A highly stereoselective and efficient catalytic approach for the synthesis of trans-stilbene–arenes as π-conjugated materials

Article abstract of DOI:10.1002/ejoc.201700602

The potential expansion of the variety of catalytic methods for carbon–carbon bond formation is explored in many research centers all over the world. In this work, we describe very precise and controlled catalytic transformations as useful tools for the synthesis of new trans-π-conjugated molecular organic compounds. The combination of Suzuki–Miyaura coupling and cross-metathesis reactions is established as a simple and efficient method for the design of new (E)-stilbenes in the presence of well-defined transition-metal catalysts at 0.0001–1 % loadings. All of the desired products are isolated in good-to-excellent yields (up to 96 % isolated yield) with high purity.

Full text of DOI:10.1002/ejoc.201700602

DOI: 10.1002/ejoc.201700602
Full Paper
Conjugation
A Highly Stereoselective and Efficient Catalytic Approach for
the Synthesis of trans-Stilbene–Arenes as π-Conjugated
Materials
Mariusz Majchrzak,*[a] Grzegorz Wilkowski,[a] and Maciej Kubicki[a]
Abstract: The potential expansion of the variety of catalytic coupling and cross-metathesis reactions is established as a sim-
methods for carbon–carbon bond formation is explored in ple and efficient method for the design of new (E)-stilbenes in
many research centers all over the world. In this work, we de- the presence of well-defined transition-metal catalysts at
scribe very precise and controlled catalytic transformations as 0.0001–1 % loadings. All of the desired products are isolated in
useful tools for the synthesis of new trans-π-conjugated molec- good-to-excellent yields (up to 96 % isolated yield) with high
ular organic compounds. The combination of Suzuki–Miyaura purity.
Introduction
catalyze the synthesis of trans-stilbenes from organozinc rea-
gents and carbonyl compounds have been reported.[14] Orga-
nozinc halides react with carbonyl compounds in the presence
of the palladium(II) complex PdCl2(PPh3)2 and a silylating agent
to give the corresponding (E)-stilbenes in good-to-excellent
yields under mild conditions. Other unsymmetrical (E/Z)-
stilbenes can be synthesized from vinyl acid pinacol ester deriv-
atives and several types of substituted 2-, 3-, and 4-styrenes or
allyl arenes.[15,16] The formation of carbon–carbon bonds is of
vital importance in preparative organic processes from the syn-
thesis of molecular models to macromolecular and nanomateri-
als science. Metathesis coupling reactions are exceptionally
helpful in the syntheses of compounds containing carbon–
carbon vinyl (Vi) or vinylene bonds [e.g., H2C=CH–R, H2C=CH–
(CH2)n–R, or R–HC=CH–R].[17–20] The metathesis transformations
used extensively in total synthesis include ring-closing metathe-
sis (RCM), cross-metathesis (CM), ring-opening metathesis
(ROM), and ring-opening metathesis polymerization (ROMP).
The most common catalysts used for these transformations in-
clude Schrock and Grubbs catalysts.[21–25] We previously de-
scribed the synthesis of mono- and distyryl derivatives for the
design of hybrid materials through the modification of organo-
silicon compounds.[26,27]
Highly conjugated hydrocarbons (CHCs), including polyaro-
matic hydrocarbons (PAHs) and their analogs, have attracted
much attention in recent years.[1,2] The design and synthesis of
new CHCs poses a challenge to synthetic chemists. The ob-
tained CHCs are expected to be used in advanced materials,
such as light-emitting devices and molecule-based electronics,
including field-effect transistors and lithium batteries.[3] More-
over, CHCs provide supramolecular synthons with attractive π–
π interactions.[4] Stilbene derivatives are one of the most impor-
tant groups of CHCs. They are becoming increasingly important
owing to their biological activities for the prevention of cancer
and cardiovascular diseases.[5] They are also an important family
of building blocks for the design of conjugated materials with
optical properties.[6,7] Many synthetic routes to stilbenes for use
in total synthesis have been reported. The McMurry reductive
coupling reaction is an organic reaction in which two ketone
or aldehyde groups are coupled to an alkene in the presence
of TiCl3 and a reducing agent.[8,9] Other reactions such as the
Wittig and Wittig–Horner reactions[10,11] constitute a privileged
approach for the synthesis of stilbene derivatives but they gen-
erate stoichiometric amounts of phosphine oxides and, hence,
require fastidious purification.
Herein, we present an efficient, convenient, and stereoselect-
ive method for the preparation of new π-conjugated styryl and
stilbene compounds. These arylene derivatives are synthesized
through the combination of two types of reactions, that is, a
suitably selected catalytic transformation such as a Suzuki–
Miyaura (SM) coupling and cross-metathesis (CM) catalyzed by
well-defined transition-metal complexes (Pd0 and RuII). The
combination with the CM reaction is a very useful tool for the
design of new structures. The potentially broad applications of
such a catalysis arrangement prompted us to explore the im-
pact of the catalytic method, reaction conditions, and com-
plex.
The Heck coupling reaction is also a good method for the
synthesis of stilbene derivatives.[12] It is especially important for
the synthesis of symmetrical trans-stilbenes, which can be syn-
thesized by a double Heck reaction of amines (arylazo) with
vinyltriethoxysilane.[13] Palladium catalysts that stereoselectively
[a] Faculty of Chemistry, Department of Organometallic Chemistry,
Adam Mickiewicz University in Poznań,
Umultowska 89b, 61-614 Poznan, Poland
E-mail: mariusz.majchrzak@amu.edu.pl
https://chemia.amu.edu.pl
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/ejoc.201700602.
