Enantiodivergent conversion of chiral secondary alcohols into tertiary alcohols
Enantiodivergent conversion of chiral secondary alcohols into tertiary alcohols
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DOI：
10.1038/nature07592
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发表时间：
2008-12-11
期刊：
影响因子：
64.8
通讯作者：
Aggarwal, Varinder K.
中科院分区：
文献类型：
--
作者：
Stymiest, Jake L.;Bagutski, Viktor;Aggarwal, Varinder K.
从鼻子中的受体到超分子生物聚合物，自然界在识别手性分子方面表现出显着的特异性，导致两种形式的镜像排列引起完全不同的生物反应（1，2）。因此，在手性分子的化学合成期间，仅产生两个三维排列中的一个是至关重要的。尽管某些类别的手性分子（例如仲醇（3，4））现在容易选择性地以单一镜像形式制备，但一类-含有季立体中心（具有四个不同非氢取代基的碳原子）的那些-仍然是巨大的挑战（5-8）。在这里，我们提出了一个通用的解决方案，这个问题，使容易获得的仲醇在其单一的镜像形式，并在一个两步序列将它们转化为叔醇（四元立体中心）。整个过程包括除去仲醇的氢原子（连接到碳上），并用烷基、烯基或芳基有效地取代它。此外，从仲醇的单一镜像形式开始，可以以高水平的立体控制制备叔醇的任一镜像形式。因此，现在可以通过该方法以非常高的选择性容易地制备宽范围的叔醇。我们预计，这种方法可以找到广泛的应用，因为中间体叔硼酸酯可以潜在地转化为一系列的官能团与保留的配置。
From receptors in the nose to supramolecular biopolymers, nature shows a remarkable degree of specificity in the recognition of chiral molecules, resulting in the mirror image arrangements of the two forms eliciting quite different biological responses(1,2). It is thus critically important that during a chemical synthesis of chiral molecules only one of the two three- dimensional arrangements is created. Although certain classes of chiral molecules ( for example secondary alcohols(3,4)) are now easy to make selectively in the single mirror image form, one class - those containing quaternary stereogenic centres ( a carbon atom with four different non- hydrogen substituents) - remains a great challenge(5-8). Here we present a general solution to this problem which takes easily obtainable secondary alcohols in their single mirror image form and in a two- step sequence converts them into tertiary alcohols ( quaternary stereogenic centres). The overall process involves removing the hydrogen atom ( attached to carbon) of the secondary alcohol and effectively replacing it with an alkyl, alkenyl or aryl group. Furthermore, starting from a single mirror image form of the secondary alcohol, either mirror image form of the tertiary alcohol can be made with high levels of stereo control. Thus, a broad range of tertiary alcohols can now be easily made by this method with very high levels of selectivity. We expect that this methodology could find widespread application, as the intermediate tertiary boronic esters can potentially be converted into a range of functional groups with retention of configuration.