ethyl (E)-4,4-difluoro-5-hydroxy-5-phenylpent-2-enoate

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: ethyl (E)-4,4-difluoro-5-hydroxy-5-phenylpent-2-enoate
• 化学式: C₁₃H₁₄F₂O₃
• 分子量: 256.249
• InChiKey: VXPNQLMUJISDIJ-CMDGGOBGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl (E)-4,4-difluoro-5-hydroxy-5-phenylpent-2-enoate 在 二异丁基氢化铝 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 3.0h， 以98%的产率得到(E)-4,4-difluoro-5-phenyl-2-pentene-1,5-diol
  参考文献：
  名称：

  通过区域选择性氢化还原烯丙醇衍生物制备δ-氟代均丙醇衍生物

  摘要：

  可以通过区域选择性SN2'反应分别通过LiAlH 4还原δ，δ-二氟烯丙基醇和γ-氯二氟甲基烯丙基醇来有效地制备δ-Fluoro和δ，δ-difluorohomoallylic醇衍生物，其中游离羟基是必不可少的反应进行。

  DOI：

  10.1016/s0022-1139(02)00150-1
• 作为产物：
  描述：

  ethyl 4,4-difluoro-3-(triethylsilyl)but-3-enoate 、 苯甲醛 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以64%的产率得到ethyl (E)-4,4-difluoro-5-hydroxy-5-phenylpent-2-enoate
  参考文献：
  名称：

  New approach to synthesize β,β-difluorohomoallylic alcohols

  摘要：

  Treatment of ethyl 4,4-difluoro-3-(triethylsilyl)but-3-enoate (3) with TBAF in the presence of MS4 angstrom followed by addition of an aromatic aldehyde afforded ethyl (E)-4,4-difluoro-5-hydroxy-5-arylpent-2-enoate (I) that was a versatile intermediate for constructing a stable isostere of peptide or fluorinated sugar molecules. This strategy offers straightforward approach to synthesize such a versatile intermediate (1). (C) 2013 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.jfluchem.2012.12.011

文献信息

• An efficient synthetic method for Z-fluoroalkene dipeptide isosteres: Application to the synthesis of the dipeptide isostere of Sta-Ala
  作者：Yuko Nakamura、Midori Okada、Minoru Koura、Manabu Tojo、Akio Saito、Azusa Sato、Takeo Taguchi

  DOI：10.1016/j.jfluchem.2005.11.016

  日期：2006.5

  followed by reaction with alkyl halides provided the corresponding (Z)-α-alkylated products in high yields. The latter reaction was applied to the preparation of the dipeptide (Z)-fluoroalkene isostere of Sta-Ala, which is the central dipeptide unit in Pepstatin, a natural inhibitor of aspartate proteases.

  发现具有δ-羟基的γ，γ-二氟-α，β-烯酸酯与三烷基铝（R 3 Al）的反应被CuI·2LiCl促进，并以SN2'方式进行，从而产生了α-烷基化的（Z）-γ-氟-β，γ-烯酸酯，同时用Me 2 CuLi还原γ，γ-二氟-α，β-烯酸酯，然后与卤代烷反应，得到相应的（Z）-α-烷基化产物高产。后一反应用于制备Sta-Ala的二肽（Z）-氟烯烃等排物，它是天冬氨酸蛋白酶的天然抑制剂Pepstatin中的中心二肽单元。
• Synthesis of α-Alkylated (<i>Z</i>)-γ-Fluoro-β,γ-enoates through Organocopper Mediated Reaction of γ,γ-Difluoro-α,β-enoates: A Different Reactivity of R₃Al-Cu(I) and Me₂CuLi
  作者：Midori Okada、Yuko Nakamura、Akio Saito、Azusa Sato、Hiroaki Horikawa、Takeo Taguchi

  DOI：10.1246/cl.2002.28

  日期：2002.1

  Reaction of γ,γ-difluoro-α,β-enoates having a δ-hydroxyl group with trialkylaluminum (R3Al) in the presence of CuI•2LiCl proceeded in SN2′-type manner to give α-alkylated (Z)-γ-fluoro-β,γ-enoates, while reductive defluorination of γ,γ-difluoro-α,β-enoates with Me2CuLi followed by reaction with alkyl halides provided the corresponding (Z)-α-alkylated products.

