In the hydrogenation of ketopantolactone, the (R,R) and (R,S) diastereomers of a new chiral modifier, pantoyl-naphthylethylamine, afforded 74 and 40% ee, respectively, to (R)-pantolactone. On the basis of NOE studies and theoretical calculations, the different properties of the diastereomers and in particular the effect of acid on the modifier structure are deduced from differences in conformational rigidity and steric constraint. In case of the (R,R)-diastereomer, a loose, extended structure in apolar solvent changes to a compact conformation via an additional intramolecular hydrogen bond, resulting in a more defined “chiral pocket� available for the reactant on the Pt surface.

O-Phenylcinchonidine (PhOCD) is known to efficiently induce inversion of enantioselectivity with respect to cinchonidine (CD) in the enantioselective hydrogenation of various activated ketones on Pt/Al₂O₃. To understand the origin of the switch of enantioselective properties of the catalyst, the adsorption of PhOCD has been studied by in situ ATR-IR spectroscopy, in the presence of organic solvent and dissolved hydrogen, i.e., under conditions used for catalytic hydrogenation. The adsorption structures and energies of the anchoring group of CD and PhOCD were calculated on a Pt 38 cluster, using relativistically corrected density functional theory (DFT). Both approaches indicate that both modifiers are adsorbed via the quinoline ring and that the spatial arrangement of the quinuclidine skeleton is critical for the chiral recognition. New molecular level information on the conformation of CD relative to PhOCD adsorbed on a surface is extracted from the ATR spectra and supported by DFT calculations. The result is a clearer picture of the role played by the phenyl group in defining the chiral space created by the modifiers on Pt. Moreover, when CD was added to a pre-equilibrated adsorbed layer of PhOCD, a chiral adsorbed layer was formed with CD as the dominant modifier, indicating that CD adsorbs more strongly than PhOCD. Conversely, when PhOCD was added to preadsorbed CD, no significant substitution occurred. The process leading to nonlinear effects in heterogeneous asymmetric catalysis has been characterized by in situ spectroscopy, and new insight into a heterogeneous catalytic R−S switch system is provided.

The enantioselective hydrogenation of ring-substituted acetophenones that possess no functional group in the α-position to the keto group represents the latest extension of the application range of the Pt–cinchona system. The influence of the type of solvent, pressure, temperature, and modifier/substrate/Pt molar ratios was investigated in the hydrogenation of 3,5-di(trifluoromethyl)acetophenone. Modification of a 5 wt% Pt/Al₂O₃ catalyst by cinchonidine (CD) afforded the corresponding (S)-1-phenylethanol (69.5% ee). Working in strongly polar solvents, addition of trifluoroacetic acid in a weakly polar solvent, and replacing CD by its ether derivatives resulted in the inversion of enantioselectivity. Addition of CD or any of its derivatives always led to a lower reaction rate, contrary to the generally observed rate acceleration in the hydrogenation of α-functionalized activated ketones over the same catalyst system. Another fundamental difference to the hydrogenation of α-functionalized activated ketones is that both the quinuclidine N and the OH functions of CD influence the stereochemical outcome of the reaction, as clarified by using O- and N-substituted derivatives of CD. Ab initio calculations confirmed these remarkable mechanistic differences. Inversion of enantioselectivity in the presence of strongly polar and acidic solvents is attributed to special interactions with the OH function of CD, and to the formation of a CD–acid ion pair, respectively. A possible explanation for the moderate ee's in the hydrogenation of ring-substituted acetophenones is that a reaction pathway without involvement of the OH function of CD is also feasible. This competing pathway is even faster and provides low ee to the opposite enantiomer.

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.

