J Org Chem.
2007 Apr 18;
Double Dearomatization of Bis(diphenylphosphinamides) through Anionic Cyclization. A Facile Route of Accessing Multifunctional Systems with Antitumor Properties
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Ruiz-Gomez G, Iglesias MJ , Serrano-Ruiz M , Garcia-Granda S , Francesch A , Lopez-Ortiz F, Cuevas C .
Area de Quimica OrgAnica, Universidad de Almeria, Carretera de Sacramento, 04120 Almeria, Spain, Area de Quimica InorgAnica, Universidad de Almeria, Carretera de Sacramento, 04120 Almeria, Spain, Departamento de Quimica Fisica y Analitica, Universidad de Oviedo, Avda. JuliAn Claveria 8, 33006 Oviedo, Spain, and PharmaMar S.A. Av. de los Reyes, 1, P.I. La Mina, 28770 Colmenar Viejo, Madrid, Spain.
The sequential one-pot double dearomatization of bis(N-benzyl-P,P-diphenylphosphinamides) via anionic cyclization is described for the first time. Protonation and alkylation of the dearomatized dianions provide bis(tetrahydro-2,1-benzazaphospholes) in good yield and with very high regio- and stereocontrol. Acid-catalyzed methanolysis of the bisheterocycles affords bis(methyl gamma-aminophosphinates) stereospecifically. The doubly phosphorylated systems proved to be active against a series of cancer cell lines.