Domino carbocationic rearrangement of Aryl-2-(1-N-methyl/benzyl-3-indolyl)cyclopropyl ketones: A serendipitous route to 1H-cyclopenta[c]carbazole framework

Article abstract of DOI:10.1021/jo025827l

Aryl-2-(N-methyl/benzyl-3-indolyl)cyclopropyl ketones 2a-m are shown to undergo a novel unexpected domino carbocationic rearrangement in the presence of SnCl₄/CH₃NO₂ yielding 2-aroyl-3-aryl-1H-cyclopenta [c] carbazoles 3a-m in good yields. The possible mechanistic pathway for this interesting transformation involves a series of cascade events, (a) electrophilic ring opening of cyclopropyl ketone, (b) intermolecular enol capture of the resulting zwitterionic intermediate, (c) electrophilic dimerization of indole moieties to give tetrahydrocarbazole intermediate and its subsequent aromatization by elimination of an indole moiety and dehydrogenation, and (d) intramolecular aldol condensation of the side chain to give a cyclopentene ring. The overall transformation involves formation of three carbon-carbon bonds along with a fused benzene and a substituted cyclopentene ring in one-pot operation from simple indole precursors.

Full text of DOI:10.1021/jo025827l

cyclization by means of stabilized zwitterionic intermedi-
ates.8 We have previously described in a series of papers
a novel carbocationic domino process that relies upon
initial electrophilic ring opening of 2-aryl(or styryl)-
cyclopropyl[bis(methylthio)methylene]alkyl ketones or
carbinols and subsequent intramolecular 5-exo-trig cap-
ture of the resulting carbocation by electron-rich bis-
(methylthio)methylene double bond to give a cyclopen-
tane ring bearing a stable bis(methylthio)methyl carbo-
cationic side chain.9 Subsequent trapping of this car-
bonium ion by electron-rich pendant arene or olefinic
nucleophiles affords cyclopentanoindane,10a,b diquinane,10b
bicyclo[3.2.1]octane,10c or 1-arylindane10d frameworks in-
volving a series of rearrangement and termination events.
We have also reported earlier the synthesis and Lewis
acid induced rearrangement of novel push-pull cyclo-
propyl ketones derived from vinylogous oxoketene dithio-
acetals furnishing substituted and spirocyclopentenes in
good yields.11 Recently, we have developed a highly regio-
and stereoselective synthesis of polyene esters via an
interesting even number 1,4- to 1,12-reductive and alkyl-
ative carbonyl transposition strategy involving these
novel push-pull cyclopropyl ketones.12 In the course of
these studies, we became interested in examining Lewis
acid induced rearrangement of aryl 2-(N-methyl/benzyl-
3-indolyl)cyclopropyl ketones of the general structure 2
that, to our surprise, yielded novel 2,3-substituted 1H-
cyclopenta[c]carbazoles 3 in good yields (Scheme 1). We
report in this paper the results of this new domino
carbocationic process that entails a series of cascade
events involving intermolecular trapping of zwitterionic
intermediate with concomitant formation of three carbon-
carbon bonds along with a fused benzene and substituted
Dom in o Ca r boca tion ic Rea r r a n gem en t of
Ar yl-2-(1-N-m eth yl/
ben zyl-3-in d olyl)cyclop r op yl Keton es:
A Ser en d ip itou s Rou te to
1H-Cyclop en ta [c]ca r ba zole F r a m ew or k
C. Venkatesh,† H. Ila,*,† H. J unjappa,*,†
Sanjay Mathur,‡ and Volka Huch‡
Department of Chemistry, Indian Institute of Technology,
Kanpur-208016, India, and Institute of Inorganic
Chemistry, Saarland University,
D-66041 Saarbruecken, Germany
hila@iitk.ac.in
Received April 16, 2002
Abstr a ct: Aryl-2-(N-methyl/benzyl-3-indolyl)cyclopropyl ke-
tones 2a -m are shown to undergo a novel unexpected dom-
ino carbocationic rearrangement in the presence of SnCl4/
CH3NO2 yielding 2-aroyl-3-aryl-1H-cyclopenta[c]carbazoles
3a -m in good yields. The possible mechanistic pathway for
this interesting transformation involves a series of cascade
events, (a) electrophilic ring opening of cyclopropyl ketone,
(b) intermolecular enol capture of the resulting zwitterionic
intermediate, (c) electrophilic dimerization of indole moieties
to give tetrahydrocarbazole intermediate and its subsequent
aromatization by elimination of an indole moiety and dehy-
drogenation, and (d) intramolecular aldol condensation of
the side chain to give a cyclopentene ring. The overall trans-
formation involves formation of three carbon-carbon bonds
along with a fused benzene and a substituted cyclopentene
ring in one-pot operation from simple indole precursors.
