Novel synthesis of 5-substituted 5H-benzo[b]carbazole-6,11-diones via double Buchwald-Hartwig reaction

Article abstract of DOI:10.1055/s-0034-1379235

2-Bromo-3-(2-bromophenyl)naphthalene-1,4-dione was synthesized as a key precursor to obtain a number of functionalized benzo[b]carbazole-6,11-diones by double Buchwald-Hartwig coupling reaction.

Full text of DOI:10.1055/s-0034-1379235

LETTER
▌2765
lNettoervel Synthesis of 5-Substituted 5H-Benzo[b]carbazole-6,11-diones via
Double Buchwald–Hartwig Reaction
5
-Substituted 5H-Benzo[b]carbazole-6,11-diones
a
b
a
a
b
Khrystyna Bolibrukh, Omar Khoumeri, Svyatoslav Polovkovych, Volodymyr Novikov, Thierry Terme,
Patrice Vanelle*b
a
Department of Technology of Biologically Active Substances, Pharmacy and Biotechnology, Lviv Polytechnic National University,
Bandera Str. 12, Lviv, 79013, Ukraine
Fax +38(32)2582478; E-mail: vnovikov@polynet.lviv.ua
b
Aix-Marseille Univ, CNRS, Institut de Chimie Radicalaire ICR, UMR 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de
Pharmacie, 27 Bd J. Moulin, Marseille Cedex 05, 13385, France
Fax +33(4)91794677; E-mail: patrice.vanelle@univ-amu.fr
Received: 23.07.2014; Accepted after revision: 11.09.2014
R1
Abstract: 2-Bromo-3-(2-bromophenyl)naphthalene-1,4-dione was
synthesized as a key precursor to obtain a number of functionalized
benzo[b]carbazole-6,11-diones by double Buchwald–Hartwig cou-
pling reaction.
O
O
O
OH
OH
MeO
N
Me
OH
O
O
O
O
Key words: quinone, anilines, Buchwald–Hartwig reaction, carba-
zole, one-pot
R4
O
Me
Me
Me
O
N
O
2
R
MeO
NH2
R3
2
CN
Quinones are not only important for synthesis but also
1
3
4
Me
1
daunorubicin R = R = H, R = OH, R = OMe
possess a wide range of biological activities. Nitrogen-
1
2
3
4
doxorubicin R = OH, R = H, R = OH, R = OMe
O
containing heterocyclic quinones are known to demon-
H
Me
2
3
strate antibacterial, antifungal, and cytotoxic activities.
O
O
The clinical significance of these heterocyclic quinones
and the strong biological activity of some natural com-
pounds of this group is raising interest in the synthesis of
renieramycin M
5N
N
calothrixin A
calothrixin B (N5-deoxy)
H
4
quinonoid compounds. As a result of isolation and struc-
O
tural determination of a number of antibiotics and pig-
ments, it has been established that heterocyclic quinones
are widely distributed in nature. This privileged core
Figure 1 Structure of DNA-damaging agents
5
structure is common to numerous antitumor drugs and
6
plays an important role in DNA intercalation. Doxorubi-
cin, mitomycin, actinomycin D, and streptonigrin are sig-
nificant examples of these DNA-damaging agents (Figure
In continuation of our research program centered on the
design and synthesis of novel bioactive molecules, we
were interested in developing a new approach utilizing
quinone-based substrates to allow access to the corre-
sponding functionalized benzo[b]carbazole-6,11-diones.
13
1
). Moreover, several studies in vitro have shown that
7
8
calothrixin and renieramycin have antiproliferative ac-
tivity in different cancer cell lines.
We report herein the first one-pot double palladium-cata-
lyzed Buchwald–Hartwig coupling reaction in a quinon-
oid series for the synthesis of 5-substituted 5H-benzo-
Palladium-catalyzed coupling reactions have been widely
used in organic chemistry and their success can be at-
tributed to cost and to the tolerance of many functional
[
b]carbazole-6,11-diones.
