Stereoinversion of tertiary alcohols to tertiary-alkyl isonitriles and amines
Stereoinversion of tertiary alcohols to tertiary-alkyl isonitriles and amines
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DOI：
10.1038/nature12472
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发表时间：
2013-09-12
期刊：
影响因子：
64.8
通讯作者：
Shenvi, Ryan A.
中科院分区：
文献类型：
--
作者：
Pronin, Sergey V.;Reiher, Christopher A.;Shenvi, Ryan A.
S（N）2反应（双分子亲核取代）是一种众所周知的化学转化，可用于将两个较小的分子连接在一起成为一个较大的分子或将一个官能团交换为另一个官能团。S（N）2反应以一种非常可预测的方式进行：取代发生在立体化学反转的情况下，由亲核试剂对亲电碳的“背面攻击”引起。S（N）2反应的一个显著限制是它对叔碳原子的不耐受性：而伯醇和仲醇是可行的前体底物，叔醇及其衍生物通常不能反应或产生产物的立体化学混合物（1-3）。在这里，我们报告的立体化学反转手性叔醇与含氮亲核试剂促进路易斯酸催化溶剂分解。该方法对仲醇和伯醇具有化学选择性，从而补充了S（N）2反应的选择性。此外，这种碳-氮键形成的方法模拟了合成海洋萜类化合物（4）中的假定生物合成步骤，并且能够从相应的陆地萜类化合物制备它们。我们期望该方法的一般属性将允许手性叔醇被认为是立体转化反应的可行底物。
The S(N)2 reaction (bimolecular nucleophilic substitution) is a well-known chemical transformation that can be used to join two smaller molecules together into a larger molecule or to exchange one functional group for another. The S(N)2 reaction proceeds in a very predictable manner: substitution occurs with inversion of stereochemistry, resulting from the 'backside attack' of the electrophilic carbon by the nucleophile. A significant limitation of the S(N)2 reaction is its intolerance for tertiary carbon atoms: whereas primary and secondary alcohols are viable precursor substrates, tertiary alcohols and their derivatives usually either fail to react or produce stereochemical mixtures of products(1-3). Here we report the stereochemical inversion of chiral tertiary alcohols with a nitrogenous nucleophile facilitated by a Lewis-acid-catalysed solvolysis. The method is chemoselective against secondary and primary alcohols, thereby complementing the selectivity of the S(N)2 reaction. Furthermore, this method for carbon-nitrogen bond formation mimics a putative biosynthetic step in the synthesis of marine terpenoids(4) and enables their preparation from the corresponding terrestrial terpenes. We expect that the general attributes of the methodology will allow chiral tertiary alcohols to be considered viable substrates for stereoinversion reactions.