Radical cyclization reactions produce mono- or polycyclic products through the action of radical intermediates. Because they are intramolecular transformations, they are often very rapid and selective. Selective radical generation can be achieved at carbons bound to a variety of functional groups, and reagents used to effect radical generation are numerous. The radical cyclization step usually involves the attack of a radical on a multiple bond. After this step occurs, the resulting cyclized radicals are quenched through the action of a radical scavenger, a fragmentation process, or an electron-transfer reaction. Five- and six-membered rings are the most common products; formation of smaller and larger rings is rarely observed.
Three conditions must be met for an efficient radical cyclization to take place:
* A method must be available to generate a radical selectively on the substrate.
* Radical cyclization must be faster than trapping of the initially formed radical.
* All steps must be faster than undesired side reactions such as radical recombination or reaction with solvent.
Advantages: because radical intermediates are not charged species, reaction conditions are often mild and functional group tolerance is high and orthogonal to that of many polar processes. Reactions can be carried out in a variety of solvents (including arenes, alcohols, and water), as long as the solvent does not have a weak bond that can undergo abstraction, and products are often synthetically useful compounds that can be carried on using existing functionality or groups introduced during radical trapping.
Disadvantages: the relative rates of the various stages of radical cyclization reactions (and any side reactions) must be carefully controlled so that cyclization and trapping of the cyclized radical is favored. Side reactions are sometimes a problem, and cyclization is especially slow for small and large rings (although macrocyclizations, which resemble intermolecular radical reactions, are often high yielding).