Methyl pyruvate

Treatment of a TIPDS group with methyl pyruvate (TMSOTf, 0° to rt, 69-99% yield) converts the group to the pyruvate acetal. ... 

In the presence of catalytic amounts of TMSOTf 20 methyl pyruvate reacts with N,N-bis(trimethylsilyl)formamide 22c in CCI4 to give the silylated 0,N-acetal 433 in 83% yield ]44] this, with allyltrimethylsilane 82 and excess TMSOTf 20, after 30 h at 78 °C in CH2CI2, affords 72% of the methyl ester of 2-allyl-N-formylala-... 

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 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... 

Pd/Si02 was prepared at ICI Katalco and 4% Pd/Fe20j at Johnson Matthey Reactants used are shown in Table 1. Trifluorotiglic acid and its ester were synthesised by D Hunter at Glasgow University. The other unsaturated carboxylic acids (Aldrich), methyl pyruvate (Fluka), but-3-en-2-one (Aldrich), cinchonidine (Aldrich), cinchonine (Hopkin and Williams), ethanol (AnalaR grade, BDH) and THF (non stabilised, Fisons) were used as received... 

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... 

Deuterium distributions in methyl pyruvate and methyl lactate (X = H or D) ... 

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 following substrates were obtained from commercial sources, methyl pyruvate (1), methyl acetoacetate (2), methyl 4-oxopentanoate (1), and methyl 3-oxopentanoate ( ). Alkyl 5-oxohexanoates (4, 5 and 6) were prepared by condensation of methyl acetoacetate and methyl acrylate followed by acidic hydrolysis, decarboxylation, and esterification [8]. Methyl 3-oxo-4-methylpentanoate... 

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). 

We have modelled the [CDopen - methyl pyruvate] complex. The result is shown in Figure 2. In this complex there is no steric hindrance to prevent the free rotation of the substrate around the quinuclidine nitrogen. Thus, in complex shown in Figure 2. there is no preferential stabilization of the substrate. In earlier computer modeling it was suggested that Pt is involved in the stabilization of the [CDopew-a-lfeto ester] complex, i.e. the Pt surface prevent the free rotation of the substrate, however the driving force for enantio-differentiation, i.e. for preferential adsorption of the substrate, was not discussed [14]. 

Monte-Carlo simulation method was used to investigate the interaction of the [CDdosed-MePy] complexes with Pt (111) surface. The result shown in Figure 5 indicates that the shielded complex can maintain its entity even after adsorption. Further computer modeling indicated that there are other molecules with the ability to induce SE. In this respect Troger s bases are of particular interest. The calculated Troger s base-methyl pyruvate complex (R form) is shown in Figure 6. 

Figure 3. The shielded form of [CD-methyl pyruvate] complex, (R ) form...

Figure 2 The open fonn of cinchonidine-methyl pyruvate complex.

Figure 5. The adsorption of CD - methyl pyruvate complex over Pt(l 11) surface.

Figure 6, Troger s base-methyl pyruvate complex.

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. 

The transesterification reaction can be attributed to the perturbation of the ester carbonyl group in the [CDc/o5e< -substrate] complex. The possibility of this side reaction was predicted by earlier quantum-chemical calculations [18]. These results indicated that the reaction pocket in methyl pyruvate for the nucleophilic attack is situated between the two carbonyl groups, i.e. both carbonyl groups can be perturbed by a nucleophile provided both carbonyl groups have the right "directionality". However, the right "directionality" for both carbonyl groups can be obtained if they are in syn position. 

The conformational analysis of methyl pyruvate shows that it can have two conformers. In the second conformer the two carbonyls are in syn position. The anti-syn conformational change requires 3 kcal. The [CDqIq qJ - methyl pyruvate ] complex ((R) form) was also calculated and shown in Figure 8. In the above complex the "directionality" of the lone pair of electrons of the quinuclidine nitrogen is advantageous for interactions with both the keto and the ester carbonyl groups. 

Entry 4 shows the reaction of 9-(E-2-butenyl)-9BBN with methyl pyruvate. This reaction is not very stereoselective, which is presumably due to a modest preference for the orientation of the methyl and methoxycarbonyl groups in the TS. Only use of an extremely sterically demanding pyruvic ester achieved high diastereoselectivity. 

Especially reactive carbonyl compounds such as methyl pyruvate can trap the carbonyl oxide component. For example, ozonolysis of cyclooctene in the presence of methyl pyruvate leads to 5 when treated with triethylamine 5 is converted to 6, in which the two carbons of the original double bond have been converted to different functionalities.205... 

A crystal structure of the C02 derivative of (8), K[Co(salen)( 71-C02)], haso been reported in which the Co—C bond is 1.99 A, the C—O bonds are both equivalent at 1.22 A and the O-C-O angle is 132°.125 Carboxylation of benzylic and allylic chlorides with C02 in THF-HMPA was achieved with (8) electrogenerated by controlled-potential electrolysis,126 in addition to reductive coupling of methyl pyruvate, diethyl ketomalonate and / -tolylcarbodiimide via C—C bond formation. Methyl pyruvate is transformed into diastereomeric tartrates concomitant with oxidation to the divalent Co(salen) and a free-radical mechanism is proposed involving the homolytic cleavage of the Co—C bond. However, reaction with diphenylketene (DPK) suggests an alternative pathway for the reductive coupling of C02-like compounds. 

Aliphatic thiosemicarbazones reveal varying coordination behavior dependent on the degree of deprotonation. The X-ray structure of the zinc complex of methyl pyruvate thiosemicarbazone shows different coordination of the two thiosemicarbazone ligands in the monomer, with one tridentate NOS and the other monodentate.868... 

Methyl pyruvate thiosemicarbazone in the presence of zinc chloride or acetate resulted in the formation of complexes with the ligand hydrolyzed or transesterified. The complexes with pyruvate thiosemicarbazone, ZnL2, or ethyl pyruvate thiosemicarbazone, ZnLCl2 were structurally characterized by single-crystal X-ray crystallography showing respectively a distorted octahedral and distorted square pyramidal geometry.874... 

In addition to aldehydes and a-diketones, a-ketoesters can also be used in the domino process, as shown by Tietze and coworkers [396]. Reaction of methyl pyruvate 2-791 with dimethylbarbituric acid (2-747) and the enol ether 2-792 in the presence of trimethyl orthoformate (TMOF) and a catalytic amount of EDDA gave the cycloadduct 2-793 in 84% yield (Scheme 2.176). 

METHYL PYRUVATE (Pyruvic acid, methyl ester)... 

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