Cationic olefinic cyclizations initiated by acid-induced
ring opening of rigid or nonrigid cyclopropyl ketones
followed by intramolecular participation of suitably
disposed olefinic centers are shown to be useful synthetic
transformations in organic chemistry.1,2 The possibility
of initiating a tandem or domino carbocationic cyclization
involving olefinic participation and efficient trapping of
the resulting carbocation by the enol generated via
acylcyclopropane ring opening has also been demon-
strated.2c,3 This strategy has been successfully employed
by Corey and co-workers in the synthesis of (()-cedrene
and (()-cedrol.4 Murphy has reported simple routes to
1-aryltetralones,5 related lignans,6 and other polycyclic
carbon skeletons7 via Lewis acid induced ring opening
of arylcyclopropyl ketones and endocyclic capture of the
resulting formal or incipient carbocation by an aryl group.
Of particular interest are donor- and acceptor-substituted
cyclopropyl ketones that undergo facile ring opening and
(5) (a) Murphy, W. S.; Wattanasin, S. Tetrahedron Lett. 1980, 21,
1887. (b) Murphy, W. S.; Wattanasin, S. J . Chem. Soc., Perkin Trans.
1 1981, 2920. (c) Murphy, W. S.; Wattanasin, S. Tetrahedron Lett. 1980,
21, 3517. (d) Murphy, W. S.; Wattanasin, S. J . Chem. Soc., Perkin
Trans. 1 1982, 1029.
(6) (a) Murphy, W. S.; Wattanasin, S. J . Chem. Soc., Chem. Com-
mun. 1980, 262. (b) Murphy, W. S.; Wattanasin, S. J . Chem. Soc.,
Perkin Trans. 1 1982, 271.
(7) (a) Hantawong, K.; Murphy, W. S.; Russell, N. Tetrahedron Lett.
1984, 25, 999. (b) Murphy, W. S.; Culhane, A.; J uo, R.-R. J . Chem.
Soc., Perkin Trans. 1 1989, 2123.
(8) (a) Harvey, D. F.; Brown, M. F. Tetrahedron Lett. 1991, 32, 2871.
(b) Sakito, Y.; Suzukamo, G. Chem. Lett. 1986, 621. (c) Davies, H. M.
L.; Hu, B. J . J . Org. Chem. 1992, 57, 4309. (d) Davies, H. M. L.; Hu,
B. Tetrahedron Lett. 1992, 33, 453. (e) Davies, H. M. L.; Clark, T. J .;
Church, L. A. Tetrahedron Lett. 1989, 30, 5057. (f) Reissig, H.-U. Top.
Curr. Chem. 1988, 144, 73. (g) Kunz, T.; Reissig, H.-U. Tetrahedron
Lett. 1989, 30, 2079. (h) Wienand, A.; Reissig, H.-U. Chem. Ber. 1991,
124, 957. (i) Doyle, M. P.; Leusen, D. V. J . Org. Chem. 1982, 47, 5326.
(j) Dowd, P.; Kaufman, C. Paik, Y. H. Tetrahedron Lett. 1985, 26, 2283.
(k) Davies, H. M. L.; Hu, B. J . Org. Chem. 1992, 57, 3186.
(9) (a) Deb, B.; Asokan, C. V.; Ila, H.; J unjappa, H. Tetrahedron Lett.
1988, 29, 2111. (b) Deb, B.; Ila, H.; J unjappa, H. J . Chem. Res., Synop.
1990, 356; J . Chem. Res., Miniprint 1990, 2728. (c) Patro, B.; Deb, B.;
Ila, H.; J unjappa, H. J . Org. Chem. 1992, 57, 2257. (d) Patro, B.; Deb,
B.; Ila, H.; J unjappa, H. Tetrahedron 1994, 50, 255.
* To whom correspondence should be addressed. Fax: 91-0512-
597436, 91-0512-590260.
† Indian Institute of Technology.
‡ Saarland University.
(1) Review: (a) Wong, H. N. C.; Hon, M.-Y.; Tse, C.-W.; Yip, Y.-C.;
Tanko, J .; Hudlicky, T. Chem. Rev. 1989, 89, 165. (b) Wenkert, E. Acc.
Chem. Res. 1980, 13, 27. (c) Wenkert, E.; Arrhenius, T. S. J . Am. Chem.
Soc. 1983, 105, 2030.
