Dearomatizing anionic cyclization of phosphonamides. A route to phosphonic acid derivatives with antitumor properties
Gloria Ruiz-Gómez1, Andrés Francesch, María José Iglesias
1Area de Química Orgánica, Universidad de Almería, Carretera de Sacramento, 04120 Almería, Spain.
Abstract:
Deprotonation of bis(N-benzyl-N-methyl)-P-arylphosphonic diamides with s-BuLi in THF at -90 degrees C takes place selectively at the benzylic position. The anions undergo intramolecular attack to the P-aryl ring leading to dearomatized species that were trapped with a series of electrophiles (MeOH, ArOH, BnBr, aliphatic and aromatic aldehydes, and benzophenone) in very high yield, and with high regio- and stereocontrol. The dearomatized products were smoothly transformed into gamma-aminophosphonic acids under acidic conditions. Preliminary screening for antitumor activity showed promising levels of activity.
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