Asymmetric Synthesis of Δ ²-Isoxazolines

Significance

The synthesis of di- and trisubstituted Δ²-isoxazolines from isoxazoles by reduction or conjugate addition reactions is reported. In the former method, an excess of sodium borohydride is required and leads predominantly to trans-isoxazolines, the exception being for the reaction of R² = CH₂OH substituted isoxazoles for which the cis-isomer was obtained as the major product (20:70, cis:trans). Using the Luche methodology (Tetrahedron Lett. 1988, 29, 5373-5374), the highly stereoselective and high-yielding conjugate addition using a combination of zinc dust, cuprous iodine and an alkyl iodide leads exclusively to C5-alkylated trans-isoxazolines.