3α-fluoro-5α-cholestane | 3856-83-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 3α-fluoro-5α-cholestane
• 英文别名: 3α-fluorocholestane；3α-Fluor-5α-cholestan；(3R,5S,8R,9S,10S,13R,14S,17R)-3-fluoro-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene
• CAS: 3856-83-5
• 化学式: C₂₇H₄₇F
• 分子量: 390.669
• InChiKey: BLHJQKQSKMFGKZ-FBVYSKEZSA-N

物化性质

• 熔点：
  104-106 °C(Solv: isopropyl ether (108-20-3); methanol (67-56-1))
• 沸点：
  446.4±14.0 °C(Predicted)
• 密度：
  0.96±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  10.4
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  3β-胆甾烷醇 在 四氟苯基膦烷 作用下， 以 四氯化碳 为溶剂， 生成 3α-fluoro-5α-cholestane
  参考文献：
  名称：

  Studies on organic fluorine compounds. XVI. Stereochemistry in fluorination of sterols with phenylfluorophosphoranes.

  摘要：

  研究了苯基四氟磷烷与醇的氟化反应的立体化学，特别是在类固醇醇的情况下。5α-胆烷-3β-醇和3α-醇分别给出了3α-和3β-氟-5α-胆烷，这表明氟化反应是通过SN2机制进行的；而胆固醇和3β-乙酰氧基-5-溴-5α-胆烷-6β-醇则生成了保持构型的氟化化合物，这表明在特定情况下，邻近基团可能参与了稳定碳正离子中间体。二苯基三氟磷烷也得到了类似的结果。

  DOI：

  10.1248/cpb.23.196

文献信息

• Studies on organic fluorine compounds. XVI. Stereochemistry in fluorination of sterols with phenylfluorophosphoranes.
  作者：YOSHIRO KOBAYASHI、ITSUMARO KUMADAKI、AKIO OHSAWA、MASAMITSU HONDA、YUJI HANZAWA

  DOI：10.1248/cpb.23.196

  日期：——

  Stereochemistry of the fluorination of an alcohol with phenyltetrafluorophosphorane was investigated in the case of steroidal alcohols. 5α-Cholestan-3β-ol and 3α-ol gave 3α- and 3β-fluoro-5α-cholestane, respectively, which suggests that the fluorination proceeded through SN2 mechanism ; while, cholesterol and 3β-acetoxy-5-bromo-5α-cholestane-6β-ol gave fluoro compounds with retention of configuration, which shows that a neighboring group may have participated in stabilizing the carbonium intermediate in special cases. Diphenyltrifluorophosphorane gave similar results.

  研究了苯基四氟磷烷与醇的氟化反应的立体化学，特别是在类固醇醇的情况下。5α-胆烷-3β-醇和3α-醇分别给出了3α-和3β-氟-5α-胆烷，这表明氟化反应是通过SN2机制进行的；而胆固醇和3β-乙酰氧基-5-溴-5α-胆烷-6β-醇则生成了保持构型的氟化化合物，这表明在特定情况下，邻近基团可能参与了稳定碳正离子中间体。二苯基三氟磷烷也得到了类似的结果。
• Fluorination of Secondary and Primary Alcohols by Thermal Decomposition of Electrochemically Generated Alkoxy Triphenylphosphonium Tetrafluoroborates.
  作者：Hatsuo MAEDA、Takashi KOIDE、Sayaka MATSUMOTO、Hidenobu OHMORI

  DOI：10.1248/cpb.44.1480

  日期：——

  Replacement of hydroxyl groups in secondary and primary alcohols (1) with a fluorine atom arising from tetrafluorobote anion has been performed by the electrochemical formation of alkoxy triphenylphosphonium tetrafluoroborarates (2) from 1, followed by their thermal decomposition. The procedure is quite simple, involving : (1) constant-current electrolysis of a mixture of 1, Ph3P, and Ph3PH·BF4 in CH2Cl2 in an undivided cell; (2) refluxing a tetrahydrofuran or dioxane solution of the residue afforded by evaporation of the solvent in vacuo after the electrolysis. Cyclic secondary alcohols such as 3β-hydroxy steroids and 2-adamantanol are transformed into the corresponding fluorides in satisfactory yields when the geometry of the leaving group in 2 is suitable for the substitution or an elimination process for 2 to give an alkene is stereochemically forbidden. The fluorination of steroidal alcohols and 4-phenyl-1-cyclohexanol proceeded with complete inversion, demonstrating that a fluorine atom from the tetrafluoroborate anion attacks from the side opposite to the phosphonium moiety in 2 via an SN2 mechanism rather than as SN1 mechanism. The fluorination of acyclic secondary and primary alcohols was performed by the present method in reasonable yields, although the reaction for the latter required more forcing conditions, such as refluxing in dioxane.

