Unusual dimerization of N-protected bromomethylindoles/benzyl bromide with arylmetal halides: generation of indolylmethyl/benzyl radical

Article abstract of DOI:10.1016/j.tet.2007.12.047

A detailed study on the interaction of N-protected bromomethylindoles with various types of aryl/alkyl Grignard is reported. Full experimental details on the mechanism of the unusual dimerization reaction are presented.

Full text of DOI:10.1016/j.tet.2007.12.047

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 2071e2079
www.elsevier.com/locate/tet
Unusual dimerization of N-protected bromomethylindoles/benzyl bromide
with arylmetal halides: generation of indolylmethyl/benzyl radical
Neelamegam Ramesh, Chandran Prakash, Radhakrishnan Sureshbabu, Vasudevan Dhayalan,
*
Arasambattu K. Mohanakrishnan
Department of Organic Chemistry, University of Madras, Guindy Campus, Chennai 600 025, Tamil nadu, India
Received 30 April 2007; received in revised form 4 December 2007; accepted 20 December 2007
Available online 24 December 2007
Abstract
A detailed study on the interaction of N-protected bromomethylindoles with various types of aryl/alkyl Grignard is reported. Full experimen-
tal details on the mechanism of the unusual dimerization reaction are presented.
Ó 2007 Elsevier Ltd. All rights reserved.
Keywords: Bromomethylindole; Benzylbromide; Alkyl/aryl Grignard; Indolylmethyl/benzyl radical
1. Introduction
phenylmagnesium chloride or 4-methoxyphenylmagnesium
bromide at room temperature. In that report, we proposed
the formation of dimer 2a via the intermediacy of an indolyl-
methyl Grignard 3, Scheme 1. In both the conditions, i.e.,
a slow addition of phenylmagnesium chloride to the solution
of bromo compound 1a0 in THF or reverse addition of bromo
compound to the Grignard, the dimer 2a was obtained in
almost comparable yield.
Indole and its myriad of derivatives are important segments
of a large number of natural products of both marine and ter-
restrial origin, and hence it continues to capture the attention
of the synthetic organic chemist. Over the years, synthetic
elaboration of N-protected bromomethylindoles has been thor-
oughly exploited to effect the syntheses of different types of
indole based natural products.1 In continuation of our interest
in the synthesis of carbazole-based alkaloids,2 we wanted to
develop a viable procedure for the arylation of N-protected
bromomethylindoles, as the existing procedure is applicable
only to electron rich arenes.3 In the course of this investigation,
we discovered an unusual dimerization of N-protected bromo-
methylindoles with the interaction of arylmagnesium halides.
PhMgCl/THF
SPh
Br
(or)
PhS
N
SPh
4-MeO-C6H4MgBr
N
rt, N2 atm.
15 h, 50%
N
SO2Ph
SO2Ph
SO2Ph
1a'
2a
SPh
1a'
2a
MgX
N
2. Results and discussion
SO2Ph
3a X = Cl/Br
In continuation of our synthetic studies on indole deriva-
tives, recently, we have reported4 an unusual dimerization of
N-protected 2-bromomethylindoles 1a0 via interaction with
Scheme 1.
The unusual dimerization reaction was then tested with
a variety of bromomethylindoles 1a0ej and the results obtained
are presented in Table 1. In general, the phenylmagnesium
* Corresponding author. Tel.: þ91 44 24451108; fax: þ91 44 22300488.
E-mail address: mohan_67@hotmail.com (A.K. Mohanakrishnan).
0040-4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.12.047

2072
N. Ramesh et al. / Tetrahedron 64 (2008) 2071e2079
Table 1
Dimerization of N-protected bromomethyl indoles using PhMgCl
Entry
Bromo/chloro indole5
Conditions
Dimerized product
Yielda (%)
SPh
1.2 equiv PhMgCl, rt, 3 h
1.2 equiv MeOC6H4MgBr, rt, 5 h
60
52
SPh
SO2Ph
N
X
N
1
1.2 equiv
, rt, 5 h
MgBr
N
SO2Ph
48
S
SO2Ph
PhS
1.2 equiv MeSC6H4MgBr, rt, 4 h
1.2 equiv PhMgCl, rt, 5 h
51
48
1a' X = Br
1a00 X¼Cl
2a
SO2Ph
N
CN
Br
CN
2
1.2 equiv PhMgCl, rt, 8 h
20
N
N
SO2Ph
1b
SO2Ph
NC
2b
Me
Br
SO2Ph
N
Me
1.2 equiv PhMgCl, rt, 5 h
1.2 equiv PhMgCl, rt, 7 h
48
43
N
SO2Ph
1c' X = Br
3
N
SO2Ph
2c
1c00 X¼Cl
Me
Ph
O
N
Br
N
4
1.2 equiv PhMgCl, rt, 5 h
42
N
Ph
O
Ph
2d
O
1d
N
SO2Ph
Br
5
1.2 equiv PhMgCl, rt, 10 h
45
N
N
SO2Ph
2e
SO2Ph
1e
N
SO2Ph
N
0
Br
SO2Ph
2f
N
6
1.2 equiv PhMgCl, rt, 5 h
SO2Ph
1f
50
N
SO2Ph
4
Br
CO2Et
N
7
8
2 equiv PhMgCl, rt, 6 h
No reaction
SO2Ph
1g
Br
Br
Br
PhO2S
N
71
1.2 equiv PhMgCl, rt, 10 h
N
N
SO2Ph
PhO2S
Br
2h
1h

N. Ramesh et al. / Tetrahedron 64 (2008) 2071e2079
2073
Table 1 (continued)
Entry
Bromo/chloro indole5
Conditions
Dimerized product
SO2Ph
Yielda (%)
R
CO2Et
R
CO2Et
Br
N
R
N
1.2 equiv PhMgCl, rt, 6 h
48
55
N
PhO2S
9
EtO2C
2i R = H
SO2Ph
1i R = H
1j R¼OMe
Isolated yield after column chromatography.
1.2 equiv PhMgCl, rt, 6 h
2j R¼OMe
a
chloride induced dimerization was found to occur with a wide
variety of bromomethylindoles with the exception of 3-bromo-
methylindoles 1f and 1g (entries 6 and 7). The dimerization of
bromo compound 1a0 proceeded in reasonable yields with
aryl/heteroaryl Grignards (entry 1). The rate and yield of the di-
merization were found to be somewhat less with the correspond-
ing N-protected chloromethylindoles (entries 1 and 3). The
presence of cyano group at the 3-position significantly lowers
the yield of the dimerization process (entry 2). On the other
hand, the bromo compounds 1i and 1j containing an ethyl ester
at the indole-3-position smoothly proceeded with the dimeriza-
tion process to afford the respective products 2i and 2j in 48
and 55% yields (entry 9). The observed dimerization was found
to be successful with 1-phenylsulfonyl-4-bromomethylindole
1e (entry 5). However, contrary to our earlier observation,4
the interaction of 1-phenylsulfonyl-3-bromomethylindole with
phenylmagnesium chloride did not produce the dimer 2f, instead
column chromatographic purification led to isolation of the
corresponding phenylated indole 4 in 50% yield (entry 6).
