Enantioselective hydrogenation of ethyl pyruvate

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. 

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],... 

New modifiers have traditionally been discovered by the trial-and-error method. Many naturally occurring chiral compounds (the chiral pool38) have been screened as possible modifiers. Thus, the hydrogenation product of the synthetic drug vinpocetine was discovered to be a moderately effective modifier of Pt and Pd for the enantioselective hydrogenation of ethyl pyruvate and isophorone.39 Likewise, ephedrine, emetine, strychnine, brucine, sparteine, various amino acids and hydroxy acids, have been identified as chiral modifiers of heterogeneous catalysts.38... 

Torok B, Karoly F, Gerda S, Mihaly B (1997) Sonochemical enantioselective hydrogenation of ethyl pyruvate over platinum catalysts. Ultrason Sonochem 4(4) 301-304... 

Scheme 9.11 Enantioselective hydrogenation of ethyl pyruvate with platinum colloids stabilized by protonated-dihydrocinchonidine.

Scheme 9.12 Reusable aqueous suspension of Pt nanoparticles for enantioselective hydrogenation of ethyl pyruvate.

Figure 6.18 Enantioselective hydrogenation of ethyl pyruvate on heterogeneous chiral catalysts. Activity as a function of time for the following catalysts ( ) Pt/(-)-MenSnBu3, ( ) Rh/ (-)-MenSnBu3 and (A) Ni/(-)-MenSnBu3. (Reproduced from Reference [45].)...

Recently, the enantioselective hydrogenation of ethyl pyruvate catalyzed by cinchona modified Pt/Al203 (ref. 1) was shown to be a ligand accelerated reaction (ref. 2). The rate of reaction for the fully modified system is more than 10 times faster than the racemic hydrogenation using unmodified catalyst. Under certain reaction conditions, this liquid phase hydrogenation exhibits a turn-over frequency of up to 50 s 1 (3.4 mol/kg-cat s). Emphasis until now has been directed at empirically increasing optical yields (ref. 3,4). 

We have identified reaction conditions where intrinsic kinetics can be obtained for the very fast enantioselective hydrogenation of ethyl pyruvate using a commercially available Pt/Al203 powder catalyst, modified with dihydrocinchonidine. We conclude that this is in pan due to i) the egg-shell structure of the catalyst, ii) the high turbulence achieved in the reactor and iii) the density and/or the viscosity of the solvent used. In solvents like ethyl pyruvate, liquid-solid transpon problems can arise. 

Minder et al. studied various modifiers containing a nitrogen base for the enantioselective hydrogenation of ethyl pyruvate.223,224 Up to 82% ee with (R)-l-(l-naphthyl)ethylamine and up to 75% ee with (/ )-2-( 1 -pyrrolidinyl)-1 -(1 -naphthyl)-ethanol as modifiers were achieved in the hydrogenation of ethyl pyruvate to (R)-ethyl lactate over Pt-Al203 in acetic acid. 

The Pt-catalyzed enantioselective hydrogenation of ethyl pyruvate to (/ )-ethyl lactate was considerably faster (by a factor of 3-3.5) in supercritical ethane than in the conventional apolar solvent toluene, whereas the enantioselectivity was unaffected. Complete catalyst deactivation was observed in C02, which was shown by FTIR to be due to the reduction of C02 to CO via reverse water gas shift reaction. The catalyst could be regenerated by exposing it to ambient air, while hydrogen treatment was less efficient. This is the first evidence to the limitation of catalytic hydrogenations over Pt metals in supercritical C02. 

Enantioselective hydrogenation of ethyl pyruvate in supercritical and conventional solvents... 

ESMS was employed to identify reactive intermediates in the enantioselective hydrogenation of ethyl pyruvate on Pt-alumina, Pt black, and Pt black+alumina catalysts modified by dihydrocinchonidine in acetic acid [56]. The ESMS spectra of the raw product revealed a large number of species which fell into four groups (1) dihydrocinchonidine and its hydrogenated derivatives (2) the adducts of ethyl pyruvate and its oligomers (3) (R)-ethyl lactate, the product of the enantioselective hydrogenation, and its adducts and (4) oxonium compounds formed from alumina. The latter most likely play a decisive role in the development of the chiral environment of the catalyst surface. As suggested by the authors, these oxonium cations could make the so-called electrostatic catalysis [57],based on electrostatic acceleration, possible. 

Minder, B. Mallat, T. Pickel, K.H. Steiner, K. Baiker, A. Enantioselective hydrogenation of ethyl pyruvate in supercritical fluids. Catal. Lett. 

Wandeler R, Kunzle N, Schneider MS, Mallat T, Baiker A. Continuous enantioselective hydrogenation of ethyl pyruvate in supercritical ethane relation between phase behavior and catalytic performance. J Catal 2001 200 377-388. 

Enantioselective hydrogenation of ethyl pyruvate and isophorone over modified Pt and Pd catalysts... 

Controlling the Enantioselective Hydrogenation of Ethyl Pyruvate Using Zeolites as Catalyst Support... 

The materials were impregnated with 5 wt.-% Pt using an aqueous solution based on H2Pt(OH)6 and HNOj. The precursors were conditioned in a nitrogen stream (16 h at 523 K, flow 10 I h ) and afterwards reduced in a hydrogen stream (3 h at 523 K, flow 8 1 h ). The catalysts were used for the enantioselective hydrogenation of ethyl pyruvate to ethyl lactate immediately after having been reduced. 

There is an ongoing interest in the mode of action of the enantioselective hydrogenation of ethyl pyruvate (etpy) with modified Pt-catalysts [1-3]. Garland and Blaser described a kinetic model which is able to explain the dependence of rate and e.e. on the modifier concentration... 

Enantioselective hydrogenation of ethyl pyruvate was carried out in a 300 ml stirred autoclave (Parr Instruments, Illinois) at 20 °C and the pressure kept constant at 60 bar with a high pressure H2 burette. Reaction rates were determined from the drop in H2 pressure measured in the burette. Conversion and enantiomeric excess were determined by quantitative analysis by a GC equipped with a chiral capillary column for enantiomeric separation (for details see [6]). 

Figure 4 Activity and enantiomeric excess of the chiraily stabilized Pt-colloid entrapped in different polyanions and used in the enantioselective hydrogenation of ethyl pyruvate in cyclohexane.

Figure 8 shows the comparison of the content of CIN derivatives in reaction solution at different times in the enantioselective hydrogenation of ethyl pyruvate formed on conventional Pt/Al203 at 60 bar and 20 °C using acetic acid [6] or cyclohexane as solvent. In both solvents the modifier CIN is hydrogenated rapidly to DH-CIN which is also an efficient modifier in the enantioselective hydrogenation of ethyl pyruvate. At a conversion of approximately 70 %, DH-CIN is the main alkaloid in reaction solution. Only traces of CIN were detected and a small amount of the different HH-CINs were found both in acetic acid and in cyclohexane at 70 % conversion. 

Figure 8 Comparison of the content of alkaloid derivatives in reaction solution at different times in the enantioselective hydrogenation of ethyl pyruvate on Pt/Al203 using acetic acid or cyclohexane as solvent.

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