Radical quinoline-2-carboxylates

Interestingly, when carboxylate derivatives are considered, the SET process is irreversible (due to release of CO ) and the degradation rate is maximum when this mechanism is supposed to be operating. On the contrary, when a radical cation or a semiquinone intermediate is invoked, as in the case of quinoline or hydroxy-methoxy-chloro benzenes [60,64], the rate is minimum due to the back reaction. 

Alkyl radicals for such reactions are available from many sources such as acyl peroxides, alkyl hydroperoxides, particularly by the oxidative decarboxylation of carboxylic acids using peroxy-disulfate catalyzed by silver. Pyridine and various substituted pyridines have been alkylated in the 2-position in high yield by these methods. Quinoline similarly reacts in the 2-, isoquinoline in the 1-, and acridine in the 9-position. Pyrazine and quinoxaline also give high yields of 2-substituted alkyl derivatives <74AHC(16)123). 

Radical nucleophile oxidation based on one-electron oxidation, known as the Minisci reaction, is employed for the functionalization of /V-heterocycles with acidic hydrogen peroxide in the presence of iron(II) salts (Figure 3.112).472 A range of A-heterocycles (pyridines, pyrazines, quinolines, etc.) which are activated towards attack by nucleophilic radicals when protonated are suited to this chemistry. The Minisci reaction is suitable for the preparation of carboxylic amides (from formamide), carboxylic esters (from pyruvic esters via a hydroxyhydroperoxide), aldehydes (from 1,3,5-trioxane) and alkylated pyridines (either from carboxylic acids or from alkyl iodides in dimethyl sulfoxide).473 The latter reaction uses dimethyl sulfoxide as the source of methyl radical (Figure 3.112). 

The easy follow-up oxidation of intermediates at the electrode is illustrated by the oxidation of trimethylacetic acid. The decarboxylation of carboxylate by peroxidisulfate/ Ag(I) is a good way to simulate the Kolbe anodic oxidation in a homogeneous solution [34]. The oxidation of trimethylacetic acid with S20g /Ag(I) in the presence of protonated quinoline affords by reaction of the intermediate t-butyl radicals in an SRAr substitution a high yield of r-butylated product [Eq. (2)] [35]. 

Photolysis of alkyl carboxylic acids with lead (IV) acetates can generate alkyl radicals by decarboxylation and this has been used to place an aryl group on a cubane. Thus photolysis of a benzene solution of the cubane dicarboxylic acid (136) containing lead tetraacetate yields the phenyl cubane (137). A mechanistically related procedure uses iodosobenzene diacetate for the photochemical arylation of cyclohexane carboxylic acid with heteroaromatics such as pyridine or quinoline. 

The Minisci reaction has successfully been applied for the alkylation of various heteroarenes, i. e. lepidine, pyrazine, quinoline and quinoxaline [2e, 2g, 10]. Organic compounds such as alkanes, alkenes, carboxylic acids, esters, amides, amines, alcohols, ethers, aldehydes, ketones, halides etc. have been successfully used as radical precursors in the Minisci reaction. A good overview of the different methods which have been applied to generate the alkyl radicals in these processes is summarized in [10b]. 

A well documented radical addition is given by the a-alkylation of quinolines which proceeds with radicals generated in a variety of different ways. As a photoreaction driven by visible light with a carboxylic acid as the radical source the reaction is highly accelerated by Fe2(S04)3 in diluted... 

In general, the PET decarboxylation of carboxylic acids exhibits low product selectivity, due to the subsequent radical coupling in solution however, the PET reaction between potassium propionate and the methyl ester of N-methyltrimellitic acid imide is highly regioselective to the para-addition product. This contrasts with other intramolecular and intermolecular PET reactions of quinolinic acid imides, which do not show a high degree of regioselectivity (Scheme S)." ... 

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