Highly efficient Pd(acac)2/TFA catalyzed head-to-tail dimerization of vinylarenes at room temperature

Article abstract of DOI:10.1016/j.tetlet.2011.01.056

Pd(acac)₂ catalyzed dimerization of vinylarenes to form dimers under mild condition with excellent yields and stereoselectivities. In particular, the use of TFA highly promoted the activity and selectivity of the dimerization. The studies on mechanism for the reaction displayed clearly that the dimerization of styrenes is 100% atom economic reaction.

Full text of DOI:10.1016/j.tetlet.2011.01.056

Tetrahedron Letters 52 (2011) 1569–1573
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Highly efficient Pd(acac)2/TFA catalyzed head-to-tail dimerization
of vinylarenes at room temperature
⇑
Hengchang Ma, Qiangsheng Sun, Wenfeng Li, Jinxia Wang, Zhe Zhang, Yaoxia Yang, Ziqiang Lei
Key Laboratory of Polymer Materials of Gansu Province, Key Laboratory of Eco-Environment-Related Polymer Materials Ministry of Education, College of
Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou 730070, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
Pd(acac)2 catalyzed dimerization of vinylarenes to form dimers under mild condition with excellent
yields and stereoselectivities. In particular, the use of TFA highly promoted the activity and selectivity
of the dimerization. The studies on mechanism for the reaction displayed clearly that the dimerization
of styrenes is 100% atom economic reaction.
Received 17 November 2010
Revised 4 January 2011
Accepted 14 January 2011
Available online 1 February 2011
Ó 2011 Published by Elsevier Ltd.
Keywords:
Styrenes
Arenes
Dimerization
Palladium
Catalysis
Catalytic dimerization of aryl alkenes is one of the current inter-
esting and useful reactions to construct a new C–C bond.1 Consid-
erable attention has been focused on the transformations because
of the demand for the formation of important intermediates in the
fields of material engineering and pharmaceuticals.2 The dimeriza-
tion of alkenes could be carried out following three ways to date:
head-to-head, head-to-tail, and tail-to-tail.3 In particular, since a
new allylic carbon stereogenic center is formed, the head-to-tail
dimerization is considered more attractive.4 Furthermore, several
compounds contain a diarylmethane motif, which is of great inter-
est as it is a part of the various valuable biologically active com-
pounds and pharmaceuticals, such as the warfarin derivative
phenprocoumone, enantiomerically-enriched non-steroidal anti-
inflammatory naproxen, nafenopin and dimentindene.5 (Fig. 1)
Generally, the plausible mechanism of the transition metal cata-
lyzed dimerization reactions follows three main pathways
(Scheme 1).3a,e,6
A range of catalytic systems have been reported for the head-
to-tail dimerization of alkenes: Dawans disclosed that [Ni(p-C3H5)
(OCOCF3)]2 could catalyze dimerization of styrenes to afford 1,3-
diaryl-1-butene in moderate selectivity.7 Shirakawa8 and Cheng9
reported that the catalyst systems of Pd(OAc)2 (1 mol %)/PPh3
(1 mol %)/In(OTf)3 (5 mol %) and CoX2(PPh3)3 (10 mol %)/PPh3
(30 mol %)/Zn (1.5 equiv) showed high catalytic activity for the
same dimerization reaction. Yi and co-workers described that
dimerization of styrene catalyzed by Ni(dppp)Cl2/Bu3N gave prod-
ucts with excellent yields.6a The most recent development can be
linked to the discovery that the cooperation of FeCl3 and AgNTf2
enable dimerization of alkenes into 1,3-diaryl-1-butenes.12
Although these methods are efficient, drastic reaction conditions
(up to 130 °C, 24 h) are always employed resulting in low selectiv-
ity and low turnover of frequency (TOF) (43.5 mol/mol/h). Addi-
tionally, the need of expensive phosphorus ligands and additives,
as well as generation of oligomers or polymers can be a significant
drawback.6a,7–9 Therefore, in view of the demand for more efficient
processes, the development of direct catalytic carbon–carbon
bond-forming reactions of arenes with more simple methodologies
is an important task.
OH
N
N
O
O
Phenprocoumone
COOH
Dimetindene
O
Nafenopin
Figure 1. Biologically active compounds.
⇑
Corresponding author. Tel./fax: +86 931 797 0359.
E-mail addresses: leizq@nwnu.edu.cn, mahczju@hotmail.com (Z. Lei).
