Nolla-Saltiel Roberto, Ariki Zachary T, Schiele Stefanie, Alpin Jana, Tahara Yasuyo, Yokogawa Daisuke, Nambo Masakazu, Crudden Cathleen M
Department of Chemistry, Chernoff Hall, Queen's University, Kingston, Ontario, Canada.
Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Nagoya, Japan.
Nat Chem. 2024 Sep;16(9):1445-1452. doi: 10.1038/s41557-024-01594-x. Epub 2024 Aug 5.
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.
高效形成碳-碳键并控制立体化学的方法对于构建复杂分子至关重要。交叉偶联反应是构建分子最有效且应用最广泛的反应之一，最近在这个强大的工具库中增加了能够保留或引入手性的反应。砜是稳定、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性；然而，自1979年首次使用它们的例子以来，尚无其用于对映选择性、对映体特异性或对映体汇聚性交叉偶联的例子。砜的高酸度使得不清楚这种转化在叔体系之外是否甚至可能。在此我们报道了环状砜与格氏试剂的对映体特异性交叉偶联。尽管格氏试剂组分碱性很强，但观察到高达99%的手性转移。原位监测表明，交叉偶联在动力学上与竞争性去质子化相互竞争，导致高度对映选择性转化。
