Density functional theory investigation of Ru(II) and Os(II) asymmetric transfer hydrogenation catalysts

Transition metal ions have a unique ability to organise and control the steric and electronic effects around a substrate in the active site of a catalyst. We consider half-sandwich Ru(II) (Noyori-type) and Os(II) sulfonyldiamine 16-electron active catalysts [Ru/Os(η6-p-cymene)(TsDPEN-H2)], where TsDPEN is N-tosyl-1,2-diphenylethylenediamine containing S,S or R,R chiral centres, which catalyse the highly efficient asymmetric transfer hydrogenation of aromatic ketones to chiral alcohols using formic acid as a hydride source. We discuss the recognition of the prochiral ketone acetophenone by the catalyst, the protonation of a ligand NH and transfer of hydride from formate to the metal, subsequent transfer of hydride to one enantiotopic face of the ketone, followed by proton transfer from metal-bound NH2, and regeneration of the catalyst. Our DFT calculations illustrate the role of the two chiral carbons on the N,N-chelated sulfonyldiamine ligand, the axial chirality of the π-bonded p-cymene arene, and the chirality of the metal centre. We discuss new features of the mechanism, including how a change in metal chirality of the hydride intermediate dramatically switches p-cymene coordination from η6 to η2. Moreover, the calculations suggest a step-wise mechanism involving substrate docking to the bound amine NH2 followed by hydride transfer prior to protonation of the O-atom of acetophenone and release of the enantio-pure alcohol. This implies that formation and stability of the M–H hydride intermediate is highly dependent on the presence of the protonated amine ligand. The Os(II) catalyst is more stable than the Ru(II) analogue, and these studies illustrate the subtle differences in mechanistic behaviour between these 4d6 and 5d6 second-row and third-row transition metal congeners in group 8 of the periodic table.