Synthesis of molecular chains: Application of cross-coupling and bromo by iodo exchange reactions

Article abstract of DOI:10.1016/j.tet.2015.06.072

The synthesis of a series of molecular chains by use of C-S, C-N and C-Alkyne cross coupling, as well as bromo by iodo exchange reactions, has been reported. Two different types of chains R-C₆H₄-S-C₆H₄-CC-C₆H₄-NH-C₆H₄-Br, and R-C₆H₄-S-C₆H₄-NH-C₆H₄-CC-C₆H₄-Br (R=MeO, CN, NO₂) could be obtained starting from the same thioether but applying different reaction sequences. Compounds R-C₆H₄-CC-C₆H₄-S-C₆H₄-NH-C₆H₄-Br were prepared from diaryl acetylenes after two bromo by iodo replacements alternated with a C-S and a C-N cross coupling.

Full text of DOI:10.1016/j.tet.2015.06.072

Tetrahedron 71 (2015) 5506e5512
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of molecular chains: application of cross-coupling
and bromo by iodo exchange reactions
*
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
Jesus M. Fernandez-Hernandez, Veronica Camara, Jose Vicente
ꢀ
ꢀ
Grupo de Química Organometalica, Departamento de Química Inorganica, Facultad de Química, Universidad de Murcia, Apdo. 4021, 30071 Murcia,
Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 22 April 2015
Received in revised form 16 June 2015
Accepted 17 June 2015
Available online 24 June 2015
The synthesis of a series of molecular chains by use of CeS, CeN and C-Alkyne cross coupling, as well as
bromo by iodo exchange reactions, has been reported. Two different types of chains
ReC6H4eSeC6H4eC^CeC6H4eNHeC6H4eBr,
and
ReC6H4eSeC6H4eNHeC6H4eC^CeC6H4eBr
(R¼MeO, CN, NO2) could be obtained starting from the same thioether but applying different reaction
sequences. Compounds ReC6H4eC^CeC6H4eSeC6H4eNHeC6H4eBr were prepared from diaryl acety-
lenes after two bromo by iodo replacements alternated with a CeS and a CeN cross coupling.
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Molecular chains
CeS cross coupling reaction
CeN cross coupling reaction
Bromo by iodo exchange
Thiols
1. Introduction
functionalized groups would provide new interesting properties to
the final chains. For example, ethynyl substituents are interesting
In the last decades, the synthesis of molecular chains has
attracted a growing interest as a consequence of its applications in
a great variety of fields such as, pharmaceuticals,1,2 sensors,2,3 opto-
electronic, non-linear optical and photonic devices,4e6 catalysis,7
etc.8 One of the most common strategies to prepare this type of
molecules involves the step-by-step repetition of coupling
reactions.9e11
We have previously reported a stepwise synthesis of molecular
chains.10,11 Our approach involves the Pd-catalyzed C-X coupling
between AreI and HXAr0Br (X¼S, Ar¼aryl, Ar0¼phenylene) to give
ArXAr0Br, taking advantage of the different reactivity of Br and I
derivatives, followed by a Br by I replacement to give ArXAr0I. This
unit could be reacted with HXAr0Br in the next growing step. In this
way, we have proved that it is possible to prepare molecules of
great interest such as phenylene thioethers of different sizes and
ending groups. Thus, thioether oligomers ReC6H4e(SeC6H4)neBr,
prepared by Pd-catalyzed CeS cross coupling, afforded molecules
of the type ReC6H4e(SeC6H4)neI (Fig. 1) after the Cu-catalyzed
replacement of bromo by iodo.10 We also predicted the extension
of this methodology to prepare chains such as Ar-(XeAr0)n-Br
where X could be C^C, NH, S or O. Indeed, introducing new
because of their rigid structure and their p electrons, which could
confer interesting photophysical properties that could lead to the
possibility of using the final molecules in optoelectronic de-
vices.5,12,13 Additionally, amines are strong donor groups that have
been included in oligomers with different applications.4,12,14
With the aim of extending the scope of this method, we present
here the synthesis of six molecular chains of the type
ReC6H4eXeC6H4eX0eC6H4eX00eC6H4eR0, R and R0 being either
donor or acceptor groups such as NO2, MeO, CN, Br or I and X, X0 and
X00, S, NH or C^C. The NH, and alkyne functions could be introduced
into the chain by well-known CeN and C-alkyne cross coupling
* Corresponding author. Tel.: þ34 868 88 4143; fax: þ34 868 88 7585; e-mail
address: jvs1@um.es (J. Vicente).
Fig. 1. Phenyl thioether described previously.
http://dx.doi.org/10.1016/j.tet.2015.06.072
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.