Eur. J. Org. Chem. 2017, 4291–4299
4291
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Results and Discussion
At the beginning of our research, we focused on developing
the best, fully controlled catalytic method for the synthesis of
We were interested in studying the effect of catalytic transfor- vinylbiphenyl derivative through the Suzuki coupling of two
mations in efficient and selective syntheses of trans-stilbene de- substrate systems (4-vinylphenyl boronic acid and bromophenyl
rivatives. At the same time, we compared potential synthetic or 4-bromostyrene with phenylboronic acid; see Scheme 1, top,
routes. The first route (Scheme 1, top, Method IA and IB) was a Method IA and IB). The typical reaction system consisted of a
combination of Suzuki coupling and metathesis reactions. In 0.5
the second route (Scheme 1, bottom, Method IIA and IIB), the (2
M
solution of the styrene derivative in toluene/ethanol/base
K2CO3 or Na2CO3), the boronic acid, and a suitable palla-
M
metathesis reaction was used as the starting process, and then dium(0) catalyst [Pd(η2-dba){P(o-tolyl)3}2] (1). The molar ratio of
the Suzuki coupling was used. To map a structurally conjugated the reaction mixture was [catalyst]/[olefin]/[boronic acid] = 0.5–
stilbene system, we used several procedures to form (E)-4,4′- 1 × 10–2:1:1.01 or 0.5–1 × 10–2:1:1.05. The system was placed in
di(phenyl)stilbene (15) as a typical example (Scheme 1).
For the abovementioned reactions, we chose well-defined
air-stable 16e complexes with σ-donating and labile phosphine
ligands, namely, one palladium(0) complex (1) with bulky tris(o-
tolyl)phosphine and dibenzylideneacetone (dba) ligands and
three ruthenium(II) carbene species with tricyclohexylphos-
an oil bath at 70–85 °C for 4–24 h. A series of catalytic tests
were performed to optimize the reaction conditions for the se-
lective formation of this styryl olefin. We examined the first sys-
tem (Method IA) and determined the catalytic conditions to
obtain 4-vinylbiphenyl[28] (7) as the main product (see Table 1).
At the same time, we tested Method IB and observed a slight
phine and strong electron-donating 1,3-bis(2,4,6-trimethyl- decomposition of (OH)2B–Ph to benzene. The progress of the
phenyl)-4,5-dihydroimidazol-2-ylidene (H2IMes) ligands [Grubbs reaction was not satisfactory, although we used a 5 mol-% ex-
first-generation (2, G1), Grubbs second-generation (3, G2), and cess of boronic acid (see Scheme 1, top, B). The formation of
Hoveyda–Grubbs second-generation (4, HG) catalysts; see Fig- biphenyl as a byproduct was observed. In addition, it appeared
ure 1].
that weaker bases such as sodium carbonate resulted in the
Scheme 1. Synthetic pathways for the synthesis of stilbene derivative 15. Reaction type: SM: Suzuki–Miyaura, CM: cross-metathesis; [Pd] = [Pd(η2-dba){P(o-
tolyl)3}2] (1); [Ru=CHR] = Grubbs catalyst; [Ar] = phenyl. Reaction conditions: Method I: SM: (i) toluene/ethanol/2 aq. base solution, [styrene derivative]/[Ar
derivative]/[catalyst] = 1:1.01:0.005–0.01, T = 70–85 °C; CM: (ii) DCM, [4-vinylbiphenyl]/[catalyst] = 1:0.0001–0.01, T = 25–45 °C. Method II: CM: (i) DCM, [styrene
M
derivative]/[catalyst] = 1:0.0001–0.001, T = 25–45 °C; SM : (ii) toluene/ethanol/2
M
aq. base solution, [stilbene]/[Ar derivative]/[catalyst] = 1:2.01:0.01, T = 70–
85 °C. [a] The isolated yields [%] depended on the Grubbs catalyst.
Figure 1. Structures of well-defined Pd0 and RuII complexes.
Eur. J. Org. Chem. 2017, 4291–4299
www.eurjoc.org
4292
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Table 1. Optimization of Method I with the SM + CM catalytic arrangement.[a]
Suzuki coupling (SM)
usual catalytic system containing the olefin (7) and the selected
ruthenium(II) carbene (2, 3, or 4) in DCM (0.5
M) was used.
The molar ratio of the reactants was [catalyst]/[olefin] =
1 × 10–4–1 × 10–2:1. The system was kept at room temperature
or placed in an oil bath at 45 °C for 3–24 h and monitored by
TLC and GC–MS methods. Each test was performed under a
slow flow of argon and with dry solvent. A preliminary study of
the reaction conditions revealed that the metathesis product
was obtained quantitatively if the reaction was performed at
high temperature for at least 3 or 6 h for 0.01 and 0.001 mol-
Cat.
