Stereocontrolled synthesis of polyhydroxylated hexahydro-1H-cyclopent[c]isoxazoles by intramolecular oxime olefin cycloadditions: an approach to aminocyclopentitols

Abstract

A series of alk-5-enyl aldehydes derived from various carbohydrates (D-glucose, D-mannose, D-galactose, D-glucal) can be transformed into the corresponding oximes. Thermolysis of these oximes results in the isolation of hexahydro-1H-cyclopent[c]isoxazoles in good yields via intramolecular oxime olefin cycloadditions. Modest to excellent levels of diastereocontrol are observed in these cycloaddition reactions depending on the precise nature of the oxime precursor. In the best case, D-glucose-derived oxime 4 produces hexahydro-1H-cyclopent[c]isoxazole 5 as the sole product in quantitative yield. When the oxime possesses a substituent (OBn or OBz) adjacent to the oxime carbon atom, it is observed that reactions show a preference to produce the diastereomeric cycloadduct in which this substituent is located in an exo orientation relative to the newly formed hexahydro-1H-cyclopent[c]isoxazole ring system. The role of the solvent polarity on the diastereochemical outcome of these reactions is briefly discussed. Unsuccessful efforts to extend this chemistry to oximes derived from alk-4-enyl aldehydes are also presented. Finally, it is demonstrated that the hexahydro-1H-cyclopent[c]isoxazoles can be transformed into stereochemically defined aminocyclopentitols.