The required starting material for this coupling reaction,
-bromo-3-(2-bromophenyl)naphthalene-1,4-dione 3,
9
groups. In particular, the palladium-catalyzed Suzuki re-
action, for the synthesis of biaryl compounds from aryl
halides and boronic acids, has been successfully exploited
2
1
0
was synthesized by Suzuki–Myaura reaction between 2,3-
dibromo-1,4-naphthoquinone (1) and 2-bromophenylbo-
ronic acid (2) using Pd(PPh ) as a catalyst and Na CO as
in medicinal chemistry. Furthermore, C–N bond forma-
tion via Buchwald–Hartwig reaction has recently
3
4
2
3
emerged as an effective synthetic methodology for pre-
paring aromatic and heteroaromatic amines.11 However,
a base in a toluene–water mixture at 80 °C for 12 hours
1
4
(
Scheme 1). Only the monoaryl product was obtained
only a few examples of double Buchwald–Hartwig cou-
pling reactions have been reported.12
due to the sterically hindered bromine atom in the ortho
1
5
position.
We used this key 2-bromo-3-(2-bromophenyl)naphtha-
lene-1,4-dione for the one-pot coupling reaction with ani-
line derivatives catalyzed by palladium. Heating by
SYNLETT 2014, 25, 2765–2768
Advanced online publication: 16.10.2014
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0034-1379235; Art ID: st-2014-d0622-l
Georg Thieme Verlag Stuttgart · New York
©

2766
K. Bolibrukh et al.
LETTER
O
O
O
O
Br
Br
(HO)2B
Br
Pd(PPh3)4, Na2CO3
+
toluene, H2O, 80 °C, 12 h
Br
Br
6
2%
1
2
3
Scheme 1 Preparation of 2-bromo-3-(2-bromophenyl)naphthalene-1,4-dione
microwave irradiation was applied to decrease reaction zo[b]carbazole-6,11-diones involved a stage where the
time.
intermediate product 5a was formed. Increasing the reac-
tion time to two hours led to the main product 6a, instead
of a mixture of 5a and 6a. When cesium carbonate was
used as a base it gave a good yield of uncondensed product
Depending on the conditions, the reaction gave a mixture
of two products, the substituted naphthoquinone 5a and
the ring-closed benzocarbazoloquinone 6a (Scheme 2).
We initiated this study with 4-nitroaniline (4a) in the pres-
5a.
ence of Pd(OAc) (15 mol%), BINAP (15 mol%), and To determine the structure of intermediate compound 5a
2
K CO (2 equiv) as a base at 80 °C in toluene for two we determined the X-ray structure of its analogue 5b (Fig-
2
3
hours (Table 1, entry 1). The reaction furnished only the ure 2), which was obtained from 2-bromo-3-(2-bro-
cyclic 5-(4-nitrophenyl)-5H-benzo[b]-carbazole-6,11-di- mophenyl)-naphthalene-1,4-dione (3) and aniline 4b
one (6a) in 83% yield. To optimize the one-pot coupling using Pd(OAc) (15 mol%), BINAP (15 mol%), and
2
reaction, we employed different catalysts [Pd(OAc)2, K CO (2 equiv) as a base at 100 °C in toluene for two
2
3
1
7
Pd(PPh ) ], in the presence of bases (K CO , Cs CO ) at hours (Table 1, entry 4). This proved the attack by the
3
4
2
3
2
3
different temperatures and times of reaction. The best aniline nitrogen on the C–Br bond in the quinone frag-
yield of 5-(4-nitrophenyl)-5H-benzo[b]carbazole-6,11-di- ment, due to the higher reactivity of this position. The aryl
one (6a, 85%) was observed using Pd(OAc) (15 mol%), substituents are twisted out of the plane of the naphthoqui-
2
BINAP (15 mol%), and K CO (2 equiv) as a base at none moiety.
2
3
1
6
1
00 °C in toluene for two hours (Table 1, entry 2). The
To widen the scope of this method, the reaction of 2-bro-
mo-3-(2-bromophenyl)naphthalene-1,4-dione (3) with a
number of substituted anilines was performed under mi-
crowave irradiation. Interactions were carried out using
optimized conditions (Table 1, entry 2), and the corre-
sponding 5-substituted 5H-benzo[b]carbazole-6,11-di-
same reaction conducted under conventional heating fur-
nished the compound 6a in 68% yield after 24 hours.
