Pd-catalyzed reactions of o-diiodoarenes with alkynes for aromatic ring extension

Article abstract of DOI:10.1021/ol049176m

(Equation Presented) A new and efficient palladium-catalyzed reaction of o-diiodoarenes with internal alkynes produces naphthalenes or anthracenes in good to excellent yields. This procedure provides a simple, catalytic, and straightforward ring-extension method for constructing substituted polycyclic aromatic compounds.

Full text of DOI:10.1021/ol049176m

ORGANIC
LETTERS
2
004
Vol. 6, No. 14
429-2431
Pd-Catalyzed Reactions of
o-Diiodoarenes with Alkynes for
Aromatic Ring Extension
2
Wenying Huang, Xin Zhou, Ken-ichiro Kanno, and Tamotsu Takahashi*
Catalysis Research Center and Graduate School of Pharmaceutical Sciences,
Hokkaido UniVersity and SORST, Japan Science and Technology Corporation (JST),
Kita-ku, Sapporo 001-0021 Japan
tamotsu@cat.hokudai.ac.jp
Received May 6, 2004
ABSTRACT
A new and efficient palladium-catalyzed reaction of o-diiodoarenes with internal alkynes produces naphthalenes or anthracenes in good to
excellent yields. This procedure provides a simple, catalytic, and straightforward ring-extension method for constructing substituted polycyclic
aromatic compounds.
Development of synthetic methods of linearly fused aromatic
compounds has received considerable attention in organic
pling reaction of dihaloarenes with zirconacyclopentadienes
in the presence of CuCl (eq 2).
4
1
synthesis because of their increasing importance in the field
2
of organic electroactive materials. Among possible strategies
to construct acene skeletons, a straightforward aromatic ring
extension reaction as shown in eq 1 seems the simplest and
the most attractive one.
However, this reaction needs a stoichiometric amount of
the zirconium reagent and CuCl. So far, catalytic aromatic
ring extension from dihaloarenes has never been reported,
although some catalytic reactions using mono- or difunc-
5
,6
tionalized benzene are known.
In this paper, we report the first efficient palladium-
During the course of our investigations of the reactions
of zirconacyclopentadienes,3,4 we developed a general cou-
catalyzed aromatic ring extension reaction of o-diiodoarenes
(f) Takahashi, T.; Kotora, M.; Xi, Z. Chem. Commun. 1995, 361. (g) Xi,
Z.; Li, Z.; Umeda, C.; Guan, H.; Li, P.; Kotora, M.; Takahashi, T.
Tetrahedron 2002, 58, 1107. (h) Kotora, M.; Noguchi, Y.; Takahashi, T.
Collect. Czech. Chem. Commun 1999, 64, 1119.
(
1) (a) Saito, S.; Yamamoto, Y. Chem. ReV. 2000, 100, 2901. (b) Watson,
M. D.; Fethtenk o¨ tter, A.; M u¨ llen, K. Chem. ReV. 2001, 101, 1267. (c) Fu,
P. P.; Harvey, R. G. Chem. ReV. 1978, 78, 317.
(4) Condensations of zirconacyclopentadienes with dihaloarenes: (a)
Takahashi, T.; Li, Y.; Stepnicka, P.; Kitamura, M.; Liu, Y.; Nakajima, K.;
Kotora, M. J. Am. Chem. Soc. 2002, 124, 576. (b) Takahashi, T.; Hara, R.;
Nishihara, Y.; Kotora, M. J. Am. Chem. Soc. 1996, 118, 5154.
(5) Benzannulation from monofunctionalized benzenes: (a) Sakakibara,
T.; Tanaka, Y.; Yamasaki, S.-I. Chem. Lett. 1986, 797. (b) Wu, G.;
Rheingold, A. L.; Geib, S. J.; Heck, R. F. Organometallics 1987, 6, 1941.
(c) Yasukawa, T.; Satoh, T.; Miura, M.; Nomura, M. J. Am. Chem. Soc.
2002, 124, 12680. (d) Kawasaki, S.; Satoh, T.; Miura, M.; Nomura, M. J.
Org. Chem. 2003, 68, 6836.
(2) (a) Katz, H. E.; Bao, Z.; Gilat, S. L. Acc. Chem. Res. 2001, 34, 359.
(
b) Dimitrakopoulos, C. D.; Malenfant, P. R. L. AdV. Mater. 2002, 14, 99.
(3) Benzannulations with zirconacyclopentadienes: (a) Takahashi, T.;
Ishikawa, M.; Huo, S. J. Am. Chem. Soc. 2002, 124, 388. (b) Duan, Z.;
Nakajima, K.; Takahashi, T. Chem. Commun. 2001, 1672. (c) Takahashi,
T.; Kitamura, M.; Shen, B.; Nakajima, K. J. Am. Chem. Soc. 2000, 122,
2876. (d) Takahashi, T.; Tsai, F.-Y.; Li, Y.; Nakajima, K.; Kotora, M. J.
Am. Chem. Soc. 1999, 121, 11093. (e) Takahashi, T.; Xi, Z.; Yamazaki,
A.; Liu, Y.; Nakajima, K.; Kotora, M. J. Am. Chem. Soc. 1998, 120, 1672.
1
1
0.1021/ol049176m CCC: $27.50 © 2004 American Chemical Society
Published on Web 06/17/2004

