Understanding ketone hydrogenation catalysis with anionic iridium() complexes : the crucial role of counterion and solvation

Catalytic asymmetric hydrogenation of ketones is an important approach to prepare valuable chiral alcohols. Understanding how transition metals promote these reactions is key to the rational design of more active, selective and sustainable catalysts. A highly unusual mechanism for asymmetric hydrogenation of acetophenone catalysed by an anionic IrIII hydride system, including a strong counterion dependence on catalyst activity, is explored and rationalised here. The active catalyst, generated in situ from [IrCl(COD)]2 and a bidentate ligand (P,SR) under H2 in the presence of a strong base (M+iPrO− in isopropanol, M = Li, Na, K), is the solvated M+[Ir(H)4(P,SR)] salt (P,SR = CpFe[1,2-C5H3(PPh2)(CH2SR)], with R = iPr, Ph, Bz and Cy). Catalyst activity increases, for all R derivatives, significantly as the counterion is varied in the order Li < Na < K. For the most active K system, the addition of 18-crown-6 drastically reduces the activity. While the cation strongly affects catalyst activity, it does not significantly affect enantioselectivity. DFT calculations explored these effects in detail and showed that the solvation model used in the calculations is critical. Only a hybrid implicit/explicit solvent model including sufficient explicit solvent molecules to properly describe the first solvation shell of the cation is able to reproduce the experimental observations. This model revealed the fundamental importance of the alkali-metal cation coordination sphere in understanding the counterion effects. The turnover-determining states in the catalytic cycle are those involved in outer-sphere hydride transfer to the substrate. This step leads to coordination of the alkoxide product to the alkali-metal cation, with a significant rearrangement of the coordination sphere of M, whereas there is little change in the geometrical parameters around Ir or the alkoxide. The DFT calculations also pinpointed the major enantio-discriminating interactions and rationalised the insensitivity of the enantioselectivity on the alkali metal cation placement.