Since the pioneering works of Kochi in the 1970s,13
alkenylation of alkyl Grignard reagents has been exten-
sively studied.14 However, alkenylation of aryl Grignard
reagents under iron salt catalysis has received much less
attention.15 In these instances, this transformation has
often been devoted to aliphatic vinyl halides and very
rarely to β-styryl halides. To the best of our knowledge,
only one example is reported for the coupling with a simple
R-bromostyrene (Fe(dbm)3 in DME),15a probably because
of the more difficult oxidative addition step and, hence,
higher requirements to the catalytic system. From a syn-
thetic viewpoint, the development of cross-coupling
reactions with R-styryl halides as viable coupling
partners would be of great interest for the synthesis of
1,1-diarylethylenes in the context of medicinal chemistry
programs.3,4 Herein we disclose a general and very efficient
coupling of polyoxygenated R-styryl halides with function-
alized aryl Grignard reagents. We found that the coupling
occurred in the presence of the new catalytic system
combining FeCl3 and copper(I) thiophene-2-carboxylate
(CuTC) under mild conditions to give the corresponding
cross-coupling products in good to excellent yields. This
bimetallic combination catalytic system16 is clearly more
efficient than the corresponding Fe-catalyzed Grignard
procedure mentioned above15a and offers an efficient
alternative to the Pd- and Ni-catalyzed procedures used
until now.
Figure 1. Structures of some bioactive 1,1-diarylethylenes.
Pd catalysis.4a,6 Traditional cross-coupling reactions of vinyl
or aryl halides with aryl- or vinylmetal derivatives (Sn,7 Si,8
B,9 Mg,10 Zn11) have also been reported. To be successful,
these transformations require the presence of palladium or
nickel as catalysts. These metals are costly or toxic and often
necessitate sophisticated and expensive ligands of high mo-
lecular weight. There is a great need for cheap and environ-
mentally friendly catalysts that do not require complicated
ligands.
In recent years, iron salts have emerged as a promising
alternative as a catalyst for CÀC bond-forming reactions
because of their low cost and toxicity and offer attractive
industrial possibilities in terms of sustainable chemistry.12
(6) (a) Barluenga, J.; Moriel, P.; Valdes, C.; Aznar, F. Angew. Chem.,
ꢀ
Int. Ed. 2007, 46, 5587. (b) Barluenga, J.; Valdes, C. Angew. Chem., Int.
Ed. 2011, 50, 7486. (c) Brachet, E.; Hamze, A.; Peyrat, J.-F.; Brion, J.-D.;
Alami, M. Org. lett. 2010, 12, 4042. (d) Treguier, B.; Hamze, A.; Provot,
O.; Brion, J. D.; Alami, M. Tetrahedron Lett. 2009, 50, 6549. (e)
Table 1. Fe/Cu Co-catalyzed Cross-Coupling of 1-Arylvinyl
Iodide 3a with 4-Methoxyphenylmagnesium Bromidea
ꢀ
Rasolofonjatovo, E.; Treguier, B.; Provot, O.; Hamze, A.; Morvan,
E.; Brion, J.-D.; Alami, M. Tetrahedron Lett. 2011, 52, 1036.
(7) (a) Hamze, A.; Veau, D.; Provot, O.; Brion, J. D.; Alami, M.
J. Org. Chem. 2009, 74, 1337. (b) Belema, M.; Nguyen, V. N.; Christo-
pher Zusi, F. Tetrahedron Lett. 2004, 45, 1693.
(8) Nakao, Y.; Imanaka, H.; Chen, J.; Yada, A.; Hiyama, T.
J. Organomet. Chem. 2007, 692, 585.
(9) (a) Berthiol, F.; Doucet, H.; Santelli, M. Eur. J. Org. Chem. 2003,
[Fe] cat.
[Cu] cat.
€
€
entry
(0.1 equiv)
(0.1 equiv)
solvent
DME
yieldb (%)
1091. (b) Buttner, M. W.; Natscher, J. B.; Burschka, C.; Tacke, R.
Organometallics 2007, 26, 4835. (c) Hansen, A. L.; Ebran, J.-P.; Gogsig,
T. M.; Skrydstrup, T. Chem. Commun. 2006, 4137.
(10) (a) Sabarre, A.; Love, J. Org. Lett. 2008, 10, 3941. (b) Gauthier,
D.; Beckendorf, S.; Gøgsig, T. M.; Lindhardt, A. T.; Skrydstrup, T.
