Epoxide Migration (Payne Rearrangement) and Related Reactions

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. Keywords: mechanism; stereochemistry; epoxide migration; thermodynamics; kinetic control; epoxide migration; payne rearrangement; nonbasic conditions; nucleophilic trapping; electrophilic trapping; aza-payne rearrangements; thia-payne rearrangements; scope; limitations; equilibration; acyclic systems; nucleophilic opening; three-step equivalent sequence; diol-sulfide method; opening method; synthesis; chirality inversion; cyclic systems; comparison of methods; asymmetric dihydroxylation; stereochemical reaction sequence; neighboring group assistance; cyclic sulfate; c-3 sulfonate; diol-sulfonate; titanium mediated; lithium salt induced