Development and Application of the Asymmetric Synthesis Using Chiral Oxonium Ion Species from Acetals

缩醛手性氧鎓离子不对称合成的研究进展及应用

• 批准号: 12672054
• 负责人: FUJIOKA Hiromichi
• 金额: $ 2.5万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12672054/
• 关键词: (R, R)-hydrobenzoin; cvclohexa-2. 5-dienyl methyl aldehyde; ene acetal; intramolecular bromoetherification; stenine; 3-endo-phenylnorbornene aldehyde; meso-1. 4-diols; asymmetric desymmetrization; 分子内ブロモエーテル化反応; 3-エンドフェニルノルボルネンアルデヒ; (R,R)-ヒドロベンゾ

Development and application of the asymmetric synthesis using chiral oxonium Ions formed by an intramolecular haloetherification of ene acetals have been studied in two directions, 1 and 2.1) Stereoselective construction of multi-chiral centers Synthetic study of stemona alkaloids : An intramolecular bromoetherification of the ene acetal, prepared fromeyelohexa-2, 5-dienyl methyl aldehyde diethyl acetal and (R,R)-hydrobenzoin, by NBS in the presence of MeOH proceeded stereoselectively to give the cyclohexene acetal by discrimination of the two olefins. Further transformations proceeded stereoselectively for the sake of conformational fixation by the acetal to form the three new asymmetric centers leading to the compound having the same configuration as stenine carbon skeleton. Thus obtained compound was converted to 9a-epi-stenine.2) Asymmetric desymmetrization of meso-diols : Optically pure 2-exo-methyl-3-endo-phenyl-5norbornene-2-carboxaldehyde was obtained by our kinetically controlled optical resolution method. Using this auxiliary, deasymmetrization of meso-1, 4-diols was achieved in a highly enantioselective manner in a four step sequence : 1) acetalization of an aldehyde with a diol, 2) an intramolecular bromoetherification in the presence of MeOH followed by acid hydrolysis, 3) protection of the resulting alcohol, and 4) debromoetherification. The method was applied to meso-1,2- and 1,3-diols, and similar high enantioselectivity was observed.

通过烯缩醛的分子内卤代醚化形成的手性氧鎓离子的不对称合成的开发和应用已经在两个方向1和2上进行了研究。1）多手性中心的立体选择性构建百部生物碱的合成研究：由十六-2，5-二烯基甲醛二乙缩醛和（R，R）-氢化苯偶姻制备的烯缩醛的分子内溴醚化反应，在甲醇存在下，通过NBS对两种烯烃的区分，立体选择性地得到环己烯缩醛。进一步的立体选择性转化是为了通过缩醛的构象固定而形成三个新的不对称中心，导致化合物具有与stenine碳骨架相同的构型。2）内消旋二醇的不对称去对称化：通过我们的动力学控制的光学拆分方法获得光学纯的2-外-甲基-3-内-苯基-5-异戊烯-2-甲醛。使用该助剂，以高度对映选择性的方式，通过四步序列实现了内消旋-1，4-二醇的去不对称化：1）醛与二醇的缩醛化，2）在MeOH存在下的分子内溴醚化，随后酸水解，3）所得醇的保护，和4）脱溴醚化。将该方法应用于meso-1，2-和1，3-二醇，并观察到类似的高对映选择性。

项目成果

Fujioka, Hiromichi: "Optical Resolution of Racemic Norbornene Aldehydes : Kinetically Controlled Intramolecular Haloetherification of Ene Acetals"Tetrahedron Letter. 41. 1829-1832 (2000)

Fujioka、Hiromichi：“外消旋降冰片烯醛的光学拆分：烯缩醛的动力学控制分子内卤醚化”四面体信件。

Fujioka, Hiromichi: "Optical Resolution of Racemic Norbornene Aldehydes : Kinetically Controlled Intramolecular Haloetherification of Ene Acetals"Tetrahedron Letters. 41. 1829-1832 (2000)

Fujioka，Hiromichi：“外消旋降冰片烯醛的光学拆分：烯缩醛的动力学控制分子内卤醚化”四面体字母。

Fujioka, Hiromichi: "Optical Resolution of Racemic Norbornene Aldehydes : Kinetically Con trolled Intramolecular Heloetherification of Ene Acetals"Tetrahedroh Letters. 41. 1829-1832 (2000)

Fujioka, Hiromichi：“外消旋降冰片烯醛的光学拆分：烯缩醛的动力学控制分子内异醚化”四面体字母。

Fuijioka, Hiromichi: "Asymmetric Desymmetrization of Saturated and Unsaturated meso -1,2- Diols"Tetrahedron. 56. 10141-10151 (2000)

Fuijioka，Hiromichi：“饱和和不饱和内消旋-1,2-二醇的不对称去对称化”四面体。

Fujioka, Hiromichi: "Asymmetric Desymmetrization of Saturated and Unsaturated meso-1,2-Diols"Tetrahedron. 56. 10141-10151 (2000)

Fujioka、Hiromichi：“饱和和不饱和内消旋 1,2-二醇的不对称去对称化”四面体。