Cycloaddition and Annulation Reactions with Donor‐Acceptor Cyclobutanes

Abstract Donor‐acceptor (DA) cyclobutanes are emerging as valuable synthetic intermediates due to their ring strain and polarized C─C bonds, which allow for 1,4‐dipolar reactions. This review highlights recent advances in DA cyclobutane reactivity, particularly (4+2) annulation reactions used to construct six‐membered rings. It discusses the development of annulations involving carbon‐, oxygen‐, and nitrogen‐based donor groups, initiated by Lewis acid catalysis, Brønsted acid, and electrocatalysis. Additionally, enantioselective transformations and the challenges associated with diester acceptor motifs and their replacement with monoester groups are presented. Overall, this review provides a comprehensive overview of annulation reactions with donor‐acceptor cyclobutanes and emphasizes their potential in stereoselective syntheses of functionalized carbo‐ and hetero‐cycles embedded in complex natural product frameworks.