Cyclopalladated ferrocenylimine as an efficient catalyst for the syntheses of diarylmethane derivatives

Article abstract of DOI:10.1002/aoc.2859

The cyclopalladated ferrocenylimine adducts Ia-c were evaluated in the Suzuki cross-coupling reaction of benzyl halides with arylboronic acids. The tricyclohexylphosphine adduct Ia exhibited highly catalytic activity for the coupling of aryl and heteroaryl boronic acids containing various functional groups with benzylic bromides and chlorides (up to 99% yield), furnishing diarylmethane derivatives with low catalyst loading (1 mol%). It is worth noting that catalyst Ia can be reused eight times without losing its catalytic activity. Copyright

Full text of DOI:10.1002/aoc.2859

Full Paper
Received: 14 January 2012
Revised: 29 February 2012
Accepted: 12 March 2012
Published online in Wiley Online Library
(wileyonlinelibrary.com) DOI 10.1002/aoc.2859
Cyclopalladated ferrocenylimine as an efficient
catalyst for the syntheses of diarylmethane
derivatives
Ajuan Yu, Xiangdong Li, Dongpo Peng, Yangjie Wu* and Junbiao Chang*
The cyclopalladated ferrocenylimine adducts Ia–c were evaluated in the Suzuki cross-coupling reaction of benzyl halides with
arylboronic acids. The tricyclohexylphosphine adduct Ia exhibited highly catalytic activity for the coupling of aryl and hetero-
aryl boronic acids containing various functional groups with benzylic bromides and chlorides (up to 99% yield), furnishing dia-
rylmethane derivatives with low catalyst loading (1 mol%). It is worth noting that catalyst Ia can be reused eight times without
losing its catalytic activity. Copyright © 2012 John Wiley & Sons, Ltd.
Keywords: cyclopalladated ferrocenylimines; arylboronic acids; benzylic halides; diarylmethane derivatives
obtained for aryl and heteroaryl boronic acids containing various
functional groups with benzyl bromides and chlorides in the
Introduction
Transition metal-catalyzed cross-coupling of arylboronic acids with
haloarenes or aryltriflates is one of the most powerful methods for
presence of 1 mol% complex Ia. Meanwhile, the recyclability of
catalyst Ia was also examined.
[
1–3]
the formation of symmetric and nonsymmetric biaryls,
which
[
4]
are found in polymers and other biologically active com-
pounds. Similarly, diarylmethane derivatives, which are important
building blocks in organic synthesis, can also be obtained by a
Suzuki–Miyaura reaction by using benzylic halides in the place of
aryl halides. However, compared with most reactions involving
[5]
[
6]
Results and Discussion
To evaluate the activity of the cyclopalladated ferrocenylimine
b,l,m
[
7–10]
adducts Ia–c[35
] (Scheme 1), the reaction of benzyl bromide
Pd-catalyzed Suzuki coupling of aryl halides,
the coupling of
with phenylboronic acid was initially chosen as a model reaction
benzylic halides with arylboronic acids has been scarcely studied.
Maddaford and Keay coupled benzyl chloride under Suzuki
ꢀ
in toluene at 110 C with 1 mol% catalyst loading. The results are
[
11]
summarized in Table 1. To our delight, when 1a and 2a were
reacted in the presence of the tricyclohexylphosphine adduct
Ia, employing K PO as base and toluene as solvent, diphenyl-
3 4
methane 3a was isolated in good yield (Table 1, entry 1), and a
trace of biphenyl formed by the homo-coupling reaction
of phenylboronic acid was the main sub-product. However,
complexes Ib and Ic only gave moderate yields under the same
reaction condition (Table 1, entries 2–3). Therefore, Ia was chosen
conditions for the first time. A number of catalyst systems have
[
12]
[13]
been developed in the laboratories of Flaherty,
Molander and others.
Kuwano,
[9]
[14–22]
Despite recent developments allow-
ing access to a range of diarylmethanes, several drawbacks are
associated with the methodologies aimed at their synthesis. Inferior
tolerance of functional groups, use of toxic reagents and longer
reaction times are the disadvantages associated with some of the
reported methods involving Suzuki cross-coupling reaction.
Furthermore, the requirement of an additional step for the prepara-
tion of electrophilic precursors is the principal drawback of these
procedures, which strongly limits their application in industrial
as catalyst for the following study as PCy
is stable at high temperature.
3
is cheap and its adduct
The various reaction conditions were examined by fixing 1 mol
% loading of catalyst Ia. It was found that the base played a crit-
ical role in catalytic efficiency. Stronger bases such as t-BuONa,
[23–33]
processes.
Palladacycles are one class of the fascinating organometallic
reagents and efficient catalysts for constructing carbon–carbon
bonds. Moreover, they are easily synthesized, easily modified
K
3
PO
and 75% yields, respectively (Table 1, entries 5, 1, 7). Surprisingly,
Na CO only gave a trace of 3a (Table 1, entry 6), while an
4 2 3
and Cs CO afforded the desired product in 78%, 85%
[
34]
2
3
and of comparative stability.
During the past decade, there
has been a growing interest in the utility of palladacycles as
[34]
catalyst precursors.
In our previous work we focused on the
*
Correspondence to: Yangjie Wu and Junbiao Chang, College of Chemistry and
Molecular Engineering, Henan Key Laboratory of Chemical Biology and Organic
Chemistry, Key Laboratory of Applied Chemistry of Henan Universities, Zhengzhou
University, Zhengzhou 450052, People’s Republic of China. E-mail: wyj@zzu.edu.cn
application of cyclopalladated ferrocenylimines in cross-coupling
reactions[35 ] and found that they were highly versatile in
a–l
Suzuki reaction, Heck reaction, Kumada reaction, Sonogashira
reaction and so on. This prompted us to explore the potential
applications of such palladacycles (Scheme 1) in the Suzuki
cross-coupling reaction of benzyl halides with arylboronic acids
to synthesize diarylmethane derivatives. Yields of 40–99% were
College of Chemistry and Molecular Engineering, Henan Key Laboratory of
Chemical Biology and Organic Chemistry, Key Laboratory of Applied Chemistry
of Henan Universities, Zhengzhou University, Zhengzhou450052, People’s
Republic of China
Appl. Organometal. Chem. (2012)
Copyright © 2012 John Wiley & Sons, Ltd.

