Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Nature. 2013 Sep 12;501(7466):195-9. doi: 10.1038/nature12472.
The SN2 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 SN2 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 SN2 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. 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 SN2 reaction. Furthermore, this method for carbon-nitrogen bond formation mimics a putative biosynthetic step in the synthesis of marine terpenoids 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.
SN2 反应（双分子亲核取代反应）是一种众所周知的化学反应，可以将两个较小的分子连接成一个较大的分子，或者将一个官能团交换为另一个官能团。SN2 反应以非常可预测的方式进行：取代反应伴随着立体化学的反转，这是由于亲电碳原子被亲核试剂的“背面攻击”所致。SN2 反应的一个显著限制是它不能容忍叔碳原子：尽管伯醇和仲醇是可行的前体底物，但叔醇及其衍生物通常要么不反应，要么产生立体化学混合物的产物。在这里，我们报告了在路易斯酸催化的溶剂解作用下，氮亲核试剂促进手性叔醇的立体化学反转。该方法对仲醇和伯醇具有化学选择性，从而补充了 SN2 反应的选择性。此外，这种碳-氮键形成方法模拟了海洋萜类化合物合成中的一个假定生物合成步骤，并能够从相应的萜类化合物制备它们。我们预计该方法的一般属性将使手性叔醇能够被视为立体反转反应的可行底物。
