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Enantioselective Henry and Aza-Henry Reaction in the Synthesis of (R)-Tembamide Using Efficient, Recyclable Polymeric CuII Complexes as Catalyst

Authors

  • Anjan Das,

    1. Discipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research Institute (CSIR-CSMCRI), Bhavnagar 364021, Gujarat (India), Fax: (+91) 0278-2566970
    2. Academy of Scientific and Innovative Research (AcSIR), CSIR-CSMCRI, Bhavnagar 364021, Gujarat (India)
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  • Manoj K. Choudhary,

    1. Discipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research Institute (CSIR-CSMCRI), Bhavnagar 364021, Gujarat (India), Fax: (+91) 0278-2566970
    2. Academy of Scientific and Innovative Research (AcSIR), CSIR-CSMCRI, Bhavnagar 364021, Gujarat (India)
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  • Dr. Rukhsana I. Kureshy,

    Corresponding author
    1. Discipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research Institute (CSIR-CSMCRI), Bhavnagar 364021, Gujarat (India), Fax: (+91) 0278-2566970
    2. Academy of Scientific and Innovative Research (AcSIR), CSIR-CSMCRI, Bhavnagar 364021, Gujarat (India)
    • Discipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research Institute (CSIR-CSMCRI), Bhavnagar 364021, Gujarat (India), Fax: (+91) 0278-2566970===

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  • Tamal Roy,

    1. Discipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research Institute (CSIR-CSMCRI), Bhavnagar 364021, Gujarat (India), Fax: (+91) 0278-2566970
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  • Dr. Noor-ul H. Khan,

    1. Discipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research Institute (CSIR-CSMCRI), Bhavnagar 364021, Gujarat (India), Fax: (+91) 0278-2566970
    2. Academy of Scientific and Innovative Research (AcSIR), CSIR-CSMCRI, Bhavnagar 364021, Gujarat (India)
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  • Dr. Sayed H. R. Abdi,

    1. Discipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research Institute (CSIR-CSMCRI), Bhavnagar 364021, Gujarat (India), Fax: (+91) 0278-2566970
    2. Academy of Scientific and Innovative Research (AcSIR), CSIR-CSMCRI, Bhavnagar 364021, Gujarat (India)
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  • Dr. Hari C. Bajaj

    1. Discipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research Institute (CSIR-CSMCRI), Bhavnagar 364021, Gujarat (India), Fax: (+91) 0278-2566970
    2. Academy of Scientific and Innovative Research (AcSIR), CSIR-CSMCRI, Bhavnagar 364021, Gujarat (India)
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Abstract

Chiral copper(II) polymeric [H4]salen (salen=bis[(salicylidene)ethylenediaminato]) complexes CuII-13 were generated in situ and used as efficient catalysts in the asymmetric Henry and aza-Henry reaction of various aromatic and aliphatic aldehydes and N-tosylimines in the presence of various nitroalkanes at room temperature (27±2 °C) for 20 hours. This group of polymeric [H4]salen complexes demonstrated excellent performance (product yield and enantiomeric excess ee up to 98 %) in the formation of β-nitroalcohol by using nitromethane with low catalyst loading of 1 mol % (with respect to the monomeric salen unit) and high enantioinduction (ee 94 %) in the aza-Henry product; β-nitroamines were obtained with moderate yield (78 %). This catalytic system also worked well with nitroethane and 1-nitropropane in the case of Henry reaction, to furnish the corresponding products in high yields and enantioselectivities for syn diastereomers. The CuII-2 complex retained its performance at the gram level and was expediently recycled eight times with no significant loss in its performance. The kinetic study with CuII-2 complex for the enantioselective aza-Henry reaction of N-Ts-benzylimine (Ts=tosyl) revealed a first-order dependence on catalyst and nitromethane concentration and was zero order with respect to the substrate. The product obtained was transformed straightforwardly to the pharmaceutically important enantiomerically pure (R)-tembamide (β-adrenergic agonist) drug in good yield by the asymmetric nitroaldol reaction of 4-methoxybenzaldehyde in three successive steps.

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