5128
J. Phys. Chem. C 2007, 111, 5128-5140
The Role of Modifier Structure in Heterogeneous Enantioselective Hydrogenation: One-to-One Interactions of 1-Phenyl-1,2-propanedione and Methyl Pyruvate with Modifiers on the Pt(111) Surface Antti Taskinen,† Ville Nieminen,*,‡ Matti Hotokka,† and Dmitry Yu. Murzin‡ Department of Physical Chemistry, Åbo Akademi UniVersity, FIN-20500, Turku-Åbo, Finland, and Laboratory of Industrial Chemistry, Process Chemistry Centre, Åbo Akademi UniVersity, FIN-20500, Turku-Åbo, Finland ReceiVed: October 26, 2006; In Final Form: January 17, 2007
Density functional theory (DFT) at the B3LYP/T(ON)DZP level was used to model one-to-one reactantmodifier interactions relevant to the enantioselective hydrogenation of 1-phenyl-1,2-propanedione and methyl pyruvate over platinum catalysts. Two protonated modifiers, cinchonidine and 9-methoxycinchonidine, in the Open(3) and Open(5) conformations, were considered. So-called bifurcated and cyclic hydrogen-bonded complexes were investigated. The effects of a flat Pt(111) surface on the complexes were taken into account using molecular mechanics with the COMPASS force field. Only the bifurcated reactant-modifier(Open3) complexes were suggested to contribute to the enantioselectivity of the hydrogenation reaction due to their thermodynamic stability. The stabilization of the π and π* orbitals of the reactants’ keto carbonyl moieties, that is, the kinetic factor, indicated that the substitution of cinchonidine’s hydroxyl group with a methoxy group does not have any notable effect on the enantiomeric excess of (R)-methyl lactate but decreases the enantiomeric excess of (R)-1-hydroxy-1-phenylpropanone. These results are well in accord with the experimentally observed enantiomeric excesses, thus supporting the validity of the studied reactant-modifier interaction model. The DFT calculations at the RI-BP86/SV(P) level indicated that protonated cinchonidine and 10,11-dihydrocinchonidine are more stable on Pt when adopting the so-called QA-Open(4) conformation rather than the Open(3) conformation that dominates in solution. The QA-Open(4) conformation of a modifier is adsorbed on the surface via both its quinoline and quinuclidine moieties, and a reactant may interact simultaneously with the protonated quinuclidine nitrogen and the functional group at the C(9) position of the modifier.
1. Introduction A challenging application for heterogeneous catalysis is to develop chirally selective catalyst systems that allow the production of a single enantiomer instead of a racemate of a substance. A widely studied subject is the enantioselective hydrogenation of the carbonyl group (CdO) to the corresponding alcohol using supported Pt catalysts modified by cinchona alkaloids (Figure 1), reviewed in several papers.1-8 This reaction, originally reported by Orito et al.9,10 for R-keto esters, gives up to 98% enantiomeric excess (ee (%) ) 100 × ([R] - [S])/([R] + [S]), where [R] and [S] are the concentrations of the (R) and (S) product enantiomers).11 Today, one of the main research goals is to understand the observed selectivity in the heterogeneous enantioselective hydrogenation reactions. Several mechanistic models have been suggested (see, e.g., ref 2 and references therein). The most widely discussed is the 1:1 reactant-modifier hydrogen bond model originally proposed by Baiker et al.12 to rationalize enantiodifferentiation in the hydrogenation of ethyl pyruvate over cinchonidine-modified Pt. Still, a detailed molecular-level reaction mechanism that would rationalize all experimental data including the origin of stereoselection remains speculative in many respects and is under active debate. For example, the role * Corresponding author. E-mail:
[email protected]. † Department of Physical Chemistry. ‡ Laboratory of Industrial Chemistry.
of the OH function of the cinchonidine (Cd) modifier in the enantioselective hydrogenation of CdO and CdC double bonds has been studied13-28 but not yet completely understood. In the hydrogenation of activated R-substituted ketones such as ethyl pyruvate, the ee with 9-methoxycinchonidine (MeOCd) is very similar to the one with Cd.13-16 On the other hand, the replacement of Cd’s hydroxyl group by a methoxy group is known to lead to a remarkable loss of enantioselectivity or even inversion of the ee in the hydrogenation of ring-substituted acetophenones,21 1-phenyl-1,2-propanedione,18,19 and R-hydroxyketones24 on Pt catalysts. To gain further insight into the role of Cd’s OH group in the enantiodifferentiating mechanism, one-to-one hydrogen-bonding reactant-modifier interactions were investigated with density functional theory (DFT) calculations. 1-Phenyl-1,2-propanedione (PPD) and methyl pyruvate (MP) were used as model reactants and Cd and MeOCd adopting the Open(3) and Open(5) conformations as the modifiers (Figures 1 and S1, Supporting Information (SI)). Open(3) has been shown21,29-33 to be the most stable conformer of Cd in the gas phase and in solution but a recent study17 indicated that Open(5) might also be important in complex formation on the surface. Two kinds of hydrogenbonded reactant-modifier interaction modes were investigated: (i) bifurcated, in which both carbonyl oxygens of the reactant interact with the proton attached to the modifier’s quinuclidine nitrogen, and (ii) cyclic, in which one of the carbonyl oxygens of the reactant also interacts with the
10.1021/jp067017+ CCC: $37.00 © 2007 American Chemical Society Published on Web 03/09/2007
Heterogeneous Enantioselective Hydrogenation
J. Phys. Chem. C, Vol. 111, No. 13, 2007 5129
Figure 1. Hydrogenation of methyl pyruvate and 1-phenyl-1,2-propanedione can be carried out enantioselectively over cinchona alkaloid modified Pt catalysts.
