Search

Graphite oxide (GrO), graphene oxide (GnO) and their sulphated derivatives (GrOs, GrOo, GnOs, GnOo) were prepared from graphite (Gr) and graphene (Gn) as starting materials, using various methods. Previous experience suggests that in the course of sulphation relatively few functional groups get incorporated, which are mainly located along the edges of the layers. In the course of oxidation the layers are also converted to a significant extent, although aromatic regions are also retained, depending on the strength of the oxidative conditions. Proline impregnation of the functionalized catalyst supports obtained in this way enables the synthesis of Pro-GrO and Pro-GnO chiral catalysts. Proline interacts with the functional groups building up on the layers in a mostly reversible fashion and is relatively easily removed therefrom, whereas over sulphated materials groups forming on the edges allowed stronger bonding of proline. An asymmetric aldol reaction between 2-nitrobenzaldehyde and acetone with a selectivity of 90 % and an enantioselectivity of 77 % can be catalysed using these materials. The catalysts lifetime, however, is still limited at the present stage of our studies. Catalysts prepared from graphenes usually proved to be more active than those prepared from graphite, which was suggested to be due to the accessibility and amount of the functional groups created on the edges of the graphene sheets.

We report the aldol addition of acetone to aromatic aldehydes in the presence of a large amount of water where the stereochemical outcome of the reactions can be tuned with achiral salt additives using a single proline-derived catalyst. Depending on the nature of the added salt the ( R ) and ( S ) enriched products could be obtained. In the reaction of 2-nitrobenzaldehyde with acetone, NaOAc promoted the formation of the ( S )-enantiomer (20% ee) while using NH 4 Cl the ( R )-enantiomer was obtained in excess (58% ee). A similar inversion was observed for several other aromatic aldehydes.

The aim of this article is to collect the results published from the beginning (2000) on asymmetric direct aldol reactions taking place in the presence of immobilized chiral organocatalysts. The seven groups of organocatalysts discussed are: asymmetric direct aldol reactions catalyzed by: (1) covalently bonded immobilized hydroxyproline organocatalysts; (2) covalently bonded immobilized prolinamide organocatalysts; (3) covalently bonded immobilized peptide organocatalysts; (4) other covalently bonded immobilized chiral organocatalysts; (5) chiral organocatalysts bonded by ionic groups; (6) chiral organocatalysts with adsorptive bonding; and (7) other types of immobilized chiral organocatalysts. The main objective of this article based on results obtained by using about 360 immobilized organocatalysts, to bring to the focus of catalyst systems in which the aldol reactions yield beta-hydroxyketones of maximal optical purity, while keeping catalyst concentrations and reaction times as low and as short as pos...

We examined the activity of a series of L-hydroxyproline derivatives in enantioselective alpha-amination reaction between diethyl azodicarboxylate and propanal both in organic and aqueous media. In organic media most of the catalysts showed high activity and enantioselectivities comparable to that accessible with L-proline that is among the best catalysts in the reaction. The catalysts showed good activity under aqueous conditions as well; however, only low enantioselectivities were obtained in this case, primarily due to the racemisation of the product under the reaction conditions. Thus, the attempted achiral acid/base additive-driven stereocontrol was not feasible on a practical level.

The heterogeneous asymmetric direct aldol reactions between aldehydes (2-nitrobenzaldehyde, 2-methylpropanal) and ketones (acetone, cyclohexanone) in the presence of polystyrene (PS) resin supported di- and tripeptides were studied under otherwise identical experimental conditions at room temperature in batch reactor. For all three asymmetric aldol reactions reversal of enantiomeric excess was observed on H-Pro-Pro-Glu(OH)-PS catalyst (ee 39–50%) as compared to the H-Pro-Glu(OH)-PS catalyst (ee 52–95%). The determinant role of the conformation of the intermediate adducts held responsible for chiral induction is interpreted by quantum chemical calculations.

