Discovery and development of cyclobutanone-based free radical ring expansion and annulation reactions

This article describes the discovery and recent progresses of cyclobutanone-based free radical ring expansion and annulation reactions. Mechanisms associated with these reaction processes are also discussed. Ring expansion reactions rely on selective beta-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 cyclopropane-containing 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.