0040-4039/$ - see front matter Ó 2011 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2011.01.056

1570
H. Ma et al. / Tetrahedron Letters 52 (2011) 1569–1573
Path A
Path B
MH
M
[M]
Ar
Ref. 3a, 6a
H
[M-H]
Ref. 6b
Ar
-[M-H]
M
M
Path C
M
M(OTf)n
[M0]
M(OTf)n
H
M(OTf)n
Ref. 6c
Ar
M
M(OTf)n
Scheme 1. Plausible mechanism of the head-to-tail dimerization of styrene.
Table 1
Thus, we explored the high selectivity and efficiency of the
head-to-tail dimerization of styrene under very mild reaction con-
ditions. The reaction was performed in the presence of Pd(acac)2
without any additional phosphorus ligand at ambient temperature.
TFA was employed for accelerating dimerization, as well as CH2Cl2
which was used as solvent. In the course of our study, we found
that TFA is indispensable and the dimerization of styrene is 100%
atom economic reaction, that is, all of the atoms in the starting
materials are incorporated into the products (Scheme 2). It is wor-
thy of note that the generation of dimers from vinylarenes occurs
rapidly without giving any oligomers and polymers.
We chose styrene as the standard substrate to screen the opti-
mum reaction conditions (Table 1). Of the palladium catalysts
examined, Pd(acac)2 (5.0 mol %) showed the highest catalytic activ-
ity and 1b was obtained in 96% isolated yield with complete E
selectivity (entry 9). PdCl2 and Pd(OAc)2 also showed moderate
catalytic capabilities (entries 1–4). In contrast, styrene polymer-
ized immediately in the case of using TFA as solvent (entry 11).
Notably, the reaction could not have occurred in the absence of
palladium catalyst (entry 12). The influence of the solvent was then
investigated. The commonly used solvent CH2Cl2 proved to be the
best reaction medium. The use of TFA/1.0 mmol is essential for the
success of the highly efficient dimerization. However, CH3COOH
and Cl3CCOOH could not be served as effective addictives. When
TFA was used, the dimerization became highly selective and rapid
at ambient temperature. Therefore, the optimum reaction condi-
tions are: Pd(acac)2 (5.0 mol %)/CH2Cl2(2.0 mL)/TFA(1.0 mmol)/
styrene (1.0 mmol).
Optimization of reaction conditions
Catalyst/additive
Solvent, 2 mL
rt, 5 min.
1a, 1 mmol
1b
Entry
Solvent
Catalyst
TFA (mmol)
Yielda (%)
1
2
3
4
5
6
7
8
CHCl3
THF
PdCl2 5.0 mol %
PdCl2 5.0 mol %
PdCl2 5.0 mol %
0.2
0.2
0.2
0.2
0.2
0.4
0.6
0.8
1.0
1.0
58
64
72
78
80
85
91
94
96b
92
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
TFA
Pd(OAc)2 5.0 mol %
Pd(acac)2 5.0 mol %
Pd(acac)2 5.0 mol %
Pd(acac)2 5.0 mol %
Pd(acac)2 5.0 mol %
Pd(acac)2 5.0 mol %
Pd(acac)2 3.0 mol %
Pd(acac)2 5.0 mol %
9
10
11
12
c
d
—
1.0
—
e
CH2Cl2
—
n.r.f
a
b
c
d
e
f
GC yield.
Isolated yield.
TFA was used as solvent.
most of the substrate was consumed, but yielding no dimerization product.
Pd(acac)2 was not used.
No reaction.
could be transformed into the corresponding trans-1,3-diaryl-1-
butenes with excellent yields. In the case of strong electron-donat-
ing and withdrawing group substituted examples, the satisfied
yields were achieved (7a, 8a). Thus, this methodology established
easily a library of diversified trans-1,3-diaryl-1-butenes containing
allylic carbon stereogenic center. Meanwhile, some inevitable lim-
itations are obvious, for instance, the application scope could not
be expended to heteroatoms-containing substrates, 3-vinylpyri-
dine,4-vinylpyridine (10a), and multi-substituted styrene, such as
(Z) and (E)-1,2-diphenylethene,1,1-diphenylethene (9a).
With the optimized reaction condition in hand, the scope and
generality of this reaction have been explored using various com-
mercially available vinylarenes. As shown in Figure 2,10,11 beside
1a, both alkyl-substituted and halogenated vinylarenes were all
able to give the corresponding products under the optimized con-
ditions. Methyl group in the p, m or o position has no apparent
effect on the yields of products (2a, 3a, 4a). Notably, other more
fragile functional groups also could tolerate the reaction conditions
(5a, 6a). For instance, the fluorinated and brominated substrates
H
H
H
H
H
H
H
H
H
H
D
H
H
H
CF3COOD
H
H
H
YES
100 % atom economy
NO
no 100 % atom economy
H
Scheme 2. 100% atom economic transformation.

