Decarboxylative iodination

Decarboxylativehalogenation (12,417). The Hunsdiecker reaction is not useful for aromatic acids, but decarboxylative halogenation of these acids can be effected in useful yield by radical bromination or iodination of the thiohydroxamic esters, as reported earlier for aliphatic acids.1 Thus when the esters 2 are heated at 100° in the presence of AIBN, carbon dioxide is evolved and the resulting radical is trapped by BrCCl3 to provide bromoarenes (3). Decarboxylative iodination is effected with iodoform or methylene iodide as the iodine donor. 

Pyridine, treated with iodine in the vapor phase, gave only poor yields of 3,5-di- and penta-iodopyridines (57JCS387). Decarboxylative iodination of the mercury(II) salt of nicotinic acid gave a 44% yield of 3-iodopyridine (83JOC3297). 

Using this methodology, iodocubanes are prepared by decarboxylative iodination in presence of 2,2,2-trifluoroiodoethane595. ortho-Bromobenzoic acid derivatives are prepared from phthalic acids (equation 69)596. 

Another cyclic system was also constructed from the 4-hydroxyproHne derivative 29, which was subjected to the decarboxylation-iodination protocol (Scheme 17). Allylation at C-1 followed by a radical-mediated allylation at C-2 and ring-closing metathesis provided the bicyclic ring system 30 known from many naturally occurring alkaloids. 

Scheme 17 A further example on the application of the decarboxylation-iodination protocol to the synthesis of bicyclic systems...

Electrophilic substitutions accompanied decarboxylation are induced by an electron-donating ort/jo-amino group (Equation (2)). Replacement of the carboxylic acid in 3-amino-5,6-dichloro-pyrazinecarboxylic acid (42 X = Cl) by a nitro group is accomplished by treatment with nitric acid in sulfuric acid, producing compound (43 X = N02) <83JHC1089>. Decarboxylative iodination of... 

An excellent alternative to the classical Hunsdiecker reaction and its variants, which totally avoids the use of heavy metal salts and potent electrophilic reagents, consists of the simple photolysis or thermolysis of Barton esters in refluxing bromotri-chloromethane for the bromides or tetrachloromethane for the chlorides [4], The analogous decarboxylative iodination can also be achieved using iodoform as the reagent in a benzene/cyclohexene solvent system (Scheme 5). For the cases of vinylic and aromatic acids, where the usual problems of chain efficiency are encountered, the addition of azobisisobutyronitrile (AIBN) is also required [10]. Nevertheless, since this method can operate on both electron-rich and electron-poor aromatic systems, and moreover does not suffer from the competitive electrophilic aromatic bromination found with electron rich aromatics under normal Hunsdiecker conditions, this route to synthetically useful aryl iodides and bromides should find widespread application. 

The PhI(OAc)2-l2 system has been used for the oxidative decarboxylation/iodination of carboxylic acids [120-123]. This reaction was employed in the efficient syntheses of enantiopure l-benzoyl-2(5)-7er7-butyl-3-methylperhydropyrimidin-4-one [120] and 2-substituted-5-halo-2,3-dihydro-4(//)-pyrimidin-4-ones [123],... 

The Hunsdiecker decarboxylative iodination is also a successful approach for the synthesis of iodoalkynes (Scheme 7.161 and Example 7.39) [172, 246]. The chemistry is... 

---