α-cyano-N-<(ethoxycarbonyl)phenylmethyl>-α-fluorophenylacetamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: α-cyano-N-<(ethoxycarbonyl)phenylmethyl>-α-fluorophenylacetamide
• 英文别名: Ethyl 2-[(2-cyano-2-fluoro-2-phenylacetyl)amino]-2-phenylacetate
• 化学式: C₁₉H₁₇FN₂O₃
• 分子量: 340.354
• InChiKey: QIDSHLNWCDCXBJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  79.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (S)-(-)-α-cyano-α-fluorophenylacetic acid 在 吡啶 、 草酰氯 作用下， 以 四氯化碳 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 α-cyano-N-<(ethoxycarbonyl)phenylmethyl>-α-fluorophenylacetamide
  参考文献：
  名称：

  Chemistry of novel compounds with multifunctional carbon structure. 9. Molecular design, synthetic studies, and NMR investigation of several efficient chiral derivatizing reagents which give very large 19F NMR .DELTA..delta. values in enantiomeric excess determination

  摘要：

  In order to develop efficient ee-determining reagents potentially superior to MTPA (1), some multifunctional compounds 2-5 were rationally designed. From NMR investigations of the analogous diastereomeric derivatives it was found that the chemical shift differences for each pair of diastereomers (DELTAdelta values) for CFPA derivatives 5d-f were approximately five times greater in F-19 NMR spectra and two times greater in H-1 NMR spectra than those of 1d-f. Synthesis of the optically pure CFPA, (-)-5a and (+)-5a, was achieved by nitrosation of each diastereomer of the optically active N-(1-phenylethyl)amides, 5f(M) and 5f(L), followed by thermal decomposition. Various derivatives were prepared by the condensation of 5b and lb with alcohol and amine nucleophiles, and both DELTAdelta(F) and DELTAdelta(H) Values were obtained for each compound. The CFPA derivatives 5d-m have proven to be significantly superior for ee determinations when compared to the corresponding MTPA derivatives 1d-m, particularly in compounds having remotely disposed chiral centers.

  DOI：

  10.1021/jo00059a036

文献信息

• The remarkably high reactivity of α-cyano-α-fluorophenylacetyl chloride (CFPA–Cl) towards hindered nucleophiles in enantiomeric excess determination
  作者：Yoshio Takeuchi、Noriaki Itoh、Toru Koizumi

  DOI：10.1039/c39920001514

  日期：——

  The reaction of PhCF(CN)COCl 2b with 3,3-dimethylbutan-2-ol 5 was found to proceed more than 500 times faster than that of PhCCF3(OMe)COCl (MTPA–Cl)1b, suggesting that the CFPA method should potentially lead to much less kinetic resolution than the currently much-used MTPA method in enantiometric excess determinations.

  PhCF(CN)COCl与3,3-二甲基丁醇的反应速度被发现比PhCCF3(OMe)COCl（MTPA–Cl）的反应快超过500倍，这表明CFPA方法在对映体过量测定中有可能导致的动力学分辨率远低于目前广泛使用的MTPA方法。
• Chemistry of Novel Compounds with Multifunctional Carbon Structure. 8. Application of the α-Cyano-α-fluorophenylacetic Acid (CFPA) Method to the Enantiomeric Excess Determination of Some Hindered Alcohols in Asymmetric and Natural Product Syntheses
  作者：Yoshio Takeuchi、Noriaki Itoh、Shun-ichi Kawahara、Toru Koizumi

  DOI：10.1016/s0040-4020(01)80542-1

  日期：1993.2

  pinacolyl alcohol was found to proceed more than 500 times faster than that of MTPA chloride (1b) suggesting that the CFPA method induces potentially much less kinetic resolution than the widely used MTPA method in enantiomeric excess (ee) determination. Some applications of CFPA method were also investigated to evaluate practical use of CFPA reagent in ee determination of some hindered alcohols in asymmetric

  发现CFPA氯化物（2b）与松香烯醇的反应比MTPA氯化物（1b）的反应快500倍以上，这表明CFPA方法在对映体过量（ee ） 决心。还研究了CFPA方法的一些应用，以评估CFPA试剂在不对称和天然产物合成中某些受阻醇的ee测定中的实际应用。
• Chemistry of novel compounds with multifunctional carbon structure. 9. Molecular design, synthetic studies, and NMR investigation of several efficient chiral derivatizing reagents which give very large 19F NMR .DELTA..delta. values in enantiomeric excess determination
  作者：Yoshio Takeuchi、Noriaki Itoh、Toshihiro Satoh、Toru Koizumi、Kentaro Yamaguchi

  DOI：10.1021/jo00059a036

  日期：1993.3

  In order to develop efficient ee-determining reagents potentially superior to MTPA (1), some multifunctional compounds 2-5 were rationally designed. From NMR investigations of the analogous diastereomeric derivatives it was found that the chemical shift differences for each pair of diastereomers (DELTAdelta values) for CFPA derivatives 5d-f were approximately five times greater in F-19 NMR spectra and two times greater in H-1 NMR spectra than those of 1d-f. Synthesis of the optically pure CFPA, (-)-5a and (+)-5a, was achieved by nitrosation of each diastereomer of the optically active N-(1-phenylethyl)amides, 5f(M) and 5f(L), followed by thermal decomposition. Various derivatives were prepared by the condensation of 5b and lb with alcohol and amine nucleophiles, and both DELTAdelta(F) and DELTAdelta(H) Values were obtained for each compound. The CFPA derivatives 5d-m have proven to be significantly superior for ee determinations when compared to the corresponding MTPA derivatives 1d-m, particularly in compounds having remotely disposed chiral centers.