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论文类型：期刊论文

发表时间：2022-06-28

发表刊物：化学学报

所属单位：化工学院

卷号：72

期号：7

页面范围：820-824

ISSN号：0567-7351

摘要：Asymmetric hydrogenation of N-hetero aromatics offers a very straightforward and efficient method to obtain the corresponding chiral N-hetero cyclic saturated or partially saturated compounds. As one of the most challenging substrates, asymmetric hydrogenation of isoquinolines has met with limited success probably because of lower reactivity and the catalyst deactivation resulted from strong coordination. Considering the prevalence of the chiral 1,2,3,4-tetrahydroisoquinoline motif in natural alkaloids and drug molecules, the development of new catalyst system for asymmetric hydrogenation of isoquinolines is highly desirable and significant. Herein, a novel chiral anion metathesis strategy successfully applied for asymmetric transfer hydrogenation of isoquinolines is reported. N-Protected 1-substituted 1,2-dihydroisoquinolines were obtained with high yield and up to 79% ee in the presence of Hantzsch ester and chloroformate using chiral phosphoric acid as catalyst. The phosphate salt and the activated N-acyl isoquinolinium chloride undergo anion metathesis to form chiral contact ion pair, which leads to a highly enantioselective transfer hydrogenation of isoquinolines. After systematically investigating the effects of activating reagent, solvent, base, hydride donor and catalyst on this transfer hydrogenation reaction, the best result was achieved under the optimized condition as follows: 5 mol% H8-BINOL-derived chiral phosphoric acid as catalyst, 1.2 equivalent 2,2,2-trichloroethyl chloroformate as activator, 1.5 equivalent dimethyl 2,6-diethyl-1,4-dihydropyridine-3,5-dicarboxylate as hydride donor, 1.5 equivalent sodium carbonate as base and cyclohexane as solvent. The reaction is tolerant toward a broad range of aryl or alkyl 1-substituted isoquinoline substrates. This methodology represents one of the rare examples of asymmetric hydrogenation of this challenging substrate. The utilizing of chiral anion metathesis strategy could enable chiral phosphoric acid to catalyze more asymmetric transformation process and further researching is ongoing in our laboratory.

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