Claisen Rearrangement

In 1912, German chemist Rainer Ludwig Claisen published the rearrangement of allyl phenyl ethers to their corresponding C-allyl phenols, as well as the conversion of the O-allylated acetoacetic ester to its C-allylated isomer upon treatment with ammonium chloride, followed by distillation. The thermal rearrangement of allyl vinyl ethers to their corresponding γ,δ-unsaturated carbonyl compounds has since been known as the Claisen rearrangement.

The precursor allyl vinyl ethers can be prepared in several ways, such as from the allylic alcohols via mercuric ion-catalyzed exchange with ethyl vinyl ether, or by Wittig olefination of allyl formates and carbonyl compounds.

A modification is the Johnson-Claisen rearrangement, in which an allylic alcohol is heated with trialkyl orthoacetate under mildly acidic conditions to produce a γ,δ-unsaturated ester.

The Claisen rearrangement has been used in many successful total synthesis campaigns, including K.C. Nicolaou and colleagues' synthesis of 1-O-methylforbesione via tandem Claisen rearrangement/Diels-Alder reactions.