Oxidation decarboxylation, oxidative

There are, however, certain types of natural reactions that occur in many situations, that are probably brought about by similar enzymes, and that may profit from an electrochemical study. Three of these that we have worked on for many years have been phenol oxidation, oxidative decarboxylation, and indole oxidation. The coupling of aromatic ethers electrochemically is unlikely to be a natural reaction, but the results have been so interesting and so analogous to phenol coupling, that this topic will be discussed briefly also. 

Regioselectivity of C—C double bond formation can also be achieved in the reductiv or oxidative elimination of two functional groups from adjacent carbon atoms. Well estab llshed methods in synthesis include the reductive cleavage of cyclic thionocarbonates derivec from glycols (E.J. Corey, 1968 C W. Hartmann, 1972), the reduction of epoxides with Zn/Nal or of dihalides with metals, organometallic compounds, or Nal/acetone (seep.lS6f), and the oxidative decarboxylation of 1,2-dicarboxylic acids (C.A. Grob, 1958 S. Masamune, 1966 R.A. Sheldon, 1972) or their r-butyl peresters (E.N. Cain, 1969). 

Synthetic phenol capacity in the United States was reported to be ca 1.6 x 10 t/yr in 1989 (206), almost completely based on the cumene process (see Cumene Phenol). Some synthetic phenol [108-95-2] is made from toluene by a process developed by The Dow Chemical Company (2,299—301). Toluene [108-88-3] is oxidized to benzoic acid in a conventional LPO process. Liquid-phase oxidative decarboxylation with a copper-containing catalyst gives phenol in high yield (2,299—304). The phenoHc hydroxyl group is located ortho to the position previously occupied by the carboxyl group of benzoic acid (2,299,301,305). This provides a means to produce meta-substituted phenols otherwise difficult to make (2,306). VPOs for the oxidative decarboxylation of benzoic acid have also been reported (2,307—309). Although the mechanism appears to be similar to the LPO scheme (309), the VPO reaction is reported not to work for toluic acids (310). 

Alkyl radicals produced by oxidative decarboxylation of carboxylic acids are nucleophilic and attack protonated azoles at the most electron-deficient sites. Thus imidazole and 1-alkylimidazoles are alkylated exclusively at the 2-position (80AHC(27)241). Similarly, thiazoles are attacked in acidic media by methyl and propyl radicals to give 2-substituted derivatives in moderate yields, with smaller amounts of 5-substitution. These reactions have been reviewed (74AHC(i6)123) the mechanism involves an intermediate cr-complex. 

Other interactions of /3-lactams with electrophiles include the oxidative decarboxylation of the azetidin-2-one-4-carboxylic acid (85) on treatment with LTA and pyridine (81M867), and the reaction of the azetidin-2-one-4-sulfinic acid (86) with positive halogen reagents. This affords a mixture of cis- and trans-4-halogeno-/3-lactams (87), the latter undergoing cyclization to give the bicyclic /3-lactam (88) (8UOC3568). 

Azetidine, 7V-bromo-, 7, 240 Azetidine, AT-r-butyl- N NMR, 7, 11 Azetidine, AT-t-butyl-3-chloro-transannular nucleophilic attack, 7, 25 Azetidine, 3-chloro-isomerization, 7, 42 Azetidine, AT-chloro-, 7, 240 dehydrohalogenation, 7, 275 Azetidine, 7V-chloro-2-methyl-inversion, 7, 7 Azetidine, 3-halo-synthesis, 7, 246 Azetidine, AT-halo-synthesis, 7, 246 Azetidine, AT-hydroxy-synthesis, 7, 271 Azetidine, 2-imino-stability, 7, 256 Azetidine, 2-methoxy-synthesis, 7, 246 Azetidine, 2-methyl-circular dichroism, 7, 239 optical rotatory dispersion, 7, 239 Azetidine, AT-nitroso-deoxygenation, 7, 241 oxidation, 7, 240 synthesis, 7, 246 Azetidine, thioacyl-ring expansion, 7, 241 Azetidine-4-carboxylic acid, 2-oxo-oxidative decarboxylation, 7, 251 Azetidine-2-carboxylic acids absolute configuration, 7, 239 azetidin-2-ones from, 7, 263 synthesis, 7, 246... 

Glycol and o -hydroxy acid cleavage Oxidative decarboxylation Oxidative rearrangement of olefins... 

One-electron oxidation of carboxylate ions generates acyloxy radicals, which undergo decarboxylation. Such electron-transfer reactions can be effected by strong one-electron oxidants, such as Mn(HI), Ag(II), Ce(IV), and Pb(IV) These metal ions are also capable of oxidizing the radical intermediate, so the products are those expected from carbocations. The oxidative decarboxylation by Pb(IV) in the presence of halide salts leads to alkyl halides. For example, oxidation of pentanoic acid with lead tetraacetate in the presence of lithium chloride gives 1-chlorobutane in 71% yield ... 

