Synthetic Utility of Arylmethylsulfones: Annulative π-Extension of Aromatics and Hetero-aromatics Involving Pd(0)-Catalyzed Heck Coupling Reactions

Article abstract of DOI:10.1021/acs.joc.7b01813

A straightforward and general method for the synthesis of annulated thiophene, dibenzothiophene, and carbazoles analogues has been achieved involving alkylation of 2-bromo-1-(phenylsulfonylmethyl)arene/heteroarene with arylmethyl bromides/heteroarylmethyl bromides using t-BuOK as a base in DMF, followed by Pd(0)-mediated intramolecular Heck coupling in the presence of K₂CO₃ in DMF at 80-140 °C. The attractive feature of this protocol is that a wide variety of π-conjugated heterocycles could be readily accessed by an appropriate choice of arylmethylsulfones and benzylic bromides.

Full text of DOI:10.1021/acs.joc.7b01813

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Note
Synthetic Utility of Arylmethylsulfones: Annulative #-Extension of Aromatics
and Hetero-Aromatics involving Pd(0)-catalyzed Heck coupling reactions
Elumalai Sankar, Potharaju Raju, Jayachandran Karunakaran, and Arasambattu Kannan Mohanakrishnan
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b01813 • Publication Date (Web): 14 Nov 2017
Downloaded from http://pubs.acs.org on November 14, 2017
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Synthetic Utility of Arylmethylsulfones: Annulative πꢀExtension of
Aromatics and HeteroꢀAromatics involving Pd(0)ꢀcatalyzed
Heck coupling reactions
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Elumalai Sankar, Potharaju Raju, Jayachandran Karunakaran and Arasambattu K.
Mohanakrishnan*
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Department of Organic Chemistry, School of Chemistry, University of Madras
Guindy Campus, Chennai 600 025, Tamil Nadu, India
Email: mohanakrishnan@unom.ac.in; mohan_67@hotmail.com
ABSTRACT: A straightforward and general method for synthesis of annulated thiophene,
dibenzothiophene and carbazoles analogues have been achieved involving alkylation of
2ꢀbromoꢀ1ꢀ(phenylsulfonylmethyl)arene/heteroarene
with
arylmethylbromides/
heteroarylmethylbromides using tꢀBuOK as a base in DMF followed by Pd(0)ꢀmediated
intramolecular Heck coupling in the presence of K2CO3 in DMF at 80ꢀ140 oC. The attractive
feature of this protocol is that a wide variety of πꢀconjugated heterocycles could be readily
accessed by an appropriate choice of arylmethyl sulfones and benzylic bromides.
Sulfones display a diverse range of behaviour and possess unique features that make them
as a highly valuable precursor for various types of synthetic transformation.1 Ability of
sulfone to stabilize an adjacent carbanion has been well recognized and exploited in organic
synthesis.2 For the first time, Trost and Ghadiri outlined displacement ability of sulfone by
carbon nucleophile in the presence of AlCl3.3 Recently, sulfone unit has been explored as an
leaving group in different types of arylation as well as crossꢀcoupling reactions.4
Synthesis of polycyclic aromatic heterocycles involving annualtive πꢀextension5 has
played major role in accessing required materials for optical applications. In particular,
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polycyclic aromatic compounds have received significant interest as versatile and high
performance active components in optical devices.6 The various types of synthetic protocols
available for accessing phenanthrenes and its heterocyclic counter parts are outlined (Figure
1). The earliest method available for phenanthrene involves photocyclization of
1,2ꢀdiarylethylenes.7 Tojo and coworkers employed this methodology for synthesis of wide
variety of phenanthrenoids and their heteroꢀanalogues involving photocyclization of stilbenes
containing a tosyl group under oxidative condition or in the presence of base.8 Using
photocyclization of tosyl stilbene as a key step, synthesis of analogues antitumour agent
CCꢀ1065 was also achieved.9 An intramolecular radical cyclization of cisꢀ2ꢀiodostilbenes
provided a rapid and predictable method for phenanthrenes in high yields.10 Syntheses of
phenanthrene and their analogues are also achieved involving Pdꢀmediated intramolecular
Heck coupling reactions of 1,2ꢀdiarylethanes followed by dehydrogentation.11 Elongated
polycyclic arenes, dinaphthoanthracenes with different carboxylic substitution pattern were
realized through Pdꢀmediated twoꢀfold cyclization of 1,2ꢀdiarylethylene analogues.12 The
elongated heteroarenes (fused dibenzothiophene/carbazole) are also available by an
alternative methodology involving intramolecular cyclization of sulfinyl units.13 Multiꢀfold
intramolecular Heck coupling of complex 1,2ꢀdiarylethanes containing bromine group at one
of the aryl unit led to the formation fullerenes and their precursors.14 Ray and coꢀworkers
reported a wide variety of phenanthrene and chrysene derivatives involving Pdꢀmediated
intramolecular Heck arylation of 1ꢀhydroxyꢀ1,2ꢀdiarylethanes followed by acid catalyzed
dehydration.15 Yadav and coꢀworkers reported assembly of phenanthrenes and polycyclic
heteroarenes involving Pdꢀmediated cyclization of corresponding 1,2ꢀdisubstitutedꢀ1,2ꢀ
diaryl(heteroaryl)ethylenes.16 Oxidative cyclization of 1,2ꢀdiarylethylenes employing FeCl3,17
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MoCl5,18 MnO2, DDQ20 and other oxidizing agents21 are also known.
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Figure 1. Summary of synthetic protocols for phenanthrene analogues
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In a further continuation of our interest in annulated heterocycles,22 we report herein our
results one pot synthesis of hetero analogues of phenanthrenes involving Pdꢀmediated
cyclization of easily accessible 1ꢀphenylsulfonylꢀ1,2ꢀdiaryl(heteroaryl)ethanes.
The
reaction
of
2ꢀbromoꢀ1ꢀ(phenylsulfonylmethyl)thiophene
1
with
o
3ꢀbromomethylthiophene 2a23 using tꢀBuOK in DMF at 0ꢀ10 C followed by workup
furnished 2ꢀbromoꢀ3ꢀ(1ꢀ(phenylsulfonyl)ꢀ2ꢀ(thiophenꢀ3ꢀyl)ethyl)thiophene 3a in 85% yield.
It should be noted that the alkylation of 1 with 2a was studied at room temperature using
different solvents (THF, DMF, DMSO) and bases (K2CO3, NaH, tꢀBuOK) to afford the
alkylated sulfone 3 in 20ꢀ55% yields. Purposely, the alkylation was performed at low
temperature to minimize the elimination of phenylsulfonyl unit. As expected, a subsequent
Pd(0)ꢀmediated intramolecular Heck coupling of alkylated sulfone 3a using K2CO3 as a base
o
in DMF at 80 C underwent concurrent elimination of phenylsulfinic acid to furnish
dithienobenzene 4a24 in 70% yield (Scheme 1).
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Scheme 1. Domino reaction of 2ꢀbromoꢀ3ꢀ(phenylsulfonylmethyl)thiophene 1 with 3ꢀ
bromomethylthiophene 2a
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To enhance the yield of dithienobenzene 4a, the Pd(OAc)2/PPh3ꢀmediated domino reaction
of alkylated sulfone 3a was explored using different conditions (Table 1). The transformation
of alkylated sulfone 3a into dithienobenzene 4 was found to proceed in moderate yields in the
o
presence of K2CO3/Cs2CO3 at 100ꢀ110 C (Table 1, entries 1ꢀ3). The Pd(0)ꢀmediated
coupling followed by elimination was also found to be successful in the presence of Cs2CO3
at 140 oC in oꢀDCB as well as DMF (Table 1, entries 4 and 5). However, the use of Cs2CO3 in
o
DMF at 140 C was found to be detrimental (Table 1, entry 6). To our delight, the use of
o
K2CO3 in DMF at 140 C for 2 h furnished dithienobenzene 4 in a highest yield (Table 1,
o
entry 7). The conditions such as K2CO3 in acetonitrile at 80 C as well as tꢀBuOK in DMF at
140 oC led to the formation of 4 in negligible yields (Table 1, entries 8 and 9).
Table 1. Condition optimization for heterocycle 4
Entry Solvent
Conditionsa
Yield (%)b
1
2
3
4
5
6
7
8
9
Toluene
K2CO3/110 oC, 12 h
42
58c
55
1,4ꢀDioxane K2CO3/100 oC, 10 h
1,4ꢀDioxane Cs2CO3/110 oC,10 h
oꢀDCB
Xylenes
DMF
Cs2CO3/140 oC,12 h
Cs2CO3/140 oC,10 h
Cs2CO3/140 oC, 6 h
K2CO3/140 oC, 2 h
K2CO3/80 oC, 8 h
35
50
15c
DMF
75
CH3CN
DMF
05d
10c
tꢀBuOK/140 oC, 8 h
aDomino reaction of sulfone 3 (1 equiv) using Pd(OAc)2 (10 mol%), PPh3 ( 20 mol% ) and base (2.0 equiv) at
o
c
80ꢀ140 C. bIsolated yield of 4 by column chromatography. A major portion of dithiophenylstilbene was
detected by 1H NMR. dA major portion of starting material 3 was recovered.
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To extend the scope of this Pd(OAc)2/PPh3ꢀmediated domino reaction protocol, alkylation of
5
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sulfone 1 was performed with various benzyl bromides 2bꢀj using tꢀBuOK as a base in DMF
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8
o
at 0ꢀ10 C to furnish respective arylꢀ as well as heteroarylꢀmethylated sulfones 3bꢀj. As
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expected, Pd(0)ꢀmediated intramolecular Heck coupling of the sulfones 3bꢀj using K2CO3 in
DMF at 80ꢀ140 oC afforded annulated thiophenes 4bꢀj in 30ꢀ75% yields (Table 2).
Table 2. Synthesis of annulated thiophenes 4bꢀj
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Benzylic halides Conditions
Product
Yield (%)a
Pd(OAc)2/PPh3
DMF/K2CO3
68
80 oC, 2 h
4b
2b
Pd(OAc)2/PPh3
DMF/K2CO3
(i) 80 oC, 1 h
(ii) 140 oC, 1 h
60
4c
2c
Pd(OAc)2/PPh3
DMF/K2CO3
(i) 80 oC, 1 h
(ii) 140 oC, 1 h
70
64
2d
4d
Pd(OAc)2/PPh3
DMF/K2CO3
(i) 80 oC, 1 h
(ii) 140 oC, 5 h
4e
4f
2e
2f
Pd(OAc)2/PPh3
DMF/K2CO3
80 oC, 2 h
65
Pd(OAc)2/PPh3
DMF/K2CO3
80 oC, 2 h
70
75
4g
4h
2g
2h
Pd(OAc)2/PPh3
DMF/K2CO3
80 oC, 2 h
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Pd(OAc)2/PPh3
DMF/K2CO3
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(i) 80 oC, 1 h
(ii) 140 oC, 1 h
2i
2j
4i
30
4j
Pd(OAc)2/PPh3
DMF/K2CO3
(i) 80 oC, 6 h
(ii) 140 oC, 30 h
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aIsolated yield of annulated heterocycles 4bꢀj from respective
alkylated sulfones 3bꢀj.
The Pd(0)ꢀmediated domino reaction of arylmethylated sulfones 3bꢀe furnished the respective
carboꢀannulated thiophenes 4bꢀe in 60ꢀ70% yields. Among the isomeric naphthylmethylated
sulfones 3c and 3d, the Pdꢀmediated coupling preference at 1ꢀposition of naphthalene led to
the formation phenanthro[4,3ꢀb]thiophene 4d in a relatively better yield than phenanthro[1,2ꢀ
b]thiophene 4c. Due to the similar reasons, indolylmethylated sulfones 2g and 2h also
afforded respective heterocycles 4g and 4h in better yields than benzo[b]thiophenyl
counterpart 2f. The phenanthrenylmethylated sulfone 2i gave corresponding annulated
heterocycle 4i in 62% yield. Finally, the bisꢀalkylation of 2ꢀbromoꢀ3ꢀ
phenylsulfonylmethylthiophene 1 with 1,4ꢀbis(bromomethyl)benzene 2j followed by
Pd(OAc)2/PPh3ꢀmediated cyclization in the presence of K2CO3 in DMF at 80ꢀ140 oC afforded
dithienoanthracene 4j in 30% yield. It should be noted that the Pd(0)ꢀmediated domino
reaction of sulfones 3bꢀj was initially performed at moderate temperature (80 oC) followed by
o
elevated temperature (140 C) to avoid the elimination of phenylsulfonyl unit prior to
cyclization.
Under
identical
conditions,
the
alkylation
of
2ꢀbromoꢀ3ꢀ
(phenylsulfonylmethyl)benzo[b]thiophene 5 with arylmethyl/heteroarylmethyl bromides
using tꢀBuOK/DMF followed by Pd(OAc)2/PPh3ꢀmediated intramolecular Heck coupling of
o
resulting sulfone 6aꢀf in the presence of K2CO3 in DMF at 80ꢀ140 C furnished annulated
dibenzothiophenes 7aꢀf in 60ꢀ72% yields (Table 3). As observed earlier, the Pd(0)ꢀmediated
domino reaction proceeded in relatively better yields with heteroarylmethylated sulfones 6cꢀf
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than arylmethylated sulfones 6a and 6b. In the case of naphthylated sulfone 6a, the Pd(0)ꢀ
mediated cyclization led to the formation of an inseparable mixture of annulation products 7a
and 7aꞌ in 5:1 ratio (based on 1H NMR).