modifier’s hydroxyl group. Since modeling reactant-modifiersurface interactions with DFT is extremely challenging due to the huge demand of computer resources, the effect of the Pt catalyst surface as a steric constraint on the reactant-modifier complexes was studied by molecular mechanics (MM). It is shown that the Pt surface not only eliminates some of the DFT optimized reactant-modifier complexes due to steric constraints but also enables new kinds of interaction geometries that are unstable without the presence of the surface. The possibility for these previously not considered structures are verified by cluster model DFT calculations. The conclusions on the effect of the modifier structure on enantioselectivity are based on thermodynamic and kinetic aspects, that is, relative stability of the pro-(R) and pro-(S) complexes and the stabilization of the reactant’s keto carbonyl orbitals in these complexes. It should be noted that in this theoretical study, the actual chemical system has been simplified considerably. Enantiomeric excess does not depend only on the structure of modifiers and reactants, but it is also a function of solvent, modifier concentration, temperature, and hydrogen pressure among others, as have been discussed elsewhere,1,3,6 and these factors have been neglected in this study. However, the most important parameter, which defines the formed enantiomer is the interaction between the reactant and the modifier and this is the one we have addressed carefully. It is to be noted that formation of one enantiomer, for example formation of (R) can be switched to (S) by changing the modifier structure,1 but similar effect has not been observed by changing hydrogen pressure, modifier concentration, temperature, etc., clearly pointing out the crucial influence of the reactant-modifier interactions. 2. Background In 1994, Baiker et al.12 proposed a 1:1 hydrogen bond model to rationalize enantiodifferentiation in the hydrogenation of ethyl pyruvate over cinchonidine-modified Pt. Two distinctly different models were suggested by Margitfalvi and Hegedu¨s34 and Augustine et al.35 Recently, Vayner et al.29 and McBreen et al.36 put forward new ideas to explain enantioselectivity in the Orito reaction.9,10 Baiker’s theoretical model is the most widely discussed and will be applied in this paper. According to it, the important stage in the reaction is the formation of a surface
bound complex of a single modifier and a reactant molecule interacting through hydrogen bonds. It is probable that the interaction mechanism depends on the structures of the modifiers and the reactants as well as the reaction conditions including the medium.1 Anyhow, depending on the possible orientations of the pro-chiral reactant molecule with respect to the surface and the modifier, its adsorption at modified chiral surface sites leads to enantiodifferentiating pro-(R) and pro-(S) intermediate complexes, which are converted to (R) and (S) product enantiomers by hydrogenation, respectively. The notation of the complexes indicates the configuration of the reaction products as a result of hydrogen uptake from the surface. Computer simulation work in this area has concentrated on the conformations of the modifiers and their interaction with the reactant molecules. For a large part, the effect of a solvent or a catalyst metal surface have been ignored in the calculations since studying the full catalytic system with first-principles electronic structure calculations demands computational resources beyond the scope of most computational chemists.37 In principle, having a mechanistic model at hand, the molecular modeling results may let one infer the sense of selectivity, that is, which of the possible chiral products will be formed in excess. However, extremely small energy differences (close to the error expected in current simulations) in the pathways to two enantiomers during adsorption and surface reaction can lead to large effects on selectivity. For example, using a simple kinetic model of an enantioselective reaction, it was pointed out that if the adsorption energy of the two pro-chiral intermediates is the only differentiating factor, an ee value of 66.7% can be achieved with an adsorption energy difference of just 4 kJ mol-1.37 Therefore, direct calculation of the ee is a challenging problem. Due to the incompleteness of the computational methods and models used to describe the catalytic system, only a qualitative understanding of the system can often be achieved. The factors that determine the enantioselectivity of a heterogeneous hydrogenation reaction are thermodynamics, that is, the relative stability (and consequently, relative amount) of the pro-(R) and pro-(S) reactant-modifier complexes adsorbed on the surface, and kinetics, that is, the intrinsic hydrogenation rates of those complexes.6,37-39 For example, if one diastereomeric intermediate complex is more stable and reacts faster than the
5130 J. Phys. Chem. C, Vol. 111, No. 13, 2007 other intermediate complex, an excess of the corresponding product enantiomer is formed. In general, the complexes leading to the (R) and (S) enantiomers can be hydrogenated at different rates independent of their thermodynamic stability. Consequently, the most abundant (thermodynamically most stable) surface species is not necessarily the most reactive one. Potential energy diagrams, including transition-state energies for whole reaction paths on metal surface, can be determined from firstprinciples calculations if the systems under study are small enough.40,41 This would be computationally extremely demanding for enantioselective hydrogenations over metal surfaces, and therefore, simplifications are needed. When studying the hydrogenation of substituted acetophenones over Pt, Vargas et al.38,39 found that the reaction rate correlated with the stability of the reactive keto carbonyl π orbitals of isolated reactants calculated at the HF/6-31G* level; the sum of bonding π and antibonding π* orbital stabilization was proposed to be the most general parameter as a measure for the reactivity. The orbital stabilization results in lowering of the transition state energy, hence decreasing the activation energy and increasing the rate of the hydrogenation reaction. Applied to the enantioselective hydrogenation, a difference in the stabilization of the keto carbonyl orbitals between the two complexes leading to the (R) and (S) enantiomers affects the enantioselectivity. For example, if the reactant’s keto carbonyl orbitals were more stable in the pro-(R) than in the pro-(S) complex, the pro-(R) complex would be hydrogenated faster, that is, kinetics would favor the formation of the (R) enantiomer. More pronounced π orbital stabilization in the pro-(R) complex was thought to be an explanation for the experimentally observed enantiomeric excess of (R)-1-hydroxy-1-phenylpropanone in the enantioselective hydrogenation of 1-phenyl-1,2-propanedione over cinchonidinemodified Pt (Figure 1).42 Heterogeneous enantioselective hydrogenation of methyl/ ethyl pyruvate to methyl/ethyl lactate over cinchona alkaloid modified platinum catalysts is an extensively researched topic.5,7,8,12-16,29,43-63 Spectroscopic and theoretical data support the model assumption that the modifier (e.g., cinchonidine) is strongly adsorbed via its quinoline moiety oriented preferentially parallel to the Pt surface.64-75 The quinoline part of the modifier is adsorbed even under hydrogenation conditions.66,69,74 The studies on adsorption of R-keto esters on a metal surface indicate that adsorption is affected by the presence of coadsorbed hydrogen and that lone-pair- and π-bonded R-keto esters possibly coexist on the surface.52,61,76-81 The π-bonded species adopting the s-cis conformation has been suggested to be relevant in the enantiodifferentiating diastereomeric 1:1 transition state complex between a reactant and a modifier.52,76 1:1 Complexes between a prochiral reactant, methyl pyruvate, and a chiral modifier, (S)-(-)-1-(1-naphthyl)ethylamine, on Pt(111) in the presence of coadsorbed hydrogen has been observed by scanning tunneling microscopy (STM).82 In situ attenuated total reflection (ATR) infrared spectroscopy studies during the enantioselective hydrogenation of ethyl pyruvate over cinchonidine-modified Pt/Al2O3 catalyst show the preferential adsorption of ethyl pyruvate as an s-cis conformer and indicate a hydrogen bond between the keto-oxygen atom of ethyl pyruvate and the quinuclidine nitrogen of coadsorbed Cd.83 A similar N+-H‚‚‚ OdC hydrogen bonding interaction has also been observed experimentally between ketopantolactone and Cd over Pt/Al2O3 catalyst.84 As have been discussed previously,42 the protonation of the quinuclidine nitrogen of cinchonidine is probable due to its high proton affinity in case there are proton donors available, as in acidic media (e.g., acetic acid). In aprotic media (e.g.,
