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Highlights: [•] CNTs are applied as nanoreactor for Pd-catalyzed asymmetric hydrogenation. [•] The catalytic performance of Pd catalyst is enhanced when confined in CNTs. [•] The chiral modifier, additive, and reactant can be enriched in the channels of CNTs. [ABSTRACT FROM AUTHOR]

Abstract: The influence of the configuration at the C8 and C9 positions of cinchona alkaloids was investigated by comparing the efficiency of cinchonidine, cinchonine, and 9-epi-cinchonidine as chiral modifiers. In the hydrogenation of ketones (methyl benzoylformate, ketopantolactone, methylglyoxal dimethylacetal, 2,2,2-trifluoroacetophenone) on Pt, a change in the configuration at C9 did not affect the absolute configuration of the main products; however, the ees and rates dropped significantly. In the hydrogenation of α-functionalized olefins (E-2-methyl-2-hexenoic acid, 2-phenylcinnamic acid, and 4-methoxy-6-methyl-2H-pyran-2-one) on Pd, replacement of cinchonidine or cinchonine by epi-cinchonidine diminished the rates and almost eliminated the enantioselection, indicating that a subtle combination of C8 and C9 configurations is required on Pd. DFT calculations of the adsorption of the modifiers and the nonlinear behavior of modifier mixtures revealed that the lower reaction rates observed for 9-epi-cinchonidine-modified surfaces cannot be related to different adsorption strength of this modifier. Additionally, substrate–modifier docking interactions are presented. [Copyright &y& Elsevier]

Abstract: The influence of acidic and basic supports on the enantioselective hydrogenation of acetophenone and its aryl-substituted derivates was studied. The Pt/Al2O3, Pt/Al2O3–SiO2, and Pt/Al2O3–Cs2O catalysts were prepared by single-step flame spray pyrolysis, and cinchonidine (CD) was used as chiral modifier. For all five aromatic ketones, the acidic support improved the ee, while the basic support diminished it. Opposite tendencies were observed for the reaction rate: acidic support lowered and basic support enhanced the rate of ketone conversion. In situ investigation of the hydrogenation of the quinoline ring of CD revealed for the first time that degradation of the modifier leads to remarkable variation in the substrate/modifier ratio. This effect and a possible catalyst deactivation due to aldol condensation of the ketones may be the origin of the decrease in ee with conversion. Following the diastereoselectivity during hydrogenation of the heteroaromatic ring of the quinoline unit of CD proved dominantly pro(S) adsorption mode on Pt/Al2O3 and Pt/Al2O3–SiO2, and pro(R) on Pt/Al2O3–Cs2O catalysts. Changes in the adsorption mode were minor during hydrogenation of aromatic ketones. This, together with the small effect of ketones on the hydrogenation rate of CD, is interpreted as an indication to weak substrate–modifier interactions, in contrast to the situation during the hydrogenation of α-ketoesters (methyl benzoylformate). [Copyright &y& Elsevier]

Abstract: The role of metal–support interaction in the hydrogenation of cinchonidine (CD) was studied on acid- and base-doped flame-made Pt/alumina. Analysis of the product distribution revealed that on Pt/alumina and Pt/alumina–silica CD adsorbs on Pt in pro(S) geometry, but doping the support with only 0.25wt.% Cs2O is sufficient to invert the major adsorption mode to pro(R). The origin of differences between the effect of an acidic additive and support acidity is discussed. [Copyright &y& Elsevier]