ꢀ
ꢀ
J.M. Fernandez-Hernandez et al. / Tetrahedron 71 (2015) 5506e5512
5507
reactions of the appropriate AreI and HXAr0Br (X¼N or alkyne)
compounds. Thus, to illustrate the method, we have prepared
chains with different sequential distribution of the functional
groups by choosing the suitable starting material and reaction
sequence.
2. Results and discussion
2.1. Synthesis of chains starting from a thioether
Compounds 2aec (Scheme 1) are the starting materials to
synthesize several thioether chains containing the ethynyl phe-
nylene amino unit. These compounds were prepared following the
two steps procedure we have previously described:10 i) the
palladium-catalyzed CeS cross coupling reaction between iodoar-
enes and 4-bromobenzenethiol and ii) the copper-catalyzed re-
placement of bromo by iodo (Scheme 1). Interestingly, the CeS
coupling reaction was significantly improved compared to what we
previously described,10 since the reaction time was reduced from 3
days to 2 h by increasing the temperature to 100 ꢀC.
Scheme 3. Synthesis of the chains 7aec. i) [PdCl2(PPh3)2] (5 mol %), CuI (5 mol %),
THF:iPr2NH (50:1), rt; ii) Pd(dba)2 (5 mol %), rac-Binap (5 mol %), NaOtBu (1.3 equiv),
toluene at 80 ꢀC.
following a modified Sonogashira C-alkyne coupling16 of com-
pounds 4aec with bromo-4-ethynylbenzene in the presence of
5 mol % of the catalytic mixture of PdCl2(PPh3)2 and CuI in
THF:iPr2NH (50:1) at room temperature. Although the reaction
time required to complete this last step increased from 18 h when
R¼CN (5a) to 36 h (R¼NO2, 5c), the yields are very similar for the
three prepared compounds. Thus, a priori, this process is in-
dependent of the mesomeric effect of the R substituent.
The isomers of type 7 were obtained inverting the coupling
processes sequence (Scheme 3). In this case, we firstly carried out
the C-alkyne coupling process, and then, the CeN coupling, without
any Br by I exchange reaction between both steps (Scheme 3).
The reaction conditions of the C-alkyne and CeN cross couplings
to afford compounds 6aec and 7aec were the same than those
employed to obtain 5aec and 3aec, respectively, with the excep-
tion of the temperature, which ranges from 100 ꢀC for 3aec, to
80 ꢀC for 7aec. Observing the results in both cases, we could con-
clude that, the CeN cross coupling is more effective when 4-
bromoaniline is used instead of 4-bromoiodobenzene. An excep-
tion to this is the reaction giving 7b in which, despite of using
a lower temperature than in the case of its analogous 3b, both the
reaction time and the yield are better.
Scheme 1. Synthesis of iodo thioether compounds. i) NaOtBu (1 equiv), Pd(dba)2
(5 mol %), dppf (5 mol %) 2 h at 100 ꢀC; ii) CuI (7 mol %), dmcd (13 mol %), NaI (2 equiv);
[a] Ref. 10.
Compounds 5aec (Scheme 2) or 7aec (Scheme 3) were pre-
pared from the diaryl thiothers 2aec, but following different syn-
thetic strategies.
Remarkably, when both coupling reactions required to obtain
7aec (Scheme 3) were performed via one-pot, the process stopped
at the C-alkyne coupling to afford 6aec.
2.2. Synthesis of chains starting from alkynes
With the aim of introducing in the first step of the process the
alkynyl unit, we have prepared compounds 8aec by a C-alkyne
cross coupling reaction between the corresponding aryl iodide and
bromo-4-ethynylbenzene (Scheme 4).16 Subsequently, an exchange
reaction of bromo by iodo was performed to give rise to 9aec. Just
as we did for 7aec, we tried to obtain 9aec via one-pot reaction.
However, when the C-alkyne coupling and the bromo by iodo
exchange reactions were carried out in the same flask without
isolating the bromo derivates, 8aec were obtained instead of 9aec.
In this case, the reaction sequence also stopped at the C-alkyne
coupling.
Compounds 10aec were obtained in good yields by a CeS cross
coupling with 4-bromobenzenethiol, under the same reaction
conditions as above. The arylamino group was introduced by an
exchange of bromo by iodo to afford 11aec, followed by a CeN cross
coupling with 4-bromoaniline to afford 12aec (Scheme 4). This last
step of the process gave low yield for substrates containing electron
withdrawing end groups (R¼NO2, CN).
Scheme 2. Synthesis of the chains 5aec. i) Pd(dba)2 (5 mol %), rac-Binap (5 mol %),
NaOtBu (1.3 equiv), toluene at 100 ꢀC; ii) CuI (7 mol %), NaI (2 equiv), dmcd (13%), di-
oxane, 48 h at 140 ꢀC; iii) [PdCl2(PPh3)2] (5 mol %), CuI (5 mol %), THF:iPr2NH (50:1), rt.