Taskinen et al. toluene), the protonation can take place either in the liquid phase by the residual water, always present to some extent, or alternatively on the catalyst surface, which is covered by hydrogen. Also, the acid sites of alumina support may be involved in the protonation. The DFT calculations have evidenced that the proton can be picked up by the quinoline N from the hydrogen-rich surface leaving the negative charge on the metal.73 It is still not clear where the additional electron goes but, for example, in the case of dihydrogen on Pt, the nitrogen-promoted charge separation would generate a hydride that can readily react as a nucleophile with the keto-carbonyl.73 Regardless of the mechanism of protonation, there is experimental evidence which supports the protonation of cinchonidine on the catalyst surface.82 Hydrogen bond interactions between methyl/ethyl pyruvate and protonated modifier have also been investigated computationally.12,46,47,49,50,59 The complexes where the pyruvate adopts the s-cis conformer are substantially more stable than the complexes with the s-trans conformer.12,49,50,59 The steric constraints imposed by the adsorption of the complexes on a metal surface have been modeled implicitly using geometry restrictions in the calculations.49,50 The Pt(111) surface has been taken explicitly into account only in some theoretical studies by molecular mechanics17,29,55,62 and by DFT.45,85 To the best of our knowledge, full DFT calculations on methyl pyruvatecinchonidine interactions on Pt have not been published. Enantioselective hydrogenation of 1-phenyl-1,2-propanedione (PPD, Figure 1) has also been actively investigated.18,19,33,42,86-91 When carried out over Pt catalysts modified by Cd, the reaction leads to a notable enantiomeric excess (ee ) 55-65%) of (R)1-hydroxy-1-phenylpropanone.18,19,42,87,88 PPD has two reactive carbonyl groups which upon hydrogenation yield two kinds of regioisomeric intermediates, 1-hydroxy-1-phenylpropanone and 2-hydroxy-1-phenylpropanone, with over 90% excess of the 1-hydroxy intermediates.42 The main hydrogenation product of PPD, (R)-1-hydroxy-1-phenylpropanone, is an important intermediate in pharmaceutical synthesis particularly in the production of ephedrine derivatives.92 The R-hydroxyketone intermediates can be further hydrogenated enantioselectively to diols.17,19,42 3. Computational Methods All density functional theory93 (DFT) calculations were performed with the TURBOMOLE program package.94-97 The structures of the reactant-modifier complexes were optimized using the B3LYP functional98-100 and the TZP basis set for oxygen and nitrogen and the DZP basis set for the other elements from the TURBOMOLE basis set library.101 With this basis (referred hereafter as T(ON)DZP), the basis set superposition error (BSSE) calculated with the counterpoise (CP) method102 was 5.6-5.8 kJ mol-1 for the cyclic MP-CdH+(Open3) complexes and 6.1-6.3 kJ mol-1 for the cyclic PPD-MeOCdH+(Open5) complexes. The analysis of the keto carbonyl bonding and antibonding π-molecular orbitals of the reactants was performed using the Kohn-Sham (KS) orbitals. The KS orbitals have often been viewed just as physically meaningless auxiliary quantities useful only for calculating the total energy and density, but it has been shown that they are a good basis for qualitative interpretation of molecular orbitals and, thus, very suitable for qualitative analysis of chemical properties.102-106 In addition, the KS orbitals have recently17 been applied with success for the same purpose as in this study. The adsorption of the modifiers on platinum surface was studied using the cluster model approach with the BP86
Heterogeneous Enantioselective Hydrogenation gradient-corrected exchange-correlation functional98,107 in combination with the resolution-of-the-identity (RI) approximation.108-110 The BP86 functional has previously been used to study, for example, the adsorption of benzene on Pt(111).111 Relativistic effects were taken into account implicitly by using relativistic effective core potential (ECP) from the TURBOMOLE library (“def-ecp”) to represent the 60 core electrons of Pt.112 The 18 valence electrons of platinum and all electrons of the other elements were treated explicitly using the SV(P) basis set (“def-SV(P)”).113 A cluster consisting of 38 Pt atoms and two layers with the (111) surface was employed to model the catalyst surface. The distance between the Pt atoms were fixed to the bulk value of 277.5 pm and the nine middle atoms on the top layer were let to fully relax. All the calculations were done spin unrestricted with the total spin state of S ) 3 (six extra up-spin-orbitals). It has been stated that a low-spin state should be chosen to represent the electronic structure of a nonmagnetic metal surface (such as Pt) and it is customary to use the lowest energy low-spin cluster electronic state for the naked cluster as well as for the cluster plus its corresponding adsorbate.114 More justification for the use of S ) 3 for the Pt38 cluster can be found in Supporting Information. The effect of the Pt(111) surface on the geometries and stabilities of the reactant-modifier complexes was modeled by molecular mechanics (MM) with the COMPASS (Condensedphase Optimized Molecular Potentials for Atomistic Simulation Studies) force field115 as implemented in the Forcite molecular mechanics module in Materials Studio 3.2 (Accelrys Software Inc.). As the force fields cannot be used to model chemisorption and, consequently, exact structures of the adsorbed molecules, the role of the metal surface in these MM calculations was mainly to act as a steric constraint to the complex formation, similarly as in a recent study.17 The COMPASS force field has been used recently to explain the observed selectivities in the hydrogenation of chiral R-hydroxyketones on Pt(111)17 and, for example, to model gas diffusion and sorption on the surface of metal oxides116 and H-bond interactions in polyurethanes.117 In this study, the flat Pt(111) surface was represented by a threelayer slab of dimensions 3.4 nm × 3.3 nm × 0.5 nm containing 182 platinum atoms in the upper- and lowermost layers and 195 atoms in the middle. During the calculations, all Pt-Pt distances were kept fixed to the experimental value of 277.5 pm of bulk Pt. The atomic charges of the reactants and modifiers were determined using the QEq charge equilibration method118 as implemented in Materials Studio (cf. also ref 17). The charges of all Pt atoms were set to zero. 4. Results 4.1. Modifier Conformations. The conformations of cinchonidine and 9-methoxycinchonidine mainly considered in this study are so-called Open(3) and Open(5) (Figure S1, Supporting Information (SI)). Contribution of Cd’s Open(5) conformation for enantiodifferentiation has barely been studied before,21 probably because the Open(3) conformation has been thought to be the most stable and, thus, the most relevant conformation.29-33 In a recent paper,17 however, a question arose about the role of the Open(5) conformation in complex formation. Some stable complexes between 1-hydroxy-1-phenylpropanone and CdH+ adopting a conformation very close to Open(5) were found on the Pt(111) surface.17 The Open(5) conformation enables a reactant to simultaneously interact with the hydroxyl group and the proton attached to the quinuclidine nitrogen of cinchonidine. The DFT calculations at the B3LYP/T(ON)DZP level on protonated Cd’s conformations show that in the gas phase,
