Regioselective synthesis of mono- and bis-decahydrobenzocarbazoles via tandem reactions of α-diazo ketones

Article abstract of DOI:10.1016/j.tet.2004.06.053

Regioselective intermolecular 1,3-dipolar cycloaddition reactions of rhodium generated carbonyl ylides with indoles are reported in this paper. Intermolecular 1,3-dipolar cycloaddition reactions of five-membered-ring cyclic carbonyl ylides with indole and

Full text of DOI:10.1016/j.tet.2004.06.053

Tetrahedron 60 (2004) 7885–7897
Regioselective synthesis of mono- and bis-decahydrobenzo-
q
carbazoles via tandem reactions of a-diazo ketones
*
Sengodagounder Muthusamy, Chidambaram Gunanathan and Eringathodi Suresh
Department of Organic Chemistry, Central Salt and Marine Chemicals Research Institute, GB Marg, Bhavnagar 364 002, India
Received 29 February 2004; revised 19 May 2004; accepted 10 June 2004
Available online 15 July 2004
Abstract—Regioselective intermolecular 1,3-dipolar cycloaddition reactions of rhodium generated carbonyl ylides with indoles are reported
in this paper. Intermolecular 1,3-dipolar cycloaddition reactions of five-membered-ring cyclic carbonyl ylides with indole and substituted
indoles afforded hexahydro-2H-carbazol-2-ones in a regioselective manner. Similarly, reactions of cyclic carbonyl ylides were carried out to
afford decahydrobenzo[c]carbazoles or decahydrocyclopenta[c]carbazoles with high regioselectivity. Interestingly, the other possible
regioisomer decahydrobenzo[a]carbazoles were also obtained by the reaction of cyclic carbonyl ylides and indoles having electron
withdrawing substituents. The structure and stereochemistry of regioisomers 6,11c-epoxy-1,2,3,4,4a,5,6,6a,11b,11c-decahydro-4a-methyl-
5
-oxo-7H-benzo[c]carbazole and 11-benzenesulfonyl-6,11b-epoxy-2,3,4,4a,5,6,6a,11,11a,11b-decahydro-4a-methyl-5-oxo-1H-benzo[a]-
carbazole were unequivocally corroborated by single-crystal X-ray analyses. To advance this study, regioselective double 1,3-dipolar
cycloaddition reaction of five-membered-ring cyclic carbonyl ylides has been demonstrated for the first time with biindoles having various
aryl and alkyl spacers. This process constructed up to eight stereocenters, four carbon–carbon and two carbon–oxygen bonds in a single step
with an excellent molecular complexity and stereoselectivity.
q 2004 Elsevier Ltd. All rights reserved.
1
. Introduction
of a variety of heterocyclic systems. Reactions based on
carbenoid transformations are among the synthetically most
useful to increase the molecular complexity. Carbenoid
3
Achieving the maximum pertinent complexity increase
while minimizing step count is an ideal synthesis in organic
chemistry. Reaction leading to many carbon–carbon bond
reactions provide transient carbonyl ylides, which can
readily be trapped inter- or intramolecularly with p-bonds
via a range of 1,3-dipolar cycloaddition reactions to afford
oxygen-containing polycyclic systems that are amenable
to further diverse transformations. Pioneering studies by
Padwa and co-workers have established Rh(II)-catalyzed
tandem carbonyl ylide formation-1,3-dipolar cycloaddition
of diazo carbonyl compounds as an excellent method for the
synthesis of oxapolycycles. The carbonyl ylide 1,3-dipolar
cycloaddition methodology has been applied to the
1
formations through tandem processes, which can rapidly
generate the molecular complexity in a controlled and
predictable manner, is a contemporary theme in modern
organic synthesis and finds application in accessing newer
entities. Complexity and brevity mostly rely on the coupling
of individual transformations into one synthetic process.
Tandem processes of diverse nature, promoted through
thermal or photochemical activation or catalysis, have
already proven their utility in organic synthesis and found
many applications in the acquisition of complexity in the
4
synthesis of various natural products such as illudin
5
6
(sesquiterpene), phorbol esters (diterpene), brevicomin
(pheromone) and further utilized to approach zaragozic
form of functionalized carbo- and heterocyclic systems.
2
7
8
1
,3-Dipolar cycloaddition reaction offers a versatile route
acid and cis-nemorensic acids. In addition, complex
oxapolycyclics can be readily manouvered to furnish
carbocyclic compounds and the reactions of carbonyl ylides
have therefore found applications in the synthesis of both
heterocyclic as well as carbocyclic systems. The reactions
of diazo carbonyl compounds mediated by rhodium(II)
acetate catalyst offer in the synthesis of complex oxa-
polycyclic systems, which are mainly useful for alkaloid
and terpenoid synthesis. Indole could prove to be an
appropriate starting material for further alkaloid synthesis if
suitable chemistry can be developed from this parent
skeleton. Successful endeavor has been made to use the
for the construction of several synthetically useful complex
five-membered heterocycles. Intermolecular 1,3-dipolar
cycloadditions have found wide application in the synthesis
q
Supplementary data associated with this article can be found in the online
version at doi:10.1016/j.tet.2004.06.053
Keywords: Carbazoles; Carbonyl ylides; a-Diazo ketones; Rhodium
carbenoids.
*
Corresponding author. Tel.: þ91-278-2567760; fax: þ91-278-2567562;
e-mail address: smuthus@yahoo.com
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.06.053

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S. Muthusamy et al. / Tetrahedron 60 (2004) 7885–7897
Figure 1.
Scheme 1.
2
,3-double bond of indole in 1,3-dipolar cycloaddition
9
reaction of carbonyl ylides, which lead to the synthesis of
Table 1. Hexahydro-2H-carbazol-2-ones produced via Scheme 1
1
1
1
0
1
2
benzocarbazole derivatives; well known antitumor agents
and also used as photoreceptors in electrophotography.
Our persisting interest in the chemistry of diazo ketones
2
a
Entry
R
Time
Product
Yield
1
2
3
H
CH3
CH
1.45 h
30 min
30 min
6a
6b
6c
86
89
87
1
3
and 3-diazooxindole systems encouraged us to investigate
the detailed reactions of carbonyl ylides with indoles. The
synchronizing effects of coupling more than one 1,3-dipolar
cycloaddition reaction in a single step can lead to desirable
increase in molecular complexity as well as brevity.
However, no such attempt has so far been made to couple
the 1,3-dipolar carbonyl ylide cycloaddition reactions.
Herein, we report highly effective, regioselective rhodium-
(II) acetate catalyzed 1,3-dipolar cycloaddition reactions of
carbonyl ylides with indoles and biindole systems.
2
Ph
a
Yields refer to isolated and chromatographically pure compounds 6.
bridged hexahydro-2H-carbazol-2-one system 6a. All these
spectral data clearly revealed that the carbonyl ylide
underwent 1,3-dipolar cycloaddition to the 2,3-p-bond of
the indole systems. Exclusive exo-cycloaddition was
observed and the assignment of exo-addition was made
3
1
upon inspection of the H NMR spectra; the bridgehead H-1
proton of compound 6a showed a singlet without any
coupling. This exo-diastereoselection is unique to the
intermolecular 1,3-dipolar cycloaddition of carbonyl ylides
with indoles. In contrast, the intramolecular cycloaddition
reactions with indoles proceeded by endo-cycloaddition
directed to the a-face of the isom u¨ nchnone 1,3-dipoles as
2
. Results and discussion
a-Diazo ketones 1 and 2 are used to generate the transient
cyclic five-membered-ring carbonyl ylides 3, 4 (Fig. 1) in
the presence of rhodium(II) acetate catalyst. Intramolecular
formation and intermolecular 1,3-dipolar cycloaddition
reactions of diazo ketones 1 and 2 with heteroaromatic p
bonds are investigated in this account. a-Diazo ketone 1 was
obtained from ethyl 2,2-dimethyl-3-oxobutyrate and com-
pounds 2a-c were prepared according to our earlier work
from the corresponding carboethoxy cycloalkanones. The
required substituted indoles were obtained according to
16
observed by Padwa and recently in carbonyl ylides by
17
Boger. The reaction of the a-diazo ketone 1 was further
carried out with indoles having an electron donating
substituent on the nitrogen atom 5b,c for generality.
Further studies of the Rh(II)-catalyzed behavior of the
a-diazo ketone 2a with unsubstituted indole 5a and
substituted indoles 5b-c furnished the cycloadducts 7a-c,
respectively, in very good yields (Scheme 2, Table 2) in a
regioselective manner. We were further interested to study
1
4
1
5
literature methods.
We explored the rhodium(II)-catalyzed behavior of the
above a-diazo ketones 1, 2 with indoles 5 in an
intermolecular fashion. The reaction of a-diazo ketone 1
and indole (5a) with 0.3 mol% rhodium(II) acetate dimer
catalyst in dry dichloromethane was stirred at room
temperature under an argon atmosphere for 1.45 h. The
chromatographic purification of the above reaction mixture
using neutral alumina column furnished the product 6a in
8
6% yield (Scheme 1, Table 1) as a single regioisomer.
The presence of a singlet at d 4.30 for the bridgehead H-1
proton, two doublets at d 3.85 and 4.24 for the H-4a and
1
H-9a protons, respectively, in the H NMR spectrum; an
oxygen attached tertiary bridgehead CH-signal (C-1) at d
1
3
85.1 and a quaternary carbon (C-4) at d 91.9 in the C NMR
and DEPT experiments confirmed the formation of the oxa-
Scheme 2.

S. Muthusamy et al. / Tetrahedron 60 (2004) 7885–7897
7887
Table 2. Synthesis of decahydrobenzocarbazoles
located at C-11b. On the other hand, the regioisomers 8i and
j showed characteristic NOE interaction of the proton of
8
1
2
R
a
Entry
n
R
Method
Products
the C-13 methyl group with the proton at C-11a.
Additionally, the proton at C-11b of the cycloadducts 7a-j
and C-6a of the cycloadducts 8i-j showed the NOE
interaction with a proton present in the aromatic part of
the carbazole ring. The protons at 6a of products 7i-j and
C-11a of products 8i-j experienced the NOE interactions
with the aromatic protons of the benzoyl or benzenesulfonyl
groups. A few selected results of NOE interactions are
depicted in Figure 2 for the regioisomers 7a, 7i, 7j, 8i.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
0
0
1
1
H
H
H
H
A
A
A
B
B
B
A
A
A
A
7a
7b
7c
7d
7e
7f
7g
7h
7i/8i
7j/8j
CH
CH
H
CH
CH
H
CH
COPh
SO Ph
3
2
Ph
COOEt
COOEt
COOEt
H
H
H
H
3
2
Ph
3
10
2
a
Alternatively, to characterize the stereo- and regiochemical
assignments of the products precisely, we planned to study
Method A, reactions were carried out in CH
were performed in dry benzene at reflux conditions.
2 2
Cl at rt. Method B, reactions
1
8
the single-crystal X-ray analysis. The compound 7a was
recrystallized in chloroform–hexane to provide plate-
shaped colorless crystals and subjected to X-ray crystallo-
graphic analysis. The X-ray structure of the compound 7a
is shown in Figure 3 and confirms the exact stereochemistry
of 6,11c-epoxy-1,2,3,4,4a,5,6,6a,11b,11c-decahydro-4a-
methyl-5-oxo-7H-benzo[c]carbazole (7a). The single-
crystal X-ray structure revealed that the methyl group at
the ring junction is endo with respect to the oxa-bridge and
the observed angle of oxa-bridge (C6–O12–C11c) is 97.708
in the compound 7a.
the rhodium(II)-catalyzed reactions with a different ring size
1
(
n) and substituent (R ) on the diazo substrate 2. The
reaction of a-diazo ketone 2b with indole, N-methylindole
or N-benzylindole afforded only decahydrobenzo[c]carba-
zole derivatives 7d-f in good yields with regioselectivity.
Although the reaction of 1-diazo-2-(1-methyl-2-oxocyclo-
pentyl)-ethan-2-one (2c) with indoles 5a-b delivered the
decahydrocyclopentacarbazoles 7g,h as the only products,
the observed yields are low when compared to the diazo
ketones 2a,b. This may be the result of steric hindrance
present in decahydrocyclopentacarbazoles 7g,h. The yield
of products 7a-h indicated at the maximum of 86% for
indoles having electron donating groups (see Section 4).
The presence of an electron withdrawing substituent on the
indole nitrogen atom (5d-e) afforded a mixture of
regioisomers 7i, 8i and 7j, 8j with the yields of 36 and
3
2%, respectively. This indicates that the introduction of
electron withdrawing substituents on N-atom of indole ring
not only affected the regioselectivity but also reduced the
reactivity of the indole heteroaromatic p-bond towards the
1
,3-dipolar cycloaddition reactions.
To characterize the regioisomers 7 and 8, NOE experiments
were performed at 25 8C in CDCl on the products 7a-j to
3
explicitly indicate that the protons at C-13 on the methyl
function underwent an NOE interaction with the proton
Figure 3. X-ray crystal structure of the cycloadduct 7a.
The stereochemistry of the product 8j was unequivocally
corroborated by the single crystal analysis. Slow evapo-
ration of a ethyl acetate–hexane solution containing the
compound 8j provided plate-shaped colorless crystals that
belongs to the space group P2 /n,a. The X-ray structure of
1
the compound 8j is shown in Figure 4. The angle of an
Figure 2.
Figure 4. X-ray crystal structure of the cycloadduct 8j.

