Ternary Aldehyde–Copper–Iridium Catalysis Enables Stereodivergent Allylation via α‐C‐H Functionalization of Primary Amines
Abstract
Abstract α‐Chiral primary amines are recognized as one of the most valuable and versatile synthetic intermediates, widely utilized in the construction of diverse amine‐containing natural products, pharmaceuticals, and agrochemicals. The direct asymmetric α‐C‐H functionalization of unprotected primary amines is the most straightforward method for creating these motifs. However, this transformation remains underdeveloped, particularly in stereodivergent synthesis of primary amines with multiple stereocenters. Herein, we report an aldehyde/copper/iridium ternary catalytic system, which was successfully employed for the direct enantio‐ and diastereodivergent α‐allylation of primary α‐amino‐chromanone without requiring additional protection or activation of the NH 2 group. A wide range of α‐tertiary primary amines bearing vicinal stereocenters were prepared in high yields with excellent enantio‐ and diastereoselectivities (generally >20:1 dr and >99% ee). Notably, all four stereoisomers of the α‐tertiary amines can be readily prepared by simply switching the configuration combinations of the two chiral metal catalysts. Furthermore, the asymmetric induction model for the α‐C‐H functionalization of primary amines was meticulously elucidated through comprehensive density functional theory (DFT) calculations.
Article Details
Authors (7)
Zijiao Liu
Shanghai University of Medicine & Health Sciences Affiliated Sixth People's Hospital South Campus Shanghai 201499 China
Panpan Li
Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, State Key Laboratory of Synergistic Chem-Bio Synthesis, Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China
Haoyang Wang
Jiacheng Zhang
State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Key Laboratory of Electrical Insulation and Thermal Ageing
Xiaohong Huo
Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, State Key Laboratory of Synergistic Chem-Bio Synthesis, Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China
Zhen‐Liang Sun
Shanghai University of Medicine & Health Sciences Affiliated Sixth People's Hospital South Campus Shanghai 201499 China
Wanbin Zhang
Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, State Key Laboratory of Synergistic Chem-Bio Synthesis, Zhengzhou Industrial Technology Research Institute of Shanghai Jiao Tong University, School of Chemistry and Chemical Engineering