with alkynes, which produces naphthalenes or anthracenes
in good to excellent yields.
A representative procedure is as follows (Scheme 1): To
Table 2. Effect of Additives on Palladium-Catalyzed Ring
Extension Reactions of o-Diiodoarenes with Alkynes
a
entry
additive
amount (equiv)
yield of 3bb (%)
1
2
3
4
5
6
7
8
9
none
-
0
46
99
38
47
19
7
Scheme 1
AgOAc
AgOAc
Ag3PO4
Ag2CO3
AgNO3
K2CO3
Cs2CO3
Et3N
1.0
2.0
0.7
1.0
2.0
1.0
1.0
6.0
8
0
a
The reaction was performed using o-diiodobenzene 1a (1.0 mmol) and
4
-octyne 2b (6.0 mmol) in the presence of Pd (OAc)2 (0.05 mmol) in toluene
a solution of o-diiodobenzene 1a (1.0 mmol), Pd(OAc)
mmol), and AgOAc (2.0 mmol) in toluene (6 mL) was added
-hexyne 2a (6.0 mmol) at room temperature. After the
2
(0.05
b
at 110 °C for 24 h. The yields were determined by GC analyses and based
on the amount of 1a.
3
mixture was stirred for 6 h at 110 °C, 1,2,3,4-tetraethyl-
naphthalene 3a was formed in 92% GC yield along with the
formation of hexaethylbenzene (0.16 mmol). At room
temperature the reaction did not proceed. An excess amount
of alkyne was needed in these reactions to consume 1a
consumed completely, and the yield of 3b was relatively
lower (entry 2). The other silver salts such as Ag CO , Ag -
2 3 3
Table 3. Palladium-Catalyzed Ring Extension Reactions of
Various o-Diiodoarenes with Alkynesa
completely. As a catalyst, Pd(OAc)
2
gave better results than
, and PdCl (Table 1).
Pd (dba) , Pd(PPh , [PdCl(π-allyl)]
2
3
3
)
4
2
2
Table 1. Palladium-Catalyzed Reaction of o-Diiodobenzene 1a
with 4-Octyne 2ba
amount of 2b
Pd catalystb
(mol %)
yield of 3bc
entry
(equiv)
(%)
1
2
3
4
5
6
7
3.0
6.0
6.0
6.0
6.0
6.0
6.0
Pd(OAc)2 (5.0)
Pd(OAc)2 (5.0)
Pd2(dba)3 (2.5)
Pd(PPh3)4 (5.0)
[PdCl(C3H5)]2 (2.5)
PdCl2(PBu3)2 (5.0)
PdCl2 (5.0)
63d
99 (80)
93
63
78
75
83
a
The reaction was performed using o-diiodobenzene 1a (1.0 mmol) and
4
-octyne 2b in the presence of Pd catalyst and AgOAc (2.0 mmol) in toluene
b
at 110 °C for 24 h unless otherwise noted. Amounts of Pd catalysts are
based on the amount of 1a used. GC yields. Isolated yield is given in
parentheses. 3.0 mmol of AgOAc was used.
c
d
It is worth noting that the silver additive plays an important
role in this reaction as shown in Table 2. It is known that
7
silver salts produce Pd cation species. In the absence of
additives, this reaction could not proceed (entry 1). If the
amount of AgOAc was less than 2.0 equiv, 1a could not be
(
6) Benzannulation from difunctionalized benzenes: (a) Iwasawa, N.;
Shido, M.; Maeyama, K.; Kusama, H. J. Am. Chem. Soc. 2000, 122, 10226.
b) Larock, R. C.; Tian, Q.; Oletnev. A. A. J. Am. Chem. Soc. 1999, 121,
(
3
3
238. (c) Tian, Q.; Pletnev, A. A.; Larock, R. C. J. Org. Chem. 2003, 68,
39. (d) Asao, N.; Takahashi, K.; Lee, S.; Kasahara, T.; Yamamoto, Y. J.
a
Am. Chem. Soc. 2002, 124, 12650. (e) Pe n˜ a, D.; Escudero, S.; P e´ rez, D.;
Guiti a´ n, E.; Castedo, L. Angew. Chem., Int. Ed. 1998, 37, 2659. (f) Pe n˜ a,
D.; P e´ rez, D.; Guiti a´ n, E.; Castedo, L. J. Am. Chem. Soc. 1999, 121, 5827.
Unless otherwise noted, diiodoarene (1.0 mmol), alkyne (6.0 mmol),
Pd(OAc)2 (0.05 mmol), and AgOAc (2.5 mmol) were refluxed in toluene
b
for 48 h. GC or NMR yields. Isolated yields are given in parentheses.
c
2.0 mmol of AgOAc was used and refluxed for 24 h. d 3.0 mmol of diynes
(
g) Pe n˜ a, D.; P e´ rez, D.; Guiti a´ n, E.; Castedo, L. J. Org. Chem. 2000, 65,
944. (h) Yoshikawa, E.; Radhakrishnan, K. V.; Yamamoto, Y. J. Am.
Chem. Soc. 2000, 122, 7280.
7) Bebgoa, E. G.; Cuerva, J. M.; Echavarren, A. M.; Martorell, G.
Angew. Chem., Int. Ed. Engl. 1997, 36, 767.
2c was used. e Another isomer, 1,4-dipropyl-2,3-dipentyn-1-ylnaphthalene
(3e), was also obtained in 25% GC yield. Reference 10. g 2b (12 mmol),
Pd(OAc)2 (0.1 mmol), and AgOAc (6.0 mmol) were used.
6
f
(
2430
Org. Lett., Vol. 6, No. 14, 2004