To our surprise, interaction of N-phenylsulfonyl-2-carb-
ethoxy-3-bromomethylindole 1g with phenylmagnesium chlo-
ride produced neither dimer nor phenylated product, only the
starting bromo compound was recovered unchanged (entry 7).
Even though the formation of the dimer 2a was proposed
through the intermediacy of indolylmethylmagnesium halide,4
there is no literature precedence for this type of Grignard
exchange between benzylic halides and aryl Grignards. To
our delight, the interaction of bromo compound 1a0 with phe-
nylmagnesium chloride followed by a careful column chro-
matographic separation led to the isolation of biphenyl 5 in
63% yield in addition to the dimer 2a, Scheme 2. Similarly,
the interaction of the bromo compound 1a0 with freshly pre-
pared phenylmagnesium bromide led to the isolation of dimer
2a and biphenyl 5 in 65 and 67% yields, respectively. The
formation of biphenyl 5 is possible only when radical interme-
diate is involved. Obviously, the interaction of bromo com-
pounds with aryl Grignards produced the indolylmethyl
radical 6 and phenyl radical 7. Self-dimerization of these
radicals must lead to the dimer 2a and biphenyl 5, Scheme 2.
In order to understand the mechanistic rational behind this
dimerization process, as a representative case the dimerization
of bromo compound 1a0 was planned at low temperature. Ac-
cordingly, a solution of bromo compound 1a0 was interacted
with phenylmagnesium chloride in dry THF at ꢀ78 ꢁC for
2 h followed by quenching of the reaction mixture with aq
NH4Cl led to the quantitative recovery of the bromo com-
pound 1a0. However, when the mixture of bromo compound
1a0 with phenylmagnesium chloride in dry THF was slowly
raised from ꢀ78 ꢁC to room temperature followed by usual
workup, dimer 2a, biphenyl 5, and phenylated product 86
were isolated in 60, 52, and 10% yields, respectively. Under
the identical conditions, interaction of the bromo compound
1a0 with in situ generated PhCu also afforded the products
2a and 5 along with minor amount of the 2-benzylindole 8,
Scheme 3. The formation of benzylindole 8 in minor portions
might be due to the cross-coupling between indolylmethyl
radical 6 and phenyl radical 7.
i) PhMgCl/ THF
SPh
-78 °C, 2 h
1a'
2a
+
5 (52%) +
(60%)
ii) -78 °C to rt
iii) rt, 1 h
N
SO2Ph
8 (10%)
i) CuI/THF, -78 °C
30 min
ii) 1a'/THF
-78 °C to rt, 3 h
(5%)
+
2a (56%) + 5 (48%)
8
PhMgCl
Scheme 3.
Finally, the reaction of bromo compound 1a0 with PhMgCl
and in situ generated PhZnBr or PhCu were carried out at dif-
ferent temperatures. The results obtained under these condi-
tions are outlined in Scheme 4. In all the cases, the biphenyl
8 was isolated around 40e55% yields.
PhMgCl (or) PhMgBr
2a
1a'
+
rt, N2 atm.
5
SPh
CH2
+
PhMgCl/PhZnBr/PhCu
THF
N
SO2Ph
6
1a'
8
2a
5
+
+
-60 °C to -10 °C , 5 h
7
Scheme 2.
Scheme 4.

2074
N. Ramesh et al. / Tetrahedron 64 (2008) 2071e2079
phenylthio-2-methylindole 10.12 It should be mentioned that
Table 2
Temperature (ꢁC)
Yield of 2a (%)
Yield of 8 (%)
in the case of isopropylmagnesium bromide not even a trace
of dimeric product 2a was observed. However, the reaction
of bromo compound 1a0 with BuMgBr/Bu2Mg furnished
the dimer 2a along with butylated product 11. When the
bromo compound 1a0 was reacted with freshly prepared
TMSCH2MgCl, N-phenylsulfonyl cleaved dimer 12 and
N-protected dimer 2a were isolated in 35 and 18% yields, re-
spectively. The observed cleavage of phenylsulfonyl group of
2a may be due to the nucleophilic character of TMSCH2MgCl.
The isolation of compound 10 in the case of isopropylmag-
nesium bromide confirms the intermediacy of indolylmethyl-
magnesium chloride 3. On the other hand, the absence of
compound 10 in the case of BuMgBr/Bu2Mg/TMSCH2MgCl
effectively rules out the intermediacy of indolylmethyl
Grignard and hence in these cases, the observed dimerization
might proceed only through an indolylmethyl radical.
ꢀ60
ꢀ30
ꢀ10
No reaction
40, 40, 42
54, 45, 40
No reaction
20, 18, 15
08, 10, 12
Interaction of bromo compound 1a0 with PhMgCl or in situ
generated PhZnBr/PhCu at ꢀ60 ꢁC for 5 h led to the recovery
of starting material. The yield of dimerization/addition prod-
ucts obtained at ꢀ30, ꢀ20, and at ꢀ10 ꢁC using respective
aryl nucleophiles are presented in Table 2. Now it is clear
that at low temperature, the self-dimerization of indolylmethyl
radical 6 led to the formation of dimer 2a. The cross-coupling
of indolylmethyl radical 6 with phenyl radical 7 produced the
2-benzylindole 8. This could be the reason why 2-benzylin-
dole 8 was always formed in minor amounts irrespective of
the nature of the aryl nucleophiles employed, i.e., PhMgCl
or PhZnBr or PhCu.
It should be mentioned that Negishi and Qian observed7
a small amount of similar dimerization process during a Pd-
mediated coupling of benzyl bromide with phenylethynylzinc
bromide. Okamoto and co-workers also observed (in minor
amount) the dimerization of benzyl bromide during a cobalt-
catalyzed benzyl-alkynyl coupling.8 There are plenty of re-
ports of the formation of radical intermediates using Grignard
reagents in the presence of transition metal catalyst.9 However,
there have been only a few reports10 for involvement of radical
intermediates during the interaction of halo compounds and
Grignards reagents. Recently, Oshima and co-workers11 re-
ported an ethylmagnesium bromide-mediated radical cycliza-
tion of allyl b-iodoacetals.
Alternatively, the dimer 2a could also be prepared via the
interaction of the bromo compound 1a0 with Bu3SnH and
AIBN or in situ generated Cp2TiCl, Scheme 6.
Bu3SnH/AIBN
benzene, reflux, 3 h
56%
SPh
CH2
SO2Ph
6
(or)
1a'
2a
+
10 (10%)
Cp2TiCl2/Zn
THF, rt, 5 h
53%
N
Scheme 6.
In order to generalize the dimerization process, the reaction
has to be tested with benzylic systems. To our surprise, benzyl
bromide 13 also underwent a smooth dimerization when inter-
acted with phenylmagnesium chloride at room temperature to
yield 1,2-diphenyl ethane 1413,14 and biphenyl 5 in 56 and
53% yields, Scheme 7. Since benzylmagnesium chloride is
stable and commercially available, it is certain that the dimer-
ization of 13 might proceed only through the intermediacy of
benzyl radical.
