The organocatalytic [3+2] cycloaddition of azomethine ylides and α,β-unsaturated aldehydes as a convenient tool for the enantioselective synthesis of pyrrolizidines and indolizidines

Abstract

We have developed a simple and straightforward procedure for the enantioselective preparation of densely substituted bicyclic and tricyclic nitrogen heterocycles using conveniently substituted enantiopure pyrrolidines as common synthetic intermediates, which are easily accessible by our recently developed organocatalytic enantioselective [3+2] cycloaddition of α,β-unsaturated aldehydes and azomethine ylides. The designed synthetic pathway makes use of a ring-closing metathesis reaction for building up the pyrrolizidine and indolizidine skeletons, while the access to the hexahydrocyclopenta[a]pyrrolizine structure has been carried out relying on a fully diastereoselective intramolecular Pauson–Khand reaction.