Synthesis of highly substituted 1,3-butadienes by palladium-catalyzed arylation of internal alkynes

Article abstract of DOI:10.1002/anie.200460409

Four molecules are coupled together by the single treatment of aryl boronic acids with alkynes in the absence or presence of iodobenzene under palladium catalysis to afford 1,4-diaryl-1,3-butadienes as the major product. Addition of a silver salt as oxidant and/or base effectively enables the selective catalytic production of the π-conjugated compounds.

Full text of DOI:10.1002/anie.200460409

Angewandte
Chemie
Multicomponent Coupling
addition of iodobenzene as the third component allows the
construction of 1,3-dienes that bear two different aryl groups
Synthesis of Highly Substituted 1,3-Butadienes by at C1 and C4. Among the related reactions reported to
[
5–12]
Palladium-Catalyzed Arylation of Internal
Alkynes**
date
are the palladium-catalyzed and -promoted aryla-
[
5]
[6]
tions of alkynes with aryl tin and aryl magnesium reagents,
respectively, in each of which 2:1 coupling occurs to give 1,2-
diaryl ethenes selectively. Meanwhile, the palladium-cata-
lyzed three-component coupling of aryl iodides, alkynes, and
[
7]
Tetsuya Satoh, Shinji Ogino, Masahiro Miura,* and
Masakatsu Nomura
[
11]
aryl boronic acids was also examined with KHCO as base.
3
In this case, 1:1:1 coupling takes place to give 1,2-diaryl
ethenes effectively. This contrasts markedly with the present
1:2:1 coupling.
The transition-metal-catalyzed arylation of alkynes by halo-
genated or metalated aromatic reagents through carbometa-
lation is a powerful tool for constructing p-conjugated
[
12]
When phenylboronic acid (1a) was treated with diphenyl-
acetylene (2a) (1 equiv) in the presence of Pd(OAc)2
(2.5 mol%) and Ag CO (1 equiv) in 1-propanol/H O (9:1)
[
1]
molecules. Some of these reactions are conducted in the
presence of terminators such as hydrogen sources or organo-
metallic reagents to give rise to three-component coupling
products. In other cases, the reactions involve cyclometalation
in the termination step to yield cyclic compounds.
2
3
2
at 1208C for 0.5 h, 1,1,2,3,4,4-hexaphenyl-1,3-butadiene (3a)
was formed in 70% yield along with a minor amount of
1,1,2,2-tetraphenylethene (4a) (Table 1, entry 1). The yield of
[
2a]
As examples for the latter case, we reported rhodium-,
3a was somewhat lower in the absence of H O, but the
2
[
2b]
[2c]
iridium-, and palladium-catalyzed coupling reactions of
alkynes with aroyl chlorides or aryl iodides to afford the
corresponding indenones or naphthalenes. In the palladium-
catalyzed reaction of aryl iodides, the use of silver(i) salts as
base was essential for the effective sequential insertion of two
alkyne molecules and the successive ring closure (Scheme 1,
formation of 4a was suppressed (Table 1, entry 2). The
reaction also proceeded smoothly in 1,4-dioxane/H O,
2
whereas MeCN/H O and DMF/H O were not effective
2
2
(Table 1, entries 3–5). Ag O and AgOAc could be used as
2
oxidants instead of Ag CO , albeit with lower efficiency
2
3
(Table 1, entries 6 and 7). Cu(OAc) did not catalyze the
2
[
2c,3]
route A).
reaction (Table 1, entry 8).
Table 1: Reaction of phenylboronic acid (1a) with diphenylacetylene (2a)
[
a]
with varying oxidants and solvents.
Scheme 1. Coupling of aryl iodides and aryl boronic acids with alkynes.
