| Abstract
| - 4-Alkoxycarbonyl and aminocarbonyl-substituted isoxazoles undergo conjugate reduction to give Δ2-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 presenceof zinc dust and copper(I) iodide. These reactions are analogous to those observed with acrylates andacrylamides. The behavior is characteristic of the 4-substituted isoxazoles but not the 5-substitutedregioisomers. The reductions of 4,5-disubstituted isoxazoles and the C5 alkylations of 4-substitutedisoxazoles generally afford trans-4,5-disubstituted isoxazolines. Incorporating chiral auxiliaries into thealkoxycarbonyl group maintains this relative stereoselectivity. It does not provide significant levels ofasymmetric induction in the reductions, but the alkylations occur with good levels of stereocontrol atboth C4 and C5. Because both enantiomers of the auxiliaries are available, this provides access to eitherenantiomer of the products, in 93 to ≥98% de. The methodology, therefore, provides a complementaryapproach to nitrile oxide cycloadditions to alkenes for the asymmetric synthesis of Δ2-isoxazolines.
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