Kinetic Studies of the Asymmetric Transfer Hydrogenation of Imines with Formic Acid Catalyzed by Rh−Diamine Catalysts

Abstract

Kinetic studies of the asymmetric transfer hydrogenation of imines with HCOOH using Rh-chiral diamine catalysts reveal anomalous concentration dependences attributed to the participation of both reactant and product in the formation of formate salts. The resting state of the catalyst is suggested to be the Rh hydride species 5. The role of bases such as Et 3 N in metering HCOOH into the catalytic cycle is discussed. A practical reaction protocol for achieving high productivity based on slow addition of HCOOH is presented. These studies highlight the value of in situ reaction monitoring techniques in developing a detailed mechanistic picture of a complex reaction system. IntroductionAsymmetric hydrogenation of CdO and CdN groups via transfer of hydrogen from an organic molecule has come under recent attention as an attractive alternative to reduction using gaseous hydrogen. Ru, Rh and Ir precursor complexes together with chiral diamine ligands have been shown to effect these reactions in high enantioselectivity and high efficiency. 1 Noyori and co-workers 2 have studied the mechanism of the reaction for ketones with both simple alcohols and formic acid as the source of hydrogen, and they were the first to propose that the reaction proceeds outside the coordination sphere of the metal. Such a concerted mechanism involving the transfer of both a metal hydride and a ligand proton has been supported by theoretical studies. 3 In addition, DFT (density functional theory) calculations 4 and deuterium-labeling studies 5 for ketone substrates suggested a similar mechanism for transfer hydrogenation and dehy-

Chiral Amines from Transition‐Metal‐Mediated Hydrogenation and Transfer Hydrogenation

“…The catalysts gave high ee values for the reduction of 1-alkyl-3,4-dihydroisoquinolines (entry 3) and moderate ee values for that of benzoisothiazole dioxides (entry 2), but struggled to induce any enantioselectivity when reducing 1-aryl-3,4-dihydroisoquinolines (entry 4) or acyclic imines (entry 1). Blackmond and coworkers performed a kinetic analysis of this catalyst system and showed that its activity could be further improved by the slow addition of HCO 2 H [173]. a) Conversion to and ee of amine product.…”

Imino Reductions by Transfer Hydrogenation

“…Recent kinetic studies have been carried out on the Rh(III) catalyst system by Blackmond [22,23] which have served to shed further light on the mechanism of the reduction of imines. The study revealed that the resting state of the catalyst was as the Rh -hydride species, that is, where the chloride of the " precatalyst " is replaced by a hydride.…”

“…The study revealed that the resting state of the catalyst was as the Rh -hydride species, that is, where the chloride of the " precatalyst " is replaced by a hydride. The successful operation of the catalyst is shown to depend upon the acid -base equilibria, and this observation has led to a highly valuable, improved experimental protocol in which formic acid is added slowly to the solution rather than as a single dose at the start [22] . The observed importance of the solution pH mirrors Xiao ' s observations in the aqueous ketone reduction process [24] .…”

Hyperplane Intercept Vector Calibration Method in Grey Analytical Systems

“…This information can be used for fundamental mechanism study, 1,2 reaction kinetic investigation [3][4][5] and process control. [6][7][8][9] As for mid-IR monitoring of some less complicated reactions, calibration using a single frequency or the ratio of two frequencies has been proved adequate to obtain concentration profiles.…”