Room-temperature and transition-metal-free Mizoroki-Heck-type reaction. Synthesis of E-stilbenes by photoinduced C-H functionalization

Article abstract of DOI:10.1021/jo501474w

We report a conceptually different approach toward E-stilbene syntheses by photoinduced direct C-H arylation of alkenes at rt without the addition of transition metals, with a broad range of aryl halides, including ArI, ArBr, and even ArCl. This is the first time that this reaction has been produced without extra solvent but with 18-crown-6 ether and t-BuOK in only 15 min of reaction.

Full text of DOI:10.1021/jo501474w

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Article
Room Temperature, Solvent and Transition-Metal-Free Mizoroki-Heck-Type
Reaction. Synthesis of E-Stilbenes by Photoinduced C-H Functionalization
Javier Fernando Guastavino, María Eugenia Budén, and Roberto Arturo Rossi
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo501474w • Publication Date (Web): 03 Sep 2014
Downloaded from http://pubs.acs.org on September 4, 2014
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Room Temperature and Transition-Metal-Free Mizoroki-Heck-Type Reaction.
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Synthesis of E-Stilbenes by Photoinduced C-H Functionalization.
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Javier F. Guastavino, María E. Budén, and Roberto A. Rossi*
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INFIQC, Departamento de Química Orgánica. Facultad de Ciencias Químicas. Universidad
Nacional de Córdoba, X5000HUA Córdoba. Argentina.
CORRESPONDING AUTHOR FOOTNOTE
e-mail: rossi@fcq.unc.edu.ar
TOC
ABSTRACT
A conceptually different approach toward E-stilbene syntheses by photoinduced direct C-H
arylation of alkenes at rt without the addition of transition metals, with a broad range of
aryl halides, including ArI, ArBr and even ArCl. This is the first time that this reaction has
been produced without extra solvent but with 18-crown-6 ether and t-BuOK in only 15 min
of reaction.
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INTRODUCTION
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Stilbene-based compounds have become of particular interest to chemists because of their
broad range of different biological activities.1, 2 For example, trans-Resveratrol1a, 3 (1,
Figure 1) has been shown to possess antioxidative, anticarcinogenic, and antitumor
properties. Piceatannol (2, Figure 1) is a biologically active molecule that naturally occurs
in several plants. This molecule is a powerful antioxidant and it exhibits much higher
antioxidant activity than 1.4 Furthermore, Piceatannol can suppress proliferation of a
variety of tumor cells, including leukemia, lymphoma, and melanoma.5 Tamoxifen6 (3,
Figure 1) currently being used in the treatment of several types of breast cancer.
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OH
OH
OH
HO
HO
NMe2
OH
OH
O
1
2
3
Figure 1. Structures of trans-Resveratrol (1), Piceatannol (2) and Tamoxifen (3).
Although stilbenes can be obtained by different reactions and transformations, the
most commonly used are Wittig reactions,7 metal-catalyzed cross-coupling reactions,8 the
Meerwein reaction9 or Mc-Murry couplings,10 Horner-Wadsworth-Emmons (HWE
reactions),11 among others.2 Nevertheless, the use of Mizoroki-Heck8, 12 and Heck-Matzuda
reactions13 to obtain E-stilbenes, seems to be the most promising.
Contrary to majority of modern methods of synthesis do not need transition metal
catalysis so the products can be directly used in pharmaceutical and other industries.
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Transition-metal free coupling reactions offer an inexpensive, yet efficient route to C-C
bond formations, since transition metal catalysts and impurities can be avoided. This area
has been an important development in the last few years,14 as examples applied to stilbenes
synthesis In 2011, it was reported that t-BuO- anion promoted direct arylation with ArX of
different stilbenes (5 equiv) in the presence of 20% mol of EtOH as additive in DMF at
80ºC giving same outcome that the transition-metal Mizoroki-Heck reaction (Scheme 1, eq
1).15 In a similar sense the olefination reaction proceeded in the presence of t-BuOK and a
catalytic amount of bathophenanthroline in benzene as the solvent at 110ºC for 36 hours
(Scheme 1, eq 2).16 This methodology was also applied to the construction of several
benzofurans in an intramolecular reaction of allyl 2-halophenyl ethers in the presence of
1,10-phenanthroline in mesitylene, although a higher reaction temperature was necessary
(eq 3).17
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Shirakawa and co-workers
t-BuOK (3 equiv)
EtOH (0.2 equivl)
Ar1
55-74 %
Ar1-X
+
Ar2
Ar2
(1)
DMF, 80 ºC, 2-6 h
5 equiv
Shi and co-workers
Ar2
t-BuOK (3 equiv)
bathophen (0.3 equiv)
Ar3
Ar2
Ar1-X
+
(2)
Ar1
Ar3
Benzene, 110 ºC, 36 h
3 equiv
41-90 %
Rueping and co-workers
O
t-BuOK (3 equiv)
1,10-Phen (0.4 equiv)
O
Ar1
(3)
Ar1
Ar2
Mesitylene, 160 ºC, 2 h
Ar2
X
34-68%
Scheme 1. Transition-metal-free Mizoroki-Heck-type reaction.
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In this reaction the ArX (4) is activated by electron transfer (ET) reaction to
generate a radical anion 5 which fragments to aryl radical (Ar.) and the X- anion. The
addition of aryl radical to styrene derivates (6) provide a benzylic radical intermediate 7,
which by deprotonation by the t-BuO- anion form the radical anion of the stilbene derivate
8. A subsequent ET generates the E-stilbene derivative 9 and a new 5 thereby continue the
chain process (Scheme 2).
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Ar
4
ArX ( )
Ar1
9
ET
4
ArX
X
Ar
5
Ar1
8
Ar
t-BuOH
Ar
t-BuOK
H
Ar1
Ar1
7
6
Scheme 2. Mechanisms of Mizoroki-Heck-type reaction mediated by t-BuOK.
Transition metal free coupling reactions was intensively studied and used efficiently
in biaryl construction by base-promoted Homolytic Aromatic Substitution (BHAS).18, 19, 20
However, to difference of BHAS, the synthesis of stilbenes by Mizoroki-Heck-type
reaction has not been extensively investigated15-17 and has not development new synthetic
protocols or applications since 2011. Given the importance of these compounds, we believe
research for development of efficient methods is a great challenge.
Recently, we reported biaryl syntheses by photoinduced21 direct C-H arylation of
benzene and thiophene in the presence of t-BuOK.22 Particularly noteworthy was the fact
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that this protocol worked at rt with only a base and light being necessary. Taking this into
account, we speculated that this methodology could also be applicable to alkenes 6, which
would provide a very promising approach for a clean, efficient, and cheap synthesis of
stilbenes moieties 9 from different ArX (4) (eq 4).
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R1
H
Ph
R
R1
Ar
Ph
R
ν
t-BuOK, h
+
Ar-X
(4)
DMSO, rt
4
6
9
RESULTS AND DISCUSSION
Applying the above hypothesis, the reaction of 4-iodoanisole (4a) with styrene (6a), 3
equiv t-BuOK in DMSO under photostimulation21 for 1.5 hours gave 67% (61% of E
isomer) of 4-methoxystilbene 9-aa (Table 1, entry 1), with the same result being obtained
in the presence of 10 equiv of 6a (Table 1, entry 2). In contrast, a lower yield with a low
conversion was observed when the reaction was carried out with only 1 equiv of t-BuOK
(30% of 9-aa, entry 3) or with a lower amount of DMSO (entry 4). Furthermore, the use of
THF, pyridine, dioxane, dimethoxyethane solvents, did not afford any 9-aa. However, in
DMF the reaction proceeded, but a longer reaction time was required (entries 5 and 6 for
4a, and entries 10 and 11 for 4-iodotoluene (4b)). This trend was observed for different
substrates, so we believe that DMSO is the most suitable solvent for this methodology
although both solvents were investigated.23 It is worth nothing that, in contrast with thermal
reaction,15 a low yield of stilbene was observed when EtOH (20 mol%) was used, which
have lower basicity (pKa 29.8) and is more hydrogen-atom donor than t-BuOK (pKa
32.2).24 In this regards, when 4b reacted with 6a in DMF, 50% of 9-ba were obtained while
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in presence of EtOH (20 mol%) the stilbene 9-ba were afforded in only 35% yield (entries
5
6
11 and 12).