Abstract: It is commonly accepted that the origin of enantioselection on chirally modified metals is the control of the adsorption and reactivity of the substrate by the chiral environment of the modifier. Here, we provide the first experimental evidence to a mutual process, namely, that the substrate controls the adsorption and reactivity of cinchonidine (CD) on the metal surface. Our approach is to follow the competing hydrogenation of the quinoline ring, the anchoring moiety of CD, in the presence or absence of an activated ketone substrate. On Pt/Al2O3 in the weakly interacting solvent toluene, CD (and 10,11-dihydro-CD) favors a C(4′) – pro(S) adsorption geometry and saturation of the heteroaromatic ring gives 1′,2′,3′,4′(S),10,11-hexahydro-CD {(S)-CDH6} in excess. Addition of methyl benzoylformate, ketopantolactone, or ethyl pyruvate inverts the dominant conformation of CD to C(4′) – pro(R) as indicated by the major product (R)-CDH6, and even the rate is higher by about 30% (“inverse ligand acceleration”). Acetic acid that interacts strongly with CD exerts a similar effect on quinoline hydrogenation. In contrast, the product α-hydroxyester interacts weakly with CD, decelerates the hydrogenation of the quinoline ring and the de of CDH6 depends on the chirality of the α-hydroxyester. These unexpected observations provide a fundamentally new insight into the complexity of the surface conformation of CD and the origin of high enantioselectivity on cinchona–modified Pt. [Copyright &y& Elsevier]

Abstract: Kinetic behaviour of different substrates such as purified ethyl pyruvate, dimer containing (20%) ethyl pyruvate, methylbenzoyl formate and ketopantolactone was investigated in both racemic and enantioselective hydrogenation over Pt/Al2O3 catalysts. Upon introducing the chiral modifier by injection under condition of racemic hydrogenation an immediate increase in reaction rate is observed in the case of all substrates. Consequently, significant rate enhancement (RE) was obtained in the case of all substrates. The RE increased in the following order: ketopantolactone

Relationship between substrate structure and enantioselectivity is studied for the asymmetric hydrogenation of 42 different (E)--disubstituted acrylic acids (propenoic acids) over cinchonidine-modified Pd/C. The β-phenyl group is indispensable for high enantioselectivity of α-phenylcinnamic acid (2,3-diphenylpropenoic acid, 81% ee), and substitution on this group affects markedly the selectivity. The high ee up to 92% was achieved by the -alkoxyphenyl substitution, and the selectivity is ascribed mainly to stronger interaction of the substrate with the chiral modifier on the catalyst surface. In contrast, substitution on the α-phenyl group does not affect notably the enantioselectivity (80–82% ee) or even the α-phenyl group itself is not indispensable but replaceable with a properly bulky group for the high enantioselectivity. [Copyright &y& Elsevier]

Abstract: A series of 0.5–4.3 wt% Rh/Al2O3 catalysts were prepared by flame synthesis. STEM indicated relatively narrow particle size distributions for all catalysts and the mean particle size increased almost linearly with the Rh content in the range 0.96–1.65 nm. A DRIFTS study of CO adsorption on as prepared Rh/Al2O3 and after heat treatment in hydrogen at 400 °C revealed that there was no Rh oxide present at the catalyst surface after the high temperature reduction, which procedure is commonly used prior to enantioselective hydrogenation. In the hydrogenation of ethyl pyruvate and ethyl 3-methyl-2-oxobutyrate the cinchona-modified 4.3 wt% Rh/Al2O3 gave considerably higher ee than those achieved with the best known Rh catalyst. A decrease of the metal loading and thus the mean Rh particle size, led to a loss of ee to (R)-lactate by a factor of up to seven at 1 bar and up to two at 10–100 bar. Our interpretation is that the performance of Rh/Al2O3 is strongly distorted at atmospheric pressure by catalyst deactivation due to the Al2O3-catalyzed aldol condensation of the substrate. During the fast reactions at 100 bar the contribution of strongly adsorbed impurities is small and the variation of ee is mainly due to an intrinsic particle size effect. The structure sensitivity observed under optimal conditions, at high surface hydrogen concentration, is mainly due to steric effects: a small, ca. 1 nm Rh particle cannot accommodate the enantiodifferentiating diastereomeric substrate–modifier complex and the hydrogenation on its surface leads to racemic product. A practical conclusion is that there is no advantage of using small nanoparticles and low metal loading in the enantioselective hydrogenation of α-ketoesters. [Copyright &y& Elsevier]