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Table 3. Synthesis of annulated dibenzothiophene analogues 7aꢀf
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Benzylic halides Conditions
Product
Yield (%)a
65b
Pd(OAc)2/PPh3
DMF/K2CO3
(i) 80 oC, 1 h
(ii) 140 oC, 5 h
2d
OMe
Pd(OAc)2/PPh3
DMF/K2CO3
(i) 80 oC, 1 h
(ii) 140 oC, 5 h
62
68
Br
OMe
2e
7b
Pd(OAc)2/PPh3
DMF/K2CO3
80 oC, 2 h
2f
7c
Pd(OAc)2/PPh3
DMF/K2CO3
80 oC, 2 h
70
72
2g
7d
Pd(OAc)2/PPh3
DMF/K2CO3
80 oC, 2 h
2h
2k
7e
7f
Pd(OAc)2/PPh3
DMF/K2CO3
80 oC, 2 h
65
aIsolated yield of annulated heterocycles 7aꢀf from respective
alkylated sulfones 6aꢀf. bObtained as a 5:1 (1H NMR) mixture
of 7a & 7aꞌ.
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Next, heteroaryl methylation of 2ꢀbromophenylmethylsulfone 825 using tꢀBuOK as a base
o
in DMF at 0ꢀ10 C followed by Pd(OAc)2/PPh3ꢀmediated intramolecular Heck coupling of
6
7
8
resulting sulfones afforded corresponding annulated compounds 9bꢀd in 56ꢀ65% yields
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(Scheme 2).
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Scheme 2. Domino reaction of benzylmethylsulfone 8
and veratrylmethylsulfone 10
However, it should be noted that the alkylation of phenylmethylsulfone 8 with
1ꢀbromomethylnaphthalene 2c followed by Pd(0)ꢀmediated domino reaction using K2CO3 in
o
DMF at 140 C failed to produce chrysene, only a nonꢀaromatized sulfone 9aꞌ was obtained
in 36% yield. Under the established conditions, heteroaryl methylation of
veratrylmethylsulfone
10
with
3ꢀbromomomethylthiophene
2a/3ꢀbromomethyl
benzo[b]thiophene 2f followed by Pd(OAc)2/PPh3ꢀmediated intramolecular Heck coupling
o
using K2CO3 in DMF at 140 C led to the formation of an inseparable mixture of annulated
heterocycles 11a + 11b (~2:3 confirmed by 1H NMR) and 11c + 11d (~2:3 confirmed by 1H
NMR). The formation of annulated heterocycles 11b and 11d containing bromine atom can
be realized through Pdꢀmediated veratrylation at thiophene and benzo[b]thiophene 2ꢀ
positions, respectively. However, indolylmethylation of veratrylmethylsulfone 10 with
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isomeric 2ꢀ/3ꢀbromomethylindoles 2g/2h followed by Pd(0)ꢀcatalyzed domino reaction
furnished the respective benzo[c]carbazole 11e and benzo[a]carbazole 11f as exclusive
products.
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As expected, the indolylmethylations of 1ꢀbromoꢀ2ꢀphenylsulfonylmethylnaphthalene 1225
with 2ꢀbromomethylindole 2g/3ꢀbromomethylindole 2h followed by followed by Pd(0)ꢀ
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o
mediated domino reaction using K2CO3 in DMF at 140 C afforded the corresponding
naphtho[c]carbazole 13 and naphtho[a]carbazole 13 in 70 and 62% yields, respectively
(Scheme 3). The structure of the representative 1ꢀphenylsulfonylꢀ1,2ꢀdiheteroarylethane 6e
and naphtho[a]annulated carbazole 14 were confirmed through single crystal Xꢀray analyses.
(see SI).26
Scheme 3. Domino reaction of 1ꢀbromoꢀ2ꢀphenylsulfonylmethylnaphthalene 13
Next, the reaction of 2ꢀindolylmethylsulfone 1527 with 2ꢀbromomethylindole 16 using
K2CO3 as a base in DMF afforded indolylmethylated sulfone 17 in 78% yield. As expected,
an intramolecular cyclization of compound 17 using Pd(OAc)2/PPh3 in the presence of
o
K2CO3 in DMF at 110 C for 4 h led to the formation of indolocarbazole 18 in 78% yield
(Scheme 4). After considerable experimentations, the intramolecular cyclization of
compound 17 using Pd(OAc)2/PPh3 in the presence of K2CO3 as base in DMF at 140 oC in a
sealed tube
afforded parent indolocarbazole 19 in 75% yield. The isomeric
3ꢀindolylmethylsulfone 20 upon indolylmethylation with 2ꢀbromomethylindole 17 using
K2CO3 in DMF furnished the required precursor 21 of indolocarbazole. As expected,
compound 21 upon reaction with Pd(OAc)2/PPh3 in a sealed tube underwent intramolecular
coupling followed by aromatization and cleavage of phenylsulfonyl unit to afford
indolocarbazole 22 in 68% yield.
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Scheme 4. Synthesis of indolocarbazoles 18, 19 and 22
Br
Br
6
7
8
N
Br
N
SO2Ph
16
PhO2S
SO2Ph
N
K2CO3/DMF
rt, 12 h
78%
N
SO2Ph
SO2Ph
PhO2S
15
17
9
Pd(OAc)2/PPh3
K2CO3/DMF
Pd(OAc)2/PPh3
K2CO3/DMF
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17
140 oC, 6 h
75%
110 oC, 4 h
78%
N
NH
N
HN
SO2Ph
PhO2S
18
19
PhO2S
Pd(OAc)2/PPh3
K2CO3/DMF
SO2Ph
H
16
N
SO2Ph
N
K2CO3/DMF
N
N
SO2Ph
140 oC, 6 h
68%
N
H
rt, 12 h
78%
Br
PhO2
S
21
20
22
In summary, we have developed an efficient and straightforward protocol for the syntheses
of annulated thiophene, dibenzothiophene and carbazole derivatives involving benzylation of
sulfonyl stabilized carbanion followed by an intramolecular Heck coupling reaction as a key
step. The methodology was found to be useful for procuring biologically important
indolocarbazoles as well. Annulative πꢀextension of a wide variety of aromatic as well as
heteroaromatic systems were achieved in a facile manner involving Pd(0)ꢀmediated
cyclization of an easily accessible 1ꢀphenylsulfonylꢀ1,2ꢀdiaryl(heteroaryl)ethanes followed
by aromatization via elimination of phenylsulfinic acid. In most of the cases, the Pd(0)ꢀ
catalyzed domino reactions were found to proceed in better yields with electron rich
heteroaromatic systems. By the appropriate choice of base and temperature control, the
Pd(0)ꢀcatalyzed domino reaction can be fine tuned to access wide of variety of annulated
heterocycles.
The
structures
of
the
representative
1ꢀphenylsulfonylꢀ1,2ꢀ
diaryl(heteroaryl)ethane and annulated heteroarenes were confirmed through single crystal Xꢀ
ray analyses. For the first time, a wide variety of annulated heteroarenes could be easily
achieved by exploiting the synthetic utility of sulfonyl stabilized carbanion.
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Experimental Section
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General Methods. All melting points were uncorrected. Solvents were dried by standard
procedures. All the experiments carried out under the nitrogen atmosphere unless otherwise
stated. The progression of the reaction was monitored by TLC using hexanes/ethyl acetate
(EA) mixture. Column chromatography was carried out on Silica gel (230ꢀ400 mesh, Merck)
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by increasing polarity. H, 13C spectra were recorded in CDCl3 using TMS as an internal
standard on Bruker 300 MHz ,400 MHz and 500 MHz spectrometer at room temperature.
Chemical shift values were quoted in parts per million (ppm) and coupling constants were
quoted in hertz (Hz). HRMS were recorded on JEOL GC Mate II (EI) and Xevo G2S QTof.
2ꢀBromoꢀ3ꢀmethythiophene. To a solution of 3ꢀmethylthiophene (2 g, 20.4 mmol) in DMF
(10 mL), finally powdered NBS (3.81 g, 21.4 mmol) was added. Then, the reaction mixture
was wrapped with black cover (to exclude light) and stirred at room temperature for 24 h. It
was then poured into water (50 mL), extracted with ethyl acetate (2 x 30 mL) and dried
(Na2SO4). Removal of solvent under vacuo furnished 2ꢀbromoꢀ3ꢀmethylthiophene as a
colorless liquid (4.5 g). The crude product was used as such for next step.
2ꢀBromoꢀ3ꢀ(bromomethyl)thiophene. To a solution of crude 2ꢀbromoꢀ3ꢀmethylthiophene
(3.4 g, 19.2 mmol) in dry carbon tetrachloride (60 mL), AIBN (0.05 g) and finely powdered
NBS (3.76 g, 21.1 mmol) were added. The reaction mixture was refluxed for 0.5 h and cooled
to room temperature. The floated succinimide was filtered off and washed with carbon
tetrachloride (15 mL). The combined filtrate was concentrated in vacuo to afford 2ꢀbromoꢀ3ꢀ
bromomethythiophene (4 g) as colorless liquid. The crude product was used as such for next
step.
2ꢀBromoꢀ3ꢀ(phenylsulfonylmethyl)thiophene (1). To
a
solution of 2ꢀbromoꢀ3ꢀ
(bromomethyl)thiophene (4 g, 15.6 mmol) in DMF (40 mL), benzenesulfinic acid sodium salt
(2.82 g, 17.2 mmol) was added. Then, the reaction mixture was stirred at room temperature
for 6 h. After completion of the reaction, it was poured into crushed ice (200 g). The solid
obtained was filtered and dried. The crude product was crystallized from methanol to furnish
2ꢀbromoꢀ3ꢀ(phenylsulfonylmethyl)thiophene 1 as a colorless solid (3.92 g, 80 %); mp 78ꢀ80
oC; 1HꢀNMR (300 MHz, CDCl3): δ 7.58ꢀ7.56 (m, 3H), 7.42ꢀ7.39 (m, 2H) 7.21 (d, J = 5.7 Hz,
1H) 6.98 (d, J = 5.7 Hz, 1H) 4.29 (s, 2H, CH2) ppm. 13CꢀNMR (75 MHz, CDCl3): δ 137.6,
134.0, 129.2, 129.1, 128.6, 128.3, 126.4, 115.5, 56.4 ppm. DEPTꢀ135 (75 MHz, CDCl3): δ
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134.0, 129.2, 129.1, 128.6, 126.4, 56.4 ppm. HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for
C11H10BrO2S2 316.9306; Found 316.9298.
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2ꢀBromoꢀ3ꢀ(1ꢀ(phenylsulfonyl)ꢀ2ꢀ(thiophenꢀ3ꢀyl)ethyl)thiophene (3a). To a solution of
2ꢀbromoꢀ3ꢀ(phenylsulfonylmethyl)thiophene 1 (0.7 g, 2.21 mmol) in DMF (20 mL), tꢀBuOK
(0.37 g 3.32 mmol) and 3ꢀbromomethylthiophene 2a (0.43 g, 2.43 mmol) were added. Then,
the reaction mixture was stirred at room temperature for 15 min. After completion of the
reaction, it was poured into crushed ice (100 g), extracted with ethyl acetate (3 x 20 mL) and
dried (Na2SO4). Removal of solvent under vacuo furnished 2ꢀbromoꢀ3ꢀ(1ꢀ(phenylsulfonyl)ꢀ2ꢀ
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(thiophenꢀ3ꢀyl)ethyl)thiophene 3a as a colorless liquid (0.86 g, 95%); HꢀNMR (300 MHz,
CDCl3): δ 7.71ꢀ7.51(m, 3H), 7.51ꢀ7.33 (m, 2H), 7.33ꢀ7.21 (m, 2H), 6.73 (s, 1H), 6.73ꢀ6.63
13
(m, 2H), 4.52ꢀ4.49 (m, 1H), 3.80ꢀ3.75 (m, 1H), 3.39ꢀ3.31 (m, 1H) ppm. CꢀNMR (75 MHz,
CDCl3): δ 137.2, 136.0, 133.9, 132.4, 128.9, 128.8, 127.8, 126.8, 126.5, 125.8, 122.3, 116.2,
65.7, 28.0 ppm. HRMS (ESIꢀTOF) m/z: [MꢀSO2Ph]+ Calcd for C10H8BrS2 270.9251; Found
270.9247.
3ꢀ(2ꢀ(2ꢀBromophenyl)ꢀ2ꢀ(phenylsulfonyl)ethyl)thiophene (3b). To a solution of 2ꢀbromoꢀ3ꢀ
(phenylsulfonylmethyl)thiophene 1 (0.7 g, 2.21 mmol) in DMF (20 mL), tꢀBuOK (0.37 g,
3.32 mmol) and benzyl bromide 2b (0.42 g, 2.43 mmol) were added. Then, the reaction
mixture was stirred at room temperature for 15 min. The usual workup adopting the
procedure
similar
to
that
of
3a
furnished
2ꢀbromoꢀ3ꢀ(2ꢀphenylꢀ2ꢀ
1
(phenylsulfonyl)ethyl)thiophene 3b as colorless liquid (0.85 g, 95%); HꢀNMR (300 MHz,
CDCl3): δ 7.69 (d, J = 7.2 Hz, 2H), 7.61ꢀ7.56 (m, 1H), 7.47ꢀ7.42 (m, 3H), 7.22ꢀ7.20 (m, 1H),
7.06ꢀ7.01 (m, 3H), 6.94ꢀ6.93 (m, 1H), 6.89ꢀ6.86 (m, 1H), 4.57 (dd, J1 = 11.7 Hz, J2 = 3.0 Hz,
1H), 3.91ꢀ3.86 (m, 1H), 3.85ꢀ3.32 (m, 1H) ppm. 13CꢀNMR (100 MHz, CDCl3): δ 137.3,
136.1, 133.8, 132.1, 128.8, 128.8, 128.7, 128.5, 128.5, 126.9, 126.9, 126.4, 116.1, 66.4, 33.3
ppm. HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for C18H16BrO2S2 406.9775; Found 406.9770.