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Table 1. Photostimulated reaction of 4a-4b and 6a.a
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I
Ph
t-BuOK (3 equiv)
+
Ph
R
ν
h , solvent,
rt, 1.5 h
R
4a,
6a
9-aa
(R=OMe)
R=OMe
4b, R=Me
9-ab (R= Me)
recovered
yield of
4a-bb (%)
4a (4)
yield of 9aa-ab c
(yield of E)d
Entry
Conditions
I- %e
1
DMSO
67 (61)
66 (57)
30 (21)
33 (30)
(30)
86
90
52
58
44
81
8
2f
3
DMSO
DMSO, 1 equiv t-BuOK
DMSO
4 f,g
(39)
5
DMF
6
DMF, 5 h
64 (51)
4
7
DMSO, 30% mol TEMPO
DMSO, 30% mol m-DNB
8
(62)
8 (7)
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9f
DMSO, dark
17 (16)
(74)
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89
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4b
DMSO, 1h
DMF, 5h
(50)
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DMF, 5h, 20% mol EtOH
(35)
a
The photostimulated reaction was carried out under an N2 atmosphere using 4a-4b (1
equiv, 0.5 mmol), t-BuOK (3 equiv), 6a (5 equiv) with 1 mL of solvent in a sealed tube for
b
1.5 hours. Yields of recovered 4a-b were determined by GC (internal standard method).
cYields of 9-aa or 9-ba were determined by GC and corresponding to Z and E isomers.
d
Yields were determined by GC. I- anions were determined potentiometrically. With 10
e
f
equiv of 6a. g 0.5 mL of DMSO was used.
We suggest that the formation of aryl radicals and radical anions were the key steps
(Scheme 2), which was supported by the results of the experiments performed in the
presence of the radical scavenger TEMPO and the good electron acceptor m-dinitrobenzene
(m-DNB) that inhibited the reaction (Table 1, entries 7 and 8). In addition this reaction
occurs in very low yield in dark conditions (entry 9).
The substrate scope for this reaction was examined, with the best results obtained
with method A being shown in Scheme 3.23 PhI and ArI with electron-donating groups
(EDG) in the para position (OMe, Me, Ph) underwent the coupling with 6a in good or very
good yields (see 9-aa, 9-ba, 9-ca and 9-fa). However, a slight prolonged reaction time was
necessary for orto-substituted ArI (9-da and 9-ea). In addition, the reaction of the ArI with
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electron-withdrawing groups (EWG) (F and CF3) gave the stilbenes 9-ga and 9-ha in
regular yields. When aryl radical had an EWG, it was converted into arene, probably
through further reduction to aryl anions or by H-abstraction from the solvent. Similar
results were obtained for the 1- and 2-naphthyl system to afford 9-ia and 9-ja stilbenes. In
contrast, the addition of dimsyl anion to alkene was observed when 1,1-diphenylethylene
6b, cis-stilbene 6c and α-methylstyrene 6d were employed, and stilbenes 9-cb, 9-bc, 9-bd
and 9-ad being obtained in regular yields. It should be noted that in these cases a high
conversion was found, despite the product yields being moderated. To investigate if these
problems could be overcome we decided to study this reaction without any solvent.
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Scheme 3. Direct arylation of 4a-k with alkenes 6a-d.a
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R
R
t-BuOK (3 equiv)
Ar1
X-
+
Ar1-X +
ν
h , rt
Ph
Ph
Method A or B
R1
6a
6b
R1
4 a-k
9
1
, R= R =H
1
, R= Ph, R =H
6c, R= H, R1= Ph
6d, R= Me, R1= H
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Method A: 1 equiv Ar1X, 5 equiv of6, 3 equiv of t-BuOK in DMSO (1 mL)
Method B: 1 equiv Ar1X, 10 equiv of 6, 3 equiv of t-BuOK and 3 equiv 18-crown-6 ether(15 min)
MeO
OMe
Ph
Ph
Ph
Ph
9-da
9-aa
9-ba
9-ca
A, 25% (I-= 97%), 5 h
B, 64% (I-= 84%), 30 min
A, 61% (I-= 86%), 2 h A, 74% (I-= 89%), 1.5 h A, 59% (I-= 94%), 2 h
B, 87% (I-= 95%)
B,b 64% (I-= 70%)
B, 79% (I-= 82%)
Me
Ph
F
F3C
Ph
Ph
Ph
Ph
9 ea
9-fa
9-ga
9-ha
A, 73% (I-= 100%), 2.5 h A, 53% (I-= 92%), 2 h A, 48% (I-= 98%), 2 h A, 24% (I-= 98%), 1.5 h
B, 55% (I-= 78%)
B, 71% (I-= 98%)
B, 65% (Br-= 92%)
B, 46% (I-= 93%)
B, 30% (I-= 80%), 30 min
N
Ph
Ph
Ph
Ph
Ph
9-ia
9-ja
9-ka
9-cb
A, 47% (I-= 94%), 2 h A, 26% (Br-= 94%), 2.5 h A, 10% (Cl-= 75%), 1.5 h A,* 20% (I-= 31%), 5 h
B, 54% (I-= 91%)
B, 62% (Br-= 99%)
B, 71% (Cl-= 94%), 1h
B, 75% (Br-= 95%)
B, 53% (Cl-= 84%), 1h
B, 69% (I-= 75%), 2h
* in DMF
Me
MeO
Me
Me
Me
Ph
Ph
Ph
9-bc
9-bd
9-ad
Ph
A, 27% (I-= 86%), 2 h A, 25% (I-= 78%), 2 h
B, 45%c (I-= 92%) B, 65% (I-= 91%)
A, 26% (I-= 86%), 2 h
B, 82% (I-= 97%)
a These reactions were carried out under an N2 atmosphere of 4 in the presence of alkene 6
and t-BuOK under photostimulation in a sealed Schlenk tube. Yields of E isomer were
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determined by GC (internal standard method). Z isomer was detected (low yield) in all
reactions but was not quantified. b In 1 mL benzene as the solvent. c Yield of E + Z isomer.
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When the reaction without solvent was carried out (entry 1, Table 2), the product 9-
aa was not found, probably due to the insolubility of the base in the reaction media. To
overcome this, we explored the reaction in presence of different ligands such as diglyme
and 1,10-phenathroline (entries 2 and 3), but unlike reported methodology (Scheme 1, eq 2
and 3) no reaction took place under this condition. The breakthrough came when we used
18-crown-6 ether (18-C-6) (3 equiv) for coordinating the potassium cation. In this case, the
reaction provided stilbene 9-aa in 76% yield (entry 4, Table 2). It is proposed that 18-C-6
coordinated the potassium cation, which suppresses ion-pairing in t-BuOK salt. In this
condition, the free anion t-BuO- could be act as an electron donor. It is known that t-BuOK
can form radical anion type 5 by ET in photostimulated SRN1 reactions, which can start the
chain process.25
Then, a screening of equivs of t-BuOK, 18-C-6, and alkene, and the reaction time
was carried out (entries 5-8, Table 2),26 with the best result being obtained in the
photostimulated reaction of 4a (1 equiv) with 6a (10 equiv), t-BuOK (3 equiv) and 18-C-6
(3 equiv), which after 15 minutes gave a 90% yield of 9-aa (87% of E isomer 9-aa, entry 8,
Table 2). It is noteworthy that the amount of alkene or base can be lowered but the yields of
9-aa was slightly lower.