Thus, microwave irradiation gave a superior yield in a
shorter reaction time than conventional heating. It was ob-
served that the formation of the 5-substituted 5H-ben-
O
O
O
NH2
Pd, ligand
+
base
Br
Br
+
NH
N
O
Br
O
O
3
4a
NO2
5a
6a
NO2
NO2
Scheme 2 Reaction of 2-bromo-3-(2-bromophenyl)naphthalene-1,4-dione (3) and 4-nitroaniline (4a)
Table 1 Optimization of the Reaction between 2-Bromo-3-(2-bromophenyl)naphthalene-1,4-dione and 4-Nitroanilinea
Entry
Temp (°C) Time (h)
Catalyst, ligand
Base
Heating
Yield of 5a (%) Yield of 6a (%)b
1
2
3
4
5
80
100
100
100
100
100
2
2
Pd(OAc) , BINAP
K CO
MW
0
0
83
85
52
0
2
2
3
3
3
Pd(OAc) , BINAP
K CO
MW
2
2
1
Pd(OAc) , BINAP
K CO
MW
34
74
0
2
2
2
Pd(OAc) , BINAP
Cs CO
MW
2
2
3
24
2
Pd(OAc) , BINAP
K CO
conventional
MW
68
0
2
2
3
3
6
Pd(PPh3)4
K CO
0
2
a
All reactions are performed using 10 mol% Pd, 15 mol% ligand, and 2 equiv of base.
All yields refer to chromatographically pure products based on substrate 3.
b
Synlett 2014, 25, 2765–2768
© Georg Thieme Verlag Stuttgart · New York

LETTER
5-Substituted 5H-Benzo[b]carbazole-6,11-diones
2767
thoxy-substituted anilines (70–75%). With halogenated
anilines (4c,e,f,i) yields of 52–73% were obtained.
In conclusion, in this study we prepared 2-bromo-3-
(
2-bromophenyl)naphthalene-1,4-dione (3) by Suzuki–
Miyaura reaction from 2,3-dibromo-1,4-naphthoquinone
and 2-bromoboronic acid. This product was a good candi-
date for the one-pot palladium-catalyzed double
Buchwald reaction with substituted anilines to synthesize
the corresponding 5-substituted 5H-benzo[b]carbazole-
6,11-diones 6a–k.
Acknowledgment
This work was supported by the Centre National de la Recherche
Scientifique, Aix-Marseille University and Lviv Polytechnic Natio-
nal University. We express our thanks to V. Remusat for recording
Figure 2 ORTEP view of intermediate 5b
1
13
H NMR and C NMR spectra and T. Schembri for recording mass
spectra. We are also grateful to the Ministry of Education and Scien-
ce of Ukraine for supporting K. Bolibrukh’s internship at Aix-Mar-
seille University.
Table 2 Reaction of 2-Bromo-3-(2-bromophenyl)naphthalene-1,4-
dione (3) with some Aniline Derivatives
a
Entry Aromatic amine
R
Product Yield
b
6
(%)
Supporting Information for this article is available online
at
http://www.thieme-connect.com/products/ejournals/journal/
1
2
3
4
5
6
7
8
9
0
1
4-nitroaniline
4-NO2
H
6a
6b
6c
6d
6e
6f
85
61
73
75
62
52
85
83
63
70
71
10.1055/s-00000083.SunogIpimrfiantoSuIpg
n
ori
m
aniline
3-chloroaniline
4-methyl-3-nitroaniline
3,4-dichloroaniline
2-chloroaniline
3-nitroaniline
3-Cl
References and Notes
3-NO , 4-Me
(1) Thomson, R. H. Naturally Occurring Quinones IV;
Chapman and Hall: London, 1997, 583.
2
3,4-Cl
(
2) (a) Hong, S. Y.; Chung, K. H.; You, H. J.; Choi, I. H.; Chae,
M. J.; Han, J. Y.; Jung, O. J.; Kang, S. J.; Ryu, C. K. Bioorg.
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Shin, K. H.; Lee, B. H. Bioorg. Med. Chem. 2000, 10, 1589.
2-Cl
3-NO2
6g
6h
6i
2-cyano-4-nitroaniline
2-CN, 4-NO2
(d) Ryu, C. K.; Choi, K. U.; Shim, J. Y.; You, H. J.; Choi, I.
4-(trifluoromethyl)aniline 4-F C
3
H.; Chae, M. J. Bioorg. Med. Chem. 2003, 11, 4003. (e) Ryu,
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1
4-methoxy-2-nitroaniline
2-methyl-3-nitroaniline
2-NO , 4-MeO 6j
2
1
2-Me, 3-NO2
6k
(3) (a) Kuo, S. C.; Ibuka, T.; Huang, L. J.; Lien, J. C.; Yean, S.
R.; Hung, S. C.; Lednicer, D.; Morris-Natschke, S.; Lee, K.
