Cyclizations

Cyclization refers to a chemical process in which a linear or branched precursor closes upon itself to form a ring, typically by forming one or more new covalent bonds. Most cyclizations are intramolecular, joining two reactive ends of the same molecule to give a cyclic product. The outcome depends on tether length, substituents, and ring strain; shorter tethers favor smaller rings, while longer tethers can lead to larger rings or macrocycles. In synthetic settings, dilution and choice of solvent help minimize competing intermolecular reactions.

Cyclizations occur through diverse mechanisms. Pericyclic cyclizations such as electrocyclizations and cycloadditions follow orbital symmetry rules and can be driven thermally or photochemically. Radical cyclizations begin with a radical on a tether and proceed via rapid intramolecular C–C bond formation. Ionic cyclizations use nucleophiles or electrophiles to form rings, often in tandem with rearrangements. Transition-metal catalysis enables efficient cyclizations, including ring-closing metathesis to form cycloalkenes and various intramolecular couplings that forge heterocycles and carbocycles.

Ring size favorability: five- and six-membered rings are generally easiest to form; three- and four-membered rings incur substantial strain. Larger rings can be obtained with careful design but may require activation or templating. Applications include the biosynthesis of natural products, medicinal chemistry, and polymer science, where cyclizations are common steps in constructing core frameworks.