Double Dearomatization of Bis(diphenylphosphinamides) through Anionic Cyclization. A Facile Route of Accessing Multifunctional Systems with Antitumor Properties

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 γ-aminophosphinates) stereospecifically. The doubly phosphorylated systems proved to be active against a series of cancer cell lines.