Enantiodivergent Hydrogenation of Exocyclic α,β‐Unsaturated Lactams Enabled by Switching the N‐Chirality of Iridium Catalyst

• Published in: Angewandte Chemie International Edition 2023-03, Vol.62 (11), p.e202213600-n/a
• Main Authors: Zhang, Ronghua, Xu, Shan, Luo, Zhou, Liu, Yuanyuan, Zhang, Junliang
• Format: Article
• Language: English
• Subjects: Asymmetric Catalysis; Catalysts; Catalytic activity; Chirality; Computer applications; Design; Enantio-Divergent; Hydrogenation; Iridium; Iridium compounds; Ligands; N-Chirality; P,N-Ligand
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202213600

Central chirality is an important chiral element used in the design of chiral ligands and catalysts. Mostly, the attention of organic chemists is focused on developing of chiral ligands with stable stereogenic centers. However, the N‐chirality in chiral ligand design has been rarely explored due to its flexibility. Here we demonstrate the design, synthesis, and application of a class of simple P,N‐ligands with flexible N‐chirality and their derived iridium complexes with fixed N‐chiral stereocenters. Both fixed configurations of the N‐stereocenter of the iridium complexes could be selectively formed from the same chiral ligand. This pair of diastereoisomeric iridium complexes showed good performance in the enantiodivergent asymmetric hydrogenation of exocyclic α,β‐unsaturated lactams. The N−H group plays an impressive role in catalytic activity. Computational studies emphasized the importance of N‐chirality and N−H group. An unprecedented N‐stereogenic center playing an impressive role in the iridium/Rong‐Phos‐catalyzed enantio‐divergent asymmetric hydrogenation was observed. Rong‐Phos is easily prepared from readily available starting materials, which selectively form two diastereoisomeric Ir‐complexes with fixed N‐chirality depending on the coordination conditions.