Heterogeneous asymmetric direct aldol reactions between aldehydes (2-nitrobenzaldehyde, 2-methylpropanal) and acetone catalyzed by polystyrene resin (PS) supported di- and tripeptides H-Pro-Pro-, H-Pro-Pro-Pro-, H-Pro-Glu(OH)-, H-Pro-Pro-Glu(OH)-, H-Pro-Asp(OH)-, H-Pro-Pro-Asp(OH)-, H-Ser-Glu(OH)-, H-Ser-Ser-Glu(OH)-, H-Val-Glu(OH)-, H-Val-Val-Glu(OH)-MBHA-PS, were studied under identical experimental conditions at room temperature in a continuous-flow fixed-bed reactor (CFBR) system. In the asymmetric aldol reactions reversal of enantioselectivity was observed on H-Pro-Pro-Glu(OH)- and H-Pro-Pro-Asp(OH)-MBHA-PS-supported catalysts (ee 42–67% S) as compared to the H-Pro-Glu(OH)- and H-Pro-Asp(OH)-MBHA-PS-supported catalyst (ee 28–82% R). In the case of H-Pro-Pro- and H-Pro-Pro-Pro-MBHA-PS-supported catalysts reversed enantioselectivity was observed by using the benzoic acid additive (12% S) as compared to the H-Pro-MBHA-PS catalyst (25% R). The stability of the catalysts in the flow system was consistent with the heterogeneous character of the reaction, as was the linear behavior obtained using mixtures of L- and D-enantiomers of the supported H-Pro-MBHA-PS catalyst. The enamine character of the reaction intermediates was supported by ESI-MS measurements. Based on these and the computed structure of the peptides, the conformation of the intermediate adducts is held responsible for chiral induction, therefore for the enantioselectivity inversion observed in these reactions.

We report new results on the aldol reactions between aldehydes of three different types (aromatic, aliphatic and cycloaliphatic) and acetone/cycloalkanones as reaction partners, driven by organic–inorganic hybrid catalyst Pro/γ-Al2O3. In contrast to the homogeneous liquid-phase reaction, over Pro/γ-Al2O3 reversal of the enantioselection in up to 20–40 % ee depending on the structure of the aldehyde was observed in reactions of acetone. Reversal of the ee in the presence of γ-Al2O3 cannot be generalized, as it has only been observed for acetone among the ketones studied by us. It was proven using methods of a great variety such as ultrasonic irradiation, reuse measurements on used catalyst and the filtrate of the first reaction, measurements on the l-Pro-l-Pro(OH) dipeptide, studies using mixtures of l-Pro and d-Pro that the organic–inorganic hybrid catalyst Pro/γ-Al2O3 formed in situ is responsible for reversal of the ee. In the reactions of cycloalkanones there is presumably competition between the liquid-phase and the surface reaction over Pro/γ-Al2O3 with preference for the former. Based on these results a surface reaction pathway was proposed. Although, the ees obtained under heterogeneous catalytic conditions are low, further studies may lead to application of this unusual phenomenon for obtaining chiral heterogeneous catalysts suitable for the preparation of the desired enantiomer of a chiral compound using the same chiral source.

The development of a novel heterogeneous catalytic asymmetric cascade reaction for the synthesis of tetrahydroquinolines from 2-nitrophenylpyruvates is reported. Optically enriched 3-hydroxy-3,4-dihydroquinolin-2(1H)-ones are prepared by enantioselective hydrogenation of the activated keto group over a Cinchona alkaloid-modified Pt catalyst, reduction of the nitro group and spontaneous cyclization cascade. Acceleration of the enantioselective hydrogenation of the activated keto group over the catalyst modified by Cinchona alkaloids ensured high tetrahydroquinolinone selectivities. The scope of the reaction was checked using twelve substrates. Both yields and enantioselectivities were significantly influenced by the nature and position of the substituents on the phenyl ring. Substituents adjacent to the nitro group considerably increased the product yield, due to their effect on the nitro group′s reduction rate; however, had only a limited effect on enantioselectivities.

The enantioselective hydrogenation of ketopantolactone (KPL) on Pt–alumina catalyst modified by β-isocinchonine (β-ICN) and O -phenylcinchonidine (PhOCD) in toluene, acetic acid and their mixtures under otherwise identical experimental conditions was studied. Reversal of the enantioselection was obtained dependent on the concentration of acetic acid (ee max = 17% ( S ) on Pt–PhOCD and 50% ( R ) on Pt–β-ICN, respectively). The possible role in enantioselection of adducts forming in the reaction mixture and the stability of PhOCD under the conditions of the hydrogenation was investigated by ESI-MS. The results of the nonlinear phenomenon measurements on β-ICN + PhOCD mixtures suggest that the intermediate surface complexes β-ICN–KPL and PhOCD–KPL responsible for the opposite enantioselection include different types of interactions and the enantioselection is directed by the competition between these interactions.