In order to get further insight into the mechanism of the
observed dimerization process, the interaction of bromo com-
pound 1a0 with alkylmagnesium halides such as isopropylmag-
nesium bromide, BuMgBr, Bu2Mg, and TMSCH2MgCl was
planned, Scheme 5. The reaction of bromo compound 1a0
with isopropylmagnesium bromide yielded the corresponding
alkylated products
9
along with 1-phenylsulfonyl-3-
Me
MgBr
i)
SPh
SPh
Me
Me
ii) H3O+
Me
Br
PhMgCl/THF
1a'
+
N
Me
N
+
5 (53%)
rt, 2 h
SO2Ph
SO2Ph
14 (56%)
13
9 (40%)
10 (20%)
i) PhMgCl/THF
ii) ZnBr2/THF
BuMgBr/THF
(or)
Bu2Mg/THF
rt, 1 h
13
+
14 (52%)
5 (40%)
SPh
Bu
1a'
2a
+
(40%, 55%)
N
Ph OH
SO2Ph
PhMgCl/THF
13
13
+
11 (30%, 20%)
O
15 (70%)
PhS
SPh
TMSCH2MgCl
rt, 1 h
rt, 2 h
2a (18%)
+
1a'
N
H
Scheme 7.
N
H
12 (35%)
Similar to the case of bromomethylindole 1a0, interaction of
benzyl bromide 12 with in situ generated phenylzinc bromide
Scheme 5.

N. Ramesh et al. / Tetrahedron 64 (2008) 2071e2079
2075
also furnished the dimer 14 and biphenyl 5. An attempt was
made to trap the intermediate benzyl radical as reported by
Roy and co-workers15 through the interaction of benzyl bro-
mide 13 and phenylmagnesium chloride in the presence of
cyclohexen-1-one. However, workup of the reaction afforded
Grignard addition product 15 [Mþ, 174.02 (87%)] and benzyl
bromide 13 was recovered unchanged, Scheme 7.
Finally, a cross-coupling experiment was performed with
mixture of bromo compounds 1a0 and 1e, Scheme 8. The inter-
action of 1:1 mixture of these bromo compounds with excess
of phenylmagnesium chloride followed by workup led to the
formation of respective self-dimerization products 2a/2e and
arylated products 8/16.6 It should be mentioned that not
even a trace of cross-coupled dimer 17 was observed.
internal standard on a JEOL 400, 500 and Bruker-300 spec-
trometers, respectively. Mass spectra were recorded on
a JEOL DX 303 HF spectrometer. Elemental analyses were
carried out on a PerkineElmer 240 B instrument.
4.2. Representative procedure for dimerization
1-Phenylsulfonyl-3-phenylthio-2-bromomethylindole 1a0
(0.5 g, 1.09 mmol) dissolved in dry THF (10 mL) was
stirred at 0e10 ꢁC under nitrogen atmosphere. To this
phenylmagnesium chloride (0.65 mL, 1.31 mmol, 2.0 M in
THF) was added slowly. The reaction mixture was slowly
raised to room temperature and stirred for 5 h. Then it
was quenched with saturated ammonium chloride solution
(10 mL), extracted with ethyl acetate (2ꢂ20 mL), and the
extracts were combined and dried (Na2SO4). Removal of
solvent followed by column chromatographic purification
(silica gel, hexane/EtOAc 9:1) afforded 2a (0.25 g, 60%).
PhMgCl/THF
1a'
1e
+
+
+
+
2a
2e
8
0 °C to rt, N2
5 h
N
4.2.1. 1,2-Bis(1-phenylsulfonyl)-3-(phenylthio)-1H-indol-2-
ylethane 2a
SO2Ph
16
SPh
Compound 2a (0.25 g, 60%) was obtained as a colorless
solid; mp 220 ꢁC; [Found: C, 66.30; H, 4.40; N, 3.92; S,
16.81. C42H32N2O4S4 requires C, 66.64; H, 4.26; N, 3.70; S,
16.94%]; Rf (10% EtOAc/hexane) 0.55; nmax (KBr) 1365,
1172 cmꢀ1; dH (400 MHz, CDCl3) 8.22 (2H, d, J 8.3 Hz,
ArH), 7.73 (4H, d, J 7.3 Hz, ArH), 7.53e7.51 (2H, m, ArH),
7.37 (4H, t, J 8.3 Hz, ArH), 7.32e7.27 (2H, m, ArH), 7.24
(2H, t, J 7.3 Hz, ArH), 7.16 (2H, t, J 7.8 Hz, ArH), 6.94e
6.92 (6H, m, ArH), 6.68e6.65 (4H, m, ArH), 3.77 (4H, s,
CH2); dC (75.5 MHz, CDCl3) 144.6, 138.8, 137.3, 136.6,
134.1, 130.9, 129.5, 128.7, 126.5, 126.3, 125.4, 125.2,
124.4, 120.3, 115.6, 113.7, 28.1; m/z (EI) 378 (Mþ, 16%).
N
SO2Ph
N
SO2Ph
17
Scheme 8.
Thus, the PhMgCl induced dimerization observed in the
case of bromomethylindoles was found to be successful even
with benzylbromide. Hence, it may be concluded that the ob-
served dimerization of benzyl/indolylmethyl bromides occurs
only through the intermediacy of the respective benzyl/indol-
ylmethyl radical.
4.2.2. 1,2-Bis(1-phenylsulfonyl)-3-(cyano)-1H-indol-2-
ylethane 2b
3. Summary
Following the general procedure, compound 2b (80 mg,
20%) was obtained as a colorless solid; mp 230 ꢁC; [Found:
C, 65.31; H, 3.91; N, 9.35; S, 10.67. C32H22N4O4S2 requires
C, 65.07; H, 3.75; N, 9.49; S, 10.86%]; Rf (10% EtOAc/hex-
ane) 0.50; nmax (KBr) 2221, 1366, 1187 cmꢀ1; dH (400 MHz,
CDCl3) 8.25 (2H, d, J 8.8 Hz, ArH), 7.86 (4H, d, J 7.8 Hz,
ArH), 7.61 (2H, t, J 7.4 Hz, ArH), 7.55 (2H, d, J 7.8 Hz,
ArH), 7.49 (4H, t, J 8.1 Hz, ArH), 7.44e7.42 (2H, m, ArH),
7.37 (2H, t, J 7.1 Hz, ArH), 3.82 (4H, s, CH2); dC
(100.6 MHz, CDCl3) 146.7, 137.6, 135.9, 134.8, 129.8,
127.1, 126.5 (2C), 125.1, 119.5, 115.1, 112.9, 96.5, 28.9.
