Hydroalkenylation: Palladium catalyzed co-dimerization of unactivated alkenes

Article abstract of DOI:10.1016/j.tetlet.2016.01.034

A highly efficient co-dimerization of styrene and cyclopentene was developed in the presence of palladium and a BF₃ source, selectively forming a new C-C bond. The complex [Pd(PPh₃)₂]⁺BF₄^-

Full text of DOI:10.1016/j.tetlet.2016.01.034

Tetrahedron Letters 57 (2016) 815–818
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Tetrahedron Letters
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Hydroalkenylation: palladium catalyzed co-dimerization of
unactivated alkenes
Nima Zargari, Gilles de Prevoisin, Yeseul Kim, Kelly Kaneshiro, Riley Runburg, Jiwon Park, Kelsey LaCroix,
⇑
Reshma Narain, Byung Do Lee, Joo Ho Lee, Kyung Woon Jung
Loker Hydrocarbon Research Institute and Department of Chemistry, University of Southern California, Los Angeles, CA 90089, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
A highly efficient co-dimerization of styrene and cyclopentene was developed in the presence of palla-
dium and a BF3 source, selectively forming a new C–C bond. The complex [Pd(PPh3)2]+BF4À is believed
to generate palladium hydride (Pd-H), which catalyzes the reaction between various styrenes and
cyclopentene in excellent yields as single isomers. This co-catalytic system provides a new efficient C–
C bond forming method.
Received 17 December 2015
Revised 8 January 2016
Accepted 10 January 2016
Available online 11 January 2016
Ó 2016 Elsevier Ltd. All rights reserved.
Keywords:
Hydroalkenylation
Alkene cross coupling
Palladium catalysis
Tetrafluoroborate
Pd-hydride
Seminally, the discovery of palladium catalyzed cross-coupling
reactions has changed the field of modern organic chemistry.1
Recently, many transition metal catalyzed hydroalkenylation reac-
tions have been reported in the literature,2 utilizing palladium cat-
alysts in conjunction with tetrafluoroborate additives in order to
activate various alkenes.3 Sen,4 Shmidt,5 and Tkach,6 among others,
have used this co-catalytic system in order to dimerize or polymer-
ize olefins; however, they have not been able to couple two differ-
ent alkenes efficiently. Herein we report a vinyl arene coupling
reaction utilizing a palladium(0) source and a tetrafluoroborate
co-catalyst. In sharp contrast to the previous work, this reaction
is a chemoselective and stereoselective cross-coupling of different
alkenes without the need of a leaving or activating group on the
olefins.
Initially, we used our NHC-amidate Pd(II) complex 1 (Fig. 1) by
activating with AgBF4 to remove the chlorine ligand and form a
cationic palladium(II) complex.7 Under mild conditions, we were
able to successfully couple styrene and cyclopentene in a high
yield, while minimizing the homo-coupled side product of styrene
(Scheme 1).
and Pd(TFA)2 (entries 1 and 2), yielded low to good results, respec-
tively. Pd(dba)2 (entry 3) was slightly less effective as Pd(TFA)2;
however, Pd(PPh3)4 (entry 4) produced the desired product in com-
parable yields as 1. No reaction took place in the absence of a pal-
ladium source (entry 5) or in the absence of AgBF4 (entry 6). Using
AgPF6 as the silver source drastically lowered the yield of the reac-
tion (entry 7), while other silver(I) salts provided no catalytic activ-
ity (entries 8 and 9). This led us to discover the significance of
AgBF4.
Since AgBF4 was previously used to remove chloride in 1, its
necessity with Pd(PPh3)4 was tested by screening Pd(PPh3)4 against
various tetrafluoroborate and boron trifluoride additives (Table 2).
NaBF4 by itself or in the presence of acids such as hydrochloric or
p-toluenesulfonic acid provided no products (entries 1–3). How-
ever, NaBF4 in the presence of acids such as methanesulfonic or
sulfuric acid provided the product in low yields (entries 4 and 5).
Importantly, in the absence of the tetrafluoroborate salt, no
We then endeavored to determine the most favorable source of
palladium by screening different palladium and silver complexes
(Table 1). Similarly to 1, other palladium sources provided the
desired product as well. Palladium(II) sources such as Pd(OAc)2
⇑
Corresponding author. Fax: +1 213 821 4096.
E-mail address: kwjung@usc.edu (K.W. Jung).
Figure 1. Structure of our NHC-amidate Pd(II) complex.
http://dx.doi.org/10.1016/j.tetlet.2016.01.034
0040-4039/Ó 2016 Elsevier Ltd. All rights reserved.

