Oxidative coupling of indoles using thallium(III) trifluoroacetate

Article abstract of DOI:10.1016/j.tet.2008.05.133

The oxidative coupling of polysubstituted electron-rich indoles mediated by thallium trifluoroacetate was found to be a facile, clean, and high yielding reaction. Indolic coupling sites were determined by the nature of the substituents present, with dimerisation at the indole 2-position being the dominant outcome. Indoles bearing two potential reaction sites with similar reactivity were additionally found to undergo heterocoupling.

Full text of DOI:10.1016/j.tet.2008.05.133

Tetrahedron 64 (2008) 7787–7795
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Oxidative coupling of indoles using thallium(III) trifluoroacetate
,
a
a
a
Paul A. Keller a , Nageshwar R. Yepuri , Michael J. Kelso , Michael Mariani ,
*
Brian W. Skelton b, Allan H. White b
a School of Chemistry, University of Wollongong, Wollongong, NSW 2522, Australia
b School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, Crawley WA 6009, Australia
a r t i c l e i n f o
a b s t r a c t
Article history:
The oxidative coupling of polysubstituted electron-rich indoles mediated by thallium trifluoroacetate
was found to be a facile, clean, and high yielding reaction. Indolic coupling sites were determined by the
nature of the substituents present, with dimerisation at the indole 2-position being the dominant out-
come. Indoles bearing two potential reaction sites with similar reactivity were additionally found to
undergo heterocoupling.
Received 22 March 2008
Received in revised form 12 May 2008
Accepted 30 May 2008
Available online 5 June 2008
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
effecting oxidative dimerisations of electron-rich naphthyl com-
pounds,8 2-substituted indoles9 and indolocarbazoles.10 We now
Numerous synthetic methods are available for introducing the
biaryl linkage into organic compounds.1,2 The popular Suzuki re-
action and its related organometallic cousins employ specific
functionality to direct the sites of reaction and many examples have
of course been reported.3 Also well known are oxidative coupling
methods,4 where biaryl bonds are formed directly at unsubstituted
aryl sites, which have been activated either by the aryl units
themselves or by ring substituents. The clear advantage of oxidative
coupling over organometallic methods, particularly for the forma-
tion of biaryl dimers is that it requires no prior functionalisation of
the aromatic reaction site(s).1
As part of our ongoing investigations into the biological activi-
ties of homo- and hetero-dimeric aromatic systems,5 we wished to
identify simple methods for constructing focused libraries of
symmetrical and non-symmetrical biindoles incorporating biaryl
linkages at the indole 2 and 7-positions. While there have been
many syntheses of 2,20-biindoles,6 the procedures usually involve
numerous steps and are impractical for preparing multiple ana-
logues. In the case of 7,70-biindoles, very few syntheses have been
reported but one notable example7 describes the oxidative cou-
pling of 4,6-dimethoxy-2,3-diphenylindole in the presence of qui-
none, chloranil or dichlorodicyanoquinone to yield the
homodimeric 7,70-coupled biindole in 100%, 70% and 60% yields,
respectively.
wish to report that thallium(III) trifluoroacetate, in combination
with BF3$Et2O, is an effective reagent for the oxidative coupling of
electron-rich polysubstituted indoles.
2. Results and discussion
2.1. Synthesis of 7,70-biindoles
Our preliminary investigations focussed on the 7,70-dimerisa-
tion of a model compound 2,3-dicarbomethoxy-4,6-dimethoxy-
indole 1. This indole monomer had its most reactive positions (C2
and C3) blocked, allowing the two methoxy substituents to activate
the C7-position to oxidative dimerisation. The use of thallium tri-
fluoroacetate/BF3$Et2O as oxidant afforded the 7,70-dimer 2 as the
sole product in excellent yield (Scheme 1). This rapid and selective
reaction was superior to the previously reported oxidation, which
employed ICl and produced 2 in 34% yield along with 31% of the
iodinated monomer 3.7
2.2. Synthesis of 2,20-biindoles
Formation of 2,20-biindoles by oxidative dimerisation of 3-aryl-
4,6-dimethoxyindoles using thallium trifluoroacetate/BF3$Et2O
was explored next. These monomers had two potential dimerisa-
tion sites (C2 and C7) but initial experiments showed that indole N-
protection limited dimerisation at the 7-position (data not shown).
The substituted indole monomers 4–711 were NH protected using
sodium hydride and benzenesulfonyl chloride to give 8–11 after
recrystallisation from methanol (Scheme 2). Clean formation of the
2,20-dimers was achieved by treating an acetonitrile solution of the
Attracted by the simplicity of oxidative coupling methods, we
sought to identify a suitable oxidant for preparing our biindole li-
braries. Thallium(III) trifluoroacetate has previously been used for
* Corresponding author. Tel.: þ61 2 4221 4692; fax: þ61 2 4221 4287.
E-mail address: keller@uow.edu.au (P.A. Keller).
protected indole monomers with
a half-mole equivalent of
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.05.133

7788
P.A. Keller et al. / Tetrahedron 64 (2008) 7787–7795
OMe
CO2Me
CO2Me
OMe
I
CO2Me
CO2Me
OMe
i. Tl(CF3CO2)3, AcCN
ii. BF3.OEt2
CO2Me
CO2Me
N
MeO
H
N
MeO
H
H
N
N
MeO
OMe
H
MeO2C
MeO2C
OMe
83%
2
1
3
Scheme 1.
12–15 can exist as atropoisomers due to the presence of four ortho
substituents. Presumably both of these isomers were formed in
each of the products as racemic mixtures.
i. NaH
ii. benzenesulfonyl
chloride
OMe
OMe
X
X
Based on a mechanism previously proposed for thallium(III)
promoted oxidative dimerisations,8 we postulate that oxidative
2,20-dimerisation of these indoles proceeds via an initial one-
electron transfer from the electron-rich indole substrate to thal-
lium(III) to form an indole radical cation (Scheme 3). Subsequent
electrophilic substitution with a second indole substrate, followed
by oxidative aromatisation, gives the symmetrical 2,20-dimers.
Initial attempts to remove the benzenesulfonyl protecting group
from the dimers using thionyl chloride at room temperature yiel-
ded complex mixtures. Deprotection was eventually achieved, al-
beit in disappointing yields of 10–15%, by heating the dimers at
reflux for 4 h in a 20% solution of sodium hydroxide. Dimer 17 was
spectroscopically identical to the reported compound that had
previously been synthesised in only 1.5% yield.12
N
R
N
MeO
MeO
H
8-11
4-7
_
ACN/0°C
0.5 equiv. TTFA
10 equiv. BF3.OEt2
RT
R =
SO2
OMe
X
OMe
NaOH
X
H
N
20%
MeO
Δ
)
N
H
OMe
2
N
R
MeO
X
MeO
The poor outcome in the final deprotection step led us to in-
vestigate indole 2,20-dimerisations using alternative protecting
groups. A selection of 3-arylsubstituted indoles were N-protected
with various aryl or alkyl sulfonates and then subjected to the
dimerisation/deprotection sequence. These results are summarised
in Scheme 4. All of the protection and dimerisation reactions pro-
ceeded smoothly and in good yield with the exception of N-4-
nitrobenzenesulfonyl-3-(p-nitrophenyl)indole 21, which produced
no dimer and quantitatively returned the starting material even
after prolonged reaction times. This was not unexpected given the
failure of compound 11 to undergo dimerisation. Confirmation of
16-18
12-15
Yield
X
deprotected
dimer
monomer
dimer
p -MeOC6H4
Ph
p-BrC6H4
p-NO2C6H4
65% 8
70% 9
65% 10
65% 11
70% 12
70% 13
74% 14
0% 15
15% 16
15% 17
10% 18
N/A
Scheme 2.
thallium(III) trifluoroacetate, followed by addition of excess
BF3$Et2O. After 1 h of stirring at room temperature, the dimers
were isolated and recrystallised from methanol/dichloromethane.
Compound 11 bearing the strongly electron-withdrawing p-
NO2C6H4 at the indole 3-position did not couple under these con-
ditions, even after prolonged reaction.
As a representative example, the structure of 12 was supported
by analysis of the mass spectrum (ES), which showed a peak at m/z
845 assigned as the [Mþ1] ion. Further support was provided by
the 1H NMR spectra, which showed the disappearance of a peak at
7.31 ppm assigned to H2 in 8. The presence of only ‘one set’ of peaks
in the 1H NMR spectrum was consistent with the formation of
a symmetrical dimer. Comparison of the 1H NMR spectrum of 12
with that of the monomer 8 showed a shift in the aromatic peaks
assigned to the benzenesulfonyl group from 7.89–7.56 to 7.53–
7.30 ppm, and those assigned to the 3-aryl ring from 7.47–6.92 to
7.03–6.65 ppm. The structure of 12 was eventually confirmed by
a single crystal X-ray study (Fig. 1), which indicated that both
phenyl rings are aligned to one side of the molecule, accounting for
the downfield shifts of the aromatic signals in the NMR spectra of
the dimer 12 relative to the monomer 8. The 2,20-dimeric indoles
Figure 1. Molecular (ORTEP) projection of 12 down the quasi-two-fold axis.

P.A. Keller et al. / Tetrahedron 64 (2008) 7787–7795
OMe
7789
OMe
X
X
TTFA
N
N
MeO
OMe
MeO
R
R
X
N
MeO
R
OMe
OMe
X
X
R
N
-e
H
MeO
MeO
)
-2H
2
N
R
N
R
H
X
Scheme 3.
the structure of 28 was provided from a single crystal X-ray study
(Fig. 2).
Figure 2. Molecular (ORTEP) projection of 28 down the crystallographic two-fold axis.
Different reaction conditions were trialled for deprotection of
the dimers using thiophenol, DMF and K2CO3 at room temperature.
Only 29 gave the deprotected 2,20-biindole 16 in 25% yield, a slight
improvement over the 15% obtained from 12 by heating at reflux in
NaOH (Scheme 2). All other deprotection reactions again resulted in
complex mixtures.
2.3. Oxidative dimerisation with N-acyl protected indoles
The effects of indole N-protection were further explored using
acetyl, trifluoroacetyl and Boc groups. The results from the pro-
tection, dimerisation and deprotection reactions are summarised in
Scheme 5.