  具有δ-羟基的γ,γ-二氟-α,β-烯酸盐与三烷基铝（R3Al）在 CuI-2LiCl 存在下发生 SN2′-型反应，生成α-烷基化 (Z)-γ-氟-β、γ-烯酸盐，而 γ,γ-二氟-α,β-烯酸盐与 Me2CuLi 还原脱氟，然后与烷基卤化物反应，可得到相应的 (Z)-α 烷基化产物。
• Preparation of δ-fluorinated homoallylic alcohol derivatives via regioselective hydride reduction of allylic alcohol derivatives
  作者：Yuko Nakamura、Midori Okada、Hiroaki Horikawa、Takeo Taguchi

  DOI：10.1016/s0022-1139(02)00150-1

  日期：2002.10

  δ-Fluoro and δ,δ-difluorohomoallylic alcohol derivatives can be efficiently prepared by LiAlH4 reduction of the δ,δ-difluoroallylic alcohols and the γ-chlorodifluoromethylallylic alcohols, respectively, through regioselective SN2′ reaction, in which the free hydroxyl group is essential for the reaction to proceed.

  可以通过区域选择性SN2'反应分别通过LiAlH 4还原δ，δ-二氟烯丙基醇和γ-氯二氟甲基烯丙基醇来有效地制备δ-Fluoro和δ，δ-difluorohomoallylic醇衍生物，其中游离羟基是必不可少的反应进行。
• New approach to synthesize β,β-difluorohomoallylic alcohols
  作者：Masaaki Omote、Tatsuya Miake、Atsushi Tarui、Kazuyuki Sato、Itsumaro Kumadaki、Akira Ando

  DOI：10.1016/j.jfluchem.2012.12.011

  日期：2013.3

  Treatment of ethyl 4,4-difluoro-3-(triethylsilyl)but-3-enoate (3) with TBAF in the presence of MS4 angstrom followed by addition of an aromatic aldehyde afforded ethyl (E)-4,4-difluoro-5-hydroxy-5-arylpent-2-enoate (I) that was a versatile intermediate for constructing a stable isostere of peptide or fluorinated sugar molecules. This strategy offers straightforward approach to synthesize such a versatile intermediate (1). (C) 2013 Elsevier B.V. All rights reserved.
• Stereoselective synthesis of (Z)-fluoroalkenes directed to peptide isosteres: copper mediated reaction of trialkylaluminum with 4,4-difluoro-5-hydroxyallylic alcohol derivatives
  作者：Yuko Nakamura、Midori Okada、Azusa Sato、Hiroaki Horikawa、Minoru Koura、Akio Saito、Takeo Taguchi

  DOI：10.1016/j.tet.2005.04.034

  日期：2005.6

  Copper mediated alkyl-transfer reaction of trialkylaluminum (R3Al) with (E)-4,4-difluoro-5-hydroxyallylic alcohol derivative smoothly proceeded to give the corresponding 2-alkylated 4-fluoro-5-hydroxyhomoallylic alcohol derivative with completely Z and 2,5-syn selective manner. Regio- and stereoselective conversion of the C5-hydroxyl group of the fluoroolefin thus obtained to amino group could be achieved

  三烷基铝（R 3 Al）与（E）-4,4-二氟-5-羟基烯丙基醇衍生物的铜介导的烷基转移反应顺利进行，得到相应的带有完全Z的2-烷基化的4-烷基-5-氟代羟基烯丙基醇衍生物和2，5-顺式选择性方式。如此获得的氟代烯烃的C5-羟基向氨基的区域和立体选择性转化可以通过一锅式甲磺酰化和叠氮化反应来实现。