Palladium-mediated intramolecular C-O and C-C coupling reactions: An efficient synthesis of benzannulated oxazepino- and pyranocarbazoles

Article abstract of DOI:10.1055/s-0030-1260965

An efficient route towards the synthesis of benzannulated oxazepino- and pyranocarbazoles has been accomplished via palladium-catalyzed intramolecular C-O and C-C cross-coupling reactions, respectively. Georg Thieme Verlag Stuttgart . New York.

Full text of DOI:10.1055/s-0030-1260965

LETTER
1835
Palladium-Mediated Intramolecular C–O and C–C Coupling Reactions:
An Efficient Synthesis of Benzannulated Oxazepino- and Pyranocarbazoles
S
ynthesis of Benza
u
nnulatedOx
m
azepino- and
P
yra
n
a
o-carbazole
r
s
esan Prabakaran,a Matthias Zeller,b Karnam Jayarampillai Rajendra Prasad*a
a
Department of Chemistry, Bharathiar University, Coimbatore 641046, India
Fax +91(422)2422387; E-mail: prasad_125@yahoo.com
b
Department of Chemistry, Youngstown State University, One University Plaza, Youngstown, OH 44555, USA
Received 21 March 2011
ber of compounds with diverse biological activities has
been obtained. However, to the best of our knowledge,
there are no reports describing the preparation of benzan-
nulated analogues of oxazepinocarbazoles and pyranocar-
bazoles. This may be due to the lack of a general synthetic
route towards these classes of heteroaromatics from easily
accessible precursors.
Abstract: An efficient route towards the synthesis of benzannulat-
ed oxazepino- and pyranocarbazoles has been accomplished via
palladium-catalyzed intramolecular C–O and C–C cross-coupling
reactions, respectively.
Key words: C–O and C–C coupling, intramolecular arylation, pal-
ladium catalysis, oxazepinocarbazoles, pyranocarbazoles.
In view of the importance of oxazepines and coumarins,
several methods have been developed for the synthesis of
oxazepine14 and coumarin15 compounds by palladium-
catalyzed cyclization reactions. However, many of the
synthetic protocols reported so far suffer from disadvan-
tages, such as harsh reaction conditions, multistep reac-
tion, expensive reagents, extended reaction time, need for
large quantities of catalyst or low yields. Therefore, a new
protocol with reagent economy, minimum of catalyst, and
improved yields is desirable.
In continuation of our interest,16 we herein report a simple
and efficient synthetic protocol for the synthesis of benz-
annelated oxazepino- and pyrano-carbazoles such as
benzo[f][1,4]oxazepino[4,3,2-l,m]carbazol-9-ones or iso-
chromeno[3,4-a]carbazol-2(13H)-one using palladium-
catalyzed intramolecular arylation of starting materials
based on readily available 1-hydroxycarbazole17 such as
1-hydroxy-9-(2-halobenzoyl)carbazole or 9H-carbazol-1-
yl 2-halobenzoate.
Palladium-catalyzed reactions are one of the most versa-
tile methods for creation of covalent bonds in organic
chemistry. The tremendous impact of reactions such as
the Suzuki coupling, Heck reaction, Negishi coupling,
Stille reaction, and Sonogashira coupling on synthetic or-
ganic chemistry was recognized in 2010 with the Nobel
Prize in Chemistry. Palladium-catalyzed reactions have
proven to be especially useful for the construction of car-
bon–carbon, as well as carbon–heteroatom bonds of ring
systems,1 and they offer an extremely efficient entry to
complex cyclic compounds from relatively simple precur-
sors.2 Intramolecular biaryl coupling reactions are of con-
siderable interest due to their utility in the synthesis of
many condensed heteroaromatic compounds, such as in-
doles, quinolines, and carbazoles.3 Among these,
carbazoles4 and their fused derivatives, such as pyrido,5
pyrrolo,6 and pyranocarbazoles7 have received consider-
able attention from both medicinal as well as synthetic
chemists as these compounds display a wide range of bio-
logical activities such as anticancer,8 anti-HIV,9 DNA-
intercalator,10 and antimicrobial.11 Some examples of nat-
ural products containing the pyranocarbazole core struc-
ture include clauszoline-H (I), girinimbine (II), and
pyrayafoline B (III, Figure 1).12 Over recent years consid-
erable efforts have been made towards the preparation and
synthetic manipulation of these compounds.4c,7,13 A num-
The desired benzoylated products were prepared by the
reaction of 2-halobenzoyl chloride 2 with 1-hydroxycar-
bazoles 3 under various reaction conditions (Table 1) as
depicted in Scheme 1. In the presence of triethylamine in
THF only the N-benzoylated product was obtained18
(Table 1, entry 1). The identity of 4a was confirmed by its
spectroscopic data as well as single-crystal structural X-
ray analysis. The case where 3c failed to give 4c and 5c
H3C
CH3
H3C
H3CO
CH3
N
O
HO
H
O
CH3
O
CH3
CH3
N
CH3
H
N
H
H2C
pyrayafoline-B (III)
clauszoline-H (I)
girinimbine (II)
Figure 1
SYNLETT 2011, No. 13, pp 1835–1840
x
x
.x
x
.2
0
1
1
Advanced online publication: 21.07.2011
DOI: 10.1055/s-0030-1260965; Art ID: D08811ST
© Georg Thieme Verlag Stuttgart · New York