  次级和初级醇(1)中的羟基被四氟硼酸根衍生的氟原子取代，通过电化学形成烷氧基三苯基膦四氟硼酸盐(2)，然后进行热分解来实现。该过程相当简单，包括：(1)在无隔膜电池中对1、Ph3P和Ph3PH·BF4的CH2Cl2混合物进行恒电流电解；(2)将电解后在真空下蒸发溶剂得到的残渣的四氢呋喃或二氧六环溶液回流。当2中的离去基团的构型适合取代或消除过程，且2生成烯烃的立体化学被禁止时，环状次级醇如3β-羟基甾体和2-金刚烷醇可转化为相应的氟化物，产率令人满意。甾醇和4-苯基-1-环己醇的氟化反应进行完全反转，表明四氟硼酸根阴离子中的氟原子通过SN2机制从2中膦部分的对面攻击，而不是SN1机制。通过本方法，无环次级和初级醇的氟化反应在合理产率下进行，尽管后者的反应需要更强烈条件，如在二氧六环中回流。
• Efficient protocol for the SO2F2-mediated deoxyfluorination of aliphatic alcohols
  作者：Cayo Lee、Joey Lai、Maxim Epifanov、Cindy Xinyun Wang、Glenn M. Sammis

  DOI：10.1016/j.jfluchem.2021.109888

  日期：2021.11

  the development of new synthetic methods to access these important fluorinated motifs. Herein we report the sulfuryl fluoride-mediated deoxyfluorination of alcohols using room temperature reaction conditions in only an hour. A wide range of primary aliphatic alcohols were efficiently converted to the corresponding fluoride in 46-70% isolated yields. Secondary alcohols were also effectively deoxyfluorinated

  烷基氟在制药和农业化学工业中都很普遍。因此，过去 40 年来，人们对开发新的合成方法以获取这些重要的氟化基序产生了浓厚的兴趣。在此，我们报告了使用室温反应条件仅在一小时内硫酰氟介导的醇的脱氧氟化。范围广泛的伯脂肪醇以 46-70% 的分离产率有效地转化为相应的氟化物。仲醇也被有效地脱氧氟化，产率为 50-92%。手性仲醇被干净地转化为相应的烷基氟，对映体富集只有轻微的恶化。类固醇衍生物也以 50% 的产率和 5.9:1 dr 进行脱氧氟化，
• Synthesis of Alkyl Fluorides by Silver‐Catalyzed Radical Decarboxylative Fluorination of Cesium Oxalates
  作者：Émilie Vincent、Julien Brioche

  DOI：10.1002/ejoc.202100344

  日期：2021.5.7

  Readily available from alcohols, cesium oxalates undergo radical deoxyfluorination reaction in the presence of silver salts catalyst and Selectfluor® to produce alkyl fluorides. Herein, the scope of the fluorination protocol and a brief mechanistic study is described.

  草酸铯很容易从醇中获得，在银盐催化剂和Selectfluor®存在下进行自由基脱氧氟化反应，生成烷基氟化物。在此，描述了氟化方案的范围和简要的机理研究。
• Synthesis of Fluorinated Steroids Using a Novel Fluorinating Reagent Tetrabutylammonium Difluorodimethylphenylsilicate (TAMPS)
  作者：Pavel Herrmann、Jaroslav Kvíčala、Vladimír Pouzar、Hana Chodounská

  DOI：10.1135/cccc20081825

  日期：——

  Steroidal 3-fluoroderivatives were prepared from corresponding tosylates using tetrabutylammonium difluorodimethylphenylsilicate as fluorinating agent. The reaction was tested on all four possible C-3 and C-5 stereoisomers of cholestane and 17-oxoandrostane skeletons. In this reaction only one isomer was always formed with opposite configuration at C-3 to starting tosylate. The reaction is accompanied by elimination which affords a mixture of corresponding olefines.

  使用四丁基铵二氟二甲基苯基硅酸酯作为氟化试剂，从相应的tosylates制备了类固醇3-氟衍生物。该反应在胆甾烷和17-氧基雄甾烷骨架的所有四个可能的C-3和C-5立体异构体上进行了测试。在这个反应中，只形成了一个异构体，其C-3位置的构型与起始的tosylate相反。该反应伴随着消除作用，产生相应的烯烃混合物。