Anionic [4+2] cycloaddition strategy in the regiospecific synthesis of carbazoles: formal synthesis of ellipticine and murrayaquinone A

Article abstract of DOI:10.1016/j.tet.2007.02.060

Anionic [4+2] cycloaddition of furoindolones (e.g., 7 and 10) has been developed as an effective means to the synthesis of carbazoles. This reaction has been shown to be feasible with a wide variety of Michael acceptors to give carbazoles and fused carbaz

Full text of DOI:10.1016/j.tet.2007.02.060

Tetrahedron 63 (2007) 3768–3781
Anionic [4D2] cycloaddition strategy in the regiospecific
synthesis of carbazoles: formal synthesis of ellipticine
and murrayaquinone A
*
Dipakranjan Mal, Bidyut Kumar Senapati and Pallab Pahari
Department of Chemistry, Indian Institute of Technology, Kharagpur 721 302, West Bengal, India
Received 22 September 2006; revised 4 February 2007; accepted 15 February 2007
Available online 20 February 2007
Abstract—Anionic [4+2] cycloaddition of furoindolones (e.g., 7 and 10) has been developed as an effective means to the synthesis of carb-
azoles. This reaction has been shown to be feasible with a wide variety of Michael acceptors to give carbazoles and fused carbazoles in good
yields. The scope and limitations of the reaction have been briefly studied. The nature of N-protection of the furoindolones (cf. 7) plays a major
role in the success of annulation.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
Polymeric carbazole derivatives are used as organic mate-
rials due to their photoreactive, photoconductive, and light
emitting properties.3 Recently, functionalized carbazoles
have also been recognized as a useful scaffold in anion bind-
ing studies.4 Consequently, the synthesis of carbazoles con-
tinues to be a vigorously active research area.5a,b Moreover,
problems related to regiochemistry, efficacy, and generality
are often encountered in a carbazole synthesis.
The substituted carbazoles are embodied in many naturally
occurring compounds as well as synthetic materials. During
the past four decades, a wide variety of biologically active
carbazole alkaloids (Fig. 1) have been isolated from plant
sources. Many of these natural products possess interesting
biological properties, which include antitumor, psychotro-
pic, anti-inflammatory, and antihistaminic, antibiotic, and
antioxidative activities.1 The publication of Knollker’s re-
cent review2 is a testament of the intense activity in the field.
The conventional methodologies for the synthesis of carb-
azoles center around utilization of three classes of starting
Me
Me
N
O
Me
OMe
Me
N
N
N
H
N
H
N
H
N
H
OMe
Me
O
OMe
Ellipticine (1)
Murrayafoline-A (3)
Murrastifoline-F (4)
Ellipticine quinone (2)
O
N
N
H
O
Calothrixin B (5)
Figure 1. Structures of few representative naturally occurring carbazoles.
Keywords: Carbazole quinone; Anionic cycloaddition; Furoindolone.
* Corresponding author. Tel.: +91 3222 283318; fax: +91 3222 282252; e-mail: dmal@chem.iitkgp.ernet.in
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.02.060

D. Mal et al. / Tetrahedron 63 (2007) 3768–3781
3769
X
X
X
R
R
E
R
base
O
O
O
O
O
E
E
N
P
O
S
H3O
for X = H
for X = SO2Ph
HO
HO
R
R
R
O
R
O
oxidation
E
E
E
E
N
P
N
P
OH
N
P
OH
O
N
P
I
P = protecting group, E = electron withdrawing group, X= H or SO2Ph
Scheme 1. Proposed methodology for the synthesis of carbazole quinones and carbazoles.
materials such as 20-nitrogen substituted biaryls,6a–k diaryl-
amines,6l,m and substituted indole derivatives.6n–r We now
2. Results and discussion
2.1. Synthesis of ellipticine quinone
wish to report a new synthesis of carbazole quinones and
1-oxygenated carbazoles by benzannulation (anionic [4+2]
cycloaddition) of furoindolones10 (e.g., 7 and 10) with vari-
ous Michael acceptors. This methodology provides a very
simple and straightforward regiospecific route to carbazole
quinones and 1-oxygenated multi-substituted carbazoles.
We also report the formal synthesis of ellipticine (1) and
murrayaquinone A (21).
In view of importance of ellipticine quinone (2)14 as a cyto-
toxic compound against HeLa cell lines as well as a
late-stage intermediate in the synthesis of ellipticine (1), we
examined the proposed strategy for its synthesis. The start-
ing furoindolone 6a was prepared in 40% yield by Fischer
indolization of 3-(2-phenylhydrazono)dihydrofuran-2(3H)-
one in the presence of HCl.10 Compound 6a was then trans-
formed into N-ethoxycarbonyl derivative 7 (92%, Scheme 2)
by treatment with triethylamine and ethyl chloroformate.
Similarly, N-phenylsulfonyl derivative 7b was prepared
in 68% yield from compound 6a, using benzenesulfonyl
chloride, K2CO3, and benzyltriethylammonium chloride.
The anionic [4+2] cycloaddition of isobenzofuranones is a
well-known reaction for the synthesis of condensed aro-
matics and hydroaromatics7,9 but to date it has not been
extended to the synthesis of a heterocyclic quinone com-
pound.8 Therefore, we became interested in the synthesis
of ellipticine11a–d (1) and calothrixin11e–g (5) by application
of the Hauser annulation,12 a widely studied anionic cyclo-
addition. The formulated strategy (Scheme 1) was based
on lateral lithiation of a suitably N-protected furoindolone
(cf. S) followed by Michael initiated ring closure. In two
recent communications,13 we reported the successful appli-
cation of this methodology in the synthesis of carbazole
quinones and 1-hydroxycarbazoles. Herein we report a full
account of a study in this area.
Furoindolone 7a was further functionalized at C-1 with
a phenylsulfonyl group (Scheme 3) in line with the original
work12b of Hauser and Rhee on benzoisofuranones. Bromi-
nation of compound 7a with N-bromosuccinimide in the
presence of benzoyl peroxide gave 1-bromo derivative 8 in
70% yield. Treatment of compound 8 with thiophenol in
the presence of triethylamine gave phenylsulfanyl derivative
9 in 77% yield. Exposure of compound 9 to m-CPBA did not
Br
X
X
h for 9
1
see legends
(a-f) below
7
O
i for 10
O
g (for 7b)
O
O
N
R
O
N
CO2Et
3
N
H
O
5
8
7a: R = CO2Et, X = H
7b: R = SO2Ph, X = H
7c: R = COCMe3, X = H
7d: R = Me, X = H
7e: R = CH2Ph, X = H
7f: R = CH2Ph, X = OMe
6a: X = H
6b: X = OMe
X
O
O
N
COOEt
9: X = SPh
j
10: X = SO2Ph
Scheme 2. Preparation of furoindolones. Reagents and conditions: (a) ClCO2Et, Et3N, CH2Cl2, 0 ꢀC to rt, 12 h, 92% for 7a; (b) PhSO2Cl, K2CO3, TEBAC, rt,
6 h, 68% for 7b; (c) nBuLi, Me3COCl, THF, 71% for 7c; (d) LDA, MeI, THF, 84% for 7d; (e) K2CO3, PhCH2Cl, NaI, Me2CO, 62% for 7e; (f) K2CO3, PhCH2Cl,
NaI, Me2CO, 69% for 7f; (g) NBS, Bz2O2, 70%; (h) PhSH, Et3N, CHCl3, 77% for 9; (i) PhSO2Na, DMF, 85% for 10; (j) m-CPBA.

