Efficient synthesis of isoxazolidine-substituted bisphosphonates by 1,3-dipolar cycloaddition reactions

Several bisphosphonates bearing a substituted isoxazolidine ring have been synthesized in good yield by direct 1,3-dipolar cyclization reaction, under microwaves catalysis, in the absence of solvent. The method allows the simultaneous incorporation, on the geminal position of the bisphosphonate framework, of a basic nitrogen and of an oxygen atom, as third hook. Hydrophobicity-hydrophilicity of BPs is discussed with the help of distribution coefficients. © 2011 Elsevier Ltd.