Preparation of benzodithiophene (4a)28. To a solution of 2ꢀbromoꢀ3ꢀ(1ꢀ(phenylsulfonyl)ꢀ
2ꢀ(thiophenꢀ3ꢀyl)ethyl)thiophene 3a (0.82 g, 1.98 mmol) in DMF (15 mL), Pd(OAc)2 (0.04 g,
0.19 mmol), PPh3 (0.1 g, 0.39 mmol) and K2CO3 (0.55 g, 3.96 mmol) were added. Then, the
reaction mixture was refluxed for 2 h. After that, the reaction mixture was filtered through
celite bed and washed with ethyl acetate (2 x 10 mL). The combined organic layer was
washed with water (3 x 20 mL) and dried (Na2SO4). Removal of solvent followed by column
chromatographic purification (Silica gel, 100% Hexane) afforded benzodithiophene 4a as a
pale yellow liquid (0.28 g, 75%); 1HꢀNMR (400 MHz, DMSOꢀd6): δ 7.85 (m, 1H), 7.72 (d, J
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= 5.2 Hz, 1H), 7.57 (d, J = 5.2 Hz, 1H), ppm. 13CꢀNMR (100 MHz, DMSOꢀd6): δ 137.0,
132.6, 125.3, 125.2, 120.6 ppm. HRMS (ESIꢀTOF) m/z: [M]+ Calcd for C10H6S2 189.9911;
Found 189.9904.
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Naphtho[1,2ꢀb]thiophene (4b). To a solution of crude 2ꢀbromoꢀ3ꢀ(2ꢀphenylꢀ1ꢀ
(phenylsulfonyl)ethyl)thiophene 3b (0.83 g, 2.03 mmol) in DMF (15 mL), Pd(OAc)2 (0.05 g,
0.20 mmol), PPh3 (0.10 g, 0.40 mmol) and K2CO3 (0.56 g, 4.06 mmol) were added. Then, the
reaction mixture was refluxed for 2 h. The usual workup adopting the procedure similar to
that of 4a followed by column chromatographic purification (Silica gel, 100% Hexane)
afforded naphtho[1,2ꢀb]thiophene 4b as a colorless liquid (0.25 g, 68%); 1HꢀNMR (300 MHz,
CDCl3): δ 8.22 (d, J = 8.1 Hz, 1H), 7.95 (d, J = 7.5 Hz, 1H), 7.85 (d, J = 8.7 Hz, 1H), 7.79 (d,
J = 8.4 Hz, 1H), 7.69ꢀ7.64 (m, 1H), 7.62ꢀ7.60 (m, 1H), 7.58ꢀ7.54 (m, 1H), 7.53ꢀ7.51 (m, 1H)
ppm. 13CꢀNMR (75 MHz, CDCl3): δ 137.4, 130.9, 128.9, 128.8, 127.2, 126.7, 125.7, 125.4,
125.2, 125.1, 123.7, 122.1ppm. HRMS (ESIꢀTOF) m/z: [M]+ Calcd for C12H8S 184.0347;
Found 184.0330.
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Phenanthro[1,2ꢀb]thiophene
(4c).
Alkylation
of
2ꢀbromoꢀ3ꢀ
(phenylsulfonylmethyl)thiophene 1 (0.7 g, 2.21 mmol) with 1ꢀbromomethylnapthalene 2c
o
(0.54 g, 2.43 mmol) using tꢀBuOK (0.37 g, 3.32 mmol) in DMF (20 mL) at 5ꢀ10 C for 15
min followed by workup adopting the procedure similar to that of 3a furnished 2ꢀbromoꢀ3ꢀ(2ꢀ
(naphthalenꢀ1ꢀyl)ꢀ1ꢀ(phenylsulfonyl)ethyl)thiophene 3c as a colorless solid (0.92 g, 91%). To
a solution of alkylated sulfone 3c (0.92 g, 2.01 mmol) in DMF (15 mL), Pd(OAc)2 (0.05 g,
0.20 mmol), PPh3 (0.10 g, 0.40 mmol) and K2CO3 (0.56 g, 4.02 mmol) were added. The
o
o
reaction mixture was initially maintained at 80 C for 1 h. It was then heated at 140 C for
additional 1 h. After completion of the reaction, usual workup adopting the procedure similar
to that of 4a followed by column chromatographic purification (Silica gel, 100% Hexane)
o
furnished phenanthro[1,2ꢀb]thiophene 4c as a colorless solid (0.28 g, 60%); mp 146ꢀ148 C;
1HꢀNMR (300 MHz, CDCl3): δ 8.66 (d, J = 8.4 Hz, 1H), 8.57 (d, J = 8.7 Hz, 1H), 8.01 (d, J =
9.0 Hz, 1H), 7.95 (d, J = 8.7 Hz, 1H), 7.86 (d, J = 8.1 Hz, 1H), 7.81 (d, J = 9.0 Hz, 1H), 7.61
(d, J = 7.6 Hz, 1H), 7.55ꢀ7.44 (m, 3H) ppm. 13CꢀNMR (75 MHz, CDCl3): δ 138.6, 138.0,
131.8, 130.9, 128.9, 127.8, 127.2, 127.0, 126.9, 126.2, 125.8, 124.9, 123.1, 122.9, 122.2,
119.8 ppm. HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for C16H11S 235.0581; Found 235.0599.
Phenanthro[4,3ꢀb]thiophene
(4d).
Alkylation
of
2ꢀbromoꢀ3ꢀ
(phenylsulfonylmethyl)thiophene 1 (0.7 g, 2.21 mmol) with 2ꢀbromomethylnapthalene 2d
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(0.54 g, 2.43 mmol) using tꢀBuOK (0.37 g, 3.32 mmol) in DMF (20 mL) at 5ꢀ10 C for 15
min followed by workup adopting the procedure similar to that of 3a furnished 2ꢀbromoꢀ3ꢀ(2ꢀ
(naphthalenꢀ2ꢀyl)ꢀ1ꢀ(phenylsulfonyl)ethyl)thiophene 3d as colorless liquid (0.88 g, 87%). To
a solution of alkylated sulfone 3d (0.88 g, 1.93 mmol) in DMF (15 mL), Pd(OAc)2 (0.04 g,
0.19 mmol), PPh3 (0.10 g, 0.38 mmol) and K2CO3 (0.53 g, 3.84 mmol) were added. The
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o
o
reaction mixture was initially maintained at 80 C for 1 h. It was then heated at 140 C for
additional 1 h. After completion of the reaction, usual workup adopting the procedure similar
to that of 4a followed by column chromatographic purification (Silica gel, 100% Hexane)
furnished phenanthro[4,3ꢀb]thiophene 4d as a colorless solid (0.32 g, 70%); mp 92ꢀ94 oC; 1Hꢀ
NMR (300 MHz, CDCl3): δ 9.18 (d, J = 7.4 Hz, 1H), 7.97ꢀ7.95 (m, 2H), 7.93ꢀ7.94 (m, 4H),
7.63 (d, J = 7.2 Hz, 1H), 7.60 (d, J = 9.0 Hz, 1H), 7.57 (m, 1H) ppm. 13CꢀNMR (75 MHz,
CDCl3): δ 139.3, 134.8, 132.8, 130.6, 129.4, 128.9, 127.7, 126.8, 126.6, 126.3, 126.2, 126.1,
126.0, 125.9, 124.5, 123.8 ppm. DEPTꢀ135: δ 129.1, 127.9, 126.9, 126.8, 126.3, 126.3, 126.1,
126.0, 124.7, 123.0 ppm. HRMS (ESIꢀTOF) m/z: [M+H]+Calcd for C16H11S 235.0581; Found
235.0587.
6,9ꢀDimethoxynaphtho[1,2ꢀb]thiophene
(4e).
Alkylation
of
2ꢀbromoꢀ3ꢀ
(phenylsulfonylmethyl)thiophene 1 (0.7 g, 2.21 mmol) with 2ꢀ(bromomethyl)ꢀ1,4ꢀ
dimethoxybenzene 2e (0.56 g, 2.43 mmol) using tꢀBuOK (0.37 g, 3.32 mmol) in DMF (20
o
mL) at 5ꢀ10 C for 15 min followed by workup adopting the procedure similar to that of 3a
furnished 2ꢀbromoꢀ3ꢀ(2ꢀ(2,5ꢀdimethoxyphenyl)ꢀ1ꢀ(phenylsulfonyl)ethyl)thiophene 3e as a
colorless solid (0.91 g, 88%). To a solution of alkylated sulfone 3e (0.91 g, 1.94 mmol) in
DMF (15 mL), Pd(OAc)2 (0.04 g, 0.19 mmol), PPh3 (0.10 g, 0.38 mmol) and K2CO3 (0.54 g,
o
3.88 mmol) were added. The reaction mixture was initially maintained at 80 C for 1 h. It
o
was then heated at 140 C for additional 5 h. After completion of the reaction, usual workup
adopting the procedure similar to that of 4a followed by column chromatographic purification
(Silica gel, EtOAcꢀhexane 1:27) furnished 6,9ꢀdimethoxynaphtho[1,2ꢀb]thiophene 4e as a
1
colorless solid (0.30 g, 64%); mp 118ꢀ120 oC; HꢀNMR (300 MHz, CDCl3): δ 8.10 (d, J =
8.7 Hz, 1H), 7.62 (d, J = 9.0 Hz, 1H), 7.52 (d, J = 5.4 Hz, 1H), 7.42 (d, J = 5.4 Hz, 1H), 6.83
(d, J = 8.7 Hz, 1H), 6.74 (d, J = 8.4 Hz, 1H) 4.01 (s, 3H, OCH3), 3.92 (s, 3H, OCH3) ppm.
13CꢀNMR (75 MHz, CDCl3): δ 149.0, 148.0, 136.8, 132.0, 126.5, 122.6, 122.4, 121.1, 121.1,
117.6, 104.0, 102.6, 55.0, 54.9 ppm. DEPT 135: δ 126.5, 122.4, 121.2, 117.6, 104.0, 102.6,
55.0, 54.9 ppm. HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for C14H12O2S 245.0636; Found
245.0615.
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Preparation of compound (4f). Alkylation of 2ꢀbromoꢀ3ꢀ(phenylsulfonylmethyl)thiophene
1 (0.7 g, 2.21 mmol) with 3ꢀ(bromomethyl)benzo[b]thiophene 2f (0.7 g, 2.43 mmol) using
o
tꢀBuOK (0.37 g, 3.32 mmol) in DMF (20 mL) at 5ꢀ10 C for 15 min followed by workup
7
8
9
adopting the procedure similar to that of 3a furnished 3ꢀ(2ꢀ(2ꢀbromothiophenꢀ3ꢀyl)ꢀ2ꢀ
(phenylsulfonyl)ethylbenzo[b]thiophene 3f as a colorless solid (0.94 g, 92%). To a solution
of alkylated sulfone 3f (0.94 g, 2.02 mmol) in DMF (15 mL), Pd(OAc)2 (0.05 g, 0.20 mmol),
PPh3 (0.10 g, 0.40 mmol) and K2CO3 (0.56 g, 4.04 mmol) were added. The reaction mixture
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was heated at 80 C for 2 h. The usual workup adopting the procedure similar to that of 4a
followed by column chromatographic purification (Silica gel, 100% Hexane) furnished 4f as
a colorless solid (0.32 g, 65%); mp 112ꢀ114 oC; 1HꢀNMR (300 MHz, CDCl3): δ 8.11ꢀ8.08 (m,
1H), 8.03 (d, J = 8.4 Hz, 1H), 7.84ꢀ7.79 (m, 2H), 7.40 (m, 4H) ppm. 13CꢀNMR (75 MHz,
CDCl3): δ 138.9, 138.7, 136.3, 133.6, 133.2, 132.5, 126.4, 125.5, 124.9, 124.8, 123.0, 121.7,
120.5, 118.1 ppm. HRMS (ESIꢀTOF) m/z: [M]+ Calcd for C14H8S2 240.0067; Found
240.0071.
6ꢀ(Phenylsulfonyl)ꢀ6Hꢀthieno[3,2ꢀc]carbazole
(4g).