Parameters influencing dual stereocontrol in aldol reactions of water miscible acetone with aromatic aldehydes in the presence of a large amount of water using hydroxyproline based catalysts were studied. Stereocontrol was achieved by changing the acidity and basicity of the reaction media by the addition of achiral salts in the presence of a single chiral catalyst. Under acidic conditions (NH 4 Cl salt) the ( R )-aldol product was formed in excess while basic aqueous media (carboxylate salts) led to the enrichment of the ( S )-enantiomer. Reaction conditions under which the reaction is feasible were optimised and the effect of the structure of the hydroxyproline-based catalysts was investigated. The results show that the formation of a biphasic micellar system and the presence of an appropriate catalyst are both crucial for the reaction to occur. Although the catalyst structure influenced the formation and stabilisation of the micellar system to a large extent, its effect on the enantioselectivities were found to be less pronounced.

The preparation and application of heterogeneous chiral catalysts are described. Heterogeneous Pd, Ir and Ru catalysts were tested in the enantioselective hydrogenations of N-heterocyclic compounds, namely 6,7-dimethoxy-3,4-dihydroisoquinoline and 1-methylene-2-ethoxycarbonyl-6,7-dimetoxy-3,4-dihydroisoquinoline in the presence of optically pure cinchonidine, (S,S)- and (R,R)-Ts-DPEN ligands. Cinchonidine-modified metal catalysts exhibited low ee, whereas catalysts stabilized by triphenylphosphane and modified by (S,S)-Ts-DPEN afforded promising ee values (70–80 %). Immobilized Ru(II)-aminophosphane complexes were found to be active in these hydrogenations producing the corresponding tetrahydroisoquinoline derivatives in high optical purities (up to 97 %). The latter catalysts were characterized by infrared spectroscopy, solid-state MAS NMR spectroscopy and elemental analysis. Recycling of these catalysts showed constant or increasing activities in racemic hydrogenation, whereas the presence of the chiral ligands led to leaching of the active species in the liquid phase.

Under the experimental conditions of the Orito reaction the individual hydrogenation and the competitive hydrogenations of three binary mixtures of methyl benzoylformate (MBF), pyruvic aldehyde dimethyl acetal (PA) and 2,2-diethoxyacetophenone (DAP) on platinum–alumina catalysts modified by cinchonidine, cinchonine, quinine and quinidine (Pt–CD, Pt–CN, Pt–QN, Pt–QD) were studied for the first time using continuous-flow fixed-bed reactor system. Conversions of chiral (Cc) and racemic (Cr) hydrogenations of all three compounds and enantioselectivities (ee) were determined under the same experimental conditions (under 4 MPa H2 pressure, at room temperature using toluene/AcOH 9/1 as solvent).The order of the rates of the enantioselective hydrogenations of the three substrates studied is MBF > PA > DAP, and the order of their ee values is MBF ~ PA > DAP. The hydrogenation rate and the effect of rate on ee depend on the structure of the cinchona used: hydrogenation of MBF and PA may produce ee values over 90 %, however, the ee values were conspicuously low in the presence of Pt–QN and especially of Pt–QD catalysts. In the chiral hydrogenation of DAP considering racemic hydrogenation rate decrease (Cc/Cr

The effect of the achiral amine additive structure was studied on the enantioselective hydrogenation of (E)-2-methyl-2-butenoic acid and (E)-2-methyl-2-hexenoic acid over Pd/Al2O3 catalyst modified by cinchonidine. It was found that secondary amines are similarly or even more efficient in increasing the enantioselectivity as primary amines. The right basicity of the amine, which may vary in a rather wide range, should be coupled with appropriate steric properties to be effective in increasing the enantioselectivity. The best performing amines was the earlier widely used benzylamine and N-methylbenzylamine. The influence of these amines on the effect of the catalyst amount, H2 pressure and reaction temperature was studied. The effect of the amine amount on the hydrogenation of the two acids was also investigated. Based on the results the involvement of the amine additive in the formation of surface intermediates responsible for enantioselection is proposed. Decrease of the reaction temperature to 273 K increased the enantiomeric excess in the presence of amines, resulting in the hydrogenation of (E)-2-methyl-2-hexenoic acid in up to 71% enantioselectivity in favour of the S product enantiomer, the highest value obtained until now in the enantioselective hydrogenation of aliphatic unsaturated carboxylic acids over chirally modified heterogeneous catalyst.

