(2S,5R)-2-(1',1',3'-trimethyl-3'-butenyl)-5-methylcyclohexanone | 437770-20-2

• 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: (2S,5R)-2-(1',1',3'-trimethyl-3'-butenyl)-5-methylcyclohexanone
• 英文别名: (2S,5R)-2-(2,4-dimethylpent-4-en-2-yl)-5-methylcyclohexanone；(2S,5R)-2-(2,4-dimethylpent-4-en-2-yl)-5-methylcyclohexan-1-one
• CAS: 437770-20-2
• 化学式: C₁₄H₂₄O
• 分子量: 208.344
• InChiKey: RNFBHLVEVVUIQR-VXGBXAGGSA-N

物化性质

• 沸点：
  278.3±9.0 °C(Predicted)
• 密度：
  0.891±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (2S,5R)-2-(1',1',3'-trimethyl-3'-butenyl)-5-methylcyclohexanone 在 叔丁基过氧化氢 、 4-二甲氨基吡啶 、 selenium(IV) oxide 、 iron(III)-acetylacetonate 、 苯硅烷 、 三乙胺 作用下， 以 癸烷 、 乙醇 、 二氯甲烷 为溶剂， 反应 11.0h， 生成 [(1S,3aS,6R,7aS)-7a-hydroxy-1,3,3,6-tetramethyloctahydro-1H-inden-1-yl]methyl 4-bromobenzoate
  参考文献：
  名称：

  Four‐Step Synthesis of (−)‐4‐ epi ‐Presilphiperfolan‐8 α ‐ol by Intramolecular Iron Hydride Atom Transfer‐Mediated Ketone‐Alkene Coupling and Studies to Access trans ‐Hydrindanols with a Botryane Scaffold

  摘要：

  AbstractFrom an (R)‐(+)‐pulegone‐derived building block that incorporates the stereo‐defined tertiary carbon bearing a methyl group, as found in the targeted sesquiterpenoid, a four‐step synthesis of (−)‐4‐epi‐presilphiperfolan‐8‐α‐ol was achieved. The key processes involved are a ring‐closing metathesis leading to a bridged alkene‐tethered ketone and its subsequent FeIII‐mediated metal‐hydride atom transfer (MHAT) transannular cyclization. This synthetic method, implying an irreversible addition of a carbon‐centered radical upon a ketone by means of a hydrogen atom transfer upon the alkoxy radical intermediate, was also applied in the synthesis oftrans‐fused hydrindanols structurally related to botrydial compounds.

  DOI：

  10.1002/chem.202203286
• 作为产物：
  描述：

  异丁烯基三甲基硅烷 、 长叶薄荷酮 在 四氯化钛 、 potassium hydroxide 作用下， 以 甲醇 为溶剂， 以66 %的产率得到(2S,5R)-2-(1',1',3'-trimethyl-3'-butenyl)-5-methylcyclohexanone
  参考文献：
  名称：

  Four‐Step Synthesis of (−)‐4‐ epi ‐Presilphiperfolan‐8 α ‐ol by Intramolecular Iron Hydride Atom Transfer‐Mediated Ketone‐Alkene Coupling and Studies to Access trans ‐Hydrindanols with a Botryane Scaffold

  摘要：

  AbstractFrom an (R)‐(+)‐pulegone‐derived building block that incorporates the stereo‐defined tertiary carbon bearing a methyl group, as found in the targeted sesquiterpenoid, a four‐step synthesis of (−)‐4‐epi‐presilphiperfolan‐8‐α‐ol was achieved. The key processes involved are a ring‐closing metathesis leading to a bridged alkene‐tethered ketone and its subsequent FeIII‐mediated metal‐hydride atom transfer (MHAT) transannular cyclization. This synthetic method, implying an irreversible addition of a carbon‐centered radical upon a ketone by means of a hydrogen atom transfer upon the alkoxy radical intermediate, was also applied in the synthesis oftrans‐fused hydrindanols structurally related to botrydial compounds.

  DOI：

  10.1002/chem.202203286

文献信息

• Development and Elucidation of a Pd‐Based Cyclization–Oxygenation Sequence for Natural Product Synthesis
  作者：Heng Yi、Pengfei Hu、Scott A. Snyder

  DOI：10.1002/anie.201913730

  日期：2020.2.10

  recent discovery of one such reaction in the course of a total synthesis program, we delineate herein that it has significant strength, both in terms of substrate scope as well as the terminating oxygen nucleophile. As a result, the reaction proved critical in achieving total syntheses of two oxygenated natural products, one of which was prone to over-oxidation. Finally, a mechanistic proposal that accounts