1836
K. Prabakaran et al.
LETTER
COOH
COCl
SOCl2
X
X
2
1
R1
R1
R1
X
+
2
+
R2
R2
R2
N
N
N
R3
R3
H
H
OH
OH
O
3–7 R1 R2 R3
3
O
O
a
b
c
d
CH3
H
H
H
6 (X = Br)
7 (X = I)
CH3 H
X
H
H
H
CH3
H
4 (X = Br)
5 (X = I)
H
Scheme 1 Benzoylation of 1-hydroxy carbazole 3
In the next step the precursors were subjected to palladi-
um coupling conditions. When a C–O coupling reaction
was carried out with precursor 4a in the presence of 10
mol% of Pd(OAc)2 as the catalyst, Cs2CO3 as the base,
and tetrabutylammonium bromide (TBAB) as an additive
in anhydrous DMF as the solvent, reaction at 110 °C for 2
hours gave 13-methyl-benzo[f][1,4]oxazepino[4,3,2-
l,m]carbazol-9-one (8a) as the only product in 90% isolat-
ed yield (Scheme 2).20 In the 1H NMR spectrum of the re-
action product the absence of a peak at d = 12.76 ppm for
the OH proton indicated that the compound had under-
gone reaction involving a C–O coupling reaction and not
coupling with C8 of the carbazole ring. All other spectro-
scopic and analytical data confirmed the formation of the
C–O coupling product 8. The optimum conditions for the
palladium-catalyzed cyclization were found through a se-
ries of experiments where various changes were made to
the catalyst, base, additives, and the solvent used in the re-
action (Table 2). All of these variables showed to have a
profound effect on the reaction efficiency, specificity, and
yield. Without the catalyst, no reaction was observed
(Table 2, entry 1). The use of PdCl2, which is most com-
monly used in Heck-type reactions, led only to moderate
yields of cyclized product 8 (Table 2, entry 2). Without an
additive under different basic conditions with Pd(OAc)2,
the reaction afforded a moderate yield (Table 2, entries 3–
5). Use of Pd(OAc)2 as the catalyst precursor gave moder-
ate to high yields, with the exception of the system
Pd(OAc)2/Et3N/TBAB in DMF, which also did not yield
any of the desired products (Table 2, entry 6). The effect
of base on the reaction showed that use of Cs2CO3 as the
base gave high yields of 8 when the reactions were con-
ducted in DMF (Table 2, entries 7–12). Details of all reac-
tion conditions that were examined are given in Table 2.
Table 1 Reaction of 3 with 2-Halobenzoyl Chloride under Various
Experimental Conditions
Entry Reactant
Conditions
Temp Product Yield
(°C)
(%)a
72:0
24:20
41:25
32:38
0:72
55:0
70:0
52:0
n.r.
1
2
3a, 2 X = Br
Et3N–THF
r.t.
4a/6a
4a/6a
4a/6a
4a/6a
4a/6a
5a/7a
4b/6b
5b/7b
4c/6c
5c/7c
4d/6d
5d/7d
5a/7a
4b/6b
5b/7b
4c/6c
5c/7c
4d/6d
5d/7d
3a, 2 X = Br
3a, 2 X = Br
3a, 2 X = Br
3a, 2 X = Br
3a, 2 X = I
3b, 2 X = Br
3b, 2 X = I
3c, 2 X = Br
3c, 2 X = I
piperidine–CH2Cl2 100
pyridine– CH2Cl2 100
3
4
K2CO3, acetone
CH2Cl2
100
100
r.t.