(2) (a) Stork, G.; Marx, M. J . Am. Chem. Soc. 1969, 91, 2371. (b)
Stork, G.; Gregson, M. J . J . Am. Chem. Soc. 1969, 91, 2373. (c) Stork,
G.; Grieco, P. A. J . Am. Chem. Soc. 1969, 91, 2407.
(3) (a) Stork, G.; Grieco, P. A. Tetrahedron Lett. 1971, 1807. (b)
Grieco, P. A.; Finkelhor, R. S. Tetrahedron Lett. 1974, 527.
(4) Corey, E. J .; Balanson, R. D. Tetrahedron Lett. 1973, 3153.
(10) (a) Patra, P. K.; Patro, B.; Ila, H.; J unjappa, H. Tetrahedron
Lett. 1993, 34, 3951. (b) Patra, P. K.; Sriram, V.; Ila, H.; J unjappa, H.
Tetrahedron 1998, 54, 531. (c) Syam Kumar, U. K.; Patra, P. K. Ila,
H.; J unjappa, H. J . Chem. Soc., Perkin Trans. 1 2000, 1547. (d)
Mohanta, P. K.; Peruncheralathan, S.; Ila, H.; J unjappa, H. J . Org.
Chem. 2001, 66, 1503.
(11) Satyanarayana, J .; Basaveswara Rao, M. V.; Ila, H.; J unjappa,
H. Tetrahedron Lett. 1996, 37, 3565.
(12) Satyanarayana, J .; Siddiqui, I.; Ila, H.; J unjappa, H. Indian J .
Chem. 2001, 40B, 948.
10.1021/jo025827l CCC: $22.00 © 2002 American Chemical Society
Published on Web 11/23/2002
J . Org. Chem. 2002, 67, 9477-9480
9477

SCHEME 1
SCHEME 2
TABLE 1. Sn Cl4-In d u ced Rea r r a n gem en t of th e
Cyclop r op yl Keton e 2a
SnCl4
timea yieldb (%) yieldb (%)
entry substrate (equiv) solvent
(h)
3a
7a
1
2
3
4
5
6
7
2a
2a
2a
2a
2a
2a
2a
1.5
1.5
0.5
1.0
2.0
1.5
1.5
CH3NO2 5.0
CH3NO2 0.5
CH3NO2 5.0
CH3NO2 5.0
CH3NO2 5.0
60
cyclopentene ring in a one-pot operation from simple
indole precursors.
62
71
44
15
35
61
47
5
The desired aryl-2-(N-methyl/benzyl-3-indolyl)cyclo-
propyl ketones 2a -m were readily obtained in nearly
quantitative yields by cyclopropanation of the respective
1-aryl-3-(3-indolyl)-2-propen-1-ones 1a -m with dimeth-
ylsulfoxonium methylide generated from the correspond-
ing sulfonium salts in the presence of sodium hydride in
THF/DMF (Scheme 1, Table 2). These cyclopropyl ketones
CH2Cl2
C6H6
6.0
6.0
8
83
a
b
Reactions were carried out at room temperature. Isolated
yield.
mixture yielded different product identified as the dimer-
ic tetrahydrocarbazole derivative 7a (62%) on the basis
of its spectral and analytical data (Table 1, entry 2). We
therefore carried out a detailed study of the rearrange-
ment of 2a with SnCl4 with a view to get more informa-
tion on the role of solvent polarity and substrate to SnCl4
ratio on the product profile. These results are presented
in the Table 1.
It is apparent from the above studies that the dimeric
tetrahydrocarbazole 7a is an intermediate in the forma-
tion of cyclopenta[c]carbazole 3a from the cyclopropyl
ketone 2a . To further show the generality of the reaction,
the rearrangement studies were extended to other sub-
stituted indolylcyclopropyl ketones 2b-l, which were also
transformed smoothly into the corresponding substituted
cyclopenta[c]carbazoles 3b-l in 57-69% yield when
exposed to SnCl4/CH3NO2 for 3-5 h (Table 2). No
attempts were made to isolate dimeric tetrahydrocarba-
zole intermediates 7b-l from these reactions except from
the cyclopropyl ketones 2h , which also afforded the
tetrahydrocarbazole 7h (72%) when reacted with SnCl4/
CH3NO2 for a shorter reaction time (0.5 h).14 The rear-
rangement of the corresponding N-benzylindolyl cyclo-
propyl ketone 2m to cyclopenta[c]carbazole 3m required
prolonged time (8 h) under identical conditions, whereas
workup after 3 h afforded only the tetrahydrocarbazole
dimer 7m in 72% yield (Scheme 1).
