ethyl (1RS,2SR)-2-fluoro-2-(4-chlorophenyl)cyclopropanecarboxylate

• 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: ethyl (1RS,2SR)-2-fluoro-2-(4-chlorophenyl)cyclopropanecarboxylate
• 英文别名: trans-Ethyl 2-(4-chlorophenyl)-2-fluorocyclopropanecarboxylate；ethyl (1S,2R)-2-(4-chlorophenyl)-2-fluorocyclopropane-1-carboxylate
• 化学式: C₁₂H₁₂ClFO₂
• 分子量: 242.677
• InChiKey: MUZPQRQJSCNPRK-JQWIXIFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl (1RS,2SR)-2-fluoro-2-(4-chlorophenyl)cyclopropanecarboxylate 在 氢氧化钾 作用下， 以 甲醇 为溶剂， 以92%的产率得到rac-2-(4-chlorophenyl)-2-fluorocyclopropanecarboxylic acid
  参考文献：
  名称：

  Fluorinated Phenylcyclopropylamines. 2. Effects of Aromatic Ring Substitution and of Absolute Configuration on Inhibition of Microbial Tyramine Oxidase

  摘要：

  A series of para-substituted diastereopure cis- and trans-2-fluoro-2-arylcyclopropylamines were synthesized and these were investigated as inhibitors of microbial tyramine oxidase from Arthrobacter sp. All compounds were shown to be competitive inhibitors of this enzyme. The nature of the para-substituents in the more potent trans-isomer (cis-relationship between fluorine and the amino group) of 2-fluoro-2-arylcyclopropylamine influenced the inhibitory potency in a consistent fashion. Thus, electron-withdrawing groups (F, Cl) slightly decreased the activity, while the methyl group (+ I substituent) increased the activity by a factor of ca. 7 compared to trans-2-fluoro-2-phenylcyclopropylamine and by a factor of 90 compared to tranylcypromine. Activity also was strongly dependent on the absolute configuration. The (1S,2S)-enantiomer of 2-fluoro-2-phenylcyclopropylamine was an excellent inhibitor of tyramine oxidase whereas the (1R,2R)-enantiomer was essentially devoid of activity.

  DOI：

  10.1021/jm049957t
• 作为产物：
  描述：

  1-(2-溴-1-氟乙基)-4-氯苯 在 copper acetylacetonate potassium tert-butylate 作用下， 以 二氯甲烷 为溶剂， 反应 7.0h， 生成 ethyl (1RS,2SR)-2-fluoro-2-(4-chlorophenyl)cyclopropanecarboxylate
  参考文献：
  名称：

  Asymmetric Cyclopropanation of Vinyl Fluorides: Access to Enantiopure Monofluorinated Cyclopropane Carboxylates

  摘要：

  过渡金属催化的环丙烷化反应，通过与烷基二氮酸酯的反应，能够平稳地获得由烃基醇或芳香族乙烯氟化物（由相应烯烃经过溴氟化和后续去溴化反应制得）的外消旋1 : 1混合物的顺/反凉氟化环丙烷羧酸酯。采用手性纯双（噁唑啉）配体和铜（I）三氟甲磺酸盐使得该反应具备顺式立体选择性和对映选择性。例如，α-氟苯乙烯（3a）与叔丁基二氮酸酯在以(S)-叔亮氨酸为基础的催化剂11b和CuOTf的存在下反应，得到4 : 1的反-2-氟-2-苯基环丙烷羧酸酯（4e），其对映体过量率（ee）为93%，以及相应的顺式异构体5e，其对映体过量率为89%。反式异构体4e的绝对构型已经通过衍生物的X射线结构分析确定为（1S，2S）。

  DOI：

  10.1055/s-2000-7103

文献信息

• Diastereoselectivity of cyclopropanation of substituted α-fluorostyrenes versus styrenes by different methods
  作者：Katharina Bartels、Benjamin Schinor、Günter Haufe

  DOI：10.1016/j.jfluchem.2017.09.008

  日期：2017.11

  respectively, were obtained. An advantage of the latter protocol is the in situ formation of ethyl diazoacetate from ethyl glycinate hydrochloride in aqueous solution by diazotation avoiding the in-substance application of the potentially explosive ethyl diazoacetate. Accordingly, a series of diastereoisomeric ethyl 2-aryl-2-fluoro-cyclopropane carboxylates was synthesized from p- or m-substituted α-fluorostyrenes

