Reduction benzoylformates

When the resulting mixture of benzoylformic acid and (i )-mandelic acid was treated with a cell free extract of Streptomyces faecalis IFO 12964 in the presence of NADH,the keto acid can be effectively reduced to (i )-mandelic acid (Fig. 1). Fortunately the presence of A. bronchisepticus and its metabolite had no influence on the reduction of the keto acid. The regeneration of NADH was nicely achieved by coupling the reaction with reduction by formic acid with the aid of formate dehydrogenase. As a whole, the total conversion of racemic mandelic acid to the i -enantiomer proceeded with very high chemical and optical yields. The method is very simple and can be performed in a one-pot procedure [6]. 

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]. 

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 a first reactor, where benzoylformate decarboxylase (BFD) is retained, benz-aldehyde and acetaldehyde are coupled to yield (S)-hydroxy-l-phenylpropanone. This hydroxy ketone is then reduced to the corresponding diol in a second reactor by an alcohol dehydrogenase (ADH). Regeneration of the necessary cofactor is achieved by formate dehydrogenase (FDH) or by other methods. To avoid additional consumption of redox equivalents by unselective reduction of residual starting material from the first reactor, the volatile aldehydes are removed via an inline stripping module between the two membrane reactors. In this setup the diol was produced with high optical purity (ee, de > 90%) at an overall space-time yield of 32 g L d . ... 

McKenzie, A. CXXVII. — Studies in asymmetric synthesis. I. Reduction of menthyl benzoylformate. II. Action of magnesium alkyl haloids on menthyl benzoylformate. J. chem. Soc. [London] 85, 1249 (1904),... 

In the same study, redox polymers (223) were prepared that contained pendant viologens (Scheme 108). An active reducing agent was obtained by chemical reduction with dithionite or zinc, electrochemically, or by exposure to light. Utilization of the reduced poly(viologen) (224) as an electron transfer mediator was demonstrated by addition of a catalytic amount of the polymer to a mixture of zinc powder, ethyl benzoylformate (225) and water-acetonitrile (1 5). A quantitative yield of ethyl mandelate (226) was obtained after two days at room temperature (Scheme 109). Without the polymer, no reaction was observed after a month. 

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. 

Similar results are obtained on reduction of alkyl benzoylformates to alkyl (R)-man-delates (equation II). Again, the/-butyl ester is reduced with quantitative optical induction. 

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. 

Simple electrochemical reductions of carbonyl compounds and organic halides have been achieved in ionic liquids. For example, the electrochemical reduction of benzoylformic acid in [emim][Br] (emim = l-ethyl-3-methylimidazolium) gave man-delic acid in 91% yield (Equation 12.2) [7]. 

Table 1. Reduction of Ethyl Benzoylformate by l-Benzyl-l,4-di-hydronicotinamide (BNAH)...

Table 2. Asymmetric Reduction of Ethyl Benzoylformate by Optically Active N-a-Methylbenzyl-l-propyl-l,4-dihydronicotin-amide (PNPH)...

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]. 

Reductive silylation. a-Diketones are converted into l,2-(bissiloxy)ethenes, while methyl benzoylformate undergoes reductive coupling to give dimethyl 2,3-diphenyl-2,3-bis(0-trimethylsilyl)tartrate with McjSiSiMej [catalyzed by (MeiPljPdClj],... 

Reduction of a-keto esters. The reduction of a-keto esters by this substance has also been studied. Reduction of two a-keto acids to a-hydroxy acids has been effected in high yield, but only in the presence of Mg or Zn (as in enzymatic reactions of DPNH). Reduction involves direct transfer of hydrogen from the model compound. By use of a chiral derivative of 1-benzyl-1,4-di-hydronicotinamide reduction of ethyl benzoylformate to ethyl (R)-(-)-man-delate has been effected with an optical purity of 19%. 

When o-nitro-benzoylformic acid is reduced the amino compound formed loses water spontaneously and passes into isatin. Reduction of isatin chloride with zinc and acetic acid yields indigo. 

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). 

Progress in coenzyme NADH model compounds and as3Tnmetric reduction of benzoylformate 07SL2785. 

Table 1. Asymmetric reductions of ethyl benzoylformate with chiral model compounds.

The observation of the rate acceleration by a bivalent metal ion such as Mg(II) or Zn(II) in the model system readily leads to the idea that the metal ion may polarize the carbonyl group of the substrate as a Lewis acid to facilitate the reduction (Creighton et al. 1976, Hughes and Prince 1978b, Steevens and Pandit 1983). However, such a function of the metal ion cannot explain the result that the presence of the metal ion exerts an effect for the induction of chirality by PNPH into ethyl benzoylformate. A more intrinsic... 

Fig. 4. Rate-metal ion concentration profiles for the reduction (a) ethyl benzoylformate and (b) a 2-acylpyridine derivative.

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... 

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... 

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