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Table 2. Photostimulated reaction of 4a and 6a in the presence of 18-C-6 ether.a
5
6
7
8
9
reaction
time
yield 9-aa
(yield E)b
--
equiv equiv
Entry
Conditions
I- %c
6a
18-C-6
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1
5
--
--
--
3
2h
6
2
10
10
5
15 min
15 min
2h
Diglyme, 3 equiv
--
<4
<4
94
76
79
80
95
66
24
11
96
3
1,10-Phenantroline, 3 equiv
--
4
76 (72)
64 (51)
76 (73)
73 (71)
90 (87)
(59)
5d
6
5
1.5
3
2h
5
45 min
15 min
15 min
15 min
15 min
15 min
15 min
7
5
3
8
10
10
10
10
10
3
9
3
Dark
10
11
3
Dark, 30% mol TEMPO
Dark, 30% mol m-DNB
Dark, 50 °C
--
3
--
12
3
(52)
a
The photostimulated reaction was carried out under an N2 atmosphere using 4a (1 equiv,
b
0.5 mmol), t-BuOK (3 equiv), 18-C-6 (3 equiv) and 6a without solvent in a sealed tube.
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c
Yields were determined by GC (internal standard method). I- ions were determined
5
6
potentiometrically. d With 1.5 equiv of t-BuOK.
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8
In the reaction of 4a with 6a in the dark (entry 9, Table 2), the product 9-aa was
surprisingly obtained in 59 % yield. The conversion under this reaction condition was not
complete (66% of I- ions being found) even at long reaction times (48 h, results not
tabulated). One possibility is that the initiation step is via benzyne intermediate.27 It is
known that t-BuOK can react with PhI to form benzyne 10 (eq 5).28 This intermediate
undergo reactions with alkenes to yield a diradical 11,29 which then by hydrogen atom
abstractions gives a benzylic radical intermediate 7 which continue the chain process
(Scheme 2). Radicals and radical anions were intermediates for this mechanism, due to the
dark reaction being inhibited in the presence of TEMPO and m-DNB (entries 10 and 11,
Table 2). On the other hand, in dark conditions spontaneous or thermal ET from t-BuOK to
ArI 25,30 cannot be ruled out as initiation steps.
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Ph
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t-BuOK
Ph
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H-abstraction
(5)
t-BuOH + KI
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To investigate if the arylation of alkenes could effectively be promoted in absence
of the photostimulation, we decided to study the reaction at 50°C (entry 12). For these
conditions, although the conversion was complete (96% of I- ion being found), the yields of
9-aa remained unchanged with the two regio-isomers 3- and 4-methoxy-1-(tert-
butoxy)benzene products, being observed at similar ratios, which were probably formed by
benzyne intermediate. Theses outcome show that the light catalyzed the reaction, thereby
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allowing it to be completed in only 15 minutes, probably due to that the light is favoring ET
process over benzyne intermediate formation, increased the yields of stilbene. However, the
generation of stilbene under this thermal condition opens up possibilities to further
investigation to develop the stilbene synthesis from ArX and alkenes in metal free
conditions at rt (entry 9).31
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To explore further this strategy in the presence of 18-C-6 ether, several ArX were
subjected to the optimized conditions to afford the E-stilbene products, with the best results
obtained being shown in Scheme 3 (Method B, without solvent at rt). Using this
methodology, orto and para substituted ArI with EDG reacted with 6a in good to very
good yields (55-87 % yields). Once again, the reaction of ArI with EWG gave the E-
stilbene products in regular yields (46 % for 9-ga and 30 % for 9-ha). It should also be
noted that strong EWG in the ArI (e. g. associated CF3 group) were ineffective substrates in
Shirakawa protocol.15 Moreover, not only ArI, but also ArBr and even ArCl underwent
coupling when the organic moiety had an extended π–system, as biphenyl, quinolyl or 1- or
2-naphthyl group providing good to very good yields (53-75% of stilbenes 9-fa, 9-ka, 9-ia
and 9-ja). Finally, when other alkenes were tested, the trisubstituted E-stilbenes 9-cb, 9-bc,
9-bd and 9-ad were obtained in good to very good yields (45-82%).
CONCLUSIONS
In summary, we have developed a novel approach toward the stilbene syntheses,
solvent and metal-free photoinduced direct C-H functionalization at rt. This
environmentally friendly methodology effectively promoted the arylation of the unactivated
alkenes, such as 6a-d, using a broad range of ArI. Both, ArBr and ArCl, react when the
organic moiety had an extended π-system. In all cases, a high regio-selectivity was found
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with E-stilbenes being formed as main products. On the basis of these results, a plausible
chain mechanism via ET with radicals and radical anions as intermediates for this
photoinduced reaction is proposed. However in dark conditions, possibly, species generated
from the benzyne intermediate could be operating in the initiation step. Further
investigations to expand this novel method to a broad number of substrates are currently
underway in our laboratory.
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EXPERIMENTAL SECTION
General Methods: Gas chromatographic analyses were performed using a gas
chromatograph with a flame ionization detector, and equipped with the following columns:
HP1 25 m x 0.20 mm x 0.25 μm column and VF-1 ms, 15 m x 0.25 mm x 0.25 μm column.
1H NMR (400.16 MHz), 13C NMR (100.63 MHz), spectra were obtained in CDCl3 as
solvent. Coupling constants are given in Hz and chemical shifts are reported in δ values in
ppm. Data are reported as followed: chemical shift, multiplicity (s = singlet, s br = broad
singlet, d = doublet, t = triplet, dd = double doublet, dt = double triplet, ddd = double
double doublet, m = multiplet), coupling constants (Hz), and integration. Gas
Chromatographic/Mass Spectrometer analyses were carried out with a VF-5 ms, 30 m x
0.25 mm x 0.25 μm column. Irradiation was conducted in a reactor equipped with two
Philips HPI-T 400-W lamps (cooled with water). Potentiometric titration of halide ions
where performed in a pHmeter using an Ag/Ag+ electrode.
Materials: 4-iodoanisole (4a), 4-iodotoluene (4b), Iodobenzene (4c), 2-iodoanisole
(4d), 2-iodotoluene (4e), 4-iodobiphenyl (4f-1), 4-bromobiphenyl (4f-2), 1-fluoro-4-
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iodobenzene (4g), 1-iodo-4-(trifluoromethyl)benzene (4h), 1-iodonaphthalene (4i-1), 1-
bromonaphthalene (4i-2), 1-chloronaphthalene (4i-3), 2-bromonaphthalene (4j), 6-
chloroquinoline (4k), 1,1-diphenylethylene (6b), cis-stilbene (6c) and α-methylstyrene (6d)
were commercially available and used as received from the supplier. DMSO was stored
under molecular sieves (4 Å). Styrene (6a) was distillated before used. All solvents were
analytical-grade and used as received from the supplier. Silica gel (0.063-0.200 mm) was
used in column chromatography and 1 mm, 2 mm and 4 mm silica gel (60 PF 254) plates
where employed in radial thin-layer chromatography purification.
