Cinchona modified Pt catalysts

Enantioselective synthesis is a topic of undisputable importance in current chemical research and there is a steady flow of articles, reviews and books on almost every aspect involved. The present overview will concentrate on the application of solid chiral catalysts for the enantioselective synthesis of chiral molecules which are a special class of fine chemicals. Included is an account on our own work with the cinchona-modified Pt catalysts. Excluded is the wide field of immobilized versions of active homogeneous complexes or of bio-catalysts. During the preparation of this survey, several reviews have been found to be very informative [1-14]. 

The transformations that use asymmetric heterogeneous catalysis will be highlighted P-keto esters and diketone reductions by Raney nickel catalyst modified with R,R-tartaric acid and NaBr. a-Keto acid reductions with cinchona modified Pt catalysts are discussed in Chapter 18. 

The stereoselective reduction of a-keto acid derivatives at a preparative scale is performed with cinchona-modified Pt catalyst (see Chapter 18). Enantioselectivities range from 57-95% for the reduction of a-keto acid derivatives5 and is dependent on the preparation of the Pt catalyst.5 22 205 206... 

The hydrogenation of 2,4-diketo acid derivatives 6-9 to the corresponding 2-hydroxy compounds with cinchona-modified Pt catalysts as depicted in Scheme 18.1 can be carried out with chemoselectivities... 

Substituted aliphatic and aromatic a-keto ethers (Scheme 18.5) are also amenable to enantioselective hydrogenation catalyzed by cinchona-modified Pt catalysts.25 However, as opposed to the prochiral ketones discussed earlier, kinetic resolution is observed for these chiral substrates. At conversions of 20A2%, ee s of 91-98% were obtained when starting with a racemic substrate (see Table 18.5). It is somewhat surprising that a-keto ethers without substituent in the a-position, such as methoxy acetone, reacted very slowly or not at all and led to very low enantioselectivities,6 and from the results described earlier for a-ketoacetals, the same is expected if 2 substituents are present. 

FIGURE 18.6 Structures of good, medium, and bad substrates for cinchona-modified Pt catalysts. 

In this chapter, we do not attempt to give a comprehensive overview of the field, but we would rather concentrate on results where both enantioselectivity and catalyst activity are relevant to preparative application. In the first section, results obtained with cinchona-mediated homogeneous systems for the reduction of ketones are briefly reviewed. Then, heterogeneous cinchona-modified Pt catalysts applied to the hydrogenation of a-functionalized ketones and cinchona-modified Pd catalysts for the hydrogenation of activated C=C bonds are discussed from a synthetic point... 

The hydrogenation of 2,4-diketo acid derivatives to the corresponding 2-hydroxy compounds with cinchona-modified Pt catalysts as depicted in Figure 2.4 can be carried out with chemoselectivities more than 99% and enantioselectivities up to 87% (R) and 68% (S), respectively [30a]. Enrichment to more than 98% ee was possible for several substrates by recrystallization, giving rise to an efficient technical synthesis of (R)-2-hydroxy-4-phenyl butyric acid ethyl ester [30b], a building block for several ACE (angiotensin-converting enzyme) inhibitors, as well as some enantio-merically enriched a-hydroxy and a-amino acid esters (see below) [30c]. 

The first technical application of a cinchona-modified Pt catalyst was reported by Ciba-Geigy in 1986 for the synthesis of methyl (R)-2-hydroxy-4-phenyl butyrate (R)-HPB ester), an intermediate for the ACE inhibitor benazepril depicted in Figure 2.10 [44a],... 

For the hydrogenation of a-keto esters and a-keto acetals, the performance of the heterogeneous cinchona-modified Pt catalysts is equal to and in some cases superior to the best homogenous catalysts. Indeed, several industrial applications have been described that underline this statement. For most other substrates, the performance of the cinchona-modified Pd or Pt catalysts is not (yet) on a level where the application to real-world substrates has been demonstrated. 

Keywords. 3-Functionalized ketones, a-Keto acid derivatives. Cinchona modified Pt catalysts. Chiral imprints. Chiral metal surfaces. Chiral polymers. Cyanohydrin formation. Cyclic Dipeptides, Epoxidation catalysts. Heterogeneous catalysts. Hydrogenation catalysts. Modified metal oxides. Polypeptides, Tartrate-modified Nickel catalysts... 

We have demonstrated that the enantioselective hydrogenation of a-ketoadds can be earned out with mnderatg to good optical yields using cinchona modified Pt catalysts in alcoholic solvents. For the synthesis of (R)-4-phenyl-2-hydroxybutyric add we describe results which fonn a good basis for the development of a production process, since the starting materials are readily available and not very expensive. From our expraience with these chirally... 

Bartok s group described the first applieation of the heterogeneous cinchona modified Pt catalysts for the highly enantioselective synthesis of a chiral building block of an acetal with an ee of 96.5% using the hydrogenation of pyruvic aldehyde dimethyl aeetal to lactaldehyde dimethyl acetal (Scheme 5.15.). 

Blaser, H.U., Jalett, H.P., Lottenbach, W.,Studer, M. (2000) Heterogeneous enantioselective hydrogenation of ethyl p Tiivate catalysed by cinchona-modified Pt catalysts effect of modifier structure, J. Amer. Chem. Soc. 122, 12675-12682. 

Blaser, H.U., Jalett, H P., Wiehl, J. (1991) Enantioselective hydrogenation of alpha-ketoesters with cinchona-modified Pt catalysts effect of acidic and basic solvents and additives, J. Mol. Catal. A. Chem. 68, 215-222. Blaser, H.U., Jalett, H P., Monti, D.M., Baiker, A., Wehrli, J.T. (1991) Enantioselective hydrogenation of ethyl p Tuvate effect of catalyst and modifier structure, Stud. Surf Sci. Catal. 67, 147-155. 

Studer, M., Burhardt, S., Blaser, H.U. (1999) Enantioselective hydrogenation of alpha-keto acetals with cinchona modified Pt catalyst, Chem. Com-mun. 1727-1728. 

Bartok, M., Felfoldi, K., Szollosi, G., Bartok, T. (1999) Rigid cinchona conformers in enantioselective catalytic reactions new cinchona-modified Pt catalysts in the Orito reaction, Catal. Lett. 61, 1-5. 

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