Discovery and Development of Cyclobutanone-Based Free Radical Ring Expansion and Annulation Reactions

This article describes the discovery and recent progresses of cyclobutanonebased free radical ring expansion and annulation reactions. Mechanisms associated with these reaction processes are also discussed. Ring expansion reactions rely on selective β- scission of alkoxy radicals generated from the cyclization of carbon radicals onto carbonyls. Exo-substituted cyclobutanones are employed to construct cis-fused seven- and eight-membered rings, spiro-annulated medium rings, large rings, and cyclopropanecontaining compounds. Endo-substituted cyclobutanones can undergo tandem rearrangements to produce bridged rings. The cyclization of dichlorocyclobutanones followed by TMSI-induced ring opening is another ring expansion strategy for the construction of some novel ring systems. Cyclobutanones used for free radical reactions are readily prepared by well-established [2 + 2] cycloadditions of ketenes with various olefins.