Rhodium(II) catalyzed intermolecular double C-alkylation: A method for the synthesis of tetraindoles and indolophanes

Article abstract of DOI:10.1016/j.tet.2011.11.073

Double C-alkylation of cyclic diazoamides or bis-diazoamides with indoles or bis-indoles has been achieved to synthesize tetraindole derivatives using rhodium(II) acetate as a catalyst under mild reaction conditions with complete regioselectivity. The intermolecular double C-alkylation reaction strategy was successfully applied to synthesize indolophanes in moderate yield with excellent regiocontrol. The structure and stereochemistry of macrocycles were unequivocally confirmed with the help of single-crystal X-ray structure analyses.

Full text of DOI:10.1016/j.tet.2011.11.073

Tetrahedron 68 (2012) 1595e1605
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Tetrahedron
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Rhodium(II) catalyzed intermolecular double C-alkylation: a method for the
synthesis of tetraindoles and indolophanes
,
a
a
Sengodagounder Muthusamy a , Thangaraju Karikalan , Chidambaram Gunanathan ,
*
Eringathodi Suresh b
a School of Chemistry, Bharathidasan University, Palkalaiperur, Tiruchirappalli 620024, India
b Central Salt & Marine Chemicals Research Institute, Bhavnagar 364002, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Double C-alkylation of cyclic diazoamides or bis-diazoamides with indoles or bis-indoles has been
achieved to synthesize tetraindole derivatives using rhodium(II) acetate as a catalyst under mild reaction
conditions with complete regioselectivity. The intermolecular double C-alkylation reaction strategy was
successfully applied to synthesize indolophanes in moderate yield with excellent regiocontrol. The
structure and stereochemistry of macrocycles were unequivocally confirmed with the help of single-
crystal X-ray structure analyses.
Received 20 September 2011
Received in revised form 22 November 2011
Accepted 24 November 2011
Available online 1 December 2011
Keywords:
Ó 2011 Elsevier Ltd. All rights reserved.
C-Alkylation
Indolophanes
Macrocycles
Tetraindoles
1. Introduction
catalysts afforded the corresponding cyclopropanation5,9 across the
indole 2,3-double bond. Our recent report indicates that the re-
Plethora of reports are available, in which ‘rhodium(II) catalysts’
were highly selective for transformations, such as cyclo-
propanation, insertion, and ylide formation.1 Interesting de-
velopments were seen in the past few years, particularly, the
combination of transition metal-catalyzed cyclopropanation fol-
lowed by other types of reactions in a single or cascade operation.
Owing to the high strain of the three-membered ring system, there
are many possible pathways for the ring opening of cyclopropanes.
Cyclopropane rings bearing both electron-donating and -with-
drawing groups are prone to undergo ring opening2 reactions. The
reactions of metallo-carbenoids with furan,3 pyrrole4 or indole4
resulted in an initial cyclopropanation followed by a consecutive
ring opening process. Similarly, cyclopropanation of other hetero-
cycles including activated quinolines, isoquinolines,5 and benzo-
pyrylium triflates,6 followed by the ring enlargement reaction was
also reported. Many indoline alkaloids7 were synthesized via
cyclopropanation followed by ring opening strategy. The rhodium-
catalyzed intramolecular reactions of pyrrolyl and indolyl diazo-
ketones generally resulted8 in the alkylation products via cyclo-
propanation. Conversely, the inter- as well as intramolecular
reactions of diazo compounds with indole in the presence of copper
actions of metallo-carbenoids derived from diazoamides 1 with
heteroaromatic systems, such as benzofuran and benzothiophene
afforded10 the cyclopropanation products without any ring open-
ing. However, reaction of cyclic diazoamide 1 (R1¼Me) with N-
benzylindole 2 (R2¼Bn) in the presence of Rh2(OAc)4 afforded the
corresponding 3-alkylated product11 5 in quantitative yields with
the complete regioselectivity (Scheme 1). This process reveals that
the formation of product 5 might be produced via the corre-
sponding spirocyclopropanes 3 and followed by ring opening to
zwitterions 4 as intermediate in the presence of copper or rhodium
catalyst.
The design and synthesis of macrocycles containing aromatic/
heteroaromatic ring systems are an intriguing branch of organic
and supramolecular chemistry.12,13 However, aromatic units pres-
ent in the cyclophanes are mostly carbocyclic rings, such as ben-
zene or naphthalene derivatives. Our enticement in developing
a new synthetic strategies14 using diazocarbonyl compounds en-
couraged us to investigate the application of the cyclopropane/ring
opening methodology for the synthesis of indolophanes (Scheme
2). We herein report the intermolecular double C-alkylation re-
actions of cyclic diazoamides 6 in the presence of Rh2(OAc)4 cata-
lyst in a single synthetic step furnishing tetraindole derivatives
(indolophanes) with excellent regiocontrol via cyclopropanation
followed by ring opening process.
* Corresponding author. E-mail address: muthu@bdu.ac.in (S. Muthusamy).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.11.073

1596
S. Muthusamy et al. / Tetrahedron 68 (2012) 1595e1605
alkylated products 10beg as a diastereomeric mixture in very
good yield and the results are delineated in Table 1.
Scheme 1. Synthesis of 3-alkylated product 5.
Scheme 3. Synthesis of tetraindoles from cyclic diazoamides 6.
Table 1
Reaction of bis-diazoamides 6 with substituted indoles 2
Entry
Product
n
R2
Time (min)
Yielda
%
drb
1
2
3
4
5
6
7
10a
10b
10c
10d
10e
10f
1
1
1
2
2
2
2
CH3
20
20
30
15
15
15
20
85
93
82
89
89
77
80
59:41
56:44
58:42
65:35
61:39
59:41
60:40
C6H5CH2
4-CH3C6H4CH2
CH3
C6H5CH2
4-CH3C6H4CH2
Allyl
10g
a
Isolated yield.
Diastereomeric ratio based on the crude NMR spectra.
b
Scheme 2. Synthesis of indolophanes.
Having studied the reaction profile of bis-diazoamides, we next
examined the double C-alkylation reaction of bis-indoles 7 with
cyclic diazoamides 1bef. Thus, reaction of bis-indole 7a with an
excess amount of cyclic diazoamide 1b in the presence of 1 mol % of
rhodium(II) acetate catalyst at room temperature was performed.
The reaction was completed in 25 min; concentrated and chro-
matographic purification of the reaction mixture delivered the
tetraindole derivative 11a as a mixture of diastereomers in quan-
titative yields (Scheme 4). The 1H NMR spectrum of product 11a
2. Results and discussion
With an objective to synthesize macrocycles utilizing rhodiu-
m(II) carbenoids, the selection of spacers was initially planned to
interconnect the indole and diazoamide units that provide flexi-
bility with respect to the ring size and the kind of structural units to
be incorporated in the macrocycles. Based on our earlier research
work10,11,14b on C-alkylation, we designed the double in-
termolecular C-alkylation reactions of bis-diazoamides 6 with in-
doles 2 or bis-indoles 7. To demonstrate the double C-alkylation
reaction, bis-diazoamides 6a,b having aliphatic spacers were syn-
thesized in good yield via N-alkylation of diazoamide 1a with 1,3-
dibromopropane (9a) or 1,4-dibromobutane (9b) using K2CO3/
DMF. The double C-alkylation reaction of bis-diazoamides 6a,b was
investigated to determine the course of reaction. Treatment of 6a
with an excess amount of N-methylindole 2a in the presence of
1 mol % of rhodium(II) acetate catalyst for 20 min at room tem-
perature furnished the corresponding double C-alkylated product
10a in 85% yield as a mixture of diastereomers in the ratio of 1:1
(Scheme 3). No mono-alkylated product was observed. The 1H NMR
spectrum of compound 10a exhibited a characteristic signal at
exhibited a characteristic signal at
d 4.87 as a singlet for two C*eH
protons, which indicates the presence of symmetry.
The NMR spectrum showed the complete symmetry for other
protons as well as carbons because the stereocenters present in
diastereomers are well separated. Thus, the diastereomeric ratio
could not be determined. Spectroscopic analyses confirmed the
double C-alkylation reaction of bis-indoles with complete regio-
selectivity. Similarly, the reaction of bis-indoles 7a,b with
substituted cyclic diazoamides 1bef furnished the corresponding
double-alkylated products 11bej as a mixture of diastereomers in
quantitative yield and the results are delineated in Table 2.
Next, double alkylation reactions of bis-indoles 7 having aro-
matic spacers were planned to furnish tetraindole derivatives. Re-
action of bis-indole containing aromatic spacer 7c with cyclic
diazoamide 1b afforded the alkylated product 12a as a mixture of
diastereomers (Scheme 5). However, 1H NMR spectrum of product
d
4.81 and 4.85 as two separate singlets for two C*eH protons of
each diastereomer. Similarly, reaction of bis-diazoamides 6a,b with
substituted indoles 2aed furnished the corresponding double-
12a exhibited a characteristic singlet resonance at
d 4.86 for two

S. Muthusamy et al. / Tetrahedron 68 (2012) 1595e1605
1597
Table 3
Reaction of bis-indoles 7 having aromatic spacers
Entry
Product
X
R1
Time (min)
Yielda
%
1
2
3
4
5
6
7
8
12a
12b
12c
12d
12e
12f
12g
12h
12i
2-CH2C6H4CH2
2-CH2C6H4CH2
2-CH2C6H4CH2
2-CH2C6H4CH2
2-CH2C6H4CH2
3-CH2C6H4CH2
3-CH2C6H4CH2
3-CH2C6H4CH2
3-CH2C6H4CH2
4-CH2C6H4CH2
4-CH2C6H4CH2
4-CH2C6H4CH2
CH3
10
12
10
10
10
8
10
10
10
12
10
10
97
96
96
95
94
97
96
97
95
95
94
94
C6H5CH2
4-CH3 C6H4CH2
Allyl
Propargyl
CH3
C6H5CH2
4-CH3 C6H4CH2
Propargyl
C6H5CH2
4-CH3 C6H4CH2
Allyl
9
10
11
12
12j
12k
12l
a
Isolated yield.
The reaction was then extended to include various bis-
diazoamides/bis-indoles combinations; speculation was made
that if bis-indole moieties 7 were used in the double C-alkylation
reaction of bis-diazoamides 6 then the resultant double C-alkylated
product should be an interesting macrocyclic compound (Scheme
2). This will provide a new methodology for the indolophane syn-
thesis using rhodium metal catalyst.
Macrocyclic compounds are important in modern synthetic or-
ganic chemistry in view of the fact that a large number of these
compounds have shown potential biological applications and has
emerged as one of the key areas in the field of molecular recogni-
tion.15 There is currently considerable interest in the properties and
applications of cyclophanes16 and more commonly in the control of
molecular architecture and crystal engineering. There is also
growing interest in the development of cyclophanes as hosts for
ionic guests17 and molecular recognition as synthetic receptors.18
For the synthesis of large ring macrocyclic lactones, catalytic
metal carbene transformation emerged as an exciting tool and has
been applied19,20 to the macrocyclization process.
Scheme 4. Synthesis of tetraindoles from bis-indoles 7a,b.
Table 2
Reaction of bis-indoles 7 having aliphatic spacers
Entry
Product
n
R1
Time (min)
Yielda
%
1
2
3
4
5
6
7
8
9
11a
11b
11c
11d
11e
11f
11g
11h
11i
1
1
1
1
1
2
2
2
2
2
CH3
25
20
20
25
25
25
20
20
25
25
98
98
95
97
95
97
98
96
95
94
C6H5CH2
4-CH3C6H4CH2
Allyl
Propargyl
CH3
C6H5CH2
4-CH3C6H4CH2
Allyl
10
11j
Propargyl
a
Isolated yield.
For the successful macrocyclization by means of in-
termolecular double C-alkylation reactions, 1 equiv of bis-indole
7a was allowed to react with 1.1 equiv of bis-diazoamide 6a
under an argon atmosphere in the presence of 1 mol % of rho-
dium(II) acetate catalyst. As observed in double C-alkylation
reactions above, the reaction was completed within 30 min. The
chromatography purification of the reaction mixture afforded
macrocyclic compounds 13a,b as a mixture of diastereomers in
moderate yield with an excellent regiocontrol (Scheme 6) and
no other oligomers and mono-alkylated product were observed.