Silver(i) salts are known to act not only as base, but also as
[b]
Entry
Oxidant (mmol)
Ag CO (2)
Solvent
Yield [%]
[
4]
oxidant, in palladium-catalyzed coupling reactions. Conse-
quently, we have undertaken alkyne arylation reactions with
aryl boronic acids instead of aryl iodides under similar
3a
4a
1
2
3
4
5
6
7
8
1-propanol/H O (9:1)
1-propanol
1,4-dioxane/H O (9:1)
MeCN/H O (9:1)
70 (67)
63
6
2
3
27
9
7
2
2
3
2
Ag CO (2)
2
3
[
2c]
conditions to those employed in route A. We found that
the predominant products were not the expected naphtha-
lenes, but rather 1,4-diaryl-1,3-butadienes by a 2:2 coupling
reaction with the formation of three carbon–carbon bonds
Ag CO (2)
65
14
42
59
40
6
2
3
2
Ag CO (2)
2
2
3
3
2
Ag
CO
(2)
DMF/H
O (9:1)
2
Ag O (2)
1-propanol
1-propanol
1-propanol
2
AgOAc (4)
(
Scheme 1, route B). Furthermore, it was revealed that the
Cu(OAc) (2)
trace
2
[
a] The reaction of 1a (2 mmol) with 2a (2 mmol) was conducted with
3
[
*] Dr. T. Satoh, S. Ogino, Prof. Dr. M. Miura, Prof. Dr. M. Nomura
Department of Applied Chemistry
Faculty of Engineering, Osaka University
Suita, Osaka 565-0871 (Japan)
Pd(OAc) (0.05 mmol) in the solvent (5 cm ) at 1208C for 0.5 h. [b] Yield
2
determined by GC. The value in parenthesis indicates the yield of the
isolated product.
Fax: (+81)6-6879-7362
E-mail: miura@chem.eng.osaka-u.ac.jp
(4-Methylphenyl)boronic acid (1b) was treated with 2a
under the conditions used for the reaction in Table 1, entry 1
Although the coupling took place similarly to give 1,4-di(4-
methylphenyl)-1,2,3,4-tetraphenyl-1,3-butadiene in 60%
yield, its NMR spectra indicated that it consists of at least
[
**] We thank Ms. E. Mochizuki, Osaka University, for X-ray crystal-
structure analysis.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or fromthe author.
Angew. Chem. Int. Ed. 2004, 43, 5063 –5065
DOI: 10.1002/anie.200460409
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5063

Communications
two geometrical isomers. As expected, the reaction of 1b with
di(4-methylphenyl)acetylene (2b) gave 1,1,2,3,4,4-hexa(4-
methylphenyl)-1,3-butadiene (3b) in 58% yield as the single
major product (Scheme 2). Interestingly, the reaction of 1a
Scheme 4. A plausible mechanism for the coupling of aryl boronic
acids and aryl iodides with alkynes.
Scheme 2. Reaction of 1b with 2b. Reaction conditions: 1b (2 mmol),
2
b (2 mmol), Pd(OAc) (0.05 mmol), Ag CO (2 mmol), 1-propanol/
2 2 3
H O (9:1), 1208C, 0.5 h.
2
Ag CO (1 mmol) in 1-propanol/H O at 1208C for 0.5 h, 1-(4-
2
3
2
methoxyphenyl)-1,2,3,4,4-pentaphenyl-1,3-butadiene
(3d)
[
18]
was produced in 71% yield (Scheme 5).
Only a minor
with 4-octyne (2c) afforded only (4Z,6Z)-4,7-diphenyl-5,6-
dipropyl-4,6-decadiene (3c) without contamination with any
other isomers (Scheme 3). The purity and structure of 3c were
amount of 1,4-di(4-methoxyphenyl)-1,2,3,4-tetraphenyl-1,3-
Scheme 3. Reaction of 1a with 2c. Reaction conditions: 1a (2 mmol),
Scheme 5. Reaction of 1 with 2a and 5. Reaction conditions: 1
2
c (2 mmol), Pd(OAc) (0.05 mmol), Ag CO (2 mmol), 1208C, 0.5 h.
