Isoxazolidines synthesis from oximes

Further examples of intramolecular 1,3-dipolar cycloadditions (cf. Section 10.21.9.2.2(ii)) include the synthesis of an isoxazolidine from nitrone 193 (Equation 128) <1997J(P1)1805>, and a pyrazolo heterocycle from the nitrile oxide generated in situ from the oxime 194 (Equation 129) <1999TL3535>. 

The same methodology was employed by Tiecco to effect the cyclizations of 0-allyl oximes 164 indicated in Scheme 25. Treatment of the intermediate iminium salt 165 with sodium borohydride affords M-alkyl isoxazolidines 166 [95]. Alternatively, 165 can be treated with water to produce M-unsubstituted isoxazolidines 167 [96]. This synthesis of M-alkyl isoxazolidines represents a valid alternative to that described in Scheme 23. Moreover, the present cyclization reaction is much more stereoselective than the cyclization of 0-allyl hydro-xylamines. In fact, when the methyl derivative 168 was employed, the two isomeric isoxazolidines 153 and 154 were obtained in a ratio of 95 5. The same two products were, in contrast, formed in a 1 1 ratio when the reaction was carried out starting from the corresponding 0-allyl hydroxylamines. Clearly, the steric requirements for the selenium-induced cyclization of the 0-allyl oximes are much greater than those for the corresponding 0-allyl hydroxylamines. 

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