Department of Chemistry , Southern University of Science and Technology , Shenzhen 518000 , People's Republic of China.
Academy for Advanced Interdisciplinary Studies , Southern University of Science and Technology , Shenzhen 518000 , People's Republic of China.
J Am Chem Soc. 2018 Jul 5;140(26):8064-8068. doi: 10.1021/jacs.8b03642. Epub 2018 Jun 25.
We herein present a facile and column-free synthetic route toward a structurally unique oxa-spirocyclic diphenol, termed as O-SPINOL. Features of the synthesis include the construction of the all-carbon quaternary center at an early stage, a key double intramolecular SAr step to introduce the spirocycles and the feasibility of operating on >100 g scale. Both enantiomers of O-SPINOL can be easily accessed through optical resolution with l-proline by control of the solvent. The chiral tridentate ligand O-SpiroPAP derived from O-SPINOL has been successfully synthesized and applied in the iridium-catalyzed asymmetric hydrogenation of bridged biaryl lactones under mild reaction conditions, providing valuable and enantioenriched axially chiral molecules in excellent yields and enantioselectivities (up to 99% yield and >99% ee). This method represents a rare example of constructing axially chiral molecules by direct reduction of esters with H.
我们在此提出了一种简便且无需柱层析的方法，用于合成结构独特的氧杂螺环二酚，称为 O-SPINOL。该合成方法的特点包括在早期构建全碳季碳原子、关键的双分子内 SAr 步骤以引入螺环以及在 >100g 规模上操作的可行性。通过控制溶剂，使用 l-脯氨酸很容易通过对映体拆分得到 O-SPINOL 的两种对映异构体。从 O-SPINOL 衍生出的手性三齿配体 O-SpiroPAP 已成功合成，并在温和的反应条件下应用于桥连双芳基内酰胺的铱催化不对称氢化反应中，以优异的产率和对映选择性（高达 99%的产率和 >99%的对映体过量）提供了有价值的、手性富集的轴向手性分子。该方法代表了通过直接还原酯与 H 来构建轴向手性分子的罕见实例。
