Anomalous behavior of rigid cinchona alkaloids in the enantioselective hydrogenation of ethyl pyruvate in an aprotic solvent

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“…We should stress, therefore, that contrary to the report of Meyer et al [1], there are no contradictions in our reports [4,5], showing that ligand acceleration is not necessarily an intrinsic feature of enantioselective hydrogenation, but rather is specific to the substrate and even the substrate concentration. The differences in the rates of racemic and enantioselective hydrogenation depending on the reactant concentration domain were attributed in [5] to deactivation, caused by side reactions of EP, which are faster at higher reactant concentrations.…”

“…Ligand acceleration is readily observed in homogeneous catalysis, and in enantioselective hydrogenation over heterogeneous catalysts is associated mainly with ethyl pyruvate (EP) hydrogenation over cinchonidine (CD)-modifier Pt catalysts (Orito reaction) [2], whereas for other reactants the reaction rate does not differ much in racemic and enantioselective reactions and sometimes even rate deceleration is observed [9]. It is worth emphasizing that recent publications also have reported a lack of rate acceleration and high ee in liquid-phase EP [3][4][5][6] and gas-phase methyl pyruvate [7] hydrogenations. These are important experimental observations, and a detailed understanding of them plays a very important role in the development of mechanistic models for asymmetric heterogeneous catalysis.…”

“…The increased turnover rate over modified sites has been considered a key mechanistic feature of reactant-modifier interactions, supported by the experimentally observed correlation of modifier concentration, enantiomeric excess (ee), and reaction rate, as well as the up to 100-fold-higher hydrogenation rate in the presence of modifier. The increased turnover rate mechanism has been challenged by recent experimental observations [3][4][5][6][7][8], however. Ligand acceleration is readily observed in homogeneous catalysis, and in enantioselective hydrogenation over heterogeneous catalysts is associated mainly with ethyl pyruvate (EP) hydrogenation over cinchonidine (CD)-modifier Pt catalysts (Orito reaction) [2], whereas for other reactants the reaction rate does not differ much in racemic and enantioselective reactions and sometimes even rate deceleration is observed [9].…”

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“…However, in their argument, they confused the changes in the intrinsic rates and the measured (overall) rates and used the latter for mechanistic conclusions. To support their view, they cited only papers reporting on pyruvate hydrogenation in nonacidic medium [7,8,11,14,15] and did not address our critical point [1] concerning the role of solvent in catalyst deactivation. They ignored the extensive work carried out in acidic medium, the data from which support the debated link between rate acceleration and enantioselectivity in α-ketoester hydrogenation [16][17][18].…”

Enantioselective hydrogenation of ethyl pyruvate and 1-phenyl-1,2-propanedione on catalysts prepared by impregnation of colloidal platinum on SiO2

“…It has been demonstrated that, using cinchonidine chiral alkaloid, it is possible to induce a preferential formation of (R)-lactate. [43][44] In the present study the enantioselective hydrogenation of ethyl pyruvate was carried out in liquid phase at 298 K and 40 bar overall pressure on colloidal platinum and on Pt-CD/SiO 2 catalysts obtained by impregnation of the colloids on the support. Experimental variables such as the weight of the catalysts and the concentration of CD added with the substrate during the reaction were also studied.…”