Synthesis of Phosphane Oxides and Phosphonates by Cerium-Mediated Addition of Organolithium Compounds to Chloro-Phosphorus Compounds

Abstract

The addition of organocerium reagents 2a–g to phosphinoyl chloride 1a or chlorophosphates 1b leads to the synthesis of phosphane oxides 3aa–ag and phosphonates 3bb, be in good to high yield. The reaction can be extended to cerium enolates 4 (of ketones) and 6 (of nitriles) except when a benzyl group bound to the carbonyl moiety should be metallated. The latter reaction is the first reported synthesis of β‐oxophosphane oxides by a simple reaction between enolates and a phosphorus(V) halide.

Phosphine Oxides from a Medicinal Chemist’s Perspective: Physicochemical and in Vitro Parameters Relevant for Drug Discovery

“…Symmetric tertiary aryldialkylphosphine oxides I can be synthesized in numerous ways, most conveniently starting from corresponding phosphorus­(V) H-phosphine oxide precursors via transition metal catalyzed cross coupling methodologies (Scheme , A) . Alternatively, nucleophilic arylation of dialkylphosphinoyl chlorides (Scheme , B) and double nucleophilic addition of organometallic species to arylphosphoryl dichlorides and arylphosphonic acid esters (Scheme , C) have been described. In addition, P­(III)-precursors like dialkylphosphinyl chlorides and aryldichlorophosphines are reported to react with C-nucleophiles (Scheme , D and E), and arylphosphines can be alkylated using alkyl halides (Scheme , F).…”