Gram-scale enantioselective formal synthesis of morphine through an ortho-para oxidative phenolic coupling strategy.
Gram-scale enantioselective formal synthesis of morphine through an ortho-para oxidative phenolic coupling strategy.
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DOI：
10.1002/anie.201408435
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发表时间：
2014-12
影响因子：
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通讯作者：
M. Tissot;Robert J. Phipps;C. Lucas;Rafael León;R. Pace;Tifelle Ngouansavanh;M. Gaunt
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文献类型：
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作者：
M. Tissot;Robert J. Phipps;C. Lucas;Rafael León;R. Pace;Tifelle Ngouansavanh;M. Gaunt
本文报道了一种克级催化的对映选择性合成吗啡的方法。合成的关键步骤涉及邻位-对位氧化酚偶联和所得环己二烯酮的高度非对映选择性“去对称化”，其在一个步骤中产生四个吗啡喃环连接立体中心中的三个。立体化学由通过催化对映选择性氢化安装的单个甲醇中心控制。这些转化使得能够制备大量的关键中间体，并且可以支持吗啡和相关衍生物的实用且可规模化的合成。
A gram-scale catalytic enantioselective formal synthesis of morphine is described. The key steps of the synthesis involve an ortho-para oxidative phenolic coupling and a highly diastereoselective "desymmetrization" of the resulting cyclohexadienone that generates three of the four morphinan ring junction stereocenters in one step. The stereochemistry is controlled from a single carbinol center installed through catalytic enantioselective hydrogenation. These transformations enabled the preparation of large quantities of key intermediates and could support a practical and scalable synthesis of morphine and related derivatives.