No abstract

Chiral 1,2,3,4-tetrahydroisoquinolines are ubiquitous structural motifs in many natural alkaloids and biologically active compounds. [1] Among the various catalytic methods developed for the construction of chiral tetrahydroisoquinolines during the past decades, [2] 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 [3] for substrates such as quinolines, [4] quinoxalines, [5] indoles, [6] pyrroles, [7] pyridines, [8] furans, [9] imidazoles, [10] thiophenes [11] and aromatic carbocyclic rings. [12] 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. [13] Very recently, an enantioselective hydrogenation of 3,4-disubstituted isoquinolines employing catalyst activation was successfully described, [14] nevertheless, this strategy is not suitable for 1substituted 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 3substituted isoquinolines is still a very valuable and challenging area of chemical research.Recently, our group successfully documented the iridiumcatalyzed asymmetric hydrogenation of simple pyridinium salts, which were formed by using benzyl bromide and possess higher reactivity than the corresponding pyridines. [15] As part of our ongoing efforts to promote the development of asymmetric hydrogenation of heteroaromatic compounds, [3a,b] and considering the similar structure of pyridine to isoquinoline, we envisioned that activating isoquinoline as the N-benzyl isoquinolinium salt would effectively improve the reactivity to facilitate hydrogenation (Scheme 1). Herein, we report the iridium-catalyzed asymmetric hydrogenation of 1-