Van Tamelen (I24a) has reported a useful and specific synthetic method for the production of enamines by the oxidative decarboxylation of N,N-dialkyl a-amino acids with sodium hypochlorite. 

Pyruvate produced by glycolysis is a significant source of acetyl-CoA for the TCA cycle. Because, in eukaryotic ceils, glycolysis occurs in the cytoplasm, whereas the TCA cycle reactions and ail subsequent steps of aerobic metabolism take place in the mitochondria, pyruvate must first enter the mitochondria to enter the TCA cycle. The oxidative decarboxylation of pyruvate to acetyl-CoA,... 

It is worth noting that the carbon-carbon bond cleaved in the TCA pathway entered as an acetate unit in the previous turn of the cycle. Thus, the oxidative decarboxylations that cleave this bond are just a cleverly disguised acetate C—C cleavage and oxidation. 

Finally, citrate can be exported from the mitochondria and then broken down by ATP-citrate lyase to yield oxaloacetate and acetyl-CoA, a precursor of fatty acids (Figure 20.23). Oxaloacetate produced in this reaction is rapidly reduced to malate, which can then be processed in either of two ways it may be transported into mitochondria, where it is reoxidized to oxaloacetate, or it may be oxidatively decarboxylated to pyruvate by malic enzyme, with subse-... 

Oxidative decarboxylation of 2 pyruvate to 2 acetyl-CoA 2 NADH produce 2.5 ATP each + 5 + 5... 

Little data is available, but methyl groups a and y to ring nitrogens appear to be activated. 2-Methyl and 6-methyl substituents in pyrido[3,2-d]pyrimidines undergo bromination 38.79,12.9 oxidative decarboxylation, and form styryl compounds.The 6-methyl group in pyrido[2,3-d]pyrimidines could not be brominated. ... 

The first stage of the reaction is a special case of the oxidative decarboxylation of amino acids, for which two general mechanistic hypotheses are under discussion.This is followed by aromatiz-ation. A possible mechanism (241- 242- 243- 245) has been... 

The Cg-amine, originally obtained by the methanolysis of kasugamycin, on treatment with lead tetraacetate or sodium periodate afforded a nitrile amine, with evolution of carbon dioxide, showing a maximum at 2200 cm.-1. This reaction is explained only by the structure (13). The -N-C=N group of the product can be formed by oxidative decarboxylation and can be easily rationalized by the present understanding of such reagents (2, 13) as shown below. On the other hand, the treatment... 

Step 4 of Figure 29.12 Oxidative Decarboxylation The transformation of cr-ketoglutarate to succinyl CoA in step 4 is a multistep process just like the transformation of pyruvate to acetyl CoA that we saw in Figure 29.11. In both cases, an -keto acid loses C02 and is oxidized to a thioester in a series of steps catalyzed by a multienzynie dehydrogenase complex. As in the conversion of pyruvate to acetyl CoA, the reaction involves an initial nucleophilic addition reaction to a-ketoglutarate by thiamin diphosphate vlide, followed by decarboxylation, reaction with lipoamide, elimination of TPP vlide, and finally a transesterification of the dihydrolipoamide thioester with coenzyme A. 

A cursory inspection of key intermediate 8 (see Scheme 1) reveals that it possesses both vicinal and remote stereochemical relationships. To cope with the stereochemical challenge posed by this intermediate and to enhance overall efficiency, a convergent approach featuring the union of optically active intermediates 18 and 19 was adopted. Scheme 5a illustrates the synthesis of intermediate 18. Thus, oxidative cleavage of the trisubstituted olefin of (/ )-citronellic acid benzyl ester (28) with ozone, followed by oxidative workup with Jones reagent, affords a carboxylic acid which can be oxidatively decarboxylated to 29 with lead tetraacetate and copper(n) acetate. Saponification of the benzyl ester in 29 with potassium hydroxide provides an unsaturated carboxylic acid which undergoes smooth conversion to trans iodolactone 30 on treatment with iodine in acetonitrile at -15 °C (89% yield from 29).24 The diastereoselectivity of the thermodynamically controlled iodolacto-nization reaction is approximately 20 1 in favor of the more stable trans iodolactone 30. 

TPP-dependent enzymes are involved in oxidative decarboxylation of a-keto acids, making them available for energy metabolism. Transketolase is involved in the formation of NADPH and pentose in the pentose phosphate pathway. This reaction is important for several other synthetic pathways. It is furthermore assumed that the above-mentioned enzymes are involved in the function of neurotransmitters and nerve conduction, though the exact mechanisms remain unclear. 

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