ViPh–[R] Ph–[R]
T/t [°C]/[h]
Conversion of Yield of
[Ar]–Br[b] [%]
7
[b] [%]
1
2
1
1
1
1
1
1
1
1
1
1
–B(OH)2 –Br
–B(OH)2 –Br
–B(OH)2 –Br
–B(OH)2 –Br
70/4
44,[c] 52[d]
67,[c] 72[d]
86,[c] 93[d]
92,[c] 99[d]
33,[c] 41[d]
57,[c] 69[d]
81,[c] 89[d]
69,[c] 89[d]
85,[c] 96[d]
94,[c] 99[d]
52
72
93
99
41
69
89
89
96
99
70/12
70/24
85/2
–Br
–Br
–Br
–Br
–Br
–Br
–B(OH)2
–B(OH)2
–B(OH)2
–B(OH)2
–B(OH)2
–B(OH)2
70/4
70/12
70/24
85/4
85/12
85/24
1
% of 3, respectively, as shown in Table 1. The MS and H NMR
spectra of 15 were analyzed carefully, and the structure of the
trans product H9C12–HC=CH–C12H9 (δ = 7.12 ppm, s, 2 H) was
complementary to that reported previously.[30] We also per-
formed the subsequent reaction by adding 0.01 mol-% of com-
plex G2 to the reaction mixture for Method IA. As a result, a
small amount of trans-stilbene (12–14 %, as confirmed by GC–
MS) was observed. Thus, it was possible to perform all of the
synthetic procedures in one flask without the isolation of the
olefin. Moreover, we tried to synthesize (E)-arylene–stilbene de-
rivatives by another catalytic route. We tested Method IIA and
IIB simultaneously and tried to define the optimum reactions
conditions (CM and SM). In the first part of our study, the cross-
metathesis of 4-bromostyrene and vinylphenylboronic acid pro-
Cross-metathesis (CM)
Cat.
Cat. conc.
[mol-%]
t [h]
Conversion of 7[b]
Yield of
15[b]
[%]
Room temp. 45 1 °C
[%]
3
4
5
2 (G1)
2 (G1)
2 (G1)
3 (G2)
3 (G2)
3 (G2)
1 × 10–2
1 × 10–3
1 × 10–4
1 × 10–2
1 × 10–3
1 × 10–4
3/6/12
3/6/12
13/31/59
14/30/43
59/65/90
57/66/89
90
89
72
99
99
93
95
83
80
3/6/12/24 10/23/31/39 33/61/72
3/6/12
3/6/12
3/6/12
3/6/12
3/6/12
3/6/12
25/58/72
27/56/68
21/54/67
21/41/60
22/38/55
18/29/33
99 (3 h)
99 (6 h)
93 (12 h)
95 (6 h)
83 (6 h)
80 (12 h)
4 (HG1) 1 × 10–2
4 (HG1) 1 × 10–3
4 (HG1) 1 × 10–4
[a] Reaction conditions: SM: [4-bromostyrene]/[(HO)2BPh] or [4-(HO)2B-styr-
ene]/[Br–Ph]/[Pd] = 1:1.01–1.05:0.005–0.01; CM: [olefin]/[Ru] = 1:0.0001–0.01,
Table 2. Optimization of the CM catalytic arrangement for Method II.[a]
DCM (0.75
M concentration of olefin). [b] Determined by GC (decane was
[c]
Method IIA: ViPh–B(OH)2
used as an internal standard: 5 vol.-%) and GC–MS methods. [c] 0.5 mol-%.
[d] 1 mol-%. Open systems, argon.
Cat.
Cat. conc.
[mol-%]
t [h]
Conversion of
ViPh-R[b] [%]
45 1 °C
Yield of
17[b] [%]
r.t.
formation of 4-vinylbiphenyl with a low productivity of 54 % at
a relatively high catalyst loading (1) of 1 mol-%. The progress
of this process was monitored by TLC and analyzed by GC and
GC–MS methods (see Supporting Information, the MS spectra
are included). This study of catalytic combinations allowed us
to confirm that the best system for the SM reaction afforded
the product olefin with a very high yield of almost 100 %
(Table 1, Entry 1, 85 °C). Next, the olefin was used for the CM
reaction to give the final product, 15. To the best of our knowl-
edge, there have been no previous reports on the CM of large
styryl derivatives with the very productive and useful Grubbs
catalysts. The substrate scope for CM has been investigated by
Grubbs and co-workers.[24,25] We know that 4-vinylbiphenyl (7)
could be classified similarly to styrene as a type II olefin (those
that undergo homodimerization) for catalysts 2 and 3.[29] At
this point of our research, we were interested in the effects of
small amounts of catalysts (2–4) and their reactivities in the CM
of 7. This olefin was chosen because of the similarity of this
system to the well-known CM of styrene and the structural simi-
larity of the final product and our arylene–stilbenes. Moreover,
this one could be separated readily from any unreacted sub-
strate in the product through ordinary SiO2 column chromatog-
raphy with hexane/dichloromethane (10:1) as the eluent. Cata-
lytic screening was performed to determine the best conditions
for the CM reaction of 7. To optimize the reaction conditions
with the respect to the catalyst loading, activity, temperature
and time, the model reaction of 7 and the Grubbs catalyst dis-
solved in dichloromethane (DCM) was used (Scheme 1). The
1
2
3 (G2)
3 (G2)
3 (G2)
3 (G2)
3 (G2)
3 (G2)
4 (HG2)
4 (HG2)
4 (HG2)
4 (HG2)
4 (HG2)
4 (HG2)
1 × 10–3
1 × 10–3
1 × 10–3
1 × 10–4
1 × 10–4
1 × 10–4
1 × 10–3
1 × 10–3
1 × 10–4
1 × 10–4
1 × 10–4
1 × 10–4
6
11
18
29
10
20
27
8
15
21
5
38
45
38
45
12
24
6
12
24
6
12
24
6
12
24
79, 81,[e] 85[f] 79, 81,[e] 85[f]
32
41
32
41
62, 69,[e] 75[f] 62, 69,[e] 75[f]
16
28
67
19
27
16
28
67
19
27
11
22
35, 59,[e] 64[f] 64[f]
Method IIB: ViPh–Br[d]
Cat.
Cat. conc.
[mol-%]
t [h]
Conversion of
Yield of
ViPh-R[b] [%]
45 1 °C
16[b] [%]
r.t.