1
were pure enough for their characterization by H and
13C NMR spectra and used as such for the further
transformation.13
The ketone 2a was subjected to electrophilic ring open-
ing in the presence of common Lewis acids such as TiCl4,
BF3.Et2O or SnCl4 in various solvents. It was envisaged
that Lewis acid induced ring opening of 2, which is fur-
ther assisted by indole nitrogen lone pair, should initially
produce a stable zwitterionic intermediate 4. If the dipo-
lar intermediate 4 has longer lifetime enough to isomerize
to Z-4, there exists possibility of its intramolecular
interception by the enol moiety leading to the formation
of cyclopentano[b]indole 5 (Scheme 2). However, no cyclo-
pentano-fused derivative such as 5a (Ar ) 4-MeOC6H4)-
was observed from 2a under the influence of various
Lewis acids.
The only product formed in varying yields under these
conditions was characterized as 2-(4-methoxybenzoyl)-
3-(4-methoxyphenyl)-6-N-methyl-1H-cyclopenta[c]carba-
zole (3a ) (Scheme 1). The structure of 3a was confirmed
with the help of spectral, analytical, and X-ray crystal-
lographic data. Under optimized conditions, the rear-
rangement of 2a to 3a was found to be most facile and
clean (in terms of yield and workup) with SnCl4 in
nitromethane affording 3a in 60% yield after 5 h (Table
1, entry 1). However, when the same reaction was run
for a shorter reaction time (0.5 h), workup of the reaction
The possible mechanism for the formation of the
observed products 3 is shown in Scheme 3. The Lewis
acid assisted ring opening of cyclopropyl ketones 2
produces expected zwitterionic intermediate 4, which is
further stabilized by delocalization of positive charge on
(13) Most of the cyclopropyl ketones 2a -l were obtained as viscous
liquids, whereas the corresponding N-benzylcyclopropyl ketone 2m
could be purified by recrystallization from hexanes-ethyl acetate to
give analytically pure sample.
9478 J . Org. Chem., Vol. 67, No. 26, 2002

TABLE 2. 2,3-Su bstitu ted 1H-Cyclop en ta [c]ca r ba zole
3a -m
SCHEME 3
time yield 3
entry
1
2
X
Ar
R
3
(h)
(%)
1
2
3
4
1a 2a
1b 2b
1c 2c
1d 2d
H
H
H
H
4-MeOC6H4
C6H5
3,4-(MeO)2C6H3 Me 3c
3,4-(methylene- Me 3d
dioxy)C6H3
4-ClC6H5
2-thienyl
C6H5
Me 3a
Me 3b
5
5
3
5
60
65
60
63
5
6
7
8
9
1e 2e
1f 2f
H
H
Me 3e
Me 3f
Me 3g
Me 3h
3
61
68
67
69
68
4
1g 2g Br
1h 2h Br
3
4-MeOC6H4
3,4-(methylene- Me 3i
5a
5
1i
2i
Br
dioxy)C6H3
10
11
12
13
1j
2j
MeO C6H5
Me 3j
Me 3k
Me 3l
Bn 3m
4
68
63
57
54
1k 2k MeO 4-MeOC6H4
1l 2l MeO 4-ClC6H5
1m 2m C6H5
3
5
H
8b
a
Workup after 0.5
h gave tetrahydrocarbazole 7h (72%).
b
Workup after 3 h gave only the tetrahydrocarbazole 7m (72%).
indole ring. The intermediate 4 undergoes an interesting
dimerization via intermolecular capture of one of the
zwitterionic species by the enol functionality of the other
affording the dimeric indole intermediate 8.15 Subsequent
intramolecular trapping of the 3-indolylcarbinyl cation
in the intermediate 8 by the electron-rich 2-position of
the other indole ring leads to dimeric tetrahydrocarbazole
intermediate 7, which could be isolated in a few cases
(7a , 7h , and 7m ) under varying conditions (Table 2). The
tetrahydrocarbazole intermediate 7 subsequently under-
goes a series of events, i.e., (a) Lewis acid assisted
elimination of indole,16 (b) dehydrogenation of dihydro-
carbazole, and (c) Lewis acid induced intramolecular
Aldol condensation of suitably disposed carbonyl side
chains leading to the formation of the observed cyclo-
penta[c]carbazoles 3.17
In summary, we have described a novel domino car-
bocationic rearrangement of aryl 2-(N-methyl/benzyl-3-
indolyl)cyclopropyl ketones leading to unexpected forma-
tion of 2,3-substituted 1H-cyclopenta[c]carbazoles as most
typical products in synthetically useful yields. Several
interesting pathways are involved in the final disposition
of the putative zwitterionic intermediate including an
interesting intermolecular enol capture of zwitterionic
intermediate, electrophilic dimerization along with the
elimination of indole moiety and finally an intramolecular
Aldol condensation to form an additional C-C bond and
a cyclopentene ring. These observations suggest that a
wide range of domino sequence18 can be designed involv-
ing cationic ring opening and cyclization of appropriately
substituted cyclopropyl ketones with diverse cationic
olefinic trapping groups. Our efforts in this direction are
underway and will be reported elsewhere.
