(5R)-5-((1S)-2-phenyl-1-phthalimidoethyl)dihydrofuran-2(3H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: (5R)-5-((1S)-2-phenyl-1-phthalimidoethyl)dihydrofuran-2(3H)-one
• 英文别名: 2-[(1S)-1-[(2R)-5-oxooxolan-2-yl]-2-phenylethyl]isoindole-1,3-dione
• 化学式: C₂₀H₁₇NO₄
• 分子量: 335.359
• InChiKey: AOCDGPDBPAMAEP-DLBZAZTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  63.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  ethynyl, [2-isopropyl-5-methylcyclohexyl(1R,2S,5R)]ether 、 2(S)-[2-phenyl-1(S)-phthalimidoethyl]oxirane 在 正丁基锂 、 三氟化硼乙醚 、 水 作用下， 生成 [(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexyl] (4R,5S)-5-(1,3-dioxoisoindol-2-yl)-4-hydroxy-6-phenylhexanoate 、 (5R)-5-((1S)-2-phenyl-1-phthalimidoethyl)dihydrofuran-2(3H)-one
  参考文献：
  名称：

  A General, Catalytic, and Enantioselective Synthesis of (S)-γ-[(S)-1-Aminoalkyl]-γ-lactones

  摘要：

  A catalytic asymmetric synthesis of N-phthaloyl (S)-gamma-[(S)-1-aminoalkyl]-gamma-lactones, widely used intermediates in the preparation of hydroxyethylene dipeptide isosteres, is described. The highly enantiopure epoxy alcohols arising from the Sharpless epoxidation of (E)-allyl alcohols are first converted to (S)-N-phthaloyl-[(S)-1-aminoalkyl]oxiranes by means of an efficient four-step sequence involving the regio- and stereoselective ring opening of the starting epoxide by azide, reduction, phthaloylation, and intramolecular Mitsunobu cyclization of the intermediate phthalimido diol. Treatment of the resulting oxirane with lithium (1R)-menthyloxyacetylide in the presence of boron trifluoride etherate, followed by in situ hydrolysis of the ynol ether, leads to a (4R, 5S)-5-phthalimido-4-hydroxy ester. A Mitsunobu reaction with p-nitrobenzoic acid (which establishes the correct (S)configuration at C-4) and subsequent selective saponification of the benzoate and cyclization of the inverted hydroxy ester afford the target N-protected (S)-gamma-[(S)-1-aminoalkyl]-gamma-lactones. Using this methodology, lactones 19 and 26 were obtained in seven steps from the readily available epoxy alcohols 5 and 20, respectively, in high enantiomeric purity.

  DOI：

  10.1021/jo9720851

文献信息

• A General, Catalytic, and Enantioselective Synthesis of (<i>S</i>)-γ-[(<i>S</i>)-1-Aminoalkyl]-γ-lactones
  作者：Núria Aguilar、Albert Moyano、Miquel A. Pericàs、Antoni Riera

  DOI：10.1021/jo9720851

  日期：1998.5.1

  A catalytic asymmetric synthesis of N-phthaloyl (S)-gamma-[(S)-1-aminoalkyl]-gamma-lactones, widely used intermediates in the preparation of hydroxyethylene dipeptide isosteres, is described. The highly enantiopure epoxy alcohols arising from the Sharpless epoxidation of (E)-allyl alcohols are first converted to (S)-N-phthaloyl-[(S)-1-aminoalkyl]oxiranes by means of an efficient four-step sequence involving the regio- and stereoselective ring opening of the starting epoxide by azide, reduction, phthaloylation, and intramolecular Mitsunobu cyclization of the intermediate phthalimido diol. Treatment of the resulting oxirane with lithium (1R)-menthyloxyacetylide in the presence of boron trifluoride etherate, followed by in situ hydrolysis of the ynol ether, leads to a (4R, 5S)-5-phthalimido-4-hydroxy ester. A Mitsunobu reaction with p-nitrobenzoic acid (which establishes the correct (S)configuration at C-4) and subsequent selective saponification of the benzoate and cyclization of the inverted hydroxy ester afford the target N-protected (S)-gamma-[(S)-1-aminoalkyl]-gamma-lactones. Using this methodology, lactones 19 and 26 were obtained in seven steps from the readily available epoxy alcohols 5 and 20, respectively, in high enantiomeric purity.