Abstract: A magnetic Pt/SiO2/Fe3O4 catalyst consisting of chirally modified platinum supported on silica coated magnetite nanoparticles was prepared using an easy synthetic route and successfully applied for the enantioselective hydrogenation of various activated ketones. The magnetic catalyst modified with cinchonidine showed a catalytic performance (activity, enantioselectivity) in the asymmetric hydrogenation of various activated ketones in toluene comparable to the best known Pt/alumina catalyst used for these reactions. The novel catalyst can be easily separated from the reaction solution by applying an external magnetic field and recycled several times with almost complete retention of activity and enantioselectivity. [Copyright &y& Elsevier]

Abstract: A simple transient method—replacement of the chiral modifier in the reactor feed with a second modifier that gives the opposite enantiomer of the product in excess—was used to investigate the competition of cinchona alkaloids on a commercial Pt/Al2O3 catalyst. Ethyl pyruvate was hydrogenated in a continuous-flow fixed-bed reactor with high enantiomeric excess (up to 89%) and reaction rate (TOF 12,700 h−1) at a modifier/substrate molar ratio of only 307 ppm. The rate of modifier replacement indicates the following order of adsorption strength on Pt: cinchonidine > cinchonine > quinidine, which is in line with that observed with other techniques. The dynamics of the competition was investigated under different reaction conditions. The study supports the contention that the origin of “ligand acceleration” is not the suppression of catalyst deactivation by addition of the chiral modifier, because under appropriate conditions, catalyst deactivation is negligible in pyruvate hydrogenation. The catalytic experiments were completed with an ATR-IR study in a high-pressure, continuous-flow reactor cell in which the formation of (R)- and (S)-lactate, and the competition of cinchonidine and quinidine at the Pt surface, could be followed in situ. [Copyright &y& Elsevier]

Abstract: The directing effect of the CF3 group on Pt/alumina modified by cinchonidine in the enantioselective hydrogenation of activated ketones was studied experimentally and theoretically using aliphatic -trifluoromethyl ketones as model compounds. -Trifluoromethyl ketones with varying steric hindrances of the groups on the two sides of the keto group (methyl-trifluoromethyl ketone 1a, adamantyl-trifluoromethyl ketone 2a, and tert-butyl-trifluoromethyl ketone 3a) were examined. The catalytic results show that in weakly polar solvents, in which the interaction of the solvent with the substrate, modifier, and Pt is less important, the three alcohols 1b, 2b, and 3b have the same absolute configuration (R). This indicates that enantioselectivity is guided by the trifluoromethyl substitution rather than by the relative bulkiness of the substituents at the two sides of the carbonyl group. The fluorinated substrate has a preferential interaction on the side of the -trifluoromethyl group, as corroborated by the calculation of hydrogen–bonding interactions. When this interaction mode is calculated for the system alkaloid–trifluoroacetone, an energy difference between the Pro(R) and the Pro(S) configurations is found. Our findings suggest that electronic effects give a bias toward the formation of the (R)-enantiomer. [Copyright &y& Elsevier]

Abstract: Steric effects in the Pt-catalyzed asymmetric hydrogenation of nine different α-ketoesters were studied by variation of the bulkiness at the keto and ester side of the substrates, and by using cinchonidine (CD), its 6′-methoxy derivative quinine, and o-phenyl derivative PhOCD as chiral modifiers. In the presence of CD, the (R)-enantiomer always formed in good to high ee (up to 96%), independent of the steric bulkiness of the α-ketoester. None of the mechanistic models developed for ketone hydrogenation on Pt are conform to the observations. Only additional steric effects in the modifiers and replacement of toluene by acetic acid as a reaction medium enhanced the sensitivity of the catalyst system to steric effects in the substrates (). An important mechanistic consequence of the observations is that on CD-modified Pt preferred adsorption of the α-ketoester on the si-side is directed by the position of the ester group relative to the modifier, independent of the steric bulkiness on any side of the keto-carbonyl group. Ester, carboxyl, amido, carbonyl, acetal, and trifluoromethyl functions have similar directing effects, but when both trifluoromethyl and an ester or carbonyl groups are present in the molecule, the latter function is dominant. The directing effect of the electron-withdrawing (-activating) function on adsorption of the ketone is obviously related to the electronic environment provided by the chiral modifier. The critical role of electronic interactions is supported by the remarkable influence of aryl substituents in the hydrogenation of ethyl benzoylformates. [Copyright &y& Elsevier]

