Cyclobutylidenecyclopropane: New synthesis and use in 1,3-dipolar cycloadditions - A direct route to spirocyclopropane-annulated azepinone derivatives

Cyclobutylidenecyclopropane (7) was prepared in multigram quantities by a n ew three-step sequence starting from ethyl cyclobutanecarboxylate (4) (39% overall yield), 1,3-Dipolar cycloadditions of phenyl- (9), pyridyl- (10), a nd the newly prepared (four steps, 43% overall yield) spirocyclic nitrone 1 1 onto 7 resulted in the regioselective formation of the corresponding addu cts 15-17, with the spirobutane moieties adjacent to the oxygen atom in the oxazolidine rings, in 52, 84, and 48% yields, respectively. Under flash va cuum pyrolysis conditions, the cycloadducts 15-17 underwent thermal rearran gement with opening of the four-membered ring, to afford the spirocycloprop anated azepinones 21-23 in 32, 30, and 19% yields, respectively. In the cas e of 17, the indolizidinone 25 was also isolated (13% yield). Mechanistical ly this rearrangement is interpreted in terms of a cyclobutylmethyl-to-pent en-5-yl radical rearrangement.