The position of equilibrium in both cyclic and acyclic systems may be predicted from the structures of the two equilibrating epoxides. In acyclic systems, these rules have been established:
* Greater substitution on the epoxide ring is favored.
* Among disubstituted epoxides, trans isomers are favored over cis isomers.
* Isomers with primary hydroxyl groups are favored.
* Electron-donating substituents on the epoxide are stabilizing and electron-withdrawing substituents are destabilizing.
Pyranosides are the most heavily studied cyclic systems. Studies of epoxide migration in pyranosides and other cyclic epoxy alcohols have revealed three generalizations:
* As in acyclic systems, greater substitution on the epoxide ring is favored.
* The favored isomer is the one with more pseudoequatorial substituents.
* Intramolecular hydrogen bonding and other through-space interactions do not play a role in equilibrium ratios.
Conformationally locked pyranosides reveal the thermodynamic preference of cyclic substrates for more pseudoequatorial groups.
Under aprotic conditions, nucleophilic opening of epoxide isomers can be achieved with hydrides or organocuprates. Nucleophilic attack generally takes place at the least substituted carbon, yielding the more substituted diol product.
Under protic conditions, opening at the least substituted position is also usually favored. Nucleophiles that may be used under protic conditions include phenols, secondary amines, azide anion, and sulfides.
Intermolecular nucleophilic trapping of a single epoxide isomer is difficult, as reaction of the epoxy alcohol with the electrophile is typically faster than migration. However, intramolecular electrophies are often effective for trapping a single epoxide isomer. For instance, a second nearby epoxide in the starting material of equation (9) is trapped by a single epoxide isomer, leading to a tetrahydrofuran.