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Various propenoic acid stereoisomers 2,3-disubstituted with thienyl and/or phenyl groups were synthesised and their aggregation behaviour was studied both in solution and in the solid state by experimental (mid-range FT-IR spectroscopy) and computational (semiempirical and ab initio) methods. Experimental approach embraced the identification of potential hydrogen bonding sites through finding the relevant IR bands and monitoring their displacement upon increasing the acid concentration in solution and on going from solution to the solid state. In solution O H⋯O hydrogen bonds were only found providing short-range ordering, while in the solid state C H⋯S hydrogen bonds were identified. Hydrogen bonding sites could be assigned and relevant aggregate models could be built. Molecular modelling allowed obtaining good estimates for hydrogen bond lengths and angles and visualisation of the geometric arrangements.

Various F-substituted E-2,3-diphenyl propenoic acid molecules were synthesised and their aggregation behaviour was studied by experimental (FT-IR spectroscopy) and computational (semiempirical and DFT) methods. Experimental approach embraced the identification of potential hydrogen bonding sites through finding the relevant IR bands and monitoring their shifts upon increasing the acid concentration and on going to the solid state. It was found that fluorine engaged in C H…F hydrogen bonding easily, where the carbon atom could be of any kind available in the molecule (aromatic, aliphatic or olefinic). Shifts were found even in moderately concentrated solutions and in the solid state too. Hydrogen bonding sites could be assigned and relevant aggregate models could be built. Molecular modelling allowed obtaining good estimates for hydrogen bond lengths and angles and visualisation of the geometric arrangements even of extended networks also became feasible.

The hydrogenation of two 2,3-diarylpropenoic acids bearing heteroaromatic substituents, i.e. ( E )-2-phenyl-3-(2-furyl)propenoic acid and ( E )-2-(3-pyridyl)-3-phenylpropenoic acid was studied over cinchonidine modified Pd catalyst for the first time. The 2-furyl substituted compound was selectively hydrogenated to 2-phenyl-3-(2-furyl)propionic acid in the presence of cinchonidine in up to 73% ee. The hydrogenation of the acid bearing 3-pyridyl substituent afforded lower ee as compared to ( E )-2,3-diphenylpropenoic acid, reaching up to 61% in presence of benzylamine additive. The differences in the results were assumed to be due to the different adsorption strengths and modes of these acids and deviations in their interactions with the adsorbed modifier.

The enantioselective hydrogenation of methoxy- and fluorine-substituted (E)-2,3-diphenylpropenoic acid derivatives was studied over cinchonidine-modified, supported palladium catalysts in the absence and presence of benzylamine as additive. The fluorine substituent in the appropriate position was even more efficient than the methoxy group in increasing the optical purity of the saturated product. High enantioselectivities, up to 96%, were obtained in the hydrogenation of some disubstituted derivatives, unprecedented in the hydrogenation of prochiral unsaturated carboxylic acids over modified heterogeneous catalyst. The best optical purities were reached in the hydrogenation of derivates bearing a para-substituent on the β phenyl and an ortho-substituent on the a phenyl ring, respectively. The influence of the substituent on the β phenyl ring was attributed to the increase in the efficiency of the modifier-substrate interaction by electronic effects or to a decrease in the adsorption strength of the substituted acid over modified surface sites. The beneficial effect of the ortho-substituent on the a phenyl ring was assumed to be due to the additional interaction of this substituent with the modifier on the surface, its steric hindrance contributing only in a small part to the observed effect. These suggestions were supported by results obtained in the hydrogenations of some methyl-substituted derivatives.

Hydrogenation of α-ketoesters containing steroid groups at the ester side and at the keto carbonyl function of substrates was investigated the first time on Pt–alumina–cinchona alkaloids chiral catalysts using mild experimental conditions (room temperature, 1 bar hydrogen pressure, modifier concentration 1 mM) in the presence of acetic acid. Catalysts modified by cinchona alkaloids ensured enantioselective hydrogenation with 10–70% ee, depending on the steric structure of the substrate. In the absence of cinchonas racemic hydrogenation takes place, i.e. the chiral centers of the substrates do not participate in chiral induction. Experimental data so far obtained support the assumption that under stereochemical conditions not inhibiting adsorption of the substrate and after optimization of the experimental conditions, the Orito reaction may be rendered suitable for the asymmetric hydrogenation of bulky activated ketones. These results also supply additional evidence for the determinant role of the H-bonded adsorbed intermediate, the 1:1 complex of cinchona alkaloid and substrate in chiral induction under protic conditions.