OMe
X
OMe
X
i. NaH
ii. sulfonylchloride
N
R
MeO
N
MeO
Indole acetylation was achieved using tetrabutylammonium
hexafluorophosphate with potassium hydroxide and CH2Cl2 under
phase transfer conditions. Trifluoroacetyl protection of the indoles
was carried out using a modified literature protocol.11 Oxidative
dimerisation was attempted on compounds 30–34 using the con-
ditions described above. In stark contrast to monomers 8 and 24
(which contain 3-p-methoxyphenyl indolic substituents and N-
phenylsulfonyl and N-methylsulfonyl groups, respectively) the
analogous N-acetyl and N-trifluoroacetyl-protected indoles 30 and
32 yielded no 2,20-biindoles. Inexplicably, the corresponding N-Boc
derivative 34 produced a complex mixture of products. Further-
more, given that compounds 11 and 21 (which carry 3-p-nitro-
phenyl indolic substituents) failed to undergo dimerisation, it was
very surprising to find that the N-acetyl protected 3-(p-nitro-
phenyl)indole 31 dimerised to 35 in 30% yield! What was perhaps
even more surprising was the finding that the 3-(p-nitro-
phenyl)indole 33 gave no trace of the 2,2-dimer but instead pro-
duced the 2,70,7,700-terindole 36 in 35% yield (Scheme 5). The
remaining mass was identified as the starting indole 33 and its N-
deprotected precursor.
H
19-24
0.5 equiv. TTF,A
10 equiv. BF3·O(Et)2, CH3CN, 0 °C
OMe
X
)
2
N
R
MeO
25-29
thiophenol,
DMF, K2CO3
OMe
X
H
MeO
N
N
H
OMe
X
MeO
16
Support for the structure of the trimer 36 was provided by its
mass spectrum (ES), which showed a peak at 1179 corresponding to
the Mþ1 ion. Analysis of the 1H NMR spectrum showed singlet
peaks at 6.73, 6.66 and 6.44 ppm corresponding to the H50, H5 and
H500 protons. These three protons showed no meta-coupling to their
respective H7 protons (usually observed), suggesting the molecule
contains 2,70- and 7,700-linkages. Additionally, one H2 signal was
absent from the 1H NMR spectrum while there were clearly two
other singlets at 7.21 and 6.95 ppm corresponding to the H20 and
H200 protons. The proposed structure was fully supported by
gHMBC, gCOSY and NOESY correlations.
The mechanism for the formation of 36 is not clear, although on
the basis of current knowledge about TTFA promoted oxidations
and dimerisation of indoles,8,13 it may be due to the p-nitro group
and trifluoroacetate group at the N1-position not activating the 2-
position to the same level as occurs in the examples that un-
derwent coupling. This would allow reaction at the C7-position to
Yield
R
X
deprotected
dimer
Complex
mixture
Complex
mixture
monomer dimer
p-Me
C6H4SO2
p-BrC6H4
70% 19 70% 25
p-NO2
C6H4SO2
70% 26
p-BrC6H4
65% 20
65% 21
p-
p-NO2
C6H4SO2
NR
-
NO2C6H4
Complex
mixture
Complex
mixture
MeSO2
MeSO2
MeSO2
Ph
75% 22 70% 27
70% 23
p-BrC6H4
75% 28
p-
25% 16
75% 24 70% 29
OMeC6H4
Scheme 4.

7790
P.A. Keller et al. / Tetrahedron 64 (2008) 7787–7795
NO2
starting material recovered. Interestingly, 4,6-dimethoxy-3-(p-
nitrophenyl)indole 6 gave only the 2,70-dimer 37 (20%) with no
traces of formation of 2,20-dimer.
OMe
OMe
5'
5
OMe
X
OMe
H
OMe
N
N
R
MeO
RN
R
N
N
H
MeO
OMe
2'
X
NO2
OMe
2''
16,18
2,2'-biindole
5''
OMe
OMe
X
36
O2N
CH3CN, 0 °C, 0.5 equiv. TTFA,
3 equiv. BF3·O(Et)2
N
MeO
H
CH3CN, 0 °C, 0.5 equiv. TTFA,
12 equiv. BF3.OEt2
R = COCF3
X
4, 6, 7
OMe
OMe
X
OMe
OMe
X
OMe
N
MeO
H
N
N
R
MeO
HN
MeO
H
X
37
30-34
2,7'-biindole
Yield
CH3CN, 0 ºC, 0.5 equiv. TTFA,
12 equiv. BF3.OEt2
R = COCH3
X
2,2′-dimer
2,7′-dimer
p-OMePh
p-BrPh
35% 16
20% 18
-
-
NO2
-
p-NO2Ph
15% 37
OMe
R
N
OMe
Scheme 6.
N
R
MeO
For all oxidative coupling reactions attempted without N-pro-
tecting groups the reactions took longer and returned significant
quantities of starting material, suggesting that dimerisation is fa-
cilitated by N-protection. The results also suggest that the alkyl or
arylsulfonyl groups may help in the regiospecificity of the 2,20-
dimerisation provided the 3-aryl substituent is mildly electron-
withdrawing or electron-donating.
OMe
O2N
35
Yield
dimer
R
X
monomer
trimer
NR
p-OMePh
COCH3
65% 30
NR
3. Conclusions
COCH3 p-NO2Ph
COCF3 p-OMePh
COCF3 p-NO2Ph
57% 31
60% 32
60% 33
2,2′- dimer
-
30% 35
Oxidative coupling of indoles with thallium(III) trifluoroacetate
provides good to excellent yields of 2,20-dimers. Protecting groups
such as benzenesulfonyl, tosyl or methanesulfonyl aid formation of
the 2,20-dimer, providedthat the para substituentonthe 3-aryl ring is
mildly deactivating or an electron-donating group. When the
3-aryl ring bears a para substituent, which is a strong electron-
withdrawing group, e.g., NO2, no reaction is observed unless an N-
acetyl protecting group is present, which leads to 2,70-dimerisation.
Changing the indole N-protecting group to a trifluoroacetate group
deactivatesC2andactivatesC7suchthattrimeric-indolesareformed.
NR
NR
-
-
2,7′,7,7′′- trimer
35% 36
Boc
p-OMePh
99% 34
-
Scheme 5.
become a significant process. The 2,70-dimer could then undergo
further oxidative coupling between the 7 and 70-positions yielding
the 2,70,7,700-trimer 36.
4. Experimental
4.1. General
2.4. Thallium(III) trifluoroacetate mediated coupling of
4,6-dimethoxy-3-aryl indoles without N-protection
Melting point determinations were carried out on a Gallenkamp
melting point apparatus. Chemical ionisation (CI) and electron
impact (EI) mass spectra were obtained on a Shimadzu QP-5000
mass spectrometer by a direct insertion technique with an electron
beam energy of 70 eV. Electrospray (ESI) mass spectra were
obtained on a VG Autospec spectrometer. High-resolution mass
spectra (HRMS) were determined on a micromass QTof2 spec-
trometer using polyethylene glycol or polypropylene glycol as the
internal standard. The m/z values are stated with their peak
The oxidative dimerisation of indoles 4,
6 and 7 using
thallium(III) trifluoroacetate was attempted in the absence of NH
protecting groups. After preliminary optimisation reactions, it was
found that 3–5 equiv of the Lewis acid were best added at 0 ꢀC
before continued stirring at room temperature for 3 h. The results
are summarised in Scheme 6. Indole 4 gave the 2,20-dimer 16 in 35%
yield, the remainder being starting material and other baseline
products. Indole 6 gave 20% of 2,20-dimer 18 with 50% of the

P.A. Keller et al. / Tetrahedron 64 (2008) 7787–7795
7791
intensity as a percentage in parentheses. Proton and carbon nuclear
magnetic resonance (NMR) spectra were obtained as specified on
a Varian Mercury 300 MHz or Varian Inova 500 MHz spectrometer.
Spectra were recorded in the specified deuterated solvent, and
referenced to the residual non-deuterated solvent signal. Chemical
(0.32 g, 8.0 mmol) and benzenesulfonyl chloride (1.40 g, 7.9 mmol)
to give the indole 9 (2.14 g, 69%) as a white solid, mp 125–128 ꢀC. 1H
NMR
7.36 (1H, s, H2), 7.20 (1H, d, J¼3.0 Hz, H7), 6.33 (1H, d, J¼3.0 Hz, H5),
3.95 (1H, s, C4 OCH3), 3.65 (1H, s, C6 OCH3). 13C NMR
: 159.5 (C6),
d
: 7.90–7.54 (5H, m, sulfonyl ArH00), 7.46–7.36 (5H, m, ArH0),
d
shifts (d) in parts per million were measured relative to the internal
154.5 (C4), 139.0 (C7a), 138.0 (ArC40), 134.0 (sulfonylArC400), 129.5
(sulfonyl ArC200 and 600), 129.2 (sulfonyl ArC100), 129.0 (sulfonyl
ArC300 and 500), 128.0 (ArC40), 127.5 (ArC20 and 60), 127.0 (ArC30 and
50), 124.7 (C3), 122.0 (C2), 112.5 (C3a), 95.0 (C7), 90.0 (C5), 56.0 (C4
OCH3), 55.7 (C6 OCH3). ES-MS m/z: 394 ([Mþ1]þ, 80%), 310 (25),
254 (100), 187 (50), 141 (20); ES-HRMS m/z: calcd for [Mþ1]þ
C22H20NO4S 394.1113; found 394.1108.
standard. Analytical thin layer chromatography (TLC) was carried
out on Merck silica gel 60 F254 pre-coated aluminium plates with
a thickness of 0.2 mm. All column chromatography was performed
under ‘flash’ conditions on Merck silica gel 60 (230–400 mesh).
Chromatography solvent mixtures were measured by volume. So-
dium hydride was used as a dispersion in oil. Organic solvent ex-
tracts were dried with anhydrous magnesium sulfate. All
compounds were judged to be of greater than 95% purity based
upon 1H NMR and TLC analysis.
