(1S,3R,4S)-3-(Methoxymethoxy)-1-<(Z)-2-(p-methoxyphenoxy)vinyl>-7,7-dimethyl-2-norbornanone | 162790-66-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (1S,3R,4S)-3-(Methoxymethoxy)-1-<(Z)-2-(p-methoxyphenoxy)vinyl>-7,7-dimethyl-2-norbornanone
• 英文别名: (1S,3R,4S)-3-(methoxymethoxy)-1-[(Z)-2-(4-methoxyphenoxy)ethenyl]-7,7-dimethylbicyclo[2.2.1]heptan-2-one
• CAS: 162790-66-1
• 化学式: C₂₀H₂₆O₅
• 分子量: 346.423
• InChiKey: WLCRAQIVVPFKEX-HZAXMOSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-溴-1,4-二氧杂螺[4.5]癸-6-烯 、 (1S,3R,4S)-3-(Methoxymethoxy)-1-<(Z)-2-(p-methoxyphenoxy)vinyl>-7,7-dimethyl-2-norbornanone 在 叔丁基锂 作用下， 以 四氢呋喃 、 正戊烷 为溶剂， 以72%的产率得到(1S,2R,3R,4S)-2-(1,4-Dioxaspiro<4.5>dec-6-en-6-yl)-3-(methoxymethoxy)-1-<(Z)-2-(p-methoxyphenoxy)vinyl>-7,7-dimethyl-2-norbornanol
  参考文献：
  名称：

  Evaluation of 2-Bromocyclohexenone Acetals as Vehicles for the Introduction of C-7 Oxygen Preliminary to the Synthesis of Taxane Diterpenes

  摘要：

  The coupling of an optically pure, camphor-derived, beta,gamma-unsaturated, bicyclic ketone with a suitable vinyl organometallic is recognized to result in 1,2-addition from the endo face. Anionic oxy-Cope rearrangement of these carbinols proceeds via an ''endo-chair'' transition state to deliver a strained and reactive enolate that is formed regioselectively and is amenable to alpha-methylation from the top face. These steps, which are preliminary to a broad-based approach to the taxane diterpenes, had not yet accommodated suitable introduction of a C-7 oxygen substituent as required of taxol. Typically, an ether substituent at this site experiences beta-elimination once the enolate anion intermediate is accessed. Herein it is demonstrated that the parent 2-bromocyclohexenone acetal is well suited to resolving this complication. Halogen-metal exchange proceeds well to provide a suitably nucleophilic building block. Direct charge-accelerated sigmatropic rearrangement of the carbinol products does proceed with beta-elimination, but under the present circumstances the second C-O bond remains in the form of a vinylogous ester. Alternatively, the carbinols are amenable to chemoselective hydrolysis of the acetal, thereby unmasking a conjugated cyclohexenone part structure. These intermediates have been found to rearrange along completely analogous reaction trajectories to provide enolates of a beta-diketone subunit. The extent to which these anions undergo C- versus O-methylation under various conditions has been examined. When O-methylation does occur, it is the C-7 oxygen (and not the one at C-9) that is engaged in reaction.

  DOI：

  10.1021/jo00109a021
• 作为产物：
  描述：

  氯甲基甲基醚 、 (1S,3R,4S)-3-Hydroxy-1-<(Z)-2-(p-methoxyphenoxy)vinyl>-7,7-dimethyl-2-norbornanone 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以88%的产率得到(1S,3R,4S)-3-(Methoxymethoxy)-1-<(Z)-2-(p-methoxyphenoxy)vinyl>-7,7-dimethyl-2-norbornanone
  参考文献：
  名称：

  Stereocontrolled Oxygenation of Camphor Derivatives as a Prelude to the Complete .beta.-Ring Functionalization of Potential Precursors to Taxol and Structural Analogs Thereof

