Cycloaddition reactions of azomethine ylides provide a convenient method for the preparation of pyrrolidines. We have been studying the application of this chemistry as a route to various alkaloids via the formation of three rings in one pot.  Condensation of a suitable aldehyde with an amino acid (or amino ester) leads to the in situ formation of a cyclic azomethine ylide (after N-alkylation) and thereby (after intramolecular cycloaddition) the preparation of three rings in one pot.  In all cases, the cycloaddition is completely regio- and stereoselective.

Three members of the Aspidosperma alkaloid family have been synthesised using the methodology.  Cycloadduct 2 was prepared from aldehyde 1, itself prepared by alkylation of butyronitrile.  This was converted to aspidospermidine 4 (R=R¹=H), aspidospermine 4 (R=OMe, R¹=Ac) and quebrachamine 5 by condensation with the relevant hydrazine and Fischer indole synthesis.  This constitutes the shortest synthesis to-date of aspidospermine.