Solid-Phase Pyrrolidine Synthesis via 1,3- Dipolar Cycloaddition of Azomethine Ylides Generated by the Decarboxylative Route

Abstract

Although solid-phase pyrrolidine synthesis via dipolar cycloaddition of ester-stabilized azomethine ylides has been demonstrated on several occasions, this reaction with nonstabilized azomethine ylides, generated on solid support by a decarboxylative pathway, has never been reported. Herein we present the first solid-phase synthesis of pyrrolidines via this route and demonstrate that the reacting azomethine ylide can be generated both from a resin-bound aldehyde or amino acid. Using cyclic and acyclic dipolarophiles, bi- and monocyclic resin-bound pyrrolidines were obtained. The modest to high degree of regio-and diastereoselectivity observed in the reaction can be tuned by the substituents of the partners of this three-component process.