(14) In one case, i.e., cyclopropyl ketone 2l, workup of the reaction
mixture after 3 h afforded the corresponding 3,4-disubstituted carba-
zole 6l (65%), which is apparently formed by aromatization of the
corresponding tetrahydrocarbazole dimer 7l through dehydrogenation
and elimination of the indole moiety. The carbazole 6l was transformed
into the corresponding cyclopenta[c]carbazole 3l either by warming of
the reaction mixture (85 °C, 0.5 h) or by further stirring (2 h) at room
temperature.
Exp er im en ta l Section
Gen er a l Meth od s. 1H NMR (400 MHz) and 13C NMR (100
MHz) spectra were recorded in CDCl3, and TMS was used as
an internal reference. Melting points are uncorrected. Chro-
matographic purification was conducted by column chromatog-
raphy using 60-120 mesh silica gel obtained from Acme
Synthetic Chemicals. X-ray crystallographic data was collected
on
a Stoe AED 2 diffractometer operating with graphite-
monochromated Mo KR (λ ) 0.710 73 A) radiation using the ω
- θ scan technique. DMF was distilled over CaH2 and stored
over molecular sieves. THF was distilled over sodium/benzophe-
none prior to use. NaH (as 40% suspension in oil), SnCl4 and
nitromethane (AR grade) were purchased from standard firms
and used directly. 1-N-Methylindole-3-aldehyde and the corre-
sponding N-benzyl derivative were prepared according to a
(15) Sheu, J .-H.; Chen, C.-A.; Chen, B.-H. J . Chem. Soc., Chem.
Commun. 1999, 203.
(16) In one case (2k ), the 5-methoxyindole could be isolated in 10%
yield. For acid induced elimination of indole: Stachel, S. J .; Nilges,
M.; Van Vranken, D. L. J . Org. Chem. 1997, 62, 4756. The possible
mechanism for elimination of indole can be shown as follows:
(17) The slower rate of the conversion of N-benzyltetrahydrocarba-
zole dimer 7m to the corresponding cyclopenta[c]carbazole 3m is
probably due to bulkier N-benzyl group resisting elimination of
N-benzylindole and intramolecular Aldol condensation steps.
(18) Review: (a) Tietze, L. F. Chem. Rev. 1996, 96, 115. (b) Tietze,
L. F.; Beifuss, U. Angew. Chem., Int. Ed. Engl. 1993, 32, 131. (c) Bunce,
R. A. Tetrahedron 1995, 51, 13103. (d) Thebtranonth, C.; Thebtranonth,
Y. Tetrahedron 1990, 46, 1385. (e) Ho. T.-L. Tandem Reactions in
Organic Synthesis; Wiley-Interscience: NewYork, 1992. (f) Thematic
issue. Frontiers in Organic Synthesis; Wender, P. A., Guest Ed. Chem.
Rev. 1996, 96, 31.
J . Org. Chem, Vol. 67, No. 26, 2002 9479

reported procedure.19 The known20 indole chalcones 1a -c,e and
the unknown 1d ,1f-m were prepared according to a literature
procedure21 in nearly quantitative yields.
9-Br om o-2-(4-m eth oxyben zoyl)-3-(4-m eth oxyp h en yl)-6-
N-m eth yl-1H-cyclop en ta [c]ca r ba zole (3h ): yield 69% (0.19
g); yellow crystals; mp 230-231 °C; Rf 0.51 (3.0:1.0 hexanes-
1
EtOAc); IR (KBr) 3064, 2927, 1600, 1471, 1350, 1245 cm-1; H
Gen er a l P r oced u r e for th e P r ep a r a tion of Cyclop r op yl
Keton es (2a -m ). A suspension of NaH (0.12 g, 2 mmol, 40%)
and trimethylsulfoxonium iodide (0.26 g, 1.2 mmol) in THF/DMF
(12 mL, 5:1) was stirred at 0 °C for 0.5 h under N2 atmosphere.