Prominent nonlinear effects in enantioselectivity were observed with a transient technique when ethyl pyruvate was hydrogenated over Pt/Al₂O₃ in the presence of two cinchona alkaloids, which alone afford the opposite enantiomers of ethyl lactate in excess. The changes in reaction rate and ee, detected after injection of the second alkaloid, varied strongly with type and amount of the alkaloid, and with the order of their addition to the reaction mixture. For example, under ambient conditions in acetic acid cinchonidine (CD) afforded 90% ee to (R)-ethyl lactate and addition of equimolar amount of quinidine (QD) reduced the ee to (R)-ethyl lactate only to 88%, though QD alone provided 94% ee to (S)-lactate in a slightly faster reaction. The stronger adsorption of CD on Pt in the presence of hydrogen and acetic acid was proved by UV–vis spectroscopy. The different adsorption strengths result in an enrichment of CD on the Pt surface and also in a crucial difference in the dominant adsorption geometries. CD is assumed to adsorb preferentially via the quinoline rings laying approximately parallel to the Pt surface. In this position it can interact with ethyl pyruvate during hydrogen uptake and control the enantioselectivity. The weaker adsorbing QD adopts mainly a position with the quinoline plane being tilted relative to the Pt surface and these species are not involved in the enantioselective reaction. Competing hydrogenation of the alkaloid, and steric and electronic interactions among the adsorbed species, can also influence the alkaloid efficiency and the product distribution. Hydrogenation of the quinoline rings at low alkaloid concentration resulted in unprecedented swings in the enantiomeric excess.

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.

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.

The influence of acetic acid (AcOH) and trifluoroacetic acid (TFA) on the hydrogenation of ethyl-4,4,4-trifluoroacetoacetate has been investigated by using Pt/Al₂O₃ modified by cinchonidine and O-methylcinchonidine. We have shown that the sometimes dramatic changes in enantioselectivity and rate cannot simply be interpreted by protonation of the alkaloid modifier. We propose a new three-step reaction pathway, involving interaction of the carboxylic acid with the reactant and the chiral modifier. The mechanism is supported by IR spectroscopic identification of cyclic TFA–modifier ion pairs. This new approach can rationalise the poorly understood role of acids in the enantioselective hydrogenation of activated ketones over cinchona-modified platinum metals.

The mechanism of alcohol oxidation was investigated using the conversion of cinnamyl alcohol (1) over Pd-based catalysts as a sensitive test reaction. Studies in a slurry reactor revealed that dehydrogenation and oxidative dehydrogenation of 1 follow the same reaction pathways independent of the presence or absence of oxygen and reaction conditions. Hydrogenation and hydrogenolysis side reactions indicated the presence of hydrogen on the metal surface during reactions. Catalyst deactivation in Ar is attributed to decarbonylation reactions and site blocking by CO. Introduction of molecular oxygen induced a dramatic enhancement of alcohol conversion rate by a factor of up to 285 due to oxidative removal of CO. Strong adsorption of CO on Pd/Al₂O₃ and its rapid removal by oxygen were corroborated by in situ ATR-IR spectroscopy. All these observations conform to a model according to which oxidation of 1 follows the classical dehydrogenation mechanism, and the key role of oxygen is the continuous oxidative removal of CO and other degradation products from the active sites. This oxidative cleaning of the metal surface allows a high rate of alcohol dehydrogenation even when the oxidation of the co-product hydrogen is slow and incomplete. It is likely that the observed effects are not limited to the oxidation of 1 on Pd, and regeneration of the active sites by oxygen generally plays an important role during aerobic oxidation of alcohols on platinum metals.

Enantioselective hydrogenation of the pseudo-aromatic 4-hydroxy-6-methyl-2-pyrone to the corresponding 5,6-dihydropyrone has been studied over cinchonidine-modified Pd/Al₂O₃ and Pd/TiO₂ catalysts. A mechanistic model for enantiodifferentiation is proposed, involving two H-bond interactions (N–H···O and O–H···O) between the deprotonated reactant and the protonated chiral modifier. The model can rationalize (i) the sense of enantiodifferentiation, i.e., the formation of (S)-product in the presence of cinchonidine as modifier; (ii) the complete loss of enantioselectivity when the acidic OH group of the reactant is deprotonated by a base stronger than the quinuclidine N of the alkaloid; and (iii) the poor enantiomeric excesses obtained in good H-bond donor or acceptor solvents. NMR and FTIR investigations, and ab initio calculations, of reactant–modifier interactions support the suggested model. Several factors, such as catalyst prereduction conditions, trace amounts of water, presence of strong bases and acids, and competing hydrogenation of acetonitrile to ethylamines, were found to affect the efficiency of this catalytic system.

