Straightforward access to functionalized pentaarylbenzene derivatives through a quick lithiation

Article abstract of DOI:10.1016/j.tetlet.2008.06.111

A straightforward route to functionalized pentaarylbenzene derivatives is described, involving the effective lithiation method of 1-iodo-2,3,4,5,6-pentaarylbenzene. The activated pentaarylbenzene is a potential synton for producing organic materials.

Full text of DOI:10.1016/j.tetlet.2008.06.111

Tetrahedron Letters 49 (2008) 5244–5246
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Tetrahedron Letters
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Straightforward access to functionalized pentaarylbenzene derivatives
through a quick lithiation
*
Tetsuo Iwasawa , Toshinori Kamei, Kento Hama, Yoshiki Nishimoto, Masaki Nishiuchi,
*
Yasuhiko Kawamura
Department of Chemical Science and Technology, Faculty of Enginnering, The University of Tokushima, Minami-jyosanjima-cho, Tokushima 770-8506, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A straightforward route to functionalized pentaarylbenzene derivatives is described, involving the effec-
tive lithiation method of 1-iodo-2,3,4,5,6-pentaarylbenzene. The activated pentaarylbenzene is a poten-
tial synton for producing organic materials.
Received 7 June 2008
Revised 22 June 2008
Accepted 26 June 2008
Available online 1 July 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Polyarylbenzene derivatives reported by Müllen and co-wokers
have drawn significant attention because of their potential applica-
tion in organic materials science,1 for example, electroluminescent
materials,2 optical devices,3 supramolecular electronics,4 and cata-
lysts.5 The essential core structure among the polyarylbenzene
derivatives is based on a pentaarylbenzene moiety. Thus, the
installation of functional groups into the core structure would
amplify the potentiality. Hence, the fine tuning of chemical modi-
fication on the skeletal moiety is well worth developing.
Two procedures for permitting the chemical modification were
mainly known: one is cobalt-catalyzed trimerization,6,7 and the
other is Diels–Alder cyclization.8 Both install the functional groups
along with construction of the core skeleton. The former allows
symmetrically introducing the functionality, while it is laborious
to obtain desymmetrically functionalized molecules.9 The latter
system, the reaction of tetraarylcyclopentadienone with terminal
or internal ethynylarene, enables to desymmetrically functionalize,
as well as to monofunctionalize.1,2,5 The Diels–Alder reaction, for
the present, is suitable for installation of diverse functionality into
the core structure. However, the severe heat is required to limit the
range of available functionalities.4g,10,11
Herein, we report a straightforward procedure for giving the
fine tuning of chemical modification on the pentaarylbenzene core,
which is outlined in Scheme 1. First, the Diels–Alder adduct 1 was
synthesized to overcome the limited solubility of 4 in organic sol-
vents. Then, the clean lithiation of sterically demanding 1 at À20 °C
in toluene was found to quickly occur just in 5 min, thus providing
a convenient access to functionalized pentaarylbenzene molecules.
At the outset of our study, the lithiation conditions of the novel
iodide 112 were surveyed through the reactions with dimethyl
disulfide, which afforded the methyl sulfide adduct 2 (E = SMe).
The results were summarized in Table 1. The iodide 1 was prepared
Scheme 1. Functionalizing a pentaary benzene through the lithiation.
* Corresponding authors. Tel.: +81 88 656 7405; fax: +81 88 655 7025 (T.I.).