3
4
3 (G2)
3 (G2)
3 (G2)
3 (G2)
3 (G2)
3 (G2)
4 (HG2)
4 (HG2)
4 (HG2)
4 (HG2)
4 (HG2)
4 (HG2)
1 × 10–3
1 × 10–3
1 × 10–3
1 × 10–4
1 × 10–4
1 × 10–4
1 × 10–3
1 × 10–3
1 × 10–3
1 × 10–4
1 × 10–4
1 × 10–4
6
31
50
62
33
46
58
21
41
60
17
28
45
87
99
–
81
99
–
74
81
87
99
–
81
99
–
74
81
94
41
49
83
12
18
6
12
18
6
12
18
6
12
18
92, 94[g]
41
49
71, 83[g]
[a] Reaction conditions: CM: [olefin]/[Ru] = 1:0.0001–0.001. [b] Determined by
GC (decane was used as an internal standard: 5 vol.-%), GC–MS, and 1H NMR
spectroscopy methods. [c] Toluene. [d] DCM (0.25–0.5
M concentration of
olefin). [e] 60 °C. [f] 70 °C. [g] 24 h. Open systems, argon.
Eur. J. Org. Chem. 2017, 4291–4299
www.eurjoc.org
4293
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
ceeded very effectively in high yields [85 % for the (E)-4,4′-
The system with the boronic acid derivative was more diffi-
diboronic acid stilbene derivative (17) and 99 % for (E)-4,4′-di- cult to catalyze and analyze by TLC and GC–MS than the system
bromostilbene (16)], as shown in Table 2. In many previously with 4-bromostyrene. Thus, we applied 1H NMR spectroscopy
reported examples of CM reactions, 2.5 to 10 mol-% of the typi- to confirm the structure of 4,4′-bis(boronic acid)-(E)-1,2-diphen-
cal metathesis catalyst was used.[29] In our experiments with ylethene (17). To do so, we added an appropriate amount of
the Grubbs catalysts, we tried to reduce the amount of catalyst ethane-1,2-diol to prepare in situ a sample of (E)-4,4′-di(1,3,2-
and keep the range between 0.001 and 0.0001 mol-% for the dioxaborol-2-yl)stilbene (18). The efficient condensation and
selected ruthenium(II) carbene complexes 3 and 4. For the CM cyclization processes to form the diester derivative were per-
of 4-bromostyrene (Method IIB), the best results were obtained formed at room temp. for 20 min. The trace of water was re-
for a process time of 6–12 hours at 45 °C (see Table 2, Entry 3). moved from the sample by MgSO4 (Scheme 2).
Species 3 was more active than 4, and yields of almost 99 %
In addition, we prepared the new styrene boronic ester 2-(4-
were obtained. We observed that 3 was still really effective even vinylphenyl)-1,3,2-dioxaborolane (19) as a standard to enable
1
at 0.0001 mol-% and gave a very good yield of 99 % after 12 h. the correct identification of the signals. The H NMR spectra of
We assumed that it would be possible catalyst for 4 to convert 18 and of our standard 19 matched the literature data for the
all of the substrate to the final product if the reaction time was trans-stilbene isomer:[32] δ = 7.19 [s, 2 H, –HC=CH–, Hd from the
longer. In the next experiment, we prolonged the reaction time (E)-vinylene unit], 4.39 ppm (s, 8 H, –O–CH2–CH2–O–). The spec-
to 30 h and observed almost complete conversion of the sub- tra of the styrylboronic ester (Figure 2A) and the reaction mix-
strate (99 %). As a few catalytic tests of Method IIA with DCM ture (Figure 2B) showed a very clean, gradual catalytic transfor-
as the solvent were not very successful, we changed the solvent mation to the final product. Although the reaction mixture con-
to dry toluene, which is sometimes used for CM reactions.
tained unreacted substrate and a crude product (see Table 2,
Scheme 2. Synthesis of 4,4′-bis(1,3,2-dioxaborol-2-yl)-(E)-1,2-diphenylethene (18) for 1H NMR analysis. Reaction type: CM: cross-metathesis, CC: condensation–
cyclization; [Ru=CHR] = 2, 3, or 4. Reaction conditions: CM: (i) toluene, [ViPhB(OH)2]/[catalyst] = 1:0.0005–0.01, T = 45–50 °C; CC: (ii) [stilbene(BOH2)2]/[diol] =
1:2, t = 20 min, room temp., MgSO4.
Figure 2. 1H NMR spectra of (A) 19 and (B) the reaction mixture in CDCl3 at 25 °C.
Eur. J. Org. Chem. 2017, 4291–4299
www.eurjoc.org
4294
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Scheme 3. Catalytic approach for the synthesis of 4,4′-di(phenyl)stilbene (15). Reaction type: SM: Suzuki–Miyaura; [Pd] = [Pd(η2-dba){P(o-tolyl)3}2] (1); [Ar] =
phenyl. Reaction conditions: base solution – K2CO3, KHCO3; [4-(Br- or -B(OH)2)stilbene]:[(Ar)-X or -B(OH)2]:[cat.] = 1:2.01:0.01.
Entry 1, cat. 3 after 12 h), which could be separated readily by
typical column chromatography, in most of the tests, the crude
product precipitated from the solvent, and we continued this
process in a heterogeneous system. Catalyst 3 was the most
promising an gave high CM yields for both systems. Finally,
under the optimized reaction conditions, stilbene precursors for
the Suzuki reaction catalyzed by 1 were synthesized. Further-
more, we designed a new and useful procedure for the synthe-
sis of aromatic dioxaborol derivatives. Next, we selected the
best reaction conditions and used them in preliminary tests to
obtain a simple trans isomer as the first example of the new
4,4′-di(arylene)-stilbenes (Scheme 3).