The enantioselective hydrogenation of mono and dimethoxy-substituted 2,3-diphenylpropenoic acids has been studied over cinchonidine modified supported Pd catalyst. The hydrogenation of the six monosubstituted methoxy derivatives of ( E )-2,3-diphenylpropenoic acid showed that the position of the substituent has a decisive influence on the initial reaction rate and the enantioselectivity. High enantioselectivities, 86–90%, were obtained in the hydrogenation of mono-substituted derivatives with a favourable substituent position. The results were rationalized in terms of either the electronic or the steric effects of the methoxy substituent determined by its position. These suggestions were also applicable in interpreting the results obtained in the hydrogenation of substituted ( Z )-2,3-diphenylpropenoic acids and selected dimethoxy ( E )-2,3-diphenylpropenoic acids. The combined steric and electronic effects of the substituents on the α- and β-phenyl rings ensured the highest enantioselectivities, up to 92% ee, in the hydrogenation of ( E )-2-(2-methoxyphenyl)-3-(4-methoxyphenyl)propenoic acid.

The hydrogenation of trifluoromethyl substituted prochiral α,β-unsaturated carboxylic acids has been studied over cinchona alkaloid modified palladium heterogeneous catalysts. Low enantioselectivities were obtained in the hydrogenation of all three test compounds, 2-trifluoromethylacrylic acid, 4,4,4-trifluoro-3-methyl-2-butenoic acid and ( E )-4,4,4-trifluoro-3-phenyl-2-butenoic acid, respectively. Significant increase in the enantioselectivity, up to 43%, was obtained in the hydrogenation of 4,4,4-trifluoro-3-methyl-2-butenoic acid by using benzylamine as additive. The presented results showed for the first time the possibility of enantioselective hydrogenation of α-unsubstituted β-disubstituted α,β-unsaturated carboxylic acids in the cinchonidine modified palladium catalytic system, that resulted in optically enriched saturated acids having the chiral center in β position.

Enantioselective hydrogenation of seven different esters of phenylglyoxylic acid was investigated by variation of the bulkiness at ester side of the substrates [Ph C(O) C(O)OR, R = Me ( l ), cyclohexyl ( 2 ), adamantyl ( 3 ), cis -decahydro-1-naphthyl ( 4 ), phenyl ( 5 ), 1-naphthyl ( 6 ), 2-naphthyl ( 7 )] on Pt-alumina-cinchonidine (CD) and Pt-alumina- β -isocinchonine ( β -ICN) chiral catalysts using mild experimental conditions (273 K and room temperature, hydrogen pressure of 1–25 bar) in solvents of AcOH and toluene. Hydrogenation on Pt-alumina-CD chiral catalyst produced high values of ee for all but the 5 and 7 compounds. The formation of ( R )-mandelic acid esters was 86–91% in AcOH and 79–94% in toluene. The experiments verified the general applicability of the Orito reaction in the preparation of enantiomers of α -hydroxyesters. Under the experimental conditions applied, the magnitude of ee is affected by the steric size of α -ketoesters and by solvents. In the enantioselective hydrogenation of substrates over a Pt-alumina- β -ICN catalyst in toluene, inversion of enantioselectivity occurred; ( R )-mandelic acid esters formed with a medium ee of 30–54%. The conformation of the adsorbed modifier plays a more determining role than the bulkiness of the substrate in the formation of the intermediate complex responsible for enantioselection.

The enantioselective hydrogenation of ethyl pyruvate (EtPy) was studied on Pt-alumina catalysts modified by C3-substituted cinchonidines (NC, A, B, C1, C2in Fig. 1) and for comparison by DHCDand MeO-DHCDin AcOH. The effect of the C3-substituent on the reaction rate and the enantioselectivity were examined. Using the Engelhard 4759 catalyst under mild experimental conditions (room temperature, hydrogen pressure 1 bar) such as DHCDthe (R)-ethyl lactate formed in excess (e.e.max: 79-91%)

We synthesized C9-O-silyl ethers of cinchonidine and dihydrocinchonidine (1-8), seven of which have not been known before. The structures of the compounds were verified by ESI-ion-trap MS and 1H-NMR. Fragmentation of silyl ethers containing Si-phenyl bonds was studied for the first time. The compounds obtained will be utilized as chiral catalysts of certain asymmetric syntheses.

