Reduction of methyl benzoylformate

Pyrrolopyridine derivatives, such as compound 144, in the presence of Mg salts such as magnesium perchlorate, serve as chiral and nonchiral NADH models in the reduction of organic nitro compounds <1996JHC1211>. Similar derivatives, such as compound 145, serve as NADH models in the asymmetric reduction of methyl benzoylformate and A -acetyl enamines <1997TA3309>. 

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. 

The viologen reduction by EDTA in reverse micelles in the presence of Ru(bpy)3 is another example of vectorial photoinduced electron transfer [106], The accumulation of photoproducts is associated with the catalytic cycles depicted in Fig. 10(b). The oxidative quenching of the ruthenium complex occurs at the micelle outer boundary, while the regeneration of the dye takes place by the oxidation of EDTA in the inner core of the micelle. The reduction of the final product 4-dimethylaminoazobenzene is further mediated by the acceptor 1-benzylnicotinamide (BNA ). In Fig. 10(c), the photocatalytic reduction of methyl benzoylformate (MBF) by thiosulfate is described in the presence of the porphyrin ZnTPPS and the mediator quinolinium-3-carboxiamide (DCA ) [107]. This sequence of reactions occurs only in micelles such as those formed by hexadecyl-trimethylammonium bromide, which contain in the interior the ultimate donor acceptor. Finder illumination, ZnTPPS photoreduces DCA to DCQ, which is subsequently extracted into the micelle core. Within the microenvironment, DCA is regenerated via reduction of MBF, while the oxidized porphyrin is reduced by thiosulfate outside the micelle. 

Fuji et al. separated the atropisomers of 277 on Chiralcel OD-H at the preparative scale. CD spectra were recorded but the absolute configuration was not established. Reduction of each atropisomers afforded axially chiral NAD(P)H models that were engaged in the enantioselective reduction of methyl benzoylformate (95% ee) (92JCS(CC)905). 

In the reduction of methyl benzoylformate in the presence of magnesium perchlorate and in the reduction of a,a,a-trifluoroacetophenone, the products were obtained in 27 4 I e.e. and 5 2 % e.e., respectively. It should be noted that the former value of 27 which can be translated into a ratio of the enantiomeric composition in the product of S/R = 1.74 0.15, nearly equals the ratio of the confor-mers (1.65) mentioned above. In this connection they proposed kinetically controlled induction of asymmetry for this system. The result was discussed on the basis of the equations (1) and (2). 

Ohno A, Ikeguchi M, Kimura T, Oka S (1978c) Asymmetric reduction of methyl benzoylformate with a chiral NAD(P)H-model compound. J Chem Soc Chem Commun 328-329... 

Figure 9.1 Reduction of methyl benzoylformate with T. thermophilus ADH (TtADH) by way of an in situ NADH-recyding system involving 6. stearothermophilus ADH (BsADH) and ethanol or Isopropanol.

I.4.3.2.3. Keto Esters Asymmetric transfer hydrogenation of functionalized ketones is rare. However, an excellent optical yield is obtainable in reduction of methyl benzoylformate by using 2-propanol and with a catalyst system consisting of [RhCl(CgHjq)]2, (S,5)-DMDPEN, and KOH (Scheme 1.89) [313],... 

This high selectivity of the orientation of methyl benzoylformate toward the 1,4-dihydronicotinamide moiety largely stems from the coordinating adhesion by Mg(II). Considering the result that the enantiomeric purity of the product in the reduction without Mg(Il) falls to 52.5 it is obvious that Mg(II) plays an essential role in the asymmetric reduction by Me2PNPH. How does Mg(Il) exert the... 

Studies on the asymmetric reduction with 1,4-dihydronicotinamide derivatives that contain chiral centers within their amide moieties have been widely extended after the first report on this subject COhnishi et al. 1975a,b). To improve the optical yield and to obtain further insights into the stereochemical course of the reduction, a variety of model compounds have been synthesized and subjected to the reduction. Table 4 lists the optical yields from the reduction of methyl or ethyl benzoylformate which has frequently been used as a substrate for these 1,4-dihydropyridine derivatives. 

It has been found that the stereochemical course of the reduction of methyl or ethyl benzoylformate by a 1,4-dihydropyridine derivative is controlled by a variety of factors. First of all, the optical yield is influenced by a variation of the atom connecting the carbonyl and a-methylbenzyl groups as shown in Scheme 17 (Ohno et al. 1976). It is concluded that the basicity of the carbonyl oxygen affects the optical yield because the change.in the basicity is directly correlated with the ability to coordinate onto Mg(II). 

Stereochemistry of the product from this reduction system can be explained in terms of the discussion previously mentioned that methyl benzoylformate is reduced through a transition state where the polar group in the substrate (methoxycarbonyl moiety) interacts with the polar group in the reductant (carbamoyl moiety). This orientation of methyl benzoylformate with the predominant conformer of R-5S which is shown in Fig. 19 should give methyl S-mandelate, which is in accord with the experimental result. The low e.e. value in the reduction of a,a,a-trifluoroacetophenone with R-ZS is due to the low... 

Reductions of keto esters to esters are not very frequent. Both Clemmensen and Wolff-Kizhner reductions can hardly be used. The best way is desulfurization of thioketals with Raney nickel (p. 130). Thus ethyl acetoacetate was reduced to ethyl butyrate in 70% yield, methyl benzoylformate (phenylglyoxy-late) to methyl phenylacetate in 79% yield, and other keto esters gave equally high yields (74-77%) [82J]. 

The photolysis of hexachloroacetone or tribromoacetaldehyde in methanol does not yield any alcoholysis product253. The major reaction is reduction. On the other hand, a,a,a-tribromoacetophenone yields the alcoholysis product methyl benzoylformate in good yield (equation 56)254. The initial photomethanolysis product is a,a-dibromo-a-methoxy-acetophenone, which in a dark reaction is converted into the benzoylformate. The methyl benzoate is formed by nucleophilic attack on the carbonyl carbon. 

Alkenes. Alk-3-en-l-ynes are obtain in the presence of SnC and (PhiPl.PdCl.-carboxylic acids are degraded by one cartx Reductive silylation. a-Diketoncs i while methyl benzoylformate undergoei 2,3-diphenyl-2,3-bis(( -trimethylsilyl)tartn (Me,P)2PdCl2]. 

There are two main characteristic features in the present reduction. First of all, as can be seen from the result that methyl benzoylformate can be reduced without Mg(II), Me2PNPH exhibits a high... 

Enantioselective reduction of ketopantolactone and methyl benzoylformate was also examined by the same authors. Quite recently, Bakos and coworkers reported an enantioselective hydrogenation of dehydroalanine using an in situ-produced [Rh (COD)(S)-MonoPhos)2]Bp4 complex on AI2O3 [83,84]. After the optimization of the flow reaction conditions, a highly enantioselective production of (R)-acetylalanine methyl ester (>99% conversion and 96-97% ee) was achieved. 

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