Synthesis of carbazoles and dibenzofurans via cross-coupling of o-iodoanilines and o-iodophenols with silylaryl triflates and subsequent Pd-catalyzed cyclization

Article abstract of DOI:10.1016/j.tet.2006.10.071

An efficient route to a variety of carbazoles and dibenzofurans has been developed. It involves the reaction of o-iodoanilines or o-iodophenols with silylaryl triflates in the presence of CsF to afford the N- or O-arylated products, which are subsequently cyclized using a Pd catalyst to carbazoles and dibenzofurans in good to excellent yields. By using this methodology, the carbazole alkaloid, mukonine has been synthesized in 76% overall yield in three steps.

Full text of DOI:10.1016/j.tet.2006.10.071

Tetrahedron 63 (2007) 347–355
Synthesis of carbazoles and dibenzofurans via cross-coupling
of o-iodoanilines and o-iodophenols with silylaryl triflates
and subsequent Pd-catalyzed cyclization
*
Zhijian Liu and Richard C. Larock
Department of Chemistry, Iowa State University, Ames, IA 50011, United States
Received 5 September 2006; revised 24 October 2006; accepted 25 October 2006
Available online 13 November 2006
Abstract—An efficient route to a variety of carbazoles and dibenzofurans has been developed. It involves the reaction of o-iodoanilines or
o-iodophenols with silylaryl triflates in the presence of CsF to afford the N- or O-arylated products, which are subsequently cyclized using a Pd
catalyst to carbazoles and dibenzofurans in good to excellent yields. By using this methodology, the carbazole alkaloid, mukonine has been
synthesized in 76% overall yield in three steps.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
improvements, there are still limitations in the present
methods. For example, (a) stoichiometric amounts of palla-
dium are needed in the oxidative cyclization reaction, (b)
harsh reaction conditions are usually needed and some pro-
cesses cannot tolerate many functional groups, and (c) the
yields usually are not very good. One simple, new, efficient
and general method to synthesize both the carbazole and
dibenzofuran ring systems would be quite attractive because
of the growing interest in these compounds.13
Heterocycles are a very important class of organic com-
pounds, because of their wide application in medicine, agri-
culture, and technology.1 Among nitrogen heterocycles,
carbazole alkaloids are a growing class of natural products,
which display a wide variety of biological activities, such
as antitumor, antibacterial, antimicrobial and anti-inflamma-
tory activities.2 Recently, a number of carbazole derivatives
have been used as organic materials, due to their well-known
photoconducting3 and semiconducting properties,4 and their
charge-transport and high thermal properties.5 Dibenzo-
furans and their derivatives have also attracted the attention
of organic chemists for many years due to their occurrence
in a wide variety of pharmaceuticals and natural products
possessing useful biological activities.6 Considerable effort
has been devoted to the development of efficient methods
for the synthesis of a wide range of substituted carbazoles,
including the reductive cyclization of 2-nitrobiphenyl deriv-
atives by suitable organophosphorus reagents7 and the clas-
sical Fisher–Borsche synthesis starting with appropriate
cyclohexanone arylhydrazones.8 Recently, transition metal
catalysts have also been widely used to construct these ring
systems. For example, the palladium-mediated oxidative
cyclization of N,N-diarylamines to carbazoles9 and diaryl
ethers to dibenzofurans,10 and the palladium-catalyzed
double N-arylation of primary amines with 2,2-dihalo-
biphenyls11 have been employed to prepare carbazoles and
dibenzofurans. Quite recently, Wu et al. have utilized anionic
cycloaromatization to synthesize 5-substituted dibenzo-
furans and carbazoles.12 Despite these significant recent
Although arynes have historically received much attention
from organic chemists, their use as reagents in synthetic
organic chemistry has been somewhat limited due to the
harsh reaction conditions needed to generate arynes and the
often uncontrolled reactivity exhibited by these species.14
Recently, silylaryl triflate 1a15 has been employed in the
presence of CsF to generate benzyne under very mild reac-
tion conditions. The resulting aryne readily undergoes a vari-
ety of electrophilic and nucleophilic reactions,16 several
novel insertion reactions,17 and even Pd-catalyzed annula-
tion reactions.18 We have reported that silylaryl triflates can
react with a variety of nucleophiles, such as anilines and
phenols to generate very high yields of the corresponding
N- and O-arylated products and even more important is the
fact that halides, such as iodides and bromides, are readily
tolerated by the reaction conditions.16c,d We have taken
advantage of this methodology to develop a simple, econo-
mical, and efficient one-pot, two-step procedure to synthe-
size the carbazole and dibenzofuran ring systems in good
to excellent yields through the cross-coupling of o-iodoani-
lines or o-iodophenols with silylaryl triflates in the presence
of CsF, followed by palladium-catalyzed intramolecular cy-
clization.19 Herein, we wish to provide a full account of the
* Corresponding author. Tel.: +1 515 294 4660; e-mail: larock@iastate.edu
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.10.071

348
Z. Liu, R. C. Larock / Tetrahedron 63 (2007) 347–355
scope and limitations of this chemistry. We have also applied
this chemistry to the high yield three-step synthesis of an
interesting carbazole alkaloid, mukonine.
