Hunsdiecker Reaction

In 1861, Russian chemist Alexander Borodin prepared methyl bromide from silver acetate in a combined decarboxylation and halogenation reaction. Building on this work in 1939, German chemists Cläre and Heinz Hunsdiecker demonstrated that when silver salts of carboxylic acids react with a halogen, an alkyl halide is formed which possesses one fewer carbon atoms than the substrate. Subsequently, this reaction became known as the Hunsdiecker reaction or sometimes the Hunsdiecker–Borodin reaction, referencing Borodin’s earlier work.

The silver salts are usually prepared from the corresponding carboxylic acid by treatment with silver oxide. However, in order to obtain high yields, the salts must be pure and extremely dry, which can be challenging to achieve. Subsequently, several modifications were introduced, including the use of acid chlorides as a more reactive functional group and the use of thallium(I) carboxylates in place of silver. The Cristol-Firth modification employs an excess of red mercuric oxide and one equivalent of the halogen, while the Suarez modification treats the acid with hypervalent iodine reagents.

Another derivation known as the Barton modification exploits the thermal or photolytic decomposition of thiohydroxamate esters in halogen donor solvents. This modification is compatible with almost all functional groups, and was used in the asymmetric total synthesis of antimitotic agents (+)- and (-)-spirotryprostatin B.