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Experimental procedures
METHOD A. Photostimulated reaction of 4-iodoanisole (4a) with styrene (6a) in
DMSO: The reaction was carried out in a 20 mL flame-dried Schlenk tube, equipped with a
nitrogen inlet and magnetic stirrer at rt. DMSO (1 mL) was dried and deoxygenated, then
styrene (6a, 5 equiv, 0.290 mL), substrate 4a (1.0 equiv, 0.117 g, 0.5 mmol) and t-BuOK
(3.0 equiv, 0.168 g, 1.5 mmol) were added and the reaction mixture was irradiated for 1.5
h. The reaction was quenched with water and ammonium nitrate in excess. The residue was
extracted with ethyl acetate (3 x 20 mL) and the organic extract was washed with water,
dried with anhydrous Na2SO4 and filtered. The solvent was removed to leave the crude
product. The product 9-aa was purified by radial thin-layer chromatography on silica gel
eluting with pentane and was isolated as white solid.
METHOD B. Photostimulated reaction of 4-iodoanisole (4a) with styrene (6a) and
18-crown-6 ether (18-C-6): The reaction was carried out in a 5 mL flame-dried Schlenk
tube, equipped with a nitrogen inlet and magnetic stirrer at room temperature. Styrene (6a,
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10 equiv, 0.580 mL, 5 mmol), 18-C-6 (3 equiv, 396.5 mg, 1.5 mmol), substrate 4a (1.0
equiv, 0.117 g, 0.5 mmol) and t-BuOK (3.0 equiv, 0.168 g, 1.5 mmol) were added and the
reaction mixture was irradiated for 15 minutes. The reaction was quenched with water and
ammonium nitrate in excess. The residue was extracted with ethyl acetate (3 x 20 mL) and
the organic extract was washed with water, dried with anhydrous Na2SO4 and filtered. The
solvent was removed to leave the crude product. The product 9-aa was purified by radial
thin-layer chromatography on silica gel eluting with pentane and was isolated as white
solid.
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METHOD C. Reaction of 4-iodoanisole (4a), styrene and 18-crown-6 ether with
conventional heating: The reaction was carried out in a 5 mL flame-dried Schlenk tube,
equipped with a nitrogen inlet and magnetic stirrer at 50 ºC. Styrene (6a, 10 equiv, 0.580
mL, 5 mmol), 18-crown-6 ether (3 equiv, 396.5 mg, 1.5 mmol), substrate 4a (1.0 equiv,
0.117 g, 0.5 mmol) and t-BuOK (3.0 equiv, 0.168 g, 1.5 mmol) were added and the reaction
mixture was heating at 50 ºC for 15 minutes. The reaction was quenched with water and
ammonium nitrate in excess. The residue was extracted with ethyl acetate (3 x 20 mL) and
the organic extract was washed with water, dried with anhydrous Na2SO4 and filtered. The
solvent was removed to leave the crude product. The product 9-aa was purified by radial
thin-layer chromatography on silica gel eluting with pentane and was isolated as white
solid.
Characterization data
(E)-1-Methoxy-4-styrylbenzene (9-aa):15,32,33,34 [1142-15-0] Compound 9-aa was
obtained according to the general procedure. The product was purified by column
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chromatography on silica gel eluting with a pentane/diethyl ether gradient (100:0→80:20)
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and was isolated a white solid (Method B, 91.5 mg, 87% yield). H NMR (400 MHz,
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CDCl3, TMS) δ 7.50 - 7.48 (m, 2H, CH), 7.47 – 7.44 (m, 2H, CH) 7.36 – 7.32 (m, 2H, CH),
7.26 – 7.21 (m, 1H, CH), 7.07 (d, J = 16.3 Hz, 1H, CH), 6.97 (d, J = 16.3 Hz, 1H, CH),
6.90 (m, 2H, CH), 3.83 (s, 3H, CH3). 13C NMR (101 MHz, CDCl3) δ 159.5 (C), 137.8 (C),
130.3 (C), 128.8 (CH), 128.4 (CH), 127.9 (CH), 127.4 (CH), 126.8 (CH), 126.4 (CH),
114.3 (CH), 55.5 (CH3). 1H-1H COSY NMR (400 MHz, CDCl3) δH/δH 7.49/7.34, 7.49/7.23,
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7.49/6.97, 7.45/7.07, 7.45/6.90, 7.34/7.23, 7.34/6.97, 7.07/6.97. H-13C HSQC NMR (400
MHz, CDCl3) δH/δC 7.49/126.4, 7.45/127.9, 7.34/128.8, 7.23/127.4, 7.07/128.4, 6.97/126.8,
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6.90/114.3, 3.83/55.5. H-13C HMBC NMR (400 MHz, CDCl3) δH/δC 7.49/127.4,
7.45/159.5, 7.45/128.4, 7.34/137.8, 7.23/126.4, 7.07/137.8, 6.97/137.8, 6.97/130.3,
6.97/128.4, 6.97/126.4, 6.90/159.5, 6.90/130.3, 3.83/159.5. GC-MS (70eV): m/z (%): 211
(M+ +1, 16), 210 (M+, 100), 209 (18), 195 (20), 179 (14), 178 (9), 167 (32), 166 (12), 165
(37), 152 (24), 115 (7), 89 (11), 82 (11).
(E)-1-Methyl-4-styrylbenzene (9-ba):,32,33,34,35 [1860-17-9] Compound 9-ba was obtained
according to the general procedure. The product was purified by column chromatography
on silica gel eluting with petroleum ether and was isolated a white solid (Method A, 71.9
mg, 74% yield). 1H NMR (400 MHz, CDCl3, TMS) δ 7.37 (d, J = 7.5 Hz, 2H, CH), 7.28 (d,
J = 8.0 Hz, 2H, CH), 7.21 (t, J = 7.5 Hz, 2H, CH), 7.11 (t, J = 7.3 Hz, 1H, CH), 7.03 (d, J =
8.0 Hz, 2H, CH), 6.99 – 6.90 (m, 2H, CH), 2.22 (s, 3H, CH3). 13C NMR (101 MHz, CDCl3)
δ 137.6 (C), 137.5 (C), 134.7 (C), 129.5 (CH), 128.7 (CH), 127.8 (CH), 127.5 (CH), 126.6
1
(CH), 126.5 (CH), 21.3 (CH3). H-1H COSY NMR (400 MHz, CDCl3) δH/δH 7.37/7.21,
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7.28/7.03, 7.28/2.22, 7.21/7.11, 7.03/2.22. H-13C HSQC NMR (400 MHz, CDCl3) δH/δC
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7.37/126.5, 7.28/126.6, 7.21/128.7, 7.11/127.5, 7.03/129.5, 6.98/128.7, 6.98/127.8,
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2.22/21.3. H-13C HMBC NMR (400 MHz, CDCl3) δH/δC 7.37/127.5, 7.37/126.5,
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7.28/137.5, 7.28/128.7, 7.28/126.6, 7.21/137.6, 7.21/128.7, 7.11/128.7, 7.11/127.8,
7.11/126.6, 7.03/134.7, 7.03/129.5, 7.03/21.3, 6.98/137.5, 6.98/134.7, 6.98/128.7,
6.98/127.8, 6.98/126.6, 2.22/137.5, 2.22/129.5. GC-MS (70eV): m/z (%): 195 (M+ +1, 15),
194 (M+, 91), 193 (25), 180 (16), 179 (100), 178 (90), 165 (10), 115 (11), 96 (16), 89 (13),
82 (15).