Alkylation
of
2ꢀbromoꢀ3ꢀ
(phenylsulfonylmethyl)thiophene (0.7 g, 2.21 mmol) with 2ꢀbromomethylꢀ1ꢀ
1
phenylsulfonylindole 2g (0.85 g, 2.43 mmol) using tꢀBuOK (0.37 g, 3.32 mmol) in DMF (20
o
mL) at 5ꢀ10 C for 15 min followed by workup adopting the procedure similar to that of 3a
furnished
2ꢀ(2ꢀ(2ꢀbromothiophenꢀ3ꢀyl)ꢀ2ꢀ(phenylsulfonyl)ethyl)ꢀ1ꢀ(phenylsulfonyl)ꢀ1Hꢀ
indole 3g as a colorless solid (1.16 g, 90%). To a solution of alkylated sulfone 3g (1.16 g,
1.97 mmol) in DMF (15 mL), Pd(OAc)2 (0.04 g, 0.19 mmol), PPh3 (0.10 g, 0.39 mmol) and
o
K2CO3 (0.55 g, 3.94 mmol) were added. Then, the reaction mixture was heated at 80 C for
2 h. The usual workup adopting the procedure similar to that of 4a followed by column
chromatographic purification (Silica gel, EtOAcꢀhexane 1: 27) furnished 6ꢀ(phenylsulfonyl)ꢀ
o
6Hꢀthieno[3,2ꢀc]carbazole 4g as a colorless solid (0.50 g, 70%); mp 144ꢀ146 C; 1HꢀNMR
(300 MHz, CDCl3): δ 8.38 (d, J = 8.7 Hz, 2H), 7.56 (d, J = 7.2 Hz, 1H), 7.66 (d, J = 9.0 Hz,
1H), 7.81 (d, J = 7.8 Hz, 2H), 7.50ꢀ7.40 (m, 4H), 7.32 (t, J = 7.5 Hz, 1H), 7.19 (t, J = 7.2 Hz,
2H) ppm. 13CꢀNMR (75 MHz, CDCl3): δ 135.9, 135.4, 134.6, 133.3, 131.4 , 129.7, 126.6,
124.6, 124.0, 123.2, 122.8, 122.0, 121.6, 120.3, 118.9, 117.9, 112.8, 110.0 ppm. HRMS (ESIꢀ
TOF) m/z: [M+H]+ Calcd for C20H14NO2S2 364.0466; Found 364.0439.
3ꢀ(2ꢀ(2ꢀBromothiophenꢀ3ꢀyl)ꢀ2ꢀ(phenylsulfonyl)ethyl)ꢀ1ꢀ(phenylsulfonyl)ꢀ1Hꢀindole (3h).
To a solution of 2ꢀbromoꢀ3ꢀ(phenylsulfonylmethyl)thiophene 1 (0.7 g, 2.21 mmol) in DMF
o
(20 mL) at 5ꢀ10 C, tꢀBuOK (0.37 g, 3.32 mmol) and 3ꢀbromomethylindole 2h (0.85 g, 2.43
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mmol) were added. Then, the reaction mixture was stirred at the same temperature for 15
min. The usual workup adopting the procedure similar to that of 3a furnished 3ꢀ(2ꢀ(2ꢀ
6
7
8
9
bromothiophenꢀ3ꢀyl)ꢀ2ꢀ(phenylsulfonyl)ethyl)ꢀ1ꢀ(phenylsulfonyl)ꢀ1Hꢀindole
3h
as
a
o
1
colorless solid (1.15 g, 89%); mp 160ꢀ162 C; HꢀNMR (300 MHz, CDCl3): δ 7.83 (d, J =
7.2 Hz, 1H), 7.57ꢀ7.43 (m, 5H), 7.43ꢀ7.35 (m, 4H), 7.32ꢀ7.28 (m, 2H), 7.25ꢀ7.13 (m, 4H),
6.98 (s, 1H), 4.57 (dd, J1 = 11.7 Hz, J2 = 3.0 Hz, 1H), 3.85ꢀ3.80 (m, 1H), 3.41ꢀ3.32 (m, 1H)
ppm. 13CꢀNMR (100 MHz, CDCl3): δ 137.9, 137.0, 134.9, 134.0, 133.7, 132.3, 130.2, 129.2,
128.9, 128.8, 126.8, 126.6, 126.5, 125.0, 123.9, 123.4, 119.0, 117.3, 116.2, 133.8, 64.3, 23.3
ppm. HRMS (ESIꢀTOF) m/z: [MꢀC12H10O4S2]+ Calcd for C14H10BrNS 302.9717; Found
302.9694. [MꢀC12H10O4S2]2+ Calcd for C14H10BrNS 304.9697; Found 304.9691.
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10ꢀ(Phenylsulfonyl)ꢀ10Hꢀthieno[2,3ꢀa]carbazole (4h). To
a
solution of 3ꢀ(2ꢀ(2ꢀ
bromothiophenꢀ3ꢀyl)ꢀ2ꢀ(phenylsulfonyl)ethyl)ꢀ1ꢀ(phenylsulfonyl)ꢀ1Hꢀindole 3h (0.96 g, 1.53
mmol) in DMF (15 mL), Pd(OAc)2 (0.03 g, 0.15 mmol), PPh3 (0.08 g, 0.30 mmol) and
o
K2CO3 (0.42 g, 3.06 mmol) were added. Then, the reaction mixture was heated at 80 C for
2 h. The usual workup adopting the procedure similar to that of 4a followed by column
chromatographic purification (Silica gel, EtOAcꢀhexane 1:27) furnished 10ꢀ(phenylsulfonyl)ꢀ
10Hꢀthieno[2,3ꢀa]carbazole 4h as a colorless solid (0.46 g, 75%); mp 184ꢀ186 C; 1HꢀNMR
o
(300 MHz, CDCl3): δ 8.35 (d, J = 8.4 Hz, 1H), 7.78 (d, J = 7.8 Hz, 1H), 7.77ꢀ7.75 (m, 2H),
7.56 (d, J = 7.8 Hz, 2H), 7.49ꢀ7.47 (m, 1H), 7.42ꢀ7.37 (m, 2H), 7.32ꢀ7.26 (m, 2H), 7.13ꢀ7.07
(m, 2H) ppm. 13CꢀNMR (75 MHz, CDCl3): δ 141.5, 138.7, 137.1, 134.0, 133.6, 128.9, 127.9,
127.7, 127.3, 126.9, 126.8, 124.7, 124.4, 121.3, 119.5, 116.8, 116.3 ppm. HRMS (ESIꢀTOF)
m/z: [M+H]+ Calcd for C20H14NO2S2 364.0466; Found: 364.0440.
Triphenyleno[1,2ꢀb]thiophene
(4i).
Alkylation
of
2ꢀbromoꢀ3ꢀ
(phenylsulfonylmethyl)thiophene 1 (0.7 g, 2.21 mmol) with 9ꢀ(chloromethyl)phenanthrene
o
2i (0.54 g, 2.43 mmol) using tꢀBuOK (0.37 g, 3.32 mmol) in DMF (20 mL) at 5ꢀ10 C for 15
min followed by workup adopting the procedure similar to that of 3a furnished 2ꢀbromoꢀ3ꢀ(2ꢀ
(phenanthrenꢀ9ꢀyl)ꢀ1ꢀ(phenylsulfonyl)ethyl)thiophene 3i as a colorless solid (1.04 g, 93%).
To a solution of alkylated sulfone 3i (1.04 g, 2.04 mmol) in DMF (15 mL), Pd(OAc)2 (0.05 g,
0.20 mmol) PPh3 (0.11 g, 0.40 mmol) and K2CO3 (0.56 g, 4.08 mmol) were added. The
o
o
reaction mixture was initially maintained at 80 C for 1 h. It was then heated at 140 C for
additional 1 h. The usual workup adopting the procedure similar to that of 4a furnished
triphenyleno[1,2ꢀb]thiophene 4i by column chromatographic purification (Silica gel, 100%
1
Hexane) as a colorless solid (0.36 g, 62%); mp 124ꢀ126 oC; HꢀNMR (300 MHz, CDCl3): δ
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9.211 (d, J = 8.4 Hz, 1H), 8.70 (d, J = 8.4 Hz, 1H), 8.63ꢀ8.60 (m, 3H), 8.01 (d, J = 8.7 Hz,
1H), 7.79ꢀ7.74 (m, 1H), 7.70ꢀ7.65 (m, 1H), 7.62ꢀ7.58 (m, 3H), 7.51ꢀ7.50 (m, 1H) ppm. 13Cꢀ
NMR (75 MHz, CDCl3): δ 140.0, 135.6, 130.5, 130.3, 129.4, 129.4, 128.0, 127.4, 127.1,
127.1, 126.9, 126.6, 126.5, 126.3, 124.4, 124.0, 123.4, 123.3, 123.2, 120.5 ppm. DEPTꢀ135: δ
127.4, 127.1, 127.1, 126.9, 126.6, 126.5, 124.4, 124.0, 123.4, 123.3, 123.2, 120.5 ppm.
HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for C20H13S 285.0738; Found 285.0715.
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Preparation of compound (4j). Alkylation of 2ꢀbromoꢀ3ꢀ(phenylsulfonylmethyl)thiophene
1 (1.76 g, 5.57 mmol) with 1,4ꢀbis(bromomethyl)benzene 2j (0.7 g, 2.65 mmol) using tꢀ
o
BuOK (0.37 g, 3.31 mmol) in DMF (20 mL) at 5ꢀ10 C for 15 min followed by workup
adopting the procedure similar to that of 3a furnished 1,4ꢀbis(2ꢀ(2ꢀbromothiophenꢀ3ꢀyl)ꢀ2ꢀ
(phenylsulfonyl)ethyl)benzene thiophene 3j as a colorless solid (1.52 g, 94%). To a solution
of alkylated sulfone 3j (1.52 g, 2.06 mmol) in DMF (15 mL), Pd(OAc)2 (0.05 g, 0.20 mmol),
PPh3 (0.10 g, 0.38 mmol) and K2CO3 (0.42 g, 4.12 mmol) were added. The reaction mixture
o
o
was initially maintained at 80 C for 6 h. It was then heated at 140 C for 30 h. After
completion of the reaction, usual workup adopting the procedure similar to that of 4a
followed by column chromatographic purification (Silica gel, EtOAcꢀhexane 1:49) furnished
o
4j as a yellow solid (0.18 g, 30%); mp 226ꢀ228 C; 1HꢀNMR (300 MHz, CDCl3): δ 8.73 (s,
2H), 7.91 (d, J = 8.7 Hz, 2H), 7.83 (d, J = 8.7 Hz, 2H), 7.56 (d, J = 5.4 Hz, 2H), 7.50 (d, J =
5.4 Hz, 2H) ppm. 13CꢀNMR (75 MHz, CDCl3): δ 137.2, 136.8, 129.9, 127.2, 125.6, 125.4,
124.9, 122.6, 122.5 ppm. DEPTꢀ135: δ 125.6, 125.4, 125.0, 122.6, 122.5 ppm. HRMS (ESIꢀ
TOF) m/z: [M]+ Calcd for C18H10S2 290.0224; Found 290.0222.
2ꢀBromoꢀ3ꢀmethylbenzo[b]thiophene. To a solution of 3ꢀmethylbenzo[b]thiophene (8 g,
54.0 mmol) in DMF (60 mL), finally powdered NBS (10.46 g, 59.5 mmol) was added. Then,
the reaction mixture was wrapped with black cover (to exclude light) and stirred at room
temperature for 24 h. It was then poured into water (50 mL), extracted with ethyl acetate (2 x
30 mL) and dried (Na2SO4). Removal of solvent under vacuo furnished 2ꢀbromoꢀ3ꢀ
methylbenzo[b]thiophene (12.3 g) as a colorless liquid. The crude product was used as such
for next step.
2ꢀBromoꢀ3ꢀ(bromomethyl)benzo[b]thiophene. To a solution of crude 2ꢀbromoꢀ3ꢀ
methylbenzo[b]thiophene (5.21 g, 23.0 mmol) in dry carbon tetrachloride (60 mL), AIBN
(0.05 g) and finely powdered NBS (4.50 g, 25.3 mmol) were added. The reaction mixture was
refluxed for 0.5 h. The floated succinimide was filtered off and washed with carbon
tetrachloride (15 mL). The combined filtrate was concentrated in vacuo to afford 2ꢀbromoꢀ3ꢀ
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bromomethylbenzo[b]thiophene as colorless liquid (6.2 g). The crude product was used as
such for next step.
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2ꢀBromoꢀ3ꢀ(phenylsulfonylmethyl)benzo[b]thiophene (5). To a solution of 2ꢀbromoꢀ3ꢀ
(bromomethyl)benzo[b]thiophene (3.86 g, 12.6 mmol) in DMF (50 mL), benzenesulfinic acid
sodium salt (2.66 g, 16.4 mmol) was added. Then, the reaction mixture was stirred at room
temperature for 6 h. The usual workup adopting the procedure similar to that of 1 furnished
2ꢀbromoꢀ3ꢀ(phenylsulfonylmethyl)benzo[b]thiophene 5 as a colorless solid (3.70 g, 80 %);
mp 152ꢀ154 oC; 1HꢀNMR (300 MHz, CDCl3): δ 7.76ꢀ7.75 (m, 1H), 7.73ꢀ7.65 (m, 1H), 7.63ꢀ
7.60 (m, 2H), 7.56 (d, J = 8.7 Hz, 1H), 7.39ꢀ7.34 (m, 2H), 7.31ꢀ7.29 (m, 2H), 4.57 (s, 2H,
CH2) ppm. 13CꢀNMR (100 MHz, CDCl3): δ 139.3, 137.8, 137.5, 134.1, 129.2, 128.8, 125.3,
125.2, 123.4, 122.8, 121.6, 120.0, 55.6 ppm. HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd for
C15H11BrNaO2S2 388.9282; Found 388.9275; M+Na]2+ Calcd for C15H11BrNaO2S2 390.9261;
Found 390.9254.