H. Ma et al. / Tetrahedron Letters 52 (2011) 1569–1573
1571
CH3
Pd(acac)2
R
R
R
TFA/CH2Cl2
r.t., 5 min
1b ~ 8b/TON/TOFa/Yield%
1a ~ 8a
CH3
CH3
CH3
CH3
H3C
CH3
CH3
2b/19/226/94
3b/19/226/94
1b/19/230/96
CH3
CH3
CH3
H3C
CH3
F
F
Br
Br
4b/19/228/95
6b/19/221/92
5b/19/223/93
CH3
CH3
F3C
OCH3
CF3
H3CO
8b/19/228/95
7b/19/223/93
N
10a/No Reaction
9a/No Reaction
a TOF is expressed as mol/mol/h
Figure 2. Pd(acac)2 catalyzed dimerization of styrene.
To elucidate the mechanism of the reaction deuterium labeling
experiment using CF3COOD was performed for the dimerization of
styrene 1a. The reaction predominantly gave no deuterated prod-
generally recognized that the [M]–H species was a key intermedi-
ate, which could promote the styrene dimerization through an
addition/b-hydrogen elimination mechanism.6b
We also carried this transformation in the mixture of TFA
(1.0 mmol) and anhydrous CH2Cl2 (2 mL) with a small amount of
D2O, several alkenes, such as 4-CF3, 4-Br, 4-CH3 substituted sub-
strates also gave the corresponding no deuterated products. These
facts confirmed that there is no intermolecular proton migration
between styrene with TFA, or H2O.
uct (1b), m/z = 208 [M+], and almost no [
D
]-1b, m/z = 209 [M+]
was obtained. Correspondently, DEPT spectrum also confirmed this
result (Fig. 3). It proved that the deuterium atom does not partici-
pate in the formation of the product 1b. This deuterium immigra-
tion also suggests that there is no formation of a palladium
deuteride ([Pd]–H/D) between palladium with CF3COOH/D. It is
Figure 3. DEPT NMR of 1,3-diphenylbut-1-ene.

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H. Ma et al. / Tetrahedron Letters 52 (2011) 1569–1573
treated with CF3COOD under the same reaction conditions, no deu-
terium atom incorporation into product was observed. This result
strongly suggests that deuterium exchange occurs with the start-
ing substance 11a, and not with the formed 1,1,3-trimethyl-3-phe-
nyl-2,3-dihydro-1H-indene. The reaction was performed under
nitrogen atmosphere, and using anhydrous CH2Cl2 as solvent, the
CF3COOH / 0.2mmol
with Pd 0 or II with out Pd
96 % yield
CH2Cl2 / 2 mL
11b
11a
both of mixture of 11b and D-11b could be obtained. What was be-
Scheme 3.
yond our expectations was that the mixture of deuterated and non-
deuterated products always could be formed even using CF3COOD
as solvent. As a result, we assumed that after the electrophilic
substitution reaction, H+ dropped from the aromatic ring of
Additionally, the result of dimerization of
a
-methylstyrene 11a
affording analogously Friedel–Crafts product attracted our
attention. (Scheme 3) The dimerized product 1,1,3-trimethyl-3-
phenyl-2,3-dihydro-1H-indene 11b could be obtained in the
presence of TFA and without using palladiums. Although, several
palladium catalysts were used, the same product 11b was formed
with unique selectivity. Our urgent desire to investigate reactions
a-position substituted styrene led us to ponder that there are
possibly competitive reactions between proton involved electro-
philic addition and palladium/TFA cooperated dimerization
a-methylstyrene competes with D+ to afford the deuterated and
non-deuterated products. The possible process is depicted in
Scheme 4. Further study confirmed that in the TFA/11a reaction
mixture the main product was a single isomer of 11b (M+ at m/z
236) but also revealed the presence of trace quantities (<2%) of
12b and 13b. Both of them originated from the successive electro-
philic addition reactions following Markovnikov and anti-Mark-
ovnikov rule (Scheme 5).
of
transformation. Possibly, due to the steric hindrance, a-methylsty-
The greater reactivities of styrenes encouraged us to explore
their co-dimerization. Unfortunately, all reactions with mixtures
of olefins failed to induce hetero-dimerization reactions. For in-
stance, reacting a 1:1 mixture of 1a and 4a led to the formation
of 1b and 4b only. This homo-coupling result also could be
achieved in the presence of mixture of 1a and 11a. As a result,
the remarkable self-dimerization renders this methodology with
unique chemoselectivity.
rene prefers to H+ promoted electrophilic addition route, which
also prevents the activating of C@C double bonds by palladium
species.
