Barton Radical Decarboxylation Reaction

Conversion of a carboxylic acid to a thiohydroxamate ester, followed by heating the product in the presence of a suitable hydrogen donor such as tri-n-butyltin hydride, produces a reductive decarboxylation. This sequence of reactions is called the Barton decarboxylation reaction and may be used to remove a carboxylic acid and replace it with other functional groups. 

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.  

A doubie Barton radicai decarboxyiation was utilized during the one-step total synthesis of tyromycin A and its analogs by M. Samadi et al. The b/s-thiohydroxamic ester was irradiated in the presence of citraconic anhydride, and the resulting product was stirred for two days at room temperature to ensure complete elimination. 

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Related reactions Barton radical decarboxylation reaction ... 

Barton, D. H. R., Zard, S. Z. A novel radical decarboxylation reaction. Janssen Chim. Acta 1986,4, 3-9. 

Zhu, J., Klunder, A. J. H., Zwanenburg, B. Synthesis of 6-functionalized tricyclodecadienones using Barton s radical decarboxylation reaction. Generation of tricyclo[5.2.1.0 ]decatrienone, a norbornene annulated cyclopentadienone. Tetrahedron 1995, 51, 5099-5116. 

In most other cases, however, the diene system simply becomes too unreactive to participate in radical chain reactions. Thus, the reductive decarboxylation of ester 7 by Barton-POC ester methodology20 or as the selenoester21 gives the reduced product 8, cleanly without any trace of product in which the diene system has participated in the reaction (equation 4)20-21. 

The allyl alcohol trapping reaction was further studied by Crich and coworkers, who applied the Barton decarboxylation reaction as radical source,... 

Hexenyl radicals cyclize to cyclopentylmethyl radicals (see Volume 4, Chapter 4.2). Thus radical decarboxylation of 6-heptenoic acids, by whatever means, usually results in die formation of five-mem-v beied rings. Although this fact had been appreciated previously it is only recendy, widi the advent of the 0-acyl thiohydroxamates, that it has been exploited from a syndietic point of view. An example is provided by the synthesis of bicyclo[4.3.0]proline derivatives from aspartic acid carried out by the Barton group (equation 51). It will be noted that activation of die C—C double bond acting as a radical trap is not necessary in these intramolecular reactions. 

Taddei [7] has studied the use of the Barton decarboxylation reaction in solid-phase chemistry. FeasibiUty studies began with the preparation of simple immobihzed Barton ester 37 from Wang resin-derived acid 36 (Scheme 8). Irradiation of 37 followed by acid cleavage gave 38 in good overall yield. Attempts to prepare bromide 39 by interception of the intermediate radical... 

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