5
6
Et3N–THF
Et3N–THF
Et3N–THF
Et3N–THF
Et3N–THF
Et3N–THF
Et3N–THF
CH2Cl2
7
r.t.
8
r.t.
9
r.t.
10
11
12
13
14
15
16
17
18
19
r.t.
n.r.
3d, 2 X = Br
3d, 2 X = I
3a, 2 X = I
3b, 2 X = Br
3b, 2 X = I
3c, 2 X = Br
3c, 2 X = I
r.t.
72:0
58:0
0:52
0:70
0:41
0:72
0:45
0:76
0:41
r.t.
100
100
100
100
100
100
100
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
3d, 2 X = Br
CH2Cl2
3d, 2 X = I
CH2Cl2
a n.r. = no reaction.
We next turned our attention towards the palladium-cata-
lyzed intramolecular C–C coupling of compounds 6a–d
and 7a–d (Scheme 3). In our initial attempt to initiate cy-
clization of 6a in the absence of Pd catalyst, no reaction
was observed (Table 3, entry 1). Reactions using a PdCl2
catalyst system, which is generally employed in such
cyclization reactions, provided a mixture of 10-methyl-
isochromeno[3,4-a]carbazol-2(13H)-one (9a) and debro-
minated product (Table 3, entry 2). The structure of 9a
can be readily explained by the steric effect of the methyl
substituent at C8, which prevents reaction at the N-9 posi-
tion. However, piperidine, pyridine, and potassium car-
bonate yielded a mixture of both N- and O-benzoylated
products (Table 1, entries 2–4). In the absence of base, the
reaction afforded only O-benzoylated product19 (Table 1,
entry 5).
Synlett 2011, No. 13, 1835–1840 © Thieme Stuttgart · New York

LETTER
Synthesis of Benzannulated Oxazepino- and Pyranocarbazoles
1837
mize the reaction conditions using PdCl2 and different
bases gave similar mixtures of the two compounds. There-
fore, we decided to focus the optimization attempts on the
Pd(OAc)2/Ph3P system.
R1
R1
Pd(OAc)2
Cs2CO3
R2
R2
N
TBAB, DMF
110 °C
OH
N
A study of the influence of various solvents (DMF and
DMSO) suggested that DMF is the best choice. No reac-
tion was found to occur below 90 °C. Switching to the
mild base Cs2CO3 under these conditions gave the desired
cyclized product 9a without any debrominated byproduct.
The best results were achieved using Cs2CO3 as the base,
Pd(OAc)2 as the catalyst, along with Ph3P as ligand and
DMF as a solvent at 110 °C. After four hours reaction time
this procedure provided a 85% yield of the cyclized prod-
uct 9a (Table 3, entry 5).22 The results are summarized in
Table 3.
O
O
O
4,5,8 R1 R2 R3
X
a
b
d
CH3
H
H
H
H
8
4 (X = Br)
5 (X = I)
CH3 H
H
H
Scheme 2 Synthesis of benzo[f][1,4]oxazepino[4,3,2-l,m]carbazol-
9-one
was confirmed by its spectroscopic and analytical data as
well as single-crystal X-ray analysis.21 Without addition
of triphenylphosphine as an additional ligand with
Ag2CO3 as the base only debrominated product was ob-
tained (Table 3, entry 3). In the presence of KOAc as the
base, triphenylphosphine as an additional ligand in DMF
as the solvent, the cyclized product 9a was isolated in
70% yield along with a small amount (8%) of the debro-
minated side product (Table 3, entry 4). Use of other bases
such as K2CO3, KOAc, or Ag2CO3 gave decreased yields
of 9a with more of the side product. All attempts to opti-
To examine the versatility and scope of this intramolecu-
lar palladium-catalyzed cyclization, isochromeno-annu-
lated carbazole derivatives 9b–d were synthesized by
employing the optimized reaction conditions Pd(OAc)2/
Ph3P/Cs2CO3/DMF (Table 3, entries 5–12). It was ob-
served that the use of o-iodobenzoyl derivatives dramati-
cally improves the yield of the desired products.
