4-(2,6-Dimethoxyphenyl)-6,6-dimethylbicyclo<3.1.1>hept-3-en-2-one | 130799-44-9

• 分子结构分类: 有机化合物
• 英文名称: 4-(2,6-Dimethoxyphenyl)-6,6-dimethylbicyclo<3.1.1>hept-3-en-2-one
• 英文别名: (1S,5R)-4-(2,6-dimethoxyphenyl)-6,6-dimethylbicyclo[3.1.1]hept-3-en-2-one
• CAS: 130799-44-9
• 化学式: C₁₇H₂₀O₃
• 分子量: 272.344
• InChiKey: JZTOYELNSSKILD-NWDGAFQWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.33
• 重原子数：
  20.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  35.53
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  4-(2,6-Dimethoxyphenyl)-6,6-dimethylbicyclo<3.1.1>hept-3-en-2-one 在 jones' reagent 、 丙烷-1-硫醇 、 氨 、 lithium 、 sodium hydride 作用下， 反应 5.08h， 生成 4-(2-Hydroxy-6-methoxyphenyl)-6,6-dimethylbicyclo<3.1.1>heptan-2-one
  参考文献：
  名称：

  Synthesis of both enantiomers of nabilone from a common intermediate. Enantiodivergent synthesis of cannabinoids

  摘要：

  Both enantiomers of the synthetic cannabinoid nabilone (4) have been synthesized from a common intermediate, enone 7. Enone 7 was prepared by reaction of [2,6-dimethoxy-4-(1,1-dimethylheptyl)phenyl]lithium with (+)-apoverbenone (2), followed by PDC oxidation. Li/NH3 reduction of 7 gave saturated ketone 9, which, after ether cleavage to 10, afforded (6aS,10aR)-hexahydrodibenzopyran 15 on reaction with SnCl4. Isomerization to 6aR,10aR ketone 16 followed by ether cleavage gave the 6aR,10aR enantiomer of nabilone (4). The 6aS,10aS enantiomer of 4 (24) was prepared from 7 by ether cleavage to 18 and rearrangement to nonracemic tetrahydrodibenzopyran 20 using AlCl3. Dissolving metal reduction of 20 followed by ether cleavage gave the 6aS,10aS enantiomer of nabilone (24). A model sequence employing (2,6-dimethoxyphenyl)lithium at the first step was carried out and the structure of one of the intermediates, ketone 12, was established by X-ray crystallography. A new preparation of apoverbenone (2) has been developed.

  DOI：

  10.1021/jo00006a021
• 作为产物：
  描述：

  (+)-apoverbenone 在 正丁基锂 、 jones' reagent 作用下， 以 丙酮 为溶剂， 反应 21.5h， 生成 4-(2,6-Dimethoxyphenyl)-6,6-dimethylbicyclo<3.1.1>hept-3-en-2-one
  参考文献：
  名称：

  Synthesis of (.+-.)-11-nor-9-carboxy-.DELTA.9-tetrahydrocannabinol. New synthetic approaches to cannabinoids

  摘要：

  A completely regioselective synthesis of (+/-)-11-nor-9-carboxy-DELTA-9-tetrahydrocannabinol (1), a principal human metabolite of DELTA-9-tetrahydrocannabinol (2), has been carried out in seven steps and 14% overall yield from apoverbenone (9) and the bis-MOM ether of olivetol. Condensation of 9 with the aryllithium derived from the bis-MOM ether of olivetol gives an unstable tertiary allylic alcohol that undergoes oxidative rearrangement to give enone 42. Reaction of 42 with acid results in hydrolysis of the MOM ethers and cyclization to benzopyranone 21. Conversion to MOM ether 39 followed by Li/NH3 reduction and trapping of the enolate with N-phenyltriflimide gives vinyl triflate 40 plus the isomer with a cis ring fusion. Palladium-catalyzed carboxylation, hydrolysis of the MOM ether, and separation from cis acid 41 gives pure 1. Model experiments employing unsubstituted resorcinol derivatives that lead to ester 27 are described, as are a number of alternative approaches to acid 1.

  DOI：

  10.1021/jo00004a027

文献信息

• HUFFMAN, JOHN W.;ZHANG, XUEHAI;WU, MING-JUNG;JOYNER, H. HOWARD;PENNINGTON+, J. ORG. CHEM., 56,(1991) N, C. 1481-1489
  作者：HUFFMAN, JOHN W.、ZHANG, XUEHAI、WU, MING-JUNG、JOYNER, H. HOWARD、PENNINGTON+

  DOI：——

  日期：——