Iodine-Promoted Metal-Free Head-to-Tail Dimerization of Styrenes Affording 1,3-Diarylbut-1-enes

Article abstract of DOI:10.1055/s-0036-1589214

A convenient and efficient iodine-mediated head-to-tail dimerization of styrenes to produce the corresponding dimers in the presence of triethyl phosphite is reported. The advantages of the present protocol are metal-free conditions, short reaction time, simplicity, and high efficiency.

Full text of DOI:10.1055/s-0036-1589214

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© Georg Thieme Verlag Stuttgart · New York
2016, 27, A–D
letter
A
D. Wang et al.
Letter
Synlett
Iodine-Promoted Metal-Free Head-to-Tail Dimerization of Styrenes
Affording 1,3-Diarylbut-1-enes
Dingyi Wang
R
I2
R
Yanjiao Fang
Qihuang Xie
Zhaohua Yan
Sen Lin*
P(OEt)3
R
DCE, 80 °C
5–30 min
Shengmei Guo*
R = H, Me, F, Cl,
10 examples
58–78% yields
Br, t-Bu, AcO
College of Chemistry, Nanchang University, Nanchang,
Jiangxi 330031, P. R. of China
senlin@ncu.edu.cn
smguo@ncu.edu.cn
senlin@ncu.edu.cn
smguo@ncu.edu.cn
Received: 02.07.2016
Accepted after revision: 21.08.2016
Published online: 12.09.2016
DOI: 10.1055/s-0036-1589214; Art ID: st-2016-w0425-l
Ar
Ar
B
Abstract A convenient and efficient iodine-mediated head-to-tail di-
merization of styrenes to produce the corresponding dimers in the
presence of triethyl phosphite is reported. The advantages of the pres-
ent protocol are metal-free conditions, short reaction time, simplicity,
and high efficiency.
Ar
Ar
A
C
Ar
Ar
Ar
A = tail-to-tail dimerization
Key words styrenes, arenes, dimerization, iodine, mediate
B = head-to-tail dimerization
C = head-to-head dimerization
Carbon–carbon bond formation has been extensively
studied and developed in organic synthesis.1 Among all car-
bon–carbon coupling reactions, dimerization of olefins
plays an important role in contemporary synthetic organic
chemistry since these dimers often appear in many natural
products.2 In the industrial sector, dimerization of olefins
has received attention because of the demand for the for-
mation of important intermediates in several fields, such as
medicinal chemistry, functional materials science, and so
on.3 To date, the dimerization of olefins could be completed
according to the following three approaches: head-to-head,
head-to-tail, and tail-to-tail (in Scheme 1).4 Among them,
the head-to-tail dimerization is interesting because a novel
allylic carbon stereogenic center is generated.5
Over the past decades, a number of transition-metal-
catalyst systems have been developed for the head-to-tail
dimerization of olefins, such as palladium, nickel, cobalt,
and so on (Scheme 2).6 For instance, Lei and co-workers6a
described that Pd(acac)2/TFA could catalyze head-to-tail di-
merization of styrenes to form dimers in high selectivity
with excellent yields under mild conditions. In 2013, Lim6b
found an efficient catalyst which is the combination of a
transition-metal complex with a Lewis acid. The same di-
Scheme 1 Three possible modes of dimerization of α-olefins
merization reaction was carried out in good yields at room
temperature. Hua6c disclosed that cationic nickel-catalyzed
head-to-tail dimerization of styrenes to produce 1,3-diaryl-
but-1-enes. From the foregoing, the transition-metal cata-
lysts were often used in such type of dimerization affording
1,3-diarylbut-1-enes. However, metal-free reagent- or cata-
lyst-promoted head-to-tail dimerization of styrenes to af-
ford 1,3-diarylbut-1-enes is rare. Recently, Zhao’s group re-
ported a highly efficient TfOH-catalyzed head-to-tail di-
merization of vinylarenes.7 Hence, the development of an
operationally simple, inexpensive, high selective metal-free
promoter for the styrene dimerization reaction is still re-
quired.
Simple iodine as desirable promoter has been exten-
sively applied to various reactions due to its several advan-
tages, such as ready availability, less toxicity, operational
simplicity, and inexpensiveness.8 And further exploration
of this enchanted territory is highly desirable in synthetic
chemistry. This desire prompted us to develop a simple and
highly efficient method for dimerization of aryl alkenes uti-
lizing iodine as an accelerant. Herein we report head-to-tail
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–D