Under the experimental conditions of the Orito reaction the competitive hydrogenations of four binary mixtures of ethyl pyruvate (EP), methyl benzoylformate (MBF), pyruvic aldehyde dimethyl acetal (PA) and 2,2-diethoxyacetophenone (DAP) on unmodified Pt/Al2O3 (racemic hydrogenation) and catalyst modified by cinchonidine (chiral hydrogenation) were studied using continuous-flow fixed-bed reactor system (CFBR). Conversions of chiral and racemic hydrogenations were determined under 4 MPa H2 pressure, at 293 K using toluene/acetic acid 9/1 as solvent. In the competitive chiral hydrogenation of MBF + EP and DAP + PA binary mixtures (S1 + S2) a new phenomenon was observed: namely the EP and PA are hydrogenated faster than MBF and DAP, whereas in racemic one the MBF and DAP are hydrogenated faster than the former ketones. The phenomenon verified for the first time in CFBR is dependent on the adsorption mode of the surface complexes of various compositions (S1–Pt, S2–Pt, S1–CD–Pt, S2–CD–Pt, CD = cinchonidine). In the chiral hydrogenation of DAP a rate decrease, i.e., “ligand deceleration” was observed instead of rate enhancement.

Competitive hydrogenations of eight binary mixtures of ethyl pyruvate (EP), methyl benzoylformate (MBF), ketopantolactone (KPL), pyruvic aldehyde dimethyl acetal (PA) and trifluoroacetophenone (TFAP) on platinum/alumina catalysts unmodified (racemic hydrogenation) and modified by cinchonidine (chiral hydrogenation) were studied under the experimental conditions of the Orito reaction. Reaction rates of chiral and racemic hydrogenations were determined and relative adsorption coefficients were calculated. In the competitive chiral hydrogenation of EP + MBF, EP + TFAP and KPL + MBF binary mixtures a new phenomenon was observed: namely the EP and KPL are hydrogenated faster than MBF and TFAP, whereas in racemic one the MBF and TFAP are hydrogenated faster than EP or KPL. Effects of the activated ketones structure on their reactivity and the stability of the surface complexes are discussed. It was found that differences in rate enhancement are caused by the differences both in the adsorptivity and in the reactivity of adsorbed substrates and adsorbed intermediate complexes.

Natural cinchona alkaloids and their derivatives were applied as chiral modifiers in the enantioselective hydrogenation of (E)-2-(2-methoxyphenyl)-3-(4-fluorophenyl)propenoic acid over Pd/Al2O3 cat...

The enantioselective hydrogenation of ( E )-2,3-diphenylpropenoic acids over Pd/Al 2 O 3 modified by ( R )C 8 ( S )C 9 cinchona ethers resulted in the inversion of the sense of the enantioselectivity. To find the explanation of the phenomenon, the interaction of acids bearing different substituents with cinchona alkaloids was studied in solution by NMR spectroscopy and experiments using mixtures of modifiers were carried out. The prominent non-linear behaviour obtained revealed the altered adsorption of the cinchona methyl ethers when compared with the parent alkaloids. The investigations indicated that the interaction of the ether derivatives with the unsaturated acids is more flexible and the presence of the methyl group reshapes the chiral surface sites. The combination of these effects complemented by the bulkiness of the diaryl substituted acrylic acids may lead to the inversion of the docking preference of the substrates in the altered chiral pocket of the adsorbed modifier and consequently results in decrease in the enantioselectivity or even in the inversion of its sense. Novel evidence on the ligand-accelerated mechanism in the enantioselective hydrogenation of ( E )-2,3-diphenylpropenoic acids over cinchona alkaloid-modified Pd in the presence of benzylamine was also presented.

The effect of the chlorine position on the C–Cl bond hydrogenolysis and the enantioselective hydrogenation of Cl substituted ( E )-2,3-diphenylpropenoic acid derivatives has been studied over cinchonidine-modified Pd/Al 2 O 3 . In contrast to the fast hydrodechlorination of the β-phenyl- para -Cl substituted acids the Cl on the α-phenyl ring was barely hydrogenolized. These observations were interpreted by the different arrangements of the two phenyl rings on the surface, with the α- and β-phenyl rings adsorbed tilted and parallel, respectively. The results confirmed the beneficial effect of the α-phenyl- ortho -substituents on the chiral discrimination, thus the 2,3-diphenylpropionic acids substituted by Cl on the α-phenyl ring could be prepared in good yields and optical purities. The conclusions were used for the rational design of an acid, i.e. ( E )-2-(2-methoxyphenyl)-3-(3,4-difluorophenyl)propenoic acid, which afforded the best optical purity ( ee up to 95% at 295 K) described until now in this heterogeneous system.