The effect of the structure of C9-O-substituted cinchona alkaloids as chiral modifiers of Pt on the enantioselectivity of the Pt-alumina-catalyzed hydrogenation of ethyl pyruvate under mild experimental conditions (room temperature, hydrogen pressure of 1 bar, mainly toluene and tetrahydrofurane as solvents) was investigated. Although C9-O-substituted bulky chiral modifiers also have the open3 conformation, which is a prerequisite of high ee, the ee values observed were still low and even opposite to that expected. Based on the experimental data of a great variety of experiments (ESI-ion-trap-MS, modifier mixtures, selective hydrogenation of chiral modifiers, computational studies) the inversion can explain by tilted adsorption of chiral modifier, namely by a conformational change in the adsorbed chiral modifier and reactant 1:1 intermediate complex.

The hydrogenation of β-isocinchonicine (β-ICNN) was studied on Pt- and Pd-alumina catalysts for the first time. Using mild experimental conditions (293 K, 1 bar hydrogen pressure) in toluene and in AcOH as solvents it was established that the enolo-ethereal C C double bond of β-ICNN is hydrogenated to the two DH-β-ICNN diastereomers. In toluene, hydrogenation proceeds at a significantly higher rate on Pd-alumina catalyst than on Pt-alumina. In AcOH, hydrogenation is fast on both catalysts. There was no significant difference between the selectivities of diastereomer formation on Pd and Pt catalysts. The presence of cinchonidine (CD) and cinchonine (CN) reduced the hydrogenation rate of β-ICNN and had no effect on the stereoselectivity of hydrogenation. Ethyl pyruvate (EtPy) hydrogenation on Pt-alumina catalyst modified with β-ICNN proceeded with low enantioselectivity, which is another piece of evidence for the essential role of the conformation of the chiral modifier in the Orito reaction.

Methyl-3α-acetoxy-23-oxo-5β-cholan-24-oate is hydrogenated with 78% enantioselection at C23 atom over Pt-alumina catalyst modified with cinchona alkaloids, in liquid phase under mild experimental conditions (293-297 K, hydrogen pressure: 1 bar, concentration of modifiers: 0.1 mmol/L, solvent: THF).

While in the unsubstituted Z-2,3-diphenylpropenoic acid and its methyl ester the olefinic protons rarely were part of any hydrogen bonding interaction, upon substitution by CF3 group, the possibility of (aromatic)C–H⋯F intermolecular hydrogen bond appeared and indeed realised for the molecules (E-2,3-diphenyl-3-CF3-propenoic acid and its methyl ester) in the solid state. This type of close contact was indicated experimentally by FT-IR spectroscopy.

The conformations of E-2-phenyl-3(2'-furyl)propenoic acid and its methyl ester were investigated by NMR spectroscopy. Applying various solvents (methanol, chloroform and dimethyl sulfoxide) the possible conformers in solutions were studied by two-dimensional NOESY measurements. Irrespective to the solvents and whether the investigated moiety was the ester or the acid dimer, no conformational preferences could be identified experimentally.

The enantioselective hydrogenation of ethyl pyruvate (EtPy) in toluene was studied on a Pt-alumina catalyst modified with α -isocinchonine ( α -ICN) and β -isocinchonine ( β -ICN). The effects of the modifier concentration, temperature, and hydrogen pressure on the reaction rate and the enantioselectivity were examined. Using the Engelhard 4759 catalyst under mild experimental conditions, we observed the formation of an excess of ( S )-ethyl lactate (EtLt) in the presence of α -ICN formed (ee max : 27%). In the case of β -ICN, an inversion of enantioselectivity was observed and ( R )-EtLt formed in excess (ee max : 50%). α -ICN mainly undergoes hydrogenation during the reaction, followed by desorption, whereas β -ICN works as a chiral modifier, and the hydrogenation of EtPy is the main transformation. The results of ESI-MS-MS, HPLC-ESI-ion-trap-MS, NMR, UV–vis measurements, and experiments with modifier mixtures strongly suggest that β -ICN, with a rigid, open conformation, is responsible for enantioselection and inversion. The proposed structure of the intermediate responsible for the inversion of enantioselectivity is a 1:1 β -ICN–EtPy surface complex in which the β -ICN acts as a nucleophile and binds EtPy.