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15,32,33,34,35
(E)-1,2-Diphenylethene (9-ca):
[103-30-0] Compound 9-ca was obtained
according to the general procedure and was isolated a white solid (Method B, 71.2 mg, 79%
yield). GC-MS (70eV): m/z (%): 181 (M+ +1, 12), 180 (M+, 100), 179 (84), 178 (62), 177
(10), 176 (11), 165 (45), 152 (11), 102 (9), 90 (11), 89 (26), 77 (9), 76 (21), 63 (8), 51 (9).
(E)-1-Methoxy-2-styrylbenzene (9-da):36 [52805-92-2] The product 9-da was separated
by radial thin-layer chromatography (4 mm) on silica gel eluting with petroleum ether and
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was isolated a white solid (Method B, 67.3 mg, 64% yield). H NMR (400 MHz, CDCl3,
TMS) δ 7.59 (dd, J = 7.7, 1.6 Hz, 1H, CH), 7.54 – 7.51 (m, 2H, CH), 7.48 (d, J = 16.5 Hz,
1H, CH), 7.36 – 7.32 (m, 2H, CH), 7.26 – 7.21 (m, 2H, CH), 7.11 (d, J = 16.5 Hz, 1H),
13
6.98 – 6.94 (m, 1H, CH), 6.89 (dd, J = 8.3, 0.8 Hz, 1H, CH), 3.88 (s, 3H, CH3). C NMR
(101 MHz, CDCl3) δ 157.1 (C), 138.1 (C), 129.3 (CH), 128.8 (CH), 128.7 (2 CH), 127.5
(CH), 126.7 (2 CH), 126.6 (C), 126.5 (CH), 123.7 (CH), 120.9 (CH), 111.1 (CH), 55.7
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(CH3). H-1H COSY NMR (400 MHz, CDCl3) δH/δH 7.59/7.48, 7.59/7.23, 7.59/6.94,
7.53/7.34, 7.53/7.23, 7.53/7.11, 7.48/7.11, 7.48/6.94, 7.34/7.23, 7.23/6.94, 7.23/6.89,
6.94/6.89, 6.89/3.88. 1H-13C HSQC NMR (400 MHz, CDCl3) δH/δC 7.59/126.5, 7.53/126.7,
7.48/123.7, 7.34/128.7, 7.23/128.8, 7.23/127.5, 7.11/129.3, 6.94/120.9, 6.89/111.1,
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3.88/55.7. H-13C HMBC NMR (400 MHz, CDCl3) δH/δC 7.59/157.1, 7.59/128.8,
7.59/123.7, 7.59/111.1, 7.53/129.3, 7.53/127.5, 7.53/126.7, 7.48/157.1, 7.48/138.1,
7.48/126.7, 7.48/126.6, 7.34/138.1, 7.34/128.7, 7.23/157.1, 7.23/126.6, 7.11/126.7,
7.11/126.6, 7.11/111.1, 6.94/126.6, 6.94/111.1, 6.89/157.1, 6.89/126.6, 6.89/120.9,
3.88/157.1. GC-MS (70eV): m/z (%): 211 (M+ +1, 14), 210 (M+, 100), 179 (15), 178 (11),
167 (24), 166 (13), 165 (47), 152 (28), 119 (23), 104 (25), 91 (36), 89 (16), 82 (23), 76 (7).
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(E)-1-Methyl-2-styrylbenzene (9-ea):15,34,37 [74685-42-0] Compound 9-ea was obtained
according to the general procedure. The product was purified by column chromatography
on silica gel eluting with a pentane/CH2Cl2 (100:0→80:20) and was isolated as a yellow oil
(Method A, 70.9 mg, 73% yield). 1H NMR (400 MHz, CDCl3, TMS) δ 7.59 (d, J = 7.0 Hz,
1H, CH), 7.55 – 7.49 (m, 2H, CH), 7.38 – 7.31 (m, 3H, CH), 7.28 – 7.24 (m, 1H, CH), 7.23
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– 7.20 (m, 1H, CH), 7.19 – 7.17 (m, 2H, CH), 7.00 (d, J = 16.2 Hz, 1H), 2.43 (s, 3H). C
NMR (101 MHz, CDCl3) δ 137.8 (C), 136.5 (C), 135.9 (C), 130.5 (CH), 130.1 (CH), 128.8
(2 CH), 127.8 (CH), 127.7 (CH), 126.7 (3 CH), 126.3 (CH), 125.5 (CH), 20.1 (CH3).1H-1H
COSY NMR (400 MHz, CDCl3) δH/δH δ 7.59/7.22, 7.59/2.43, 7.52/7.34, 7.52/7.26,
7.52/6.98, 7.34/7.26, 7.34/2.43, 7.22/6.98. H-13C HSQC NMR (400 MHz, CDCl3) δH/δC
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7.59/125.5, 7.52/126.7, 7.34/128.8, 7.34/126.7, 7.26/127.8, 7.22/126.3, 7.18/130.5,
7.18/127.7, 7.00/130.1, 2.43/20.1. H-13C HMBC NMR (400 MHz, CDCl3) δH/δC
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7.59/135.9, 7.59/127.7, 7.52/130.1, 7.52/127.7, 7.52/126.7, 7.34/137.7, 7.34/135.9,
7.34/128.8, 7.34/125.5, 7.26/126.7, 7.22/130.5, 7.22/125.5, 7.18/136.5, 7.18/130.5,
7.18/126.3, 7.18/20.1, 2.43/135.9, 2.43/130.5. GC-MS (70eV): m/z (%): 195 (M+ +1, 12),
194 (M+, 85), 193 (13), 180 (13), 179 (100), 178 (72), 165 (12), 152 (9), 116 (20), 115 (30),
96 (24), 91 (10), 89 (17), 82 (13).
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(E)-4-Styryl-1,1'-biphenyl (9-fa):15,38 [21175-18-8] Compound 9-fa was obtained
according to the general procedure. The product was recrystallized from CH2Cl2 as a white
solid (Method B, 91.0 mg, 71% yield from 4f-1). 1H NMR (400 MHz, CDCl3, TMS) δ 7.63
– 7.56 (m, 6H, CH), 7.54 – 7.52 (m, 2H, CH), 7.44 (t, J = 7.6 Hz, 2H, CH), 7.38 – 7.32 (m,
3H, CH), 7.28 – 7.24 (m, 1H, CH), 7.15 (s, 2H, CH). 13C NMR (101 MHz, CDCl3) δ 140.9
(C), 140.5 (C), 137.5 (C), 136.6 (C), 129.0 (CH), 128.9 (CH), 128.4 (CH), 127.8 (CH),
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127.5 (CH), 127.4 (CH), 127.1 (CH), 127.0 (CH), 126.7 (CH). H-1H COSY NMR (400
MHz, CDCl3) δH/δH 7.59/7.44, 7.59/7.35, 7.59/127.0, 7.53/7.35, 7.53/7.26, 7.53/7.15,
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7.44/7.35, 7.35/7.26, 7.35/7.15. H-13C HSQC NMR (400 MHz, CDCl3) δH/δC 7.59/127.5,
7.59/127.1, 7.53/126.7, 7.44/129.0, 7.35/128.9, 7.35/127.4, 7.26/127.8, 7.15/129.0,
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7.15/128.4. H-13C HMBC NMR (400 MHz, CDCl3) δH/δC 7.59/140.9, 7.59/140.5,
7.59/136.6, 7.59/128.4, 7.59/127.5, 7.53/129.0, 7.53/127.8, 7.53/126.7, 7.44/140.9,
7.44/129.0, 7.35/137.5, 7.35/128.9, 7.35/127.1, 7.26/126.7, 7.15/137.5, 7.15/136.6,
7.15/129.0, 7.15/128.4, 7.15/127.1, 7.15/126.7. GC-MS (70eV): m/z (%): 257 (M+ +1, 23),
256 (M+, 100), 255 (26), 254 (9), 253 (13), 252 (13), 241 (15), 240 (15), 239 (16), 179 (16),
178 (22), 165 (19), 113 (9), 91 (9).
