CoBr2(Bpy): A Catalyst for Direct Conjugate Addition
SCHEME 1. General Procedure for the Cobalt-Catalyzed
Conjugate Addition Process
SCHEME 2. Procedure for the Conjugate Addition of Ethyl
para-Bromobenzoate onto Ethyl Acrylate
we have developed a new process for the addition of the
electrochemically prepared arylzinc species onto activated
olefins via a cobalt catalysis.10 However, the main difficulty of
these different methods is the preliminary preparation of
organometallic reagents, especially when the aromatic nucleus
bears a reactive group. Consequently, some chemical or
electrochemical processes have been developed to avoid this
step by direct activation of aryl halides. Homogeneous catalysis
involving in situ reduction of transition-metal complexes remains
of high interest.11 For aryl halides, the catalyst precursor is
generally a nickel complex, reduced either by an excess of zinc
or electrochemically. In the first case, only a few examples of
reactions utilizing aryl halides as coupling partners are reported
and the majority of these are restricted to aryl iodides. Besides,
direct electrochemical arylation of electron-deficient olefins
performed with either nickel12 or cobalt13 catalysts in association
with a sacrificial anode appears to be a suitable method for
various aromatic halides.14 Nevertheless, these electrochemical
methods present some limitations. First, nickel is hazardous for
environmental reasons. Second, in the cobalt-catalyzed reaction,
CoBr2 is only an efficient catalyst for the electrochemical
addition of aryl bromides functionalized by electron-withdrawing
groups onto methyl vinyl ketone. Moreover, all electrochemical
reactions are generally considered as being more difficult to
handle than conventional chemical methods. Given the impor-
tance of this reaction and the interest in cobalt-catalyzed
reactions,15 we have developed a new direct chemical procedure
for the conjugate addition of different substituted aryl bromides,
chlorides, and even triflates, bearing an electron-donating or
-withdrawing group, on various activated olefins (Scheme 1).16
This one-step chemical procedure requires the use of CoBr2(2,2′-
bipyridine) as the catalyst. The in situ generated low-valent
cobalt species obtained by chemical reduction in the presence
of the appropriate reducing metal activates aryl halides or
triflates through this unprecedented procedure. The correspond-
ing “aryl cobalt” species undergoes addition onto activated
olefins to afford conjugate adducts. The use of manganese as a
benign stoichiometric reducing agent in combination with an
effective metal salt has already been originally described.17
This method avoids the prior preparation of organometallic
reagents and exhibits high tolerance toward sensitive functional
groups on the aromatic nucleus. Conjugate addition of a broad
range of aromatic reagents can be obtained in a one-step
reaction, under mild conditions, with quite short reaction times
and furthermore onto various Michael acceptors such as R,â-
unsaturated esters or nitriles. Herein, we wish to report the scope
and limitations of this cobalt-catalyzed direct 1,4-addition of
aromatic compounds.
Results and Discussion
Optimization of the Cobalt-Catalyzed Conjugate Addition.
To optimize the reaction conditions, we have first investigated
the reaction between ethyl para-bromobenzoate and ethyl
acrylate modifying various parameters. The corresponding
conjugate adduct is synthesized in the presence of 10 mol % of
CoBr2(2,2′-bipyridine), 1.1 equiv of ethyl acrylate, 1 equiv of
H2O, and 1 equiv of anhydrous lithium bromide in a mixture
of DMF/pyridine at 50 °C. The reducing metal (Mn, 2 equiv)
is activated by traces of trifluoroacetic acid (Scheme 2). The
resulting amount of the coupling product is measured by GC
using an internal standard (alkane) before isolation. Three
byproducts such as the reduction product ArH, the homocou-
pling product Ar-Ar, and the unsaturated product of the Heck
type could be observed in small amounts.
The presence of a lithium salt such as LiBr allows us to
increase the reaction rate2a,18 and the yields. With the use of 1
equiv of LiBr with respect to the aryl bromide, the conjugate
adduct is obtained with a satisfactory isolated yield (80%).
Concerning the nature of the salt, similar results are obtained
with FeBr2 or MnBr2. When TMSCl is used as a reagent to
“trap” the enolate anion generated and as an accelerating factor
for 1,4-addition,2a,19 it results, in our case, in a rapid conversion
(10) Gomes, P.; Gosmini, C.; Pe´richon, J. Synlett 2002, 1673-1676.
(11) (a) Boldrini, G. P.; Savoia, D.; Tagliavini, E.; Trombini, C.; Umani
Ronchi, A. J. Organomet. Chem. 1986, 301, C62-C64. (b) Lebedev, S.
A.; Lopatina, V. S.; Petrov, E. S.; Beletskaya, I. P. J. Organomet. Chem.
1988, 344, 253-259. (c) Sustmann, R.; Hopp, P.; Holl, P. Tetrahedron
Lett. 1989, 30, 689-692. (d) Bontempelli, G.; Magno, F.; Daniele, S.;
Schavion, G. J. Electroanal. Chem. 1983, 159, 117-126. (e) Subburaj, K.;
Montgomery J. J. Am. Chem. Soc. 2003, 125, 11210-11211
(12) (a) Condon, S.; Dupre´, D.; Falgayrac, G.; Ne´de´lec, J.-Y. Eur. J.
Org. Chem. 2002, 105-111. (b) Condon, S.; Ne´de´lec, J.-Y. Synthesis 2004,
3070-3078.
(13) (a) Gomes, P.; Gosmini, C.; Ne´de´lec, J.-Y.; Pe´richon, J. Tetrahedron
Lett. 2000, 41, 3385-3388. (b) Gomes, P.; Gosmini, C.; Ne´de´lec, J.-Y.;
Pe´richon, J. Tetrahedron Lett. 2002, 43, 5901-5903.
(14) Chaussard, J.; Folest, J.-C.; Ne´de´lec, J.-Y.; Pe´richon, J.; Sibille, S.;
Troupel, M. Synthesis 1990, 369-380.
(15) For recent reports on cobalt-catalyzed coupling reactions, see: (a)
Ohmiya, H.; Yorimitsu, H.; Oshima, K. J. Am. Chem. Soc. 2006, 128, 1886-
1889. (b) Ikeda, Y.; Nakamura, T.; Yorimitsu, H.; Oshima, K. J. Am. Chem.
Soc. 2002, 124, 6514-6515. (c) Cahiez, G.; Avedissian, H. Tetrahedron
Lett. 1998, 39, 6159-6162. (d) Avedissian, H.; Be´rillon, L.; Cahiez, G.;
Knochel, P. Tetrahedron Lett. 1998, 39, 6163-6166. (e) Nishii, Y.;
Wakasugi, K.; Tanabe, Y. Synlett 1998, 67-69. (f) Korn, T. J.; Knochel,
P. Angew. Chem., Int. Ed. 2005, 44, 2947-2951. (g) Sezen, B.; Sames, D.
Org. Lett. 2003, 5, 3607-3610. (h) Chang, K.-J.; Rayabarapu, D. K.; Cheng,
C.-H. J. Org. Chem. 2004, 69, 4781-4787. (i) Shukla, P.; Hsu, Y.-C.;
Cheng, C.-H. J. Org. Chem. 2006, 71, 655-658.
(16) Amatore, M.; Gosmini, C.; Pe´richon, J. Patent FR2865203, July
22, 2005.
(17) Fu¨rstner, A.; Shi, N. J. Am. Chem. Soc. 1996, 118, 2533-2534. (b)
Fu¨rstner, A. Chem.-Eur. J. 1998, 4, 567-570.
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