Ring strain, isoxazolidines

If this reaction is assumed to be thermoneutral (neglecting the effects of heteroatoms on conformation and on ring strain), the predicted enthalpy of formation of isoxazolidine is 11.6 kJmoC. Admitting that it may be simplistic, as well as simple, to have assnmed thermoneutrality, we take these two predicted values of 6 and 11.6 kJ moH to be in satisfactory agreement and choose an average value of 9 kJmol for the enthalpy of formation of isoxazolidine. 

These authors also showed that the indolizidine skeleton can be prepared from cyclopropyl dipolarophiles (Scheme 1.16). The cycloaddition of alkyhdenecyclo-propanes 67 with various nitrones (e.g., 68) afforded the expected isoxazolidine adducts 69 and 70, commonly forming the C(5) substituted adducts 70 (97,105-108) predominantly but not exclusively (109-111). Thermally induced rearrangement of the spirocyclopropyl isoxazolidine adduct 70 afforded the piperidinones 71 (107,108). These authors propose reaction via initial N—O bond homolysis of 70 to diradical 72 followed by ring expansion through relief of the cyclopropyl ring strain forming the carbonyl of a second diradical intermediate 73, which cyclizes to afford the isolated piperidinone 71. 

Isoxazolidines with a highly strained cyclopropane ring spiro-fused at the 5-position show a special reactivity and can be converted into different classes of azaheterocycles depending on the substitution pattern and the reaction conditions <2004M649>. 

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