In summary, we have carried out the interaction of N-phe-
nylsulfonyl-2/3/4-bromomethylindoles with alkyl Grignards
and arylmetal halides. The observed dimerization was ex-
tended to the benzylic bromide as well. Through different
set of reactions, an involvement of indolylmethyl/benzyl radi-
cal for the observed dimerization has been proved. An attempt
to trap the benzylic radical with cyclohexen-1-one was unsuc-
cessful. Further work is in progress to trap benzylic radical/
indolylmethyl radical through an intramolecular pathway.
Considering the enormous scope for tin free radical reaction,
radical generation using arylmetal halides may find applica-
tion in organic synthesis.
4.2.3. 1,2-Bis(1-phenylsulfonyl)-3-(methyl)-1H-indol-2-
ylethane 2c
4. Experimental
Following the general procedure, compound 2c (0.19 g,
48%) was obtained as a colorless solid; mp 268 ꢁC; [Found:
C, 67.52; H, 5.02; N, 4.97; S, 11.23. C32H28N2O4S2 requires
C, 67.58; H, 4.96; N, 4.93; S, 11.28%]; Rf (10% EtOAc/hex-
ane) 0.52; nmax (KBr) 1369, 1167 cmꢀ1; dH (300 MHz,
CDCl3) 8.22 (2H, d, J 8.1 Hz, ArH), 7.67 (4H, d, J 7.2 Hz,
ArH), 7.47 (2H, t, J 7.5 Hz, ArH), 7.35 (4H, t, J 7.2 Hz, ArH),
4.1. General
All melting points are uncorrected. IR spectra were re-
corded on a SHIMADZU FT-IR 8300 instrument. 1H and
13C NMR spectra were recorded in CDCl3 using TMS as an

2076
N. Ramesh et al. / Tetrahedron 64 (2008) 2071e2079
7.29e7.21 (6H, m, ArH), 3.45 (4H, s, CH2), 1.84 (6H, s,
CH3); dC (75.5 MHz, CDCl3) 138.7, 136.7, 135.2, 133.5,
131.7, 129.1, 126.2, 124.4, 123.6, 119.4, 118.7, 115.1,
29.7, 8.5.
4.2.8. Diethyl-2,20-(ethane-1,2-diyl)bis[1-(phenylsulfonyl)-
1H-indole-3-carboxylate] 2i
Following the general procedure, compound 2i (0.19 g,
48%) was obtained as a colorless solid; mp 178 ꢁC; [Found:
C, 63.19; H, 4.63; N, 4.02; S, 9.42. C36H32N2O8S2 requires
C, 63.14; H, 4.71; N, 4.09; S, 9.37%]; Rf (20% EtOAc/hexane)
0.48; nmax (KBr) 1707, 1377, 1175 cmꢀ1; dH (300 MHz,
CDCl3) 8.28 (2H, d, J 8.1 Hz, ArH), 7.96 (2H, d, J 7.8 Hz,
ArH), 7.83 (4H, d, J 7.8 Hz, ArH), 7.54 (2H, t, J 7.3 Hz,
ArH), 7.43 (4H, t, J 7.5 Hz, ArH), 7.35e7.24 (4H, m, ArH),
4.09 (4H, s, CH2), 3.57 (4H, q, J 7.2 Hz, COOCH2CH3),
1.02 (6H, t, J 6.9 Hz, COOCH2CH3); dC (75.5 MHz, CDCl3)
163.8, 145.7, 139.1, 136.2, 134.2, 129.5, 127.5, 126.4,
124.9, 124.2, 121.9, 114.4, 113.8, 60.2, 26.9, 13.9.
4.2.4. 1,2-Bis(1-benzoyl)-1H-indol-2-ylethane 2d
Following the general procedure, compound 2d (0.16 g,
42%) was obtained as a colorless liquid; [Found: C, 82.11;
H, 5.13; N, 5.91. C32H24N2O2 requires C, 82.03; H, 5.16; N,
5.98%]; nmax (KBr) 1690 cmꢀ1; Rf (5% EtOAc/hexane) 0.57;
dH (300 MHz, CDCl3) 7.63 (4H, d, J 6.9 Hz, ArH), 7.52
(2H, t, J 7.5 Hz, ArH), 7.56 (6H, t, J 7.8 Hz, ArH), 7.34e
7.28 (2H, m, ArH), 7.11 (4H, d, J 3.6 Hz, ArH), 6.32 (2H, s,
ArH), 4.24 (4H, s, CH2); dC (75.5 MHz, CDCl3) 170.0,
138.5, 137.2, 135.6, 132.9, 130.2, 130.1, 128.5, 122.7,
122.6, 119.8, 114.3, 108.6, 30.2.
4.2.9. Diethyl-2,20-(ethane-1,2-diyl)bis[5-methoxy-1-
(phenylsulfonyl)-1H-indole-3-carboxylate] 2j
4.2.5. 1,2-Bis(1-phenylsulfonyl)1H-indol-4-ylethane 2e
Following the general procedure, compound 2e (0.17 g,
45%) was obtained as a colorless solid; mp 200 ꢁC; [Found:
C, 66.59; H, 4.51; N, 5.23; S, 11.92. C30H24N2O4S2 requires
C, 66.65; H, 4.47; N, 5.18; S, 11.86%]; Rf (10% EtOAc/hex-
ane) 0.36; nmax (KBr) 1375, 1181 cmꢀ1; dH (300 MHz,
CDCl3) 7.86e7.80 (6H, m, ArH), 7.54e7.51 (2H, m, ArH),
7.46e7.41 (6H, m, ArH), 7.14 (2H, t, J 7.5 Hz, ArH), 6.92
(2H, d, J 7.2 Hz, ArH), 6.48 (2H, d, J 3.0 Hz, ArH), 3.20
(4H, s, CH2); dC (75 MHz, CDCl3) 138.3, 134.7, 134.5,
133.8, 129.9, 129.2, 126.8, 125.8, 124.7, 122.9, 111.4,
107.1, 34.1.
Following the general procedure, compound 2j (0.23 g,
55%) was obtained as a colorless solid; mp 224 ꢁC; [Found:
C, 61.19; H, 4.79; N, 3.71; S, 8.68. C38H36N2O10S2 requires
C, 61.28; H, 4.87; N, 3.76; S, 8.61]; Rf (20% EtOAc/hexane)
0.46; nmax (KBr) 1707, 1369, 1171 cmꢀ1; dH (300 MHz,
CDCl3) 8.16 (2H, d, J 9.3 Hz, ArH), 7.80 (4H, d, J 7.8 Hz,
ArH), 7.57e7.40 (8H, m, ArH), 6.94 (2H, dd, J 2.7 and
9.1 Hz, ArH), 4.04 (4H, s, CH2), 3.81 (6H, s, OCH3), 3.68
(4H, q, J 7.2 Hz, COOCH2CH3), 1.08 (6H, t, J 7.2 Hz,
COOCH2CH3); dC (75.5 MHz, CDCl3) 163.9, 156.9, 146.3,
138.9, 134.1, 130.7, 129.5, 128.7, 126.3, 115.3, 114.1,
113.6, 104.1, 60.3, 55.5, 27.2, 13.9.
