Study on the new synthetic reactions using β-Keto phosphonates

Abstract

Dephosphonylation of β-keto phosphonates involving α-proton were studied. Metal enolates of substituted β-keto phosphonates, readily generated from the corresponding beta-keto phosphonates $(EtO)_2P(O)CH(R)COR``$ and base such as NaH(or n-BuLi), were treated with $LiAlH_4$ in THF at room temperature to afford alpha-alkylated ketones $RCH_2COR``$ in good to excellent yields. A mechanism of the P-C bond cleavage is discussed. The reaction is applicable to a variety of α- or γ-substituted beta-keto phosphonate involving α-proton. Also studied were dephosphonylation of α-fully substituted β-keto phosphonates, the substituted β-keto phosphonates react with n-BuLi to give the corresponding lithium enolates. The reaction of enolate with LAH and subsequent quenching give the corresponding ketones. The mechanism study indicated that dephosphonylation is consistent with that of the previous procedure. A facile synthetic method for the preparation of 1-alkynylphosphonate were studied. 1-Alkynylphosphonates were prepared by in situ beta-elimination of enol phosphate which are readily generated by the reaction of sodium enolates of beta-keto phosphonates with diethyl chlorophosphate. Also studied were transesterification of diethyl 1-alkynylphosphonates with t-BuOK and facile synthesis of monoethylesters of 1-alkynylphosphonic acids. Various t-butylethyl 1-alkynylphosphonates were prepared by the reaction of diethyl 1-alkynylphosphonates with t-BuOK and 1-alkynylphosphonic acids ethyl monoester can also be prepared by mild hydrolysis of t-butylethyl 1-alkynylphosphonates in aq. MeOH in presence of acetic acid.