Synthesis of alkylated benzo[2,1-b:3,4-6′]dithiophenes by annulative coupling and their direct arylation under palladium catalysis

Article abstract of DOI:10.1246/cl.2007.1336

The annulative coupling of 3,3′-diiodo-2,2′-bithiophene with internal alkynes efficiently proceeds in the presence of a palladium catalyst to afford the corresponding benzo[2,1-b:3,4-b′]dithiophene derivatives. The dithiophenes also undergo palladium-cata

Full text of DOI:10.1246/cl.2007.1336

1336
Chemistry Letters Vol.36, No.11 (2007)
Synthesis of Alkylated Benzo[2,1-b:3,4-b0]dithiophenes by Annulative Coupling
and Their Direct Arylation under Palladium Catalysis
Hiroyuki Watanabe, Jun Kumagai, Hayato Tsurugi, Tetsuya Satoh, and Masahiro Miuraꢀ
Department of Applied Chemistry, Faculty of Engineering, Osaka University, Suita, Osaka 565-0871
(Received August 27, 2007; CL-070914; E-mail: miura@chem.eng.osaka-u.ac.jp)
The annulative coupling of 3,30-diiodo-2,20-bithiophene
with internal alkynes efficiently proceeds in the presence of a
palladium catalyst to afford the corresponding benzo[2,1-b:3,4-
b0]dithiophene derivatives. The dithiophenes also undergo palla-
dium-catalyzed direct arylation with aryl bromides at the 2- and
7-positions selectively.
Table 1. Reaction of 3,30-diiodo-2,20-bithiophene (1) with 4-
octyne (2a)a
I
I
Pd(OAc)2
+
base
solvent
S
S
1
2a
Poly- and oligoaryl compounds involving a thiophene unit
have become increasingly important for the organic components
of electronic devices, and thus, the synthesis of thiophene-fused
aromatic compounds having benzothiophene and thienothio-
phene skeletons as well as oligothiophenes as the ꢀ-conjugated
moieties has recently attracted much attention.1
+
S
S
S
S
3a
4
Yieldb/%
Entry
Base
Solvent
Time/h
3a
4
On the other hand, the transition-metal-catalyzed annulation
of functionalized arenes such as aryl halides with alkynes is now
recognized to be a potential tool for preparing condensed aro-
matics.2 In the context of our study of catalytic arylation reac-
tions,3 we have undertaken the annulation of a bithiophene with
an aliphatic alkyne, aiming at developing a facile method for
constructing an alkylated benzodithiophene unit that has both
planarity and solubility. It has been found that 3,30-diiodo-2,20-
bithiophene (1) efficiently couples with internal aliphatic al-
kynes in a formal ½4 þ 2ꢁ manner by using Pd(OAc)2 and an ap-
propriate tertiary amine as catalyst and base to selectively afford
the corresponding annulated benzodithiophenes.4,5 Furthermore,
the catalytic direct arylation of the dithiophenes has been exam-
ined.
1
2
3
4
5
6
7d
8
Na2CO3
K2CO3
Ag2CO3
Bu3N
CyNMe2 DMF
Cy2NMe DMF
Cy2NMe DMF
Cy2NMe o-xylene
DMF
DMF
toluene
DMF
8
8
8
8
8
4
2
8
48
54
5
11
29c
>95
92
>95 (84)
>95
32
aReaction conditions: [1]:[2a]:[Pd(OAc)2]:[base] = 0.2:0.6:
0.02:0.6 (in mmol), at 100 ꢂC under N2. bGC yield based
on the amount of 1 used. Value in parentheses is isolated
yield. cE/Z = 12:1. d[1]:[2a]:[Pd(OAc)2]:[base] = 0.2:0.24:
0.01:0.48 (in mmol), at 130 ꢂC.
When the diiodide 1 (0.2 mmol) was treated with 4-octyne
(2a) (0.6 mmol) in the presence of Pd(OAc)2 (0.02 mmol) and
Na2CO3 (0.6 mmol) as catalyst and base, respectively, in DMF
at 100 ꢂC for 8 h, 4,5-dipropylbenzo[2,1-b:3,4-b0]dithiophene
(3a) (48%) was formed along with an inseparable byproduct,
4-propenyl-5-propylbenzo[2,1-b:3,4-b0]dithiophene (4) (5%),
the starting material 1 (36%) being recovered (Table 1,
Entry 1). The reaction with K2CO3 as base also gave 3a and 4
(Entry 2).4a Use of Ag2CO3 in toluene4c unexpectedly led to
selective formation of 4, although the yield was low (Entry 3).
It was fortunately found that use of trialkylamines as base
in DMF suppressed the formation of 4 and allowed selective
synthesis of 3a with high yield (Entries 4–6). A bulky amine,
Cy2NMe (Cy = cyclohexyl) was relatively more effective than
Bu3N and the reaction was completed within 2 h at 130 ꢂC even
with reduced amounts of Pd(OAc)2 (0.01 mmol) and 2a
(0.24 mmol) (Entry 7). The reaction in o-xylene was sluggish
(Entry 8). It is noted that the annulation of 3,30-dibromo-2,20-bi-
thiophene in place of 1 with 2a using various phosphine ligands
did not proceed.
PdI
I
PdI2
−PdI2
Pd0
(a)
2a
3a
1
S
S
S
S
B
A
−HPdI
(b)
.
PdI
−HPdI
I
Pd0
4
S
S
S
S
C
D
Scheme 1. Proposed mechanism leading to 3a and 4.
which is followed by insertion of 2a to produce vinylpalladium
A. The subsequent formation of palladacycle B (path a) and re-
ductive elimination affords 3a together with PdI2. The reduction
of PdI2 to catalytically active Pd0 may be enhanced by an amine
added.6 In an alternative pathway from A, ꢁ-H elimination gives
allene C (path b).7 The reaction of C with Pd0 leading to benzyl-
palladium D and ꢁ-H elimination in D give 4.7 Use of an amine
base is considered to suppress path b, whereas an inorganic
A plausible mechanism for the reaction of 1 with 2a leading
to 3a and 4 is illustrated in Scheme 1. The first step involves ox-
idative addition of 1 to Pd0 generated in the reaction medium,
Copyright Ó 2007 The Chemical Society of Japan

