Ketoesters hydrogenation

Fig. 6. Influence of the solvent polarity on the optical yield of various a-ketoester hydrogenations. a),b) catalyst not pre-modified, cinchonidine (Cd) added to the reaction mixture [33, 62] c) catalyst pre-modified with Cd, no Cd added, d) catalyst pre-modified with Cd and Cd added [31].

The data in Table 3 suggest that the nature of enantiodifferentiation in the hydrogenation of a,(X,a-trifluoromethyl ketones is only partly similar to that of a-ketoester hydrogenation. Apparently, the OH group of CD has some role in enantioselection during... 

The effectiveness of representative members of three families of alkaloids were evaluated as modifiers for the hydrogenation of NADPAME (I) over Pd/alumina (Table 1). These alkaloids all induce enantioselectivity in a-ketoester hydrogenation. The results are shown in Table 1. 

The resulting porous polymer was used in a transesteriflcation reaction giving ee values of 8% [39]. Reactants are confined in the pores and able to interact with pyridyl group attached to the chiral center. Subsequently, ee values of greater than 90% were reported for P-ketoester hydrogenation reactions over chiral porous zirconium phosphonates containing 2,2 -bis(diphenylphosphino)-l,T-binaphthyl... 

The application of rhodium-diphosphonite catalysts (where diphosphonites are Reetz s ligands with BINOL and ferrocene subvmits) for alkene, ketone, and ketoester hydrogenation resulted in practically enantiospecific reaction (ee higher than 99.5%) (173,223). 

Selective fluonnation in polar solvents has proved commercially successful in the synthesis of 5 fluorouracil and its pyrimidine relatives, an extensive subject that will be discussed in another section Selective fluonnation of enolates [47], enols [48], and silyl enol ethers [49] resulted in preparation of a/phn-fluoro ketones, fieto-diketones, heta-ketoesters, and aldehydes The reactions of fluorine with these functionalities is most probably an addition to the ene followed by elimination of fluonde ion or hydrogen fluoride rather than a simple substitution In a similar vein, selective fluonnation of pyridmes to give 2-fluoropyridines was shown to proceed through pyridine difluondes [50]... 

Under the conditions used for the reductive cleavage of the O—N bond in isoxazoles, a similar reaction readily occurs with isoxa-zolines, e.g. on treatment with organomagnesium compounds and on catalytic hydrogenation.- Hydrogenolysis of the O—N bond (180 181 182 183) was used to elucidate the structure of isoxa-zolones from -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...

Scheme 14 Top Plausible catalytic cycle as supported by deuterium labeling. Bottom ESI mass spectrum of a reaction mixture aliquot diluted 5000-fold in methanol from the hydrogen-mediated coupling of gaseous acetylene to an a-ketoester (Ar = p-N02Ph)...

Pt/Al2C>3-cinchona alkaloid catalyst system is widely used for enantioselective hydrogenation of different prochiral substrates, such as a-ketoesters [1-2], a,p-diketones, etc. [3-5], It has been shown that in the enantioselective hydrogenation of ethyl pyruvate (Etpy) under certain reaction conditions (low cinchonidine concentration, using toluene as a solvent) achiral tertiary amines (ATAs triethylamine, quinuclidine (Q) and DABCO) as additives increase not only the reaction rate, but the enantioselectivity [6], This observation has been explained by a virtual increase of chiral modifier concentration as a result of the shift in cinchonidine monomer - dimer equilibrium by ATAs [7],... 

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). 

A common theme is the existence of modified (enantioselective) sites and unmodified (racemic) sites. For the case of the tartaric acid modified Ni, it is postulated that the tartaric acid is adsorbed on the surface and stereodirects (through hydrogen bonding) adsorption of the incoming 3-ketoesters.18 19 Support for this comes from an isotope effect from deuterium labeling.23 Increased enantioselectivities resulting from co-modification with NaBr is believed to result from poisoning the racemic sites.24 A similar technique in... 

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