The CeN coupling of 4-bromoaniline with 2aec in the presence
of a slight excess of NaOtBu, and 5 mol % of the catalytic mixture of
Pd(dba)2 and rac-Binap (toluene, 100 ꢀC, 24 h) afforded compounds
3aec (Scheme 2). The Cu-catalyzed exchange reactions of bromo by
iodo gave rise to iodo derivatives 4aec. The reaction is a slightly
modified version of the Cu-catalyzed halogen exchange reaction
reported by Buchwald,15 using 7 mol % of CuI, 13 mol % of racemic
trans-N,N0-dimethyl-1,2-cyclohexane diamine (dmcd), and 2 equiv
of NaI (dioxane, 140 ꢀC, 48 h). Compounds 5aec were prepared

ꢀ ꢀ
J.M. Fernandez-Hernandez et al. / Tetrahedron 71 (2015) 5506e5512
5508
Scheme 4. Synthesis of chains derived from bromo-4-ethynylbenzene. i) [PdCl2(PPh3)2] (5 mol %), CuI (5 mol %), THF:iPr2NH (50:1), rt; ii) CuI (7 mol %), NaI (2 equiv), dcm (13%),
dioxane, 48 h at 140 ꢀC; iii) Pd(dba)2 (5 mol %), dppf (5 mol %), NaOtBu (1 equiv), toluene, 2 h at 100 ꢀC; iv) Pd(dba)2 (5 mol %), rac-Binap (5 mol %), NaOtBu (2 equiv), toluene.
3. Conclusions
corrected. Abbreviations used: br (broad), s (singlet), d (doublet), m
(multiplet), v (virtual). Chromatographic separations were carried
out on silica gel either by preparative TLC using a fluorescent in-
dicator or by column chromatography. High-resolution ESI mass
spectra were recorded on an Agilent 6220 Accurate-Mass TOF LC/
MS spectrometer.
We have prepared a series of molecular chains containing an
alkynyl, a thio and an amino group. Their syntheses are based on
the application of a step-by-step sequential method consisting of
CeN, CeS, or C-Alkyne cross coupling reaction including a bromo
by iodo exchange reaction. Thus, starting from the same thioether
compound, two types of chains could be prepared depending on
the next step being a CeN or a C-alkyne coupling. Isomeric chains
have also been prepared, but using a different starting material and
reactions sequence. In conclusion, the application of several cross
coupling and exchange reactions allows the formation of isomeric
chains ReC6H4eXeC6H4eX0eC6H4eX00eC6H4eR0, where R, R0,
could be either donor or acceptor groups, NO2, MeO, CN, Br or I,
while X, X0 and X00 could be S, NH or C^C. The presence of a CeBr
end group allows the easy additional growing of the chains.
4.2. General method for the bromo by iodo exchange
The exchange of bromo by iodo was carried out as previously
described.11 A Carius tube was charged successively with the bromo
derivate, CuI (7 mol %), NaI (2 equiv), dmcd (13 mol %) and 1,4-
dioxane. The reaction mixture was stirred at 140 ꢀC for 2 days.
After cooling down to room temperature, the solvent was removed
under vacuum, and the residue extracted with Et2O (30 mL) and
filtered. The filtrate was concentrated to dryness, and the residue
was purified by washing with cold n-hexane (Method A) or by
chromatography in CH2Cl2/n-hexane (1:1) (Method B).
4. Experimental section
4.1. General
4.2.1. 4-((4-Iodophenyl)thio)benzonitrile (2a). Method A. Colourless
solid. Yield: 88%. 1H NMR (300.1 MHz, CDCl3):
d 7.74 (vd, 2H,
4-Bromobenzenethiol, 4-iodonitrobenzene, 4-iodoanisole, 4-
bromobenzonitrile, 4-bromoiodobenzene, KOtBu, NaOtBu, dppf
J¼8.0 Hz), 7.50 (vd, 2H, J¼8.0 Hz), 7.22e7.18 (m, 4H). 13C{1H} NMR
(75.45 MHz, CDCl3): d 144.4 (CN), 138.9 (CH), 135.6 (CH), 132.4 (CH),
(1,10-Bis(diphenylphosphino)ferrocene),
rac-Binap
(rac-1,10-
131.2 (C), 127.8 (CH), 118.5 (C), 109.2 (C), 95.3 (C). Elemental anal-
yses (%) calcd for C13H8INS: C, 46.31; H, 2.39; N, 4.15; S, 9.51; found:
C, 46.48; H, 2.45; N, 4.50; S, 9.49. MS (EI) m/z (%): 337 (95), 338 (30),
339 (11).
