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4-Alkoxycarbonyl and aminocarbonyl-substituted isoxazoles undergo conjugate reduction to give delta2-isoxazolines on treatment with sodium borohydride and sodium trifluoroacetoxyborohydride, respectively. They are also alkylated at C5 through sonication with secondary and tertiary alkyl iodides in the presence of zinc dust and copper(I) iodide. These reactions are analogous to those observed with acrylates and acrylamides. The behavior is characteristic of the 4-substituted isoxazoles but not the 5-substituted regioisomers. The reductions of 4,5-disubstituted isoxazoles and the C5 alkylations of 4-substituted isoxazoles generally afford trans-4,5-disubstituted isoxazolines. Incorporating chiral auxiliaries into the alkoxycarbonyl group maintains this relative stereoselectivity. It does not provide significant levels of asymmetric induction in the reductions, but the alkylations occur with good levels of stereocontrol at both C4 and C5. Because both enantiomers of the auxiliaries are available, this provides access to either enantiomer of the products, in 93 to > or = 98% de. The methodology, therefore, provides a complementary approach to nitrile oxide cycloadditions to alkenes for the asymmetric synthesis of delta2-isoxazolines.

This paper is dedicated to Professor James M. Coxon (Jim) on the occasion of his 65 th birthday, and in recognition of his many contributions to chemistry Abstract Four spiroisoxazolines have been prepared, by cycloaddition of aceto-, pivalo-, benzo-and mesito-nitrile oxide with 3-methylenequinuclidine. The reactions were completely regioselective, within the limits of detection. None of the isoxazolines showed significant inhibition of acetylcholinesterase.

Isoxazole derivatives R 02404-Alkoxycarbonyl-and Aminocarbonyl-Substituted Isoxazoles as Masked Acrylates and Acrylamides in the Asymmetric Synthesis of ∆ 2 -Isoxazolines. -It is found that isoxazoles substituted at the 4 position with alkoxycarbonyl or aminocarbonyl groups undergo unusual conjugate reduction and alkylation to afford ∆ 2 -isoxazolines. Thus, they can be regarded as masked acrylates and acrylamides. The reactions generally proceed with excellent trans-selectivity. The alkylation of chiral isoxazoles also occurs with a high level of asymmetric induction. Asymmetric reduction, however, is inefficient. Additionally, it is found that regioisomeric 5-functionalized isoxazoles cannot be transformed into ∆ 2 -isoxazolines. -(LEE, C. K. Y.; HERLT, A. J.; SIMPSON, G. W.; WILLIS, A. C.; EASTON*, C.