(4.0 mL) under air. Then Pd(OAc)2 (3.1 mg, 5 mol %) and
PCy3 (7.0 mg, 10 mol %) were added and the reaction
heated to 100 ꢀC for 1 d under argon.
We next studied the scope and limitations of this two-step
cross-coupling process by allowing a wide variety of iodo-
anilines and their derivatives to react with silylaryl triflates
1a–d. The results are summarized in Table 1. A variety of
o-iodoanilines react with silylaryl triflates 1a, 1b or 1c to
afford, after Pd-catalyzed cyclization, high yields of the
desired carbazoles (Table 1, entries 1–9). When a slight ex-
cess (1.1 equiv) of silylaryl triflate 1a was allowed to react
with o-iodoaniline (entry 1), the desired carbazole was ob-
tained in a 77% yield under our standard reaction conditions.
When 2.4 equiv of silylaryl triflate 1a was allowed to react
with o-iodoaniline, N-phenylcarbazole was isolated in only
a 66% yield (entry 2). o-Iodoaniline also reacts with the
methoxy-substituted silylaryl triflate 1b, followed by palla-
dium-catalyzed cyclization, to afford two carbazole deriva-
tives 4 and 5 in a 5:1 ratio (entry 3). The fact that
carbazole 4 is the major product can be easily explained
by a steric effect during the Pd-catalyzed cyclization. The
Pd-catalyzed cyclization is occurring at the less hindered
position away from the methoxy group. When silylaryl
triflate 1c was employed with 2-iodo-4-methylaniline, we
obtained the desired product in a 68% yield (entry 4). Ap-
proximately a 4% yield of the isomeric product 1,2,6-tri-
methylcarbazole was also observed as detected by GC/MS.
Again the Pd-catalyzed cyclization is occurring with high
regioselectivity for the less hindered position away from the
methyl group. When substituted iodoanilines were allowed
to react with silylaryl triflate 1a, the corresponding carbazole
derivatives could be obtained in good to excellent yields
(entries 5–8). Similarly, 2,4-dichloro-6-iodoaniline reacts
with 1.1 equiv of silylaryl triflate 1c to afford the desired
product in an 85% yield. Approximately a 5% yield of the
isomeric product 6,8-dichloro-1,2-dimethylcarbazole was
also observed as detected by GC/MS (entry 9). The presence
of a chlorine in the starting anilines does not appear to inter-
fere with the overall process (entries 7–9). N-Methylcarb-
azole is also readily obtained in an 82% yield when
N-methyl-2-iodoaniline was employed as the substrate
(entry 10). N-Phenylcarbazole was obtained in a slightly
higheryieldbythiscross-couplingprocedure, whenN-phenyl-
2-iodoaniline was employed, instead of 2-iodoaniline, in
the presence of an excess of the aryne (compare entries 2
and 12). N-(2-Iodophenyl)methanesulfonamide and ethyl
2-iodophenylcarbamate and their derivatives also react well
with silylaryl triflate 1a or 1c to afford high yields of the cor-
responding products (entries 13–18); again, only about 5% of
a product isomeric with the products shown in entries 16 and
18 was observed by GC/MS analysis. Interestingly, when
silylaryltriflate1dwasallowedtoreactwithN-(2-iodophenyl)-
methanesulfonamide, we did not obtain the expected
2. Results and discussion
2.1. Preparation of the aryne precursors
The arynes 1a–d were selected as substrates for our experi-
ments. Aryne precursor 1a was selected as the simplest
and most readily available aryne to study the scope of this
chemistry, since it is commercially available. Aryne precur-
sor 1b was selected to study the regioselectivity of the palla-
dium-catalyzed cyclization step. The synthesis of silylaryl
triflates 1a,15 1b,20 1c,21 and 1d22 have previously been
reported.
OMe
TMS
OTf
Me
Me
TMS
OTf
TMS
OTf
TMS
OTf
1a
1b
1c
1d
2.2. Synthesis of carbazoles and analogs
The essential elements of our approach to the carbazole ring
system are shown in Scheme 1. o-Iodoaniline is first allowed
to react with the silylaryl triflate under very mild reaction
conditions to afford the N-arylated o-iodoanilines A,16c
which subsequently undergo intramolecular palladium-
catalyzed arylation in the same pot to produce the carbazole
derivatives B in good yields.
