Weijun Tang, Lijin Xu, Q. Fan
Nov 16, 2009
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118
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Angewandte Chemie
Abstract
The 1,2,3,4-tetrahydroquinoxaline ring system is an important structural unit in many bioactive compounds. [1–3] Optically pure tetrahydroquinoxaline derivatives have shown great potential for pharmaceutical applications. For example, chiral compound A has been pursued as a potent vasopressin V2 receptor antagonists, [1d] and optically pure compound B is a promising inhibitor of cholesteryl ester transfer protein. [1e] In both cases, the chirality of the compounds was found to play a very important role in the relevant bioactivity of these compounds. The most convenient and straightforward route to chiral tetrahydroquinoxalines is the asymmetric hydrogenation of quinoxalines. Although several kinds of heteroaromatic compounds, [4] such as quinolines, [5] indoles, [6] furans, [7] pyr-idines, [8] and pyrazines [9] have been successfully hydrogenated with good to excellent enantioselectivities and yields in the presence of chiral transition-metal catalysts, the enantiose-lective hydrogenation of substituted quinoxaline derivatives has been less extensively studied. [3] In 1987, Murata et al. first reported the rhodium-catalyzed asymmetric hydrogenation of 2-methylquinoxaline with only 3 % ee. [3a] Later Bianchini et al. enantioselectively hydrogenated 2-methylquinoxaline with an orthomelated dihydride iridium complex to produce the product with up to 90 % ee, [3b,c] but the reduction suffered from lower conversions. The performance of [RuCl 2 (diphosphine)(diamine)] complexes [3d,e] and Ir/PQ-phos [3f] (PQ-phos =