To the best our knowledge, the use of well-defined, three-
coordinate palladium catalysts consisting of tris(o-tolyl) phos-
phine and dba ligands in Suzuki–Miyaura coupling reaction has
not been reported previously. This catalytic form is usually gen-
erated in situ and participates in the polymerization reaction,[31]
and the organometallic species changes.[32,33] Furthermore, the
catalytic mixture of Pd2(dba)3 and tris(o-tolyl)phosphine is used
regularly in coupling reactions[34] to generate catalytic species
(undefined catalyst form). Two p-substituted stilbene deriva-
tives (16 and 17) were used for the catalytic screening of Suzuki
coupling catalyzed by 1. All details of the reaction conditions
are shown in Table 3. The following procedure was conducted:
1 equiv. of di(boronic acid)stilbene or dibromostilbene deriva-
tive, 2 equiv. of bromobenzene or 2.04 equiv. of phenyl boronic
Table 3. Optimization of the reaction conditions of the Suzuki coupling in the
presence of 1.[a]
(E)-Di[4-B(OH)2]stilbene (17)
T [°C]
t [h]
Conversion of
Yield of
Yield of
Ph–Br[b] [%]
byproduct[b] [%] 15[b] [%]
1
70
70
70
70
80
80
80
80
4
8
12
24
4
8
12
24
16
27
32
–
3
5
6
16
27
32
53
32
37
42
70
40, 53[c]
26
–
39
trace
6
7
42
58, 70[c]
(E)-Di(4-bromo)stilbene (16)
T [°C]
t [h]
Conversion of
Yield of
Yield of
16[b] [%]
byproduct[b] [%] 15[b] [%]
2
70
70
70
70
80
80
80
80
4
8
12
24
4
8
12
24
32
59
78
–
32
59
78
89
55
76
84
99
trace
3
5
–
84 92[c]
55
76
84
99
–
trace
trace
[a] Reaction conditions: [stilbene]/[(Ph–R)]/[Pd] = 1:2(2.01):1; toluene (0.25–
0.5
M concentration of olefin), ethanol, base. [b] Determined by GC–MS and
1H NMR spectroscopy. [c] 48 h. Open system, argon.
Through MS analysis, byproducts were identified in both sys-
tems (from trace amounts to 7 %). We know that the Br–Ci bond
is more reactive and stable than the B–Ci bond.
acid, catalyst 1 (1 mol-%), toluene (0.5
M solution), ethanol, and
K2CO3 (2 solution) were added to a typical glass system (small
M
two-neck glass reactor equipped with a reflux condenser) and
connected to a vacuum line, charged under an argon atmos-
As a result of the series of catalytic tests, a successful proce-
phere, and heated for 4–60 h at 70–85 °C to afford the final dure that ensures a highly efficient reaction pathway was devel-
product in a good yield of up to 98 % and a byproduct (3–7 %), oped. The optimized conditions for the above reactions permit-
which resulted from a homocoupling process that occurred ow- ted us to use the most effective catalytic system for the select-
ing to the trace amounts of oxygen in the system, for example, ively controlled synthesis of new stilbene materials, according
from the incomplete degassing of solvents.[35,36] Furthermore, to Scheme 4.
in a few experiments, we used another weak base, KHCO3, and
checked the progress of the catalytic transformation. In most
cases, the performance of this salt was much poorer than that
of the primary dry potassium carbonate.
We focused on the reactions with well-known complexes,
that is, [Pd(η2-dba){P(o-tol)3}2] (1) for the first step and [(Cl2)-
(IMesH2)(PCy3)Ru(CHPh)] – G2 (3) for the second one. The SM
reaction of vinylphenyl boronic acid (1.01 equiv.) with bromo-
Generally, the best results were obtained for a reaction time arene (1 equiv.) was accomplished by the typical procedure
of 24 h at 85 °C with the dibromo compound as the core mate- with palladium catalyst 1 (0.5 mol-% per Br-arene) and a bi-
rial. In this way, it was possible to achieve nearly 99 % conver- phasic solvent system of toluene (0.25–0.50
sion of 16 to (E)-di(4-phenyl)stilbene (15). the halide), ethanol (2.5 mL), and base (3.5 mL, 2
M
concentration for
solution).
M
Eur. J. Org. Chem. 2017, 4291–4299
www.eurjoc.org
4295
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
olefin was isolated and transferred to another flask, and the
CM reaction was started. It proceeded in the following way:
Styrylarene (0.178 mmol) and DCM (2–5 mL, depending on the
olefin solubility) were added to a small glass reactor. The reac-
tion mixture was warmed to 45–47 °C in an oil bath, and then
catalyst 3 (1.78 × 10–8 mol) was added, and the reaction pro-
ceeded for 24 h (up to 100 % conversion of the arylene deriva-
tive, under an argon atmosphere). Each product was isolated
by a simple method with a flush-fast filtration system or precipi-
tated from solution (DCM/hexane, CHCl3/hexane). In the pres-
ence of 3, the styrylarenes afforded stilbenes 20–26 in very
good yields, and ethylene was released as a byproduct
(Scheme 4). Furthermore, these reactions proceeded well with
smaller amounts of the catalysts, which makes them more eco-
nomical. The reaction systems were homogeneous yellowish
and pink-brown solutions, and no reduction to black palladium
or ruthenium species occurred. The reaction parameters had a
significant impact on the total control of both processes. We
assumed that the use of the catalysts would allow us to perform
1
the coupling reactions efficiently. The MS and H NMR spectra
of the reaction mixtures showed only one type of product. The
stereoselective formation of the E isomer was observed. The 1H
NMR spectrum of 22 reveals the presence of a pure stilbene
derivative (Figure 3). Signal A is attributed to the (E)-vinylene
unit (Ci–HC=CH–Ci), and signals B and C (coupling constants
8.1 Hz) are from the aromatic stilbene core (–C6H4–). During the
study, we observed that the CM reaction was slower as the
extent of the conjugated part of the olefin increased. The bulky
Scheme 4. Catalytic pathway for the synthesis of new (E)-stilbenes 20–26.
