Katalin Balázsik

Enantiodifferentiation in asymmetric sonochemical hydrogenations

The effect of sonochemical pretreatment on the enantioselectivity of Pt/Al2O3–cinchonidine-catalyzed ethyl pyruvate hydrogenation was studied at different hydrogen pressures in various solvents, mainly in acetic acid. The sonochemical pretreatment of a commercial Pt/Al2O3–cinchonidine catalytic system in acetic acid resulted in enhanced enantioselectivity providing excellent ee values (97% ee) under mild and widely varied experimental conditions. Moreover, the application of ultrasonics provides a possibility of the catalyst recycling without regeneration. The catalyst was tested by transmission electron microscopy to determine the effect of the sonication on the metal particle size morphology.

Asymmetric sonochemical reactions. Enantioselective hydrogenation of α-ketoesters over platinum catalysts

The sonochemical enantioselective hydrogenation of different alpha-ketoesters to the corresponding hydroxy derivatives over cinchona modified Pt catalysts is described. Ultrasonic irradiation was found to be beneficial in improving the optical yields. Besides studying the reaction rates and enantioselectivities, the effect of ultrasonics on the catalyst-modifier system and the scale-up of the process will also be considered.

Ultrasonics in asymmetric syntheses. Sonochemical enantioselective hydrogenation of prochiral C=O groups over platinum catalysts

The sonochemical enantioselective hydrogenation of various prochiral carbonyl compounds to the corresponding (R)-hydroxy derivatives over different platinum catalysts using cinchonidine as chiral modifier is described. The carbonyl derivatives studied were trifluoromethyl ketones and α- and β-ketoesters. The sonochemical pretreatment of the catalyst-modifier system was found to be mostly advantageous in increasing the optical yield. Moreover, the ultrasonically promoted reactions provided the best enantiomeric excesses (ee%) ever obtained in this heterogeneous catalytic system (methyl pyruvate 95 ee%, ethyl 4-phenyl-2-oxobutyrate 95 ee%, and ethyl benzoylformate 92 ee%). In a few cases, however, the insonation did not result in enhancement in enantioselectivities. On the basis of the comparison with conventional reactions the limitations of the ultrasonic irradiation in asymmetric hydrogenations are also drawn. Chirality 11:470–474, 1999.

Asymmetric reactions in sonochemistry

Sonochemical processes involved in asymmetric synthesis are reviewed. The goal of this overview is to provide a comprehensive picture about the fields of both enantioselective and diastereoselective reactions accelerated or initiated by ultrasounds. Since the most, in many cases comparative, data are available in heterogeneous metal catalysis, the emphasis will be placed on these enantioselective hydrogenations, however, other applications such as phase transfer catalysis etc. will also be cited.

Homogeneous and heterogeneous asymmetric reactions. Part X: Enantioselective hydrogenations over K-10 montmorillonite supported noble metal catalysts with immobilized modifier

Abstract The preparation, characterization and application of new K-10 montmorillonite supported noble metal catalysts containing immobilized chiral modifier are described. The active contents of the catalysts were Pt, Pd and Rh, while cinchonidine was used as chiral modifier. The preparation was carried out by two methods. Method I consists of the modification of the parent K-10 montmorillonite by direct surface reaction or ion exchange followed by impregnation with metal salts, and finally, reduction. Method II, in contrast, starts with the deposition of the metal by impregnation, and then reduction, which is followed by the immobilization of the modifier. The catalysts thus prepared were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), solid state 29 Si NMR and infrared (FT-IR) spectroscopies. The samples were tested in enantioselective hydrogenation of ethyl pyruvate, as well. Only Pt and Rh catalysts were found to be active in the hydrogenation producing moderate to good enantioselectivities (up to 75% ee for the R isomer). To the best of our knowledge, the results described here are the first data concerning the preparation of clays chirally modified with cinchona alkaloids.

Heterogeneous asymmetric reactions 20. Effect of ultrasonic variables on the enantiodifferentiation in cinchona-modified platinum-catalyzed sonochemical hydrogenations

The effect of sonochemical variables on a cinchona alkaloid modified Pt/Al2O3 catalyst system and its application in α-ketoester hydrogenation are described. The sonochemical pretreatment of these commercial Pt/Al2O3-cinchonidine catalysts resulted in excellent ee values (up to 92-98% ee) under mild experimental conditions. To gain more insight into the nature of the ultrasonic effect the reactions were screened under widely varied conditions (ultrasound source, frequency, insonation time). Besides investigating the reactions, the catalyst-modifier system was also studied. The changes in metal particle size were determined by transmission electron microscopy, while the alteration of modifier concentration in the solvent upon sonication was followed by UV-vis spectroscopy. The transformation of the modifier during the pretreatment was detected by GC-MS and verified by NMR. Summarizing the results, the major effects of the sonochemical activation on the cinchona-modified supported Pt catalyst system can be described. The ultrasonic pretreatment increased the quantity of adsorbed cinchona and blocked its hydrogenation to provide more and highly stable chiral active sites for enantioselection.

