(1R,3S)-6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid | 1276098-04-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: (1R,3S)-6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
• CAS: 1276098-04-4
• 化学式: C₁₈H₁₉NO₄
• 分子量: 313.353
• InChiKey: WZMLWLWLTRNYIH-WMLDXEAASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  67.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (1R,3S)-6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid 在 palladium 10% on activated carbon 、 氢气 、 氯甲酸乙酯 、 potassium hydrogencarbonate 、 N,N-二异丙基乙胺 、 ytterbium(III) triflate 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 120.0 ℃ 、101.33 kPa 条件下， 反应 8.0h， 生成 (1R,3S)-2-(N,N'-dicyclohexylcarbamimidoyl)-N-[2,6-di(propan-2-yl)phenyl]-6,7-dimethoxy-1-phenyl-3,4-dihydro-1H-isoquinoline-3-carboxamide
  参考文献：
  名称：

  带有四氢异喹啉骨架的胍有机催化剂的微波辅助合成及其在迈克尔加成反应中的评价

  摘要：

  报道了手性胍有机催化剂的简单实用合成及其在丙二酸酯和β-酮酯与硝基烯烃的不对称迈克尔加成反应中的评价。这些有机催化剂是同类中第一个基于四氢异喹啉骨架的催化剂。此外，还报道了将胍单元引入氨基酰胺衍生物的微波辅助程序。获得的手性产物具有定量化学效率（高达 99% 的产率）和出色的对映选择性（高达 97% ee）。

  DOI：

  10.1002/ejoc.201200303
• 作为产物：
  描述：

  左旋多巴 在 盐酸 、 10% palladium on activated charcoal 、 水 、 氢气 、 potassium carbonate 、 potassium hydrogencarbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 水 、 丙酮 为溶剂， 生成 (1R,3S)-6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
  参考文献：
  名称：

  Novel tetrahydroisoquinoline based organocatalysts for asymmetric Diels–Alder reactions: insight into the catalytic mode using ROESY NMR and DFT studies

  摘要：

  For the first time an organocatalyst bearing a secondary nitrogen within a cyclohexane ring has been evaluated in the asymmetric Diels-Alder reaction. This organocatalyst is also the first of its kind based on a (1R,3S)-6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline backbone. These catalysts were tested over a range of dienes and dienophiles and displayed promising chemical conversions of up to 100% with up to 64% ee with triflic acid as the cocatalyst. Density functional theory computational studies and 20 NMR spectroscopy were used to determine the structure of the intermediate iminium ion formed between the most efficient catalyst and cinnamaldehyde. The reaction profile for each of the four possibilities in this reaction were calculated and it was found that the iminium intermediate leading to the major product is higher in energy but kinetically preferred. The activation energies of all possible reaction paths were calculated and the results correlated with the observed products. These experiments revealed that the presence of both (E)- and (Z)-isomers of the cinnamaldehyde were contributing factors for the low enantioselectivity of the reaction products. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2010.11.010

文献信息

• Microwave-Assisted Synthesis of Guanidine Organocatalysts Bearing a Tetrahydroisoquinoline Framework and Their Evaluation in Michael Addition Reactions
  作者：Tricia Naicker、Per I. Arvidsson、Hendrik G. Kruger、Glenn E. M. Maguire、Thavendran Govender

  DOI：10.1002/ejoc.201200303

  日期：2012.6

  simple and practical syntheses of chiral guanidine organocatalysts and their evaluation in the asymmetric Michael addition reaction of malonates and beta-keto esters with nitro-olefins is reported. These organocatalysts are the first of their kind based on a tetrahydroisoquinoline framework. In addition, a microwave-assisted procedure for introducing the guanidine unit onto amino amide derivatives is reported

  报道了手性胍有机催化剂的简单实用合成及其在丙二酸酯和β-酮酯与硝基烯烃的不对称迈克尔加成反应中的评价。这些有机催化剂是同类中第一个基于四氢异喹啉骨架的催化剂。此外，还报道了将胍单元引入氨基酰胺衍生物的微波辅助程序。获得的手性产物具有定量化学效率（高达 99% 的产率）和出色的对映选择性（高达 97% ee）。
• Novel tetrahydroisoquinoline based organocatalysts for asymmetric Diels–Alder reactions: insight into the catalytic mode using ROESY NMR and DFT studies
  作者：Tricia Naicker、Katja Petzold、Thishana Singh、Per I. Arvidsson、Hendrik G. Kruger、Glenn E.M. Maguire、Thavendran Govender

  DOI：10.1016/j.tetasy.2010.11.010

  日期：2010.12

  For the first time an organocatalyst bearing a secondary nitrogen within a cyclohexane ring has been evaluated in the asymmetric Diels-Alder reaction. This organocatalyst is also the first of its kind based on a (1R,3S)-6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline backbone. These catalysts were tested over a range of dienes and dienophiles and displayed promising chemical conversions of up to 100% with up to 64% ee with triflic acid as the cocatalyst. Density functional theory computational studies and 20 NMR spectroscopy were used to determine the structure of the intermediate iminium ion formed between the most efficient catalyst and cinnamaldehyde. The reaction profile for each of the four possibilities in this reaction were calculated and it was found that the iminium intermediate leading to the major product is higher in energy but kinetically preferred. The activation energies of all possible reaction paths were calculated and the results correlated with the observed products. These experiments revealed that the presence of both (E)- and (Z)-isomers of the cinnamaldehyde were contributing factors for the low enantioselectivity of the reaction products. (C) 2010 Elsevier Ltd. All rights reserved.