Radical Cyclization Reactions

TLDR: Radical cyclization reactions are among the most powerful and versatile methods for the construction of mono-and polycyclic systems as discussed by the authors, which offer high functional group tolerance and mild reaction conditions combined with high levels of regio- and stereochemistry.

Abstract: Radical cyclization reactions are among the most powerful and versatile methods for the construction of mono- and polycyclic systems. The advantages these reactions offer to the synthetic organic chemist include high functional group tolerance and mild reaction conditions combined with high levels of regio- and stereochemistry. Furthermore, the recent progress in radical chemistry has led to the development of a broad range of very useful practical methods to conduct radical cyclization reactions. In general, radical cyclization reactions comprise three basic steps: selective radical generation, radical cyclization, and conversion of the cyclized radical to the product. For the generation of the initial radical a broad variety of suitable precursors can be employed, such as halides, thio- and selenoethers, alcohols, aldehydes and hydrocarbons. The cyclization step usually involves the intramolecular addition of a radical to a multiple bond. Most often carbon–carbon multiple bonds are employed; however, there are also examples known for the addition to carbon–oxygen and carbon–nitrogen bonds. Depending on the method employed, the cyclized radical is converted to the desired product by trapping with a radical scavenger, by a fragmentation reaction, or by an electron transfer reaction. The section Mechanism, Regio- and Stereochemistry provides an introduction to the key features of radical cyclization with a special emphasis on the factors controlling the regio- and stereochemistry. The section Scope and Limitations covers the different methods used to conduct radical cyclization. The basic principles of radical chemistry and general practical considerations when conducting radical cyclizations are not discussed in detail. Several excellent review articles and books dealing with these topics are available. Keywords: radical cyclization reactions; mechanism; regiochemistry; steroechemistry; small rings; scope; limitations; medium-sized rings; formation; monocycles; macrocyclizations; bi-cycles; polycycles; metal hydride; tin hydride; mercury hydride; fragmentation methods; thiohydroxamine; methods; Barton method; atom transfer; hydrogen atom transfer; halogen atom transfer; radical/radical coupling; redox methods; sequential reactions; experimental conditions; experimental procedures; comparison of methods; tabular survey