The diastereomeric mixture was present in the ratio of 1:1 and
separated by column chromatography. The 1H NMR spectrum of
C*eH protons indicating the presence of symmetry and the di-
astereomeric ratio could not be determined. In order to generalize
the above reaction, a number of double-alkylated products 12bel
was obtained in quantitative yields with the complete regiose-
lectivity (Table 3) as described above. All these reactions were
completed within 8e12 min.
product 13a exhibited a characteristic singlet resonance at
for two CH protons. The 1H NMR spectrum of product 13b
exhibited a characteristic singlet resonance at 5.02 for two CH
d 4.87
d
protons. The 13C, DEPT-135, and DEPT-90 NMR spectra of com-
pounds 13a and 13b showed peaks for four CH2 carbons, ten CH
carbons, and six quaternary carbons. The single-crystal X-ray
analyses21 of diastereomers 13a (anti) and 13b (syn) were
also performed (Fig. 1). The crystal packing arrangement of
13a and 13b showed the presence of intermolecular CeH/O
and CeH/
p
interactions.22 The spectroscopic and X-ray
analyses confirmed the proposed macrocyclic structures of
13a,b. Similarly, reaction of bis-diazoamides 6a,b with bis-
indole 7b furnished the respective double C-alkylated macro-
cyclic compounds 14a,b and 15a,b as a mixture of diastereomers
with an excellent regiocontrol and the results are summarized
in Table 4.
The reaction was further extended to bis-indoles and bis-
diazoamides having aromatic spacers. Reaction of bis-diazoamide
Scheme 5. Synthesis of tetraindoles from bis-indoles 7cee.

1598
S. Muthusamy et al. / Tetrahedron 68 (2012) 1595e1605
6a and bis-indole 7c was performed as described above to afford
the macrocyclic compounds 16a,b as a mixture of diastereomers.
The stereochemistry of the diastereomer 16b was unequivocally
demonstrated by the single-crystal X-ray analysis21 and found as
syn-isomer (Fig. 2). The stereochemistry of the diastereomer 16a
was tentatively assigned as an anti-isomer. Similarly, reaction of
bis-diazoamide 6a with bis-indole 7d yielded the corresponding
macrocyclic compounds 17a,b as a mixture of diastereomers. The
stereochemistry of the diastereomer 17b was unequivocally
assigned by the single-crystal X-ray analysis21 and found as syn-
isomer (Fig. 2). Finally, we investigated the reaction of bis-
diazoamide 6c23 with bis-indole 7c, both containing aromatic
spacers, under similar reaction conditions as described above. The
chromatographic purification of the reaction mixture led to the
interesting macrocycle 18 having aryl and heteroaryl units as
a mixture of diastereomers. However, numerous attempts to sep-
arate the diastereomeric mixture by crystallization or chromatog-
raphy failed.
3. Conclusions
In summary, the intermolecular double C-alkylation reactions
Scheme 6. Synthesis of indolophanes.
were performed for the first time using rhodium(II) acetate as
Fig. 1. X-ray structures of indolophanes 13a and 13b (solvent molecule was removed for clarity).
Table 4
catalyst to furnish tetraindole derivatives with complete regiose-
lectivity. This methodology using rhodium(II) catalyst was suc-
cessfully extended to apply for the synthesis of indolophanes with
excellent regiocontrol and forms a new approach for the synthesis
of macrocycles. The structure and stereochemistry of macrocycles
were unequivocally confirmed with the help of single-crystal X-ray
structure analyses. The cavity of the macrocycles can be varied
using the different spacers. Further studies with different spacers to
change the size of the cavity of macrocycles and their supramo-
lecular chemistry are in progress.
Synthesis of macrocycles via double C-alkylation method 13e18
Entry
Macrocycle
X
Y
Yielda
%
drb
1
2
3
4
5
6
13
14
15
16
17
18
e(CH2)3e
e(CH2)3e
e(CH2)4e
e(CH2)3e
e(CH2)3e
3-CH2C6H4CH2
e(CH2)3e
e(CH2)4e
e(CH2)4e
2-CH2C6H4CH2
3-CH2C6H4CH2
2-CH2C6H4CH2
50
52
55
63
54
50
58:42
53:47
51:49
27:73
36:64
56:44
a
Isolated yield.
Diastereomeric ratio based on the crude NMR spectra.
b
Fig. 2. X-ray structures of indolophanes 16b (solvent molecule was removed for clarity) and 17b.

S. Muthusamy et al. / Tetrahedron 68 (2012) 1595e1605
1599
4. Experimental section
4.1. General
4.83 (s, 2H, CH), 5.20e5.25 (m, 4H, NCH2), 6.85 (q, 2H, J¼6.8 Hz,
ArH), 6.97e7.02 (m, 4H, ArH), 7.03 (d, 4H, J¼6.4 Hz, ArH), 7.08e7.14
(m, 8H, ArH), 7.20e7.28 (m, 10H, ArH); 13C NMR (100 MHz, CDCl3)
d
29.73 (CH2), 38.19 (CH2), 44.35 (CH), 50.11 (CH2) 108.16 (]CH),
Melting points are uncorrected. IR spectra were recorded using
KBr pellets or in CH2Cl2. Proton nuclear magnetic resonance (1H
NMR) spectra were recorded on 200 MHz or 400 MHz using CDCl3
108.28 (]CH), 109.86 (quat-C), 110.0 (]CH), 119.55 (]CH), 119.72
(]CH), 122.18 (]CH), 122.66 (]CH), 125.06 (]CH), 126.87 (]CH),
127.10 (]CH), 127.27 (]CH), 127.63 (]CH), 128.27 (quat-C), 128.77
(]CH), 129.24 (quat-C), 137.05 (quat-C), 137.31 (quat-C), 143.23
(quat-C), 176.92 (quat-C); MS (ESI) m/z 739 [MþþNa]; Anal. Calcd
(%) for C49H40N4O2 (716.31): C, 82.10; H, 5.62; N, 7.82. Found: C,
82.36; H, 5.73; N, 7.87.
in parts per million (
internal standard. The data are reported as follows; chemical shift
in parts per million (ppm,
d
) related to tetramethylsilane (
d
¼0.00) as an
d
units), multiplicity (br¼broad,
s¼singlet, d¼doublet, m¼multiplet), spinespin coupling J (hertz),
and integration. Carbon-13 nuclear magnetic resonance (13C NMR)
spectra were recorded at 50.3 MHz or 100 MHz in CDCl3. Chemical
4.2.3. 1,3-Bis[(10-(4-methylbenzyl)-1,3-dihydro-10H-[3,30]biindolyl-
shifts are reported in delta (
d
) units, parts per million (ppm) relative
2-on)-1-yl]propane (10c). Light pink color solid (82%); IR (KBr)
3055, 2925, 1710, 1611, 1486, 1465, 1356, 1264, 1179, 1086, 1020,
742 cmꢁ1 1H NMR (400 MHz, CDCl3)
2.26e2.32 (m, 8H),
n
to the center of the triplet at 77.7 ppm for CDCl3. Carbon types were
determined from 13C NMR and DEPT experiments. Mass analyses
were performed with an ionizing voltage of 70 eV or FDþ method or
by FAB technique and reported as m/z (relative intensity). Diffrac-
tion data for the compounds are collected on a diffractometer with
ꢀ
;
d
3.85e3.91 (m, 4H, CH2), 4.85 (s, 2H, CH), 5.13e5.20 (m, 4H, NCH2),
6.84 (q, 2H, J¼6.0 Hz, ArH), 6.98e7.03 (m, 10H, ArH), 7.06 (d, 4H,
J¼7.6 Hz, ArH), 7.01e7.14 (m, 4H, ArH), 7.19e7.25 (m, 6H, ArH); 13C
graphite monochromatized Mo K
a
radiation (
l¼0.71703 A) at room
NMR (100 MHz, CDCl3) d 20.81 (CH3), 22.79 (CH2), 31.67 (CH2),
temperature using the program SMART24 and processed by
SAINT.25 Absorption correction was applied by SADABS.26 The
structure was solved by direct methods and refined using full-
matrix least-squares/difference Fourier techniques using SHELXL
97.27 All the non-hydrogen atoms were refined with anisotropic
displacement parameters. Hydrogen atoms were located from the
difference Fourier map or placed at idealized positions and refined
as riding atoms with the relative isotropic parameters to which
they are attached. All solvents were purified by distillation fol-
lowing standard procedures. Thin layer chromatography was per-
formed on silica or alumina plates and components visualized by
observation under iodine/UV light. Column chromatography was
performed on silica gel (100e200 mesh). 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. Synthesis of substituted diazoamides14d 1, bis-
diazoamides23,14d 6, bis-indoles28 7aee were prepared by using
literature methods.
44.30 (CH), 49.92 (CH2) 108.28 (]CH), 109.88 (quat-C), 110.06 (]
CH), 119.55 (]CH), 119.69 (]CH), 122.15 (]CH), 122.70 (]CH),
125.12 (]CH), 126.97 (]CH), 127.17 (quat-C), 127.33 (]CH), 128.31
(quat-C), 129.33 (quat-C), 129.47 (]CH), 134.32 (]CH), 137.09
(quat-C), 137.34 (quat-C), 143.24 (quat-C), 176.07 (quat-C); MS (ESI)
m/z (%) 745 (Mþ1, 14), 744 (Mþ, 21), 639 (21), 523 (14), 231 (7), 105
(100); Anal. Calcd (%) for C51H44N4O2 (744.35): C, 82.23; H, 5.95; N,
7.52. Found: C, 82.04; H, 5.89; N, 7.64.
4.2.4. 1,4-Bis[(10-methyl-1,3-dihydro-10H-[3,30]biindolyl-2-on)-1-yl]
butane (10d). Light brownish solid (89%); IR (KBr)
1711, 1611, 1486, 1466, 1357, 1265, 1156, 1091, 1015, 745 cmꢁ1
NMR (400 MHz, CDCl3) 1.85 (s, 4H, CH2), 3.71 (s, 6H, NCH3),
n
3054, 2932,
;
1H
d
3.80e3.86 (m, 4H, CH2), 4.85 (s, 2H, CH), 6.88 (d, 2H, J¼7.6 Hz, ArH),
6.93 (s, 2H, ArH), 6.97e7.02 (m, 4H, ArH), 7.17e7.28 (m, 10H, ArH);
13C NMR (100 MHz, CDCl3)
d 24.85 (CH2), 29.74 (NCH3), 39.65 (CH2),
44.38 (CH), 108.43 (]CH), 109.36 (]CH), 109.46 (]CH), 119.38 (]
CH), 121.96 (]CH), 122.51 (]CH), 124.96 (]CH), 126.89 (quat-C),
127.73 (]CH), 128.22 (]CH), 129.38 (quat-C), 129.48 (quat-C),
137.40 (quat-C), 143.43 (quat-C), 176.60 (quat-C); MS (ESI) m/z (%)
601 [MþþNa]; Anal. Calcd (%) for C38H34N4O2 (578.21): C, 78.87; H,
5.92; N, 9.68. Found: C, 78.65; H, 5.86; N, 9.59.
4.2. General procedure for the synthesis of compounds 10
To a stirred, degassed dichloromethane (25 mL) solution of bis-
diazoamide 6 (1 mmol) and indole 2 (2.50 mmol) was added rho-
dium(II) acetate dimer (1 mol %) catalyst at 25 ꢀC. After the reaction
was completed (15e30 min, TLC monitoring), the reaction mixture
concentrated in vacuum. The residue was purified by flash chro-
matography (SiO2, hexane/EtOAc 55:45) to afford the correspond-
ing product 10 as an inseparable mixture of diastereomers. NMR
data provided for the major isomer only.
4.2.5. 1,4-Bis[(10-benzyl-1,3-dihydro-10H-[3,30]biindolyl-2-on)-1-yl]
butane (10e). Brown solid (89%); IR (KBr)
1487, 1466, 1357, 1265, 1177, 1156, 1092, 1026, 738 cmꢁ1
(400 MHz, CDCl3) 1.82e1.84 (m, 4H, CH2), 3.77e3.85 (m, 4H, CH2),
n
3055, 2928, 1711, 1611,
;
1H NMR
d
4.86 (s, 2H, CH), 5.17e5.23 (m, 4H, NCH2), 6.88 (d, 2H, J¼8.0 Hz,
ArH), 6.96e7.02 (m, 6H, ArH), 7.05e7.14 (m, 6H, ArH), 7.18e7.29 (m,
14H, ArH); 13C NMR (100 MHz, CDCl3)
d 24.89 (CH2), 39.67 (CH2),
4.2.1. 1,3-Bis[(10-methyl-1,3-dihydro-10H-[3,30]biindolyl-2-on)-1-yl]
44.45 (CH), 50.10 (CH2) 108.48 (]CH), 110.0 (]CH), 110.14 (quat-C),
119.58 (]CH), 122.18 (]CH), 122.55 (]CH), 124.99 (]CH), 126.87
(]CH), 127.17 (]CH), 127.64 (]CH), 128.27 (]CH), 128.79 (]CH),
129.20 (quat-C), 129.27 (quat-C), 137.06 (quat-C), 137.36 (quat-C),
143.41 (quat-C), 176.49 (quat-C); MS (ESI) m/z 753 (MþþNa); Anal.
