Benzoyl formate

The mandelate pathway in Pseudomonas putida involves successive oxidation to benzoyl formate and benzoate, which is further metabolized via catechol and the 3-ketoadipate pathway (Figure 8.35a) (Hegeman 1966). Both enantiomers of mandelate were degraded through the activity of a mandelate racemase (Hegeman 1966), and the racemase (mdlA) is encoded in an operon that includes the next two enzymes in the pathway—5-mandel-ate dehydrogenase (mdlB) and benzoylformate decarboxylase (mdlC) (Tsou et al. 1990). 

Table 42.3 Enantioselective hydrogenation of methyl benzoyl formate using [Rh(COD) (L-L)][OTf] SHB catalysts supported on Davison silicas of different pore sizes [28]. 

Decreased Benzoyl Formate Decarboxylation Activity of Variant 55E4... 

The potential of benzoylformate decarboxylase (BFD, E.C. 4.1.1.7) to catalyze C-C bond formation was first reported by Wilcocks at al. using crude extracts of Pseudomonas putidsL [50]. They observed the formation of (S)-2-hydroxy-l-phenylpro-panone (S)-2-HPP when benzoyl formate was decarboxylated in the presence of acetaldehyde. Advantageously, aldehydes - without a previous decarboxylation step - can be used instead of the corresponding more expensive a-keto acids [51]. We could show that BFD is able to bind a broad range of different aromatic, heteroaromatic, and even cyclic aliphatic and conjugated olefinic aldehydes to ThDP before ligation to acetaldehyde or other aldehydes (Table 2.2.7.3) [52]. 

Glazer, J., and E. E. Turner The Mutarotation of laevo menthyl benzoyl-formate in alcoholic solutions. J. chem. Soc. [London] 1949 Suppl., 169. 

The sulfinyl chirality has shown [86] considerable utility in asymmetric synthesis, particularly for carbon-carbon bond formation (see Sections 2.6.2 and 4.2.8). Its use as the chiral source in a NADH mimic has been reported [240]. Reduction of methyl benzoyl formate by enantiopure l-propyl-(S)-3-(p)-tolyl)sulfinyl-l,4-dihydropyridine yielded the (/ )-mandelate with 96% e.e. 

Carbonyl groups can be transformed into amines via formation of their hydrazones followed by transfer hydrogenation. Thus the benzoyl formate shown in Scheme 4.35 was converted into the phenylhydrazone under microwave irradiation in ethylene glycol as solvent. Subsequent reduction using ammonium formate and 10% Pd/C as a catalyst provides the amine in an overall reaction time of 10 min and a total yield of 83%.14... 

The mandelate and jS-ketoadipate pathways are a good example of gene duplication, with strong evidence of the former evolving from the latter the congruence of MR and MLE, (S)-ManDH and benzoate dihydrodiol dehydrogenase, and possibly benzoyl formate decarboxylase and protocatechuate decarboxylase. 

However, an ElcB-type process was reported as a novel mechanism for hydrolysis of a /3-sultam. In the case of the N-a -methoxycarbon y I /3-sultam, deprotonation of the acidic exocyclic hydrogen leads to the formation of a carbanion, which then undergoes a rate-limiting conversion to a ring-opened species with expulsion of a sulfinate anion. Then, hydrolysis of the imine species produces benzoyl formate as the principal product detected (Scheme 14) <2002CC772>. 

The a-keto acid decarboxylases such as pyruvate (E.C. 4.1.1.1) and benzoyl formate (E.C. 4.1.1.7) decarboxylases are a thiamine pyrophosphate (TPP)-dependent group of enzymes, which in addition to nonoxidatively decarboxylating their substrates, catalyze a carboligation reaction forming a C-C bond leading to the formation of a-hydroxy ketones.269-270 The hydroxy ketone (R)-phenylacetylcarbinol (55), a precursor to L-ephedrine (56), has been synthesized with pyruvate decarboxylase (Scheme 19.35). BASF scientists have made mutations in the pyruvate decarboxylase from Zymomonas mobilis to make the enzyme more resistant than the wild-type enzyme to inactivation by acetaldehyde for the preparation of chiral phenylacetylcarbinols.271... 