E-mail addresses: iwasawa@chem.tokushima-u.ac.jp (T. Iwasawa), kawamura@chem.tokushima-u.ac.jp (Y. Kawamura).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.06.111

T. Iwasawa et al. / Tetrahedron Letters 49 (2008) 5244–5246
5245
Table 1
all starting 1 just in 5 min; however, unfortunately a large number
of side-product 3 were observed (entry 6).14,15 Then, 2.0 equiv of n-
BuLi in toluene was reduced to 1.5 equiv and 1.2 equiv (entries 7
and 8). Both reactions efficiently furnished methyl sulfide 2 in
91% yields, and any unreacted 1 was not observed in TLC. Thus,
the clean lithiation of 1 in toluene solution was proved to quickly
proceed at À20 °C in 5 min, in spite of the sterically demanding
carbanion.16,17
After determining the condition for lithiation of 1 (at À20 °C for
5 min in toluene), we examined the scope of the reactivity, by pre-
paring a series of 1-substituted-2,3,4,5-tetrakis(p-methylphenyl)-
6-phenylbenzenes 7–17 (Fig. 1). The electrophile MeSSMe listed
in Table 1 completed the reaction at À20 °C for 1 h; however, at
À20 °C, other electrophiles were not so easy to react with the carb-
anion. Actually, none of the reaction reached completion even in
overnight stirring. The electronic and steric discord between reac-
tion partners would cause the addition step sluggish. Thus, the
reaction temperature at the addition step raised to ambient tem-
perature, and the results are summarized in Table 2.20
A survey on the lithiation conditions conducted via Scheme 1
Entry 1 or 4 n-BuLi (equiv) T (°C) Time (min) 2 or 5a (%) 3 or 6a (%)
1b,c
2
3
4
4
1
1
1
1
1
1
1
2.0
2.0
2.0
2.0
2.0
2.0
1.5
1.2
À20
À20
À45
À78
À20
À78
À20
À20
30
30
30
30
5
5
5
5
32
89
83
19
92
62
91
91
54
2
1
<2
<1
27
<1
4
5
6d
7
8
a
b
c
Isolated yields with silica gel column chromatography.
The reaction mixture was terribly suspended.
Unreacted 4 was recovered in 9%.
d
THF was used as a solvent.
At entry 1, the hexaarylbenzene derivative 7 was obtained in
91% yield through the reaction with 1,2-dibromobenzene at ambi-
ent temperature for 2 h, although the reaction at À20 °C was slug-
to compensate for poor solubility of 4 in organic solvents.13 Actu-
ally, the necessary amount of toluene to dissolve 1 g of iodides 1
and 4 was 15 mL and 138 mL, respectively. The iodide 1 bearing
tetramethyl groups was dissolved in toluene ca. nine times higher
as compared with 4. The difference in the solubility affected the
lithiation of 1 and 4 by n-BuLi, and the resultant yields of 2 and
5, which were observed at entries 1 and 2. The lithiation of 4 in tol-
uene with muddy state gave the desired 5 in only 32% yield (entry
1). Additionally, tremendous amounts of side-product 6 were
found in 54% yield, along with 9% of the starting material 4. On
the other hand, the lithiation of 1 in a clear toluene solution
yielded the desired 2 in 89% with suppressing the side-product 3
in only 2% yield, and the remaining 1 was not observed in TLC
monitoring (entry 2). Thus, 1 endowed with four methyl groups
was at a distinct advantage over 4, and the efficient conditions
for lithiation of 1 were further evaluated (entries 3–8). Low tem-
perature conditions at À45 °C and À78 °C afforded 2 in 83% and
19% yields, respectively (entries 3 and 4). They did not exceed
89% yield given at À20 °C in entry 2. At the adequate temperature
À20 °C, the aging time for the lithiation was shortened in from
30 min to 5 min (entry 5). Surprisingly, the starting material 1
was completely disappeared in TLC monitoring, providing 2 in
92% yield. The solvent of THF was also found to quickly lithiate
Table 2
Evaluation of the reactivity of the lithiated 1 with electrophilesa
Entry
Electrophiles
Productsb
Yieldc (%)
Time (h)
1
2
3
1,2-Dibromobenzene
Benzaldehyde
Pivalaldehyde
4-Methoxybenzoyl chloride
3,4,5-Trimethoxybenzoyl chloride
Acetic anhydride
N,N-Dimethylformamide
Carbon dioxide
7
8
9
91
90
91
78
71
51
82
72
88
26
14
2
1
2
2
8
4
5
2
2
2
2
4
10
11
12
13
14
15
16
17
5
6d
7
8e
9
Tributyltin chloride
Trimethylborate
2,3-Dichloropyrazine
10
11f
a
All reactions were performed in accordance with the representative procedure
in Ref. 20, unless otherwise stated.
b
Elemental analysis data of all products showed good match.
