An efficient asymmetric synthesis of azetidine 2-phosphonic acids

Substituted azetidinic 2-phosphonates were prepared in diastereoisomerically and enantiomerically pure form, starting from readily available β-amino alcohols. This synthesis involved a three-step sequence: (i) N-alkylation of the starting amino alcohol with a methylene phosphonate moiety, (ii) chlorination of the alcohol, and (iii) stereoselective 4-exo-tet ring closure through an intramolecular alkylation of the lithiated aminophosphonate.