The transformations of a-ICN and b-ICN were studied in the presence of hydrogen in AcOH over Pt-alumina catalyst under the conditions of the enantioselective hydrogenation of EtPy (hydrogen pressure 1-30 bar, temperature 298-323 K). It was established that the quinoline skeleton of the alkaloids is hydrogenated even under mild experimental conditions, whereas hydrogenolysis of the oxazacycloalkane structure only takes place at hydrogen pressures exceeding 1 bar. ESI-MS-MS, HPLC-ESI-ion-trap MS and NMR made possible the identification of several hydrogenated cinchona alkaloid derivatives with so far unknown structures. According to these experimental results, the conformation of isocinchona alkaloids remains unchanged under the conditions of the enantioselective hydrogenation of activated ketones, making them suitable for utilization as chiral modifiers of well-defined conformation.

The enantioselective heterogeneous catalytic hydrogenation of trifluoromethylcyclohexyl ketone (2), on Pt-alumina (E4759) modified by different chiral compounds in toluene and ethanol solution with and without trifluoroacetic (TFA) has been investigated. The effects of the type of modifiers and their concentration (0–10 mmol/l), hydrogen pressure (1–100 bar), temperature (273–301 K) and conversion on the reaction rate and the enantioselectivity (ee) were studied. The achieved ee was 48% in the case of CD. Depending on solvents the inversion of enantioselectivity was observed. The available information suggests that the compounds responsible for chiral induction are different intermediates, the structure of which depends mostly on the acidic or non-acidic nature of the hydrogenation medium.

The reaction mixture for the hydrogenation of ethyl pyruvate on Pt-alumina catalyst modified with isocinchona alkaloids (α-ICN (I) and β-ICN (II)) was studied by electrospray ionization tandem mass spectrometry (ESI-MS/MS). It was established that part of the chiral modifiers themselves are converted into ions of m/z 299, 305 and 309 in the course of chiral hydrogenation. The experimental data allowed the determination of the probable structure of the ions mentioned. According to ESI-MS/MS spectra the structure of the new cinchona alkaloids was assumed: tetrahydro-isocinchonines (III–VI), decahydro-isocinchonines (VII, VIII) and hydrogenated compounds of VII and VIII by scission of their CN and CO bonds (IX/1, IX/2, X). Fragmentation pathways are proposed for these new compounds. Copyright © 2004 John Wiley & Sons, Ltd.

The enantioselective hydrogenation of ethyl pyruvate (EtPy) was studied on Pt-alumina catalysts modified by high-purity α -isocinchonine ( α -ICN) and β -isocinchonine ( β -ICN) in AcOH. The effect of the modifier concentration, temperature, and hydrogen pressure on the reaction rate and the enantioselectivity was examined. Using the Engelhard 4759 catalyst under medium experimental conditions (273 K, hydrogen pressure of 25 bar, α -ICN concentration of 1 mmol/L) an optical yield of 93–94% can be achieved. In the case of β -ICN, maximum ee is 70–72% (297 K, 20 bar, β -ICN concentration of 1 mmol/L); at the same time, the rate of EtPy hydrogenation is higher than in the case of dihydrocinchonine (DHCN) or α -ICN. Chiral modifiers themselves are converted under the conditions of hydrogenation. The results of ESI-MS, ESI-MS-MS, HPLC-MS, and desorption measurements strongly suggest that α -ICN and β -ICN compounds with a rigid structure are responsible for chiral induction, since DHCN and hydrogenated products of DHCN were not identifiable among the reaction products. These experimental results support the earlier assumption that it is cinchona alkaloids in the “open 3” (in another terminology “antiopen”) conformation that participate in enantioselection. However, based on other experimental observations of this work, the participation of other, so far unknown factors in enantioselection may not be excluded either.

Measurements by infrared (FT-IR) spectroscopy in the solid state as well as in solution and molecular modeling calculations revealed that the major structure forming force (short range ordering) between 2-phenyl-3(2′-furyl)propenoic acid stereoisomers was the CO⋯H–O intermolecular hydrogen bonding between the carboxylic groups. For the E isomer no other secondary intermolecular interaction could be measured nor calculated. Molecular modeling showed that long-range ordering was possible between the hydrogen-bonded dimers of the Z isomer via (phenyl)C–H⋯(furyl)O close contacts. The methyl esters also had short-range ordering through (phenyl)C–H⋯(carbonyl)O interaction, while only the Z isomer offered the possibility of long-range order. Chain-like structures were formed via (phenyl)C–H⋯(furyl)O hydrogen bonds.