(E)-1-Fluoro-4-styrylbenzene (9-ga):33,35 [718-25-2] The product 9-ga was separated by
radial thin-layer chromatography (4 mm) on silica gel eluting with pentane and was isolated
a white solid (Method B, 45.6 mg, 46% yield). 1H NMR (400 MHz, CDCl3, TMS) δ 7.50 -
7.44 (m, 4H, CH), 7.37 – 7.33 (m, 2H, CH), 7.27 – 7.23 (m, 1H, CH), 7.08 – 6.98 (m, 4H,
13
CH). C NMR (101 MHz, CDCl3) δ 162,5 (d, J = 247.3 Hz, C), 137.4 (C), 133.7 (d, J =
3.3 Hz, C), 128.9 (2 CH), 128.7 (d, J = 2.2 Hz, CH), 128.1 (d, J = 7.9 Hz, 2 CH), 127.8
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(CH), 127.7 (CH) 126.6 (2 CH), 115.8 (d, J = 21.6 Hz, 2 CH). H-1H COSY NMR (400
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7.03/127.7, 7.03/115.8. H-13C HMBC NMR (400 MHz, CDCl3) δH/δC 7.47/162.5,
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7.47/127.8, 7.47/126.6, 7.35/137.4, 7.35/128.9, 7.25/126.6, 7.03/162.5, 7.03/137.4,
7.03/133.7, 7.03/128.1, 7.03/127.7, 7.03/126.6. GC-MS (70eV): m/z (%): 199 (M+ +1, 13),
198 (M+, 100), 197 (66), 196 (44), 183 (39), 178 (11), 177 (28), 176 (11), 170 (10), 98 (17),
85 (11).
(E)-1-Styryl-4-(trifluoromethyl)benzene (9-ha):33 The product 9-ha was separated by
radial thin-layer chromatography (4 mm) on silica gel eluting with pentane and was isolated
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a white solid (Method B, 37.2 mg, 30% yield). H NMR (400 MHz, CDCl3, TMS) δ 7.60
(br s, 4H, CH), 7.54 – 7.52 (m, 2H, CH), 7.40 – 7.36 (m, 2H, CH), 7.32 – 7.28 (m, 1H,
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CH), 7.19 (d, J = 16.4 Hz, 1H, CH), 7.11 (d, J = 16.3 Hz, 1H, CH). F NMR (377 MHz,
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CDCl3) δ -62.47. C NMR (101 MHz, CDCl3) δ 141.0 (C), 136.8 (C), 131.4 (CH), 129.5
(q, J = 32.3 Hz, C), 128.9 (2 CH), 128.4 (CH), 127.3 (CH), 126.9 (2 CH), 126.7 (2 CH),
125.8 (q, J = 3.7 Hz, 2 CH), 123.0 (CF3).1H-1H COSY NMR (400 MHz, CDCl3) δH/δH
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7.54/7.38, 7.54/7.30, 7.54/7.19, 7.38/7.30, 7.19/7.11. H-13C HSQC NMR (400 MHz,
CDCl3) δH/δC 7.60/126.7, 7.60/125.8, 7.53/126.9, 7.38/128.9, 7.30/128.4, 7.19/131.4,
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7.11/127.3. H-13C HMBC NMR (400 MHz, CDCl3) δH/δC 7.60/141.0, 7.60/129.5,
7.60/127.3, 7.60/125.8, 7.60/123.0, 7.53/131.4, 7.53/128.4, 7.53/127.3, 7.38/136.8,
7.38/128.9, 7.19/141.0, 7.19/126.9, 7.11/136.8, 7.11/131.5, 7.11/126.7. GC-MS (70eV):
m/z (%): 249 (M+ +1, 12), 248 (M+, 100), 233 (13), 229 (7), 227 (16), 180 (10), 179 (86),
178 (78), 176 (9), 89 (12), 76 (9).
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(E)-1-Styrylnaphthalene (9-ia):15,33,34 [2840-87-1] Compound 9-ia was obtained
according to the general procedure. The product was purified by column chromatography
on silica gel eluting with a pentane/CH2Cl2 (100:0→90:10) and was isolated a colorless oil
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(Method B, 71.4 mg, 62% yield from 1-bromonaphthalene). H NMR (400 MHz, CDCl3,
TMS) δ 8.21 (d, J = 8.1 Hz, 1H, CH), 7.90 – 7.85 (m, 2H, CH), 7.79 (d, J = 8.2 Hz, 1H,
CH), 7.74 (d, J = 7.2 Hz, 1H, CH), 7.61 – 7.59 (m, 2H, CH), 7.53 – 7.48 (m, 3H, CH), 7.41
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– 7.37 (m, 2H, CH), 7.31 – 7.29 (m, 1H, CH), 7.14 (d, J = 16.0 Hz, 1H, CH). C NMR
(101 MHz, CDCl3) δ 137.8 (C), 135.2 (C), 133.9 (C), 131.9 (CH), 131.6 (C), 128.9 (2 CH),
128.8 (CH), 128.2 (CH), 127.9 (CH), 126.8 (2 CH), 126.2 (CH), 126.0 (2 CH), 125.8 (CH),
123.9 (CH), 123.8 (CH). H-1H COSY NMR (400 MHz, CDCl3) δH/δH 8.21/7.51,
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7.87/7.51, 7.87/7.14, 7.79/7.51, 7.74/7.51, 7.60/7.39, 7.60/7.30, 7.39/7.30. H-13C HSQC
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NMR (400 MHz, CDCl3) δH/δC 8.21/123.9, 7.87/128.8, 7.87/126.0, 7.79/128.2, 7.74/123.8,
7.60/126.8, 7.51/126.2, 7.51/126.0, 7.51/125.8, 7.39/128.9, 7.30/127.9, 7.14/131.9. H-13C
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HMBC NMR (400 MHz, CDCl3) δH/δC 8.21/135.2, 8.21/133.9, 8.21/126.0, 8.21/125.8,
7.87/137.8, 7.87/131.9, 7.87/131.6, 7.87/128.2, 7.87/126.2, 7.87/123.8, 7.87/123.9,
7.79/131.6, 7.79/128.8, 7.79/123.8, 7.74/13.6, 7.74/128.2, 7.74/126.0, 7.60/131.9,
7.60/128.9, 7.60/127.9, 7.60/126.8, 7.51/135.2, 7.51/133.9, 7.51/131.6, 7.51/128.8,
7.51/123.9, 7.51/123.8, 7.39/137.8, 7.39/128.9, 7.39/126.8, 7.30/126.8, 7.14/137.8,
7.14/135.2, 7.14/126.8. GC-MS (70eV): m/z (%): 231 (M+ +1, 17), 230 (M+, 94), 229
(100), 228 (33), 227 (14), 226 (16), 215 (24), 202 (11), 153 (12), 152 (28), 115 (11), 114
(27), 113 (16), 101 (18).
