Asymmetric reduction of racemic 2-isoxazolines

Article abstract of DOI:10.1016/j.tetasy.2008.11.005

The kinetic resolution of racemic 2-isoxazolines was carried out by asymmetric reduction using borane with 1,2-amino alcohols as a chiral source. Using excess BH₃-THF in the presence of (-)-norephedrine, optically active 1,3-amino alcohol derivatives were obtained with good ee but in lower yield, while the optically active substrates 2-isoxazolines were recovered with modest ee. The asymmetric reduction using 2.0 equiv of BH₃-SMe₂ was investigated as an alternative strategy for the synthesis of optically active products. After reduction, treatment of the resulting mixture with Et₃N was successful in providing optically active isoxazolidine derivatives in good yields and with good ee. The choice of chiral source was also shown to have a significant effect. In particular, the use of (S)-α,α-diphenyl-2-pyrrolidinemethanol reversed the enantioselectivity of the recovered substrates.