(R)-7-[²H₁]-benzyl fluoride | 23059-53-2

• 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: (R)-7-[²H₁]-benzyl fluoride
• 英文别名: [(R)-deuterio(fluoro)methyl]benzene
• CAS: 23059-53-2
• 化学式: C₇H₇F
• 分子量: 111.123
• InChiKey: MBXXQYJBFRRFCK-MUFQJMLISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  8
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (R)-7-[²H₁]-benzyl fluoride 在 sodium periodate 、 ruthenium(III) trichloride hydrate 、 sodium hydroxide 作用下， 以 四氯化碳 、 水 、 乙腈 为溶剂， 反应 48.0h， 以17%的产率得到sodium (R)-[2-²H₁]-fluoroacetate
  参考文献：
  名称：

  Chiral fluoroacetic acid: synthesis of (R)- and (S)-[2H1]-fluoroacetate in high enantiopurity

  摘要：

  A two-step synthesis of (R)- and (S)-[H-2(1)]-fluoroacetate (sodium salts) in high enantioselectivity is reported. The synthesis is the development of a previous one in which the enantioselectivity has been increased from similar to 38% ee to >95% ee. The improvement in enantioselectivity applied Bio's methodology, which involved a deoxyfluorination reaction with DAST on either enantiomer of [H-2(1)]-benzyl alcohol, adding TMS-morpholine to the reaction. The additive promotes an S(N)2 inversion process, and suppresses a competing non-stereospecific S(N)1 reaction course, and as a result significantly improves the stereointegrity of the C-F bond formation. The intermediate [H-2(1)]-benzyl alcohols, [H-2(1)]-benzyl fluorides and the product [H-2(1)]-fluoroacetates as their hexyl esters were separately assayed for their stereochemical integrity, using the Courtieu method. This method involved measuring their H-2 NMR spectra in a chiral matrix of poly-gamma-benzyl L-glutamate. The chiral assay demonstrated that there was no significant loss in stereointegrity during the deoxyfluorination reaction and showed that the enantiomers of [H-2(1)]-fluoroacetate were generated with high enantiomeric purity (95% ee). (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2013.05.001
• 作为产物：
  描述：

  苯甲醛 在 N-(三甲基硅基)吗啉 、 甲酸-d2 、 二乙胺基三氟化硫 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 (R)-7-[²H₁]-benzyl fluoride
  参考文献：
  名称：

  苄基氟CF活化反应的立体化学结果。

  摘要：

  近年来，与其他CX卤素键相比，高极性CF键尽管对传统亲核试剂的反应性低，但已用于活化化学中。Paquin的小组报告了使用一系列氢键供体（例如水，三醇或六氟异丙醇（HFIP））作为活化剂的苄基氟化物的CF活化以进行亲核取代和Friedel-Crafts反应的广泛研究。这项研究通过使用苄基氟化物的对映体纯异构体来确定CF活化反应的立体完整性，从而确定反应条件是否有利于解离（SN1）或缔合（SN2）途径。

  DOI：

  10.3762/bjoc.14.6

文献信息

• Stereochemical outcomes of C–F activation reactions of benzyl fluoride
  作者：Neil S Keddie、Pier Alexandre Champagne、Justine Desroches、Jean-François Paquin、David O'Hagan

  DOI：10.3762/bjoc.14.6

  日期：——

  In recent years, the highly polar C-F bond has been utilised in activation chemistry despite its low reactivity to traditional nucleophiles, when compared to other C-X halogen bonds. Paquin's group has reported extensive studies on the C-F activation of benzylic fluorides for nucleophilic substitutions and Friedel-Crafts reactions, using a range of hydrogen bond donors such as water, triols or hexafluoroisopropanol

  近年来，与其他CX卤素键相比，高极性CF键尽管对传统亲核试剂的反应性低，但已用于活化化学中。Paquin的小组报告了使用一系列氢键供体（例如水，三醇或六氟异丙醇（HFIP））作为活化剂的苄基氟化物的CF活化以进行亲核取代和Friedel-Crafts反应的广泛研究。这项研究通过使用苄基氟化物的对映体纯异构体来确定CF活化反应的立体完整性，从而确定反应条件是否有利于解离（SN1）或缔合（SN2）途径。
• Chiral fluoroacetic acid: synthesis of (R)- and (S)-[2H1]-fluoroacetate in high enantiopurity
  作者：Rudy D.P. Wadoux、Xiaowei Lin、Neil S. Keddie、David O’Hagan

  DOI：10.1016/j.tetasy.2013.05.001

  日期：2013.6

  A two-step synthesis of (R)- and (S)-[H-2(1)]-fluoroacetate (sodium salts) in high enantioselectivity is reported. The synthesis is the development of a previous one in which the enantioselectivity has been increased from similar to 38% ee to >95% ee. The improvement in enantioselectivity applied Bio's methodology, which involved a deoxyfluorination reaction with DAST on either enantiomer of [H-2(1)]-benzyl alcohol, adding TMS-morpholine to the reaction. The additive promotes an S(N)2 inversion process, and suppresses a competing non-stereospecific S(N)1 reaction course, and as a result significantly improves the stereointegrity of the C-F bond formation. The intermediate [H-2(1)]-benzyl alcohols, [H-2(1)]-benzyl fluorides and the product [H-2(1)]-fluoroacetates as their hexyl esters were separately assayed for their stereochemical integrity, using the Courtieu method. This method involved measuring their H-2 NMR spectra in a chiral matrix of poly-gamma-benzyl L-glutamate. The chiral assay demonstrated that there was no significant loss in stereointegrity during the deoxyfluorination reaction and showed that the enantiomers of [H-2(1)]-fluoroacetate were generated with high enantiomeric purity (95% ee). (C) 2013 Elsevier Ltd. All rights reserved.