A series of titania–silica aerogels with 0–100 wt% TiO₂ content were synthesized and characterized by N₂ physisorption, DRIFT, UV-Vis, XPS, and ²⁹Si CP/MAS NMR analysis. It is shown that kinetic analysis of the epoxidation of 2-cyclohexene-1-ol (1) with TBHP is an informative test reaction providing insight in the nature of active sites. The surface area, pore volume, hydrophobicity, and relative abundance of Ti–O–Si linkages in the aerogels decreased with increasing Ti/Si ratio. Parallel to these changes, the initial rate of epoxide formation per Ti site (TOF) and the epoxide selectivity decreased but the productivity of the catalysts went through a maximum at 10 wt% TiO₂. We propose that due to kinetic effects in the sol–gel synthesis the whole range of active Ti sites may be present in the mixed oxides, spanning from tetrahedral Ti isolated by four SiO groups to octahedral Ti surrounded by six TiO groups in titania nanodomains. Ether formation from 1 was catalyzed by Brønsted sites present only on high titania-containing aerogels. Oligomerization was a major side reaction on all catalysts including Ti-free silica. Si-free titania was the most active in allylic oxidation of 1 to cyclohexenone. Silylation, or amine (Me₂BuN) addition to the reaction mixture, eliminated ether formation and suppressed oligomerization.

IR and NMR experiments revealed that the enantioselective hydrogenation of ethyl pyruvate in nonacidic solvents is complicated by the simultaneously occurring self-condensation (aldol reaction) of the reactant. Both enantioselective reactions are catalyzed by the chiral base cinchona alkaloid, but the hydrogenation is faster by several orders of magnitude than the aldol reaction. Catalytic experiments proved that the aldol products are not spectator species. The enol form of the major aldol product protonates the quinuclidine N of cinchonidine and enhances the enantiomeric excess of the hydrogenation reaction. The significance of this observation with respect to kinetic and mechanistic studies is discussed.

The catalytic synthesis of 1,3-diaminopropane from 1,3-propanediol and ammonia was studied in a continuous fixed-bed reactor in the pressure range 50 to 150 bar. The unsupported Co-based catalysts applied were characterized by N₂physisorption, XRD, XPS, TPR, and ammonia adsorption using pulse thermal analysis and DRIFT spectroscopy. The latter investigations revealed that the best catalyst, 95 wt% Co–5 wt% Fe, contained only very weak acidic sites, unable to chemisorb ammonia. The absence of strong acidic and basic sites was crucial to suppress the various acid/base-catalyzed side reactions (retro-aldol reaction, hydrogenolysis, alkylation, disproportionation, dimerization, oligomerization). Other important requirements for improved diaminopropane formation were the use of excess ammonia (molar ratio NH₃/diol>20) and the presence of the metastable β-Co phase. A small amount of Fe additive could efficiently hinder the transformation of this phase into the thermodynamically stable α-Co phase and thus prevent catalyst deactivation up to 10 days on stream. Application of supercritical ammonia almost doubled the selectivity to amino alcohol and diamine. The selectivity enhancement in the near-critical region is attributed to elimination of the interphase mass transport limitations and to the resulting higher surface ammonia concentration.

A new modifier, 2-phenyl-9-deoxy-10,11-dihydrocinchonidine, has been synthesized for the enantioselective hydrogenation of ketopantolactone and α-ketoesters over chirally modified Pt/alumina. The results indicate flat adsorption of cinchonidine with the quinoline ring oriented parallel to the surface and, furthermore, give some insight into the conformation of the modifier within the transition state complex. Comparison of the structures and catalytic behaviors of 9-deoxycinchonidine and the new modifier allows to exclude the previously proposed perpendicular or tilted adsorption of the quinoline ring via the N atom.

The mechanism of enantiodifferentiation in the hydrogenation of alkenoic acids over cinchona-modified Pd has been investigated using the tiglic acid → 2-methyl-butanoic acid transformation as test reaction. Application of simple derivatives of cinchonidine, modified at the (C-9)–OH and/or the quinuclidine nitrogen, proved that both functional groups are involved in the enantiodiscriminating step. Addition of a strong base (1,8-diazabicyclo[5.4.0]undec-7-ene, DBU) to tiglic acid prior to hydrogenation revealed that one cinchonidine molecule interacts with a dimer of tiglic acid on the metal surface. Ab initio calculations corroborate the existence of an energetically favored acid dimer–cinchonidine intermediate stabilized by hydrogen bonding, involving both the OH and the quinuclidine nitrogen of cinchonidine.