Calcd (%) for C50H42N4O2 (730.33): C, 82.16; H, 5.79; N, 7.67. Found:
C, 82.42; H, 5.72; N, 7.82.
propane (10a). Brown solid (85%); IR (KBr)
1486, 1467, 1359, 1265, 738 cmꢁ1 1H NMR (400 MHz, CDCl3)
2.03e2.20 (m, 2H, CH2), 3.68 (s, 6H, NCH3), 3.88e3.90 (m, 4H,
CH2), 4.81 (s, 2H, CH), 6.80e7.03 (m, 8H, ArH), 7.14e7.25 (m, 10H,
ArH); 13C NMR (100 MHz, CDCl3)
26.29 (CH2), 33.36 (NCH3), 38.78
n 3055, 2931, 1711, 1612,
;
d
d
(CH2), 44.84 (CH), 108.75 (]CH), 108.82 (]CH), 109.94 (quat-C),
110.05 (]CH), 119.91 (]CH), 122.54 (]CH), 123.21 (]CH), 125.61
(]CH), 127.43 (quat-C), 128.25 (]CH), 128.83 (]CH), 130.54 (quat-
C), 137.98 (quat-C), 143.86 (quat-C), 177.17 (quat-C); HRMS (ESI)
calcd for C37H32N4O2Na [MþþNa] 587.2423, found 587.2433.
4.2.6. 1,4-Bis[(10-(4-methylbenzyl)-1,3-dihydro-10H-[3,30]biindolyl-
2-on)-1-yl]butane (10f). Light brown solid (77%); IR (KBr)
2929, 1710, 1612, 1487, 1466, 1357, 1265, 1178, 1093, 1020, 739 cmꢁ1
1H NMR (400 MHz, CDCl3)
1.80e1.83 (m, 4H, CH2), 2.29 (s, 6H,
CH3), 3.73e3.85 (m, 4H, CH2), 4.79 (s, 2H, CH), 5.15e5.20 (m, 4H,
NCH2), 6.87e7.21 (m, 26H, ArH); 13C NMR (100 MHz, CDCl3)
20.64
n 3054,
;
d
4.2.2. 1,3-Bis[(10-benzyl-1,3-dihydro-10-[3,30]biindolyl-2-on)-1-yl]
propane (10b). Light brown solid (93%); IR (KBr)
1713, 1611, 1487, 1465, 1358, 1265, 1087, 1022, 742 cmꢁ1
(400 MHz, CDCl3) 2.16e2.25 (m, 2H, CH2), 3.85e3.92 (m, 4H, CH2),
n
3055, 2927, 1713,
d
;
1H NMR
(CH3), 24.43 (CH2), 39.19 (CH2), 43.93 (CH), 49.41 (CH2) 107.95 (]
CH), 109.51 (]CH), 119.12 (]CH), 121.61 (]CH), 121.96 (]CH),
d

1600
S. Muthusamy et al. / Tetrahedron 68 (2012) 1595e1605
124.51 (]CH), 126.52 (]CH), 126.71 (]CH), 127.82 (]CH), 128.81
(quat-C), 128.82 (quat-C), 129.03 (]CH), 133.81 (quat-C), 136.83
(quat-C), 136.86 (quat-C), 143.04 (quat-C), 176.13 (quat-C); MS (ESI)
m/z 781.3 (MþþNa), 758.3 (Mþ); Anal. Calcd (%) for C52H46N4O2
(758.36): C, 82.29; H, 6.11; N, 7.38. Found: C, 82.42; H, 6.04; N, 7.47.
and ArCH3), 3.94e4.09 (m, 4H, CH2), 4.79e5.00 (m, 6H, NCH2 and
CH), 6.80 (d, 2H, J¼7.6 Hz, ArH), 6.87e7.39 (m, 24H, ArH); 13C NMR
(100 MHz, CDCl3)
d 21.60 (ArCH3), 30.56 (CH2), 43.84 (CH2), 44.31
(CH2), 44.96 (CH), 109.63 (]CH), 110.09 (]CH), 110.58 (quat-C),
120.05 (]CH), 120.37 (]CH), 122.64 (]CH), 123.13 (]CH), 125.34
(]CH), 127.42 (]CH), 127.61 (quat-C), 128.12 (]CH), 128.60 (]CH),
129.67 (quat-C), 129.94 (]CH), 133.55 (quat-C), 137.17 (quat-C),
137.80 (quat-C), 143.94 (quat-C), 176.93 (quat-C); MS (EI) m/z (%)
744 (Mþ, 34), 743 (49), 507 (19), 403 (16), 365 (34), 261 (67), 105
(100); Anal. Calcd (%) for C51H44N4O2 (744.35): C, 82.23; H, 5.95; N,
7.52. Found: C, 82.47; H, 6.12; N, 7.41.
4.2.7. 1,4-Bis[(10-allyl-1,3-dihydro-10H-[3,30]biindolyl-2-on)-1-yl]bu-
tane (10g). Brown solid (80%); IR (KBr)
1487, 1466, 1356, 1263, 1178, 1156, 1092, 928, 741 cmꢁ1
(400 MHz, CDCl3) 1.82e1.85 (m, 4H, CH2), 3.81 (br s, 4H),
n
3055, 2926, 1711, 1611,
;
1H NMR
d
4.58e4.59 (m, 4H), 4.77 (s, 2H, CH), 5.01e5.15 (m, 4H, C]CH2),
5.81e5.99 (m, 2H, allyl CH), 6.76 (d, 2H, J¼8.1 Hz, ArH), 6.85e7.01
(m, 6H, ArH), 7.10e7.32 (m, 10H, ArH); 13C NMR (100 MHz, CDCl3)
4.3.4. 1,3-Bis[(10-allyl-10,30-dihydro-10H-[3,30]biindolyl-20-on)-1-yl]
d
25.81 (CH2), 40.13 (CH2), 44.83 (CH), 49.33 (CH2), 108.93 (]CH),
propane (11d). Brown solid (97%); mp 76e78 ꢀC; IR (KBr)
n
3055,
110.32 (]CH), 118.04 (]CH2), 119.98 (]CH), 122.52 (]CH), 123.03
(]CH),125.43 (]CH), 127.21 (]CH),127.64 (quat-C), 128.76 (]CH),
129.83 (quat-C), 129.92 (quat-C), 133.91 (]CH), 137.32 (quat-C),
143.91 (quat-C), 177.06 (quat-C); HRMS (ESI) calcd for
C42H38N4O2Na [MþþNa] 653.2995, found 653.2984.
2927, 1712, 1612, 1487, 1467, 1355, 1265, 1205, 738 cmꢁ1
(400 MHz, CHCl3)
;
1H NMR
d
2.21 (br s, 2H), 3.88 (t, 4H, J¼6.5 Hz, NCH2),
4.35e4.38 (m, 4H, NCH2), 4.86 (s, 2H, CH), 5.17e5.30 (m, 4H, C]
CH2), 5.76e5.94 (m, 2H, allyl CH), 6.86e7.05 (m, 8H, ArH), 7.09e7.29
(m,10H, ArH); 13C NMR (100 MHz, CDCl3)
d 30.41 (CH2), 43.12 (CH2),
43.82 (CH2), 44.81 (CH), 109.54 (]CH), 110.11 (]CH), 110.58 (quat-
C), 118.27 (]CH2), 120.13 (]CH), 120.21 (]CH), 122.67 (]CH),
123.12 (]CH), 125.35 (]CH), 127.17 (]CH), 127.35 (]CH), 127.71
(quat-C), 128.60 (]CH), 129.65 (quat-C), 132.21 (¼CH), 137.15 (quat-
C), 143.97 (quat-C), 176.47 (quat-C); HRMS (ESI) calcd for
C41H36N4O2Na [MþþNa] 639.2738, found 639.2729.
4.3. General procedure for the synthesis of compounds 11 and
12
To
a stirred dichloromethane solution of bis-indole 7
(1.00 mmol) and diazoamide 1 (2.50 mmol) at 25 ꢀC was added
rhodium(II) acetate dimer (1 mol %) catalyst. The solvent was
concentrated in vacuo. The residue was purified by flash chroma-
tography (SiO2, hexane/EtOAc 60:40) to afford the product 11 or 12
as an inseparable mixture of diastereomers.
4.3.5. 1,3-Bis[(10-(prop-2-ynyl)-10,30-dihydro-10H-[3,30]biindolyl-20-
on)-1-yl]propane (11e). Brown solid (95%); mp 161e163 ꢀC; IR (KBr)
n
3285, 2929, 1715, 1611, 1487, 1466, 1351, 1164, 1010, 739 cmꢁ1; 1H
NMR (400 MHz, DMSO-d6)
d 2.34 (br s, 2H), 3.44 (s, 2H, CCH),
4.3.1. 1,3-Bis[(10-methyl-10,30-dihydro-10H-[3,30]biindolyl-20-on)-1-
4.24e4.31 (m, 4H, CH2), 4.60e4.70 (m, 4H, NCH2), 5.16 (s, 2H, CH),
6.92e6.99 (m, 2H, ArH), 7.05e7.29 (m, 10H, ArH), 7.43e7.49 (m, 6H,
yl]propane (11a). Colorless solid (98%); mp 121e123 ꢀC; IR (KBr)
n
3054, 2927, 2855, 1713, 1612, 1492, 1468, 1373, 1347, 1265, 1173,
ArH); 13C NMR (100 MHz, DMSO-d6)
d 28.91 (CH2), 30.43 (CH2),
1125, 1087, 739 cmꢁ1 1H NMR (400 MHz, CDCl3)
;
d
2.35e2.39 (m,
42.97 (CH2), 43.65 (CH), 74.34 (CH), 78.15 (quat-C), 109.18 (]CH),
109.29 (quat-C), 109.76 (]CH), 118.82 (]CH), 119.13 (]CH), 121.48
(]CH), 122.59 (]CH), 124.35 (]CH), 126.34 (quat-C), 127.58 (]
CH), 127.94 (]CH), 129.18 (quat-C), 136.22 (quat-C), 142.12 (quat-C),
174.99 (quat-C); MS (ESI) m/z (%) 635 (MþþNa); Anal. Calcd (%) for
C41H32N4O2 (612.25): C, 80.37; H, 5.26; N, 9.14. Found: C, 80.26; H,
5.33; N, 8.99.
2H, CH2), 3.29 (s, 6H, NCH3), 4.03 (t, 4H, J¼6.8 Hz, NCH2), 4.87 (s, 2H,
CH), 6.91e6.94 (m, 4H, ArH), 7.00e7.03 (m, 4H, ArH), 7.11e7.20 (m,
6H, ArH), 7.26e7.34 (m, 4H, ArH); 13C NMR (100 MHz, CDCl3)
d
26.51 (NCH3), 29.74 (CH2), 43.38 (NCH2), 44.34 (CH), 108.12 (]
CH), 109.56 (]CH), 110.01 (quat-C), 119.62 (]CH), 119.70 (]CH),
122.15 (]CH), 122.71 (]CH), 124.78 (]CH), 126.56 (]CH), 126.69
(quat-C), 128.24 (]CH), 129.19 (quat-C), 136.61 (quat-C), 144.26
(quat-C), 176.42 (quat-C); MS (ESI) m/z (%) 587 (MþþNa); Anal.
Calcd (%) for C37H32N4O2 (564.25): C, 78.70; H, 5.71; N, 9.92. Found:
C, 78.99; H, 5.87; N, 9.70.
