ORGANIC
LETTERS
2008
Vol. 10, No. 15
3367-3370
Iron(II) Bromide-Catalyzed Synthesis of
Benzimidazoles from Aryl Azides
Meihua Shen and Tom G. Driver*
Department of Chemistry, UniVersity of Illinois at Chicago, 845 West Taylor Street,
Chicago, Illinois, 60607-7061
Received May 30, 2008
ABSTRACT
The identity of the ortho-substituent of an aryl azide influences its reactivity toward transition metals. Substitution of a vinyl group with an
imine disables rhodium(II)-mediated C-H amination and triggers a Lewis acid mechanism catalyzed by iron(II) bromide to facilitate benzimidazole
formation.
Controlling the reactivity of azides to provide functionalized
products continues to inspire substantial research interest in
the synthetic community.1 Thermolysis or photolysis of
azides produces nitrenes,2,3 which react with pendant olefins
and C-H bonds.4 The nucleophilicity of azides has also been
exploited to form C-N bonds selectively.1a,c,5 These pro-
cesses, however, often proceed through highly reactive
intermediates, which can react unselectively6 or decompose
to afford undesirable products.7 As a consequence, recent
methods have employed transition metal catalysts to harness
this reactivity to improve selectivity and diminish side
reactions.8,9
In the course of our studies on the reactivity of azides
toward transition metals,10 we discovered that rhodium(II)
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35, 146. (b) Bra¨se, S.; Gil, C.; Knepper, K.; Zimmermann, V. Angew. Chem.,
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297. (e) L’abbe´, G. Angew. Chem., Int. Ed. 1975, 14, 775.
(6) Thermal [3 + 2] cycloaddition reactions of azides often afford
mixtures of 1,4- and 1,5-disubstituted triazoles. See: Huisgen, R. 1,3-Dipolar
Cycloaddition Chemistry; Padwa, A., Ed.; Pergamon: Oxford, 1984; p 1.
(7) The formation of tars and dimerization products can plague thermal
reactions of azides. See: Abramovitch, R. A.; Challand, S. R.; Scriven,
E. F. V. J. Am. Chem. Soc. 1972, 94, 1374.
(2) For aryl azides, see: (a) Sundberg, R. J.; Gillespie, D. W.; DeGraff,
B. A. J. Am. Chem. Soc. 1975, 97, 6193. (b) Sundberg, R. J.; Russell, H. F.;
Ligon, W. V.; Lin, L.-S. J. Org. Chem. 1972, 37, 719. (c) von E. Doering,
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J. Am. Chem. Soc. 1962, 84, 480. (e) Huisgen, R. Angew. Chem. 1955, 67,
(8) For nitogen-atom transfer reviews, see: (a) Cenini, S.; Gallo, E.;
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2006, 250, 1234. (b) Katsuki, T. Chem. Lett. 2005, 34, 1304
.
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Y.; Zhang, X. P. Org. Lett. 2008, 10, 1995. (b) Bosch, L.; Vilarrasa, J.
Angew. Chem., Int. Ed. 2007, 41, 3926. (c) Ruppel, J. V.; Kamble, R. M.;
Zhang, X. P. Org. Lett. 2007, 9, 4889. (d) Chiba, S.; Wang, Y. F.; Lapointe,
G.; Narasaka, K. Org. Lett. 2008, 10, 313. (e) D´ıez-Gonza´lez, S.; Correa,
A.; Cavallo, L.; Nolan, S. P. Chem.-Eur. J. 2006, 12, 7558. (f) Zhang, L.;
Chen, X.; Xue, P.; Sun, H. H. Y.; Williams, I. D.; Sharpless, K. B.; Fokin,
V. V.; Jia, G. J. Am. Chem. Soc. 2005, 127, 15998. (g) Gorin, D. J.; Davis,
N. R.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 11260. (h) Rostovtsev,
V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew. Chem., Int. Ed.
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Chem. 2000, 65, 8326. (j) Bach, T.; Ko¨rber, C. J. Org. Chem. 2000, 65,
749. (f) Smith, P. A. S.; Brown, B. B. J. Am. Chem. Soc. 1951, 73, 2435
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(3) For vinyl azides, see: (a) Moody, C. J. Stud. Nat. Prod. Chem. 1988,
1, 163. (b) Henn, L.; Hickey, D. M. B.; Moody, C. J.; Rees, C. W. J. Chem.
Soc., Perkin Trans. 1 1984, 2189. (c) Hemetsberger, H.; Knittel, D. Monatsh.
Chem. 1972, 103, 194. (d) Hemetsberger, H.; Knittel, D.; Weidmann, H.
Monatsh. Chem. 1970, 101, 161. (e) Isomura, K.; Kobayashi, S.; Taniguchi,
H. Tetrahedron Lett. 1968, 9, 3499
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(4) For reviews, see: (a) So¨derberg, B. C. G. Curr. Org. Chem. 2000,
4, 727. (b) Moody, C. J. ComprehensiVe Organic Synthesis; Trost, B. M.,
; Fleming, I., ; Ley, S., Eds.; Pergamon: Oxford, 1991; Vol. 7, p 21. (c)
Azides and Nitrenes, ReactiVity and Utility; Scriven, E. F. V., Ed.; Academic
Press: London, 1984. (d) Nitrenes; Lwowski, Ed.; Wiley: New York, 1970.
(5) (a) Milligan, G. L.; Mossman, C. J.; Aube´, J. J. Am. Chem. Soc.
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2358
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(10) (a) Shen, M.; Leslie, B. E.; Driver, T. G. Angew. Chem., Int. Ed.
2008, 47, 5056. (b) Dong, H.; Shen, M.; Redford, J. E.; Stokes, B. J.;
Pumphrey, A. L.; Driver, T. G. Org. Lett. 2007, 9, 5191. (c) Stokes, B. J.;
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(d) Aube´, J.; Milligan, G. L. J. Am. Chem. Soc. 1991, 113, 8965
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10.1021/ol801227f CCC: $40.75
Published on Web 07/03/2008
2008 American Chemical Society