Enantioselective Construction of a Polyhydroxylated Pyrrolidine Skeleton from 3‑Vinylaziridine-2-carboxylates: Synthesis of (+)-DMDP and a Potential Common Intermediate for (+)-Hyacinthacine A₁ and (+)-1-<i>epi</i>-Australine

Abstract

We report an enantioselective synthesis of the polyhydroxylated pyrrolidine alkaloid (+)-DMDP. The key steps in the synthesis were guanidinium ylide mediated asymmetric aziridination, stereospecific ring opening of <i>trans</i>-3-vinylaziridine-2-carboxylate with an oxygen nucleophile, iodine-mediated 5<i>-endo-trig</i> amino cyclization, and Prévost displacement. In addition, a potential common intermediate for the polyhydroxylated pyrrolizidine alkaloids (+)-hyacinthacine A₁ and (+)-1-<i>epi</i>-australine was synthesized from a diastereoisomeric <i>cis</i>-aziridine coformed in the asymmetric aziridination using the same strategy. A rationale for the diastereoselectivity observed for the iodine-mediated amino cyclization reactions is proposed on the basis of the heats of formation of the products