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a
All reactions were performed using 10 mol% Pd(OAc), 15 mol%
BINAP, and 2 equiv of K CO in toluene for 2 h at 100 °C under MW
irradiation.
All yields refer to chromatographically pure products based on sub-
strate 3.
2
3
b
(d) Lee, H. J.; Kim, J. S.; Park, S. Y.; Suh, M. E.; Kim, H. J.;
Seo, E. K.; Lee, C. O. Bioorg. Med. Chem. 2004, 12, 1623.
(e) Manzanaro, S.; Vicent, M. J.; Martín, M. J.; Salvador-
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ones 6a–k were obtained in good yields (52–85%,
Scheme 3, Table 2). The best yields were obtained with 3-
and 4-nitroaniline (85%) or 2-cyano-4-nitroaniline (83%).
Intermediate yields were obtained with methyl- or me-
6505. (f) Benites, J.; Valderrama, J. A.; Rivera, P.; Rojo, L.;
O
O
NH2
Pd(OAc)2, BINAP, K2CO3
toluene, 100 °C
+
N
R
Br
Br
O
R
O
3
4a–k
6a–k
Scheme 3 Synthesis of 5-substituted 5H-benzo[b]carbazole-6,11-diones 6a–k
©
Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 2765–2768

2768
K. Bolibrukh et al.
LETTER
Campos, N.; Pedro, M.; Nascimento, M. S. J. Bioorg. Med.
Chem. 2008, 16, 862.
stirred at 80 °C overnight. After cooling the mixture was
diluted with CH Cl , washed 3 times with H O, and dried
2
2
2
(4) (a) Tandon, V. K.; Chhor, R. B.; Singh, R. V.; Rai, S.;
over MgSO . After filtration and evaporation, the crude
4
Yadav, D. B. Bioorg. Med. Chem. Lett. 2004, 14, 1079.
product was purified by silica gel chromatography (CH Cl –
2
2
(
b) Tandon, V. K.; Singh, R. V.; Yadav, D. B. Bioorg. Med.
PE, 5:5) giving 3 as yellow crystals, mp 126 °C, yield 1.2 g
1
Chem. Lett. 2004, 14, 2901. (c) Tandon, V. K.; Yadav, D. B.;
Singh, R. V.; Yaish, M.; Chaturvedi, A. K.; Shukla, P. K.
Bioorg. Med. Chem. Lett. 2005, 15, 3463. (d) Tandon, V. K.;
Yadav, D. B.; Singh, R. V.; Chaturvedi, A. K.; Shukla, P. K.
Bioorg. Med. Chem. Lett. 2005, 15, 5324.
(62%). H NMR (200 MHz, CDCl ): δ = 7.22 (dd, 1 H,
3
J = 7.4, 1.8 Hz, ArH), 7.30–7.49 (m, 2 H, ArH), 7.7 (dd, 1 H,
J = 7.9, 1.2 Hz, ArH), 7.76–7.85 (m, 2 H, Ar), 8.14–8.27 (m,
1
3
2 H, ArH). C NMR (50 MHz, CDCl ): δ = 122.0 (C), 127.6
3
(2 × CH), 127.8 (CH), 128.3 (C), 129.9 (CH), 130.8 (CH),
131.3 (C), 131.7 (C), 132.9 (CH), 134.3 (CH), 134.7 (CH),
136.2 (C), 140.4 (C), 150.2 (C), 178.0 (CO), 180.6 (CO).
Anal. Calcd for C H Br O : C, 49.02; H, 2.06. Found: C,
(
5) Thomson, R. H. Naturally Occuring Quinones IV; Blackie
Academic: London, 1997.
6) (a) Lin, A. J.; Cosby, L. A.; Shansky, C. W.; Sartorelli, A. C.
J. Med. Chem. 1972, 15, 1247. (b) Moore, H. W. Science
(
1
6
8
2
2
49.65; H, 1.98.
1
977, 197, 527. (c) Arcamone, F. Cancer Res. 1985, 45,
(15) (a) Best, W. M.; Sims, C. G.; Winslade, M. Aust. J. Chem.
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(
7) (a) Chen, X.; Smith, G. D.; Waring, P. J. Appl. Phycol. 2003,
1
5, 269. (b) Bernardo, P. H.; Chai, Ch. L. L.; Heath, G. A.;
(16) General Procedure for the Double Buchwald–Hartwig
Reaction for the Synthesis of 5-Substituted 5H-
benzo[b]carbazole-6,11-diones 6a–k
Mahon, P. J.; Smith, G. D.; Waring, P.; Wilkes, B. A. J. Med.