4.2.3. N-Benzenesulfonyl-3-(4-bromophenyl)-4,6-
dimethoxyindole (10)
This was prepared by general procedure (A) using 4,6-di-
methoxy-3-(4-bromophenyl)indole 6 (2.50 g, 7.5 mmol), sodium
hydride (0.30 g, 7.5 mmol, 60% dispersion in oil) and benzene-
sulfonyl chloride (1.33 g, 7.5 mmol) to give the indole 10 (2.49 g,
4.1.1. 7,70-Bi(4,6-dimethoxyindolyl)-2,20,3,30-tetracarboxylate (2)
To a solution of dimethyl 4,6-dimethoxyindole-2,3-dicarboxy-
late 1 (460 mg, 1.57 mmol) and thallium trifluoroacetate (432 mg,
0.79 mmol) in dry acetonitrile (40 mL) was added BF3$(CH3CH2)2O
70%) as a white solid, mp 137–139 ꢀC. 1H NMR
d: 7.96 (2H, d,
(785 mL, 0.79 mmol) and the reaction allowed to stir at room tem-
J¼8.7 Hz, sulfonyl ArH200 and 600), 7.56 (2H, m, sulfonyl ArH300 and
500), 7.49–7.54 (4H, m, ArH20, 30, 50 and 60), 7.25–7.48 (1H, m, sul-
fonyl ArH400), 7.34 (1H, s, H2), 7.19 (1H, d, J¼1.8 Hz, H7), 6.33 (1H, d,
J¼1.8 Hz, H5), 3.88 (3H, s, C4 OCH3), 3.71 (3H, s, C6 OCH3). 13C NMR
perature for 40 min. The reaction was then extracted with water
(100 mL) and CH2Cl2 (4ꢁ50 mL). The combined organic extracts
were dried (MgSO4) and concentrated and the residue subjected to
flash silica gel column chromatography (5:1 CH2Cl2/EtOAc) to yield
the dimer 2 (420 mg, 83%) as a pale yellow powder, which was
spectroscopically identical to that reported.7
d
: 160.0 (C6), 154.0 (C4), 138.3 (C7a), 138.0 (ArC40), 134.0 (sulfonyl
ArC100),133.0 (sulfonyl ArC400), 131.3 (ArC20 and 60), 130.9 (ArC30 and
50), 129.5 (sulfonyl ArC200 and 600), 127.0 (sulfonyl ArC300 and 500),
123.7 (ArC100),121.7 (C2),121.4 (C3),112.9 (C3a), 96.0 (C7), 90.0 (C5),
58.5 (C4 OCH3), 58.0 (C6 OCH3). CIMS m/z: 474 ([Mþ1]þ 81Br 20%),
332 (15), 173 (30), 159 (75), 143 (100); EI-HRMS m/z: calcd for
4.2. General procedure (A) for the synthesis of protected
indole starting materials
C
22H18NO4S79Br 471.0139; found 471.0126.
To a stirred solution of 4,6-dimethoxy-3-phenylindole (1 mol) in
CH2Cl2 under a nitrogen atmosphere was added sodium hydride
(1 mol, 60% dispersion in oil) and the reaction then stirred for
25 min. The sulfonyl chloride (1 mol) was then added and the re-
action left to stir at 25 ꢀC for an additional 2 h. The solvent was then
removed under reduced pressure and the resultant residue was
suspended in water (50 mL) and extracted with CH2Cl2 (3ꢁ100 mL).
The organic fractions were combined, dried (MgSO4), concentrated
under reduced pressure and the residue recrystallised from meth-
anol yielding the corresponding protected indole.
4.2.4. N-Benzenesulfonyl-4,6-dimethoxy-3-(4-nitrophenyl)-
indole (11)
This was prepared by general procedure (A) using 4,6-di-
methoxy-3-(4-nitrophenyl)indole 7 (2.00 g, 6.7 mmol), sodium
hydride (0.27 g 6.7 mmol) and benzenesulfonyl chloride (1.18 g,
6.7 mmol) to give the indole 10 (1.78 g, 61%) as a white solid, mp
150–152 ꢀC. 1H NMR
d
: 8.22 (2H, d, J¼9.0 Hz, ArH20 and 60), 7.93
(2H, d, J¼9.0 Hz, ArH30 and 50), 7.69 (2H, d, J¼8.7 Hz, sulfonyl ArH200
and 600), 7.59–7.45 (2H, m, sulfonyl ArH300, 400 and 500), 7.19 (1H, d,
J¼2.1 Hz, H7), 6.36 (1H, d, J¼2.1 Hz, H5), 3.90 (3H, s, C4 OCH3), 3.79
4.2.1. N-Benzenesulfonyl-4,6-dimethoxy-3-(4-methoxyphenyl)-
indole (8)
(3H, s, C6 OCH3). 13C NMR
d: 159.8 (C6), 154.6 (C4), 146.9 (sulfonyl
ArC100), 141.1 (sulfonyl ArC100), 138.1 (C7a), 137.7 (ArC4), 134.4
(sulfonyl ArC400), 130.3 (ArC20 and 60), 129.6 (sulfonyl ArC30 and 50),
127.1 (ArC30 and 50), 123.1 (sulfonyl ArC200 and 600), 122.7 (C2), 112.3
(C3a), 95.6 (C7), 89.9 (C5), 56.6 (C4 OCH3), 55.4 (C6 OCH3). ES-MS
m/z: 439 ([Mþ1]þ, 100%); EI-HRMS m/z: calcd for C22H18N2O6S
438.0885; found 438.0907.
This was prepared by general procedure (A) using 4,6-di-
methoxy-3-(4-methoxyphenyl)indole
4 (2.00 g, 7.0 mmol), so-
dium hydride (0.28 g, 7.0 mmol in 60% oil dispersion) and
benzenesulfonyl chloride (1.23 g, 7.0 mmol) to give the indole 8
(2.11 g, 73%) as a white solid, mp 131–133 ꢀC. 1H NMR
d: 7.89 (2H,
d, J¼7.5 Hz, sulfonyl ArH200 and 600), 7.59–7.41 (3H, m, sulfonyl
ArH300, 400 and 500), 7.47 (2H, d, J¼8.7 Hz, ArH20 and 60), 7.31 (1H,
s, H2), 7.20 (1H, d, J¼1.8 Hz, H7), 6.92 (2H, d, J¼8.7 Hz, ArH30 and
50), 6.32 (1H, d, J¼1.8 Hz, H5), 3.88 (3H, s, C4 OCH3), 3.84 (3H, s,
4.2.5. 3-(4-Bromophenyl)-4,6-dimethoxy-N-(40-methylphenyl-
sulfonyl)indole (19)
This was prepared by general procedure (A) using 4,6-di-
methoxy-3-(4-bromophenyl)indole 6 (2.00 g, 6.0 mmol), sodium
hydride (0.24 g, 6.0 mmol) and p-toluenesulfonyl chloride (0.19 g,
6.0 mmol) to give the indole 19 (2.20 g, 76%) as white solid, mp
C6 OCH3), 3.71 (3H, s, ArC4 OCH3). 13C NMR
d
: 159.5 (ArC40),
159.0 (C6), 155.0 (C4), 138.5 (C7a), 137.5 (sulfonyl ArC100), 134.0
(sulfonyl ArC400), 130.8 (sulfonyl ArC200 and 600), 129.4 (sulfonyl
ArC300 and 500), 126.9 (C3), 124.4 (ArC10), 121.1 (C2), 113.3 (ArC30
and 50), 110.0 (C3a), 96.0 (C7), 90.0 (C5), 55.5 (C4 OCH3), 54.5 (C6
OCH3), 54.3 (ArC4 OCH3). CIMS m/z: 424 ([Mþ1]þ, 10%), 391 (15),
340 (10), 284 (30), 149 (20), 125 (15), 113 (50), 97 (70), 85 (100);
ES-HRMS m/z: calcd for [Mþ1]þ C23H22NO5S 424.1219; found
424.1230.
138–140 ꢀC. 1H NMR
d
: 7.78 (2H, d, J¼7.8 Hz, ArH20 and H60), 7.49
(2H, d, J¼9.0 Hz, tosyl ArH300 and 500), 7.39 (2H, d, J¼9.0 Hz, tosyl
ArH200 and 600), 7.34 (1H, s, H2), 7.25 (2H, d, J¼7.8 Hz, Ar3H0 and 50),
7.18 (1H, d, J¼1.8 Hz, H7), 6.32 (1H, d, J¼1.8 Hz, H5), 3.88 (3H, s, C4
OCH3), 3.70 (3H, s, C6 OCH3), 2.35 (3H, s, CH3). 13C NMR
d: 159.4
(C6), 154.6 (C4), 145.2 (tosyl C100), 137.5 (C7a), 135.1 (ArC40), 133.0
(ArC40), 131.3 (ArC20 and 60), 130.9 (ArC30 and 50), 130.1 (tosyl ArC200
and 600), 127.0 (tosyl ArC300 and 500), 125.0 (tosyl ArC400), 123.4 (C3),
121.3 (ArC10), 121.7 (C2), 112.8 (C3a), 95.4 (C7), 90.0 (C5), 56.1 (C4
4.2.2. N-Benzenesulfonyl-4,6-dimethoxy-3-phenylindole (9)
This was prepared by general procedure (A) using 4,6-di-
methoxy-3-phenylindole 5 (2.00 g, 7.9 mmol), sodium hydride

7792
P.A. Keller et al. / Tetrahedron 64 (2008) 7787–7795
OCH3), 55.5 (C6 OCH3), 22.0 (CH3). EI-HRMS m/z: calcd for
23H20NO4S79Br 485.0296; found 485.0293.
(ArC10), 123.0 (C3), 122.0 (C2), 112.0 (C3a), 96.0 (C7), 90.0 (C5), 55.0
(C4 OCH3), 54.5 (C6 OCH3), 42.0 CH3. CIMS m/z: 412 ([Mþ1]þ, 81Br,
20%), 332 (15), 254(10), 113 (25), 97(30), 81 (100); ES-HRMS m/z:
calcd for [Mþ1]þ C17H17NO4S79Br 410.0062; found 410.0061.
