Cinchona modified heterogeneous

Blaser, H.U., Hoenig, H., Studer, M., Wedemeyer-Exl., C. (1999) Enantioselective synthesis of ethyl nipecotinate using cinchona modified heterogeneous catalysts, J. Mol Catal A. Chem. 139, 253-257. 

The chapter Chiral Modification of Catalytic Surfaces [84] in Design of Heterogeneous Catalysts New Approaches based on Synthesis, Characterization and Modelling summarizes the fundamental research related to the chiral hydrogenation of a-ketoesters on cinchona-modified platinum catalysts and that of [3-ketoesters on tartaric acid-modified nickel catalysts. Emphasis is placed on the adsorption of chiral modifiers as well as on the interaction of the modifier and the organic reactant on catalytic surfaces. 

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. 

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... 

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. 

Historically, the chiral modification of classical heterogeneous hydrogenation catalysts was the first successful approach to practically useful enantioselective catalysts [7]. (For a detailed update, see Chapter 11.) However, despite considerable efforts only two types of catalytic system are of practical importance for preparative purposes, namely Ni catalysts modified with tartaric acid, and cinchona-modified Pt (and to some extent Pd) catalysts. 

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... 

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. 

Felfoldi, K., Szori, K., Bartok, M. (2003) Heterogeneous as5nnmetric reactions. Part 35. Enantioselective hydrogenation of 2-oxoglutaric acid over cinchona modified Pt/Al203 catalysts, A/ip/. Catal. A. Gen. 251, 457-460. 

Perosa, A., Tundo, P., Selva, M. (2002) Multiphase heterogeneous catal54ic enantioselective hydrogenation of acetophenone over cinchona-modified Pt/C, J. Mol Catal A. Chem. 180, 169-175. 

Torok, B., Balazsik, K., Torok, M., Felfoldi, K., Bartok, M. (2002) Heterogeneous asymmetric reactions 20. Effect of ultrasonic variables on the enantiodifferentiation in cinchona-modified platinum-catalyzed sonoche-mical hydrogenations, Catal. Lett. 81, 55-62. 

Biirgi T, Vargas A, Baiker A (2002) VCD spectroscopy of chiral cinchona modifiers used in heterogeneous enantioselective hydrogenation conformation and binding of non-chiral acids. J Chem Soc Perkin Trans 2 1596-1601... 

Among the various strategies [34] used for designing enantioselective heterogeneous catalysts, the modification of metal surfaces by chiral auxiliaries (modifiers) is an attractive concept. However, only two efficient and technically relevant enantioselective processes based on this principle have been reported so far the hydrogenation of functionalized p-ketoesters and 2-alkanons with nickel catalysts modified by tartaric acid [35], and the hydrogenation of a-ketoesters on platinum using cinchona alk oids [36] as chiral modifiers (scheme 1). 

The enantioselective hydrogenation of prochiral substances bearing an activated group, such as an ester, an acid or an amide, is often an important step in the industrial synthesis of fine and pharmaceutical products. In addition to the hydrogenation of /5-ketoesters into optically pure products with Raney nickel modified by tartaric acid [117], the asymmetric reduction of a-ketoesters on heterogeneous platinum catalysts modified by cinchona alkaloids (cinchonidine and cinchonine) was reported for the first time by Orito and coworkers [118-121]. Asymmetric catalysis on solid surfaces remains a very important research area for a better mechanistic understanding of the interaction between the substrate, the modifier and the catalyst [122-125], although excellent results in terms of enantiomeric excesses (up to 97%) have been obtained in the reduction of ethyl pyruvate under optimum reaction conditions with these Pt/cinchona systems [126-128],... 

In order to evaluate the catalytic characteristics of colloidal platinum, a comparison of the efficiency of Pt nanoparticles in the quasi-homogeneous reaction shown in Equation 3.7, with that of supported colloids of the same charge and of a conventional heterogeneous platinum catalyst was performed. The quasi-homogeneous colloidal system surpassed the conventional catalyst in turnover frequency by a factor of 3 [157], Enantioselectivity of the reaction (Equation 3.7) in the presence of polyvinyl-pyrrolidone as stabilizer has been studied by Bradley et al. [158,159], who observed that the presence of HC1 in as-prepared cinchona alkaloids modified Pt sols had a marked effect on the rate and reproducibility [158], Removal of HC1 by dialysis improved the performance of the catalysts in both rate and reproducibility. These purified colloidal catalysts can serve as reliable... 

In fact, there are only two heterogeneous catalysts that reliably give high enantioselectivities (e.s. s) (90% e.e. or above). These are Raney nickel (or Ni/Si02) system modified with tartaric acid (TA) or alanine for hydrogenation of /(-kctocstcrs [12-30], and platinum-on-charcoal or platinum-on-alumina modified with cinchona alkaloids for the hydrogenation of a-ketoesters [31-73],... 

Enantioselective hydrogenation of a-ketoesters on cinchona alkaloid-modified Pt/Al203 is an interesting system in heterogeneous catalysis [143-146], The key feature is that on cinchonidine-modified platinum, ethyl pyruvate is selectively hydrogenated to R-ethyl lactate, whereas on einchonine-modified platinum, S-ethyl pyruvate is the dominant product (Figure 16) [143]. 

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