Abstract: The conformations of cinchonidine (CD) adsorbed on a Pt(111) surface were studied using first-principles methods. Eight conformationally different adsorption states due to different degrees of rotation around the and degrees of freedom were identified and their possible role in the formation of chiral surface sites relevant to enantioselective hydrogenation investigated in light of the currently existing experimental evidence. Comparison of the conformational behavior of CD in solution and on platinum has revealed the effect of the metal surface on the internal mobility of the alkaloid. Although the study corroborates the outstanding role of the adsorbed Open(3) conformer suggested previously, the rich conformational flexibility observed on the platinum surface points to the possibility that other conformers of CD also may be involved in enantiodifferentiation. Closed conformations of CD are found to play an important role in the conformational equilibria on the surface due to their stability and are identified as precursors of the less stable, but presumably more active, open conformers. Although the open and closed conformers are closely related to the correspondent ones found in solution, surface species that are also adsorbed via quinuclidine moiety are characteristic of the metal–modifier interaction and should serve as precursors to catalytically active conformations. [Copyright &y& Elsevier]

Abstract: The Orito reaction with ethyl benzoylformate on Pt/Al2O3 was performed in a piecewise continuous manner with a chiral fixed-bed reactor (CFBR), using a variety of chemical and physicochemical methods to pretreat or clean the chiral fixed bed between multiple hydrogenation reactions. It was observed that after an enantioselective hydrogenation with cinchonidine as modifier at 0 °C, the CFBR could be effectively cleaned at 0 °C, and that a racemic unmodified hydrogenation could be performed thereafter. This implies the effective desorption of chiral species from the surface during cleaning. In sharp contrast, it was observed that after the same enantioselective hydrogenation at 0 °C, and after a cleaning treatment of the CFBR at 50 °C, a reproducible unmodified enantioselective hydrogenation, with a marked (ca. −9% to −18%) enantiomeric excess (e.e.), resulted. This reversal in the e.e. was stable over time. Similar experiments were conducted with ethyl pyruvate and (a) Pt/Al2O3 and cinchonine or (b) Pt/C and powdered Pt catalysts with cinchonidine. The e.e. reversal was again observed in (a), and residual chiral induction but e.e. retention was observed in (b). It is suggested that the e.e. reversal in the unmodified hydrogenation on Pt/Al2O3 can be explained by a superposition of two more or less irreversible modifications of the surfaces during the 50 °C cleaning phase. One modification is associated with a more or less irreversible change of the Pt and a minor e.e. retention effect, and the other modification is associated with the presence of the support Al2O3 and a predominant e.e. reversal effect. These two effects constitute a previously unknown origin for stereodifferentiation in the Orito reaction. [Copyright &y& Elsevier]

Abstract: The enantioselective hydrogenation of -unsaturated acids catalyzed by cinchonidine-modified Pd/C was found to be highly dependent on the pretreatment temperature of the catalyst. An asymmetric yield as high as 92% was achieved in the hydrogenation of (E)-2,3-di(4-methoxyphenyl)propenoic acid using a conventional 5%Pd/C catalyst activated in situ at elevated temperatures before modification with cinchonidine. [Copyright &y& Elsevier]

Abstract: The adsorption mode of cinchonidine on platinum is discussed in the light of new computational studies in which the alkaloid is adsorbed on a large metal cluster. Previous computations focused on the role of 1(S)-(4-quinolinyl)ethanol as anchoring group, but in the present study the role of the quinuclidine ring is analyzed, leading to a consistent view of the roles of both moieties of the alkaloid in the adsorption process. The tertiary nitrogen of the quinuclidine moiety can participate in the anchoring of the alkaloid and can be protonated by surface hydrogen. The conformational flexibility of the quinuclidine moiety was investigated by attenuated total reflection infrared experiments under nearly in situ conditions, by comparing the adsorption behavior of cinchonidine and O-phenyl-cinchonidine on platinum. Close agreement was found between experimental observations and theoretical calculations. A mechanism is proposed whereby the tertiary nitrogen can promote charge polarization of hydrogen and its transfer to the substrate. [Copyright &y& Elsevier]