Chemistry Letters Vol.36, No.11 (2007)
1337
References and Notes
1
R
R
I
I
R
a) J. Roncali, Chem. Rev. 1997, 97, 173. b) U. Mitschke, P.
Bauerle, J. Mater. Chem. 2000, 10, 1471. c) H. E. Katz, Z.
Pd(OAc)2
+
¨
S
S
Cy2NMe/DMF
130 oC, 2-3 h
Bao, S. L. Gilat, Acc. Chem. Res. 2001, 34, 359. d) Y.
Sun, Y. Liu, D. Zhu, J. Mater. Chem. 2005, 15, 53. e) I. F.
Perepichka, D. F. Perepichka, H. Meng, F. Wudl, Adv.
Mater. 2005, 17, 2281. f) K. Takimiya, Y. Kunugi, T.
Otsubo, Chem. Lett. 2007, 36, 578.
R
S
S
3b: R = n-C5H11, 62%a
3c: R = n-C7H15, 74%a, 64%b
3d: R = Ph, 39%c
2b: R = n-C5H11
2c: R = n-C7H15
2d: R = Ph
1
Scheme 2. Reaction of 3,30-diiodo-2,20-bithiophene (1) with
2
3
a) R. C. Larock, Top. Organomet. Chem., 2005, Vol. 14,
p. 147. b) J. Tsuji, Palladium Reagents and Catalysts, 2nd
ed., John Wiley & Sons, Chichester, UK, 2004, pp. 231–265.
Selected reports on catalytic annulation of alkynes from our
laboratory: a) T. Yasukawa, T. Satoh, M. Miura, M. Nomura,
J. Am. Chem. Soc. 2002, 124, 12680. b) S. Kawasaki, T.
Satoh, M. Miura, M. Nomura, J. Org. Chem. 2003, 68,
6836. c) K. Ueura, T. Satoh, M. Miura, J. Org. Chem.
2007, 72, 5362.
a) The related Pd-catalyzed annulation of 1,8-diiodonaphtha-
lene with alkynes was reported. It was described that the
reaction with 2a in the presence of Pd(OAc)2 and K2CO3–
Bu4NBr gave the expected acenaphthylene derivative in a
moderate yield with contamination of an isomer (13%) bear-
ing one exo-cyclic double bond. It would have a similar
structure to that of 4: G. Dyker, J. Org. Chem. 1993, 58,
234. b) Cr-Promoted reaction of 2,20-dibromo-1,10-biphenyl
with alkynes: K. Kanno, Y. Liu, A. Iesato, K. Nakajima, T.
Takahashi, Org. Lett. 2005, 7, 5453. c) Pd-Catalyzed 1:2
coupling of 1,2-diiodobenzene with alkynes: W. Huang, X.
Zhou, K. Kanno, T. Takahashi, Org. Lett. 2004, 6, 2429.
a) Dialkoxynaphtho[2,1-b:3,4-b0]dithiophene: J. D. Tovar,
A. Rose, T. M. Swager, J. Am. Chem. Soc. 2002, 124,
7762. b) Dialkylbenzo[1,2-b;4,3-b0]dithiophene: Y. Nishide,
Y. Inagaki, H. Ogura, K. Tanaka, Phosphorus, Sulfur Silicon
Relat. Elem. 2005, 180, 1479. c) K. Tanaka, H. Osuga, N.
Tsujiuchi, M. Hisamoto, Y. Sakaki, Bull. Chem. Soc. Jpn.
2002, 75, 551.
a
alkynes 2b–2d. [1]:[2]:[Pd]:[Cy2NMe] = 0.2:0.24:0.01:0.48,
c
b1:1.2:0.01:2.4, 1:1.2:0.05:2.4 (in mmol).
n-C7H15
n-C7H15
Pd(OAc)2/
2P(2-biphenyl)(t-Bu)2
a
+
3c
ArBr
Cs2CO3/DMF
R
S
S
R
5: R = H, 67%b
6: R = Ph, 62%
4
n-C7H15
n-C7H15
S
S
7: 54%
Scheme 3. Reaction of 3c with ArBr. a[ArBr]:[3c]:
[Pd(OAc)2]:[Cs2CO3] = 0.55:0.25:0.025:0.55 (in mmol), in
DMF at 150 ꢂC for 24–48 h. b[PhBr] = 1.0.
carbonate base induces the undesirable ꢁ-H elimination.
The reaction of 1 with 1.2 equiv. of 6-dodecyne (2b) and
8-hexadecyne (2c) in the presence of 0.01–0.05 equiv. of