7888
S. Muthusamy et al. / Tetrahedron 60 (2004) 7885–7897
oxa-bridge (C6–O12–C11b) is observed as 98.308 in
the product 8j. Moreover, the crystal structure confirms
the complete diastereoselectivity and is the result of exo-
cycloaddition.
the exo-isomers of oxa-bridged hexahydrocarbazoles/dec-
ahydrobenzocarbazoles/decahydrocyclopentacarbazoles. In
order to further functionalize the decahydrobenzocarba-
zoles, an attempt was performed in the presence of
n-butyllithium to afford the nucleophilic addition product
9 in a stereoselective manner. Decahydrobenzo[c]carbazole
7b was reacted with n-butyllithium in THF at 25 8C, which
gave the nucleophilic addition product 9 (Scheme 3). The
product 9 was characterized by the spectral data and the
stereochemistry of the butyl group was tentatively assigned
based on the favourable exo-addition.
The presence of a methyl group at the ring junction in the
cycloadducts 7a and 8j endo with respect to the oxa-bridge
is tentatively assigned for other products based on their
similarity in spectral data. In all reactions, the exclusive
products in the presence of indoles as dipolarophiles were
After studying the successful intermolecular 1,3-dipolar
cycloaddition of the carbonyl ylides, we embarked on the
investigation of multiple intermolecular 1,3-dipolar cycload-
dition reactions. To perform the rhodium(II)-catalyzed
tandem ylide generation and multiple cycloaddition reac-
1
9
tions, biindoles 10a-c were selected as prototypical
substrates. Initially, the reaction of biindole 10a and diazo
ketone 2a in the presence of rhodium(II) acetate catalyst
Scheme 3.
(0.5 mol%) at room temperature (Method A) was performed.
An excess amount of diazo ketone was used and the reaction
monitored by TLC. The column chromatographic purifi-
cation of the reaction mixture afforded the products 11a, 12a
in 40 and 52% yield, respectively (Scheme 4). Spectroscopic
analyses revealed that the compound 11a was a mono-
cycloaddition product and that the compound 12a resulted
from an interesting bis-cycloaddition of the carbonyl ylide.
Next, the diazo ketone 2b was reacted with the biindole 10a
in the presence of rhodium(II) acetate dimer catalyst (Method
B) to deliver the bis-cycloadduct 12b in good yield. In an
attempt to increase the yield of bis-cycloaddition products,
reactions were carried out using various solvents such as 1,2-
dichloroethane, hexane and toluene. The reaction in toluene
furnished the expected cycloadduct with comparable yield
but the yield was reduced in hexane. To our delight, the
reactions of diazo ketone 2b with biindoles 10 in 1,2-
dichloroethane (Method C) furnished only the respective bis-
cycloadducts 12 in higher yields with almost none or
negligible quantities of mono-cycloadducts 11 (Table 3).
Unfortunately, at room temperature the reaction of mono-
substituted diazo ketone 2a in 1,2-dichloroethane (Method
C) did not produce any significant improvement. Thus in a
single step, four carbon–carbon bonds, two carbon–oxygen
bonds and eight stereocenters are formed to furnish the
highly functionalized polycyclic products in a stereo-
selective manner.
Scheme 4.
Table 3. Regioselective synthesis of bis-decahydrobenzocarbazoles having aryl spacer
1
2
R
a
Entry
R
Method
Product
Yield of 11 (%)
Yield of 12 (%)
1
2
3
4
5
6
7
8
9
H
CO
H
CO
H
CO
H
CO
CO
CO
2-Indol-1-methyl
2-Indol-1-methyl
3-Indol-1-methyl
3-Indol-1-methyl
4-Indol-1-methyl
4-Indol-1-methyl
2-Indol-1-methyl
2-Indol-1-methyl
3-Indol-1-methyl
4-Indol-1-methyl
A
B
A
B
A
B
C
a
b
c
d
e
f
a
b
d
f
40
27
36
24
45
9
39
—
—
—
52
68
63
70
50
80
48
85
89
84
2
2
2
Et
Et
Et
b
2
2
2
Et
Et
Et
C
b
C
b
10
C
a
Method A, reactions were carried out in CH
performed in 1,2-dichloroethane at rt.
Reactions were refluxed.
2 2
Cl at rt. Method B, reactions were performed in dry benzene at reflux conditions. Method C, reactions were
b

S. Muthusamy et al. / Tetrahedron 60 (2004) 7885–7897
7889
observed in these reactions even in the presence of excess
a-diazo ketone.
The above results show that the mechanism by which 1 and
2
a-c were converted into cycloadducts involves rapid
cyclization of the rhodium carbenoid onto the carbonyl
group present at g-position to give the five-membered cyclic
carbonyl ylides 3, 4a-c, respectively, as intermediates,
followed by [3þ2]-cycloaddition with the indole derivatives
5
, 10, 13 as dipolarophiles. The cycloaddition of carbonyl
ylides to indoles was highly regio- and stereoselective. The
presence of a fused cyclohexane ring and a methyl group in
dipole 4a makes it facially dissymmetric for the approach of
þ
2
a dipolarophile. The reactive center (CvO –C ) of dipole
a is completely planar and the fused cyclohexane ring
adopts a chair-like conformation. Indoles as dipolarophile
4
preferably approach the syn face to the methyl group of
1,3-dipole 4a to yield the exclusive exo-cycloadducts,
which is similar to our earlier experimental and theoretical
1
2b,14
studies.
Thus, we observe only one stereoisomer in the
Scheme 5.
mono-cycloaddition with very good yield. We did not
observe any other stereoisomers. In the case of bisindoles,
the second indole unit also underwent exo-addition to the
carbonyl ylide intermediate in a similar manner. The
assignment of exo-addition in bis-cycloadducts was con-
firmed based on a characteristic singlet resonance signal for
After the successful attainment of bis-cycloaddition of
carbonyl ylide dipoles with biindoles having aromatic
spacers, we were interested to elaborate the utility of the
bis 1,3-dipolar cycloaddition processes with the biindoles
having aliphatic spacers (Table 4). The biindolyl derivatives
1
the bridgehead OCH proton in the H NMR spectrum.
Further, no products resulting from the potential competi-
1
3a-b were synthesized and reacted with diazo ketone 2a
2
1
tive intramolecular C–H insertion and intermolecular
2
using Method A. The reaction proceeds smoothly and the
chromatographic purification afforded the products 14a, 15a
in 23 and 65% yield (Scheme 5). Gratifyingly, this multiple
bond forming reaction delivered the product 15a in a
stereospecific manner. The treatment of a-diazo ketone
2
2
N–H insertion reactions (when R ¼H) of the rhodium
carbenoid could be detected.
3. Conclusion
2
b with 13a-b in the presence of rhodium(II) acetate
We have demonstrated that the five-membered-ring cyclic
carbonyl ylides 3 and 4, generated from the rhodium(II)-
catalyzed reaction of a-diazo ketones 1 and 2, undergo
successful 1,3-dipolar cycloaddition reaction across indole
p-bonds to provide novel oxa-bridged mono- and bis-
decahydrobenzocarbazoles/decahydrocyclopentacarbazoles
in a facile manner. The presence of an electron withdrawing
substituent on the indole nitrogen atom provided lower
reactivity towards the carbonyl ylide cycloaddition and
loss of regioselectivity was observed. This tandem intra-
molecular cyclization–intermolecular cycloaddition
sequence is particularly attractive as eight stereocenters,
four carbon–carbon bonds and two carbon–oxygen bonds
are formed concomitantly in a single step with a high degree
of stereo- and regiocontrol under mild experimental
conditions. The stereo- and regiochemistry of the products
were unequivocally confirmed by the NOE and X-ray
crystallographic studies. Polycyclic compounds with
specific stereochemistry are quickly and efficiently gener-
ated from simple starting materials. These highly functio-
nalized polycyclic products could serve as flexible building
blocks for complex target synthesis.
following Method C resulted in the selective formation of
products 15b and 15d (entries 2 and 4, Table 4) respectively,
with added functionality. In the presence of excess diazo
ketones, it is known that the intermediate carbonyl ylide
cycloadd to the carbonyl group of the formed cycloadduct.
Interestingly, no 2:1 (16, Fig. 5) or 3:1 cycloadducts were
20
Table 4. Regioselective synthesis of bis-decahydrobenzocarbazoles having
aliphatic spacer
1
Entry
R
m
Method Product Yield of 14 Yield of 15
a a
(
%)
(%)
1
2
3
4
H
0
0
1
1
A
C
A
C
a
b
c
23
—
29
—
65
85
57
80
COOEt
H
COOEt
d
a
Yields refer to (with respect to indoles 13) isolated and chromato-
graphically pure compounds of 14 and 15.
4. Experimental
4.1. General
Figure 5. Possible 2:1 cycloadduct.
Melting points were determined on a capillary melting point

7890
S. Muthusamy et al. / Tetrahedron 60 (2004) 7885–7897
apparatus and are uncorrected. IR spectra were recorded on
a Perkin–Elmer Spectrum GX FT-IR spectrophotometer
using KBr pellets or in CH Cl . Proton nuclear magnetic
4.2. General procedure for the synthesis of epoxy-
bridged hexahydro-2H-carbazol-2-ones (6a-c)
2
2
1
resonance ( H NMR) spectra were recorded on a Bruker
DPX 200 at 200 MHz using CDCl in ppm (d) related to
To a dry CH Cl solution (10 mL) of an appropriate indole
2
2
(5, 1.5 mmol) and a catalytic amount (0.3 mol%) of
Rh (OAc) taken in a dried round-bottom flask, the
3
tetramethylsilane (d¼0.00) as an internal standard and are
2
4
reported as follows; chemical shift (ppm), multiplicity
CH Cl solution (10 mL) of diazo ketone 1 (1.0 mmol)
2 2
(
multiplet), coupling constant (Hz) and integration. Car-
br¼broad, s¼singlet, t¼triplet, quat¼quartet, m¼
was added slowly under an argon atmosphere using syringe
at room temperature. The reaction was monitored by TLC.
After completion of the reaction, the solvent was evaporated
in vacuo and the residue purified by neutral alumina column
chromatography using hexane/ethyl acetate as eluant.
1
3
bon-13 nuclear magnetic resonance ( C NMR) spectra
were recorded at 50.3 MHz in CDCl . Chemical shifts are
3
reported in delta (d) units, parts per million (ppm) relative to
the center of the triplet at 77.7 ppm for CDCl . Carbon types
3
1
3
were determined from C NMR and DEPT experiments.
Mass analyses were performed on Jeol DX-303 (with an
4.2.1. 1,4-Epoxy-3,3,4-trimethyl-1,3,4,4a,9,9a-hexahy-
dro-2H-carbazol-2-one (6a). Light brownish solid (86%).
Mp 120–122 8C. IR (KBr) 3416 (NH), 2978, 2875, 1758,
þ
ionizing voltage of 70 eV), Jeol M Station 700 (FD method
1607, 1486, 1468, 1385, 1092, 909, 734 cm2 ; H NMR
1 1
in absolute dichloromethane) mass spectrometers or by FAB
technique and reported as m/z (relative intensity). Elemental
analyses were performed on a Perkin Elmer Model 2400
analyzer. X-ray crystallographic analyses were carried out
in a Endraf Nonius CAD-4 difractometer with Mo Ka
radiation. All solvents were purified by distillation follow-
ing standard procedures. Thin layer chromatography was
performed on silica or alumina plates and components
visualized by observation under iodine/UV light at 254 nm.
Column chromatography was performed on neutral
alumina. All air sensitive reactions were conducted in
oven-dried glassware under a positive pressure of argon
with magnetic stirring. Reagents were added via syringes
through septa. Care has been taken to avoid light during the
course of reaction in the synthesis of a-diazo ketones and its
further conversion. Biindoles 13a-b were prepared by the
(200 MHz, CDCl ) d 1.08 (s, 3H, CH ), 1.15 (s, 3H, CH ),
3
3
3
1.38 (s, 3H, CH ), 1.91 (s, 1H, NH), 3.85 (d, 1H, J¼8.2 Hz,
3
H-4a), 4.24 (d, 1H, J¼8.2 Hz, H-9a), 4.30 (s, 1H, OCH,
H-1), 6.58 (d, 1H, J¼8.0 Hz, ArH), 6.71 (t, 1H, J¼7.1 Hz,
1
3
ArH), 7.01–7.08 (m, 2H, ArH); C NMR (50.3 MHz,
CDCl ) d 13.7 (CH ), 19.7 (CH ), 21.5 (CH ), 52.1
3
3
3
3
(quat-C), 52.3 (CH), 64.9 (NCH), 88.5 (OCH), 91.9
(quat-C), 110.0 (arom-CH), 119.0 (arom-CH), 126.9
(quat-C), 127.2 (arom-CH), 129.0 (arom-CH), 153.1
(quat-C), 218.3 (quat-C, CvO); MS (EI) m/z 244 (Mþ1,
þ
33), 243 (M , 55), 223 (11), 200 (12), 186 (6), 158 (14), 157
(20), 144 (8), 131 (8), 130 (71). Anal. Calcd for C H NO :
17
15
2
C, 74.05; H, 7.04; N, 5.76. Found: C, 74.26; H, 7.16; N,
5.85.
1
9
literature procedure.
4.2.2. 1,4-Epoxy-3,3,4,9-tetramethyl-1,3,4,4a,9,9a-hexa-
hydro-2H-carbazol-2-one (6b). Colorless solid (89%).
Mp 106–107 8C. IR (KBr) 2976, 1755, 1603, 1491, 1376,
CAUTION! Even though we have noted no explosive
tendencies of these a-diazo ketones, it is strongly
recommended that they be handled with great care and
proper precaution.
1321, 908 cm2 ; H NMR (200 MHz, CDCl ) d 1.06 (s, 3H,
1 1
3
CH ), 1.16 (s, 3H, CH ), 1.37 (s, 3H, CH ), 2.83 (s, 3H,
3
3
3
NCH ), 3.78 (d, 1H, J¼8.3 Hz, H-4a), 3.94 (d, 1H, J¼
3
8
.3 Hz, H-9a), 4.42 (s, 1H, OCH, H-1), 6.36 (d, 1H, J¼
4
.1.1. Synthesis of 1-diazo-3,3-dimethyl-pentane-2,4-
dione (1). Hydrolysis of ethyl 2,2-dimethyl-3-oxobutyrate
3.0 g, 19.0 mmol) was carried out using 5% aqueous KOH
7.9 Hz, ArH), 6.60 (t, 1H, J¼6.9 Hz, ArH), 6.97 (d, 1H,
1
3
J¼7.2 Hz, ArH), 7.12 (d, 1H, J¼7.8 Hz, ArH); C NMR
(
(50.3 MHz, CDCl ) d 13.4 (CH ), 19.9 (CH ), 21.4 (CH ),
3
3
3
3
solution (20 mL) for 5 h to afford 2,2-dimethyl-3-oxo-
butyric acid (2.3 g, 91%). To a reaction mixture containing a
solution of crude 2,2-dimethyl-3-oxobutyric acid (1.9 g,
33.9 (NCH ), 50.4 (CH), 52.4 (quat-C), 72.2 (CH), 85.1
3
(OCH), 92.2 (quat-C), 106.5 (arom-CH), 116.1 (arom-CH),
126.7 (quat-C), 126.8 (arom-CH), 129.1 (arom-CH), 154.3
þ
þ
Anal. Calcd for C H NO : C, 74.68; H, 7.44; N, 5.44.
14.6 mmol) in dry ether (25 mL) was added oxalyl chloride
1.9 mL, 21.9 mmol) at room temperature for 3 h under an
(quat-C), 218.6 (quat-C, CvO); MS (FD ) m/z 257 (M ).
(
1
6
19
2
argon atmosphere, concentration at reduced pressure
afforded the crude acid chloride which was treated with a
solution containing triethylamine (2.6 mL, 19.0 mmol) and
ethereal diazomethane solution (300 mL, 30 mmol) under
an argon atmosphere at 0 8C for 3 h. After the appropriate
period the reaction mixture was stirred at room temperature
for 3 h. Concentration under vacuum and purification
through a short alumina column afforded 1-diazo-3,3-
dimethylpentane-2,4-dione (1) (1.5 g, 67%) as a yellow
liquid; IR (neat) 3101, 2982, 2106, 1713, 1643, 1468,
Found: C, 74.79; H, 7.56; N, 5.53.
4.2.3. 1,4-Epoxy-9-benzyl-3,3,4,-trimethyl-1,3,4,4a,9,9a-
hexahydro-2H-carbazol-2-one (6c). Yellow solid (87%).
Mp 109–110 8C. IR (KBr) 2977, 1757, 1604, 1493, 1455,
1384, 1325, 1006, 909, 734 cm2 ; H NMR (200 MHz,
1
1
CDCl ) d 1.05 (s, 3H, CH ), 1.13 (s, 3H, CH ), 1.41 (s, 3H,
3
3
3
CH ), 3.84 (d, 1H, J¼8.3 Hz, H-4a), 4.09 (d, 1H, J¼8.3 Hz,
3
H-9a), 4.24 (s, 1H, OCH, H-1), 4.41 (s, 2H, NCH ), 6.34 (d,
2
1H, J¼7.9 Hz, ArH), 6.66 (t, 1H, J¼6.9 Hz, ArH), 7.00–
150 cm2 ; H NMR (200 MHz, CDCl ) d 1.34 (s, 6H,
1
1
7.07 (m, 2H, ArH), 7.21–7.29 (m, 5H, ArH); C NMR
(50.3 MHz, CDCl ) d 13.6 (CH ), 19.2 (CH ), 21.4 (CH ),
13
1
CH ), 2.17 (s, 3H, CH ), 5.54 (s, 1H, CHN ); C NMR
3
1
3
3
3
2
3
3
3
3
(
50.3 MHz, CDCl ) d 22.0 (CH ), 26.3 (CH ), 54.3 (CH),
3
50.6 (CH), 51.7 (NCH ), 50.4 (CH), 52.5 (quat-C), 71.1
2
3
3
60.5 (quat-C), 194.9 (CvO), 207.5 (CvO). Anal. Calcd for
C H N O : C, 54.54; H, 6.54; N, 18.19. Found: C, 54.65;
H, 6.60; N, 18.21.
(CH), 85.6 (OCH), 92.3 (quat-C), 106.5 (arom-CH), 117.3
(arom-CH), 126.5 (quat-C), 127.0 (arom-CH), 127.7 (arom-
CH), 129.2 (arom-CH), 129.4 (arom-CH), 138.5 (quat-C),
7
10 2 2

