Mechanistic Aspects of Using Formate as a Hydrogen Donor in Aqueous Transfer Hydrogenation

Asymmetric transfer hydrogenation of ketones is an important chemical reaction. In aqueous solution, Ru(p-cymene)[TsDPEN] is an efficient catalyst for asymmetric transfer hydrogenation via a metal–ligand bifunctional mechanism with either 2-propanol or formate as hydrogen donors. Here, we provide novel insight for two key steps in the catalytic cycle of transfer hydrogenation cycle, using a computational model of Ru(p-cymene)[TsDPEN] with an explicit aqueous solvent. Employing ab initio molecular dynamics simulations, we model the hydride transfer between formate and the protonated and deprotonated catalyst, and the dissociation of the ruthenium-formato complex. It is shown that the aqueous solvent provides a significant contribution to the reaction barriers, increasing the hydride transfer barrier, while decreasing the dissociation barrier for ruthenium-formato complex, when compared with a gas-phase model. These effects can be attributed to hydrogen-bond structure around the formate, which favors the formate to be in solution. Furthermore, the hydride transfer barrier was significantly higher for the deprotonated catalyst, suggesting that the catalyst protonation state is an important factor. Our results demonstrate that a first-principles molecular dynamics approach, incorporating a molecular description of the solvent, is able to capture the full complexity of catalytic reactions in an aqueous solvent. This approach can provide an important contribution to understanding the reactions as well as provide directions for novel developments in catalysis.