The reactions of ethyl pyruvate with acetic anhydride and pyridine were studied by electrospray ionization mass spectrometry (ESI-MS). Ethyl 2-acetoxy-2-pyridiniumpropionate (1) (m/z 238) resulting from the reaction of the acetylpyridinium cation with ethyl pyruvate, and the adduct of ethyl 2-acetoxyacrylate with a pyridinium cation (2), bound together by non-covalent interactions (m/z 238), were identified by ESI-MS for the first time. Structures 1 and 2 cannot be distinguished, probably because one may be converted into the other and vice versa.

The enantioselective hydrogenation of ethyl benzoylformate to (R)-ethyl mandelate over dihydrocinchonidine (DHCD)-modified Pt/Al2O3 catalyst in acetic acid was studied as a function of modifier concentration, hydrogen pressure and reaction temperature. The maximum enantioselectivity obtained under optimized conditions (DHCD concentration 1 mmol dm-3, 25 bar H2, 0 °C, AcOH/toluene 1:1) was 98% ee. The difference between the rates of racemic and enantioselective hydrogenation was less significant than in the case of ethyl pyruvate. This indicates that the high reaction rate in the enantioselective heterogeneous hydrogenation of α-ketoesters is not a necessary condition of the chiral induction.

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.

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.

Measurements by infrared (FT-IR) spectroscopy revealed that in solutions of low concentration the major structure forming force (short-range ordering) between methoxy-substituted α-phenylcinnamic acid stereoisomers was the CO⋯H–O intermolecular hydrogen bonding between the carboxylic groups. Under 10 −3 mol/dm 3 concentration no other secondary intermolecular interaction was found. In solid state, using IR spectroscopy, FT-IR and 13 C NMR spectroscopies, it was possible to detect (aromatic)C–H⋯O hydrogen bonds, which were thought to be responsible for long-range ordering. Through the comparison of 13 C chemical shifts in the liquid phase and the solid state (olefinic)C–H⋯O interactions were sought for. Such interactions could not be found for the methoxy derivatives. Molecular modeling provided structural semiquantitative information for the hydrogen bonds detected by IR spectroscopy and gave additional proof for the existence of (aromatic)C–H⋯O and the non-existence of (olefinic)C–H⋯O hydrogen bonds.

The electron impact ionisation (EI) and electrospray ionisation (ESI) mass spectra using in-source collision-induced dissociation of nine different cinchona alkaloid derivatives [iso-cinchona alkaloids (ethereal isomers) and 10-Br(Cl) containing cinchona compounds] have been studied. In the case of the EI method for iso-cinchona alkaloids the observed fragmentation directions are as follows: isomerisation of the cyclic ethers to the corresponding C9 ketone, the formation of [M − 15]+, [M − 29]+ and [M − 57]+ fragments as a result of the loss of methyl, ethyl and butyl radicals, and the cleavage of the C8–C9 bond. The fragmentation of the compounds containing C10–Br(Cl) bonds started with the scission of this bond. The primary bond rupture is followed by the fragmentation of the primary product into two parts across the C8–C9 bond. In the case of the ESI method at low capillary exit voltage only the peak of the protonated molecule ([M + H]+), and in a significantly lower abundance, the peak of the [M + 2H]2+ ion can be observed. Increasing the capillary exit voltage causes fragmentation to occur. For iso-cinchona alkaloids the main direction is the cleavage of C8–C9 bond. For the C10–Br(Cl) compounds, the primary fragmentations are the cleavage of the C9–O and C10–Br(Cl) bonds. Fragmentation pathways are discussed.

Intermolecular hydrogen bonding interactions in stereoisomeric α-substituted cinnamic acid methyl esters (methyl 2,3-diphenylpropenoate, methyl 2-phenyl-3-(2′-methoxyphenyl)-propenoate, methyl 2-(2′-methoxyphenyl)-3-phenylpropenoate and methyl-2,3-bis(2′-methoxyphenyl)-propenoate) were studied by FT–IR spectroscopy and model calculations at the semi-empirical quantum chemical level of theory. Intermolecular hydrogen bonds of C–H…O types were found to be general in the solid state, but rare in solution. In this hydrogen bond the carbon may be part of either aromatic ring or the olefinic bond. The hydrogen bond acceptor may be the carbonyl oxygen or the oxygen in the methoxy substituent. Modeling helped in determining probable hydrogen bonding sites and their positions and provided with approximate geometric parameters (bond lengths and angles). Pointing out differences between the stereoisomers was also possible.

