4‐Exo‐Trig Radical Cyclization: A Promising Approach to Four‐Membered Rings

The 4‐exo‐trig radical cyclization represents a formidable challenge owing to the unfavorable thermodynamics associated with the formation of highly strained four‐membered rings. Stimulated by the explosive advancements of radical chemistry over the past decades, significant progresses have been made in this area, including the SmI₂‐mediated 4‐exo‐trig carbonyl‐alkene cyclization, n‐Bu₃SnH‐mediated 4‐exo cyclization of functionalized alkenes or alkynes, transition metal‐catalyzed 4‐exo‐trig ring closures, and visible light‐induced 4‐exo‐trig cyclization cascade, providing efficient protocols to overcome the inherent limitations and expand the synthetic utility of this methodology. Representative examples, reaction mechanism, scope and limitations, and synthetic applications are presented and discussed in detail. We believe that the systematic review of recent advances on 4‐exo‐trig radical cyclization will provide more insights in this field, and may enable further development of this cyclization process for the concise synthesis of four‐membered carbo‐ and heterocycles that are difficult to access via traditional methods.