N-methyl-N-((R(p))-[2.2]paracyclophan-4-yl)-2,3-dimethylpent-4-enethioamide

• 分子结构分类: 有机化合物 - 苯类化合物
• 英文名称: N-methyl-N-((R(p))-[2.2]paracyclophan-4-yl)-2,3-dimethylpent-4-enethioamide
• 英文别名: (2R,3R)-N,2,3-trimethyl-N-(5-tricyclo[8.2.2.24,7]hexadeca-1(13),4,6,10(14),11,15-hexaenyl)pent-4-enethioamide
• 化学式: C₂₄H₂₉NS
• 分子量: 363.567
• InChiKey: YIMZZVHHGGSFQX-QZTJIDSGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  35.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  N-methyl-N-((R(p))-[2.2]paracyclophan-4-yl)-propionamide 在 劳森试剂 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 0.5h， 生成 N-methyl-N-((R(p))-[2.2]paracyclophan-4-yl)-2,3-dimethylpent-4-enethioamide
  参考文献：
  名称：

  Combined Theoretical and Experimental Study on High Diastereoselective Chirality Transfer Based on [2.2]Paracyclophane Derivative Chiral Reagent

  摘要：

  We report a paracyclophane N-Me thioamide chiral reagent for the asymmetric thio-Claisen rearrangement with high diasteroselectivity. Comparisons between candidate chiral reagent N-phenyl-N-([2.2]paracyclophan-4-yl)amide, N-methyl amide, N-phenyl thioamide, and N-methyl thioamide are made both by experiment and theoretical calculations to clarify the principle behind the high diasteroselectivity. Dynamic H-1 NMR phenomenon tested by varying temperature (VT) experiments has proved that N-Ph amides have triple splitting peaks, while N-Ph thioamide would reduce the number to two, further substituting the Ph to Me made dynamic phenomenon disappear. So the side chain is thought to be the most rigid in N-Me thioamide, which accounts for a structure prerequisite favoring high efficient chirality transfer. This is confirmed by theoretical calculation: remarkable energy difference exists between the Re and Si faces of the chiral molecule. To further clarify the possible pathways for thio-Claisen rearrangement, theoretical prediction is adopted. The result implies that the cisoid pathways will dominate the process. Further experiment confirmed this: with N-Me thioamide, the asymmetrical reaction affords gamma-unsaturated thioamides in good yields and high diastereoselectivities up to 98%. After removing the thioamide auxiliaries under hydrolysis conditions, product beta,gamma-substituted chiral alcohols reached high enantiopurity of 98% ee.

  DOI：

  10.1021/jo202186e

文献信息

• Combined Theoretical and Experimental Study on High Diastereoselective Chirality Transfer Based on [2.2]Paracyclophane Derivative Chiral Reagent
  作者：Biao Jiang、Lei Han、Yong-Le Li、Xiao-Long Zhao、Yang Lei、Dai-Qian Xie、John Z. H. Zhang

  DOI：10.1021/jo202186e

  日期：2012.2.17

  We report a paracyclophane N-Me thioamide chiral reagent for the asymmetric thio-Claisen rearrangement with high diasteroselectivity. Comparisons between candidate chiral reagent N-phenyl-N-([2.2]paracyclophan-4-yl)amide, N-methyl amide, N-phenyl thioamide, and N-methyl thioamide are made both by experiment and theoretical calculations to clarify the principle behind the high diasteroselectivity. Dynamic H-1 NMR phenomenon tested by varying temperature (VT) experiments has proved that N-Ph amides have triple splitting peaks, while N-Ph thioamide would reduce the number to two, further substituting the Ph to Me made dynamic phenomenon disappear. So the side chain is thought to be the most rigid in N-Me thioamide, which accounts for a structure prerequisite favoring high efficient chirality transfer. This is confirmed by theoretical calculation: remarkable energy difference exists between the Re and Si faces of the chiral molecule. To further clarify the possible pathways for thio-Claisen rearrangement, theoretical prediction is adopted. The result implies that the cisoid pathways will dominate the process. Further experiment confirmed this: with N-Me thioamide, the asymmetrical reaction affords gamma-unsaturated thioamides in good yields and high diastereoselectivities up to 98%. After removing the thioamide auxiliaries under hydrolysis conditions, product beta,gamma-substituted chiral alcohols reached high enantiopurity of 98% ee.