Stereoselective Synthesis of Pyrrolizidines

Abstract

Reported here is a DBU-mediated domino reaction of 1,4-dien-3-ones with ethyl isocyanoacetate allowing the formation of three C-C bonds and a C-N bond affording pyrrolizidine derivatives. Under the optimal conditions, the 1,4-dien-3-one 1 tolerates various aromatic, hetero­cyclic and alkyl groups R¹ to give single diastereo­isomers in moderate to good yields. The reaction was then extended to the 1,4-dien-3-ones 2 and 3 to lead to products bearing three and four adjacent stereocenters, respectively. A plausible mechanism involves a double Michael addition followed by an intramolecular cyclization and a final 1,3-acyl migration. The absolute configuration was determined by X-ray diffraction analyses on selected derivatives.