binaphthalene-2,20-diyl)bis(diphenylphosphine)), dmcd (trans-
N,N0-Dimethylcyclohexane-1,2-diamine), and dba (dibenziylide-
neacetone) were obtained from commercial sources. 4-
18
Ethynylaniline,17 bromo-4-ethynylbenzene, Pd(dba)2
and
PdCl2(PPh3)2 were prepared according to previously reported
methods. Compounds 1b, 1c, 2b and 2c were prepared following
a slightly modified version of a procedure previously reported by
our group.10,11 The reactions were carried out under an inert at-
mosphere. CH2Cl2, Et2O and Toluene were degassed and dried using
a Pure Solv MD-5 solvent purification system while 1,4-dioxane was
obtained from commercial sources and deoxygenated by bubbling
N2. n-Hexane and n-pentane were used as received. Elemental
analyses were carried out with Carlo Erba 1106 and LECO CHNS-932
microanalyzers. NMR spectra were recorded on Bruker Avance 200,
300, and 400 instruments. 1H chemical shifts were referenced to
TMS, and 13C{1H} NMR spectra were referenced to CDCl3
(77.0 ppm). The temperature values in NMR experiments were not
4.2.2. 4-((4-((4-Iodophenyl)amino)phenyl)thio)benzonitrile
(4a). Method A. Colourless solid. Yield: 95%. 1H NMR (400.9 MHz,
CDCl3):
7.12e7.10 (m, 2H), 7.09e7.05 (m, 2H), 6.94e6.91 (m, 2H), 5.88 (br s,
1H, NH). 13C{1H} NMR (100.8 MHz, CDCl3):
147.4 (C), 144.4 (C),
d 7.62e7.58 (m, 2H), 7.47e7.44 (m, 2H), 7.43e7.39 (m, 2H),
d
141.3 (C), 138.3 (CH), 136.9 (CH), 132.2 (CH), 126.1 (CH), 121.1 (CH),
119.9 (C),118.9 (C),117.7 (CH), 108.0 (C), 84.4 (C). Elemental analyses
(%) calcd for C19H13IN2S: C, 53.28; H, 3.06; N, 6.54; S, 7.49; found: C,
53.40; H, 3.08; N, 6.55; S, 7.61. MS (EI) m/z (%): 428.1 (100), 429.1
(20), 430 (6).
4.2.3. 4-Iodo-N-(4-((4-methoxyphenyl)thio)phenyl)aniline
(4b). Method B. Colourless solid. Yield: 70%. 1H NMR (400.9 MHz,

ꢀ
ꢀ
J.M. Fernandez-Hernandez et al. / Tetrahedron 71 (2015) 5506e5512
5509
CDCl3):
d
7.50 (vd, 2H, J¼16.0 Hz), 7.32 (vd, 2H, J¼8.8 Hz), 7.20 (vd,
(MeO). Elemental analyses (%) calcd for C21H15IOS: C, 57.02; H, 3.42;
2H, J¼8.4 Hz), 6.94 (vd, 2H, J¼8.4 Hz), 6.85 (vd, 2H, J¼8.8 Hz), 6.79
S, 7.25 found: C, 57.07; H, 3.62; S, 7.22. HRMS (ESIþ) m/z calcd for
(vd, 2H, J¼8.4 Hz), 5.73 (br s, 1H, NH), 3.79 (s, 3H, Me). 13C{1H} NMR
MHþ: 442.9967; found: 442.9965.
D
¼0.45 ppm.
(100.8 MHz, CDCl3): d 159.1 (C), 142.6 (C), 141.3 (C), 138.1 (CH), 133.3
(CH), 131.9 (CH), 128.7 (C), 126.7 (C), 119.6 (CH), 118.8 (CH), 114.8
(CH), 82.6 (C), 55.3 (MeO). Elemental analyses (%) calcd for
4.2.10. (4-Iodophenyl)(4-((4-nitrophenyl)ethynyl)phenyl)thioether
(11c). Method B. Pale yellow solid. Yield: 84%. 1H NMR (400.9 MHz,
C
19H16INOS: C, 52.67; H, 3.72; N, 3.23; S, 7.40; found: C, 52.61; H,
CDCl3):
(m, 2H, Ar), 7.27e7.25 (m, 2H, Ar), 7.15e7.12 (m, 2H, Ar). 13C{1H}
NMR (100.8 MHz, CDCl3): 146 (C), 138.4 (CH), 137.8 (C), 134.1 (C),
133.7 (CH), 132.4 (CH), 132.2 (CH), 129.9 (C), 129.7 (CH), 123.7
(CH), 120.4 (C), 94.1 (C), 93.5 (C), 88.4 (C). Elemental analyses (%)
calcd for C20H12INO2S: C, 52.53; H, 2.65; N, 3.06; S, 7.01; found:
C, 52.42; 2.98; 3.06; S, 6.84. MS (EI) m/z (%): 457 (100), 458 (27),
459 (8).
d 8.24e8.20 (m, 2H, Ar), 7.68e7.64 (m, 4H, Ar), 7.47e7.45
3.72; N, 3.20; S, 7.46. HRMS (ESIþ) m/z calcd for [MþH]þ: 434.0076;
found: 434.0075.
