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“含立体磷原子的新型膦酸膦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-立体磷酸膦。我们还开发了几个新的反应，如不对称Horner-Wadsworth-Emmons(HWE)反应和去共轭酯化反应。在三乙胺或DBU的存在下，Z-选择性HWE试剂双(2，2，2-三氟乙基)膦乙酸甲酯与各种醇类反应很容易合成外消旋的膦-乙酸酯。在PLE催化下，一些外消旋的膦酸膦类化合物以高效的方式进行了拆分，得到了新型的P-立体生成的膦酸膦酸酯类化合物。含(-)-薄荷醇的对位立体膦-乙酸酯作为手性助剂的非对映选择性HWE反应，以84%的产率得到相应的四取代烯烃。此外，我们还展示了一种新的非对映选择性HWE反应，用于合成具有手性轴的四取代烯烃。以SnO(OSO2CF3)2和N-乙基哌啶为催化剂，研究了α-对称4-甲基环己酮与一种新型的含N-苄基异构体的HWE试剂的不对称HWE反应。合成了具有手性轴的四取代烯烃α-甲基-a，β-不饱和酯。另一方面，以1-乙基-3-(3-二甲氨基丙基)碳二亚胺盐酸盐为偶联剂，4-(吡咯烷基-1-基)吡啶催化2-环己基乙酸异丙酯的反共轭酯化反应。而4-(吡咯烷基-1-基)吡啶催化与1，3-二环己基碳二亚胺的酯化反应不伴随去共轭反应，生成2-环己基乙酸异丙酯，