Synthesis of 1,1-diaryl ethylenes by Cu-catalyzed arene C-H addition to aryl acetylenes

Article abstract of DOI:10.1016/j.tetlet.2008.12.031

An unprecedented copper-catalyzed C-H addition of arenes to aryl acetylenes provides a facile route to 1,1-diaryl ethylenes in moderate to excellent yields. Arylboronic acids were likewise used along with aryl acetylenes in generating 1,1-diaryl ethylene.

Full text of DOI:10.1016/j.tetlet.2008.12.031

Tetrahedron Letters 50 (2009) 893–896
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Tetrahedron Letters
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Synthesis of 1,1-diaryl ethylenes by Cu-catalyzed arene C–H addition
to aryl acetylenes
Sachin V. Bhilare a, Nitin B. Darvatkar a, Amol R. Deorukhkar b, Dilip G. Raut b,
Girish K. Trivedi a, Manikrao M. Salunkhe b,
*
a Department of Chemistry, The Institute of Science, 15, Madam Cama Road, Mumbai 400032, India
b Department of Chemistry, Shivaji University, Vidyanagar, Kolhapur 416 004, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An unprecedented copper-catalyzed C–H addition of arenes to aryl acetylenes provides a facile route to
1,1-diaryl ethylenes in moderate to excellent yields. Arylboronic acids were likewise used along with aryl
acetylenes in generating 1,1-diaryl ethylene.
Received 23 October 2008
Revised 1 December 2008
Accepted 4 December 2008
Available online 13 December 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Arene
Aryl acetylenes
1,1-Diaryl ethylenes
Arylboronic acids
Hydroarylation
Developing reliable methods for catalytic C–H functionalization
has been a long-term goal in synthetic organic chemistry. For
example, the catalytic addition of arene C–H bonds to unsaturated
substrates continues to be a subject of interest for synthetic chem-
ists.1 Palladium complexes are known to catalyze arene C–H addi-
tion to simple alkenes and alkynes and provide various valuable
synthetic intermediates in an atom-economical manner.2,6 A few
late-transition-metal complexes, including those containing Ru,3
Rh,4 Ir,5 and Au,7 have also been shown to catalyze these transfor-
mations, many of the systems requiring activated substrates or
forcing conditions. However, to the best of our knowledge, there
is no report on the Cu-catalyzed arene C–H additions to aryl acet-
ylenes. Herein, we report a novel reagent system for arene C–H
addition to aryl acetylenes, which facilitates a useful new synthesis
of 1,1-diaryl ethylenes from aryl acetylenes.
The reaction of mesitylene and phenyl acetylene was initially
investigated under Fujiwara’s C–H activation conditions,8 where
Pd was replaced by Cu in TFA. To our delight, a 10% yield of the de-
sired product was obtained by employing 2 mmol of mesitylene,
1 mmol of phenyl acetylene, and 0.1 mmol of Cu(OTf)2 in 2 mL of
TFA at room temperature for 24 h (Table 1, entry 1). The addition
of either THF, nitrobenzene or DMSO had little effect on the reac-
tion (Table 1, entries 2–4). One possible explanation for the ineffec-
tiveness of additives could be the impediment of the ligand
Me
Me
Catalyst
r.t.
+
Solvent
Me
Me
Me
Me
Scheme 1. Cu-catalyzed reaction of mesitylene and phenyl acetylene.
Table 1
Optimization of reaction parametersa
Entry
Catalyst
Solvent + additiveb
% Yieldc
1
2
3
4
5
6
7
8
9
10% Cu(OTf)2
10% Cu(OTf)2
10% Cu(OTf)2
10% Cu(OTf)2
10% Cu(OTf)2
TFA
10
11
10
13
87 (80)
89 (83)
0
0
0
0
0
TFA + THF
TFA + nitrobenzene
TFA + DMSO
TMSA
20% Cu(OTf)2
TMSA
TMSA
TMSA
TMSA
TMSA
TMSA
—
AlCl3
TiCl4
Cu(OAc)2
CuI
10
11
a
All reactions were run by employing 2.0 mmol of mesitylene, 1.0 mmol of
phenyl acetylene, and 0.10 mmol of Cu(OTf)2 in 2 mL of TMSA at room temperature
for 24 h, followed by hydrolysis.
b
The equivalents of additive are based on phenyl acetylene.
GC yields; yield of products obtained by column chromatography are reported
c
in parentheses.
* Corresponding author. Tel./fax: +91 22 22816750.
E-mail address: mmsalunkhe@hotmail.com (M.M. Salunkhe).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.12.031