Our initial studies were directed toward achieving the
optimal reaction conditions for the palladium-catalyzed
intramolecular arylation step (A/B) (Scheme 1). A range
of palladium catalysts were employed. We found that
Pd(OAc)2 was the best catalyst. All other palladium catalysts
[PdCl2(PPh3)2, Pd(PPh3)4, Pd(dba)2] examined afforded
either comparable or lower yields. The ligand added to the
reaction did not make much difference. Thus, the ligands
dppe, dppm, and PCy3 (Cy¼cyclohexyl) all worked well
in our system. However, the solvent had a big effect on this
cross-coupling reaction; DMF and toluene both gave very
low yields of the carbazole products, while MeCN proved
to be the best solvent for this process. The first step in this
sequence had already been optimized during some of our
earlier work on the N-arylation of amines.16c After our opti-
mization work was complete, we settled on the following
standard two-step procedure. The iodoaniline (0.25 mmol),
silylaryl triflate (1.1 equiv) and CsF (3.0 equiv) were
allowed to react at room temperature for 10 h in acetonitrile
R1
H
N
R1 5% Pd(OAc)2
TMS
TfO
R1
R1
I
3.0 CsF
MeCN
10% PCy3
R1
+
1.1
NH2
R1
100 °C, 1 d
r.t., 10 h
N
I
H
A
B
1a or 1c
1a: R1 = H; 1c: R1 = CH3
77-85%
Scheme 1.

Z. Liu, R. C. Larock / Tetrahedron 63 (2007) 347–355
349
Table 1. Synthesis of carbazoles and analogsa
Entry
Substrate
NH2
Aryl triflate
CsF (equiv)
3.0
Product
Isolated yield (%)
77
2
1
1a
1
N
H
I
3
2
1
1a
5.0
66b
N
Ph
OMe
N
4
H
+
MeO
3
1
1b
3.0
61 (5:1)
N
H
5
CH3
CH3
H3C
NH2
6
4
1c
1a
1a
1a
1a
1c
1a
3.0
3.0
3.0
3.0
3.0
3.0
3.0
68
69
68
72
87
85
82
H3C
I
N
H
7
H3C
5
6
N
H
8
MeO2C
NH2
6
9
N
MeO2C
I
10
H
Cl
NH2
11
7
Cl
I
N
12
H
Cl
Cl
NH2
8
13
N
14
Cl
I
H
Cl
Cl
CH3
9
13
CH3
N
H
15
Cl
NHCH3
16
10
17
N
CH3
I
CH3
CH3
11
16
1c
3.0
71
N
CH3
18
(continued)

350
Z. Liu, R. C. Larock / Tetrahedron 63 (2007) 347–355
Table 1. (continued)
Entry
Substrate
Aryl triflate
CsF (equiv)
3.0
Product
Isolated yield (%)
76c
NHPh
19
3
12
13
1a
N
Ph
I
NHCO2Et
20
21
1a
3.0
3.0
85
85
N
CO2Et
I
CH3
CH3
22
14
20
1c
1a
N
CO2Et
Cl
NHCO2Et
15
3.0
86
N
CO2Et
23
24
Cl
I
CH3
Cl
CH3
16
17
18
23
1c
1a
1c
3.0
3.0
3.0
85
85
85
N
25
CO2Et
NHMs
26
N
Ms
27
I
CH3
CH3
26
26
N
Ms
28
TMS
OTf
19
3.0
62
N
H
1d
29
N
31
Ts
NHTs
+
O
S
Ph
20
1a
3.0
83 (1:1)
30
O
N
I
32
CH3
Ms
N
NHMs
33
34
21
1a
3.0
66
I
(continued)

Z. Liu, R. C. Larock / Tetrahedron 63 (2007) 347–355
351
Table 1. (continued)
Entry
Substrate
Aryl triflate
CsF (equiv)
3.0
Product
Isolated yield (%)
62
O
S
O
Bn
SO2NHBn
35
N
22
1a
36
I
a
Reaction conditions: 0.25 mmol of aryl iodide is allowed to react with 1.1 equiv of aryl triflate and the number of equiv of CsF shown in table in 4.0 mL of
MeCN as the solvent at room temperature for 10 h, followed by the addition of 5 mol % Pd(OAc)2 and 10 mol % PCy3 and heating for 1 d at 100 ꢀC.
Aryl triflate (2.4 equiv) was employed and the reaction was run at room temperature for 2 d, followed by the addition of 5 mol % Pd(OAc)2 and 10 mol %
PCy3 and heating for 1 d at 100 ꢀC.
b
c
The reaction was run at room temperature for 1.5 d, followed by the addition of 5 mol % Pd(OAc)2 and 10 mol % PCy3 and heating for 1 d at 100 ꢀC.
product, but rather the deprotected dibenzo[a,c]carbazole in
commercially available 4-amino-3-methoxybenzoic acid
(Scheme 2). 3-Methoxy-4-aminobenzoic acid reacts with
methanol to afford methyl 3-methoxy-4-aminobenzoate in
a 98% yield. Iodination using ICl in dichloromethane affords
methyl 4-amino-3-iodo-5-methoxybenzoate in an 82%
yield. Employing our standard reaction conditions on methyl
4-amino-3-iodo-5-methoxybenzoate, mukonine can be ob-
tained in a 95% yield in only one additional step.
