10.1021/ja0676758.s001
Alexandre Gagnon
Alexandre
Gagnon
Miguel St-Onge
Miguel
St-Onge
Kelly Little
Kelly
Little
Martin Duplessis
Martin
Duplessis
Francis Barabé
Francis
Barabé
Direct <i>N</i>-Cyclopropylation of Cyclic Amides and Azoles Employing a
Cyclopropylbismuth Reagent
American Chemical Society
2007
carbon atom
nitrogenated compounds
cyclopropyl group
Cyclopropylbismuth ReagentCyclopropanes
nonpyrophoric cyclopropylbismuth reagent
Azoles Employing
Cyclic Amides
method
copper acetate
cyclic amides
cyclopropyl transfer reaction
liver microsomes
2007-01-10 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Direct_i_N_i_Cyclopropylation_of_Cyclic_Amides_and_Azoles_Employing_a_Cyclopropylbismuth_Reagent/3033718
Cyclopropanes are commonly found in medicinal chemistry since they provide unique spatial and electronic features, combined with high metabolic stability in liver microsomes. Although many methods are found in the chemist's arsenal to connect a cyclopropyl group to a carbon atom, none exist that perform the direct transfer of this useful fragment onto the nitrogen of a heterocycle or an amide. Considering the importance of nitrogenated compounds in the pharmaceutical industry, we sought to develop an expedient method to <i>N</i>-cyclopropylate azoles and amides. We report herein the direct cyclopropyl transfer reaction onto cyclic amides, isatins, oxindoles, imides, and carbamates employing a nonpyrophoric cyclopropylbismuth reagent. The reaction is catalyzed by copper acetate and proceeds smoothly in dichloromethane at 50 °C in the presence of pyridine. The <i>N</i>-cyclopropylation reaction can also be applied to the preparation of <i>N</i>-cyclopropyl indoles, benzimidazoles, pyrroles, and pyrazoles.