Hans-Peter Jalett

Enantioselective hydrogenation of α-ketoesters using cinchona modified platinum catalysts and related systems: A review

Abstract The state of the art for the heterogeneous enantioselective hydrogenation of α-ketoesters using cinchona modified Pt catalysts and related systems is reviewed. The effect of the following elements of the catalytic system are well known: Catalyst. Supported Pt catalysts with relatively low dispersion (particle diameter >2 nm) are preferred for the hydrogenation of α-ketoacid derivatives, Pd catalysts for functionalized olefins. Most support materials are suitable. Substrate. The reacting function is preferentially a ketone or a C=C bond, a carbonyl group in a-position is necessary for good optical yields. Modifier. The minimal requirements for an efficient modifier for the hydrogenation of α-ketoesters is the presence of a basic nitrogen atom close to one or more stereogenic centers and connected to an extended aromatic system (preferentially quinolyl or naphthyl). The presence of an alcohol or ether in β-position to the basic nitrogen often gives better enantioselectivities. Solvent. Solvents with adielectric constant between 2 and 10 give best selectivities for a-ketoesters with best e.e.s in acetic acid. For the hydrogenation of substrates with a free acid function aqueous polar solvents are preferred. The highest optical yields for the different substrate types: 95% e.e. for α-ketoesters, 85% for a-ketoacids and 70% for α,)-unsaturated acids. Practical problems for the use of the catalytic system are low e.e.s at the start of the reaction, the instability of the modifier and some side reactions as well as the purity of the ethyl pyruvate. Mechanistic investigations have established interactions between substrate and modifier in solution and adsorption of the ethyl pyruvate and cinchonidine on the catalyst. The dependence of rate and e.e. on catalyst, cinchonidine, ethyl pyruvate and hydrogen concentration has been established for ethyl pyruvate hydrogenation using Pt/Al 2 O 3 -cinchona. A Langmuir-Hinshelwood scheme is well suited for explaining the observed kinetic results. Based on the kinetic results, the effect of modifier and substrate structure, and molecular modeling studies, the following mechanistic model has been developed: On the unmodified catalyst, the a-ketoester and hydrogen are reversibly adsorbed and the addition of the first hydrogen atom is rate determining. A modified active site is formed by adsorption of one cinchona molecule. It is postulated that a protonated adsorbed modifier interacts with the α-ketoester and forms a stabilized half hydrogenated intermediate. The rate determining step for the preferred enantiomer is the addition of the second hydrogen. The rate acceleration and the enantiodiscrimination is therefore due to the preferential stabilization of one of the two diastereomeric intermediates. Alternative mechanisms are discussed but considered to be less satisfying.

Tunable ferrocenyl diphosphine ligands for the Ir-catalyzed enantioselective hydrogenation of N-aryl imines

Abstract Ferrocenyl diphosphines R2PF-P(R′)2 are effective, tunable ligands for the iridium catalyzed enantioselective hydrogenation of N-aryl imines in the presence of iodide and acid promoters. Structure–activity/selectivity correlations were found for the hydrogenation of N-(2-ethyl-6-methylphenyl)-N-(1′-methoxymethyl)-ethylidene-amine (MEA-imine) and for 2,3,3-trimethylindolenine (TMI). Extremely high catalytic activity and moderate to good enantioselectivity were observed for the MEA imine using a catalyst generated in situ from [Ir(cod)Cl]2 and (R)-(S)-PPF–P(3,5-Xyl)2 (xyliphos). With the same type of catalysts, several other N-aryl imines can be hydrogenated with enantioselectivities between 31 and 96%, albeit with lower catalyst activities.

Enantioselective Hydrogenation of α-Ketoacids Using Platinum Catalysts Modified With Cinchona Alkaloids

Abstract The enantioselective hydrogenation of α-ketoacids using modified heterogeneous catalysts can be carried out with moderate to good (

Mass Transfer Considerations for the Enantioselective Hydrogenation of α-KETO Esters Catalyzed by Cinchona Modified Pt/Al2O3

Abstract For the enantioselective hydrogenation of ethyl pyruvate catalyzed by a commercially available Pt/Al 2 O 3 powder catalyst modified with dihydrocinchonidine, turnover frequencies of up to 50 s −1 at 20 °C and 10.0 MPa were observed. Generally, the optical yields were 80% but under certain conditions lower enantioselectivities were observed. An integrated program of catalyst characterization, transport calculations and kinetic experiments was undertaken to quantify the mass transfer parameters. Catalyst characterization suggested that the powder catalyst was in fact of ‘egg-shell’ design. By using catalyst fractions of varying mean particle diameter, negligible intrapaiticle resistance was found (Koros/Nowak and Madon/Boudart criterion). Further, calculations and experiments indicated that, under specific conditions, the lower ees were due to liquid-solid transport resistance. Conditions can now be identified where intrinsic kinetics, not affected by transport problems, can be measured for future mechanistic studies.

Enantioselective catalysis for agrochemicals: Synthetic routes to (S)-metolachlor, (R)-metalaxyl and (αS, 3R)-clozylacon

The application of enantioselective catalytic methods for the technical preparation of chiral agrochemicals is illustrated for three active ingredients of the acylanilide type. The key step for the technical synthesis of the herbicide (S)-metolachlor is the enantioselective hydrogenation of an imine intermediate using a novel iridium ferrocenyldiphosphine catalyst with an unprecedented high activity and 80% ee. (R)-metalaxyl and (αS,3R)-clozylacon were synthesized via the enantioselective hydrogenation of corre-sponding enamide precursors with Rh and Ru/binap catalysts with >95% and 99% enantiomeric purity, respectively.