Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, East China University of Science & Technology, Shanghai, 200237, China.
Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, USA.
Angew Chem Int Ed Engl. 2022 Sep 5;61(36):e202207536. doi: 10.1002/anie.202207536. Epub 2022 Jul 25.
Herein, we leverage the Ni-catalyzed enantioselective reductive dicarbofunctionalization of internal alkenes with alkyl iodides to enable the synthesis of chiral pyrrolidinones bearing vicinal stereogenic centers. The application of newly developed Quinim is critical for formation of two contiguous stereocenters in high yield, enantioselectivity, and diastereoselectivity. This catalytic system also improves both the yield and enantioselectivity in the synthesis of α,α-dialkylated γ-lactams. Computational studies reveal that the enantiodetermining step proceeds with a carbamoyl-Ni intermediate that is reduced by the Mn reductant prior to intramolecular migratory insertion. The presence of the t-butyl group of the Quinim ligand leads to an unfavorable distortion of the substrate in the TS that leads to the minor enantiomer. Calculations also support an improvement in enantioselectivity with Quinim compared to Quinim.
在这里，我们利用镍催化的内部烯烃与烷基碘化物的对映选择性还原双官能化反应，实现了具有毗邻手性中心的手性吡咯烷酮的合成。新开发的 Quinim 的应用对于以高产率、对映选择性和非对映选择性形成两个连续的立体中心至关重要。该催化体系还提高了α，α-二烷基化γ-内酰胺合成的产率和对映选择性。计算研究表明，手性决定步骤是通过碳酰胺-Ni 中间体进行的，该中间体在分子内迁移插入之前被 Mn 还原剂还原。Quinim 配体的叔丁基的存在导致底物在 TS 中发生不利的扭曲，导致生成较少的对映异构体。计算还支持与 Quinim 相比，Quinim 可提高对映选择性。
