Synthesis of N-acylcarbazoles through palladium-catalyzed aryne annulation of 2-haloacetanilides

Article abstract of DOI:10.1021/jo3021727

N-Acylcarbazoles have been synthesized in moderate to good yields by the annulation of in situ generated arynes with 2-haloacetanilides in the presence of a palladium catalyst and CsF. Both C-C and C-N bonds are formed simultaneously, and a variety of fun

Full text of DOI:10.1021/jo3021727

Article
pubs.acs.org/joc
Synthesis of N‑Acylcarbazoles through Palladium-Catalyzed Aryne
Annulation of 2‑Haloacetanilides
Chun Lu, Nataliya A. Markina, and Richard C. Larock*
Department of Chemistry, Iowa State University, Ames, Iowa 50011, United States
S
* Supporting Information
ABSTRACT: N-Acylcarbazoles have been synthesized in moderate to good yields by the annulation of in situ generated arynes
with 2-haloacetanilides in the presence of a palladium catalyst and CsF. Both C−C and C−N bonds are formed simultaneously,
and a variety of functional groups are tolerated in this reaction.
INTRODUCTION
RESULTS AND DISCUSSION
■
■
Optimization Studies. We have optimized the reaction of
Carbazoles have been found to possess a variety of biological
activities, including antibacterial, antifungal, antiviral, anti-
inflammatory, and antitumor properties.1 In addition to their
use in the pharmaceutical field, some carbazole derivatives also
find applications in material science, for example, as photo-
refractive materials.2 A number of synthetic routes has been
developed for construction of the carbazole core.3 The majority
of these methods require multiple synthetic steps or highly
prefunctionalized starting materials, whereas efficient one-step
methodologies for the formation of carbazoles from readily
available starting materials are still very limited. Synthetic
applications of aryne chemistry have attracted considerable
attention4 since a convenient approach to aryne generation by
the fluoride-induced 1,2-elimination of o-(trimethylsilyl)aryl
triflates was first reported in 1983.5 The high electrophilicity of
arynes has been used extensively in our group in the
construction of heteroaromatic structures via either simple
nucleophilic reactions6 or annulation reactions.7 Palladium-
mediated reactions are, by far, the most powerful metal-
catalyzed processes for constructing carbocycles and hetero-
cycles,8 due to the high efficiency with which they construct C−
C and C−X (X = O, N) bonds and their high compatibility
with functional groups. To take advantage of the high reactivity
and tremendous synthetic utility of arynes and the tremendous
versatility of organopalladium chemistry, we9 and several other
groups10 have been exploring the palladium-catalyzed annula-
tion reactions of arynes.
2-iodoacetanilide (1a) and the benzyne precursor o-
(trimethylsilyl)phenyl trifluoromethanesulfonate (2a) in 4:1
toluene/acetonitrile with CsF as the fluoride source (Table 1).
In all cases, side product 4a was always generated by the
cyclotrimerization of benzyne10g,11 as was the desired benzyne
annulation product 3a (eq 1). Optimization work was
conducted with respect to different palladium catalysts, ligands,
and solvents, and the results are shown in Table 1.
Utilizing Pd(dba)2 as the catalyst, several ligands were
examined (entries 1−9) in a 4:1 toluene/acetonitrile mixed
solvent. When employing tri(o-tolyl)phosphine as the ligand
(entry 1), the desired product was obtained in a low yield
(23%), alongside large amounts of unreacted aryl halide 1a.
Bidentate ligands were also tested. Both dppm and dppb gave
low yields, 42% (entry 2) and 27% (entry 3), respectively.
However, the use of dppf improved the yield of the desired
product dramatically to 69% (entry 4). Several different
biarylphosphine ligands (L1−L5, Scheme 1) have also been
examined in this process (entries 5−9), but yields no more than
50% have been obtained. Besides various ligands, several
commonly used Pd catalysts, including Pd(OAc)2 and Pd-
(PPh3)4, were also tested in this reaction (entries 10 and 11).
Pd(dba)2 still proved to be the most efficient catalyst. An effort
to lower the ligand loading (entry 12) was made, but 10% dppf
seemed necessary to maintain a higher yield. On the basis of
our previous experience, the solvent can often prove critical for
palladium-catalyzed benzyne reactions, mostly because the
benzyne is generated at vastly different rates in different
solvents.9 For toluene/acetonitrile mixtures and CsF as the
fluoride source, benzyne is generated more slowly in mixtures
Herein, we wish to report the palladium-catalyzed annulation
of arynes by substituted 2-haloacetanilides to produce N-
acylcarbazoles in moderate to good yields. In this reaction, C−
C and C−N bonds are formed simultaneously to generate this
important heterocyclic ring system.
Received: October 17, 2012
Published: December 5, 2012
© 2012 American Chemical Society
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a
Table 1. Optimization of the Pd-Catalyzed Annulation of Benzyne (eq 1)
b
entry
catalyst (5 mol %)
ligand (mol %)
solvent ratio (toluene/MeCN)
% yield of 3a
1
2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(OAc)2
Pd(PPh3)4
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
P(o-tol)3 (10)
dppm (10)
dppb (10)
dppf (10)
4:1
23
42
27
69
45
54
56
51
17
54
60
60
54
35
61
45
4:1
3
4:1
4
4:1
c
5
L1 (10)
4:1
c
6
L2 (10)
4:1
c
7
L3 (10)
4:1
c
8
L4 (10)
4:1
c
9
L5 (10)
4:1
10
11
12
13
14
15
16
dppf (10)
dppf (10)
dppf (5)
4:1
4:1
4:1
dppf (10)
dppf (10)
dppf (10)
dppf (10)
3:1
5:1
C3H7CN
d
DME
a
All reactions were run using substrate 1a (0.25 mmol), 2.0 equiv of 2a, 5.0 equiv of CsF, and 10 mL of solvent at 110 °C for 24 h, unless otherwise
b
c
d
specified. Isolated yield. See L in Scheme 1. Reaction was conducted at 90 °C for 36 h.
Scheme 1. Phosphine Ligands Examined
with less acetonitrile, because CsF has a lower solubility in
toluene. Therefore, the solvent ratio was tested, and 4:1
toluene/acetonitrile afforded the best result (entries 13 and
14). In case of a 3:1 ratio, more side product, trimer 4a, was
formed. With a 5:1 ratio, the benzyne was generated too slowly,
leading to a lower yield. Other solvents, including butyroni-
trile12 (entry 15) and DME (entry 16), afforded only moderate
yields. In the end, we have chosen the reaction conditions
reported in entry 4 of Table 1 as our optimal conditions.
