Enantioselective Indium-Catalyzed Hydrogenation of 1- and 3-Substituted Isoquinoliniuni Salts

摘要

Chiral 1,2,3,4-tetrahydroisoquinolines are ubiquitous structural motifs in many natural alkaloids and biologically active compounds. Among the various catalytic methods developed for the construction of chiral tetrahydroisoquinolines during the past decades, asymmetric hydrogenation of isoquinolines unquestionably serves as one of the most straightforward and powerful methods. So far, significant progress on the asymmetric hydrogenation of aromatic compounds has been implemented successfully for substrates such as quinolines, quinoxalines, indoles, pyrroles, pyridines, furans, imidazoles, thiophenes and aromatic carbocyclic rings. However, the development of the enantioselective hydrogenation of isoquinolines has met with limited success, probably owing to lower reactivity and strong coordination to the catalyst. In 2006, our group reported the first iridium-catalyzed asymmetric hydrogenation of isoquinolines, which were activated by chloroformates, with moderate enantioselectivity and yield. Very recently, an enantioselective hydrogenation of 3,4-disubstituted isoquinolines employing catalyst activation was successfully described, nevertheless, this strategy is not suitable for 1-substituted isoquinolines. Moreover, there is no report on the asymmetric hydrogenation of 3-substituted isoquinolines heretofore. Therefore, the development of a general and efficient strategy for asymmetric hydrogenation of 1- and 3-substituted isoquinolines is still a very valuable and challenging area of chemical research.