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

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 alpha,beta-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.

Automated summary

Central chirality is an important aspect in the design of chiral ligands and catalysts. This study focuses on the exploration of N-chirality in chiral ligand design, which has been rarely studied before. The authors demonstrate the design, synthesis, and application of a class of P,N-ligands with flexible N-chirality and their derived iridium complexes with fixed N-chiral stereocenters. Computational studies emphasize the importance of N-chirality and the N-H group in the catalytic activity of these complexes.