3770
D. Mal et al. / Tetrahedron 63 (2007) 3768–3781
give the desired sulfone 10, which was, alternatively pre-
pared in 85% yield by direct displacement of the bromine
of 8 with sodium benzenesulfinate ion in DMF. We briefly at-
tempted to prepare the 1-cyano derivative of 7a by treating
8 with KCN in the presence of 18-crown-6 ether without
success.
at the ring junction of 11c than that in 11e. Again, the 13C
NMR spectrum of 12e could not be recorded due to its
poor solubility in common deuterated solvents. The similar
loss of a methoxy group from a ketal was earlier noted in
our laboratory.17 Similarly, PhI(OAc)2 oxidation of methyl
6-hydroxy-1,2,3,4-tetrahydro-2-naphthalene-2-carboxylate
yielded an inseparable 4:1 mixture of quinol ethers 11d and
11f. Interestingly, when the mixture of quinol ethers (11d
and 11f) was reacted with 10, only 11f underwent annulation
with 10, to give carbazole quinone 12f in 70% yield (with
respect to 11f) and 11d was recovered in 98% yield. The
corresponding annulation product 12d was not formed.
O
X = H
N
H
O
X
Li
14 (64%)
X = H or N
LDA
O
O
Next, we focused our attempts to extend the work to naph-
thoquinol ether. Accordingly, aromatic quinol ether 11g17
was prepared from b-naphthol by usual PhI(OAc)2 oxidation
and reacted with 10 in the presence of t-BuOLi at ꢁ60 ꢀC to
give carbazole quinone 12g in 67% yield. Similarly, the re-
action of aromatic quinol ether 11h18 with furoindolone 10
afforded carbazole quinone 12h in 76% yield. The same re-
action gave a different product, for example, N-protected
quinone 12i, when the work-up was carried out at 0 ꢀC in-
O
-78 °C, THF
N
COOEt
13
X = N
N
+
2
N
H
O
15
Scheme 3. Base-promoted cyclization of furoindolone (7a) with aryne and
heteroaryne.
1
After successful preparation of compound 10, we investi-
gated its cycloaddition reactivity as proposed in Scheme 1.
When it was treated with LDA (3.0 equiv), followed by 2-cy-
clohexenone (2 equiv) at ꢁ78 ꢀC, and the resulting mixture
warmed to room temperature, the expected quinol or respec-
tive quinone was not obtained. Nor were the starting mate-
rials recovered. Both the substrates had been destroyed.
The failure of the reaction was attributed to extensive base
catalyzed self-condensation15 of 2-cyclohexenone. Conse-
quently, we chose to work with quinol ether 11a,16 which
is known to be stable to LDA in THF even at room temper-
ature. When the light yellow anion of the sulfone 10, gener-
ated by treating with LDA at ꢁ78 ꢀC, was reacted with 11a,
the color of the reaction mixture changed to deep red. The
reaction mixture was allowed to stir for 3 h at ambient tem-
perature and worked up to afford expected compound 12a in
70% yield (Table 1). The yield of carbazole quinone 12a
improved to 85% when the base was changed to lithium-
tert-butoxide. It is interesting to note that under the reaction
conditions (LDA or t-BuOLi) N-ethoxycarbonyl group was
removed. Upon brief experimentation, it was found that
the cleavage took place at room temperature. Likewise, the
reaction between 10 and 11b17 gave ring-fused carbazole
12b in 62% and 75% yield in the presence of LDA and t-
BuOLi, respectively. Compound 12b was fully characterized
by analysis of its IR, 1H NMR, and mass spectral data. Un-
fortunately, a 13C NMR spectrum of 12b could not be re-
corded due to its poor solubility in common deuterated
solvents. We generalized the annulation reaction with few
more quinol ethers, prepared by phenyliodine(III) diacetate
(PIDA) oxidation of the corresponding phenols. Oxidation
of 5,6,7,8-tetrahydro-2-naphthol with PhI(OAc)2 yielded
a 7:3 mixture of two inseparable compounds 11c and
11e.17 Annulation of this mixture (11c and 11e) with 10 pro-
duced pentacyclic carbazole quinone 12e in 72% (method B)
yield corresponding to compound 11e, and compound 11c
was recovered in 95% yield after usual work-up of the reac-
tion mixture. The quinol ether 11e was annulated, and 11c
remained inert to annulation with compound 10. The ex-
pected compound 12c was not obtained. The failure may
be attributed due to the presence of greater steric crowding
stead of room temperature. H NMR signals at d 4.62 (q,
2H, J¼8.0 Hz) and d 1.54 (t, 3H, J¼8.0 Hz) indicated the
presence of N-ethoxycarbonyl protection. Likewise, quinol
ether 11j16 (prepared from o-cresol by PhI(OAc)2 oxidation)
reacted successfully with furoindolone 10 to afford carba-
zole quinone 12j in 78% yield. The same reaction furnished
N-protected quinone 12k in 75% yield, when the work-up
was carried out at 0 ꢀC instead of room temperature. Due
to the poor solubility in common deuterated solvents, 13C
NMR spectrum of 12j could not be recorded.
Although a good number of Michael acceptors were reactive
toward furoindolone 10, simple acceptors like cyclohexe-
none, methyl crotonate, ethyl cinnamate, coumarin, and
ethyl 2-oxo-1(2H)-quinolinecarboxylate were not. While
the failure with former two acceptors could be explained
in terms of their instability toward strong bases, that with
the latter three was inexplicable. In view of the recent find-
ing19 that a phenylsulfanyl in the place of a phenylsulfonyl
group would suffice in the Hauser annulation, we
experimented with compound 9 that contains a 3-phenyl-
sulfanyl group. When it was treated with lithium diisopropyl-
amide (3.0 equiv), followed by methyl crotonate at ꢁ78 ꢀC,
and the resulting mixture processed in the usual manner, the
expected carbazole quinol was not obtained. Nor were the
starting materials recovered, meaning that both substrates
had been destroyed. Therefore, we performed the above
cycloaddition reaction of 9 with base-stable acceptor 11a
and again we failed to obtain the expected quinone 12a
derivative.
Following the results in Table 1, we were interested in exam-
ining the reactivity of 10 to arynes. We first carried out the
cycloaddition reaction between compound 10 and bromo-
benzene under the benzyne-generating conditions reported20
by Sammes et al. and found that the expected product 14 was
not obtained. The same result was found when the above re-
action was performed with compound 9. On the other hand,
the reaction of 7b with bromobenzene in the presence of
LDA provided the quinone 14 in only 10% yield. The corre-
sponding product with N-SO2Ph was not obtained, meaning

D. Mal et al. / Tetrahedron 63 (2007) 3768–3781
Table 1. Preparation of carbazole quinones from furoindolone 10 and Michael acceptors
3771
Entry
Michael donor
Michael acceptors
Product (s)
% Yield
70a, 85b
PhO2S
O
O
Me
OH
O
O
1
N
H
O
N
Me OMe
11a
CO2Et
10
12a
O
O
2
10
62a, 75b
N
H
O
MeO
11b
O
OH
R
12b
O
MeO
R
11c R = H
11d R = CO2Me
3
10
0
N
H
O
OH
12c R = H
12d R = CO2Me
O
O
OMe
OMe
4
10
10
10
72b
70b
67b
OMe
N
H
OH
O
12e
11e
O
CO2Me
OMe
OMe
O
5
OMe
OMe
N
H
CO2Me
11f
OH
O
12f
O
O
OMe
OMe
6
7
N
H
OH
O
12g
11g
O
OMe
O
76b (12h), 72b (12i)
N
R
10
10
OMe
MeO
OH
O
11h
12h R = H,12i R = CO2Et
O
MeO
O
H3C
8
78b (12j), 75b (12k)
CH3
N
R
MeO OMe
11j
OH
O
12j R = H,12k R = CO2Et
a
Method A: LDA, ꢁ78 ꢀC, THF, 3 h.
Method B: t-BuOLi, ꢁ60 ꢀC, THF, 3 h.
b
that the phenylsulfonyl group was cleaved under the reaction
conditions or during work-up. Reaction between 7a and bro-
mobenzene in the presence of LDA furnished quinone 14 in
64% yield (Scheme 3), and the corresponding product with
the N-CO2Et protecting group was not obtained. In order
to establish that deprotection took place with LDA, com-
pound 7a was treated with LDA at room temperature to
give respective deprotected compound 6a.

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D. Mal et al. / Tetrahedron 63 (2007) 3768–3781
Table 2. Preparation of N-protected carbazoles using N-methylfuroindolone
7d and Michael acceptors
The study was then extended to a heteroaryne for the syn-
thesis of ellipticine quinone 2 (Scheme 3). Annulation of
furoindolone 7a with 3-pyridyne21 prepared in situ from 3-
bromopyridine under the previously described conditions
yielded an inseparable mixture of two compounds. Detailed
comparison of the NMR data14,22 with those reported for el-
lipticine quinone 2 and isoellipticine quinone 15 (45% com-
bined yield) confirmed their formation. Although there were
no significant differences in the pattern of their NMR data,
the two singlets at d 9.19 and 9.21 were indicative of 2:1 for-
mation of the two isomers, ellipticine quinone 2 being the
major product. Since both ellipticine quinone (2) and iso-
ellipticine quinone (15) have been previously transformed
to ellipticine (1) and isoellipticine,23 respectively, this study
constitutes the formal syntheses of these alkaloids.
Entry Furoindolone
Michael
acceptor
Carbazole
% Yielda
(products)
O
CO2Me
N
Me
7d
N
Me
O
1
2
72
78
OH
CO2Me
16a
Me
CO2Me
Me
N
OR
Me
7d
CO2Me
16b: R = H
b
76%
16c: R = Me
2.2. Synthesis of 1-hydroxycarbazoles
CN
Following the above successes, we extended the study to the
preparation of the title compounds. Attempted annulation re-
action between compound 7a and methyl crotonate in the
presence of LDA for the construction of substituted carb-
azole derivatives did not lead to any condensed product but
provided compound 6a. This observation clearly indicated
that N-ethoxycarbonyl protection of 7a cleaved under the in-
fluence of LDA before the expected annulation with methyl
crotonate. Due to the formation of amide anion upon the
cleavage, the formation of C-1 carbanion, which would re-
sult in a dianion, was difficult and the anticipated cyclocon-
densation was precluded. However, these results provided an
important clue for further investigations.
N
Me
16d
3
4
7d
7d
81
65
OH
CN
SO2Ph
N
OR
Me
SO2Ph
b
73%
16e: R = H
16f: R = Me
a
Method A: LDA, ꢁ78 ꢀC, THF, 3 h.
b
Me2SO4, K2CO3, Me2CO.
reacted with 7d in the presence of LDA at ꢁ78 ꢀC and the
desired 1,2,3-trisubstituted carbazoles 16b was obtained in
78% yield. To confirm its structure, it was converted to O-
methyl derivative 16c. In striking contrast to the above, ethyl
cinnamate did not undergo annulation with 7d under similar
conditions. Both N-methylfuroindolone 7d and ethyl cinna-
mate were recovered, after usual work-up of the reaction.
Similarly, methyl vinyl ketone and mesityl oxide were not
compatible for the reaction with 7d, both these ketones
were destroyed during the reaction. On the other hand,
cyano-containing and sulfone-containing Michael acceptors
(entries 3 and 4) underwent smooth annulations with com-
pound 7d to give 16d (81%) and 16e (65%), respectively.
The structure of carbazole 16e was confirmed by its conver-
sion to O-methyl derivative 16f as well as by an X-ray
crystallographic analysis.
We decided to examine protecting group stable to LDA
(Scheme 2) and their reactivity toward simple Michael
acceptors as proposed in Scheme 1 to access substituted
carbazoles. Since N-pivaloyl group of an indole has been re-
ported24 to be stable to LDA up to 40–45 ꢀC, we examined
reactivity of compound 7c (Scheme 2). This was readily pre-
pared in 71% yield from parent furoindolone 6a by pivaloyl-
ation with n-BuLi and pivaloyl chloride at ꢁ78 ꢀC. When
compound 7c was treated with LDA (3.0 equiv), followed
by methyl acrylate at ꢁ78 ꢀC, and the resulting mixture pro-
cessed in the usual manner, the expected carbazole was not
obtained. Compound 6a was recovered in a substantial
amount, meaning that the pivaloyl group of 7c was cleaved
in the presence of LDA before it could undergo annulation.
The instability of 7c to LDA led to the choice of more robust
N-methylfuroindolone 7d as a synthon. This was prepared in
84% yield from compound 6a by methylation with LDA and
iodomethane. N-Methylation of 6a involving NaH/CH3I in
DMF or K2CO3/CH3I-phase transfer catalyst was not at all
satisfactory with respect to the yields obtained. Treatment
of 7d with LDA, followed by methyl acrylate gave the
desired annulated product 16a in 72% yield. It was clearly
evident from this result that stability of N-protection to
LDA was crucial to the success of the proposed annulation.
Although the annulation of phthalides (isobenzofuranones)
has been established to involve intermediacy of a hydroxy-
tetrahydronaphthalene,25 no such intermediate (cf. I, Scheme
1) could be isolated in the reaction with 7d. The results of
similar annulations of 7d with various Michael acceptors
are summarized in Table 2. When methyl crotonate was