Reaction type: SM: Suzuki–Miyaura, CM: cross-metathesis; [Pd] = [Pd(η2-
dba){P(o-tolyl)3}2] (1); [Ru=CHR] = [Cl2(IMesH2)(PCy3)Ru(CHPh)] (3).
The crude mixture was extracted with DCM/H2O, and a small
amount of sodium chloride was used to disperse the slurry.
Then, the mixture was left over fresh magnesium sulfate for
approximately 4–6 h. When the process was completed, the
Figure 3. Example of the 1H NMR spectrum of 22 in CDCl3 at 25 °C.
Eur. J. Org. Chem. 2017, 4291–4299
www.eurjoc.org
4296
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Figure 4. Anisotropic ellipsoid representation of 26: ellipsoids are drawn at the 50 % probability level, and hydrogen atoms are shown as spheres of arbitrary
radii. The unlabeled part is related to the labeled one with the symmetry operation 2 – x, 1 – y, –z.
aromatic part of the resulting stilbene was responsible for the
increased reaction time. Importantly, the reaction product al-
ways precipitated from the solution, and the system became
heterogeneous even if the concentration of the main fraction
was very small. The compounds were moderately or poorly sol-
uble in conventional organic solvents [DCM, tetrahydrofuran
(THF), CHCl3, toluene (hot), or dimethyl sulfoxide (DMSO)]. The
solid-state structure of 26 was determined by X-ray crystallogra-
Figure 5. A fragment of the crystal structure of 26; the blue lines denote
weak C–H···π contacts.
phy (Figure 4).
To the best of our knowledge, this is the first crystallographic
characterization of a stilbene–ferrocene derivative.
pounds 20–26 were synthesized in yields of almost 97 %. The
reported procedures ensure the efficiency of both reactions.
Furthermore, they allow the reactions to proceed without the
formation of unwanted polymeric materials, which can form
through the thermal radical polymerization of the vinyl group.
Therefore, there was no need to use any polymerization inhibi-
tors in these systems, as the optimal amount of reagents and
mild reaction conditions prevented the formation of polymeric
side-products.
X-ray Structure
The molecule is Ci-symmetrical, and the center of inversion lies
at the middle point of the central C=C double bond (Figure 4).
The cyclopentadienide (Cp) rings are almost parallel [di-
hedral angle 2.8(2)°], and the central –Ph–HC=CH–Ph– linker is
planar (the phenyl planes are parallel owing to symmetry de-
mands) and only slightly inclined with respect to the Cp ring
[dihedral angle 11.3(2)°]. The Fe–C distances are typical and al-
most equal [mean value 2.049(9) Å], and the length of the cen-
tral bond [1.333(6) Å] proves its double-bond character. In the
crystal structure there are some relatively short C–H···π con-
tacts, which are probably weak hydrogen bonds (see Table 4
and Figure 5).
Conclusions
This is the first report of a selective method for the effective
synthesis of (E)-arylene stilbenes consisting of differently sized
aromatic parts without (20–23) or with heteroatoms [such as
sulfur (24) and nitrogen (25)] or a metallocene (26). Complex 1
is an efficient homogeneous catalyst in the Suzuki coupling of
vinylphenyl boronic acid with bromoarenes. We have presented
a highly selective method for the synthesis of new π-conju-
gated olefins (8–14), which were obtained in high yields (81–
96 %) and selectivities (>99 %). The 1H NMR spectroscopy analy-
sis confirms the quantitative formation of the E geometry of
the resulting vinylene bond between the two phenyl rings. The
cross-metathesis reactions of styryl derivatives (7–14) to afford
trans-stilbenes was successfully performed at significantly re-
duced catalyst loadings for the Pd0 (1, 0.5 mol-%) and RuII cata-
lysts (3, 0.0001 mol-%). The final organic materials can be read-
ily isolated and purified. The combination of Suzuki coupling
Table 4. Distances [Å] and angles [°] for weak C–H···π contacts; Cg1, Cg2, and
Cg3 are the centroids of the C1···C5, C6···C10 and C11···C16 rings, respec-
tively.[a]
D
H
A
D–H
H···A
D···A
D–H···A
C15
C7
H15
H7
Cg1i
Cg2ii
Cg3iii
0.95
0.95
0.95
2.70
3.07
3.00
3.608(6)
3.891(6)
3.773(6)
161
146
139
C13
H13
[a] Symmetry codes: (i) x, 3/2 – y, –1/2 + z; (ii) 1 – x, 1/2 + y, 1/2 – z;
(iii) 2 – x, –1/2 + y, 1/2 – z.
These hydrogen-bond interactions result in the assembly of
the molecules into sandwich-type structures, and one of the
interfacing layers can be placed perpendicular to the other two.
