Ferrier Reaction

The allylic rearrangement of tri-O-acetyl-D-glucal to the corresponding 2,3-unsaturated hemiacetal when heated under aqueous conditions was first reported in 1914 by German chemist Emil Fischer. However, it was the British chemist Robert Ferrier, who in the 1960s ultimately realized the synthetic utility of this reaction. Subsequently, the Lewis acid-promoted rearrangement of unsaturated carbohydrates has become known as the Ferrier reaction/rearrangement.

Commonly used Lewis acids include boron trifluoride etherate, tin tetrachloride, iodine, iron(III) chloride, and a mixture of trimethylsilyl trifluoromethanesulfonate and silver perchlorate.

In 1979, a second Ferrier rearrangement was identified. Labelled Type II, exocyclic enol ethers are converted to substituted cyclohexanones upon treatment with mercury(II) salts. This form of the rearrangement became synthetically important due to the precursors being readily available from carbohydrates, as well as the fact that the Lewis acids used in catalytic amounts allowed the presence of acid-sensitive functionalities.

The Ferrier reaction has been widely used in total synthesis campaigns, including the stereoselective total synthesis of the antimitotic alkaloid (+)-lycoricidine, which used the Type II Ferrier rearrangement for the synthesis of the optically active cyclohexanone fragment.