D. Mal et al. / Tetrahedron 63 (2007) 3768–3781
3773
Table 3. Preparation of N-protected carbazoles from furoindolones (7e and 7f) and Michael acceptors
Entry
Furoindolone
Michael acceptor
Carbazole
% Yielda
O
CO2Me
N
O
N
1
64
CO2Me
OH
Ph
17a
Ph
7e
Me
CO2Me
Me
N
R
17b:
OH
2
3
7e
7e
67
CO2Me
R = CH2Ph
b
81%
17c: R = H
CO2Me
CO2Me
COOMe
COOMe
N
85
58
OH
Ph
17d
Me
MeO
MeO
CO2Me
Me
O
N
R
4
OH
N
O
CO2Me
Ph
17e: R = CH2Ph
76%
b
7f
17f: R = H
a
Method A: LDA, ꢁ78 ꢀC, THF, 3 h.
b
AlCl3, CH2Cl2.
N-Demethylation of carbazole nitrogen of compound 16b
was examined in order to reveal the utility of the products
16a–16f. Methods26 (e.g., AlCl3/CH2Cl2, BBr3/CH2Cl2,
HBr/AcOH, Bz2O2) tested on 16b resulted in intractable
mixtures of products. The difficulty in removing N-methyl
protection led us to scrutinize benzyl derivative 7e as an an-
nulating agent. N-Benzylation of 6a with benzyl chloride in
the presence of potassium carbonate and sodium iodide
(Scheme 2) furnished 7e. Annulation of compound 7e with
methyl acrylate in the presence of LDA afforded compound
17a in 64% yield. Compound 7e also reacted with methyl
crotonate to furnish the annulated product 17b. In the
same manner, annulation between 7e and dimethyl maleate
afforded trisubstituted carbazole 17d in 85% yield. Com-
pound 7f, prepared from 6b27 also responded to the above
annulation reaction with methyl crotonate and produced tet-
rasubstituted carbazole 17e. In contrast to demethylation of
16, which was a difficult task, N-debenzylation of 17b and
17e could be readily accomplished with anhydrous AlCl3
in CH2Cl2 to give carbazoles 17c (81%) and 17f (76%),
respectively. For compound 17f, deprotection proved to
be benzyl-selective (Table 3).
Me
CF3COOH/H2O
or
NaOH, MeOH
reflux, 10 h
74%
CO2H
t-BuOK/ether
N
Me
CO2Me
or
OH
Cu-powder/
quinoline
Ph
18
N
Me
OH
KOH, MeOH
Ph
17b
reflux, 5 h
56%
N
Me2SO4, K2CO3
Acetone, reflux
OH
Ph
19
77%
O
Me
Me
Me
two steps31
CF3CO2H
CF3SO3H (cat.)
72%
N
H
N
N
H
O
OMe
OMe
Ph
21
3
20
murrayaquinone-A
murrayafoline-A
single step32
murrastifoline-F (4)
Scheme 4. Synthesis of murrayafoline-A (3).

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D. Mal et al. / Tetrahedron 63 (2007) 3768–3781
2.2.1. Synthesis of murrayafoline-A (3). As a finale, the
utility of compound 17b was established as a key intermedi-
ate in the synthesis of natural product murrayafoline-A28 (3).
Elemental analyses were carried out by using an elemental
analyzer VARIO EL instrument.
Dry solvents used for reactions were purified, before use,
according to the standard protocols. All solvents for chroma-
tography (column and preparative layer chromatography)
were distilled prior to use. In most of the column chromato-
graphic separations, ethyl acetate and petroleum ether (60–
80 ꢀC) were used as eluents. Columns were prepared with
silica gel (60–120 mesh). For preparative thin layer chroma-
tographic (plc) separations, the layer was formed over a glass
plate using water gel. The silica gel-GF254 was used for the
plc plate preparation.
Although the sequence depicted in Scheme 4 appeared to be
trivial, it required rigorous experimentation. For the crucial
demethoxycarbonylation of 17b, few literature methods29
(e.g., NaOH, MeOH, reflux; DBU, toluene, reflux; HBr,
AcOH, reflux; KOH, MeOH, reflux) were attempted.
When it was reacted with NaOH and the reaction stopped af-
ter stipulated time, the corresponding acid derivative 18 was
obtained. Decarboxylation of 18 by methods as CF3COOH/
H2O, t-BuOK/ether, Cu-powder/quinoline was not success-
ful. In all cases, the reaction ended up in an intractable mix-
ture of products. The reaction of 17b with HBr in AcOH
returned the starting material even after long reflux time.
Similar was the fate of 17b, when treated with DBU in
toluene at reflux. The differential behavior of sodium and
potassium salts of phenol in classic Kolbe–Schmidt synthe-
sis of salicylic acid prompted us to examine KOH in place of
NaOH. Indeed, demethoxycarbonylation of 17b underwent
smoothly with concentrated KOH solution in methanol to
give 19 in moderate yield (56%). For full characterization,
compound 19 was immediately converted to the O-methyl
derivative 20 (77%) with a mixture of K2CO3 and Me2SO4
in acetone at reflux. Debenzylation of compound 20 to com-
pound 3 proved problematical. Literature methods30 (e.g.,
H2, Pd/C, MeOH; H2, Pd/C, MeOH, 1–2 drops of formic
acid; AlCl3, CH2Cl2; CF3COOH, reflux) were investigated
without success. Finally, it was successfully accomplished
by treatment of 20 with refluxing TFA with a catalytic
amount of TfOH for 20–25 min. The synthesis of murraya-
foline-A (3) reported herein constitutes formal synthesis of
the fully aromatic alkaloids murrayaquinone-A31 (21) and
murrastifoline-F32 (4), since they had been synthesized
previously from 3.
4.2. General procedure for the annulation with LDA
(method A)
In a flame-dried flask flushed with nitrogen, LDA (3 mmol)
was prepared by adding diisopropylamine (3.6 mmol) to
a solution of n-BuLi (3 mmol, 1.6 M in hexane) in THF
(20 mL) at ꢁ78 ꢀC under nitrogen atmosphere. After the
solution was stirred for 10 min at ꢁ78 ꢀC, an appropriate
furoindolone (3 mmol) in THF (10 mL) was added dropwise
over 15 min. The reaction mixture was stirred at ꢁ78 ꢀC for
15 min and then allowed to warm to ꢁ40 ꢀC. A solution of
appropriate Michael acceptor (3 mmol) in THF (10 mL)
was added dropwise over 15 min at ꢁ40 ꢀC (bromobenzene
and 3-bromopyridine were dried over calcium hydride
and distilled). The reaction mixture was further stirred and
allowed to warm slowly to room temperature over 3 h. The
dark reddish-brown solution was then quenched with a satu-
rated ammonium chloride solution. The resulting mixture
was concentrated under reduced pressure and the residue
extracted with ethyl acetate (3ꢂ100 mL). The combined ex-
tracts were washed with brine (3ꢂ1/3 vol), dried (Na2SO4),
and concentrated to provide crude product, which was puri-
fied by column chromatography on silica gel using mixtures
of ethyl acetate and petroleum ether as eluents.
3. Conclusion
4.3. General procedure for the annulation reaction
with lithium tert-butoxide (method B)
In conclusion, the anionic [4+2] cycloaddition of furoindo-
lones has been introduced as a facile method for synthesiz-
ing carbazole quinones and 1-oxygenated carbazoles. The
method is regiospecific, efficient, and applicable to a range
of Michael acceptors. The starting furoindolones are readily
accessible. It is to be noted that the choice of N-protection
could be crucial, and further work is warranted for finding
out a more suitable one.
To a stirred solution of lithium tert-butoxide (9.84 mmol) in
THF (40 mL) at ꢁ60 ꢀC (chloroform/liquid N2 bath) under
an inert atmosphere was added a solution of furoindolone
(3.28 mmol) in THF (5 mL). The resulting yellowish solu-
tion was stirred at ꢁ60 ꢀC for 25 min, after which a solution
of a Michael acceptor (1 equiv unless otherwise stated) in
THF (5 mL) was added to it. The cooling bath was removed
after about 1 h at ꢁ60 ꢀC and the reaction mixture was
brought to room temperature over a period of 1 h and further
stirred for 5–6 h. The reaction was then quenched with 10%
NH4Cl (15 mL) and the resulting solution was concentrated
under reduced pressure. Generally, a bright yellow solid
appeared, which was filtered and washed with 1:1 mixture
(20 mL) of diethyl ether and petroleum ether. Otherwise,
the residue was diluted with ethyl acetate (50 mL) and the
layers were separated. The aqueous layer was extracted
with ethyl acetate (3ꢂ25 mL). The combined extracts
were washed with brine (3ꢂ1/3 vol), dried (Na2SO4), and
concentrated to provide crude product. The crude solid prod-
uct was purified by column chromatography on silica gel or
by recrystallization to get a pure product.
4. Experimental
4.1. General
Melting points were determined in open capillary tubes and
are uncorrected. Among the spectra, H NMR spectra and
1
13C NMR spectra were recorded on 200, 300 or 500 MHz
2
€
spectrometer (Brucker) as solution in H-Chloroform with
TMS as the internal standard. Chemical shifts are expressed
1
in d unit and H–1H coupling constant in hertz. IR spectra
were recorded on a Thermo Nicolet Nexus 870 FTIR spec-
trophotometers using KBr pellet. EIMS (70 eV) spectra
were taken using a VG Autospec M mass spectrometer.