D
¼0.23 ppm.
d
4.2.4. 4-Iodo-N-(4-((4-nitrophenyl)thio)phenyl)aniline (4c). Method
B. Orange solid. Yield: 70%. 1H NMR (400.9 MHz, CDCl3):
d
8.07e8.03 (m, 2H), 7.62e7.58 (m, 2H), 7.44e7.40 (m, 2H),
7.14e7.11 (m, 2H), 7.10e7.06 (m, 2H), 6.95e6.92 (m, 2H), 5.96 (br s,
1H, NH). 13C{1H} NMR (100.8 MHz, CDCl3):
150.2 (C), 144.9 (C),
d
144.6 (C), 141.2 (C), 138.3 (CH), 137.0 (CH), 132.4 (C), 125.6 (C), 123.9
(CH), 121.2 (CH), 119.5 (C), 117.7 (CH), 84.6 (C). Elemental analyses
(%) calcd for C18H13IN2O2S: C, 48.23; H, 2.92; N, 6.25; S, 7.15; found:
C, 48.13; H, 3.01; N, 6.04; S, 7.17. HRMS (ESIþ) m/z calcd for [MþH]þ:
4.3. General method for the CeS coupling reactions
The CeS coupling was carried out by a modification of a pro-
cedure described recently by our group.10 The reaction time was
reduced from 3 days to 2 h by increasing the temperature to 100 ꢀC.
Thus, a Carius tube was charged with the corresponding thiol
(1 equiv), aryl iodide (1.05 equiv), Pd(dba)2 (5 mol %), dppf (5 mol
%), NaOtBu (1 equiv), and toluene. The resulting mixture was
heated at 100 ꢀC for 2 h. After removing the solvent under vacuum,
the residue was extracted with CH2Cl2 (30 mL) and filtered. The
organic filtrate was concentrated and purified by chromatography
using CH2Cl2/n-hexane (1:1) as eluent.
448.9815; found: 448.9827.
D¼2.67 ppm.
4.2.5. 4-((4-Iodophenyl)ethynyl)benzonitrile (9a). Method B. Col-
ourless solid. Yield 83%. 1H NMR (400.9 MHz, CDCl3):
7.74e7.71
(m, 2H), 7.66e7.59 (m, 4H), 7.27e7.25 (m, 2H). 13C{1H} NMR
(100.8 MHz, CDCl3): 137.2 (CH), 132.6 (C), 131.6 (CH), 131.5 (CH),
d
d
127.3 (C), 121.2 (C), 117.9 (C), 111.2 (C), 94.8 (C), 92.2 (C), 88.5 (C).
Elemental analyses (%) calcd for C15H8IN: C, 54.74, H, 2.45; N, 4.26;
found: C, 54.81; H, 2.41; N, 4.21. HRMS (ESIþ) m/z calcd for
[MþNa]þ: 351.9594; found: 351.9588.
¼1.70 ppm.
D
4.3.1. 4-((4-Bromophenyl)thio)benzonitrile (1a). Colourless solid.
4.2.6. 1-Iodo-4-((4-methoxyphenyl)ethynyl)benzene (9b). Method A.
Yield: 80%. 1H NMR (400.9 MHz, CDCl3):
d
7.57e7.53 (m, 2H),
7.52e7.48 (m, 2H), 7.37e7.35 (m, 2H), 7.20e7.17 (m, 2H). 13C{1H}
NMR (100.8 MHz, CDCl3): 144.6 (CN), 135.6 (CH), 133.1 (CH), 132.5
Colourless solid. Yield: 90%. 1H NMR (400.9 MHz, CDCl3):
d
7.69e7.65 (m, 2H), 7.48e7.43 (m, 2H), 7.26e7.21 (m, 2H),
6.90e6.85 (m, 2H), 3.83 (s, 3H, MeO). 13C{1H} NMR (100.8 MHz,
CDCl3): 159.8 (C), 137.5 (CH), 133.1 (C), 132.9 (CH), 123.2 (C), 115.0
d
(CH), 130.3 (C), 127.7 (CH), 123.8 (C), 118.6 (C), 109.3 (C). Elemental
analyses (%) calcd for C13H8BrNS: C, 53.81; H, 2.78; N, 4.83; S, 11.05;
found: C, 53.88; H, 2.69; N, 5.19; S, 10.82. MS (EI) m/z (%): 289 (90),
290 (16), 291 (87), 292 (15).
