(1S,2R,4R)-2-(2,3-dihydrofuran-5-yl)-5,8,8-trimethylbicyclo[2.2.2]oct-5-en-2-ol | 131544-49-5

• 分子结构分类: 有机化合物
• 英文名称: (1S,2R,4R)-2-(2,3-dihydrofuran-5-yl)-5,8,8-trimethylbicyclo[2.2.2]oct-5-en-2-ol
• CAS: 131544-49-5
• 化学式: C₁₅H₂₂O₂
• 分子量: 234.338
• InChiKey: QJXIYRUZCUZCTD-TYNCELHUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.03
• 重原子数：
  17.0
• 可旋转键数：
  1.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  29.46
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  (1S,2R,4R)-2-(2,3-dihydrofuran-5-yl)-5,8,8-trimethylbicyclo[2.2.2]oct-5-en-2-ol 在 palladium on activated charcoal 六甲基磷酰三胺 、 sodium tetrahydroborate 、 cerium(III) chloride 、 氢气 、 lithium diisopropyl amide 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 48.0h， 生成 (3aS,4R,5aS,9aS,9bS)-3a,6,6,9a-Tetramethyl-1,2,3a,4,5,5a,6,7,9a,9b-decahydro-naphtho[2,1-b]furan-4-ol
  参考文献：
  名称：

  Enantioselective total synthesis of (-)-9-epi-Ambrox, a potent ambergris-type olfactory agent

  摘要：

  Addition of the cerium reagent derived from 5-lithio-2,3-dihydrofuran and anhydrous CeCl3 to bicyclic enone 5 (92% ee by lipase hydrolysis of its chloroacetate precursor) affords 6 selectively. Anionic oxy-Cope rearrangement of 6 in refluxing THF induces [3,3] sigmatropy and subsequent enolate ion equilibration. This tandem sequence of reactions allows for an efficient pathway to (-)-2.

  DOI：

  10.1021/jo00003a004
• 作为产物：
  描述：

  5-lithio-2,3-dihydrofuran 、 (-)-(1S,4R)-5,8,8-Trimethylbicyclo<2.2.2>oct-5-en-2-one 在 cerium(III) chloride 作用下， 生成 (1S,2R,4R)-2-(2,3-dihydrofuran-5-yl)-5,8,8-trimethylbicyclo[2.2.2]oct-5-en-2-ol 、 (1S,2S,4R)-2-(2,3-dihydrofuran-5-yl)-5,8,8-trimethylbicyclo[2.2.2]oct-5-en-2-ol
  参考文献：
  名称：

  Enantioselective total synthesis of (-)-9-epi-Ambrox, a potent ambergris-type olfactory agent

  摘要：

  Addition of the cerium reagent derived from 5-lithio-2,3-dihydrofuran and anhydrous CeCl3 to bicyclic enone 5 (92% ee by lipase hydrolysis of its chloroacetate precursor) affords 6 selectively. Anionic oxy-Cope rearrangement of 6 in refluxing THF induces [3,3] sigmatropy and subsequent enolate ion equilibration. This tandem sequence of reactions allows for an efficient pathway to (-)-2.

  DOI：

  10.1021/jo00003a004

文献信息

• Adaptation of oxyanionic sigmatropy to the convergent enantioselective synthesis of ambergris-type odorants
  作者：Robert E. Maleczka、Leo A. Paquette

  DOI：10.1021/jo00023a018

  日期：1991.11

  (-)-(1S,4R)-5,8,8-Trimethylbicyclo[2.2.2]oct-5-en-2-one has been prepared in high optical purity in order to adapt its beta,gamma-unsaturated ketone component to an anionic oxy-Cope strategy aimed at several labdane-like tricyclic ethers. Condensation reactions with the dichloro cerate derivatives of 2,3-dihydrofuran and dihydropyran proceeded regioselectively from the less hindered pi-surface, thereby setting the stage for anionically accelerated [3,3] sigmatropic shift. The resulting enolate anions are electronically destabilized relative to their tautomers, which are consequently formed efficiently. These are captured by reaction with phenylselenenyl chloride. Once selenoxide elimination and reduction with NaBH4-CeCl3 had been accomplished, the stage was set for installation of trans A/B ring stereochemistry. Direct saturation of the original dienones led instead to the cis A/B isomers. The enantioselective syntheses were completed by conversion to the respective xanthates and reduction of these intermediates under free-radical conditions. The results indicate that a practical route to certain potent olfactory agents has been developed.

  为了将β,γ-不饱和酮组分适应于针对几种类似labdane的三环醚的阴离子氧-Cope策略，已成功制备了具有高光学纯度的(-)-(1S,4R)-5,8,8-三甲基双环[2.2.2]辛-5-烯-2-酮。与2,3-二氢呋喃和二氢吡喃的二氯铈衍生物进行的缩合反应从受阻较少的π表面区域选择性地进行，从而为阴离子加速的[3,3]σ位移奠定了基础。所形成的烯醇负离子相对于其互变异构体在电子上不稳定性更高，从而能够高效地生成互变异构体。这些互变异构体通过与苯基硒烷基氯的反应被捕获。在完成硒氧化物消除和NaBH4-CeCl3还原后，即可进行反式A/B环立体化学的构建。然而，直接对原始的二烯酮进行饱和处理反而生成了顺式A/B异构体。通过将这些化合物转化为相应的环状碳硫酯，并在自由基条件下对这些中间体进行还原，最终完成了手性选择性合成。研究结果表明，一种实用的途径已成功开发，可制备某些具有强嗅觉活性的化合物。