2
2
3
(
(
1 mmol), 2a (1 mmol), 5 (1 mmol), Pd(OAc) (0.05 mmol), Ag CO
2 2 3
Yield of 3c: 41% in 1,4-dioxane/H O (9:1); 36% in 1-propanol.
2
1 mmol), 1-propanol/H O (9:1), 1208C, 0.5 h. [a] Yield determined by
2
GC (The value in parenthesis indicates the yield of the isolated
product).
[
13]
confirmed by NMR spectroscopic studies and X-ray
crystal-structure analysis (see Supporting Information).
[
14]
The first step of the present reaction may involve
butadiene (5%), which may be the result of an oxidative 2:2
coupling of 1c with 2a, was detected by GC–MS. The use of
the substrates in the ratio 1c/2a/5 = 1:2:1 resulted in a
decrease in the yield of 3d (45%). (4-Cyanophenyl)- and
(2-methylphenyl)boronic acids, 1d and 1e respectively, also
reacted with 2a and 5 to afford the corresponding dienes 3e
and 3 f. In these cases, the oxidative 2:2 coupling products
were not detected. In each case, the major product 3 was
found to consist of two possible isomers (ꢀ 2:1) by NMR
spectroscopic analysis.
transmetalation to give an aryl palladium species A
[
8,9b–d]
(
Scheme 4).
Subsequently, the insertion of two alkyne
molecules forms a dienylpalladium intermediate C. The
successive second transmetalation and reductive elimination
[
15]
give 1,4-diarylated 1,3-diene 3.
The palladium(0) species
generated in the last step may be reoxidized by the silver(i)
[
16]
species to close the catalytic cycle. The result of the reaction
of 1b with 2a implies that E/Z isomerization in B and C may
[
17]
take place. However, the reason why it did not occur in the
coupling of 1a with 2c is not clear.
In summary, we have demonstrated that the coupling
reactions of aryl boronic acids with alkynes in the absence and
presence of iodobenzene can be performed with a palladium
catalyst and a silver salt to give selectively 2:2 and 1:2:1
coupling products, respectively. These reactions offer a
straightforward route to multiarylated butadienes, which are
of interest for their photochemical, electrochemical, and
The intermediate A may be generated directly through
oxidative addition of aryl halides to a palladium(0) species
dotted arrow in Scheme 4). Thus, we next examined three-
component reaction of aryl boronic acids, alkynes, and
iodobenzene. When a mixture of (4-methoxyphenyl)boronic
acid (1c; 1 mmol), 2a (1 mmol), and iodobenzene (5; 1 mmol)
(
[
19]
was treated in the presence of Pd(OAc) (0.05 mmol) and
biological properties.
2
5
064
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
Angew. Chem. Int. Ed. 2004, 43, 5063 –5065

Angewandte
Chemie
[
[
13] CCDC-236664 contains the supplementary crystallographic data
Experimental Section
for this paper. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cam-
bridge Crystallographic Data Centre, 12, Union Road, Cam-
bridge CB21EZ, UK; fax: (+ 44)1223-336-033; or deposit@
ccdc.cam.ac.uk).
Typical procedure: A mixture of 1 (2 mmol), 2 (2 mmol), Pd(OAc)
2
(0.05 mmol, 11 mg), and Ag CO3 (2 mmol, 550 mg) in 1-propanol/
2
H O (9:1, 5 mL) was stirred under N2 at 1208C. After 0.5 h, the
2
mixture was cooled to room temperature, Et O (100 mL) was added,
2
and insoluble materials were removed by filtration through filter
paper. The product was isolated by recrystallization from toluene/
hexane and/or column chromatography on silica gel with hexane/
EtOAc as eluent. Characterization data of products are summarized
in the Supporting Information.
