cyclization

Cyclization, or cyclisation, is a chemical reaction in which two ends of a chain react to form a ring, either within a single molecule (intramolecular cyclization) or by joining separate chains (intermolecular ring formation). True cyclization is usually intramolecular and is a key step in constructing carbocycles and heterocycles.

Mechanisms vary widely. Pericyclic cyclizations, such as electrocyclizations and cycloadditions, proceed via concerted bonding changes. Radical cyclizations involve a radical intermediate that forms a ring intramolecularly. Nucleophilic or electrophilic cyclizations include intramolecular aldol and Dieckmann condensations, lactonizations, and lactamizations that yield cyclic esters and amides. Intramolecular Williamson ether synthesis forms cyclic ethers. Ring-closing metathesis and related metal-catalyzed processes enable efficient formation of alkenyl rings and heterocycles. Photochemical cyclizations also contribute to natural-product formation.

Factors: Ring size strongly influences cyclization. Five- and six-membered rings are generally favored due to lower strain and favorable entropy, while larger rings face higher entropic costs and slower rates. Dilution, tether length, and conformational constraints affect reaction efficiency. Catalysts or reagents (acids, bases, Lewis acids, or transition metals) can promote specific cyclizations, and conditions are often tuned to minimize competing intermolecular reactions.

Applications: Cyclization is central to natural-product synthesis, pharmaceutical discovery, and polymer chemistry, enabling macrocycles, lactones, lactams, and cyclic ethers. It is also used to generate cyclic peptides and other constrained motifs.