d
(C), 114.1 (C), 93.6 (C), 90.9 (C), 87.2 (C), 55.3 (MeO). Elemental
analyses (%) calcd for C15H11IO: C, 53.92; H, 3.32; found: C, 53.62; H,
3.45. MS (EI) m/z (%): 334 (100), 335 (24).
4.3.2. 4-((4-((4-Bromophenyl)thio)phenyl)ethynyl)benzonitrile
4.2.7. 1-Iodo-4-((4-nitrophenyl)ethynyl)benzene (9c). Method B.
(10a). Colourless solid. Yield: 80%. 1H NMR (400.9 MHz, CDCl3):
Pale yellow solid. Yield: 84%. 1H NMR (200.1 MHz, CDCl3):
d
8.23
d
7.65e7.58 (m, 4H), 7.49e7.43 (m, 4H), 7.29e7.23 (m, 4H). 13C{1H}
(vd, 2H, J¼16.0 Hz), 7.74e7.64 (m, 4H), 7.30e7.26 (m, 2H). 13C{1H}
NMR (100.8 MHz, CDCl3): d 137.8 (C), 133.7 (CH), 133.2 (C), 132.6
NMR (50.3 MHz, CDCl3):
d
147.1 (C), 137e7 (CH), 133.1 (CH), 132.2
(CH), 132.4 (CH), 132.0 (CH), 132.0 (CH), 129.5 (CH), 128.0 (C), 122.1
(C), 120.5 (C), 118.4 (C), 111.5 (C), 93.1(C), 88.5 (C). Elemental anal-
yses (%) calcd for C21H12BrNS: C, 64.62; H, 3.10; N, 3.59; S, 8.22;
found: C, 64.55; H, 3.12; N, 3.71; S, 8.02. HRMS (ESIþ) m/z calcd for
(CH), 129.8 (C), 123.6 (CH), 121.6 (C), 95.4 (C), 93.6 (C), 88.8 (C).
Elemental analyses (%) calcd for C14H8INO2: C, 48.16; H, 2.31; N,
4.01 found: C, 48.54; H, 2.38; N, 3.95. Owing to the poor ionization
of the compound, we were not able to obtain a useful mass
spectrum.
MNaþ: 411.9746; found: 411.9744.
D¼4.85 ppm.
4.3.3. (4-Bromophenyl)(4-((4-methoxyphenyl)ethynyl)phenyl)thio-
4.2.8. 4-((4-((4-Iodophenyl)thio)phenyl)ethynyl)benzonitrile
ether (10b). Colourless solid. Yield: 80%. 1H NMR (400.9 MHz,
(11a). Method B. Colourless solid. Yield: 90%. 1H (300.8 MHz,
CDCl3):
d
7.45 (m, 6H), 7.26e7.21 (m, 4H), 6.89e6.87 (m, 2H), 3.83
159.7 (C),135.4 (C),
CDCl3):
d
7.68e7.57 (m, 6H), 7.46e7.43 (m, 2H), 7.27e7.24 (m, 2H),
138.5 (CH), 137.6
(s, 3H, MeO). 13C{1H} NMR (100.8 MHz, CDCl3):
d
7.14e7.11 (m, 2H). 13C{1H} (75.45 MHz, CDCl3):
d
134.4 (C), 133.1 (CH), 132.8 (CH), 132.4 (CH), 132.2 (CH), 130.5 (CH),
122.5 (C), 121.5 (C), 115.1 (C), 114.0 (C), 90.5 (C), 87.4 (C). Elemental
analyses (%) calcd for C21H15BrOS: C, 63.80; H, 3.82; S, 8.11; found:
C, 63.74; H, 3.92; S, 8.20. HRMS (ESIþ) m/z calcd for MHþ: 395.0105;
(C), 134.2 (C), 133.6 (CH), 132.4 (CH), 132.0 (CH), 129.0 (CH), 127.9
(C), 120.7 (C), 118.5 (C), 111.6 (C), 93.3 (C), 93.1 (C), 88.6 (C). Ele-
mental analyses (%) calcd for C21H12INS: C, 57.68; H, 2.77; N, 3.20; S,
7.33; found: C, 57.85; H, 2.79; N, 3.14; S, 7.72. HRMS (ESIþ) m/z calcd
found: 395.0107.
D¼0.51 ppm.
for MNaþ 459.9627; found: 459.9620.
D¼1.52 ppm.