A study on the hydrogenation of ethyl pyruvate, methyl benzoylformate and 2,2,2-trifluoroacetophenone over Pt–cinchona alkaloid chiral catalysts and over the “unmodified” catalysts resulted after a cleaning step at 323 K of the chirally modified surfaces in continuous-flow fixed-bed reactor system is presented. According to these investigations the sense of the residual ee observed in the reactions carried out in the absence of modifiers over the catalysts rinsed after the chiral hydrogenations was influenced by the solvent and the structure of the activated ketone, pointing on the effect of these parameters on the structure of the adsorbed intermediate complexes and implicitly on the chiral induction.

Fumonisin mycotoxins which are hazardous to humans and animals were produced in a Fusarium verticillioides-infected solid rice culture. To decrease the possibility of the formation of artifacts, the fumonisins were analysed by reversed-phase high-performance liquid chromatography/electrospray ionization time-of-flight (RP-HPLC/ESI-TOFMS) and ion trap mass spectrometry (RP-HPLC/ESI-ITMS) immediately after the extraction of the culture material, without any further sample clean-up. The fumonisin isomers were separated by using a flat gradient on a special, high-coverage C 18 , narrow-bore HPLC column (YMC-Pack J'sphere ODS H80) suggested for the separation of structural isomers by the manufacturer. Exact mass measurements (TOFMS) of the protonated molecules and extraction of the ion chromatogram corresponding to the empirical formula (C 34 H 59 NO 15 ) of FB 1 toxins led to the identification of 29 peaks and shoulders, including those of FB 1 . The FB 1 toxin and 28 of its isomers were also detected by ITMS after separation with RP-HPLC. The characteristic m/z values of the product ions, including the backbones obtained by ITMS 2 , undoubtedly indicated the structures of the FB 1 isomers for 28 peaks and shoulders. In the MS 2 spectra of the protonated molecules of the FB 1 isomers, with some exceptions, 15 characteristic product ions including the hydrocarbon backbone at m/z 299 were observed. The abundance ratio of the cation at m/z 299 ranged up to 5.8%. The relative quantities of the isomers found in the sample extract were expressed as percentages of the FB 1 content (0.001-0.579%). The total amount of the 28 FB 1 isomers was 2.803% of the quantity of FB 1 that is important from the aspect of food and feed safety.

The enantioselective hydrogenation of 2,2,2,-trifluoroacetophenone over Pt/Al2O3 catalysts modified by cinchona alkaloids was investigated for the first time using continuous-flow fixed-bed reactor system in toluene/AcOH 9/1 solvent mixture in absence and presence of 0.1 v/v% trifluoroacetic acid (TFA). The enantioselective hydrogenations yielded the (R)-product in excess on Pt–CD, Pt–CN, Pt–QN and Pt–QD catalysts in toluene/AcOH mixture; consequently, unexpected inversion took place on the Pt–CN and Pt–QD catalysts. Hydrogenation in the presence of 0.1% (v/v) TFA follows the general rule of the Orito reaction, according to which the products formed in excess are (R)-alcohols on Pt–CD and Pt–QN and (S)-alcohols on Pt–CN and Pt–QD. Since there is no inversion in the presence of TFA, the observed unexpected inversion can be interpreted on the basis of the nucleophilic intermediate complex.

The enantioselective hydrogenation of 2,2,2-trifluoroacetophenone (TFAP) was investigated over Pt-cinchonidine (CD) and Pt-cinchona alkaloid derivatives chiral catalysts not yet studied in this reaction, such as Pt-cinchonine (CN), Pt-quinine (QN), Pt-quinidine (QD), Pt-β-isocinchonine (β-ICN), Pt-cinchona-C9-methyl ethers, Pt-hydroquinine- and -hydroquinidine-4-chlorobenzoate. As a result of the studies in toluene, toluene + trifluoroacetic acid, 2-propanol, acetic acid and dichloromethane, relationships were established between the structure and concentrations of the chiral modifiers in different solvents and the reaction rates and enantioselectivities (ee). As compared with the enantioselective hydrogenation of other activated ketones low to medium ee values and low rate enhancements were obtained which is probably due to the structure of the adsorbed intermediate complexes responsible for enantioselection. It has been confirmed by NMR measurements that, under the conditions of the hydrogenations, TFAP is present in the form of H-bonded dimers and oligomers in the liquid phase, which accounts for the low hydrogenation rate. When CN, QD and their C9-ether and ester derivatives were used as modifiers inversion of the sense of the enantioselection was observed, which amounted up to ee 30% over the cinchonine methyl ether and β-ICN modified catalysts. The present study is the first to report inversion of the enantioselectivity over Pt-CN chiral catalyst in the hydrogenation of an activated ketone.