D. Mal et al. / Tetrahedron 63 (2007) 3768–3781
3775
4.4. General procedure of O-methylation of phenolic
compounds
for 6 h at room temperature. It was then filtered and washed
with ethyl acetate (3ꢂ40 mL). The combined organic phase
was washed with brine (20 mL), dried (Na2SO4), and con-
centrated under reduced pressure to get a crude yellow resi-
due. This was purified by column chromatography (1:5
CHCl3/ethyl acetate, Rf¼0.45) to give 7b (1.23 g, 68%) as
a white solid. Mp 215–217 ꢀC; FTIR (KBr) cmꢁ1 3070,
2937, 1774 (s), 1582, 1460, 1378, 1272, 1187, 1120, 1046,
979, 766; 1H NMR (200 MHz, CDCl3) d 8.38 (d, 1H,
J¼8.6 Hz), 8.15 (dd, 2H, J1¼1.4 Hz, J2¼7.0 Hz), 7.32–
7.65 (m, 6H), 5.29 (s, 2H); 13C NMR (50 MHz, CDCl3)
d 160.3, 144.0, 143.0, 138.01, 134.4, 129.4, 129.1, 127.8,
127.4, 124.5, 121.7, 121.2, 115.7, 65.5; MS ESI [M+Na]+
336.2. Anal. Calcd for C16H11NO4S: C, 61.33; H, 3.54; N,
4.47. Found: C, 61.82; H, 3.72; N, 4.68.
A hydroxy compound (3.0 mmol) was dissolved in dry ace-
tone under N2-atmosphere. To this solution were added dry
K2CO3 (15 mmol) and Me2SO4 (6 mmol; freshly washed
with cold water, saturated NaHCO3 solution, and brine and
then dried over anhydrous K2CO3). After 2 h of reflux, on
completion of the reaction, the inorganic salts were removed
by filtration and the filtrate concentrated. The residue was di-
luted with diethyl ether (30 mL), treated with Et3N (6 mmol)
at room temperature, and stirred for 30 min. The reaction
mixture was then diluted with ethyl acetate (50 mL), washed
with water (40 mL), 5% aqueous HCl solution (15 mL), and
brine (3ꢂ1/3 vol), dried (Na2SO4), and concentrated to get
a crude residue, which was further purified by recrystalliza-
tion or by column chromatography on silica gel to give
a pure methoxy compound.
4.4.4. 1,4-Dihydro-4-(2,2-dimethyl-1-oxopropyl)-3H-
furo[3,4-b]indol-3-one (7c). To a stirred solution of n-butyl-
lithium (0.44 mL, 0.7 mmol) in THF (20 mL) at ꢁ78 ꢀC
temperature (ethyl acetate/liquid N2 bath) under an inert at-
mosphere was added a solution of 6a (0.1 g, 0.578 mmol) in
THF (5 mL). The resulting solution was stirred at ꢁ78 ꢀC
for 15 min, after which a solution of pivaloyl chloride
(0.2 mL, 1.73 mmol) in THF (5 mL) was added. The cooling
bath was removed after about 1 h at ꢁ78 ꢀC temperature and
the reaction mixture was brought to room temperature over
a period of 1 h and further stirred for 30 min. The reaction
was then quenched with 10% NH4Cl (15 mL) and the re-
sulting solution was concentrated. The aqueous layer was
extracted with diethyl ether (3ꢂ25 mL). The combined
organic phase was washed with brine (20 mL), dried
(Na2SO4), and concentrated under reduced pressure to get
a crude residue. The crude product was purified by column
chromatography (3:7 CHCl3/petroleum ether, Rf¼0.82) to
get 7c (0.105 g, 71%) as a white solid. Mp 130 ꢀC; FTIR
(KBr) cmꢁ1 1742 (s), 1682 (s), 1580, 1530; 1H NMR
(200 MHz, CDCl3): d 7.86 (d, 1H, J¼8.0 Hz), 7.62 (d, 1H,
J¼8.0 Hz), 7.51 (t, 1H, J¼7.2 Hz), 7.30 (t, 1H, J¼7.8 Hz),
5.39 (s, 2H), 1.51 (s, 9H); 13C NMR (50 MHz, CDCl3)
d 177.1, 163.7, 144.1, 134.2, 134.7, 128.7, 127.8, 121.0,
120.3, 111.6, 66.9, 42.5, 29.1. Anal. Calcd for C15H15NO3:
C, 70.02; H, 5.88; N, 5.44. Found: C, 69.86; H, 5.84; N, 5.18.
4.4.1. 1-Methoxy-3-methyl-9H-carbazole (3). A solution
of N-benzylmurrayafoline-A 23 (0.04 g, 0.132 mmol) in tri-
fluoroacetic acid (2 mL) and two drops of trifluoromethane-
sulfonic acid was heated at reflux for 15 min. The solution
was then taken up in water (30 mL) and extracted with di-
chloromethane (3ꢂ30 mL). The combined organic extracts
were washed with brine (3ꢂ20 mL), dried (Na2SO4), and
concentrated to give crude residue. Purification of the crude
residue by chromatography (1:4 ethyl acetate/petroleum
ether, Rf¼0.67) gave compound 331 (0.02 g, 77%) as an
1
oily material. H NMR (200 MHz, CDCl3) d 8.21 (br s,
1H), 7.96 (d, 1H, J¼8.0 Hz), 7.46 (s, 1H), 7.40–7.15 (m,
3H), 6.78 (s, 1H), 4.01 (s, 3H), 2.51 (s, 3H). These data
were in agreement with the reported values.31
4.4.2. Ethyl 1,3-dihydro-3-oxo-4H-furo[3,4-b]indole-4-
carboxylate (7a). To an ice-cold solution of 6a (2 g,
11.56 mmol) and triethylamine in dry CH2Cl2 (50 mL)
was added a solution of ethyl chloroformate (1.12 mL,
11.56 mmol) in dry CH2Cl2 (10 mL). The temperature of
the mixture was slowly increased to room temperature. After
12 h of stirring, the resulting reaction mixture was poured
into 5% aqueous HCl (30 mL) and extracted with CH2Cl2
(3ꢂ40 mL). The combined organic layers were washed
with 5% NaHCO3 solution (20 mL), brine (20 mL), dried
(Na2SO4), and concentrated under reduced pressure. The
crude product was chromatographed (1:1 CHCl3/petroleum
ether, Rf¼0.62) to give 7a (2.6 g, 92%) as a white crystalline
solid. Mp 121–123 ꢀC; FTIR (KBr) cmꢁ1 2923, 2857, 1777
(s), 1742 (s), 1599, 1441, 1381, 1321, 1269, 1235, 1115,
4.4.5. 1,4-Dihydro-4-methyl-3H-furo[3,4-b]indol-3-one
(7d). In a flame-dried flask flushed with nitrogen, LDA
(6.36 mmol) was prepared by adding diisopropylamine
(7.62 mmol) to a solution of n-BuLi (6.36 mmol, 1.6 M in
hexane) in THF (40 mL) at ꢁ78 ꢀC under nitrogen atmo-
sphere. After the solution was stirred for 10 min at
ꢁ78 ꢀC, compound 6a (1.0 g, 5.78 mmol) in THF (10 mL)
was added dropwise over 15 min. The reaction mixture
was stirred at ꢁ78 ꢀC for 15 min and then allowed to
warm to ꢁ40 ꢀC. Thereafter, a solution of MeI (0.396 mL,
6.36 mmol) in THF (10 mL) was added dropwise over
15 min. The reaction mixture was further stirred and allowed
to warm slowly to room temperature over 3 h. The reaction
was then quenched with 10% NH4Cl (25 mL) and the result-
ing solution was concentrated under reduced pressure. It
was extracted with diethyl ether (3ꢂ50 mL). The combined
organic layers were washed with brine (20 mL), dried
(Na2SO4), and concentrated under reduced pressure to get
a crude residue. The crude product was purified by column
chromatography (1:4 ethyl acetate/petroleum ether,
1
1043, 755; H NMR (200 MHz, CDCl3) d 8.39 (d, 1H,
J¼8.6 Hz), 7.52–7.65 (m, 2H), 7.38 (t, 1H, J¼7.6 Hz),
5.34 (s, 2H), 4.56 (q, 2H, J¼5.8 Hz), 1.529 (t, 3H,
J¼5.8 Hz); 13C NMR (50 MHz, CDCl3) d 160.4, 149.9,
143.3, 142.6, 128.8, 127.8, 124.0, 121.4, 120.6, 116.8,
65.1, 63.9, 14.0. Anal. Calcd for C13H11NO4: C, 63.67; H,
4.52; N, 5.71. Found: C, 63.83; H, 4.34; N, 5.62.
4.4.3. 1,4-Dihydro-4-(phenylsulfonyl)-3H-furo[3,4-b]-
indol-3-one (7b). To a stirred solution of compound 6a
(1.0 g, 5.78 mmol) in toluene (20 mL) were successively
added K2CO3 (7.98 g, 57.8 mmol), benzenesulfonyl chlo-
ride (5.8 g, 33 mmol), and triethyl benzyl ammonium chlo-
ride (0.33 g, 1.44 mmol). The reaction mixture was stirred