  苯乙烯和α-氟苯乙烯与重氮乙酸酯的环丙烷化的非对映选择性取决于所用催化剂以及氟取代基的存在与否。苯乙烯与重氮乙酸酯的Cu（acac）2催化反应产生3：1的选择性，有利于反式-2-苯基环丙烷羧酸酯，而α-氟苯乙烯则提供了1：1的顺式/反式异构体混合物。竞争实验证明，与苯乙烯本身相比，α-氟苯乙烯的反应更慢。用较大的四苯基铁（III）-卟啉氯化物作为催化剂，分别得到10∶1或3∶1的混合物。后一种协议的优点是原位通过重氮化从水溶液中的甘氨酸乙酯盐酸盐中生成重氮乙酸乙酯，从而避免了潜在爆炸性的重氮乙酸乙酯的实质性应用。因此，非对映异构系列2-芳基-2-氟-环丙烷羧酸的合成自p -或米取代α-氟苯乙烯。
• Asymmetric Cyclopropanation of Vinyl Fluorides: Access to Enantiopure Monofluorinated Cyclopropane Carboxylates
  作者：Oliver G. J. Meyer、Roland Fröhlich、Günter Haufe

  DOI：10.1055/s-2000-7103

  日期：——

  The transition metal catalyzed cyclopropanation with alkyl diazoacetates of aliphatic or aromatic vinyl fluorides, prepared from the corresponding alkenes by bromofluorination and subsequent dehydrobromination, provides a smooth access to racemic 1 : 1 mixtures of cis/trans isomeric monofluorinated cyclopropane carboxylates. The application of enantiopure bis(oxazoline) ligands and copper(I) triflate makes the reaction trans-diastereoselective and enantioselective. For example, treatment of α-fluorostyrene (3a) with tert-butyl diazoacetate in the presence of 2 mol% of the catalyst prepared from (S)-tert-leucine-based 11b and CuOTf gave a 4 : 1 mixture of trans-2-fluoro-2-phenylcyclopropanecarboxylate (4e) with 93% ee and the corresponding cis-isomer 5e with 89% ee. The absolute configuration of the trans-isomer 4e has been determined to be (1S,2S) by X-ray structure analysis of a derivative.

  过渡金属催化的环丙烷化反应，通过与烷基二氮酸酯的反应，能够平稳地获得由烃基醇或芳香族乙烯氟化物（由相应烯烃经过溴氟化和后续去溴化反应制得）的外消旋1 : 1混合物的顺/反凉氟化环丙烷羧酸酯。采用手性纯双（噁唑啉）配体和铜（I）三氟甲磺酸盐使得该反应具备顺式立体选择性和对映选择性。例如，α-氟苯乙烯（3a）与叔丁基二氮酸酯在以(S)-叔亮氨酸为基础的催化剂11b和CuOTf的存在下反应，得到4 : 1的反-2-氟-2-苯基环丙烷羧酸酯（4e），其对映体过量率（ee）为93%，以及相应的顺式异构体5e，其对映体过量率为89%。反式异构体4e的绝对构型已经通过衍生物的X射线结构分析确定为（1S，2S）。
• Fluorinated Phenylcyclopropylamines. 2. Effects of Aromatic Ring Substitution and of Absolute Configuration on Inhibition of Microbial Tyramine Oxidase
  作者：Thomas C. Rosen、Shinichi Yoshida、Roland Fröhlich、Kenneth L. Kirk、Günter Haufe

  DOI：10.1021/jm049957t

  日期：2004.11.1

  A series of para-substituted diastereopure cis- and trans-2-fluoro-2-arylcyclopropylamines were synthesized and these were investigated as inhibitors of microbial tyramine oxidase from Arthrobacter sp. All compounds were shown to be competitive inhibitors of this enzyme. The nature of the para-substituents in the more potent trans-isomer (cis-relationship between fluorine and the amino group) of 2-fluoro-2-arylcyclopropylamine influenced the inhibitory potency in a consistent fashion. Thus, electron-withdrawing groups (F, Cl) slightly decreased the activity, while the methyl group (+ I substituent) increased the activity by a factor of ca. 7 compared to trans-2-fluoro-2-phenylcyclopropylamine and by a factor of 90 compared to tranylcypromine. Activity also was strongly dependent on the absolute configuration. The (1S,2S)-enantiomer of 2-fluoro-2-phenylcyclopropylamine was an excellent inhibitor of tyramine oxidase whereas the (1R,2R)-enantiomer was essentially devoid of activity.