Table 2 Synthesis of Benzo[f][1,4]oxazepino[4,3,2-l,m]carbazol-9-ones 8 under Various Experimental Conditions
R1
R1
R2
R2
N
N
OH
4,5,8 R1 R2
O
O
O
a
b
d
CH3
H
H
H
CH3
H
X
8
4 (X = Br)
5 (X = I)
Entry
1
Reactant
4a
Catalyst (10 mol%) Ligand (15 mol%)Base (1.5 equiv)
Additive (1.5 equiv)Solvent
Yield (%)a
–
Ph3P
Cs2CO3
Cs2CO3
NaOAc
KOAc
TBAB
TBAB
–
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
n.r.
45
46
52
66
n.r.
90
88
92
93
90
94
2
4a
PdCl2
Ph3P
3
4a
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
–
–
–
–
–
–
–
–
–
–
4
4a
–
5
4a
Cs2CO3
Et3N
–
6
4a
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
7
4a
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
8
4b
9
4d
10
11
12
5a
5b
5d
a n.r. = no reaction.
Synlett 2011, No. 13, 1835–1840 © Thieme Stuttgart · New York

1838
K. Prabakaran et al.
LETTER
R1
R1
R2
Pd(OAc)2
Ph3P
X
R2
Cs2CO3, DMF
110 °C
N
N
R3
R3
H
H
O
O
O
O
6,7,9 R1 R2 R3
9
6 (X = Br)
7 (X = I)
a
b
c
d
CH3
H
H
H
CH3
H
H
H
CH3
H
H
H
Scheme 3 Synthesis of isochromeno[3,4-a]carbazol-2(13H)-one
In conclusion, we have developed a convenient and high-
yielding route for the construction of a new class of benz-
annelated oxazepinocarbazoles as well as isochromeno-
carbazoles via palladium-catalyzed intramolecular
arylation. Use of mild base reaction conditions for these
C–O and C–C bond-forming process proved to result in
effective transformations.
Acknowledgment
K.P. thanks CSIR, New Delhi for providing a CSIR-Senior Re-
search Fellowship. Our sincere thanks go to The Chairman, SAIF,
IIT Madras, Chennai for providing access to mass spectrometric
and NMR spectroscopic facilities. The diffractometer was funded
by NSF grant 0087210, by the Ohio Board of Regents grant CAP-
491, and by Youngstown State University.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
Table 3 Synthesis of Isochromeno[3,4-a]carbazol-2(13H)-ones 9 under Various Experimental Conditions
R1
R1
R2
R2
dehalogenated
product
+
N
H
N
R3
R3
6,7,9 R1 R2 R3
10
H
O
O
X
a
b
c
d
CH3
H
H
H
O
O
6 (X = Br)
7 (X = I)
9
CH3 H
H
H
H
CH3
H
H
Entry
1
Reactant
6a
Catalyst (10 mol%) Ligand (20 mol%) Base (2 equiv)
Additive (2 equiv) Solvent
Yield of 9/10 (%)
n.r.a
–
Ph3P
Ph3P
Ph3P
Ph3P
Ph3P
Ph3P
Ph3P
Ph3P
Ph3P
Ph3P
Ph3P
Ph3P
Cs2CO3
KOAc
–
DMF
DMF
DMSO
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
2
6a
PdCl2
TBAB
40:35
0:80
3
6a
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Ag2CO3
K2CO3
TBAB
4
6a
–
–
–
–
–
–
–
–
–
70:8
5
6a
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
85:0
6
6b
78:0
7
6c
76:0
8
6d
82:0
9
7a
89:0
10
11
12
7b
85:0
7c
84:0
7d
87:0
a n.r. = no reaction.
Synlett 2011, No. 13, 1835–1840 © Thieme Stuttgart · New York

LETTER
Synthesis of Benzannulated Oxazepino- and Pyranocarbazoles
1839
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(18) General Procedure for the Preparation of 4 and 5
To 2-halobenzoic acid (2.5 mmol) was added SOCl2 (2 mL).
The solution was refluxed for 2 h, after which the excess of
SOCl2 was removed under reduced pressure, and the residual
traces were then removed by coevaporation with dry toluene.
The acid chloride was then added to a solution of 1-hydroxy-
carbazole (2.5 mmol) and Et3N (2 mL) in dry THF (10 mL)
at 0 °C. After the addition of the acid chloride, the mixture
Synlett 2011, No. 13, 1835–1840 © Thieme Stuttgart · New York

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K. Prabakaran et al.
LETTER
was allowed to warm up to r.t. while stirring under a nitrogen
atmosphere. After stirring overnight, the mixture was diluted
with H2O and neutralized with 4% HCl to pH 7. The
precipitated amide was then filtered off and washed with 4%
HCl and copious amounts of H2O. The crude product was
purified by chromatography using 1% EtOAc and afforded 4
and 5.
