title: Stereospecific nucleophilic substitution of optically pure H-phosphinates: a general way for the preparation of chiral P-stereogenic phosphine oxides.
abstract: Contrary to the generally held view, it is found that the rapid epimerization of (-)-menthyl (RP)-phenylphosphinate under basic conditions is not due to the so far believed inherent stereolability of its corresponding anion but due to a reaction of the hydrogen phosphinate ester with a metal alkoxide. This finding successfully leads to a discovery that, by adding an H-phosphinate to organolithiums or Grignard reagents at a low temperature, the nucleophilic substitution of the alkoxy group of the H-phosphinate with organolithiums or Grignard reagents proceeds stereospecifically with inversion of configurations at phosphorus to give a wide range of P-stereogenic secondary phosphine oxides and tertiary phosphine oxides, by quenching the reaction mixture with water and alkyl halides, respectively. This finding establishes a general protocol for the preparation of optically active secondary phosphine oxides and tertiary phosphine oxides from the easily accessible optically pure H-phosphinates. Mechanistic studies show that the substitution reactions of H-phosphinates with organolithiums and Grignard reagents proceed via two competing reaction paths, that is, a two-step reaction path involving first a deprotonation of H-phosphinates followed by a substitution of the corresponding anion with inversion of configuration at phosphorus and a direct substitution of RM with H-phosphinates generating the SPO directly.
authors.affiliation: National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8565, Japan.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xu
authors.forename: Chang-Qiu
authors.initials: CQ
authors.lastname: Zhao
authors.forename: Li-Biao
authors.initials: LB
authors.lastname: Han