S. Muthusamy et al. / Tetrahedron 60 (2004) 7885–7897
7891
1
3
1
53.9 (quat-C), 218.3 (quat-C, CvO); MS (EI) m/z 335
þ
47 (8), 223 (10), 220 (10), 207 (7), 91 (100). Anal. Calcd
C NMR (50.3 MHz, CDCl ) d 16.7 (4a-CH ), 21.0 (CH ),
3
3
2
(
Mþ2, 5), 334 (Mþ1, 24), 333 (M , 78), 290 (7), 276 (9),
22.6 (CH ), 25.7 (CH ), 30.9 (CH ), 33.7 (7-CH ), 50.6
2 2 2 3
2
for C H NO : C, 79.25; H, 6.95; N, 4.20. Found: C, 79.42;
H, 7.12; N, 4.29.
(C-11b), 51.4 (C-4a), 72.0 (C-6a), 85.2 (C-6), 91.2 (C-11c),
106.4 (arom-CH), 116.9 (arom-CH), 125.8 (quat-C), 126.5
(arom-CH), 129.1 (arom-CH), 154.6 (quat-C), 218.4 (C-5);
2
2
23
2
þ
þ
MS (FD ) m/z 283 (M ). Anal. Calcd for C H NO : C,
2
1
8
21
4.3. General procedure for the synthesis of decahydro-
benzocarbazole/decahydrocyclopentacarbazole
76.29; H, 7.47; N, 4.94. Found: C, 76.09; H, 7.32; N, 5.13.
4
.3.3. 7-Benzyl-6,11c-epoxy-2,3,4,4a,5,6,6a,7,11b,11c-
Method A. In an oven-dried flask, a solution containing
appropriate diazo ketone (2, 1.0 mmol) and appropriate
indole (5, 1.5 mmol) in 15 mL of dry CH Cl was degassed
decahydro-4a-methyl-5-oxo-1H-benzo[c]carbazole (7c).
Colorless solid (85%). Mp 204–206 8C. IR (KBr) 2938,
1748, 1600, 1492, 1356, 1299, 1005, 737 cm2 ; H NMR
1 1
2
2
under an argon atmosphere. To this reaction mixture,
.3 mol% of rhodium(II) acetate dimer was added at room
(200 MHz, CDCl ) d 1.12 (s, 3H, CH ), 1.24–1.77 (m, 7H),
3
3
0
2.03–2.06 (m, 1H), 3.75 (d, 1H, J¼8.2 Hz, H-11b), 4.07 (d,
temperature. The reaction mixture was allowed to stir and
followed by TLC until the disappearance of the starting
material. The solvent was removed under reduced pressure
and the residue purified by neutral alumina column
chromatography (EtOAc/hexane) to afford the decahydro-
benzocarbazole/decahydrocyclopentacarbazoles.
1H, J¼8.2 Hz, H-6a), 4.33 (s, 1H, H-6), 4.41 (s, 2H, NCH ),
2
6.35 (d, 1H, J¼7.8 Hz, ArH), 6.60 (t, 1H, J¼7.6 Hz, ArH),
1
3
6.97–7.07 (m, 2H, ArH), 7.21–7.31 (m, 5H, ArH);
NMR (50.3 MHz, CDCl ) d 16.8 (CH ), 21.0 (CH ), 22.7
C
3
3
2
(CH ), 25.9 (CH ), 30.9 (CH ), 50.9 (C-11b), 51.0 (C-4a),
2
2
2
51.7 (NCH ), 70.9 (C-6a), 85.9 (C-6), 91.3 (C-11c), 106.6
2
(
arom-CH), 117.1 (arom-CH), 125.8 (quat-C), 126.8 (arom-
Method B. By following Method A, dry benzene is used as
solvent and the reaction mixture was refluxed.
CH), 127.8 (arom-CH), 127.9 (arom-CH), 129.3 (arom-
CH), 129.3 (arom-CH), 138.5 (quat-C), 153.9 (quat-C),
þ
C H NO : C, 80.19; H, 7.01; N, 3.90. Found: C, 80.02; H,
þ
217.9 (C-5); MS (FD ) m/z 359 (M ). Anal. Calcd for
4
4
.3.1. 6,11c-Epoxy-1,2,3,4,4a,5,6,6a,11b,11c-decahydro-
a-methyl-5-oxo-7H-benzo[c]carbazole (7a). Colorless
2
4
25
2
7.16; N, 3.76.
solid (71%). Mp 173–175 8C. IR (KBr) 3401 (NH), 2923,
2
1 1
2
858, 1752 (CvO), 1603, 1483, 1325, 994, 744 cm ; H
NMR (200 MHz, CDCl ) d 1.13 (s, 3H, CH ), 1.32–1.97
4.3.4. [6,11c-Epoxy-1,2,3,4,4a,5,6,6a,11b,11c-decahydro-
4a-methyl-5-oxo-7H-benzo[c]carbazole]-6-carboxylic
acid ethyl ester (7d). Brown solid (69%). Mp 155–157 8C.
IR (KBr) 3433 (NH), 2939, 1748, 1606, 1489, 1320, 1234,
3
3
(
m, 8H), 3.72 (d, 1H, J¼8.2 Hz, H-11b), 4.04 (br s, 1H,
H-7), 4.16 (d, 1H, J¼8.2 Hz, H-6a), 4.34 (s, 1H, H-6), 6.54
1083 cm2 ; H NMR (200 MHz, CDCl ) d 1.21 (s, 3H,
1 1
(
(
d, 1H, J¼7.8 Hz), 6.66 (t, 1H, J¼7.8 Hz, ArH), 6.97–7.02
m, 2H, ArH); C NMR (50.3 MHz, CDCl ) d 16.8 (CH ),
3 3
3
1
3
CH ), 1.35 (t, 3H, J¼7.1 Hz, OCH CH ), 1.38–2.07 (m,
3
2
3
2
0.9 (CH ), 22.6 (CH ), 25.9 (CH ), 30.9 (CH ), 52.1
2
8H), 3.85 (d, 1H, J¼8.2 Hz, H-11b), 4.15 (br s, 1H, H-7),
2
2
2
(
1
(
C-4a), 52.2 (C-11b), 64.7 (C-6a), 88.4 (C-6), 91.0 (C-11c),
09.9 (arom-CH), 118.6 (arom-CH), 126.3 (quat-C), 126.8
arom-CH), 128.9 (arom-CH), 157.9 (quat-C), 217.8 (C-5);
4.29–4.42 (m, 2H, OCH CH ), 4.51 (d, 1H, J¼8.2 Hz,
2
3
H-6a), 6.56 (d, 1H, J¼7.8 Hz, ArH), 6.66 (t, 1H, J¼7.7 Hz,
1
3
ArH), 6.98–7.06 (m, 2H, ArH); C NMR (50.3 MHz,
CDCl ) d 14.9 (OCH CH ), 17.1 (4a-CH ), 20.9 (CH ), 22.5
þ
þ
MS (FD ) m/z 269 (M ). Anal. Calcd for C H NO : C,
2
1
7
19
3
2
3
3
2
7
5.81; H, 7.11; N, 5.20. Found: C, 75.67; H, 7.24; N, 5.39.
(CH ), 25.7 (CH ), 31.3 (CH ), 51.7 (C-4a), 52.9 (C-11b),
2 2 2
62.8 (OCH ), 67.1 (C-6a), 90.3 (C-11c), 95.2 (C-6), 110.2
2
X-ray crystal data for the compound 7a. C H NO ,
2
(arom-CH), 118.8 (arom-CH), 125.2 (quat-C), 126.9 (arom-
CH), 129.4 (arom-CH), 152.8 (quat-C), 165.7 (COOEt),
211.6 (C-5); MS (FD ) m/z 341 (M ). Anal. Calcd for
1
7
19
3
M¼269.33, 0.20£0.16£0.12 mm , triclinic, P-1, a¼
˚
˚
˚
˚
þ
C H NO : C, 70.36; H, 6.79; N, 4.10. Found: C, 70.59; H,
þ
7
.104(2) A, b¼8.469(3) A, c¼11.607(2) A, a¼82.91(2)8,
3
b¼75.74(2)8, g¼89.48(2)8, V¼671.5(3) A , T¼293(2) K,
2
0
23
4
R ¼0.0564, wR ¼0.1562 on observed data, z¼2, D
¼
6.87; N, 4.32.
1
2
calcd
3
1
.332 mg/m , F(000)¼288, absorption coefficient¼0.087
2
1
˚
mm , l¼0.7107 A, 1745 reflections were collected on a
CAD-4 diffractometer, 1392 observed reflections (I$2s(I)).
The largest difference peak and hole¼0.195 and
4.3.5. [4a,7-Dimethyl-6,11c-epoxy-2,3,4,4a,5,6,6a,7,
11b,11c-decahydro-5-oxo-1H-benzo[c]carbazole]-6-car-
boxylic acid ethyl ester (7e). Brown solid (82%). Mp 150–
152 8C. IR (KBr) 2935, 1747, 1602, 1494, 1315, 1141, 1084,
˚
0.313 eA , respectively. Crystallographic data for this
23
2
2
3
21
1
compound have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication
numbers CCDC 232210.
757 cm ; H NMR (200 MHz, CDCl ) d 1.21 (s, 3H,
3
4a-CH ), 1.37 (t, 3H, J¼7.2 Hz, OCH CH ), 1.40–2.09 (m,
3
2
3
8H), 2.86 (s, 3H, 7-CH ), 3.85 (d, 1H, J¼8.2 Hz, H-11b),
3
4
.17 (d, 1H, J¼8.2 Hz, H-6a), 4.37 (q, 2H, J¼7.2 Hz,
4
1
.3.2. 4a,7-Dimethyl-6,11c-epoxy-2,3,4,4a,5,6,6a,7,
1b,11c-decahydro-5-oxo-1H-benzo[c]carbazole (7b).
OCH CH ), 6.45 (d, 1H, J¼7.7 Hz, ArH), 6.65 (t, 1H,
2 3
J¼7.6 Hz, ArH), 6.96 (d, 1H, J¼7.7 Hz, ArH), 7.10 (t, 1H,
1
3
Colorless solid (84%). Mp 115–117 8C. IR (KBr) 2940,
2
J¼7.7 Hz, ArH); C NMR (50.3 MHz, CDCl ) d 14.9
3
1 1
1750 (CvO), 1603, 1495, 1382, 1302, 993, 746 cm ; H
NMR (200 MHz, CDCl ) d 1.13 (s, 3H, 4a-CH ), 1.27–1.94
(OCH CH ), 17.1 (4a-CH ), 20.9 (CH ), 22.4 (CH ), 25.9
2
3
3
2
2
(CH ), 31.4 (CH ), 31.1 (NCH ), 51.4 (C-4a), 52.2 (C-11b),
3
3
3
2
2
(
m, 8H), 2.82 (s, 3H, 7-CH ), 3.68 (d, 1H, J¼8.2 Hz,
62.5 (OCH ), 75.6 (C-6a), 89.6 (C-11c), 94.5 (C-6), 109.1
2
3
H-11b), 3.92 (d, 1H, J¼8.2 Hz, H-6a), 4.50 (s, 1H, H-6),
(arom-CH), 118.3 (arom-CH), 125.8 (quat-C), 126.4 (arom-
CH), 129.3 (arom-CH), 155.6 (quat-C), 165.0 (COOEt),
6
6
.35 (d, 1H, J¼7.8 Hz, ArH), 6.58 (t, 1H, J¼7.8 Hz, ArH),
.94 (d, 1H, J¼7.8 Hz, ArH), 7.07 (t, 1H, J¼7.8 Hz, ArH);
þ
211.1 (C-5); MS (FD ) m/z 355. Anal. Calcd for

