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Efficient Synthesis of Substituted 3-Azabicyclo[3.1.0]hexan-2-ones from 2-Iodocyclopropanecarboxamides Using a Copper-Free Sonogashira Coupling

Authors

  • Benoît de Carné-Carnavalet,

    1. Laboratoire de Chimie Organique, ESPCI ParisTech, CNRS (UMR 7084), 10 rue Vauquelin 75231 Paris Cedex 05 (France), Fax: (+33) 1-40-79-46-60
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  • Alexis Archambeau,

    1. Laboratoire de Chimie Organique, ESPCI ParisTech, CNRS (UMR 7084), 10 rue Vauquelin 75231 Paris Cedex 05 (France), Fax: (+33) 1-40-79-46-60
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  • Dr. Christophe Meyer,

    Corresponding author
    1. Laboratoire de Chimie Organique, ESPCI ParisTech, CNRS (UMR 7084), 10 rue Vauquelin 75231 Paris Cedex 05 (France), Fax: (+33) 1-40-79-46-60
    • Laboratoire de Chimie Organique, ESPCI ParisTech, CNRS (UMR 7084), 10 rue Vauquelin 75231 Paris Cedex 05 (France), Fax: (+33) 1-40-79-46-60
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  • Prof. Dr. Janine Cossy,

    Corresponding author
    1. Laboratoire de Chimie Organique, ESPCI ParisTech, CNRS (UMR 7084), 10 rue Vauquelin 75231 Paris Cedex 05 (France), Fax: (+33) 1-40-79-46-60
    • Laboratoire de Chimie Organique, ESPCI ParisTech, CNRS (UMR 7084), 10 rue Vauquelin 75231 Paris Cedex 05 (France), Fax: (+33) 1-40-79-46-60
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  • Dr. Benoît Folléas,

    1. DiverChim, 6 rue du Noyer, ZAC du Moulin 95700 Roissy-en-France (France)
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  • Dr. Jean-Louis Brayer,

    1. DiverChim, 6 rue du Noyer, ZAC du Moulin 95700 Roissy-en-France (France)
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  • Dr. Jean-Pierre Demoute

    1. DiverChim, 6 rue du Noyer, ZAC du Moulin 95700 Roissy-en-France (France)
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Abstract

The copper-free Sonogashira coupling between N-substituted cis- 2-iodocyclopropanecarboxamides and terminal aryl-, heteroaryl-alkynes or enynes, followed by 5-exo-dig cyclization of the nitrogen amide onto the carbon–carbon triple bond, provides a remarkably efficient access to a variety of substituted 4-methylene-3-azabicyclo[3.1.0]hexan-2-ones in excellent yields. Protonation of these latter enamides generates bicyclic N-acyliminium ions that can be involved in Pictet–Spengler cyclizations leading to new 3-azabicyclo[3.1.0]hexan-2-ones, possessing a quaternary stereocenter at C4, with high diastereoselectivities. This strategy constitutes an attractive complementary alternative to the classical route that relies on the addition of organometallic reagents to cyclopropyl imides.

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