Chem. 2004, 47, 4958.
(
8) Cheun-Arom, T.; Chanvorachote, P.; Sirimangkalakitti, N.;
Chuanasa, T.; Saito, N.; Abe, I.; Suwanborirux, K. J. Nat.
Prod. 2013, 76, 1468.
A mixture of 2-bromo-3-(2-bromophenyl)naphthalene-1,4-
dione (3, 0.1 g, 0.25 mmol), aniline (1.5 g, 0.38 mmol equiv)
in toluene (10 mL), K CO (105 g, 0.76 mmol), Pd(OAc)
2
3
2
(
9) (a) Diederich, F.; Stang, P. J. Metal-catalyzed cross-
coupling reactions; Wiley-VCH: Weinheim, 1998. (b) King,
A. O.; Yasuda, N. Top. Organomet. Chem. 2004, 6, 205.
(0.0098 g, 0.05 mmol), and BINAP (0.042 g, 0.06 mmol)
was placed in a 4 mL sealed vial in a Biotage microwave-
reactor cavity. The mixture was irradiated at 100 °C for 2 h.
After cooling, the reaction mixture was diluted with CH Cl ,
(
c) Carey, J. S.; Laffan, D.; Thomson, C.; Williams, M. T.
Org. Biomol. Chem. 2006, 4, 2337.
10) (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
2
2
washed with H O (3 × 40 mL), and dried over MgSO . After
2
4
(
filtration and evaporation, the crude product was purified by
silica gel chromatography (CH Cl –PE, 5:5).
(
(
b) Suzuki, A. J. Organomet. Chem. 1999, 576, 147.
c) Chemler, S. R.; Trauner, D.; Danishefsky, S. J. Angew.
2
2
5-(4-Nitrophenyl)-5H-benzo[b]carbazole-6,11-dione (6a)
1
Chem. Int. Ed. 2001, 40, 4544.
Yellow solid; mp 287 °C. H NMR (200 MHz, CDCl ):
3
(
11) (a) Kosugi, M.; Kameyama, M.; Migita, T. Chem. Lett.
δ = 7.15–7.20 (m, 1 H, ArH), 7.44–7.50 (m, 2 H, ArH),
7.65–7.79 (m, 5 H, ArH), 8.05 (dd, 2 H, J = 7.0, 1.7 Hz,
ArH), 8.25 (dd, 2 H, J = 7.0, 1.0 Hz, ArH), 8.46–8.56 (m, 2
1
983, 927. (b) Wolfe, J. P.; Rennels, R. A.; Buchwald, S. L.
Tetrahedron 1996, 52, 7525. (c) Hartwig, J. F. Angew.
Chem. Int. Ed. 1998, 37, 2046. (d) Wolfe, J. P.; Wagaw, S.;
Marcoux, J. F.; Buchwald, S. L. Acc. Chem. Res. 1998, 31,
1
3
H, ArH). C NMR (50 MHz, CDCl ): δ = 111.5 (CH), 124.1
3
(C), 124.2 (CH), 124.9 (2 × CH), 125.3 (CH), 126.7 (2 ×
CH), 128.4 (CH), 129.0 (2 × CH), 133.3 (2 × C), 133.5 (CH),
133.9 (C), 134.3 (CH), 135.3 (C), 140.5 (C), 142.5 (C),
147.9 (C), 177.7 (CO), 181.7 (CO). Anal. Calcd for
C H N O : C, 71.74; H, 3.28; N, 7.61. Found: C, 71.66; H,
805. (e) Hartwig, J. F. Acc. Chem. Res. 1998, 31, 852.
(
(
f) Hartwig, J. F. Pure Appl. Chem. 1999, 71, 1417.
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1
999, 576, 125. (h) Muci, A. R.; Buchwald, S. L. Top. Curr.
2
2
12
2
4
Chem. 2002, 219, 131.
3.22; N, 7.61..
(
(
12) (a) Nozaki, K.; Takahashi, K.; Nakano, K.; Hiyama, T.;
Tang, H.-Z.; Fujiki, M.; Yamaguchi, S.; Tamao, K. Angew.
Chem. Int. Ed. 2003, 42, 2051. (b) Kitawaki, T.; Hayashi,
Y.; Ueno, A.; Chida, N. Tetrahedron 2006, 62, 6792.
