ORGANIC
LETTERS
2007
Vol. 9, No. 17
3253-3254
Iron-Catalyzed Alkylation of Alkenyl
Grignard Reagents
Ge´rard Cahiez,* Christophe Duplais, and Alban Moyeux
Laboratoire de Synthe`se Organique Se´lectiVe et de Chimie Organome´tallique
(SOSCO), UMR 8123 CNRS-UCP-ESCOM, 5 Mail Gay-Lussac, NeuVille/Oise,
F-95031 Cergy-Pontoise Cedex, France
Received May 18, 2007
ABSTRACT
The first iron-catalyzed cross-coupling reaction between alkenyl Grignard reagents and n- or s-alkyl bromides is described. The reaction is
stereoselective and takes place in the presence of 5 mol % of [Fe(acac)3/TMEDA/HMTA] (1:2:1) under very mild conditions (THF, 0 C, 45 min).
°
Transition-metal-catalyzed cross-coupling reactions have
been extensively developed in recent years.1 However, in
spite of the considerable number of reports, some couplings
are always difficult to achieve. Thus, the use of nonactivated
secondary alkyl halides is often delicate because of the slow
oxidative addition to transition-metal complexes and the
â-hydride elimination from the intermediate organometallic
species involved in the catalytic process.2 Lately, this
problem has received considerable attention; however, to the
best of our knowledge, no general procedure3 was described
to couple alkenylmagnesium reagents with secondary alkyl
halides. Herein, we report the first example of iron-catalyzed
reaction to perform such a coupling.
tions.1m,4,5 Actually, organomagnesium compounds are one
of the most accessible and cheapest organometallics, and iron
(3) To the best of our knowledge, only two specific cases were reported
with Grignard reagents. (a) The Cu-catalyzed reaction of 1,3-butadien-2-
ylmagnesium with 2-iodooctane (yield: 45%): Nunomoto, S.; Kawagami,
Y.; Yamashita Y. J. Org. Chem. 1983, 48, 1912. (b) The Co-catalyzed
coupling of 1-(trimethylsilyl)ethenylmagnesium bromide with various
secondary alkyl bromides: Ohmiya, H.; Yorimitsu, H.; Oshima, K. Org.
Lett. 2006, 8, 3093. The procedure described in this report is limited to
this special Grignard reagent. Two examples of Suzuki reaction were also
reported: (c) Zhou, J.; Fu, G. C. J. Am. Chem. Soc. 2004, 126, 1340.
(4) For reviews on iron-mediated coupling reactions, see: (a) Fu¨rstner,
A.; Martin, R. Chem. Lett. 2005, 34, 624. (b) Bolm, C.; Legros, J.; Le
Paih, J.; Zani, L. Chem. ReV. 2004, 104, 6217.
(5) (a) Cahiez, G.; Chavant, P.-Y.; Metais, E. Tetrahedron Lett. 1992,
33, 5245. (b) Cahiez, G.; Marquais, S. Tetrahedron Lett. 1996, 37, 1773.
(c) Cahiez, G.; Avedissian, H. Synthesis 1998, 1199. (d) Dohle, W.; Kopp,
F.; Cahiez, G.; Knochel, P. Synlett, 2001, 1901. (e) Fu¨rstner, A.; Leitner,
A.; Me´ndez, M.; Krause, H. J. Am. Chem. Soc. 2002, 124, 13856. (f)
Fu¨rstner, A.; Leitner, A. Angew. Chem., Int. Ed. 2002, 41, 609. (g) Quintin,
J.; Frank, X.; Hocquemiller, R.; Figade`re, B. Tetrahedron Lett. 2002, 43,
3547. (h) Fu¨rstner, A.; Me´ndez, M. Angew. Chem., Int. Ed. 2003, 42, 5355.
(i) Seidel, G.; Laurich, D.; Fu¨rstner, A. J. Org. Chem., 2004, 69, 3950. (j)
Martin, R.; Fu¨rstner, A. Angew. Chem., Int. Ed. 2004, 43, 3955. (k) Scheiper,
B.; Bonnekessel, M.; Krause, H.; Fu¨rstner, A. J. Org. Chem. 2004, 69,
3943. (l) Nakamura, M.; Matsuo, K.; Ito, S.; Nakamura, E. J. Am. Chem.
Soc. 2004, 126, 3686. (m) Duplais, C.; Bures, F.; Korn, T.; Sapountzis, I.;
Cahiez, G.; Knochel, P. Angew. Chem., Int. Ed. 2004, 43, 2968. (n) Dos
Santos, M.; Franck, X.; Hocquemiller, R.; Figade`re, B.; Peyrat, J.-F.; Provot,
O.; Brion, J.-D.; Alami M. Synlett, 2004, 2697. (o) Nagano, T.; Hayashi,
T. Org. Lett. 2004, 6, 1297. (p) Bedford, R. B.; Bruce, D. W.; Frost, R.
M.; Goodby, J. W.; Hird, M. Chem. Commun. 2004, 2822. (q) Martin, R.;
Fu¨rstner, A. Angew. Chem., Int. Ed. 2004, 43, 3955. (r) Nagano, T.; Hayashi,
T. Org. Lett. 2005, 7, 491. (s) Cahiez, G.; Chaboche, C.; Mahuteau-Betzer,
F.; Ahr, M. Org. Letters, 2005, 7, 1943. (t) Bedford, R. B.; Bruce, D. W.;
Frost, R.; M. Hird, M. Chem. Commun. 2005, 4161. (u) Bedford, R. B.;
Betham, M.; Bruce, D. W.; Danopoulos, A. A.; Frost, R.; Hird, M. J. Org.
Chem. 2006, 71, 1104. (v) Ottesen, L. K.; Ek, F.; Olsson, R. Org. Lett.
2006, 8, 1771.
The development of iron-catalyzed coupling reactions from
Grignard reagents is a very challenging research area because
of the considerable potential interest for large-scale applica-
(1) (a) Kumada, M. Pure Appl. Chem. 1980, 52, 669. (b) Neghishi, E.
Acc. Chem. Res. 1982, 15, 340. (c) Suzuki, A. Pure Appl. Chem. 1985, 57,
1749. (d) Stille, J. K. Angew. Chem., Int. Ed. 1986, 98, 505. (e) Tamao,
K.; Kumada, M. In The Chemistry of the Metal-Carbon bond; Hartley, F.
R., Ed.; Wiley & Sons: New York, 1987; p 819. (f) Erdik, E. Tetrahedron
1992, 48, 9577. (g) Kalini, V. N. Synthesis 1992, 413. (h) Knochel, P.;
Singer, R. D. Chem. ReV. 1993, 93, 2117. (i) Stanford, S. Tetrahedron 1998,
54, 263. (j) Luh, T.-Y.; Leung, M.-K.; Wong, K.-T. Chem. ReV. 2000, 100,
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Chem. ReV. 2002, 102, 1359. (l) Terao, J.; Kambe, N. J. Synth. Org. Chem.
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(2) Hills, I. D.; Netherton, M. R.; Fu, G. C. Angew. Chem., Int. Ed. 2003,
42, 5749. For general reviews on cross-coupling reactions with alkyl halides,
see: (a) Frisch, A. C.; Beller, M. Angew. Chem., Int. Ed. 2005, 44, 674.
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10.1021/ol7016092 CCC: $37.00
© 2007 American Chemical Society
Published on Web 07/27/2007