Decarboxylation cyclic ketone synthesis

The synthesis may thus be seen to be an intramolecular Claisen ester condensation, which is known as the Dieckmann reaction. The procedure is an important method for the synthesis of five- and six-membered ring systems, and the cyclic /2-keto ester product may be converted into the corresponding cyclic ketone by hydrolysis followed by decarboxylation (ketonic hydrolysis, see Section 5.8.5, p. 619). The base catalyst used in Expt 7.8 is sodium ethoxide, but sodium hydride as a 50 per cent dispersion in oil is a recommended alternative. 

Fig. 13.29. Synthesis of complicated ketones in analogy to the acetoacetic ester synthesis II generation of a cyclic ketone. In the first step, the /3-ketoester is alkylated at its activated position. In the second step, the /3-ketoester is treated with Li I . SN2 reaction of the iodide at the methyl group generates the /3-ketocar-boxylate ion as the leaving group. The /3-ketocarboxylate decarboxylates immediately under the reaction conditions (temperature above 100 °C) and yields the enolate of a ketone.

Irradiation of 2-[N-(pentafluorophenyI)amino]-3-phenylcyclopropenone promotes decarbonylation to give N-(pentafluorophenyl)phenylethynamine and 2-phenyl-3-[N-(pentafluorophenyl)amino]acrylic acid by a process for which there is no known precedent,and the photoextrusion of carbon monoxide from l,3-bis(ethylenedioxy)indan-2-one has been used as the first step in a new synthesis of 1,2-dioxobenzocyclobutene. This represents an unusual example of the decarbonylation of a five-membered cyclic ketone in the preparation of a highly strained and functionalised cyclobutane derivative. The photolysis of a-naphthaleneacetic acid in aqueous solution proceeds by decarboxylation and oxidation of the aromatic ring, and has been carried out at a variety of different wavelengths. The primary step occurs by pseudo-first order kinetics and the optimum photolysis rate has been observed using Ti02 as photocatalyst. Within the cavity of P-cyclodextrin, naproxene (129) has been photodecarboxylated to... 

The butylated /J-ketoester C of Figure 13.26 is not the final synthetic target of the acetoacetic ester synthesis of methyl ketones. In that context, the /J-ketoester C is converted into the corresponding /J-ketocarhoxylic acid via acid-catalyzed hydrolysis (Figure 13.27 for the mechanism, see Figure 6.22). This /i-ketocarboxylic acid is then heated either in the same pot or after isolation to effect decarboxylation. The /f-ketocarboxylic acid decarboxylates via a cyclic six-membered transition state in which three valence electron pairs are shifted at the same time. The reaction product is an enol, which isomerizes immediately to a ketone (to phenyl methyl ketone in the specific example shown). 

The Chemistry of Ringc.—The modification of ring c has centred on making available relays that are suitable for elaboration into more complex diterpenoids, the diterpenoid alkaloids, and triterpenoids. The unsaturated ketone (53) has proved to be a valuable relay for synthesis. It had been prepared previously from neoabietic acid, which is difficult to obtain pure. It has now been obtained from the levopimaric acid-formaldehyde adduct (50). Oxidation of the adduct with potassium permanganate not only formed the glycol but in an unusual step converted the cyclic ether into the (5-lactone (51). Dehydration, ozonolysis of the newly formed double bond, and then treatment of the keto-acetate (52) with chromous chloride afforded the a -unsaturated ketone (53). The last step involved hydrogenolysis, / -elimination. and decarboxylation. 

The construction of a y-pyrone is essentially the construction of a 1,3,5-tricarbonyl compound since such compounds easily form cyclic hemiacetals then requiring only dehydration. Several methods are available for the assembly of such precursors the synthesis of chelidonic acid (4-pyrone-2,6-dicarboxylic acid) represents the obvious approach of bringing about two Claisen condensations, one on each side of a ketone carbonyl group. Chelidonic acid can be decarboxylated to produce y-pyrone itself. ... 

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