4.3.4. (4-Bromophenyl)(4-((4-nitrophenyl)ethynyl)phenyl)thioether
4.2.9. (4-Iodophenyl)(4-((4-methoxyphenyl)ethynyl)phenyl)thio-
(10c). Pale yellow solid. Eluent CH2Cl2/n-hexane (1:3), Rf¼0.33.
ether (11b). Method B. Pale yellow solid. Yield: 76%. 1H NMR
Yield: 65%. 1H NMR (400.9 MHz, CDCl3):
d 8.24e8.21 (m, 2H),
(300.8 MHz, CDCl3):
7.29e7.24 (m, 2H), 7.07 (vd, 2H, J¼12.0 Hz), 6.87 (vd, 2H, J¼12.0 Hz),
3.83 (MeO). 13C{1H} NMR (75.45 MHz, CDCl3):
159.7 (C), 138.3
(CH), 135.5 (C), 135.1 (C), 133.1 (CH), 132.8 (CH), 132.2 (CH), 130.7
(CH), 122.7 (C), 115.1 (C), 114.0 (CH), 92.6 (C), 90.6 (C), 87.4 (C), 55.3
d
7.62 (vd, 2H, J¼12.0 Hz), 7.47e7.42 (m, 4H),
7.67e7.64 (m, 2H), 7.50e7.44 (m, 4H), 7.30e7.27 (m, 2H), 7.26e7.23
(m, 2H). 13C{1H} NMR (100.8 MHz, CDCl3):
d
147.0 (C), 138.2 (C),
d
133.9 (CH), 133.1 (C), 132.6 (CH), 132.5 (CH), 132.2 (CH), 130.0 (C),
129.5 (CH), 123.7 (CH), 122.3 (C), 120.4 (C), 94.0 (C), 88.3 (C). Ele-
mental analyses (%) calcd for C20H12BrNO2S: C, 58.55; H, 2.95; N,

ꢀ ꢀ
J.M. Fernandez-Hernandez et al. / Tetrahedron 71 (2015) 5506e5512
5510
3.41; S, 7.82 found: C, 58.28; H, 2.77; N, 3.35; S, 8.04. HRMS (ESIþ)
m/z calcd for MHþ: 409.9850; found: 409.9863.
¼3.17 ppm.
(m, 4H), 7.08e7.05 (m, 2H), 6.93e7.89 (m, 2H), 6.93e7.89 (m, 2H),
6.61e6.59 (m, 2H), 3.82 (s, 3H, MeO), 3.80 (s, 2H, NH2). 13C{1H} NMR
D
(100.8 MHz, CDCl3):
d 160.0 (C), 146.6 (C), 138.7 (C), 135.7 (CH),
4.4. General method for the C-alkyne coupling reactions
132.9 (CH), 131.7 (CH), 127.4 (CH), 123.4 (C), 121.0 (C), 115.1 (CH),
114.7 (CH), 112.5 (C), 90.4 (C^), 87.0 (C^), 55.3 (MeO). Elemental
analyses (%) calcd for C21H17NOS: C, 76.10; H, 5.17; N, 4.23; S, 9.68;
found: C, 75.96; H, 5.31; N, 4.35; S, 9.89. HRMS (ESIþ) m/z calcd for
A Schlenk tube under a nitrogen atmosphere was charged with
the iododerivate, 4-ethynylaniline (1.1 equiv) or bromo-4-
ethynylbenzene (1.1 equiv), CuI (5 mol %), and [PdCl2(PPh3)2]
(5 mol %). Sequentially, THF (5 mL) and iPr2NH (0.1 mL) were added.
The reaction mixture was stirred for X h at room temperature, and
extracted with CH2Cl2 (30 mL) and water (2ꢁ10 mL). The organic
phase was dried over MgSO4, and the resulting solution was con-
centrated to about 1 mL. Addition of cold Et2O (Method A) or col-
umn chromatography (Method B) gave the desired compound.
MHþ: 332.1104; found: 332.1095.
D
¼2.71 ppm.