Isolated yields with silica gel column chromatography.
Side-product 3 was yielded in 40%.
The gaseous CO2 was bubbled for 1 h.
c
d
e
f
The solution of 2,3-dichloropyrazine in 0.5 mL THF was added.
Figure 1. A series of 1-substituted-2,3,4,5-tetrakis(p-methylphenyl)-6-phenylbenzenes.

5246
T. Iwasawa et al. / Tetrahedron Letters 49 (2008) 5244–5246
504; (e) Lee, M.; Kim, J.-W.; Peleshanko, S.; Larson, K.; Yoo, Y.-S.; Vankin, D.;
Markutsya, S.; Tsukruk, V. V. J. Am. Chem. Soc. 2002, 124, 9121–9128; (f) Van de
Craats, A. M.; Warman, J. M.; Fechtenkötter, A.; Brand, J. D.; Harbison, M. A.;
Müllen, K. Adv. Mater. 1999, 11, 1469–1472; (g) Adam, D.; Schuhmacher, P.;
Simmerer, J.; Häussling, L.; Siemensmeyer, K.; Etzbach, K. H.; Ringsdorf, H.;
Haarer, D. Nature 1994, 371, 141–143.
gish. With respect to the aldehyde, both aryl and alkyl aldehydes
efficiently reacted with lithiated 1 to provide the corresponding
alcohols 8 and 9 in excellent yields (entries 2 and 3). At entries 4
and 5, acid chlorides also gave target ketones 10 and 11 in good
yields, while a longer reaction time was required for consuming
3,4,5-trimethoxybenzoyl chloride. This lithiation system worked
in the reaction with acetic anhydride (entry 6), but the tremendous
amount of 3 was produced in 40% yield.
The derivatives allowing for further functionalizations were
obtained through the reactions with N,N-dimethylformamide and
carbon dioxide (entries 7 and 8). Each electrophile furnished alde-
hyde 13 and carboxylic acid 14 in 82% and 72% yields, respectively.
Then, the nucleophilic attack to a heteroatom, tributyltin chloride,
afforded the desired tin molecule 15 in 88% yield (entry 9). On the
other hand, the laborious bond-forming reactions were observed
with trimethylborate, and 2,3-dichloropyrazine (entries 10 and
11).
In summary, we have developed a new procedure for leading
functionalized pentaarylbenzene derivatives. The synthetic
approach, which employs simple reagents 1 in toluene and n-BuLi,
accomplished to quickly react with several electrophiles in good
yields, providing novel functionalized molecules. Because of the
necessity of a functionalized pentaarylbenzene moiety, we antici-
pate that this approach is likely to find widespread use in the field
of organic materials science.
5. (a) Iwasawa, T.; Komano, T.; Tajima, A.; Tokunaga, M.; Obora, Y.; Tsuji, Y.
Organometallics 2006, 25, 4665–4669; (b) Aoyama, H.; Tokunaga, M.; Kiyosu, J.;
Iwasawa, T.; Obora, Y.; Tsuji, Y. J. Am. Chem. Soc. 2005, 127, 10474–10475; (c)
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4306–4322; (b) Wu, J.; Watson, M. D.; Zhang, L.; Wang, Z.; Müllen, K. J. Am.