14] In this case, the formation of a small
amount of the 1:3 coupling product was
observed (1% in dioxane/H O, 3% in 1-
2
propanol). The structure of the by-product
shown below was unambiguously deter-
mined by its 2D NMR spectra and NOE
experiments. A similar product is formed
by the reaction of iodobenzene with 3-
Received: April 22, 2004
Revised: July 26, 2004
hexyne: G. Wu, A. L. Rheingold, S. J. Gelb,
R. F. Heck, Organometallics 1987, 6, 1941.
Keywords: alkynes · arylation · CÀC coupling ·
.
homogeneous catalysis · palladium
[
15] Although the reason why only two molecules of the alkynes are
selectively incorporated into the products is not definitive at the
present stage, it may be attributed to stabilization of the
dienylpalladium intermediate (C in Scheme 4) by chelation;
see: X. Zeng, Q. Hu, M. Qian, E.-I. Negishi, J. Am. Chem. Soc.
[
1] a) I. Marek, J. F. Normant in Metal-catalyzed Cross-coupling
Reactions (Eds.: F. Diederich, P. J. Stang), Wiley-VCH, Wein-
heim, 1998, p. 271; b) S. Bräse, A. de Meijere in Handbook of
Organopalladium Chemistry for Organic Synthesis (Ed: E.
Negishi), Wiley-Interscience, New York, 2002, p. 1369; c) K.
Fagnou, M. Lautens, Chem. Rev. 2003, 103, 169.
2003, 125, 13636.
[
16] The silver salts may also promote the transmetalation step: Y.
Nishihara, H. Onodera, K. Osakada, Chem. Commun. 2004, 192.
A referee for this paper suggested an alternative pathway, in
I
which the vinyl moiety of B migrates to Ag and thermal
[
2] a) K. Kokubo, K. Matsumasa, M. Miura, M. Nomura, J. Org.
Chem. 1996, 61, 6941; b) T. Yasukawa, T. Satoh, M. Miura, M.
Nomura, J. Am. Chem. Soc. 2002, 124, 12680; c) S. Kawasaki, T.
Satoh, M. Miura, M. Nomura, J. Org. Chem. 2003, 68, 6836.
3] M. Kotora, H. Matsumura, G. Gao, T. Takahashi, Org. Lett. 2001,
decomposition occurs to afford the diene: G. M. Whitesides,
C. P. Casey, J. K. Krieger, J. Am. Chem. Soc. 1971, 93, 1379. It
was confirmed that without addition of the silver salt, the
stoichiometric reaction of 1a (0.5 mmol) with 2a (0.5 mmol) in
[
[
the presence of Pd(OAc)2 (0.25 mmol) in 1-propanol/H O at
2
3, 3467.
1208C for 0.5 h gave predominantly diene 3a in 56% yield, along
4] For examples, see: a) Y. Fujiwara, C. Jia in Handbook of
Organopalladium Chemistry for Organic Synthesis (Ed.: E.
Negishi), Wiley-Interscience, New York, 2002, p. 2859; b) A. G.
Myers, D. Tanaka, M. R. Mannion, J. Am. Chem. Soc. 2002, 124,
with a small amount of 4a (2%). This result indicates that the
diene formation can take place on Pd and that the participation
of vinyl silver(i) species cannot be excluded.
[
17] G. Dyker, A. Kellner, Tetrahedron Lett. 1994, 35, 7633.
Z,Z Butadienes are also known to undergo thermal isomer-
ization to the corresponding E,E isomers via cyclobutenes: G. A.
Doorakian, H. H. Freedman, J. Am. Chem. Soc. 1968, 90, 5310.
18] An alternative pathway initiated by the oxidative cyclization of
11250; c) L. M. Klingensmith, N. E. Leadbeater, Tetrahedron
Lett. 2003, 44, 765.
[
5] H. Oda, M. Morishita, K. Fugami, H. Sano, M. Kosugi, Chem.
Lett. 1996, 811.
[
[
[
6] C. Broquet, H. Riviere, J. Organomet. Chem. 1982, 226, 1.
