Laboratory of Molecular Recognition and Synthesis, Department of Chemistry, Zhejiang University, 310027, Hangzhou, Zhejiang, People's Republic of China.
Nat Commun. 2019 Jan 31;10(1):507. doi: 10.1038/s41467-018-07908-1.
Metal-catalyzed enantioselective construction of the loosening axial allene chirality spreading over three carbon atoms using a chiral ligand is still a significant challenge. In the literature, steric effect of the substrates is the major strategy applied for such a purpose. Herein, we present a general palladium-catalyzed asymmetrization of readily available racemic 2,3-allenylic carbonates with different types of non-substituted and 2-substituted malonates using (R)-(-)-DTBM-SEGPHOS as the preferred ligand to afford 1,3-disubstituted chiral allenes with 90~96% ee. This protocol has been applied to the first enantioselective synthesis of natural product, (R)-traumatic lactone. Control experiments showed that in addition to the chiral ligand, conducting this transformation via Procedure C, which excludes the extensive prior coordination of the allene unit in the starting allene with Pd forming a species without the influence of the chiral ligand, is crucial for the observed high enantioselectivity.
使用手性配体实现金属催化的对映选择性构建具有三个碳原子的松散轴向丙二烯手性扩展仍然是一个重大挑战。在文献中，底物的空间效应是为此目的应用的主要策略。在此，我们提出了一种通用的钯催化方法，使用（R）-（-）-DTBM-SEGPHOS 作为首选配体，对不同类型的未取代和 2-取代丙二酸盐对易得的外消旋 2,3-烯丙基碳酸酯进行不对称化，以提供具有 90-96%ee 的 1,3-二取代手性丙二烯。该方案已应用于天然产物（R）-创伤内酯的首次对映选择性合成。控制实验表明，除了手性配体外，通过排除起始丙二烯中丙二烯单元与 Pd 形成的无手性配体影响的物种的广泛预配位的程序 C 进行这种转化对于观察到的高对映选择性至关重要。