J. Phys. Chem. C, Vol. 111, No. 13, 2007 5131 Open(5) is more stable than Open(3) by 2.2 kJ mol-1 if the electronic energy is considered (Figure S1). Substitution of the hydroxyl group of CdH+ with a methoxy group further increases the energy difference between these conformers to 5.8 kJ mol-1. However, if Gibbs energies at 298 K are considered (frequencies scaled by a factor of 0.9614), Open(3) is slightly more stable conformer than Open(5) for both modifiers (Figure S1). The molecular mechanics (MM) calculations with the COMPASS force field suggest that there exist two conformations for CdH+ and MeOCdH+ that are more stable than Open(3) and Open(5) on the Pt(111) surface and that are also able to form hydrogen-bonding complexes with adsorbed reactants (Table S1, Figure S2). These modifier conformations are adsorbed on the surface via the quinuclidine moiety in addition to the quinoline ring. In this paper they are called Quinuclidine Adsorbed-Open(3) [QA-Open(3)] and Quinuclidine AdsorbedOpen(4) [QA-Open(4)] since they can be generated from the adsorbed Open(3) and Open(4) conformations, respectively, by rotating around the C(4’)-C(9) bond (Figure 1). Similar kinds of cinchonidine conformations have been found to exist on the Pt(111) surface by a recent molecular dynamics study71 and by DFT calculations.75 According to the MM calculations, QA-Open(4) is the most stable conformation of CdH+ on the flat Pt(111) surface (Table S1). QA-Open(3) is less stable than QA-Open(4) by 19 kJ mol-1 while Open(3) and Open(5) are considerably more unstable. The Open(4) and Open(6) conformations are not stable on the surface but they relaxed to some other conformation during the geometry optimization calculations. In contrast, the Closed(1) and Closed(2) conformations119 are stable and have 55 and 62 kJ mol-1 higher energy than the QA-Open(4) conformation on Pt(111), respectively. However, they cannot form such catalytically active complexes as proposed by Baiker since the quinuclidine NH+ points toward the anchoring group, the quinoline ring, thus not being able to interact via hydrogen bonds with a reactant adsorbed on the surface. For comparison purposes the conformations of unprotonated cinchonidine were also studied. It was found that QA-Open(4) and QA-Open(3) are notably more stable conformations than Open(3) and Open(5) whether the quinuclidine nitrogen of Cd is protonated or not (Table S1). The order of stability for various conformations of MeOCdH+ on Pt(111) is the same as for the conformations of CdH+ by the MM calculations (Table S1). In the absence of the surface, the isolated Open(3) conformation of CdH+ is more stable than QA-Open(3) but QA-Open(4) is still the most stable conformation. No stable QA-Open(3) conformation was found for isolated Cd. Only the Open(3) and Open(5) conformations of isolated MeOCd and MeOCdH+ are stable by the MM calculations. According to the DFT calculations at the B3LYP/T(ON)DZP level, all isolated QA-Open conformations of protonated and unprotonated Cd and MeOCd are unstable. The results from the MM calculations indicate that the Pt surface has a significant effect on the relative stabilities of the modifier conformations. However, it is stressed that the conformational analysis performed on the Pt surface at the MM level should be regarded only as indicative due to the method applied. The MM calculations do not take electronic effects into account and do not allow, for instance, charge transfer between the charged adsorbate and the electrically neutral adsorbent. Chemisorption and, consequently, rehybridization of atoms of the adsorbate molecule cannot be observed, either. However, the force fields are able to describe physisorption and steric constraints imposed by the surface. Thus, the MM calculations give valuable
5132 J. Phys. Chem. C, Vol. 111, No. 13, 2007
Taskinen et al.
Figure 2. Side and top views of the RI-BP86/SV(P) optimized Open(3) and QA-Open(4) conformations of cinchonidine, 10,11-dihydrocinchonidine, and their protonated counterparts on the Pt38 cluster. The adsorption energies as defined in the text are given in parentheses (in kJ mol-1).
suggestions about possible molecular structures that can exist on the surface. The DFT calculations confirm the possibility for the modifiers to adopt QA-Open conformations on Pt(111). The RI-BP86/ SV(P) optimized Open(3) and QA-Open(4) conformations of Cd, 10,11-dihydrocinchonidine (dihydro-Cd), and their protonated counterparts on the Pt38 cluster are illustrated in Figure 2. The adsorption energies (Eads, Figure 2) were calculated with respect to the stable Open(3) conformation using the equation Eads ) Emodifier+cluster - EOpen(3) - Ecluster, where Emodifier+cluster is the energy of the cluster with the modifier adsorbed, and EOpen(3) and Ecluster are the energies of the isolated Open(3) conformation and the isolated cluster, respectively. The adsorption energies show that the Open3 conformation of Cd is more stable than the QA-Open(4) conformation by 20 kJ mol-1 on Pt(111). This is contrary to the MM results (Table S1) which state that QA-Open(4) is the most stable conformation. As the quinuclidine N of Cd is protonated, the QA-Open(4) conformation adsorbs more strongly (by 15 kJ mol-1) on the surface than the Open(3) conformation. This is in qualitative agreement with the MM results. It is noted that Vargas and Baiker75 found a conformation for unprotonated Cd that resembles QA-Open(4) but is more stable than Open(3) on Pt(111). However, this socalled SVB(1) conformation is chemisorbed on the surface via its vinyl moiety C(10)dC(11) in addition to the quinoline ring and cannot be a stable structure under reduction conditions due to the fast hydrogenation and subsequent detachment of the vinyl moiety.75 The QA-Open conformations of Cd and its derivatives have at least two interesting features: (i) the quinuclidine nitrogen and the functional group at the C(9) position are spatially close together which enables their simultaneous interaction with a reactant molecule, probably also on the surface, and (ii) the vinyl group [C(10)dC(11)] in the quinuclidine moiety is close to the
surface, consistent with its fast hydrogenation observed experimentally under catalytic conditions.15,64,66 According to the DFT calculations, the saturation of the vinyl group does not have any considerable effect on the adsorption geometries or the adsorption energies of the Open(3) and QA-Open(4) conformations of Cd (see Figure 2). Instead, the adsorption energies of the CdH+ conformations increase by 5-16 kJ mol-1 as the vinyl group is hydrogenated (Figure 2). As a result, the QA-Open(4) conformation of dihydro-CdH+ is 26 kJ mol-1 more stable than the Open(3) conformation on Pt(111). These results indicate that the QA-Open(4) conformation is stable species on the Pt(111) surface before and also after the saturation of the modifier’s vinyl group, that is, under hydrogenation conditions. Thus, the QA-Open conformations of the modifiers may affect the enantiodifferentiation in the enantioselective hydrogenation over cinchona-modified Pt surface. In contrast, Vargas and Baiker75 considered structurally similar cinchonidine conformations bound via the vinyl moiety to play no role in enantioselective hydrogenation. To the best of our knowledge, interactions between the QAOpen(3)/QA-Open(4) conformations and reactant molecules have not been studied before. According to the DFT calculations at the B3LYP/T(ON)DZP level, the isolated QA-Open conformations as well as the complexes between them and the reactants are not stable but relax to some other structures during the geometry optimization calculations. For example, the isolated QA-Open(4) conformation relaxes either to the Open(4) or the Open(3) conformation. Therefore, the stability and other properties of the reactant-modifier(QA-Open) complexes can only be investigated in the presence of the surface. However, studying systems consisting of the modifier, reactant, and surface with DFT is challenging due to the huge demand of computer resources. In this paper, results based on molecular mechanics calculations will be reported for such systems.
Heterogeneous Enantioselective Hydrogenation
J. Phys. Chem. C, Vol. 111, No. 13, 2007 5133
Figure 4. The B3LYP/T(ON)DZP optimized geometries of the PPDMeOCdH+ complexes.
Figure 3. The B3LYP/T(ON)DZP optimized geometries of the PPDCdH+ complexes.