B
D. Wang et al.
Letter
Synlett
the standard conditions. Halogen group in the ortho, meta,
para position has no noticeable impact on the yields of
products 2b–d. When the reaction was carried out utilizing
phenylethylenes with electron-drawing group as substrates
(such as F, Br, and acetoxyl group), the target product was
obtained in moderate yields (2e–g). However, for phenyl-
ethylens bearing electron-donating groups on the benzene
ring, the yield of the corresponding dimeriztaion products
decreased. For example, the substrates with Me and t-Bu
group could be transformed into the desired compounds
with lower yields (2h,i). But the reaction could be complet-
ed within five minutes. It is worth noting that when the re-
action time was prolonged to 30 minutes, the yield of the
corresponding compound decreased for phenylethylenes
with an electron-donating group. We reason that side reac-
tion could result from the presence of iodine. Meanwhile,
when phenylethylene with a strong electron-withdrawing
group (4-NO2) was used as substrate, no target product
formed. The same result was obtained when the reaction
was accomplished using heterocyclic compounds as sub-
strates (Scheme 3).
Previous work:
[M]
[M] = Pd, Ni, Co, In
This work:
I
2 (2.0 equiv)
P(OEt)3 (1.0 equiv)
DCE, 85 °C
5–30 min
Scheme 2 Head-to-tail dimerization of styrenes to give substituted
1,3-diarylbut-1-enes
dimerization of styrenes under metal-free conditions to ob-
tain the corresponding dimers.
First of all, styrene 1a was used as model substrate to
optimize the reaction conditions including iodides, addi-
tives, and solvents. At first, various iodides such as iodine,
tetrabutylammonium iodide (TBAI), NaI, and NH4I were ex-
amined to increase the reaction yield (Table 1, entries 1–4).
Among them, iodine showed the highest effective accelera-
tor to produce the corresponding product in 40% yield. Of
three additives investigated, triethyl phosphite proved to be
the most effective additive in this transformation (Table 1,
entries 1, 5, and 6). Then we screened a sequence of sol-
vents to obtain the optimal solvent. The commonly used
solvent 1,2-dichloroethane (DCE) was found to be the best
reaction medium (Table 1, entries 1, 7–13). Under the stan-
dard conditions, different amounts of iodine ranging from
1.0–2.5 equivalents were applied in the reactions. The
yields reach the maximum as the amount of iodine in-
creased up to 2.0 equivalents (Table 1, entry 14 and 15).
Meanwhile, we changed the amount of the molar ratio of
triethyl phosphite, and the best result was obtained with
1.0 equivalent of triethyl phosphite (Table 1, entry 17).
However, when the reaction was carried out in the absence
of additive, only small amounts of desired product was de-
tected (Table 1, entry 16). Thus we believe that triethyl
phosphite is indispensable in the reaction. It is worth not-
ing that the reaction was completed within ten minutes. Fi-
nally, when the reaction was performed at room tempera-
ture, only trace amount of corresponding product was af-
forded (Table 1, entry 18). On the basis of the results shown
in Table 1, the I2–P(OEt)3 system in DCE in reflux for 30
minutes emerged as the optimum conditions for follow-up
studies.
Table 1 Optimization of Reaction Conditionsa
iodide
additive
solvent
Entry
Iodide (equiv)
Additive (equiv)
Solvent
Yield (%)b
1
2
I2 (1.0)
TBAI (1.0)
NaI (1.0)
NH4I (1.0)
I2 (1.0)
I2 (1.0)
I2 (1.0)
I2 (1.0)
I2 (1.0)
I2 (1.0)
I2 (1.0)
I2 (1.0)
I2 (1.0)
P(OEt)3 (0.5)
P(OEt)3 (0.5)
P(OEt)3 (0.5)
P(OEt)3 (0.5)
PPh3 (0.5)
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
dioxane
DMSO
DMF
40
trace
trace
trace
36
3
4
5
6
PO(OEt)2 (0.5)
P(OEt)3 (0.5)
P(OEt)3 (0.5)
P(OEt)3 (0.5)
P(OEt)3 (0.5)
P(OEt)3 (0.2)
P(OEt)3 (0.5)
P(OEt)3 (0.5)
P(OEt)3 (0.5)
P(OEt)3 (0.5)
–
18
7
trace
trace
trace
51
8
9
10
11
12
13
14
15
16
17
18c
DCE
toluene
EtOH
H2O
24
trace
11
I
2 (2.0)
DCE
62
I2 (2.5)
I2 (2.0)
I2 (2.0)
I2 (2.0)
DCE
61
DCE
27
P(OEt)3 (1.0)
P(OEt)3 (1.0)
DCE
78
With the optimized reaction conditions in hand, various
styrenes have been used to investigate the scope and gener-
ality of this reaction (Table 2). It was exhilarating to find
that a range of halogenated phenylethylenes dimerized to
afford the target products in moderate to good yields under
DCE
21
a Reaction conditions: 1a (0.20 mmol), solvent (1.0 mL), reflux, 30 min.
b Yield of isolated product.
c At room temperature.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–D

