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X. Wang et al. / Journal of Catalysis 355 (2017) 101–109
Table 2
PPPd-catalyzed Suzuki-Miyaura coupling reactions of challenging partners.
1, X = Br, 99%[a]
5, X = Br, 99%
2
[b], X = Br, 0%
3, X = Br, 98%
7, X = Br, 92%
4, X = Br, 100%
8, X = Br, 99%
6, X = Br, 100%
9, X = Br, 100% (98%)
13, X = Cl, 100%
10, X = Br, 100%
11, X = Br, 100% (98%)
15[c], X = Br, 99% (97%)
12, X = Cl, 99%
14, X = Cl, 97% [8 cycles]
16[c], X = Cl, 94% (96%)
17, X = Br, 98% (95%)
18[c][d], X = I, 60%
19[c][d], X = Br, 88%
[a]
[b]
[c]
[d]
GC yield with isolated yield in parentheses.
1 mol% Pd was used.
0.2 mol% Pd was used.
24 h.
mides were employed which again displayed encouraging reactiv-
ity and selectivity (Table 2, entry 1 and 3–11). It should be men-
tioned that substrates employed here with functions of fluoride,
furan, amine, indole, pyridine, carboxylic acid, and thiophene, are
all general and important intermediates for the synthesis of agro-
chemicals, pharmaceuticals and natural products. The bipolar
benzo[1,2,5]thiadiazole has wide applications in organic light-
emitting diodes (OLEDs) as an emissive group [33,34]. The excel-
lent activity and functional group tolerance of PPPd revealed its
high potential in real applications in these fields. No coupling pro-
duct was obtained when (2-bromophenyl) diphenylphosphane
was employed as substrate, possibly due to its sterically hindered
nature, suggesting that the reactions occur inside the pores. The
activation of the CACl bond (ꢀ79 kcal/mol) is much more difficult
than the CABr (ꢀ66 kcal/mol) and CAI (ꢀ52 kcal/mol) bonds due
to its slow oxidative addition to palladium, especially in heteroge-
neous catalysis system; thus, harsher reaction conditions are gen-
erally required [35]. For this reason, coupling of aryl chlorides and
aryl boronic acids is commonly selected as a standard reaction to
demonstrate the high reactivity of a catalyst [22,36]. At a Pd load-
ing of 0.1%, 99% yield of biphenyl was obtained after heating
chlorobenzene and benzeneboronic acid at 80 °C for 6 h (Table 2,
entry 12). Other aryl chlorides bearing electron-giving groups such
as –OMe or –CF3 gave high quantitative yields within 6 h. Notably,
the electron deficient 1-chloro-4-nitrobenzene also gave a high
and reproducible yield in 8 continuous cycles (Table 2, entry 14).
More impressively, coupling of benzyl halides with phenylboronic
acid, which is a rarely reported, challenging reaction but important
in heterogeneous catalysis [22], also performed very well (Table 2,
entry 15, 16). This further demonstrates the high activity of PPPd
for coupling benzyl halide and phenylboronic acid.
Encouraged by these impressive results, we further exposed the
substrate to vinyl and alkyl boronic acids. The alkylation of aryl
halides with vinyl- or alkylboron derivatives may provide a simple
and easy way to obtain the corresponding aryl-vinyl or aryl-alkyl
derivatives. Normally, these reactions are performed using 9-BBN
compounds as reactants, which are not air stable thus difficult to
operate, and the processes are not economical [37]. In the last dec-
ade, several palladium catalysts associated with electro-rich phos-
phine ligands have been developed to achieve the coupling of
alkylboronic esters or acids in homogeneous conditions. To the
best of our knowledge, very few cases have been reported for these
reactions in heterogeneous systems, which typically gave very low
yields [38,39]. In our system, the coupling of 2-bromo-6-
methylpyridine with (E)-(4-methoxystyryl) boronic acid occurred
smoothly, leading to a 95% isolated yield in the coupled product.
The coupling of aryl iodide and aryl bromide with n-butylboronic
acid was also successfully achieved in a longer reaction time. Inter-
estingly, the aryl bromide reacted faster than the aryl iodide, which
suggests that in the case of cross-coupling of aryl iodide with alkyl
boronic acid, oxidative addition may not be the rate-limiting step
of the catalytic cycle. Such phenomenon was also observed in a
homogeneous Suzuki cross-coupling system [40]. Importantly,
such reactions cannot be achieved with homogeneous catalyst of
Pd(PPh3)4.
The biaryl motif is of great importance in biological products, as
well as in asymmetric catalysis, thus stimulating numerous con-
struction methodologies [41]. In addition to the original and the
most widely used copper-mediated Ullmann couplings,
palladium-catalyzed reductive homo-couplings of aryl halides
have also been reported, and advantages were found [42]. One
big challenge in Pd mediated homo-coupling of aryl halides is