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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Minimizing risk: The synthesis of arylhydrazines through C[BOND]N cross-coupling of aryl chlorides with hydrazine is described. Through the use of continuous flow, the hazards associated with the use of hydrazine in the presence of transition metals are decreased. In addition, multistep flow sequences have also been developed for the generation of functionalized heterocycles utilizing the arylhydrazine intermediates.

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