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

Andreas K. Steib; Sarah Fernandez; Olesya M. Kuzmina; Martin Corpet; Corinne Gosmini; Paul Knochel

doi:10.1055/s-0034-1380178

Synlett, Table of Contents

Synlett 2015; 26(08): 1049-1054
DOI: 10.1055/s-0034-1380178

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

Andreas K. Steib

^aDepartment of Chemistry, Ludwig-Maximilians-Universität, Butenandtstr. 5–13, 81377 Munich, Germany Email: paul.knochel@cup.uni-muenchen.de

,

Sarah Fernandez

^aDepartment of Chemistry, Ludwig-Maximilians-Universität, Butenandtstr. 5–13, 81377 Munich, Germany Email: paul.knochel@cup.uni-muenchen.de

,

Olesya M. Kuzmina

^aDepartment of Chemistry, Ludwig-Maximilians-Universität, Butenandtstr. 5–13, 81377 Munich, Germany Email: paul.knochel@cup.uni-muenchen.de

,

Martin Corpet

^bLaboratoire de Chimie Moléculaire, Ecole Polytechnique, CNRS, 91128 Palaiseau Cedex, France Email: corinne.gosmini@polytechnique.edu

,

Corinne Gosmini

^bLaboratoire de Chimie Moléculaire, Ecole Polytechnique, CNRS, 91128 Palaiseau Cedex, France Email: corinne.gosmini@polytechnique.edu

,

Paul Knochel*

^aDepartment of Chemistry, Ludwig-Maximilians-Universität, Butenandtstr. 5–13, 81377 Munich, Germany Email: paul.knochel@cup.uni-muenchen.de

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Abstract

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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.

Key words

chromium - amination - magnesium amides - heterocycles - pyridine

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References

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

6a Hartwig JF. Acc. Chem. Res. 2008; 41: 1534
6b Hartwig JF. Synlett 2006; 1283
6c Hartwig JF In Palladium-Catalyzed Amination of Aryl Halides and Related Reactions. Wiley; New York: 2002: 1051
6d Hartwig JF. Synlett 1997; 329

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.

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