Synthesis of (-)-Morphine: Application of Sequential Claisen/Claisen Rearrangement of an Allylic Vicinal Diol
Synthesis of (-)-Morphine: Application of Sequential Claisen/Claisen Rearrangement of an Allylic Vicinal Diol
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DOI：
10.1002/chem.201203284
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发表时间：
2013-01-01
影响因子：
4.3
通讯作者：
Chida, Noritaka
中科院分区：
文献类型：
--
作者：
Ichiki, Masato;Tanimoto, Hiroki;Chida, Noritaka
描述了基于连续的[3,3]-迁移重排对（-）-吗啡合成的详细探究。烯丙基邻二醇的连续克莱森/克莱森重排通过一步操作实现了两个连续碳中心（包括一个空间位阻的季碳）的立体选择性形成。在该反应中生成的两个乙酯在随后的傅-克类型环化过程中被成功区分。在第一代合成中，（-）-吗啡的双键是在后期引入的，但在第二代合成中是在较早期形成的，从而产生了一条通向最终产物的更高效路线。
A detailed exploration of the synthesis of (-)-morphine based on sequential [3,3]-sigmatropic rearrangements is described. The sequential Claisen/Claisen rearrangements of an allylic vicinal diol resulted in the stereoselective formation of the two contiguous carbon centers, including a sterically encumbered quaternary carbon, in a single operation. The two ethyl esters generated in this reaction were successfully differentiated during a subsequent Friedel-Crafts-type cyclization. The (-)-morphine double bond was introduced at a late stage in our first-generation synthesis, but was formed at an earlier stage in the second-generation synthesis, resulting in a more efficient route to the end product.