4.2.6. 3-Benzyl-1-(phenylsulfonyl)-1H-indole 4
Interaction of bromo compound 1f with 1.2 equiv of phe-
nylmagnesium chloride using the above-mentioned procedure
followed by workup and column chromatographic purification
(silica gel, hexane/EtOAc 95:5) afforded 4 (0.25 g, 50%) as
a colorless solid; mp 65 ꢁC; [Found: C, 72.55; H, 4.89; N,
4.10; S, 9.25. C21H17NO2S requires C, 72.60; H, 4.93; N,
4.03; S, 9.23%]; Rf (5% EtOAc/hexane) 0.76; nmax (KBr)
1369, 1182 cmꢀ1; dH (300 MHz, CDCl3) 7.98 (1H, d, J
8.4 Hz, ArH), 7.83 (2H, d, J 7.5 Hz, ArH), 7.49 (1H, t, J
7.2 Hz, ArH), 7.41e7.35 (3H, m, ArH), 7.31e7.14 (8H, m,
ArH), 3.99 (2H, s, CH2); dC (75.5 MHz, CDCl3) 138.9,
138.2, 135.6, 133.7, 130.9, 129.2, 128.7, 128.6, 126.7,
126.5, 124.9, 123.9, 123.2, 122.8, 119.9, 113.8, 31.4.
4.2.10. Dimerization of bromo compound 1a0 using
phenylmagnesium chloride at low temperature
Phenylsulfonyl-3-phenylthio-2-bromomethylindole 1a0
(0.55 g, 1.20 mmol) dissolved in dry THF (10 mL) was stirred
at ꢀ78 ꢁC under a N2 atmosphere. To this phenylmagnesium
chloride (1.5 mL, 3.0 mmol, 2.0 M in THF) was added and
stirred for 3 h. Then the reaction mixture was slowly raised
to room temperature (by discontinuing the cooling system of
the low temperature bath), quenched with saturated NH4Cl so-
lution (5 mL), extracted with ethyl acetate (2ꢂ20 mL), and the
combined organic extract was dried (Na2SO4). Removal of the
solvent followed by column chromatographic purification (sil-
ica gel, hexane/EtOAc 95:5) afforded 2a (0.28 g, 60%), 5
(0.10 g, 52%), and 8 (50 mg, 10%).
4.2.7. 1,2-Bis(1-phenylsulfonyl)-3-(bromo)-1H-indol-2-
ylethane 2h
Data for 5: colorless solid; mp 71 ꢁC [lit.16 mp 70 ꢁC]; Rf
(hexane) 0.98; dH (300 MHz, CDCl3) 7.58 (4H, d, J 7.5 Hz,
ArH), 7.41 (4H, t, J 7.8 Hz, ArH), 7.31 (2H, t, J 7.5 Hz,
ArH); dC (75.5 MHz, CDCl3) 141.3, 128.9, 127.4, 127.3.
Data for 8: colorless solid; mp 122 ꢁC; [Found: C, 71.24;
H, 4.59; N, 3.13; S, 14.00. C27H21NO2S2 requires C, 71.18;
H, 4.65; N, 3.07; S, 14.08%]; Rf (10% EtOAc/hexane) 0.60;
nmax (KBr) 1367, 1178 cmꢀ1; dH (300 MHz, CDCl3) 8.26
(1H, d, J 8.4 Hz, ArH), 7.52 (1H, d, J 7.8 Hz, ArH), 7.46e
7.37 (4H, m, ArH), 7.31e7.12 (11H, m, ArH), 7.03 (2H, d,
J 6.6 Hz, ArH), 4.79 (2H, s, CH2); dC (75.5 MHz, CDCl3)
144.2, 138.4, 138.1, 136.7, 136.2, 133.6, 130.5, 129.5,
Following the general procedure, compound 2h (0.29 g,
71%) was obtained as a colorless solid; mp 208 ꢁC; [Found:
C, 51.51; H, 3.41; N, 4.16; S, 8.98. C30H22Br2N2O4S2 requires
C, 51.59; H, 3.17; N, 4.01; S, 9.18%]; Rf (20% EtOAc/hexane)
0.84; nmax (KBr) 1373, 1184 cmꢀ1; dH (400 MHz, CDCl3)
8.22 (2H, d, J 8.3 Hz, ArH), 7.77 (4H, d, J 7.3 Hz, ArH),
7.53e7.51 (2H, m, ArH), 7.43e7.25 (10H, m, ArH), 3.65
(4H, s, CH2); dC (100.6 MHz, CDCl3) 139.1, 136.7, 134.7,
130.1, 129.9, 129.4, 127.9, 126.3, 124.9, 120.3, 115.6,
104.8, 28.2.

N. Ramesh et al. / Tetrahedron 64 (2008) 2071e2079
2077
129.0, 128.9, 128.8, 128.4, 126.6, 126.4, 125.6, 125.4, 124.3,
120.1, 115.2, 112.8, 32.2.
Data for 10: colorless needles; mp 70 ꢁC [lit.13 mp 70 ꢁC];
Rf (10% EtOAc/hexane) 0.70; nmax (KBr) 1366, 1177 cmꢀ1
;
dH (300 MHz, CDCl3) 8.25 (1H, d, J 8.1 Hz, ArH), 7.79
(2H, d, J 7.5 Hz, ArH), 7.55 (1H, t, J 7.5 Hz, ArH), 7.44
(3H, t, J 6.2 Hz, ArH), 7.32 (1H, t, J 6.9 Hz, ArH), 7.21
(1H, t, J 6.9 Hz, ArH), 7.14e7.02 (3H, m, ArH), 6.93 (2H,
d, J 6.9 Hz, ArH), 2.74 (3H, s, CH3).
4.2.11. Dimerization of bromo compound 1a0 using in situ
generated phenylcopper at low temperature
Phenylmagnesium chloride (1.5 mL, 3.0 mmol, 2.0 M in
THF) was added to a stirred suspension of CuI (0.68 g,
3.59 mmol) in dry THF (20 mL) at ꢀ78 ꢁC. After 30 min, 1-
phenylsulfonyl-3-phenylthio-2-bromomethylindole 1a0 (0.55 g,
1.20 mmol) dissolved in dry THF (10 mL) was added and
stirred for 2 h. Then, the reaction mixture was slowly raised
to room temperature and quenched with saturated NH4Cl solu-
tion (5 mL). It was then extracted with ethyl acetate (2ꢂ
20 mL) and the combined organic extract was dried (Na2SO4).
Removal of solvent followed by column chromatographic pu-
rification (silica gel, hexane/EtOAc 95:5) afforded 2a (0.26 g,
56%), 5 (90 mg, 48%), and 8 (30 mg, 5%).