Synthesis of N-Acylcarbazoles. To explore the scope and
limitations of this process, a number of 2-haloacetanilides were
synthesized and allowed to react with 2-(trimethylsilyl)phenyl
trifluoromethanesulfonate (2a) under our optimized condi-
tions. The results are summarized in Table 2.
Different substituents in the acyl groups of the starting
amides, including alkyl (entries 1−4), benzyl (entry 5), and
phenyl (entries 6−8) groups, have been examined, and
moderate to good yields have been produced, except for the
reaction of amide 1d, which generated only trace amounts of
the desired product 3d, along with a large amount of
dehalogenated product and unidentified polymeric material. It
is worth noting that the electronic nature of the phenyl group
in the acyl substituent has a significant impact on the reaction
yield (compare entries 6, 7, and 8). Thus, a substrate with a
more electron-rich substituent on a phenyl ring (1g) (entry 7)
afforded a much higher yield than a similar substrate with a
more electron-deficient trifluoromethyl group on a phenyl ring
(1h) (entry 8). This phenomenon can be explained as follows.
An electron-donating OMe group can increase the nucleophil-
icity of the nitrogen, which promotes nucleophilic attack of the
nitrogen on Pd(II) in the cyclization step in going from
complex III to complex V (see Scheme 2). On the other hand,
an electron-withdrawing CF3 group decreases the nucleophil-
icity, inhibiting the cyclization step. These experimental results
suggest that the nucleophilicity of nitrogen, which is involved in
the cyclization of complex III to complex V (see Scheme 2), is
critical for this reaction. A lower yield of product 3g (60%) was
produced when using the corresponding bromo-aryl equivalent
of 1g. This is not surprising, since for most palladium-catalyzed
reactions of aryl halides, iodine-containing substrates provide
better results than bromine-containing substrates, because their
oxidative addition to Pd(0) is easier and faster. An acetanilide
with a thiophenyl substituent (1i, entry 9) has also been tested,
and the reaction was observed to provide a larger number of
side products than the analogous reaction of an alkyl-
substituted substrate, and thus produced a lower yield of 50%.
To further test the scope and the limitations of the reaction,
we examined a variety of N-(2-iodophenyl)benzamides with
various functional groups, including halogens (entries 17−21),
electron-donating groups (entries 10−16), and electron-
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a b c d
, , ,
Table 2. Pd-Catalyzed Annulation of Benzyne 2a
a
Representative procedure: 1 (0.25 mmol), 2.0 equiv of 2, 5.0 equiv of CsF, 5 mol % Pd(dba)2, 10 mol % dppf in 10 mL of 4:1 toluene/MeCN at
b
c
d
110 °C for 24 h, unless otherwise specified. Isolated yield. Yield in parentheses starting from 2-bromobenzamide. Yield in parentheses for the
reaction conducted in 10 mL of 1:1 toluene/MeCN.
withdrawing groups (entries 22−26). Halogen atoms, including
Br (entry 17), Cl (entries 18 and 19), and F (entries 20 and
21), are tolerated in this chemistry, and moderate to good
yields are obtained for the corresponding carbazoles 3q−3u.
These products provide a valuable extension of the developed
methodology, since further elaboration of these products via
versatile metal-catalyzed reactions is possible, leading to a
variety of polysubstituted carbazoles. Amides with a slightly
electron-donating methyl group in positions 4 (entry 11) and 5
(entry 10) and amides substituted with two methyl groups
(entry 13) afford products 3k, 3j, and 3m in 74, 65, and 77%
yields, respectively. An amide with a methyl group ortho to the
iodine generates a much lower yield of product 3l (44%) (entry
12), presumably because the steric hindrance caused by the
methyl group disfavors the oxidative addition step (see the later
mechanistic discussion). Amides with strong electron-donating
methoxy groups (entries 14−16) provide lower yields of
products 3n−3p (34−59%). Again, this is presumably because
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electron-rich aryl halides undergo more sluggish oxidative
addition to Pd(0). Strong electron-withdrawing CF3, CN, ester,
and NO2 groups (entries 22−26) lower the yield as well,
providing products 3v−3z in 30−54% yields. Although these
electron-withdrawing groups electronically benefit oxidative
addition of the aryl halide to Pd(0), they strongly disfavor
nucleophilic attack of the nitrogen on Pd(II) in complex III in
the cyclization step to form complex V (see Scheme 2).
In addition to the above reactions, which examined only the
use of the benzyne precursor triflate 2a as an annulation
partner, other aryne precursors have been examined in our
methodology (Table 3). When 4,5-dimethylbenzyne precursor
2b was allowed to react with amide 1g under our optimized
conditions, it provided the corresponding annulation product
3m in a 62% yield. The dimethoxybenzyne precursor 2c was
also examined, and a longer reaction time was necessary to get a
40% yield of the annulation product 3p (Table 3, entry 2). The
low yield for 2c may be attributed to the slower rate of
Scheme 2. Tentative Mechanisms
a b c d
, , ,
Table 3. Investigation of Different Arynes in the Pd-Catalyzed Annulation of 2-Haloacetanilide 1g
a
Representative procedure: 1g (0.25 mmol), 2.0 equiv of the aryne precursor, 5.0 equiv of CsF, 5 mol % Pd(dba)2, 10 mol % dppf in 10 mL of 4:1
b
c
d
toluene/MeCN at 110 °C for 24 h. Isolated yield. Reaction was conducted for 48 h. Complex reaction mixture with large amounts of leftover 1g
was obtained.
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139.9, 138.5, 138.3, 129.3, 127.1, 127.0, 122.6, 114.3, 86.3, 55.7, 21.5;
HRMS (EI) calcd for C15H15INO2: 368.0142, found 368.0150.
N-(2-Iodo-4-methylphenyl)-4-methoxybenzamide (1k): White
generation of the 4,5-dimethoxybenzyne compared with the
generation of benzyne from 2a, as has been suggested by earlier
work in our group.9a,b The difluorobenzyne precursor 2d was
also allowed to react with 1g under the optimal conditions
(Table 3, entry 3), but none of the desired product was
observed and a large amount of 1g was left unreacted. This
might be due to the lack of stability of the difluorobenzyne in
the reaction system. The unsymmetrical aryne precursor 2e
afforded a complex mixture of unknown products, and a
significant amount of the starting material 1g was left
unreacted.