PO
entry 4-6). In addition, common bases such as K
CO , and triethylamine showed little or no efficiency for the
reaction (entries 7-9).
Table 3 summarizes the results of the reactions of various
o-diiodoarenes with alkynes catalyzed by Pd(OAc) in the
4
, and AgNO
3
gave 3b in much lower yields than AgOAc
carried out with monoiodobenzene, o-chloroiodobenzene, and
p-diiodobenzene, the corresponding cyclopentadiene deriva-
tives 4a, 4b, and 4c were obtained in 67, 93, and 21% yields,
(
2
CO , Cs
3
2
-
3
9
respectively (Scheme 2). The formation of the cyclopenta-
2
Scheme 2
presence of AgOAc. o-Diiodoarenes can be easily prepared
from either direct iodination of aromatic compounds with
iodine and periodic acid8 or condensation of 1,2,4,5-
tetraiodobenzene and zirconacyclopentadienes as we reported
4
a
previously. When diyne 2c was employed for the reaction,
the tricyclic compound 3c was formed in high yield (entry
3
). The reaction with conjugated diyne 2d gave the corre-
sponding bisalkynylnaphthalene as a mixture of regioisomers
entry 4). Highly congested persubstituted naphthalene 3f
(
could be prepared from diiodotetramethylbenzene 1b in a
good yield (entry 5). The reaction could be applied to not
only diiodobenzenes but also to diiodonaphthalene 1c to
afford the corresponding anthracene 3g in 71% yield (entry
diene ring is consistent with the results reported by Heck.5b
These results clearly show that the good leaving group at
the ortho position on the haloarene ring is essential for the
present benzannulation reaction.
In conclusion, this new catalytic procedure provides a
simple and straightforward ring extension method for
constructing substituted polycyclic aromatic compounds.
Further study to elucidate precise mechanism of this reaction
and to extent the scope of synthetic utility for construction
of multisubstituted polycyclic aromatic compounds are now
in progress.
6). In this case, no phenanthrene derivative was detected in
the reaction mixture. Furthermore, the reaction similarly
proceeded with heteroaromatic diiodide 1d to produce the
corresponding dibenzothiophene 3h in 68% isolated yield
(entry 7). A double-benzannulation reaction was also possible
with 1,2,4,5-tetraiodobenzene to produce the corresponding
anthracene derivative 3g (entry 8).
Among the investigated dihaloarenes, o-dibromobenzene
and o-bromoiodobenzene showed much lower reactivity for
the reactions with 4-octyne (2b) under the same reaction
conditions as used here. Naphthalene 3b was formed in 13
and 24% yields, respectively, while o-dichlorobenzene did
not react. On the other hand, when the same reactions were
Supporting Information Available: Details of the ex-
perimental procedure and analytical data for compounds
a-j and 4a-c. This material is available free of charge
via the Internet at http://pubs.acs.org.
3
OL049176M
(
9) The structures of compounds 3d,e and 4a-c were characterized by
(8) (a) Mattern, D. L. J. Org. Chem. 1984, 49, 3051. (b) Suzuki, H.
NMR and NOE experiments. See the Supporting Information.
Org. Synth. 1971, 51, 94 and references therein.
(10) Muraki, T.; Togo, H.; Yokoyama, M. Synlett 1998, 286.
Org. Lett., Vol. 6, No. 14, 2004
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