Decarboxylative cleavage

Photolysis of 2-oxetanones gives decarboxylative cleavage to alkenes, similar to pyrolysis, but subsequent photoaddition reactions of the alkene product may lead to complex reaction mixtures. A very useful example of 2-oxetanone photolysis is that of 5-oxabicyclo[2.2.0]oct-2-en-6-one, the photoisomer of a-pyrone when it was irradiated in a argon matrix at 80 K, carbon dioxide and cyclobutadiene were formed (equation 7) (73JA1337). 

Table 3.45. Generation of C-H bonds upon decarboxylative cleavage from supports.

Plants. Metabolism involves hydroxylation, decarboxylation, cleavage of the acid side-chain, and ring opening... 

Soil. Microbial degradation involves hydroxylation, decarboxylation, cleavage of the acid side-chain, and ring opening. Half-life in soil <7 days. Rapid degradation in the soil prevents significant downward movement... 

Bi2, cyanocobalamin racemization, decarboxylation, cleavage, synthesis, dehydration, and desulfhydration Methylation of homocysteine to mefliionine. 

These substances, as well as the parent compound, are p-keto esters and undergo hydrol3rtio cleavage in two directions. One type of cleavage, ketonlc hydrolysis, is effected by the action of dilute caustic alkali in the cold, followed by acidification and boiling the free acetoacetic acid produced has a carboxyl and carbonyl group on the same carbon atom and therefore readily undergoes decarboxylation to yield a ketone, for example ... 

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). 

Diall l Peroxydicarbonates. Some commercially available diaLkyl peroxydicarbonates and their corresponding 10-h half-life temperatures (deterrnined in trichloroethylene solutions) are Hsted in Table 7 (45). These peroxides are active at low temperatures and initially undergo homolytic cleavage to produce alkoxycarbonyloxy radical pairs that may subsequendy decarboxylate to produce alkoxy radicals ... 

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

FIGURE 18.18 Thiamine pyrophosphate participates in (a) the decarboxylation of n-keto acids and (b) the formation and cleavage of n-hydroxyketones. 

The biologically active form of vitamin Bg is pyridoxal-5-phosphate (PEP), a coenzyme that exists under physiological conditions in two tautomeric forms (Figure 18.25). PLP participates in the catalysis of a wide variety of reactions involving amino acids, including transaminations, a- and /3-decarboxylations, /3- and ") eliminations, racemizations, and aldol reactions (Figure 18.26). Note that these reactions include cleavage of any of the bonds to the amino acid alpha carbon, as well as several bonds in the side chain. The remarkably versatile chemistry of PLP is due to its ability to... 

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. 

Ring cleavage of l-oxo-l,2,3,4-tetrahydro-jS-carboline derivatives (374) may be accomplished by base-catalyzed hydrolysis to yield tryptamine-2-carboxylic acids (375). In the case of the 1,9-dimethyl derivative decarboxylation accompanied acid-catalyzed ring-opening, and the corresponding tryptamine (376) was obtained directly. 

The mechanism for the conversion of the A -oxide (94) to the o-methylaminophenylquinoxaline (96) involves an initial protonation of the A -oxide function. This enhances the electrophilic reactivity of the a-carbon atom which then effects an intramolecular electrophilic substitution at an ortho position of the anilide ring to give the spiro-lactam (98). Hydrolytic ring cleavage of (98) gives the acid (99), which undergoes ready dehydration and decarboxylation to (96), the availability of the cyclic transition state facilitating these processes. ... 

Decarboxylation of isoxazole-3-carboxylic acids is related to the nucleophilic cleavage of the isoxazole ring as far as the nature of the reaction products is concerned. It occurs at temperatures above 200°C and is accompanied by the cleavage of the nitrogen-oxygen bond of the heterocyclic ring to yield a j8-ketonitrile. It was first reported by Claisen with 5-methyl- and 5-phenyl-isoxazole-3-carboxylic acids (153- 154).Under the reaction conditions, j8-ketonitriles condense... 

Standard retrosynthetic manipulation of PGA2 (1) converts it to 5 (see Scheme 2). A conspicuous feature of the five-membered ring of intermediate 5 is the /(-keto ester moiety. Retrosynthetic cleavage of the indicated bond in 5 furnishes triester 6 as a potential precursor. Under basic conditions and in the synthetic direction, a Dieck-mann condensation4 could accomplish the formation of a bond between carbon atoms 9 and 10 in 6 to give intermediate 5. The action of sodium hydroxide on intermediate 5 could then accomplish saponification of both methyl esters, decarboxylation, and epi-merization adjacent to the ketone carbonyl to establish the necessary, and thermodynamically most stable, trans relationship between the two unsaturated side-chain appendages. 

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. 

A completely different concept13 makes use of a highly reduced bilane 5 which is oxidatively cyclized to an isobacteriochlorin 6 with copper(II) acetate. The ring closure is initiated by ester cleavage with trifluoroacetic acid and decarboxylative formylation with trimethyl orthoformate to yield a dialdehyde. One of the aldehyde functions forms the desired methine bridge whereas the other is lost during cyclization. 

The starting material could be synthesized from the corresponding known dibenzyl tetrapyrrole-dicarboxylate17 by hydrogenolytic cleavage of the benzyl esters followed by decarboxylative Clezy formylation.18... 

The greater ease of reaction compared to nitrosodeprotonation may arise from the greater ease of carbon-carbon bond cleavage compared to carbon-hydrogen bond cleavage for in the latter reaction this is partly rate-determining and may so be in the decarboxylation as well. 

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