C
4.2.6. 3-(4-Bromophenyl)-4,6-dimethoxy-N-(p-nitrobenzene-
sulfonyl)indole (20)
This was prepared by general procedure (A) using 4,6-di-
methoxy-3-(4-bromophenyl)indole 6 (2.00 g, 6.0 mmol), sodium
hydride (0.29 g, 6.0 mmol, 50% dispersion in oil) and
p-nitrobenzenesulfonyl chloride (1.33 g, 6.0 mmol) to give the
4.2.10. N-Methanesulfonyl-4,6-dimethoxy-3-(4-methoxyphenyl)-
indole (24)
This was prepared by general procedure (A) using 4,6-di-
methoxy-3-(40-methoxyphenyl)indole 4 (2.00 g, 7.0 mmol), sodium
hydride (0.28 g, 7.0 mmol) and methanesulfonyl chloride (0.81 g,
7.1 mmol) to give the indole 27 (1.99 g, 79%) as white solid, mp 145–
indole 20 (2.25 g, 73%) as yellow solid, mp 220–222 ꢀC. 1H NMR
d:
8.29 (2H, d, J¼8.7 Hz, Ar2H0 and 60), 8.05 (2H, d, J¼8.7 Hz, ArH30 and
50), 7.49 (2H, d, J¼6.6 Hz, sulfonyl ArH300 and 500), 7.37 (2H, d,
J¼6.6 Hz, sulfonyl Ar2H00 and 600), 7.3 (1H, s, H2), 7.17 (1H, d,
J¼1.8 Hz, H7), 6.36 (1H, d, J¼1.8 Hz, H5), 3.89 (3H, s, C4 OCH3), 3.71
148 ꢀC. 1H NMR
d
: 7.50 (2H, d, J¼9.0 Hz, ArH20 and 60), 7.17 (1H, s,
H2), 7.10 (1H, d, J¼2.1 Hz, H5), 6.93 (2H, d, J¼9.0 Hz, ArH30 and 50),
6.40 (1H, d, J¼2.1 Hz, H7), 3.88 (3H, s, C4 OCH3), 3.85 (3H, s, C6
(3H, s, C6 OCH3). 13C NMR
d: 160.0 (C6), 155.0 (C4), 151.5 (sulfonyl
OCH3), 3.77 (3H, s, ArC4 OCH3), 3.09 (3H, s, CH3). 13C NMR
d: 159.9
ArC100),143.5 (ArC40),138.0 (C7a),133.0 (ArC10),131.3 (ArC20 and 60),
131.0 (ArC30 and 50), 128.2 (sulfonyl ArC200 and 600), 125.0 (sulfonyl
ArC400), 124.8 (sulfonyl ArC300 and 500), 122.0 (C3), 121.1 (C2), 113.4
(C3a), 95.9 (C7), 90.1 (C5), 56.1 (C4 OCH3), 55.4 (C4 OCH3). CIMS m/
(ArC40), 158.5 (C6), 155.0 (C4), 138.0 (C7a), 132.0 (ArC20 and 60),
126.0 (ArC10),124.0 (C3),121.0 (C2),114.0 (ArC30 and 50),110.0 (C3a),
96.0 (C7), 90.0 (C5), 56.0 (C4 OCH3), 55.6 (C6 OCH3), 55.7 (ArC4
OCH3), 40.0 (CH3). CIMS m/z: 362 ([Mþ1]þ, 90%), 340 (15), 284 (30),
149 (15), 113 (20), 97 (25), 81 (100); EI-HRMS m/z: calcd for
z: 519 ([Mþ1]þ, 81Br, 100%), 455 (10), 332 (50), 236 (10); EI-HRMS
79
m/z: calcd for C
H
BrN2O6S 515.9990; found 515.9982.
C18H19NO5S 361.0983; found 361.0989.
22 17
4.2.7. 4,6-Dimethoxy-N-(p-nitrobenzenesulfonyl)-3-(4-nitro-
phenyl)indole (21)
This was prepared by general procedure (A) using 4,6-di-
methoxy-3-(40-nitrophenyl)indole 7 (2.00 g, 6.7 mmol) sodium
hydride (0.32 g, 6.7 mmol) and p-nitrobenzenesulfonyl chloride
(1.48 g, 6.7 mmol) to give the indole 21 (2.17 g, 67%) as a pale yellow
4.2.11. N-Acetyl-4,6-dimethoxy-3-(4-methoxyphenyl)indole (30)
To a solution of 4,6-dimethoxy-3-(4-methoxyphenyl)indole 4
(0.50 g, 1.80 mmol), acetyl chloride (0.14 g, 1.80 mmol) and potas-
sium hydroxide (0.10 g, 1.80 mmol) in CH2Cl2 (15 mL) was added
a catalytic amount of the phase transfer catalyst tetrabutylammo-
nium hexafluorophosphate (20 mol %) in CH2Cl2 (25 mL) under a ni-
trogen atmosphere. The reaction mixture was stirred for 12 h before
water (30 mL) was added and the organic layer separated. The sol-
vent was then removed under reduced pressure, and the oily liquid
subjected to flash chromatography (ethylacetate/hexane 2:8) to yield
the indole 31 (0.37 g, 65%) as a white solid, mp 145–158 ꢀC. 1H NMR
solid, mp 190–193 ꢀC. 1H NMR
d
: 8.34 (2H, d, J¼9.0 Hz, ArH2 and 6),
8.24 (2H, d, J¼8.7 Hz, sulfonyl ArH3 and 5), 8.10 (2H, d, J¼9.0 Hz,
ArH3 and 5), 7.68 (2H, d, J¼8.7 Hz, sulfonyl ArH2 and 6), 7.26 (1H, s,
H2), 7.18 (1H, d, J¼1.8 Hz, H7), 6.39 (1H, d, J¼1.8 Hz, H5), 3.91 (3H, s,
C4 OCH3), 3.73 (3H, s, C6 OCH3). 13C NMR
d: 160.1 (C6), 156.0 (C4),
146.1 (ArC4), 144.0 (ArC1), 141.0 (C7a), 148.0 (sulfonyl ArC4), 131.0
(ArC2 and 60), 128.1 (sulfonyl ArC2 and 6), 125.5 (ArC3 and 5), 125.0
(sulfonyl ArC1), 123.0 (C2), 122.0 (ArC2 and 6), 121.0 (C3), 113.0
(C3a), 96.0 (C7), 90.0 (C5), 58.0 (C4 OCH3), 56.0 (C6 OCH3). CIMS m/
z: 484.0 ([Mþ1]þ, 100%), 420 (10), 299 (30); EI-HRMS m/z: calcd for
d
: 7.77 (1H, d, J¼1.8 Hz, H7), 7.51 (2H, d, J¼9.0 Hz, Ar20 and 60), 7.10
(1H, s, H2), 6.94 (2H, d, J¼9.0 Hz, Ar30 and 50), 6.40 (1H, d, J¼1.8 Hz,
H5), (3.89, 3.85 and 3.75, 3ꢁOCH3), 2.61 (3H, s, COCH3). 13C NMR
d:
169.1 (C¼O), 159.8 (ArC40), 159.0 (C6), 154.4 (C4), 138.4 (C7a), 130.7
(ArC20 and 60), 127.0 (ArC10),124.2 (C3), 120.4 (C2), 113.3 (ArC30 and
50), 112.8 (C3a), 95.9 (C7), 93.1 (C5), (55.9, 55.5 and 55.4 3ꢁOCH3),
24.4 (COCH3). CIMS m/z: 326 ([Mþ1]þ, 100%), 283 (20), 268 (10). EI-
HRMS m/z: calcd for C19H19NO4 325.1314; found 325.1398.
C
22H17N3O8S 483.0736; found 483.0746.
4.2.8. N-Methanesulfonyl-4,6-dimethoxy-3-phenylindole (22)
This was prepared by general procedure (A) using 4,6-di-
methoxy-3-phenylindole 5 (2.00 g, 7.9 mmol) sodium hydride
(0.32 g, 8.0 mmol) and methanesulfonyl chloride (0.90 g, 7.9 mmol)
to give the indole 23 (1.96 g, 75%) as white solid, mp 140–142 ꢀC. 1H
4.2.12. N-Acetyl-4,6-dimethoxy-3-(40-nitrophenyl)indole (31)
To a solution of 4,6-dimethoxy-3-(4-nitrophenyl)indole 7 (0.50 g,
1.70 mmol), acetyl chloride (0.13 g, 1.70 mmol) and potassium hy-
droxide (0.10 g, 1.8 mmol) in CH2Cl2 (15 mL) was added a catalytic
amount of phase transfer catalyst tetrabutylammonium hexa-
fluorophosphate (20 mol %) in CH2Cl2 (25 mL) under a nitrogen at-
mosphere. The reaction mixture was stirred for 12 h. To the reaction
mixture water was added, and the organic layer separated. The
solvent was removed under reduced pressure, and the oily liquid
then purified by flash chromatography (ethylacetate/hexane, 2:8) to
yield the indole 32 (0.32 g, 57%) as a white solid, mp 180–182 ꢀC. 1H
NMR
d
: 7.57 (2H, d, J¼8.4 Hz, ArH20 and 60), 7.38–7.34 (3H, m, ArH30,
40 and 50), 7.23 (1H, s, H2), 7.10 (1H, d, J¼2.1 Hz, H5), 6.41 (1H, d,
J¼2.1 Hz, H7), 3.89 (3H, s, C4 OCH3), 3.76 (3H, s, C6 OCH3), 3.11 (3H,
s, CH3). 13C NMR : 160.0 (C6), 155.0 (C4), 138.0 (C7a), 134.0 (ArC10),
d
130.0 (ArC20 and 60), 128.0 (ArC30 and 50), 127.6 (ArC40), 125.0 (C3),
122.0 (C2), 113.0 (C3a), 96.0 (C7), 90.0 (C5), 56.0 (C4 OCH3), 55.6 (C6
OCH3), 40.0, CH3. CIMS m/z: 332 ([Mþ1]þ, 45%), 270 (15), 132 (15),
103 (20), 71 (100); ES-HRMS m/z: calcd for [Mþ1]þ C17H18NO4S
332.0957; found; 332.0959.