  摘要：

  The possibility of realizing the predominant exo a-hydroxylation of camphor-related ketones is described. Both the direct oxidation of enolate anions with 1-phenyl-N-(phenylsulfonyl)oxaziridine or exposure of the derived silyl enol ethers to dimethyl dioxirane are conducive to exo attack. Following conversion to MOM derivatives, the acidity of the alpha-carbonyl proton is reduced sufficiently to allow direct condensation of these hindered ketones with cyclohexenyllithium reagents. The subsequent anionic oxy-Cope rearrangement of the resulting exo carbinols results in direct conversion to tricyclic products that feature the characteristic C-2,C-9,C-10 B-ring oxygenation pattern resident in taxol. Further, the stereogenic centers are introduced in their proper absolute configuration. The steric demands of the [3,3] sigmatropic shift are discussed and the stereochemical features conducive to the minimization of steric compression subjected to experimental verification.

  DOI：

  10.1021/jo00109a020

文献信息

• Stereocontrolled Oxygenation of Camphor Derivatives as a Prelude to the Complete .beta.-Ring Functionalization of Potential Precursors to Taxol and Structural Analogs Thereof
  作者：Steven W. Elmore、Leo A. Paquette

  DOI：10.1021/jo00109a020

  日期：1995.2

  The possibility of realizing the predominant exo a-hydroxylation of camphor-related ketones is described. Both the direct oxidation of enolate anions with 1-phenyl-N-(phenylsulfonyl)oxaziridine or exposure of the derived silyl enol ethers to dimethyl dioxirane are conducive to exo attack. Following conversion to MOM derivatives, the acidity of the alpha-carbonyl proton is reduced sufficiently to allow direct condensation of these hindered ketones with cyclohexenyllithium reagents. The subsequent anionic oxy-Cope rearrangement of the resulting exo carbinols results in direct conversion to tricyclic products that feature the characteristic C-2,C-9,C-10 B-ring oxygenation pattern resident in taxol. Further, the stereogenic centers are introduced in their proper absolute configuration. The steric demands of the [3,3] sigmatropic shift are discussed and the stereochemical features conducive to the minimization of steric compression subjected to experimental verification.
• Evaluation of 2-Bromocyclohexenone Acetals as Vehicles for the Introduction of C-7 Oxygen Preliminary to the Synthesis of Taxane Diterpenes
  作者：Leo A. Paquette、Zhuang Su、Simon Bailey、Francis J. Montgomery

  DOI：10.1021/jo00109a021

  日期：1995.2

  The coupling of an optically pure, camphor-derived, beta,gamma-unsaturated, bicyclic ketone with a suitable vinyl organometallic is recognized to result in 1,2-addition from the endo face. Anionic oxy-Cope rearrangement of these carbinols proceeds via an ''endo-chair'' transition state to deliver a strained and reactive enolate that is formed regioselectively and is amenable to alpha-methylation from the top face. These steps, which are preliminary to a broad-based approach to the taxane diterpenes, had not yet accommodated suitable introduction of a C-7 oxygen substituent as required of taxol. Typically, an ether substituent at this site experiences beta-elimination once the enolate anion intermediate is accessed. Herein it is demonstrated that the parent 2-bromocyclohexenone acetal is well suited to resolving this complication. Halogen-metal exchange proceeds well to provide a suitably nucleophilic building block. Direct charge-accelerated sigmatropic rearrangement of the carbinol products does proceed with beta-elimination, but under the present circumstances the second C-O bond remains in the form of a vinylogous ester. Alternatively, the carbinols are amenable to chemoselective hydrolysis of the acetal, thereby unmasking a conjugated cyclohexenone part structure. These intermediates have been found to rearrange along completely analogous reaction trajectories to provide enolates of a beta-diketone subunit. The extent to which these anions undergo C- versus O-methylation under various conditions has been examined. When O-methylation does occur, it is the C-7 oxygen (and not the one at C-9) that is engaged in reaction.