The Source of Proton in the Noyori-Ikariya Catalytic Cycle

The study of the mechanism of the Noyori-Ikariya asymmetric transfer hydrogenation of ketones spans nearly three decades of investigations. Whereas the early part of the catalytic cycle being the hydride transfer is now well-understood, the later part being the proton transfer is still ambiguous. Specifically, the source of the proton can be the N-H functionality of the catalyst and/or the O-H functionality of the reagent/solvent, leading to two conceptually different catalytic cycles or even their combination. For three popular reagents/solvents typically used in the method, namely, propan-2-ol, 5:2 HCO2H-NEt3, and water, either the source of the proton is presently unknown or the evidence is presented partially by only one approach-experimental or computational. The present work eliminates this ambiguity by means of various molecular dynamics simulation methods such as ab initio, quantum mechanics/ molecular mechanics, and path integral to include quantum tunneling effects. Here, we show that for the archetypal (S)-RuH[(R,R)-Tsdpen](mesitylene) catalyst complex, the source of the proton in propan-2-ol is the catalyst's N-H functionality, whereas in more acidic water, binary 5:2 HCO2H-NEt3, or neat formic acid, the source of the proton is the reagent/solvent. Thus, depending on the nature of the reagent/solvent, the catalyst's ligand can be either chemically non-innocent or chemically innocent in the Noyori-Ikariya reaction, which opens opportunities for outer-sphere homogeneous catalyst design.

Automated summary

The study of the mechanism of the Noyori-Ikariya asymmetric transfer hydrogenation of ketones has been investigated for nearly three decades. While the early part of the catalytic cycle is well-understood, the later part involving proton transfer is still unclear. This study eliminates the ambiguity by using molecular dynamics simulation methods and reveals that the source of the proton depends on the nature of the reagent/solvent.