It was then brought to room temperature, and a solution of
1-aryl-3-(1-N-methyl/benzyl-3-indolyl)-2-propen-1-one 1 (1 mmol)
in THF (2 mL) was added dropwise followed by further stirring
for 15 min (monitored by TLC). The reaction mixture was poured
into ice-cooled saturated NH4Cl solution (20 mL) and extracted
with chloroform (4 × 25 mL). The organic extracts were
combined, washed with water (3 × 50 mL) and brine (1 × 25
mL), and dried (Na2SO4), and the solvent was evaporated under
reduced pressure to afford the crude cyclopropyl ketone 2, which
was pure enough for characterization by 1H and 13C NMR
spectra.
1-P h en yl-2-(1-N-m eth yl-3-in dolyl)cyclopr opyl keton e (2b):
yield 98% (0.27 g); viscous liquid; Rf 0.90 (9.5:0.5 benzene-
EtOAc); 1H NMR (400 MHz, CDCl3) δ 1.59 (ddd, J ) 7.8, 6.8,
3.7 Hz, 1H, CH), 1.93 (ddd, J ) 8.9, 4.9, 3.6 Hz, 1H, CH), 2.79-
2.81 (m, 1H, CH), 2.85 (ddd, J ) 8.8, 4.6, 4.9 Hz, 1H, CH), 3.72
(s, 3H, NCH3), 6.85 (s, 1H, ArH), 7.08 (t, J ) 6.8 Hz, 1H, ArH),
7.21-7.29 (m, 2H, ArH), 7.43 (t, J ) 7.3 Hz, 2H, ArH), 7.53 (t,
J ) 7.3 Hz, 1H, ArH), 7.59 (d, J ) 8.0 Hz, 1H, ArH), 8.00-8.02
(m, 2H, ArH); 13C NMR (100 MHz, CDCl3) δ 17.7, 22.6, 27.9,
32.6, 109.3, 114.7, 118.9, 119.2, 121.9, 125.8, 127.9, 128.0, 128.5,
132.7, 137.0, 137.9, 199.2; MS (m/z) 275 (M+, 11.2), 77 (100).
Gen er a l P r oced u r e for th e Sn Cl4-In d u ced Rea r r a n ge-
m en t of Cyclop r op yl Keton es 2a -m to Cyclop en ta [c]-
ca r ba zoles 3a -m a n d Tetr a h yd r oca r ba zoles 7a ,h ,m . To a
solution of cyclopropyl ketone 2 (1 mmol) in nitromethane (25
mL) was added dropwise a solution of SnCl4 (0.18 mL, 1.5 mmol)
in nitromethane (5 mL) over a period of 0.5 h at 0 °C, and the
reaction mixture was further stirred at ambient temperature
for 3-8 h (monitored by TLC). It was then diluted with ice-cooled
saturated NaHCO3 solution (20 mL) and extracted with chlo-
roform (4 × 25 mL). The organic extracts were combined, washed
with water (3 × 25 mL) and brine (1 × 25 mL), and dried (Na2-
SO4), and the solvent was evaporated under reduced pressure
to afford crude products 3a -m which were purified by passing
through silica gel column using hexanes-ethyl acetate as eluent.
The tetrahydrocarbazoles 7a ,h ,m were isolated when the reac-
tions were run for 0.5 h (for 7a and 7h ) and 3 h (for 7m ),
respectively. The cyclopropyl ketone 2l gave the 3,4-disubstituted
carbazole 6l under the above conditions after 3 h, whereas the
cyclopenta[c]carbazole 3l was obtained by stirring the reaction
mixture for 5 h or by warming the reaction mixture at 85 °C for
0.5 h.
NMR (400 MHz, CDCl3) δ 3.72 (s, 3H, OCH3), 3.73 (s, 3H, OCH3),
3.78 (s, 3H, NCH3), 4.28 (s, 2H, CH2), 6.59 (d, J ) 8.5 Hz, 2H,
ArH), 6.72 (d, J ) 8.5 Hz, 2H, ArH), 7.22 (d, J ) 8.6 Hz, 3H,
ArH), 7.28 (d, J ) 8.3 Hz, 1H, ArH), 7.53 (dd, J ) 8.7, 1.7 Hz,
1H, ArH), 7.56 (d, J ) 8.8 Hz, 3H, ArH), 8.15 (d, J ) 1.7 Hz,
1H, ArH); 13C NMR (100 MHz, CDCl3) δ 29.4, 39.5, 55.2, 55.3,
107.4, 109.9, 112.2, 112.9, 113.6, 118.1, 120.9, 123.8, 124.3, 127.1,
128.3, 130.8, 131.1, 131.5, 136.8, 137.0, 138.1, 139.9, 141.2, 150.3,
159.3, 162.2, 193.9; MS (m/z) 538 (M+, 100). Anal. Calcd for
C31H24NO3Br (538.41): C, 69.14; H, 4.49; N, 2.60. Found: C,
69.09; H, 4.57; N, 2.53.
