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Chinese Journal of Organic Chemistry >

2023 , Vol. 43 >Issue 8: 2961 - 2967

DOI: https://doi.org/10.6023/cjoc202301029

[RuCl(p-cymene)-(S)-BINAP]Cl Catalyzed Asymmetric Preparation of trans-3-Amino-bicyclo[2.2.2]octane-2-carboxylic Acid Ethyl Ester

  • Zhangtao Zhou ,
  • Yang Wang ,
  • Bingxin Cheng ,
  • Weiping Ye
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  • Shenzhen HwaGen Pharmacuticial Co., Ltd, Shenzhen, Guangdong 518118
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Received date: 2023-01-31

  Revised date: 2023-03-14

  Online published: 2023-04-26

Supported by

The Shenzhen Science and Technology Program(KQTD20190929172447117)

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Abstract

trans-3-Amino-bicyclo[2.2.2]octane-2-carboxylic acid ester is the key common chiral fragment of some novel antiviral drugs (like Pimodivir and ZSP1273), which targets the PB2 subunit of RNA polymerase. Now, the market demand of this molecule is at level of hundreds kilograms to tons, and there are several related innovative drugs in clinical study. Here a asymmetric transfer hydrogenation strategy to directly construct trans-3-amino-bicyclo[2.2.2]octane-2-carboxylic acid ethyl ester using [RuCl(p-cymene)-(S)-BINAP]Cl as catalyst with excellent enantioselectivity (over 98% ee) and without tautomerization and protecting/de-protecting process is developed, which holds the potential of scale up production and commercial value.

Key words： influenza; Ru catalysis; asymmetric transfer hydrogenation; β-amino acid ester

Cite this article

Zhangtao Zhou , Yang Wang , Bingxin Cheng , Weiping Ye . [RuCl(p-cymene)-(S)-BINAP]Cl Catalyzed Asymmetric Preparation of trans-3-Amino-bicyclo[2.2.2]octane-2-carboxylic Acid Ethyl Ester[J]. Chinese Journal of Organic Chemistry, 2023 , 43(8) : 2961 -2967 . DOI: 10.6023/cjoc202301029

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