894
S. V. Bhilare et al. / Tetrahedron Letters 50 (2009) 893–896
Table 2
Cu-catalyzed reaction of arenes and aryl acetylenes
Entry
Arene
Aryl acetylene
Producta
Me
Yield (%)b (%)
Me
1
80
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
2
3
84
78
Br
Br
Me
Me
Me
Me
Me
Me
Me
Me
4
5
6
7
8
86
89
80
85
88
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Br
Br
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
9
10
11
80
77
Me
Me
Br
Br
Me
Me
OMe
OMe
OMe
OMe
OMe
OMe
82
81
OMe
MeO
OMe
MeO
OMe
OMe
12
OMe
OMe
a
All reactions were run by employing 2.0 mmol of arene, 1.0 mmol of aryl acetylene, and 0.10 mmol of Cu(OTf)2 in 2 mL of TMSA at room temperature for 20 h.9
Isolated yields.
b

S. V. Bhilare et al. / Tetrahedron Letters 50 (2009) 893–896
895
transfer mechanism. However, the use of trifluoromethane sulfonic
acid (TMSA) instead of TFA assisted an increase in the yield up to
80% (Table 1, entry 5). No observable change in the yield was no-
ticed even after increasing the amount of catalyst up to 20 mol %
(compare Table 1, entries 5 and 6). A control reaction without
the Cu(OTf)2 catalyst failed to give the desired alkene (Table 1, en-
try 7). Lewis acids, such as AlCl3 and TiCl4 (Table 1, entries 8 and 9),
as well as catalytic amounts of Cu(OAc)2 and CuI were ineffective
in catalyzing the reaction. (Table 1, entries 10 and 11) These results
thus demonstrate the implicit role of the Cu(OTf)2/TMSA combina-
tion as catalyst in the reaction. Under optimized reaction condi-
tions (10 mol % of Cu(OTf)2 and 2 mL of TMSA), a number of
arenes and aryl acetylenes were successfully employed in the syn-
thesis of alkenes (Table 2). Mesitylene was successfully employed
for this reaction as the model substrate and several aryl acetylenes
were tested. (Table 2, entries 1–3) Reaction proved to be highly
regeoselective as 1,1-disubstituted ethylenes were obtained as
the only product and no 1,2-disubstituted product was obtained
(Table 3).
R'
Ar
TMSA
Cu
ArH
O3SCF3
2
R'
Ar
Cu(OTf)2
1
O3SCF3
Cu
CH2
R'
O3SCF3
Cu
Ar
R'
4
TMSA
Ar
3
Figure 1. Plausible mechanism.
cat. Cu(OTf)2 / TMSA
r.t.
Ar-B(OH)2
+
Ar'
The coupling reaction was extended to 1,2,4,5-tetramethylben-
zene and 1,2,3,4,5-pentamethylbenzene affording high yields of
desired alkenes, (Table 2, entries 4–9). 1,4-Dimethoxy benzene
and 1,3,5-trimethoxy benzene also participated in the reaction
Ar
Ar'
Scheme 2. Cu-catalyzed reaction of aryl acetylenes and arylboronic acids.
Table 3
Addition of arylboronic acids to aryl acetylenes
Entry
Ar
Ar0
Producta
Yieldb (%)
72
1
2
3
4
5
6
7
8
75
73
70
85
80
88
82
45
Me
Me
Br
Br
OMe
OMe
OMe
Me
MeO
Me
MeO
MeO
Me
Me
Br
Br
Me
Me
Me
Me
9
NO2
O2N
a
All reactions were run by employing 1.0 mmol of arylboronic acid, 5.0 mmol of aryl acetylene, and 0.10 mmol of Cu(OTf)2 in 2 mL of TMSA at room temperature for 24 h.
Isolated yields.
b