4.2. Reactant-Modifier Complexes. In this section, interactions of 1-phenyl-1,2-propanedione (PPD) and methyl pyruvate (MP) with the protonated modifiers, CdH+ and MeOCdH+ are studied by DFT and MM calculations. The Open(3), Open(5), QA-Open(3), and QA-Open(4) conformations of the modifiers are considered. No stable isolated complexes were found between the reactants and the QA-Open(3) or QA-Open(4) conformations. The DFT optimized geometries of the isolated PPD-CdH+ and PPD-MeOCdH+ complexes are shown in Figures 3 and 4 and the isolated MP-CdH+ and MPMeOCdH+ complexes are shown in Figures S3 and S4 (SI). The MM optimized complexes on the Pt(111) surface are illustrated in Figures 5 and 6 (PPD-modifier) and in Figures S5 and S6 (MP-modifier). Some intermolecular (hydrogen bond) distances in these complexes together with the torsion angles of the reactants’ OdC-CdO moiety reflecting the planarity of the molecules are given in Tables S2 and S3 (SI). Tables 1-4 contain complexation energies and results from the analysis of the reactants’ keto carbonyl orbital energies. Further details of the energies can be found in Tables S4 and S5. The molecular orbitals taken into consideration are illustrated in Figures S7 and S8. The results presented below are essential in order to understand the contribution of various modifier conformations and complexation geometries (bifurcated vs cyclic) to the enantioselective hydrogenation reaction. More detailed information about the geometries and energies of the reactant-modifier complexes is given in Supporting Information. 4.2.1. DFT Optimized Isolated PPD-Modifier Complexes. The relative energies of the DFT optimized PPD-modifier complexes (Tables 1 and 2) indicate that the Open(3) conformation of CdH+ and MeOCdH+ forms 9-16 kJ mol-1 more stable complexes with PPD than the Open(5) conformation. In addition, the keto carbonyl π and π* orbitals are considerably
Figure 5. The COMPASS force field optimized PPD-CdH+ complexes on the Pt(111) surface.
more stabilized in the complexes where the modifiers adopt the Open(3) rather than the Open(5) conformation. The cyclic PPDCdH+ complexes are more stable than the bifurcated ones by 0-7 kJ mol-1. The most stable complex between PPD and CdH+(Open3) is cyclic pro-(S) while the keto carbonyl orbitals
5134 J. Phys. Chem. C, Vol. 111, No. 13, 2007
Taskinen et al. TABLE 2: Absolute Complexation Energies (Ecomplexation ) Ecomplex - Ereactant - Emodifier), Relative Energies of the Complexes (∆Ecomplex ) Ecomplex1 - Ecomplex2), and Relative Stabilization of the Keto Carbonyl Orbitals (∆Eorbital) in 1:1 Complexes between 1-Phenyl-1,2-propanedione and Protonated 9-Methoxycinchonidine Calculated at the B3LYP/T(ON)DZP Level (in kJ mol-1)a complex
Ecomplexation ∆Ecomplex ∆Eorbital ∆EMM ∆EMM on Pt
bifurcated pro-(R) bifurcated pro-(S)
-74.5 -72.1
Open(3) 0 2
0 6
6 0
4 0
bifurcated pro-(R) bifurcated pro-(S)
-52.4 -52.4
Open(5) 16 16
127 120
26 26
112 115
pro-(R)b pro-(S)b
-
QA-Open(3) -
-
-
-1 5
pro-(R)b pro-(S)b
-
QA-Open(4) -
-
-
-21 -18
a Relative energies of the isolated complexes (∆E MM) and the complexes on the Pt(111) surface (∆EMM on Pt) optimized by the COMPASS force field are also given (in kJ mol-1). The names of the complexes refer to the DFT optimized structures. b No stable isolated structure was found with DFT or MM.
Figure 6. The COMPASS force field optimized PPD-MeOCdH+ complexes on the Pt(111) surface.
TABLE 1: Absolute Complexation Energies (Ecomplexation ) Ecomplex - Ereactant - Emodifier), Relative Energies of the Complexes (∆Ecomplex ) Ecomplex1 - Ecomplex2), and Relative Stabilization of the Keto Carbonyl Orbitals (∆Eorbital) in 1:1 Complexes between 1-Phenyl-1,2-propanedione and Protonated Cinchonidine Calculated at the B3LYP/ T(ON)DZP Level (in kJ mol-1)a complex
Ecomplexation ∆Ecomplex ∆Eorbital ∆EMM ∆EMM on Pt
bifurcated pro-(R) bifurcated pro-(S) cyclic pro-(R)b cyclic pro-(S)b
-75.1 -74.2 -75.5 -76.2
Open(3) 1 2 1 0
0 52 10 38
20 22 2 0
10 0 -
bifurcated pro-(R) bifurcated pro-(S) cyclic pro-(R) cyclic pro-(S)
-56.9 -57.7 -63.5 -61.9
Open(5) 17 16 10 12
130 130 104 99
45 46 17 18
117 118 88 92
pro-(R)c pro-(S)c
-
QA-Open(3) -
-
-
-44 -42
pro-(R)c pro-(S)c
-
QA-Open(4) -
-
-
-69 -75
a
Relative energies of the isolated complexes (∆EMM) and the complexes on the Pt(111) surface (∆EMM on Pt) optimized by the COMPASS force field are also given (in kJ mol-1). The names of the complexes refer to the DFT optimized structures. b The MM optimized structure on Pt does not resemble the DFT optimized structure. c No stable isolated structure was found with DFT or MM.
of PPD are the most stabilized in the bifurcated pro-(R) complex. If CdH+ adopts the Open(5) conformation, the most stable complex is cyclic pro-(R) whereas PPD’s keto carbonyl orbitals are the most stabilized in the cyclic pro-(S) complex. Considering the PPD-MeOCdH+ complexes, it is noticed that the pro-(R) complexes are 0-2 kJ mol-1 more stable than
TABLE 3: Absolute Complexation Energies (Ecomplexation ) Ecomplex - Ereactant - Emodifier), Relative Energies of the Complexes (∆Ecomplex ) Ecomplex1 - Ecomplex2), and Relative Stabilization of the Keto Carbonyl Orbitals (∆Eorbital) in 1:1 Complexes between Methyl Pyruvate and Protonated Cinchonidine Calculated at the B3LYP/T(ON)DZP Level (in kJ mol-1)a complex
Ecomplexation ∆Ecomplex ∆Eorbital ∆EMM ∆EMM on Pt
bifurcated pro-(R) bifurcated pro-(S) cyclic pro-(R)b cyclic pro-(S)b
-86.6 -85.7 -80.6 -80.4
Open(3) 0 1 6 6
26 58 0 41
19 23 0 5
0 9 -
bifurcated pro-(R) bifurcated pro-(S) cyclic pro-(R) cyclic pro-(S)
-67.3 -68.0 -65.1 -67.5
Open(5) 17 16 19 17
140 119 74 65
42 38 13 15
120 116 78 78
pro-(R)c pro-(S)c
-
QA-Open(3) -
-
-
-39 -39
pro-(R)c pro-(S)c
-
QA-Open(4) -
-
-
-77 -80
a Relative energies of the isolated complexes (∆E MM) and the complexes on the Pt(111) surface (∆EMM on Pt) optimized by the COMPASS force field are also given (in kJ mol-1). The names of the complexes refer to the DFT optimized structures. b The MM optimized structure on Pt does not resemble the DFT optimized structure. c No stable isolated structure was found with DFT or MM.