On the basis of our experimental results and previous
experience with related processes,9b we propose that this N-
acylcarbazole synthesis proceeds through one of two possible
pathways shown in Scheme 2. One possible pathway proceeds
by the oxidative cyclization of Pd(0) with the aryne generated
from the silyl triflate to form palladacycle I (path a).13
Oxidative addition of 1a to this palladacycle forms Pd(IV)
intermediate II. However, we cannot rule out the possibility
that Pd(0) inserts directly into the C−I bond of 1a to form
intermediate IV, which then undergoes carbopalladation of the
aryne to give rise to intermediate III10d (path b); then, under
the basic conditions, intermediate V may be formed. Finally,
through reductive elimination, the desired product can be
generated alongside Pd(0), which can reenter the catalytic
cycle. There does not appear to be any particular evidence
favoring either of these pathways over the other.
1
solid, mp 146−148 °C; H NMR (300 MHz, CDCl3) δ 8.28 (d, J =
8.4 Hz, 1H), 8.13 (br s, 1H), 7.92 (dd, J = 8.1, 2.7 Hz, 2H), 7.63 (s,
1H), 7.20 (d, J = 8.4 Hz, 1H), 7.00 (dd, J = 8.7, 3.0 Hz, 2H), 3.88 (s,
3H), 2.30 (s, 3H); 13C NMR (300 MHz, CDCl3) δ 165.0, 162.9,
139.2, 136.2, 136.0, 130.3, 129.3, 127.1, 121.7, 114.3, 90.5, 55.7, 20.6;
HRMS (ESI) calcd for C15H15INO2: 368.0142, found 368.0148.
N-(2-Iodo-3-methylphenyl)-4-methoxybenzamide (1l): White
solid, mp 148−150 °C; 1H NMR (300 MHz, CDCl3) δ 8.41 (s,
1H), 8.24 (d, J = 6.0 Hz, 1H), 7.96 (d, J = 6.0 Hz, 2H), 7.27 (t, J = 9.0
Hz, 1H), 7.05−6.99 (d, J = 6.0 Hz, 3H), 3.88 (s, 3H), 2.50 (s, 3H);
13C NMR (300 MHz, CDCl3) δ 165.0, 162.9, 142.4, 138.8, 129.3,
128.9, 127.1, 125.8, 119.2, 114.3, 98.0, 55.7, 29.9; HRMS (EI) calcd
for C15H15INO2: 368.0142, found 368.0142.
N-(4,5-Dimethyl-2-iodophenyl)-4-methoxybenzamide (1m):
1
White solid, mp 125−127 °C; H NMR (300 MHz, CDCl3) δ 8.19
(s, 1H), 8.08 (s, 1H), 7.93 (d, J = 9.0 Hz, 2H), 7.55 (s, 1H), 7.00 (d, J
= 6.0 Hz, 2H), 3.88 (s, 3H), 2.26 (s, 3H), 2.20 (s, 3H); 13C NMR
(300 MHz, CDCl3) δ 164.9, 162.8, 139.1, 138.3, 136.3, 135.0, 129.2,
127.1, 123.1, 114.3, 86.8, 55.7, 20.0, 19.1; HRMS (EI) calcd for
C16H17NO2I: 382.0298, found 382.0300.
N-(2-Iodo-5-methoxyphenyl)-4-methoxybenzamide (1n): White
solid, mp 107−110 °C; 1H NMR (400 MHz, CDCl3) δ 8.23−8.22 (m,
2H), 7.93 (d, J = 8.7 Hz, 2H), 7.62 (d, J = 8.7 Hz, 1H), 7.00 (d, J = 8.7
Hz, 2H), 6.49 (dd, J = 8.7, 3.0 Hz, 1H), 3.87 (s, 3H), 3.84 (s, 3H); 13C
NMR (300 MHz, CDCl3) δ 165.0, 163.0, 160.9, 139.4, 138.7, 129.2,
126.9, 114.4, 113.2, 106.7, 78.2, 55.7, 55.7; HRMS (EI) calcd for
C15H15INO3: 383.0091, found 383.0091.
N-(2-Iodo-4-methoxyphenyl)-4-methoxybenzamide (1o): Cream
1
solid, mp 179−181 °C; H NMR (400 MHz, DMSO-d6) δ 9.77 (s,
CONCLUSIONS
■
1H), 7.97 (d, J = 8.3 Hz, 2H), 7.44 (d, J = 2.8 Hz, 1H), 7.29 (d, J = 8.7
Hz, 1H), 7.06 (d, J = 8.3 Hz, 2H), 7.01 (dd, J = 8.8, 2.9 Hz, 1H), 3.83
(s, 3H), 3.78 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 164.9, 161.9,
157.9, 133.0, 129.5, 129.2, 126.4, 123.2, 114.6, 113.6, 99.9, 55.7, 55.4;
HRMS (EI) calcd for C15H15INO3: 384.0091, found 384.0086.
N-(4,5-Dimethoxy-2-iodophenyl)-4-methoxybenzamide (1p):
In summary, we have developed a novel method for the
synthesis of N-acylcarbazoles, which involves the palladium-
catalyzed annulation of arynes by 2-haloacetanilides. This
method provides an efficient synthesis of carbazoles from
readily available starting materials. Our process has been shown
to be tolerant of various functional groups, which makes further
elaboration of these substrates possible.
1
White solid, mp 168−170 °C; H NMR (400 MHz, CDCl3) δ 8.16
(s, 1H), 8.06 (s, 1H), 7.93 (d, J = 8.0 Hz, 2H), 7.20 (s, 1H), 7.01 (d, J
= 12.0 Hz, 2H), 3.94 (s, 3H), 3.89 (s, 3H), 3.87 (s, 3H); 13C NMR
(400 MHz, CDCl3) δ 164.9, 162.8, 149.7, 146.4, 132.7, 129.1, 126.8,
120.4, 114.3, 105.9, 77.65, 56.5, 56.2, 55.6; HRMS (EI) calcd for
C16H17INO4: 414.0197, found 414.0194.
EXPERIMENTAL SECTION
■
General Remarks. The 1H and 13C NMR spectra were recorded at
300 and 75.5 MHz or 400 and 100 MHz, respectively. All melting
points are uncorrected. All coupling constants (J) are reported in hertz
(Hz). All commercially obtained chemicals were used as received
without further purification. Thin-layer chromatography was per-
formed using commercially prepared 60-mesh silica gel plates, and
visualization was effected with short wavelength UV light (254 nm).