(E)-2-Styrylnaphthalene (9-ja):15,35 Compound 9-ja was obtained according to the general
procedure. The product was purified by column chromatography on silica gel eluting with a
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pentane and was isolated a white solid (Method B, 86.3 mg, 75% yield). H NMR (400
MHz, CDCl3, TMS) δ 7.84 – 7.79 (m, 4H, CH), 7.73 (dd, J = 8.6, 1.6 Hz, 1H, CH), 7.58 –
7.52 (m, 2H, CH), 7.48 – 7.41 (m, 2H, CH), 7.39 – 7.35 (m, 2H, CH), 7.29 – 7.19 (m, 3H,
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CH). C NMR (101 MHz, CDCl3) δ 137.4 (C), 134.9 (C), 133.8 (C), 133.1 (C), 129.1
(CH), 128.8 (CH), 128.7 (CH), 128.3 (CH), 128.0 (CH), 127.8 (CH), 127.7 (CH), 126.7
(CH), 126.6 (CH), 126.4 (CH), 125.9 (CH), 123.6 (CH). H-1H COSY NMR (400 MHz,
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CDCl3) δH/δH 7.81/7.73, 7.81/7.45, 7.81/7.24, 7.73/7.24, 7.55/7.37, 7.55/7.24, 7.37/7.24.
1H-13C HSQC NMR (400 MHz, CDCl3) δH/δC 7.81/126.7, 7.8/128.0, 7.81/128.3,
7.81/127.8, 7.73/123.6, 7.55/126.6, 7.45/126.4, 7.45/125.9, 7.37/128.7, 7.24/129.1,
7.24/128.8, 7.24/127.7. H-13C HMBC NMR (400 MHz, CDCl3) δH/δC 7.81/134.9,
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7.81/133.8, 7.81/133.1, 7.81/128.8, 7.81/128.0, 7.81/127.7, 7.81/126.4, 7.81/125.9,
7.81/123.6, 7.73/133.1, 7.73/128.8, 7.73/128.7, 7.73/126.7, 7.55/129.1, 7.55/127.8,
7.55/126.7, 7.45/133.8, 7.45/133.1, 7.45/128.0, 7.45/127.8, 7.37/137.4, 7.37/128.7,
7.37/126.6, 7.24/137.4, 7.24/134.9, 7.24/129.1, 7.24/128.8, 7.24/126.7, 7.24/126.6,
7.24/123.6. GC-MS (70eV): m/z (%): 231 (M+ +1, 17), 230 (M+, 100), 229 (96), 228 (55),
227 (15), 226 (21), 215 (27), 202 (14), 152 (9), 115 (16), 114 (31), 113 (13), 108 (10), 102
(6), 101 (22).
(E)-6-Styrylquinoline (9-ka):39 [121611-55-0] Compound 9-ka was obtained according to
the general procedure. The product was recrystallized from diethyl ether as yellow crystals
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(Method B, 61.3 mg, 53% yield). H NMR (400 MHz, CDCl3, TMS) δ 8.85 (dd, J = 4.2,
1.7 Hz, 1H, CH), 8.08 (m, 2H, CH), 7.95 (dd, J = 8.8, 2.0 Hz, 1H, CH), 7.78 (d, J = 1.9 Hz,
1H, CH), 7.56 – 7.54 (m, 2H, CH), 7.41 – 7.33 (m, 3H, CH), 7.31 – 7.26 (m, 1H, CH), 7.24
(s, 2H, CH). 13C NMR (101 MHz, CDCl3) δ 150.2 (CH), 148.2 (C), 137.1 (C), 136.0 (CH),
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135.7 (C), 130.3 (CH), 129.9 (CH), 128.9 (CH), 128.7 (C), 128.1 (CH), 127.9 (CH), 127.3
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(CH), 126.8 (CH), 126.0 (CH), 121.6 (CH). H-1H COSY NMR (400 MHz, CDCl3) δH/δH
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8.85/8.08, 8.85/7.37, 8.08/7.95, 8.08/7.78, 8.08/7.37, 8.08/7.24, 7.95/7.78, 7.95/7.24,
7.78/7.24, 7.55/7.37, 7.55/7.28, 7.55/7.24, 7.37/7.28. H-13C HSQC NMR (400 MHz,
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CDCl3) δH/δC 8.85/150.2, 8.08/135.7, 8.08/129.9, 7.95/127.3, 7.78/126.0, 7.55/126.8,
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7.37/128.9, 7.37/121.6, 7.28/128.1, 7.24/130.3, 7.24/127.9. H-13C HMBC NMR (400
MHz, CDCl3) δH/δC 8.85/148.2, 8.85/136.0, 8.85/121.6, 8.08/150.2, 8.08/148.2, 8.08/135.7,
8.08/128.7, 8.08/126.0, 7.95/148.2, 7.95/127.9, 7.95/126.0, 7.78/148.2, 7.78/136.0,
7.78/129.9, 7.78/127.9, 7.78/123.7, 7.55/130.3, 7.55/128.1, 755/126.8, 7.37/150.2,
7.37/137.1, 7.37/128.9, 7.37/128.7, 7.37/126.8, 7.28/126.8, 7.24/137.1, 7.24/135.7,
7.24/130.3, 7.24/127.3, 7.24/126.8, 7.24/126.0. GC-MS (70eV): m/z (%): 232 (M+ +1, 13),
231 (M+, 81), 230 (100), 228 (11), 216 (12), 202 (17), 115 (41), 102 (11), 101 (11).
1,1,2-Triphenylethylene (9-cb):16 [58-72-0] Compound 9-cb was obtained according to
the general procedure. The 1,1-diphenylethene was distilled under reduced pressure using a
Kügelrohr apparatus. The product was purified by column chromatography on silica gel
eluting with a petroleum ether/CH2Cl2 (100:0→80:20) and was isolated as colorless oil
(Method B, 88.4 mg, 69% yield). 1H NMR (400 MHz, CDCl3, TMS) δ 7.32 – 7.27 (m, 8H,
CH), 7.22 – 7.19 (m, 2H, CH), 7.15 – 7.07 (m, 3H, CH), 7.04 – 7.02 (m, 2H, CH), 6.97 (s,
1H, CH). 13C NMR (101 MHz, CDCl3) δ 143.6 (C), 142.8 (C), 140.5 (C), 137.5 (C), 130.5
(2 CH), 129.7 (2 CH), 128.8 (2 CH), 128.4 (2 CH), 128.3 (CH), 128.1 (2 CH), 127.8 (2
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CH), 127.6 (CH), 127.5 (CH), 126.9 (CH). H-1H COSY NMR (400 MHz, CDCl3) δH/δH
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7.29/7.20, 7.11/7.03, 7.03/6.97. H-13C HSQC NMR (400 MHz, CDCl3) δH/δC 7.29/128.8,
7.29/128.4, 7.29/127.8, 7.29/127.6, 7.29/127.5, 7.20/130.5, 7.11/128.1, 7.11/126.9,
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7.03/129.7, 6.97/128.3. H-13C HMBC NMR (400 MHz, CDCl3) δH/δC 7.29/143.6,
7.29/140.5, 7.29/130.5, 7.29/128.8, 7.29/127.6, 7.20/127.5, 7.11/129.7, 7.11/127.8,
7.03/126.9, 6.97/143.6, 6.97/140.5, 6.97/129.7. GC-MS (70eV): m/z (%): 257 (M+ +1, 21),
256 (M+, 100), 255 (26), 254 (9), 253 (17), 252 (16), 241 (23), 240 (15), 239 (16), 179 (33),
178 (55), 176 (13), 165 (21), 152 (9), 126 (19), 120 (24), 113 (15).