a 62% yield (entry 19). Apparently the extended p-con-
jugation of the dibenzo[a,c]carbazole facilitates loss of the
methanesulfonyl group. It is interesting that the reaction of
N-tosyl-2-iodoaniline and silylaryl triflate 1a afforded a 1:1
ratio of compounds 31 and 32 in an 83% overall yield (entry
20). It seems rather surprising that the Pd-catalyzed cycliza-
tion onto the tosyl group competes so effectively with
cyclization onto the phenyl ring. One can also start with
N-(2-iodobenzyl)methanesulfonamide or N-benzyl-2-iodo-
benzenesulfonamide and silylaryl triflate 1a and produce
the corresponding six-membered ring products in good
yields (entries 21 and 22). None of the product from
cyclization onto the benzyl group in entry 22 is observed,
possibly because this would involve formation of a seven-
membered ring.
2.4. Synthesis of dibenzofurans and analogs
Since some effort has been devoted to the synthesis of carb-
azoles and related compounds, it seemed natural for us to ex-
tend this chemistry to the synthesis of dibenzofurans and
related compounds by using o-iodophenol and its deriva-
tives. Indeed, we have also investigated the use of o-iodo-
phenols in this process. Here, we needed to use 1.2 equiv
of silylaryl triflates 1a or 1c and 3.5 equiv of CsF to get the
yields specified. The results are summarized in Table 2.
o-Iodophenol reacts with silylaryl triflate 1a or 1c to afford,
after Pd-catalyzed cyclization, the corresponding dibenzo-
furans in 70 and 67% yields, respectively (entries 1 and 2).
A variety of substituted iodophenols have also been em-
ployed in this process; most of them work quite well and
afford the desired compounds in modest to good yields
(entries 3–10). Similar to our carbazole results, when silyl-
aryl triflate 1c was used in this cross-coupling process,
approximately 4–5% yields of the expected isomeric prod-
ucts were observed as detected by GC/MS (entries 2, 4–6,
and 8). It is noteworthy that the presence of an electron-
withdrawing ester or ketone moiety on the phenol presents
no difficulties and, in fact, these substrates gave slightly
higher yields of the desired products (entries 9 and 10). In
Although there are numerous examples in the literature of
analogous palladium-catalyzed intramolecular cyclizations,
the exact mechanism for this process is not well established
at this time. Nevertheless, it seems clear that oxidative addi-
tion of the aryl halide to Pd(0) generates an arylpalladium
species, which cyclizes to form a palladium(II)cycle, which
in turn undergoes reductive elimination to the heterocycle
while regenerating the Pd(0) catalyst.23
2.3. Synthesis of mukonine
Mukonine [1-methoxy-3-(methoxycarbonyl)carbazole] is an
alkaloid obtained from the Indian curry-leaf tree (Murraya
koenigii).24 Mukonine has been synthesized by several dif-
ferent methods.25 By employing our procedure, mukonine
can be obtained in a 76% overall yield in three steps from
NH2
NH2
NH2
H2SO4
MeOH
1. 1 ICl
2. 0 NaHCO3
H3CO
H3CO
H3CO
I
65 °C
30 min
COOH
CO2CH3
98%
CO2CH3
82%
1. 3.0 CsF
MeCN
R.T., 6 h
CO2CH3
NH2
H3CO
I
TMS
OTf
+
1.1
2. 5% Pd(OAc)2
10% PCy3
100 °C, 12 h
N
H
OCH3
CO2CH3
95%
Mukonine
76% overall yield for three steps
Scheme 2.

352
Z. Liu, R. C. Larock / Tetrahedron 63 (2007) 347–355
Table 2. Synthesis of dibenzofurans and analogsa
Entry
Substrate
Aryl triflate
CsF (equiv)
3.5
Product
Isolated yield (%)
70
OH
37
38
1
1a
1c
O
I
CH3
CH3
2
37
40
43
3.5
3.5
3.5
3.5
3.5
3.5
3.5
3.5
3.5
67b
O
39
H3C
OH
40
3
1a
1c
1a
1c
1a
1c
1a
1a
68
41
H3C
I
O
CH3
H3C
4
68b
CH3
42
O
H3C
H3C
H3C
H3C
OH
I
5
43
63
O
39
CH3
CH3
H3C
H3C
6
61b
O
O
44
Ph
OH
7
63
45
Ph
I
46
CH3
MeO
OH
8
77b,c
47
CH3
48
MeO
I
O
MeO2C
H3CCO
OH
9
80
49
50
MeO2C
H3CCO
I
O
OH
10
76
51
52
I
O
O
O
COOH
11
1a
4.0
46d
53
54
I
a
Reaction conditions: 0.25 mmol of aryl iodide is allowed to react with 1.2 equiv of aryl triflate and the number of equiv of CsF shown in the table in 4.0 mL of
MeCN as the solvent at room temperature for 10 h, followed by the addition of 5 mol % Pd(OAc)2 and 10 mol % PCy3 and heating for 1 d at 100 ꢀC.
About 4% of the isomeric product was detected by GC/MS.
In this reaction, 10 mol % Pd(OAc)2 and 20 mol % PCy3 were used.
Aryl triflate (1.5 equiv) was used.
b
c
d
this process, one can also start with 2-iodobenzoic acid and
3. Conclusions
allow it to react with silylaryl triflate 1a. Cyclization pro-
duces the desired six-membered ring product benzo[c]cou-
marin in a 46% yield (entry 11).
In summary, we have developed a simple and efficient one-
pot, two-step procedure to synthesize the carbazole and

Z. Liu, R. C. Larock / Tetrahedron 63 (2007) 347–355
353
dibenzofuran ring systems and related compounds. This pro-
cess involves the reaction of o-iodoanilines or o-iodophenols
with silylaryl triflates in the presence of CsF to afford the
N- or O-arylated products, which are subsequently cyclized
to carbazoles and dibenzofurans in situ using a Pd catalyst.
The starting materials are commercially available or can
be easily prepared using known chemistry. The yields are
of good to excellent. Several new and multisubstituted carb-
azoles and dibenzofurans have been synthesized using this
chemistry. By using this methodology, the carbazole
alkaloid, mukonine has been synthesized in 76% overall
yield in three steps from a commercially available starting
material.
fractions were dried over Na2SO4 and concentrated under
reduced pressure. The residue was purified by flash chroma-
tography on silica gel to afford the desired product. Schlenk
tube techniques are not necessary.
4.2.1. 2,3,6-Trimethylcarbazole (7). The indicated com-
pound was obtained in a 68% yield as a white solid: mp
208–209 ꢀC (lit.26 211–211.5 ꢀC); 1H NMR (300 MHz,
acetone-d6) d 2.38 (s, 6H), 2.47 (s, 3H), 7.15 (dd, J¼8.4,
1.5 Hz, 1H), 7.25 (s, 1H), 7.33 (d, J¼8.4 Hz, 1H), 7.81 (s,
1H), 9.89 (s, 1H); 13C NMR (75 MHz, acetone-d6) d 19.4,
29.1, 20.8, 110.6, 111.6, 119.7, 120.5, 121.4, 123.5, 126.3,
126.9, 127.5, 134.4, 138.6, 139.6; IR (CDCl3, cmꢁ1) 3393,
2963, 2934, 2852, 1464; HRMS m/z 209.1209 (calcd
C15H15N, 209.1204).
4. Experimental section
4.1. General
4.2.2. 2,3,9-Trimethylcarbazole (18). The indicated com-
pound was obtained in a 71% yield as a light yellow solid:
1
mp 88–89 ꢀC; H NMR (300 MHz, acetone-d6) d 2.43 (s,
1
The H and 13C NMR spectra were recorded at 300 and
3H), 2.46 (s, 3H), 3.78 (s, 3H), 7.15–7.23 (m, 2H), 7.33 (d,
J¼8.1 Hz, 1H), 7.41 (td, J¼6.9, 0.9 Hz, 1H), 7.83 (s, 1H),
8.02 (d, J¼7.8 Hz, 1H); 13C NMR (75 MHz, acetone-d6)
d 19.3, 20.3, 38.3, 114.6, 115.2, 120.2, 120.9, 124.1,
124.3, 126.5, 127.0, 132.9, 136.9, 137.4, 138.7; IR
(CDCl3, cmꢁ1) 3016, 2961, 2935, 2899, 1601; HRMS m/z
209.1209 (calcd C15H15N, 209.1204).
75.5 MHz or 400 and 100 MHz, respectively. All melting
points are uncorrected. High-resolution mass spectra were
recorded on a Kratos MS50TC double focusing magnetic
sector mass spectrometer using EI at 70 eV. All reagents
were used directly as obtained commercially unless other-
wise noted. All yields reported represent an average of at
least two independent runs. Silylaryl triflate 1a is commer-
1
cially available. The product characterization data, and H
4.2.3. Ethyl 3-chlorocarbazole-9-carboxylate (24). The in-
dicated compound was obtained in an 85% yield as a white
solid: mp 102–104 ꢀC; 1H NMR (300 MHz, CDCl3) d 1.54
(t, J¼7.2 Hz, 3H), 4.57 (q, J¼7.2 Hz, 2H), 7.24–7.50 (m,
3H), 7.84–7.88 (m, 2H), 8.18 (d, J¼9.0 Hz, 1H), 8.24 (d,
J¼9.0 Hz, 1H); 13C NMR (75 MHz, CDCl3) d 14.7, 63.5,
116.6, 117.5, 119.6, 120.0, 123.7, 124.9, 127.3, 127.4,
128.1, 129.1, 136.8, 138.8, 152.3; IR (CDCl3, cmꢁ1) 3128,
3064, 2981, 2919, 1723, 1441; HRMS m/z 273.0560 (calcd
C15H12ClNO2, 273.0556).
and 13C NMR spectra for compounds 2, 14, 15, 17, 21, 22,
27, 33, 34, 38, and 50 can be found in the supporting infor-
mation of our previous communication.19
4.1.1. Preparation of methyl 4-amino-3-iodo-5-methoxy-
benzoate. To a solution of 0.905 g of methyl 4-amino-3-
methoxybenzoate (5 mmol) and 0.84 g of NaHCO3 (10 mmol)
in 15 mL of CH2Cl2 at room temperature was added
0.893 g of ICl (5.5 mmol) in 5 mL of CH2Cl2. The reaction
mixture was stirred at room temperature for 30 min. The re-
sulting solution was washed with saturated NaHCO3
(20 mL) solution and extracted with CH2Cl2 (20 mL). The
combined CH2Cl2 fractions were dried over Na2SO4 and
concentrated under reduced pressure. The residue was puri-
fied by flash chromatography on silica gel to afford 1.25 g of
the desired product (82% yield) as a white solid: mp 93–
94 ꢀC; 1H NMR (300 MHz, CDCl3) d 3.86 (s, 3H), 3.89 (s,
3H), 4.69 (s, 2H), 7.39 (d, J¼1.8 Hz, 1H), 8.00 (d,
J¼1.8 Hz, 1H); 13C NMR (75 MHz, CDCl3) d 52.2, 56.2,
80.7, 110.7, 120.5, 133.3, 142.0, 145.3, 166.3; IR (CDCl3,
cmꢁ1) 3495, 3391, 3001, 2949, 2838, 1694, 1268; HRMS
m/z 306.9701 (calcd C9H10INO3, 306.9705).
4.2.4. Ethyl 6-chloro-2,3-dimethylcarbazole-9-carboxyl-
ate (25). The indicated compound was obtained in an 85%
yield as a yellow solid: mp 125–126 ꢀC; 1H NMR
(300 MHz, CDCl3) d 1.54 (t, J¼7.2 Hz, 3H), 2.37 (s, 3H),
2.40 (s, 3H), 4.56 (q, J¼7.2 Hz, 2H), 7.33 (dd, J¼8.7,
2.1 Hz, 1H), 7.59 (s, 1H), 7.80 (d, J¼2.1 Hz, 1H), 8.02 (s,
1H), 8.13 (d, J¼9.0 Hz, 1H); 13C NMR (75 MHz, CDCl3)
d 14.7, 20.2, 21.2, 63.4, 117.2, 117.5, 119.2, 120.4, 122.9,
126.5, 127.6, 128.9, 132.4, 136.7, 137.3, 137.6, 152.4; IR
(CDCl3, cmꢁ1) 2980, 2920, 2860, 1727, 1476; HRMS m/z
301.0873 (calcd C17H16ClNO2, 301.0869).
4.2.5. 2,3-Dimethyl-9-(methanesulfonyl)carbazole (28).
The indicated compound was obtained in an 85% yield as
4.2. General procedure for the synthesis of carbazoles
and related compounds
1
white solid: mp 123–125 ꢀC; H NMR (300 MHz, CDCl3)
d 2.41 (s, 3H), 2.43 (s, 3H), 2.93 (s, 3H), 7.38–7.45 (m,
2H), 7.74 (s, 1H), 7.91–7.94 (m, 2H), 8.12 (dd, J¼7.2,
1.2 Hz, 1H); 13C NMR (75 MHz, CDCl3) d 20.2, 21.1,
38.4, 115.0, 115.5, 120.0, 120.8, 124.3, 124.5, 126.8,
127.1, 133.2, 137.2, 137.3, 138.6; IR (CDCl3, cmꢁ1) 3061,
3032, 3012, 2930, 2856, 1471; HRMS m/z 273.0829 (calcd
C15H15NO2S, 273.0823).
In a 4 dram vial, silylaryl triflate (0.275 mmol) and CsF
(0.75 mmol) were added to a solution of o-iodoaniline
(0.25 mmol) in acetonitrile (4 mL). The reaction mixture
was allowed to stir at room temperature for 10 h under air.
The vial was then flushed with argon and Pd(OAc)2
(5 mol %, 3.1 mg) and PCy3 (10 mol %, 7.0 mg) were added
to the reaction, which was heated to 100 ꢀC for 1 d. The
resulting solution was washed with brine (20 mL) and
extracted with diethyl ether (20 mL). The combined ether
4.2.6. 9-Tosylcarbazole (31). The indicated compound was
obtained in a 41% yield as a white solid: mp 129–130 ꢀC

354
Z. Liu, R. C. Larock / Tetrahedron 63 (2007) 347–355
(lit.27 128.5–130 ꢀC); 1H NMR (300 MHz, CDCl3) d 2.34 (s,
3H), 7.22 (dd, J¼8.7, 0.6 Hz, 2H), 7.42 (td, J¼7.5, 0.9 Hz,
2H), 7.57 (td, J¼7.5, 1.2 Hz, 2H), 7.77 (dt, J¼8.4, 1.8 Hz,
2H), 8.05–8.08 (m, 2H), 8.36 (dt, J¼8.4, 0.6 Hz, 2H);
13C NMR (75 MHz, CDCl3) d 20.7, 115.2, 120.5, 124.4,
126.6, 126.7, 127.8, 130.1, 134.9, 138.5, 145.8; IR
(CDCl3, cmꢁ1) 3109, 3067, 2902, 1595, 1452; HRMS m/z
321.0827 (calcd C19H15NO2S, 321.0823).
4.3.3. 2,3,6-Trimethyldibenzofuran (42). The indicated
compound was obtained in a 68% yield as a white solid:
1
mp 97–98 ꢀC; H NMR (400 MHz, CDCl3) d 2.35 (s, 3H),
2.36 (s, 3H), 2.46 (s, 3H), 7.17 (dd, J¼8.4, 1.2 Hz, 1H),
7.28 (s, 1H), 7.37 (d, J¼8.4 Hz, 1H), 7.61 (s, 1H), 7.63 (d,
J¼0.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 20.2, 21.0,
21.6, 111.2, 112.4, 120.5, 121.0, 122.1, 124.6, 127.6,
131.2, 132.1, 136.4, 154.7, 155.6; IR (CDCl3, cmꢁ1) 3014,
2970, 2940, 2921, 1454; HRMS m/z 210.1048 (calcd
C15H14O, 210.1044).
4.2.7. 2-Methyl-5,5-dioxide-6-phenyldibenzo[c,e][1,2]-
thiazine (32). The indicated compound was obtained in
1
a 42% yield as a white solid: mp 208–210 ꢀC; H NMR
4.3.4. 2,3,6,7-Tetramethyldibenzofuran (44). The indi-
cated compound was obtained in a 61% yield as a white
solid: mp 183–184 ꢀC; 1H NMR (400 MHz, CDCl3) d 2.40
(s, 6H), 2.41 (s, 6H), 7.32 (s, 2H), 7.64 (s, 2H); 13C NMR
(100 MHz, CDCl3) d 20.2, 20.9, 112.3, 120.8, 122.3, 131.0,
135.7, 155.3; IR (CDCl3, cmꢁ1) 3026, 2971, 2919, 2856,
1454; HRMS m/z 224.1204 (calcd C16H16O, 224.1201).
(400 MHz, CDCl3) d 2.55 (s, 3H), 6.98–7.01 (m, 1H), 7.22–
7.25 (m, 2H), 7.33–7.40 (m, 6H), 7.83 (s, 1H), 7.84 (d,
J¼8.0 Hz, 1H), 8.03–8.05 (m, 1H); 13C NMR (100 MHz,
CDCl3) d 22.3, 123.4, 123.8, 125.4, 125.5, 125.7, 126.4,
128.3, 128.6, 129.5, 129.7, 132.4, 132.7, 138.4, 140.4,
143.5; IR (CDCl3, cmꢁ1) 3067, 2925, 2853, 2253,
1600, 1492; HRMS m/z 321.0827 (calcd C19H15NO2S,
321.0823).
4.3.5. 3-Phenyldibenzofuran (46). The indicated com-
pound was obtained in a 63% yield as a white solid: mp
1
4.2.8. 6-Benzyl-5,5-dioxidedibenzo[c,e][1,2]thiazine (36).
The indicated compound was obtained in a 62% yield as
a colorless oil: 1H NMR (400 MHz, CDCl3) d 5.05 (s, 2H),
7.18 (s, 5H), 7.23 (dd, J¼8.0, 1.6 Hz, 1H), 7.28 (td, J¼8.0,
1.2 Hz, 1H), 7.33 (td, J¼8.0, 1.2 Hz, 1H), 7.54 (td, J¼7.6,
1.2 Hz, 1H), 7.65 (td, J¼8.0, 1.2 Hz, 1H), 7.85 (d,
J¼8.0 Hz, 1H), 7.93 (dd, J¼7.6, 1.6 Hz, 1H), 7.99 (dd,
J¼7.6, 1.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 52.9,
122.2, 122.7, 125.6, 125.7, 125.7, 125.8, 127.7, 127.9,
128.4, 128.8, 130.4, 132.5, 132.7, 135.4, 135.9, 138.8; IR
(CDCl3, cmꢁ1) 3064, 3030, 2923, 2851, 1601, 1477;
HRMS m/z 321.0827 (calcd C19H15NO2S, 321.0823).
94–96 ꢀC; H NMR (400 MHz, CDCl3) d 7.31–7.37 (m,
2H), 7.43–7.48 (m, 3H), 7.55–7.66 (m, 5H), 7.96 (dd,
J¼7.6, 0.8 Hz, 1H), 8.11 (d, J¼1.6 Hz, 1H); 13C NMR
(100 MHz, CDCl3) d 112.0, 119.4, 120.9, 123.1, 124.5,
124.9, 126.9, 127.3, 127.6, 127.7, 129.1, 136.6, 141.6,
156.0, 156.9; IR (CDCl3, cmꢁ1) 3057, 3032, 2920, 1601,
1470; HRMS m/z 280.0892 (calcd C18H12O, 280.0888).
4.3.6. 6-Methoxy-2,3-dimethyldibenzofuran (48). The in-
dicated compound was obtained in a 67% yield as a white
1
solid: mp 97–98 ꢀC; H NMR (400 MHz, CDCl3) d 2.38
(s, 3H), 2.39 (s, 3H), 3.88 (s, 3H), 6.90 (dd, J¼8.4, 2.4 Hz,
1H), 7.05 (d, J¼2.4 Hz, 1H), 7.29 (s, 1H), 7.59 (s, 1H),
7.73 (d, J¼8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 20.2, 20.8, 55.9, 96.8, 110.7, 112.2, 117.8, 120.4, 120.7,
4.3. General procedure for the synthesis of dibenzo-
furans and related compounds
122.2, 131.3, 135.0, 155.4, 157.7, 159.6; IR (CDCl3, cmꢁ1
)
3015, 2999, 2979, 2939, 1590; HRMS m/z 226.0996 (calcd
C15H14O2, 226.0993).
In a 4 dram vial, silylaryl triflate (0.3 mmol) and CsF
(0.875 mmol) were added to a solution of o-iodophenol
(0.25 mmol) in acetonitrile (4 mL). The rest of the procedure
is the same as that used in the synthesis of the carbazoles.
Schlenk tube techniques are not necessary.
4.3.7. 3-Acetyldibenzofuran (52). The indicated compound
was obtained in a 76% yield as a white solid: mp 69–70 ꢀC;
1H NMR (300 MHz, CDCl3) d 2.71 (s, 3H), 7.38 (td, J¼7.5,
1.2 Hz, 1H), 7.70 (td, J¼7.5, 1.2 Hz, 1H), 7.57 (s, 1H), 7.60
(s, 1H), 7.99 (dd, J¼7.5, 0.6 Hz, 1H), 8.10 (dd, J¼8.7,
1.8 Hz, 1H), 8.57 (d, J¼1.8 Hz, 1H); 13C NMR (75 MHz,
CDCl3) d 27.0, 111.8, 112.2, 121.2, 121.8, 123.6, 123.9,
124.8, 128.2, 128.3, 132.7, 157.1, 159.1, 197.5; IR
(CDCl3, cmꢁ1) 3063, 3002, 2922, 2849, 1678, 1598;
HRMS m/z 210.0683 (calcd C14H10O2, 210.0680).
4.3.1. 2,3-Dimethyldibenzofuran (39). The indicated com-
pound was obtained in a 67% yield as a white solid: mp 90–
91 ꢀC; 1H NMR (300 MHz, CDCl3) d 2.39 (s, 3H), 2.40 (s,
3H), 7.34–7.42 (m, 3H), 7.52 (d, J¼7.5 Hz, 1H), 7.68 (s,
1H), 7.87 (dd, J¼7.5, 0.9 Hz, 1H); 13C NMR (75 MHz,
CDCl3) d 20.2, 20.9, 111.7, 112.4, 120.4, 121.1, 122.1,
122.6, 124.6, 126.6, 131.4, 136.6, 155.3, 156.4; IR
(CDCl3, cmꢁ1) 3046, 2968, 2941, 2922, 1448; HRMS m/z
196.0890 (calcd C14H12O, 196.0888).
Acknowledgements
4.3.2. 3-Methyldibenzofuran (41). The indicated com-
pound was obtained in a 68% yield as a white solid: mp
42–43 ꢀC; 1H NMR (400 MHz, CDCl3) d 2.49 (s, 3H),
7.22–7.25 (m, 1H), 7.31 (td, J¼7.6, 1.2 Hz, 1H), 7.40–
7.45 (m, 2H), 7.54 (d, J¼8.0 Hz, 1H), 7.73 (t, J¼0.8 Hz,
1H), 7.90 (dd, J¼8.0, 0.8 Hz, 1H); 13C NMR (100 MHz,
CDCl3) d 21.6, 111.4, 111.9, 120.8, 120.9, 122.7, 124.4,
124.5, 127.2, 128.4, 132.4, 154.7, 156.7; IR (CDCl3,
cmꢁ1) 3026, 2978, 2941, 2921, 1446; HRMS m/z
182.0734 (calcd C13H10O, 182.0731).
We are grateful to the National Institutes of Health, Kansas
University Center of Excellence in Chemical Methodologies
and Library Development (P50 GM069663) for their gener-
ous financial support.
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