All melting points are uncorrected. High-resolution mass spectra
(HRMS) were obtained using a QTOF mass spectrometer (ESI at a
voltage of 70 eV). All reagents were used directly as obtained
commercially unless otherwise noted. 4,5-Dimethyl-substituted
silylaryl triflate 2b, 4,5-dimethoxy-substituted silylaryl triflate 2c, and
4,5-difluoro-substituted silylaryl triflate 2d were prepared according to
a literature procedure.9a,11b,14
N-(4-Bromo-2-iodophenyl)-4-methoxybenzamide (1q): White
1
solid, mp 151−152 °C; H NMR (300 MHz, CDCl3) δ 8.36 (d, J =
8.7 Hz, 1H), 8.19 (s, 1H), 7.93−7.90 (m, 3H), 7.50 (dd, J = 9.0, 2.1
Hz, 1H), 7.01 (d, J = 8.7 Hz, 2H), 3.88 (s, 3H); 13C NMR (300 MHz,
CDCl3) δ 166.6, 163.1, 140.6, 137.9, 132.5, 129.7, 126.6, 122.5, 117.3,
114.4, 90.4, 55.7; HRMS (EI) calcd for C14H12IBrNO2: 431.9091,
found 431.9102.
N-(4-Chloro-2-iodophenyl)-4-methoxybenzamide (1r): White
1
solid, mp 148−150 °C; H NMR (300 MHz, CDCl3) δ 8.41 (d, J =
9.0 Hz, 1H), 8.19 (s, 1H), 7.93 (d, J = 9.0 Hz, 2H), 7.79 (d, J = 2.4 Hz,
1H), 7.37 (dd, J = 9.0, 2.4 Hz, 1H), 7.01 (d, J = 9.0 Hz, 2H), 3.89 (s,
3H); 13C NMR (300 MHz, CDCl3) δ 165.0, 163.1, 138.0, 137.5,
129.8, 129.6, 129.3, 126.6, 122.2, 114.4, 90.0, 55.7; HRMS (EI) calcd
for C14H12ClINO2: 387.9596, found 387.9597.
Experimental Details. Noncommercially available starting
materials were prepared according to literature procedures.15
N-(2-Iodophenyl)-4-(trifluoromethyl)benzamide (1h): White solid,
mp 173−175 °C; 1H NMR (300 MHz, CDCl3) δ 8.33 (d, J = 9.0 Hz,
1H), δ 7.82 (d, J = 9.0 Hz, 1H), 7.71−7.63 (m, 5H), 7.42 (t, J = 6.0
Hz, 1H), 6.92 (t, J = 9.0 Hz, 1H); 13C NMR (300 MHz, d6- DMSO) δ
165.8, 139.0, 135.8, 132.5, 130.2, 128.9, 128.5, 128.4, 128.1, 126.5,
126.4; HRMS (EI) calcd for C14H10F3INO: 391.9754, found 391.9762.
N-(2-Iodo-5-methylphenyl)-4-methoxybenzamide (1j): White
N-(5-Chloro-2-iodophenyl)-4-methoxybenzamide (1s): White
solid, mp 123−125 °C; 1H NMR (400 MHz, CDCl3) δ 8.58 (s,
1H), 8.22 (s, 1H), 7.93 (d, J = 8.0 Hz, 2H), 7.71 (d, J = 12.0 Hz, 1H),
7.02 (d, J = 8.0 Hz, 2H), 6.88 (d, J = 8.0 Hz, 1H), 3.89 (s, 3H); 13C
NMR (400 MHz, CDCl3) δ 164.9, 163.2, 139.6, 139.3, 135.8, 129.3,
126.5, 125.9, 121.5, 114.5, 86.9, 55.8; HRMS (EI) calcd for
C14H12NO2ICl: 387.9596, found 387.9597.
N-(4-Fluoro-2-iodophenyl)-4-methoxybenzamide (1t): White
1
1
solid, mp 95−98 °C; H NMR (300 MHz, CDCl3) δ 8.31 (d, J =
solid, mp 158−160 °C; H NMR (400 MHz, CDCl3) δ 8.36 (dd, J
1.8 Hz, 1H), 8.18 (s, 1H), 7.94 (d, J = 9.0 Hz, 2H), 7.66 (d, J = 8.1 Hz,
1H), 7.02 (d, J = 9.0 Hz, 2H), 6.71 (dd, J = 8.1, 2.1 Hz, 1H), 3.89 (s,
3H), 2.37 (s, 3H); 13C NMR (300 MHz, CDCl3) δ 165.0, 162.9,
= 12.0, 8.0 Hz, 1H), 8.09 (s, 1H), 7.92 (d, J = 8.0 Hz, 2H), 7.54 (dd, J
= 8.0, 4.0 Hz, 1H), 7.26 (s, 1H), 7.14 (td, J = 12.0, 4.0 Hz, 1H), 7.01
(d, J = 8.0 Hz, 2H), 3.89 (s, 3H); 13C NMR (400 MHz, CDCl3) δ
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165.0, 163.0, 160.4, 157.1, 135.2, 129.3, 126.7, 125.7, 125.4, 122.8,
122.7, 116.5, 116.2, 114.4, 89.9, 89.8, 55.7 (extra peaks due to 13C−19F
coupling); HRMS (EI) calcd for C14H12FINO2: 371.9891, found
371.9896.
(400 MHz, CDCl3) δ 178.2, 138.7, 127.5, 126.6, 123.7, 120.0, 116.5,
35.4, 19.8. The 1H NMR spectral data are in good agreement with that
previously reported.17
9-(Cyclohexylcarbonyl)carbazole (3c): 50.9 mg (73%), light brown
oil; 1H NMR (300 MHz, CDCl3) δ 8.17 (d, J = 9.0 Hz, 2H), 8.02 (d, J
= 9.0 Hz, 2H), 7.51 (dd, J = 9.0, 6.0 Hz, 2H), 7.40 (dd, J = 9.0, 6.0 Hz,
2H), 3.38 (tt, J = 12.0, 3.0 Hz, 1H), 2.14 (d, J = 12.0 Hz, 2H), 1.96 (d,
J = 12.0 Hz, 2H), 1.86−1.74 (m, 3H), 1.60−1.44 (m, 3H); 13C NMR
(300 MHz, CDCl3) δ 177.1, 138.8, 127.5, 126.6, 123.6, 120.0, 116.4,
45.5, 29.7, 26.0, 25.9; HRMS (EI) calcd for C19H20NO: 278.1539,
found 278.1539.
N-(5-Fluoro-2-iodophenyl)-4-methoxybenzamide (1u): White
1
solid, mp 133−135 °C; H NMR (300 MHz, CDCl3) δ 8.39 (dd, J
= 11.0, 2.7 Hz, 1H), 8.29 (s, 1H), 7.94 (d, J = 8.7 Hz, 2H), 7.74 (dd, J
= 8.7, 6.0 Hz, 1H), 7.03 (d, J = 8.7 Hz, 2H), 6.70−6.63 (m, 1H), 3.90
(s, 3H); 13C NMR (300 MHz, CDCl3) δ 165.1, 164.9, 163.1, 161.8,
140.0, 139.8, 139.3, 139.2, 129.3, 129.2, 126.4, 114.4, 113.1, 112.8,
109.3, 108.9, 82.5, 55.7 (extra peaks due to 13C−19F coupling); HRMS
(EI) calcd for C14H12FINO2: 371.9891, found 371.9897.
