A convenient one-pot Negishi coupling of amino-heteroaryl chlorides and alkyl bromides

Tetrahedron Letters

Volumn 47, Issue 3, 2006, Pages 341-344

  Walters, Iain A S ^a  

^a ASTRAZENECA   (United Kingdom)

Author keywords

Alkyl aminopyrazine; Halogen zinc exchange; Negishi coupling; Nickel

Indexed keywords

ALKYL GROUP; CHLORIDE; NICKEL; REAGENT; ZINC;

ARTICLE; CATALYSIS; CROSS COUPLING REACTION; REACTION ANALYSIS; STRUCTURE ANALYSIS;

EID: 28844482190     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2005.11.013     Document Type: Article

References (19)

1. N. Sato J. Heterocycl. Chem. 17 1980 143 147
2. W.B. Lutz, S. Lazarus, S. Klutchko, and R.I. Meltzer J. Org. Chem. 29 1964 415 418
3. J. Weijlard, M. Tishler, and A.E. Erickson J. Am. Chem. Soc. 67 1945 802 806
4. For a review, see: E. Negishi F. Diederich P.J. Stang Metal-Catalysed Cross-Coupling Reactions 1998 Wiley-VCH New York Chapter 1
5. E. Negishi, A.O. King, and N. Okukado J. Org. Chem. 42 1977 1821 1823
6. A. Rosowsky, and H. Chen J. Org. Chem. 66 2001 7522 7526
7. R.F.W. Jackson, R.J. Moore, and C.S. Dexter J. Org. Chem. 63 1998 7875 7884
8. J. Jensen, N. Skjærbæk, and P. Vedsø Synthesis 2001 128 134
9. J.B. Campbell, J.W. Firor, and T.W. Davenport Synth. Commun. 19 1989 2265 2272
10. C.E. Russell, and L.S. Hegedus J. Am. Chem. Soc. 105 1983 943 949
11. J.A. Miller, and R.P. Farrell Tetrahedron Lett. 39 1998 6441 6444
12. C. Janiak, S. Deblon, and H.-P. Wu Synth. Commun. 29 1999 3341 3352
13. N.Y. Adonin, V.A. Ryabinin, and V.F. Starichenko Russ. J. Org. Chem. 35 1999 913 915
14. M. Česnek, M. Hocek, and A. Holý Collect. Czech. Chem. Commun. 65 2000 1357 1373
15. N. Sato, and T. Matsuura J. Chem. Soc., Perkin Trans. 1 1996 2345 2350
16. General procedure: A 1 M THF or toluene solution of the organozinc reagent (2 mmol if diorganozinc or 4 mmol if alkylzinc halide) was added to a solution of 6-chloro-2-aminopyrazine (1 mmol) and [1,3-bis(diphenylphosphino) propane]nickel(II) chloride (0.1 mmol) in dry dioxane (5 mL) under an atmosphere of nitrogen. The reaction mixture was heated at reflux for the length of time indicated in Table 1. The reaction was quenched with methanol and concentrated in vacuo. The residue was partitioned between ethyl acetate and brine, and the organic phase dried over magnesium sulfate, filtered and evaporated. The crude product was purified by silica gel chromatography, eluting with dichloromethane/methanol, to afford the alkyl-aminopyrazines in >95% purity.
17. 2: C, 64.19; H, 5.39; N, 17.27.
18. S. Vettel, A. Vaupel, and P. Knochel J. Org. Chem. 61 1996 7473 7481
19. General procedure: Diethylzinc (5 mmol of a 1.1 M solution in toluene) was added to a solution of [1,3-bis(diphenylphosphino)propane]nickel(II) chloride (0.2 mmol) in dry dioxane (5 mL) under an atmosphere of nitrogen. The reaction mixture was stirred at room temperature for 10 min before addition of the alkyl halide (6 mmol). Stirring was continued at 65°C for 4 h, then the amino-heteroaryl halide (1 mmol) was added as a solid (or solution in 2 mL dioxane if soluble) and the reaction mixture heated at reflux for 2 h. The reaction was quenched with methanol and concentrated in vacuo. The residue was diluted with methanol (3 mL) and concentrated hydrochloric acid (3 mL) was added. The mixture was then basified with concentrated ammonia and partitioned between ethyl acetate and brine. The organic phase was dried over magnesium sulfate, filtered and evaporated. The crude product was purified by silica gel chromatography, eluting with dichloromethane/methanol, to afford the alkyl aminoheterocycles in >95% purity.