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D. Wang et al.
Letter
Synlett
Table 2 Iodine-Mediated Head-to-Tail Dimerization of Alkenesa
We found that color of the reaction mixture changed
from colorless to black in the course of the experiment. We
reason that some iodine was probably regenerated when
the target products were formed. On the basis of these pre-
liminary results above, together with previous studies,6 we
proposed a plausible reaction pathway for the generation of
1,3-diarylbut-1-enes in Scheme 5. First, the initial reaction
of iodine with triethyl phosphite would lead to the forma-
tion of diethyl phosphoriodidate 3. Other iodine was polar-
ized in the presence of 3 to produce iodonium ion which
then reacts with styrene to afford carbonium ion interme-
diate 4. Subsequently, intermediate 5 was formed when 4
reacts with unreacted styrene. Then deprotonation of inter-
mediate 5 was completed to generate iodine compound 6
and hydrogen iodide in the presence of the rest iodine an-
ion. Finally, hydrogen iodide reacts with 6 to yield the cor-
responding product 2.
I2
P(OEt)3
R
R
R
DCE
Entry
R
Time (min)
Yield (%)b
1
2
H
30
30
30
30
30
30
5
2a 78
2b 68
2c 70
2d 67
2e 70
2f 66
2-Cl
3-Cl
4-Cl
4-F
3
4
5
6
4-Br
7
4-AcO
4-Me
2g 67
2h 61
2i 58
8c
9
10
5
4-t-Bu
4-NO2
MeCH2I
10
30
2j trace
I2
(EtO)2OIP I I
(EtO)2OP
I
I2
a Reaction conditions: 1 (0.20 mmol), I2 (0.4 mmol), P(OEt)3 (0.2 mmol),
solvent (1.0 mL), reflux.
P(OEt)3
+
3
I
(EtO)2OIP I I
(EtO)2OIP
b Yield of isolated product.
c I2 (0.2 mmol), P(OEt)3 (0.1 mmol).
Ph
I
Ph
Ph
Ph
Ph
4
5
I
(EtO)2OPI
I
optimized conditions
N
HI
N
N
Ph
Ph
Ph
HI
Ph
I2
2k = 4-vinyl-4H-imidazole
2l = 4-vinylpyridine
2k, trace
2l, trace
6
2
Scheme 5 Plausible reaction pathway
Scheme 3 Heterocyclic compounds as substrates
In summary, we described a novel and convenient
method for highly selective dimerization of styrenes to
yield 1,3-diarylbut-1-enes and the saturated cyclic isomer,
1,1,3-trimethyl-3-phenyl-2,3-dihydro-1H-indene in the ab-
sence of metallic catalysts.10 This alternative approach can
be used for the synthesis of chemicals widely used in poly-
mers.
Besides, we found an interesting phenomenon when 1-
methyl-1-phenylethene was used as a substrate for this
transformation, the corresponding head-to-tail dimeriza-
tion product was not observed, but 1,1,3-trimethyl-3-phe-
nyl-2,3-dihydro-1H-indene (2m) was produced (Scheme 4).
It is generally known that 2m has found wide applications,
for instance, as a photo, plasticizer, thermo stabilizer, and
so on.9 Therefore, we believe that the synthetic method pro-
vides a new approach to synthesize indan. Meanwhile, we
found that the amounts of iodine and triethyl phosphite
could be reduced to 1.0 equivalent and 0.5 equivalents, re-
spectively.
Acknowledgment
We are grateful for the financial support from the National Natural
Science Foundation of China (21302084).
Supporting Information
exact mass: 236.16
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0036-1589214.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
o
nrtogI
f
rmoaitn
I2 (1.0 equiv)
P(OEt)3 (0.5 equiv)
2m, 78%
Scheme 4 1-Methyl-1-phenylethene as a substrate
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–D

