[(2S,3S)-3-[(E)-4-(oxan-2-yloxy)but-2-enyl]oxiran-2-yl]methanol | 153896-17-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧烷类
• 英文名称: [(2S,3S)-3-[(E)-4-(oxan-2-yloxy)but-2-enyl]oxiran-2-yl]methanol
• CAS: 153896-17-4
• 化学式: C₁₂H₂₀O₄
• 分子量: 228.288
• InChiKey: YFYULEXTJYXWLK-UCYSPUAUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [(2S,3S)-3-[(E)-4-(oxan-2-yloxy)but-2-enyl]oxiran-2-yl]methanol 在 titanium(IV) isopropylate 、 sodium periodate 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 2.25h， 生成 [(E,2R)-6-(oxan-2-yloxy)-1-oxohex-4-en-2-yl] benzoate
  参考文献：
  名称：

  Stereocontrolled Synthesis of Cyclic Ethers by Intramolecular Hetero-Michael Addition. 5. Synthesis of All Diastereoisomers of 2,3,5,6-Tetrasubstituted Tetrahydropyrans

  摘要：

  A systematic approach to the enantiomeric synthesis of all possible diastereoisomers of 2,6-dialkyl-3,5-dioxytetrahydropyrans is described. The key step in the described methodology is the intramolecular cyclization of enantiomerically enriched (greater than or equal to 95% ee) 7-hydroxy-4-(benzoyloxy)-2,3-unsaturated esters. Infused systems, six of the eight diastereoisomers for one enantiomeric series were synthesized using this procedure as a key step. Using those with the suitable stereochemistry, the two left were synthesized by simple chemical transformations: in one case by the basic isomerization of the carbon with the (methoxycarbonyl)methyl substituent or by a Mitsunobu inversion of a secondary alcohol available from the benzoyloxy group,in the remaining one by a consecutive sequence of oxidation and reduction reactions again over the free secondary alcohol. The stereochemistry of the intramolecular hetero-Michael addition leading to 2,3-disubstituted tetrahydropyrans is highly predictable when kinetic conditions (low temperature and sodium or potassium bases) are used and can be rationalized by invoking a model of a chair-like transition state in which the benzoyloxy group is located in the equatorial mode and the stereochemical course of the approach of the alpha,beta-unsaturated ester is controlled by the geometry of the double bond. As a rule of thumb, the cyclization using E double bonds yielded cis-2,3-disubstituted tetrahydropyrans, while (Z)-unsaturated esters yielded the trans compounds. This empirical rule is followed in highly substituted systems, leading to fused 2,3,5,6-tetrasubstituted tetrahydropyrans, with the same absolute configuration in the carbon where the nucleophilic oxygen is located and the one where the benzoyloxy group is located. Those systems having opposite configurations yield the same trans-2,3-disubstituted compound. The isomerization under thermodynamic conditions (room or higher temperature with excess of base) of the diastereoisomers with the (methoxycarbonyl)methyl substituent in the axial mode led quantitatively to those in which such a group was located equatorially. The scope and limitations of the method are described in both the synthesis of the unsaturated precursor and the stereochemistry reached in the cyclization step.

  DOI：

  10.1021/jo9619241
• 作为产物：
  描述：

  4-(tetrahydro-pyran-2-yloxy)-but-2-yn-1-ol 在 copper(I) chloride 、 titanium(IV) isopropylate 、 叔丁基过氧化氢 、 lithium aluminium tetrahydride 、 L-(+)-酒石酸二乙酯 、 3 Angstroem MS 、 四丁基氟化铵 、 三乙胺 、 lithium bromide 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.25h， 生成 [(2S,3S)-3-[(E)-4-(oxan-2-yloxy)but-2-enyl]oxiran-2-yl]methanol
  参考文献：
  名称：

  通过分子内杂-迈克尔加成立体控制环醚的合成。3.高度官能化和稠合的四氢吡喃的对映体合成

  摘要：

  描述了一种基于分子内异迈克尔加成的功能适当的烷氧基-γ-苯甲酰氧基-α，β-不饱和酯的方法，用于合成高度取代和稠合的海洋聚醚毒素的聚四氢吡喃核，并完全控制所有立体中心。

  DOI：

  10.1016/s0040-4039(00)73936-0

文献信息

• Stereocontrolled synthesis of cyclic ethers by intramolecular hetero-Michael addition. 3. Enantiomeric synthesis of highly functionalized and fused tetrahydropyrans
  作者：José M. Palazón、Marcos A. Soler、Miguel A. Ramírez、Victor S. Martin

  DOI：10.1016/s0040-4039(00)73936-0

  日期：1993.1

  A methodology based on intramolecular hetero-Michael addition of properly functionalized alkoxy-γ-benzoyloxy-α,β-unsaturated esters for the synthesis of highly substituted and fused poly-tetrahydropyran nuclei of marine polyether toxins with absolute control of all the stereocentres is described.

  描述了一种基于分子内异迈克尔加成的功能适当的烷氧基-γ-苯甲酰氧基-α，β-不饱和酯的方法，用于合成高度取代和稠合的海洋聚醚毒素的聚四氢吡喃核，并完全控制所有立体中心。
• Stereocontrolled Synthesis of Cyclic Ethers by Intramolecular Hetero-Michael Addition. 5. Synthesis of All Diastereoisomers of 2,3,5,6-Tetrasubstituted Tetrahydropyrans
  作者：Juan M. Betancort、Víctor S. Martín、José M. Padrón、José M. Palazón、Miguel A. Ramírez、Marcos A. Soler

  DOI：10.1021/jo9619241

  日期：1997.7.1

  A systematic approach to the enantiomeric synthesis of all possible diastereoisomers of 2,6-dialkyl-3,5-dioxytetrahydropyrans is described. The key step in the described methodology is the intramolecular cyclization of enantiomerically enriched (greater than or equal to 95% ee) 7-hydroxy-4-(benzoyloxy)-2,3-unsaturated esters. Infused systems, six of the eight diastereoisomers for one enantiomeric series were synthesized using this procedure as a key step. Using those with the suitable stereochemistry, the two left were synthesized by simple chemical transformations: in one case by the basic isomerization of the carbon with the (methoxycarbonyl)methyl substituent or by a Mitsunobu inversion of a secondary alcohol available from the benzoyloxy group,in the remaining one by a consecutive sequence of oxidation and reduction reactions again over the free secondary alcohol. The stereochemistry of the intramolecular hetero-Michael addition leading to 2,3-disubstituted tetrahydropyrans is highly predictable when kinetic conditions (low temperature and sodium or potassium bases) are used and can be rationalized by invoking a model of a chair-like transition state in which the benzoyloxy group is located in the equatorial mode and the stereochemical course of the approach of the alpha,beta-unsaturated ester is controlled by the geometry of the double bond. As a rule of thumb, the cyclization using E double bonds yielded cis-2,3-disubstituted tetrahydropyrans, while (Z)-unsaturated esters yielded the trans compounds. This empirical rule is followed in highly substituted systems, leading to fused 2,3,5,6-tetrasubstituted tetrahydropyrans, with the same absolute configuration in the carbon where the nucleophilic oxygen is located and the one where the benzoyloxy group is located. Those systems having opposite configurations yield the same trans-2,3-disubstituted compound. The isomerization under thermodynamic conditions (room or higher temperature with excess of base) of the diastereoisomers with the (methoxycarbonyl)methyl substituent in the axial mode led quantitatively to those in which such a group was located equatorially. The scope and limitations of the method are described in both the synthesis of the unsaturated precursor and the stereochemistry reached in the cyclization step.