Subscribe to RSS
DOI: 10.1055/s-2007-967979
Copper-Catalyzed Cyanation of Heteroaryl Bromides: A Novel and Versatile Catalyst System Inspired by Nature
Publication History
Publication Date:
21 February 2007 (online)
![](https://www.thieme-connect.de/media/synlett/200704/lookinside/thumbnails/10.1055-s-2007-967979-1.jpg)
Abstract
An improved copper catalyst system for the cyanation of heteroaryl halides leading to substituted heteroaryl nitriles is described. The catalyst system consists of simple CuI and N-alkylimidazoles, and mimics known Cu-containing metalloproteins. It is stable, commercially available, cheap and easily tunable. By using inexpensive and non-toxic K4[Fe(CN)6] and the novel Cu catalysts we were able to cyanate both activated and non-activated heteroarenes with high yield and selectivity. The generality of the procedure is demonstrated by a variety of different examples, some of which did not react under other known methods.
Key words
copper - coupling - cyanation - heterocycles - nitriles
- 1
Grundmann C. In Houben-Weyl: Methoden der Organischen Chemie 4th ed., Vol. E5:Falbe J. Georg Thieme Verlag; Stuttgart: 1985. p.1313-1527 - 2
Lindley J. Tetrahedron 1984, 40: 1433 - 3For a recent catalytic variant of the Sandmeyer reaction, see:
- 3
Beletskaya IP.Sigeev AS.Peregudov AS.Petrovskii PV. J. Organomet. Chem. 2004. 689: p.3810 -
4a
Hagedorn F.Gelbke H.-P. In Ullmanns Enzyklopädie der Technischen Chemie 4th ed., Vol. 17:Bartholomé E.Biekert E.Hellmann H.Ley H.Weigert WM.Weise E. Verlag Chemie; Weinheim: 1979. p.333 -
4b
Ellis GP.Romney-Alexander TM. Chem. Rev. 1987, 87: 779 - 5
Sundermeier M.Zapf A.Beller M. Eur. J. Inorg. Chem. 2003, 3513 - 6
Sundermeier M.Zapf A.Beller M.Sans J. Tetrahedron Lett. 2001, 42: 6707 - 7
Ramnauth J.Bhardwaj N.Renton P.Rakhit S.Maddaford SP. Synlett 2003, 2237 - 8
Sundermeier M.Zapf A.Beller M. Angew. Chem. Int. Ed. 2003, 42: 1661 - 9
Sundermeier M.Mutyala S.Zapf A.Spannenberg A.Beller M. J. Organomet. Chem. 2003, 684: 50 - 10
Chobanian HR.Fors BP.Lin LS. Tetrahedron Lett. 2006, 47: 3303 - Recent examples:
-
11a
Jensen RS.Gajare AS.Toyota K.Yoshifuji M.Ozawa F. Tetrahedron Lett. 2005, 46: 8645 -
11b
Veauthier JM.Carlson CN.Collis GE.Kiplinger JL.John KD. Synthesis 2005, 2683 -
11c
Chidambaram R. Tetrahedron Lett. 2004, 45: 1441 - 12
Schareina T.Zapf A.Beller M. Chem. Commun. 2004, 1388 - 13
Schareina T.Zapf A.Beller M. J. Organomet. Chem. 2004, 689: 4576 - 14
Schareina T.Zapf A.Beller M. Tetrahedron Lett. 2005, 46: 2585 -
15a
Weissman SA.Zewge D.Chen C. J. Org. Chem. 2005, 70: 1508 -
15b
Grossman O.Gelman D. Org. Lett. 2006, 8: 1189 - 16
Zanon J.Klapars A.Buchwald S. J. Am. Chem. Soc. 2003, 125: 2890 - 17
Cristau H.-J.Ouali A.Spindler J.-F.Taillefer M. Chem. Eur. J. 2005, 11: 2483 - 18
Stetter J.Lieb F. Angew. Chem. Int. Ed. 2000, 39: 1724 ; Angew. Chem. 2000, 112, 1792 -
19a
Fadda E.Chakrabarti N.Pomes R. J. Phys. Chem. B 2005, 109: 22629 -
19b
Syme CD.Nadal RC.Rigby SEJ.Viles JH. J. Biol. Chem. 2004, 279: 18169 -
19c
Atwood CS.Perry G.Zeng H.Kato Y.Jones WD.Ling KQ.Huang XD.Moir RD.Wang DD.Sayre LM.Smith MA.Chen SG.Bush AI. Biochemistry 2004, 43: 560 -
19d
Nakamura M.Nakajima T.Ohba Y.Yamauchi S.Lee BR.Ichishima E. Biochem. J. 2000, 350: 537 -
19e
Banci L.Bertini I.Ciofi-Baffoni S.Katsari E.Katsaros N.Kubicek K.Mangani S. Proc. Natl. Acad. Sci. U.S.A. 2005, 102: 3994 - 20 For the application of 1-alkylimidazoles as solubilizing additives, see:
Welleman JA.Hulsbergen FB.Reedijk J. Makromol. Chem. 1981, 182: 785
References and Notes
Initial amination reactions of bromobenzenes in the presence of Cu/1-butylimidazole showed that these catalysts are also active for other coupling reactions.
22All chemicals are commercially available and were used without further purification. Products were fully characterized after isolation (NMR, IR, MS, EA) or in the case of commercially available products by comparison of GCMS data.
General Procedure: First, K4[Fe(CN)6]·3H2O is ground to a fine powder and dried in vacuum (ca. 2 mbar) at 80 °C overnight. Then, 0.4 mmol dry K4[Fe(CN)6], 0.2 mmol copper precursor, the additive, and 2 mmol aryl halide are placed in a pressure tube under argon. Afterwards, 200 µL tetradecane (internal standard for GC) and 2 mL solvent are added. The pressure tube is sealed and heated for 16 h at the temperature specified in Table
[1]
and Table
[2]
. After cooling to r.t., 3 mL CH2Cl2 are added and the mixture is analyzed by GC. Conversion and yield are calculated as an average of two parallel runs. For isolation of the products the reaction mixture is washed with H2O and the organic phase is dried over Na2SO4. After evaporation of the solvents the residue is subjected to column chromatography (silica, hexane-EtOAc). All prepared nitriles are known compounds and identified by comparison with commercially available materials.
Analytical data of 5-cyanopyrimidine: 1H NMR (300 MHz, CDCl3, 300 K): δ = 9.42 (s, 1 H), 9.04 (s, 2 H).
13C NMR (75 MHz, CDCl3, 300 K): δ = 160.5, 159.5, 114.0, 110.2.