Benzoic acid (Z)-(R)-1-((2S,3R)-3-hydroxy-tetrahydro-pyran-2-ylmethyl)-3-methoxycarbonyl-allyl ester | 192122-57-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Benzoic acid (Z)-(R)-1-((2S,3R)-3-hydroxy-tetrahydro-pyran-2-ylmethyl)-3-methoxycarbonyl-allyl ester
• 英文别名: [(Z,2R)-1-[(2S,3R)-3-hydroxyoxan-2-yl]-5-methoxy-5-oxopent-3-en-2-yl] benzoate
• CAS: 192122-57-9
• 化学式: C₁₈H₂₂O₆
• 分子量: 334.369
• InChiKey: MIGLUYABUMJZJG-PRWMKCNKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  82.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Benzoic acid (Z)-(R)-1-((2S,3R)-3-hydroxy-tetrahydro-pyran-2-ylmethyl)-3-methoxycarbonyl-allyl ester 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以89%的产率得到Benzoic acid (2S,3R,4aS,8aR)-2-methoxycarbonylmethyl-octahydro-pyrano[3,2-b]pyran-3-yl ester
  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：

  Benzoic acid (Z)-(R)-1-[(2S,3R)-3-(tert-butyl-diphenyl-silanyloxy)-tetrahydro-pyran-2-ylmethyl]-3-methoxycarbonyl-allyl ester 在 氢氟酸 作用下， 以 乙腈 为溶剂， 反应 12.0h， 以94%的产率得到Benzoic acid (Z)-(R)-1-((2S,3R)-3-hydroxy-tetrahydro-pyran-2-ylmethyl)-3-methoxycarbonyl-allyl ester
  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