Diastereoselective Synthesis of Racemic 3,4-cis and 3,4-trans Isomers of Isoxazolidine-4,5-diols and their Derivatives

A new synthetic approach to racemic 3,4-cis- and 3,4-trans-isoxazoldine-4,5-diols and their derivatives is presented. Dihydroxylation reactions of 3-substituted 2,3-dihydroisoxazoles with K(2)OsO(4)2H(2)O in the presence of NMO in acetone-water proceeded from the less hindered side and provided the major 3,4-trans-isoxazolidine-4,5-diols in moderate to good yields. 3,4-cis-5-Methoxyisoxazolidin-4-ol was prepared diastereoselectively from the mixture of 3,4-cis- and 3,4-trans-4-bromo-5-hydroxyisoxazolidines using base-promoted intramolecular cyclization in anhydrous methanol. Representative derivatives of 3,4-cis- and 3,4-trans-5-cyanoisoxazolidin-4-ols are also presented as potentially useful building blocks for the synthesis of various C5-substituted isoxazolidines.