The origin of rate enhancement in the enantioselective heterogeneous catalytic hydrogenation of ethyl pyruvate on Pt modified with the parent cinchonas, as compared to the unmodified Pt, was studied in a solvent mixture toluene/AcOH 9/1. Hydrogenation experiments were carried out in a continuous-flow fixed-bed reactor and in several cases for comparison in batch reactors over E4759 catalyst. Our results obtained using a novel procedure, namely racemic hydrogenation followed by three changes of the chiral modifier (on the same catalyst) supported an intrinsic “ligand acceleration” character of the rate enhancement in ethyl pyruvate hydrogenation.

The effect of the structure of the achiral primary amine additive on the enantioselective heterogeneous catalytic hydrogenation of (E)-2-methyl-2-butenoic acid over cinchonidine modified Pd/Al2O3 was studied. It was found that a variety of amines increase the enantioselectivity, which was always accompanied by decrease in the initial rate of the hydrogenations. Based on these results, the participation of the amine additive in the formation of the intermediate complex responsible for enantioselection was suggested. A decrease in the reaction temperature resulted in further increase in the optical purity of the product up to 67%, the highest value reported in the hydrogenation of unsaturated aliphatic acids in this heterogeneous catalytic system so far.

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.

A study on the origin of rate enhancement (RE) in the enantioselective heterogeneous catalytic hydrogenation of methyl benzoylformate (MBF), ketopantolactone (KPL) and pyruvic aldehyde dimethyl acetal (PA) under the Orito reaction conditions over Pt catalyst modified with parent cinchona alkaloids, as compared to the unmodified catalyst is presented. The hydrogenations were carried out in continuous-flow fixed-bed reactor system over 20–100 mg Pt/Al 2 O 3 catalyst in 1 mL min −1 flow of toluene/acetic acid 9/1 solvent mixture under 40–80 bar H 2 pressure, at 283 or 293 K using 0.044–2 mM modifier concentration and 45 mM substrate concentration. Our results obtained using racemic hydrogenations followed by three changes of the chiral modifier (on the same catalyst) supported the so-called “ligand acceleration” phenomenon in the enantioselective hydrogenation of activated ketones such as MBF, KPL and PA. In our opinion, RE produced by the first modifier added after racemic hydrogenation can also be explained by the purifying effect of the cinchona. REs observed following further exchanges of modifiers are indicative of the intrinsic character of the phenomenon. This research suggested that the origin of enantiodifferentiation and rate enhancement is the same, namely, both may be traced back—probably in different ways—to the role of the intermediate complexes of the hydrogenation, to its formation and transformation, which in turn depends on numerous factors.

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 nonlinear phenomenon (NLP) was studied for the first time in the enantioselective hydrogenation of ethyl pyruvate (EP) and ketopantolactone (KPL) under identical conditions, on Pt catalyst modified by quinine and cinchonine, and for comparison with cinchonidine-cinchonine pair. The data obtained using the three methods allowed recognition of a new observation, namely that the NLP depends not only on the chiral modifier but also on the substrate to be hydrogenated. This observation can presumably be interpreted on the basis of differences in the structure of the substrate-modifier complexes formed and in the adsorption-desorption processes of the complexes, thus the NLP is not solely dependent on the adsorption of cinchona alkaloids, as suggested by earlier experimental data.

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 N -methyl-3,4-dehydronipecotic acid (arecaidine) over Pd/Al 2 O 3 catalyst in presence of cinchona alkaloids and benzylamine additive results in the quantitative formation of N -methylnipecotic acid in good (up to 60%) optical purity. The reaction is a novel example of the efficient use of chirally modified heterogeneous metal catalysts allowing the preparation of enantioenriched N -heterocyclic carboxylic acids.

