Alkaloid modifiers

The molecular modelling approach, taking into account the pyruvate—cinchona alkaloid interaction and the steric constraints imposed by the adsorption on the platinum surface, leads to a reasonable explanation for the enantio-differentiation of this system. Although the prediction of the complex formed between the methyl pyruvate and the cinchona modifiers have been made for an ideal case (solvent effects and a quantum description of the interaction with the platinum surface atoms were not considered), this approach proved to be very helpful in the search of new modifiers. The search strategy, which included a systematic reduction of the cinchona alkaloid structure to the essential functional parts and validation of the steric constraints imposed to the interaction complex between modifier and methyl pyruvate by means of molecular modelling, indicated that simple chiral aminoalcohols should be promising substitutes for cinchona alkaloid modifiers. Using the Sharpless symmetric dihydroxylation as a key step, a series of enantiomerically pure 2-hydroxy-2-aryl-ethylamines... 

Hydrogenation of the free acids over unmodified catalyst occurred slowly, proceeded to completion in 20 h and gave racemic product as expected Enantioselective hydrogenation occurred at a slower rate over alkaloid-modified catalyst, cinchonidine modification providing an excess of S-product and cinchonine an excess ofR-product... 

Enantioselective hydrogenation Z-2-methyl-pent-2-enoic and Z-2-ethyl-hex-2-enoic acids occurred over alkaloid-modified Pd/SiOa as described in Table 2 Enantioselectivity was favoured by an increase in hydrogen pressure to 50 bar The enantiomeric excess of 27% in Z-2-methyl-pent-2-enoic acid hydrogenation was the highest value recorded in this study. 

Catalytic asymmetric hydrogenation is a relatively developed process compared to other asymmetric processes practised today. Efforts in this direction have already been made. The first report in this respect is the use of Pd on natural silk for hydrogenating oximes and oxazolones with optical yields of about 36%. Izumi and Sachtler have shown that a Ni catalyst modified with (i ,.R)-tartaric acid can be used for the hydrogenation of methylacetoacetate to methyl-3-hydroxybutyrate. The group of Orito in Japan (1979) and Blaser and co-workers at Ciba-Geigy (1988) have reported the use of a cinchona alkaloid modified Pt/AlaO.i catalyst for the enantioselective hydrogenation of a-keto-esters such as methylpyruvate and ethylpyruvate to optically active (/f)-methylacetate and (7 )-ethylacetate. 

The mobility factor acknowledges the fact that organic molecules seem to move about on surfaces. For example, Blackmond and Augustine and associates have identified an induction period in the cinchona alkaloid modified... 

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... 

The main features of the cinchona alkaloid-modified metal system are illustrated in Scheme 14.9. 

The alkaloid-modified catalyst can be easily prepared either by stirring the metal catalyst with a solution of the alkaloid in air and subsequent separation by decantation, as described by Orito and coworkers [103], or by in situ addition of alkaloid to the reactant mixture [226], Good OYs are achieved with both methods. Reactions are generally carried out at room temperature, or slightly above, and at hydrogen pressures in the range 1 to 10 MPa. The best solvent is AcOH. Under optimal reaction conditions the decrease in e.e. can be ascribed to the hydrogenation of the modifier. 

Much work [42] has been devoted to cinchona alkaloid modified Pd and Pt catalysts in the enantioselective hydrogenation of a-keto esters such as ethyl pyruvate (Scheme 5.11). Optimal formulation and conditions include supported Pt, the inexpensive (—)-cinchonidine, acetic acid as solvent, 25 °C and 10-70 bar H2. Presently, the highest e.e. is 97.6% [to (R)-ethyl lactate]. 

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.]...

Heterogeneous enantioselective hydrogenation over Cinchona alkaloid modified platinum 04ACR909. 

P-ketoesters and their analogues. As tartaric acid is tightly adsorbed onto the catalyst surface and is stable under the hydrogenation condihons, the modified catalyst can be used for the recover/reuse process, which is different from the cinchona alkaloid-modified plahnum and palladium systems. 

Platinum and palladium dominate the enantioselective catalysis scene as far as alkaloid modifiers are concerned. Of the other platinum group metals, Ir follows Pt in cinchona-modified pyruvate ester hydrogenation,132 the fact that Rh can hydrogenolyse alkaloids adsorbed at its surface133 makes it unlikely to function successfully and Ru tends to be too easily oxidised by adventitious oxygen in these reactions. 

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