Abstract: Recently a new mechanism for the enantioselective hydrogenation of (activated) ketones has been suggested, involving a zwitterionic intermediate between the tertiary amine function of the chiral modifier and the keto–carbonyl group of the reactant. The present NMR study indicates that the mechanistic model is probably based on erroneous interpretation of the experimental data; the NMR spectra that have been reported for zwitterion formation may arise from an aldol addition product between the ketone and solvent acetone. Steric effects and the regioselectivity of the hydrogenolysis of the hypothetic zwitterionic intermediate also exclude this mechanism for ketone hydrogenation on Pt. [Copyright &y& Elsevier]

Abstract: The mechanistic models developed for the enantioselective hydrogenation of ethyl pyruvate are based on the fundamental observation that transformation of the basic quinuclidine N atom of cinchonidine to quaternary cinchonidinium salts results in the complete loss of enantioselectivity. Astonishingly, the N-methyl, N-benzyl, and -dimethyl derivatives of cinchonidine are effective chiral modifiers of Pt in the hydrogenation of a cyclic α-ketoester, ketopantolactone. All three alkaloid derivatives gave (S)-pantolactone in excess, the configuration that is the opposite of that provided by cinchonidine, O-methyl cinchonidine, and cinchonidinium hydrochloride. Under mild conditions at 3 bar, Pt/Al2O3 modified by -dimethyl-cinchonidinium chloride afforded 44.5% ee, which is comparable to the performance of cinchonidine (51.5% ee). A mechanistic model is proposed that is based on an electrostatic interaction between the cinchonidinium cation and the free electrons of the keto group of the reactant. The observations highlight the importance of the structural rigidity of the reactant in the enantioselection and the frequently reported substrate specificity of chirally modified Pt. Under certain conditions (dichloromethane, -dimethyl-cinchonidinium chloride as modifier), doubling of the ee with conversion was observed. The reason for this phenomenon could not be clarified, but it may be due to some restructuring of the nanoparticle surfaces on the atomic scale. [Copyright &y& Elsevier]

Abstract: The nonlinear behavior of modifier mixtures has been studied with the use of the enantioselective hydrogenation of ketopantolactone to pantolactone as an industrially important model reaction. A 5 wt% Pt/Al2O3 catalyst was modified by pairs of enantiomers, diastereomers, and chemically different chiral compounds possessing the same or different anchoring moieties (i.e., the part of the molecule responsible for the strong adsorption on the metal surface). The linear correlation observed with mixtures of the two enantiomers ()- and ()-pantoyl-naphthylethylamine is in agreement with the generally accepted 1:1 type reactant:modifier interaction. A strong nonlinear phenomenon was observed only when the anchoring moieties of the two modifiers were different. The dramatic nonlinearity induced by the addition of cinchonidine to (S)-naphthylethylamine or ()-pantoyl-naphthylethylamine is traced to the different adsorption behaviors of the quinoline and naphthalene fragments of the modifiers on Pt. In an extreme case, (R)-pantolactone was produced with 26.5% enantiomeric excess (ee) with the use of a mixture containing only 0.5 mol% cinchonidine, although the (S)-product was obtained with 74% ee when ()-pantoyl-naphthylethylamine was applied alone as a modifier. The results indicate that (i) 1:1 type interactions determine the enantioselectivity, and ordered two-dimensional chiral arrays do not play a role; (ii) the nonlinear phenomenon is traced mainly to the different adsorption strengths of the modifiers, although there is no general correlation between the adsorption strength and the effectiveness of the modifiers used alone; (iii) only traces of a strongly adsorbing impurity (≪1 mol%) can significantly distort the ee, but large amounts (≈50 mol%) of a weakly adsorbing impurity may have a negligible influence on the enantioselection. [Copyright &y& Elsevier]