Thus, these interactions are responsible for the arrangement and cross-metathesis is a very convenient synthetic route and
of the ferrocenyl–stilbene molecules into layers. All of the led to the design of a powerful and fully controlled synthetic
styrylarenes and (E)-stilbenes were isolated and characterized tool. The methodology presented in this article opens up the
spectroscopically. In this way, new π-conjugated organic com- possibility to synthesize a new class of E-π-conjugated organic
Eur. J. Org. Chem. 2017, 4291–4299
www.eurjoc.org
4297
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
at 45 °C, and Grubbs catalyst (3 or 4; 1 × 10–3-1 × 10–4 mol) was
added (previously dissolved in DCM). The reaction progress was
monitored by TLC (eluent: DCM/hexane 5:1, Rf = 0.40–0.60 in rela-
tion to biphenyl), GC (decane was used as an internal standard: 5
vol.-%), GC–MS, or NMR spectroscopy. The structures of the 4,4′-
di(substituted)stilbenes (15 and 16) were identified and confirmed
by 1H NMR spectroscopy and MS (for the analytic data, see the
Supporting Information).
compounds. On the basis of the obtained results, we are focus-
ing on the development of promising materials with interesting
optoelectronic and thermal properties.
Experimental Section
Instruments and Analysis: The 1H (300, 400, 600 MHz) and 13C
NMR (75, 101, 150 MHz) spectra were recorded with a Varian XL
300 MHz spectrometer, a Varian VNMR-S 400 MHz spectrometer,
and a Varian 600 MHz spectrometer with samples in CDCl3 and
CD2Cl2 solutions. The chemical shifts are reported in ppm and were
referenced to the residual solvent signals (CDCl3: δH = 7.26 ppm,
δC = 77.36 ppm; CD2Cl2: δH = 5.32 ppm, δC = 53.52 ppm). GC analy-
ses were performed with a Varian Star 3400CX instrument with a
DB-5 fused silica capillary column (30 m × 0.15 mm) and a thermal
Supporting Information (see footnote on the first page of this
article): general synthetic procedures and characterization for 5–19,
1H and 13C NMR spectra, MS spectra.
Acknowledgments
We gratefully acknowledge financial support from the National
conductivity detector (TCD). The mass spectra of the substrates and Centre of Research and Development NCBiR, Poland, Project
products were obtained by GC–MS analysis (Varian Saturn 2100 T)
with a CP-SLI 6CB capillary column (30 m × 0.25 mm) and an ion-
trap detector. HRMS was performed with an AMD-402 mass spec-
trometer. Elemental analysis was performed with a Vario EL Elemen-
tar (Germany) elemental analyzer. The melting points were deter-
mined with a MPA120 EZ-Melt automated melting point apparatus
from Stanford Research Systems [temperature resolution 0.1 °C; Pt
resistance temperature detector (RTD)]. TLC was performed with
precoated plates (plastic sheet with 250 μm thick silica gel; Poly-
gram SilG/UV254, ROTH), and column chromatography was con-
ducted with silica gel 60 (70–230 mesh, Fluka).
PBS2/A5/40/2014.
Keywords: Homogeneous catalysis · Conjugation · Synthesis
design · Cross-coupling · Metathesis
[1] J. C. Fetzer, Chemical Analysis Vol. 158: Large (C ≥ 24) Polycyclic Aromatic
Hydrocarbons: Chemistry and Analysis, Wiley Interscience, New York,
2000.
[2] M. D. Watson, A. Fechtenkötter, K. Müllen, Chem. Rev. 2001, 101, 1267–
1300.
CCDC 1497642 (for 24) contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre.
[3] A. C. Grimsdale, J. Wu, K. Müllen, Chem. Commun. 2005, 2197–2204.
[4] M. J. MacLachlan, Pure Appl. Chem. 2006, 78, 873–888.
[5] D. Simoni, M. Roberti, F. P. Invidiata, E. Aiello, S. Aiello, P. Marchetti, R.
Baruchello, M. Eleopra, A. Di Cristina, S. Grimaudo, N. Gebbia, L. Crosta,
F. Dielli, M. Tolomeo, Bioorg. Med. Chem. Lett. 2006, 16, 3245–3248 and
references therein.
[6] B. Nohra, S. Graule, C. Lescop, R. R. Au, J. Am. Chem. Soc. 2006, 128,
3520–3521.
[7] A. Kraft, A. C. Grimsdale, A. B. Holmes, Angew. Chem. Int. Ed. 1998, 37,
402–428; Angew. Chem. 1998, 110, 416.
[8] J. E. McMurry, M. P. Fleming, J. Am. Chem. Soc. 1974, 96, 4708–4709.
[9] M. Ephritikhine, Chem. Commun. 1998, 2549–2554.
[10] O. H. Wheller, N. Battle de Pabon, J. Org. Chem. 1965, 30, 1973–1976.
[11] P. Rajakumar, M. Dhanaseharan, S. Selvam, Synthesis 2006, 8, 1257–1262.
[12] K. Ferré-Filmon, L. Delaude, A. Demonceau, A. F. Noels, Coord. Chem. Rev.
2004, 248, 2323–2336.
[13] S. Saumitra, K. S. Subir, Org. Synth. 2004, 10, 263–268.
[14] J.-X. Wang, K. Wang, L. Zhao, H. Li, Y. Fu, Y. Hu, Adv. Synth. Catal. 2006,
348, 1262–1270.
[15] Ch. B. Baltus, I. S. Chuckowree, N. J. Press, I. J. Day, S. J. Coles, J. Spencer,
G. J. Tizzard, Tetrahedron Lett. 2013, 54, 1211–1217.
[16] R. Hemelaere, F. Caijo, M. Mauduit, F. Carreaux, B. Carboni, Eur. J. Org.
