Acta Chimica Sinica ›› 2014, Vol. 72 ›› Issue (7): 820-824.DOI: 10.6023/A14050391 Previous Articles     Next Articles

Special Issue: 不对称催化与合成



时磊a,b, 姬悦a, 黄文学a, 周永贵a   

  1. a 中国科学院大连化学物理研究所 大连 116023;
    b 大连理工大学精细化工国家重点实验室 大连 116024
  • 投稿日期:2014-05-19 发布日期:2014-06-17
  • 通讯作者: 时磊, 周永贵;
  • 基金资助:

Application of Chiral Anion Metathesis Strategy in Asymmetric Transfer Hydrogenation of Isoquinolines

Shi LeiJia,b, Yue Huanga, Wen xuea, Zhou Yongguia   

  1. a Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China;
    b State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, China
  • Received:2014-05-19 Published:2014-06-17
  • Supported by:
    Project supported by the National Natural Science Foundation of China (No. 21202162) and the State Key Laboratory of Fine Chemicals (No. KF1110).

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.

Key words: chiral phosphoric acid, chiral anion metathesis, transfer hydrogenation, isoquinolines