Barton decarboxylation procedure

More recently, radical additions to fluoroethenes have attracted attention. Eguchi et al. [125] applied the Barton decarboxylation procedure to add a range of alkyl radicals to l,l-dichloro-2,2-difluoroethene. Addition was regioselective and the terminal carbon could be hydrolysed to a carboxyl group with silver(I) mediation (Eq. 39). The fluoroalkene is effectively an equivalent for either difluoroacetyl anion or cation synthons, because the adding radical can be approached from either polarity manifold. 

The Barton decarboxylation procedure was used in the total synthesis of (-)-verrucarol by K. Tadano et al. The initially formed thiohydroxamic ester was decarboxylated to leave a methylene radical on the cyclopentyl ring, which was then trapped by molecular oxygen. Reductive work-up in the presence of f-BuSH finally provided the hydroxylated product. ... 

In some examples, the stereochemistry of radical reactions was controlled by chiral carbohydrate auxiliaries. As a radical counterpart to the ionic conjugate additions discussed above, Garner et al. [169] prepared carbohydrate linked radicals that were reacted with a,P-unsaturated esters. The radical precursor, the carboxylic acid 256, generated by the addition of ( Sj-methyl lactate to tri-O-benzyl-D-glucal and subsequent ester hydrolysis, was decarboxylated by Barton s procedure (Scheme 10.84) [170]. Trapping of the chiral radical 258 with methyl acrylate furnished the saturated ester 259 in 61% yield and with high diastereoselectivity (11 1). The auxiliary caused a preferential addition to the si-facQ of radical 258, probably due to entropic effects. The ester 259 was transformed in acceptable yield to the y-butyrolactone 261 by reductive removal of the thiopyridyl group followed by acid hydrolysis. 

Side-chain halogenated amino acid derivatives are reduced, deuterated, allylated and alkylated with stannanes and related reagents in free-radical processes [53]. Other side-chain functional groups may also be manipulated to produce amino acid radicals [8, 54-58], and, in particular. Barton decarboxylation of aspartate and glutamate derivatives has been applied in this manner (Scheme 8) [55]. Related procedures have been developed to generate amino acid radicals by dehydrox-ylation of hydroxy amino acid derivatives [56]. Hydroxy amino acid derivatives may also be converted to nitrate esters, from which the corresponding alkoxy radi-... 

The stereoselective total synthesis of (+)-epiquinamide 301 has been achieved starting from the amino acid L-allysine ethylene acetal, which was converted into piperidine 298 by standard protocols. Allylation of 297 via an. V-acyliminium ion gave 298, which underwent RCM to provide 299 and the quinolizidine 300, with the wrong stereochemistry at the C-l stereocenter. This was corrected by mesylation of the alcohol, followed by Sn2 reaction with sodium azide to give 301, which, upon saponification of the methyl ester and decarboxylation through the Barton procedure followed by reduction and N-acylation, gave the desired natural product (Scheme 66) <20050L4005>. 

Loss of a carbon atom from the precursor need not always result. Barton and Crich have introduced a related procedure based on the chemistry of mixed oxalates, an example of which is provided in Scheme 49.159 Double decarboxylation is involved in the decomposition of oxalate precursors, such as (39). Unfortunately, there are indications that this method may to be limited to tertiary alcohols one secondary alcohol derived mixed oxylate did not fragment completely to the alkyl radical. 

The decarboxylation of carboxylic acid via thiohydroxamate derivatives (often called Barton esters ) is an efficient procedure for the generation of radicals. When this reaction is performed in the presence of diphenyl diselenide, the corresponding selenides are obtained in excellent yield [Eq. (42)] [104]. For example, this reaction has been used for the preparation of AT,Se-acetals from a-aminoacids [105,106]. 

In addition to dehydroxylation, a useful protocol for decarboxylation has been developed. The procedure was introduced by Barton, using thiohydroxamic esters 9, prepared from activated carboxylic acids (RCOX) and the sodium salt of N-hydroxypyridine-2-thione. Simple thermolysis or photolysis of the esters (homolysis of the N—O bond) results in the production of alkyl radicals R, which can attack the sulfur atom of the thiocarbonyl group to propagate the fragmentation (4.9). 

Figure 10.23 Alternative halo-decarboxylation following the Barton procedure...

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