Total synthesis of the alkoxydioxines (+)- and (-)-chondrillin and (+)- and (-)-plakorin via singlet oxygenation/radical rearrangement
Total synthesis of the alkoxydioxines (+)- and (-)-chondrillin and (+)- and (-)-plakorin via singlet oxygenation/radical rearrangement
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DOI：
10.1021/jo981128q
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发表时间：
1999-03-19
影响因子：
3.6
通讯作者：
Woller, KR
中科院分区：
文献类型：
--
作者：
Dussault, PH;Eary, CT;Woller, KR
单重态氧化和过氧基自由基重排的顺序应用为4-过氧基-2-烯醇和4-过氧基-2-烯酮提供了一个不对称的入口，对映异构富集的2-羟基-过氧基-3-烯醇，通过O-1(2)在z -烯醇上的羟基定向加成，进行立体定向自由基重排形成4-羟基-2-烯醇。在过量的叔丁基过氧化氢存在下，重排的产率得到提高，这限制了底物过氧自由基的二聚化。然而，重排平衡不受极性共溶剂的存在或能够选择性地与产物过氧化氢形成氢键的基团的影响。(E)-4-羟基-2-烯酮重排产物的光异构化导致不可逆的环闭合，以提供对映异构富集的二恶英醇的非对映体混合物。将该策略应用于烷氧二氧嘧啶天然产物软骨素和铂林的全合成。合成材料的旋光度与文献报道的比较表明，天然产物要么是对映体纯的，要么是对映体高度富集的。此外，我们的结果最终证明，报告的软骨素的配置是错误的。
The sequential application of singlet oxygenation and peroxyl radical rearrangement provides an asymmetric entry to 4-peroxy-2-enols and 4-peroxy-2-enones, Enantiomerically enriched 2-hydroperoxy-3-alkenols, obtained via hydroxyl-directed addition of O-1(2) to Z-allylic alcohols, undergo stereospecific radical rearrangement Do form 4-hydroperoxy-2-alkenols. The yields of the rearrangement are improved in the presence of excess tert-butyl hydroperoxide, which limits dimerization of the substrate peroxyl radicals. However, the rearrangement equilibrium is unaffected by the presence of polar co-solvents or by the incorporation of a group able to selectively hydrogen bond to the product hydroperoxide. Photoisomerization of the (E)-4-hydraperoxy-2-enone rearrangement products results in irreversible ring closure to furnish diastereomeric mixtures of enantiomerically enriched dioxinols. The strategy is applied to the total synthesis of the alkoxydioxine natural products chondrillin and plakorin. Comparison of the optical rotation of the synthetic material against literature reports indicates that the natural products are either enantiomerically pure or highly enriched in one enantiomer. In addition, our results conclusively demonstrate that the reported configuration of chondrillin is in error.