4.3.6. 1,4-Bis[(10-methyl-10,30-dihydro-10H-[3,30]biindolyl-20-on)-1-
yl]butane (11f). Colorless solid (97%); mp 168e170 ꢀC; IR (KBr)
n
3055, 2928, 1713, 1612, 1492, 1469, 1371, 1347, 1265, 1160, 1087,
743 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
1.81 (br s, 4H, CH2), 3.28 (s,
4.3.2. 1,3-Bis[(10-benzyl-10,30-dihydro-10H-[3,30]biindolyl-20-on)-1-
yl]propane (11b). Light yellow solid (98%); mp 115e117 ꢀC; IR (KBr)
6H, NCH3), 3.99e4.00 (m, 4H, NCH2), 4.84 (s, 2H, CH), 6.91 (d,
J¼6.0 Hz, 4H, ArH), 6.98e7.01 (m, 4H, ArH), 7.16 (q, 4H, J¼7.6 Hz,
ArH), 7.20e7.27 (m, 4H, ArH), 7.31 (t, 2H, J¼7.6 Hz, ArH); 13C NMR
n
3045, 2925, 1710, 1611, 1486, 1465, 1348, 1178, 1010, 908,
738 cmꢁ1 1H NMR (400 MHz, CDCl3)
;
d
1.84 (s, 2H), 4.01e4.03 (m,
(100 MHz, CDCl3) d 26.49 (NCH3), 27.74 (CH2), 44.36 (CH), 45.97
4H, NCH2), 4.89e5.05 (m, 6H, NCH2 and CH), 6.82 (d, 2H, J¼8.0 Hz,
ArH), 6.94e6.98 (m, 6H, ArH); 7.13e7.21 (m, 6H, ArH), 7.23e7.32 (m,
10H, ArH), 7.35 (d, 4H, J¼6.8 Hz, ArH); 13C NMR (100 MHz, CDCl3)
(CH2), 108.06 (]CH), 109.50 (]CH), 109.65 (quat-C), 119.45 (]CH),
119.64 (]CH), 122.0 (]CH), 122.66 (]CH), 124.80 (]CH), 126.64
(]CH), 126.68 (quat-C), 128.18 (]CH), 129.20 (quat-C), 136.63
(quat-C),144.27 (quat-C),176.40 (quat-C); MS (EI) m/z (%) 579 (Mþ1,
38), 578 (Mþ, 94), 433 (13), 432 (25), 407 (11), 316 (20), 315 (16),
314 (32), 312 (18), 309 (10), 287 (28), 286 (100), 285 (28), 283 (18),
261 (90), 248 (38), 233 (31), 219 (36); HRMS (ESI) calcd for
C38H34N4O2Na [MþþNa] 601.2661, found 601.2661.
d
27.77 (CH2), 44.11 (CH2), 44.54 (CH), 45.99 (CH2), 109.13 (]CH),
109.58 (]CH), 109.71 (quat-C), 119.71 (]CH), 119.82 (]CH), 122.07
(]CH), 122.75 (]CH), 124.97 (]CH), 126.90 (]CH), 126.95 (]CH),
127.67 (quat-C), 127.71 (]CH), 128.14 (]CH), 128.82 (]CH), 129.22
(quat-C), 136.11 (quat-C), 136.72 (quat-C), 143.40 (quat-C), 176.58
(quat-C); MS (EI) m/z (%) 716 (Mþ, 34), 715 (57), 493 (15), 403 (11),
351 (45), 272 (67), 231 (16), 130 (21), 91 (100); Anal. Calcd (%) for
C49H40N4O2 (716.86): C, 82.10; H, 5.62; N, 7.82. Found: C, 82.34; H,
5.76; N, 7.69.
4.3.7. 1,4-Bis[(10-benzyl-10,30-dihydro-10H-[3,30]biindolyl-20-on)-1-
yl]butane (11g). Light yellow solid (98%); mp 122e124 ꢀC; IR (KBr)
n
3030, 2925, 1711, 1609, 1485, 1465, 1348, 1199, 1160, 1077, 741 cmꢁ1
1H NMR (400 MHz, CDCl3)
1.78e1.92 (m, 4H), 3.94 (br s, 4H, CH2),
4.83e5.04 (m, 6H, NCH2 and CH), 6.80 (d, 2H, J¼7.6 Hz, ArH),
6.93e7.31 (m, 26H, ArH); 13C NMR (100 MHz, CDCl3)
28.31 (CH2),
;
d
4.3.3. 1,3-Bis[(10-(4-methylbenzyl)-10,30-dihydro-10H-[3,30]biindolyl-
20-on)-1-yl]propane (11c). Brown solid (95%); mp 122e124 ꢀC; IR
d
(KBr)
n
3054, 2927, 1711, 1612, 1515, 1486, 1467, 1354, 1265, 1200,
2.25 (s, 8H, CH2
44.70 (CH2), 45.14 (CH), 46.52 (CH2) 109.73 (]CH), 110.19 (]CH),
110.33 (quat-C), 120.02 (]CH), 120.38 (]CH), 122.74 (]CH), 123.3
1180, 1012, 738 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d

S. Muthusamy et al. / Tetrahedron 68 (2012) 1595e1605
1601
(]CH), 125.65 (]CH), 127.57 (]CH), 128.32 (]CH), 128.76 (]CH),
129.41 (]CH), 129.83 (quat-C), 136.75 (quat-C), 137.28 (quat-C),
144.02 (quat-C), 177.10 (quat-C); MS (EI) m/z (%) 732 (Mþ2, 6), 731
(Mþ1, 26), 730 (Mþ, 72), 639 (12), 286 (19), 247 (11), 223 (17), 222
(10), 170 (13), 91 (100); HRMS (ESIþ) calcd for C50H42N4O2Na
[MþþNa] 753.3208, found 753.3212.
(quat-C), 134.61 (quat-C), 137.06 (quat-C), 144.26 (quat-C), 176.35
(quat-C); MS (ESI) m/z (%) 649 (MþþNa); Anal. Calcd (%) for
C42H34N4O2 (626.26): C, 80.49; H, 5.47; N, 8.94. Found: C, 80.68; H,
5.34; N, 8.99.
4.3.12. 1,2-Bis[((10-benzyl-10,30-dihydro-10H-[3,30]biindolyl-20-on)-1-
yl)methyl]benzene (12b). Light brown solid (96%); mp 126e128 ꢀC;
4.3.8. 1,4-Bis[(10-(4-methylbenzyl)-10,30-dihydro-10H-[3,30]biindolyl-
20-on)-1-yl]butane (11h). Colorless solid (96%); mp 134e136 ꢀC; IR
IR (KBr)
n
3054, 2923, 1710, 1611, 1486, 1465, 1347, 1177, 1098, 1008,
4.87e5.04 (m, 6H, NCH2 and
737 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
(KBr)
n
3054, 2927, 1712, 1612, 1486, 1467, 1355, 1265, 1180, 908,
CH), 5.15 (s, 4H, ArCH2N), 6.81 (d, 2H, J¼7.6 Hz, ArH), 6.89 (t, 2H,
742 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
1.83 (br s, 4H), 2.30 (s, 6H,
J¼4 Hz, ArH), 6.91e6.97 (m, 5H, ArH), 7.07e7.28 (m, 19H, ArH), 7.32
ArCH3), 3.93e3.96 (m, 4H, CH2), 4.85e5.00 (m, 6H, NCH2 and CH),
6.82 (d, 2H, J¼8.0 Hz, ArH), 6.91e6.97 (m, 6H, ArH), 7.09 (d, 4H,
J¼8.0 Hz, ArH), 7.13e7.25 (m, 14H, ArH); 13C NMR (100 MHz, CDCl3)
(d, 4H, J¼7.6 Hz, ArH); 13C NMR (100 MHz, CDCl3)
d 44.11 (CH2),
45.57 (CH), 47.58 (CH2), 109.16 (]CH), 109.86 (]CH), 110.63 (quat-
C), 119.87 (]CH), 119.90 (]CH), 122.47 (]CH), 122.77 (]CH),
124.92 (]CH), 127.02 (]CH), 127.12 (]CH), 127.64 (]CH), 127.71
(]CH), 128.18 (]CH), 128.38 (]CH), 128.49 (]CH), 128.82 (quat-
C), 129.12 (quat-C), 134.67 (quat-C), 136.07 (quat-C), 137.14 (quat-C),
143.38 (quat-C), 176.47 (quat-C); HRMS (ESI) calcd for
C54H42N4O2Na [MþþNa] 801.3205, found 801.3210.
d
21.19 (ArCH3), 27.76 (CH2), 43.87 (CH2), 44.52 (CH), 46.00 (CH2)
109.14 (]CH), 109.55 (]CH), 109.74 (quat-C), 119.43 (]CH), 119.84
(]CH), 122.04 (]CH), 122.66 (]CH), 124.91 (]CH), 126.88 (]CH),
126.93 (]CH), 126.98 (]CH), 127.67 (]CH), 128.10 (]CH), 129.21
(quat-C), 129.46 (]CH), 133.08 (quat-C), 136.70 (quat-C), 137.36
(quat-C), 143.44 (quat-C), 176.51 (quat-C); MS (EI) m/z (%) 758 (Mþ,
13), 653 (10), 539 (8), 435 (8), 434 (23), 352 (11), 247 (21), 231 (7),
219 (8), 218 (9), 170 (14), 106 (21), 104 (10); Anal. Calcd (%) for
C52H46N4O2 (758.36): C, 82.29; H, 6.11; N, 7.38. Found: C, 82.47; H,
6.18; N, 7.47.
4.3.13. 1,2-Bis[((10-(4-methylbenzyl)-10,30-dihydro-10H-[3,30]biin-
dolyl-20-on)-1-yl)methyl] benzene (12c). Brown solid (96%); mp
116e118 ꢀC; IR (KBr)
n
3054, 2926, 1713, 1612, 1486, 1466, 1354,
1265, 1180, 1012, 908, 740 cmꢁ1 1H NMR (400 MHz, CDCl3)
;
d
2.28
(s, 6H, ArCH3), 4.82e5.00 (m, 6H, NCH2 and CH), 5.13 (s, 4H,
ArCH2N), 6.81 (d, 2H, J¼7.6 Hz, ArH), 6.88 (q, 2H, J¼4.4 Hz, ArH),
6.92e6.97 (m, 6H, ArH), 7.06e7.23 (m, 20H, ArH); 13C NMR
4.3.9. 1,4-Bis[(10-allyl-10,30-dihydro-10H-[3,30]biindolyl-20-on)-1-yl]
butane (11i). Colorless solid (95%); mp 178e180 ꢀC; IR (KBr)
n
3055,
2928, 1709, 1610, 1485, 1465, 1353, 1266, 1206, 1186, 1159, 923,
739 cmꢁ1 1H NMR (400 MHz, CDCl3)
1.83 (br s, 4H), 4.00e4.01
(100 MHz, CDCl3)
d 21.20 (ArCH3), 43.89 (CH2), 44.60 (CH), 47.58
;
d
(CH2), 109.21 (]CH), 109.88 (]CH), 110.67 (quat-C), 119.91 (]CH),
122.46 (]CH), 122.72 (]CH), 124.89 (]CH), 127.05 (]CH), 127.15
(]CH), 127.18 (]CH), 127.66 (quat-C), 128.17 (]CH), 128.36 (]CH),
128.48 (]CH), 129.16 (]CH), 129.50 (]CH), 133.06 (quat-C), 134.70
(quat-C), 137.16 (quat-C), 137.37 (quat-C), 143.45 (quat-C), 176.46
(quat-C); MS (ESI) m/z 829 (MþþNa); Anal. Calcd (%) for C56H46N4O2
(806.36): C, 83.36; H, 5.75; N, 6.94. Found: C, 83.51; H, 5.68; N, 6.99.
(m, 4H), 4.41 (d, J¼4.0 Hz, 4H), 4.88 (s, 2H, CH), 5.22e5.31 (m, 4H,
C]CH2), 5.83e5.91 (m, 2H, allyl CH), 6.91e6.93 (m, 4H), 7.00 (t,
J¼7.6 Hz, 4H), 7.16 (q, 4H, J¼7.6 Hz, ArH), 7.21e7.30 (m, 6H, ArH); 13C
NMR (100 MHz, CDCl3) d 27.76 (CH2), 42.62 (CH2), 44.36 (CH), 45.98
(CH2), 108.98 (]CH), 109.54 (]CH), 109.65 (quat-C), 117.75 (]CH2),
119.46 (]CH), 119.69 (]CH), 122.02 (]CH), 122.63 (]CH), 124.92
(]CH), 126.70 (]CH), 127.01 (quat-C), 128.08 (]CH), 129.14 (quat-
C), 131.65 (]CH), 136.65 (quat-C), 143.44 (quat-C), 176.08 (quat-C);
HRMS (ESI) calcd for C42H38N4O2Na [MþþNa] 653.2995, found
653.2992.