896
S. V. Bhilare et al. / Tetrahedron Letters 50 (2009) 893–896
2. For selective examples, see: (a) Zhou, C.; Larock, R. C. J. Am. Chem. Soc. 2004, 126,
2302; (b) Boele, M. D. K.; van Strijdonck, G. P. F.; de Vries, A. H. M.; Kamer, P. C.
J.; de Vries, J. G.; van Leeuwen, P. W. N. M. J. Am. Chem. Soc. 2002, 124, 1586; (c)
Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. Rev. 2002, 102, 1731. and references cited
therein.
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Youn, S. W.; Pastine, S. J.; Sames, D. Org. Lett. 2004, 6, 581; (c) Kakiuchi, F.; Murai,
S. Acc. Chem. Res. 2002, 35, 826.
4. (a) Lenges, C. P.; Brookhart, M. J.Am. Chem. Soc. 1999, 121, 6616; (b) Thalji, R.
K.; Ahrendt, K. A.; Bergman, R. G.; Ellman, J. A. J. Am. Chem. Soc. 2001, 123,
9692.
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Chem. Soc. 2000, 122, 7414; (b) Dorta, R.; Togni, A. Chem. Commun. 2003,
760.
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N.; Mitsuboshi, T.; Setoguchi, H.; Inoue, Y. J. Am. Chem. Soc. 2003, 125,
12102.
7. (a) Reetz, M.; Sommer, K. Eur. J. Org. Chem. 2003, 3485; (b) Mamane, V.; Hannen,
P.; Fürstner, A. Chem. Eur. J. 2004, 10, 4556.
8. (a) Jia, C.; Piao, D.; Oyamada, J.; Lu, W.; Kitamura, T.; Fujiwara, Y. Science
2000, 287, 1992; (b) Jia, C.; Lu, W.; Oyamada, J.; Kitamura, T.; Matsuda,
K.; Irie, M.; Fujiwara, Y. J. Am. Chem. Soc. 2000, 122, 7252; (c) Jia, C.;
Kitamura, T.; Fujiwara, Y. Acc. Chem. Res. 2001, 34, 633. and references
cited therein.
with equal ease. The desired alkenes were obtained in high yields,
(Table 2, entries 10–12).
A plausible mechanism for the reaction involving the steps
shown in Figure 1 could be (1) electrophilic metalation of the arene
by the Cu(II) catalyst 1, which generates arylcopper species 2; (2)
coordination of the acetylene to the Cu; (3) the intramolecular
rearrangement of intermediate 2 to a transient vinyl copper spe-
cies, 3; and (4) protonation of 3 by TMSA, which affords the prod-
uct alkene 4 and regenerates the Cu(II) catalyst (Scheme 1).
This mechanism suggests that the arylcopper species 2, if gen-
erated by some other means, should also react under similar reac-
tion conditions with aryl acetylenes.2a Indeed, we have found that
arylboronic acids react under our optimized reaction conditions
with phenyl acetylene to provide the corresponding 1,1-disubsti-
tuted alkene in high yield (Scheme 2). Most likely these reactions
proceed by transmetalation between arylboronic acid and Cu(II)
generating arylcopper species 2, followed by the coordination of
acetylene to 2, which on subsequent rearrangement generates
transient vinyl copper species 3 (Fig. 1). Several arylboronic acids
were reacted with different aryl acetylenes to synthesize desired
alkenes in high yields. In all the cases, formation of only 1,1-disub-
stituted ethylenes was observed.
9. Typical experimental procedure
Reaction of arenes and aryl acetylenes: The arene (2.0 mmol), the aryl acetylene