NMR
d
: 8.27 (2H, d, J¼9.0 Hz, ArH20 and 60), 7.87 (2H, d, J¼9.0 Hz,
ArH30 and 50), (1H, s, H2), 7.70 (1H, d, J¼1.8 Hz, H7), 6.53 (1H, d,
4.2.9. 3-(4-Bromophenyl)-N-methanesulfonyl-4,6-dimethoxy-
indole (23)
J¼1.8 Hz, H5), 3.84 (3H, s, C4 OCH3), 3.79 (3H, s, C6 OCH3), 2.68 (3H,
s, acetyl CH3). 13C NMR
d: 160.0 (C6), 154.0 (C4), 149.0 (C]O), 142.0
This was prepared by general procedure (A) using 4,6-di-
methoxy-3-(40-bromophenyl)indole 6 (2.00 g, 6.0 mmol), sodium
hydride (0.24 g, 6.0 mmol) and methanesulfonyl chloride (0.69 g,
6.0 mmol) to give the indole 25 (1.72 g, 70%) as a white solid, mp
(ArC40), 139.0 (C7a), 131.0 (ArC20 and 60), 123.0 (ArC30 and 50), 122.0
(C2), 121.8 (C3), 112.0 (C3a), 97.0 (C7), 93.0 (C5), 56.0 (C4 OCH3), 55.0
(C6 OCH3), 26.0 (COCH3). CIMS m/z: 341 ([Mþ1]þ, 100%); EI-HRMS
m/z: calcd for C18H16N2O5 340.1059; found 340.1072.
147–150 ꢀC. 1H NMR
d
: 7.51 (2H, d, J¼9.0 Hz, ArH20 and 40), 7.43 (2H,
d, J¼9.0 ArH30 and 50), 7.22 (1H, s, H2), 7.02 (1H, d, J¼2.1 Hz, H7),
4.2.13. N-tert-Butylcarbamate-4,6-dimethoxy-3-(4-methoxy-
phenyl)indole (34)
To a solution of 4,6-dimethoxy-3-(40-methoxyphenyl)indole 4
(0.50 g, 1.80 mmol) and di-tert-butyldicarbonate (0.37 g,
6.40 (1H, d, J¼2.1 Hz, H5), 3.89 (3H, s, C4 OCH3), 3.77 (3H, s, C6
OCH3), 3.13 (s, Me). 13C NMR
d
: 160.0 (C6), 156.5 (C4), 138.0 (C7a),
134.0 (ArC40), 130.5 (ArC20 and 60), 130.0 (ArC30 and 50), 124.0

P.A. Keller et al. / Tetrahedron 64 (2008) 7787–7795
7793
1.80 mmol) in CH2Cl2 (25 mL) was added a catalytic amount of
DMAP and the reaction stirred under a nitrogen atmosphere for
30 min. To the reaction mixture was added water, the organic layer
separated, the solvent removed under reduced pressure, and the
solid then recrystallised from methanol to yield the indole 35
m/z: 785.0 ([Mþ]þ, 30%), 746.2 (20), 649.4 (25), 552.2 (20), 413, 304,
272, 244 (100); ES-HRMS m/z: calcd for [Mþ1]þ C44H37N2O8S2
785.1991; found 785.1978.
4.3.3. 2,20-Bi-[N-benzenesulfonyl-3-(4-bromophenyl)-
4,6-dimethoxy]indole (14)
(0.68 g, 99%), as a white solid, mp 151–153 ꢀC. 1H NMR
d: 8.22 (1H,
d, J¼1.8 Hz, H7), 7.51 (2H, d, J¼9.0 Hz, ArH20 and 60), 6.92 (2H, d,
J¼9.0 Hz, ArH30 and 50), 6.47 (1H, d, J¼1.8 Hz, H5), 6.35 (d, J¼2.1 Hz),
3.88 (3H, s, ArC4 OCH3), 3.83 (3H, s, C4 OCH3), 3.74 (3H, s, C6 OCH3).
This was prepared using general procedure (B) using
thallium(III) trifluoroacetate (0.29 g, 0.53 mmol), N-benzenesulfonyl-
3-(4-bromophenyl)-4,6-dimethoxyindole 10 (0.50 g, 1.06 mmol) and
boron trifluoride diethyletherate (1.12, 7.90 mmol). The residue was
recrystallised from CH2Cl2/methanol to give the indole 14 (0.37 g,
13C NMR
d
: 159.9 (C¼O), 159.8 (C6), 154.3 (C4), 150.0 (C7a), 130.8
(ArC20 and 60), 127.4 (ArC10), 121.1 (C2), 113.2 (ArC30 and 50), 106.8
(C3a), 95.0 (C7), 91.7 (C5), 84.0 (CO2C(CH3)), (55.8, 55.4 and 55.4,
3ꢁOCH3), 28.4 (3ꢁC, t-BOC). CIMS m/z: 383 ([Mþ]þ, 90%), 370 (15),
327 (100), 283 (30), 268 (10); ES-HRMS m/z: calcd for [Mþ1]þ
C22H26NO5 384.1811; found 384.1807.
74%) as a white solid, mp 263–265 ꢀC. 1H NMR
d: 7.90 (2H, d,
J¼9.0 Hz, sulfonyl ArH200 and 600), 7.55–7.34 (7H, m, sulfonyl ArH300
and 400, 500 and ArH20, 30, 50 and 60), 7.19 (1H, d, J¼1.8 Hz, H7), 6.34
(1H, d, J¼1.8 Hz, H5), 3.88 (3H, s, C4 OCH3), 3.72 (3H, s, C6 OCH3). 13
C
NMR d
: 159.3 (C6), 154.5 (C4), 137.8 (C7a), 137.4 (ArC40), 134.1
4.3. General procedure (B) for the synthesis of bisindoles:
oxidative dimerisation
(sulfonyl ArC40), 132.8 (C2), 131.2 (sulfonyl ArC200 and 600), 130.7
(sulfonyl ArC300 and 500), 129.9 (ArC10), 129.4 (ArC10), 129.2 (ArC20
and 60), 126.8 (ArC30 and 50), 123.5 (C3), 113.0 (C3a), 95.3 (C7), 89.9
(C5), 56.0 (C4 OCH3), 55.3 (C6 OCH3). ES-MS m/z: 942.7 ([Mþ1]þ,
81Br, 30%), 761.3 (10), 488.0 (20), 392.2 (30), 338.4 (30), 316.3 (35),
314.2 (70), 288.3 (60), 270.2 (50), 244.2 (45), 174.8 (30), 166.9 (40),
144.9 (70), 125.8 (80), 103.9 (100); ES-HRMS m/z: calcd for [Mþ1]þ
C44H35N2O789Br2S2 941.0202; found 941.0254.
Solid thallium(III) trifluoroacetate (0.53 mmol) was mixed with
the solid protected indole (1.06 mmol) under a nitrogen atmo-
sphere. Dry acetonitrile (7 mL) was added and the resultant mix-
ture cooled to 0 ꢀC. Boron trifluoride diethyletherate (8.0 mmol)
was then added slowly into the reaction mixture, and allowed to
stir for 1 h. The reaction mixture was poured into water and
extracted with CH2Cl2 (5ꢁ50 mL). The combined organic layers
were concentrated to give a dark residue.
4.3.4. 2,20-Bi-[4,6-dimethoxy-3-(4-methoxyphenyl)]indole (16)
A solution of 2,20-bi[N-benzenesulfonyl-4,6-dimethoxy-3-(4-
methoxyphenyl)]indole 12 (0.30 g, 0.3 mmol) in dioxane (20 mL)
with 20% aqueous sodium hydroxide (5 mL) was heated at reflux
for 4 h. The reaction mixture was poured onto cold water
(60 mL) and partitioned with CH2Cl2 (3ꢁ50 mL). The solvent was
evaporated under vacuum and the residue recrystallised from
CH2Cl2/methanol to give the indole 16 (0.03 g, 15%) as a pale
4.3.1. 2,20-Bi-[N-benzenesulfonyl-4,6-dimethoxy-3-(4-methoxy-
phenyl)]indole (12)
This was prepared by general procedure (B) using N-benzene-
sulfonyl-3-(4-methoxyphenyl)-4,6-dimethoxyindole
8
(0.50 g,
1.18 mmol), thallium(III) trifluoroacetate (0.32 g, 0.55 mmol) and
boron trifluoride diethyletherate (1.12 g, 7.9 mmol). The residue
was recrystallised from CH2Cl2/methanol to give the indole 12
yellow solid, mp 197–200 ꢀC. 1H NMR
d: 11.2 (1H, s, NH), 6.93
(2H, d, J¼9.0 Hz, ArH20 and 60), 6.59 (2H, d, J¼9.0 Hz, ArH30 and
50), 6.41 (1H, d, J¼1.8 Hz, H5), 6.10 (1H, d, J¼1.8 Hz, H7), 3.74 (3H,
s, C4 OCH3), 3.66 (3H, s, C6 OCH3), 3.60 (3H, s, ArC40 OCH3). 13C
(0.35 g, 70%) as a white solid, mp 242–246 ꢀC. 1H NMR
d: 7.53 (2H, d,
J¼6.0 Hz, sulfonyl ArH200 and 600), 7.46 (1H, t, sulfonyl ArH400), 7.30
(2H, t, sulfonyl ArH300 and 500), 7.03 (2H, d, J¼12.0 Hz, ArH20 and 60),
7.02 (1H, d, J¼1.8 Hz, H7), 6.65 (2H, d, J¼12.0 Hz, ArH30 and 50), 6.25
(1H, d, J¼1.8 Hz, H5), 3.76 (3H, s, C4 OCH3), 3.75 (3H, s, C6 OCH3),
NMR (DMSO d6) d
: 158.3 (ArC40), 158.2 (C60), 154.3 (C40), 138.0
(C7a), 132.0 (ArC20 and 60), 128.5 (ArC10), 124.6 (C2), 116.3 (C3),
112.2 (ArC30 and 50), 112.0 (C3a), 92.0 (C5), 87.2 (C7), 55.9 (C4
OCH3), 55.6 (C6 OCH3), 55.4 (ArC4 OCH3); CIMS m/z:
564([Mþ1]þ, 60%), 338 (100), 285 (10), 197 (5), 153 (10), 137 (25),
121 (30), 97 (30); ES-HRMS m/z: calcd [Mþ1]þ C34H33N2O6
564.2260; found 564.2259.
