Cyclobutanones and Cyclobutenones in Nature and in Synthesis [New Synthetic Methods(71)]

The chemical reactivity of cyclobutanones and cyclobutenones is considerably different from that of cyclic ketones with larger rings; this is due to their ring strain of ca. 25 kcal/mol. Detailed knowledge regarding the influence of this ring strain on regio‐, chemo‐ and stereoselective transformations of four‐membered ring ketones is of particular importance. While several reactions, such as the Baeyer–Villiger reaction, the Beckmann and Favorskii rearrangements and cine‐substitution often proceed in a manner specific to four‐membered rings, other reactions such as the facile ring‐opening by nucleophiles, the rearrangement to tropolones, the thermal [2+2]‐cycloreversion, the isomerization to vinylketenes and the photochemical formation of oxacarbenes are rather specific to cyclobutanones and cyclobutenones. The remarkable selectivity and the excellent yields of such transformations, which are favored or caused by ring strain as the inherent driving force, offer the synthetic chemist fascinating possibilities for the development of new strategies for the synthesis of natural products and biologically active compounds. At first academic curiosities, four‐membered ring compounds have emerged as excellent tools of organic synthesis during the past few decades. Substituted cyclobutanones and cyclobutenones are among the most accessible cyclobutane derivatives. Their chemical reactivity differs markedly from that of larger cyclic ketones; a major reason is the high ring strain of about 25 kcal mol‐1. A detailed knowledge of the influence of this ring strain on the regio‐, chemo‐, and stereoselective transformations of four‐membered ring ketones is of special value.