the pro-(S) complexes. The keto carbonyl orbitals of PPD are more stabilized in the pro-(R) complex when MeOCdH+ adopts the Open(3) conformation; when MeOCdH+ adopts the Open(5) conformation, these orbitals are more stable in the pro-(S) complex. The relative stabilization of PPD’s keto carbonyl orbitals depends considerably on the modifier. For example, the orbitals are 52 kJ mol-1 more stabilized in the bifurcated pro-(R) than in the bifurcated pro-(S) complex when the modifier is CdH+(Open3) but this stability difference reduces to 6 kJ mol-1 when the modifier is MeOCdH+(Open3). 4.2.2. DFT Optimized Isolated MP-Modifier Complexes. The relative energies of the DFT optimized MP-modifier complexes
Heterogeneous Enantioselective Hydrogenation
J. Phys. Chem. C, Vol. 111, No. 13, 2007 5135
TABLE 4: Absolute Complexation Energies (Ecomplexation ) Ecomplex - Ereactant - Emodifier), Relative Energies of the Complexes (∆Ecomplex ) Ecomplex1 - Ecomplex2), and Relative Stabilization of the Keto Carbonyl Orbitals (∆Eorbital) in 1:1 Complexes between Methyl Pyruvate and Protonated 9-Methoxycinchonidine Calculated at the B3LYP/T(ON)DZP Level (in kJ mol-1)a complex
Ecomplexation ∆Ecomplex ∆Eorbital ∆EMM ∆EMM on Pt
bifurcated pro-(R) bifurcated pro-(S)
-85.9 -85.1
Open(3) 0 1
0 33
0 3
0 10
bifurcated pro-(R) bifurcated pro-(S)
-64.6 -64.8
Open(5) 15 15
112 100
23 16
111 107
pro-(R)b pro-(S)b
-
QA-Open(3) -
-
-
2 -3
pro-(R)b pro-(S)b
-
QA-Open(4) -
-
-
-24 -26
a Relative energies of the isolated complexes (∆E MM) and the complexes on the Pt(111) surface (∆EMM on Pt) optimized by the COMPASS force field are also given (in kJ mol-1). The names of the complexes refer to the DFT optimized structures. b No stable isolated structure was found with DFT or MM.
(Tables 3 and 4) indicate that the Open(3) conformation of CdH+ and MeOCdH+ forms 11-17 kJ mol-1 more stable complexes with MP than the Open(5) conformation. In addition, the keto carbonyl orbitals of the reactant are considerably more stabilized in the complexes where the modifiers adopt the Open(3) conformation, just as in the case of the PPD-modifier complexes. The bifurcated MP-CdH+ complexes are 0-6 kJ mol-1 more stable than the cyclic MP-CdH+ complexes. However, the stabilization of the keto carbonyl orbitals of MP is more pronounced in the cyclic complexes than in the corresponding bifurcated complexes by 17-66 kJ mol-1. If the modifiers adopt the Open(3) conformation, the pro-(R) complexes are slightly more stable than the corresponding pro-(S) complexes, whereas if the modifiers adopt the Open(5) conformation, the pro-(S) complexes are thermodynamically preferred over the pro-(R) complexes. The keto carbonyl orbitals are more stabilized in the pro-(R) complexes by 32-41 kJ mol-1 as the modifiers adopt the Open(3) conformation. As the modifiers adopt the Open(5) conformation, the keto carbonyl orbitals are 9-21 kJ mol-1 more stable in the pro-(S) complexes. Unlike in the case of PPD, the relative stabilization of MP’s keto carbonyl orbitals does not depend notably on the modifier. For example, the orbitals are 32-33 kJ mol-1 more stable in the bifurcated pro-(R) than in the bifurcated pro-(S) complexes whether the modifier is CdH+(Open3) or MeOCdH+(Open3). 4.2.3. MM Optimized Isolated Reactant-Modifier Complexes. The MM calculations were performed to study whether the DFT optimized structures of the various type of reactant-modifier complexes could exist on a flat platinum(111) surface. For comparison, the DFT optimized isolated complexes were reoptimized using the COMPASS force field. Generally, the structures of the force field optimized isolated reactant-modifier complexes are fairly close to those obtained at the DFT level. This can be found by comparing the intermolecular distances in Tables S2 and S3. In addition, the force field optimized isolated MP-CdH+ complexes are illustrated in Figure S9 and may be compared to those optimized by DFT (Figure S3). Despite the fact that MM and DFT do not give exactly the same relative energies for all complexes (Tables 1-4), the important thing to observe is that all DFT optimized structures are also stable at the MM level.
4.2.4. MM Optimized PPD-Modifier Complexes on Pt(111). The MM calculations suggest that it is energetically most favorable for PPD, MP, CdH+, and MeOCdH+ to adsorb parallel to the Pt(111) surface (i.e., flat adsorption, Figures 5, 6, S5, and S6). According to the DFT calculations52,70,73,75 (see also Figure 2), the hybridization of the carbon atoms in the carbonyl, phenyl and quinoline moieties changes from sp2 toward sp3 upon adsorption parallel to the Pt(111) surface. Obviously, MM cannot model chemisorption and rehybridization of the atoms. The phenyl ring together with the OdC-CdO moiety of both reactants as well as the quinoline ring of the modifiers remain essentially planar on the surface. The MM calculations on the PPD-modifier complexes on the Pt(111) surface suggest that the most stable PPD-CdH+ complexes are formed when CdH+ adopts the QA-Open(4) conformation (Table 1). The PPD-CdH+(QA-Open3) complexes are ca. 30 kJ mol-1 less stable. The PPD-CdH+(Open3) and PPD-CdH+(Open5) complexes have 75-85 and 163-193 kJ mol-1 higher energy, respectively, than the most stable PPDCdH+(QA-Open4) complex. The energy differences between the aforementioned complexation geometries become less pronounced when the hydroxyl group of CdH+ is substituted with a methoxy group but the relative stabilities of the complexes follow the same order as above (Table 2). However, the complexes where MeOCdH+ adopts either the Open(3) or the QA-Open(3) conformation are of equal stability. The thermodynamical preference of the PPD-modifier(QA-Open4) and PPD-modifier(QA-Open3) complexes over the PPDmodifier(Open3) and PPD-modifier(Open5) complexes can be explained by the high stability of the QA-Open conformations on the surface (Table S1). The pro-(R) PPD-CdH+ complexes are more stable than the corresponding pro-(S) complexes by 2-4 kJ mol-1 when CdH+ adopts the Open(5) or the QA-Open(3) conformation. Otherwise pro-(S) is more stable than pro-(R) by 6-10 kJ mol-1. The pro(R) PPD-MeOCdH+ complexes are more stable than the corresponding pro-(S) complexes except when MeOCdH+ adopts the Open(3) conformation. The cyclic PPD-CdH+(Open3) complexes are not stable on the Pt(111) surface. 4.2.5. MM Optimized MP-Modifier Complexes on Pt(111). The MM calculations on the MP-modifier complexes on the Pt(111) surface suggest that the most stable MP-CdH+ complexes are formed when CdH+ adopts the QA-Open(4) conformation (Table 3), such as in the case of the PPD-modifier complexes. The MP-CdH+(QA-Open3) complexes are ca. 40 kJ mol-1 less stable. The MP-CdH+(Open3) and MP-CdH+(Open5) complexes have 80-200 kJ mol-1 higher energy than the most stable MP-CdH+(QA-Open4) complex. The energy differences between the aforementioned complexation geometries become less pronounced when the hydroxyl group of cinchonidine is substituted with a methoxy group but the order of stability of the complexes is the same as above (Table 4). Nevertheless, the complexes where MeOCdH+ adopts either the Open(3) or the QA-Open(3) conformation are almost of equal stability. The pro-(S) complexes are more stable than the corresponding pro-(R) complexes by 0-5 kJ mol-1 except in the case of bifurcated MP-modifier(Open3) complexes where pro-(R) is 9-10 kJ mol-1 more stable than pro-(S). No stable cyclic MP-CdH+(Open3) complexes exist on the Pt(111) surface. 5. Discussion Enantioselective hydrogenation of 1-phenyl-1,2-propanedione over cinchonidine modified Pt catalysts leads to a notable
