Synlett 2015; 26(08): 1049-1054
DOI: 10.1055/s-0034-1380178
letter
© Georg Thieme Verlag Stuttgart · New York

Chromium(II)-Catalyzed Amination of N-Heterocyclic Chlorides with Magnesium Amides

Andreas K. Steib
a  Department of Chemistry, Ludwig-Maximilians-Universität, Butenandtstr. 5–13, 81377 Munich, Germany   Email: paul.knochel@cup.uni-muenchen.de
,
Sarah Fernandez
a  Department of Chemistry, Ludwig-Maximilians-Universität, Butenandtstr. 5–13, 81377 Munich, Germany   Email: paul.knochel@cup.uni-muenchen.de
,
Olesya M. Kuzmina
a  Department of Chemistry, Ludwig-Maximilians-Universität, Butenandtstr. 5–13, 81377 Munich, Germany   Email: paul.knochel@cup.uni-muenchen.de
,
Martin Corpet
b  Laboratoire de Chimie Moléculaire, Ecole Polytechnique, CNRS, 91128 Palaiseau Cedex, France   Email: corinne.gosmini@polytechnique.edu
,
Corinne Gosmini
b  Laboratoire de Chimie Moléculaire, Ecole Polytechnique, CNRS, 91128 Palaiseau Cedex, France   Email: corinne.gosmini@polytechnique.edu
,
Paul Knochel*
a  Department of Chemistry, Ludwig-Maximilians-Universität, Butenandtstr. 5–13, 81377 Munich, Germany   Email: paul.knochel@cup.uni-muenchen.de
› Author Affiliations
Further Information

Publication History

Received: 16 December 2014

Accepted after revision: 22 January 2015

Publication Date:
26 February 2015 (eFirst)

Abstract

We report a ligand-free chromium(II)-catalyzed amination reaction of various N-heterocyclic chlorides. CrCl2 regioselectively catalyzes the reaction of chloropyridines and dichloropyridines, dichloroquinolines, dichloroisoquinolines and dichloroquinoxalines with a range of aliphatic, allylic, benzylic and saturated (hetero)cyclic magnesium amides in the presence of lithium chloride as additive. The reactions were performed at 50 °C in THF and led to the desired aminated products in 56–96% yield.

Supporting Information

 
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  • 15 However, a longer reaction time (20 h at 50 °C) also led to full conversion.
    • 16a Typical procedure for the Cr-catalyzed amination using CrCl2 : The previously prepared solution of the magnesium amide was transferred via syringe to a second dry and argon-flushed Schlenk tube, containing water-free CrCl2 (0.1 equiv) and the N-heterocyclic halide in THF (1 equiv, 2 M in THF) at 23 °C. The resulting reaction mixture was stirred at 50 °C until the N-heterocyclic halide was consumed. The solvent was evaporated in vacuo and the crude product was purified on silica gel to afford the desired product.
    • 16b Typical procedure for the Cr-catalyzed amination using Cr(acac)3 : The previously prepared solution of the magnesium amide was transferred via syringe to a second dry and argon-flushed Schlenk tube, containing Cr(acac)3 (0.1 equiv) and the N-heterocyclic halide in THF (1 equiv, 2 M in THF) at 23 °C. The resulting reaction mixture was stirred at 50 °C until the N-heterocyclic halide was consumed. The solvent was evaporated in vacuo and the crude product was purified on silica gel to afford the desired product.
  • 17 No diamination product was observed in the aminations involving 1c, 1d, 1e and 1h.
  • 18 Magnesium chloride indolin-1-ide (2e) reacted rapidly with 1d but the related magnesium chloride methylanilide underwent the amination reaction in only 32% yield, showing the limits of the CrCl2 catalysis.