CF3COOD also was used to explore the pathway of the transfor-
mation. The DEPT spectrum and GC–MS displayed that the final
products contained both deuterated (m/z = 237 [M+]) and non-deu-
terated (m/z = 236 [M+]) arenes. (Fig. 4) When isolated 11b was
Figure 4. DEPT NMR of 1,1,3-trimethyl-3-phenyl-2,3-dihydro-1H-indene.
H
D
H
H
D
H
H+
D
H
CF3COOD
H
H
H
Ph
H
H
H
Ph
H
H
H
H
H
H+
H
H+
H
H
Scheme 4. Dimerization of a-methylstyrene.

H. Ma et al. / Tetrahedron Letters 52 (2011) 1569–1573
1573
CF3COOH / 0.2 mmol
11b
12b
11a
11a
CH2Cl2 / 2 mL
12b
13b
H
-H+
+ H+
11a
anti - Markovnikov Rule
H
H
H
-H+
H
H
13b
11a
+ H+
Markovnikov Rule
11a
H
Scheme 5.
We also thank Key Laboratory of Eco-Environment-Related Poly-
mer Materials (Northwest Normal University), Ministry of Educa-
tion, for financial support.
L
L
Ph
L
Pd
I
Ph
L
H
TFA
Pd
Pd
Pd
L
L
L
OOCCF3
L
Ph
Ph
Ph
Ph
III
II
References and notes
L
VIII
1. (a) Luh, T.-Y.; Leung, M.-K.; Wong, K.-T. Chem. Rev. 2000, 100, 3187; (b) Chin, C.
S.; Won, G.; Chong, D.; Kim, M.; Lee, H. Acc. Chem. Res. 2002, 35, 218; (c) Fagnou,
K.; Lautens, M. Chem. Rev. 2003, 103, 169; (d) Prajapati, D.; Gohain, M.
Tetrahedron 2004, 60, 815; (e) Shibasaki, M.; Vogl, E. M.; Ohshima, T. Adv. Synth.
Catal. 2004, 346, 1533; (f) Li, C.-J. Chem. Rev. 2005, 105, 3095.
L
L
Ph
Pd
Pd
H
Ph
H
Ph
Ph
IV
V
2. RajanBabu, T. V. Chem. Rev. 2003, 103, 2845.
3. (a) Kondo, T.; Takagi, D.; Tsujita, H.; Ura, Y.; Wada, K.; Mitsudo, T.-A. Angew.
Chem., Int. Ed. 2007, 46, 5958; (b) Jiang, Z.-Z.; Sen, A. J. Am. Chem. Soc. 1990, 112,
9655; (c) Kabalka, G. W.; Dong, G.; Venkataiah, B. Tetrahedron Lett. 2004, 45,
2775; (d) Hauptman, E.; Sabo-Etienne, S.; White, P. S.; Brookhart, M.; Garner, J.
M.; Fagan, P. J.; Calabreset, J. C. J. Am. Chem. Soc. 1994, 116, 8038; (e) Peng, J.-J.;
Li, J.-Y.; Qiu, H.-Y.; Jiang, J.-X.; Jiang, K.-Z.; Mao, J.-J.; Lai, G.-Q. J. Mol. Catal. A:
Chem. 2006, 255, 16.
Ph
L
H
Ph
Pd
H
Ph
Ph
Ph Ph
4. Bedford, R.-B.; Betham, M.; Blake, M.-E.; Garcés, A.; Millara, S. L.; Prasharc, S.
Tetrahedron 2005, 61, 9799.
VII
VI
5. (a) Rueping, M.; Nachtsheim, B. J.; Scheidt, T. Org. Lett. 2006, 8, 3717; (b)
Kischel, J.; Jovel, I.; Mertins, K.; Zapf, A.; Beller, M. Org. Lett. 2006, 8, 19.
6. (a) Yi, C.-Y.; Hua, R.-M.; Zeng, H.-X. Catal. Commun. 2008, 9, 85; (b)
Myagmarsuren, G.; Tkach, V. S.; Shmidt, F. K.; Mohamad, M.; Suslov, D.-S. J.
Mol. Catal. A: Chem. 2005, 235, 154.
7. Dawans, F. Tetrahedron Lett. 1971, 12, 1943.
8. Tsuchimoto, T.; Kamiyama, S.; Negoro, R.; Shirakawa, E.; Kawakami, Y. Chem.
Commun. 2003, 852.
