butane; 2), BINAP (2,2'-bis(diphenylphosphino)-1,1'-binaphthyl; 3), DIOP (2,2-dimethyl-4,5-bis((diphenylphosphino)methyl)-1,3-dioxolane; 4), and NAPHOS (2,2'-bis((diphenylphosphino)methyl)-1,1'-binaphthyl; 5) have been calculated with a combined QM/MM method. On the basis of the RSAI (requirement of synchronous asymmetric inductions), which states that all ligand coordination modes favor transition states with the same asymmetric induction, we demonstrate that the performance of C-2-symmetric bidentate phosphine ligands is governed by two interdependencies, namely induction influence of the chelate ring and backbone flexibility. In a further step, the NAPHOS derivatives 6 (2,2'-bis((2-dinaphthylphosphino)-methyl)-1,1'-binaphthyl) and 7 (2,2'-bis((1-dinaphthylphosphino)methyl)-1,1'-binaphthyl) which to our knowledge have not been tested experimentally up to now, have been investigated in the same manner. 7 fulfills the RSAI and will be tested experimentally. Our explanations and predictions release asymmetric hydroformylation from its predominantly empirical character, although the magic formula for ligand development is still unknown.