4.2.14. Interaction of bromo compound 1a0 with
n-butylmagnesium bromide
1-Phenylsulfonyl-3-phenylthio-2-bromomethylindole 1a0
(0.6 g, 1.31 mmol) dissolved in dry THF (10 mL) was stirred
at 0 ꢁC under a N2 atmosphere. To this freshly prepared n-bu-
tylmagnesium bromide [Mg, 0.21 g, 8.54 mmol; n-butyl bro-
mide, 0.90 g, 0.7 mL, 6.57 mmol in dry THF (30 mL) reflux
for 1 h] was added slowly. The reaction mixture was stirred
for 3 h, quenched with saturated NH4Cl solution (5 mL),
extracted with ethyl acetate (2ꢂ20 mL), and the combined
organic extract was dried (Na2SO4). Removal of the solvent
followed by column chromatographic purification (silica gel,
hexane/EtOAc 95:5) afforded 2a (0.2 g, 40%) and 11
(0.17 g, 30%).
4.2.12. 2-Benzyl-1-(phenylsulfonyl)-3-(phenylthio)-1H-
indole 8
Phenylmagnesium chloride (0.47 mL, 0.94 mmol) was
added to a stirred solution of B(OMe)3 (0.2 mL, 1.76 mmol)
in THF (10 mL) at 0 ꢁC under nitrogen atmosphere. After
20 min, Pd(PPh3)4 (0.12 g, 0.10 mmol) and 1-phenylsulfonyl-
3-phenylthio-2-bromomethylindole 1a0 (0.43 g, 0.94 mmol)
were added, and the reaction mixture was stirred at room
temperature for 12 h. It was then quenched with saturated
ammonium chloride solution (10 mL), extracted with ethyl
acetate (3ꢂ15 mL), and the combined organic extract was
dried (Na2SO4). The solvent was completely removed under
vacuo to afford 8 (0.27 g, 60%) as a colorless solid, mp
122 ꢁC.
Data for 11: thick orange liquid; [Found: C, 68.89; H, 5.87;
N, 3.19; S, 14.81. C25H25NO2S2 requires C, 68.93; H, 5.78; N,
3.22; S, 14.72%]; Rf (10% EtOAc/hexane) 0.80; nmax (KBr)
1366, 1190 cmꢀ1; dH (300 MHz, CDCl3) 8.23 (1H, d, J 8.4 Hz,
ArH), 7.73 (2H, d, J 7.8 Hz, ArH), 7.55 (1H, t, J 7.5 Hz, ArH),
7.44e7.34 (3H, m, ArH), 7.31 (1H, t, J 7.5 Hz, ArH), 7.20
(1H, t, J 7.2 Hz, ArH), 7.12e7.04 (3H, m, ArH), 6.88 (2H,
d, J 8.1 Hz, ArH), 3.20 (2H, t, J 7.5 Hz, CH2(CH2)3CH3),
1.65 (2H, quintet, J 7.5 Hz, CH2CH2(CH2)2CH3), 1.35e
1.28 (4H, m, CH2CH2(CH2)2CH3), 0.84 (3H, t, J 6.9 Hz,
CH2(CH2)3CH3); dC (75.5 MHz, CDCl3) 147.6, 138.8,
136.9, 136.7, 133.8, 130.9, 129.3, 128.8, 126.3, 126.1,
125.2, 125.1, 124.3, 119.7, 115.3, 111.1, 31.7, 30.6, 27.4,
22.3, 13.9.
4.2.13. Interaction of bromo compound 1a0 with
isopropylmagnesium bromide
1-Phenylsulfonyl-3-phenylthio-2-bromomethylindole 1a0
(0.5 g, 1.09 mmol) dissolved in dry THF (10 mL) was stirred
at 0 ꢁC under a N2 atmosphere. To this isopropylmagnesium
bromide (0.64 mL, 1.42 mmol, 1.0 M in THF) was added.
The reaction mixture was stirred for 1 h, quenched with satu-
rated NH4Cl solution (5 mL), extracted with ethyl acetate
(2ꢂ20 mL), and the combined organic extract was dried
(Na2SO4). Removal of solvent followed by column chromato-
graphic purification (silica gel, hexane/EtOAc 95:5) afforded 9
(0.18 g, 40%) and 10 (80 mg, 20%).
4.2.15. Interaction of bromo compound 1a0 with
dibutylmagnesium
1-Phenylsulfonyl-3-phenylthio-2-bromomethylindole 1a0
(0.6 g, 1.31 mmol) dissolved in dry THF (10 mL) was stirred
at 0 ꢁC under a N2 atmosphere. To this dibutylmagnesium
(2.6 mL, 2.61 mmol, 1.0 M in THF) was added. The reaction
mixture was stirred for 1 h, quenched with saturated NH4Cl
solution (10 mL), extracted with ethyl acetate (2ꢂ20 mL),
and the combined organic extract was dried (Na2SO4). Re-
moval of the solvent followed by column chromatographic pu-
rification (silica gel, hexane/EtOAc 95:5) afforded 2a (0.27 g,
55%) and 11 (0.11 g, 20%).
Data for 9: colorless solid; mp 90 ꢁC; [Found: C, 68.32; H,
5.45; N, 3.23; S, 15.17. C24H23NO2S2 requires C, 68.38; H,
5.50; N, 3.32; S, 15.21%]; Rf (10% EtOAc/hexane) 0.80;
nmax (KBr) 1372, 1167 cmꢀ1; dH (300 MHz, CDCl3) 8.22
(1H, d, J 8.4 Hz, ArH), 7.73 (2H, d, J 7.5 Hz, ArH), 7.52
(1H, t, J 7.6 Hz, ArH), 7.36e7.12 (6H, m, ArH), 7.00e6.88
(2H, m, ArH), 6.66e6.63 (2H, m, ArH), 3.11 (2H, d, J
8.8 Hz, CH2CH(CH3)2), 2.16 (1H, m, CH2CH(CH3)2), 0.94
(6H, d, J 6.6 Hz, CH2CH(CH3)2); dC (75.5 MHz, CDCl3)
146.4, 138.4, 136.5, 135.8, 134.0, 133.8, 131.0, 129.4,
128.7, 127.1, 126.4, 125.3, 124.1, 119.6, 115.7, 114.6, 35.8,
22.3, 13.5.
4.2.16. Interaction of bromo compound 1a0 with
trimethylsilylmethylmagnesium chloride
1-Phenylsulfonyl-3-phenylthio-2-bromomethylindole 1a0
(0.5 g, 1.09 mmol) dissolved in dry THF (10 mL) was stirred
at 0 ꢁC under a N2 atmosphere. To this freshly prepared trime-
thylsilylmethylmagnesium chloride [Mg, 70 mg, 2.92 mmol;
TMSCH2Cl, 0.27 g, 0.3 mL, 2.18 mmol in dry THF (20 mL)

2078
N. Ramesh et al. / Tetrahedron 64 (2008) 2071e2079
reflux for 1 h] was added slowly. The reaction mixture was
stirred for 1 h, quenched with saturated NH4Cl solution
(5 mL), extracted with ethyl acetate (2ꢂ20 mL), and the com-
bined organic extract was dried (Na2SO4). Removal of the sol-
vent followed by column chromatographic purification (silica
gel, hexane/EtOAc 95:5) afforded 2a (80 mg, 18%) and 12
(90 mg, 35%).