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N. Zargari et al. / Tetrahedron Letters 57 (2016) 815–818
palladium catalyst produced low yields (entry 1). Doubling the
ratio of tetrafluoroboric acid significantly increased the yield, while
doubling the ratio of boron trifluoride modestly increased the yield
of the desired product (entry 2). A four-time excess of either
tetrafluoroborate or boron trifluoride loading to the palladium cat-
alyst produced the highest amount of the desired product (entry 3),
while the yield of the reaction decreased, with higher ratio
amounts (entry 4). These results further support our belief of the
activated catalyst complex, since increased amounts of the boronic
cocatalyst would shift the equilibrium of the palladium complex
toward more of an ionic character species.
The solvent effect of both AgBF4 and HBF4 was then tested sep-
arately (Table 4). Both AgBF4 and HBF4 reacted similarly in polar
and nonpolar halogenated solvents (entries 1–3). In the case of
using benzene as the solvent, HBF4 produced moderate yields,
while the same reaction using AgBF4 did not produce the desired
product (entry 4). Other polar solvents inhibited the reaction
(entries 5–8). This is thought to be due to the solvent’s interaction
with BF3, deactivating the cocatalyst.
Scheme 1. Initial reaction conditions utilizing complex 1.
Table 1
Screening of varying palladium and silver sourcesa
Entry
Palladium source
Silver source
Yieldb (%)
1
2
3
4
5
6
7
8
9
Pd(OAc)2
Pd(TFA)2
Pd(dba)2
Pd(PPh3)4
—
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
AgBF4
AgBF4
AgBF4
AgBF4
AgBF4
—
AgPF6
AgOTf
AgNO3
37
79
73
93
—
—
13
—
—
We then examined the electronics of the reaction by varying the
substituents on styrene in order to determine how electron with-
drawing or donating groups would affect the yield of the desired
product. These reactions were tested with HBF4 as the boronic
cocatalyst (Table 5). Interestingly, electron deficient styrene sub-
strates produced the highest amount of the desired product
(entries 2–6). Electron rich styrene substrates produced drastically
lower yields (entries 7 and 8), while the most electron rich sub-
stituent, 4-methoxystyrene, produced the lowest yield. Regardless
of acid loading and temperature variations, 4-methoxystyrene
polymerized under these reaction conditions. Such electronic
trends imply that the electron deficient styrene substrates are
the most reactive in these reaction conditions, since they are more
readily activated by palladium hydride complexes (vide infra).
Preforming the reaction using deuterated styrene revealed
interesting mechanistic implications (Scheme 3). Critically, the
final product was not deuterated on the cyclopentene ring. The
deuterated ratio at the benzylic position of the product was 2:1,
revealing that there were no proton or deuterium shifts during
the reaction.
a
Reaction conditions: 100
ladium source, and 20 mol silver source were dissolved in 0.7 mL 1,2-DCE and
stirred at 50 °C for 16 h.
lmol styrene, 1250 lmol cyclopentene, 5 lmol pal-
l
b
Determined by 1H NMR using DMSO as an internal standard.
Table 2
Screening of varying tetrafluoroborate and boron trifluoride additivesa
Entry
Additive 1
Additive 2
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
NaBF4
NaBF4
NaBF4
NaBF4
NaBF4
—
—
HCl
—
—
—
15
35
—
TsOH
MsOH
H2SO4
MsOH
H2SO4
—
—
—
HBF4
BF3ÁOEt2
AlCl3
85
76
—
—
—
a
Reaction conditions: 100
lmol styrene, 1250
lmol cyclopentene, 5
lmol Pd
Sen et al. suggested a carbocationic mechanism for the dimer-
(PPh3)4, 20
lmol additive 1, and 20
lmol additive 2 were dissolved in 0.7 mL 1,2-
ization of styrene, using Pd(PPh)2(BF4)2 in the late 1980’s;4b
DCE and stirred at 50 °C for 16 h.
b
Determined by 1H NMR using DMSO as an internal standard.
however, this theory has been long challenged. Such
a
carbocationic mechanism involves the participation and
abstraction of free H+ and would be very sensitive to the
temperature fluctuations. Later findings have refuted this belief
and proposed that the coupling of unactivated alkenes with
similar catalytic systems may be propagated by palladium
hydride complexes9 or hydrido-palladium species.10 Though
hydrido-palladium species selectively provide head-to-tail prod-
ucts, we favor the palladium hydride complex as the active cat-
alytic species, due to its direct methodology and long list of
precedence.
It is well known that Brønsted acids, such as HBF4, complex
with Pd(0) sources, forming palladium hydride complexes, for
example, HPd(L2)BF4.11 Moreover, in the presence of trace amounts
of water from solvent and substrates, silver hexafluorophosphate,
tetrafluoroborate counter ions, and boron trifluoride diethyl ether-
ate have been shown to hydrolyze and form HF and activate palla-
dium species.8a,d,12 Scheme 4 proposes the coupling of styrene and
cyclopentene via a palladium hydride complex.9,13 Initially, the
coordinately unsaturated palladium hydride species I coordinates
to the alkene of styrene, while two monodentate phosphine
ligands also coordinate to the palladium center, forming structure
products were observed when methanesulfonic or sulfuric acid
was used alone (entries 6 and 7). The best results were observed
when HBF4 was used as the tetrafluoroborate additive, producing
the product in 85% yield (entry 8). Further, boron trifluoride diethyl
etherate was also used as a trifluoride additive, which produced a
significant amount of the desired product, revealing that the reac-
tion may not solely be catalyzed by fluoroboric acid (entry 9). Crit-
ically, employing other Lewis acids such as AlCl3 did not produce
any product (entry 10). These results strongly suggested that the
tetrafluoroborate or boron trifluoride additives were responsible
for activating the catalytic system.
Based on these results and the work done by Shmidt et al., it is
believed that trace amounts of fluoride in the solution form palla-
dium-fluorine dimers (Scheme 2). With increasing amounts of BF3,
the active catalytic species is formed, wherein BF3 is complexed to
the palladium source either via a fluorine atom (FÁBF3) or as a BF4À
anion.8
The ratio between palladium source and the boronic cocatalyst
has been extensively studied, in the dimerization or oligomeriza-
tion of alkenes. The loading of both tetrafluoroboric acid and boron
trifluoride was examined under our standard reaction conditions
(Table 3). Stoichiometric equivalents of the boronic source to the
II. The palladium then forms a
p complex with the abundant
cyclopentene, forming structure III and initiating the cross-
coupling reaction. Lastly, beta-elimination of IV terminates the