7892
S. Muthusamy et al. / Tetrahedron 60 (2004) 7885–7897
C H NO : C, 70.96; H, 7.09; N, 3.94. Found: C, 70.69; H,
2
3.73 (d, 1H, J¼8.0 Hz, H-11b), 4.70 (s, 1H, H-6), 4.88 (d,
1H, J¼8.0 Hz, H-6a), 6.97–7.00 (m, 2H, ArH), 7.11–7.15
1
25
4
7
.21; N, 4.15.
13
(
m, 2H, ArH), 7.46–7.56 (m, 5H, ArH); C NMR
4
.3.6. [7-Benzyl-6,11c-epoxy-2,3,4,4a,5,6,6a,7,11b,11c-
(50.3 MHz, CDCl ) d 16.7 (CH ), 20.7 (CH ), 22.8 (CH ),
3 3 2 2
decahydro-4a-methyl-5-oxo-1H-benzo[c]carbazole]-6-
carboxylic acid ethyl ester (7f). Colorless solid (86%). Mp
26.0 (CH ), 30.9 (CH ), 49.0 (C-11b), 50.9 (C-4a), 66.7
2 2
(C-6a), 85.9 (C-6), 91.4 (C-11c), 115.8 (arom-CH), 123.4
(arom-CH), 127.2 (arom-CH), 127.5 (arom-CH), 128.6
(arom-CH), 129.1 (quat-C), 129.5 (arom-CH), 131.2 (arom-
CH), 137.1 (quat-C), 144.9 (quat-C), 169.3 (NCO), 215.6
1
1
1
1
3
78–180 8C. IR (KBr) 2933, 1770, 1719, 1598, 1487, 1325,
2
1 1
242, 1127, 1016, 762 cm ; H NMR (200 MHz, CDCl ) d
3
.16 (t, 3H, J¼7.2 Hz, OCH CH ), 1.19 (s, 3H, 4a-CH ),
2
3
3
þ
þ
.29–1.39 (m, 2H), 1.66–1.86 (m, 5H), 2.06–2.15 (m, 1H),
.73–3.98 (m, 3H), 4.29 (d, 1H, J¼16.6 Hz), 4.37 (d, 1H,
(C-5); MS (FD ) m/z 373 (M ). Anal. Calcd for
C H NO : C, 77.19; H, 6.21; N, 3.75. Found: C, 77.03;
H, 6.34; N, 3.87.
2
4
23
3
J¼8.2 Hz, H-6a), 4.61 (d, 1H, J¼16.6 Hz), 6.28 (d, 1H,
J¼8.0 Hz), 6.66 (t, 1H, J¼7.8 Hz, ArH), 6.95–7.02 (m, 2H,
1
3
ArH), 7.14–7.31 (m, 5H, ArH); C NMR (50.3 MHz,
CDCl ) d 14.5 (OCH CH ), 17.0 (4a-CH ), 20.8 (CH ), 22.4
Data for 11-benzoyl-6,11b-epoxy-2,3,4,4a,5,6,6a,11,
11a,11b-decahydro-4a-methyl-5-oxo-1H-benzo[a]carba-
zole (8i). Colorless solid (14%). Mp 161–163 8C. IR (KBr)
3
2
3
3
2
(
CH ), 25.8 (CH ), 31.2 (CH ), 51.3 (C-4a), 52.5 (C-11b),
2 2 2
2941, 1758, 1646, 1482, 1378, 1216, 1003, 756 cm2 ; H
1 1
5
5.9 (NCH ), 62.3 (OCH ), 74.3 (C-6a), 89.4 (C-11c), 95.0
2 2
(
C-6), 109.4 (arom-CH), 118.5 (arom-CH), 126.0 (quat-C),
NMR (200 MHz, CDCl ) d 1.19 (s, 3H, CH ), 1.22–2.18
3
3
1
1
26.4 (arom-CH), 127.3 (arom-CH), 127.3 (arom-CH),
29.0 (arom-CH), 129.2 (arom-CH), 139.2 (quat-C), 155.2
(m, 8H), 3.83 (d, 1H, J¼7.9 Hz, H-6a), 4.44 (s, 1H, H-6),
13
5.31 (d, 1H, J¼7.9 Hz, H-11a), 6.89–7.02 (m, 2H, ArH),
þ
(
quat-C), 164.8 (COOEt), 211.2 (C-5); MS (FD ) m/z 431
þ
7.22–7.26 (m, 2H, ArH), 7.47–7.54 (m, 5H, ArH);
C
(
M ). Anal. Calcd for C H NO : C, 75.15; H, 6.77; N,
4
NMR (50.3 MHz, CDCl ) d 16.4 (CH ), 21.2 (CH ), 22.6
3 3 2
2
7
29
3
.25. Found: C, 75.31; H, 6.82; N, 3.39.
(CH ), 24.8 (CH ), 31.3 (CH ), 48.3 (C-6a), 50.2 (C-4a),
2 2 2
65.2 (C-6a), 85.5 (C-6), 92.9 (C-11b), 115.8 (arom-CH),
4
3
.3.7. 5,10c-Epoxy-1,2,3,3a,4,5,5a,6,10b,10c-decahydro-
a-methyl-4-oxo-cyclopenta[c]carbazole (7g). Brown
124.9 (arom-CH), 125.6 (arom-CH), 127.9 (arom-CH),
128.1 (quat-C), 128.8 (arom-CH), 129.6 (arom-CH), 131.3
(arom-CH), 137.2 (quat-C), 144.3 (quat-C), 170.9 (NCO),
solid (34%). Mp 148–150 8C. IR (KBr) 3392 (NH), 2963,
2
NMR (200 MHz, CDCl ) d 1.11 (s, 3H, CH ), 1.92–2.35
931, 1753, 1653, 1606, 1485, 1461, 1334, 751 cm2 ; H
1
1
216.7 (C-5); MS (FD ) m/z 373 (M ). Anal. Calcd for
C H NO : C, 77.19; H, 6.21; N, 3.75. Found: C, 77.43; H,
6.05; N, 3.63.
þ
þ
3
3
24 23
3
(
m, 6H), 3.88 (d, 1H, J¼7.8 Hz, H-10b), 3.97 (br s, 1H,
H-6), 4.29 (s, 1H, H-5), 4.33 (d, 1H, J¼7.8 Hz, H-5a), 6.59
(
7
d, 1H, J¼7.8 Hz, ArH), 6.70 (t, 1H, J¼7.6 Hz, ArH), 7.01–
4.3.10. Crystal data for the compound 8j. C H NO S,
2
3
23
4
1
3
3
.33 (m, 2H, ArH); C NMR (50.3 MHz, CDCl ) d 19.4
3
M¼409.48, 0.18£0.14£0.10 mm , monoclinic, P2 /n,a¼
1
˚
˚
˚
(
CH ), 23.9 (CH ), 28.4 (CH ), 34.9 (CH ), 47.5 (C-10b),
3
15.018(4) A, b¼8.054(5) A, c¼16.571(6) A, b¼94.8(2)8,
˚
1 2
2
2
2
3
6
0.4 (C-3a), 72.8 (C-5a), 85.9 (C-5), 104.6 (C-10c), 106.3
V¼1997.3(15) A , T¼293(2) K, R ¼0.0778, wR ¼0.2328
3
(
(
arom-CH), 117.8 (arom-CH), 125.8 (arom-CH), 127.9
quat-C), 127.3 (arom-CH), 155.8 (quat-C), 218.3 (C-4);
on observed data, z¼4, D
¼1.362 mg/m , F(000)¼864,
calcd
2
1
˚
absorption coefficient¼0.192 mm , l¼0.7107 A, 2602
reflections were collected on a CAD-4 diffractometer,
1576 observed reflections (I$2s(I)). The largest difference
þ
5.27; H, 6.71; N, 5.49. Found: C, 75.44; H, 6.65; N, 5.63.
þ
MS (FD ) m/z 255 (M ). Anal. Calcd for C H NO : C,
2
7
1
6
17
˚
23
peak and hole¼0.406 and 20.655 eA , respectively.
4
1
.3.8. 3a,6-Dimethyl-5,10c-epoxy-1,2,3,3a,4,5,5a,6,
0b,10c-decahydro-5-oxo-cyclopenta[c]carbazole (7h).
Crystallographic data for this compound have been
2
3
deposited with the Cambridge Crystallographic Data
Centre as supplementary publication numbers CCDC
232211.
Brown solid (44%). Mp 134–136 8C. IR (KBr) 2938,
1
NMR (200 MHz, CDCl ) d 1.09 (s, 3H, 3a-CH ), 1.90–2.19
1 1
754, 1605, 1498, 1460, 1301, 1096, 990, 740 cm2 ; H
3
3
(
m, 6H), 2.85 (s, 3H, 6-CH ), 3.79 (d, 1H, J¼8.1 Hz,
4.3.11. Compound 9. Addition of n-butyllithium in hexane
(1.6 M, 0.46 mL, 7.4 mmol, 7.0 equiv.) to a solution of 4a,7-
dimethyl-6,11c-epoxy-2,3,4,4a,5,6,6a,7,11b,11c-decahydro-
5-oxo-1H-benzo[c]carbazole (7b, 30 mg, 0.11 mmol) in dry
THF (5 mL), was performed under an argon atmosphere at
25 8C provided stirring. The reaction was followed by TLC,
the complete disappearance of the starting material 7b took
place after 10 min. The reaction mixture was quenched by
dilute hydrochloric acid. The acidic aqueous layer was
washed with EtOAc (3£5 mL). The organic layer was
washed with water, brine dried over anhydrous sodium
sulfate and the solvent was evaporated under reduced
pressure. The residue was purified by column chroma-
tography (6:94 hexane–EtOAc) to yield 9 as a greenish
solid (23 mg, 64%). Mp 162–164 8C. IR (KBr) 3466 (OH),
3
H-10b), 4.07 (d, 1H, J¼8.1 Hz, H-5a), 4.43 (s, 1H, H-5),
6
6
1
(
1
.33 (d, 1H, J¼7.8 Hz, ArH), 6.58 (t, 1H, J¼7.6 Hz, ArH),
1
3
.98–7.11 (m, 2H, ArH); C NMR (50.3 MHz, CDCl ) d
3
9.2 (3a-CH ), 23.6 (CH ), 28.0 (CH ), 33.4 (NCH ), 34.6
3
2
2
3
CH ), 47.4 (C-10b), 59.9 (C-3a), 72.5 (C-5a), 85.5 (C-5),
2
03.5 (C-10c), 105.9 (arom-CH), 117.1 (arom-CH), 124.8
arom-CH), 127.3 (quat-C), 129.1 (arom-CH), 153.9 (quat-
(
C), 216.0 (C-4); MS (FD ) m/z 269 (M ). Anal. Calcd for
þ
C H NO : C, 75.81; H, 7.11; N, 5.20. Found: C, 75.59; H,
þ
1
7
19
2
6
.97; N, 5.09.
4
7
4
.3.9. Reaction of 2a with N-benzoylindole (5d). Data for
-benzoyl-6,11c-epoxy-2,3,4,4a,5,6,6a,7,11b,11c-decahydro-
a-methyl-5-oxo-1H-benzo[c]carbazole (7i). Colorless
2
1
solid (22%). Mp 164–166 8C. IR (KBr) 2939, 1760, 1646
2931, 1604, 1491, 1381, 1298, 1144, 1028, 909, 735 cm
1
;
21
1
(NCO), 1483, 1382, 1273, 1160, 999, 756 cm ; H NMR
(200 MHz, CDCl ) d 1.19 (s, 3H, CH ), 1.22–2.24 (m, 8H),
H NMR (200 MHz, CDCl ) d 0.88–0.99 (m, 3H, CH ),
3 3
1.08 (s, 3H, CH ), 1.22–1.82 (m, 15H), 2.79 (s, 3H, NCH ),
3 3
3
3