3776
D. Mal et al. / Tetrahedron 63 (2007) 3768–3781
Rf¼0.78) to get 7d (0.908 g, 84%) as a white solid. Mp
147 ꢀC; FTIR (KBr) cmꢁ1 2942, 2362, 1747 (s), 1571,
1456, 1321 (m), 1199, 1047, 979, 740; 1H NMR
(200 MHz, CDCl3): d 7.64 (d, 1H, J¼8.2 Hz), 7.40–7.50
(m, 2H), 7.15–7.30 (m, 1H), 5.39 (s, 2H), 3.95 (s, 3H); 13C
NMR (50 MHz, CDCl3) d 163.8, 144.3, 133.8, 128.6,
126.1, 121.0 (2 ‘C’); 120.2, 111.3, 66.9, 30.0; HRMS ESI:
for C11H9NO2 [M+H]+ calcd 188.0712, found 188.0709.
1H, J¼8.2 Hz), 7.72 (d, 1H, J¼7.8 Hz), 7.62 (t, 1H,
J¼8.2 Hz), 7.45 (t, 1H, J¼7.8 Hz), 7.35 (s, 1H), 4.55 (q,
2H, J¼7.2 Hz), 1.52 (t, 3H, J¼7.2 Hz); 13C NMR
(50 MHz, CDCl3) d 156.7, 149.6, 144.9, 142.9, 129.6,
126.9, 124.8, 120.8, 120.3, 116.9, 68.6, 64.5, 14.1. Anal.
Calcd for C13H10BrNO4: C, 48.17; H, 3.11; N, 4.32. Found:
C, 48.39; H, 2.87; N, 4.36.
4.4.9. Ethyl 1,3-dihydro-3-oxo-1-phenylsulfanyl-4H-
furo[3,4-b]indole-4-carboxylate (9). To a stirred solution
of NaSPh (0.815 g, 6.17 mmol) in MeOH (40 mL) at room
temperature under an argon atmosphere was added a solution
of compound 8 (2.0 g, 6.17 mmol). The reaction mixture
was heated at reflux for 3.5 h and then cooled to room tem-
perature. The contents of the flask were diluted with water
(50 mL) and then extracted into diethyl ether (3ꢂ40 mL).
The combined organic layers were washed with brine
(30 mL), dried (Na2SO4), and concentrated under reduced
pressure to get a crude residue. The residue was purified
by chromatography (1:5 ethyl acetate/petroleum ether,
Rf¼0.46) to give 9 (1.68 g, 77%) as a white solid. Mp
155–157 ꢀC; FTIR (KBr) cmꢁ1 2924, 1742 (s), 1680 (s),
1596, 1414, 1378, 1321, 1238, 1109, 1037, 747, 695, 618;
1H NMR (200 MHz, CDCl3) d 8.3 (d, 1H, J¼7.6 Hz), 8.05
(d, 1H, J¼8.8 Hz), 7.20–7.60 (m, 7H), 4.41 (q, 2H,
J¼6.8 Hz), 1.37 (t, 3H, J¼6.8 Hz); 13C NMR (50 MHz,
d6-DMSO) d 162.0, 150.1, 135.9, 133.6, 131.4, 129.3,
128.1, 127.6, 127.2, 125.5, 123.2, 123.0, 122.5, 114.3,
64.2, 50.6, 13.6. Anal. Calcd for C19H15NO4S: C, 64.58;
H, 4.28; N, 3.96. Found: C, 64.96; H, 4.32; N, 4.12.
4.4.6. 1,4-Dihydro-4-(phenylmethyl)-3H-furo[3,4-b]-
indol-3-one (7e). This compound was prepared as a white
solid in 62% yield by reaction of compound 6a with benzyl
chloride following the general procedure for the N-benzyl-
ation described for 6b to 7f. The crude product was purified
by column chromatography (1:5 ethyl acetate/petroleum
ether, Rf¼0.62). Mp 112 ꢀC; FTIR (KBr) cmꢁ1 2937,
2885, 1741 (s), 1560, 1442 (m), 1325 (m), 1265, 1178,
1
1058, 983, 737; H NMR (200 MHz, CDCl3): d 7.64 (d,
1H, J¼7.8 Hz), 7.33–7.47 (m, 3H), 7.18–7.29 (m, 5H),
5.54 (s, 2H), 5.41 (s, 2H); 13C NMR (50 MHz, CDCl3)
d 163.7, 143.6, 136.6, 134.6, 128.7 (two ‘C’), 128.3,
127.8, 127.3, 126.3, 121.2, 120.5, 112.1, 67.0, 47.5;
HRMS ESI: for C17H13NO2 [M+H]+ calcd 264.1025, found
264.1020.
4.4.7. 1,4-Dihydro-7-methoxy-4-(phenylmethyl)-3H-
furo[3,4-b]indol-3-one (7f). To a stirred solution of 6b
(0.2 g, 0.985 mmol) in dry acetone (20 mL) under an inert
atmosphere was added K2CO3 (0.679 g, 4.92 mmol) and
NaI (0.295 g, 1.97 mmol). After 25 min, a solution of benzyl
chloride (0.16 mL, 1.97 mmol) in dry acetone (5 mL) was
added to this mixture. The resulting mixture was further
stirred for 3 h and then extracted with diethyl ether
(3ꢂ50 mL). The combined organic layers were washed
with brine (30 mL), dried (Na2SO4), and concentrated under
reduced pressure to get a crude residue. The residue on col-
umn chromatographic purification (3:7 ethyl acetate/petro-
leum ether, Rf¼0.71) afforded 7f (0.2 g, 69%) as a light
yellowish solid. Mp 135 ꢀC; FTIR (KBr) cmꢁ1 2935, 1740
(s), 1623, 1558, 1504 (m), 1456, 1306, 1242 (m), 1168,
4.4.10. Ethyl 1,3-dihydro-3-oxo-1-(phenylsulfonyl)-4H-
furo[3,4-b]indole-4-carboxylate (10). To a well-stirred
solution of 8 (1.8 g, 5.55 mmol) in dry DMF (20 mL) was
added solid sodium benzenesulfinate (0.91 g, 5.55 mmol)
in portions. The mixture was stirred overnight at room tem-
perature and the resulting mass was poured into cold water
(50 mL). The yellow crystalline material precipitated was
filtered and recrystallized (1:5 CH2Cl2/hexane, Rf¼0.58) to
give 10 (1.82 g, 85%) in white crystalline state. Mp 220–
222 ꢀC; FTIR (KBr) cmꢁ1 2362, 2356, 1801 (s), 1734 (s),
1
983, 792, 752; H NMR (200 MHz, CDCl3): d 7.15–7.70
1
(m, 6H), 7.05–7.13 (m, 1H), 7.0 (s, 1H), 5.56 (s, 2H), 5.36
(s, 2H), 3.83 (s, 3H); 13C NMR (50 MHz, CDCl3) d 163.6,
154.9, 138.9, 136.6, 133.6, 128.7, 128.5, 127.7, 127.2,
120.6, 117.4, 112.9, 101.6, 66.8, 55.6, 47.5; HRMS ESI:
for C18H15NO3 [M+H]+ calcd 294.1130, found 294.1140.
1560, 1447, 1384, 1350, 1312, 1150, 995, 750; H NMR
(200 MHz, CDCl3) d 8.36 (d, 1H, J¼8.6 Hz), 8.05 (d, 1H,
J¼7.6 Hz), 7.86 (dd, 2H, J1¼8.0 Hz, J2¼8.6 Hz), 7.45–7.8
(m, 5H), 6.25 (s, 1H), 4.51 (q, 2H, J¼7.0 Hz), 1.51 (t, 3H,
J¼7.0 Hz); 13C NMR (50 MHz, CDCl3) d 156.9, 149.5,
142.9, 136.6, 135.1, 134.3, 129.9, 129.7, 129.5, 129.3,
125.2, 122.7, 121.3, 116.8, 87.5, 64.5, 14.1; HRMS ESI:
for C19H15NO6S [M+H]+ calcd 386.0728, found 386.0722.
Anal. Calcd for C19H15NO6S: C, 59.21; H, 3.92; N, 3.63.
Found: C, 59.35; H, 3.84; N, 3.76.
4.4.8. Ethyl 1-bromo-1,3-dihydro-3-oxo-4H-furo[3,4-
b]indole-4-carboxylate (8). A mixture of 7 (2.0 g,
8.16 mmol), NBS (1.6 g, 8.97 mmol), and benzoyl peroxide
(70 mg) in CCl4 (40 mL) was heated at reflux under the ex-
posure of a 100-W bulb for 2 h. The completion of the reac-
tion was ascertained by the disappearance of NBS from the
bottom of the flask. The mixture was cooled to 0 ꢀC, filtered,
and then concentrated under reduced pressure. The residue
was diluted with water (50 mL). The mixture was extracted
with ether (3ꢂ30 mL). The combined organic extracts were
washed with NaHCO3 solution (25 mL), brine, and concen-
trated. Purification of the crude residue by chromatography
(1:4 CHCl3/petroleum ether, Rf¼0.38) gave 8 (1.85 g,
70%) as a brownish white solid. Mp 132–134 ꢀC; FTIR
(KBr) cmꢁ1 2922, 1799 (s), 1748 (s), 1444, 1383, 1230,
1145, 977, 822, 760; 1H NMR (200 MHz, CDCl3) d 8.4 (d,
4.4.11. 7-Hydroxy-10-methyl-5H-benzo[b]carbazole-
6,11-dione (12a). This compound was prepared as a red
solid in 85% yield (70% by method A) by condensation of
10 and 11a, according to general procedure for the annul-
ation with lithium tert-butoxide (method B). Mp 308–
310 ꢀC; FTIR (KBr) cmꢁ1 3305, 2925, 2362, 1630 (s),
1629 (s), 1533, 1460, 1411, 1384, 1205, 1172, 1106, 746;
1H NMR (200 MHz, CDCl3+2 drops of d6-DMSO) d 12.65
(s, 1H), 12.23 (br, 1H), 8.05 (d, 1H, J¼7.8 Hz), 7.31 (d,
1H, J¼7.8 Hz), 7.0–7.20 (m, 3H), 6.81 (d, 1H, J¼8.6 Hz),
2.48 (s, 3H). 13C NMR (50 MHz, d6-DMSO) d 182.6,

