Hydrogenation of a, p-unsaturated acids

The enantioselective hydrogenation of a,p-unsaturated acids or esters, using 5wt% Pt/Al203 or Pd/Al203 commercial catalysts doped with cinchonidine (CD), was deeply investigated to evidence the specific activity of Pd or Pt and the role of the reaction parameters and solvent polarity. Finally, the steric and electronic effects of different substituent groups were also studied. 

Chiral heterogeneous catalysts, although have lower enantioselectivity and stability than homogeneous catalysts, are often preferable because of their handling and separation properties (5). Aim of this work was to shed light on the enantioselective hydrogenation of a,p-unsaturated acids or their... 

Another important factor in the hydrogenation of a,p-unsaturated acids was the solvent by increasing the polarity of the solvent used (n-hexane < toluene < methyl acetate < THF < methanol) a progressive decrease in ee was observed. This was probably due to the fact that H2 and the a,p-unsaturated acids were more soluble in the apolar solvents and also that CD was present in the open conformation, the enantioselective conformation (8). In fact, the highest conversion and ee were obtained with n-hexane (Figure 2). 

Replacement of aryl rings by cyclohexyl groups has shown encouraging results. Achiwa and coworkers [114] recommended diphosphines 336 (R = c-CgHj j, Ar = Ph, R tart-BuO, MeO, MeNH) as ligands for rhodium in asymmetric hydrogenation of a,P-unsaturated acids 3.40 (Rg - R - H). The appropriate ketolactone precursor can also be reduced to (R)-pantolactone 1.16. 

Ir catalysts supported on binary oxides of Ti/Si and Nb/Si were prepared and essayed for the hydrogenation of a,P-unsaturated aldehydes reactions. The results of characterization revealed that monolayers of Ti/Si and Nb/Si allow a high metal distribution with a small size crystallite of Ir. The activity test indicates that the catalytic activity of these solids is dependent on the dispersion obtained and acidity of the solids. For molecules with a ring plane such as furfural and ciimamaldehyde, the adsorption mode can iirfluence the obtained products. SMSI effect (evidenced for H2 chemisorption) favors the formation of unsaturated alcohol. 

The enantioselective hydrogenation of oc,p-unsaturated acids (or their esters) and a-ketoesters, mainly pyruvates, (Figure 1) is a subject of high industrial relevance in the pharmaceutical and agrochemical areas, considering the very different activity of pure enantiomers (1,2). However, the former reaction has been up to today less investigated, evidencing a lower enantioselectivity (maximum ee 38% in comparison to 90% for the ethyl pymvate) (3,4). 

Prochiral organic acids were hydrogenated on clay-supported Rh-chiral phosphine complexes.205,206 Hectorite-supported chiral Rh(I)-phosphine complexes were used for the asymmetric hydrogenation of a,P-unsaturated carboxylic acids.207 It was found that the interaction between the a-ester group of itaconates and phenyl groups of phosphine can play an important role in the determination of the configuration of products. 

CAMPHOS catalyst, asymmetric hydrogenation of a,p-unsaturated carboxlic acids, 25 107-109, 112 -carbon bond, COj insertion, 28 132-134 -carbon dioxide complex, coordination, 28 125, 126, 128 oxide formation, 28 27 as catalyst, 26 335... 

Table 2.1.5.3 Asymmetric hydrogenation of a, P-unsaturated carboxylic acid derivatives.

Asymmetric Homogeneous Hydrogenation of a, p-Unsaturated Carboxylic Acids with the Rhodium(I)-(+)-CAMPHOS Catalysta... 

Asymmetric Hydrogenation of a, p- Unsaturated Carboxylic Acids A Comparison of Product Percent Enantiomeric Excess Values for Several Ligandsa c... 

The ease and the stereochemical course of hydrogenation of a,p-unsaturated ketones are particularly influenced by the nature of the solvent and the acidity or basicity of the reaction mixture. Some efforts have been made to rationalize the effect of the various parameters on the relative proportions of 1,2- to 1,4-addition, as well as on the stereochemistry of reduction. For example, the product distribution in -octalone hydrogenation in neutral media is related to the polarity of the solvent if the solvents are divided into aprotic and protic groups. The relative amount of cis- -decalone decreases steadily with decreasing dielectric constant in aprotic solvents, and increases with dielectric constant in protic solvents, as exemplified in Scheme 21 (dielectric constants of the solvents are indicated in parentheses). Similar results were observed in the hydrogenation of cholestenone and of testosterone. In polar aprotic solvents 1,4-addition predominates, whereas in a nonpolar aprotic solvent hydrogenation occurs mainly in the 1,2-addition mode. 

High catalytic activities, with turnovers of up to 9(X) cycles min , is displayed in the transfer hydrogenation of a,p-unsaturated ketones, such as benzylideneacetone and chalcone, using 2-propanol and catalytic amounts of [Ir(3,4,7,8-Me4-phen)COD]Cl (phen = 1,10-phenanthroline COD = 1,5-cyclo-octadiene) in a weakly alkaline medium. Other Ir-chelated complexes are also active catalysts in this reaction, with over 95% selectivity for the 1,4-reduction mode. Divalent lanthanide derivatives, such as Sml2 or Ybh in stoichiometric quantities, in THF and t-butyl alcohol or methanol reduce ethyl cinnamate and cinnamic acid to give the saturated derivatives. " Similarly, 3-methylcyclohexenone is reduced to 3-methylcyclohexen-l-ol in 67% yield, but a,p-unsaturated aldehydes are nonselectively reduced with these systems. 

Xiao, J., Nefkens, S. C. A., Jessop, P. G., Ikariya, T., Noyori, R. Asymmetric hydrogenation of a,P-unsaturated carboxylic acids in supercritical carbon dioxide. Tetrahedron Lett. 1996, 37, 2813-2816. 

Ashby, M. T., Halpern, J. Kinetics and mechanism of catalysis of the asymmetric hydrogenation of a,P-unsaturated carboxylic acids by bis(carboxylato) 2,2 -bis(diphenylphosphino)-1,1 -binaphthyl ruthenium(ll), [Rull(BINAP) (02CR)2]. J. Am. Chem. Soc. 1991,113, 589-594. 

Yoshikawa, K., Murata, M., Yamamoto, N., Inoguchi, K., Achiwa, K. Asymmetric reactions catalyzed by chiral metal complexes. III. The origin of the enantioselection in the ruthenium(ll)-catalyzed asymmetric hydrogenation of a,P-unsaturated carboxylic acid. Chem. Pharm. Bull. 1992, 40, 1072-1074. 

Scheme 10.10 Enantioselective hydrogenation of a,P-unsaturated carboxylic acids over Pd/C in the presence of cinchonidine, and the product ee-values under certain conditions.

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