Straightforward access to enantiomerically pure, highly functionalized pyrrolizidines by cycloaddition of maleic acid esters to pyrroline N-oxides derived from tartaric, malic and aspartic acids - Synthesis of (-)-hastanecine, 7-epi-croalbinecine and (-)-croalbinecine

The cycloaddition reactions of dimethyl maleate to three functionalized ena ntiopure pyrroline N-oxides and one related racemic nitrone are reported. T he study of the diastereoselectivity in the cycloaddition has been carried out by ample variation of the substituents at both the dipole and dipolarop hile counterparts. The major cycloadducts, derived from the preferred exo-a nti transition states and formed with 62-90% diastereoselectivity, have bee n subjected to Mo(CO)G-induced reductive ring-opening to afford directly hi ghly functionalized enantiopure pyrrolizinone derivatives, valuable as synt hetic intermediates. Applications of this strategy to a straightforward for mal synthesis of (-)-hastanecine and to the total synthesis of the novel 7- epi-croalbinecine and of (-)-croalbinecine are reported.