Pd(OAc)2 for 2–3 h afforded benzodithiophenes 3b and 3c
in 62–74% isolated yields (Scheme 2). Diphenylacetylene also
reacted to produce compound 3d.
Meanwhile, the catalytic direct arylation of five-membered
heteroarenes including thiophenes with aryl halides via C–H
bond cleavage as a useful, straightforward method for preparing
arylated heteroarenes has recently been a subject of intensive
study.8 While the dithiophene 3 has a condensed resonance
structure, it was found to effectively undergo arylation at the
2- and 7-positions on treatment with aryl bromides under similar
conditions to those used for the reaction of 2,20-bithiophene it-
self in our recent report.9 Thus, 3c reacted with bromobenzene,
4-bromobiphenyl, and 2-bromonaphthalene in the presence of
Pd(OAc)2/P(biphenyl-2-yl)(t-Bu)2 and Cs2CO3 as catalyst and
base, respectively, in DMF to give the corresponding diarylated
products 5–710 with substantial yields, albeit the conditions were
not optimized (Scheme 3).
5
6
7
F. R. S. Clark, R. O. C. Norman, C. B. Thomas, J. Chem.
Soc., Perkin Trans. 1 1975, 121.
Pd-Catalyzed reaction of aryl bromides with internal aliphat-
ic alkynes to give arylallenes: S. Pivsa-Art, T. Satoh, M.
Miura, M. Nomura, Chem. Lett. 1997, 823.
8
a) M. Miura, M. Nomura, Topics in Current Chemistry,
´
2002, Vol. 219, p. 211. b) J. Hassan, M. Sevignon, C. Gozzi,
E. Schulz, M. Lemaire, Chem. Rev. 2002, 102, 1359. c) M.
Miura, T. Satoh, Top. Organomet. Chem., 2005, Vol. 14,
p. 55. d) L.-C. Campeau, K. Fagnou, Chem. Commun.
2006, 1253. e) D. Alberico, M. E. Scott, M. Lautens, Chem.
Rev. 2007, 107, 174. f) T. Satoh, M. Miura, Chem. Lett.
2007, 36, 200.
In summary, we have shown an effective annulative cou-
pling under palladium catalysis to produce 4,5-disubstituted ben-
zo[2,1-b:3,4-b0]dithiophenes. Not only the compounds are useful
scaffolds for constructing soluble ꢀ-conjugated systems,11,12 but
also the protocol may provide valuable information for design-
ing related new catalytic cycles.
9
A. Yokooji, T. Satoh, M. Miura, M. Nomura, Tetrahedron
2004, 60, 6757.
10 ꢂabs (nm, in CH2Cl2) 5: 356; 6: 377; 7: 378. ꢂemis (nm, in
CH2Cl2) 5: 396, 416; 6: 424, 446; 7: 419, 441.
11 It is worth noting that treatment of compound 3c with NBS in
DMF selectively gave its 2,7-dibromo derivative in 97%
yield, which may be a useful substrate for various cross-
couplings.
12 Supporting Information is available electronically on the
CSJ-Journal Web site, http://www.csj.jp/journals/chem-lett/
index.html.
This work was supported, in part, by Grants-in-Aid for Sci-
entific Research from the Ministry of Education, Culture, Sports,
Science and Technology, Japan and by the Cooperative Re-
search with Sumitomo Chemical Co., Ltd.
Published on the web (Advance View) October 13, 2007; doi:10.1246/cl.2007.1336