(-)-methyl (1S,2R,3R,6S)-3-propyl-7-aza-8-oxatricyclo[4.2.1.0(3,7)]-nonane-2-carboxylate | 1243634-72-1

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: (-)-methyl (1S,2R,3R,6S)-3-propyl-7-aza-8-oxatricyclo[4.2.1.0(3,7)]-nonane-2-carboxylate
• 英文别名: (1S,2R,3R,6S)-(-)-methyl 3-propyl-7-aza-8-oxatricyclo[4.2.1.0(3,7)]nonane-2-carboxylate；(1S,2R,3R,6S)-(-)-methyI 3-propyl-7-aza-8-oxatricyclo[4,2,1,0]-nonane-2-carboxylate
• CAS: 1243634-72-1
• 化学式: C₁₂H₁₉NO₃
• 分子量: 225.288
• InChiKey: YRRVRFXNGVFRHT-UXCLJVHYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  38.77
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (-)-methyl (1S,2R,3R,6S)-3-propyl-7-aza-8-oxatricyclo[4.2.1.0(3,7)]-nonane-2-carboxylate 在 5%-palladium/activated carbon 、 氢气 作用下， 以 甲醇 、 苯 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 96.0h， 生成 (+)-methyl (1R,2R,3S,5S)-1-propyl-3-(hydroxy)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate methanesulfonic acid salt
  参考文献：
  名称：

  Enantioselective Synthesis of Cocaine C-1 Analogues using Sulfinimines (N-Sulfinyl Imines)

  摘要：

  The first examples of cocaine analogues having substituents (methyl, ethyl, n-propyl, n-pentyl, and phenyl) at the C-1 position of the cocaine tropane skeleton were prepared by heating sulfinimine-derived alpha,beta-unsaturated pyrrolidine nitrones. In the presence of the Lewis acid Al((OBu)-Bu-t)(3) the nitrones undergo an intramolecular [3 + 2] cycloaddition to give tricyclic isoxazolidines that were transformed in three steps to the cocaine analogues. In the absence of the Lewis acid, lactams were formed resulting from rearrangement of the nitrone to an oxaziridine. A novel Pd-and base-promoted rearrangement of methanesulfonate salts of isoxazolidine to bridge bicyclic[4.2.1]isoxazolidines was discovered.

  DOI：

  10.1021/jo202652f
• 作为产物：
  描述：

  (Ss,5S,2E)-(+)-methyl N-(p-toluenesulfinyl)-5-amino-7-(2-propyl-1,3-dioxolan-2-yl)-hept-2-enoate 在 盐酸 、 过氧化脲素 、 甲基三氧化铼(VII) 、 aluminum tri-tert-butoxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 甲苯 为溶剂， 反应 103.0h， 生成 (-)-methyl (1S,2R,3R,6S)-3-propyl-7-aza-8-oxatricyclo[4.2.1.0(3,7)]-nonane-2-carboxylate
  参考文献：
  名称：

  Enantioselective Synthesis of Cocaine C-1 Analogues using Sulfinimines (N-Sulfinyl Imines)

  摘要：

  The first examples of cocaine analogues having substituents (methyl, ethyl, n-propyl, n-pentyl, and phenyl) at the C-1 position of the cocaine tropane skeleton were prepared by heating sulfinimine-derived alpha,beta-unsaturated pyrrolidine nitrones. In the presence of the Lewis acid Al((OBu)-Bu-t)(3) the nitrones undergo an intramolecular [3 + 2] cycloaddition to give tricyclic isoxazolidines that were transformed in three steps to the cocaine analogues. In the absence of the Lewis acid, lactams were formed resulting from rearrangement of the nitrone to an oxaziridine. A novel Pd-and base-promoted rearrangement of methanesulfonate salts of isoxazolidine to bridge bicyclic[4.2.1]isoxazolidines was discovered.

  DOI：

  10.1021/jo202652f

文献信息

• Asymmetric Total Synthesis of (<i>S</i>)-(+)-Cocaine and the First Synthesis of Cocaine C-1 Analogs from <i>N</i>-Sulfinyl β-Amino Ester Ketals
  作者：Franklin A. Davis、Naresh Theddu、Ram Edupuganti

  DOI：10.1021/ol1017118

  日期：2010.9.17

  Sulfinimine-derived α,β-unsaturated pyrrolidine nitrones, on heating with Al(O-t-Bu)3, undergo a highly stereoselective intramolecular [3 + 2] cycloaddition to give tricyclic isoxazolidines, which are transformed in three-steps to give C-1 substituted cocaine analogs.

  亚砜胺衍生的α，β-不饱和吡咯烷腈与Al（O- t- Bu）3加热时，经历高度立体选择性的分子内[3 + 2]环加成反应，得到三环异恶唑烷，将其分三步转化为C -1个取代的可卡因类似物。