9. Wang, C.-C.; Lin, P.-S.; Cheng, C.-H. Tetrahedron Lett. 2004, 45, 6203.
10. General information: All organic starting materials were analytically pure and
used without further purification. 1H and 13C NMR spectra were recorded on
MERCURY (400 MHz for 1H NMR, 100 MHz for 13C NMR) spectrometers,
chemical shifts are expressed in ppm (d units) relative to TMS signal as internal
reference in CDCl3. Gas chromatography (GC) analysis was performed on a
Scheme 6. The plausible mechanism of the dimerization reaction.
Sen et al. suggested a carbocationic mechanism for the dimer-
ization of styrene over [Pd(MeCN)4](BF4)2 and Pd(PPh)2(BF4)2
complexes.12 Apparently, such mechanism involves free H+ partic-
ipation and abstraction processes. However, the opposite observa-
tion in the deuterated reaction led us to discard this mechanism for
the reason that deuterium atom really did not incorporated into
the products. Although we have not carried out detailed mechanis-
tic studies of the interaction of Pd(acac)2 and TFA in the presence of
styrene, we also disfavor a mechanism that involves a palladium
hydride species, which is formed between palladium with TFA.
According to the literatures,13 we proposed that the product was
formed through the hydrido-Pd species [LnPdH]+ IV (Scheme 6).
Subsequent insertion of olefins into [Pd]–H bond, followed by
reductive elimination would give dimer VII.
In summary, a convenient approach to ligand-free head-to-tail
dimerization of vinylarenes in the presence of Pd(acac)2 promoted
by TFA has been developed. Preliminary studies on the details of
the reaction mechanism demonstrate that the head-to-tail dimer-
ization of styrene is 100% atom economic reaction. Extension of
this preliminary work is undergoing in our laboratory now.
Shimadezu GC-2010 equipped with
capillary column and oxyhydrogen flame detector. Mass spectra were
obtained on HP5988 mass spectrometer. Typical procedure for the
dimerization of styrene 1a affording 1b: mixture of 1a (104.0 mg,
1.0 mmol), Pd(acac)2 (15.0 mg, 5.0 mol %) in CH2Cl2 (2.0 mL) in round-
a
15 m  0.53 mm  1.5 lm RTX-1
a
a
A
a
bottomed flask was stirred at room temperature. Then, TFA (1.0 mmol) was
added. The mixture was magnetically stirred at room temperature for 5 min
until the complete consumption of styrene (observed by TLC). The mixture was
subjected to silica gel column chromatography using a mixture eluent of ethyl
acetate and petroleum ether (1:20 in volume). Compound 1b was isolated as
viscous oil (99.8 mg, 0.48 mmol, 96%)
11. The NMR data for representative products: 1,3-Diphenylbut-1-ene (1b) MS (EI,
70 eV): m/z (%) = 208 (100) M+; 1H NMR (400 MHz, CDCl3): d = 1.65 (d,
J = 4.8 Hz, 3H), 3.82–3.85 (dd, J = 4.8, 6.2 Hz 1H), 6.60 (d, J = 4.8 Hz, 2H),
7.36–7.56 (m, 10H); 13C NMR (100 MHz, CDCl3): d = 21.16, 42.50, 126.10,
126.17, 127.00, 127.25, 128.44, 135.12, 137.47, 145.51. 1,3-Bis(4-
fluorophenyl)but-1-ene (5b) 1H NMR (400 MHz, CDCl3): d = 1.42 (d,
J = 6.8 Hz, 3H), 3.59–3.62 (m, J = 6.8 Hz, 1H), 6.21–6.36 (m, 2H), 6.95–7.31
(m, 8H); 13C NMR (100 MHz, CDCl3): d = 21.28, 41.75, 115.10, 115.24, 115.30,
115.46, 127.50, 127.53, 127.60, 128.59, 128.67, 133.52, 133.56, 134.75, 134.77,
141.08, 141.12, 161.41 (J = 242 Hz), 162.06 (J = 245 Hz).
Acknowledgments
We are grateful for the financial support of the National Natural
Science Foundation of China (Nos. 20376071, 20674063 and
20774074) and Young Teacher Research Foundation of Northwest
Normal University (NWNU-LKQN-08-8, NWNU-kjcxgc-03-73).
12. (a) Jiang, Z.; Sen, A. Organometallics 1993, 12, 1406; (b) Sen, A.; Lai, T.-W.;
Thomas, R. R. J. Organomet. Chem. 1988, 358, 567.
13. Sui-Seng, C.; Groux, L. F.; Zargarian, D. Organometallics 2006, 25, 571.