Payne rearrangement

What is Payne rearrangement?

The reaction involving the stereospecific migration of 2,3-epoxy alcohols into isomeric epoxy alcohols with an inversion of configuration at the C-2 carbon of the original epoxide ring. This reaction was initially referred to as a β-oxanol rearrangement. It was first reported by Kohler et al. in 1931 and its mechanism was proposed by Angyal and Gilham in 1957. However, after Payne’s extensive study in 1962, it is now commonly known as the Payne rearrangement or Payne epoxide migration, and ocasionally Payne reaction.

Payne rearrangement - general reaction scheme - Payne epoxide migration - Payne reaction
Payne rearrangement

R = alkyl, aryl (see list of acronyms)

The Payne rearrangement is reversible, and the equilibrium generally favors the more substituted epoxide isomer. The solvent plays an important role in this reaction, and the choice of solvent can affect the yield of the product.

For example, treating the epoxy alcohol with sodium hydride in THF may not yield the expected product, but treating it with NaOH in aqueous solution will. The rearrangement between 2,3-epoxy amine and aziridine alcohol under similar conditions is known as the aza-Payne rearrangement, and the migration between 2,3-epoxy thiol and thiirane alcohol is referred to as the thia-Payne rearrangement.

However, unlike the normal Payne rearrangement, the aza-Payne and thia-Payne rearrangements have the potential to form different products. The forward aza- and thia-Payne rearrangements are favored by complexation with Lewis acid, such as BF3, AlMe3, and TMSOTf. The aza-Payne rearrangement followed by a ring opening has been used for the preparation of hydroxyethylamine dipeptide isostere (HDI) structures.

The use of the Payne rearrangement is widespread in organic synthesis, particularly in combination with the ring-opening of the resulting epoxide with various nucleophiles.