4.3.14. 1,2-Bis[((10-allyl-10,30-dihydro-10H-[3,30]biindolyl-20-on)-1-yl)
methyl]benzene (12d). Brown solid (95%); mp 97e99 ꢀC; IR (KBr)
n
3055, 2926, 1711, 1612, 1487, 1466, 1355, 1265, 1204, 1184, 929,
738 cmꢁ1; 1H NMR (400 MHz, CDCl3)
4.39 (s, 4H, ArCH2), 4.88 (s,
2H, CH), 5.06 (s, 4H), 5.17e5.30 (m, 4H), 5.78e5.92 (m, 2H, allyl CH),
6.80e7.27 (m, 22H, ArH); 13C NMR (100 MHz, CDCl3)
43.15 (CH2),
d
4.3.10. 1,4-Bis[(10-(prop-2-ynyl)-10,30-dihydro-10H-[3,30]biindolyl-20-
on)-1-yl]butane (11j). Colorless solid (94%); mp 137e139 ꢀC; IR
d
(KBr)
n
3285 (CCH), 3055, 2929, 1715, 1611, 1487, 1466, 1351, 1164,
44.95 (CH), 47.95 (CH2), 109.54 (]CH), 110.41 (]CH), 111.04 (quat-
C), 118.24 (]CH2), 120.24 (]CH), 120.39 (]CH), 122.89 (]CH),
123.15 (]CH), 125.37 (]CH), 127.58 (]CH), 128.59 (]CH), 128.63
(]CH),128.84 (]CH), 129.59 (quat-C), 132.13 (]CH), 135.15 (quat-
C), 137.63 (quat-C), 143.95 (quat-C), 176.46 (quat-C); HRMS (ESI)
calcd for C46H38N4O2Na [MþþNa] 701.2908, found 701.2910.
1010, 739 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
1.83 (br s, 4H),
2.25e2.27 (m, 2H, CCH), 4.01e4.02 (m, 2H, CH2), 4.56e4.58 (m, 4H,
NCH2), 4.89 (s, 2H, CH), 6.92 (d, 2H, J¼7.6 Hz, ArH), 6.97e7.06 (m,
4H, ArH), 7.06e7.25 (m, 12H, ArH), 7.32 (t, 2H, J¼7.4 Hz, ArH); 13C
NMR (100 MHz, CDCl3) d 28.20 (CH2), 29.62 (CH2), 44.83 (CH), 46.09
(CH2), 74.19 (quat-C), 78.68 (CH), 109.85 (]CH), 110.43 (quat-C),
110.69 (]CH), 119.52 (]CH), 120.16 (]CH), 122.23 (]CH), 123.34
(]CH), 125.30 (]CH), 127.54 (quat-C), 128.53 (]CH), 128.71 (]
CH), 130.42 (quat-C), 137.54 (quat-C), 143.28 (quat-C), 175.93 (quat-
C); HRMS (ESI) calcd for C42H34N4O2Na [MþþNa] 649.2682, found:
649.2678.
4.3.15. 1,2-Bis[((10-(prop-2-ynyl)-10,30-dihydro-10H-[3,30]biindolyl-
20-on)-1-yl)methyl]benzene (12e). Brown solid (94%); mp
144e146 ꢀC; IR (KBr)
n
3302 (CCH), 3055, 2924, 1714, 1613, 1487,
1467, 1351, 1265, 1182, 1012, 909, 741 cmꢁ1 1H NMR (400 MHz,
CDCl3) 2.23 (s, 2H, CCH), 4.55e4.56 (m, 4H, NCH2), 4.87 (s, 2H, CH),
5.09 (s, 4H, ArCH2N), 6.81e7.35 (m, 22H, ArH); 13C NMR (100 MHz,
CDCl3) 30.08 (CH2), 45.04 (CH), 48.13 (CH2), 72.93 (quat-C), 77.72
;
d
4.3.11. 1,2-Bis[((10-methyl-10,30-dihydro-10H-[3,30]biindolyl-20-on)-1-
yl)methyl]benzene (12a). Light brown solid (97%); mp 108e110 ꢀC;
d
(CH), 109.73 (]CH), 110.41 (]CH), 110.89 (quat-C), 120.33 (]CH),
120.53 (]CH), 123.04 (]CH), 123.69 (]CH), 125.54 (]CH), 127.52
(quat-C), 127.71 (]CH), 128.84 (]CH), 129.04 (]CH), 129.48 (quat-
C), 135.18 (]CH), 137.55 (quat-C), 142.86 (quat-C), 175.90 (quat-C);
MS (ESI) m/z 697 (MþþNa); Anal. Calcd (%) for C46H34N4O2 (674.27):
C, 81.88; H, 5.08; N, 8.30. Found: C, 81.71; H, 5.01; N, 8.38.
IR (KBr)
n
3052, 2929, 1710, 1611, 1492, 1468, 1372, 1344, 1248, 1123,
1085, 1017, 739 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
3.29 (s, 6H,
NCH3), 4.86 (s, 2H, CH), 5.16 (s, 4H, ArCH2N), 6.89e6.92 (m, 6H,
ArH), 6.98e7.03 (m, 4H, ArH), 7.10e7.11 (m, 4H, ArH), 7.18 (d, 2H,
J¼7.2 Hz, ArH) 7.20e7.25 (m, 4H, ArH), 7.31 (t, 2H, J¼7.6 Hz, ArH);
13C NMR (100 MHz, CDCl3)
d 26.54 (NCH3), 44.46 (CH), 47.53 (CH2),
108.14 (]CH), 110.83 (]CH), 110.53 (quat-C), 119.70 (]CH), 119.91
(]CH), 122.41 (]CH), 122.73 (]CH), 124.77 (]CH), 126.96 (]CH),
127.08 (quat-C), 128.26 (]CH), 128.30 (]CH), 128.42 (]CH), 129.13
4.3.16. 1,3-Bis[((10-methyl-10,30-dihydro-10H-[3,30]biindolyl-20-on)-1-
yl)methyl]benzene (12f). Colorless solid (97%); mp 144e146 ꢀC; IR
(KBr)
n 3055, 2935, 1713, 1612, 1469, 1347, 1265, 1171, 1125, 1087,

1602
S. Muthusamy et al. / Tetrahedron 68 (2012) 1595e1605
1018, 909, 743 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
3.28 (s, 6H, NCH3),
7.19 (d, 8H, J¼8.0 Hz, ArH), 7.22e7.29 (m, 6H, ArH), 7.33 (d, 4H,
4.88 (s, 2H, CH), 5.19 (s, 4H, ArCH2N), 6.91 (d, 2H, J¼8 Hz, ArH),
6.94e7.03 (m, 8H, ArH), 7.11 (t, 2H, J¼7.6 Hz, ArH), 7.17 (d, 2H,
J¼8.8 Hz, ArH), 7.20 (t, 2H, J¼3.6 Hz, ArH), 7.24 (s, 2H, ArH), 7.28 (dd,
2H, J1¼8 Hz, J2¼3.2 Hz, ArH), 7.32 (d, 2H, J¼7.6 Hz, ArH); 13C NMR
J¼6.8 Hz, ArH); 13C NMR (100 MHz, CDCl3)
d 44.11 (CH2), 44.55 (CH),
49.79 (CH2), 109.14 (]CH), 109.96 (]CH), 110.23 (quat-C), 119.69
(]CH), 119.69 (]CH), 119.82 (]CH), 122.29 (]CH), 122.75 (]CH),
125.00 (]CH), 127.09 (quat-C), 127.33 (]CH), 127.67 (]CH), 127.72
(]CH), 128.17 (]CH), 128.82 (]CH), 129.13 (quat-C), 136.10 (quat-
C),136.88 (quat-C),137.05 (quat-C),143.42 (quat-C),176.50 (quat-C);
MS (ESI) m/z (%) 779 (Mþ1, 48), 778 (Mþ, 100), 687 (19), 556 (17),
440 (29), 337 (38), 307 (25), 222 (40), 154 (83); Anal. Calcd (%) for
C54H42N4O2 (778.37): C, 83.26; H, 5.43; N, 7.19. Found: C, 83.47; H,
5.34; N, 7.11.
(100 MHz, CDCl3) d 27.15 (NCH3), 44.85 (CH), 49.95 (CH2), 108.72 (]
CH), 110.51 (]CH), 110.79 (quat-C), 120.33 (]CH), 122.87 (]CH),
123.21 (]CH), 125.44 (]CH), 126.03 (]CH), 126.79 (]CH), 127.83
(]CH), 128.81 (]CH), 129.73 (quat-C), 129.92 (]CH), 137.61 (quat-
C), 138.64 (quat-C), 144.93 (quat-C), 176.90 (quat-C); MS (ESI) m/z
649 (MþþNa); Anal. Calcd (%) for C42H34N4O2 (626.27): C, 80.49; H,
5.47; N, 8.94. Found: C, 80.61; H, 5.38; N, 8.99.
4.3.21. 1,4-Bis[((10-(4-methylbenzyl)-10,30-dihydro-10H-[3,30]biin-
4.3.17. 1,3-Bis[((10-benzyl-10,30-dihydro-10H-[3,30]biindolyl-20-on)-1-
yl)methyl]benzene (12g). Brown solid (96%); mp 132e134 ꢀC; IR
dolyl-20-on)-1-yl)methyl]benzene (12k). Colorless solid (94%); mp
136e138 ꢀC; IR (KBr)
n
3054, 2926, 1713, 1612, 1515, 1486, 1466,
1354, 1265, 1179, 1014, 909, 748 cmꢁ1 1H NMR (400 MHz, CDCl3)
d 2.29 (s, 6H, ArCH3), 4.83e5.00 (m, 6H, NCH2 and CH), 5.19 (s, 4H,
(KBr)
909, 738 cmꢁ1
NCH2 and CH), 5.15 (s, 4H, ArCH2N), 6.80 (d, 2H, J¼7.6 Hz, ArH),
6.93e7.31 (m, 30H, ArH); 13C NMR (100 MHz, CDCl3)
44.71 (CH2),
n
3055, 2926, 1713, 1612, 1486, 1466, 1356, 1265, 1179, 1011,
;
;
1H NMR (400 MHz, CDCl3)
d
4.84e5.06 (m, 6H,
ArCH2N), 6.82 (d, 2H, J¼8.0 Hz, ArH), 6.94 (t, 4H, J¼7.6 Hz, ArH), 7.03
d
(s, 6H, ArH), 7.09 (d, 6H, J¼7.6 Hz, ArH), 7.17e7.19 (m, 8H, ArH), 7.23
45.14 (CH), 50.62 (CH2), 109.73 (]CH), 110.59 (]CH), 110.92 (quat-
C), 120.29 (]CH), 120.42 (]CH), 122.89 (]CH), 123.28 (]CH),
125.64 (]CH), 126.12 (]CH), 126.93 (]CH), 127.72 (quat-C), 128.02
(]CH), 128.29 (]CH), 128.83 (]CH), 129.41 (]CH), 130.04 (]CH),
136.72 (quat-C), 137.74 (quat-C), 138.73 (quat-C), 143.88 (quat-C),
177.15 (quat-C); MS (EI) m/z (%) 778 (Mþ, 2), 339 (15), 338 (95), 247
(100), 219 (16), 105 (29), 91 (64); HRMS (ESI) calcd for
C54H42N4O2Na [MþþNa] 801.3208, found: 801.3213.
(d, 4H, J¼7.6 Hz, ArH); 13C NMR (100 MHz, CDCl3)
d 21.84 (ArCH3),
44.54 (CH2), 45.13 (CH), 50.41 (CH2), 109.72 (]CH), 110.51 (]CH),
110.89 (quat-C), 120.21 (]CH), 120.43 (]CH), 122.85 (]CH), 123.21
(]CH), 125.53 (]CH), 127.72 (quat-C), 127.91 (]CH), 128.38 (]CH),
128.69 (]CH), 129.79 (quat-C), 130.12 (]CH), 133.73 (quat-C),
137.51 (quat-C), 137.71 (quat-C), 137.92 (quat-C), 144.12 (quat-C),
177.01 (quat-C); MS (ESI) m/z (%) 829 (MþþNa); Anal. Calcd (%) for
C56H46N4O2 (806.36): C, 83.35; H, 5.75; N, 6.94. Found: C, 83.19; H,
5.81; N, 6.98.