Benzoyl formate decarboxylase from Pseudomonas putida has been used to synthesize chiral 2-hydroxy ketones and bis(a-hydroxy) ketones, which find their use as pharmaceutical intermediates and as new multidentate ligands for asymmetric transition metal catalysis, respectively.272 273 Combining this decarboxylase activity with AdH has allowed all the stereoisomers of 1 -phenyl-propane- 1,2-diol to be synthesized.274... 

Izawa et have reported the photochemical alcoholysis of the acetamide derivatives (122) to afford the esters (123). Related to this is the photochemical alcoholysis of ft),a>,ft)-tribromoacetophenone yielding benzoyl formate. Irradiation of the cycloalkanones (124) in methanol at 300 nm affords high yields of the corresponding dimethylacetals. The authors discount an acid-catalysed process even though the presence of sodium acetate suppresses the acetal formation. 

Asymmetric reduction of carbonyls has also been achieved by Dupas and coworkers by reaction of achiral NADH equivalents mediated by chiral aluminum Lewis acids [23]. They reduced methyl benzoyl formate with the dihydropyrido[2,3-h]indole 86 and chiral aluminum Lewis acids whose structures are drawn and 89 and 90 (Sch. 12). Asymmetric induction was quite low. Details of the reaction, including the conditions used, were not provided nor were the procedures used for the preparation of the chiral Lewis acids 89 and 90. 

N-Ethylbenzisoxazolium fluoroborate, 364 Ethyl benzoate, 296, 585, 1069 Ethyl benzoyl formate, 993,1048 Ethyl a-benzoylisobutyrate, 1258,1259 Ethyl N-benzylcarbamate, 1097 Ethyl bromide, 374, 861 Ethyl bromoaeetate, 303 Ethyl a-bromobutyrate, 298 Ethyl 2-bromo-2-methylcyclopropanecar-boxylate, 1078... 

Corey and Schaefer studied the kinetics of the oxidation of desoxybenzoin to benzil and suggested a mechanism for the reaction. They also developed an efficient synthesis of a-keto esters involving oxidation of an a-bromoketone in an anhydrous solvent, as illustrated by a procedure for the preparation of ethyl benzoyl formate. o OO OO... 

Production of Benzaldehyde from Benzoyl Formate or Mandelic Acid... 

Benzaldehyde can be produced from benzoyl formate with whole cells of Pseudomonas putida ATCC 12633 as biocatalyst119 201 (Fig. 16.6-5). Alternatively, but less effectively, mandelic acid can be used as starting material. A pH of 5.4 was found to be optimal for benzaldehyde accumulation. At this proton concentration, partial inactivation of the benzaldehyde dehydrogenase isoenzymes and activation of the benzoyl formate decarboxylase are reported. Fed-batch cultivation prevented substrate inhibition. In situ product removal is necessary to prevent product inhibition. 

Liquid-phase enantioselective hydrogenations of a-ketoesters by alkaloid-modified Pt has been investigated intensively and reviewed. " The first reported reactions of this type were the hydrogenations of methyl pyruvate, MeCOCOOMe, and of methyl benzoyl formate, PhCOCOOMe, over Pt modified by the cinchona alkaloids." ... 

Sutyinszki, M., Szori, K., Felfoldi, K., Bartok, M. (2002) 98% Enantio-selectivity in the asymmetric synthesis of a useful chiral building block by heterogeneous method enantioselective hydrogenation of ethyl benzoyl-formate over cinchona modified Pt/Al203 catalysts, Catal. Commun. 3,... 

The gas-phase elimination kinetics of several ethyl esters of 2-oxocarboxylic acid have been found to be homogeneous, unimolecular, and follow a first-order rate law. ° Ethyl oxalyl chloride undergoes only decarboxylation, while both ethyl piperidinegly-oxilate and ethyl benzoyl formate exhibit parallel decarboxylation and decarbonylation reactions. The mechanisms of these decomposition reactions were described in terms of concerted discrete polar cyclic TS structures. 

