Homolytic decarboxylation

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 ... 

Complementary to the work with aqueous acidic media is the study of the homolytic decompositions of Co(III) carboxylates in carboxylic acid media by Lande and Kochi . For example, Co(III) is reduced in pivalic acid media with first-order kinetics with E = 30.6 kcal.mole , AS = 8 eu and k ko = 1.28+0.10 (69 °C). The main oxidation products were found to be isobutylene and tert-butyl pivalate, which suggests that (CH3)3C- is an intermediate. Oxidative decarboxylation is the probable course in the analogous oxidations of n-butyric and isobutyric acids, in view of the production of propane and CO2 under normal... 

Successful syntheses involving radical initiated decarboxylation are mainly limited to monoorganomercurials, where the method has extensive uses. Homolytic decarboxylation mechanisms have been discussed in Section II,C. 

Two sources of acyl radicals have proved to be useful for the homolytic acylation of protonated heteroaromatic bases the oxidation of aldehydes and the oxidative decarboxylation of a-keto acids. The oxidation... 

The usual sources used for the homolytic aromatic arylation have been utilized also in the heterocyclic series. They are essentially azo- and diazocompounds, aroyl peroxides, and sometimes pyrolysis and photolysis of a variety of aryl derivatives. Most of these radical sources have been described in the previous review concerning this subject, and in other reviews concerning the general aspects of homolytic aromatic arylation. A new source of aryl radicals is the silver-catalyzed decarboxylation of carboxylic acids by peroxydisulfate, which allows to work in aqueous solution of protonated heteroaromatic bases, as for the alkyl radicals. 

In comparison, photodecarboxylation of various other carboxylic acids has been studied extensively. For example, photodecarboxylation of 23 in water presumably involves electron transfer from the carboxylate anion to the phenyl ring (Scheme 16). The electron transfer is followed by decarboxylation to form the anion 24, which is protonated by the solvent. As shown in Scheme 16, in less polar aprotic solvents, homolytic cleavage leads to decarboxylation subsequent to charge transfer in 23. 

Minisci-type substitution is one of the most useful reactions for the synthesis of alkyl- and acyl-substituted heteroaromatics. The acyl radicals are formed by the redox decomposition from aldehyde and /-butyl hydroperoxide or by silver-catalyzed decarboxylation of a a-keto acid with persulfate. Synthesis of acylpyrazines 70 as ant pheromones are achieved by this methodology using trialkyl-substituted pyrazines 69 with the acyl radicals generated from aldehydes or a-keto acids (Equation 10) <1996J(P1)2345>. The latter radicals are highly effective for the acylation. Homolytic alkylation of 6-chloro-2-cyanopyrazine 71 is performed by silver-catalyzed decarboxylation of alkanoic acids to provide 5-alkyl-substituted pyrazines 72 (Scheme 18) <1996CCC1109>. 

Some homolytic fragmentation reactions are driven by formation of small, stable molecules. Alkyl acyloxyl radicals (RCOp decarboxylate rapidly (fe > 1 x 10 s ) to give alkyl radicals, and even aryl acyloxyl radicals (ArCOp decarboxylate to aryl radicals with rate constants in the 10 s range." Azo radicals produced in the homolysis of azo initiators eliminate nitrogen rapidly. Elimination of carbon monoxide from acyl radicals occurs but is slow enough (fe 10" -10 such that the acyl radical can be trapped in a bimolecular process,... 

Initiation normally requires molecules with weak bonds to undergo homolytic cleavage to produce free radicals. Since bond homolysis even of weak bonds is endothermic, energy in the form of heat (A) or light (hv) is usually required in die initiation phase. However, some type of initiation is required to get any free-radical reaction to proceed. That is, you must first produce free radicals from closed-shell molecules in order to get free-radical reactions to occur. Benzoyl peroxide contains a weak 0-0 bond that undergoes thermal cleavage and decarboxylation (probably a concerted process) to produce phenyl radicals which can initiate free-radical chain reactions. 

