Many methods in ester synthesis can also be applied to that of lactones. Lactonization competes with polymerization for longer hydroxy acids, or the strained βlactones. γLactones, on the other hand, are so stable that 4-hydroxy acids (R-CH(OH)-(CH)-COH) spontaneously cyclise.
In one industrial synthesis of oxandrolone the key lactone-forming step is an organic reaction - esterification.
In halolactonization, an alkene is attacked by a halogen via electrophilic addition with the cationic intermediate captured intramolecularly by an adjacent carboxylic acid.
Specific methods include Yamaguchi esterification, Shiina macrolactonization, Corey-Nicolaou macrolactonization, Baeyer–Villiger oxidation and nucleophilic abstraction.
The γ-lactones γ-octalactone, γ-nonalactone, γ-decalactone, γ-undecalactone can be prepared in good yield in a one-step process by radical addition of primary fatty alcohols to acrylic acid, using di-tert-butyl peroxide as a catalyst.
An alternative radical reaction yielding γ-lactones is the manganese-mediated coupling.