4,4,6,6,6-pentafluoro-5,5-dihydroxy-1-phenylhexan-3-one | 1338328-42-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4,4,6,6,6-pentafluoro-5,5-dihydroxy-1-phenylhexan-3-one
• CAS: 1338328-42-9
• 化学式: C₁₂H₁₁F₅O₃
• 分子量: 298.21
• InChiKey: NQJMTIGGQAZZEY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.07
• 重原子数：
  20.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  57.53
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  4,4,6,6,6-pentafluoro-5,5-dihydroxy-1-phenylhexan-3-one 在 碘 、 ketoreductase K₂₃₄ 、 三乙胺 、 异丙醇 、 还原型辅酶II(NADPH)四钠盐 、 lithium bromide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 12.0h， 生成 (S)-1,1-difluoro-1-iodo-4-phenylbutan-2-ol
  参考文献：
  名称：

  氟烷基酮的生物催化不对称还原以获得对映体纯氟烷基仲醇

  摘要：

  据报道，使用商业 NADPH 依赖性酮还原酶 K234 和 2-丙醇作为 NADPH 再生的共底物，可有效生物催化还原二氟烷基酮以获得手性氟烷基仲醇。这种生物还原反应可应用于广泛的前手性氟酮，包括芳基二氟酮、脂肪族二氟酮和三氟苯乙酮，在高底物浓度（100 g L -1). 这些结果表明 K234 在工业生产有价值的手性氟代醇方面具有潜力。此外，该生物催化方案在不添加外部烟酰胺辅助因子的情况下也可以有效，这为酮还原酶 K234 在手性仲醇不对称合成中的进一步应用提供了有用的指导。

  DOI：

  10.1039/d3ob00193h
• 作为产物：
  描述：

  (E)-4,4,6,6,6-pentafluoro-5,5-dihydroxy-1-phenylhex-1-en-3-one 在 palladium on activated charcoal 、 氢气 作用下， 以 乙醇 为溶剂， 反应 12.0h， 以86%的产率得到4,4,6,6,6-pentafluoro-5,5-dihydroxy-1-phenylhexan-3-one
  参考文献：
  名称：

  Synthesis of α-Halo-α,α-difluoromethyl Ketones by a Trifluoroacetate Release/Halogenation Protocol

  摘要：

  Three series of alpha-halo-alpha,alpha-difluoromethyl ketones are prepared from highly alpha-fluorinated gem-dials by exploiting the facile release of trifluoroacetate, followed by immediate trapping of the liberated alpha,alpha-difluoroenolate with an electrophilic chlorine, bromine, or iodine source. The products are typically isolated in good yields, even in the case of sensitive, alpha-iodo-alpha,alpha-difluoromethyl ketones. Also, we demonstrate that an alpha-iodo-alpha,alpha-difluoromethyl ketone will participate in a copper-promoted reaction to forge a new carbon-carbon bond.

  DOI：

  10.1021/jo2017179

文献信息

• Conversion of methyl ketones and methyl sulfones into α-deutero-α,α-difluoromethyl ketones and α-deutero-α,α-difluoromethyl sulfones in three synthetic steps
  作者：Munia F. Sowaileh、Changho Han、Robert A. Hazlitt、Eun Hoo Kim、Jinu P. John、David A. Colby

  DOI：10.1016/j.tetlet.2016.12.018

  日期：2017.2

  Deuterodifluoromethyl ketones and sulfones were assembled in three synthetic steps from methyl ketones and sulfones, respectively. The key synthetic transformation is the deuteration of the difluorocarbanion generated by the release of trifluoroacetate from highly α-fluorinated gem-diols. High levels of deuterium on the "CF2D" group were routinely observed. This strategy is mild and versatile and it

