Decarboxylation of /1-lactones

Another reaction in which the solvent plays an enormous role is in the decarboxylation of lactones. In one study of this type, Ocampo, Dolbier, Bartberger, and Paredes (1997) investigated the decarboxylation of a,a-difluoro )8-lactones in several solvents and in the gas phase. The reaction for the dialkyl compounds can be shown as foUows. 

The derivative (18) of 3-deoxv-L-gulo-2-octulosonic acid has been prepared by NBS-catalysed hydrolysis of a dithioacetal, in a similar manner to the method illustrated in Scheme 6,23 and the octulosonic acid itself has been made via oxidative decarboxylation of lactone (19).24... 

Unsaturated 19-norsteroids are also obtained by thermal decarboxylation of A -19-acids (obtained by zinc reduction of the 5a-halo-6/3,19-lactones). 

As the mechanism, a radical and a cationic pathway are conceivable (Eq. 31). The stereochemical results with rac- or mcjo-1,2-diphenyl succinic acid, both yield only trans-stilbene [321], and the formation of a tricyclic lactone 51 in the decarboxylation of norbornene dicarboxylic acid 50 (Eq. 32) [309] support a cation (path b, Eq. 31) rather than a biradical as intermediate (path a). 

Decarboxylation of p-lactones (see 17-27) may be regarded as a degenerate example of this reaction. Unsymmetrical diacyl peroxides RCO—OO—COR lose two molecules of CO2 when photolyzed in the solid state to give the product RR. Electrolysis was also used, but yields were lower. This is an alternative to the Kolbe reaction (11-37). See also 17-29 and 17-40. 

Decarboxylation, Masamune reaction, and diazotransfer Diazo 25 was prepared under optimized conditions, as summarized in Scheme 2.9. Decarboxylation of the malonate could be done under either acidic or basic conditions. Reaction of 17 under acidic conditions provided the desired mono-carboxylic acid 18 but lactone 35 was simultaneously formed (Figure 2.2). Under basic conditions,... 

The photolysis of carboxylic acids and derivatives as lactones, esters and anhydrides can yield decarboxylated products 253>. This reaction has been utilized in the synthesis of a-lactones from cyclic diacyl peroxides 254) (2.34) and in the synthesis of [2,2]paracyclophane by bis-decarboxylation of a lactone precursor (2.35) 255). This latter product was also obtained by photoinduced desulfurization of the analogous cyclic sulfide in the presence of triethyl phosphite 256). 

Oxidative bisdecarboxylation.1 A new route to lactones is based on the ability of CAN to effect oxidative decarboxylation of a-hydroxymalonic acids to carboxylic acids (11, 143-144) and of a-alkoxymalonic acids to lactones. 

Decarboxylation of p-lactones to olefins,4 6 stereoselective reactions of p-lactones with a variety of electrophiles,6 9 and the regioselective fission of p-lactones by many different nucleophiles10 12 make these highly reactive compounds versatile intermediates for organic syntheses.13 Although several methods exist for the preparation of p-lactones, most p-lactones are now synthesized by [2+2] cycloaddition... 

Esters are hydrolysed under basic conditions in the presence of quaternary ammonium salts [e.g. 1-7], Microwave activation of basic soliddiquid systems without an added solvent enhances the rate of saponification and the reaction is not affected by steric factors [3], Microwave irradiation has also been used in the hydrolysis and decarboxylation of malonic esters [8] and p-keto esters [9] (>90%). Lactones... 

In continuation of previous work, the reactions of gibberellin A, and Aj with neutral manganese dioxide have been examined. The products include those of decarboxylation and of lactonization on to C-15. The full paper describing the interesting bridgehead C-13 fluorination of gibberellins with fluoramine has appeared. ... 

As will be seen in the following section the most widespread use of the alkylation of lactones is that of y-lactones. Clearly the need for a-substitution of y-lactones was present before the advent of Creger s non-nucleophilic base. The most versatile method was the reaction of a-substitutcd malonic or acetoacetic esters with epoxyethane or 2-chloroethanol, followed by hydrolysis and decarboxylation or ketonic cleavage5. Another common approach was the condensation of butyrolactones (y-lactones) with aldehydes and subsequent hydrogenation5,s. It should be mentioned at this point that these older methods still have their merits, especially for large scale production. 

The mechanism of decarboxylation of /3-lactones has attracted much attention. The gas-phase decomposition of 2-oxetanone is a unimolecular first-order process. It has a considerably lower energy of activation than the pyrolysis of oxetane and a much higher entropy of activation, indicating a loose activated complex (69JA7743). The ease of the reaction is greatly affected by the electronic effect of substituents at position-4, but not at position-3. The Hammett treatment of a series of rrans-4-aryl-3-methyl-2-oxetanones gave a good correlation with [Pg.374]

Almotriptan has also been synthesized via decarboxylation of the carboxylic acid intermediate 65, but a detailed preparation of 65 was not provided in the patent literature (Scheme 22)." The patent indicates that the carboxy indole 65 was prepared according to the method of Gonzalez.°° Thus, (2-oxo-tetrahydro-3-furanyl)-glyoxylic acid ethyl ester (62) was heated in aqueous H2SO4 to give 2-oxo-5-hydroxypentanoic acid in situ, which was treated with hydrazine 59 to produce hydrazone 63. Fischer cyclization of 63 using HCl gas in DMF gave the lactone 64, which was converted to carboxylic acid 65. Decarboxylation of 65 was catalyzed by cuprous oxide in quinoline at 190 °C to afford almotriptan (5)." ... 

Decarboxylation of (3-Hydroxy Carboxylic Acids and of (3-Lactones Carboxy-hydroxy-elimination... 

A kinetic study of the thermal decarboxylation of a,a-difluoro /1-lactones (223 R = H, Me) in the gas phase and in various solvents has been reported.198 Ab initio calculations have also been carried out. 

A systematic study of the impact of geminal a-fluorine substitution upon the rate of decarboxylation of /1-lactones has included investigation of die thermolysis of a,a-difluoro /1-lactones, to give CO2 and 1,1-difluoroalkenes, in die gas phase and in solution.48 The gas-phase results have been interpreted, with reference to ab initio calculations on the fluoro- and non-fluormated /1-lactone systems, in terms of a probable concerted, asynchronous, non-polar mechanism. However, a polar mechanism which probably involves formation of an intermediate zwirterion has been invoked to explain the solvent dependence observed. 

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