(17) Compounds 5a,b were formed by the same protocol but
using Cs CO as base.
2
3
2-(2-Bromophenyl)-3-(4-nitrophenylamino)naphthlene-
1,4-dione (5a)
Orange solid; mp 220 °C. H NMR (200 MHz, CDCl ):
1
(c) Zhou, Y.; Verkade, J. G. Adv. Synth. Catal. 2010, 352,
3
6
16.
δ = 6.84 (d, 2 H, J = 8.9 Hz, ArH), 6.89–7.14 (m, 3 H, ArH),
7.31 (dd, 1 H, J = 8.0, 0.7 Hz, ArH), 7.70–7.87 (m, 4 H,
ArH), 7.89 (s, 1 H, NH), 8.20 (dd, 2 H, J = 7.6, 1.4 Hz, ArH).
13) (a) Vanelle, P.; Maldonado, J.; Madadi, N.; Gueiffier, A.;
Teulade, J.-C.; Chapat, J.-P.; Crozet, M. P. Tetrahedron Lett.
1
3
1
990, 31, 3013. (b) Crozet, M. P.; Giraud, L.; Sabuco, J.-F.;
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c) Delmas, F.; Gasquet, M.; Timon-David, P.; Madadi, N.;
Vanelle, P.; Vaille, A.; Maldonado, J. Eur. J. Med. Chem.
993, 28, 23. (d) Amiri-Attou, O.; Terme, T.; Vanelle, P.
C NMR (50 MHz, CDCl ) :δ = 119.4 (C), 122.8 (2 × CH),
3
123.5 (2 × CH), 124.6 (CH), 126.7 (CH), 127.2 (CH), 127.3
(CH), 129.9 (CH), 130.2 (C), 132.3 (CH), 133.0 (CH), 133.1
(C), 133.2 (C), 134.0 (C), 134.4 (CH), 140.8 (C), 143.1 (C),
143.7 (C), 181.6 (CO), 182.4 (CO). Anal. Calcd for
(
1
Molecules 2005, 10, 545. (e) Amiri-Attou, O.; Terme, T.;
Vanelle, P. Synlett 2005, 3047. (f) Montana, M.; Terme, T.;
Vanelle, P. Tetrahedron Lett. 2006, 47, 6573. (g) Curti, C.;
Laget, M.; Ortiz Carle, A.; Gellis, A.; Vanelle, P. Eur. J.
Med. Chem. 2007, 42, 880. (h) Crozet, M. D.; Botta, C.;
Gasquet, M.; Curti, C.; Remusat, V.; Hutter, S.; Chapelle,
O.; Azas, N.; De Meo, M. P.; Vanelle, P. Eur. J. Med. Chem.
C H BrN O : C, 58.82; H, 2.92; N, 6.24. Found: C, 85.77;
H, 2.87; N, 6.33.
2-(2-Bromophenyl)-3-(phenylamino)naphthalene-1,4-
2
2
13
2
4
dione (5b)
1
Red solid; mp 161 °C. H NMR (200 MHz, CDCl ):
3
δ = 6.78–6.99 (m, 7 H, ArH), 7.24 (d, 1 H, J = 9.6 Hz, ArH),
7.69–7.82 (m, 3 H, ArH), 8.18 (dd, 2 H, J = 7.6, 1.4 Hz,
1
3
2
009, 44, 653.
ArH). H NMR (50 MHz, CDCl ): δ = 116.3 (C), 124.5 (2
3
(
14) 2-Bromo-3-(2-bromophenyl)naphthalene-1,4-dione (3)
× CH), 125.2 (CH), 125.3 (C), 126.5 (CH), 126.6 (CH),
127.0 (CH), 127.9 (2 × CH), 129.0 (CH), 130.4 (C), 132.3
(CH), 132.5 (CH), 132.8 (CH), 133.5 (C), 134.5 (C), 135.1
(CH), 136.9 (C), 141.9 (C), 181.6 (CO), 188.9 (CO).
To a mixture of 2,3-dibromonaphthalene-1,4-dione (0.786 g,
2.49 mmol) and boronic acid (0.5 g, 2.49 mol%) in toluene
(
10 mL) was added Pd(PPh ) (0.172 g, 0.15 mmol) and 2 M
3
4
aq Na CO solution (5 mL). The resulting mixture was
2
3
Synlett 2014, 25, 2765–2768
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