Chameleon thermal behavior of cycloadducts of nitrones to methyl 2-chloro-2-cyclopropylidene- and 2-chloro-2-spiropentylideneacetates

Methyl 2-chloro-2-cyclopropylideneacetate (2) and its spiropentane analogue 3 cycloadd to dihydroisoquinoline N-oxide (9), pyrroline N-oxide (12), and C-phenyl-N-methylnitrone (16) to give 5-spirocyclopropaneisoxazolidines in good yields (58-93%). The thermal behavior of the 5-spirocyclopropaneisoxa zolidines is rather differentiated, depending strongly on the constitution of the nitrone and the solvent. As nitrone 9 has the tendency to undergo cy cloreversion reactions, the ketoamide rearrangement products 20 and 21 from its cycloadduct derive from the thermodynamically favored 4-spirocycloprop aneisoxazolidine regioisomers formed after the cycloreversion process. In D MSO as solvent different rearrangement processes take place, leading to ben zoindolizinones in modest yields (15-21%). The cycloadducts from 12 and 16 undergo a cyclopropyl to cyclobutyl ring enlargement facilitated by the pre sence of a chlorine substituent on the carbon a to the spirocyclopropane ri ng. Whereas these compounds from nitrone 16 demonstrated an unusual stabili ty, those from nitrone 12 undergo a cascade rearrangement to yield indolizi none derivatives 34, 35 cleanly (73-83% yield). This overall transformation offers a new method for the synthesis of the indolizine skeleton.