Results on nonlinear phenomenon (NLP) in the liquid phase hydrogenation of methyl benzoylformate (MBF) and pyruvaldehyde dimethyl acetal (PA) on chiral Pt-cinchona catalyst are reported for the first time (enantiomeric excess 90–95%). The new data support the conclusions of the NLP studies on ethyl pyruvate (EP) and ketopantolactone (KPL). Namely, the order of the adsorption strengths of the parent cinchona alkaloids are: CD > CN > QN ~ QD and the results of the NLP measurements indirectly verify the so-called 1:1 model of enantioselection. The new data, however, call attention to a new, substrate and modifier dependent phenomenon, which necessitates further experiments for a better understanding of the mechanism of the Orito reaction.

Experimental evidence (measured by NMR) is given for the correlation between the solution-state concentration of the nucleophilic 1:1 modifier–substrate complex and the ee on enantioselective hydrogenation of ketopantolactone using Pt– β -isocinchonine chiral catalyst. The relationship displays a saturation-type curve, which may indicate an underlying adsorption process involving the catalytically relevant nucleophilic complex.

The enantioselective hydrogenation of methyl benzoylformate (MBF) and pyruvaldehyde dimethyl acetal (PA) was investigated under mild experimental conditions on Pt-alumina catalyst modified with MeOCD, MeOCN, MeOQN and MeOQD alkaloid derivatives in acetic acid (AcOH) and in toluene (T). Besides low rate high ee's were achieved (>90%) in the case of PA using MeOCD and MeOQN modifiers in AcOH. Under similar experimental conditions in the case of MBF the highest ee's (50–80%) were obtained in T. Hydrogenation in the presence of MeOCN and MeOQD proceeded with low ee's, namely 4–8% for MBF in AcOH and 40–50% for PA in T. Studies on the hydrogenation of MBF and PA suggested that the low ee are attributable to repulsive interactions of OMe and ethyl groups of the modifiers with the substrates and with Pt surface. The formation of the complex responsible for enantioselection and, as a consequence, for high ee may be presumed to necessitate a two-point interaction between the cinchona alkaloid and the substrate. The two-point interaction requires a closer geometrical fit as compared to a one-point interaction, while the cinchona alkaloid and the substrate are bound to active sites of the catalyst through the quinoline skeleton and the oxo group to be hydrogenated, respectively. These new experimental results can be interpreted on the basis of adsorbed 1:1 interaction model not only of electrophilic mechanism but also in toluene by the nucleophilic mechanism, too.

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.

The enantioselective hydrogenations of ethyl pyruvate (EP), methyl benzoylformate (MBF), ketopantolactone (KPL) and pyruvaldehyde dimethylacetal (PADA) were studied on Pt–alumina catalyst modified by a new modifier namely α-isoquinine (α-IQ) with rigid conformation and for comparison by quinine (Q) in toluene and in acetic acid. The effects of modifier concentration, mixtures of modifiers, hydrogenation of α-IQ and theoretical calculations were examined on the interpretation of features of reactions. Using the Engelhard 4759 catalyst under mild experimental conditions (room temperature, 1 bar hydrogen pressure) the ees were lower in the case of α-IQ than for Q. The inversion of enantioselectivity observed in the case of the previously studied β-isocinchonine (β-ICN) containing C8( R ) and C9( S ) atoms in toluene as solvent failed to occur in the presence of α-IQ containing C8( S ) and C9( R ) atoms. Indirect experimental evidence for structure of adsorbed chiral modifier was supported by studies on hydrogenation and relative adsorption strength of α-IQ as well as by theoretical calculations. The significant enantioselectivity changes along the series of otherwise structurally related modifiers (Q, α-IQ and β-ICN) were compared with the ab initio computed geometrical features. The results revealed that besides the effects disclosed up to now in the literature, the orientational angle of the N-lone pair in the quinuclidine moiety relative to the quinoline also influences the structure and the adsorption mode of the intermediate responsible for the enantioselection.

The organocatalytic aldol reaction between acetone and α-substituted β-keto esters is presented. The α-unsubstituted or α-chloro ethyl acetoacetates failed to react with acetone when l -proline was used as catalyst. l -Proline or other optically pure pyrrolidine derivatives catalyzed the direct aldol reaction of acetone and α-fluorinated β-keto esters affording δ-keto-β-hydroxy-α-fluoro esters in high yields. Both the α-fluoro- and α,α-difluoro-β-keto esters functioned as aldol acceptors in these reactions. High ee values, up to 83% coupled with low diastereoselectivities were obtained in the reaction of ethyl 2-fluoroacetoacetate. Our study revealed a novel extension of the scope of the organocatalytic direct aldol reaction catalyzed by chiral organic bases, being the first report in which an asymmetric organocatalytic fluoroketone–ketone aldol addition has been described.