The electrospray ionization (ESI) mass spectra of 16 cinchona alkaloid compounds were studied for the first time. The electron ionization (EI) spectra of 22 cinchona alkaloids were also recorded, 14 of which had not been examined previously. In the case of EI the characteristic direction of the fragmentation is the scission of the C8-C9 bond. Under EI the cleavage of the C4'-C9 bond occurs only in the case of hydrogenated cinchona alkaloids, whereas the C9-O bond cleavage can be observed in the case of ester and ether derivatives. At a low capillary exit voltage (CapEx) in the ESI measurements there is no fragmentation, and only the [M + H](+) and in some cases the double protonated [M + 2H](2+) ions can be detected. On increasing the CapEx the characteristic primary direction is the cleavage of the C9-O bond, which was observed in the case of epialkaloids and esterified or etherified cinchona derivatives, respectively. Copyright 2000 John Wiley & Sons, Ltd.

The enantioselective hydrogenation of ethyl pyruvate to (S)-ethyl lactate over Pt/Al2O3 catalyst was investigated using the new modifier β-isocinchonine (40% ee) which has oxazatwistane structure. These studies supply additional evidence for the widely accepted reaction mechanism.

The use of cinchona alkaloids (cinchonidine, cinchonine, quinine, quinidine, α-isocinchonine, α-isoquinidine, γ-isoquinidine) in the Orito reaction (hydrogenation of ethyl pyruvate and ethyl benzoylformate) strongly supports the structure of the intermediate complex (cinchona alkaloid “anti‐open” conformer–pyruvate 1 : 1 complex); in addition, so far unknown stereochemical conditions have been identified and the utilization of rigid cinchona conformers in the study of asymmetric syntheses have been generalized.

The transformation of cinchonidine was studied in the presence of hydrogen on Pt/alumina by electrospray ionization mass spectrometry using in‐source CID. So far unknown compounds were identified. Further studies on the basis of these new observations may permit to establish a more comprehensive mechanism of enantioselective hydrogenation of α-ketoesters.

Enantioselective sonochemical hydrogenation of α,α,α-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/SiO 2 , Pt/K-10 and Pt/Al 2 O 3 catalysts under conventional conditions. Since Pt/Al 2 O 3 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 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. © 1999 Wiley-Liss, Inc.

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.

Extremely high (98%) enantioselectivity of the hydrogenation of ethyl benzoylformate on Pt/Al 2 O 3 modified with dihydrocinchonidine was achieved. The difference between the rates of racemic and enantioselective hydrogenation was less significant than in the case of ethyl pyruvate. This indicates that ligand acceleration is a welcome effect but no necessary prerequisite for achieving high enantioselectivity.

An investigation was made of the hydrosilylation of 2,2,4,4-tetramethyl-1,3-cyclobutanedione with alkyl- and arylsilanes, catalysed by a variety of rhodium(I) complexes. Tle selectivity of the reduction depends strongly on the steric requirements of the silane molecules. An appropriate selection of hydrosilanes (di- and certain trialkylsilanes) provides a new selective method for the preparation of 3-hydroxy-2,2,4,4-tetramethylcyclobutanone. Diphenylsilane and amylsilane are selective in the formation of isomeric diols, diphenylsilane favouring formation of the cis-diol, and amylsilane yielding mainly the trans-diol.

The potassium salt of E- and Z-2,3-diphenylpropenoic acids prepared in situ could be esterified efficiently in DMSO with the appropriate alkyl halides at room temperature. In this way 10 previously undescribed esters of these acids were synthesised and characterised. Excellent yields were observed for most of the E isomers and the more hindered Z esters were also obtained in good yields, far better than those obtained applying the classical acid-catalysed esterification reaction.

