Angewandte
Communications
Chemie
Cross-Coupling
Preparation of Vinyl Arenes by Nickel-Catalyzed Reductive Coupling
of Aryl Halides with Vinyl Bromides
Jiandong Liu, Qinghua Ren,* Xinghua Zhang,* and Hegui Gong*
Abstract: This work emphasizes the synthesis of substituted
vinyl arenes by reductive coupling of aryl halides with vinyl
bromides under mild and easy-to-operate nickel-catalyzed
reaction conditions. A broad range of aryl halides, including
heteroaromatics, and vinyl bromides were employed to yield-
ing products in moderate to excellent yields with high func-
tional-group tolerance. The nickel-catalytic system displays
good chemoselectivity between the two C(sp2)-halide coupling
partners, thus demonstrating a mechanistic pathway distinct
from other stepwise protocols.
C
hemoselective transformations are a fundamental chal-
lenge in the development of reductive cross-coupling methods
between two structurally similar electrophiles.[1,2] For
instance, although the Wurtz and Ullmann reactions have
Scheme 1. Cobalt- and nickel-catalyzed reductive coupling of aryl with
vinyl halides. cod=1,5-cyclooctadiene.
been disclosed for more than a century,[3] only recently was
a nickel-catalyzed reductive protocol explored for C(sp )
C(sp ) and C(sp ) C(sp ) bond constructions based on the
coupling of alkyl halides with other electrophiles.[4–9] In this
context, good to excellent chemoselectivities have been
achieved. Weix and co-workers further demonstrated that
a palladium and nickel dual catalytic method enabled
3
À
3
3
2
À
but good yields are limited to sterically bulky a-vinyl
bromides and favors formation of aryl–MgBr.[15]
Herein, we report the chemoselective construction of
vinyl arenes under mild nickel-catalyzed reductive coupling
between aryl halides and 1–1.5 equivalents of a vinyl bromide
(Scheme 1). The method displays broad substrate scope and
excellent functional-group tolerance. More importantly, het-
eroaromatic bromides were compatible, and may find appli-
cations in the synthesis of highly decorated vinyl-conjugated
scaffolds.
We commenced our studies with the reaction of methyl 4-
iodobenzoate and 1.2 equivalents of b-bromostyrene (E/Z =
86:14). By employing a combination of [Ni(cod)2]/4a/MgCl2/
Zn in THF we obtained the vinyl arene 3 in 81% yield
(Table 1, entry 1). Temperatures lower than 218C appeared to
be crucial for high yields (entry 2).[18] The equimolar reaction
afforded 3 in 75% yield, thus signifying intrinsically high
chemoselectivity between the two coupling partners (entry 3).
In the context of olefin conformation, the use of pure (E)-
vinyl bromide generated 3 in 82% yield, whereas the
Z isomer failed to yield product (entries 4 and 5; see
Table S2a in the Supporting Information).[18] Rather, recov-
ery of (Z)-2 and formation of the (Z)-vinyl iodide was
detected (see Tables S2a–S2c).[18] Other nickel sources and
ligands, as well as reduced catalyst loadings resulted in
decreased yields (entries 6–13). Control studies indicated
MgCl2 was important (entry 14). The reaction was suitable for
gram scale using 5 mol% of Ni(ClO4)2·6H2O as the precata-
lyst (entry 15).
À
efficient construction of aryl–aryl and vinyl–vinyl C C
bonds through the equimolar reactions of C(sp2)–bromides
with C(sp2)–triflates.[10–12]
It was however surprising to note that investigations on
the reductive coupling between aryl and vinyl electrophiles
are exceptionally rare,[13–16] although vinyl arenes are a so-
called privileged scaffold found in bioactive natural products,
pharmaceuticals, and polymers.[17] An example known in the
literature emphasizes a strategy involving cobalt cataly-
sis.[13,14] However, this method is constrained to very limited
vinyl substrates. Dropwise addition of vinyl halides to
2 equivalents of an aryl bromide was key to avoiding the
dimerization of individual halides (Scheme 1). An iron-
catalyzed in situ Kumada process has also been reported,
[*] Prof. Q. H. Ren, Prof. H. Gong
Center for Supramolecular Materials and Catalysis and
Department of Chemistry, Shanghai University
99 Shang-Da Road, Shanghai 200444 (China)
E-mail: qinghua.ren@shu.edu.cn
J. Liu, Dr. X. Zhang
School of Chemical and Environmental Engineering
Shanghai University of Technology
100 Hai-Quan Road, Shanghai 201418 (China)
E-mail: xhzhang@sit.edu.cn
To further probe the applicability, coupling of a range of
substituted aryl iodides with aryl-conjugated b-vinyl bromides
was carried out using method A (Figure 1). Iodobenzenes
bearing electron-withdrawing and electron-neutral substitu-
Supporting information for this article can be found under:
Angew. Chem. Int. Ed. 2016, 55, 1 – 6
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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