Because many reagents exist for radical generation and trapping, establishing a single prevailing mechanism is not possible. However, once a radical is generated, it can react with multiple bonds in an intramolecular fashion to yield cyclized radical intermediates. The two ends of the multiple bond constitute two possible sites of reaction. If the radical in the resulting intermediate ends up outside of the ring, the attack is termed "exo"; if it ends up inside the newly formed ring, the attack is called "endo." In many cases, exo cyclization is favored over endo cyclization (macrocyclizations constitute the major exception to this rule). 5-hexenyl radicals are the most synthetically useful intermediates for radical cyclizations, because cyclization is extremely rapid and exo selective. Although the exo radical is less thermodynamically stable than the endo radical, the more rapid exo cyclization is rationalized by better orbital overlap in the chair-like exo transition state (see below).
Substituents that affect the stability of these transition states can have a profound effect on the site selectivity of the reaction. Carbonyl substituents at the 2-position, for instance, encourage 6-endo ring closure. Alkyl substituents at positions 2, 3, 4, or 6 enhance selectivity for 5-exo closure.
Cyclization of the homologous 6-heptenyl radical is still selective, but is much slower—as a result, competitive side reactions are an important problem when these intermediates are involved. Additionally, 1,5-shifts can yield stabilized allylic radicals at comparable rates in these systems. In 6-hexenyl radical substrates, polarization of the reactive double bond with electron-withdrawing functional groups is often necessary to achieve high yields. Stabilizing the initially formed radical with electron-withdrawing groups provides access to more stable 6-endo cyclization products preferentially.
Cyclization reactions of vinyl, aryl, and acyl radicals are also known. Under conditions of kinetic control, 5-exo cyclization takes place preferentially. However, low concentrations of a radical scavenger establish thermodynamic control and provide access to 6-endo products—not via 6-endo cyclization, but by 5-exo cyclization followed by 3-exo closure and subsequent fragmentation (Dowd-Beckwith rearrangement). Whereas at high concentrations of the exo product is rapidly trapped preventing subsequent rearrangement to the endo product Aryl radicals exhibit similar reactivity.
Cyclization can involve heteroatom-containing multiple bonds such as nitriles, oximes, and carbonyls. Attack at the carbon atom of the multiple bond is almost always observed. In the latter case attack is reversible; however alkoxy radicals can be trapped using a stannane trapping agent.