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12. Synthetic procedure for the iodide 1: To the 100 mL flask charged with 2,3,4,5-
tetrakis(p-methylphenyl)cyclopenta-2,4-dienone18 (1.19 g, 2.7 mmol) under
an argon atmosphere was added (iodoethynyl)benzene19 (800 mg, 3.5 mmol)
in distilled ortho-xylene (4.5 mL), and the mixture was refluxed for 11 h. After
evaporation of the solvent, the residue was reprecipitated from CHCl3/MeOH
system. Purification by silica gel column chromatography with hexane/CH2Cl2
(2:1) as an eluent gave the desired compound 1 in 71% (1.22 g) as white solid
materials. 1H NMR (400 MHz, CDCl3) d 7.21–7.11 (m, 5H), 7.05–6.97 (m, 4H),
6.75–6.62 (m, 12H), 2.27 (s, 3H), 2.09 (s, 3H), 2.07 (s, 3H), 2.06 (s, 3H). 13C NMR
(100 MHz, CDCl3) d 145.9, 145.7, 145.6, 142.9, 141.5, 141.1, 141.0, 137.5, 137.4,
136.7, 135.9, 134.6, 134.5, 134.3, 130.7, 130.5, 130.3, 130.1, 127.9, 127.1, 126.4,
107.4, 21.3, 21.0 (three peaks were overlapped). MS (EI) m/z: 640 (M+). Anal.
Calcd for C40H33I: C, 75.00; H, 5.19. Found: C, 75.13; H, 5.16.
Acknowledgments
We are grateful to Kato Foundation for Promotion of Science for
the financial support. We are pleased to thank Ms. Yasuko Yoshio-
ka for assistance with mass spectrometry.
13. To dissolve 1 g of iodide 1 at room temperature, each solvent of CHCl3, and
CHCl2, and THF required 11 mL, and 6.6 mL, and 17 mL, respectively. On the
other hand, in the case of iodide 4, each solvent of CHCl3, and CHCl2, and THF
required 105 mL, and 88 mL, and 99 mL, respectively.
14. We attributed this annoying side-product 3 to a partial protonation of the
lithio intermediate by THF; see Ref. 15.
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5540; (b) Kosugi, Y.; Akakura, M.; Ishihara, K. Tetrahedron 2007, 63, 6191–
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Supplementary data
Supplementary data associated with this article can be found,
in the online version, at doi:10.1016/j.tetlet.2008.06.111.
17. Tomioka, K. Synthesis 1990, 541–549.
18. Xu, W.; Chen, Q.-Y. J. Org. Chem. 2002, 67, 9421–9427.
19. Field, L. D.; Ho, K. M.; Masters, L. A. F.; Webb, A. G. Aust. J. Chem. 1990, 43, 281–
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References and notes
20. Representative experimental procedure for Table 2, entry 9, compound 15: To a
solution of 1 (256 mg, 0.4 mmol) in anhydrous toluene (6 mL) at À20 °C was
added n-BuLi (0.48 mmol, 1.6 M in hexane) dropwise over 5 min, and the
solution was stirred for 5 min. The electrophile of tributyltin chloride (0.16 mL,
0.6 mmol) was slowly added over 5 min, and the mixture was allowed to warm
to ambient temperature, and stirred for 2 h. After the reaction was quenched
with methanol (3 mL), the solvent was evaporated. The resultant residue was
purified by silica gel column chromatography with hexane/CH2Cl2 (4:1) as an
eluent to give the desired compound 15 in 88% yield (284 mg) as white
powders. 1H NMR (400 MHz, CDCl3) d 7.18–7.08 (m, 5H), 7.04 (d, J = 8.2 Hz,
2H), 6.92 (d, J = 8.2 Hz, 2H), 6.75–6.70 (m, 6H), 6.65–6.60 (m, 6H), 2.26 (s, 3H),
2.08 (s, 3H), 2.07 (s, 3H), 2.04 (s, 3H), 1.18–1.06 (m, 12H), 0.80 (t, J = 7.1 Hz,
9H), 0.13–0.08 (m, 6H). 13C NMR (100 MHz, CDCl3) d 148.8, 144.7, 143.1, 141.8,
141.7, 140.1, 139.9, 138.3, 138.2, 138.0, 135.6, 134.13, 134.11, 134.07, 131.5,
131.3, 131.23, 131.20, 131.0, 128.0, 127.3, 127.15, 127.13, 126.2, 29.3, 27.4,
21.3, 21.2, 13.7, 11.9. MS (ESI) m/z: 827 ([M+Na]+). Anal. Calcd for C52H60Sn: C,
77.71; H, 7.52. Found: C, 77.76; H, 7.43.
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