Phenylcinnamic acid hydrogenation

Here the phenylacetic anhydride, possessing more reactive a-hydrogen atoms, condenses with benzaldehyde to give a-phenylcinnamic acid. The preparation of the latter is an example of the Oglialoro modiflcation of the Perkin reaction. 

Neither tritium or deuterium gas, with zero dipole moments, can be expected to interact positively with microwave radiation. Their low solubilities are seen as a further disadvantage. Our thoughts therefore turned towards an alternative procedure, of using solid tritium donors and the one that has found most favor with us is formate, usually as the potassium, sodium or ammonium salt. Catalytic hydrogen transfer of this kind is remarkably efficient as the results for a-methylcinnamic acid show [50]. The thermal reaction, when performed at a temperature of 50 °C, takes over 2 h to come to equilibrium whereas the microwave-enhanced reaction is complete within 5 min. A further advantage is that more sterically hindered al-kenes such as a-phenylcinnamic acid which are reduced with extreme difficulty when using H2 gas and Wilkinson s catalyst are easily reduced under microwave-enhanced conditions. 

Note that there are virtually no data for the asymmetric hydrogenation of the C=C bond over heterogeneous catalysts. The first example474 described the chiral hydrogenation of a-phenylcinnamic acid with 15% ee. 

Up to 72% ee has been achieved in the hydrogenation of a diphenyl-substituted reactant, (trans)-a-phenylcinnamic acid, with a Pd/Ti02 catalyst and cinchonidine at 1 bar in strongly polar solvent mixtures [49]. For aliphatic a,/ -unsaturated acids the enantioselectivities that can be attained are much lower. Therefore, for these type of substrates, homogeneous metal-catalysts are preferred. 

Cinchonidine modified catalysts, though, have been effectively used for several other enantioselective hydrogenations. Platinum-cinchonidine catalysts have been used for the hydrogenation of the a ketolactone, 36, to D-pantolactone (37) in 35% ee at complete conversion (Eqn. 14.26) while palladium-cinchonidine catalysts have been used for the enantioselective dehydrohalogenation of a,a-dichloro-2-benazapinone (38) (Eqn. 14.27) and the hydrogenation of (E) a phenylcinnamic acid (39) to (S) 2, 3-diphenylpropionic acid (40) in a 44% ee (Eqn. 14.28). ... 

Enantioselective hydrogenation of ( )-a-phenylcinnamic acid on cinchonidine-modified palladium catalysts influence of support... 

This catalyst was reduced in flowing hydrogen at 200°C in order to increase the crystallite size of Pd. In this case, the first results on hydrogenation of (. -2-phenylcinnamic acid reached an of ee 44%. With the addition of 7% water to the solvent mixture of EtOAc and EtOH the ee reached 58% (Nitta etal. 

In optimal conditions the hydrogenation of (.E)-2-phenylcinnamic acid proceeded with an ee of 72% (Nitta et al. whereas the hydrogenation of the C=C bond in isophorone on Pd modified with (-)-dihydroapovin-caminic aeid ethyl ester, (-)-DHVin, reached an ee of 55% (Tungler, Nitta et al. ). The differences in ee values were explained by the interactions between modifier and the reactant and by their different basicities. 

The pore diameter limitation also was found for Pd-Cnd catalysts active in the C=C hydrogenation of ( )-2-phenylcinnamic acid. On a 5% Pd-silica catalyst the ee s increased with increasing average pore diameter of silica, and the conclusion was that Pd metal particles should be located in pores large enough to accommodate the bulky alkaloid-modifier molecules and the substrate forming intermediate complex modifier-reactant that have been identified on the surface of Pd-titania catalyst (Nitta et al. ). Palladium metal particles in smaller pores are difficult to modify and they behave therefore as non-selective centers. 

The comparison of a number of Pd-supported catalysts on non-po-rous and porous materials confirmed that non-porous ultrafine carriers like titania, seem to be most suitable for hydrogenation of ( )-2-phenylcinnamic acid. Thus, for porous and non-porous supports results of hydlrogenation were as follows on Si02 49.1% and 30.7%, on Ti02 62.0% and 29.4%, respectively (Nitta et al. ). 

In the case of Pd catalysts supported on non-porous carriers, like Si02 or Ti02, ee s depend on dispersion as found in the case of Pd-Ti02-Cnd in the hydrogenation of ( )-2-phenylcinnamic acid (Nitta et al. ). These results showed that the reaction is mildly structure sensitive in the dispersion range higher than 0.2, but at lower Pd dispersions, it is similar to Pt and Ni catalysts... 

Figure 5.5. Correlation between the dispersion of palladium and the enantioselec-tivity in the hydrogenation of ( )-2-phenylcinnamic acid on Pd-Xi02...

The as5munetric inductions of (-)-DHVin and Cnd as chiral modifiers were compared in the Pd catalyzed hydrogenation of the C=C double bonds of 2-phenylcinnamic acid and isophorone. The differences in their effects and behaviors were attributed to the differences in the interactions between the... 

In the system Cnd-2-phenylcinnamic acid the alkaloid interacts with the acid via two hydrogen bonds Interaction of the C9-OH group is the crucial influence in the chiral induction. Substitution of OH for OMe will weaken the interaction between modifier and the substrate. A second hydrogen bond between the N-atom in the quiniclidine group and the carboxylic group was revealed by experiments of modification of Pd-titania catalyst with a mixture of (Cnd + 9-MeO-DHCnd). Therefore esterification of the carbox-yhc group resulted in complete loss of enantioselectivity. 

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