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Benzo[b]phenanthro[3,4ꢀd]thiophene (7a)29a & anthra[2,1ꢀd]benzo[b]thiophene (7aꞌ).29b
Alkylation of 2ꢀbromoꢀ3ꢀ(phenylsulfonylmethyl)benzo[b]thiophene 5 (0.7 g, 1.91 mmol)
with 2ꢀbromomethylnaphthalene 2d (0.46 g, 2.10 mmol) using tꢀBuOK (0.32 g, 2.87 mmol)
in DMF (20 mL) at 5ꢀ10 oC followed by workup adopting the procedure similar to that of 3a
furnished 2ꢀbromoꢀ3ꢀ(2ꢀ(naphthalenꢀ2ꢀyl)ꢀ1ꢀ(phenylsulfonyl)ethyl)benzo[b]thiophene 6a as a
colorless solid (0.87 g, 90%). To a solution of alkylated sulfone 6a (0.87 g, 1.73 mmol) in
DMF (15 mL), Pd(OAc)2 (0.04 g, 0.17 mmol), PPh3 (0.09 g, 0.35 mmol) and K2CO3 (0.48 g,
3.46 mmol) were added. The reaction mixture was initially maintained at 80 oC for 1 h. It was
o
then heated at 140 C for 5 h. The usual workup adopting the procedure similar to that of 4a
followed by column chromatographic purification (Silica gel, 100% Hexane) furnished a
1
mixture (5:1, based H NMR integration value) of benzo[b]phenanthro[3,4ꢀd]thiophene 7a
and anthra[2,1ꢀd]benzo[b]thiophene 7aꞌ as a colorless solid (0.32 g, 65 % two steps); mp 114ꢀ
o
1
116 C; HꢀNMR (400 MHz, CDCl3): δ 9.31 (d, J = 8.4 Hz, 1H), 8.65 (s, 0.25H), 8.41 (s,
0.29H), 8.40 (d, J = 8.0 Hz, 1H), 8.30 (d, J = 9.2 Hz, 8.06ꢀ8.04 (m, 0.34H), 8.03ꢀ8.02 (m,
0.81H), 8.01ꢀ7.99 (m, 3H), 7.94ꢀ7.92 (m, 1H), 7.88ꢀ7.85 (m, 2H), 7.73ꢀ7.72 (m, 1H), 7.56ꢀ
13
7.53 (m, 2H) ppm. CꢀNMR (100 MHz, CDCl3): δ 139.3, 135.0, 134.8, 133.0, 132.5, 130.0,
129.0, 128.0, 127.9, 127.4, ,126.9, 126.6, 126.4 (2C), 126.1, 126.0, 125.7, 124.8, 123.0,
122.6, 122.5, 122.3, 121.5, 120.2, 119.5 ppm. HRMS (ESIꢀTOF) m/z: [M]+ Calcd for 7a + 7aꞌ
C20H12S 284.0660; Found 284.0664.
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1,4ꢀDimethoxybenzo[d]naphtho[1,2ꢀb]thiophene (7b). Alkylation of
2ꢀbromoꢀ3ꢀ
(phenylsulfonylmethyl)benzo[b]thiophene 5 (0.7 g, 1.91 mmol) with 2ꢀ(bromomethyl)ꢀ1,4ꢀ
dimethoxybenzene 2e (0.49 g, 2.10 mmol) using tꢀBuOK (0.32 g, 2.87 mmol) in DMF (20
o
mL) at 5ꢀ10 C followed by workup adopting the procedure similar to that of 3a furnished
2ꢀbromoꢀ3ꢀ(2ꢀ(2,5ꢀdimethoxyphenyl)ꢀ1ꢀ(phenylsulfonyl)ethyl)benzo[b]thiophene 6b as a
colorless solid (0.90 g, 91%). To a solution of alkylated sulfone 6b (0.90 g, 1.75 mmol) in
DMF (15 mL), Pd(OAc)2 (0.04 g, 0.17 mmol), PPh3 (0.09 g, 0.35 mmol) and K2CO3 (0.49 g,
3.50 mmol) were added. The reaction mixture was initially maintained at 80 oC for 1 h. It was
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then heated at 140 C for 5 h. The usual workup adopting the procedure similar to that of 4a
followed by column chromatographic purification (Silica gel, EtOAcꢀhexane 1:24) furnished
1,4ꢀdimethoxybenzo[d]naphtho[1,2ꢀb]thiophene 7b as a colorless solid (0.31 g, 62%); mp
168ꢀ170 oC; 1HꢀNMR (300 MHz, CDCl3): δ 8.34ꢀ8.27 (m, 3H), 8.03ꢀ8.01 (m, 1H), 7.54ꢀ7.49
(m, 2H), 6.94 (d, J = 8.4 Hz, 1H), 6.66 (d, J = 8.4 Hz, 1H), 4.14 (s, 3H, OCH3), 4.04 (s, 3H,
13
OCH3) ppm. CꢀNMR (75 MHz, CDCl3): δ 150.1, 149.5, 141.0, 134.9, 133.6, 133.1, 125.9,
125.4, 124.0, 122.3, 121.3, 119.6, 118.9, 105.3, 104.1, 56.1, 56.0 ppm. DEPTꢀ135: δ 125.9,
124.1, 122.3, 121.3, 119.6, 118.9, 105.3, 104.1, 56.1, 56.0 ppm. HRMS (ESIꢀTOF) m/z: [M]+
Calcd for C18H14O2S 294.0715; Found 294.0701.
Preparation
of
compound
(7c).30
Alkylation
(0.7 g,
of
1.91
2ꢀbromoꢀ3ꢀ
mmol) with
(phenylsulfonylmethyl)benzo[b]thiophene
5
3ꢀ(bromomethyl)benzo[b]thiophene 2f (0.48 g, 2.10 mmol) using tꢀBuOK (0.32 g, 2.87
mmol) in DMF (20 mL) at 5ꢀ10 oC followed by workup adopting the procedure similar to that
of
3a
furnished
3ꢀ(2ꢀ(benzo[b]thiophenꢀ3ꢀyl)ꢀ1ꢀ(phenylsulfonyl)ethyl)ꢀ2ꢀ
bromobenzo[b]thiophene 6c as a colorless solid (0.89 g, 91%). To a solution of alkylated
sulfone 6c (0.89 g, 1.55 mmol) in DMF (15 mL), Pd(OAc)2 (0.03 g, 0.15 mmol), PPh3 (0.08
g, 0.30 mmol) and K2CO3 (0.43 g, 3.10 mmol) were added. Then, the reaction mixture was
o
heated at 80 C for 2 h. The usual workup adopting the procedure similar to that of 4a
followed by column chromatographic purification (Silica gel, EtOAcꢀhexane 1:49) furnished
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7c as a colorless solid (0.34 g, 68%); mp 270ꢀ272 C; HꢀNMR (500 MHz, CDCl3): δ 8.23ꢀ
8.22 (m, 1H), 8.22ꢀ8.21 (m, 3H), 7.93ꢀ7.92 (m, 1H), 7.92 (m,1H), 7.53ꢀ7.47 (m, 4H) ppm.
HRMS (ESIꢀTOF) m/z: [M]+ Calcd for C18H10S2 290.0224; Found 290.0211.
Preparation
of
compound
(7d).
Alkylation
of
2ꢀbromoꢀ3ꢀ
(phenylsulfonylmethyl)benzo[b]thiophene 5 (0.7 g, 1.91 mmol) with 2ꢀbromomethylindole
o
2g (0.74 g, 2.10 mmol) using tꢀBuOK (0.32 g, 2.87 mmol) in DMF (20 mL) at 5ꢀ10 C
followed by workup adopting the procedure similar to that of 3a furnished 2ꢀ(2ꢀ
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a
colorless solid (1.09 g, 90%). To a solution of alkylated sulfone 6d (1.09 g, 1.71 mmol) in
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DMF (15 mL), Pd(OAc)2 (0.04 g, 0.17 mmol), PPh3 (0.09 g, 0.34 mmol) and K2CO3 (0.47 g,
o
3.42 mmol) were added. Then, the reaction mixture was heated at 80 C for 2 h. The usual
workup adopting the procedure similar to that of 4a followed by column chromatographic
purification (Silica gel, EtOAcꢀhexane 1:24) furnished 7d as a colorless solid (0.49 g, 70%);
mp 184ꢀ186 oC; 1HꢀNMR (300 MHz, CDCl3): δ 8.40 (d, J = 9.0 Hz, 1H), 8.35 (d, J = 8.1 Hz,
1H), 8.14ꢀ8.07 (m, 2H), 7.96 (d, J = 7.5 Hz, 1H), 7.82ꢀ7.73 (m, 3H), 7.50ꢀ7.29 (m, 6H), 7.20
(d, J = 7.2 Hz, 1H) ppm. 13CꢀNMR (75 MHz, CDCl3): δ 139.1, 138.5, 137.8, 137.3, 135.0,
133.9, 132.4, 132.1, 129.1, 127.2, 126.5, 126.4, 125.6, 124.9, 124.4, 122.9, 121.6, 121.5,
120.6, 120.4, 115.2, 112.1 ppm. DEPTꢀ135: δ 134.0, 129.1, 127.3, 126.5, 126.4, 124.9, 124.4,
122.9, 121.6, 121.5, 120.4, 115.2, 112.1ppm. HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for
C24H16NO2S2 414.0622; Found 414.0628.
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3ꢀ(2ꢀ(2ꢀBromobenzo[b]thiophenꢀ3ꢀyl)ꢀ2ꢀ(phenylsulfonyl)ethyl)ꢀ1ꢀ(phenylsulfonyl)ꢀ1Hꢀ
indole (6e). To a solution of 2ꢀbromoꢀ3ꢀ(phenylsulfonylmethyl)benzo[b]thiophene 5 (0.7 g,
1.91 mmol) in DMF (20 mL) at 5ꢀ10 oC, tꢀBuOK (0.32 g, 2.87 mmol) and
3ꢀbromomethylindole 2h (0.74 g, 2.10 mmol) were added. Then, the reaction mixture was
stirred at the same temperature for 15 min. After completion of the reaction, it was poured
into crushed ice (100 g), the solid obtained was filtered and dried. The crude product was
crystallized from methanol
to furnish 3ꢀ(2ꢀ(2ꢀbromobenzo[b]thiophenꢀ3ꢀyl)ꢀ2ꢀ
(phenylsulfonyl)ethyl)ꢀ1ꢀ(phenylsulfonyl)ꢀ1Hꢀindole 6e as a colorless solid (1.12 g, 92%);
mp184ꢀ186; 1HꢀNMR (400 MHz, CDCl3): δ 8.85 (d, J = 8.4Hz, 1H), 7.86 (d, J = 8.4Hz, 1H),
7.70 (d, J = 8.0Hz, 1H), 7.61ꢀ7.59 (m, 3H), 7.57ꢀ7.54 (m, 3H), 7.50ꢀ7.47 (m, 2H), 7.47ꢀ7.41
(m, 1H), 7.38ꢀ7.31 (m, 4H), 7.28ꢀ7.24 (m, 1H), 7.19ꢀ7.15 (m, 1H), 6.96 (s, 1H), 5.04 (dd, J1
= 10.4 Hz, J2 = 4.4 Hz, 1H), 4.04ꢀ4.00 (m, 1H), 3.98ꢀ3.95 (m, 1H) ppm. 13CꢀNMR (100 MHz,
CDCl3): δ 139.4, 137.9, 137.4, 135.4, 134.9, 134.0, 133.7, 129.9, 129.2, 128.9, 128.6, 126.5,
125.3, 125.3, 125.0, 124.3, ,124.1, 123.4, 122.0, 121.2, 118.9, 117.5, 113.7, 66.9, 21.7 ppm.
HRMS (ESIꢀTOF) m/z: [MꢀC12H10O4S2]+Calcd for C18H12BrNS 352.9874; Found 352.9824.
[Mꢀ C12H10O4S2] +2 Calcd for C18H12BrNS 354.9853; Found 354.9845.
Preparation of compound (7e). To a solution of crude 3ꢀ(2ꢀ(2ꢀbromobenzo[b]thiophenꢀ3ꢀ
yl)ꢀ2ꢀ(phenylsulfonyl)ethyl)ꢀ1ꢀ(phenylsulfonyl)ꢀ1Hꢀindole 6e (0.95 g, 1.50 mmol) in DMF
(15 mL), Pd(OAc)2 (0.03 g, 0.15 mmol), PPh3 (0.08 g, 0.30 mmol) and K2CO3 (0.41 g, 3.00
o
mmol) were added. Then, the reaction mixture was heated at 80 C for 2 h. The usual
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workup adopting the procedure similar to that of 4a followed by column chromatographic
purification (Silica gel, EtOAcꢀhexane 1:24) furnished 7e as a colorless solid (0.45 g, 72%);
mp 182ꢀ184 oC; 1HꢀNMR (300 MHz, CDCl3): δ 8.34 (d, J = 8.1 Hz, 1H), 8.02ꢀ7.96 (m, 2H),
7.63 (d, J = 7.2 Hz, 1H), 7.53 (d, J = 7.8 Hz, 2H), 7.53 (d, J = 7.8 Hz, 2H), 7.41ꢀ7.34 (m,
3H), 7.29ꢀ7.23 (m, 1H), 7.21ꢀ7.14 (m, 1H), 7.04ꢀ7.02 (m, 2H) ppm. 13CꢀNMR (75 MHz,
CDCl3): δ 140.3, 139.3, 136.8, 135.2, 134.1, 133.6, 128.8 (2C), 127.6, 127.4 (3C), 127.2,
126.9, 124.9, 124.5, 122.2, 121.4, 119.7, 118.8, 117.2, 116.4 ppm. DEPTꢀ135: δ 133.6, 128.8,
127.4, 126.9, 125.0, 124.5, 122.3, 121.4, 119.7, 118.8, 117.2, 116.4 ppm. HRMS (ESIꢀTOF)
m/z: [M+H]+ Calcd for C24H16NO2S2 414.0622; Found 414.0624.