4.3.18. 1,3-Bis[((10-(4-methylbenzyl)-10,30-dihydro-10H-[3,30]biin-
dolyl-20-on)-1-yl)methyl] benzene (12h). Light brown solid (97%);
4.3.22. 1,4-Bis[((10-allyl-10,30-dihydro-10H-[3,30]biindolyl-20-on)-1-
yl)methyl]benzene (12l). Colorless solid (94%); mp 123e125 ꢀC; IR
mp 124e126 ꢀC; IR (KBr)
n
3054, 2926, 1713, 1612, 1486, 1466, 1354,
1265,1180,1012, 908, 741 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
2.27 (s,
(KBr)
740 cmꢁ1; 1H NMR (400 MHz, CDCl3)
2H, CH), 4.97e5.29 (m, 8H), 5.78e5.91 (m, 2H, allyl CH), 6.73e7.43
(m, 22H, ArH); 13C NMR (100 MHz, CDCl3)
43.10 (CH2), 44.93 (CH),
n
3054, 2924, 1711, 1613, 1482, 1469, 1265, 1200, 1189, 921,
6H, ArCH3), 4.82e5.00 (m, 6H, NCH2 and CH), 5.15 (s, 4H, ArCH2N),
6.80e6.82 (m, 2H, ArH), 6.93e6.97 (m, 8H, ArH), 7.03e7.18 (m, 16H,
d
4.14 (s, 4H, ArCH2), 4.87 (s,
ArH), 7.22 (d, 4H, J¼6.8 Hz, ArH); 13C NMR (100 MHz, CDCl3)
d
21.23
d
(ArCH3), 43.90 (CH2), 44.60 (CH), 50.01 (CH2), 109.20 (]CH), 110.00
(]CH), 110.32 (quat-C), 119.71 (]CH), 119.87 (]CH), 122.31 (]CH),
122.71 (]CH), 124.96 (quat-C), 125.49 (]CH), 126.27 (]CH), 127.14
(]CH), 127.44 (]CH), 127.52 (]CH), 127.71 (]CH), 128.17 (]CH),
129.20 (]CH), 129.42 (quat-C), 129.51 (quat-C), 133.10 (]CH),
137.13 (quat-C), 137.39 (quat-C), 138.10 (quat-C), 144.39 (quat-C),
176.51 (quat-C); MS (EI) m/z (%) 806 (Mþ, 7), 702 (9), 701 (17), 587
(20), 482 (22), 456 (12), 353 (12), 352 (62), 351 (33), 247 (100), 235
(10); Anal. Calcd (%) for C56H46N4O2 (806.36): C, 83.35; H, 5.75; N,
6.94. Found: C, 83.48; H, 5.69; N, 6.81.
50.21 (CH2), 109.49 (]CH), 110.46 (]CH), 110.70 (quat-C), 118.23
(]CH2), 120.19 (]CH), 122.72 (]CH), 123.13 (]CH), 125.45 (]CH),
127.76 (]CH),128.62 (]CH),129.61 (quat-C),132.17 (]CH),137.351
(quat-C), 137.52 (quat-C), 143.98 (quat-C), 176.49 (quat-C); HRMS
(ESI) for C46H38N4O2Na [MþþNa] 701.2973, found: 701.2965.
4.4. Synthesis of macrocycles 13a and 13b
A solution of bis-indole 6a (100 mg, 0.37 mmol), bis-diazoamide
7a (143 mg, 0.40 mmol), and rhodium(II) acetate (1.6 mg) in
dichloromethane (50 mL) was stirred at room temperature for 1 h.
The reaction mixture was concentrated in vacuo and purified on
silica (hexane/acetone, 65:35) to yield 13a and 13b as a mixture of
diastereomers (ratio 58:42) in 50% yield.
4.3.19. 1,3-Bis[((10-(prop-2-ynyl)-10,30-dihydro-10H-[3,30]biindolyl-
20-on)-1-yl)methyl]benzene (12i). Colorless solid (95%); mp
188e190 ꢀC; IR (KBr)
n
3303, 3055, 2927, 1714, 1612, 1487, 1467,
1351, 1265, 1181, 1098, 909, 740 cmꢁ1 1H NMR (400 MHz, CDCl3)
2.25 (s, 2H, CCH), 4.56e4.57 (m, 4H, NCH2CCH), 4.90 (s, 2H, CH),
5.18 (s, 4H, ArCH2N), 6.77e7.37 (m, 22H, ArH); 13C NMR (100 MHz,
CDCl3) 30.05 (CH2), 45.14 (CH), 50.48 (CH2), 72.86 (quat-C), 77.75
;
d
4.4.1. Macrocycle 13a. Colorless solid; mp 255e257 ꢀC; IR (KBr)
3052, 2933, 1700, 1609, 1484, 1467, 1359, 1340, 1184, 759 cmꢁ1; 1H
NMR (200 MHz, CD2Cl2)
n
d
d
¼2.23 (t, 2H, J¼6.8 Hz, CH2), 2.38 (t, 2H,
(CH), 109.73 (]CH), 110.52 (]CH), 120.31 (]CH), 122.89 (]CH),
123.56 (]CH), 125.45 (]CH), 125.89 (]CH), 126.79 (]CH), 127.64
(quat-C), 127.86 (]CH), 128.82 (]CH), 129.47 (quat-C), 129.87 (]
CH), 137.61 (quat-C), 138.63 (quat-C), 142.92 (quat-C), 175.91 (quat-
C); MS (ESI) m/z 675 (MþþNa); Anal. Calcd (%) for C46H34N4O2
(674.27): C, 81.88; H, 5.08; N, 8.30. Found: C, 82.03; H, 5.13; N, 8.42.
J¼6.5 Hz, CH2), 3.50e3.67 (m, 4H), 4.06e4.256 (m, 4H), 4.87 (s, 2H,
CH), 6.80 (s, 2H, ArH), 6.93e7.01 (m, 4H, ArH), 7.16e7.40 (m, 10H,
ArH), 7.79e7.82 (m, 2H, ArH); 13C NMR (50.3 MHz, CD2Cl2)
d 28.74
(CH2), 29.53 (CH2), 38.43 (CH2), 43.72 (CH, observed in DEPT-90
NMR) 109.10 (]CH), 110.82 (]CH), 112.00 (quat-C), 119.45 (]CH),
120.46 (]CH), 122.67 (]CH), 123.14 (]CH), 125.30 (]CH), 127.75
(]CH), 128.65 (]CH), 129.84 (quat-C), 131.65 (quat-C), 136.9 (quat-
C), 144.31 (quat-C), 177.90 (quat-C); HRMS (ESI) calcd for
C38H32N4O2Na [MþþNa] 599.2423, found 599.2417. Crystal data for
compound 13a: (CCDC-832919) Colorless plate crystal. C38H32N4O2,
M¼576.68, 0.15ꢂ0.12ꢂ0.08 mm3, monoclinic, space group C2/c
4.3.20. 1,4-Bis[((10-benzyl-10,30-dihydro-10H-[3,30]biindolyl-20-on)-1-
yl)methyl]benzene (12j). Brown solid (95%); mp 138e140 ꢀC; IR
(KBr)
n
3055, 2927, 1712, 1612, 1487, 1466, 1354, 1265, 1179, 1013,
4.87e5.04 (m, 6H, NCH2
909, 745 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
¼90ꢀ,
ꢀ
ꢀ
ꢀ
and CH), 5.19 (s, 4H, ArCH2N), 6.81 (d, 2H, J¼7.6 Hz, ArH), 6.95 (t, 4H,
with a¼43.37(2) A, ꢀ b¼8.517(4) A, c¼16.561(7) A,
a
3
¼104.126(15)ꢀ,
g
¼90 , V¼5932(4) A , T¼273(2) K, R1¼0.0641,
ꢀ
J¼7.6 Hz, ArH), 7.02e7.04 (m, 6H, ArH), 7.11 (t, 2H, J¼7.6 Hz, ArH),
b

S. Muthusamy et al. / Tetrahedron 68 (2012) 1595e1605
1603
wR2¼0.1085 on observed data, z¼8, Dcalcd¼1.291 g cmꢁ3, F(000)¼
135.97 (quat-C), 143.39 (quat-C), 176.74 (quat-C); HRMS (ESI) calcd
for C39H34N4O2Na [MþþNa] 613.2579, found 613.2573.
2432, Absorption coefficient¼0.081 mmꢁ1
,
l
¼0.71073 A, 14,489
ꢀ
reflections were collected on a Smart Apex CCD single-crystal dif-
fractometer, 5219 observed reflections (Iꢃ2
s
(I)). The largest dif-
4.6. Synthesis of macrocycles 15a and 15b
ꢀꢁ3
ference peak and hole¼0.182 and ꢁ0.148 e A , respectively.
A solution of bis-indole 7b (100 mg, 0.37 mmol), bis-diazoamide
6b (140 mg, 0.40 mmol), and rhodium(II) acetate (1.6 mg) in
dichloromethane (50 mL) was stirred at room temperature for
45 min. The reaction mixture was concentrated in vacuo and pu-
rified on silica (hexane/acetone, 65:35) to obtain 15a and 15b as
a mixture of diastereomers (ratio 51:49) in 55% yield.
4.4.2. Macrocycle 13b. Colorless solid; mp 220e222 ꢀC; IR (KBr)
n
3050, 2938, 1694, 1611, 1487, 1466, 1368, 1209, 1125, 743 cmꢁ1; 1H
NMR (200 MHz, DMSO-d6)
d
¼1.25e1.27 (m, 1H), 1.73e1.76 (m,
1H), 2.04e2.09 (m, 2H), 3.66e3.97 (overlapping m, 8H), 5.02 (s,
2H, CH), 6.37 (s, 2H, ArH), 7.05 (t, 2H, J¼6.8 Hz, ArH), 7.13e7.34 (m,
10H, ArH), 7.51 (d, 2H, J¼8.1 Hz, ArH), 7.93 (d, 2H, J¼7.7 Hz, ArH);
13C NMR (50.3 MHz, DMSO-d6)
d
26.60 (CH2), 32.13 (CH2), 37.04
4.6.1. Macrocycle 15a. Colorless solid; mp 150e154 ꢀC; IR (neat)
3050, 2932, 1702, 1609, 1463, 1349, 1237, 1154, 1091, 1014,
870 cmꢁ1 1H NMR (400 MHz, CD2Cl2)
n
(CH2), 42.50 (CH2), 43.00 (CH), 109.22 (]CH), 110.21 (]CH),
113.23 (quat-C), 119.69 (]CH), 119.87 (]CH), 122.39 (]CH),
122.83 (]CH), 123.97 (]CH), 124.90 (]CH), 127.51 (quat-C),
128.46 (]CH), 130.74 (quat-C), 136.73 (quat-C), 142.95 (quat-C),
176.78 (quat-C); HRMS (ESI) calcd for C38H32N4O2Na [MþþNa]
599.2423, found 599.2439. Crystal data for compound 13b:
(CCDC-832920) Colorless plate crystal. C39H32Cl3N4O2, 695.04,
;
d
¼1.64e1.66 (m, 8H, CH2),
3.28e3.42 (m, 2H, NeCH2), 3.56e3.60 (m, 2H, NeCH2), 3.83e3.89
(m, 2H, OCH2), 4.07e4.10 (m, 2H, OCH2), 4.69 (s, 2H, CH), 6.21 (s, 2H,
ArH), 6.74e6.79 (m, 3H, ArH), 6.92e6.98 (m, 3H, ArH) 7.12e7.15 (m,
3H, ArH) 7.20e7.25 (m, 7H, ArH); 13C NMR (100 MHz, CDCl3)
d 24.72
(CH2), 28.02 (CH2), 39.69 (CH2), 43.41 (CH, observed in DEPT-135
NMR), 46.18 (CH2), 108.78 (]CH), 109.23 (]CH), 109.83 (quat-C),
119.65 (]CH), 120.14 (]CH), 122.14 (]CH), 122.50 (]CH), 124.80
(]CH), 125.14 (]CH), 128.21 (]CH), 128.42 (quat-C), 136.09 (quat-
C), 143.59 (quat-C), 176.89 (quat-C); HRMS (ESI) calcd for
C40H36N4O2Na [MþþNa] 627.2771, found 627.2780.
