Transition-Metal-Free Decarboxylative Bromination of Aromatic Carboxylic Acids

The brominative decarboxylation  reaction was demonstrated over a hundred and fifty years ago by Borodin (the famous composer, whose day job was as Professor of Organic Chemistry) and later developed by Hunsdiecker, whose name the reaction now bears. From an industrial viewpoint the transformation would be useful but the need to have a stoichiometric silver salt present means the reaction is costly unless the salt can be recycled and reused. More recently the groups of Glorius (Chem-Eur J, 2016, 22 9971-4) and Li (Org Lett, 2017, 19, 1634-7) have  extended the reaction from aromatic to aliphatic carboxylic acids using silver or iridium catalysts.

Now the group of Larrosa at the University of Manchester, UK, has built on their recent decarboxylative iodination process to find conditions where aromatic carboxylic acids can be decarboxylatively brominated (ArCO2H to ArBr;  Chem Sci, 2018, 9, 3860-5).Treatment of a variety of aromatic carboxylic acids, in the presence of potassium phosphate (1 eq) in acetonitrile at 100 deg C for 16h with tetrabutylammonium tribromide gives yields of 70-99% of the corresponding bromo-aromatic. The reaction was extended to heterocycles including pyridines, indoles, benzothiophenes, thiazoles etc. (though sometimes dibromination occurs!) and promises to be a very useful transformation for those heterocycles which are difficult to brominate directly.

Whereas the Hunsdiecker reaction is proposed to proceed via a radical mechanism, evidence suggests that this new metal free process proceeds in a concerted fashion via a four membered ring transition state from the intermediate ArCO-O-Br intermediate.