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Preparation
of
compound
(7f).
Alkylation
of
2ꢀbromoꢀ3ꢀ
(phenylsulfonylmethyl)benzo[b]thiophene 5 (0.7 g, 1.91 mmol) with 2ꢀ(bromomethyl)
benzo[b]thiophene 2k (0.48 g, 2.10 mmol) using tꢀBuOK (0.32 g, 2.87 mmol) in DMF (20
o
mL) at 5ꢀ10 C followed by workup adopting the procedure similar to that of 3a furnished
3ꢀ(2ꢀ(benzo[b]thiophenꢀ2ꢀyl)ꢀ1ꢀ(phenylsulfonyl)ethyl)ꢀ2ꢀbromobenzo[b]thiophene 6f as a
colorless solid (0.84 g, 86%). To a solution of alkylated sulfone 6f (0.84 g, 1.63 mmol) in
DMF (15 mL), Pd(OAc)2 (0.04 g, 0.16 mmol), PPh3 (0.08 g, 0.32 mmol) and K2CO3 (0.45 g,
o
3.33 mmol) were added. Then, the reaction mixture was heated at 80 C for 2 h. The usual
workup adopting the procedure similar to that of 4a followed by column chromatographic
purification (Silica gel, EtOAcꢀhexane 1:49) furnished 7f as a colorless solid (0.31 g, 65%);
mp 166ꢀ168 oC; 1HꢀNMR (300 MHz, CDCl3): δ 8.50 (d, J = 7.5 Hz, 1H), 8.25 (d, J = 8.1 Hz,
2H), 8.02ꢀ7.94 (m, 3H), 7.66 (t, J = 7.5 Hz, 1H), 7.59ꢀ7.53 (m, 3H) ppm. 13CꢀNMR (75 MHz,
CDCl3): δ 139.8, 138.6, 138.5, 135.1, 134.9, 133.8, 133.0, 129.5, 126.4, 126.3, 124.8, 124.8,
124.0, 122.9, 122.8, 121.4, 120.0, 119.2 ppm. DEPTꢀ135: δ 126.4, 126.3, 124.8, 124.8, 124.0,
122.9, 122.8, 121.4, 119.9, 119.2 ppm. HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for C18H11S2
291.0302; Found 291.0305.
6ꢀ(Phenylsulfonyl)ꢀ5,6ꢀdihydrochrysene
(9aꞌ).
Alkylation
of
2ꢀbromoꢀ3ꢀ
(phenylsulfonylmethyl)benzene 9 (0.7 g, 2.25 mmol) with 1ꢀbromomethylnaphthalene 2c
(0.54 g, 2.48 mmol) using tꢀBuOK (0.38 g, 3.38 mmol) in DMF (20 mL) 5ꢀ10 oC for 15 min
followed by workup adopting the procedure similar to that of 3a furnished 1ꢀ(2ꢀ(2ꢀ
bromophenyl)ꢀ2ꢀ(phenylsulfonyl)ethyl)naphthalene as a colorless solid (0.91 g, 90%). To a
solution of the alkylated sulfone (0.91 g, 1.82 mmol) in DMF (15 mL), Pd(OAc)2 (0.04 g,
0.18 mmol), PPh3 (0.09 g, 0.36 mmol) and K2CO3 (0.50 g, 3.64 mmol) were added. The
reaction mixture was initially maintained at 80 oC for 2 h. It was then heated at 140 oC for 12
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h. The usual workup adopting the procedure similar to that of 4a followed by column
chromatographic purification (Silica gel, EtOAcꢀhexane 1:12) furnished 6ꢀ(phenylsulfonyl)ꢀ
o
1
5,6ꢀdihydrochrysene 9aꞌ as a colorless solid (0.29 g, 36% two steps); mp 192ꢀ194 C; Hꢀ
NMR (300 MHz, CDCl3): δ 8.20 (d, J = 7.5 Hz, 1H), 8.03ꢀ8.7.97 (m, 2H), 7.89ꢀ7.86 (m, 2H),
7.80ꢀ7.78 (m, 2H), 7.67ꢀ7.59 (m, 1H), 7.57ꢀ7.52 (m, 2H), 7.43ꢀ7.37 (m, 1H), 7.21ꢀ7.16 (m,
1H), 7.01ꢀ6.97 (m, 1H), 6.66 (d, J = 7.2 Hz, 1H), 6.28 (d, J = 7.5 Hz, 1H), 4.42 (dd, J1 = 11.3,
J2 = 3.0 Hz, 1H), 4.24 (dd, J1 = 13.5, J2= 2.7 Hz, 1H), 2.93ꢀ2.89 (m, 1H) ppm. 13CꢀNMR (75
MHz, CDCl3): δ 134.0, 133.9, 132.7, 132.3, 131.8, 131.5, 131.4, 129.5, 129.0, 128.7, 128.2,
128.0, 126.7, 126.5, 126.2, 125.9, 125.4, 125.0, 123.3, 64.0, 34.8 ppm. HRMS (ESIꢀTOF)
m/z: [M+H]+ Calcd for C24H19O2S 371.1106; Found 371.1119.
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Benzo[d]naphtho[1,2ꢀb]thiophene
(phenylsulfonylmethyl)benzene
(9b).
Alkylation
of
2ꢀbromoꢀ3ꢀ
9
(0.7 g, 2.25 mmol)
with 3ꢀ(bromomethyl)
benzo[b]thiophene 2f (0.56 g, 2.48 mmol) using tꢀBuOK (0.38 g, 3.38 mmol) in DMF (20
o
mL) 5ꢀ10 C for 15 min followed by workup adopting the procedure similar to that of 3a
furnished 3ꢀ(2ꢀ(2ꢀbromophenyl)ꢀ2ꢀ(phenylsulfonyl)ethyl)benzo[b]thiophene as a colorless
solid (0.92 g, 90%). To a solution of the alkylated sulfone (0.92 g, 2.02 mmol) in DMF (15
mL), Pd(OAc)2 (0.04 g, 0.20 mmol), PPh3 (0.10 g, 0.40 mmol) and K2CO3 (0.56 g, 4.04
mmol) were added. Then, the reaction mixture was heated at 80 oC for 2 h. The usual workup
adopting the procedure similar to that of 4a followed by column chromatographic purification
(Silica gel; EtOAcꢀhexane 1:49) furnished benzo[d]naphtho[1,2ꢀb]thiophene 9b as a colorless
o
1
solid (0.34 g, 65% two steps); mp 180ꢀ82 C; HꢀNMR (300 MHz, CDCl3): δ 8.26ꢀ8.22 (m
2H), 8.18ꢀ8.15 (m, 1H), 8.02ꢀ7.98 (m, 2H), 7.89 (d, J = 8.4 Hz, 1H), 7.67ꢀ7.59 (m, 2H), 7.56ꢀ
13
7.49 (m, 2H) ppm. CꢀNMR (75 MHz, CDCl3): δ 139.1, 137.3, 136.6, 132.7, 132.4, 129.0,
128.9, 126.8, 126.3, 126.2, 125.5, 124.6, 124.5, 123.0, 121.6, 119.7 ppm. HRMS (ESIꢀTOF)
m/z: [M]+ Calcd for C16H10S 234.0503; Found 234.0501.
7ꢀ(Phenylsulfonyl)ꢀ7Hꢀbenzo[c]carbazole
(9c).
Alkylation
of
2ꢀbromoꢀ3ꢀ
(phenylsulfonylmethyl)benzene 9 (0.7 g, 2.25 mmol) with 2ꢀbromomethylindole 2g (0.86 g,
o
2.48 mmol) using tꢀBuOK (0.38 g, 3.38 mmol) in DMF (20 mL) 5ꢀ10 C for 15 min
followed by workup adopting the procedure similar to that of 3a furnished 2ꢀ(2ꢀ(2ꢀ
bromophenyl)ꢀ2ꢀ(phenylsulfonyl)ethyl)ꢀ1ꢀ(phenylsulfonyl)ꢀ1Hꢀindole as a colorless solid
(1.14 g, 88% ). To a solution of the alkylated sulfone (1.14 g, 1.98 mmol) in DMF (15 mL),
Pd(OAc)2 (0.04 g, 0.19 mmol), PPh3 (0.10 g, 0.38 mmol) and K2CO3 (0.55 g, 3.96
mmol)were added. Then, the reaction mixture was initially maintained at 80 oC for 2 h. It was
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then heated at 140 C for 3 h. The usual workup adopting the procedure similar to that of 4a
followed by column chromatographic purification (Silica gel, EtOAcꢀhexane 1:19) furnished
7ꢀ(phenylsulfonyl)ꢀ7Hꢀbenzo[c]carbazole 9c as a colorless solid (0.45 g, 57% two steps); mp
4
5
6
7
8
9
o
1
160ꢀ162 C; HꢀNMR (300 MHz, CDCl3): δ 8.64 (d, J = 8.4 Hz, 1H), 8.53 (d, J = 9.3 Hz,
1H), 8.45ꢀ8.39 (m, 2H), 7.95ꢀ7.87 (m, 2H), 7.73 (d, J = 7.8 Hz, 2H), 7.64ꢀ7.62 (m, 1H), 7.50ꢀ
7.31 (m, 3H), 7.28 (d, J = 8.4 Hz, 1H), 7.23ꢀ7.18 (m, 2H) ppm. 13CꢀNMR (75 MHz, CDCl3):
δ 138.1, 138.0, 136.6, 133.9, 131.1, 129.2, 129.1, 128.9, 128.7, 127.4, 127.2, 126.4, 126.3,
125.0, 124.4, 123.6, 122.2, 120.0, 115.4, 114.9 ppm. HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd
for C22H16NO2S 358.0902; Found 358.0906.
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11ꢀ(Phenylsulfonyl)ꢀ11Hꢀbenzo[a]carbazole
(9d).
Alkylation
of
2ꢀbromoꢀ3ꢀ
(phenylsulfonylmethyl)benzene 9 (0.7 g, 2.25 mmol) with 3ꢀbromomethylindole 2h (0.86 g,
o
2.48 mmol) using tꢀBuOK (0.38 g, 3.38 mmol) in DMF (20 mL) 5ꢀ10 C for 15 min
followed by workup adopting the procedure similar to that of 3a furnished 3ꢀ(2ꢀ(2ꢀ
bromophenyl)ꢀ2ꢀ(phenylsulfonyl)ethyl)ꢀ1ꢀ(phenylsulfonyl)ꢀ1Hꢀindole as a colorless solid
(1.0 g, 80%). To a solution of the alkylated sulfone (1.0 g, 1.72 mmol) in DMF (15 mL),
Pd(OAc)2 (0.04 g, 0.17 mmol), PPh3 (0.09 g, 0.34 mmol) and K2CO3 (0.49 g, 3.54 mmol)
were added. The reaction mixture was initially maintained at 80 oC for 2 h. It was then heated
at 140 oC for 3 h. The usual workup adopting the procedure similar to that of 4a followed by
column chromatographic purification (Silica gel, EtOAcꢀhexane 1:24) furnished
11ꢀ(phenylsulfonyl)ꢀ11Hꢀbenzo[a]carbazole 9d as a colorless solid (0.43 g, 56% two steps);
mp 140ꢀ142 oC; 1HꢀNMR (300 MHz, CDCl3): δ 8.91 (d, J = 8.7 Hz, 1H), 8.24 (d, J = 8.1 Hz,
1H), 7.85 (d, J = 8.1 Hz, 1H), 7.73 (d, J = 8.4 Hz, 1H), 7.63 (d, J = 8.7 Hz, 1H), 7.59ꢀ7.55
(m, 2H), 7.47 (t, J = 7.2 Hz, 1H), 7.35 (t, J = 7.2 Hz, 1H), 7.24 (t, J = 7.2 Hz, 1H), 7.16ꢀ7.10
(m, 1H), 6.85ꢀ6.83 (m, 4H) ppm. 13CꢀNMR (75 MHz, CDCl3): δ 141.7, 136.7, 134.1, 133.9,
133.3, 130.1, 128.3, 127.9, 127.8, 127.7, 127.0, 126.9, 126.7, 126.2, 126.2, 126.0, 125.8,
119.9, 119.4, 117.4 ppm. HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for C22H16NO2S 358.0902;
Found 358.0911.
2ꢀBromoꢀ4,5ꢀdimethoxyphenyl)methanol.
To
a
solution
of
2ꢀbromoꢀ4,5ꢀ
dimethoxybenzaldehyde (3 g, 12.2 mmol) in THF (30 mL) at 0ꢀ10 oC , NaBH4 (1.39 g, 36.7
mmol) was added. Then, the reaction mixture was stirred at room temperature for 2 h. It was
then poured into water (50 mL), extracted with DCM (3 x 30 mL) and dried (Na2SO4).
Removal of solvent under vacuo furnished 2ꢀbromoꢀ4,5ꢀdimethoxyphenyl)methanol as a
colourless liquid (3.5 g). The crude product was used as such for next step.