(1.0 mmol), Cu(OTf)2 (0.10 mmol), and TMSA (2 mL) were stirred at room
temperature for 20 h. Water (20 mL) was added to the reaction mixture and was
extracted with diethyl ether (3 ꢀ 15 mL). The combined organic layers were
treated with saturated NaHCO3 solution and dried over anhydrous Na2SO4. The
solvent was evaporated under reduced pressure to obtain a 1,1-diaryl ethylene
product. The crude product was purified by chromatography on a silica gel
column.
ArBðOHÞ2 þ CuðOTfÞ2 ! ArCuðOTfÞ ð2Þ þ ðOHÞ2—B—OTf
Equation 1: Transmetalation.
In conclusion, we report an efficient metalation of aromatic C–H
bonds at room temperature by Cu(II) species in trifluoromethane
sulfonic acid (TMSA), leading to the addition of simple arenes to
the C„C bond. The addition to aryl alkynes exclusively affords the
1,1-diaryl ethylenes. The hydroarylation of alkynes has also been
achieved by the reaction of arylboronic acids and aryl alkynes.
The reaction of arylboronic acids and aryl acetylenes: The arylboronic acid
(1.0 mmol), the aryl acetylene (5.0 mmol), Cu(OTf)2 (0.10 mmol), and TMSA
(2 mL) were stirred at room temperature for 24 h. Water (20 mL) was added to
the reaction mixture and was extracted with diethyl ether (3 ꢀ 15 mL). The
combined organic layers were treated with saturated NaHCO3 solution and
dried over anhydrous Na2SO4. The solvent was evaporated under reduced
pressure to obtain a 1,1-diaryl ethylene product. The crude product was purified
by chromatography on a silica gel column.
Spectral data of compounds
1,3,5-Trimethyl-2-(1-phenyl-vinyl)-benzene (Table 1, entry 1) colorless oil; 1H
NMR (300 MHz, CDCl3) d 2.10 (s, 6H), 2.31 (s, 3H), 5.08 (s, 1H), 5.94 (s, 1H), 6.90
(s, 2H), 7.23–7.28 (m, 5H); 13C NMR (75 MHz, CDCl3) d 20.08, 21.03, 114.50,
125.81, 127.52, 128.10, 128.39, 136.11, 136.38, 138.16, 139.54, 146.86; MS (EI)
m/z (rel. intensity) 222 (M+, 44), 207 (100), 192 (81), 178 (08), 165 (11), 152
(05), 128 (11), 115 (12), 96 (11), 77 (10).
Acknowledgments
This work was financially supported by the Council of Scientific
and Industrial Research (CSIR), New Delhi, India. S.V.B., N.B.D.,
A.R.D., and D.G.R. gratefully acknowledge CSIR, New Delhi, for
Senior Research Fellowship.
1,2,3,4,5-Pentamethyl-6-(1-phenyl-vinyl)-benzene (Table 1, entry 7) white solid;
1H NMR (300 MHz, CDCl3) d 2.10 (s, 6H), 2.16 (s, 3H), 2.26 (s, 6H), 5.06 (s,
1H), 5.96 (s, 1H), 7.23– 7.28 (m, 5H); 13C NMR (75 MHz, CDCl3)
d 15.89,
16.56, 17.87, 20.54, 114.29, 126.00, 127.43, 128.35, 128.94, 132.28 132.33,
133.71, 139.99, 148.63; MS (EI) m/z (rel. intensity) 250 (M+, 46), 235 (78),
220 (100), 205 (18), 189 (07), 178 (09), 165 (09),141 (06), 128 (06), 110 (09),
96 (09), 77 (08).
References and notes
1. For selective reviews, see: (a) Shilov, A. E.; Shul’pin, G. B. Chem. Rev. 1997, 97,
2879; (b) Labinger, J. A.; Bercaw, J. E. Nature 2002, 417, 507; (c) Kakiuchi, F.;
Chatani, N. Adv. Synth. Catal. 2003, 345, 1077.