Pt-alumina-Cnd catalysts

Table 5.3. shows dependence of the ee values on the polarities of solvents in the hydrogenation of EtPy on Pt-zeolite catalysts in comparison with Pt-alumina-Cnd catalysts. 

Solvent effects were studied in the enantioselective hydrogenation of l-phenylpropane-l,2-dione over Pt-alumina-Cnd catalyst. The ee values and reaction rates are dependent on the hydrogen solubilities and dielectric constants in different solvents. The highest ee, 65%, of (i )-1-hydroxy-1-phenyl-propanone was obtained in toluene. It decreased non-linearly with increasing solvent dielectric constant becoming close to zero in MeOH (Toukonitty et al. )... 

Analogous to the pyruvates, the same decrease in ee with increasing solvent polarity was found in the enantioselective hydrogenation of ketopan-tolactone into pantolactone over Pt-alumina-Cnd catalyst (Schuerch et al. ). The most suitable solvent proved to be toluene ee 78%) but in acetic acid solution the strong increase of ee, which was observed in the case of pyruvates, was not seen and the optical yield of pantolactone reached only up to 35% (see results in Part 5.4.). 

Table 5.14. Effect of solvents and additives on the enantioselective hydrogenation of MePy into (5)-(+)-MeLa on 5% Pt-C-Cnd and 5% Pt-alumina-Cnd catalysts (0.5 g catalysts, 70 bar, RT) (according to Orito ).

Figure 5.10. Comparative study of enantioselective hydrogenation of EtPy into ( )-(-)-EtLa on Pt-alumina-Cnd catalyst as a function of the catalyst to substrate weight ratio in ethanol solution ( , at 60 bar, 22 C as subcritical solvent) and in the supercritical solvent ethane ( , at 60...

Figure 5.10. shows an example of the application of SC-ethane as solvent in the hydrogenation of EtPy over Pt-alumina-Cnd catalyst. For all practical purposes the ee values of the resulting EtLa did not change with increasing amounts of catalyst if the reaction was carried out in SC-ethane, whereas these values fall sharply in ethanol. 

Enantioselective hydrogenation of EtPy on Pt-alumina-Cnd catalyst at 60 bar, 40°C, in supercritical solvent ethane (subcritical condition for ethane are 48.2 bar and 32.2°C) can be compared with hydrogenation in ethanol at 60 bar, 22°C as subcritical solvent (SCF are 61 bar and 241 C) (according to Baiker... 

If the reactivity of the substrate in the shielded [substrate-modifier] complexes is higher than that of the free keto ester, enantioselectivity can occur. According to Margitfalvi the quinuclidine N, which aims towards the keto carbonyl group in the keto ester, provides the increased reactivity of the keto carbonyl group. This shielding model, can e q)lain enantioselectivity and rate acceleration effects for almost all substrates used in many examples, for example, hydrogenation of MePy, MBf, ketopanto-lactone, and trifluoroacetophenone over Pt-alumina-Cnd catalysts. 

Additional crucial evidence against a mechanism based on such associations formed in solution is supported by the fact that under these conditions on Pt-alumina-Cnd catalysts C=C prochiral bonds, which are unable to form associations like Cnd-MePy, can be enantioselectively hydrogenated with good ee s. 

It was found that reactions with unmodified catalyst proved to be much faster than those with Cnd modified catalyst, which also is quite different from the results reported for Pt-alumina-Cnd catalysts in the hydrogenation of alpha-keio esters. Reuse of catalysts resulted in almost complete loss of ee and indicates elution and absence of Cnd fi om the surface of the catalyst. 

Reschetilowski et al. also gives a comparison of the efficacy of Pt-zeolite-Cnd catalysts in the hydrogenation of EtPy based on alumina enriched with zeolite Y or ZSM-35 and silica enriched Zeolite Beta or ZSM-5 as carriers (Fig.5.L). 

Von Arx et al. studied the hydrogenation of 4-oxoisophorone (2,6,6-trimethylcyclohex-2-en-l,4-dione) over Pt-alumina and Pd-alumina catalysts modified with Cnd and discovered (over Pt-alumina-Cnd) the first example of an unprecedented selectivity in hydrogenation of a sterically bin-... 

The first enantioselective heterogeneous hydrogenation of KPL was reported in a Japanese patent (Niwa ). Over a 5% Pt/C catalyst previously modified with Cnd in ethanolic solution at reflux, KPL was hydrogenated in benzene at 60 bar to (R)-PL with an ee of 36%. Later, a Pd/C catalyst modified with Cnd proved to be more effective and gave (R)-PL with an ee of 52% (see Baiker "). Even more effective proved to be a Pt-alumina-DHCnd catalysts that produced (R)-(-)-PL with an ee of 79% under optimal conditions (22°C and 70 bar) in toluene at low concentrations of alkaloid (Schuerch et al. ). 