0.14ꢂ0.10ꢂ0.06 mm3, Monoclinic, space group
P
with
ꢀ
ꢀ
ꢀ
a¼8.6282(9) A, b¼ꢀ 17.7685(19) A, c¼21.078(2) A,
a
¼90ꢀ,
3
b
¼95.647(2)ꢀ,
g
¼90 , V¼3215.8(6) A , T¼273(2) K, R1¼0.1173,
ꢀ
wR2¼0.3723 on observed data, z¼4, Dcalcd¼1.436 g cmꢁ3, F(000)¼
1444, Absorption coefficient¼0.329 mmꢁ1
,
l
¼0.71073 A, 12,773
ꢀ
reflections were collected on a smart apex CCD single-crystal
diffractometer, 4200 observed reflections (Iꢃ2
s
(I)). The largest
4.6.2. Macrocycle 15b. Colorless solid; mp 220e224 ꢀC; IR (neat)
3052, 2935, 1704, 1610, 1486, 1464, 1352, 1264, 1155, 1091, 1014,
876 cmꢁ1 1H NMR (400 MHz, CDCl3)
n
ꢀꢁ3
difference peak and hole¼0.731 and ꢁ1.852 e A , respectively.
;
d
¼1.54e1.65 (m, 8H, CH2),
3.26e3.30 (m, 2H, NeCH2), 3.57e3.60 (m, 2H, NeCH2), 4.11e4.18
(m, 4H, OCH2), 4.79 (s, 2H, CH), 6.35 (s, 2H, ArH), 6.79 (d, 2H,
J¼7.6 Hz, ArH), 6.98 (t, 2H, J¼7.2 Hz, ArH), 7.09e7.86 (m, 10H, ArH),
4.5. Synthesis of macrocycles 14a and 14b
A solution of bis-indole 7b (100 mg, 0.37 mmol), bis-diazoamide
6a (136 mg, 0.40 mmol), and rhodium(II) acetate (1.6 mg) in
dichloromethane (50 mL) was stirred at room temperature for
45 min. The reaction mixture was concentrated in vacuo and pu-
rified on silica (hexane/acetone, 65:35) to furnish 14a and 14b as
a mixture of diastereomers (ratio 53:47) in 52% yield.
7.88 (d, 2H, J¼7.6 Hz, ArH); 13C NMR (100 MHz, CDCl3)
d 24.73 (CH2),
27.98 (CH2), 39.70 (CH2), 43.41 (CH, observed in DEPT-135 NMR),
46.16 (CH2), 108.74 (]CH), 109.20 (]CH), 109.92 (quat-C), 119.64
(]CH), 120.13 (]CH), 122.13 (]CH), 122.48 (]CH), 124.79 (]CH),
125.12 (]CH), 128.41 (]CH), 128.40 (quat-C), 136.12 (quat-C),
143.59 (quat-C), 175.88 (quat-C); HRMS (ESI) calcd for
C40H36N4O2Na [MþþNa] 627.2771, found 627.2766.
4.5.1. Macrocycle 14a. Colorless solid; mp 202e203 ꢀC; IR (neat)
3053, 2940, 1708, 1611, 1466, 1357, 1264,1175, 1086, 1018, 728 cmꢁ1
1H NMR (400 MHz, CDCl3)
n
;
4.7. Synthesis of macrocycles 16a and 16b
d¼1.36e1.42 (m, 2H, CH2), 1.51e1.55 (m,
2H, CH2), 1.86e1.89 (m, 2H, CH2), 3.35e3.41 (m, 2H, NeCH2),
3.55e3.59 (m, 2H, NeCH2), 3.85e3.90 (m, 2H, OCH2), 4.07e4.13 (m,
2H, OCH2), 4.75 (s, 2H, CH), 6.25 (s, 2H, ArH), 6.80 (d, 2H, J¼8.0 Hz,
ArH,), 6.93 (t, 2H, J¼7.6 Hz, ArH,), 7.08e7.23 (m, 10H, ArH), 7.75 (d,
A solution of bis-indole 7c (100 mg, 0.30 mmol), bis-diazoamide
6a (120 mg, 0.33 mmol), and rhodium(II) acetate (1.3 mg) in
dichloromethane (50 mL) was stirred at room temperature for 1 h.
The reaction mixture was concentrated in vacuo and purified on
silica (hexane/acetone, 65:35) to yield 16a and 16b as a mixture of
diastereomers (ratio 27:73) in 63% yield.
2H, J¼7.6 Hz, ArH); 13C NMR (100 MHz, CDCl3)
d 25.19 (CH2), 27.76
(CH2), 37.45 (CH2), 43.17 (CH, observed in DEPT-135 NMR), 45.90
(CH2), 108.27 (]CH), 109.31 (]CH), 111.26 (quat-C), 119.56 (]CH),
119.72 (]CH), 122.05 (]CH), 122.58 (]CH), 125.06 (]CH), 125.33
(]CH), 128.0 (quat-C), 128.39 (]CH), 129.38 (quat-C), 135.99 (quat-
C), 143.40 (quat-C), 176.76 (quat-C); HRMS (ESI) calcd for
C39H34N4O2Na [MþþNa] 613.2579, found 613.2563.
4.7.1. Macrocycle 16a. Colorless solid; mp 210e212 ꢀC; IR (neat)
3055, 2929, 1707, 1610, 1485, 1463, 1356, 1179, 729 cmꢁ1 1H NMR
(400 MHz, CDCl3) 2.05e2.10 (m, 2H), 3.50e3.56 (m, 2H),
n
d
3.87e3.94 (m, 2H), 4.71 (d, 2H, J¼16.0 Hz, NCH2), 4.73 (s, 2H, CH),
5.00 (d, 2H, J¼16.0 Hz, NCH2), 6.77 (s,1H, ArH), 6.83 (d, 2H, J¼7.6 Hz,
ArH), 6.91e6.94 (m, 3H, ArH), 7.02e7.23 (m, 14H, ArH), 7.40 (d, 2H,
4.5.2. Macrocycle 14b. Colorless solid; mp 225e227 ꢀC; IR (neat)
3054, 2933, 1708, 1610, 1465, 1356, 1264, 1175, 1086, 1021,
729 cmꢁ1 1H NMR (400 MHz, CDCl3)
n
J¼8.0 Hz, ArH); 13C NMR (100 MHz, CDCl3)
d 26 (CH2), 37.97 (CH2),
;
d
¼1.43e1.60 (m, 2H, CH2),
43.3 (CH), 48.1 (CH2),108.1 (]CH),109.7 (]CH),111.5 (quat-C),118.9
(]CH), 119.9 (]CH), 122.0 (]CH), 122.6 (]CH), 125.0 (]CH), 126.7
(]CH), 128.0 (quat-C), 128.1 (]CH), 128.3 (]CH), 128.8 (]CH),
130.0 (quat-C), 134.5 (quat-C), 136.5 (quat-C), 143.4 (quat-C), 177.5
(quat-C); MS (EI) m/z (%) 639 (Mþ1, 7), 638 (Mþ,17), 421 (6), 306 (5),
220 (6), 219 (25), 218 (74), 217 (100), 189 (5), 117 (11); HRMS (ESIþ)
calcd for C43H34N4O2Na [MþþNa] 661.2682, found 661.2674.
1.92 (br s, 2H, CH2), 1.93e1.95 (m, 2H, CH2), 3.42e3.49 (m, 2H,
NeCH2), 3.61e3.64 (m, 2H, NeCH2), 3.91e3.99 (m, 2H, OCH2),
4.13e4.17 (m, 2H, OCH2), 4.81 (s, 2H, CH), 6.32 (s, 2H, ArH), 6.87 (d,
2H, J¼8.0 Hz, ArH), 6.97e7.01 (m, 2H, ArH), 7.14e7.29 (m, 10H, ArH),
7.82 (d, 2H, J¼7.2 Hz, ArH); 13C NMR (100 MHz, CDCl3)
d 25.17 (CH2),
27.76 (CH2), 37.43 (CH2), 43.17 (CH, observed in DEPT-135 NMR),
45.90 (CH2), 108.25 (]CH), 109.28 (]CH), 111.26 (quat-C), 119.55
(]CH), 119.71 (]CH), 122.03 (]CH), 122.56 (]CH), 125.04 (]CH),
125.30 (]CH), 128.00 (quat-C), 128.37 (]CH), 129.35 (quat-C),
4.7.2. Macrocycle 16b. Colorless solid; mp 216e218 ꢀC; IR (neat)
3057, 3019, 2934, 1708, 1612, 1486, 1466, 1359, 1265, 1216, 909,
n

1604
S. Muthusamy et al. / Tetrahedron 68 (2012) 1595e1605
757 cmꢁ1
;
1H NMR (200 MHz, CDCl3)
d
1.87e1.94 (m, 1H, CH2),
observed reflections (Iꢃ2
s (I)). The largest difference peak and
hole¼0.247 and ꢁ0.220 e A , respectively.
ꢀꢁ3
2.60e2.67 (m, 1H, CH2), 3.42e3.57 (m, 2H), 3.99e4.13 (m, 2H), 4.85
(s, 2H, CH), 4.93 (d, 2H, J¼15.8 Hz, NCH2), 5.03 (d, 2H, J¼15.8 Hz,
NCH2), 6.82e7.23 (m, 20H, ArH), 7.42 (d, 2H, J¼7.8 Hz, ArH); 13C
4.9. Synthesis of macrocycle 18
NMR (50 MHz, CDCl3) d 25.6 (CH2), 37.8 (CH2), 43.7 (CH), 47.4 (CH2),
107.7 (]CH), 109.5 (]CH), 111.1 (quat-C), 119.2 (]CH), 119.6 (]CH),
121.9 (]CH), 122.2 (]CH), 124.9 (]CH), 126.6 (]CH), 127.6 (quat-
C), 127.8 (]CH), 128.3 (]CH), 128.9 (]CH), 129.9 (quat-C), 134.4
(quat-C), 136.9 (quat-C), 143.2 (quat-C), 176.5 (quat-C); MS (EI) m/z
(%) 639 (Mþ1, 7), 638 (Mþ, 17), 421 (6), 306 (5), 220 (6), 219 (25),
218 (74), 217 (100), 189 (5), 117 (11); HRMS (ESI) calcd for
C43H34N4O2Na [MþþNa] 661.2682, found 661.2670. Crystal data for
compound 16b: (CCDC-832921) Colorless plate crystal.
C45H34Cl6N4O2, 875.46, 0.14ꢂ0.10ꢂ0.08 mm3, Triclinic, space group
A solution of bis-indole 7c (90 mg, 0.27 mmol), bis-diazoamide
6c (105 mg, 0.30 mmol), and rhodium(II) acetate (1.2 mg) in
dichloromethane (50 mL) was stirred at room temperature for 1 h.
The reaction mixture was concentrated in vacuo and purified on
silica (hexane/acetone, 60:35) to obtain the product 18 (50%) as an
inseparable mixture of diastereomers (diastereomeric ratio 56:44).
Colorless solid; IR (KBr)
1358, 1265, 1180, 1187, 1016, 896, 740 cmꢁ1
CDCl3) 4.43e4.73 (m, 2H), 4.90 (s, 2H, CH), 4.98e5.28 (m, 6H),
n
3055, 2987, 1711, 1611, 1486, 1466, 1422,
;
1H NMR (200 MHz,
d
ꢀ
ꢀ
ꢀ
Pꢁ1 with a¼10.9507(19) A, b¼12.664(2) A, c¼15.465(3) A,
6.85e7.04 (m, 9H, ArH), 7.08e7.34 (m, 15H, ArH), 7.52e7.70 (m, 2H,
3
¼97.505(4)ꢀ,
b
¼92.949(3)ꢀ,
g
¼98.717(4)ꢀ, V¼2096.1(6) A ,
ꢀ
ArH); 13C NMR (50.3 MHz, CDCl3, The * symbol represents signals
a
T¼273(2) K, R1¼0.1280, wR2¼0.3429 on observed data, z¼2,
due to the minor amount of diastereomer)
d 44.8 (CH2), 45.0 (CH),
Dcalcd¼1.387
g
cmꢁ3
,
F(000)¼900,
Absorption
45.2* (CH2), 48.6 (CH2), 48.8* (CH2), 108.9* (]CH), 109.0 (]CH),
110.3 (]CH), 110.5* (]CH), 110.8 (quat-C), 119.7 (]CH), 120.4 (]
CH), 122.7 (]CH), 123.1* (]CH), 123.2 (]CH), 125.4* (]CH), 125.5
(]CH), 127.5 (]CH), 128.1 (]CH)*, 128.2 (]CH), 128.5 (]CH),
128.6* (]CH), 129.0* (]CH), 129.1 (]CH), 129.5 (]CH), 129.7* (]
CH), 130.5 (quat-C), 130.6* (quat-C), 131.1 (quat-C), 135.4 (quat-C),
135.6* (quat-C), 137.0 (quat-C), 137.4* (quat-C), 137.8 (quat-C), 143.7
(quat-C), 177.3 (quat-C); MS (FAB) m/z 700 (Mþ); HRMS( ESI) calcd
for C48H36N4O2Na (MþþNa) 723.2738, found 723.2722.
coefficient¼0.453 mmꢁ1
,
l
¼0.71073 A, 8409 reflections were col-
ꢀ
lected on a smart apex CCD single-crystal diffractometer, 5440
observed reflections (Iꢃ2
s (I)). The largest difference peak and
hole¼0.710 and ꢁ0.775 e A , respectively.
