6,7-Dimethoxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid ((1S,2R,3S,4R)-3-hydroxy-4,7,7-trimethyl-bicyclo[2.2.1]hept-2-yl)-amide | 184346-48-3

• 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: 6,7-Dimethoxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid ((1S,2R,3S,4R)-3-hydroxy-4,7,7-trimethyl-bicyclo[2.2.1]hept-2-yl)-amide
• CAS: 184346-48-3
• 化学式: C₂₂H₃₂N₂O₄
• 分子量: 388.507
• InChiKey: ZFZWATNMBXKRAE-YHFKFMBFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.96
• 重原子数：
  28.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  71.03
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  6,7-Dimethoxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid ((1S,2R,3S,4R)-3-hydroxy-4,7,7-trimethyl-bicyclo[2.2.1]hept-2-yl)-amide 在 三氯氧磷 作用下， 以 甲苯 为溶剂， 以70%的产率得到(1R,2S,6R,7S)-4-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-1,10,10-trimethyl-3-oxa-5-azatricyclo[5.2.1.02,6]dec-4-ene
  参考文献：
  名称：

  1-Magnesiotetrahydroisoquinolyloxazolines as Chiral Nucleophiles in Stereoselective Additions to Aldehydes:  Auxiliary Optimization, Asymmetric Synthesis of (+)-Corlumine, (+)-Bicuculline, (+)-Egenine, and (+)-Corytensine, and Preliminary ¹³C NMR Studies of 1-Lithio- and 1-Magnesiotetrahydroisoquinolyloxazolines

  摘要：

  Transmetalation of 1-lithiotetrahydroisoquinolyloxazolines with magnesium halides affords Grignard reagents that add to aldehydes with up to 80% selectivity for one of the four possible diastereomeric products. An oxazoline chiral auxiliary derived from camphor provides an optimal blend of diastereoselectivity and isomer separability. Synthetic applications of the optimal auxiliary, patterned after a literature approach in the racemic series, comprise an improved (formal) synthesis of bicuculline, egenine, and corytensine, as well as an efficient synthesis of corlumine. Preliminary NMR studies show that both 1-lithio- and 1-magnesiotetrahydroisoquinolyloxazolines are dynamic mixtures in THF solution at low temperatures. The barrier to pyramidal inversion of the secondary Grignard reagent is in the 9.8-10.1 kcal/mol range, while an upper limit of about 8.2 kcal/mol can be assigned to the barrier to the organolithium inversion.

  DOI：

  10.1021/jo961164u
• 作为产物：
  描述：

  (1R,4S)-3-hydroxyimino-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one 在 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 乙醚 为溶剂， 反应 49.0h， 生成 6,7-Dimethoxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid ((1S,2R,3S,4R)-3-hydroxy-4,7,7-trimethyl-bicyclo[2.2.1]hept-2-yl)-amide
  参考文献：
  名称：

  1-Magnesiotetrahydroisoquinolyloxazolines as Chiral Nucleophiles in Stereoselective Additions to Aldehydes:  Auxiliary Optimization, Asymmetric Synthesis of (+)-Corlumine, (+)-Bicuculline, (+)-Egenine, and (+)-Corytensine, and Preliminary ¹³C NMR Studies of 1-Lithio- and 1-Magnesiotetrahydroisoquinolyloxazolines

  摘要：

  Transmetalation of 1-lithiotetrahydroisoquinolyloxazolines with magnesium halides affords Grignard reagents that add to aldehydes with up to 80% selectivity for one of the four possible diastereomeric products. An oxazoline chiral auxiliary derived from camphor provides an optimal blend of diastereoselectivity and isomer separability. Synthetic applications of the optimal auxiliary, patterned after a literature approach in the racemic series, comprise an improved (formal) synthesis of bicuculline, egenine, and corytensine, as well as an efficient synthesis of corlumine. Preliminary NMR studies show that both 1-lithio- and 1-magnesiotetrahydroisoquinolyloxazolines are dynamic mixtures in THF solution at low temperatures. The barrier to pyramidal inversion of the secondary Grignard reagent is in the 9.8-10.1 kcal/mol range, while an upper limit of about 8.2 kcal/mol can be assigned to the barrier to the organolithium inversion.

  DOI：

  10.1021/jo961164u

文献信息

• Second-generation auxiliary for the asymmetric addition of metalated tetrahydroisoquinolines to aldehydes
  作者：Pingsheng Zhang、Robert E. Gawley

  DOI：10.1016/s0040-4039(00)79567-0

  日期：1992.5

  The selectivity of asymmetric addition of tetrahydroisoquinolyloxazoline Grignard reagents to aldehydes has now been improved to 78-82% ds through the use of a camphor-derived auxiliary. The new auxiliary has broad applicability, with overall yields of chemically and diastereomerically pure addition products now in the 50-58% range.