2-(4-Ch lor oben zoyl)-3-(4-ch lor op h en yl)-9-m eth oxy-6-N-
m eth yl-1H-cyclop en ta [c]ca r ba zole (3l): yield 66% (0.15 g);
yellow crystals; mp 224-225 °C; Rf 0.53 (8.5:1.5 hexanes-
1
EtOAc); IR (KBr) 3074, 2934, 1597, 1483, 1342 cm-1; H NMR
(400 MHz, CDCl3) δ 3.87 (s, 3H, OCH3), 3.98 (s, 3H, NCH3), 4.43
(s, 2H, CH2), 7.09 (d, J ) 8.1 Hz, 2H, ArH), 7.18-7.20 (m, 5H,
ArH), 7.34 (d, J ) 8.5 Hz, 1H, ArH), 7.37 (d, J ) 9.0 Hz, 1H,
ArH), 7.45 (t, J ) 8.8 Hz, 3H, ArH), 7.63 (d, J ) 2.4 Hz, 1H,
ArH); 13C NMR (100 MHz, CDCl3) δ 29.5, 39.3, 56.3, 104.9, 107.7,
109.5, 115.1, 119.0, 120.3, 122.5, 127.8, 128.3, 130.4, 130.8, 133.1,
134.2, 135.3, 136.5, 137.0, 137.2, 137.6, 138.4, 142.0, 152.2, 154.2,
193.4; MS (m/z) 498 (M+, 68). Anal. Calcd for C30H21NO2Cl2
(498.38): C, 72.29; H, 4.24; N, 2.81. Found: C, 72.37; H, 4.29;
N, 2.78.
3-(4-Ch lor oben zoyl)-6-m eth oxy-9-N-m eth yl-4-[2′-(4-ch lo-
r oben zoyl)-eth yl]ca r ba zole (6l): yield 65% (0.17 g); yellow
crystals; mp 186-187 °C; Rf 0.75 (3.0:1.0 hexanes-EtOAc); IR
(KBr) 3068, 2924, 1676, 1642, 1582, 1480 cm-1 1H NMR (400
;
MHz, CDCl3) δ 3.61-3.72 (m, 4H, CH2-CH2), 3.87 (s, 3H, OCH3),
3.88 (s, 3H, NCH3), 7.18 (dd, J ) 8.9, 2.4 Hz, 1H, ArH), 7.26 (d,
J ) 7.6 Hz, 1H, ArH), 7.38 (d, J ) 9.0 Hz 1H, ArH), 7.41-7.47
(m, 5H, ArH), 7.77-7.79 (m, 3H, ArH), 8.01 (d, J ) 8.8 Hz, 2H,
ArH); 13C NMR (100 MHz, CDCl3) δ 26.6, 29.3, 39.2, 56.0, 105.4,
105.5, 109.5, 115.5, 121.4, 122.5, 127.9, 128.4, 128.5, 128.9, 129.7,
131.8, 134.9, 136.4, 137.6, 138.4, 138.9, 139.5, 142.8, 154.4, 197.1,
198.9; MS (m/z) 516(M+, 62), 515 (100). Anal. Calcd for C30H23
-
NO3Cl2 (516.39): C, 69.77; H, 4.48; N, 2.71. Found: C, 69.74;
H, 4.56; N, 2.83.