  在三个合成步骤中，分别从甲基酮和砜中组装了氘代二氟甲基酮和砜。关键的合成转化是由高度α-氟化的宝石二醇释放出三氟乙酸盐而产生的二氟乙二酮的氘代。常规观察到“ CF2D”组的氘水平很高。该策略温和且用途广泛，可用于酮和砜，而无需担心过度氟化或氟化不足。另外的例子解决了当具有其他酸性质子的化合物经受反应条件时的氘化过度的问题。该过程不仅证明了安装“ CF2D”基团的新方法，而且将三氟乙酸盐释放的范围扩展到了砜。
• Copper‐Catalyzed Three‐Component Reactions of 2‐Iodo‐2,2‐difluoroacetophenones, Alkynes, and Trimethylsilyl Cyanide
  作者：Pingjie Wu、Cheng Zheng、Xia Wang、Jingjing Wu、Fanhong Wu

  DOI：10.1002/ejoc.202001650

  日期：2021.3.5

  Cu(I)‐catalyzed three‐component reaction of 2‐iodo‐2,2‐difluoroacetophenones, alkynes, and TMSCN for the synthesis of useful difluoroacyl‐substituted nitriles is described. This method has broad substrate scope and excellent stereoselectivity. Preliminary mechanistic investigation indicated that a radical‐mediated process was involved in this cyanodifluoroalkylation reaction.

  描述了Cu（I）催化的2-碘-2-2,2-二氟苯乙酮，炔烃和TMSCN的三组分反应，用于合成有用的二氟酰基取代的腈。该方法具有广泛的底物范围和优异的立体选择性。初步的机理研究表明，该氰基二氟烷基化反应涉及自由基介导的过程。
• Synthesis of Pentafluorinated β-Hydroxy Ketones
  作者：Peng Zhang、Christian Wolf

  DOI：10.1021/jo3017583

  日期：2012.10.5

  LHMDS-promoted in situ generation of difluoroenolates from readily available 1-aryl and 1-alkyl 2,2,4,4,4-pentafluorobutan-1,3-dione hydrates has been used to produce a series of pentafluorinated β-hydroxy ketones in up to 95% yield. The reaction proceeds under mild conditions, tolerates a wide range of functional groups, and is complete within 10 min. Reduction toward the corresponding 1,3-diol with DIBAL

  由LHMDS促进的从容易获得的1-芳基和1-烷基2,2,4,4,4-五氟丁烷-1,3-二酮水合物中原位生成二氟烯酸酯已被用于生产一系列五氟化β-羟基酮高达95％的产量。反应在温和的条件下进行，可耐受各种官能团，并在10分钟内完成。用DIBAL还原为相应的1，3-二醇给出定量的量并有利于顺式异构体的形成。
• Indium-mediated 1,2-addition of iododifluoromethyl ketones with α, β-unsaturated ketones
  作者：Zhuang Ni、Ran Sun、Jihong Wu、Chao Xu、Jinwen Huang、Fanhong Wu

  DOI：10.1016/j.tet.2022.132855

  日期：2022.7

  iododifluoromethyl ketones with α, β-unsaturated ketones, which provides an obviously significant route to access 1,2-addition product with excellent regioselectivity. This method has a wide range of substrate scope, good efficiency, and mild reaction conditions. In addition, this method was applied to the synthesis of difluoro derivatives of biologically active molecules containing unsaturated ketone structures

  一种新的铟介导的碘二氟甲基酮与 α, β-不饱和酮的二氟烷基化反应，为获得具有优异区域选择性的 1,2-加成产物提供了一条明显重要的途径。该方法底物范围广、效率好、反应条件温和。此外，该方法还可用于合成含有不饱和酮结构的生物活性分子的二氟衍生物，可作为药物发现中潜在有价值的氟化中间体。
• Iron‐Catalyzed Intermolecular Azidabenzoyl Difluoromethylation of Alkenes to Access <i>β</i> ‐Difluoroacyl Azides
  作者：Xia Wang、Mougui Fang、Shiguang Wu、Jingjing Wu、Fanhong Wu

  DOI：10.1002/ejoc.202201213

  日期：2022.12.12

  AbstractA Fe(II)‐catalyzed three‐component reaction of 2‐iodo‐2,2‐difluoroacetophenones, alkenes and TMSN3 is described, which provides a particularly valuable route to access difluoroalkylated azides with high yields. The method permits the efficient azidation of varied β‐difluoroacyl‐benzylic radicals in mild conditions with high functional group tolerance. Preliminary mechanistic investigation indicated that a radical‐mediated process was involved in this azidadifluoroacylation reaction.