加拿大女王大学Cathleen M. Crudden团队近日取得一项新成果，他们的最新研究提出了环烷基砜的对映特异性交叉偶联。2024年8月5日，国际知名学术期刊《自然-化学》发表了这一成果。

有效形成碳-碳键并控制立体化学的方法对于复杂分子的构建至关重要。交叉偶联反应是构建分子最有效和最广泛的反应之一，可以保持或安装手性的交叉偶联反应则是这个强大工具箱最新的添加。

砜是一种稳健且易于获得的有机亲电试剂，作为交叉偶联伙伴具有许多吸引人的特征。然而，自1979年的第一个应用例子以来，没有使用其在对映选择性、对映特异性或对映收敛交叉偶联的例子。砜的高酸性使得这种转变在三级体系之外是否可能发生都不清楚。

在该研究中，团队报道了环砜与格氏试剂的对映特异性交叉偶联反应。尽管格氏组分的碱性很强，但仍观察到高达99%的手性转移。原位监测表明，交叉偶联与竞争性去质子化在动力学上是竞争的，导致高度的对映选择性转化。

附：英文原文

Title: Enantiospecific cross-coupling of cyclic alkyl sulfones

Author: Nolla-Saltiel, Roberto, Ariki, Zachary T., Schiele, Stefanie, Alpin, Jana, Tahara, Yasuyo, Yokogawa, Daisuke, Nambo, Masakazu, Crudden, Cathleen M.

Issue&Volume: 2024-08-05

Abstract: Methods to form carbon–carbon bonds efficiently and with control of stereochemistry are critical for the construction of complex molecules. Cross-coupling reactions are among the most efficient and widely used reactions to construct molecules, with reactions enabling the retention or installation of chirality as recent additions to this powerful toolbox. Sulfones are robust, accessible organic electrophiles that have many attractive features as cross-coupling partners; however, since the first example of their use in 1979, there have been no examples of their use in enantioselective, enantiospecific or entantioconvergent cross-couplings. The high acidity of sulfones makes it unclear whether this transformation is even possible outside tertiary systems. Here we report the enantiospecific cross-coupling of cyclic sulfones and Grignard reagents. Up to 99% chirality transfer is observed despite the strong basicity of the Grignard components. In situ monitoring reveals that the cross-coupling is kinetically competitive with competing deprotonation, resulting in a highly enantioselective transformation.

DOI: 10.1038/s41557-024-01594-x

Source: https://www.nature.com/articles/s41557-024-01594-x