Iridium-Catalyzed Enantioselective Hydrogenation of 3-Substituted Isoquinolinium Salts

Chiral tetrahydroisoquinolines (THIQ) is a highly important molecular skeleton in natural alkaloids and biologically active compounds, and its derivatives are often used as key intermediates for the synthesis of drugs. Herein, we described an efficient enantioselective hydrogenation of 3-substituted isoquinolinium salts catalyzed by a bromine-bridged dimeric complex [{Ir(H)[(R,S,S-ax)-Ph-ax-Josiphos]}(2)(mu-Br)(3)]Br-+(-). This efficient enantioselective transformation could provide a series of useful chiral cyclic amines, which were of great potential value in natural product modification and drug molecular preparation in high yields and moderate to excellent enantioselectivities (68-97% ee). Additionally, turnover number experiments and a gram-scale synthesis of chiral 3-phenyltetrahydroisoquinoline were conducted.

Automated summary

An efficient enantioselective hydrogenation method was described for the preparation of chiral cyclic amines, which are useful for natural product modification and drug molecular preparation. High yields and moderate to excellent enantioselectivities were achieved, making this method valuable for synthesis applications.