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(Z, E) (1-(p-Tolyl)ethene-1,2-diyl)dibenzene (9-bc): 40 [70603-14-4] Compound 9-bc was
obtained according to the general procedure. The cis-stilbene was distilled under reduced
pressure using a Kügelrohr apparatus. The product was purified by column chromatography
on silica gel eluting with a petroleum ether/CH2Cl2 (100:0→80:20) and was isolated a
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white solid as a mixture of Z, E isomers (Method B, 60.8 mg, 45% yield). H NMR (400
MHz, CDCl3, TMS) δ 7.33 – 7.25 (m, 4H, CH), 7.22 – 7.18 (m, 2H, CH), 7.14 – 7.00 (m,
8H, CH), 6.93, 6.92 (s, s, sum=1H), 2.37, 2.34 (s, s, sum=3H). 13C NMR (101 MHz,
CDCl3) δ 143.9 (C), 142.7 (C), 142.6 (C), 140.8 (C), 140.7 (C), 137.7 (C), 137.6 (C), 137.5
(C), 137.4 (C), 137.2 (C), 130.5 (CH), 130.4 (CH), 129.7 (CH), 129.6 (CH), 129.5 (CH),
129.1 (CH), 128.7 (CH), 128.3 (CH), 128.1 (CH), 127.8 (CH), 127.6 (CH), 127.5 (CH),
127.4 (CH), 127.3 (CH), 126.8 (CH), 126.7 (CH), 21.5 (CH3), 21.3 (CH3). H-1H COSY
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NMR (400 MHz, CDCl3) δH/δH 7.29/7.20, 7.20/7.11, 7.11/2.37, 7.11/2.34. H-13C HMBC
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(400 MHz, CDCl3) δ 7.29/128.1, 7.29/127.5, 7.20/130.5, 7.20/127.8, 7.07/130.6,
7.07/129.7, 7.07/129.6; 7.07/129.5, 7.07/128.1, 7.07/126.8, 6.93/127.6, 6.92/128.3,
2.37/21.5, 2.34/21.3. GC-MS (70eV): m/z (%):271 (M+ +1, 23), 270 (M+, 100), 269 (10),
255 (48), 254 (23), 253 (28), 252 (20), 240 (14), 239 (10), 193 (12), 192 (12), 179 (19), 178
(41), 176 (10), 165 (11), 126 (26), 120 (10), 119 (14), 113 (14).
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(E)-1-Methyl-4-(2-phenylprop-1-en-1-yl)benzene (9-bd):41 Compound 9-bd was
obtained according to the general procedure. The α-methylstyrene was distilled under
reduced pressure using a Kügelrohr apparatus. The product was purified by column
chromatography on silica gel eluting with a petroleum ether/diethyl ether (100:0→80:20)
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and was isolated a white solid (Method B, 67.7 mg, 65% yield). H NMR (400 MHz,
CDCl3, TMS) δ 7.52 – 7.50 (m, 2H, CH), 7.37 – 7.33 (m, 2H, CH), 7.28 – 7.25 (m, 3H,
CH), 7.18 (d, J = 8.0 Hz, 2H), 6.80 (s, 1H, CH), 2.36 (s, 3H, CH3), 2.27 (d, J = 1.3 Hz, 3H,
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CH3). C NMR (101 MHz, CDCl3) δ 144.1 (C), 136.7 (C), 136.1 (C), 135.4 (C), 129.1
(CH), 128.9 (CH), 128.3 (CH), 127.6 (CH), 127.0 (CH), 125.9 (CH), 21.2 (CH3), 17.4
(CH3). H-1H COSY NMR (400 MHz, CDCl3) δH/δC δ 7.57/7.41, 7.41/7.33, 7.33/7.23,
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7.33/2.42, 7.23/2.42, 6.87/2.33. H-13C HSQC NMR (400 MHz, CDCl3) δH/δC 7.57/125.9,
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7.41/128.3, 7.33/129.1, 7.33/127.0, 7.23/128.9, 6.87/127.6, 2.42/21.2, 2.33/17.4. H-13C
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HMBC NMR (400 MHz, CDCl3) δH/δC 7.57/136.7, 7.57/127.0, 7.57/125.9, 7.41/144.1,
7.41/128.3, 7.33/136.1, 7.33/129.1, 7.33/127.6, 7.33/125.9, 7.23/135.4, 7.23/128.9,
7.23/21.2, 6.87/144.1, 6.87/129.1, 6.87/17.45, 2.42/136.1, 2.42/128.9, 2.33/144.1,
2.33/136.7, 2.33/127.6. GC-MS (70eV): m/z (%):209 (M+ +1, 15), 208 (M+, 100), 194 (14),
193 (88), 192 (21), 191 (14), 189 (10), 179 (13), 178 (66), 165 (14), 115 (32), 103 (11), 95
(14), 91 (13), 89 (19), 82 (11), 77 (11).
(E)-1-Methoxy-4-(2-phenylprop-1-en-1-yl)benzene (9-ad):42 [83832-04-6] Compound 9-
ad was obtained according to the general procedure. The α-methylstyrene was distilled
under reduced pressure using a Kügelrohr apparatus. The product was purified by column
chromatography on silica gel eluting with a petroleum ether/diethyl ether (100:0→80:20)
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and was isolated a white solid (Method B, 91.9 mg, 82% yield). H NMR (400 MHz,
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CH), 6.77 (s, 1H, CH), 3.81 (s, 3H, CH3), 2.27 (d, J = 1.4 Hz, 3H, CH3). C NMR (101
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MHz, CDCl3) δ 158.3 (C), 144.3 (C), 136.0 (C), 131.1 (C), 130.5 (CH), 128.4 (CH), 127.4
(CH), 127.1 (CH), 126.1 (CH), 113.8 (CH), 55.4 (CH3), 17.6 (CH3). H-1H COSY NMR
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(400 MHz, CDCl3) δH/δC 7.49/7.30, 7.30/6.90, 7.30/6.77, 7.30/2.27, 6.78/2.27. H-13C
HSQC NMR (400 MHz, CDCl3) δH/δC 7.49/128.4, 7.49/126.1, 7.30/130.5, 7.30/128.4,
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7.30/127.1, 7.30/113.8, 6.90/130.5, 6.90/113.8, 6.77/127.4, 3.81/55.5, 2.27/17.6. H-13C
HMBC NMR (400 MHz, CDCl3) δH/δC 7.49/136.0, 7.49/127.1, 7.49/126.1, 7.30/158.3,
7.30/144.3, 7.30/130.5, 7.30/128.4, 7.30/127.4, 7.30/126.1, 7.30/113.8, 6.90/158.3,
6.90/131.1, 6.90/113.8, 6.77/144.3, 6.77/130.5, 6.77/17.6. GC-MS (70eV): m/z (%): 225
(M+ +1, 14), 224 (M+, 100), 223 (14), 209 (26), 208 (10), 194 (12), 193 (12), 181 (12), 178
(17), 166 (19), 165 (29), 121 (14), 115 (22), 103 (9), 91 (10), 89 (8), 82 (6), 77 (12).
ACKNOWLEDGMENTS
This work was supported in part by Agencia Córdoba Ciencia, the Consejo Nacional
de Investigaciones Científicas y Técnicas (CONICET), Secretaría de Ciencia y Tecnología,
Universidad Nacional de Córdoba, and Fondo para la Investigación Científica y
Tecnológica Argentina.
SUPPORTING INFORMATION
Completes tables reactions and copies of 1H, 13C, COSY, HSQC, and HMBC NMR
spectra of all compounds are available in Experimental Supporting Information. This
material is available free of charge via the Internet at http://pubs.acs.org.
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