3-(4-Met h oxyb en zoyl)-9-N-m et h yl-1-(1-N-m et h yl-3-in -
d olyl)-4-[2′-(4-m et h oxyb en zoyl)et h yl]-1,2,3,4-t et r a h yd r o-
ca r ba zole (7a ): yield 62% (0.19 g); yellow crystals; mp 177-
178 °C; Rf 0.50 (3.0:1.0 hexanes-EtOAc); IR (KBr) 3049, 2933,
1666, 1597, 1466, 1257 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.21
(ddd, J ) 12.6, 12.3, 4.6 Hz, 1H, CH), 2.32-2.39 (m, 2H, CH2),
2.64 (d, J ) 12.7 Hz, 1H, CH), 2.69-2.84 (m, 2H, CH2), 3.53 (s,
3H, OCH3), 3.65-3.67 (m, 1H, CH), 3.70 (s, 3H, OCH3), 3.75 (s,
3H, NCH3), 3.81 (s, 3H, NCH3), 4.03-4.08 (m, 1H, CH), 4.64 (t,
J ) 4.3 Hz, 1H, CH), 4.64 (brs, 1H, ArH), 6.51-6.55 (m, 3H,
ArH), 6.77 (d, J ) 8.8 Hz, 2H, ArH), 7.13 (dt, J ) 7.8, 0.9 Hz,
2H, ArH), 7.21-7.25 (m, 1H, ArH), 7.29-7.34 (m, 1H, ArH), 7.39
(d, J ) 8.3 Hz, 1H, ArH), 7.43 (d, J ) 8.8 Hz, 2H, ArH), 7.60 (d,
J ) 8.1 Hz, 1H, ArH), 7.67 (d, J ) 8.8 Hz, 2H, ArH), 7.75 (d, J
) 7.8 Hz, 1H, ArH); 13C NMR (100 MHz, CDCl3) δ 28.5, 29.2,
30.2, 32.8, 34.0, 34.7, 35.3, 43.4, 55.3, 55.4, 108.8, 109.5, 111.5,
113.4, 113.5, 116.0, 118.9, 119.1, 119.3, 119.7, 120.9, 122.0, 126.3,
126.5, 128.4, 129.0, 129.8, 130.2, 130.6, 137.1, 137.4, 137.6, 163.1,
163.2, 199.0, 200.7; MS (m/z) 611 (M+, 100), 480 (42), 460 (90).
Anal. Calcd for C40H38N2O4 (610.72): C, 78.66; H, 6.27; N, 4.58.
Found: C, 78.60; H, 6.21; N, 4.62.
2-(4-Meth oxyben zoyl)-3-(4-m eth oxyp h en yl)-6-N-m eth yl-
1H-cyclop en ta [c]ca r ba zole (3a ): yield 60% (0.14 g); yellow
crystals; mp 219-220 °C; Rf 0.56 (9.5:0.5 benzene-EtOAc); IR
(KBr) 3531, 3407, 1608, 1501, 1349, 1248 cm-1 1H NMR (400
;
MHz, CDCl3) δ 3.75 (s, 3H, OCH3), 3.76 (s, 3H, OCH3), 3.90 (s,
3H, NCH3), 4.43 (s, 2H, CH2), 6.62 (d, J ) 8.6 Hz, 2H, ArH),
6.76 (d, J ) 8.6 Hz, 2H, ArH), 7.27 (dd, J ) 8.5, 3.2 Hz, 2H,
ArH), 7.32-7.39 (m, 3H, ArH), 7.46 (d, J ) 8.3 Hz, 1H, ArH),
7.54 (t, J ) 7.1 Hz, 1H, ArH), 7.60 (dd, J ) 6.5, 2.1 Hz, 2H,
ArH), 8.19 (d, J ) 7.9 Hz, 1H, ArH); 13C NMR (100 MHz, CDCl3)
δ 29.4, 39.6, 55.2, 55.3, 107.2, 108.6, 112.8, 113.5, 119.2, 119.5,
120.3, 122.0, 122.3, 125.8, 127.3, 130.9, 131.3, 131.6, 136.5, 136.9,
138.1, 141.1, 141.4, 150.7, 159.2, 162.2, 194.2; MS (m/z) 459 (M+,
37.2), 326 (23.7), 325 (85.3), 135 (100). Anal. Calcd for C31H25
-
NO3 (459.51): C, 81.02; H, 5.48; N, 3.04. Found: C, 81.13; H,
5.75; N, 3.21.
Ack n ow led gm en t. C.V. thanks CSIR for a junior
research fellowship. Financial assistance under a CSIR
project is also acknowledged.
(19) (a) J ames, P. N.; Synder, H. R. In Organic Syntheses; Rabjohn,
N., Ed.; J ohn Wiley and Sons: NewYork, 1963; Collect. Vol. 4, p 539.
(b) Ottoni, O.; Cruz, R.; Alves, R. Tetrahedron 1998, 54, 13915.
(20) (a) Tsukerman, S. V.; Bugai, A. I.; Nikitchenko, V. M.; Lavrushin,
V. F. Chem. Heterocycl. Compd. 1970, 6, 370. (b) Van Order, R. B.;
Lindwall, H. G. J . Org. Chem. 9145, 10, 128.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectral data for compounds 2a ,e,m , 3b-g,i-k ,m , and 7h ,m .
This material is available free of charge via the Internet at
http://pubs.acs.org.
(21) Miguel, J . F. Bull. Soc. Chim. Fr. 1961, 1369.
J O025827L
9480 J . Org. Chem., Vol. 67, No. 26, 2002