9-(Benzylcarbonyl)carbazole (3e): 43.4 mg (61%), white solid, mp
123−124 °C; 1H NMR (400 MHz, CDCl3) δ 8.28 (d, J = 8.0 Hz, 2H),
8.04 (d, J = 8.0 Hz, 2H), 7.51−7.47 (t, J = 8.0 Hz, 2H), 7.43−7.40 (m,
4H), 7.38−7.34 (m, 3H), 4.53 (s, 2H); 13C NMR (300 MHz, CDCl3)
δ 166.6, 138.7, 133.7, 129.7, 129.0, 127.7, 126.8, 126.1, 124.0, 120.1,
116.7, 45.6; HRMS (EI) calcd for C20H16NO: 286.1226, found
286.1226.
N-[2-Iodo-4-(trifluoromethyl)phenyl]-4-methoxybenzamide (1v):
White solid, mp 148−150 °C; 1H NMR (300 MHz, CDCl3) δ 8.63 (d,
J = 9.0 Hz, 1H), 8.38 (s, 1H), 8.04 (s, 1H), 7.94 (d, J = 9.0 Hz, 2H),
7.64 (d, J = 6.0 Hz, 1H), 7.02 (d, J = 9.0 Hz, 1H), 3.89 (s, 3H); 13C
NMR (300 MHz, CDCl3) δ 165.1, 163.3, 141.7, 135.9, 129.4, 126.8,
126.3, 120.8, 114.4, 88.9, 82.3, 55.7; HRMS (EI) calcd for
C15H12F3INO2: 421.9859, found 421.9855.
N-[2-Iodo-5-(trifluoromethyl)phenyl]-4-methoxybenzamide (1w):
White solid, mp 146−148 °C; 1H NMR (300 MHz, CDCl3) δ 8.83 (d,
J = 2.1 Hz, 1H), 8.34 (s, 1H), 7.97−7.92 (m, 3H), 7.11 (dd, J = 8.1,
2.1 Hz, 1H), 7.03 (d, J = 8.7 Hz, 2H), 3.90 (s, 3H); 13C NMR (300
MHz, CDCl3) δ 165.1, 163.3, 139.4, 139.4, 129.4, 126.3, 122.1, 122.0,
118.2, 118.1, 114.5, 93.7, 55.8; HRMS (EI) calcd for C15H12F3INO2:
421.9859, found 421.9867.
9-(Phenylacetyl)carbazole (3f): 40.9 mg (60%), yellow oil; 1H
NMR (400 MHz, CDCl3) δ 8.02 (d, J = 7.1 Hz, 2H), 7.74 (d, J = 7.7
Hz, 2H), 7.67 (d, J = 7.7 Hz, 1H), 7.54 (t, J = 7.5 Hz, 4H), 7.35 (m,
4H); 13C NMR (400 MHz, CDCl3) δ 169.8, 139.3, 135.9, 132.6,
129.3, 129.1, 126.2, 123.6, 120.0, 116.0; HRMS (ESI) calcd for
C19H14NO: 272.1070, found 272.1072.
9-(4-Methoxybenzoyl)carbazole (3g): 57.4 mg (76%), white solid,
mp 162−164 °C; 1H NMR (300 MHz, CDCl3) δ 8.02−7.99 (m, 2H),
7.72 (d, J = 8.7 Hz, 2H), 7.57−7.52 (m, 2H), 7.36−7.30 (m, 4H), 6.99
(d, J = 9.0 Hz, 2H), 3.90 (s, 3H); 13C NMR (300 MHz, CDCl3) δ
169.3, 163.4, 139.5, 132.0, 127.7, 126.8, 126.0, 123.2, 120.0, 115.7,
114.3, 55.7; HRMS (EI) calcd for C20H16NO2: 302.1176, found
302.1177.
N-(4-Cyano-2-iodophenyl)-4-methoxybenzamide (1x): White
1
solid, mp 83−85 °C; H NMR (300 MHz, CDCl3) δ 8.77 (d, J =
6.0 Hz, 1H), 8.60 (s, 1H), 7.92−7.87 (d, J = 6.0 Hz, 2H; s, 1H), 7.66
(d, J = 9.0 Hz, 1H), 7.03 (d, J = 9.0 Hz, 2H), 3.90 (s, 3H); 13C NMR
(300 MHz, CDCl3) δ 166.6, 163.5, 140.4, 132.9, 129.4, 126.0, 121.1,
117.7, 114.6, 113.1, 108.0, 82.3, 55.8; HRMS (EI) calcd for
C15H12IN2O2: 378.9938, found 378.9933.
9-[4-(Trifluoromethyl)benzoyl]carbazole (3h): 28.2 mg (33%),
white solid, mp 101−103 °C; 1H NMR (300 MHz, CDCl3) δ 8.00 (d,
J = 9.0 Hz, 2H), 7.93 (d, J = 9.0 Hz, 1H), 7.79−7.70 (m, 2H), 7.53 (d,
J = 6.0 Hz, 1H), 7.44−7.27 (m, 6H); 13C NMR (300 MHz, CDCl3) δ
166.6, 138.9, 132.9, 131.0, 129.2, 128.6, 127.5, 126.8, 124.4, 120.1,
116.3; HRMS (EI) calcd for C20H13F3NO: 340.0944, found 340.0949.
9-(Thiophen-2-ylcarbonyl)carbazole (3i): 34.9 mg (50%), light
yellow solid, mp 95−98 °C; 1H NMR (300 MHz, CDCl3) δ 8.04−8.01
(m, 2H), 7.76−7.70 (m, 3H), 7.60 (d, J = 3.0 Hz, 1H), 7.39−7.36 (m,
4H), 7.16 (dd, J = 6.0, 3.0 Hz, 1H); 13C NMR (300 MHz, CDCl3) δ
163.0, 139.4, 138.0, 134.0, 133.4, 127.9, 126.8, 125.6, 123.5, 120.1,
115.5; HRMS (EI) calcd for C17H12NOS: 278.0634, found 278.0636.
9-(4-Methoxybenzoyl)-2-methylcarbazole (3j): 51.3 mg (65%),
white solid, mp 129−131 °C; 1H NMR (300 MHz, CDCl3) δ 7.98 (d,
J = 6.0 Hz, 1H), 7.90 (d, J = 9.0 Hz, 1H), 7.74 (d, J = 9.0 Hz, 2H),
7.54 (s, 1H), 7.40−7.24 (m, 3H), 7.19 (d, J = 9.0 Hz, 1H), 7.01 (d, J =
9.0 Hz, 2H), 3.93 (s, 3H), 2.46 (s, 3H); 13C NMR (300 MHz, CDCl3)
δ 169.3, 163.4, 140.0, 139.5, 137.5, 132.0, 127.8, 126.1, 124.6, 123.6,
123.1, 119.8, 119.6, 116.1, 115.6, 114.2, 55.7, 22.4; HRMS (EI) calcd
for C21H18NO2: 316.1332, found 316.1339.