S. Muthusamy et al. / Tetrahedron 60 (2004) 7885–7897
7893
3
1
1
1
.63 (d, 1H, J¼8.1 Hz, H-11b), 4.23 (s, 1H, H-6), 4.34 (d,
H, J¼8.1 Hz, H-6a), 6.35 (d, 1H, J¼7.8 Hz, ArH), 6.58 (t,
H, J¼7.3 Hz, ArH), 6.91 (d, 1H, J¼7.2 Hz, ArH), 7.03 (t,
Data for compound 1,2-di[6,11c-epoxy-2,3,4,4a,5,6,6a,
7,11b,11c-decahydro-4a-methyl-5-oxo-1H-benzo[c]carba-
zole-7-ylmethyl]benzene (12a). Yellow solid (52%). Mp
215–217 8C. IR (CH Cl ) 2933, 1755, 1603, 1491,
1
3
H, J¼7.8 Hz, ArH); C NMR (50.3 MHz, CDCl ) d 14.7
3
2
2
1268 cm2 ; H NMR (200 MHz, C D ) d 0.94 (s, 6H,
1
1
(
CH ), 16.7 (4a-CH ), 23.1 (CH ), 23.4 (CH ), 24.0 (CH ),
3
3
2
2
2
6 6
2
7.6 (CH ), 27.9 (CH ), 34.0 (CH ), 35.1 (NCH ), 37.0
2
CH ), 0.99–1.05 (m, 2H), 1.17–2.12 (m, 12H), 1.99–2.07
3
2
2
3
(
CH ), 49.3 (quat-C), 50.0 (CH), 72.0 (CH), 82.1 (quat-C),
2
(m, 2H), 3.45–3.53 (m, 2H, CHAr), 3.77–3.93 (m, 2H,
NCH), 4.10 (s, 2H, OCH), 4.15–4.26 (m, 2H, NCH Ar),
8
5.8 (CH), 91.1 (quat-C), 107.1 (arom-CH), 116.7 (arom-
CH), 126.9 (arom-CH), 128.2 (quat-C), 128.6 (arom-CH),
2
4.37–4.52 (m, 2H, NCH Ar), 6.37 (d, J¼7.4 Hz, 2H, ArH),
2
þ
C H NO : C, 76.30; H, 7.47; N, 4.94. Found: C, 76.17; H,
þ
1
55.3 (quat-C); MS (FD ) m/z 341 (M ). Anal. Calcd for
6.77 (t, J¼7.1 Hz, 2H, ArH), 6.92 (d, J¼6.9 Hz, 2H, ArH),
1
3
7.10–7.23 (m, 4H, ArH), 7.42–7.25 (m, 2H, ArH);
C
2
2
31
2
7
.59; N, 4.81.
NMR (50.3 MHz, C D ) d 16.5 (CH ), 21.0 (CH ), 22.7
6 6 3 2
(
50.9 (CHAr), 51.1 (quat-C, CqCH ), 71.6 (NCH), 71.7
CH ), 25.9 (CH ), 31.0 (CH ), 49.4 (NCH ), 49.7 (NCH ),
2 2 2 2 2
4.4. General procedure for the double 1,3-dipolar
cycloaddition of carbonyl ylides with biindoles
3
(NCH), 85.7 (OCH), 85.9 (OCH), 91.1 (quat-C), 106.5
(
arom-CH), 106.8 (arom-CH), 117.2 (arom-CH), 117.4
Method A. An appropriate biindole (1.0 mmol) was taken in
a freshly distilled dry CH Cl with a catalytic amount
(arom-CH), 126.9 (arom-CH), 128.6 (arom-CH), 129.0
(arom-CH), 129.2 (arom-CH), 136.2 (quat-C), 136.4 (quat-
C), 153.9 (quat-C), 215.9 (quat-C, CvO); MS (FAB) m/z
2
2
(
mixture the CH Cl solution of diazo ketones 2a (4.0 mmol)
0.5 mol%) of Rh (OAc) . To the above stirred reaction
2 4
þ
640 (M ). Anal. Calcd for C H N O : C, 78.72; H, 6.92;
42 44 2 4
2
2
was added slowly using syringe at rt under an argon
atmosphere. The reaction was followed by TLC. After
completion of the reaction, the solvent was evaporated in
vacuo and the residue purified by neutral alumina column
chromatography.
N, 4.37. Found: C, 78.95; H, 6.76; N, 4.48.
4.4.2. Reaction of diazo ketone 2b with 1,2-di[(indol-1-
yl)methyl]benzene (10a). Method B. Data for compound
[6,11c-epoxy-2,3,4,4a,5,6,6a,7,11b,11c-decahydro-7-yl-[2-
indol-1-ylmethylbenzyl]-4a-methyl-5-oxo-1H-benzo[c]car-
bazole]-6-carboxylic acid ethyl ester (11b). Brown solid
(27%). Mp 187–189 8C. IR (CH Cl ) 3055, 2938, 1769,
Method B. An appropriate biindole (1.0 mmol), diazo
carbonyl compound (4.0 mmol) and the catalyst
2
2
1747, 1604, 1489, 1266 cm2 ; H NMR (200 MHz, CDCl3)
1 1
(
0.5 mol%) was taken together in dry benzene at the outset,
the reaction mixture was refluxed and proceeded further as
in Method A.
d 1.03 (t, J¼7.2 Hz, 3H, CH CH ), 1.22 (s, 3H, CH ), 1.26–
2
3
3
1.40 (m, 2H), 1.59–1.85 (m, 5H), 2.06–2.21 (m, 1H), 3.53–
3
.63 (m, 2H), 3.93 (d, J¼8.2 Hz, 1H, CHAr), 4.18 (d, J¼
Method C. An appropriate biindole (1.0 mmol), diazo
carbonyl compound (3.0 mmol) and the catalyst
17.2 Hz, 1H), 4.41 (d, J¼8.2 Hz, 1H, NCH ), 4.50 (d,
2
J¼17.2 Hz, 1H), 5.30 (s, 2H, NCH ), 6.14 (d, J¼7.8 Hz, 1H,
2
(
0.5 mol%) was taken together in dry 1,2-dichloroethane
ArH), 6.55 (d, J¼3.0 Hz, 1H), 6.65–6.78 (m, 2H, ArH),
1
3
and the reaction mixture stirred or refluxed and proceeded
further as in Method A.
6.96–7.35 (m, 9H, ArH), 7.64 (d, J¼8.2 Hz, 1H, ArH);
C
NMR (50.3 MHz, CDCl ) d 14.4 (CH ), 17.1 (CH ), 20.8
3
3
3
(
CH ), 22.5 (CH ), 25.9 (CH ), 31.3 (CH ), 48.1 (CH ), 51.3
2 2 2 2 2
4
.4.1. Reaction of diazo ketone 2a with 1,2-di[(indol-1-
yl)methyl]benzene (10a). Method A. Data for compound
,11c-epoxy-2,3,4,4a,5,6,6a,7,11b,11c-decahydro-7-yl-[2-
(quat-C, CqCH ), 52.5 (ArCH), 53.6 (CH ), 62.3 (CH ),
3 2 2
75.4 (NCH), 89.7 (quat-C), 95.1 (quat-C), 102.6 (arom-
CH), 108.7 (arom-CH), 110.3 (arom-CH), 118.7 (arom-
CH), 120.3 (arom-CH), 121.7 (arom-CH), 122.4 (arom-
CH), 126.0 (quat-C), 126.4 (arom-CH), 127.3 (arom-CH),
127.6 (arom-CH), 128.1 (arom-CH), 128.4 (arom-CH),
128.7 (arom-CH), 129.4 (arom-CH), 134.2 (quat-C), 137.0
(quat-C), 137.2 (quat-C), 155.1 (quat-C), 165.0 (quat-C),
6
indol-1-ylmethylbenzyl]-4a-methyl-5-oxo-1H-benzo[c]car-
bazole (11a). Brown solid (40%). Mp 168–170 8C. IR
2
1
1
(
(
CH Cl ) 2931, 1751, 1603, 1265 cm ;
200 MHz, C D ) d 0.73 (s, 3H, CH ), 0.76–0.85 (m, 2H),
H NMR
2
2
6
6
3
0
1
.92–1.36 (m, 5H), 1.05–1.55 (m, 1H), 3.25 (d, J¼8.2 Hz,
þ
þ
H, CHAr), 3.47–3.55 (m, 2H), 3.88–3.99 (m, 2H), 4.79 (q,
211.3 (quat-C, CvO); MS (FD ) m/z 560 (M ). Anal.
Calcd for C H N O : C, 77.12; H, 6.47; N, 5.00. Found:
C, 77.41; H, 6.35; N, 4.86.
J¼9.2 Hz, 2H, NCH ), 6.00 (d, J¼7.9 Hz, 1H, ArH), 6.01–
2
36 36 2 4
6
2
.53 (m, 2H, ArH), 6.56–6.63 (m, 2H, ArH), 6.65–6.73 (m,
H, ArH), 6.80–6.90 (m, 2H, ArH), 7.03–7.20 (m, 4H,
1
3
ArH), 7.55–7.64 (m, 1H, ArH); C NMR (50.3 MHz,
C D ) d 16.6 (CH ), 21.0 (CH ), 22.8 (CH ), 25.9 (CH ),
3
Data for compound 1,2-di[((6,11c-epoxy-2,3,4,4a,5,6,
6a,7,11b,11c-decahydro-4a-methyl-5-oxo-1H-benzo[c]car-
bazole)-6-carboxylic acid ethyl ester)-7-ylmethyl]benzene
(12b). Colorless solid (68%). Mp 213–215 8C. IR (CH Cl )
6
6
3
2
2
2
1.0 (CH ), 47.7 (NCH ), 49.9 (NCH ), 50.9 (CHAr), 51.1
2 2 2
(
quat-C, CqCH ), 71.9 (NCH), 85.9 (OCH), 91.1 (quat-C,
3
2
2
2940, 1769, 1746, 1602, 1489, 1267 cm2
1
;
(200 MHz, C D ) d 0.67–0.95 (m, 12H, CH ), 1.07–1.51
1
H NMR
C-11c), 102.8 (arom-CH), 106.8 (arom-CH), 110.5 (arom-
CH), 117.6 (arom-CH), 120.6 (arom-CH), 122.0 (arom-
CH), 122.6 (arom-CH), 126.9 (arom-CH), 127.9 (quat-C),
6
6
3
(m, 12H), 1.79–1.92 (m, 4H), 3.26–3.61 (m, 6H), 4.13–
4.28 (m, 4H), 4.41–4.55 (m, 2H), 6.15–6.33 (m, 1H), 6.31
(d, J¼7.8 Hz, 1H, ArH), 6.62–7.05 (m, 8H, ArH), 7.41 (m,
128.2 (arom-CH), 128.6 (arom-CH), 128.7 (arom-CH),
128.8 (arom-CH), 128.9 (arom-CH), 129.2 (arom-CH),
135.8 (quat-C), 136.1 (quat-C), 137.5 (quat-C), 153.8 (quat-
1
3
2H, ArH); C NMR (50.3 MHz, C D ) d 14.2 (CH ), 14.4
6
6
3
þ
þ
C), 216.0 (quat-C, CvO); MS (FD ) m/z 488 (M ). Anal.
Calcd for C H N O : C, 81.12; H, 6.60; N, 5.73. Found:
C, 80.89; H, 6.72; N, 5.86.
(CH ), 16.7 (CH ), 20.9 (CH ), 22.4 (CH ), 25.9 (CH ), 31.3
3 3 2 2 2
(CH ), 51.0 (quat-C, CqCH ), 52.5 (CH), 52.7 (CH), 53.5
2 3
(NCH ), 53.7 (NCH ), 61.9 (OCH ), 74.6 (NCH), 75.3
2 2 2
3
3
32
2
2