From the practical point of view, alkylation of heteroaromatics with Barton decarboxylation of A-acyloxy-2-thiopyridones (17), prepared from carboxylic acids and Af-hydroxy-2-thiopyridone, is very useful, since it can be used for various kinds of carboxylic acids such as sugars and nucleosides [23-26]. This reaction comprises of the initial homolytic cleavage of the N-0 bond in A-acyloxy-2-thiopyridone to form an acyloxyl radical and PyS , (3-cleavage of the acyloxyl radical to generate an alkyl radical and C02, addition to the electron-deficient position of heteroaromatics by the alkyl radical to form the adduct, and finally, abstraction of a hydrogen atom from the adduct by PyS , as shown in eq. 5.10. 

Okada, Okamoto and Oda [97] have recently described a novel method of decarboxylation through a PET bond cleavage process in IV-acyloxyphthalimides. A photoexcited electron donor such as l,6-bis(dimethylamino)pyrene (BDMAP) transfers an electron to the phthalimide to produce an anion-radical that is protonated to form a radical prior to homolytic N—O bond cleavage. Bond... 

Another representative example of a homolytic perester fragmentation is given by the thermal decarboxylation of y9-peroxylactones such as 4,4,5,5-tetramethyl-l,2-dioxolan-3-one [569] cf. Eq. (5-63). 

A radical chain reaction initiated by visible light irradiation occurs with l,2-dihydro-2-thioxo-1-pyridinyl 4-alkenylcarbamates (PTOC carbamates) 1 in the presence of a carboxylic acid and a hydrogen-atom donor, preferably tert-butyl mercaptan after homolytic cleavage of the weak N—O bond and a decarboxylation step, the aminyl radical is protonated by the carboxylic acid and cyclizes to give a carbon radical. After reaction with tert-butyl mercaptan and a base the pyrrolidine 2 is obtained. In competition with trapping by tert-butyl mercaptan, or in the absence of this, the carbon radical can react with the PTOC carbamate 1 in a chain-propagating step to give the sulfide 3 (Section 7.2.5.9.)127. 

In the absence of the activating second carbonyl functionality, it is necessary to use more ingenious methods to produce the same net effect. These procedures more often than not involve radical reactions. Among them is the thermolysis of tert-butyl esters of peroxyacids 437, which are readily synthesized in a standard esterification of tert-butyl hydroperoxide with an acid chloride. Decarboxylation proceeds via an initial homolytic cleavage of the 0-0 bond, elimination of CO2, and reduction of the incipient alkyl radical by an added hydrogen atom donor such as 438 (Scheme 2.143). Examples showing the exceptional synthetic importance of this decarboxylation procedure will be presented later. 

The silver-catalyzed decarboxylation of a-oxo acids (carboxylic acids " ) by peroxy-disulfate leads to acyl " (alkyl radicals, which can effect selective homolytic acylation (alkylation of quinoxaline. This procedure is effective in monoacylation when multiple positions of high nucleophilic reactivity are available in the heterocyclic ring. " ... 

This second mechanism is less satisfactory because cyclization of the carboxy radical 5-40 is unlikely. Alkyl carboxy radicals are highly unstable and they decarboxylate so rapidly that fragmentation would be expected to occur faster than cyclization. The previous mechanism has at least two other advantages. First, it proceeds through the radical 5-41, which is stabilized by resonance with two phenyl substituents, so that hydrogen abstraction to form 5-41 should compete effectively with homolytic scission of the acyl bromide to form 5-40. Second, it will occur rapidly because it is a radical chain process the bromine radical formed in the cyclization of 5-41 regenerates 5-41 from the acyl hypobromite. 

Imidazoles normally undergo free-radical reactions at the 2-position. For example, homolytic free-radical alkylation of histidines and histamines yields 2,3-disubstituted histidines and histamines. In these reactions, the free radical was generated via silver-catalyzed oxidative decarboxylation of acids with peroxydisulfate 433 (Scheme 103) <2001BML1133>. 

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