Dearomatizing Anionic Cyclization of Phosphonamides. A Route to Phosphonic Acid Derivatives with Antitumor Properties
journal contributionposted on 18.09.2008, 00:00 by Gloria Ruiz-Gómez, Andrés Francesch, María José Iglesias, Fernando López-Ortiz, Carmen Cuevas, Manuel Serrano-Ruiz
Deprotonation of bis(N-benzyl-N-methyl)-P-arylphosphonic diamides with s-BuLi in THF at −90 °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 γ-aminophosphonic acids under acidic conditions. Preliminary screening for antitumor activity showed promising levels of activity.
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benzophenonebenzylic positionseriesMeOHBnBraliphaticDerivativeantitumor activityPreliminary screeningacidic conditionsdiamidealdehydeintramolecular attackelectrophileDearomatizing Anionic CyclizationaminophosphonicbiregioAntitumor Properties DeprotonationArOHTHFanionstereocontroldearomatized speciesdearomatized productsPhosphonicPhosphonamide