Abstract: The use of one equivalent of benzylamine increased the enantioselectivity in the heterogeneous catalytic hydrogenation of -unsaturated carboxylic acids over cinchonidine-modified 5% Pd/Al2O3 catalyst. The beneficial effect of the amine additive was dependent on substrate structure. The highest effect, a more than sixfold increase in the enantiomeric excess, was obtained in the hydrogenation of itaconic acid. This is the first report on the enantioselective hydrogenation of a prochiral -unsaturated dicarboxylic acid over a supported heterogeneous metal catalyst. [Copyright &y& Elsevier]

1-Phenylpropane-1,2-dione was hydrogenated over chirally modified 5% Pt/Al2O3 catalyst at 10 bar H2 and 15 °C using toluene and acetic acid as solvents. The highest enantiomeric excess for the major product (R)-1-hydroxy-1-phenyl-2-propanone () was obtained using cinchonidine as the chiral modifier. The presence of the hydroxyl group in the C-9 position of the modifier was important for achieving high enantioselectivity. When the C-9 hydroxyl group of cinchonidine was replaced by a methoxy group enantioselectivity was lost and a small 2% excess of (S)-1-hydroxy-1-phenyl-2-propanone enantiomer was observed. In acetic acid the reaction with cinchonidine proceeded yielding a 7% excess of the (R)-product. Hydrogenation of the intermediate hydroxyketones in acetic acid using cinchonidine or 9-methoxy-10,11-dihydrocinchonidine as chiral modifiers gave the corresponding (1S,2R)-diol in 67 and 78% enantiomeric excesses, respectively. By changing the solvent from acetic acid to toluene, an inversion of enantioselectivity took place yielding the (1R,2S)-diol as the main product in 38% ee. A mechanism was proposed involving a two-step cycle (reactant–modifier) and a three-step cycle (reactant-modified acetic acid) in order to account for the observed enantioselectivities. [Copyright &y& Elsevier]

FTIR and NMR spectroscopy and ab initio calculations were applied to understand the nature of enantioselection in the hydrogenation of the heteroaromatic ring in furan- and benzofurancarboxylic acids over cinchonidine-modified Pd. Most probably, cinchonidine adsorbs on Pd, via its quinoline moiety, approximately parallel to the surface, and the protonated quinuclidine N atom and the OH function of the alkaloid form a cyclic complex with the deprotonated acid dimer (2:1 acid:cinchonidine). The acid dimer adsorbs via the electron-rich furan ring and the carboxylate groups close to parallel to the Pd surface; the furan O atom points toward the OH function of cinchonidine. In this position, hydrogen uptake from the Pd surface results in the (S)-enantiomer as the major product. Another cyclic complex (1:1) involving cinchonidine and only one acid molecule is also feasible in solution, but this rigid structure is thermodynamically less favored, and it may be difficult to fulfill the geometric constraints imposed by adsorption on the metal surface. [Copyright &y& Elsevier]

The adsorption of cinchonidine on platinum has been calculated with relativistically corrected density-functional theory, by first studying the interaction of the 1(S)-(4-quinolinyl)ethanol with a platinum cluster of 31 metal atoms, and by successive addition and separate optimization of the quinuclidine moiety. The conformations of the alkaloid on the surface were analyzed and their possible interactions with a surface chemisorbed methylpyruvate and acetophenone are discussed. A chiral space that is able to selectively accommodate surface enantiomers and to promote their rapid hydrogenation in a ligand-accelerated fashion has been determined. The role of the O-alkylation of the alkaloid in the modulation of enantioselectivity has been rationalized within the new interaction model. [Copyright &y& Elsevier]

Aqueous suspensions of modified cinchonidine platinum nanoparticles produced from H2PtCl6 reduction in the presence of the surfactant N,N-dimethyl-N-cetyl-N-(2-hydroxyethyl)ammonium chloride salt have shown efficient activity for the asymmetric hydrogenation of ethyl pyruvate in biphasic media under hydrogen pressure. The aqueous phase containing the Pt(0) nanocatalysts can be used for further runs with a total conservation of activity and enantioselectivity for (R)-(+)-ethyl lactate up to 55%. Characterization of the reusable catalytic system by transmission electron microscopy revealed the formation of a “colloidal superstructure.” [Copyright &y& Elsevier]