7.43 (4H, t, J 7.8 Hz, ArH), 7.35 (2H, t, J 6.0 Hz, ArH), 7.26
(4H, t, J 7.5 Hz, ArH), 7.20e7.16 (6H, m, ArH), 2.92 (4H, s,
CH2); dC (75.5 MHz, CDCl3) 141.8, 141.3, 129.7, 128.8,
128.4, 128.3, 127.3, 127.2, 37.9.
4.2.20. Dimerization of benzyl bromide 13 using in situ
generated phenylzinc bromide
Data for 12: colorless solid; mp 216 ꢁC; [Found: C, 75.63;
H, 5.01; N, 5.83; S, 13.52. C30H24N2S2 requires C, 75.59; H,
5.08; N, 5.88; S, 13.45%]; Rf (10% EtOAc/hexane) 0.52; nmax
(KBr) 3379 cmꢀ1; dH (400 MHz, CDCl3) 8.01 (2H, s, NH),
7.52 (2H, d, J 7.8 Hz, ArH), 7.17e7.10 (16H, m, ArH), 3.27
(4H, s, CH2); dC (100.6 MHz, CDCl3) 142.9, 139.3, 135.4,
130.1, 128.9, 127.6, 125.7, 124.9, 122.5, 120.9, 119.0,
111.1, 99.6, 26.3; m/z (EI) 238 (Mþ, 35%).
To a solution of phenylmagnesium chloride (5.3 mL,
10.51 mmol, 2.0 M in THF) in dry THF (20 mL), anhydrous
ZnBr2 (2.84 g, 12.61 mmol) was added and the mixture stirred
for 15 min. To this bromo compound 13 (0.5 mL, 4.21 mmol)
was added and the mixture stirred for 4 h. The usual workup
yielded mixture of diphenylethane 14 and biphenyl 5 in 52
1
and 40% yields (based on H NMR integration).
4.2.21. 2-Phenylcyclohex-2-enol 15
4.2.17. Dimerization of bromo compound 1a0 using
Bu3SnH/AIBN
To
a
stirred solution of cyclohexen-1-one (0.5 g,
5.20 mmol) in dry THF (10 mL), benzyl bromide 13
(0.74 mL, 6.25 mmol) was added at 0 ꢁC under N2 atmo-
sphere. To this phenylmagnesium chloride (5.2 mL,
10.42 mmol, 2.0 M in THF) was added. The reaction mixture
was stirred for 2 h, quenched with saturated NH4Cl solution
(10 mL), extracted with ethyl acetate (2ꢂ20 mL), and the
combined organic extract was dried (Na2SO4). Removal of
the solvent followed by column chromatographic purification
(silica gel, hexane/EtOAc 92:8) afforded 15 (0.63 g, 70%) as
a pale yellow liquid; [Found: C, 82.67; H, 8.17. C12H14O re-
quires C, 82.72; H, 8.10]; Rf (10% EtOAc/hexane) 0.30;
nmax liquid (KBr) 3415, 2933 cmꢀ1; dH (500 MHz, CDCl3)
7.51e7.48 (2H, m, ArH), 7.36e7.33 (2H, m, ArH), 7.27e
7.24 (1H, m, ArH), 6.05e6.02 (1H, m, CH]CHCH2), 5.79
(1H, d, J 10.0 Hz, CH]CH), 2.17e2.12 (2H, m, CH2), 1.99
(1H, s, OH), 1.89e1.62 (4H, m, CH2CH2); dC (125.7 MHz,
CDCl3) 147.9, 132.3, 130.8, 129.5, 128.2, 125.6, 72.3, 39.7,
25.1, 19.3.
To a stirred solution of bromo compound 1a0 (0.25 g,
1 mmol) in dry benzene (30 mL), Bu3SnH (0.2 mL,
1.2 mmol) and a catalytic amount of AIBN (20 mg) were
added under N2. Then it was refluxed for 3 h. Benzene was re-
moved in vacuo and the residue was dissolved in Et2O
(20 mL); a saturated KF solution (10 mL) was added. The re-
sulting mixture was stirred at room temperature for 4 h. Then
the organic layer was separated and washed with saturated
NaHCO3 solution (2ꢂ30 mL) followed by brine (2ꢂ20 mL)
and dried (MgSO4). Removal of the solvent followed by flash
column chromatographic purification (silica gel, 10% EtOAc
in hexane) afforded the dimerized compounds 2a (0.12 g,
56%) and 10 (20 mg, 10%).
4.2.18. Dimerization of bromo compound 1a0 using in situ
generated Cp2TiCl
A solution of titanocene dichloride (0.54 g, 2.18 mmol) in
dry THF (20 mL) was stirred with activated zinc dust (0.5 g,
7.63 mmol) for 1 h under N2. The resulting green solution
was then added dropwise to a stirred solution of bromo com-
pound 1a0 (0.5 g, 1.09 mmol) in dry THF (10 mL) at room
temperature over 30 min. The resulting mixture was stirred
for additional 5 h and decomposed with saturated aqueous so-
dium dihydrogen phosphate (10 mL) and the product extracted
using ethyl acetate (2ꢂ20 mL). The combined extracts were
washed successively with water (2ꢂ15 mL) and brine
(2ꢂ15 mL), and dried (Na2SO4). Removal of the solvent fol-
lowed by flash column chromatographic purification (silica
gel, 10% EtOAc in hexane) afforded the dimerized compounds
2a (0.22 g, 53%) and 10 (40 mg, 10%).
4.2.22. Attempted cross-coupling reaction of bromo
compound 1a0 and bromo compound 1e with
phenylmagnesium chloride
1-Phenylsulfonyl-3-phenylthio-2-bromomethylindole 1a0
(0.5 g, 1.09 mmol) and 1-phenylsulfonyl-4-bromomethylin-
dole 1e (0.38 g, 1.09 mmol) in dry THF (20 mL) were stirred
at 0 ꢁC under N2 atmosphere. To this phenylmagnesium chlo-
ride (2.7 mL, 5.45 mmol, 2.0 M in THF) was added. The reac-
tion mixture was stirred for 5 h, quenched with saturated
NH4Cl solution (10 mL), extracted with ethyl acetate
(2ꢂ20 mL), and the combined organic extract was dried
1
(Na2SO4). Removal of the solvent followed by H NMR ana-
lysis showed the presence of compounds 2a, 2e, 8, and 16.