  钯催化的序列涉及氧化加成、环化和通过分子间亲核试剂捕获的终止，具有巨大的实用性。事实上，它们可以产生大量具有多种功能的不同多环结构。然而，Pd0 /PdII 变体的一个缺陷是无法将它们与氧基物质结合起来。受最近在全合成程序过程中发现的一个此类反应的启发，我们在此描述了它在底物范围以及终止氧亲核试剂方面都具有显着的优势。结果，该反应被证明对于实现两种含氧天然产物的全合成至关重要，其中一种容易过度氧化。最后，提供了一个解释其成功的机制建议。
• Syn- and Anti-Selective Prins Cyclizations of δ,ε-Unsaturated Ketones to 1,3-Halohydrins with Lewis Acids
  作者：R. Brandon Miles、Chad E. Davis、Robert M. Coates

  DOI：10.1021/jo052142n

  日期：2006.2.1

  eroded the selectivity of the cyclizations. The trends in syn vs anti selectivity, reactivity, and effects of different Lewis acidic metal halides are rationalized by competitive reaction pathways proceeding through syn carbocation−halide ion pairs and a higher order transition state that leads to inversion of configuration and formation of trans halohydrins, along with cyclic olefins arising from proton

  在路易斯酸的存在下，在无水条件下，对十个无环和单环的δ，ε-不饱和酮（在双键上具有和不具有甲基取代基）进行了卤化物封端的Prins（halo-Prins）环化反应。TiCl 4，TiBr 4，BCl 3和BBr 3促进了顺式选择性环化成空间上拥挤的氯代和溴代醇，而SnCl 4，SnBr 4，InCl 3，ZrCl 4和其他几种路易斯酸则对提供相应的反式卤代醇。更强的路易斯酸（TiX 4和BX 3）赞成涉及轴向递送卤化物配体的顺式方法。竞争实验表明，在δ碳（甲基烯丙基烯酮）上的取代导致速率增加（40-50倍），而在ε位置（顺式和反巴豆基烯酮）上的取代会降低速率，并侵蚀环化反应的选择性。顺式与反式选择性，反应性以及不同路易斯酸性金属卤化物作用的趋势通过竞争性反应途径得以合理化，该竞争反应途径通过顺式碳正离子-卤化物离子对和更高阶的过渡态进行，从而导致构型反转和反式卤代醇的形成，以及由于质子消除而产生的环状烯烃。
• Enantiospecific Total Synthesis of the Highly Strained (−)-Presilphiperfolan-8-ol via a Pd-Catalyzed Tandem Cyclization
  作者：Pengfei Hu、Scott A. Snyder

  DOI：10.1021/jacs.7b01454

  日期：2017.4.12

  0]-bicycle, a motif present in (-)-presilphiperfolan-8-ol. This molecule also possesses a 1,3-trans stereochemical arrangement of substituents on one of its 5-membered rings, a pattern shared by a number of other terpenes. Herein, we disclose the first total synthesis of this highly strained target in 13 steps. The key operation is a Pd-catalyzed tandem cyclization that directly establishes the requisite

  天然来源分子中一种罕见的高应变元素是 [3.3.0]-自行车内 5 元环的 1,2-反式融合，这是 (-)-presilphiperfolan-8-ol 中存在的基序。该分子还在其 5 元环之一上具有取代基的 1,3-反式立体化学排列，这是许多其他萜烯共有的模式。在此，我们公开了该高度应变目标的 13 步全合成。关键操作是 Pd 催化的串联环化，它直接在一个环上建立必要的 1,3-反式立体化学排列，同时为最终结构的高应变 1,2-反式环融合的受控生成奠定基础。
• Radical Cyclization of Alkene-Tethered Ketones Initiated by Hydrogen-Atom Transfer
  作者：Mar Saladrigas、Caroline Bosch、Gisela V. Saborit、Josep Bonjoch、Ben Bradshaw

  DOI：10.1002/anie.201709659

  日期：2018.1.2

  An unprecedented C−C coupling reaction between alkenes and ketones by hydrogen‐atom transfer, using Fe(acac)3 and PhSiH3 in EtOH, is described. This mild protocol features high site selectivity and allows the construction of sterically congested structures containing tertiary alcohols and quaternary centers. The overall process introduces a novel strategic bond disconnection for ring‐closing reactions

  描述了在EtOH中使用Fe（acac）3和PhSiH 3通过氢原子转移实现烯烃与酮之间前所未有的C-C偶联反应。这种温和的方案具有很高的位点选择性，并允许构建含有叔醇和季中心的空间拥挤结构。整个过程为开环反应引入了一种新颖的策略性键断开。
• Stereoselective Prins Cyclizations of δ,ε-Unsaturated Ketones to cis-3-Chlorocyclohexanols with TiCl4
  作者：Chad E. Davis、Robert M. Coates

  DOI：10.1002/1521-3773(20020201)41:3<491::aid-anie491>3.0.co;2-3

  日期：2002.2.1