5136 J. Phys. Chem. C, Vol. 111, No. 13, 2007 enantiomeric excess (ee ) 55-65%) of the major product (R)1-hydroxy-1-phenylpropanone.18,19,42,87,88 The hydroxyl group at the C(9) position of cinchonidine is important for achieving high enantioselectivities since its replacement with a methoxy group results in a loss of enantioselectivity or even inversion of the ee.18,19 While enantioselective hydrogenation of R-keto esters, such as methyl and ethyl pyruvate, leads also to a significant ee of the (R)-product enantiomer over cinchonidinemodified Pt catalysts both in the liquid and gas phase,48,54,63 the hydroxyl group of cinchonidine can be replaced by a methoxy group without any loss of ee.15 Let us consider these experimental observations in the light of the computational results presented above. 5.1. The Role of the Modifier Conformation. According to the DFT calculations at the B3LYP/T(ON)DZP level, the Open(3) and Open(5) conformers of protonated cinchonidine and 9-methoxycinchonidine are almost equally stable (Figure S1). However, PPD forms 9-16 kJ mol-1 more stable complexes with the Open(3) conformers than with the Open(5) conformers. Similarly, the MP-modifier(Open3) complexes are 11-17 kJ mol-1 more stable than the MP-modifier(Open5) complexes. Therefore, the complexes where the modifiers adopt the Open(3) conformation should be notably more abundant than the reactant-modifier(Open5) complexes. The results from the MM calculations on both the isolated complexes and the complexes on the Pt(111) surface are in qualitative agreement with the DFT results. Thus, the role of the reactant-modifier(Open5) complexes in determining the enantioselectivity can be considered negligible from the thermodynamic point of view. When studying computationally isolated 1:1 complexes between 3,5-di(fluoromethyl)acetophenone and cinchonidine, Hess et al.21 also found that the complexes exhibited higher energies when the modifier adopted the Open(5) conformation and not the Open(3) conformation. The most abundant surface species are not necessarily the most reactive ones. Inspection of the relative stabilization of the keto carbonyl orbitals of PPD and MP in different reactantmodifier complexes (Tables 1-4) reveals that the aforementioned orbitals are always more stable if the modifier adopts the Open(3) conformation and not the Open(5) conformation. This indicates that the reactant-modifier(Open3) complexes are more reactive toward hydrogenation than the reactant-modifier(Open5) complexes. Thus, both kinetics and thermodynamics imply that the Open(5) conformation of CdH+ and MeOCdH+ is not a relevant conformation contributing to the enantioselectivity of the hydrogenation of PPD and MP over Pt. The authors would like to notice in this context that according to the calculations, the conformation of the modifier has an effect on which product enantiomer is formed in excess in the catalytic hydrogenation of MP. Both thermodynamics and kinetics favor an excess formation of the (R) product enantiomer if the modifier adopts the Open(3) conformation. However, if the modifier adopted the Open(5) conformation, the (S) product would be formed in excess according to the relative energies of the complexes and the keto carbonyl orbital stabilization. This implies that if the conformation of the modifier can be controlled under experimental conditions it will give a possibility to control the enantioselectivity. The MM and the DFT calculations indicate that there exist also other stable conformations than Open(3) and Open(5) for CdH+ and MeOCdH+ on the Pt(111) surface. As the modifier’s quinuclidine moiety rotates around the C(4’)-C(9) bond (Figure 1), the modifier can adopt conformations where it is adsorbed on the surface via its quinuclidine moiety in addition to the
Taskinen et al. quinoline ring (Figures 2 and S2). In these so-called Quinuclidine Adsorbed-Open (QA-Open) conformations the C(10)d C(11) double bond of CdH+ and MeOCdH+ lies close and almost parallel to the surface. This provides a reasonable explanation for its fast hydrogenation observed experimentally under catalytic conditions.15,64,66 Similar conformations have also been found to be stable on Pt(111) by molecular dynamics71 and by DFT calculations.75 Vargas and Baiker75 considered these conformations as transient species converting to some other conformation after the detachment of the quinuclidine moiety due to the hydrogenation of the vinyl group. In fact, the DFT calculations show that the quinuclidine moiety stays adsorbed whether the vinyl moiety of Cd is hydrogenated or not (Figure 2). In addition, if the quinuclidine N of Cd and dihydro-Cd is protonated (which is probable at the reaction conditions42,73) the QA-Open(4) conformation is more stable than the Open(3) conformation. These results are supported by the MM calculations. It should be noted, however, that the MM calculations have several defects in describing the modifier-metal interactions as discussed in ref 17. In a more complete model of the catalytic system, the presence of hydrogen adsorbed on the surface should be taken into account as well. Furthermore, the reactant-modifier(QA-Open) complexes are not stable if the impact of the catalyst surface is neglected. Therefore, no information regarding the kinetic factor (keto carbonyl orbital stabilization) and the thermodynamic factor (complex stability) at the DFT level is available. It is possible that the hydrogenation of the carbonyl group is slow in the reactant-modifier(QAOpen) complexes compared to that in the reactant-modifier(Open3) complexes and it does not contribute to the enantioselectivity. Thus, despite their high stability on Pt(111), the complexes where the modifier adopts the QA-Open conformation may be irrelevant to the hydrogenation reaction. In any case, the high stability of the QA-Open conformations on the Pt(111) surface indicates that they may have some role in the enantioselective hydrogenation over modified Pt catalysts. 5.2. The Role of the OH Group of Cinchonidine. The hydroxyl group at the C(9) position of cinchonidine is crucial for achieving high enantioselectivity in the hydrogenation of 1-phenyl-1,2-propanedione18,19 unlike in the hydrogenation of ethyl pyruvate over Pt catalyst where the ee with MeOCd is very similar to the one with Cd.13-16 In toluene, the enantiomeric excess is changed from 57% of (R)-1-hydroxy-1-phenylpropanone to 2% of (S)-1-hydroxy-1-phenylpropanone by replacing the OH group of Cd with a methoxy group.19 In principle, the methoxy substituent can influence the conformation, adsorption mode (parallel vs tilted), and electronic properties of Cd as well as induce steric effects and thereby affect the nature of active chiral sites and the enantiodifferentiating reactant-modifiermetal interactions. The results presented in this paper have shown that CdH+ and MeOCdH+ have quite similar conformational behavior both as isolated and on the Pt(111) surface. In addition, it has been experimentally observed that the MeO substituent does not change the preferred parallel adsorption mode of Cd on Pt,14 which is in agreement with our computations. These results suggest that the potential dependence of enantioselectivity on the modifier (Cd vs MeOCd) is not due to a different conformation or adsorption mode of cinchonidine compared to those of 9-methoxycinchonidine. The OH group of Cd may be involved in the hydrogen bonding interaction between the reactant and the modifier and thereby affect the ee. In the one-to-one reactant-modifier complexes studied in this work, this takes place in the cyclic complexes where CdH+ adopts either the Open(3) or Open(5)
