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 beta-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. (C) 2002 Elsevier Science Ltd. All rights reserved.