Chem. 2014, 3328–3333.
General Procedure for the Catalytic Screening of the Suzuki
Cross-coupling – Methods IA and IB: A mixture of 4-bromostyrene
or bromobenzene (0.5 mmol), 4-vinylphenylboronic acid or phenyl-
boronic acid (0.505–0.525 mmol), 2
K2CO3 or Na2CO3 depending on the combination of substrate), eth-
anol (0.75 mL), toluene (0.5 solution concentration for bromo-
M aq. base solution (1 mmol of
M
arene), and 1 (0.5–1 mol-%) was placed in a two-neck glass reactor
equipped with a magnetic stirring bar and a reflux condenser. The
suspension was degassed and heated in an oil bath at 70 or 85 °C
for 2–24 h. The reaction progress was monitored by TLC (eluent:
hexane/DCM or CHCl3 10:1, Rf = 0.52 in relation to biphenyl), GC
(decane was used as an internal standard: 5 vol.-%), and GC–MS.
The 4-vinylbiphenyl structures were identified and confirmed by MS
and NMR spectroscopy.
General Procedure for the Catalytic Screening of Cross-metath-
esis (CM) – Method I: 4-Vinylphenyl (7, 45 mg, 0.25 mmol) and
DCM (0.25
M solution, 1 mL) were added to a two-neck glass reactor
[17] K. Ferré-Filmon, L. Delaude, A. Demonceau, A. F. Noels, Eur. J. Org. Chem.
2005, 3319–3325.
[18] V. J. Ritter, S. Lex, J. Schmalz, H.-G. Schmalz, Synthesis 2006, 273–278.
[19] B. Schmidt, S. Krehl, S. Hauke, J. Org. Chem. 2013, 78, 5427–5435.
[20] B. Schmidt, N. Elizarov, R. Berger, F. Hölter, Org. Biomol. Chem. 2013, 11,
3674–3691.
equipped with a magnetic stirring bar and reflux condenser and
connected to a vacuum line under Ar. Then, the system was heated
to 45 °C, and Grubbs catalyst (2, 3, or 4; 1 × 10–2–1 × 10–4 mol) was
added (previously dissolved in DCM). The reaction progress was
monitored by TLC (eluent: DCM/hexane 5:1, Rf = 0.40–0.60 in rela-
tion to biphenyl), GC (decane was used as an internal standard: 5
vol.-%), GC–MS, or NMR spectroscopy. The structure of 15 was iden-
tified and confirmed by NMR spectroscopy and MS.
[21] H.-G. Schmalz, Angew. Chem. Int. Ed. Engl. 1995, 34, 1833–1836; Angew.
Chem. 1995, 107, 1981.
[22] N. Bajwa, M. P. Jennings, Tetrahedron Lett. 2008, 49, 390–393.
[23] R. R. Schrock, Tetrahedron 1999, 55, 8141–8153.
[24] P. Schwab, M. B. France, J. W. Ziller, R. H. Grubbs, Angew. Chem. Int. Ed.
Engl. 1995, 34, 2039–2041; Angew. Chem. 1995, 107, 2179.
[25] M. S. Sanford, J. A. Love, R. H. Grubbs, J. Am. Chem. Soc. 2001, 123, 6543–
6554.
General Procedure for the Catalytic Screening of Cross-metath-
esis (CM) – Methods IIA and IIB: 4-Bromostyrene or 4-vinylphenyl-
boronic acid (0.5 mmol) and DCM (0.5
M solution, 1 mL) or toluene
(0.5 solution, 1 mL) were placed in a two-neck glass reactor
M
equipped with a magnetic stirring bar and reflux condenser and
connected to a vacuum line under Ar. Then, the system was heated
[26] M. Majchrzak, M. Grzelak, B. Marciniec, Org. Biomol. Chem. 2016, 14,
9406–9415.
Eur. J. Org. Chem. 2017, 4291–4299
www.eurjoc.org
4298
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
[27]
[33] G. Zeni, A. L. Braga, H. A. Stefani, Acc. Chem. Res. 2003, 36, 731–738 and
references cited therein.
[34] B. Zimmermann, W. I. Dzik, T. Himmler, L. K. Goossen, J. Org. Chem. 2011,
M. Majchrzak, S. Kostera, M. Grzelak, B. Marciniec, M. Kubicki, RSC Adv.
2016, 6, 39947–39954.
[28]
[29]
Y. Liu, J. Q. Wang, Synth. Commun. 2009, 40, 196–205.
76, 8107–8112.
A. K. Chatterjee, T. L. Choi, D. P. Sanders, R. H. Grubbs, J. Am. Chem. Soc.
2003, 125, 11360–11370.
[35] C. Adamo, C. Amatore, I. Ciofini, A. Jutand, H. Lakmini, J. Am. Chem. Soc.
2006, 128, 6829–6836.
[36] M. Moreno-Manñas, M. Perez, R. Pleixats, J. Org. Chem. 1996, 61, 2346–
[30] C. K. Chien, H. C. Wang, M. Szwarc, A. J. Bard, K. Itaya, J. Am. Chem. Soc.
1980, 102, 3100–2104.
[31] J. Murage, J. W. Eddy, J. R. Zimbalist, T. B. McIntyre, Z. R. Wagner, F. E.
Goodson, Macromolecules 2008, 41, 7330–7338.
2351.
[32] F. Paul, J. Patt, J. F. Hartwig, Organometallics 1995, 14, 3030–3039.
Received: May 1, 2017
Eur. J. Org. Chem. 2017, 4291–4299
www.eurjoc.org
4299
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim