An improved method for the synthesis of carbazolones by palladium/copper-catalyzed intramolecular annulation of n -arylenaminones

Article abstract of DOI:10.1055/s-0030-1258141

An improved method for the synthesis of carbazolones via the condensation of arylamines with 1,3-cyclodiketones followed by intramolecular oxidative cyclization catalyzed by palladium acetate and copper acetate in ethanol under an oxygen atmosphere was established. The improved method has the advantage of easily available starting materials and affords good yields.

Full text of DOI:10.1055/s-0030-1258141

2926
PAPER
An Improved Method for the Synthesis of Carbazolones by Palladium/
Copper-Catalyzed Intramolecular Annulation of N-Arylenaminones
I
mprove
d
Synthe
o
sis of
C
arbaz
j
olonesie Weng, Rui Liu, Jing-Hua Li*
College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, P. R. of China
E-mail: lijh@zjut.edu.cn
Received 8 January 2010; revised 6 May 2010
are high temperature and the use of poisonous ligand,3a,d
strong base,4 and expensive substrates.3 The oxidation of
2,3,4,9-tetrahydro-1H-carbazole was reported by several
groups, however, the unit of carbazole should be synthe-
Abstract: An improved method for the synthesis of carbazolones
via the condensation of arylamines with 1,3-cyclodiketones fol-
lowed by intramolecular oxidative cyclization catalyzed by palladi-
um acetate and copper acetate in ethanol under an oxygen
atmosphere was established. The improved method has the advan- sized in advance, therefore the scope is largely limited.5
tage of easily available starting materials and affords good yields.
Söderberg developed a palladium-catalyzed annulation
via Stille coupling and reductive N-heterocyclization,
nevertheless the procedure is tedious due to unavailable
substrates and additives employed.6 The condensation of
arylhydroxylamine with 1,3-diketones for synthesizing
carbazolones was also established, however, it suffers
from narrow applications.7
Key words: carbazolones, intramolecular oxidative cyclization,
oxygen, palladium acetate, copper acetate
The carbazolone unit is one of the most abundant hetero-
cycles in natural products and biologically active com-
pounds. Furthermore substituted carbazolones are key
intermediates for the synthesis of a variety of carbazole
alkaloids1a and drugs, such as serotonin (5-HT3) receptor
antagonists (ondansetron and alosetron, Figure 1),1b,c
murrayaquinone A, koeniginequinone A, and murrayafo-
line A,1d and other compounds (such as HIV-integrase
inhibitor1e and potassium-channel blocker1f).
O
O
O
+
NHNH2
X
O
N
N
H
Fischer
ref. 2a–d
OH
Heck
O
O
CF3COOH
(CF3CO)2O
ref. 7
X = I, ref. 3a–c
X =Br, ref. 3d,e
X =Cl, ref. 4
O
N
N
N
N
hν ref. 8
oxidation
ref. 5
N
H
H
oxidation ref. 9
Me
O
ondansetron
murrayaquinone A
O
Stille coupling
annulation
ref. 6
O
H
N
N
H
O
N
H
SnBu3
NO2
N
N
I
+
Me
alosetron
Figure 1 Biologically active compounds possessing a carbazolone
unit
Scheme 1 Routes to synthesize the carbazolone unit
In 2002, Tietcheu reported a method for the synthesis of
carbazolones by using photochemical techniques.8 Kiba-
yashi developed a direct oxidation of N-arylenaminones;
unfortunately, stoichiometric amount of palladium acetate
was consumed and yields were quite low.9 Therefore,
there is still a demand to develop a novel and more conve-
nient method for the preparation of carbazolones.
Thus, various methods have been utilized for the synthesis
of carbazolones and their derivatives (Scheme 1), one of
which is the Fischer indole rearrangement using phenyl-
hydrazine and cyclohexane-1,3-dione as starting materi-
als.2 However, its drawbacks are low yields, harsh
conditions, and poor regioselectivities. The palladium- or
copper-catalyzed intramolecular cyclization reactions of
haloaryl enaminones to give carbazolone derivatives have
also been reported, yet the shortcomings of the reactions
Recently, palladium-catalyzed directly oxidative coupling
of two sp2 C–H bonds aroused great interest due to its en-
vironmentally benign strategy;10 and it has been widely
used in homocoupling,11 cross-coupling,12 and intramo-
lecular coupling.13 Inspired by Kibayashi and Glorius’s
work,14 we have developed an efficient method to synthe-
SYNTHESIS 2010, No. 17, pp 2926–2930
x
x.
x
x
.
2
0
1
0
Advanced online publication: 30.06.2010
DOI: 10.1055/s-0030-1258141; Art ID: F00710SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Improved Synthesis of Carbazolones
2927
size carbazolone derivatives via palladium-catalyzed in- time did not improve the efficiency (Table 1, entries 15,
tramolecular oxidative cyclization of arylenaminones, 16). This result was remarkably different compared to the
which could be easily prepared under solvent-free condi- recent discovery reported by Jiao,13h in which the enamine
tions in high yields according to our previous work.15
derivatives prepared by condensing aniline and dimethyl
butynedioate could be annulated in the presence of palla-
dium under oxygen atmosphere, because in our reaction
system no conversion was observed without the use of
Cu(OAc)2·H2O. It might be presumed that electron-with-
drawing group such as CO2Et, CO2Me, CN facilitated the
annulation process.
At first an array of experiments were examined in order to
get standard reaction conditions (Scheme 2, Table 1). Ini-
tially, the oxidative coupling of N-phenylenaminone 1a as
a model substrate in the presence of 0.05 equivalent of
Pd(OAc)2 and 0.2 equivalent of Cu(OAc)2·H2O in reflux-
ing ethanol for 12 hours was tried (Table 1, entry 1). As
expected, the desired product was obtained albeit in only
30% yield. The yield was comparably lower when CuBr
was used instead of Cu(OAc)2·H2O (Table 1, entry 2),
meanwhile the catalytic combination of other copper salts
and H2O2 showed negative effects under the same condi-
tions (Table 1, entries 3–6). Pd2(dba)3 and PdCl2 seemed
to be inactive (Table 1, entries 7, 8), which was similar to
the replacement of solvents by acetic acid, acetonitrile, di-
oxane, and DMF (Table 1, entries 9–12). The reaction was
slightly promoted by increasing the amount of
Cu(OAc)2·H2O or Pd(OAc)2 (Table 1, entries 13, 14). A
satisfactory result was obtained when employing the com-
bination of Pd(OAc)2 (0.15 equiv) and Cu(OAc)2·H2O
(0.4 equiv) as a catalyst under oxygen atmosphere and re-
fluxing in ethanol for 12 hours. Prolonging the reaction
O
O
catalyst
[ O ]
N
H
N
H
1a
2a
Scheme 2 Oxidative coupling of N-phenylenaminone 1a
To explore the scope of this catalytic system, a variety of
substrates were examined and the corresponding results
are listed in Table 2. We synthesized a series of interme-
diates for carbazolones through condensation of different
arylamines with cyclohexane-1,3-dione (or 5,5-dimethyl-
cyclohexane-1,3-dione) in the presence of KHSO4 and
Table 1 Optimization of the Conditions for the Oxidative Coupling of N-Phenylenaminone 1aa
Entry
1
Catalyst (amount)
Oxidant (amount)
Solvent
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
AcOH
MeCN
dioxane
DMF
Yield (%)b
Pd(OAc)2 (5 mol%)
Pd(OAc)2 (5 mol%)
Pd(OAc)2 (5 mol%)
Pd(OAc)2 (5 mol%)
Pd(OAc)2 (5 mol%)
Pd(OAc)2 (5 mol%)
Pd2(dba)3 (5 mol%)
PdCl2 (5 mol%)
Cu(OAc)2·H2O (20 mol%)
CuBr (20 mol%)
30
2
10
3
CuI (20 mol%)
0
4
CuCl (20 mol%)
0
5
Cu(OTf)2 (20 mol%)
trace
0
6
H2O2 (2 equiv)
7
Cu(OAc)2·H2O (20 mol%)
Cu(OAc)2·H2O (20 mol%)
Cu(OAc)2·H2O (20 mol%)
Cu(OAc)2·H2O (20 mol%)
Cu(OAc)2·H2O (20 mol%)
Cu(OAc)2·H2O (20 mol%)
Cu(OAc)2·H2O (40 mol%)
Cu(OAc)2·H2O (40 mol%)
Cu(OAc)2·H2O (40 mol%)
Cu(OAc)2·H2O (40 mol%)
0
8
0
9
Pd(OAc)2 (5 mol%)
Pd(OAc)2 (5 mol%)
Pd(OAc)2 (5 mol%)
Pd(OAc)2 (5 mol%)
Pd(OAc)2 (5 mol%)
Pd(OAc)2 (10 mol%)
Pd(OAc)2 (15 mol%)
Pd(OAc)2 (15 mol%)
trace
trace
tracec
<5c
35
10
11
12
13
14
15
16
EtOH
EtOH
EtOH
EtOH
50
83d
80e
a Reaction conditions: substrate 1a (0.25 mmol), catalyst, oxidant, O2 balloon, prestirred for 5 min at r.t., then refluxed for 12 h.
b Isolated yields.
c Oil bath (80 °C).
d No conversion was observed without adding Cu(OAc)2·H2O (by TLC).
e Reflux, 24 h.
Synthesis 2010, No. 17, 2926–2930 © Thieme Stuttgart · New York

2928
B. Weng et al.
PAPER
Table 2 Compounds 2 Prepared via N-Arylenaminonesa
MgSO4 by grinding them together for 10 minutes and
heating at 80 °C for 15 minutes.15,16 Carbazolones could
be prepared from arylamines and cyclohexane-1,3-diones
with simple purification of their corresponding intermedi-
ates, by decantation, which were assumed as enaminones
(see 1a).
Entry
1
X2
R1
Yield of 2 (%)b
2a, 71
H,H
H
2
H,H
3-MeO
3-Me
3-Br
1-Me
1-Cl
3-Cl
H
2b, 68
2c, 50
3
H,H
Under the optimized reaction conditions, different func-
tionalized carbazolones were synthesized in good overall
yields (Scheme 3, Table 2, entries 1–16). This reaction
tolerates several functional groups, such as methoxy,
methyl, chloro, and bromo, at different positions of the aro-
matic ring. Similarly, naphthylenaminone also exhibited
satisfactory activity under the same catalytic system with
good yield and high regioselectivity (Table 2, entry 11).
Unfortunately, when the aromatic ring bearing the 4-nitro
group was used as a substrate, the desired product could
not be obtained (Table 2, entry 17), and the intermediate,
3-(4-nitrophenylamino)cyclohex-2-enone (1q) was ob-
tained in 85% yield after recrystallization. The reason of
this phenomenon might be due to inactivation of aryl-
amine caused by nitro group.
4
H,H
2d, 60
2e, 77
5
H,H
6
H,H
2f, 74
7
H,H
2g, 48
8
Me,Me
Me,Me
Me,Me
Me,Me
Me,Me
Me,Me
Me,Me
Me,Me
Me,Me
H,H
2h, 71
2i, 62
9
3-MeO
3-Me
10
11
12
13
14
15
16
17d
2j, 68
3,4-CH=CHCH=CHc 2k, 47
1-Me
1-Cl
2l, 54
2m, 61
2n, 47
2o, 50
2p, 70
2q, 0
O
R1
3
R1
3
4
4
O
grinding
heating
3-Cl
H
Pd/Cu
+
CX2
3-Br
2
CX2
2
O2, EtOH
NH2
N
H
1
1
O
2,4-Me2
4-O2N
X = H or Me
2a–q
Scheme 3 Synthesis of a series of functional carbazolones
a Arylamine (5 mmol), 1,3-diketones (5 mmol), KHSO4 (1 g), and
MgSO4 (1 g), were ground together for 10 min at r.t., then were kept
at 80 °C for 15 min.
It has been reported recently that N-arylenaminones are
prone to react with electrophiles at the a-C position.17 The
mechanism may be assumed to involve three steps: (a) an
electrophilic palladation of the nucleophilic enamine; (b)
ortho CH activation for the formation of the six-
membered-ring transition state containing palladium; (c)
reductive elimination generating the carbazolones with
liberation of active palladium(0) species (Scheme 4). The
regenerated palladium(0) complex is oxidized to the pal-
b Isolated yields. The overall yields of 2 were enhanced approximately
3–4% by further recrystallization of the intermediates before proceed-
ing oxidative couplings.
c Caution! Starting material b-naphthylamine is carcinogenic.
d Intermediate 1q was isolated in 85% yield.
All reactions were carried out by standard Schlenk technique and
run under an O2 atmosphere. All the substrates and bases were com-
ladium(II) species by Cu(OAc)2·H2O and oxygen to com- mercially available. All products were confirmed by 1H NMR, 13
plete the whole catalytic cycle.
C
NMR spectra recorded on Bruker Avance III spectrometer (500
1
MHz for H NMR, 125 MHz for 13C NMR). Melting points were
obtained using a precision X-4 digital display apparatus from Tek-
tronix Instrument Co., Ltd. Beijing and are uncorrected. Petroleum
ether (PE) refers to the fraction boiling in the range 60–90 °C.
O
O
PdΙΙ
H
XPd
PdX2
2a
1a
2,3-Dihydro-1H-carbazol-4(9H)-one (2a);3–6 Typical Procedure
A mixture of the cyclohexane-1,3-dione (560 mg, 5 mmol), aniline
(484 mg, 5.2 mmol) and KHSO4/MgSO4 (1 g, weight ratio 1:1) was
ground in a mortar for 10 min at r.t., and then kept for 15 min in an
oil bath at 80 °C. The reaction mixture was extracted with MeOH
(20 mL). The filtrate was concentrated under reduced pressure to
give a solid, which was dissolved in 95% hot EtOH and then cooled
to r.t. The liquid was removed by decantation from the precipitated
enaminone 1a, which was used directly in the next step. The precip-
itated 1a was mixed with Cu(OAc)2·H2O (400 mg, 0.4 equiv) and
Pd(OAc)2 (168 mg, 0.15 equiv) in EtOH (20 mL). The mixture was
stirred with a magnetic stir bar for 5 min at r.t., then refluxed for 12
h under O2 atmosphere by using an O2 balloon. After the completion
of the reaction, the mixture was purified by column chromatogra-
phy on silica gel (100–200 mesh) with petroleum ether and EtOAc
N
H
N
H
Scheme 4 Possible mechanism for synthesis of carbazolones
In conclusion, an improved method for the synthesis of
carbazolones from available arylamines and 1,3-cy-
clodiketones via intramolecular oxidative cyclization cat-
alyzed by palladium acetate and copper acetate under
oxygen atmosphere in ethanol, which is environmentally
friendly and effective, has been developed. Further stud-
ies on the synthesis of the functionalized carbazolones and
their applications are currently in progress in our labora-
tory.
Synthesis 2010, No. 17, 2926–2930 © Thieme Stuttgart · New York

PAPER
Improved Synthesis of Carbazolones
2929
(1:2) as eluent to give the pure product 2a; overall yield: 164 mg
(71%); mp 218–221 °C; Rf = 0.30 (PE–EtOAc, 1:1).
13C NMR (125 MHz, DMSO-d6/TMS): d = 192.1, 151.0, 136.2,
124.3, 122.3, 121.5, 120.0, 111.6, 110.5, 51.9, 36.4, 35.3, 28.2.
1H NMR (500 MHz, DMSO-d6/TMS): d = 11.85 (s, 1 H), 7.96 (d,
J = 7 Hz, 1 H), 7.40 (d, J = 7 Hz, 1 H), 7.12–7.18 (m, 2 H), 2.96 (t,
J = 6 Hz, 2 H), 2.43 (t, J = 6 Hz, 2 H), 2.10–2.14 (m, 2 H).
13C NMR (125 MHz, DMSO-d6/TMS): d = 192.9, 152.3, 135.9,
124.5, 122.4, 121.5, 120.2, 111.8, 111.5, 37.8, 23.4, 22.7.
6-Methoxy-2,2-dimethyl-2,3-dihydro-1H-carbazol-4(9H)-one
(2i)18
Yield: 62%; mp 240 °C; Rf = 0.59 (PE–EtOAc, 1:1).
1H NMR (500 MHz, DMSO-d6/TMS): d = 11.71 (s, 1 H), 7.45 (d,
J = 2.5 Hz, 1 H), 7.29 (d, J = 8.5 Hz, 1 H), 6.78 (m, 1 H), 3.77 (s, 3
H), 2.82 (s, 2 H), 2.31 (s, 2 H), 1.08 (s, 6 H).
13C NMR (125 MHz, DMSO-d6/TMS): d = 192.1, 155.2, 151.1,
130.9, 125.1, 112.3, 111.5, 110.5, 102.4, 55.3, 51.9, 36.4, 35.2,
28.2.
6-Methoxy-2,3-dihydro-1H-carbazol-4(9H)-one (2b)18
Yield: 68%; mp 250–254 °C; Rf = 0.45 (PE–EtOAc, 1:1).
1H NMR (500 MHz, DMSO-d6/TMS): d = 11.72 (s, 1 H), 7.46 (s, 1
H), 7.29 (d, J = 8.5 Hz, 1 H), 6.79 (d, J = 7 Hz, 1 H), 3.77 (s, 3 H),
2.94 (t, J = 5.5 Hz, 2 H), 2.42 (t, J = 5.5 Hz, 2 H), 2.10 (t, J = 5.5
Hz, 2 H).
2,2,6-Trimethyl-2,3-dihydro-1H-carbazol-4(9H)-one (2j)18
Yield: 68%; mp 273–275 °C; Rf = 0.63 (PE–EtOAc, 1:1).
1H NMR (500 MHz, DMSO-d6/TMS): d = 11.71 (s, 1 H), 7.7 (s, 1
H), 7.27 (d, J = 8.5 Hz, 1 H), 6.98–6.96 (m, 1 H), 2.82 (s, 2 H), 2.38
(s, 3 H), 2.31 (s, 2 H), 1.08 (s, 6 H).
13C NMR (125 MHz, DMSO-d6/TMS): d = 192.0, 150.9, 134.4,
130.3, 124.6, 123.5, 120.0, 111.2, 110.1, 51.9, 36.4, 35.2, 28.2,
21.2.
13C NMR (125 MHz, DMSO-d6/TMS): d = 192.8, 155.2, 152.4,
130.6, 125.3, 112.2, 117.7, 111.6, 102.6, 55.3, 37.8, 23.4, 22.8.
6-Methyl-2,3-dihydro-1H-carbazol-4(9H)-one (2c)3c
Yield: 50%; mp 252–256 °C; Rf = 0.54 (PE–EtOAc, 1:1).
1H NMR (500 MHz, DMSO-d6/TMS): d = 11.73 (s, 1 H), 7.77 (s, 1
H), 7.27 (d, J = 8 Hz, 1 H), 6.98 (d, J = 8 Hz, 1H), 2.94 (t, J = 5 Hz,
2 H), 2.41 (t, J = 6 Hz, 2 H), 2.38 (s, 3 H), 2.11 (t, J = 6 Hz, 2 H).
13C NMR (125 MHz, DMSO-d6/TMS): d = 192.7, 152.1, 134.1,
130.2, 124.8, 123.7, 120.1, 111.4, 111.1, 37.8, 23.4, 22.7, 21.2.
9,9-Dimethyl-9,10-dihydro-7H-benzo[c]carbazol-11(8H)-one
(2k)20
Yield: 47%; mp 250–254 °C; Rf = 0.80 (PE–EtOAc, 1:1).
1H NMR (500 MHz, DMSO-d6/TMS): d = 12.28 (s, 1 H), 9.83 (d,
J = 8.5 Hz, 1 H), 7.92 (d, J = 8 Hz, 1 H), 7.69 (d, J = 8.5 Hz, 1 H),
7.60 (d, J = 8.5 Hz, 1 H), 7.53 (m, 1 H), 7.42 (m, 1 H), 2.95 (s, 2 H),
2.49 (s, 2 H), 1.12 (s, 6 H).
13C NMR (125 MHz, DMSO-d6/TMS): d = 192.0, 149.5, 133.2,
130.0, 128.1, 128.1, 127.4, 125.0, 123.9, 123.7, 119.6, 113.5, 113.0,
53.1, 36.9, 34.7, 27.9.
6-Bromo-2,3-dihydro-1H-carbazol-4(9H)-one (2d)3c
Yield: 60%; mp >270 °C; Rf = 0.35 (PE–EtOAc, 1:1).
1H NMR (500 MHz, DMSO-d6/TMS): d = 12.06 (s, 1 H), 8.06 (s, 1
H), 7.38 (d, J = 8 Hz, 1 H), 7.30 (d, J = 8 Hz, 1 H), 2.97 (s, 2 H),
2.43 (s, 2 H), 2.12 (s, 2 H).
13C NMR (125 MHz, DMSO-d6/TMS): d = 192.9, 153.5, 134.7,
126.2, 124.9, 122.2, 114.1, 113.6, 111.2, 37.6, 23.2, 22.7.
2,2,8-Trimethyl-2,3-dihydro-1H-carbazol-4(9H)-one (2l)18
Yield: 54%; mp 255–257 °C; Rf = 0.60 (PE–EtOAc, 1:1).
1H NMR (500 MHz, DMSO-d6/TMS): d = 11.72 (s, 1 H), 7.76 (d,
J = 7.5 Hz, 1 H), 7.04 (t, J = 7.5 Hz, 1 H), 6.96 (d, J = 7.5 Hz, 1 H),
2.86 (s, 2 H), 2.47 (s, 3 H), 2.32 (s, 2 H), 1.09 (s, 6 H).
13C NMR (125 MHz, DMSO-d6/TMS): d = 192.2, 150.8, 135.6,
124.0, 122.9, 121.6, 120.8, 117.6, 110.8, 51.9, 36.4, 35.2, 28.2,
16.7.
8-Methyl-2,3-dihydro-1H-carbazol-4(9H)-one (2e)6a
Yield: 77%; mp >280 °C; Rf = 0.53 (PE–EtOAc, 1:1).
1H NMR (500 MHz, DMSO-d6/TMS): d = 11.75 (s, 1 H), 7.78 (d,
J = 7.5 Hz, 1 H), 6.95–7.05 (m, 2 H), 2.98 (s, 2 H), 2.47 (s, 3 H),
2.42 (s, 2 H), 2.12–2.13 (m, 2 H).
13C NMR (125 MHz, DMSO-d6/TMS): d = 192.9, 152.0, 135.2,
124.2, 123.1, 121.6, 120.7, 117.7, 112.1, 37.8, 23.4, 22.7, 16.6.
8-Chloro-2,3-dihydro-1H-carbazol-4(9H)-one (2f)19
Yield: 74%; mp 279–282 °C; Rf = 0.49 (PE–EtOAc, 1:1).
8-Chloro-2,2-dimethyl-2,3-dihydro-1H-carbazol-4(9H)-one
(2m)
1H NMR (500 MHz, DMSO-d6/TMS): d = 12.19 (s, 1 H), 7.91 (d,
J = 8 Hz, 1 H), 7.25 (d, J = 8 Hz, 1 H), 7.15 (t, J = 8 Hz, 1 H), 3.00
(t, J = 6 Hz, 2 H), 2.45 (t, J = 6 Hz, 2 H), 2.11–2.16 (m, 2 H).
13C NMR (125 MHz, DMSO-d6/TMS): d = 193.1, 153.5, 132.8,
126.3, 122.7, 122.0, 119.0, 115.9, 112.5, 37.7, 23.2, 22.7.
Yield: 61%; mp 210–213 °C; Rf = 0.75 (PE–EtOAc, 1:1).
1H NMR (500 MHz, DMSO-d6/TMS): d = 12.17 (s, 1 H), 7.90 (d,
J = 8.0 Hz, 1 H), 7.25 (d, J = 8 Hz, 1 H), 7.15 (t, J = 8 Hz, 1 H),
2.89 (s, 2 H), 2.36 (s, 2 H), 1.09 (s, 6 H).
13C NMR (125 MHz, DMSO-d6/TMS): d = 192.4, 152.2, 133.2,
126.2, 122.7, 121.9, 118.9, 116.0, 111.3, 51.8, 36.3, 35.2, 28.1.
6-Chloro-2,3-dihydro-1H-carbazol-4(9H)-one (2g)3c
Yield: 48%; mp 271–276 °C; Rf = 0.48 (PE–EtOAc, 1:1).
1H NMR (500 MHz, DMSO-d6/TMS): d = 12.05 (s, 1 H), 7.90 (s, 1
H), 7.43 (d, J = 8.5 Hz, 1 H), 7.19 (d, J = 7.5 Hz, 1 H), 2.97 (t, J = 6
Hz, 2 H), 2.44 (t, J = 6 Hz, 2 H), 2.13 (t, J = 6 Hz, 2 H).
13C NMR (125 MHz, DMSO-d6/TMS): d = 192.9, 153.6, 134.4,
126.1, 125.6, 122.3, 119.2, 113.1, 111.4, 37.6, 23.2, 22.7.
6-Chloro-2,2-dimethyl-2,3-dihydro-1H-carbazol-4(9H)-one
(2n)7
Yield: 47%; mp 278 °C; Rf = 0.65 (PE–EtOAc, 1:1).
1H NMR (500 MHz, DMSO-d6/TMS): d = 12.03 (s, 1 H), 7.87 (d,
J = 1.5 Hz, 1 H), 7.42 (d, J = 8.5 Hz, 1 H), 7.18 (m, 1 H), 2.86 (s, 2
H), 2.34 (s, 2 H), 1.08 (s, 6 H).
13C NMR (125 MHz, DMSO-d6/TMS): d = 192.2, 152.4, 134.7,
126.1, 125.4, 122.2, 119.1, 113.2, 110.1, 51.7, 36.3, 35.2, 28.1.
2,2-Dimethyl-2,3-dihydro-1H-carbazol-4(9H)-one (2h)3e
Yield: 71%; mp 189–193 °C; Rf = 0.60 (PE–EtOAc, 1:1).
1H NMR (500 MHz, DMSO-d6/TMS): d = 11.83 (s, 1 H), 7.93 (m 1
H), 7.39 (m, 1 H), 7.15 (m, 2 H), 2.85 (s, 2 H), 2.33 (s, 2 H), 1.09 (s,
6 H).
6-Bromo-2,2-dimethyl-2,3-dihydro-1H-carbazol-4(9H)-one
(2o)
Yield: 50%; mp >270 °C; Rf = 0.65 (PE–EtOAc, 1:1).
Synthesis 2010, No. 17, 2926–2930 © Thieme Stuttgart · New York

2930
B. Weng et al.
PAPER
1H NMR (500 MHz, DMSO-d6/TMS): d = 12.03 (s, 1 H), 8.03 (s, 1
H), 7.38 (d, J = 8.0 Hz, 1 H), 7.30 (d, J = 8.0 Hz, 1 H), 2.86 (s, 2
H), 2.34 (s, 2 H), 1.08 (s, 6 H).
J. J. Heterocycl. Chem. 2002, 39, 965.
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74, 456. (b) Takahashi, M.; Masui, K.; Sekiguchi, H.;
Kobayashi, N.; Mori, A.; Funahashi, M.; Tamaoki, N. J. Am.
Chem. Soc. 2006, 128, 10930. (c) Hull, K. L.; Lanni, E. L.;
Sanford, M. S. J. Am. Chem. Soc. 2006, 128, 14047.
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131, 1372. (b) Li, B.-J.; Tian, S.-L.; Fang, Z.; Shi, Z.-J.
Angew. Chem. Int. Ed. 2008, 47, 1115. (c) Brasche, G.;
Garca-Fortanet, J.; Buchwald, S. L. Org. Lett. 2008, 10,
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Soc. 2007, 129, 12072.
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Fagnou, K. J. Org. Chem. 2008, 73, 5022. (b) Wada, Y.;
Nagasaki, H.; Tokuda, M.; Orito, K. J. Org. Chem. 2007, 72,
2008. (c) Wang, J.; Rosingana, M.; Watson, D. J.; Dowdy,
E. D.; Discordia, R. P.; Soundarajan, N.; Li, W.-S.
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(e) Knölker, H.-J.; Fröhner, W. Synthesis 2002, 557.
(f) Matsubara, S.; Asano, K.; Kajita, Y.; Yamamoto, M.
Synthesis 2007, 2055. (g) Watanabe, T.; Ueda, S.; Inuki, S.;
Oishi, S.; Fujii, N.; Ohno, H. Chem. Commun. 2007, 4516.
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13C NMR (125 MHz, DMSO-d6/TMS): d = 192.2, 152.2, 135.0,
126.0, 124.8, 122.1, 114.1, 113.7, 110.0, 51.7, 36.2, 35.2, 28.1.
2,2,5,7-Tetramethyl-2,3-dihydro-1H-carbazol-4(9H)-one (2p)21
Yield: 70%; mp 247–250 °C; Rf = 0.81 (PE–EtOAc, 1:1).
1H NMR (500 MHz, DMSO-d6/TMS): d = 11.66 (s, 1 H), 6.96 (s, 1
H), 6.71 (s, 1 H), 2.80 (s, 2 H), 2.76 (s, 3 H), 2.32 (s, 5 H), 1.07 (s,
6 H).
13C NMR (125 MHz, DMSO-d6/TMS): d = 190.8, 150.7, 137.2,
131.6, 130.6, 124.7, 121.8, 111.6, 108.8, 53.0, 36.8, 34.5, 28.0,
22.4, 20.9.
5,5-Dimethyl-3-(4-nitrophenylamino)cyclohex-2-enone (1q)15
Yield: 85%; mp 176–178 °C; Rf = 0.30 (PE–EtOAc–Et3N, 1:3:0.1).
1H NMR (500 MHz, CDCl3/TMS): d = 2.07–2.11 (m, 2 H), 2.42 (t,
J = 7 Hz, 2 H), 2.57 (t, J = 6 Hz, 2 H), 5.85 (s, 1 H), 6.83 (br, 1 H,
NH), 7.26 (m, 2 H), 8.20 (d, J = 9 Hz, 2 H).
13C NMR (125 MHz, CDCl3/TMS): d = 198.9, 159.9, 144.9, 143.3,
125.3, 121.3, 103.1, 36.6, 29.8, 21.7.
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Synthesis 2010, No. 17, 2926–2930 © Thieme Stuttgart · New York