N-(4-Carbomethoxy-2-iodophenyl)-4-methoxybenzamide (1y):
1
White solid, mp 165−167 °C; H NMR (300 MHz, CDCl3) δ 8.60
(d, J = 8.7 Hz, 1H), 8.47 (d, J = 2.1 Hz, 1H), 8.43 (s, 1H), 8.04 (dd, J
= 8.7, 2.1 Hz, 1H), 7.93 (d, J = 9.0 Hz, 2H), 7.01 (d, J = 9.0 Hz, 2H),
3.91 (s, 3H), 3.88 (s, 3H); 13C NMR (300 MHz, CDCl3) δ 165.4,
165.0, 163.2, 142.5, 140.3, 131.1, 129.4, 126.9, 126.4, 120.0, 114.5,
88.9, 55.7, 52.5; HRMS (EI) calcd for C16H15INO4: 412.0040, found
412.0047.
N-(2-Iodo-4-nitrophenyl)-4-methoxybenzamide (1z): White solid,
mp 158−160 °C; 1H NMR (300 MHz, CDCl3) δ 8.76 (d, J = 9.0 Hz,
1H), 8.69 (d, J = 3.0 Hz, 1H), 8.55 (s, 1H), 8.28 (dd, J = 9.0, 3.0 Hz,
1H), 7.95 (d, J = 9.0 Hz, 2H), 7.04 (d, J = 9.0 Hz, 2H), 3.90 (s, 3H);
13C NMR (300 MHz, CDCl3) δ 165.0, 163.6, 144.3, 134.4, 129.5,
126.2, 125.3, 119.7, 114.6, 87.9, 55.8; HRMS (EI) calcd for
C14H11IN2O4: 398.9833, found 398.9836.
General Procedure for the Palladium-Catalyzed Synthesis of
N-Acylcarbazoles. The 2-iodoacetanilide (1) (0.25 mmol), the 2-
(trimethylsilyl)aryl triflate 2 (2.0 equiv), CsF (5.0 equiv), Pd(dba)2 (5
mol %), dppf (10 mol %), 8 mL of toluene, and 2 mL of MeCN were
placed in a 4 dram vial, and the vial was sealed. The reaction mixture
was stirred, first, at room temperature for 1 min and then heated to
110 °C for 24 h. The mixture was allowed to cool to room
temperature, diluted with ethyl acetate, washed with brine, dried over
anhydrous MgSO4, and concentrated under reduced pressure. The
product was isolated by flash chromatography on silica gel using
hexanes/EtOAc as the eluent.
9-(4-Methoxybenzoyl)-3-methylcarbazole (3k): 58.1 mg (74%),
1
light brown oil; H NMR (300 MHz, CDCl3) δ 7.99 (dd, J = 6.0, 3.0
Hz, 1H), 7.82 (s, 1H), 7.73 (d, J = 9.0 Hz, 2H), 7.60 (dd, J = 6.0, 3.0
Hz, 1H), 7.42(d, J = 9.0 Hz, 1H), 7.37−7.33 (m, 2H), 7.16 (d, J = 9.0
Hz, 1H), 7.00 (d, J = 9.0 Hz, 2H), 3.92 (s, 3H), 2.52 (s, 3H); 13C
NMR (300 MHz, CDCl3) δ 169.2, 163.3, 139.8, 137.7, 132.9, 131.9,
129.2, 128.6, 128.0, 126.7, 126.0, 123.2, 120.1, 119.9, 115.8, 114.2,
55.7, 21.5; HRMS (EI) calcd for C21H18NO2: 316.1332, found
316.1333.
9-(4-Methoxybenzoyl)-4-methylcarbazole (3l): 34.8 mg (44%),
light brown oil; 1H NMR (400 MHz, CDCl3) δ 8.18 (m, 1H), 7.91 (d,
J = 8.4 Hz, 1H), 7.74 (d, J = 8.8 Hz, 2H), 7.65 (m, 1H), 7.44 (d, J =
8.4 Hz, 1H), 7.34−7.23 (m, 2H), 7.18−7.13 (m, 1H), 7.00 (d, J = 8.8
Hz, 2H); 13C NMR (300 MHz, CDCl3) δ 169.3, 163.4, 140.5, 139.6,
133.1, 132.1, 129.8, 126.5, 126.3, 126.0, 124.9, 123.0, 122.6, 122.4,
115.3, 114.2, 113.1, 55.8, 21.2; HRMS (EI) m/z calcd for C21H18NO2:
316.1332, found 316.1335.
9-Acetylcarbazole (3a): 35.8 mg (69%), white solid, mp 69−71 °C;
1H NMR (300 MHz, CDCl3) δ 8.20 (br d, J = 8.5 Hz, 2H), 7.98 (ddd,
J = 7.5, 1.4, 0.6 Hz, 2H), 7.47 (ddd, J = 8.5, 7.5, 1.4 Hz, 2H), 7.38 (dt,
J = 7.5, 1.0 Hz, 2H), 2.87 (s, 3H); 13C NMR (300 MHz, CDCl3) δ
1
170.1, 138.6, 127.3, 126.4, 123.6, 119.8, 116.2, 27.7. The H and 13C
NMR spectral data are in good agreement with that previously
reported.16
9-(Isopropylcarbonyl)carbazole (3b): 43.3 mg (72%), yellow oil;
1H NMR (400 MHz, CDCl3) δ 8.21 (d, J = 8.4 Hz, 2H), 8.01 (ddd, J
= 7.5, 1.2, 0.6 Hz, 2H), 7.49 (ddd, J = 8.5, 7.3, 1.4 Hz, 2H), 7.39 (td, J
= 7.5, 1.0 Hz, 2H), 3.70 (m, 1H), 1.45 (d, J = 6.7 Hz, 6H); 13C NMR
2,3-Dimethyl-9-(4-methoxybenzoyl)carbazole (3m): 63.8 mg
1
(77%), white solid, mp 156−157 °C; H NMR (300 MHz, CDCl3)
11158
dx.doi.org/10.1021/jo3021727 | J. Org. Chem. 2012, 77, 11153−11160

The Journal of Organic Chemistry
Article
δ 7.95 (d, J = 9.0 Hz, 1H), 7.76 (s, 1H), 7.72 (d, J = 9.0 Hz, 2H), 7.47
(s, 1H), 7.38 (d, J = 9.0 Hz, 1H), 7.32−7.23 (m, 2H), 6.99 (d, J = 9.0
Hz, 2H), 3.92 (s, 3H); 13C NMR (300 MHz, CDCl3) δ 169.1, 163.3,
139.4, 138.3, 136.0, 132.1, 131.9, 128.0, 126.2, 126.0, 124.0, 123.1,
120.4, 119.7, 116.5, 115.7, 114.2, 55.7, 21.1, 20.2; HRMS (EI) m/z
calcd for C22H20NO2: 330.14886, found 330.14919.
due to 13C−19F coupling); HRMS (EI) calcd for C20H15FNO2:
320.1081, found 320.1083.
