Methyl pyruvate hydrogenation

Figure 1 Variation of conversion with time on line for methyl pyruvate hydrogenation at 313 K over Pt/a-alumina. Squares unmodified catalyst diamonds catalyst pre-modified in 0.34mM cinchonidine...

Figure 2 Variation with time on line of conversion (diamonds) and of enantiomeric excess (squares) for methyl pyruvate hydrogenation at 313 K over 1% Pt/a-aluminapre-modified in 0.34mMcinchonidine...

Butanedione is only a small step away from methyl pyruvate. Hydrogenation of one group would yield (R) or (S) -3-hydroxy-butane-2-one. If the other carbonyl function is hydrogenated as well, the resulting molecule is d,l or meso - 2,3 - butanediol. Unless the reaction proceeds very selectively, five hydrogenation products are possible thus making analysis difficult. 

Sutherland, I.M., Ibbotson, A., Moyes, R.B., Wells, P.B. (1990) Enan-tioselective hydrogenation 1. Surface conditions during methyl pyruvate hydrogenation eatalysed by cinchonidine-modified Pt-silica (EUROPE-1), J. Catal. 125, 77-88. 

Figure 4. Side and top views of the energetically most favorable complexes formed between protonated cinchonidine and methyl pyruvate which would yield (R)-methyl lactate (left) and (S)-methyl lactate (right), respectively, upon hydrogenation. The complexes have been accomodated on a space filling model of platinum (111) surface in order to illustrate the space requirements of the adsorbed complexes. For the sake of clarity, in the side views the carbon atoms of the reactant are marked with a white square and the oxygen atoms with an o. Data taken from ref. [41].

The hydrogenation of methyl pyruvate proceeded over 4% Pd/Fe20 at 293 K and 10 bar when the catalyst was prepared by reduction at room temperature Racemic product was obtained over utunodified catalyst, modification of the catalyst with a cinchona alkaloid reduced reaction rate and rendered the reaction enantioselective. S-lactate was formed in excess when the modifier was cinchonidine, and R-lactate when the modifier was cinchonine... 

Although cinchona-modified Pd showed no enantioselectivity in the hydrogenation of the methyl esters of the unsaturated acids, the hydrogenation of methyl pyruvate occurred with a modest enantiomeric excess... 

Figure 2. Mechanism for exchange in methyl pyruvate and for its hydrogenation to methyl lactate via an enol intermediate. R = COOCH3...

The enantiomeric excess (ee) of the hydrogenated products was determined either by polarimetry, GLC equipped with a chiral column or H-NMR with a chiral shift reagent. Methyl lactate and methyl 3-hydroxybutanoate, obtained from 1 and 2, respectively, were analized polarimetry using a Perkin-Elmer 243B instrument. The reference values of [a]o(neat) were +8.4° for (R)-methyl pyruvate and -22.95° for methyl 3-hydroxybutcinoate. Before GLC analysis, i-butyl 5-hydroxyhexanoate, methyl 5-hydroxyhexanoate, and n-butyl 5-hydroxyhexanoate, obtained from 1, 5, and 6, respectively, were converted to the pentanoyl esters, methyl 3-hydroxybutanoate was converted to the acetyl ester, and methyl 4-methyl-3-hydroxybutanoate obtained from 2 was converted the ester of (+)-a-methyl-a-(trifluoromethyl)phenyl acetic acid (MTPA). 

One of the most interesting side reactions taking place during the enantioselective hydrogenation is the transesterification of the substrate or the reaction product. If the enantioselective hydrogenation of ethyl pyruvate was performed in methanol as a solvent the formation of methyl pyruvate and methyl lactate was observed. CD appeared to be an effective catalyst for the above transesterification reaction. 

Cinchona-modified platinum catalysts received special interest mainly because of to the results obtained for the hydrogenation of methyl pyruvate (MP) or ethyl pyruvate. E.e. s up to 80% or even higher (98% for ethyl pyruvate) made this system one of the most interesting ones from the application point of view. At present, 5% Pt/alumina with low dispersion (metal particles > 2 nm) and a rather large pore volume constitutes one of the best catalysts commercially available. 

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 product ratios were reported for the methyl pyruvate/2,3-dimethyl-2-butene photoreaction. In this case, however, a state selectivity effect is responsible for the formation of the different ether and alcohol products [31]. Obviously the existence of allylic hydrogens favors the formation of unsaturated acyclic products via hydrogen migration steps at... 

Further reports on asymmetric synthesis in the presence of Cinchona alkaloids have been made.142 " For example, hydrogenation of methyl pyruvate with a platinum-alumina catalyst containing quinine gives (+)-(/ )-methyl lactate in 87% optical yield.1426 Asymmetric induction with optical yields up to 36 and 26% has been observed in the Michael addition of thiols and nitro-alkanes to ct/ -unsaturated ketones in the presence of quaternary salts derived from the Cinchona alkaloids.142"... 

EUROPT-1 has also proved to be of exceptional value as a model catalyst to which systematic modifications may be made. The effects on its catalytic properties of the addition of silver, titania and alumina [16], chlorine, oxygen, sulfur, ammonia, and carbon monoxide have all been examined [7]. Of particular interest is its ability to be modified by alkaloids of the cinchona family, becoming in consequence enantio-selective for the hydrogenation of methyl pyruvate... 

Hydrogen peroxide with Milas reagent is also suitable for the cleavage of olefins. The system has been used to prepare aromatic aldehydes such as anisaldehyde from anethole, pipernal from isosafrole and vanilin from iso-eugenol.170,171 Hydrogen peroxide and chromium(III) can be used to cleave methyl methacrylate to methyl pyruvate.172... 

Studies on the transamination reaction between f-butyl esters of optically active amino acids and methyl pyruvate were carried out, as shown in Scheme 7. The resulting iminodicarboxylic acid (16) was partially hydrolyzed and then oxidized with f-butyl hypochlorite to form alanine. The oxidation is a generally applicable one, and the optical purity of alanine is high (50-70%). Similar asymmetric transamination between an (S)-amino acid and ketones was carried out. Catalytic hydrogenation of the Schiff s bases prepared from a-keto acid esters and amino acid esters was carried out, and a substituent and temperature effect observed (de 40-70%). ... 

Heterogeneous catalytic hydrogenation of the methyl esters of a-keto acids over modified metal catalysts other than nickel have been studied using a cinchonidine-modified platinum catalyst. " Methyl pyruvate and methyl benzoylformate were hydrogenated to form methyl (R)-lactate and (R)-mandelate with high ee (81-84%). 

Orino, Y. Imai, S. Niwa, S. Asymmetric hydrogenation of methyl pyruvate using Pt/C catalyst modified with cinchonidine. Nippon Kagaku Kaishi (J. Chem. Soc. Jpn.) 1979, 1118-1120. 

In contrast to asymmetric hydrogenation, examples of stereoselective reduction of functionalized ketones are rare. Scheme 43 illustrates the highly enantioselec-tive reduction of methyl benzoylformate in 2-propanol containing KOH using a catalyst prepared in situ from [RhCl(CgHjo)]2 and (S,S)-3 [101]. With the same catalyst, methyl pyruvate is reduced in 5% optical yield. 

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