7] In contrast to the reactions with aryl metal reagents, the use of
the corresponding methyl metal reagents results in 2:2 coupling
0
Pd species with two alkyne molecules cannot be excluded. Both
[12,18a]
[18b]
mechanisms via palladacycle
and acyclic intermediates
have been proposed for diene synthesis reactions: a) E. Shir-
akawa, H. Yoshida, Y. Nakao, T. Hiyama, J. Am. Chem. Soc.
[
5,6]
to give 1,4-dimethyl-1,3-butadienes.
[
8] For the homocoupling of aryl boronic acids, see: a) K. A. Smith,
E. M. Campi, W. R. Jackson, S. Marcuccio, C. G. M. Naeslund,
G. B. Deacon, Synlett 1997, 131; b) M. S. Wong, X. L. Zhang,
Tetrahedron Lett. 2001, 42, 4087; c) G. W. Kabalka, L. Wang,
Tetrahedron Lett. 2002, 43, 3067; d) J. P. Parrish, Y. C. Jung, R. J.
Floyd, K. W. Jung, Tetrahedron Lett. 2002, 43, 7899; e) H.
Yoshida, Y. Yamaryo, J. Ohshita, A. Kunai, Tetrahedron Lett.
1999, 121, 4290; b) H. Kinoshita, T. Nakamura, H. Kakiya, H.
Shinokubo, S. Matsubara, K. Oshima, Org. Lett. 2001, 3, 2521.
19] For recent papers, see: a) S. Hꢀnig, M. Kemmer, H. Wenner, F.
Barbosa, G. Gescheidt, I. F. Perepichka, P. Bäuerle, A. Emge, K.
Peters, Chem. Eur. J. 2000, 6, 2618; b) J.-H. Kim, S. Noh, K. Kim,
S.-T. Lim, D.-M. Shin, Synth. Met. 2001, 117, 227; c) T. Suzuki, H.
Higuchi, M. Ohkita, T. Tsuji, Chem. Commun. 2001, 1574; d) R.
Davis, V. A. Mallia, S. Das, Chem. Mater. 2003, 15, 1057; e) J. L.
Gage, H. A. Kirst, D. OꢁNeil, B. A. David, C. K. Smith II, S. A.
Naylor, Bioorg. Med. Chem. 2003, 11, 4083.
[
2003, 44, 1541.
[
9] For Heck-type coupling of aryl boronic acids, see: a) C. S. Cho, S.
Uemura, J. Organomet. Chem. 1994, 465, 85; b) X. Du, M.
Suguro, K. Hirabayashi, A. Mori, T. Nishikata, N. Hagiwara, K.
Kawata, T. Okada, H. F. Wang, K. Fugami, M. Kosugi, Org. Lett.
2001, 3, 3313; c) Y. C. Jung, R. K. Mishra, C. H. Yoon, K. W.
Jung, Org. Lett. 2003, 5, 2231; d) M. M. S. Andappan, P. Nilsson,
M. Larhed, Chem. Commun. 2004, 218.
[
10] A 1:2 coupling of vinyl boronates with alkynes to give vinylidene
[
9b]
cyclopentadienes has been reported.
[
[
11] C. Zhou, D. E. Emrich, R. C. Larock, Org. Lett. 2003, 5, 1579.
12] The use of tetramethyltin, acetylene dicarboxylates, and aryl
iodides affords 1:2:1 coupling products: a) R. van Belzen, H.
Hoffmann, C. J. Elsevier, Angew. Chem. 1997, 109, 1833; Angew.
Chem. Int. Ed. Engl. 1997, 36, 1743; b) R. van Belzen, R. A.
Klein, H. Kooijman, N. Veldman, A. L. Spek, C. J. Elsevier,
Organometallics 1998, 17, 1812.
Angew. Chem. Int. Ed. 2004, 43, 5063 –5065
www.angewandte.org
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5065