Zhang Genwei, Yang Bin, Yang Junfeng, Zhang Junliang
Department of Chemistry, Fudan University, 2005 Songhu Road, Shanghai 200438, China.
Zhuhai Fudan Innovation Institute, Zhuhai 519000, China.
J Am Chem Soc. 2024 Feb 28;146(8):5493-5501. doi: 10.1021/jacs.3c13356. Epub 2024 Feb 13.
Larock indole synthesis is one of the most straightforward and efficient methods for the synthesis of indoles; however, there has been no asymmetric version yet for the construction of indole-based axially chiral -arylindoles since its initial report in 1991. Herein we report the first example of an asymmetric Larock indole synthesis by employing a chiral sulfinamide phosphine (SadPhos) ligand (Ming-Phos) with palladium. It allows rapid construction of a wide range of axially chiral -arylindole compounds in good yields up to 98:2 er. The application of this unique chiral scaffold as an organocatalyst is promising. Furthermore, a kinetic study has revealed that the alkyne migratory insertion is the rate-determining step, which has been proven by the density functional theory (DFT) calculations. Additionally, DFT studies also suggest that the N-C dihedral difference caused by the steric hindrance of the ligand contributes to enantioselectivity control.
拉罗克吲哚合成法是合成吲哚最直接有效的方法之一；然而，自1991年首次报道以来，尚未有用于构建基于吲哚的轴手性芳基吲哚的不对称版本。在此，我们报道了首例通过使用手性亚磺酰胺膦（SadPhos）配体（明膦）与钯进行不对称拉罗克吲哚合成的实例。它能够以高达98:2的对映体过量（er）高产率快速构建多种轴手性芳基吲哚化合物。将这种独特的手性骨架用作有机催化剂具有广阔前景。此外，动力学研究表明炔烃迁移插入是速率决定步骤，这已通过密度泛函理论（DFT）计算得到证实。此外，DFT研究还表明，配体的空间位阻引起的N-C二面角差异有助于对映选择性控制。