3.56 (1H, s, ArC4 OCH3). 13C NMR : 159.3 (ArC40), 159.0 (C6), 154.5
d
(C4), 139.9 (C7a), 139.0 (sulfonyl ArC100), 133.9 (ArC4), 131.8 (sul-
fonyl ArC200 and 600), 129.5 (sulfonyl ArC300 and 500), 127.0 (C2), 126.7
(ArC20 and 60), 126.3 (C3), 126.5 (ArC10), 124.0 (C3a), 122.0 (C2),
112.5 (C3a), 112.0 (ArC30 and 50), 94.5 (C5), 92.0 (C7), 56.0 (C4
OCH3), 55.0 (C6 OCH3). ES-MS m/z: 845 ([Mþ1]þ, 35%), 797.2 (10),
704.2 (15), 625 (5), 552.3 (15), 475.4 (10), 411.2 (15), 332.3 (50),
304.3 (100), 272.3 (50), 244.2 (80), 214.0 (40), 157.9 (75), 141.8 (45),
105.9 (90); ES-HRMS m/z: calcd for [Mþ1]þ C46H41N2O10S2
845.2203; found 845.2209.
4.3.5. 2,20-Bi-(4,6-dimethoxy-3-phenyl)indole (17)
A
solution of 2,20-bi-(N-benzenesulfonyl-4,6-dimethoxy-3-
phenyl)indole 13 (0.30 g, 0.4 mmol) in dioxane (20 mL) with 20%
aqueous sodium hydroxide (5 mL) was heated at reflux for 4 h. The
reaction mixture was poured into cold water and partitioned with
CH2Cl2 (3ꢁ50 mL). The solvent was evaporated and the residue
recrystallised from CH2Cl2/methanol yielding the indole 17 (0.03 g,
4.3.2. 2,20-Bi-(N-benzenesulfonyl-4,6-dimethoxy-3-phenyl)-
indole (13)
15%) as a pale yellow solid, mp 174–178 ꢀC. 1H NMR
d: 10.00 (1H, s,
This was prepared by general procedure (B) using N-benzene-
sulfonyl-3-phenyl-4,6-dimethoxyindole 9 (0.50 g, 1.3 mmol), thal-
lium(III) trifluoroacetate (0.35 g, 0.65 mmol) and boron trifluoride
diethyletherate (1.12 g, 7.9 mmol). Recrystallisation from CH2Cl2/
methanol gave the indole 13 (0.34 g, 69% yield) as a white solid, mp
NH), 7.21–7.18 (2H, m, ArH20 and 60), 7.09–7.06 (3H, m, ArH30, 40 and
50), 6.49 (1H, d, J¼3.0 Hz, H7), 6.18 (1H, d, J¼3.0 Hz, H5), 3.77 (3H, s,
C4 OCH3), 3.66 (3H, s, C6 OCH3). 13C NMR
d: 158.0 (C6), 155.0 (C4),
138.0 (C7a), 136.0 (C3), 131.0 (ArC40), 126.7 (ArC20 and 60), 125.2
(ArC30 and 50), 125.0 (ArC10), 118.0 (C2), 112.0 (C3a), 92.0 (C7), 86.2
(C5), 55.0 (C4 OCH3), 54.5 (C6 OCH3). ES-MS m/z: 504.2 ([Mþ1]þ,
60%), 338.4 (25), 144.9 (20), 105.9 (45), 103.9 (100), 71.0 (25); ES-
HRMS m/z: calcd for [Mþ1]þ C32H29N2O4 504.2049; found
504.2054.
224–226 ꢀC. 1H NMR : 7.57–7.01 (10H, m, sulfonyl ArH200, 300, 400
d
and 600, and ArH20, 30, 40, 50 and 60), 7.00 (1H, d, J¼1.8 Hz, H7), 6.22
(1H, d, J¼1.8 Hz, H5), 3.76 (3H, s, C4 OCH3), 3.53 (3H, s, C6 OCH3). 1030C
NMR d: 159.3 (C6), 154.9 (C4), 139.0 (C7a), 139.5 (sulfonyl ArC1 ),
133.8 (C3), 133.4 (sulfonyl ArC400), 130.7 (sulfonyl ArC200 and 600),
129.1 (sulfonyl ArC300 and 500), 129.0 (ArC40), 128.5 (ArC40), 128.0
(C2), 127.5 (ArC20 and 60), 127.2 (ArC30 and 50), 126.9 (ArC10), 122.3
(C3a), 95.5 (C7), 90.8 (C5), 55.9 (C4 OCH3), 55.4 (C6 OCH3). ES-MS
4.3.6. 20,2-Bi-[3-(4-bromophenyl)-4,6-dimethoxy]indole (18)
This was prepared by general procedure (B) using 4,6-di-
methoxy-3-(4-bromophenyl)indole
6
(0.20 g,
0.6 mmol),

7794
P.A. Keller et al. / Tetrahedron 64 (2008) 7787–7795
thallium(III) trifluroacetate (0.16 g, 0.3 mmol) and boron trifluoride
diethyletherate (0.43 g, 3.0 mmol). The residue was subjected to
flash silica gel column chromatography (50:50 hexane/ethylacetate)
(C7), 155.0 (C4), 148.0 (C7a), 134.0 (ArC10), 130.0 (ArC20 and 60),
127.3 (C3), 127.1 (ArC30 and 50), 127.0 (C2), 126.5 (ArC40), 113.0 (C3a),
95.0 (C7), 90.0 (C5), 56.0 (C4 OCH3), 55.6 (C6 OCH3), 40.0 (Me). ES-
MS m/z: 661.1 ([Mþ1]þ, 50%), 348.1 (20), 132.8 (18), 105.9 (30),
103.9 (40), 71.0 (100); ES-HRMS m/z: calcd for [Mþ1]þ
C34H33N2O8S2 661.1678; found 661.1674.
yielding the indole 18 (0.04 g, 20%) as a pale yellow solid, mp 195–
1
197 ꢀC. H NMR
d
: 7.85 (2H, d, J¼7.5 Hz, ArH30 and 50), 7.21 (2H, d,
J¼7.5 Hz, ArH20 and 60), 7.28 (1H, d, J¼1.8 Hz, H7), 6.32 (1H, s, H5),
3.84 (3H, s, C4 OCH3), 3.49 (3H, s, C6 OCH3). 13C NMR (CDCl3)
d:
153.5 (C-6 and C-4), 140.0 (C-7a), 133.0 (C-2), 132.8 (C-3), 130.4
(ArC-40), 128.0 (ArC20 and 60), 127.8 (ArC20 and 50), 126.0 (C-3a),
121.6 (ArC10), 94.3 (C-7), 92.0 (C-5), 57.8 (C-4-OCH3), 56.0 (C-6-
OCH3). ES-MS m/z: 663 ([Mþ1]þ, 80Br 60%), 607 (10), 468.5 (15),
332 (40), 316 (50), 304 (50), 288 (70), 244 (100); ES-HRMS m/z:
calcd for [Mþ1]þ C32H27N2O749Br2 661.0338; found 661.0331.
4.3.10. 2,20-Bi-[3-(4-bromophenyl)-N-methanesulfonyl-
4,6-dimethoxy]indole (28)
This was prepared by general procedure (B) using N-methane-
sulfonyl-3-(4-bromophenyl)-4,6-dimethoxyindole
23
(0.50 g,
1.2 mmol), thallium(III) trifluoroacetate (0.33 g, 0.6 mmol) and
boron trifluoride diethyletherate (1.12 g, 7.9 mmol). Recrystallisa-
tion from CH2Cl2/methanol gave the indole 28 (0.40 g, 80%) as
4.3.7. 2,20-Bi-[3-(4-bromophenyl)-(N-p-methylbenzenesulfonyl)-
4,6-dimethoxy]indole (25)
a white solid, mp 179–182 ꢀC. 1H NMR
d
: 7.31 (2H, d, J¼9.0 Hz, ArH2
and 6), 7.08 (1H, d, J¼3.0 Hz, H5), 7.02 (2H, d, J¼9.0 Hz, ArH3 and 5),
This was prepared by general procedure (B) using N-(4-methyl-
6.33 (1H, d, J¼3.0 Hz, H7), 3.89 (3H, s, C4 OCH3), 3.61 (3H, s, C6
phenylsulfonyl)-3-(4-bromophenyl)-4,6-dimethoxyindole
19
OCH3), 3.06 (3H, s, CH3). 13C NMR
d: 160.2 (C6), 155.0 (C4), 138.0
(0.50 g, 1.0 mmol), thallium(III) trifluoroacetate (0.28 g 0.50 mmol)
and boron trifluoride diethyletherate (1.12 g, 7.9 mmol). Recrystal-
lisation from CH2Cl2/methanol gave the indole 25 (0.36 g 73%) as
(C7a), 132.7 (ArC40), 132.0 (ArC30 and 50), 130.3 (ArC20 and 60), 126.3
(ArC10), 123.3 (C2), 121.4 (C3), 112.6 (C3a), 95.6 (C7), 89.9 (C5), 56.8
(C4 OCH3), 56.0 (C6 OCH3), 40.0 (CH3). ES-MS m/z: 817.9 ([Mþ1]þ,
81Br, 15%), 466.8 (25), 464.7 (10), 343.8 (10), 341.4 (15), 338.4
(30), 275.9 (15), 204.9 (20), 144.9 (20), 132.8 (25), 105.9 (40), 103.9
(100), 71.0 (35), 60.1 (50); ES-HRMS m/z: calcd for [Mþ1]þ
C34H31N2O8S729Br2 816.9889; found 816.9863.
a yellow solid, mp 219 ꢀC. 1H NMR
d
: 7.45 (2H, d, J¼8.4 Hz, sulfonyl
ArH300 and 500), 7.17 (2H, d, J¼8.7 Hz, ArH20 and 60), 7.14 (2H, d,
J¼8.7 Hz, ArH30 and 50), 7.04 (1H, d, J¼2.1 Hz, H7), 6.86 (2H, d,
J¼8.4 Hz, sulfonyl ArH200 and 600), 6.26 (1H, d, J¼2.1 Hz, H5), 3.79
(3H, s, C6 OCH3), 3.57 (3H, s, C4 OCH3), 2.36 (3H, s, CH3). 13C NMR
d:
159.6 (C6), 154.8 (C4), 144.7 (sulfonyl ArC40), 138.7 (C7a), 136.7
(ArC40), 132.9 (ArC10), 132.2 (sulfonyl ArC200 and 600), 130.1 (ArC20
and 60), 129.8 (ArC30 and 50), 127.2 (sulfonyl ArC300 and 500), 126.0
(sulfonyl ArC10), 124.0 (C2), 121.4 (C3), 112.3 (C3a), 95.4 (C7), 90.8
(C5), 55.8 (C4 OCH3), 55.3 (C6 OCH3), 21.8 (Me). ES-MS m/z: 970.7
([Mþ1]þ, 81Br, 20%), 501.7 (20), 304.3 (30), 288.2 (35), 272.2 (40),
244.3 (100), 225.1 (45), 103.7 (80). ES-HRMS m/z: calcd for [Mþ1]þ
C46H37N2O2S729Br2 969.0515; found 969.0524.