A. Yu et al.
N
N
N
Pd
Fe
Pd
Pd
N
Fe
Fe
N
Cl
Cl
PCy3
PPh3
Ia
Ib
Ic
Scheme 1. Molecular structures of Ia–c
a
Table 1. Screening of catalysts, bases, temperature and solvents for the coupling of phenylboronic acid with benzyl bromide
ꢀ
b
Entry
Palladium source
Base
Solvent
T ( C)
t (h)
Yield (%)
1
2
3
4
5
6
7
8
9
Ia
K
K
K
3
3
3
PO
PO
PO
4
4
4
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Dioxane
DMF
110
110
110
110
110
110
110
110
110
60
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
6
85
73
Ib
Ic
65
Ia
K
2
CO
t-BuONa
Na CO
Cs CO
3
95
Ia
78
Ia
2
3
Trace
75
Ia
2
3
Ia
K
2
K
2
K
2
K
2
K
2
K
2
K
2
K
2
K
2
CO
3
3
3
3
3
3
3
3
3
83
Ia
CO
CO
CO
CO
CO
CO
CO
CO
N.R.
70.
N.R.
80
10
11
12
13
14
15
16
Ia
THF
Ia
DMSO
110
110
110
90
Ia (0.5 mol%)
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Ia (1.5 mol%)
95
Ia
Ia
Ia
Ia
Ia
95
80
87
90
95
1
7
K
2
CO
CO
3
90
3
95
88
18
K
2
3
90
2
a
Reaction conditions: phenylboronic acid 0.6 mmol, benzyl bromide 0.5 mmol, base 1.0 mmol, 1 mol % of Ia–Ic, under nitrogen, 2.0 ml solvent.
Isolated yield; N.R.: No reaction.
b
excellent yield was obtained when K
2
CO
3
was used as the base
transformed into the corresponding product in high yield (Table 2,
entry 14). Regarding the arylboronic acids, electronically different
arylboronic acids can be readily coupled in up to 95% yields
(Table 2, entries 2–8). 3-Thienylboronic acid was also smoothly
converted to the desired product. However, the yield was lower
than in other cases (Table 2, entry 9). On the other hand, even deac-
tivated electron-rich benzyl bromides, which are considered impor-
tant for a more precise measurement of the catalytic activity, were
compatible with this reaction system, affording the product 3b in
99% yield (Table 2, entry 10). It is interesting to note that benzyl
bromide underwent smooth coupling with phenylboronic acid,
whereas halogen such as Cl present on the aromatic ring remained
unaffected (Table 2, entry 11). It is especially attractive that benzyl
chlorides provided the coupling products in good yields (Table 2,
entries 12–14).
The reusability and efficiency of cyclopalladated complex Ia
were investigated on the model coupling reactions of benzyl bro-
mide with phenylboronic acid. The results are shown in Table 3.
High recyclable efficiency (the average GC yield of 92% for eight
consecutive runs) using the palladacycle-catalyzed system was
obtained for benzyl bromide, which demonstrated the practical
recyclable property of this catalyst.
(Table 1, entry 4).
The desired product was obtained in 95% yield when toluene
was used as solvent (Table 1, entry 4). Polar solvents such as
DMSO and DMF did not favor this reaction (Table 1, entries 9,
1
1). The yield was not improved significantly when the catalyst
loading was increased from 1 mol% to 1.5 mol% (Table 1, entry
vs. 13). On the other hand, the yield decreased when the load-
4
ing of catalyst Ia was reduced to 0.5 mol% from 1 mol% (Table 1,
entry 4 vs. 12). Moreover, the yield was not improved evidently
ꢀ
ꢀ
by increasing temperature from 90 C to 110 C (Table 1, entry 4
vs. 14 and 15) and prolonging the reaction time from 3 h to 6 h
(Table 1, entry 4 vs. 16–18).
Under the optimized reaction conditions (0.5 mmol benzyl
halide, 1.2 equiv. arylboronic acid, 2.0 equiv. K CO , 1 mol%
2
3
ꢀ
complex Ia, toluene as solvent, 90 C), an array of commercially
available benzyl halides and arylboronic acids was investigated.
As shown in Table 2, the excellent yields obtained with electroni-
cally dissimilar boronic acids indicate that the procedure is effective
regardless electronic nature of this component of the coupling.
Moreover, the reaction was shown to be invulnerable to
steric effects, as the employment of 2-chloromethylnaphthalene
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Copyright © 2012 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. (2012)

