Asymmetric Synthesis based on Intramolecular Haloetherification of Ene Acetals and Its Application

本课题主要从两个方面研究了基于分子内卤代醚化反应的不对称合成及其应用：1)σ对称二烯的不对称脱对称-多手性中心的合成；2)对称二烯的不对称脱对称-多手性中心的合成。1)σ-对称双烯的不对称脱对称-多手性中心的合成：分子内卤代醚化反应，2，5-环己二烯-1-甲基醛和手性氢安息香合成的烯缩醛，立体选择性地得到两个有区别的八元缩醛。残留的烯烃随后进行氢硼化，然后氧化得到环己酮衍生物。1，4-格氏试剂的立体选择性加成，烯醇化阴离子的硅基化，过量的Meli处理，然后与过量的烯丙基碘进行二烯丙基化，得到了具有相同碳骨架的(-)-斯汀的化合物，该化合物是球茎生物碱的主要成分。2)对称二醇的不对称去对称化：由降冰片烯甲醛和不饱和的Meso-1，2-二醇制备的烯缩醛得到不饱和和非环的Meso-1，2-二醇的不对称去对称化反应。烯烃缩醛的分子内卤代醚化反应是一个关键步骤，仅通过降冰片烯的反应就可以得到立体选择性的8元缩醛。随后的还原消除，随后的羟基保护和转缩化，以良好的产率得到光学活性的1，2-二醇衍生物和起始的烯缩醛。由外消旋降冰片烯缩醛和手性非外消旋(R，R)-氢安息香合成的烯缩醛的非对映异构体混合物以动力学控制的方式进行卤醚化反应，得到光学纯的8元烯缩醛和完整的烯缩醛。这两种缩醛都以两种对映体形式转化为光学纯的降冰片烯醛。

In this project, we studied on asymmetric synthesis based on intramolecular haloetherification of ene acetals and its application in two ways : 1) asymmetric desymmetrization of σ-symmetric dienes-synthesis of multi-chiral center, and 2) asymmetric desymmetrization of symmetric diols.1) Asymmetric desymmetrization of σ-symmetric dienes-Synthesis of multi-chiral centers : An intramolecular haloetherification reaction, treatment with NBS in the presence of MeOH, of ene acetal, prepared from 2,5-cyclohexadiene-1-methylaldehyde and chiral hydrobenzoin, proceeded stereoselectively to give 8-membered acetal discriminated two olefins. Subsequent hydroboration of the remained olefin followed by oxidation afforded the cyclohexenone derivative. Stereoselective 1, 4-addition of Grignard reagent, silylation of enolated anion, excess MeLi treatment, then diallylation with excess allyl iodide afforded the compound with the same carbon skeleton of (-)-stenine, a major component of stemona alkaloids.2) Asymmetric desymmetrization of symmetric diols : An asymmetric desymmetrization of unsaturated cyclic and acyclic meso-1, 2-diols has been developed from the ene acetals, prepared from the norbornene carboxyaldehyde and unsaturated meso-1, 2-diols. The intramolecular haloetherification of the ene acetals as a key step afforded 8-memberd acetals in a stereoselective manner just by the reaction of norbornene olefin. Subsequent reductive elimination, followed by protection of the hydroxy group and transacetalization, gave optically active 1, 2-diol derivatives and the starting ene acetals in good yields. Haloetherification reaction of diastereomeric mixture of the ene acetals, derived from racemic norbornene aldehydes and chiral non-racemic (R, R)-hydrobenzoin, proceeded in a kinetically controlled manner to give the optically pure 8-membered acetal along with the intact ene acetal. Both acetals were converted to the optically pure norbrnene aldehydes in both enantiomeric forms.