1-Hydroxy-9-(2-bromobenzoyl)-6-methylcarbazole (4a)
White solid; mp 126 °C; yield 0.682 g, 72%. IR (KBr): n =
3432 (OH), 1646 (C=O) cm–1. 1H NMR (500 MHz, CDCl3):
d = 2.42 (s, 3 H, CH3), 6.86 (t, 1 H, J = 8.0 Hz, H-3), 7.13
(dd, 1 H, Jm = 2.0 Hz, Jo = 8.0 Hz, H-7), 7.21 (dd, 1 H,
Jm = 2.0 Hz, Jo = 8.0 Hz, H-2), 7.58–7.62 (m, 2 H, Harom),
7.67–7.71 (m, 2 H, Harom), 7.75 (d, 1 H, J = 8.0 Hz, H-8),
7.85 (s, 1 H, H-5), 7.94 (dd, 1 H, Jm = 2.0 Hz, Jo = 7.5 Hz,
H-3¢), 12.76 (s, 1 H, OH). 13C NMR (125 MHz, CDCl3):
d = 21.6 (CH3), 111.0, 111.6, 116.8, 119.1, 120.2, 122.3,
122.9, 126.1, 126.5, 127.5, 128.3, 129.9, 131.8, 132.2,
132.8, 138.4, 139.3, 148.5, 165.7 (CO). LC-MS: m/z = 380
[M + H+]. Anal. Calcd (%) for C20H14BrNO2: C, 63.32; H,
3.69; N, 3.69. Found: C, 63.34; H, 3.67; N, 3.72.
washed with 1 M HCl, H2O, brine and dried (Na2SO4). The
solvent was removed by distillation, and the crude product
was purified by column chromatography over silica gel
using PE as the eluent to give the final compound 8.
13-Methylbenzo[f][1,4]oxazepino[4,3,2-l,m]carbazol-9-
one (8a)
White solid; mp 141 °C; yield 0.269 g, 90%. IR (KBr): n =
1666 (C=O) cm–1. 1H NMR (500 MHz, CDCl3): d = 2.44 (s,
3 H, CH3), 7.12 (d, 1 H, J = 8.0 Hz, H-3), 7.18 (t, 1 H, J = 8.0
Hz, H-2), 7.19 (t, 1 H, J = 7.5 Hz, H-7), 7.23 (d, 1 H, J = 8.0
Hz, H-5), 7.28 (d, 1 H, J = 8.0 Hz, H-12), 7.48 (t, 1 H, J = 7.5
Hz, H-6), 7.60 (d, 1 H, J = 7.0 Hz, H-1), 7.67 (s, 1 H, H-14),
8.05 (dd, 1 H, Jm = 1.5 Hz, Jo = 8.0 Hz, H-8), 8.55 (d, 1 H,
J = 8.5 Hz, H-11). 13C NMR (125 MHz, CDCl3): d = 21.42
(CH3), 115.84, 116.94, 117.69, 120.07, 121.34, 124.73,
125.06, 125.52, 126.59, 128.89, 129.27, 129.79, 133.36,
134.51, 134.89, 137.66, 145.62, 156.51, 164.73 (C=O). LC-
MS: m/z = 300 [M + H+]. Anal. Calcd (%) for C20H13NO2: C,
80.27; H, 4.35; N, 4.68. Found: C, 80.21; H, 4.37; N, 4.73.
(21) Complete cif files for compounds 4a and 9a were deposited
with the Cambridge Crystallographic Data Centre, CCDC
Deposit numbers 796527 and 796520. Copies of the data can
be obtained, free of charge, on application to CCDC, 12
Union Road, Cambridge, CB2 1EZ, UK [fax: +44
(1223)336033 or e-mail: deposit@ccdc.cam.ac.uk].
(22) General Procedure for the Preparation of 9
To a mixture of 6 or 7 (1 mmol), Ph3P (20 mol%), and
Cs2CO3 (2 equiv) in anhyd DMF (8 mL) was added
Pd(OAc)2 (10 mol%), and the mixture was placed in a pre-
heated oil bath at 110 °C for 4 h. After completion of the
reaction, the mixture was cooled and diluted with H2O. This
was extracted with EtOAc. The combined organic extracts
were washed with 1 M HCl, H2O, brine and dried (Na2SO4).
