Mild and Rapid Pd-Catalyzed Cross-Coupling with Hydrazine in Continuous Flow: Application to the Synthesis of Functionalized Heterocycles

Authors

  • Dr. Andrew DeAngelis,

    1. Department of Chemistry, Room 18-490, Massachusetts Institute of Technology, Cambridge, MA 02139 (USA)
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  • Dr. Dong-Hui Wang,

    1. Department of Chemistry, Room 18-490, Massachusetts Institute of Technology, Cambridge, MA 02139 (USA)
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  • Prof. Dr. Stephen L. Buchwald

    Corresponding author
    1. Department of Chemistry, Room 18-490, Massachusetts Institute of Technology, Cambridge, MA 02139 (USA)
    • Department of Chemistry, Room 18-490, Massachusetts Institute of Technology, Cambridge, MA 02139 (USA)
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  • We acknowledge Novartis International AG for funding. The Bruker NMR spectrometers used in this work were supported by grants from the National Science Foundation (CHE-9808061 and DBI-9729592) and the National Institutes of Health (1S10RR13886-01). We thank Dr. Nathan T. Jui for helpful discussions and Dr. Christine Nguyen for experimental assistance. MIT has patents on some of the ligands and precatalysts used in this work as well as metal-catalyzed cross-coupling reactions with hydrazine from which S.L.B. receives royalty payments.

Abstract

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Risikominimierung: Die Synthese von Arylhydrazinen durch C-N-Kreuzkupplung von Arylchloriden mit Hydrazin wird beschrieben. Die Reaktion wird in einem Strömungssystem durchgeführt, wodurch das Gefahrenpotential beim Umgang mit Hydrazin in Gegenwart von Übergangsmetallen gesenkt wird. Mehrstufige Strömungssequenzen für die Synthese funktionalisierter Heterocyclen aus den Arylhydrazin-Zwischenstufen wurden ebenfalls entwickelt.

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