7894
S. Muthusamy et al. / Tetrahedron 60 (2004) 7885–7897
1
1
(
(
(
(
NCH), 89.4 (quat-C), 89.6 (quat-C), 95.4 (quat-C), 108.7
arom-CH), 109.0 (arom-CH), 118.3 (arom-CH), 118.4
arom-CH), 126.4 (arom-CH), 126.7 (arom-CH), 127.1
arom-CH), 129.5 (arom-CH), 135.9 (quat-C), 136.2 (quat-
1329 cm2 ; H NMR (200 MHz, C D ) d 0.71–0.86 (m,
6 6
6H), 0.93–1.08 (m, 2H), 1.15–1.65 (m, 5H), 1.86–1.98 (m,
1H), 3.41–3.52 (m, 2H), 3.63–3.79 (m, 1H), 4.07–4.16 (m,
2H), 4.32–4.47 (m, 1H), 4.56–4.75 (m, 2H), 6.35 (d, J¼
7.2 Hz, 1H), 6.52–6.89 (m, 6H, ArH), 6.94–7.16 (m, 6H,
ArH), 7.67–7.70 (m, 1H, ArH); C NMR (50.3 MHz,
C D ) d 13.9 (CH ), 16.3 (CH ), 20.5 (CH ), 22.0 (CH ),
C), 155.4 (quat-C), 164.9 (quat-C), 210.8 (quat-C, CvO);
MS (FAB) m/z 807.3 (MþNa) , (784.3, M ). Anal. Calcd
þ
for C H N O : C, 73.45; H, 6.68; N, 3.57. Found: C,
þ
13
4
8
52
2
8
6
6
3
3
2
2
7
3.25; H, 6.56; N, 3.68.
25.5 (CH ), 30.9 (CH ), 49.9 (NCH ), 50.7 (quat-C,
2 2 2
CqCH ), 52.2 (CH), 55.3 (NCH ), 61.5 (CH ), 73.9
2
3
2
4
.4.3. Reaction of diazo ketone 2a with 1,3-di[(indol-1-
(NCH), 88.9 (quat-C), 95.1 (quat-C), 102.1 (arom-CH),
108.8 (arom-CH), 110.2 (arom-CH), 118.1 (arom-CH),
119.9 (arom-CH), 121.4 (arom-CH), 122.0 (arom-CH),
125.1 (arom-CH), 125.3 (arom-CH), 125.9 (arom-CH),
126.1 (quat-C), 126.3 (arom-CH), 128.4 (arom-CH), 128.9
(arom-CH), 129.1 (quat-C), 136.9 (quat-C), 138.7 (quat-C),
139.9 (quat-C), 155.0 (quat-C), 164.5 (quat-C), 210.4 (quat-
yl)methyl]benzene (10b). Method A. Data for compound
,11c-epoxy-2,3,4,4a,5,6,6a,7,11b,11c-decahydro-7-yl-[3-
6
indol-1-ylmethylbenzyl]-4a-methyl-5-oxo-1H-benzo[c]car-
bazole (11c). Yellow solid (36%). Mp 208–210 8C. IR
(CH Cl ) 3055, 2937, 1756, 1604, 1490, 1265 cm ; H
2 2
NMR (200 MHz, C D ) d 0.73 (s, 3H, CH ), 0.79–0.89 (m,
2
8
4
2
1 1
6
6
3
þ
þ
H), 0.94–1.71 (m, 5H), 1.80–1.87 (m, 1H), 3.20 (d, J¼
C, CvO); MS (FD ) m/z 560 (M ). Anal. Calcd for
C H N O : C, 77.12; H, 6.47; N, 5.00. Found: C, 76.85;
H, 6.39; N, 5.13.
.2 Hz, 1H, CHAr), 3.49–3.77 (m, 3H), 4.10 (s, 1H, OCH),
.52 (s, 2H, NCH ), 5.97 (d, J¼7.9 Hz, 1H, ArH), 6.43 (d,
3
6 36 2 4
2
J¼3.0 Hz, 1H, ArH), 6.54 (t, J¼7.1 Hz, 2H, ArH), 6.63–
6
1
.92 (m, 6H, ArH), 6.98–7.09 (m, 3H, ArH), 7.56–7.61 (m,
H, ArH); C NMR (50.3 MHz, C D ) d 16.6 (CH ), 21.1
Data for compound 1,3-di[((6,11c-epoxy-2,3,4,4a,5,6,6a,
7,11b,11c-decahydro-4a-methyl-5-oxo-1H-benzo[c]carba-
zole)-6-carboxylic acid ethyl ester)-7-ylmethyl]benzene
(12d). Colorless solid (70%). Mp 108–110 8C. IR
1
3
6
6
3
(
CH ), 22.8 (CH ), 25.9 (CH ), 31.1 (CH ), 50.1 (NCH ),
2 2 2 2 2
5
0.9 (NCH ), 51.2 (quat-C, CqCH ), 71.2 (NCH), 85.9
2 3
2
1 1
(
(
(
(
(
(
OCH), 91.1 (quat-C, C-11c), 102.5 (arom-CH), 106.4
arom-CH), 110.5 (arom-CH), 117.1 (arom-CH), 120.4
arom-CH), 121.9 (arom-CH), 122.5 (arom-CH), 125.8
arom-CH), 126.1 (arom-CH), 126.8 (arom-CH), 126.9
arom-CH), 128.7 (arom-CH), 129.1 (arom-CH), 129.6
(CH Cl ) 2939, 1770, 1749, 1604, 1267 cm ; H NMR
2 2
(200 MHz, C D ) d 1.09 (s, 6H, CH ), 1.10–1.14 (m, 6H),
6
6
3
1.38–1.86 (m, 12H), 2.06–2.18 (m, 4H), 3.72–4.06 (m,
6H), 4.34–4.49 (m, 4H), 4.62–4.79 (m, 2H), 6.37 (d, J¼
8.1 Hz, 1H, ArH), 6.46–6.50 (m, 2H, ArH), 6.84–7.00 (m,
1
3
arom-CH), 137.2 (quat-C), 139.0 (quat-C), 139.6 (quat-C),
þ
4H, ArH), 7.09–7.39 (m, 5H, ArH); C NMR (50.3 MHz,
C D ) d 14.4 (CH ), 16.6 (CH ), 20.9 (CH ), 22.4 (CH ),
1
53.9 (quat-C), 216.1 (quat-C, CvO); MS (FD ) m/z 488
þ
.73. Found: C, 81.36; H, 6.78; N, 5.61.
6
6
3
3
2
2
(
M ). Anal. Calcd for C H N O : C, 81.12; H, 6.60; N,
3
25.9 (CH ), 31.4 (CH ), 51.0 (quat-C, CqCH ), 52.5 (CH),
2 2 3
52.6 (CH), 55.3 (NCH ), 55.8 (NCH ), 62.0 (OCH ), 73.9
2 2 2
3
32
2
2
5
(NCH), 74.3 (NCH), 89.3 (quat-C), 95.4 (quat-C), 109.2
Data for compound 1,3-di[6,11c-epoxy-2,3,4,4a,5,6,
a,7,11b,11c-decahydro-4a-methyl-5-oxo-1H-benzo[c]car-
(arom-CH), 118.2 (arom-CH), 118.3 (arom-CH), 125.0
(arom-CH), 125.1 (arom-CH), 125.7 (arom-CH), 126.4
(arom-CH), 126.5 (arom-CH), 140.0 (quat-C), 140.1 (quat-
C), 155.3 (quat-C), 155.6 (quat-C), 164.9 (quat-C), 211.0
6
bazole-7-ylmethyl]benzene (12c). Colorless solid (63%).
Mp 209–211 8C. IR (CH Cl ) 2938, 1756, 1604,
2
2
1
266 cm2 ; H NMR (200 MHz, C D ) d 0.75 (s, 3H,
CH ), 0.78 (s, 3H, CH ), 0.83–0.96 (m, 2H), 1.04–1.44 (m,
1
1
(quat-C, CvO); MS (FAB) m/z 785 (Mþ1), 784 (M ).
þ
6
6
Anal. Calcd for C H N O : C, 73.45; H, 6.68; N, 3.57.
48 52 2 8
3
3
9
2
2
H), 1.53–1.65 (m, 3H), 1.81–1.87 (m, 2H), 3.20–3.31 (m,
H, CHAr), 3.65–3.83 (m, 6H, NCH Ar, NCH), 4.20 (s,
H, OCH), 6.01–6.11 (m, 2H, ArH), 6.52–6.59 (m, 2H,
Found: C, 73.27; H, 6.57; N, 3.82.
2
4.4.5. Reaction of diazo ketone 2a with 1,4-di[(indol-1-
yl)methyl]benzene (10c). Method A. Data for compound
6,11c-epoxy-2,3,4,4a,5,6,6a,7,11b,11c-decahydro-7-yl-[4-
indol-1-ylmethylbenzyl]-4a-methyl-5-oxo-1H-benzo[c]car-
bazole (11e). Orange solid (45%). Mp 152–154 8C. IR
ArH), 6.68–6.74 (m, 2H, ArH), 6.88–6.97 (m, 4H, ArH),
1
3
7
.04 (m, 2H, ArH); C NMR (50.3 MHz, C D ) d 16.6
6 6
(
CH ), 16.7 (CH ), 21.1 (CH ), 22.8 (CH ), 25.9 (CH ), 31.1
3 3 2 2 2
(
quat-C, CqCH ), 31.2 (CH ), 50.6 (NCH ), 50.9 (CHAr),
3 2 2
2
1 1
5
1.0 (CHAr), 51.2 (NCH ), 70.8 (NCH), 71.1 (NCH), 85.8
2
(CH Cl ) 2934, 1758, 1727, 1604, 1285 cm ; H NMR
2 2
(
OCH), 85.9 (OCH), 91.0 (quat-C, OCq), 91.1 (quat-C,
(200 MHz, C D ) d 1.10 (s, 3H, CH ), 1.18–1.99 (m, 7H),
6 6 3
OCq), 106.5 (arom-CH), 106.6 (arom-CH), 116.9 (arom-
CH), 117.0 (arom-CH), 126.1 (arom-CH), 126.9 (arom-
CH), 129.1 (arom-CH), 129.2 (arom-CH), 129.7 (arom-
2.17–2.24 (m, 1H), 3.64 (d, J¼8.2 Hz, 1H, CHAr), 4.02–
4.25 (m, 3H), 4.52 (s, 1H, OCH), 4.92 (s, 2H, NCH ), 6.37
2
(d, J¼7.8 Hz, 1H, ArH), 6.80 (d, J¼3.0 Hz, 1H, ArH),
13
CH), 139.3 (quat-C), 139.5 (quat-C), 154.0 (quat-C), 216.2
(
6.88–7.04 (m, 4H, ArH), 7.10 (d, J¼7.1 Hz, 1H), 6.19–
þ
M ). Anal. Calcd for C H N O : C, 78.72; H, 6.92; N,
quat-C, CvO); MS (FAB) m/z 663.3 (MþNa) , 640.3
7.46 (m, 6H, ArH), 7.95–7.99 (m, 1H, ArH); C NMR
(50.3 MHz, C D ) d 16.5 (CH ), 21.0 (CH ), 22.7 (CH ),
þ
(
4
2
44
2
4
6
6
3
2
2
4
.37. Found: C, 78.93; H, 6.85; N, 4.46.
25.8 (CH ), 31.0 (CH ), 49.9 (NCH ), 50.7 (NCH ), 50.9
2 2 2 2
(ArCH), 51.1 (quat-C, CqCH ), 71.1 (NCH), 85.8 (OCH),
3
4
.4.4. Reaction of diazo ketone 2b with 1,3-di[(indol-1-
91.0 (quat-C, C-11c), 102.5 (arom-CH), 106.4 (arom-CH),
110.4 (arom-CH), 117.0 (arom-CH), 120.4 (arom-CH),
121.8 (arom-CH), 122.4 (arom-CH), 126.8 (arom-CH),
127.5 (arom-CH), 127.9 (arom-CH), 128.6 (arom-CH),
129.1 (arom-CH), 137.3 (quat-C), 138.2 (quat-C), 153.8
(quat-C), 216.2 (quat-C, CvO); MS (EI) m/z 489 (Mþ1, 5),
yl)methyl]benzene (10b). Method B. Data for compound
6,11c-epoxy-2,3,4,4a,5,6,6a,7,11b,11c-decahydro-7-yl-(3-
[
indol-1-ylmethylbenzyl)-4a-methyl-5-oxo-1H-benzo[c]car-
bazole]-6-carboxylic acid ethyl ester (11d). Yellow oil
(
24%). IR (CH Cl ) 2939, 1770, 1748, 1608, 1488,
2 2