4.2.19. Dimerization of benzyl bromide 13 using
phenylmagnesium chloride
4.2.23. 4-Benzyl-1-(phenylsulfonyl)-1H-indole 16
Interaction of benzyl bromide 13 (0.5 mL, 4.21 mmol) with
phenylmagnesium chloride (6.3 mL, 12.6 mmol, 2.0 M in
THF) at room temperature for 8 h followed by the usual
workup afforded inseparable mixture of diphenylethane 14
and biphenyl 5 in 56 and 53% yields (based on 1H NMR spec-
tral data17); dH (300 MHz, CDCl3) 7.59 (4H, t, J 7.1 Hz, ArH),
Phenylmagnesium chloride (0.5 mL, 1.0 mmol) was added
to a stirred solution of B(OMe)3 (0.23 mL, 2.0 mmol) in THF
(10 mL) at 0 ꢁC under nitrogen atmosphere. After 20 min,
Pd(PPh3)4 (0.12 g, 0.10 mmol) and 1-phenylsulfonyl-4-bromo-
methylindole 1e (0.35 g, 1.0 mmol) were added and the reac-
tion mixture was stirred at room temperature for 12 h. It was

N. Ramesh et al. / Tetrahedron 64 (2008) 2071e2079
2079
3. (a) Rajeswaran, W. G.; Srinivasan, P. C. Synthesis 1992, 835e836; (b) Rajes-
waran, W. G.; Srinivasan, P. C. Indian J. Heterocycl. Chem. 1992, 2, 89e91.
4. Mohanakrishnan, A. K.; Ramesh, N.; Prakash, C. Tetrahedron Lett. 2005,
46, 6983e6985.
then quenched with saturated ammonium chloride solution
(10 mL), extracted with ethyl acetate (3ꢂ15 mL), and the
combined organic extract was dried (Na2SO4). The solvent
was completely removed under vacuo to yield 16 as a colorless
thick liquid (0.24 g, 68%); [Found: C, 72.53; H, 4.89; N, 4.11;
S, 9.28. C21H17NO2S requires C, 72.60; H, 4.93; N, 4.03; S,
9.23%]; Rf (10% EtOAc/hexane) 0.55; nmax (KBr) 1369,
1171 cmꢀ1; dH (300 MHz, CDCl3) 7.77 (3H, d, J 7.5 Hz,
ArH), 7.44e7.36 (2H, m, ArH), 7.29 (2H, t, J 7.7 Hz, ArH),
7.16e7.03 (6H, m, ArH), 6.91 (1H, t, J 7.2 Hz, ArH), 6.54
(1H, d, J 3.0 Hz, ArH), 4.04 (2H, s, CH2); dC (75.5 MHz,
CDCl3) 139.1, 137.3, 133.8, 132.8, 132.7, 129.1, 128.2,
127.7, 127.4, 125.7, 125.1, 124.9, 123.8, 122.7, 110.6,
106.5, 28.7.
5. The required bromo/chloro compounds were prepared via allylic bromina-
tion/chlorination of the corresponding methylindoles using NBS/NCS in
the presence of a catalytic amount of benzoyl peroxide in CCl4 at reflux.
6. A sample of authentic benzylindole 8/16 was prepared using a Pd-medi-
ated coupling reaction of corresponding bromo compound with in situ
generated PhB(OMe)2.
7. Qian, H.; Negishi, E. Tetrahedron Lett. 2005, 46, 2927e2930.
8. Kuno, A.; Saino, N.; Kamachi, T.; Okamoto, S. Tetrahedron Lett. 2006,
47, 2591e2594.
9. (a) Nakao, J.; Inoue, R.; Shinokubo, H.; Oshima, K. J. Org. Chem. 1997,
62, 1910e1911; (b) Terao, J.; Saito, K.; Nii, S.; Kambe, N.; Sonoda, N.
J. Am. Chem. Soc. 1998, 120, 11822e11823; (c) Hayashi, Y.; Shinokubo,
H.; Oshima, K. Tetrahedron Lett. 1998, 39, 63e66; (d) Fujioka, T.;
Nakamura, T.; Yorimitsu, H.; Oshima, K. Org. Lett. 2002, 4, 2257e
2259; (e) Ikeda, Y.; Nakamura, T.; Yorimitsu, H.; Oshima, K. J. Am.
Chem. Soc. 2002, 124, 6514e6515.
Acknowledgements
10. (a) Ward, H. R.; Lawler, R. G.; Narzilli, T. A. Tetrahedron Lett. 1970, 47,
521e524; (b) Maeda, K.; Shinokubo, H.; Oshima, K. J. Org. Chem. 1996,
61, 6770e6771; (c) Inoue, A.; Shinokubo, H.; Oshima, K. Synlett 1999,
1582e1584.
We thank CSIR, New Delhi (01(2071)/06/EMR-II) for the
financial support. N.R. and C.P. thank CSIR for CSIR-SRF fel-
lowship. R.S. and V.D. thank UGC for fellowship. Authors
thank DST-FIST for 300 MHz NMR facility.
11. Inoue, A.; Shinokubo, H.; Oshima, K. Org. Lett. 2000, 2, 651e653.
12. Nagarathnam, D.; Vedachalam, M.; Srinivasan, P. C. Synthesis 1983,
156e157.
References and notes
´
13. (a) Barrero, A. F.; Herrador, M. M.; Quılez del Moral, J. F.; Arteaga, P.;
´
Arteaga, J. F.; Piedra, M.; Sanchez, E. M. Org. Lett. 2005, 7, 2301e
´
2304; (b) Barrero, A. F.; Herrador, M. M.; Quılez del Moral, J. F.;
Arteaga, P.; Akssira, M.; Hanbali, F. E.; Arteaga, J. F.; Dieguez, H. R.;
1. (a) Gribble, G. W.; Allen, R. W.; Lehoullier, C. S.; Eaton, J.; Easton,
N. R.; Slayton, R. I.; Sibi, M. P. J. Org. Chem. 1981, 46, 1025e1026;
(b) Gribble, G. W.; Saulnier, M. G.; Sibi, M. P.; Obaza-Nutaitis, J. A.
J. Org. Chem. 1984, 49, 4518e4523; (c) Sha, C.-K.; Yang, J. F. Tetra-
hedron 1992, 48, 10645e10654; (d) Nagarathnam, D. Synthesis 1992,
743e745; (e) Mohanakrishnan, A. K.; Srinivasan, P. C. J. Org. Chem.
1995, 60, 1939e1946; (f) Mohanakrishnan, A. K.; Srinivasan, P. C. Tetra-
hedron Lett. 1996, 37, 2659e2662.
2. (a) Mohanakrishnan, A. K.; Balamurugan, R. Tetrahedron Lett. 2005, 46,
4045e4048; (b) Mohanakrishnan, A. K.; Ramesh, N. Tetrahedron Lett.
2005, 46, 4231e4233; (c) Mohanakrishnan, A. K.; Balamurugan, R.;
Ramesh, N. Tetrahedron Lett. 2005, 46, 8189e8193.
´
´
Sanchez, E. M. J. Org. Chem. 2007, 72, 2251e2254.
14. Yanglong, Q.; Guisheng, L.; Huang, Y.-Z. J. Organomet. Chem. 1990,
381, 29e34.
15. Mandal, S. K.; Jana, S.; Roy, S. C. Tetrahedron Lett. 2005, 46, 6115e
6117.
16. The Aldrich Catalogue; Sigma-Aldrich Chemicals: Bangalore, India,
2007e08; p 329.
17. Pouchert, C. J.; Behnke, J.; The Aldrich Library of 13C and 1H FTNMR
Spectra, 1st ed.; Aldrich Chemical Company: Milwaukee, WI, USA,
1993; Vol. 2, pp 8A and 28C.