9-(4-Methoxybenzoyl)-3-(trifluoromethyl)carbazole (3v): 36.9 mg
1
(40%), light yellow oil; H NMR (400 MHz, CDCl3) δ 3.93 (s, 3H),
6.99−7.03 (m, 2H), 7.39−7.43 (m, 2H), 7.50−7.54 (m, 1H), 7.60 (dd,
J = 8.8, 1.8 Hz, 1H), 7.68 (d, J = 8.8 Hz, 1H), 7.74 (d, J = 8.8 Hz, 2H),
8.04−8.10 (m, 1H), 8.29 (d, J = 1.3 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 169.1, 163.8, 143.4, 140.1, 132.2, 130.7, 129.2, 128.6, 127.7,
127.0, 125.8, 125.0, 123.7, 123.6, 123.6, 120.4, 117.5, 117.5, 115.8,
115.7, 114.5, 55.8 (extra peaks due to 19F−13C coupling); HRMS (EI)
calcd for C21H15F3NO2: 370.1049, found 370.1047.
9-(4-Methoxybenzoyl)-2-(trifluoromethyl)carbazole (3w): 49.4
mg (54%), white solid, mp 107−109 °C; 1H NMR (300 MHz,
CDCl3) δ 8.14−8.06 (m, 3H), 7.74 (d, J = 9.0 Hz, 2H), 7.63 (d, J = 9.0
Hz, 1H), 7.44−7.38 (m, 3H), 7.03 (d, J = 9.0 Hz, 2H), 3.94 (s, 3H);
13C NMR (300 MHz, CDCl3) δ 169.0, 163.8, 139.0, 138.4, 132.1,
130.5, 129.2, 128.6, 127.9, 127.0, 125.6, 123.5, 120.7, 120.7, 120.3,
115.7, 114.5, 55.8; HRMS (EI) calcd for C21H15F3NO2: 370.1049,
found 370.1051.
3-Cyano-9-(4-methoxybenzoyl)carbazole (3x): 35.2 mg (43%),
white solid, mp 175−177 °C; 1H NMR (300 MHz, CDCl3) δ 8.35 (s,
1H), 8.08−8.05 (m, 1H), 7.76−7.70 (m, 3H), 7.63 (dd, J = 9.0, 3.0
Hz, 1H), 7.50−7.40 (m, 3H), 7.03 (d, J = 9.0 Hz, 2H), 3.94 (s, 3H);
13C NMR (300 MHz, CDCl3) δ 168.9, 164.1, 141.6, 140.1, 132.4,
130.1, 128.1, 126.6, 126.2, 124.7, 124.2, 123.9, 120.5, 119.7, 116.3,
115.7, 114.6, 106.4, 55.9; HRMS (EI) calcd for C21H15N2O2:
327.1128, found 327.1134.
2-Methoxy-9-(4-methoxybenzoyl)carbazole (3n): 45.6 mg (55%),
1
white solid, mp 109−111 °C; H NMR (300 MHz, CDCl3) δ 7.92−
7.86 (d, J = 9.0 Hz, 2H), 7.73 (d, J = 9.0 Hz, 2H), 7.37−7.22 (m, 4H),
7.01−6.94 (m, 3H), 3.91 (s, 3H), 3.79 (s, 3H); 13C NMR (300 MHz,
CDCl3) δ 169.4, 163.4, 159.4, 140.9, 139.4, 132.0, 127.7, 126.1, 125.3,
123.2, 120.6, 119.4, 119.2, 115.5, 114.3, 111.8, 100.3, 55.7; HRMS
(EI) calcd for C21H18NO3: 332.1281, found 332.1289.
3-Methoxy-9-(4-methoxybenzoyl)carbazole (3o): 48.5 mg (59%),
1
light brown oil; H NMR (400 MHz, CDCl3) δ 7.96 (dd, J = 6.0, 3.1
Hz, 1H), 7.71 (d, J = 8.5 Hz, 2H), 7.53 (dd, J = 6.1, 3.3 Hz, 1H), 7.49
(d, J = 9.1 Hz, 1H), 7.47 (d, J = 2.6 Hz, 1H), 7.35 − 7.29 (m, 2H),
6.99 (d, J = 8.6 Hz, 2H), 6.94 (dd, J = 9.0, 2.6 Hz, 1H), 3.92 (s, 3H),
3.91 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 169.0, 163.2, 156.3,
140.0, 133.9, 131.8, 127.9, 126.9, 126.8, 126.0, 123.1, 119.9, 116.7,
115.9, 114.8, 114.2, 103.1, 56.0, 55.7; HRMS (EI) calcd for
C21H18NO3: 332.1281, found 332.1278.
2,3-Dimethoxy-9-(4-methoxybenzoyl)carbazole (3p): 37.9 mg
1
(40%), white solid, mp 114−116 °C; H NMR (300 MHz, CDCl3)
δ 7.89 (d, J = 9.0 Hz, 1H), 7.73 (d, J = 9.0 Hz, 2H), 7.43 (s, 1H), 7.42
(s, 1H), 7.32−7.17 (m, 4H), 7.01 (d, J = 9.0 Hz, 2H), 4.03 (s, 3H),
3.92 (s, 3H), 3.85 (s, 3H); 13C NMR (300 MHz, CDCl3) δ 169.2,
163.3, 149.3, 146.8, 139.1, 134.0, 131.9, 127.9, 126.4, 125.1, 123.2,
119.0, 118.3, 115.7, 114.3, 101.7, 99.8, 56.5, 56.2, 55.8; HRMS (EI)
calcd for C22H20NO4: 362.1387, found 362.1391.
