Epoxide Migration (Payne Rearrangement) and Related Reactions

Abstract

Under a variety of basic conditions, 2,3‐epoxy alcohols rearrange with inversion at C‐2. The reaction, originally referred to in the literature as the β‐oxanol rearrangement, is now exclusively referred to as epoxide migration or Payne rearrangement. Epoxide migration is reversible, often leading to a mixture of epoxy alcohol isomers. Furthermore, in the presence of hydroxide or other nucleophiles, in situ opening of the equilibrating species may be observed. When such opening is desired, epoxide migration becomes a powerful method for the introduction of functionality into a substrate containing a 2,3‐epoxy alcohol moiety. However, when opening is not desired, epoxide migration can become a significant problem. The epoxide migration process lends itself to other synthetically useful manipulations. For example, the anionic equilibrating species may also be trapped with electrophiles such as alkyl and silyl halides, alkyl sulfonates, and epoxides. Electrophilic trapping may be inter‐ or intramolecular, and has been used as a means of delivering functionality to either C‐2 or C‐3 selectively. The intent of this chapter is to provide a comprehensive review of epoxide migration, including factors influencing the equilibrium position, conditions leading to in situ epoxide opening, and examples of electrophilic trapping. The reaction is discussed in relation to its utility as a synthetic method as well as its prevention as an unwanted side reaction. Related rearrangements in which either the epoxide or hydroxy oxygen has been replaced with nitrogen or sulfur have also been studied. These reactions, referred to in the literature as aza‐Payne and thia‐Payne rearrangements, respectively, are comprehensively included in this chapter as well. For the purposes of this discussion, the term “forward” aza‐Payne rearrangement refers to the direction of reaction leading from oxirane to aziridine. Similarly, “forward” thia‐Payne rearrangement refers to the direction of reaction leading from oxirane to thiirane. In the case of aza‐Payne rearrangements, both forward and reverse reactions have been effected, and in this chapter the term “reverse” aza‐Payne rearrangement refers to reactions leading from aziridine to oxirane. Epoxides have long been considered important in the chemistry of carbohydrates, and epoxide migration in the context of carbohydrate chemistry has been discussed in several reviews. In addition, particularly since discovery of the catalytic asymmetric epoxidation of allylic alcohols and the rise in importance of enantiomerically enriched acyclic epoxy alcohols, epoxide migration with in situ opening in acyclic systems has been much studied. The tabular survey summarizes the literature of epoxide migration and related reactions, including equilibration, in situ opening and trapping, aza‐Payne rearrangements, and thia‐Payne rearrangements, from 1931 to 1999. Reports referring to reactions involving addition at C‐1 or C‐3 without inversion of stereochemistry at C‐2 as “Payne rearrangements” are not covered in this review.

Activation of PKC supports the anticancer activity of tigilanol tiglate and related epoxytiglianes

“…2C, Supplementary Information data file S1, S2). Whereas three isolates were observed to have undergone a Payne rearrangement 28,29 , presumably induced by nucleophilic attack (S N 2) by the adjacent hydroxyl group at C5, which resulted in epoxide formation at C5 and C6 (i.e. EBC-161, -167 and -211) (Fig.…”

Hyperconjugation

“…The presence of such intermediates leads to retention of configuration and efficient transfer of chirality in their respective ring contraction or expansion reactions . Topologically similar transformations are the key mechanistic steps of Payne and aza‐Payne rearrangements . In addition to the anchimeric assistance in the formation of bridged cationic intermediates, there is clear structural and spectroscopic evidence for homoanomeric interactions in neutral ground state molecules at their energy minimum conformations …”

Enantioselective synthesis of (R)-isocarvone from (S)-perillaldehyde

“…Attempts with a number of variations in the reaction conditions failed to significantly improve this ratio. 31 It is worth mentioning that the epoxy alcohol migration reaction proceeded in a stereoselective manner and only one stereoisomer was obtained. This stereoselectivity is in agreement with the deprotonation of the epoxy alcohol 10 to form an alkoxide, followed by direct intramolecular displacement at the adjacent epoxide center.…”