The reactions of ethyl pyruvate with acetic anhydride and pyridine were studied by electrospray ionization mass spectrometry (ESI-MS). Ethyl 2-acetoxy-2-pyridiniumpropionate (1) (m/z 238) resulting from the reaction of the acetylpyridinium cation with ethyl pyruvate, and the adduct of ethyl 2-acetoxyacrylate with a pyridinium cation (2), bound together by non-covalent interactions (m/z 238), were identified by ESI-MS for the first time. Structures 1 and 2 cannot be distinguished, probably because one may be converted into the other and vice versa.

In the enantioselective hydrogenation of ethyl pyruvate (EtPy) over beta-isocinchonine (beta-ICN) modified Pt-alumina catalysts, the major enantiomer was (R)-ethyl lactate ((R)-EtLt (ee 50%)) in toluene, while in AcOH (S)-EtLt (ee 60%) was formed; the (R) configuration is opposite to what is expected from the absolute configuration of the cinchonine backbone.

Chiral sonochemical hydrogenation of an aliphatic alpha-ketoester, ethyl pyruvate to ethyl lactate was carried out over various platinum catalysts in different solvents under atmospheric hydrogen pressure. The reaction rates and the enantiomeric excesses were determined over Pt/C, Pt/SiO2 and Pt/K-10 catalysts both under conventional and sonochemical conditions. The effect of ultrasounds on the catalytic activity and enantioselectivity was tested applying sonochemical pretreatment before the reaction. The ultrasonic irradiation was found to be highly advantageous in these hydrogenations. After insonation of the catalysts, the enantioselectivity was highly improved over Pt/SiO2 and Pt/K-10 catalysts. In addition, the reactions took place in quantitative yield and with complete chemoselectivity and the hydrogenation rates increased with one order of magnitude despite the very mild (atmospheric hydrogen pressure, room temperature) experimental conditions.

Sonochemical chemo- and enantioselective hydrogenations over supported platinum catalysts are described. We disclose our results with respect to a sonochemical modification of the chemoselective hydrogenation of cinnamaldehyde over supported platinum catalysts, and the asymmetric hydrogenation of ethyl pyruvate promoted by various ultrasonic pretreatments. The ultrasonic pretreatment of the supported platinum catalysts was found to be highly beneficial in almost every case, improving both the catalytic activity and selectivity. The effect of additional experimental variables, such as hydrogen pressure, catalyst support, temperature and the ultrasonic insonation time were also studied. The enantioselectivity of the hydrogenation of ethyl pyruvate increased up to 97.1% ee. In the case of cinnamaldehyde hydrogenation, the selective preparation of cinnamyl alcohol became possible. The theoretical aspects of the working mechanisms in comparison with ‘silent’ reactions will also be provided.

The sonochemical hydrosilylation of alkyl substituted cyclohexanones catalyzed by Rh(PPh 3 ) 3 Cl is described. The application of ultrasonic irradiation during the reaction highly enhances the reaction rates and produces higher yields than those obtained in silent reactions. The stereoselectivity of the reaction has not been changed, the isomeric distribution, i.e. the cis / trans ratio of the 2-substituted cyclohexanols formed, is very close to those obtained in conventional stirred reactions.

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.

A series of stereoisomeric o-methoxy-substituted 2,3-diphenyl propenoic acids and their methyl esters have been synthesized. The E isomers were prepared by a modified Perkin condensation (substituted benzaldehyde, phenylacetic acid, Et3N/acetic anhydride). The difficult to access Z isomers were obtained conveniently in good yields when the appropriate coumarin derivatives were allowed to react with KOH and CH3I in DMSO.

The first direct asymmetric synthesis of chiral alkyl 5-oxo-tetrahydrofuran-2-carboxylates (up to 96% ee), which are important building blocks in the synthesis of natural products by heterogeneous cinchona-modified Pt-catalyzed hydrogenation of α-ketoglutaric acid esters and subsequent cyclization of hydroxy esters is described.

The first satisfactory application of the heterogeneous cinchona-modified Pt catalyst system for the synthesis of a C3 chiral building, namely, the highly enantioselective (up to 96.5% ee) hydrogenation of pyruvaldehyde dimethyl acetal to lactaldehyde dimethyl acetal is described.

The hydrogenation of ethyl pyruvate to (S)-ethyl lactate (up to 70% ee) over a Pt/Al2O3 catalyst using α-isocinchonine as a modifier strongly supports the structure of the intermediate complex [cinchona alkaloid (open conformer)–pyruvate 1:1 complex] of this type of reactions.