Sustainable Synthesis of Diverse Privileged Heterocycles by Palladium-Catalyzed Aerobic Oxidative Isocyanide Insertion

Authors

  • Tjøstil Vlaar,

    1. Department of Chemistry & Pharmaceutical Sciences and Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam (The Netherlands)
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  • Razvan C. Cioc,

    1. Department of Chemistry & Pharmaceutical Sciences and Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam (The Netherlands)
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  • Pieter Mampuys,

    1. Organic Synthesis, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp (Belgium)
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  • Prof. Dr. Bert U. W. Maes,

    Corresponding author
    1. Organic Synthesis, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp (Belgium)
    • Organic Synthesis, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp (Belgium)
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  • Prof. Dr. Romano V. A. Orru,

    Corresponding author
    1. Department of Chemistry & Pharmaceutical Sciences and Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam (The Netherlands)
    • Department of Chemistry & Pharmaceutical Sciences and Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam (The Netherlands)
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  • Dr. Eelco Ruijter

    Corresponding author
    1. Department of Chemistry & Pharmaceutical Sciences and Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam (The Netherlands)
    • Department of Chemistry & Pharmaceutical Sciences and Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam (The Netherlands)
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  • This work was financially supported by The Netherlands Organization for Scientific Research (NWO) by means of a TOP grant to R.V.A.O, and by the Hercules Foundation. We thank Elwin Janssen for technical assistance, Sanne Bouwman for HRMS measurements, and Dr. Andreas W. Ehlers for NMR spectroscopic measurements.

Abstract

original image

O2 in, H2O out: Various diamines and related bisnucleophiles readily undergo oxidative isocyanide insertion with Pd(OAc)2 (1 mol %) as the catalyst and O2 as the terminal oxidant to give a diverse array of medicinally relevant N heterocycles. The utility of this highly sustainable method is demonstrated by a formal synthesis of the antihistamines astemizole and norastemizole.

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