ringexpansion

Ring expansion is a class of chemical transformations in which a cyclic molecule is converted into a larger ring system. The process can proceed by oxidative insertion that cleaves a bond and inserts an atom into the ring, or by rearrangements that relocate a fragment within the molecule to generate a bigger ring. Ring-expansion reactions are used to access medium- to large-sized rings that are often difficult to form by direct cyclization, and they appear in both organic synthesis and natural product biosynthesis.

Two principal mechanistic themes are common. Oxidative ring expansion, exemplified by Baeyer–Villiger oxidation of cyclic ketones to lactones, inserts an oxygen adjacent to the carbonyl and migrates a substituent to yield a larger lactone. Classic examples include cyclobutanone to gamma-butyrolactone and cyclohexanone to epsilon-caprolactone. Rearrangement-driven expansion includes carbocation- or radical-induced rearrangements such as Wagner–Meerwein and semipinacol shifts, where a 1,2-shift enlarges the ring, often from bridged or fused precursors.

Examples and scope: Baeyer–Villiger oxidations illustrate routine ring enlargement, while more elaborate rearrangements enable access to seven- or eight-membered rings that are challenging to assemble directly. Applications span synthetic routes to medium- and large rings in natural products and pharmaceuticals. Limitations include competing ring contraction, the reliance on favorable migratory aptitude for the migrating group, and sometimes reduced thermodynamic favorability for larger rings; selectivity can be sensitive to substitution, solvent, and temperature.

See also: ring contraction; Baeyer–Villiger oxidation; Wagner–Meerwein rearrangement; semipinacol rearrangement.