In the enzymatic aldol reaction, the role of the donor and acceptor is strictly determined by the specificity of the enzyme and only raie coupling product can be obtained. In contrast, the possible product range is more complex in acyloin and benzoin reactions If only a single aldehyde species is used as substrate, only one product can be obtained via homocoupling however, a pair of regioisomeric a-hydroxyketones can be obtained via heterocoupling, when two different aldehydes are used, the ratio of which is determined by the choice of substrates (e.g., benzoyl formate vs. benzaldehyde, pyruvate vs. acetaldehyde), and the specificites of enzymes, respectively (Scheme 2.198). 

BED [EC 4.1.1.7] is derived from mandelate catabolism, where it catalyzes the nonoxidative decarboxylation of benzoyl formate to yield benzaldehyde. Again, the reverse carboUgatiMi reaction is more important [1488-1490]. As may be deduced from its natural substrate, is exhibits a strong preference for large aldehydes as donor substrates encompassing a broad range of aromatic, heteroaromatic, cyclic aliphatic and olefinic aldehydes [1480]. With acetaldehyde as acceptor, it yields the complementary regio-isomeric product to PDC (Scheme 2.200). 

As has been revealed in the reduction of methyl or ethyl benzoyl-formate with Me PNPH, where the reduction takes place in only one... 

Thus, one atom from dioxygen is introduced into the substrate and the other into the resulting carboxylic acid. As a model for the enzymes, an iron(II) complex coordinated with a-keto acid has been synthesized. The complex Fe(TLA)(BF) (BF = benzoyl-formate) was prepared and its X-ray structure was determined [88, 89]. That complex is six-coordinate with a bidentate coordination of a-keto acid via the carboxylate oxygen and the carbonyl oxygen). When the complex was treated with dioxygen, decarbonylation does occur to give a carboxylate complex quantitatively. While the detailed mechanism remains to be elucidated, the addition of 2,4-di-/-butylphenol results in the formation of 0.75 mol of the corresponding biphenol per mole of the ferrous complex. 

Ketoesters.—A Japanese group has developed a route to a-ketoesters based on an additive-type Pummerer rearrangement (Scheme 40) the method awaits application to substrates other than the one shown in the scheme. An apparently simple synthesis of benzoyl formates involves addition of pyridine-A-oxide to a-bromo-phenylacetates, and treatment of the resulting pyridinium adducts (which have been... 

The species [Cu (L)(BF)], where BF = benzoyl formate, L = tris(2-pyridylmethyl)amine, has Av (= Vas —Vg) CO2 of 178 cm consistent with unidentate carboxylate. When L = bis(2-pyridylmethyl)amine or bis(2-benzimidazolylmethyl)amine, smaller Av values show that there are bidentate carboxylates in these cases.[Cu(dipn)(H20)]2TCB, where TCB = tetra-carboxylatobenzene, has VCO2 values showing the presence of amphi-unidentate (end-to-end) and anisobidentate syn and anti) carboxylates. 

HLADH ADH from horse liver UfADH ADH from Lactobacillus brevis BFR benzoyl formate ... 

Aldol condensation Aldehyde 2-Keto aoid Synthesis of 2-hydroxy ketones Pyruvate decarboxylase, benzoyl formate deoarboxylase, phenylpyruvate deoarboxylase... 

Benzoylformate decarboxylase (BFD) from P. putida (Table 10.4, entries 1-5) catalyzes the acyloin condensation of benzaldehyde or benzoyl formate derivatives to acetaldehyde, furnishing (S)-configured acyloins. BDF showed a preference for aromatic aldehydes as donors and aliphatic aldehydes as acceptors, although with lower reaction rates than BAL [14,55], The meta- and para-substituted benzaldehyde derivatives as well as heteroaromatic, olefinic, and cyclic aliphatic aldehydes are transformed with good to excellent conversions and enantioselectivities [14,55,56,63,64]... 

M. Knoll, M. Muller, J. Pleiss, M. Pohl, Factors mediating activity, selectivity, and substrate specificity for the thiamin diphosphate-dependent enzymes benzaldehyde lyase and benzoyl-formate decarboxylase, Chembiochem 7 (2006) 1928-1934. 

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