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

    Dmitry B. Ushakov, Kerry Gilmore, Daniel Kopetzki, D. Tyler McQuade, Peter H. Seeberger

    • 1Department für Biomolekulare Systeme, Max-Planck-Institut für Kolloid- und Grenzflächenforschung, Potsdam, Germany
    • 2Institut für Chemie und Biochemie, Freie Universität Berlin, Berlin, Germany
    • 3Department of Chemistry and Biochemistry, Florida State University, Tallahassee, USA

    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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