The Barton decarboxylation is a radical reaction in which a carboxylic acid is converted to a thiohydroxamate ester (commonly referred to as a Barton ester). The product is then heated in the presence of a radical initiator and a suitable hydrogen donor to afford the decarboxylated product.[1][2] This is an example of a reductive decarboxylation. Using this reaction it is possible to remove carboxylic acid moieties from alkyl groups and replace them with other functional groups.[3][4] (See Scheme 1) This reaction is named after its developer, the British chemist and Nobel laureate Sir Derek Barton (1918–1998).
Scheme 1
Mechanism
The reaction is initiated by homolytic cleavage of a radical initiator, in this case 2,2'-azobisisobutyronitrile (AIBN), upon heating. A hydrogen is then abstracted from the hydrogen source (tributylstannane in this case) to leave a tributylstannyl radical that attacks the sulfur atom of the thiohydroxamate ester. The N-O bond of the thiohydroxamate ester undergoes homolysis to form a carboxyl radical which then undergoes decarboxylation and carbon dioxide (CO2) is lost. The remaining alkyl radical (R·) then abstracts a hydrogen atom from remaining tributylstannane to form the reduced alkane (RH). (See Scheme 2) The tributyltin radical enters into another cycle of the reaction until all thiohydroxamate ester is consumed.
N-O bond cleavage of the Barton ester can also occur spontaneously upon heating or by irradiation with light to initiate the reaction. In this case a radical initiator is not required but a hydrogen-atom (H-atom) donor is still necessary to form the reduced alkane (RH). Alternative H-atom donors to tributylstannane include tertiary thiols and organosilanes.[5] The relative expense, smell, and toxicity associated with tin, thiol or silane reagents can be avoided by carrying the reaction out using chloroform as both solvent and H-atom donor.[6]
It is also possible to functionalize the alkyl radical by use of other radical trapping species (X-Y + R· -> R-X + Y·).[7] The reaction proceeds due to the formation of the stable S-Sn bond and increasing aromaticity of the thiohydroxamate ester. There is also an overall increase in entropy due to the formation of gas which drives the reaction forward.
^Barton, D. H. R.; Crich, D.; Motherwell, W. B. (1985). "The invention of new radical chain reactions. Part VIII. Radical chemistry of thiohydroxamic esters; A new method for the generation of carbon radicals from carboxylic acids". Tetrahedron Letters. 41 (19): 3901. doi:10.1016/S0040-4020(01)97173-X.
^Barton, D. H. R.; Bridon, D.; Zard, S. Z.; Fernandaz-Picot, I. (1987). "The invention of radical reactions Part XV.1 Some mechanistic aspects of the decarboxylative rearrangement of thiohydroxamic esters". Tetrahedron. 43 (12): 2733. doi:10.1016/S0040-4020(01)86878-2.
^Ko, E. J.; Savage, G. P.; Williams, C. M.; Tsanaktsidis, J. (15 April 2011). "Reducing the Cost, Smell, and Toxicity of the Barton Reductive Decarboxylation: Chloroform as the Hydrogen Atom Source". Organic Letters. 13 (8): 1944–1947. doi:10.1021/ol200290m. PMID21438514.
^Saraiva, M. F.; Couri, M.R.C.; Hyaric, M.L. (2009). "The Barton ester free-radical reaction: a brief review of applications". Tetrahedron. 65 (18): 3563. doi:10.1016/j.tet.2009.01.103.
External links
Barton decarboxylation at organic-chemistry.org [1]
