Enantio-Differentiation

The molecular modelling approach, taking into account the pyruvate—cinchona alkaloid interaction and the steric constraints imposed by the adsorption on the platinum surface, leads to a reasonable explanation for the enantio-differentiation of this system. Although the prediction of the complex formed between the methyl pyruvate and the cinchona modifiers have been made for an ideal case (solvent effects and a quantum description of the interaction with the platinum surface atoms were not considered), this approach proved to be very helpful in the search of new modifiers. The search strategy, which included a systematic reduction of the cinchona alkaloid structure to the essential functional parts and validation of the steric constraints imposed to the interaction complex between modifier and methyl pyruvate by means of molecular modelling, indicated that simple chiral aminoalcohols should be promising substitutes for cinchona alkaloid modifiers. Using the Sharpless symmetric dihydroxylation as a key step, a series of enantiomerically pure 2-hydroxy-2-aryl-ethylamines... 

Stereochemical Studies of the Enantio-differentiating Hydrogenation of Various Prochiral Ketones over Tartaric Acid-Modified Nickel Catalyst... 

Taking the above mentioned characteristics of the two modes into consideration, we introduced the concept of stereo-control in the enantio-differentiating hydrogenation of various functionalized prochiral ketones on TA-MNi based on the coexistence of 2P and IP on the site of the catalyst. That is the IP function coimteracts the 2P function when IP and 2P coexist, and the relative contribution of the two modes determine the stereochemistry of the product produced in excess and also relates qualitatively to the i factor. 

The 96% ee is the highest so far achieved by the enantio-differentiating hydrogenation over an asymmetrically modified heterogeneous catalyst. Although it is difficult to separate factor i and E/ e+N), the present results indicated that both of them are well optimized and become almost xmity. 

We have modelled the [CDopen - methyl pyruvate] complex. The result is shown in Figure 2. In this complex there is no steric hindrance to prevent the free rotation of the substrate around the quinuclidine nitrogen. Thus, in complex shown in Figure 2. there is no preferential stabilization of the substrate. In earlier computer modeling it was suggested that Pt is involved in the stabilization of the [CDopew-a-lfeto ester] complex, i.e. the Pt surface prevent the free rotation of the substrate, however the driving force for enantio-differentiation, i.e. for preferential adsorption of the substrate, was not discussed [14]. 

Hydrogenation of ethyl pyruvate in the presence of cinchonidine. In our previous studies [3, 4,14] variety of experimental data were obtained, which could not be explained by existing models [1,2] proposed earlier. These results are as follows [3,4,12] (i) the monotonic increase type behaviour of the optical yield - conversion dependencies, (ii) the complexity of the reaction kinetics, (iii) side reactions catalyzed by CD. It was also demonstrated that the enantio-differentiation can be induced if the modifier is injected into the reactor during racemic hydrogenation. 

As Figure 14.5 shows, the enantio-differentiating (e.d.) hydrogenation consists of three processes (1) catalyst preparation, (2) chiral modification, and (3) hydrogenation reaction. These processes imply preparation variables for activated nickel, as a base catalyst for modified Ni, modification variables for the activated catalyst, and reaction variables of the hydrogenation processes, respectively. All these factors should be optimized for each type of substrate. 

Modified Raney Nickel (MRNi) Catalyst Heterogeneous Enantio-Differentiating (Asymmetric) Catalyst... 

Since the pH and temperature of the modifying solution affect the enantio-differentiating ability (asymmetric activity) (EDA) of the catalyst, they are very important factors and are called modifying pH and modifying temperature, respectively. 

Since MRNi is prepared from commercially available cheap materials by the simple method described above, MRNi is one of the most economical catalysts to be devised for the practical enantio-differentiating reaction. 

In 1968, the following experimental rules were established with respect to the correlation between the structure of the modifying reagent and the EDA of MRNi (24) during the enantio-differentiating hydrogenation of MAA at 60°C ... 

The direction of enantio-differentiation (the predominant enantiomer R or S, to be produced) is decided by two factors. One factor is the configuration of the chiral structure, that is, if the catalyst modified with (S)-glutamic acid [(S)-Glu-MRNi] produces (R)-MHB from MAA, then (R)-Glu-MRNi produces (S)-MHB (2). The other factor is the nature of X. That is, when the amino acid or hydroxy acid with the same configuration is used as the modifying reagent, the configurations of the predominant products are enantiomers of each other in most cases. For example, (S)-aspartic acid-MRNi produces (R)-MHB and (S)-malic acid-MRNi produces (S)-MHB (19). 

Enantio-Differentiating Abilities of Various Catalysts Modified with Tartaric Acid"... 

The rate of hydrogenation of acetone over TA MRNi was higher than over TA NaBr-MRNi (47). Thus, the NaBr inhibits partially the hydrogenation activity of TA-MRNi, and the increase in EDA of TA- MRNi with NaBr can be ascribed to the inhibition of hydrogenation at the unmodified surface of TA-MRNi. In other words, most of the hydrogenation with TA NaBr MRNi must be performed at the enantio-differentiating site. 

As shown in Table XVI, TA-NaBr-MRNi catalyzed the enantio-differentiating hydrogenation of ketones with a much higher EDA than TA-MRNi. The increase of EDA of TA-MRNi with NaBr for each substrate can be correlated with the hydrogenation rates of each substrate at the modified surface and the unmodified surface. 

Table XVII shows the comparison of results of enantio-differentiating hydrogenations of ketones which have a general structure of R—CO— CH2—X—O— over TA-NaBr-MRNi and TA-MRNi. The EDA over TA-NaBr-MRNi was twice as much as that over TA-MRNi without exception.

Reaction conditions affect strongly the OY4 in the enantio-differentiating hydrogenation of MAA with MRNi and the stereochemical reaction mechanism. 

Also, Klabunovskii reported pressure dependences of the OYs in enantio-differentiating hydrogenations of ethyl acetoacetate (EAA) with ruthenium (67), Raney cobalt (65), and RNi catalysts (69) modified with TA, c. Additives. Additives which are added to the reaction system often exert a remarkable effect on the OY of the enantio-differentiating hydrogenation of M A A (23-25). Water is one such additive. For example, in most hydrogenations with amino acid MRNis, the direction of differentiation was reversed by the addition of small amounts of water as shown in Fig. 14 (23, 25). 

DDA is the parameter indicating the ability of the catalyst in the diastereo-differentiation. DDA is estimated by the difference (%) of diastereomers in the product. DDA is a parameter comparable to EDA in the enantio-differentiation. 

Effect of Additives on the Optical Yield in the Enantio-Differentiating Hydrogenations of 2-Octanone and MAA with TA-NaBr-MRNi... 

Sachtler s group (73) and Yasumori (64) studied the IR spectra of silica-supported Ni modified with amino acid and 2-hydroxy acid and the XPS of TA-MRNi. Both authors deduced almost the same model as proposed by Suetaka. Recently Sachtler s group proposed other models as shown in Fig. 22 from results obtained in enantio-differentiating hydrogenations of MAA with nickel catalysts modified with nickel and copper tartrates (74). The nickel tartrate adsorbs at the vacant coordination site of nickel in this model. 

For further elucidation of the reaction mechanism of MRNi, a stereochemical study of the enantio-differentiating hydrogenation of methyl... 

Scheme 2. Enantio-differentiating hydrogenation of methyl 2-methyl-3-oxobutyrate.

Enantio-Differentiating Hydrogenation of Methyl 2-Methyl-3-oxobutyrate (8) with Various Modified Nickel Catalysts ... 

TABLE XXIV. Enantio- Differential inij Ability (EDA) ojTA nr Its Analuti... 

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