The effect of acids and bases as solvents (or as additives) in the hydrogenation of EtPy on Pt-alumina-Cnd was studied by Blaser et al. The addition of AcOH to common applied solvents (toluene, ethanol) or using AcOH as the solvent exhibited unusually strong positive effects on ee"s, up to 95%, especially with catalysts modified with MeO-DHCnd (Blaser et al. ). 

In the case of the Pt-alumina-Cnd-EtPy system, increasing conversion did not change the ee even at high conversions. This is in contrast to the Ni catalysts modified with tartaric acid and suggests a different mechanism of enantioselectivity. Also, in both cases the possibility of nonlinear effects must be pointed that is, increasing enantio-purity of a product of low opticalpurity upon its exposure to a chiral catalyst (Blackmond Avalos, Kagan ). 

For C=C hydrogenations the reactions with unmodified catalyst were much faster then those with modified catalyst, such as with Cnd. This is quite different from results reported for the hydrogenation of alpha-keto esters on Pt-alumina, where the addition of the modifier alkaloid leads to chiral products and strongly accelerates the reaction (Bartok et al. Tungler, Nitta et al. 

Although cinchona alkaloids and especially cinchonidine, Cnd, proved to be the most effective chiral modifier for the catalytic system of Pt-alumina, in the liquid phase enantioselective hydrogenations of the carbonyl group in pyruvic acid esters, efforts to understand the mechanism of action of this catalyst system has continued to the present. The efforts may be divided into two categories finding natural modifiers other than cinchona alkaloids and examining new effective amino alcohols, which are modeled after the structure of known cinchona modifiers. 

For hydrogenation of both p3Tuvates and MeBf (methyl benzoylformate) Modification of Pt-alumina catalysts with Cn, Qn, or Qnd was less effective than modification with Cnd. Modifying with Cnd and Qn resulted in the (S)-(+) isomer of MeLa rather then the (/ )-(-) isomer as in the case of modifying with Cn. This indicated that the absolute configuration of the resulting hydroxy ester is determined by the configurations at the C and Cg centers in the alkaloid moleeules (see Seheme 5.6.). 

Table 5.6. shows that the enantioselectivity in the hydrogenation of EtPy into (5 -)-(+)-EtLa on 5% Pt-alumina modified with PNE, was 75%, which is similar to the 73% measured at lower pressure on a Cnd modified catalyst. 

Figure 5,7. Effect of the addition of the modifier Cnd to the hydrogenation of ethyl pyruvate on 5 % Pt-alumina catalyst (mainly according to Baiker Optical yield (left) and conversion (right) with (o) and without ( ) Cnd...

In the molecule PNE, which is simpler than the Cnd molecule, there is only a C7 center (see Scheme 5.7.), which is similar to the C9 center in Cnd, and proves to be enough for the creation of an effective modifier of Pt-alumina catalysts yielding EtLa with an ee of 70%. The function of the N-l center is to give close bonding of the modifier to the pyruvate molecule in-... 

Onto et al. also showed that the nature of the solvent proved to be important in the hydrogenation of MeBf and MePy on Pt-C and Pt-alumina catalysts modified with Cnd (Tables 5.12. and 5.13.). 

The kinetics of enantioselective hydrogenation of pyruvates on Pt-alumina (or Pt-silica) catalysts modified with Cnd (or DHCnd) was studied by the groups of Baiker Blaser Wells and Blackmond" " ... 

The effect of the action of a-iCn as a modifier with fixed conformation was compared with Cn in the hydrogenation of EtPy on 5% Pt-alumina (RT, 50 bar, AcOH solvent), and it was shown that the catalyst modified with Cnd, Cn, and a-iCn lead to EtLa with 90% (/ ), 67% (S), and 69% (S), respectively. These ee values supported the existence of conformations (b) and (c) in the reaction and discounted the suggestion of Margitfalvi et al. on the formation of an intermediate alkaloid-pyruvate in solution before adsorption on the catalyst and his criticism of the T 1 model. ... 

Using NMR spectra combined with X-ray crystallography and molecular calculations it was shown by Bartok et al. that Cnd, Cn, Qn, and Qnd must exist in their anti-open conformations as modifiers. Rotations around the C4 -C9 and C8-C9 bonds are hindered. Therefore, the alkaloids exist also in the anti-open conformations but they do not have the C8-C9 free rotation and form a rigid structure during adsorption on the surface of Pt-alumina catalyst. 

The effect of modifier structure was studied in the hydrogenation of EtPy in MeOH and in (DMF + water) Heinz et al. showed that a Pt-alumina catalyst modified with (5)-(-)-l-(l-naphthyl)ethylamine gave an ee of 82% in the hydrogenation of EtPy, whereas modification with Cnd under the same conditions gave only ee s of 73-75% but in the hydrogenation of the C=C bond in cinnamic acids ee values reached only 4-12%... 

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