Continuous-Flow Oxidative Cyanation of Primary and Secondary Amines Using Singlet Oxygen

Authors

  • Dr. Dmitry B. Ushakov,

    1. Department für Biomolekulare Systeme, Max-Planck-Institut für Kolloid- und Grenzflächenforschung, Am Mühlenberg 1, 14476 Potsdam (Germany)
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  • Dr. Kerry Gilmore,

    1. Department für Biomolekulare Systeme, Max-Planck-Institut für Kolloid- und Grenzflächenforschung, Am Mühlenberg 1, 14476 Potsdam (Germany)
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  • Dr. Daniel Kopetzki,

    1. Department für Biomolekulare Systeme, Max-Planck-Institut für Kolloid- und Grenzflächenforschung, Am Mühlenberg 1, 14476 Potsdam (Germany)
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  • Prof. Dr. D. Tyler McQuade,

    1. Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306 (USA)
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  • Prof. Dr. Peter H. Seeberger

    Corresponding author
    1. Department für Biomolekulare Systeme, Max-Planck-Institut für Kolloid- und Grenzflächenforschung, Am Mühlenberg 1, 14476 Potsdam (Germany)
    2. Institut für Chemie und Biochemie, Freie Universität Berlin, Arnimallee 22, 14195 Berlin (Germany)
    • Department für Biomolekulare Systeme, Max-Planck-Institut für Kolloid- und Grenzflächenforschung, Am Mühlenberg 1, 14476 Potsdam (Germany)

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  • We gratefully acknowledge financial support from the Max Planck Society. We thank Thomas Kolrep and Fabian Klautzsch for assistance in preparing high-resolution mass spectra. We also thank Matthew Plutschack for fruitful discussions and David Ausserhoff for a picture used in the graphical abstract.

Abstract

Primary and secondary amines can be rapidly and quantitatively oxidized to the corresponding imines by singlet oxygen. This reactive form of oxygen was produced using a variable-temperature continuous-flow LED-photoreactor with a catalytic amount of tetraphenylporphyrin as the sensitizer. α-Aminonitriles were obtained in good to excellent yields when trimethylsilyl cyanide served as an in situ imine trap. At 25°C, primary amines were found to undergo oxidative coupling prior to cyanide addition and yielded secondary α-aminonitriles. Primary α-aminonitriles were synthesized from the corresponding primary amines for the first time, by an oxidative Strecker reaction at –50 °C. This atom-economic and protecting-group-free pathway provides a route to racemic amino acids, which was exemplified by the synthesis of tert-leucine hydrochloride from neopentylamine.

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