J. Org. Chem. 2009, 74, 3536.
(11) (a) Hansen, A. L.; Ebran, J.-P.; Gøgsig, T. M.; Skrydstrup, T.
J. Org. Chem. 2007, 72, 6464. (b) Lindhardt, A. T.; Gøgsig, T. M.;
Skrydstrup, T. J. Org. Chem. 2008, 74, 135.
1
2
Fe(dbm)3
Fe(dbm)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(0)
31c
34
40
36
50
52
43
50
55
8
THF
3
THF
4
THF/NMPd
THF
5
CuI
6
CuCl
THF
(12) (a) Bolm, C.; Legros, J.; Le Paih, J.; Zani, L. Chem. Rev. 2004,
7
CuCN 2LiCl
THF
3
€
104, 6217. (b) Furstner, A.; Martin, R. Chem. Lett. 2005, 34, 624. (c)
8
Cu(acac)2
CuTC
THF
Leitner, A. In Iron Catalysis: Fundamentals and Applications; Plietker, B.,
Ed.; Wiley-VCH: Weinheim, 2008; pp 147. (d) Czaplik, W. M.; Mayer, M.;
9
THF
ꢁ
Cvengros, J.; von Wangelin, A. J. ChemSusChem 2009, 2, 396.
10
11
12
13
14
15
CuTC
THF
(13) (a) Tamura, M.; Kochi, J. K. J. Am. Chem. Soc. 1971, 93, 1487.
(b) Neumann, S. M.; Kochi, J. K. J. Org. Chem. 1975, 40, 599. (c) Smith,
R. S.; Kochi, J. K. J. Org. Chem. 1976, 41, 502.
Fe(dbm)3
Fe(OAc)2
FeCl3
CuTC
THF
50
57
82e,f,g
54
10
CuTC
THF
CuTC
THF
(14) (a) Cahiez, G.; Avedissian, H. Synthesis 1998, 1199. (b) Cahiez,
G.; Habiak, V.; Gager, O. Org. Lett. 2008, 10, 2389. (c) Dos Santos, M.;
FeCl3
THF
ꢂ
Franck, X.; Hocquemiller, R.; Figadere, B.; Peyrat, J.-F.; Provot, O.;
CuTC
THF
Brion, J.-D.; Alami, M. Synlett 2004, 2697. (d) Hamze, A.; Provot, O.;
Brion, J. D.; Alami, M. J. Org. Chem. 2007, 72, 3868. (e) Scheiper, B.;
a ArMgBr (2.0 equiv) was slowly added at À20 °C to a solution of 3a
(1 equiv), [Fe] (10 mol %), and [Cu] (10 mol %) in the solvent mentioned
above (2.0 mL, 0.25 M). b Yield of isolated product. c Reaction carried
out at 20 °C gave 4a in 30% yield. d NMP (22 equiv). e The use of
ArMgBr (1.5 equiv) gave 4a in 57% yield. f A similar yield (80%) was
obtained using 5 mol % of FeCl3 and 5 mol % of CuTC. g With 1 mol %
of FeCl3 and 1 mol % of CuTC, 4a was obtained in 60% yield.
€
Bonnekessel, M.; Krause, H.; Furstner, A. J. Org. Chem. 2004, 69, 3943.
(f) Seck, M.; Franck, X.; Hocquemiller, R.; Figadere, B.; Peyrat, J. F.;
Provot, O.; Brion, J. D.; Alami, M. Tetrahedron Lett. 2004, 45, 1881. (g)
Berthon-Gelloz, G.; Hayashi, T. J. Org. Chem. 2006, 71, 8957. For
€
applications, see: (h) Furstner, A.; Hannen, P. Chem.;Eur. J. 2006, 12,
€
3006. (i) Furstner, A.; Schlecker, A. Chem.;Eur. J. 2008, 14, 9181. (j)
Hamajima, A.; Isobe, M. Org. Lett. 2006, 8, 1205. (k) Liang, Y.; Jiang,
X.; Yu, Z.-X. Chem. Commun. 2011, 47, 6659.
Org. Lett., Vol. 14, No. 11, 2012
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