Asymmetric nitrone cycloadditions and their application to the synthesis of enantiopure pyrrolidine and pyrrolizidine derivatives

The cycloaddition reactions of a pair of chiral pyrroline-N-oxides derived from D-ribose with some typical mono and disubstituted alkenes are reported. In all these reactions with monosubstituted alkenes as well as with dimethyl maleate the preferred stereochemical outcome of the cycloaddition step comes from a 5-exo-anti transition state whereas stereoisomers from the 5-exo-syn transition state are also present as minor adducts. In the reaction with dimethyl fumarate the major adduct comes from a 4-exo-5-endo-syn transition state. The further behavior of the obtained isoxazolidines upon reductive ring opening conditions depends on the kind and the geometry of the preexisting substituents and they are transformed to enantiomerically pure pyrrolidine or pyrrolizidinone derivatives. (c) 2006 Elsevier Ltd. All rights reserved.