Enantioselective synthesis of tunable chiral pyridine-aminophosphine ligands and their applications in asymmetric hydrogenation

• Published in: Organic & biomolecular chemistry Vol. 17; no. 2; pp. 599 - 515
• Main Authors: Liu, Youran, Chen, Fei, He, Yan-Mei, Li, Chenghao, Fan, Qing-Hua
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 28.05.2019
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; KETONES; VERSATILE; SCOPE; RUTHENIUM-CATALYZED HYDROGENATION; OLEFINS; 1,5-BENZODIAZEPINES; CYCLIC IMINES; ACCESS
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c9ob00770a

A small library of tunable chiral pyridine-aminophosphine ligands were enantioselectively synthesized based on chiral 2-(pyridin-2-yl)-substituted 1,2,3,4-tetrahydroquinoline scaffolds, which were obtained in high yields and with excellent enantioselectivities via ruthenium-catalyzed asymmetric hydrogenation of 2-(pyridin-2-yl)quinolines. The protocol features a wide substrate scope and mild reaction conditions, enabling scalable synthesis. These chiral P,N ligands were successfully applied in the Ir-catalyzed asymmetric hydrogenation of benchmark olefins and challenging seven-membered cyclic imines including benzazepines and benzodiazepines. Excellent enantio- and diastereoselectivity (up to 99% ee and >20 : 1 dr), and/or unprecedented chemoselectivity were obtained in the asymmetric hydrogenation of 2,4-diaryl-3 H -benzo[ b ]azepines and 2,4-diaryl-3 H -benzo[ b ][1,4]diazepines. A small library of tunable chiral pyridine-aminophosphine ligands were synthesized based on tetrahydroquinoline scaffolds obtained via Ru-catalyzed asymmetric hydrogenation. The ligands were applied in the Ir-catalyzed asymmetric hydrogenation of olefins and imines.