ꢀꢁ3
4.8. Synthesis of macrocycles 17a and 17b
A solution of bis-indole 7d (93 mg, 0.28 mmol), bis-diazoamide
6a (110 mg, 0.31 mmol), and rhodium(II) acetate (1.2 mg) in
dichloromethane (50 mL) was stirred at room temperature for 1 h.
The reaction mixture was concentrated under reduced pressure
and purified on silica (hexane/acetone, 65:35) to furnish 17a
(32 mg) and 17b (64 mg) (diastereomeric ratio 36:64) in 54% yield.
Acknowledgements
This research was supported by Department of Science and
Technology (DST), New Delhi. C.G. and T.K. thank CSIR and UGC-
RFSMS, respectively, for a research fellowship. We thank DST,
New Delhi for providing 400 MHz NMR facility under FIST program.
4.8.1. Macrocycle 17a. Colorless solid; mp 296e298 ꢀC; IR (KBr)
3055, 2927, 1710, 1612, 1487, 1466, 1360, 1265, 1180, 1180, 1021,
738 cmꢁ1; 1H NMR (200 MHz, CDCl3)
1.68e1.95 (m,1H), 2.11e2.25
n
d
Supplementary data
(m, 1H), 3.48e3.66 (m, 2H), 3.99e4.20 (m, 2H), 4.85 (d, 2H,
J¼14.5 Hz, NCH2), 4.93 (s, 2H, CH), 5.15 (d, 2H, J¼14.5 Hz, NCH2),
6.60e6.76 (m, 2H, ArH), 6.84e7.00 (m, 4H, ArH), 7.16e7.39 (m, 14H,
Single-crystal X-ray analyses and packing diagram of com-
pounds 13a,b,16b,17b. Supplementary data related to this article
can be found online at doi:10.1016/j.tet.2011.11.073.
ArH), 7.71 (d, 2H, J¼6.5 Hz, ArH); 13C NMR (50.3 MHz, CDCl3),
d 25.9
(CH2), 37.7 (CH2), 43.2 (CH), 50.0 (CH2), 108.0 (]CH), 109.7 (]CH),
111.0 (quat-C),118.8 (]CH),119.6 (]CH),121.9 (]CH),122.4 (]CH),
124.6 (]CH), 126.1 (]CH), 126.4 (]CH), 127.2 (]CH), 127.9 (]CH),
128.7 (]CH), 128.5 (quat-C), 130.1 (quat-C), 136.6 (quat-C), 137.9
(quat-C), 142.9 (quat-C), 176.6 (quat-C); HRMS (ESI) calcd for
C43H34N4O2Na [MþþNa] 661.2682, found: 661.2665.
References and notes
1. (a) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods for Organic
Synthesis with Diazo Compounds; John Wiley: New York, NY, 1998; (b) Zhang, Z.;
Wang, J. Tetrahedron 2008, 64, 6577e6605.
2. (a) Reissig, H. H.; Zimmer, R. Chem. Rev. 2003, 103, 1151e1196; (b) Muthusamy,
S.; Srinivasan, P. Tetrahedron Lett. 2006, 47, 6297e6300.
3. (a) Caballero, A.; Díaz-Requejo, M. M.; Trofimenko, S.; Belderrain, T. R.; Perez, P.
J. J. Org. Chem. 2005, 70, 6101e6104; (b) Hahn, N. D.; Nieger, M.; Dotz, K. H. J.
Organomet. Chem. 2004, 689, 2662e2673; (c) Hughes, C. C.; Kennedy-Smith, J.
J.; Trauner, D. Org. Lett. 2003, 5, 4113e4115.
4.8.2. Macrocycle 17b. Colorless solid; mp 290e292 ꢀC; IR (KBr)
3048, 2921, 1706, 1617, 1481, 1461, 1355, 1261, 1173, 1019, 735 cmꢁ1
1H NMR (200 MHz, CDCl3)
1.59e1.83 (m, 1H), 2.01e2.17 (m, 1H),
n
ꢁ
€
;
d
3.35e3.60 (m, 2H), 3.90e4.16 (m, 2H), 4.92 (d, 2H, J¼14.5 Hz,
NCH2), 5.12 (s, 2H, CH), 5.25 (d, 2H, J¼14.5 Hz, NCH2), 6.65e7.82 (m,
2H, ArH), 6.90e7.08 (m, 4H, ArH), 7.23e7.46 (m, 14H, ArH), 7.75 (d,
4. Yadav, J. S.; Reddy, B. V. S.; Satheesh, G. Tetrahedron Lett. 2003, 44, 8331e8334.
5. Yang, J.; Song, H.; Xiao, X.; Wang, J.; Qin, Y. Org. Lett. 2006, 8, 2187e2190.
6. Rotzoll, S.; Appel, B.; Langer, P. Tetrahedron Lett. 2005, 46, 4057e4059.
7. Zhang, D.; Song, H.; Qin, Y. Acc. Chem. Res. 2011, 44, 447e457.
8. Salim, M.; Capretta, A. Tetrahedron 2000, 56, 8063e8069.
9. (a) Wenkert, E.; Alonso, M. E.; Gottlieb, H. E.; Sanchez, E. L. J. Org. Chem. 1977,
42, 3945e3949; (b) Welstead, W. J.; Stauffer, H. F., Jr.; Sancilio, L. F., Jr. J. Med.
Chem. 1974, 17, 544e547.
10. Muthusamy, S.; Azhagan, D.; Gnanaprakasam, B.; Suresh, E. Tetrahedron Lett.
2010, 51, 5662e5665.
11. Muthusamy, S.; Gunanathan, C.; Babu, S. A.; Suresh, E.; Dastidar, P. Chem.
Commun. 2002, 824e825.
2H, J¼6.5 Hz, ArH); 13C NMR (50.3 MHz, CDCl3),
d 25.5 (CH2), 36.7
(CH2), 43.4 (CH), 49.5 (CH2), 107.8 (]CH), 109.4 (]CH), 111.2 (quat-
C), 118.9 (]CH), 119.4 (]CH), 122.0 (]CH), 122.4 (]CH), 124.8 (]
CH), 125.1 (]CH), 126.1 (]CH), 127.0 (]CH), 127.7 (]CH), 128.1
(quat-C), 130.2 (quat-C), 136.8 (quat-C), 138.1 (quat-C), 142.6 (quat-
C), 176.2 (quat-C); HRMS (ESI) calcd for C43H34N4O2Na [MþþNa]
661.2682, found: 661.2671. Crystal data for compound 17b: (CCDC-
832922) Colorless plate crystal. C44H36Cl2N4O2, 722.22,
0.18ꢂ0.10ꢂ0.07 mm3, Orthorhombic, space group Pnma with
12. (a) Rajakumar, P.; Swaroop, M. G. Tetrahedron 2004, 45, 6165e6167; (b) Bod-
well, G. J.; Li, J. Org. Lett. 2002, 4, 127e130; (c) Bodwell, G. J.; Li, J. Angew. Chem.
2002, 41, 3261e3262; (d) Ortner, B.; Waibel, R.; Gmeiner, P. Angew. Chem. 2001,
40, 1283e1285; (e) Bodwell, G. J.; Li, J.; Miller, D. O. Tetrahedron 1999, 55,
ꢀ
ꢀ
ꢀ
a
a¼21.ꢀ794(3) A, b¼18.955(2) A, c¼8.8502(10) A,
¼90ꢀ,
b
¼90ꢀ,
€
12939e12956; (f) Breitenbach, J.; Boosfeld, J.; Vogtle, F. In Comprehensive Su-
3
ꢀ
€
pramolecular Chemistry; Vogtle, F., Ed.; Pergamon: New York, NY, 1996; Vol. 2;
g
¼90 , V¼3656.1(7) A , T¼273(2) K, R1¼0.0778, wR2¼0.1577 on
€
observed data, z¼4, Dcalcd¼1.315 g cmꢁ3, F(000)¼1512, Absorption
(g) Vogtle, F. Cyclopropane Chemistry; Wiley: Chichester, UK, 1993.
13. Steed, J. W.; Atwood, J. L. Supramolecular Chemistry; Wiley: New York, NY, 2000.
14. (a) Muthusamy, S.; Krishnamurthi, J.; Suresh, E. Chem. Commun. 2007, 861e863;
(b) Muthusamy, S.; Srinivasan, P. Tetrahedron 2009, 65, 1567e1573; (c)
coefficient¼0.222 mmꢁ1
,
l
¼0.71073 A, 17,541 reflections were
ꢀ
collected on a smart apex CCD single-crystal diffractometer, 3325

S. Muthusamy et al. / Tetrahedron 68 (2012) 1595e1605
1605
Muthusamy, S.; Srinivasan, P. Tetrahedron Lett. 2005, 46, 1063e1066; (d) Mu-
thusamy, S.; Srinivasan, P. Tetrahedron Lett. 2009, 50, 3794e3797.
15. Yeung, K. S.; Paterson, I. Chem. Rev. 2005, 105, 4237e4313.
16. (a) Gleiter, R.; Hopf, H. In Modern Cyclophane Chemistry; Wiley-VCH: Wein-
heim, 2004; (b) Diederich, F. Cyclophanes In Monographes in Supramolecular
Chemistry; Stoddart, J. F., Ed.; The Royal Society of Chemistry: Cambridge,
1994.
20. (a) Viehe, H. G. Chemistry of Acetylenes; Marcel Dekker: New York, NY, 1969;
597e647; (b) Trost, B. M.; Matsubara, S.; Catingi, J. J. J. Am. Chem. Soc. 1989, 111,
8745e8746.
21. CCDC-832919 (for 13a), 832920 (for 13b), 832921 (for 16b), and 832922 (for
17b) contain the supplementary crystallographic data for this paper. These data
can be obtained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
17. (a) Richard, J.; Pamart, M.; Hucher, N.; Jabin, I. Tetrahedron Lett. 2008, 49,
3848e3852; (b) Conejo-Garcia, A.; Campos, J. M.; Sanchez-Martin, R. M.; Gallo,
M. A.; Espinosa, A. J. Med. Chem. 2003, 46, 3754e3757; (c) Bruno, G.; Cafeo, G.;
Kohnke, F. H.; Nicolo, F. Tetrahedron 2007, 63, 10003e10010.
18. Diederich, F. Cyclophanes; The Royal Society of Chemistry: Cambridge,
1991; 313.
22. See Supplementary data for more details.
23. Muthusamy, S.; Gunanathan, C.; Nethaji, M. J. Org. Chem. 2004, 69, 5630e5637.
24. Bruker, A. X. S. SMART; Bruker AXS: Madison, WI, USA, 1998.
25. Bruker, A. X. S. SMART; Bruker AXS: Madison, WI, USA, 1999.
26. Blessing, R. Acta Crystallogr., Sect. A 1995, 51, 33e38.
27. Sheldrick, G. M. SHELXL97, Program for the Solution of X-ray Crystal Structures;
University of Gottingen: Germany, 1997.
19. Wessjohann, L. A.; Ruijter, E.; Garcia-Rivera, O.; Brandt, W. Mol. Diversity 2005,
9, 171e186.
28. Bloxham, J.; Moody, C. J.; Slawin, M. Z. Tetrahedron 2002, 58, 3709e3720.