Cyclobutylidenecyclopropane: New Synthesis and Use in 1,3-Dipolar Cycloadditions - A Direct Route to Spirocyclopropane-Annelated Azepinone Derivatives

Cyclobutylidenecyclopropane (7) was prepared in multigram quantities by a new three-step sequence starting from ethyl cyclobutanecarboxylate (4) (39% overall yield). 1,3-Dipolar cycloadditions of phenyl- (9), pyridyl- (10), and the newly prepared (four steps, 43% overall yield) spirocyclic nitrone 11 onto 7 resulted in the regioselective formation of the corresponding adducts 15-17, with the spirobutane moieties adjacent to the oxygen atom in the oxazolidine rings, in 52, Cyclobutylidenecyclopropane (7) was prepared in multigram quantities by a new three-step sequence starting from ethyl cyclobutanecarboxylate (4) (39% overall yield). 1,3-Dipolar cycloadditions of phenyl- (9), pyridyl- (10), and the newly prepared (four steps, 43% overall yield) spirocyclic nitrone 11 onto 7 resulted in the regioselective formation of the corresponding adducts 15-17, with the spirobutane moieties adjacent to the oxygen atom in the oxazolidine rings, in 52, 84, and 48% yields, respectively. Under flash vacuum pyrolysis conditions, the cycloadducts 15-17 underwent thermal rearrangement with opening of the four-membered ring, to afford the spirocyclopropanated azepinones 21-23 in 32, 30, and 19% yields, respectively. In the case of 17, the indolizidinone 25 was also isolated (13% yield). Mechanistically this rearrangement is interpreted in terms of a cyclobutylmethylto- penten-5-yl radical rearrangement.