The solvent was removed by distillation, and the crude was
purified by column chromatography over silica gel using PE
as eluent to give compound 9 as white solid.
(19) General Procedure for the Preparation of 6 and 7
To a solution of 1-hydroxycarbazole (3a–d, 2.5 mmol) in
dry CH2Cl2, 2-bromobenzoyl chloride, or 2-iodobenzoyl
chloride (prepared as before) in dry CH2Cl2 solution (10 mL)
was added, and the reaction mixture was heated to reflux for
12 h. The mixture was then washed with H2O and brine
solution and dried (Na2SO4). Evaporation of the CH2Cl2
gave a crude product which was purified by chromatography
with PE–EtOAc (98:2) to afford 6 and 7.
6-Methyl-9H-carbazol-1-yl 2-Bromobenzoate (6a)
White solid; mp 147 °C; yield 0.682 g, 72%. IR (KBr): n =
3389 (NH), 1741 (OC=O) cm–1. 1H NMR (500 MHz,
CDCl3): d = 2.55 (s, 3 H, CH3), 7.24–7.28 (m, 2 H, Harom),
7.35 (d, 1 H, J = 8.0 Hz, H-8), 7.39 (dd, 1 H, Jm = 1.0 Hz,
Jo = 8.0 Hz, H-4), 7.46–7.53 (m, 2 H, Harom), 7.81 (dd, 1 H,
Jm = 1.5 Hz, Jo = 7.7 Hz, H-2), 7.89 (s, 1 H, H-5), 7.97 (d, 1
H, J = 7.5 Hz, H-3¢), 8.13 [dd, 2 H, Jm = 2.0 Hz, Jo = 7.5 Hz,
H-6¢ (overlapped with NH)]. 13C NMR (125 MHz, CDCl3):
d = 21.29 (CH3), 110.66, 117.57, 117.98, 119.24, 120.29,
122.04, 123.52, 126.27, 127.38, 127.66, 129.18, 131.28,
131.68, 131.96, 133.25, 134.54, 135.59, 137.88, 163.93
(C=O). LC-MS: m/z = 380 [M + H+]. Anal. Calcd (%) for
C20H14BrNO2: C, 63.32; H, 3.69; N, 3.69. Found: C, 63.36;
H, 3.70; N, 3.72.
10-Methylisochromeno[3,4-a]carbazol-2(13H)-one (9a)
Mp >300 °C; yield 0.254 g, 85%. IR (KBr): n = 3305 (NH),
1719 (OC=O) cm–1. 1H NMR (500 MHz, CDCl3): d = 2.49
(s, 3 H, CH3), 7.25 (d, 1 H, J = 8.0 Hz, H-11), 7.37 (d, 1 H,
J = 8.0 Hz, H-12), 7.50 (t, 1 H, J = 8.0 Hz, H-4), 7.54 (d, 1
H, J = 8.0 Hz, H-7), 7.78 (d t, 1 H, Jm = 2.0 Hz, Jo = 8.0 Hz,
H-5), 7.89 (s, 1 H, H-9), 7.93 (d, 1 H, J = 8.5 Hz, H-3), 8.16
(d, 1 H, J = 8.0 Hz, H-8), 8.38 (dd, 1 H, Jm = 1.5 Hz, Jo = 8.0
Hz, H-6), 8.56 (br s, 1 H, NH). 13C NMR (125 MHz, CDCl3):
d = 21.34 (CH3), 102.32, 111.02, 116.10, 118.38, 118.66,
119.20, 120.46, 121.09, 124.52, 125.52, 126.92, 127.15,
128.00, 128.41, 132.07, 132.45, 133.05, 136.76, 158.12
(C=O). LC-MS: m/z = 300 [M + H+]. Anal. Calcd (%) for
C20H13NO2: C, 80.27; H, 4.35; N, 4.68. Found: C, 80.17; H,
4.33; N, 4.61.
(20) General Procedure for the Preparation of 8
To a mixture of 4 or 5 (1 mmol), Bu4NBr (1.5 equiv), and
Cs2CO3 (1.5 equiv) in anhyd DMF (8 mL) was added
Pd(OAc)2 (10 mol%) and the flask placed in a pre-heated
oil bath at 110 °C for 2 h. After completion of the reaction,
the mixture was cooled and diluted with H2O. This was
extracted with EtOAc. The combined organic extracts were
Synlett 2011, No. 13, 1835–1840 © Thieme Stuttgart · New York