S. Muthusamy et al. / Tetrahedron 60 (2004) 7885–7897
7895
þ
4
89 (M , 15), 376 (9), 336 (32), 298 (22), 269 (17), 255
NMR (50.3 MHz, C D ) d 14.4 (CH ), 16.6 (CH ), 20.8
6 6 3 3
(
(
27), 241 (14), 236 (14), 227 (11), 220 (36), 181 (38), 153
37), 123 (50), 111 (28), 91 (42). Anal. Calcd for
(CH ), 22.4 (CH ), 25.9 (CH ), 31.3 (CH ), 51.0 (quat-C,
2 2 2 2
CqCH ), 52.4 (CH), 52.5 (CH), 55.3 (NCH ), 62.0 (OCH ),
2
3
2
C H N O : C, 81.12; H, 6.60; N, 5.73. Found: C, 81.34;
3
62.1 (OCH ), 73.8 (NCH), 74.0 (NCH), 89.3 (quat-C), 95.4
2
3
32
2
2
H, 6.74 N, 5.62.
(quat-C), 109.2 (arom-CH), 109.4 (arom-CH), 118.3 (arom-
CH), 126.5 (quat-C), 127.4 (arom-CH), 127.6 (arom-CH),
129.2 (arom-CH), 138.2 (quat-C), 155.4 (quat-C), 164.9
Data for compound 1,4-di[6,11c-epoxy-2,3,4,4a,5,6,6a,
7,11b,11c-decahydro-4a-methyl-5-oxo-1H-benzo[c]carba-
zole-7-ylmethyl]benzene (12e). Yellow solid (50%). Mp
þ
þ
(quat-C), 210.9 (quat-C, CvO); MS (FD ) m/z (784, M ).
Anal. Calcd for C H N O : C, 73.45; H, 6.68; N, 3.57.
Found: C, 73.32; H, 6.79; N, 3.66.
4
8 52 2 8
2
1
08–210 8C. IR (CH Cl ) 2935, 1756, 1604, 1491,
2
2
286 cm2 ; H NMR (200 MHz, C D ) d 1.07 (s, 6H,
1
1
6
6
CH ), 1.22–1.83 (m, 12H), 1.92–2.04 (m, 2H), 2.16–2.27
3
4.4.7. Preparation of 1,3-di(indol-1-yl)propane (13a).
Indole (2.00 g, 17.07 mmol) was added to a suspension of
potassium hydroxide (3.83 g, 68.29 mmol) in dry DMSO
(30 mL) under nitrogen. After 0.75 h, 1,3-dibromopropane
(1.73 g, 8.54 mmol) was added at 0 8C and stirred at the
same temperature for an hour and allowed to warm to room
temperature. After 16 h, water (10 mL) was added and the
mixture extracted with dichloromethane (3£40 mL). The
combined organics were washed with water (3£40 mL),
brine (3£40 mL) and dried over anhydrous magnesium
sulfate. The solvent was removed under reduced pressure.
Purification by neutral alumina column chromatography
(EtOAc–hexane, 10:90) yielded the title compound 13a
(2.89 g, 65%) as yellow oil. IR (CH Cl ) 1512, 1461, 1400,
(
2
m, 2H), 3.65 (d, J¼8.1 Hz, 2H, CHAr), 4.08 (d, J¼8.1 Hz,
H, NCH), 4.13–4.29 (m, 4H, NCH Ar), 4.55 (s, 2H,
2
OCH), 6.42–6.52 (m, 2H, ArH), 6.92 (t, J¼7.3 Hz, 2H,
ArH), 7.10 (d, J¼7.1 Hz, 2H, ArH), 7.18–7.43 (m, 6H,
1
3
ArH); C NMR (50.3 MHz, C D ) d 22.1 (CH ), 26.6
6
6
3
(
CH ), 28.3 (CH ), 31.4 (CH ), 36.6 (CH ), 56.5 (ArCH),
2 2 2 2
5
6.7 (quat-C, CqCH ), 76.5 (NCH), 76.6 (NCH), 91.4
3
(
(
(
(
OCH), 96.6 (quat-C, OCq), 105.0 (arom-CH), 112.1
arom-CH), 122.4 (arom-CH), 131.7 (quat-C), 132.3
arom-CH), 133.7 (arom-CH), 134.7 (arom-CH), 136.7
quat-C), 143.4 (quat-C), 159.5 (quat-C), 221.7 (quat-C,
þ
CvO); MS (EI) m/z 641 (Mþ1, 3), 640 (M , 7), 488 (33),
3
1
87 (22), 376 (17), 349 (11), 336 (81), 235 (15), 124 (11),
23 (100), 104 (58). Anal. Calcd for C H N O : C, 78.72;
2
2
1315, 1242, 1174, 908, 735 cm2 ; H NMR (200 MHz,
1
1
4
2 44 2 4
H, 6.92; N, 4.37. Found: C, 78.93; H, 6.83; N, 4.45.
CDCl ) d 2.31 (p, J¼7.5 Hz, 2H, CH ), 3.99 (t, J¼6.7 Hz,
3
2
4
H, NCH ), 6.49 (d, J¼3.0 Hz, 2H, ArH), 6.97 (d, J¼
2
4
.4.6. Reaction of diazo ketone 2b with 1,4-di[(indol-1-
yl)methyl]benzene (10c). Method B. Data for compound
6,11c-epoxy-2,3,4,4a,5,6,6a,7,11b,11c-decahydro-7-yl-(4-
3.0 Hz, 2H, ArH), 7.05–7.35 (m, 6H, ArH), 7.63 (d,
J¼7.1 Hz, 2H, ArH); C NMR (50.3 MHz, CDCl ) d 30.9
1
3
3
[
(CH ), 44.1 (NCH ), 102.5 (arom-CH), 110.3 (arom-CH),
2
2
indol-1-ylmethylbenzyl)-4a-methyl-5-oxo-1H-benzo[c]car-
bazole]-6-carboxylic acid ethyl ester (11f). Brown solid
120.5 (arom-CH), 122.1 (arom-CH), 122.6 (arom-CH),
128.5 (arom-CH), 129.7 (quat-C), 136.8 quat-C).
(
1
9%). Mp 152–154 8C. IR (CH Cl ) 2942, 1769, 1746,
2 2
488, 1265 cm2 ; H NMR (200 MHz, C D ) d 0.73–0.83
1
1
4.4.8. Reaction of diazo ketone 2a with 1,3-di(indol-1-
yl)propane (13a). Method A. Data for compound 6,11c-
epoxy-2,3,4,4a,5,6,6a,7,11b,11c-decahydro-[-7-yl-(indol-1-
ylpropyl)]-4a-methyl-5-oxo-1H-benzo[c]carbazole (14a).
Brown solid (23%). Mp 128–130 8C. IR (CH Cl ) 2939,
6
6
(
(
m, 6H), 0.92–1.00 (m, 1H), 1.14–1.65 (m, 5H), 1.85–1.97
m, 2H), 3.42–3.66 (m, 3H), 4.08–4.22 (m, 2H), 4.50 (d,
J¼7.4 Hz, 1H), 4.63 (s, 2H, NCH ), 6.15–6.19 (m, 1H,
2
ArH), 6.51 (d, J¼2.1 Hz, 1H, ArH), 6.68–6.80 (m, 4H,
ArH), 6.98 (t, J¼7.4 Hz, 1H), 7.06–7.15 (m, 6H, ArH),
2
2
1755, 1604, 1489, 1462, 1159 cm2 ; H NMR (200 MHz,
1 1
1
3
7
1
3
.67–7.69 (m, 1H, ArH); C NMR (50.3 MHz, C D ) d
6
CDCl ) d 1.17 (s, 3H, CH ), 1.36–1.69 (m, 7H), 1.81–2.20
3
6
3
4.2 (CH ), 16.6 (CH ), 20.8 (CH ), 22.4 (CH ), 25.9 (CH ),
2
(m, 3H), 3.21 (t, J¼7.2 Hz, 2H, NCH ), 3.73 (d, J¼8.2 Hz,
3
3
2
2
2
1.3 (CH ), 50.0 (NCH ), 51.0 (quat-C, CqCH ), 52.5
2
1H, CHAr), 4.07 (d, J¼8.2 Hz, 1H, NCH), 4.22 (t, J¼
2
3
(
NCH), 55.4 (CH ), 61.9 (CH ), 74.1 (NCH), 85.8 (OCH),
2
6.8 Hz, 2H, NCH ), 4.47 (s, 1H, OCH), 6.22 (d, J¼7.9 Hz,
2
2
8
1
1
1
1
9.3 (quat-C, C-11c), 102.4 (arom-CH), 109.1 (arom-CH),
10.5 (arom-CH), 118.4 (arom-CH), 120.3 (arom-CH),
21.8 (arom-CH), 122.3 (arom-CH), 126.5 (arom-CH),
27.5 (arom-CH), 128.3 (arom-CH), 128.7 (arom-CH),
1H, ArH), 6.54 (d, J¼2.3 Hz, 1H, ArH), 6.62 (t, J¼7.3 Hz,
1H, CHAr), 6.95–7.34 (m, 6H, ArH), 7.66 (d, J¼7.8 Hz,
1
3
1H, ArH); C NMR (50.3 MHz, CDCl ) d 16.9 (CH ), 21.1
3
3
(CH ), 22.8 (CH ), 26.0 (CH ), 28.6 (CH ), 31.1 (CH ), 44.5
2
2
2
2
2
29.3 (arom-CH), 136.9 (quat-C), 139.1 (quat-C), 155.3
þ
(NCH ), 45.7 (NCH ), 51.0 (ArCH), 51.5 (quat-C, CqCH ),
2 2 3
(
m/z 560 (M ). Anal. Calcd for C H N O : C, 77.12; H,
6
quat-C), 164.8 (quat-C), 210.8 (quat-C, CvO); MS (FD )
70.6 (NCH), 86.2 (OCH), 91.4 (quat-C, C-11c), 102.3
(arom-CH), 107.3 (arom-CH), 110.0 (arom-CH), 117.6
(arom-CH), 120.1 (arom-CH), 121.8 (arom-CH), 122.3
þ
.47; N, 5.00. Found: C, 77.37; H, 6.63; N, 5.16.
3
6 36 2 4
(
arom-CH), 126.1 (quat-C), 126.9 (arom-CH), 128.3 (arom-
Data for compound 1,4-di[((6,11c-epoxy-2,3,4,4a,5,6,
a,7,11b,11c-decahydro-4a-methyl-5-oxo-1H-benzo[c]car-
bazole)-6-carboxylic acid ethyl ester)-7-ylmethyl]benzene
CH), 129.2 (arom-CH), 136.7 (quat-C), 138.2 (quat-C),
153.6 (quat-C), 218.0 (quat-C, CvO); MS (FAB) m/z 427
(Mþ1). Anal. Calcd for C H N O : C, 78.84; H, 7.09; N,
6
2
8 30 2 2
(
12f). Colorless solid (80%). Mp 122–124 8C. IR (CH Cl )
2
941, 1770, 1748, 1605, 1267 cm ; H NMR (200 MHz,
6.57. Found: C, 78.72; H, 7.16; N, 6.59.
2
2
1 1
2
C D ) d 0.77 (s, 6H, CH ), 0.84–1.01 (m, 6H), 1.07–1.55
Data for compound 1,3-di[6,11c-epoxy-2,3,4,4a,5,6,
6a,7,11b,11c-decahydro-4a-methyl-5-oxo-1H-benzo[c]car-
bazole-7-yl]propane (15a). Brown solid (65%). Mp 91–
93 8C. IR (CH Cl ) 3020, 2939, 1755, 1604, 1490,
6
6
3
(
m, 12H), 1.76–1.89 (m, 4H), 3.36–3.41 (m, 2H, CHAr),
3
2
6
.54–3.86 (m, 4H), 4.04–4.16 (m, 4H), 4.43 (d, J¼16.5 Hz,
H), 6.12–6.20 (m, 3H, ArH), 6.56–6.67 (m, 4H, ArH),
C
2
2
1
3
21 1
.81–6.86 (m, 2H, ArH), 7.02–7.17 (m, 3H, ArH);
1216 cm . H NMR (200 MHz, CDCl ) d 1.15 (s, 6H,
3