D. Mal et al. / Tetrahedron 63 (2007) 3768–3781
3777
182.3, 160.7, 141.7, 138.5, 135.2, 133.2, 129.9, 127.0, 123.9,
123.6, 123.2, 122.3, 118.1, 115.7, 113.5, 22.2; MS EI, m/z:
[M]+, 277 (100%), 248, 220, 204, 191, 165, 129, 112, 89,
78, 69. Anal. Calcd for C17H11NO3: C, 73.64; H, 4.00; N,
5.05. Found: C, 73.96; H, 3.80; N, 4.82.
8.23 (d, 1H, J¼8.0 Hz); 8.06 (d, 1H, J¼8.2 Hz), 7.52–7.63
(m, 3H), 7.43–7.48 (t, 1H, J¼7.5 Hz), 7.34–7.38 (t, 1H,
J¼7.5 Hz), 4.09 (s, 3H). (Due to poor solubility in common
deuterated solvents; 13C NMR could not be recorded.) MS
ESI [M+H]+ 344.1. Anal. Calcd for C21H13NO4: C, 73.46;
H, 3.82, N, 4.08. Found: C, 73.32; H, 3.95; N, 4.21.
4.4.12. 1,2,3,7-Tetrahydroindeno[6,7-b]carbazol-6,12-di-
one (12b). This compound was prepared as a red solid in
75% (62% yield by method A) yield by condensation of
10 and 11b, according to general procedure for the annula-
tion with lithium tertꢁ-b1utoxide (method B). Mp 318–
20 ꢀC; FTIR (KBr) cm 3315 (br), 2362, 1626 (s), 1629
(s), 1529, 1421, 1226 (m), 1143, 1037, 750; 1H NMR
(200 MHz, sparingly soluble in CDCl3) d 12.62 (s, 1H),
9.33 (br, 1H), 8.39 (d, 1H, J¼8.2 Hz), 7.37–7.54 (m,
3H), 7.06 (s, 1H), 3.43 (t, 2H, J¼7.4 Hz), 2.92 (t,
2H, J¼7.6 Hz), 2.06–2.25 (m, 2H). (Due to poor solubility
in common deuterated solvents, 13C NMR could not
be recorded.) MS ESI [M+H]+ 304.2. Anal. Calcd for
C19H13NO3: C, 75.24; H, 4.32; N, 4.62. Found: C, 75.15;
H, 4.57; N, 4.83.
4.4.16. 7-Hydroxy-12-methoxy-5H-naphtho[2,3-b]carb-
azol-6,13-dione (12h). This compound was prepared as an
orange yellow solid in 76% yield by condensation of 10
and 11h, according to general procedure for the annulation
with lithium tert-butoxide (method B). Mp>350 ꢀC; FTIR
(KBr) cmꢁ1: 3293, 3250, 3059, 1650, 1604 (s), 1602 (s),
1
1528 (m), 1442, 1400, 1364, 1236, 1145, 1020, 742; H
NMR (200 MHz, sparingly soluble in d6-DMSO) d 13.04
(br, 1H), 12.24 (s, 1H), 8.42 (d, 1H, J¼6.0 Hz), 8.31 (d,
1H, J¼6.0 Hz), 7.90–7.72 (m, 2H), 7.70–7.26 (m, 4H),
3.98 (s, 3H). (Due to poor solubility in common deuterated
solvents; 13C NMR could not be recorded.) MS ESI
[M+H]+ 344.1. Anal. Calcd for C21H13NO4: C, 73.46; H,
3.82; N, 4.08. Found: C, 73.67; H, 3.75; N, 4.01.
4.4.13. 6-Hydroxy-5-methoxy-1,2,3,4-tetrahydro-8H-
naphtho[2,1-b]carbazol-7,13-dione (12e). This compound
was prepared as a red solid in 72% yield by condensation of
10 and a 3:7 mixture of 11c and 11e, according to general
procedure for the annulation with lithium tert-butoxide
(method B). Mp 333–35 ꢀC; FTIR (KBr) cmꢁ1 3276 (br),
4.4.17. Ethyl 6,13-dioxo-7-hydroxy-12-methoxynaph-
tho[2,3-b]carbazole-5-carboxylate (12i). The preparative
procedure is essentially same as that for 12h, except that
the reaction mixture was quenched at 0 ꢀC with ice-cold
10% NH4Cl. Compound 12h (0.062 g, 72%) was obtained as
a deep red solid. Mp 180 ꢀC; FTIR (KBr) cmꢁ1 3432, 2991,
2931, 1755 (s), 1660, 1624 (s), 1622 (s), 1542, 1430, 1366,
1
2362, 1612 (s), 1610 (s), 1400, 1242 (m), 132, 144; H
1
NMR (200 MHz, sparingly soluble in CDCl3) d 13.05 (s,
1H), 9.32 (br s, 1H), 8.43 (d, 1H, J¼7.6 Hz), 7.97 (d, 1H,
J¼7.6 Hz), 7.35–7.50 (m, 2H), 3.99 (s, 3H), 3.25–3.40
(m, 2H), 2.60–2.90 (m, 6H). (Due to poor solubility in
common deuterated solvents, 13C NMR could not be
recorded.) MS ESI [M+H]+ 348.2. Anal. Calcd for
C21H17NO4: C, 72.61; H, 4.93; N, 4.03. Found: C, 72.73;
H, 5.07; N, 4.18.
1306, 1236, 1148, 1070, 1022, 756; H NMR (200 MHz,
CDCl3, poorly soluble) d 14.64 (s, 1H), 8.70–8.45 (m,
2H), 8.40–8.28 (m, 1H), 8.10–7.92 (d, 1H, J¼6.0 Hz),
7.90–7.75 (m, 2H), 7.70–7.45 (m, 2H), 4.62 (q, 2H,
J¼8.0 Hz), 4.11 (s, 3H), 1.54 (t, 3H, J¼8.0 Hz); 13C NMR
(50 MHz, CDCl3) d 182.2, 180.2, 162.9, 153.4, 150.5,
139.2, 135.9, 133.4, 131.2, 129.6, 129.2, 129.1, 126.4,
125.3, 125.0, 124.9, 124.3, 118.2, 113.7, 109.6, 65.1, 62.4,
13.9; MS ESI [M+H]+ 416.1. Anal. Calcd for C24H17NO6:
C, 69.39, H, 4.12; N, 3.37. Found: C, 69.67; H, 3.95; N, 3.52.
4.4.14. Methyl 6-hydroxy-5-methoxy-1,2,3,4-tetrahydro-
8H-naphtho[2,1-b]carbazole-2-carboxylate (12f). This
compound was prepared as a red solid in 70% yield by con-
densation between 10 and a 1:4 mixture of 11d and 11f,
according to the general procedure for the annulation with
lithium tert-butoxide (method B). Mp 326–28 ꢀC; FTIR
(KBr) cmꢁ1 3292 (br s), 1724 (s), 1612 (s), 1609 (s), 1533,
1477, 1405, 1334, 1255 (m), 1172, 1137, 1054, 1018, 754;
1H NMR (200 MHz, CDCl3) d 13.04 (s, 1H); 9.32 (br s,
1H), 8.37 (d, 1H, J¼8.2 Hz), 7.45 (d, 1H, J¼8.2 Hz),
7.26–7.40 (m, 2H), 4.01 (s, 3 H), 3.76 (s, 3H), 3.30–3.50
(m, 1H), 2.90–3.25 (m, 3H), 2.60–2.85 (m, 3H). (Due to
poor solubility in common deuterated solvents, 13C NMR
could not be recorded.) MS ESI [M+H]+ 406.2. Anal. Calcd
for C23H19NO6: C, 68.14; H, 4.72, N, 3.46. Found: C, 68.32;
H, 4.83; N, 3.61.
4.4.18. 7-Hydroxy-10-methoxy-8-methyl-5H-benzo[b]-
carbazole-6,11-dione (12j). This compound was prepared
as an orange yellow solid in 78% yield by condensation of
10 and 11j, according to the general procedure for the annu-
lation with lithium tert-butoxide (method B). Mp 312 ꢀC;
FTIR (KBr) cmꢁ1 3290 (br s), 2930, 2360, 1618 (s), 1616
1
(s), 1530, 1440, 1410, 1366, 1238, 1142, 1020, 756; H
NMR (200 MHz, d6-DMSO, poorly soluble) d 13.14 (s,
1H), 12.32 (s, 1H), 8.56 (d, 1H, J¼6.8 Hz), 8.04 (d, 1H,
J¼8.0 Hz), 7.38–7.70 (m, 2H), 7.30 (s, 1H), 3.88 (s, 3H),
2.30 (s, 3H). (Due to poor solubility in common deuterated
solvents; 13C NMR could not be recorded.) MS ESI
[M+H]+ 308.1. Anal. Calcd for C18H13NO4: C, 70.35; H,
4.26; N, 4.56. Found: C, 70.28; H, 4.41; N, 4.49.
4.4.15. 7-Hydroxy-8-methoxy-5H-naphtho[2,1-b]carb-
azol-6,13-dione (12g). This compound was prepared as
a pink solid in 67% yield by condensation of 10 and 11g ac-
cording to the general procedure of annulation with lithiuꢁm1
tert-butoxide (method B). Mp 342–44 ꢀC; FTIR (KBr) cm
3296 (br), 2925, 1614 (s), 1539, 1394, 1317 (m), 1132, 1060,
710; H NMR (200 MHz, sparingly soluble in d6-DMSO)
d 13.01 (s, 1H), 12.49 (s, 1H), 9.63 (d, 1H, J¼8.5 Hz),
4.4.19. Ethyl 7-hydroxy-10-methoxy-8-methyl-6,11-di-
oxo-benzo[b]carbazole-5-carboxylate (12k). Annulation
method B when applied to 10 and 11j, followed by work-
up, i.e., quenching with aq NH4Cl solution (10 mL) at
0 ꢀC, dilution with ethyl acetate (3ꢂ30 mL), washing with
brine (3ꢂ20 mL), drying (Na2SO4), concentration under
reduced pressure, and purification by column chromato-
graphy gave compound 12k as a red solid in 75% yield.
1