Cyclopalladated ferrocenylimine as catalyst for diarylmethane derivatives
Table 2. Palladacycle-catalyzed Suzuki cross-coupling of benzyl
halides with arylboronic acids
were purified before use. The other chemicals were obtained from
commercial sources and used as received unless otherwise noted.
a
General Procedure for Palladacycle-Catalyzed Suzuki
Cross-Coupling Reaction
A reaction vessel was charged with a mixture of phenylboronic
acid (0.6 mmol), K CO (1.0 mmol), catalyst Ia (1 mol%) in toluene
2
3
1
2
b
Entry
Ar (X = Cl, Br)
Ar
Product Yield (%)
(2.0 ml) and stirred for about 20 min under nitrogen atmosphere.
Benzyl bromide or benzyl chloride (0.5 mmol) was then added.
1
2
3
4
5
6
7
8
9
Ph (X = Br)
Ph (X = Br)
Ph (X = Br)
Ph (X = Br)
Ph (X = Br)
Ph (X = Br)
Ph (X = Br)
Ph (X = Br)
Ph (X = Br)
1a Ph
1a 4-MeC
1a 4-MeOC
1a 4-Me CC
1a 3-MeC
2a
2b
2c
2d
2e
2f
3a
3b
3c
3d
3e
3f
95
60
55
95
68
70
55
53
40
99
75
85
88
94
ꢀ
The mixture was heated to 90 C and incubated in an oil bath
6 4
H
ꢀ
at 90 C for 3 h under nitrogen atmosphere. After completion of
6 4
H
the reaction, the mixture was quenched by 5 ml water and then
3
6 4
H
extracted with ethyl acetate (3 Â 10 ml). The combined organic
6 4
H
4
layer was dried over MgSO . After removal of the solvent in
1a 4-ClC
1a 2-ClC
6
H
H
4
vacuo, the product was obtained by purifying by preparative
TLC, eluting with petroleum ether, and the yield was calculated
based on the benzyl bromide or benzyl chloride (the purified pro-
ducts were identified by NMR spectra and comparison of melting
points with literature data). In the recycle experiment, the residue
was subjected to a second run of the Suzuki cross-coupling
reaction by charging with the same substrates (benzyl bromide
6
4
2g
2h
2i
3g
3h
3i
1a 2,4-F
1a 3-Thienyl
(X = Br) 1b Ph
2 6 4
C H
10
11
12
13
14
4-MeC
4-ClC
6
H
4
2a
2a
2a
2b
2a
3b
3f
6
H
4
(X = Br)
1c Ph
Ph (X = Cl)
Ph (X = Cl)
1d Ph
3a
3b
3j
6 4
1d 4-MeC H
2 3
or benzyl chloride, phenylboronic acid, toluene and K CO )
1-Naphthyl (X = Cl) 1e Ph
without further addition of cyclopalladated catalyst Ia.
a
[19]
[21]
[19]
[36]
[36]
[21]
[37]
[7]
Isolated yield.
The products 3a, 3b, 3c, 3d, 3e, 3f, 3g, 3h,
b
[38]
[19]
1
Reaction conditions: arylboronic acid 0.6 mmol, benzyl halides
3i and 3j were characterized by comparing their H NMR and
13
0.5 mmol, K
2
CO
3
1.0 mmol, catalyst Ia 1 mol%, under nitrogen,
C NMR spectra with those mentioned in the references.
ꢀ
toluene 2.0 ml, 90 C, 3 h.
Acknowledgements
We are grateful to the National Natural Science Foundation of China
(no. 21172200) and the NSFC (Outstanding Young Scholarship,
no. 30825043) for financial support of this research.
Table 3. Recycling experiments for palladacycle-catalyzed Suzuki
cross-coupling reactions of benzyl bromide with phenylboronic acid
a
Number of cycles
1
2
3
4
5
6
7
8
9
References
b
Yield
95 95 95 94 94 94 92 90 85
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[
Cyclopalladated ferrocenylimine complex Ia exhibited high
catalytic activity for preparation of diarylmethane derivatives
from benzylic halides with arylboronic acids and tolerated various
functional groups. A wide range of diarylmethanes were effi-
ciently obtained in high yields. Catalyst recycling has been evalu-
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1
13
H NMR and C NMR spectra were recorded on a Bruker DPX-400
spectrometer with CDCl3 as the solvent and tetramethylsilane
TMS) as internal standard. GC analysis was performed on an Agi-
lent 4890D gas chromatograph. All the solvents in this reaction
[
[
[
(
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