7896
S. Muthusamy et al. / Tetrahedron 60 (2004) 7885–7897
1
3
CH ), 1.31–2.13 (m, 18H), 3.27 (dt, J¼19.9, 7.4 Hz, 4H,
ArH); C NMR (50.3 MHz, CDCl ) d 16.9 (CH ), 21.1
3 3
3
NCH ), 3.27 (dd, J¼8.2, 3.3 Hz, 2H, CHAr), 3.72 (dd,
(CH ), 22.7 (CH ), 25.6 (CH ), 25.9 (CH ), 28.5 (CH ), 31.0
2 2 2 2 2
(CH ), 46.8 (CH ), 47.6 (CH ), 50.9 (ArCH), 51.5 (quat-C,
2 2 2
CqCH ), 70.4 (NCH), 86.1 (OCH), 91.4 (quat-C, C-11c),
3
102.0 (arom-CH), 106.8 (arom-CH), 110.0 (arom-CH),
117.1 (arom-CH), 120.0 (arom-CH), 121.7 (arom-CH),
122.2 (arom-CH), 125.9 (quat-C), 126.8 (arom-CH), 128.3
(arom-CH), 129.1 (arom-CH), 136.6 (quat-C), 153.7 (quat-
C), 218.1 (quat-C, CvO); MS (FAB) m/z 440 (M ). Anal.
Calcd for C H N O : C, 79.06; H, 7.32; N, 6.36. Found:
C, 79.33; H, 7.46; N, 6.27.
2
J¼8.2, 3.8 Hz, 2H, NCH), 4.46 (s, 1H, OCH), 4.47 (s, 1H,
OCH), 6.35 (dd, J¼7.8, 3.7 Hz, 2H, ArH), 6.59 (t, J¼
7
.3 Hz, 2H, ArH), 6.97 (d, J¼7.2 Hz, 2H, ArH), 7.05 (t,
1
3
J¼7.8 Hz, 2H, ArH); C NMR (50.3 MHz, C D ) d 16.9
6
6
(
(
CH ), 21.1 (CH ), 22.7 (CH ), 25.5 (CH ), 25.9 (CH ), 31.0
3 2 2 2 2
CH ), 45.6 (NCH ), 45.7 (NCH ), 50.9 (CH), 51.5 (quat-C,
2
2
2
þ
CqCH ), 70.5 (NCH), 70.6 (NCH), 86.1 (OCH), 91.4 (quat-
3
C, OCq), 107.0 (arom-CH), 107.2 (arom-CH), 117.3 (arom-
CH), 126.1 (quat-C), 126.8 (arom-CH), 129.2 (arom-CH),
2
9 32 2 2
1
53.5 (quat-C), 218.1 (quat-C, CvO); MS (FAB) m/z 578
þ
.84. Found: C, 76.92; H, 7.43; N, 4.89.
(
M ). Anal. Calcd for C H N O : C, 76.79; H, 7.31; N,
3
Data for compound 1,4-di[6,11c-epoxy-2,3,4,4a,5,6,6a,7,
11b,11c-decahydro-4a-methyl-5-oxo-1H-benzo[c]carba-
zole-7-yl]butane (15c). Brown solid (57%). Mp 183–
7 42 2 4
4
2
1
4.4.9. Reaction of diazo ketone 2b with 1,3-di(indol-1-
yl)propane (13a) in 1,2-dichloroethane. Method C. Data
185 8C. IR (CH Cl ) 2938, 1754, 1604, 1491, 1286 cm
2
;
2
1
H NMR (200 MHz, CDCl ) d 0.82–1.09 (m, 2H), 1.15 (s,
3
for compound 1,3-di[((6,11c-epoxy-2,3,4,4a,5,6,6a,7,11b,
1c-decahydro-4a-methyl-5-oxo-1H-benzo[c]carbazole)-6-
6H, CH ), 1.31–2.00 (m, 16H), 2.19–2.24 (m, 2H), 3.17–
3
1
3.27 (m, 4H, NCH ), 3.71 (d, J¼8.2 Hz, 2H, ArCH), 4.01 (d,
2
carboxylic acid ethyl ester)-7-yl]propane (15b). Colorless
solid (85%). Mp 126–128 8C. IR (CH Cl ) 2941, 1769,
J¼8.2 Hz, 2H, NCH), 4.45 (s, 2H, OCH), 6.35 (d, J¼7.9 Hz,
2H, ArH), 6.58 (t, J¼7.3 Hz, 2H, ArH), 6.94 (d, J¼7.2 Hz,
2
2
2
1
1
13
1
(
746, 1603, 1488, 1374, 1325, 1017, cm
.
H NMR
200 MHz, CDCl ) d 1.19 (s, 6H, CH ), 1.27–1.51 (m,
2H, ArH), 7.06 (t, J¼7.6 Hz, 2H, ArH); C NMR
(50.3 MHz, CDCl ) d 16.9 (CH ), 21.0 (CH ), 22.7 (CH ),
3
3
3
3
2
2
1
(
2H), 1.58–1.80 (m, 10H), 2.00–2.04 (m, 2H), 3.09–3.26
m, 4H, NCH ), 3.81 (m, 2H, NCH), 4.21–4.36 (m, 4H),
25.5 (CH ), 25.8 (CH ), 25.9 (CH ), 30.4 (CH ), 31.0 (CH ),
2 2 2 2 2
47.4 (NCH ), 47.8 (NCH ), 50.9 (ArCH), 51.6 (quat-C,
2 2
2
6
.36 (dd, J¼7.6, 5.7 Hz, 2H, ArH), 6.61–6.66 (m, 2H,
CqCH ), 70.3 (NCH), 70.6 (NCH), 86.1 (OCH), 86.2
3
ArH), 6.92 (d, J¼7.2 Hz, 4H, ArH), 6.99–7.09 (m, 2H,
(OCH), 96.6 (quat-C, OCq), 106.9 (arom-CH), 117.0
(arom-CH), 126.0 (quat-C), 126.8 (arom-CH), 129.2
(arom-CH), 153.7 (quat-C), 218.2 (quat-C, CvO); MS
1
3
ArH); C NMR (50.3 MHz, CDCl ) d 14.9 (CH ), 17.0
3
3
(
(
CH ), 20.8 (CH ), 22.4 (CH ), 25.9 (CH ), 31.2 (CH ), 47.5
3 2 2 2 2
NCH ), 47.9 (NCH ), 51.2 (quat-C, CqCH ), 51.3 (quat-C,
2
þ
(FAB) m/z 592 (M ). Anal. Calcd for C H N O : C,
38 44 2 4
2
3
CqCH ), 52.2 (ArCH) 62.2 (OCH ), 72.7 (NCH), 72.9
2
77.00; H, 7.48; N, 4.73. Found: C, 77.24; H, 7.59; N, 4.66.
3
(
(
(
NCH), 89.5 (quat-C, OCq), 94.7 (quat-C, OCq), 94.8
quat-C, OCq), 109.4 (arom-CH), 118.2 (arom-CH), 126.1
quat-C), 126.2 (quat-C), 126.5 (arom-CH), 126.6 (arom-
4.4.12. Reaction of diazo ketone 2b with 1,4-di(indol-1-
yl)butane (13b) in 1,2-dichloroethane. Method C. 1,4-
Di[((6,11c-epoxy-2,3,4,4a,5,6,6a,7,11b,11c-decahydro-4a-
methyl-5-oxo-1H-benzo[c]carbazole)-6-carboxylic acid
ethyl ester)-7-yl]butane (15d). Colorless solid (90%). Mp
149–151 8C. IR (CH Cl ) 2935, 1768, 1748, 1604, 1489,
CH), 129.1 (arom-CH), 129.3 (arom-CH), 153.8 (quat-C),
1
(
54.0 (quat-C), 165.0 (quat-C), 211.0 (quat-C, CvO); MS
FAB) m/z 723 (M ). Anal. Calcd for C H N O : C,
þ
1.45; H, 6.97; N, 3.88. Found: C, 71.67; H, 6.84; N, 3.76.
4
3 50 2 8
7
2
2
462, 1372, 1323, 1281, 1131, 750 cm2
1
;
1
H NMR
1
(200 MHz, CDCl ) d 1.21 (s, 6H, CH ), 1.26–1.38 (m,
4
.4.10. Preparation of 1,4-di(indol-1-yl)butane (13b). The
3
3
procedure was followed as described for compound 13a to
yield the title compound 13b as a yellow solid (78%). Mp
14H), 1.51–1.95 (m, 10H), 2.05 (d, J¼8.3 Hz, 2H), 3.04–
3.31 (m, 4H), 3.80 (d, J¼8.2 Hz, 2H, CH), 4.23–4.39 (m,
6H), 6.35–6.41 (m, 2H, ArH), 6.63 (t, 2H, J¼7.3 Hz, ArH),
6.94 (d, J¼7.2 Hz, 2H, ArH), 7.06 (t, J¼7.6 Hz, 2H, ArH);
2
4
9
1
1
6
0 8C (lit., mp 88 8C). IR (CH Cl ) 1512, 1461, 1315,
2 2
242, 1174, 908, 735 cm ; H NMR (200 MHz, CDCl ) d
3
2
1 1
1
3
.09 (m, 4H, CH ), 3.19 (m, 4H, NCH ), 6.49 (m, 4H, ArH),
2
C NMR (50.3 MHz, C D ) d 14.8 (CH ), 16.9 (CH ), 20.7
6 6 3 3
2
.99 (d, J¼7.3 Hz, 2H, ArH), 7.12–7.26 (m, 4H, ArH), 7.70
(CH ), 22.3 (CH ), 23.9 (CH ), 24.3 (CH ), 25.7 (CH ), 31.1
2 2 2 2 2
(CH ), 49.6 (CH ), 50.0 (CH ), 51.2 (quat-C, CqCH ), 52.1
2 2 2 3
(CH), 62.3 (OCH ), 72.7 (OCH), 73.0 (OCH), 89.4 (quat-
2
1
3
(
d, J¼6.5 Hz, 2H, ArH); C NMR (50.3 MHz, CDCl ) d
3
2
7.6 (CH ), 45.5 (NCH ), 101.6 (arom-CH), 109.7 (arom-
2
2
CH), 119.9 (arom-CH), 121.6 (arom-CH), 121.9 (arom-
CH), 127.7 (arom-CH), 128.2 (quat-C), 128.6 (quat-C).
C), 94.6 (quat-C), 109.2 (arom-CH), 118.0 (arom-CH),
126.0 (quat-C), 126.5 (arom-CH), 129.1 (arom-CH), 153.8
(
quat-C), 154.0 (quat-C), 164.9 (quat-C), 211.0 (quat-C,
þ
Calcd for C H N O : C, 71.25; H, 7.23; N, 3.86. Found:
þ
4.4.11. Reaction of diazo ketone 2a with 1,4-di(indol-1-yl)-
butane (13b). Method A. Data for compound 6,11c-epoxy-
CvO); MS (FAB) m/z 759.3 (MþNa) 722.3 (M ). Anal.
4
3 52 2 8
2
4
,3,4,4a,5,6,6a,7,11b,11c-decahydro-[-7-yl-(indol-1-ylbutyl)]-
a-methyl-5-oxo-1H-benzo[c]carbazole (14c). Brown solid
C, 71.42; H, 7.41; N, 3.72.
(
1
(
(
29%). Mp 132–134. IR (CH Cl ) 3020, 2936, 1754, 1604,
2 2
490, 1216 cm2 ; H NMR (200 MHz, CDCl ) d 0.88–1.01
m, 2H), 1.13 (s, 3H, CH ), 1.27–1.92 (m, 9H), 2.61–2.76
1 1
3
Acknowledgements
3
m, 1H), 3.10–3.20 (m, 2H, NCH ), 3.67 (d, J¼8.2 Hz, 1H,
This research was supported by Department of Science and
Technology, New Delhi. We thank Professor W. Sander,
R u¨ hr university, Germany for providing mass spectral
analyses. C. G. thanks CSIR, New Delhi for the award of a
research fellowship.
2
CHAr), 3.93 (d, J¼8.2 Hz, 1H, NCH), 4.14 (t, J¼6.9 Hz,
2
H, NCH ), 4.39 (s, 1H, OCH), 6.29 (d, J¼7.9 Hz, 1H,
2
ArH), 6.49 (d, J¼3.1 Hz, 1H, ArH), 6.58 (t, J¼7.4 Hz, 1H,
CHAr), 6.95–7.34 (m, 6H, ArH), 7.62 (d, J¼7.3 Hz, 1H,

S. Muthusamy et al. / Tetrahedron 60 (2004) 7885–7897
7897
References and notes
11. Ito, A. JP 04,329,547, 1992; Chem. Abstr. 1993, 118, 180013t.
1
2. (a) Muthusamy, S.; Gunanathan, C. Chem. Commun. 2003,
440–441. (b) Muthusamy, S.; Babu, S. A.; Gunanathan, C.;
Ganguly, B.; Suresh, E.; Dastidar, P. J. Org. Chem. 2002, 67,
8019–8033. (c) Muthusamy, S.; Gunanathan, C.; Babu, S. A.
Synthesis 2002, 471–474. (d) Muthusamy, S.; Babu, S. A.;
Gunanathan, C. Tetrahedron Lett. 2002, 43, 3931–3934, and
references cited therein.
1
. (a) Ho, T. L. Tandem Organic Reactions; Wiley: New York,
1
992. (b) Nicolaou, K. C.; Montagnon, T.; Snyder, S. A.
Chem. Commun. 2003, 551–564. (c) Waldmann, H. Domino
Reaction in Organic Synthesis Highlight II; VCH: Weinheim,
1
1
995; 1–600. (d) Wender, P. A., Ed. Chem. Rev., 1996, 96,
–600. (e) Tietze, L. F.; Beifuss, U. Angew. Chem., Int. Ed.
Engl. 1993, 32, 131–163. (f) Curran, D. P. Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon:
Oxford, 1991; Vol. 4, pp 779–831.
13. (a) Muthusamy, S.; Gunanathan, C.; Nethaji, M. Synlett 2004,
639–642. (b) Muthusamy, S.; Gunanathan, C. Synlett 2003,
1599–1602. (c) Muthusamy, S.; Gunanathan, C.; Babu, S. A.;
Suresh, E.; Dastidar, P. Chem. Commun. 2002, 824–825.
(d) Muthusamy, S.; Gunanathan, C. Synlett 2002, 1783–1786.
14. Muthusamy, S.; Babu, S. A.; Gunanathan, C.; Suresh, E.;
Dastidar, P.; Jasra, R. V. Tetrahedron 2000, 56, 6307–6318.
15. Heaney, H.; Ley, S. V. J. Chem. Soc., Perkin Trans. 1 1973,
499–500.
2
. For a general discussion see: (a). 1,3-Dipolar Cycloaddition
Chemistry; Padwa, A., Ed.; Wiley-Interscience: New York,
1984; Vols. 1 and 2. (b) Padwa, A. Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford,
1
991; Vol. 4, p 1069. (c) In Synthetic Applications of 1,
-Dipolar Cycloaddition Chemistry Toward Heterocycles and
3
Natural Products; Padwa, A., Pearson, W. H., Eds.; Wiley:
New York, 2002.
16. (a) Padwa, A.; Price, A. T. J. Org. Chem. 1998, 63, 556–565.
(b) Padwa, A.; Price, A. T. J. Org. Chem. 1995, 60,
6258–6259.
3
. For reviews of metal–carbene transformations see: (a) Mehta,
G.; Muthusamy, S. Tetrahedron 2002, 58, 9477–9504.
17. Wilkie, G. D.; Elliott, G. I.; Blagg, B. S. J.; Wolkenberg, S. E.;
Soenen, D. R.; Miller, M. M.; Pollack, S.; Boger, D. L. J. Am.
Chem. Soc. 2002, 124, 11292–11294.
(
b) Hodgson, D. M.; Pierard, F. Y. T. M.; Stupple, P. A.
Chem. Soc. Rev. 2001, 30, 50–61. (c) Doyle, M. P.;
McKervey, M. A.; Ye, T. Modern Catalytic Methods for
Organic Synthesis with Diazo Compounds. From Cyclo-
propanes to Ylides; Wiley-Interscience: New York, 1998.
18. The structure was solved by direct methods and refined by full-
2
matrix least squares of F using SHELX-97 (Sheldrick, M.
SHELX-97, Program for the solution of crystal structures,
University of Gottingen, Germany, 1997.). All non-hydrogen
atoms were refined anisotropically. Some hydrogens were
located on a difference Fourier map and some were
stereochemically fixed.
(
d) Doyle, M. P.; Forbes, D. C. Chem. Rev. 1998, 98,
9
11–935. (e) Padwa, A.; Weingarten, M. D. Chem. Rev. 1996,
6, 223–269.
9
4
5
. (a) Padwa, A.; Curtis, E. A.; Sandanayaka, V. P. J. Org. Chem.
997, 62, 1317–1325. (b) McMorris, T. C.; Hu, Y.; Yu, J.;
1
19. Bloxham, J.; Moody, C. J.; Slawin, A. M. Z. Tetrahedron
2002, 58, 3709–3720.
Kelner, M. J. Chem. Commun. 1997, 315–316. (c) Kinder,
F. R. Jr.; Bair, K. W. J. Org. Chem. 1994, 59, 6965–6967.
. (a) McMills, M. C.; Zhuang, L.; Wright, D. L.; Watt, W.
Tetrahedron Lett. 1994, 35, 8311–8314. (b) Dauben, W. G.;
Dinges, J.; Smith, T. C. J. Org. Chem. 1993, 58, 7635–7637.
. Padwa, A.; Chinn, R. L.; Zhi, L. Tetrahedron Lett. 1989, 30,
20. (a) Ibata, T.; Toyoda, J. Bull. Chem. Soc. Jpn 1986, 59,
2489–2493. (b) Padwa, A.; Fryxell, G. E.; Zhi, L. J. Am.
Chem. Soc. 1990, 112, 3100–3109.
21. (a) Aburel, P. S.; Undheim, K. J. Chem. Soc., Perkin Trans. 1
2000, 1891–1896. (b) Doyle, M. P.; McKervey, M. A.; Ye, T.
Modern Catalytic Methods for Organic Synthesis with Diazo
Compounds. From Cyclopropanes to Ylides; Wiley-Inter-
science: New York, 1998; pp 112–151.
6
7
1491–1494.
. (a) Hodgson, D. M.; Bailey, J. M.; Villalonga-Barber, C.;
Drew, M. G. B.; Harrison, T. J. Chem. Soc., Perkin Trans. 1
2
000, 3432–3443. (b) Kataoka, O.; Kitagaki, S.; Watanabe,
22. (a) Bagley, M. C.; Buck, R. T.; Hind, S. L.; Moody, C. J.
J. Chem. Soc., Perkin Trans. 1 1998, 591–600. (b) Bagley,
M. C.; Moody, C. J. J. Chem. Soc., Perkin Trans. 1 1998,
601–607. (c) Bashford, K. E.; Cooper, A. L.; Kane, P. D.;
Moody, C. J.; Muthusamy, S.; Swann, E. J. Chem. Soc., Perkin
Trans. 1 2002, 1672–1687.
N.; Kobayashi, J.; Nakumura, S.; Shiro, M.; Hashimoto, S.
Tetrahedron Lett. 1998, 39, 2371–2374.
. Hodgson, D. M.; Avery, T. D.; Donohue, A. C. Org. Lett.
8
9
2
002, 4, 1809–1811.
. A part of this work has been published as preliminary
communication. See: Muthusamy, S.; Gunanathan, C.; Babu,
S. A. Tetrahedron Lett. 2001, 42, 523–526.
23. Copies of the data can be obtained, free of charge, on
application to CCDC, 12 Union Road, Cambridge CB2 1EZ,
UK [fax:þ44-1223-336033 or e-mail: deposit@ccdc.cam.ac.uk].
24. Julia, M.; Manoury, P. Bull. Soc. Chim. Fr. 1964, 1946–1953.
1
0. Sugumi, H. et al. WO 96 38,446, 1996; Chem. Abstr. 1996,
26, 89394x.
1