Synthesis of optically active 1,2,3-trisubstituted azetidines employing an organocatalytic approach with l-proline

A concise organocatalytic approach towards optically active 1,2,3-trisubstituted azetidines, including a study of the scope and limitations of the synthetic sequence, is reported. The synthesis comprises the one-pot l-proline promoted three-component reaction between substituted benzaldehydes, anilines and enolizable aldehydes, followed by the in situ reduction of the resulting β-aminoaldehydes to the corresponding γ-aminoalcohols and final intramolecular cyclization of the latter by way of the intermediate tosylates, formed in situ.