D
D. Wang et al.
Letter
Synlett
References and Notes
(7) Yue, H.-L.; Zhao, X.-H.; Jiang, L.; Shao, Y.; Mei, L.-J. Synth.
Commun. 2016, 46, 179.
(1) (a) Chin, C. S.; Won, G.; Chong, D.; Kim, M.; Lee, H. Acc. Chem.
Res. 2002, 35, 218. (b) Fagnou, K.; Lautens, M. Chem. Rev. 2003,
103, 169. (c) Shibasaki, M.; Vogl, E. M.; Ohshima, T. Adv. Synth.
Catal. 2004, 346, 1533. (d) Prajapati, D.; Gohain, M. Tetrahedron
2004, 60, 815. (e) Li, C.-J. Chem. Rev. 2005, 105, 3095.
(2) (a) Janiak, C. Coord. Chem. Rev. 2006, 250, 66. (b) Chu, C.-M.;
Huang, W.-J.; Liu, J.-T.; Yao, C.-F. Tetrahedron Lett. 2007, 48,
6881.
(8) (a) Togo, H.; Lida, S. Synlett 2006, 2159. (b) Liu, D.; Lei, A. Chem.
Asian J. 2015, 10, 806.
(9) Gerhard, M.; Yang, D.; Oskar, N. Macromol. Chem. Phys. 1994,
195, 3721.
(10) Typical Experimental Procedure for the Synthesis of Com-
pound 2a
P(OEt)3 (0.20 mmol, 33.2 mg) was added to a solution of 1a
(0.20 mmol, 20.8 mg) and I2 (0.40 mmol, 101.2 mg) in DCE (1
mL), and the reaction mixture was stirred under reflux condi-
tions for 5–30 min. After completion of the reaction, the reac-
tion mixture was diluted with EtOAc, and quenched with sat.
Na2S2O3 solution and extracted twice with EtOAc (3 × 15 mL).
The organic layer was washed with H2O and dried over anhy-
drous Na2SO4. The solvent was evaporated in vacuo, and the
residue was subjected to column chromatography using EtOAc
in PE as the eluent to afford the target compound 2a.
(E)-But-1-ene-1,3-diyldibenzene (2a)6a
(3) RajanBabu, T. V. Chem. Rev. 2003, 103, 2845.
(4) (a) Ma, H.; Sun, Q.; Li, W.; Wang, J.; Zhang, Z.; Yang, Y.; Lei, Z.
Tetrahedron Lett. 2011, 52, 1569. (b) Ho, C.-Y.; He, L. Angew.
Chem. 2010, 122, 9368. (c) Kondo, T.; Takagi, D.; Tsujita, H.; Ura,
Y.; Wada, K.; Mitsudo, T. Angew. Chem. 2007, 119, 6062.
(5) Bedford, R.-B.; Betham, M.; Blake, M.-E.; Garcés, A.; Millar, S. L.;
Prashar, S. Tetrahedron 2005, 61, 9799.
(6) (a) Ma, H.; Sun, Q.; Li, W.; Wang, J.; Zhang, Z.; Yang, Y.; Lei, Z.
Tetrahedron Lett. 2011, 52, 1569. (b) Choi, J. H.; Kwon, J. K.;
RajanBabu, T.; Lim, H. J. Adv. Synth. Catal. 2013, 355, 3633. (c) Yi,
C.; Hua, R.; Zeng, H. Catal. Commun. 2008, 9, 85. (d) Wang, C.-C.;
Lin, P.-S.; Cheng, C.-H. Tetrahedron Lett. 2004, 45, 6203. (e) Lee,
D. W.; Yi, C. S. Organometallics 2010, 29, 3413. (f) Tsuchimoto,
T.; Kamiyama, S.; Negoro, R.; Shirakawa, E.; Kawakami, Y. Chem.
Commun. 2003, 852. (g) Cai, Q.; Li, J.; Bao, F.; Shan, Y. Appl. Catal.
2005, 279, 139. (h) Wang, H.; Cui, P.; Zou, G.; Yang, F.; Tang, J.
Tetrahedron 2006, 62, 3985.
Colorless oil; yield: 16.2 mg (78%). 1H NMR (400 MHz, CDCl3): δ
= 7.37–7.18 (m, 10 H), 6.41 (d, J = 4.0 Hz, 2 H), 3.66–3.63 (m, 1
H), 1.47 (d, J = 8.0 Hz, 3 H).
1,1,3-Trimethyl-3-phenyl-2,3-dihydro-1H-indene (2m)6h
Colorless oil; yield: 18.4 mg (78%). 1H NMR (400 MHz, CDCl3): δ
= 7.28–7.11 (m, 9 H), 2.43 (d, J = 12.0 Hz, 1 H), 2.20 (d, J = 12.0
Hz, 1 H), 1.69 (s, 3 H), 1.35 (s, 3 H), 1.03 (s, 3 H).
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–D