Straightforward Access to Enantiomerically Pure, Highly Functionalized Pyrrolizidines by Cycloaddition of Maleic Acid Esters to PyrrolineN-Oxides Derived from Tartaric, Malic and Aspartic Acids − Synthesis of (−)-Hastanecine, 7-epi-Croalbinecine and (−)-Croalbinecine

Abstract

The cycloaddition reactions of dimethyl maleate to three functionalized enantiopure pyrroline N-oxides and one related racemic nitrone are reported. The study of the diastereoselectivity in the cycloaddition has been carried out by ample variation of the substituents at both the dipole and dipolarophile counterparts. The major cycloadducts, derived from the preferred exo-anti transition states and formed with 62−90% diastereoselectivity, have been subjected to Mo(CO)6-induced reductive ring-opening to afford directly highly functionalized enantiopure pyrrolizinone derivatives, valuable as synthetic intermediates. Applications of this strategy to a straightforward formal synthesis of (−)-hastanecine and to the total synthesis of the novel 7-epi-croalbinecine and of (−)-croalbinecine are reported.