The initial transient period (ITP) was studied in the enantioselective hydrogenation of activated ketones (ethyl pyruvate, pyruvaldehyde dimethyl acetal, methyl benzoyl formate) on Pt-alumina (E4759) catalyst modified by cinchonidine (CD) or dihydrocinchonidine (DHCD) under mild experimental conditions in toluene (hydrogen pressure: 1 bar, temperature: 253–298 K, modifier concentration: 0.001–1 mmol/L). The effects of temperature, modifier concentration, different pretreatments of the catalyst, and structure of the reactants on the relationship of the enantiomeric excess (ee) and conversion were studied. Our results suggest that the ITP is affected not only by impurities/contaminants present in the catalytic system but also by the competitive adsorption of reactants, modifier, and solvent. Consequently it may not be excluded that the ITP can be considered an intrinsic feature of this type of enantioselective hydrogenation reaction. [Copyright &y& Elsevier]

The enantioselective hydrogenation of vicinal diketones over cinchonidine-modified Pt resulted in enantiomeric excess of structurally similar (R)-enantiomers. Furthermore, the kinetic resolution was caused due to faster reaction of (S)-hydroxyketone further to diols, resulting in an increase of ee. The diastereoselectivities in diols were similar. The (R,S) or (S,R) diols were always the main products whereas considerably less (R,R) of (S,S) were formed. For the first time in 1-phenylpropane-1,2-dione (A) hydrogenation enantiomeric excesses of both C1&z.dbnd;O1 and C2&z.dbnd;O2 group have been reported. The ee1-OH and ee2-OH were 50 and 25%, respectively, at 50% conversion of A. Based on batch and continuous reactor experiments it could be concluded that the source of enantioselectivity is an increased formation rate of (R)-enantiomer and decreased formation rate of (S)-enantiomer. Theoretical calculations revealed that in the substrate-modifier diastereomeric complex the reactant forms a nonplanar s-cis conformation and bonds to the protonated cinchonidine either via a bifurcated hydrogen bond or with two hydrogen bonds where the OH group is involved also. Optimized diastereomeric complexes were equal in energy. The calculated proton affinity of CD was high, 1000 kJ mol-1, indicating that protonation is feasible under typical experimental conditions. [Copyright &y& Elsevier]

The influence of different dissolved gases on the adsorption of cinchonidine from CCl4 solutions onto polycrystalline platinum surfaces has been studied by in situ reflection–absorption infrared spectroscopy (RAIRS). It was observed that Ar, N2, O2, air, or CO2 neither enhances the adsorption of cinchonidine nor damages cinchonidine adlayers once they have formed on the surface. On the other hand, H2 plays a unique role, initially facilitating the uptake of cinchonidine, but later removing some of the resulting adsorbed cinchonidine from the platinum surface. It was also found that CO is a strong inhibitor, significantly retarding the adsorption of cinchonidine. Adsorbed CO can be removed by H2 dissolved in the cinchonidine solution, a process that also boosts the adsorption of cinchonidine. O2 can remove the surface adsorbed CO as well, but without facilitating cinchonidine adsorption. The cleanliness of Pt surfaces at different stages of the experiment was probed by CO adsorption. Possible correlations between the RAIRS results from the present study and reported data from catalytic studies are discussed. [Copyright &y& Elsevier]

Enantioselective hydrogenation of aromatic and heteroaromatic compounds is the field where chirally modified metal hydrogenation catalysts have the biggest potential compared to homogeneous chiral transition metal complexes. Here we report the hydrogenation of furan and benzofuran carboxylic acids over a cinchonidine-modified 5 wt% Pd/Al2O3 catalyst. (S)-Tetrahydrofuran-2-carboxylic acid was synthesized in 4 h at rt and 30 bar with 95% yield and 32% ee. The ee was lower in the hydrogenation of methylfuran carboxylic acids but up to 100% de was achieved. In the slow hydrogenation of benzofuran-2-carboxylic acid, the ee went up to 50% at 29% yield. The potential application of the method is limited by the competing hydrogenation of the quinoline rings of cinchonidine in the latter reaction, necessitating the feeding of small amounts of cinchonidine during reaction. Still, this simple method using an easily available chiral modifier and catalyst affords the highest rate and ee reported so far in the catalytic asymmetric hydrogenation of furan and benzofuran carboxylic acids, and it may be an attractive route in combination with optical resolution. We assume that the reaction mechanism is analogous to that described for α,β-unsaturated carboxylic acids over the same catalyst, involving a 1:2-type interaction between the cinchonidine and the acid dimer. [Copyright &y& Elsevier]

