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 (online)


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

 
  • References and Notes

    • 1a Yuan J, Liu C, Lei A. Chem. Commun. 2015; 51: 1394
    • 1b Vo C.-VT, Bode JW. J. Org. Chem. 2014; 79: 2809
    • 1c See: http://www.drugs.com/stats/top100/2013/sales.
    • 1d Dictionary of Natural Products. Vol. 1. Buckingham J. Cambridge University Press; Cambridge (MA, USA): 1994
    • 2a Fier PS, Hartwig JF. J. Am. Chem. Soc. 2014; 136: 10139
    • 2b Heaney H. Chem. Rev. 1962; 62: 81
    • 3a Knappke CE. I, Grupe S, Gärtner D, Corpet M, Gosmini C, Jacobi von Wangelin A. Chem. Eur. J. 2014; 20: 6828
    • 3b Corpet M, Gosmini C. Synthesis 2014; 46: 2258
    • 3c Yan X, Yang X, Xi C. Catal. Sci. Technol. 2014; 4: 4169
    • 3d Okano K, Tokuyama H, Fukuyama T. Chem. Commun. 2014; 50: 13650
    • 3e Qian X, Yu Z, Auffrant A, Gosmini C. Chem. Eur. J. 2013; 19: 6225
    • 3f Gephart RT, Warren TH. Organomet. 2012; 31: 7728
    • 3g Delvos LB, Begouin J.-M, Gosmini C. Synlett 2011; 2325
    • 3h Cahiez G, Moyeux A. Chem. Rev. 2010; 110: 1435
    • 3i Toma G, Yamaguchi R. Eur. J. Org. Chem. 2010; 6404
    • 3j Liu C, Zhang H, Shi W, Lei A. Chem. Rev. 2011; 111: 1780
    • 3k Monnier F, Taillefer M. Angew. Chem. Int. Ed. 2009; 48: 6954
    • 3l He C, Chen C, Cheng J, Liu C, Liu W, Li Q, Lei A. Angew. Chem. Int. Ed. 2008; 47: 6414
    • 3m Kienle M, Reddy Dubbaka S, Brade K, Knochel P. Eur. J. Org. Chem. 2007; 4166
    • 3n Barluenga J, Valdes C. Chem. Commun. 2005; 4891
    • 3o Schlummer B, Scholz U. Adv. Synth. Catal. 2004; 346: 1599
    • 3p Dessole G, Bernardi L, Bonini BF, Capitò E, Fochi M, Herrera RP, Ricci A, Cahiez G. J. Org. Chem. 2004; 69: 8525
    • 3q Ley SV, Thomas AW. Angew. Chem. Int. Ed. 2003; 42: 5400
    • 4a Kosugi M, Kameyama M, Sano H, Migita T. Nippon Kagaku Kaishi 1985; 547
    • 4b Kosugi M, Hagiwara I, Migita T. Chem. Lett. 1983; 12: 839
    • 5a Maiti D, Fors BP, Henderson JL, Nakamura Y, Buchwald SL. Chem. Sci. 2011; 2: 57
    • 5b Surry DS, Buchwald SL. Chem. Sci. 2011; 2: 27
    • 5c Surry DS, Buchwald SL. Angew. Chem. Int. Ed. 2008; 47: 6338
    • 5d Yang BH, Buchwald SL. J. Organomet. Chem. 1999; 576: 125
    • 7a Zeng X, Cong X. Org. Chem. Front. 2015; 2: 69
    • 7b Holzwarth MS, Plietker B. ChemCatChem 2013; 5: 1650
    • 7c Murakami K, Ohmiya H, Yorimitsu H, Oshima K. Org. Lett. 2007; 9: 1569
    • 7d Takai K, Toshikawa S, Inoue A, Kokumai R, Hirano M. J. Organomet. Chem. 2007; 692: 520
    • 7e Takai K, Toshikawa S, Inoue A, Kokumai R. J. Am. Chem. Soc. 2003; 125: 12990
    • 7f Fürstner A. Chem. Rev. 1999; 99: 991
    • 7g Takai K, Matsukawa N, Takahashi A, Fujii T. Angew. Chem. Int. Ed. 1998; 37: 152
    • 7h Fürstner A, Shi N. J. Am. Chem. Soc. 1996; 118: 12349
    • 7i Matsubara S, Horiuchi M, Takai K, Utimoto K. Chem. Lett. 1995; 24: 259
    • 7j Takai K, Tagashira M, Kuroda T, Oshima K, Utimoto K, Nozaki H. J. Am. Chem. Soc. 1986; 108: 6048
    • 7k Jin H, Uenishi J.-I, Christ WJ, Kishi Y. J. Am. Chem. Soc. 1986; 108: 5644
    • 7l Takai K, Kimura K, Kuroda T, Hiyama T, Nozaki H. Tetrahedron Lett. 1983; 24: 5281
    • 7m Okude Y, Hiyama T, Nozaki H. Tetrahedron Lett. 1977; 3829
    • 7n Okude Y, Hirano S, Hiyama T, Nozaki H. J. Am. Chem. Soc. 1977; 99: 3179
    • 8a Steib AK, Kuzmina OM, Fernandez S, Malhotra S, Knochel P. Chem. Eur. J. 2015; 21: 1961
    • 8b Steib AK, Kuzmina OM, Fernandez S, Flubacher D, Knochel P. J. Am. Chem. Soc. 2013; 135: 15346
  • 9 Kuzmina OM, Knochel P. Org. Lett. 2014; 16: 5208
  • 10 Typical procedure for the formation of magnesium amides: A dry and argon-flushed Schlenk tube was charged with the appropriate amine (2 equiv) and i-PrMgCl·LiCl (2 equiv, 1.2 M solution in THF) was added dropwise at 0 °C. This reaction mixture was warmed to r.t. (23 °C) and was stirred for approximately 1 h at this temperature in order to obtain full conversion to the corresponding magnesium amide.
    • 11a Kunz T, Knochel P. Angew. Chem. Int. Ed. 2012; 51: 1958
    • 11b Boudet N, Knochel P. Org. Lett. 2006; 8: 3737
    • 11c Ren H, Krasovskiy A, Knochel P. Org. Lett. 2004; 6: 4215
    • 11d Krasovskiy A, Knochel P. Angew. Chem. Int. Ed. 2004; 43: 3333
  • 12 CrCp2 was purchased from Alfa Aesar (>97% purity) or prepared according to: Rohde W, Goertz H.-H, Handrich U. Ger. Patent DE4337230A1, 1995
  • 13 Cr(acac)3 was purchased from Sigma Aldrich (97% purity). The air-stable and cheap Cr(acac)3 could be used in these aminations but led to either similar or, in most cases, to somewhat lower yields and/or longer reaction times.
  • 14 CrBr2 was prepared according to: Concellón JM, Rodríguez-Solla H, Blanco EG, Villa-García MA, Alvaredo N, García-Granda S, Díaz MR. Adv. Synth. Catal. 2009; 351: 2185
  • 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.