3-Carbomethoxy-9-(4-methoxybenzoyl)carbazole (3y): 26.8 mg
1
(30%), white solid, mp 134−135 °C; H NMR (300 MHz, CDCl3) δ
8.75 (s, 1H), 8.11−8.04 (m, 2H), 7.75 (d, J = 9.0 Hz, 2H), 7.60 (d, J =
9.0 Hz, 1H), 7.54 (t, J = 3.6 Hz, 1H), 7.41−7.38 (m, 2H), 7.01 (d, J =
9.0 Hz, 2H), 3.99 (s, 3H), 3.94 (s, 3H); 13C NMR (300 MHz, CDCl3)
δ 169.1, 167.4, 163.8, 141.7, 140.1, 132.3, 129.0, 128.2, 127.4, 125.9,
125.4, 125.0, 123.7, 122.2, 120.4, 115.7, 115.2, 114.4, 55.8, 52.4;
HRMS (EI) calcd m/z for C22H18NO4: 360.1230, found 360.1238.
9-(4-Methoxybenzoyl)-3-nitrocarbazole (3z): 23.3 mg (27%),
3-Bromo-9-(4-methoxybenzoyl)carbazole (3q): 56.4 mg (60%),
white solid, mp 110−112 °C; 1H NMR (300 MHz, CDCl3) δ 8.14 (s,
1H), 7.99−7.96 (m, 1H), 7.72 (d, J = 9.0 Hz, 2H), 7.52−7.42 (m,
3H), 7.38−7.35 (m, 2H), 7.01 (d, J = 6.0 Hz, 2H), 3.93 (s, 3H); 13C
NMR (300 MHz, CDCl3) δ 166.6, 163.6, 139.8, 138.3, 132.1, 129.6,
127.8, 127.5, 127.3, 124.8, 123.5, 122.9, 120.3, 117.2, 116.4, 115.8,
114.4, 55.8; HRMS (EI) calcd for C20H15BrNO2: 380.0281, found
380.0279.
1
yellow solid, mp 170−172 °C; H NMR (300 MHz, CDCl3) δ 8.94
(d, J = 2.1 Hz, 1H), 8.28 (dd, J = 9.0, 2.4 Hz, 1H), 8.14−8.11 (m, 1H),
7.78−7.71 (d, J = 9.0 Hz, 3H), 7.48−7.42 (m, 3H), 7.03 (d, J = 9.0 Hz,
2H), 3.95 (s, 3H); 13C NMR (300 MHz, CDCl3) δ 168.8, 166.6,
164.2, 142.9, 140.6, 132.4, 128.3, 126.4, 126.1, 124.7, 124.0, 122.2,
120.8, 116.4, 115.8, 115.5, 114.6, 55.9; HRMS (EI) m/z calcd for
C20H15N2O4: 347.1026, found 347.1033.
3-Chloro-9-(4-methoxybenzoyl)carbazole (3r): 46.2 mg (55%),
1
light brown oil; H NMR (300 MHz, CDCl3) δ 7.98−7.96 (m, 2H),
7.72 (d, J = 9.0 Hz, 2H), 7.56−7.49 (m, 1H), 7.37−7.29 (m, 3H), 7.01
(d, J = 9.0 Hz, 2H), 3.93 (s, 3H); 13C NMR (300 MHz, CDCl3) δ
169.0, 163.6, 140.0, 137.9, 132.0, 129.2, 128.9, 127.5, 126.8, 124.9,
123.5, 120.7, 120.3, 119.9, 116.8, 115.8, 114.4, 55.8; HRMS (EI) calcd
for C20H15ClNO2: 336.0786, found 336.0788.
ASSOCIATED CONTENT
■
S
* Supporting Information
2-Chloro-9-(4-methoxybenzoyl)carbazole (3s): 52.7 mg (63%),
1
Copies of H and 13C NMR spectra for all novel compounds.
1
white solid, mp 93−95 °C; H NMR (300 MHz, CDCl3) δ 7.98 (m,
This material is available free of charge via the Internet at
http://pubs.acs.org.
1H), 7.93 (d, J = 8.4 Hz, 1H), 7.77−7.72 (dd, J = 8.4, 1.8 Hz, 3H),
7.42 (d, J = 3.0 Hz, 1H), 7.35−7.32 (m, 3H), 7.02 (d, J = 9.0 Hz, 2H),
3.93 (s, 3H); 13C NMR (300 MHz, CDCl3) δ 169.0, 163.7, 143.5,
139.1, 132.1, 130.7, 129.2, 128.6, 126.9, 124.4, 123.8, 123.4, 120.7,
120.1, 116.0, 115.7, 114.4, 55.8; HRMS (EI) m/z calcd for
C20H15ClNO2: 336.0786, found 336.0790.
AUTHOR INFORMATION
Corresponding Author
*E-mail: larock@iastate.edu.
■
3-Fluoro-9-(4-methoxybenzoyl)carbazole (3t): 52.0 mg (65%),
white solid, mp 90−93 °C; 1H NMR (300 MHz, CDCl3) δ 7.98−7.95
(m, 1H), 7.72 (d, J = 9.0 Hz, 2H), 7.69−7.60 (m, 2H), 7.48−7.45 (m,
1H), 7.36−7.33 (d, J = 6.0 Hz, 2H), 7.09 (td, J = 9.0, 2.7 Hz, 1H), 7.02
(d, J = 6.9 Hz, 2H); 13C NMR (300 MHz, CDCl3) δ 169.1, 163.5,
161.1, 157.9, 140.2, 135.8, 132.0, 130.5, 127.6, 127.4, 123.3, 120.7,
120.3, 117.0, 116.8, 115.9, 114.5, 114.4, 114.2, 106.2, 105.9, 55.8 (extra
peaks due to 13C−19F coupling); HRMS (EI) m/z calcd for
C20H15FNO2: 320.10813, found 320.10895.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the National Institute of General Medical Sciences
(GM070620), the National Institutes of Health Kansas
University Center of Excellence for Chemical Methodologies
and Library Development (P50 GM069663), and the National
Science Foundation for their generous support of this research.
2-Fluoro-9-(4-methoxybenzoyl)carbazole (3u): 42.1 mg (53%),
1
white solid, mp 115−117 °C; H NMR (300 MHz, CDCl3) δ 7.98−
7.92 (m, 2H), 7.73 (d, J = 9.0 Hz, 2H), 7.44−7.41 (m, 2H), 7.32 (td, J
= 9.0, 3.0 Hz, 2H), 7.11 (d, J = 6.0 Hz, 1H), 7.02 (d, J = 9.0 Hz, 2H),
3.93 (s, 3H); 13C NMR (300 MHz, CDCl3) δ 169.1, 165.1, 163.6,
160.5, 143.5, 140.2, 132.0, 129.2, 128.6, 126.3, 125.6, 123.5, 120.92,
120.7, 119.8, 115.6, 114.4, 111.4, 111.2, 103.5, 103.2, 55.8 (extra peaks
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