Homogeneous and heterogeneous asymmetric reactions: Part 11. Sonochemical enantioselective hydrogenation of trifluoromethyl ketones over platinum catalysts.

Enantioselective sonochemical hydrogenation of alpha,alpha,alpha-trifluoromethyl ketones, namely, 1,1,1-trifluoroacetophenone and 1,1,1-trifluoro-phenylacetone was carried out over various platinum catalysts modified by cinchonidine in different solvents. Both compounds yielded the (R)-alcohol as major product. The reaction rates and the enantiomeric excesses were determined over Pt/C, Pt/SiO2, Pt/K-10 and Pt/Al2O3 catalysts under conventional conditions. Since Pt/Al2O3 exhibited the best catalytic performance the effect of ultrasound on the catalytic activity and enantioselectivity was tested using this catalyst applying different sonochemical pretreatments. These methods included a pretreatment before the reaction in hydrogen and oxygen or both. The ultrasonic irradiation was found to be highly advantageous in the case of trifluoroacetophenone, whereas only moderate changes were observed using trifluoro-phenylacetone. After insonation of the catalyst, the enantioselectivity was considerably improved. Both the aerobic and anaerobic sonochemical pretreatments resulted in significant improvement in optical yield (up to 49% and 17% ee, at room temperature under 10 bar in 1,2-dichlorobenzene). In parallel, the hydrogenation rates increased to a small extent (1.1-1.2-fold increase) after hydrogenative ultrasonic pretreatment, whereas the rates decreased by a factor of 1.5-2 after aerobic insonation. To obtain more insight into the process, the effect of insonation time on the activity and enantioselectivity and actual changes of the catalyst were also studied.

The first case of competitive heterogeneously catalyzed enantioselective hydrogenation of ketones

In competitive racemic hydrogenation of methyl benzoylformate (MBF) + ethyl pyruvate (EP) binary mixture over Pt/Al(2)O(3): k(MBF) > k(EP), but in competitive enantioselective hydrogenation k(MBF) < k(EP); the phenomenon verified for the first time is dependent on the adsorption strength of the surface complexes of various compositions (MBF-Pt, EP-Pt, MBF-CD-Pt, EP-CD-Pt, CD = cinchonidine).

Effect of coacid acidity on the cinchona-modified Pt-catalyzed enantioselective hydrogenations

The effect of acid strength of coacids on the enantioselective hydrogenation of ethyl pyruvate over cinchona-modified Pt/Al 2 O 3 catalysts is described. The enantioselectivity passes through a maximum as a function of acid strenght. The best value was obtained using trifluoroacetic acid as additive, which increased the optical yields from 85% to 93% ee. Chiral acids were also studied. It was found, however, that the individual chirality of acids used did not modify the basic characteristics of the outcome of the reactions. The configuration of the products were determined by the cinchona alkaloid. On the basis of separate experiments with cinchona salts a short interpretation of acid-effect is also provided.

Heterogeneous asymmetric reactions 34. New data in the enantioselective hydrogenation of ethyl pyruvate catalyzed by cinchona alkaloid-modified Pt/Al2O3 in toluene

The enantioselective hydrogenation of ethyl pyruvate (EtPy) on Pt-alumina (E 4759) catalyst modified by dihydrocinchonidine (DHCD) at a hydrogen pressure of 1 bar in toluene was studied. The effects of the modifier concentration (0.001-1 mmol l-1) and temperature (-10, 0, 24 °C) on the reaction rate and the enantioselectivity have been studied. Under mild experimental conditions (hydrogen pressure: 1 bar, temperature: -10 °C, DHCD concentration: 0.1 mmol l-1) an optical yield of 88% can be achieved. When EtPy hydrogenation was studied in AcOH under identical conditions, it was established that the DHCD/Ptsurf ratio necessary for achieving maximum enantioselectivity is highly solvent dependent: this ratio is 0.007 in AcOH and 0.12 in toluene. This large difference in DHCD/Ptsurf may be a reflection of a difference in reaction mechanism.