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1ꢀBromoꢀ2ꢀ(bromomethyl)ꢀ4,5ꢀdimethoxybenzene. To a solution of crude (2ꢀbromoꢀ4,5ꢀ
o
dimethoxyphenyl)methanol (2.69 g, 10.89 mmol) in DCM (30 mL) at 0 C, PBr3 (4.4 g,
o
16.33 mmol) was carefully added. Then, the reaction mixture was stirred 0 C for 10 min. It
7
8
9
was then poured into water (50 mL), extracted with DCM (3 x 30 mL) and dried (Na2SO4).
Removal of solvent under vacuo furnished 1ꢀbromoꢀ2ꢀ(bromomethyl)ꢀ4,5ꢀdimethoxybenzene
as a colorless solid (3.5 g). The crude product was used as such for next step.
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1ꢀBromoꢀ4,5ꢀdimethoxyꢀ2ꢀ(phenylsulfonylmethyl)benzene (10). To a solution of crude 1ꢀ
bromoꢀ2ꢀ(bromomethyl)ꢀ4,5ꢀdimethoxybenzene (2.53 g, 8.16 mmol) in DMF (30 mL),
benzenesulfinic acid sodium salt (1.73 g, 10.61 mmol) was added. Then, the reaction mixture
was stirred at room temperature for 6 h. The usual workup adopting the procedure similar to
that of 1 furnished 1ꢀbromoꢀ4,5ꢀdimethoxyꢀ2ꢀ(phenylsulfonylmethyl)benzene 10 as a
o
1
colorless solid (2.21 g, 73%); mp 142ꢀ144 C; HꢀNMR (300 MHz, CDCl3): δ 7.68ꢀ7.61 (m,
3H), 7.49ꢀ7.44 (m, 2H), 6.92 (s, 1H), 6.88 (s, 1H), 4.50 (s, 2H, CH2), 3.85 (s, 3H, OCH3),
3.84 (s, 3H, OCH3) ppm. 13CꢀNMR (100 MHz, CDCl3): δ 149.9, 148.3, 138.0, 133.9, 129.0,
129.0, 119.9, 116.4, 115.1, 114.4, 61.5, 56.1, 56.1 ppm. HRMS (ESIꢀTOF) m/z: [M+Na]+
Calcd for C15H15BrO4SNa 392.9772; Found 392.9765; [M+Na]2+ Calcd for C15H15BrO4SNa
394.9752; Found 394.9745.
Preparation
of
11a
&
11b.
Alkylation
of
1ꢀbromoꢀ4,5ꢀdimethoxyꢀ2ꢀ
(phenylsulfonylmethyl)benzene 11 (0.7 g, 1.89 mmol) with 3ꢀbromomethylthiophene 2a
(0.37 g, 2.08 mmol) using tꢀBuOK (0.32 g, 2.83 mmol) in DMF (20 mL) 5ꢀ10 oC for 15 min
followed by workup adopting the procedure similar to that of 3a furnished 3ꢀ(2ꢀ(2ꢀ
bromophenyl)ꢀ2ꢀ(phenylsulfonyl)ethyl)ꢀ1ꢀ(phenylsulfonyl)ꢀ1Hꢀindole as a colorless solid
(0.79 g, 90%). To a solution of the alkylated sulfone (0.79 g, 1.70 mmol) in DMF (15 mL),
Pd(OAc)2 (0.04 g, 0.17 mmol), PPh3 (0.10 g, 0.37 mmol) and K2CO3 (0.47 g, 3.40 mmol)
were added. The reaction mixture was initially maintained at 80 oC for 2 h. It was then heated
at 140 oC for 2 h. The usual workup adopting the procedure similar to that of 4a followed by
column chromatographic purification (Silica gel, EtOAcꢀhexane 1:49) furnished mixture of
1
11a and 11b as a brown liquid (0.28 g, 47% two steps); HꢀNMR (300 MHz, CDCl3): δ 7.63
(d, J = 8.4 Hz, 1H), 7.52 (d, J = 8.7 Hz, 1H), 7.24ꢀ7.21 (m, 1.5H), 7.18ꢀ7.16 (m, 2H), 6.95 (s,
1H), 6.92ꢀ6.89 (m, 1H), 6.84 (s, 1H), 6.78ꢀ6.75 (m, 1H), 3.99 (s, 3H, OCH3), 3.94 (s, 3H,
OCH3), 3.86 (s, 2H), 3.81 (s, 2H) ppm. 13CꢀNMR (100 MHz, CDCl3): δ 149.8, 149.2, 149.0,
148.8, 140.3, 136.3, 136.3, 130.5, 128.5 126.1, 126.0, 125.2, 124.9, 124.3, 124.1, 123.9,
121.6, 121.2, 120.3, 119.6 111.3, 108.6, 107.9, 103.2, 56.1, 56.0, 56.0, 55.9 ppm. HRMS
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(ESIꢀTOF) m/z: [M+H]+ Calcd for 11a C14H13O2S 245.0636; Found 245.0642. MS (ESI) m/z:
for 11b C11H9BrOS [MꢀC3H2O]+ 267, [MꢀC3H2O]+2 269.
6
7
8
9
Preparation
of
11c
&
11d.
Alkylation
of
1ꢀbromoꢀ4,5ꢀdimethoxyꢀ2ꢀ
with 3ꢀ(bromomethyl)
(phenylsulfonylmethyl)benzene
9
(0.7 g, 1.89 mmol)
benzo[b]thiophene 2f (0.47 g, 2.08 mmol) using tꢀBuOK (0.32 g, 2.83 mmol) in DMF (20
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60
o
mL) 5ꢀ10 C for 15 min followed by workup adopting the procedure similar to that of 3a
furnished 3ꢀ(2ꢀ(2ꢀbromoꢀ4,5ꢀdimethoxyphenyl)ꢀ2ꢀ(phenylsulfonyl)ethyl)benzo[b]thiophene
as a colorless solid (0.86 g, 88%). To a solution of the alkylated sulfone (0.86 g, 1.66 mmol)
in DMF (15 mL), Pd(OAc)2 (0.04 g, 0.16 mmol), PPh3 (0.08 g, 0.32 mmol) and K2CO3 (0.46
o
g, 3.32 mmol) were added. The reaction mixture was initially maintained at 80 C for 2 h. It
was then heated at 140 oC for 2 h. The usual workup adopting the procedure similar to that of
4a followed by column chromatographic purification (Silica gel, EtOAcꢀhexane 1:32)
1
furnished mixture of 11c and 11d as a brown liquid (0.34 g, 48% two steps); HꢀNMR (300
MHz, CDCl3): δ 8.07 (d, J = 7.2 Hz, 1H), 7.97ꢀ7.92 (m, 1H), 7.86ꢀ7.78 (m, 2H), 7.65ꢀ7.62
(m, 1H), 7.42 (s, 1H), 7.34ꢀ7.29 (m, 2H), 7.22 (s, 1H), 7.21ꢀ7.18 (m, 1H), 7.21ꢀ7.18 (m,1H),
7.14 (s, 1H), 7.06 (s, 1H), 7.02ꢀ6.99 (m, 1H), 6.79 (d, J = 8.4 Hz, 1H), 4.0 (s, 2H), 3.95 (s,
2H), 3.86 (s, 3H, OCH3), 3.83 (s, 3H, OCH3) ppm. MS (ESI) m/z for 11c C18H15O2S [M+H]+:
295. MS: m/z for 11d C18H13BrO2S [M+]: 371, [M+2]: 373.
2,3ꢀDimethoxyꢀ7ꢀ(phenylsulfonyl)ꢀ7Hꢀbenzo[c]carbazole (11e). Alkylation of 1ꢀbromoꢀ
4,5ꢀdimethoxyꢀ2ꢀ(phenylsulfonylmethyl)benzene 10 (1.0 g, 2.69 mmol)
with 2ꢀ
bromomethylindole 2g (1.03 g, 2.96 mmol) using tꢀBuOK (0.45 g, 4.03 mmol) in DMF (20
o
mL) 5ꢀ10 C for 15 min followed by workup adopting the procedure similar to that of 3a
furnished 2ꢀ(2ꢀ(2ꢀbromoꢀ4,5ꢀdimethoxyphenyl)ꢀ2ꢀ(phenylsulfonyl)ethyl)ꢀ1ꢀ(phenylsulfonyl)ꢀ
1Hꢀindole as a colorless solid (1.58 g, 92%). To a solution of the alkylated sulfone (1.30 g,
2.03 mmol) in DMF (15 mL), Pd(OAc)2 (0.04 g, 0.20 mmol), PPh3 (0.10 g, 0.40 mmol) and
K2CO3 (0.57 g, 4.08 mmol) were added. The reaction mixture was initially maintained at 80
oC for 2 h. It was then heated at 140 C for 2 h. The usual workup adopting the procedure
o
similar to that of 4a followed by column chromatographic purification (Silica gel, EtOAcꢀ
hexane 1:19) furnished 2,3ꢀdimethoxyꢀ7ꢀ(phenylsulfonyl)ꢀ7Hꢀbenzo[c]carbazole 11e as a
colorless solid (0.58 g, 68%); mp 160ꢀ162 oC; 1HꢀNMR (300 MHz, CDCl3): δ 8.21 (d, J = 8.1
Hz, 1H), 7.73 (d, J = 7.75 Hz, 2H), 7.66ꢀ7.61 (m, 1H), 7.47ꢀ7.44 (m, 2H), 7.37ꢀ7.31 (m, 3H),
7.29ꢀ7.24 (m, 2H), 7.06 (s, 1H), 6.85 (s, 1H), 3.98 (s, 3H, OCH3), 3.91 (s, 3H, OCH3) ppm.
13CꢀNMR (75 MHz, CDCl3): δ 150.0, 148.9, 139.6, 138.1, 137.5, 133.6, 131.0, 130.3, 129.0,
128.8, 126.7, 124.9, 124.2, 120.8, 119.6, 115.5, 115.3, 115.1, 109.4 ,109.1, 56.3, 56.2 ppm.
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DEPTꢀ135: δ 133.8, 130.9, 129.0, 126.7, 124.2, 120.8, 119.6, 115.5, 115.3, 109.4, 109.1,
56.3, 56.2 ppm. HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for C24H20NO4S 418.1113; Found
418.1115.
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2,3ꢀDimethoxyꢀ11ꢀ(phenylsulfonyl)ꢀ11Hꢀbenzo[a]carbazole (11f). Alkylation of 1ꢀbromoꢀ
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4,5ꢀdimethoxyꢀ2ꢀ(phenylsulfonylmethyl)benzene 10 (1.0 g, 2.69 mmol)
with 3ꢀ
bromomethylindole 2h (1.0 g, 2.69 mmol) using tꢀBuOK (1.0 g, 2.69 mmol) in DMF (20 mL)
5ꢀ10 oC for 15 min followed by workup adopting the procedure similar to that of 3a furnished
3ꢀ(2ꢀ(2ꢀbromoꢀ4,5ꢀdimethoxyphenyl)ꢀ2ꢀ(phenylsulfonyl)ethyl)ꢀ1ꢀ(phenylsulfonyl)ꢀ1Hꢀindole
as a colorless solid (1.51 g, 88%). To a solution of the alkylated sulfone (1.20 g, 1.88 mmol)
in DMF (15 mL), Pd(OAc)2 (0.04 g, 0.19 mmol), PPh3 (0.10 g, 0.38 mmol) and K2CO3 (0.52
o
g, 3.78 mmol) were added. The reaction mixture was initially maintained at 80 C for 2 h. It
was then heated at 140 oC for 2 h. The usual workup adopting the procedure similar to that of
4a followed by column chromatographic purification (Silica gel, EtOAcꢀhexane 1:19)
furnished 2,3ꢀdimethoxyꢀ11ꢀ(phenylsulfonyl)ꢀ11Hꢀbenzo[a]carbazole 11f as a colorless solid
o
(0.57 g, 72%); mp 186ꢀ188 C; 1HꢀNMR (300 MHz, CDCl3): δ 8.37 (s, 1H), 8.25 (d, J = 8.1
Hz, 1H), 7.61 (d, J = 8.4 Hz, 1H), 7.56ꢀ7.50 (m, 2H), 7.38ꢀ7.33 m, 1H), 7.28ꢀ7.24 (m, 1H),
7.19ꢀ7.14 (m, 3H), 6.89ꢀ6.88 (m, 3H), 4.11 (s, 3H, OCH3), 3.99 (s, 3H, OCH3) ppm. 13Cꢀ
NMR (75 MHz, CDCl3): δ 149.3, 149.2, 141.5, 136.1, 134.0, 133.2, 130.5, 130.0, 127.8,
126.8, 126.3, 126.0, 125.7, 121.9, 120.0, 119.1, 115.6, 107.0, 106.5, 56.2, 55.8 ppm. HRMS
(ESIꢀTOF) m/z: [M+H]+ Calcd for C24H20NO4S 418.1113; Found 418.1126.