Heterogeneous Enantioselective Hydrogenation conformation (Figures 3 and S3) and in the complexes on Pt(111) where CdH+ adopts the QA-Open(3) or QA-Open(4) conformation (Figures 5 and S5). As was argued above, the reactant-CdH+(Open5) complexes can be ruled out from examination due to their thermodynamic instability and low reactivity compared to the other complexes. The DFT calculations on isolated PPD-CdH+(Open3) complexes show that the cyclic complexes are approximately as stable as the bifurcated ones (Table 1). Further, the keto carbonyl orbitals of PPD are almost equally stable in both cyclic and bifurcated PPD-CdH+(Open3) complexes. Although thermodynamics (i.e., complex stability) does not seem to favor an excess formation of either one of the enantiomeric products, PPD’s keto carbonyl orbitals are clearly more stable in both cyclic and bifurcated pro-(R) complexes indicating that these complexes will be more reactive for hydrogenation than the pro-(S) complexes. The DFT calculations on isolated MP-CdH+(Open3) complexes show that the cyclic complexes are 5-6 kJ mol-1 less stable than the bifurcated ones (Table 3). However, the keto carbonyl orbital stabilization is more pronounced in the cyclic complexes. This would in principle lead to a higher hydrogenation rate of MP in the cyclic than in the bifurcated complexes. It is noticed that the thermodynamics and kinetics favor an excess formation of the (R) product from both bifurcated and cyclic intermediate complexes by approximately the same amount. Consequently, the ee will be similar whether the hydrogenation reaction proceeds through the bifurcated or the cyclic complexes. The MM calculations show that the cyclic PPD-CdH+(Open3) and MP-CdH+(Open3) complexes cannot exist on the Pt(111) surface due to steric constraints. Thus, the results from the DFT and MM calculations indicate together that the cyclic complexes are not important considering the enantioselectivity of the Pt catalyzed hydrogenation of 1-phenyl1,2-propanedione and methyl pyruvate. Even if the most favored interaction geometry for both the reactant-CdH+ and reactant-MeOCdH+ complexes was the same (e.g., bifurcated and the modifiers adopting the Open(3) conformation), it is possible that the thermodynamic and/or kinetic factors that control the enantioselectivity are not of the same magnitude in both cases due to steric or electronic effects. The relative energies of the bifurcated PPD-CdH+(Open3) and PPD-MeOCdH+(Open3) complexes calculated at the B3LYP/ T(ON)DZP level (Tables 1 and 2) reveal that thermodynamics favors an excess formation of (R)-1-hydroxy-1-phenylpropanone by about the same amount (1-2 kJ mol-1) in the case of both modifiers. However, stabilization of the keto carbonyl orbitals of PPD (i.e., kinetics) favors an excess formation of (R)-1hydroxy-1-phenylpropanone by 52 kJ mol-1 in the case of CdH+ but only by 6 kJ mol-1 in the case of MeOCdH+. These results indicate that the substitution of Cd’s OH with OMe decreases the enantiomeric excess of (R)-1-hydroxy-1-phenylpropanone considerably. Thus, the calculations are well in line with the experiments. The complexation energies and the stabilization of MP’s keto carbonyl orbitals in the bifurcated MP-CdH+(Open3) and MPMeOCdH+(Open3) complexes calculated at the B3LYP/T(ON)DZP level (Tables 3 and 4) indicate that thermodynamics and kinetics favor an excess formation of (R)-methyl lactate by the same amount (within 1 kJ mol-1) in the case of both modifiers. The MM calculations on isolated complexes as well as complexes on the Pt surface support these results. Experimental enantiomeric excesses are very similar with Cd and MeOCd13-16 and, therefore, the calculations are again well in accord with the experiments.
J. Phys. Chem. C, Vol. 111, No. 13, 2007 5137 Combining the results from the DFT and MM calculations has led to a reasonable explanation for the observed enantioselectivities in the hydrogenation of 1-phenyl-1,2-propanedione and methyl pyruvate over Pt catalyst modified by cinchonidine and 9-methoxycinchonidine. 5.3. Reliability of the DFT and MM Calculations. Potential energy diagrams including transition state energies for whole reaction paths on metal surface can be determined from first-principles calculations if the systems under study are small enough.40,41 However, this would be computationally extremely demanding for enantioselective hydrogenations over metal surfaces and, therefore, simplifications are needed. One level of approximation that has been used in this study is to model the system with molecular mechanics. It is to be noted, however, that the results from the MM calculations should be regarded only as qualitative and indicative; MM is too rough to accurately calculate, for example, the relative energies of corresponding pro-(R) and pro-(S) complexes, which are usually between 0 and 5 kJ mol-1. Moreover, the MM calculations do not accurately describe the interactions between the adsorbates and the metal surface. For example, chemisorption and, consequently, rehybridization of the atoms of adsorbate molecules cannot be observed. However, physisorption and steric constraints imposed by the surface are described by the MM calculations. Thus, the stabilities of the complexes on the surface are mostly affected by the restrictions induced by the surface to the various complex geometries. In this study, the MM calculations have given valuable suggestions about possible molecular structures that may exist on the surface. It may also be questionable whether the DFT methods are accurate enough to give reliable results; the energy differences between pro-(R) and pro-(S) complexes are usually small, 0-5 kJ mol-1. For example, Baboul et al.120 have reported that at the B3LYP/6-311+G(3df,2p)//B3LYP/6-31G(d) level of theory the mean absolute deviation from 299 experimental energies (enthalpies of formation, electron affinities, ionization potentials and proton affinities) in the G2/97 test set is 14 kJ mol-1. However, in the present study the absolute complexation energies are not the most important information but rather the differences between the complexation energies, that is, the relative stabilities of the complexes. The accuracy of the relative complexation energies are likely to benefit from cancellation of possible errors in the absolute values caused by deficiencies in the theoretical model. In other words, if there is an error in the calculated complexation energy of a pro-(R) complex, it is expected that there is an error of similar magnitude in the complexation energy of the corresponding pro-(S) complex. The ability of the DFT methods to predict relative energies with higher accuracy has been pointed out previously.40 It has also been found out that the level of theory (MP2/6-31G* vs HF/ 6-31G*) has only an insignificant influence,