4.3.11. 2,20-Bi-[N-methanesulfonyl-4,6-dimethoxy-(4-methoxy-
phenyl)]indole (29)
This was prepared by general procedure (B) using N-methane-
sulfonyl-3-(4-methoxyphenyl)-4,6-dimethoxyindole 24 (0.50 g,
1.3 mmol), thallium(III) trifluoroacetate (0.36 g 0.65 mmol) and
boron trifluoride diethyletherate (1.12 g, 7.9 mmol). Recrystallisa-
tion from CH2Cl2/methanol gave the indole 29 (0.38 g, 76%) as
a white solid, mp 219–222 ꢀC. 1H NMR
d
: 7.18 (2H, d, J¼9.0 Hz, ArH20
and 60), 7.12 (1H, d, J¼1.8 Hz, H7), 6.74 (2H, d, J¼9.0 Hz, ArH30 and
4.3.8. 2,20-Bi-[3-(4-bromophenyl)-4,6-dimethoxy-(N-p-nitro-
benzenesulfonyl)]indole (26)
50), 6.33 (1H, d, J¼1.8 Hz, H5), 3.88 (3H, s, C4 OCH3), 3.74 (3H, s, C6
OCH3), 3.62 (3H, s, ArC4 OCH3), 2.93 (3H, s, CH3). 13C NMR
d: 159.9
This was prepared by general procedure (B) using N-(p-nitro-
(ArC40), 158.5 (C6), 155.0 (C4), 138.0 (C7a), 132.0 (ArC20 and 60),
126.0 (ArC10), 123.8 (C3), 123.4 (C2), 113.5 (C3a), 113.0 (Ar30 and 50),
96.0 (C7), 90.0 (C5), 56.0 (C4 OCH3), 55.7 (C6 OCH3), 55.6 (ArC4
OCH3), 40.0 (CH3); ES-MS m/z: 721.2 ([Mþ1]þ, 40%), 547.4 (15),
503.9 (10), 376.1 (20), 360.4 (25), 338.4 (70), 304.2, 244.1,103.9 (50),
71.0 (50), 60.1 (100); ES-HRMS m/z: calcd for [Mþ1]þ
C36H37N2O10S2 721.1889; found 721.1883.
benzenesulfonyl)-3-(4-bromophenyl)-4,6-dimethoxyindole
20
(0.50 g, 1.1 mmol), thallium(III) trifluoroacetate (0.30 g, 0.55 mmol)
and boron trifluoride diethyletherate (1.12 g, 7.9 mmol). Recrystal-
lisation from CH2Cl2/methanol gave the indole 26 (0.33 g, 67%) as
a yellow solid, mp 232–235 ꢀC. 1H NMR
d
: 8.14 (2H, d, J¼8.7 Hz,
ArH3 and 5), 7.48 (2H, d, J¼9.0 Hz, ArH2 and 6), 7.20 (2H, d,
J¼8.7 Hz, sulfonyl ArH200 and 600), 7.02 (1H, d, J¼1.8 Hz, 7H), 7.03
(2H, d, J¼9.0 Hz, sulfonyl ArH300 and 500), 6.39 (1H, d, J¼1.8 Hz, H4),
4.3.12. 2,20-Bi[N-acetyl-4,6-dimethoxy-3-(4-nitrophenyl)]-
indole (35)
3.82 (3H, s, C4 OCH3), 3.63 (s, C6 OCH3). 13C NMR
d: 160.6 (C6),155.2
(C4), 150.3 (sulfonyl ArC4), 144.4 (sulfonyl ArC1), 139.1 (C7a), 132.3
(ArC1), 132.2 (sulfonyl ArC3 and 5), 130.4 (ArC2 and 6), 130.0 (C2),
127.9 (sulfonyl ArC2 and 6), 124.51 (ArC3 and 50), 122.9 (ArC4),
122.0 (C30), 112.4 (C3a), 96.0 (C7), 90.8 (C5), 56.0 (C4 OCH3), 55.4
(C6 OCH3 and ArC4 OCH3). ES-MS m/z: 1031 ([Mþ1]þ, 81Br, 100%),
887.3 (10), 757.9 (30), 705.9 (60), 662.0 (50), 629.8 (50), 585.9 (80),
564.0 (95), 498.8 (70), 451.6 (45), 391.6 (100); ES-HRMS m/z: calcd
for [Mþ1]þ C44H33N4O12S729Br2 1030.9903; found 1030.9919.
This was prepared by general procedure (B) using N-acetyl-4,6-
dimethoxy-3-(4-nitrophenyl)indole 32 (0.20 g, 0.6 mmol), thalliu-
m(III) trifluroacetate (0.16 g, 0.3 mmol) and boron trifluoride
diethyletherate (1.02 mL, 7.2 mmol). The residue was subjected to
flash silica gel column chromatography (70:30 hexane/ethylacetate)
yielding the indole 36 (0.06 g, 30%) as a pale yellow solid, mp 179–
181 ꢀC. 1H NMR
d
: 8.20 (2H, d, J¼9.0 Hz, ArH30 and 50), 7.61 (1H, d,
J¼2.1 Hz, H7), 7.57 (1H, d, J¼9.0 Hz, ArH20 and 60), 6.36 (1H, d,
J¼2.1 Hz, H5), 3.89 (3H, s, C4 OCH3), 3.70 (3H, s, C6 OCH3), 2.59 (3H,
4.3.9. 2,20-Bi-(N-methanesulfonyl-4,6-dimethoxy-3-phenyl)-
indole (27)
s, acetyl). 13C NMR
d
: 171.0 (C¼O),163.9 (C6),157.8 (C4),147.5 (ArC10),
146.1 (ArC40), 142.3 (C7a), 126.3 (ArC20 and 60), 124.0 (ArC30 and C50),
122.5 (C2), 104.0 (C3a), 96.5 (C7), 96.0 (C5), 56.0 (C6 OCH3), 55.7 (C4
OCH3), 26.7 (COCH3). EIMS m/z: 689 ([Mþ1]þ, 7%), 663 (100).
This was prepared by general procedure (B) using N-methane-
sulfonyl-3-phenyl-4,6-dimethoxyindole 22 (0.50 g, 1.5 mmol),
thallium(III) trifluoroacetate (0.41 g, 0.75 mmol) and boron tri-
fluoride diethyletherate (1.12 g, 7.9 mmol). Recrystallisation from
CH2Cl2/methanol gave the indole 27 (0.33 g, 67%) as a white solid,
4.3.13. 2-(4,6-Dimethoxy-3-(4-nitrophenyl)-N-trifluoroacetyl-1H-
indol-7-yl)-4,40,6,60-tetramethoxy-3,30-bi(4-nitrophenyl)-N,N0-
di(trifluoroacetyl)-1H,10H-7,70-biindole (36)
This was prepared by general procedure (B) using thallium(III)
trifluoroacetate (0.14 g, 0.25 mmol), N-trifluoro-4,6-dimethoxy-
mp 229–231 ꢀC. 1H NMR
d
: 7.25–7.16 (4H, m, ArH20, 30, 40, 50 and 60),
7.11 (1H, d, J¼3.0 Hz, H5), 6.32 (1H, d, J¼3.0 Hz, H7), 3.87 (3H, s, C4
OCH3), 3.59 (3H, s, C6 OCH3), 2.90 (3H, s, CH3). 13C NMR
: 160.0
d

P.A. Keller et al. / Tetrahedron 64 (2008) 7787–7795
7795
3-(40-nitrophenyl)-1-trifluoroacetateindole 34 (0.20 g, 0.50 mmol)
and boron trifluoride diethyletherate (0.29 g, 2.0 mmol). The resi-
due was subjected to flash silica gel column chromatography
(60:40 hexane/ethylacetate) yielding the trimer 37 (0.70 g, 35%) as
anisotropic displacement parameters for the non-hydrogen atoms,
hydrogen atom treatment following a riding model; reflection
2
weights were ðs2ðF2Þ þ ðaPÞ Þꢂ1 ðP ¼ ðF02 þ 2Fc2Þ=3Þ. Neutral atom
complex scattering factors were used within the SHELXL 97 pro-
gram.14 Pertinent results are given in Figures 1 and 2 and Ref. 15;
full .cif depositions (without structure factor amplitudes)ure are
deposited with the Cambridge Crystallographic Data Centre, CCDC
680107 and 680108.
a yellow solid, mp 165–168 ꢀC. 1H NMR
d
: 8.24 (2H, d, J¼5.1 Hz,
ArH20 and 60), 8.21 (2H, d, J¼5.1 Hz, ArH200 and 600), 7.94 (2H, d,
J¼5.1 Hz, ArH2 and 6), 7.66 (2H, d, J¼4.8 Hz, ArH30 and 50) 7.55 (2H,
d, J¼4.8 Hz, ArH300 and 500), 7.21 (1H, s, H200), 7.12 (2H, d, J¼4.8 Hz,
ArH3 and 5), 6.95 (1H, s, H20), 6.73 (1H, s, H500), 6.66 (1H, s, H5), 6.44
(1H, s, H50), 3.95 (C4 OCH300), 3.92 (C4 OCH3), 3.84 (C6 OCH300), 3.81
Acknowledgements
(C4 OCH3 ), 3.79 (C6 OCH3), 3.72 (C6 OCH3 ). 13C NMR : 160.2 (C60),
d
0
0
157.4 (C600), 156.8 (C6), 156.6 (C40), 154.8 (C400), 154.0 (C4), 147.4
(ArC40), 147.3 (ArC400), 146.4 (ArC4), 142.0 (ArC10), 141.1 (ArC100),
140.0 (ArC1), 137.2 (C7a00), 137.2 (C7a), 137.0 (C7a0), 130.4 (ArC20 and
60, ArC20 and 600, and ArC2 and 6), 128.0 (C2), 124.6 (C300), 124.3
(C30), 123.0 (ArC30 and 50 and ArC300 and 500), 122.4 (ArC3 and 5),
121.9 (C200), 121.3 (C20), 121.0 (C3), 114.2 (C3a00), 113.1 (C3a0), 112.8
(C3a), 106.2 (C700), 105.5 (C7), 100.2 (C70), 94.5 (C500), 92.6 (C5), 91.8
NRY would like to thank the University of Wollongong for
a scholarship.
