Synthesis of Novel Phosphonoacetates Bearing a Stereogenic Phosphorous Atom and Application to Asymmetric HWE Reaction

带有立构磷原子的新型膦酰乙酸酯的合成及其在不对称HWE反应中的应用

• 批准号: 17590007
• 负责人: SANO Shigeki
• 金额: $ 2.24万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590007/
• 关键词: phosphorus atom; enzymatic hydrolysis; optical resolution; axis of chirality; asymmetric HWE reaction; tetrasubstituted alkene; deconjugative esterification; isomannide; α,β-不飽和カルボン酸; β,γ-不飽和エステル; ホスホノ酢酸エステル; エステラーゼ; 不斉合成; HWE反応

In the course of studies on "Synthesis of Novel Phosphonoacetates Bearing a Stereogenic Phosphorous Atom and Application to Asymmetric HWE Reaction", we have synthesized novel P-stereogenic phosphonoacetates. We have also developed several new reactions, such as asymmetric Horner-Wadsworth-Emmons (HWE) reactions and deconjugative esterification.Racemic phosphonoacetates were readily prepared from methyl bis(2,2,2-trifluoroethyl)phosphonoacetate, a Z-selective HWE reagent, by alcoholysis with various alcohols in the presence of triethylamine or DBU. PLE-catalyzed kinetic resolution of some of these racemic phosphonoacetates proceeded in a highly effective manner to give the novel P-stereogenic phosphonoacetates. A diastereoselective HWE reaction of a P-stereogenic phosphonoacetate bearing (-)-menthol as a chiral auxiliary afforded the corresponding tetrasubstituted olefin in 84% de.In addition, we demonstrated a novel diastereoselective HWE reaction for the synthesis of tetrasubstituted alkenes with an axis of chirality. An asymmetric HWE reaction of a-symmetric 4-methylcyclohexanone and a novel HWE reagent bearing 0-benzylisoman.nide was investigated by employing Sn(OSO_2CF_3)_2 and N-ethylpiperidine. As a result, a-methyl-a,β-unsaturated ester, a tetrasubstituted alkene with an axis of chirality, was obtained in > 99% de.On the other hand, 4-(pyrrolidin-1-yl)pyridine-catalyzed deconjugative esterification of 2-cyclohexylidineacetic acids afforded isopropyl 2-(cyclohex-1-enyl)acetate by employing 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride as a coupling reagent. Whereas, 4-(pyrrolidin-1-yl)pyridine-catalyzed esterification with 1,3-dicyclohexylcarbodiimide was not accompanied by deconjugation and gave isopropy 2-cyclohexylideneacetate,

在“新型含立体磷原子磷酸酯的合成及其在不对称HWE反应中的应用”的研究过程中，我们合成了新型的p -立体磷酸酯。我们还开发了一些新的反应，如不对称的Horner-Wadsworth-Emmons （HWE）反应和解共轭酯化反应。以双（2,2,2-三氟乙基）磷酸乙酸甲酯为原料，在三乙胺或DBU的存在下与不同醇醇解制备外消旋型磷酸酯。一些外消旋磷酸酯的动力学拆分以一种非常有效的方式进行，得到了新型的p -立体磷酸酯。以（-）薄荷醇为手性助剂的p -立体磷酸乙酸酯的非对映选择性HWE反应在84%的收率中得到了相应的四取代烯烃。此外，我们还证明了一种新的非对映选择性HWE反应可以合成具有手性轴的四取代烯烃。非对称4-甲基环己酮与含0-苄基异构体的新型HWE试剂的不对称HWE反应。用Sn(OSO_2CF_3)_2和n -乙基哌啶对nide进行了研究。另一方面，以1-乙基-3-（3-二甲氨基丙基）卡二亚胺盐酸盐为偶联剂，用4-（吡咯烷-1-基）吡啶催化2-环己基乙酸解共轭酯化反应得到2-（环己基-1-烯基）乙酸异丙基。而4-（吡咯烷-1-酰基）吡啶催化与1,3-双环己基碳二亚胺的酯化反应不伴有解偶联反应，得到2-环己基乙酸异丙酯；