N. Zargari et al. / Tetrahedron Letters 57 (2016) 815–818
817
Scheme 2. Catalytically active complexes.
Table 3
Effects of tetrafluoroborate and boron trifluoride loadinga
Entry
HBF4
(l
mol)
Yieldb (%)
BF3ÁOEt2
(lmol)
Yieldb (%)
1
2
3
4
5
10
20
40
24
66
85
49
5
10
20
40
8
20
76
23
Scheme 3. Styrene-d8 study.
a
Reaction conditions: 100 lmol styrene, 1250 lmol cyclopentene, 5 lmol Pd
(PPh3)4, and varying amounts of HBF4 or BF3ÁOEt2 were dissolved in 0.7 mL 1,2-DCE
and stirred at 50 °C for 16 h.
b
Determined by 1H NMR using DMSO as an internal standard.
Table 4
a
Solvent screened with AgBF4 or HBF4
Entry
Solvent
AgBF4 yieldb (%)
HBF4 yieldb (%)
1
2
3
4
5
6
7
8
DCMc
86
93
90
—
—
—
88
85
74
59
—
—
—
—
1,2-DCE
Chloroform
Benzene
Acetonitrile
THF
MeOH
1,2-Dioxane
—
—
a
Scheme 4. Proposed mechanism via a palladium hydride complex.
Reaction conditions: 100
l
mol styrene, 1250
lmol cyclopentene, 5 lmol Pd
(PPh3)4, and 20
lmol AgBF4 or HBF4 were dissolved in 0.7 mL solvent and stirred at
50 °C for 16 h.
b
Determined by 1H NMR using DMSO as an internal standard.
Reaction was run at 25 °C.
Acknowledgments
c
We acknowledge the Hydrocarbon Research Foundation for
generous financial support, Dr. Justin O’Neill and Mr. Adam Scha-
nen for initiatives in the project, and Dr. Richard Giles for helpful
discussion.
Table 5
a
Screening styrene derivatives with HBF4
Entry
Substrate
Styrene
4-Trifluoromethylstyrene
4-Nitrostyrene
4-Chlorostyrene
2-Fluorostyrene
Yieldb (%)
Supplementary data
1
2
3
4
5
6
7
8
9
85
96
91
91
82
80
40
57
14
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2016.01.
034.
4-Fluorostyrene
4-Methylstyrene
2-Vinylnaphthalene
4-Methoxystyrene
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