The enantioselective hydrogenation of itaconic acid was studied over cinchona alkaloid-modified supported palladium catalyst in the presence of benzylamine as achiral base additive. The effect of several reaction parameters was investigated, such as the addition order of the additive, modifier and itaconic acid, hydrogen pressure, reaction temperature, amount of additive and modifier. Enantioselectivities up to 58% could be obtained by setting the appropriate conditions. The above results along with studies on the structure of the achiral amine additive, the chiral modifier and the substrate led to an interpretation of the increased enantioselection observed in the hydrogenation of itaconic acid in presence of benzylamine. According to this benzylamine plays role both on the surface of the catalyst and in the liquid phase by transforming the acid in bis-benzylammonium salt. Due to the salt formation the interaction with cinchonidine occurred through the conjugated carboxylic group, which led to increased enantioselectivity. Based on modifications in the substrate structure the effect of the unconjugated carboxylic group was also discussed.

The enantioselective hydrogenation of two N-acetyldehydroamino acids over Cinchona alkaloid-modified, supported palladium catalysts has been studied. Moderate enantioselectivities, up to 36%, were obtained in the hydrogenation of 2-acetamido-cinnamic acid over cinchonidine-modified Pd/TiO 2 under low hydrogen pressure. Increase in the pressure or use of benzylamine as additive led to a gradual decrease in the enantiomeric excess and eventually inversion of the sense of the enantioselectivity. On the contrary, the optical purity of the product resulting from the hydrogenation of 2-acetamidoacrylic acid was significantly increased by addition of benzylamine to the reaction mixture. Enantiomeric excess values up to 58% and 60% were obtained over Pd/Al 2 O 3 modified by cinchonidine and cinchonine, respectively. These optical purities are the best obtained in the hydrogenation of dehydroamino acid derivatives over chirally modified heterogeneous metal catalysts.

The enantioselective hydrogenation of four α,β-unsaturated carboxylic acids has been studied over cinchona alkaloid-modified supported Pd catalyst in a high-pressure continuous-flow system using a fixed-bed reactor. The hydrogenation of the aliphatic substrates resulted in products of slightly lower enantioselectivities as obtained in batch reactors under similar reaction conditions. The optical purity of the product formed in the hydrogenation of α-phenylcinnamic acid was over 70%, exceeding the values obtained in slurry reactor in the same solvent. It was shown that the enantioselectivity increasing effect of benzylamine is kept in the fixed-bed reactor. Based on the results obtained by changing the modifier concentration in the feed we suggest that the interaction of the substrates with cinchonidine may occur in the liquid phase and the complex formed is adsorbed on the Pd surface. Thus, relatively high concentration of such complex and consequently modifier amount is necessary for obtaining good enantioselectivities in the hydrogenation of α,β-unsaturated carboxylic acids.

The Pt-alumina-CD catalyzed enantioselective hydrogenations of ethylpyruvate (EP), ketopantolactone (KPL) and methyl benzoylformate (MBF) have been studied at first in an H-Cube flow hydrogenator in toluene and toluene + acetic acid. Based on the experience of previous studies carried out in batch-reactor and continuous flow systems, some parameters were kept constant (amount of catalyst, 380 mg; substrate concentration, 0.18 mol/L; temperature, 283 K), whereas others, namely chiral modifier (CD) concentration, hydrogen pressure and total liquid flow (TLF: substrate + modifier + solvent) were varied. In the course of enantioselective hydrogenation (R)-products were formed in excess: in the case of EP, KPL, MBF: 90, 60, 80 % enantioselectivities were obtained.

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.

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 enantioselective hydrogenation over a Cinchona alkaloid-modified supported platinum catalyst and parallel spontaneous racemization under the reaction conditions of the unreacted enantiomer of ethyl 2-fluoroacetoacetate are described. Using the appropriate reaction conditions an 82% enantiomeric excess in favor of the (2S,3R)-ethyl 2-fluoro-3-hydroxy-butanoate and a 99/1 threolerythro ratio were obtained. This novel method for producing optically enriched α-fluoro-β-hydroxy esters is the first example of dynamic kinetic resolution of a chirally labile racemic fluorinated compound over a modified heterogeneous metal catalyst carried out without using supplementary additives except the chiral modifier. The hydrogenation described here shows that the activation of the keto group of acetoacetates by one fluorine atom in the a position is also sufficient for obtaining high enantiomeric excess in the Orito reaction.