9ꢀ(Phenylsulfonyl)ꢀ9Hꢀnaphtho[2,1ꢀc]carbazole (13). Alkylation of 1ꢀbromoꢀ2ꢀ
(phenylsulfonylmethyl)naphthalene 12 (0.7 g, 1.89 mmol) with 2ꢀbromomethylindole 2g
(0.72 g, 2.07 mmol) using tꢀBuOK (0.32 g, 2.83 mmol) in DMF (20 mL) 5ꢀ10 oC for 15 min
followed by workup adopting the procedure similar to that of 3a furnished 2ꢀ(2ꢀ(1ꢀ
bromonaphthalenꢀ2ꢀyl)ꢀ2ꢀ(phenylsulfonyl)ethyl)ꢀ1ꢀ(phenylsulfonyl)ꢀ1Hꢀindole as a colorless
solid (1.12 g, 92%). To a solution of the alkylated sulfone (1.12 g, 1.77 mmol) in DMF (15
mL), Pd(OAc)2 (0.04 g, 0.17 mmol), PPh3 (0.09 g, 0.34 mmol) and K2CO3 (0.49 g, 3.54
o
mmol) were added. The reaction mixture was initially maintained at 80 C for 2 h. It was
o
then heated at 140 C for 6 h. The usual workup adopting the procedure similar to that of 4a
followed by column chromatographic purification (Silica gel, EtOAcꢀhexane 1: 24) furnished
9ꢀ(phenylsulfonyl)ꢀ9Hꢀnaphtho[2,1ꢀc]carbazole 13 as a colorless solid (0.50 g, 64% two
steps); mp 104ꢀ106 oC; 1HꢀNMR (500 MHz, CDCl3): δ 8.94 (d, J = 8.0 Hz, 1H), 8.57 (d, J =
9.0 Hz, 1H), 8.52 (d, J = 8.0 Hz, 1H), 8.43 (d, J = 8.1 Hz, 1H), 7.87ꢀ7.84 (m, 2H), 7.77 (d, J
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= 7.5 Hz, 2H),7.73ꢀ7.68 (m, 2H), 7.55ꢀ7.53 (m, 1H), 7.48ꢀ7.43 (m, 2H), 7.35ꢀ7.34 (m, 1H),
7.27ꢀ7.22 (m, 3H) ppm. 13CꢀNMR (125 MHz, CDCl3): δ 138.5, 137.8, 133.9, 133.1, 130.2,
130.0, 129.1, 128.3, 128.0, 127.7, 127.2, 126.9, 126.5, 126.3, 125.7, 124.5, 124.0, 123.1
123.0, 121.5, 117.4, 115.4, 115.0 ppm. HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for
C26H18NO2S 408.1058; Found 408.1064.
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13ꢀ(Phenylsulfonyl)ꢀ13Hꢀnaphtho[1,2ꢀa]carbazole (14). Alkylation of 1ꢀbromoꢀ2ꢀ
(phenylsulfonylmethyl)naphthalene 12 (0.7 g, 1.89 mmol) with 3ꢀbromomethylindole 2h
o
(0.72 g, 2.07 mm) using tꢀBuOK (0.32 g, 2.83 mmol) in DMF (20 mL) 5ꢀ10 C for 15 min
followed by workup adopting the procedure similar to that of 3a furnished 3ꢀ(2ꢀ(1ꢀ
bromonaphthalenꢀ2ꢀyl)ꢀ2ꢀ(phenylsulfonyl)ethyl)ꢀ1ꢀ(phenylsulfonyl)ꢀ1Hꢀindole as a colorless
solid (1.00 g, 82%). To a solution of the alkylated sulfone (1.0 g, 1.59 mmol) in DMF (15
mL), Pd(OAc)2 (0.04 g, 0.16mmol), PPh3 (0.08 g, 0.32 mmol) and K2CO3 (0.44 g, 3.14
mmol) were added. The reaction mixture was initially maintained at 80 oC for 2 h. It was then
o
heated at 140 C for 6 h. The usual workup adopting the procedure similar to that of 4a
followed by column chromatographic purification (Silica gel, EtOAcꢀhexane 1: 20) furnished
13ꢀ(phenylsulfonyl)ꢀ13Hꢀnaphtho[1,2ꢀa]carbazole 14 as a colorless solid (0.48 g, 51% two
steps); mp 78ꢀ80 oC; 1H NMR (300 MHz, CDCl3): δ 9.81 (d, J = 8.4 Hz, 1H), 8.25 (d, J = 8.1
Hz, 1H), 7.85ꢀ7.81 (m, 2H), 7.77ꢀ7.65 (m, 2H), 7.58 (d, J = 7.8 Hz, 2H), 7.57ꢀ7.53 (m, 2H),
7.40 (t, J = 7.6 Hz, 1H), 7.25 (t, J = 7.3Hz, 1H), 7.12 (t, J = 7.3 Hz, 1H), 6.80 (t, J = 7.6 Hz,
2H), 6.54 (d, J = 7.8 Hz, 2H) ppm. 13CꢀNMR (75 MHz, CDCl3): δ 142.1, 137.5, 133.1, 132.9,
132.7, 132.3, 130.9, 130.7, 130.4, 129.1, 128.2, 128.0, 127.6, 127.4, 127.1, 127.0, 127.1,
126.2, 126.2, 125.5, 120.4, 119.7, 117.7 ppm. DEPTꢀ135: δ 133.1, 129.1, 128.2, 128.0,
127.6, 127.4, 127.1, 127.0, 126.3, 126.2, 125.5, 120.4, 119.7, 117.7 ppm. HRMS (ESIꢀTOF)
m/z: [M+H]+ Calcd for C26H18NO2S 408.1058; Found 408.1049.
3ꢀBromoꢀ1ꢀ(phenylsulfonyl)ꢀ2ꢀ(2ꢀ(phenylsulfonyl)ꢀ2ꢀ(1ꢀ(phenylsulfonyl)ꢀ1Hꢀindolꢀ2ꢀ
yl)ethyl)ꢀ1Hꢀindole (17). To a solution of sulfone 1527 (0.8 g, 1.94 mmol) and 2ꢀ
bromomethylindole 16 (0.9 g, 2.14 mmol) in DMF (10 mL), K2CO3 (0.8 g, 5.83 mmol) was
added and the reaction mixture was stirred at room temperature for 12 h. After completion of
the reaction (monitored by TLC), it was then poured over crushed ice containing Conc. HCl
(5 mL). The solid obtained was filtered, washed with water (2 x 20 mL) and dried. The crude
product was recrystallized from methanol (5 mL) to afford indolylmethylated sulfone 17 as a
colorless solid (1.15 g, 78%).
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5,8ꢀBis(phenylsulfonyl)indolo[2,3ꢀc]carbazole (18). To a solution of indolylmethylated
sulfone 17 (200 mg, 0.26 mmol) in DMF (8 mL), Pd(OAc)2 (6 mg, 0.026 mmol), PPh3 (13
o
mg, 0.053 mmol) and K2CO3 (100 mg, 0.79 mmol) were added and stirred at 110 C for 4 h.
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After completion of the reaction (monitored by TLC), usual workup adopting the procedure
similar to that of 4a followed by column chromatographic purification (Silica gel, EtOAcꢀ
hexane 1: 10) afforded 8ꢀbis(phenylsulfonyl)indolo[2,3ꢀc]carbazole 18 as a colorless solid
(110 mg, 78%); mp 200ꢀ202 oC; 1HꢀNMR (300 MHz, CDCl3): δ 8.54 (s, 2H), 8.49 (d, J = 7.8
Hz, 2H), 8.43 (d, J = 8.4 Hz, 2H), 7.70 (d, J = 8.1 Hz, 4H), 7.46 (t, J = 7.2 Hz, 2H), 7.42ꢀ7.31
(m, 4H), 7.23 (t, J = 7.5 Hz, 4H) ppm. 13CꢀNMR (75 MHz, CDCl3): δ 138.9, 137.5, 136.0,
133.9, 129.0, 127.5, 126.4, 126.0, 124.0, 123.1, 120.9, 115.6, 114.4 ppm. DEPTꢀ135 (75
MHz, CDCl3): δ 133.9, 129.0, 127.5, 126.4, 124.0, 123.1, 115.6, 114.4 ppm. HRMS (ESIꢀ
TOF) m/z: [M]+ Calcd for C30H20N2O4S2 536.0864; Found: 536.0836.
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5,8ꢀDihydroindolo[2,3ꢀc]carbazole (19). In a sealed tube containing a solution of
indolylmethylated sulfone 17 (200 mg, 0.26 mmol) in DMF (8 mL), Pd(OAc)2 (6 mg, 0.026
mmol), PPh3 (13 mg, 0.053 mmol) and K2CO3 (100 mg, 0.79 mmol) were added and it was
stirred at 140 oC for 6 h. After completion of the reaction (monitored by TLC), following the
workup procedure similar to that of 4a followed by column chromatographic purification
(Silica gel, EtOAcꢀhexane 1: 5) afforded 5,8ꢀdihydroindolo[2,3ꢀc]carbazole 19 as a colorless
solid (50 mg, 75%); mp 280ꢀ282 oC; 1HꢀNMR (300 MHz, CDCl3+DMSOꢀd6): δ 8.81 (s, 2H),
7.89 (d, J = 7.8 Hz, 2H), 6.57ꢀ6.52 (m, 6H), 6.51ꢀ6.45 (m, 2H) ppm. 13CꢀNMR (75 MHz,
CDCl3 +DMSOꢀd6): δ 139.2, 134.3, 124.2, 122.6, 122.4, 118.1, 115.8, 110.6, 109.6 ppm.
DEPTꢀ135 (75 MHz, CDCl3): δ 119.3, 117.7, 113.2, 105.7, 104.8 ppm. HRMS (ESIꢀTOF)
m/z: [M]+ Calcd for C18H12N2 256.1000; Found 256.0999.
Indolo[3,2ꢀa]carbazole (22). To a solution of sulfone 20 (0.8 g, 1.94 mmol) and 3ꢀbromoꢀ
2ꢀbromomethylindole 16 (0.9 g, 2.14 mmol) in DMF (10 mL), K2CO3 (0.8 g, 5.83 mmol) was
added and stirred at rt for 12 h. After completion of the reaction followed by workup
procedure similar to that of 17 followed by crystallization from methanol afforded
indolylmethylated sulfone 21 as a colorless solid (1.18 g, 79%). In a sealed tube containing a
solution of crude indolylmethylated sulfone 21 (200 mg, 0.26 mmol) in DMF (8 mL),
Pd(OAc)2 (6 mg, 0.026 mmol), PPh3 (13 mg, 0.053 mmol) and K2CO3 (100 mg, 0.79 mmol)
were added. The reaction mixture was then stirred at 140 oC for 6 h. After completion of the
reaction (monitored by TLC), following the workup procedure similar to that of 4a followed
by column chromatographic purification (Silica gel, EtOAcꢀhexane 1: 5) afforded indolo[3,2ꢀ
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a]carbazole 22 as a colorless solid (46 mg, 68%); mp 278ꢀ280 C; HꢀNMR (300 MHz,
CDCl3+DMSOꢀd6): δ 10.35 (bs, 1H), 9.95 (bs, 1H), 7.69 (d, J = 7.5 Hz, 1H), 7.14 (m, 2H),
6.74 (d, J = 7.8 Hz, 1H), 6.65 (d, J = 8.1 Hz, 1H), 6.48ꢀ6.29 (m, 5H) ppm. 13CꢀNMR (75
MHz, CDCl3 + DMSOꢀd6): δ 138.7, 138.1, 133.4, 123.2, 123.1, 122.5, 121.0, 120.5, 118.1,
117.9, 117.8, 117.2, 114.0, 110.3, 109.9, 106.1, 102.8 ppm. DEPTꢀ135 (75 MHz, CDCl3
+DMSOꢀd6): δ 128.8, 128.1, 126.1, 123.7, 123.5, 123.4, 122.8, 115.9, 115.5, 108.4 ppm.
HRMS (ESIꢀTOF) m/z: [M]+ Calcd for C18H12N2 256.1000; Found 256.0998.
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ACKNOWLEDGMENTS
The authors graciously acknowledged the Council of Scientific and Industrial Research
(CSIR) New Delhi [02(0214)/14/EMRꢀII dt. 17/11/2014] for financial support. E. S and J. K.
thank Council of Scientific and Industrial Research (CSIR) New Delhi for fellowships. P. R.
thanks University Grants Commission (UGC) New Delhi for fellowship. The authors thank
the Department of Science and Technology Funds for the Improvement of Science and
Technology (DSTꢀFIST) New Delhi for NMR and HRMS facilities.
ASSOCIATED CONTENT
Supporting Information: Copies of 1H and 13C NMR spectra for 1, 3aꢀ3b, 3h, 4aꢀ4j, 5, 6e,
7aꢀ7f, 9aꞌꢀ9d, 11a+11b/11c+11d (1H only), 11eꢀ11f, 10, 13, 14, 18, 19, 22. Xꢀray
crystallographic information for 6e & 14 and HRMS Spectra for 4i, 4j, 7a, 7b, 7c, 14. This
material is available free of charge via the Internet at http://pubs.acs.org.
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N.; Gao, D. Chem. Rev. 2010, 110, 4498ꢀ4553.
2. a) Roy, J.; Pal, R.; Mal, D. Tetrahedron Lett. 2015, 56, 6210ꢀ6213; b) Nowaacki, M.;
Wojciechowski, K. RSC Advances, 2015, 5, 94296ꢀ94303; c) Kotha, S.; Waghule, G.
T.; Shirbhate, M. E. Eur. J. Org. Chem. 2014, 984ꢀ992; d) Li, S.ꢀY.; Wang, X.ꢀB.;
Jian, N.; Kang, L.ꢀY. Eur. J. Org. Chem. 2014, 8035ꢀ8039; e) Mukkamala, R.;
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