Nickel-Catalyzed Cross-Coupling
COMMUNICATION
at 558C 2.5 mol% of 1c can lead to 87% yield of cross-cou-
pling product, and 5 mol% of 1c gave 92% yield of cross-
coupling product. In addition, after reaction of p-
ClC6H4COOEt with 1.32 equiv of p-MeC6H4MgBr in the
presence of catalyst and additives for 2 h, injection of 0.66
additional equivalents of p-MeC6H4MgBr resulted in better
cross-coupling results. A minor part of the excess Grignard
reagent was transformed into the homocoupling product
(7.5% based the amount of the Grignard reagent added in
the reaction p-ClC6H4COOEt with p-MeC6H4MgBr cata-
lyzed by the adduct of 1c, ZnCl2 and H2O), and most of
them were hydrolyzed after the reaction. Only if in the pres-
ence of excess Grignard reagent in the reaction system, can
the aryl chloride be completely consumed. In other words,
enough concentrations of Grignard reagent must be main-
tained during the whole reaction process to ensure for the
reaction to go to completion.
Following the success of the reaction of p-ClC6H4COOEt
with p-MeC6H4MgBr, we tested reactions of different func-
tionalized aryl halides with aryl Grignard reagents catalyzed
by complexes 1c and 1d. The 1c-catalyzed reaction of more
active halides, such as p-BrC6H4COOEt and p-
IC6H4COOEt, with p-MeC6H4MgBr in a THF/NMP solvent
mixture does not require any additives, affording cross-cou-
pling products in excellent yields (entries 1 and 2, Table 4).
Complex 1d showed higher catalytic activity than complex
1c. The former can efficiently catalyze reactions of p-
ClC6H4COOEt with p-MeC6H4MgBr, o-MeC6H4MgBr and
p-MeOC6H4MgBr, respectively, in the presence of ZnCl2,
H2O and LiCl at room temperature (entries 3–6, Table 4).
Both 1c and 1d also catalyze cross-coupling of (2-chloro-
phenyl)phenylmethanone and (4-chlorophenyl)phenylmeth-
functional groups to the Ni/Mg center results in a decrease
of the catalytic activity of the Ni/Mg adduct in different
extent. This can be verified through comparison of the reac-
tion of p-ClC6H4COOEt and p-ClC6H4COOtBu with p-
ClC6H4MgBr under the same conditions, the former giving
33% yield of cross-coupling product (entry 3, Table 3),
while the latter giving 85% yield of product due to steric
hindrance which prevents combination of COOtBu with the
Ni/Mg center (entry 18, Table 4). The use of LiX may partly
prevent coordination of the functional groups in the aryl
chlorides to the Ni/Mg adduct through complexation of the
Li+ with the functional groups. The addition of ZnCl2 and
H2O could lead to formation of a Zn-O-Ni bridged com-
plex,[8c] which is a better catalyst for the reaction of func-
tionalized aryl chlorides. In order to find evidences for Zn-
O-Ni complex formation, we mixed red-brown complex 1c,
1 equiv of ZnCl2 and 1 equiv of H2O in THF. After stirring
for 6 h and then removing THF, a yellow-orange powder
was obtained. This solid species is soluble in toluene and
1
showed different H NMR spectrum from complex 1c. More
importantly, this species exhibited close activity to in situ
formed those as shown in Table 3 in catalyzing the reaction
of ethyl 4-chlorobenzoate with p-MeC6H4MgBr (74% yield
was achieved when we used the solid adduct of 1c, ZnCl2
and H2O as catalyst). Attempts to recrystallize the com-
pound for X-ray diffraction analysis were unsuccessful.
In summary, we have developed new nickel catalysts for
the Kumada reaction. The nickel complexes can efficiently
catalyze cross-coupling of unactivated and deactivated aryl
chlorides and fluorides as well as functionalized aryl chlor-
ides with aryl Grignard reagents under mild conditions,
giving cross-coupling products in excellent yields. The work
significantly expands the substrate scopes of Kumada cross-
coupling reactions. Studies on alkyl–aryl coupling of func-
tionalized substrates using these catalysts are in progress.
ACHTUNGTRENNUNGanone with p-MeC6H4MgBr in the presence of ZnCl2, H2O
and LiCl at 558C, giving 85–92% yields of coupling prod-
ucts (entries 7–10, Table 4). Both p-ClC6H4CN and p-
ClC6H4CH=NC6H4Me-4 exhibited a little different reactivity
from p-ClC6H4COOEt and p-ClC6H4COPh. The reactions of
p-ClC6H4CN and p-ClC6H4CH=N
G
Experimental Section
MeC6H4MgBr catalyzed by 1c and 1d require the presence
of 30% of ZnCl2 and 1.2 equiv of LiCl in THF/NMP. The
yields of the cross-coupling product range from 81 to 91%
depending on the substrates and catalysts (entries 11–14,
Table 4). It is surprising that the reaction of p-
ClC6H4CONEt2 with p-MeC6H4MgBr catalyzed by 1c or 1d
does not require any additives and proceeded smoothly in
THF at room temperature, giving N,N-diethyl-4-(p-tolyl)-
benzamide in excellent yields (entries 15 and 16, Table 4).
Nakamura and co-workers corroborated that in the
Kumada cross-coupling catalyzed by a nickel complex bear-
A representative procedure for the coupling of functionalized aryl chlor-
ides:
A Schlenk tube was charged with nickel complex (required
amount), NMP (1.5 mL), aryl chloride (0.5 mmol) and additives succes-
sively. To the mixture was slowly added a solution of ArMgBr (2 mL,
0.33m in THF, 0.66 mmol) at 258C with stirring. After stirring at this tem-
perature for 2 h, additional ArMgBr (1 mL, 0.33m in THF, 0.33 mmol)
was slowly added. The resulting solution was stirred at 258C for 2 h and
then quenched with water. The mixture was extracted with diethyl ether
(3ꢁ5 mL). The combined organic phases were dried over MgSO4, con-
centrated by rotary evaporation and purified by column chromatography
on silica gel.
ing a P,O-ligand Ni/Mg bimetallic cooperation promotes the
[11d,e]
À
C X-bond activation.
In our catalytic reaction a Ni/Mg
Acknowledgements
adduct may be similarly formed during the reaction process.
However, in the reaction of functionalized aryl chlorides
with a Grignard reagent the functional groups appear to
combine with the Ni/Mg adduct through coordination,
which leads to a decrease in the catalytic activity of the Ni/
Mg adduct. The difference of coordination power of the
We thank National Basic Research Program of China (2009CB825300)
and the National Natural Science Foundation of China (20772119) for fi-
nancial support. We also thank Professor D.-Q. Wang for determining the
crystal structures.
Chem. Eur. J. 2010, 16, 10332 – 10336
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
10335