3778
D. Mal et al. / Tetrahedron 63 (2007) 3768–3781
Mp 153–155 ꢀC; FTIR (KBr) cmꢁ1 3428, 3007, 2936, 1750
(s), 1628 (s), 1624 (s), 1542, 1432, 1360, 1310, 1238, 1140,
1070, 1022, 754; H NMR (200 MHz, CDCl3): d 12.93 (s,
1H), 8.55 (d, 1H, J¼6.8 Hz), 7.97 (d, 1H, J¼8.4 Hz),
7.35–7.62 (m, 2H), 7.21 (s, 1H), 4.60 (q, 2H, J¼7.2 Hz),
4.03 (s, 3H), 2.38 (s, 3H), 1.50 (t, 3H, J¼7.2 Hz); 13C
NMR (50 MHz, CDCl3) d 181.1, 180.7, 156.2, 154.0,
150.5, 139.3, 137.9, 134.6, 129.3, 125.9, 125.4, 124.4,
124.3, 123.5, 116.4, 115.2, 113.8, 65.0, 56.7, 16.6, 13.9;
MS ESI [M+H]+ 380.1. Anal. Calcd for C21H17NO6: C,
66.49; H, 4.52; N, 3.69. Found: C, 66.56; H, 4.59; N, 3.76.
J¼7.8 Hz), 7.67 (s, 1H), 7.45–7.56 (m, 1H), 7.39 (d, 1H,
J¼8.0 Hz), 7.15–7.27 (m, 2H), 4.09 (s, 3H), 4.05 (s, 3H),
3.95 (s, 3H), 2.46 (s, 3H); 13C NMR (50 MHz, CDCl3)
d 169.2, 143.1, 142.1, 142.2, 130.7, 126.3, 126.1, 125.6,
122.3, 120.3, 119.1, 117.2, 108.6, 63.7, 52.2, 30.9, 19.3.
Anal. Calcd for C17H17NO3: C, 72.07; H, 6.05; N, 4.94.
Found: C, 72.16; H, 5.96; N, 4.66.
1
4.4.24. 1-Hydroxy-9-methyl-9H-carbazole-2-carbonitrile
(16d). This compound was prepared as an off-white solid in
81% by condensation between 7d and acrylonitrile, follow-
ing general procedure for the LDA promoted annulation
(method A). Mp 120–22 ꢀC; FTIR (KBr) 3432, 3262, 2977,
4.4.20. 5H-Benzo[b]carbazole-6,11-dione (14). This com-
pound was prepared as a dark orange solid in 64% yield
by condensation of 7a and bromobenzene following general
procedure for the LDA mediated annulation (methoꢁd1A). Mp
306–308 ꢀC (lit.14 307–310 ꢀC); FTIR (KBr) cm 3261,
2362, 1644, 1648, 1527, 1525, 1390, 1398, 1232, 1213,
1
2362, 2232, 1640, 1527, 1438, 1242, 1085, 754 cmꢁ1; H
NMR (200 MHz, d6-DMSO): d 10.86 (s, 1H), 8.21 (d, 1H,
J¼8.0 Hz), 7.82 (d, 1H, J¼8.2 Hz), 7.62–7.48 (m, 2H),
7.35–7.26 (m, 2H), 4.15 (s, 3H); 13C NMR (50 MHz, d6-
DMSO): d 147.0, 141.9, 130.3, 127.0, 127.5, 122.7, 121.5,
121.8, 119.3, 118.3, 113.7, 109.8, 97.3, 31.9; HRMS ESI:
for C14H10N2O [M+H]+ calcd 264.1025, found 264.1020.
1
1014, 709; H NMR (200 MHz, d6-DMSO): d 13.07 (br,
1H), 8.19 (d, 1H, J¼7.7 Hz), 8.0–8.15 (m, 2H), 7.75–7.89
(m, 2H), 7.58 (d, 1H, J¼7.7 Hz), 7.32–7.50 (m, 2H); 13C
NMR (50 MHz, d6-DMSO) d 181.2, 178.3, 139.1, 138.0,
135.0, 134.9, 133.9, 133.5, 127.7, 126.9, 126.8, 124.8,
124.7, 123.2, 118.3, 114.7. All these data were in agreement
with the reported values.14
4.4.25. 9-Methyl-2-phenylsulfonyl-9H-carbazole-1-ol
(16e). This compound was prepared as a brown crystalline
needle form in 65% yield by reaction between 7d and vinyl
sulfone, according to general procedure for the LDA pro-
moted annulation (method A). Mp 160–162 ꢀC; FTIR
(KBr) 3062, 2975, 2355, 1602, 1482, 1455, 1320, 1147,
4.4.21. Methyl 1-hydroxy-9-methyl-9H-carbazole-2-
carboxylate (16a). This compound was prepared as a white
solid in 72% yield by condensation between 7d and methyl
acrylate, following general procedure for the LDA promotꢁed1
annulation (method A). Mp 98–100 ꢀC; FTIR (KBr) cm
3066, 2977, 2362, 1674 (s), 1640, 1585, 1446 (m), 1315
(s), 1147, 1085, 993, 873, 754; 1H NMR (200 MHz,
CDCl3): d 11.68 (s, 1H), 8.04 (d, 1H, J¼7.8 Hz), 7.50–
7.66 (m, 3H), 7.40 (d, 1H, J¼8.1 Hz), 7.21–7.24 (m, 1H),
4.23 (s, 3H), 3.97 (s, 3H); 13C NMR (50 MHz, CDCl3)
d 171.9, 150.8, 142.3, 128.6, 128.5, 126.4, 122.1, 120.8,
119.5, 119.2, 110.9, 109.1, 107.7, 52.1, 31.9; MS EI
[M+H]+ 256.1. Anal. Calcd for C15H13NO3: C, 70.58; H,
5.13; N, 5.49. Found: C, 70.30; H, 5.02; N, 5.27.
1
1088, 754 cmꢁ1; H NMR (200 MHz, CDCl3): d 9.91 (s,
1H), 8.03–7.85 (m, 2H), 7.66–7.35 (m, 7H), 7.30–7.20 (m,
2H), 4.22 (s, 3H); MS ESI [M+H]+ 338.1. Anal. Calcd for
C19H15NO4S: C, 67.64; H, 4.48; N, 4.15. Found: C, 67.92;
H, 4.64; N, 4.25.
4.4.26. 1-Methoxy-9-methyl-2-phenylsulfonyl-9H-carb-
azole (16f). This compound was prepared from 16f as a light
brown solid in 73% yield, following the general procedure
for the O-methylation of phenolic compounds using
Me2SO4. Mp 165 ꢀC; 1H NMR (200 MHz, CDCl3):
d 8.10–7.95 (m, 5H), 7.56–7.30 (m, 6H), 4.06 (s, 3H), 4.05
(s, 3H); 13C NMR (50 MHz, CDCl3): d 143.2, 142.7,
132.7, 130.7, 128.6, 127.8, 122.0, 121.0, 120.1, 119.7,
116.0, 109.2, 64.8, 31; MS ESI [M+H]+ 352.1. Anal. Calcd
for C20H17NO3S: C, 68.36; H, 4.88; N, 3.99. Found: C,
68.64; H, 4.75; N, 4.12.
4.4.22. Methyl 1-hydroxy-3,9-dimethyl-9H-carbazole-2-
carboxylate (16b). This compound was prepared as a yellow
solid in 78% yield by condensation between 7d and methyl
crotonate, following general procedure for the LDA pro-
moted annulation (method A). Mp 170 ꢀC; FTIR (KBr)
cmꢁ1 3402 (br s), 2929, 2362, 1735, 1655 (s), 1546, 1442
(m), 1376, 1319 (s), 1265, 1159; 1H NMR (200 MHz,
CDCl3): d 12.32 (s, 1H), 7.99 (d, 1H, J¼7.6 Hz), 7.25–
7.50 (m, 2H), 7.10–7.23 (m, 1H), 4.19 (s, 3H), 3.97 (s,
3H), 2.65 (s, 3H); 13C NMR (50 MHz, CDCl3) d 173.5,
152.1, 142.5, 130.1, 127.1, 126.7, 121.7, 120.7, 118.8,
113.6, 108.9, 107.7, 51.8, 31.8, 24.4; MS ESI [M+H]+
270.1. Anal. Calcd for C16H15NO3: C, 71.36; H, 5.61; N,
5.20. Found: C, 71.62; H, 5.42; N, 5.37.
4.4.27. Methyl 1-hydroxy-9-(phenylmethyl)-9H-carb-
azole-2-carboxylate (17a). This compound was prepared
as a white solid in 64% yield by condensation between 7e
and methyl acrylate, following general procedure for the
LDA promoted annulation (method A). Mp 118 ꢀC; FTIR
(KBr) cmꢁ1 3031, 2926, 1712, 1666 (s), 1445 (m), 1319
1
(s), 1261 (m), 1187, 1151, 1025, 744; H NMR (200 MHz,
CDCl3): d 11.72 (s, 1H), 8.08 (d, 1H, J¼8.0 Hz), 7.72–
7.55 (m, 2H), 7.47–7.39 (m, 2H), 7.30–7.12 (m, 6H), 5.97
(s, 2H), 3.97 (s, 3H); 13C NMR (50 MHz, CDCl3):
d 171.9, 150.6, 141.9, 138.7, 129.0, 128.5, 128.2, 127.2,
127.1, 126.5, 122.6, 121.0, 119.9, 119.6, 111.0, 109.9,
108.1, 52.2, 48.6; HRMS ESI: for C21H17NO3 [M+H]+ calcd
332.1287, found 332.1276.
4.4.23. Methyl 1-methoxy-3,9-dimethyl-9H-carbazole-2-
carboxylate (16c). This compound was prepared as a white
solid in 76% yield from 16b, following the general proce-
dure of O-methylation for the phenolic compounds de-
scribed above. Mp 90–92 ꢀC; FTIR (KBr) 3408 (br s),
2934, 2352, 1730, 1660 (s), 1543, 1438 (m), 1310 (s),
4.4.28. Methyl 1-hydroxy-3-methyl-9-(phenylmethyl)-
9H-carbazole-2-carboxylate (17b). This compound was
prepared as a white solid in 67% yield by condensation
1
1158 cmꢁ1; H NMR (200 MHz, CDCl3): d 8.03 (d, 1H,