The enantioselective hydrogenation of 4-hydroxy-6-methyl-2-pyrone (1a), 3,6-dimethyl-4-hydroxy-2-pyrone (2a), 4-methoxy-6-methyl-2-pyrone (3a), and 4,6-dimethyl-2-pyrone (4a) was studied over a 5 wt% Pd/TiO2 catalyst. Various cinchona alkaloids and their O- and N-methyl derivatives were applied as chiral modifiers. The catalytic experiments combined with FTIR, NMR, and NOESY-NMR spectroscopic analysis and ab initio calculations revealed an interesting feature of the reactions: the ee is determined by competing reactant–modifier interactions. These interactions may involve the OH function and the quinuclidine N of the alkaloid modifier. When the reactant possesses an acidic OH group (1a and 2a), the reaction via the energetically most stable bidentate complex controls the enantioselectivity. Protic or basic solvents diminish the ee in these reactions by stabilizing a single-bonded (acid–base type) interaction. Different mechanisms are proposed for the hydrogenation of the nonacidic pyrones 3a and 4a. These models can well interpret the catalytic results but require further confirmation. Besides, the studies provided the first experimental evidence for an intrinsic rate acceleration coupled with the enantiodifferentiating process over chirally modified Pd. [Copyright &y& Elsevier]

Enantioselective hydrogenation of acetophenone derivatives demonstrates the potential of the Pt–cinchona system in the synthesis of chiral alcohols that possess no functional group in the α-position to the CH&z.sbnd;OH group. Electron-withdrawing functional groups in the aromatic ring increased the reaction rate and enantiomeric excess (ee), and the position of the group (o-, m-, or p-) was also important. 60% ee was obtained in the hydrogenation of 3,5-di(trifluoromethyl)acetophenone under ambient conditions, though the special role of reaction parameters has not been investigated yet. Addition of cinchonidine slowed down all hydrogenation reactions—an unprecedented behaviour for chirally modified Pt. [Copyright &y& Elsevier]

The asymmetric hydrogenation of cyclohexane-1,2-dione over cinchonidine-modified platinum was investigated. Despite the fact that the first hydrogenation step is close to nonenantioselective, a high enantiomeric excess is obtained for the (R)-α-hydroxyketone due to kinetic resolution. In the second hydrogenation step one out of the four reactions of the network is substantially accelerated with respect to the others and with respect to the reaction in the absence of modifier, leading to an enantiomeric excess of (1R,2R)-trans-cyclohexane-1,2-diol of over 80%. Comparison with recently reported asymmetric hydrogenation of α-hydroxyethers indicates striking similarities, which hint at similar reactant–modifier interaction in both cases. The importance of cis versus trans conformation of the reactant for the reactant–modifier interaction emerges from a comparison of suggested reaction intermediates for cyclohexane-1,2-dione and butane-2,3-dione hydrogenation, respectively. [Copyright &y& Elsevier]

The enantioselective hydrogenation of 4-hydroxy-6-methyl-2-pyrone in the presence of acetic acid and trifluoroacetic acid has been studied on cinchonidine-modified Pd/TiO2. Catalytic experiments and theoretical calculations indicate the formation of a cinchonidine–trifluoroacetic acid cyclic ion pair. We propose that this is the actual modifier, which interacts with 4-hydroxy-6-methyl-2-pyrone in the enantiodifferentiating step. The new mechanistic model is assumed to be valid also for other reactions over cinchona-modified Pt or Pd, in the presence of trifluoroacetic acid. [Copyright &y& Elsevier]