8 - Barton Decarboxylation Reaction with N-Hydroxy-2-thiopyridone

Abstract

The Barton decarboxylation reaction is very useful for organic synthesis. In the early 1980s, radical decarboxylation of O-acyl esters prepared from carboxylic acids and N-hydroxy-2-thiopyridone was first reported by Barton. This reaction does not require any toxic radical reagents such as Bu3SnH, and the decarboxylatively formed alkyl radicals, derived from the corresponding carboxylic acids, can be used for functional group conversion and C–C bond formations. Sodium salt of N-hydroxy-2-thiopyridine is commercially available, and its aqueous 40% solution is also available as sodium omadine for keeping microorganisms active. Free N-hydroxy-2-thiopyridone is a stable crystal or solid under protection from light. O-acyl esters of N-hydroxy-2-thiopyridone can be purified by flash column chromatography on silica gel. The esters are light-sensitive yellow solids or oil and have typically strong absorption in the range of 1800 cm–1 on the IR spectra. Under refluxing conditions in benzene or toluene, or by irradiation with a tungsten lamp (100–300 W) at room temperature, N–O bond cleavage of the O-acyl ester readily occurs to generate a carboxyl radical and a pyridine 2-thiyl radical. β-cleavage of the formed carboxyl radical rapidly occurs to form an alkyl radical and CO2 (the rate constant for β-cleavage of RCO•2 is approximately 109 s–1). The formed alkyl radical then reacts on the thiocarbonyl sulfur atom of O-acyl ester to generate alkyl 2-pyridyl sulfide and carboxyl radical again.