Hydrogenation of a-ketoesters

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). 

Figure 5. Novel efficient modifiers for the hydrogenation of a-ketoesters over Pt/alumina...

Some neutral rhodium catalysts with chiral ligands, such as MCCPM 9 (see Scheme 33.3) [20c], Cy,Cy-oxoProNOP 15, and Cp,Cp-IndoNOP 18, demonstrate excellent enantioselectivities and reactivities in the hydrogenation of a-ketoesters and ketoamides indeed, they compare well with ruthenium-based catalysts (Table 33.2). Togni et al. have successfully used the Josiphos 47 ligand for the hydrogenation of ethyl acetoacetate [27], while the use of MannOPs has led to somewhat high enantioselectivities [18]. 

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],... 

Figure 14.9 Two cycle mechanisms proposed for enantioselective hydrogenation of a-ketoesters on chirally modified platinum [66],...

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]. 

Figure 16. Main features in enantioselective hydrogenation of a-ketoesters on cinchona alkaloid-modified metal catalysts [ 143]. [Reproduced with permission of Elsevier from Baiker, A. J. Mol. Catal. A 1997,115, 473-493.]...

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. 

Since these catalysts have never been reviewed, we will discuss the reported results in somewhat more detail. With few exceptions all the following statements are valid only for the hydrogenation of a-ketoesters 6 (mostly with R = methyl, phenyl and Rj = methyl, ethyl). 

As a rule, synthetic chemists will consider only those new reactions and catalysts for preparative purposes where the enantioselectivity reaches a certain degree (e.g. >80%) and where both the catalyst and the technology are readily available. For heterogeneous catalysts this is not always the case because the relevant catalyst parameters are often unknown. It is therefore of interest that two types of modified Nickel catalysts are now commercially available a Raney nickel/tartrate/NaBr from Degussa [64] and a nickel powder/tartrate/NaBr from Heraeus [65, 66]. It was also demonstrated that commercial Pt catalysts are suitable for the enantioselective hydrogenation of a-ketoesters [30, 31]. With some catalytic experience, both systems are quite easy to handle and give reproducible results. 

Sutherland, Ibbotson, Moyes and Wells have published a detailed account of the heterogeneous enantioseleetive hydrogenation of methyl pyruvate (CH3COCOOCH3) to R-(+)-methyl lactate over Pt/siliea surfaces modified by sorbed cinchona alkaloids.16 Kinetic, isotherm and molecular modeling calculations were used to develop an idea of the role of the cinchonidine modifier. This system is quite unusual high enantioselectivity is achieved only with Pt, only in the presence of cinchonidine modifiers and only for the hydrogenation of a-ketoesters. 

Similar but smaller effects of hydrogen concentration were observed with other aromatic and alkyl-aromatic trifluoromethyl ketones such as 2 and 3 (Table 2). On the contrary, in the hydrogenation of the aliphatic ketone 4 medium to high hydrogen pressure favoured the enantiodifferentiation. Note that this correlation is typical for the hydrogenation of a-ketoesters and other activated ketones over the Pt-CD system4. 

In the hydrogenation of a-ketoesters, high ee can be achieved only at ambient temperature or below [8]. The number of supercritical solvents, available for this temperature range, is very limited. The ee in propane is moderate (Table 1), due to the necessary high reaction temperature. Supercritical C02 seemed to be an ideal choice as solvent due to its low... 

Several zeolites have been used as supports for cinchona modified Pt in the enantioselective hydrogenation of a-ketoesters such as ethyl pyruvate ... 

Figure 12 Schematic representation of the mechanism proposed for the enantioselective hydrogenation of a-ketoesters on cin-chonidine-modified platinum catalyst. The development of general methods for imparting enantioselectivity to regular heterogeneous catalysts promises to revolutionize the pharmaceutical and agrochemical industries ...

Blaser HU, Jalett HP, Muller M, Studer M (1997) Enantioselective hydrogenation of a-Ketoesters using cinchona modified platinum catalysts and related systems. Catal Today 37 441... 

Here, the key step was the enantioselective hydrogenation of methoxyacetone (Fig. 4), in analogy with the Pt-cinchona-catalyzed hydrogenation of a-ketoesters [5] (the Ru-binap system was not known at that time). It was anticipated that the nucleophilic substitution with a clean inversion would be difficult. 

Salen palladium(II) complexes have been reported to be effective homogeneous, or when immobilized, to be active heterogeneous catalysts for the hydrogenation of alkenes [1,2]. It is also known that platinum(O) catalysts modified with cinchona alkaloids catalyze the enantioselective hydrogenation of a-ketoesters to the corresponding a-hydroxyesters[3]. The platinum(O) catalyst is attached to AI2O3 [4] or to zeolites [5,6]. 

The asymmetric hydrogenation of ketones over heterogeneous catalysts has also been studied [578, 1140], Hydrogenation of a-ketoesters must be performed on Pt/Al203 in the presence of dihydrocinchonidine 2.87 (R = H) [578, 812, 1141]. 

Liquid-phase enantioselective hydrogenations of a-ketoesters by alkaloid-modified Pt has been investigated intensively and reviewed. " The first reported reactions of this type were the hydrogenations of methyl pyruvate, MeCOCOOMe, and of methyl benzoyl formate, PhCOCOOMe, over Pt modified by the cinchona alkaloids." ... 

Torok, B., Balazsik, K., Torok, M., Szollosi, G., Bartok, M. (2000) Asymmetric sonochemical reactions. Enantioselective hydrogenation of a-ketoesters over platinum catalysts. Ultrasonics Sonochem. 7, 151-155. Torok, B., Balazsik, K., Torok, M., Felfoldi, K., Bartok, M. (2002) Heterogeneous asymmetric reactions 20. Effect of ultrasonic variables on the... 

One of the simplest approaches to the creation of an enantioselective catalyst is the adsorption of a chiral molecule (often referred to as a modifier) onto the surface of a metal catalyst. The metals most commonly employed for this type of catalysis have been the Pt group metals and Ni [29]. The most successful chiral modifiers have been naturally occurring alkaloids (Pt) and tartaric acid (Ni) (Scheme 5.2). Each system has primarily been used for hydrogenation reactions with Pt/cinchona producing ee values of greater than 90% for the hydrogenation of a-ketoesters [42, 43] ... 

Scheme 5.2 Typical reagents and chiral modifiers for the enantioselective hydrogenation of a-ketoesters and f-ketoesters. (With kind permission from Springer Science and Business Media [54].)...

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