D. Mal et al. / Tetrahedron 63 (2007) 3768–3781
3779
between 7e and methyl crotonate, following general proce-
dure for the LDA promoted annulation (method A). Mp
122–24 ꢀC; FTIR (KBr) cmꢁ1 3035, 2923 (s), 2852, 1660
(s), 1639, 1444, 1317 (m), 1263, 1157, 1022, 746; 1H
NMR (200 MHz, CDCl3): d 12.34 (s, 1H), 8.03 (d, 1H,
J¼8.0 Hz), 7.45–7.36 (m, 3H), 7.28–7.12 (m, 6H), 5.94 (s,
2H), 4.0 (s, 3H), 2.68 (s, 3H); 13C NMR (50 MHz,
CDCl3): d 173.4, 151.9, 150.7, 142.2, 138.9, 130.7, 128.4,
127.5, 127.0, 126.9, 126.4, 122.2, 120.93, 119.3, 113.7,
109.8, 108.1, 52.0, 48.4, 24.5; HRMS ESI: for C22H19NO3
[M+H]+ calcd 346.1443, found 346.1442.
4.4.32. Methyl 1-hydroxy-6-methoxy-3-methyl-9H-carb-
azole-2-carboxylate (17f). This compound was obtained
as a light brown solid in 71% yield from N-benzyl compound
17d, following the procedure adopted for compound 17c.
Mp 162–64 ꢀC; FTIR (KBr) 3402 (s), 2948, 1672 (s), 1625,
1622, 1552, 1488 (m), 1320, 1235 (m), 1160, 860 cmꢁ1; 1H
NMR (200 MHz, CDCl3) d 12.0 (s, 1H), 8.30 (br s, 1H), 7.45
(d, 1H, J¼2.3 Hz), 7.40 (s, 1H), 7.36 (s, 1H), 7.13 (d, 1H,
J¼2.3 Hz), 4.0 (s, 3H), 3.93 (s, 3H), 2.68 (s, 3H); MS ESI
[M+H]+ 286.2. Anal. Calcd for C16H15NO4: C, 67.36; H,
5.30; N, 4.91. Found: C, 67.02; H, 5.12; N, 5.04.
4.4.29. Methyl 1-hydroxy-3-methyl-9H-carbazole-2-
carboxylate (17c). To a stirred solution of 17b (0.05 g,
0.145 mmol) in dry CH2Cl2 (20 mL) solution at room tem-
perature was added anhydrous AlCl3 (0.095 g, 0.725 mmol)
under nitrogen atmosphere. The mixture was stirred over-
night and the resulting mass was poured into cold water
(30 mL). The white material precipitated was filtered off
and the filtrate was extracted with CH2Cl2 (3ꢂ30 mL). The
combined organic extracts were washed with H2O (20 mL),
brine (20 mL), and dried (Na2SO4). Concentration of the or-
ganic layer gave a solid residue. This was purified by column
chromatography (1:3 EtOAc/petroleum ether, Rf¼0.65) to
give 17c (0.03 g, 81%) as a white solid. Mp 138–40 ꢀC;
FTIR (KBr) cmꢁ1 3373 (s), 2945, 1668 (s), 1627, 1448, 1326
4.4.33. 1-Hydroxy-3-methyl-9-phenylmethyl-9H-carb-
azole-2-carboxylic acid (18). A mixture of carbazole 17b
(0.01 g, 0.289 mmol), aqueous NaOH solution (40%,
8 mL), MeOH (10 mL), and H2O (8 mL) was heated at re-
flux for 5 h. The reaction mixture was then diluted with wa-
ter (30 mL) and extracted with ethyl acetate (3ꢂ25 mL). The
combined organic extracts were washed with water (20 mL)
and 5% HCl (10 mL), brine (20 mL), dried (Na2SO4), and
concentrated. Purification of the crude residue by chromato-
graphy (1:2 ethyl acetate/petroleum ether, Rf¼0.30) gave
compound 18 (0.07 g, 74%) as a yellow solid. Mp 180–
82 ꢀC; FTIR (KBr) cmꢁ1 3435 (br s), 2925, 1641 (s), 1619
(m), 1496, 1451, 1375, 1269, 1166, 744; 1H NMR
(200 MHz, d6-DMSO): d 10.02 (br s, 1H), 8.01 (d, 1H,
J¼8.0 Hz), 7.50–7.32 (m, 3H), 7.30–7.10 (m, 6H), 5.93 (s,
2H), 2.64 (s, 3H); 13C NMR (50 MHz, d6-DMSO):
d 152.8, 143.6, 141.5, 140.6, 139.5, 131.4, 128.5, 127.2,
126.8, 126.6, 125.5, 122.8, 120.9, 119.3, 113.4, 110.2,
109.8, 47.6, 24.2. Anal. Calcd for C20H15NO3: C, 75.70;
H, 4.76; N, 4.41. Found: C, 76.04; H, 4.94; N, 4.27.
1
(s), 1261 (m), 1141, 1002, 808, 748; H NMR (200 MHz,
CDCl3): d 12.0 (s, 1H), 8.41 (br s, 1H), 8.01 (d, 1H,
J¼8.0 Hz), 7.48–7.42 (m, 1H), 7.40 (s, 1H), 7.24–7.16 (m,
2H), 4.0 (s, 3H), 2.68 (s, 3H); 13C NMR (50 MHz, CDCl3):
d 173.1, 150.2, 140.4, 130.8, 127.2, 127.1, 127.0, 122.7,
121.1, 119.6, 113.8, 111.3, 107.7, 51.9, 24.4; HRMS ESI:
for C15H13NO3 [M+H]+ calcd 256.0974, found 256.0964.
4.4.34. 3-Methyl-9-phenylmethyl-9H-carbazole-1-ol (19).
A mixture of carbazole 17b (0.01 g, 0.289 mmol), aqueous
KOH solution (40%, 8 mL), MeOH (10 mL), and H2O
(8 mL) was heated at reflux for 5 h. The reaction mixture
was diluted with water (30 mL) and extracted with ethyl
acetate (3ꢂ25 mL). The combined organic extracts were
washed with water (30 mL) and 5% HCl (15 mL), brine
(20 mL), dried (Na2SO4), and concentrated. Purification of
the crude residue by chromatography (3:7 ethyl acetate/pe-
troleum ether, Rf¼0.56) gave compound 19 (0.047 g, 56%)
as a brownish liquid. FTIR (KBr) cmꢁ1 3042, 2922, 2852,
1616, 1587, 1500, 1454, 1296, 1227, 1120, 1090, 975,
748; 1H NMR (200 MHz, CDCl3) d 8.03 (d, 1H,
J¼8.0 Hz), 7.52 (s, 1H), 7.42–7.10 (m, 8H), 6.60 (s, 1H),
5.85 (s, 2H), 4.90 (br s, 1H), 2.46 (s, 3H). No attempt
was made for preparing an analytical sample due to its pro-
pensity to decomposition on silica gel chromatography or
standing.
4.4.30. Dimethyl 1-hydroxy-9-(phenylmethyl)-9H-carb-
azole-2,3-dicarboxylate (17d). This compound was pre-
pared as a white solid in 85% yield by condensation
between 7e and dimethyl maleate, following the general pro-
cedure for the LDA promoted annulation (method A). Mp
1
158–160 ꢀC; H NMR (200 MHz, CDCl3) d 11.38 (s, 1H),
8.02 (d, 1H, J¼8.0 Hz), 7.83 (s, 1H), 7.53–7.40 (m, 2H),
7.35–7.12 (m, 6H), 5.97 (s, 2H), 3.94 (s, 3H), 3.93 (s, 3H);
13C NMR (50 MHz, CDCl3) d 170.5, 169.7, 149.5, 141.8,
137.9, 128.9, 128.3, 127.3, 126.9, 126.3, 126.1, 125.0,
122.3, 120.7, 120.09, 112.7, 109.9, 106.2, 52.4, 52.2, 48.3;
HRMS ESI: for C23H19NO5 [M+H]+ calcd 390.1341, found
390.1332. Anal. Calcd for C23H19NO5: C, 70.94; H, 4.92; N,
3.60. Found: C, 70.82; H, 4.77; N, 3.78.
4.4.31. Methyl 1-hydroxy-6-methoxy-3-methyl-9-(phe-
nylmethyl)-9H-carbazole-2-carboxylate (17e). This com-
pound was prepared as a white solid in 58% yield by
condensation between 7f and methyl crotonate, following
the general procedure for the LDA promoted annulation
(method A). Mp 146–48 ꢀC; FTIR (KBr) 3235, 2923 (s),
2852, 1666 (s), 1626 (s), 1623, 1560, 1498 (m), 1310,
4.4.35. 1-Methoxy-3-methyl-9-phenylmethyl-9H-carb-
azole (20). This compound was prepared from 19 as a light
brown solid in 77% yield, following general procedure for
the O-methylation of phenolic compounds (as in Section
4.4). Mp 95–97 ꢀC; 1H NMR (200 MHz, CDCl3) d 8.04 (d,
1H, J¼8.0 Hz), 7.53 (s, 1H), 7.40–7.30 (m, 2H), 7.23–7.10
(m, 6H), 6.76 (s, 1H), 5.85 (s, 2H), 3.86 (s, 3H), 2.53 (s,
3H); 13C NMR (50 MHz, CDCl3): d 146.6, 141.1, 139.3,
129.2, 128.4, 128.2, 126.8, 126.3, 125.5, 124.8, 123.0,
120.2, 118.8, 112.7, 109.3, 109.1, 55.6, 48.6, 21.6; HRMS:
for C21H19NO [M+H]+ calcd 302.1545, found 302.1538.
1
1239 (m), 1155, 983, 756; H NMR (200 MHz, CDCl3)
d 12.34 (s, 1H), 7.45 (d, 1H, J¼2.5 Hz), 7.38 (s, 1H),
7.30–7.0 (m, 7H), 5.91 (s, 2H), 4.0 (s, 3H), 3.90 (s, 3H),
2.67 (s, 3H); MS ESI [M+H]+ 376.2. Anal. Calcd for
C23H21NO4: C, 73.58; H, 5.64; N, 3.73. Found: C, 73.86;
H, 5.78; N, 3.86. 13C NMR could not be recorded due to
the poor solubility in common deuterated solvents.

3780
D. Mal et al. / Tetrahedron 63 (2007) 3768–3781
6. For the synthesis from nitrogen substituted biaryls, see: (a)
Freeman, A. W.; Urvoy, M.; Criswell, M. E. J. Org. Chem.
2005, 70, 5014–5019; (b) Smitrovich, J. H.; Davis, I. W. Org.
Anal. Calcd for C21H19NO: C, 83.69; H, 6.35; N, 4.65.
Found: C, 83.52; H, 6.42; N, 4.54.
€
Lett. 2004, 6, 533–535; (c) Knolker, H.-J. Chem. Soc. Rev.
Acknowledgements
€
€
1999, 28, 151–157; (d) Knolker, H.-J.; Frohner, W.; Reddy,
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Witulski, B.; Alayrac, C. Angew. Chem., Int. Ed. 2002, 41,
Financial support was provided by the DST, New Delhi and
CSIR, New Delhi. B.K.S. and P.P. gratefully acknowledge
the receipt of their Senior Research Fellowships of the
CSIR, New Delhi. The authors are thankful to Mr. Snehadri
Narayan Khatua for X-ray crystallographic analyses.
€
€
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