References and notes
1. For general reviews of biaryl synthesis, see: (a) Bringmann, G.; Walter, R.;
Weirich, R. Angew. Chem. 1990, 29, 977–991; (b) Hassan, J.; Se´vignon, M.; Gozzi,
C.; Schulz, E.; Lemaire, M. Chem. Rev. 2002, 102, 1359–1469.
0
(C50),0 57.2 (C4 OCH300), 57.1 (C4 OCH3), 56.0 (C6 OCH3 ), 55.6 (C4
OCH3 ), 55.5 (C6 OCH300), 55.3 (C6 OCH3). ES-MS m/z: 1179.2
([Mþ1]þ, 25%), 1082.3 (20), 986.3 (30), 416.2 (20), 400.3 (20), 338.4
(30), 313.2 (10), 218.9 (30), 179.0 (50), 104.0 (100); ES-HRMS m/z:
calcd for [Mþ1]þ C54H36N6O15F9 1179.2095; found 1179.2089.
2. For reviews on the atropselective synthesis of biaryls, see: (a) Bringmann, G.;
Price Mortimer, A. J.; Keller, P. A.; Garner, J.; Gresser, M. J.; Breuning, M. Angew.
Chem. 2005, 44, 5384–5427; (b) Wallace, T. Org. Biomol. Chem. 2006, 4, 3197–
3210; (c) Lloyd-Williams, P.; Giralt, E. Chem. Soc. Rev. 2001, 30, 145–157.
3. (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457–2483; (b) Suzuki, A. J.
Organomet. Chem. 1999, 576, 147–168; (c) Kotha, S.; Lahiri, K.; Kashinath, D.
Tetrahedron 2002, 58, 9633–9695; (d) Daudin, O. Eur. J. Org. Chem. 2005, 4223–
4229.
4. See Ref. 1 and (a) Gu, R.; Van Hecke, K.; Van Meervelt, L.; Toppet, S.; Dehaen, W.
Org. Biomol. Chem. 2006, 4, 3785–3789; (b) Pezzella, A.; Panzella, L.; Natangelo,
A.; Arzillo, M.; Napolitano, A.; d’Ischia, M. J. Org. Chem. 2007, 72, 9225–9230 and
references therein.
4.3.14. 4,6-Dimethoxy-2-[40,60-dimethoxy-30-(4-nitrophenylindol)-
70-yl]-3-(4-nitrophenyl)indole (37)
This was prepared by general procedure (B) using 4,6-di-
methoxy-3-(40-nitrophenyl)indole
6
(0.20 g,
0.67 mmol),
thallium(III) trifluoroacetate (0.18 g, 0.34 mmol) and boron tri-
fluoride diethyletherate (0.47 g, 3.3 mmol). The crude residue was
subjected to flash silica gel column chromatography (70:30, hexane/
ethylacetate) to give the indole 38 (0.04 g, 20%) as a yellow solid, mp
5. (a) Black, D. S.; Keller, P. A.; Kumar, N. Tetrahedron Lett. 1989, 30, 5807–5808; (b)
Keller, P. A.; Birch, C.; Leach, S. P.; Tyssen, D.; Griffith, R. J. Mol. Graphics 2003, 21,
365–373; (c) Bremner, J. B.; Coates, J. A.; Coghlan, D. R.; David, D. M.; Keller,
P. A.; Pyne, S. G. New J. Chem. 2002, 26, 1549–1552.
6. See Ref. 4a and (a) Abbiati, G.; Arcadi, A.; Beccalli, E.; Bianchi, G.; Marinelli, F.;
Rossi, E. Tetrahedron 2006, 62, 3033–3039; (b) Wada, Y.; Nagasaki, H.; Tokuda,
M.; Orito, K. J. Org. Chem. 2007, 72, 2008–2014; (c) Merlic, C. A.; You, Y.;
McInnes, D. M.; Zechman, A. L.; Miller, M. M.; Deng, Q. Tetrahedron 2001, 5199–
5212 and references therein; (d) Koza, D. J.; Euler, W. B. Heterocycl. Commun.
1999, 5, 399–402.
245–248 ꢀC. 1H NMR
d
: 8.56 (1H, s, NH), 8.18 (2H, d, J¼5.1 Hz, Ar3H00
and 500), 8.02 (2H, d, J¼5.4 Hz, ArH30 and 50), 7.94 (1H, s, NH0), 7.67
(2H, d, J¼5.1 Hz, Ar2H00 and 600), 7.55 (2H, d, J¼5.4 Hz, Ar2H0 and 60),
6.88 (1H, s, H20), 6.57 (1H, d, J¼1.8 Hz, H7), 6.41 (1H, s, H50), 6.32
(1H, d, J¼1.8 Hz, H5), 3.91 (3H, s, C6 OCH3), 3.88 (3H, s, C60 OCH3),
7. (a) Black, D. StC.; Bowyer, M. C.; Catalano, M. M.; Ivory, A. J.; Keller, P. A.; Kumar,
N.; Nugent, S. J. Tetrahedron 1994, 50, 10497–10508; (b) Keawin, T.; Rajviroongit,
S.; Black, D. StC. Tetrahedron 2005, 853–861.
3.79 (3H, s, C4 OCH3), 3.75 (3H, s, C40 OCH3). 13C NMR
d: 158.3 (C6),
155.6 (C60),154.5 (C4),155.3 (C40),145.7 (ArC100),145.4 (ArC10),144.9
(ArC40), 143.7 (ArC400), 138.2 (C7a), 137.7 (C7a0), 130.9 (ArC20 and 60),
129.8 (ArC200 and 600), 127.5 (C3), 122.8 (ArC30 and 50), 123.3 (ArC300
and 500), 122.9 (C20), 117.3 (C30), 114.9 (C2), 111.2 (C3a), 110.1 (C3a0),
97.1 (C7), 92.7 (C5), 89.7 (C50), 86.9 (C7), 55.0 (C4 OCH3), 53.5 (C40
OCH3), 53.1 (C60 OCH3), 52.0 (C6). ES-MS m/z: 594.2 ([Mþ1]þ, 15%),
338.5 (50), 336.2 (100), 147.1 (90). ES-HRMS m/z: calcd for [Mþ1]þ
C32H26N4O8 595.1829; found 595.1832.
8. McKillop, A.; Turrell, A. G.; Young, D. W.; Taylor, E. C. J. Am. Chem. Soc. 1980, 102,
6504–6512.
9. Banerji, A.; Ray, R.; Pal, S. C.; Banerji, D.; Maiti, K. K. J. Indian Chem. Soc. 1998, 75,
698–704.
10. Tholander, J.; Bergman, J. Tetrahedron 1999, 55, 12595–12602.
11. Black, D. S. C.; Bowyer, M. C.; Bowyer, P. K.; Ivory, A. J.; Kim, M.; Kumar, N.;
McConnell, D. B.; Popiolek, M. Aust. J. Chem. 1994, 47, 1741–1750.
12. Black, D. StC.; Ivory, A. J.; Kumar, N. Tetrahedron 1996, 52, 7003–7012.
13. (a) D’Ischia, M.; Napolitano, A.; Tsiakas, K.; Prota, G. Tetrahedron 1990, 46, 5789–
5796; (b) Napolitano, A.; D’Ischia, M.; Prota, G.; Schultz, T. M.; Wolfram, L. J.
Tetrahedron 1989, 45, 6749–6760.
14. Sheldrick, G. M. SHELXL 97dA Program for Crystal Structure Refinement; Uni-
versity of Go¨ttingen: Go¨ttingen, 1997.
4.4. Structure determinations
15. 12.
C
46H40N2O10S2, M¼845.0. Monoclinic, space group P21/n, a¼12.725(1),
b¼17.671(1), c¼18.158(1) Å,
b
¼91.449(2)ꢀ, V¼4082 Å3. Dc (Z¼4)¼1.375 g cmꢂ3
.
Full spheres of CCD diffractometer data were measured
mMo¼0.19 mmꢂ1; specimen: 0.10ꢁ0.09ꢁ0.08 mm; ‘T’min/max¼0.82. 2qmax¼70ꢀ;
Nt¼67457, N¼18054 (Rint¼0.077), No¼8927; R1¼0.055, wR2¼0.14 (a¼0.067).
(monochromatic Mo K
153 K) yielding Nt(otal) reflections, these merging to N unique (Rint
a
radiation,
l
¼0.71073 Å;
u-scans; T ca.
j
Drmaxj¼1.38 e Åꢂ3
.
28. C34H30Br2N2O8S2$2(CH3)2CO, M¼934.7. Monoclinic,
space group C2/c, a¼20.766(2), b¼9.7298(8), c¼22.543(2) Å,
b
¼117.101(2)ꢀ,
cited) after ‘empirical’/multiscan absorption correction (pro-
V¼4055 Å3. Dc (Z¼4)¼1.531 g cmꢂ3
.
mMo¼2.2 mmꢂ1
specimen: 0.28ꢁ0.15ꢁ
;
prietary software), No with F>4
s(F) being considered ‘observed’. All
0.12 mm; ‘T’min/max¼0.72.
2
qmax¼75ꢀ; Nt¼42853, N¼10294 (Rint¼0.045),
were used in the full matrix least squares refinement on F2, refining
No¼5440; R1¼0.037, wR2¼0.077 (a¼0.034). jDrmaxj¼0.95 e Åꢂ3
.