4.4.6. 4-((4-((4-Nitrophenyl)thio)phenyl)ethynyl)aniline
(6c). Method A. X¼52. Pale orange crystals. Further compound
could be obtained from the mother liquor. Yield: 70%. 1H NMR
(300.8 MHz, CDCl3):
(vd, 2H, J¼9.0 Hz), 7.21 (vd, 2H, J¼9.0 Hz), 6.65 (vd, 2H, J¼9.0 Hz),
3.86 (br s, 2H, NH2). 13C{1H} NMR (100.8 MHz, CDCl3):
147.9, 147.0,
d
8.08 (vd, 2H, J¼9.0 Hz), 7.56e7.46 (m, 4H), 7.3
d
4.4.1. 4-((4-((4-((4-Bromophenyl)ethynyl)phenyl)amino)phenyl)
thio)benzonitrile (5a). Method B. X¼18. Eluent EtOAc/n-hexane
(1:4), Rf¼0.5. Pale yellow solid. Yield 63%. 1H NMR (400.9 MHz,
145.5, 134.2 (CH), 133.0 (CH), 132.6 (CH), 129.8, 127.0 (CH), 125.4,
124.1 (CH), 114.7 (CH), 111.8, 92.6 (C^), 86.3 (C^). Elemental
analyses (%) calcd for C20H14IN2O2S: C, 69.35; H, 4.07; N, 8.09; S,
9.26; found: C, 69.14; H, 3.97; N, 8.28; S, 9.20. MS (EI) m/z (%): 346
(100), 347 (35), 348 (11).
CDCl3):
d 7.49e7.42 (m, 8H), 7.39e7.36 (m, 2H), 7.16e7.09 (m, 6H),
6.03 (br s, 1H, NH). 13C{1H} NMR (100.8 MHz, CDCl3):
d 147.3 (C),
143.9 (C), 141.9 (C), 136.9 (CH), 133.0 (CH), 132.8 (CH), 132.3 (CH),
131.6 (CH), 126.2 (CH), 122.4 (C), 122.2 (C), 120.5 (C), 118.9 (C), 118.3
(CH), 118.0 (CH), 116.0 (C), 108.1 (C), 90.5 (C), 87.6 (C). Elemental
analyses (%) calcd for C27H17BrN2S: C, 67.3; H, 3.56; N, 5.82; S, 6.66;
found: C, 67.46; H, 3.42; N, 6.03; S, 6.85. HRMS (ESIþ) m/z calcd for
4.4.7. 4-((4-Bromophenyl)ethynyl)benzonitrile
X¼24. Eluent CH2Cl2/n-hexane (1:5), Rf¼0.43. Colourless solid.
Yield: 85%. 1H NMR (400.9 MHz, CDCl3):
7.66e7.59 (m, 8H),
7.54e7.50 (m, 2H), 7.42e7.39 (m, 2H). 13C{1H} NMR (100.8 MHz,
CDCl3): 133.2 (CH), 132.1 (CH), 131.8 (CH), 127.8 (C), 123.5 (C), 121.1
(C), 118.4 (CN), 111.7 (C), 92.6 (C^), 88.7 (C^). Elemental analyses
(%) calcd for C15H8BrN: C, 63.86; H, 2.86; N, 4.96; found: C, 63.73; H,
2.63; N, 4.98. MS (EI) m/z (%): 281 (100), 282 (36), 283 (99), 284
(33).
(8a). Method B.
d
MNaþ: 503.0188; found: 503.0190.
D¼0.40 ppm.
d
4.4.2. 4-((4-Bromophenyl)ethynyl)-N-(4-((4-methoxyphenyl)thio)
phenyl)aniline (5b). Method B. X¼24. Eluent EtOAc/n-hexane (1:4),
Rf¼0.34. Pale yellow solid. Yield 54%. 1H NMR (400.9 MHz, CDCl3):
d
7.46 (vd, 2H, J¼8.0 Hz), 7.41e7.33 (m, 6H), 7.22 (vd, 2H, J¼8.0 Hz),
7.03e6.96 (m, 4H), 6.87 (vd, 2H, J¼8.0 Hz), 5.83 (br s, 1H, NH), 3.80
4.4.8. 1-Bromo-4-((4-methoxyphenyl)ethynyl)benzene (8b). Method
B. X¼24. Eluent CH2Cl2/n-hexane (1:5), Rf¼0.43. Colourless solid.
(s, 3H, MeO). 13C{1H} NMR (100.8.8 MHz, CDCl3):
d
159.2 (C), 143.3
(C), 140.7 (C), 133.5 (CH), 132.9 (CH), 132.8 (CH), 131.7 (CH), 131.5
(CH), 129.5 (C), 126.5 (C), 122.6 (C), 121.9 (C), 119.4 (C), 116.5 (CH),
115.8 (CH), 114.5 (C), 90.9 (C), 87.2 (C), 55.3 (MeO). Elemental
analyses (%) calcd for C27H20BrNOS: C, 66.67; H, 4.14; N, 2.88; S,
6.59; found: C, 66.54; H, 4.42; N, 3.10; S, 6.59. MS (EI) m/z (%): 485
(100), 486 (43), 487 (91), 488 (41), 489 (13).
Yield: 89%. 1H NMR (400.9 MHz, CDCl3):
d 7.48e7.44 (m, 4H),
7.38e7.35 (m, 2H), 6. 90e6.86 (m, 2H), 3.83 (s, 3H, MeO). 13C{1H}
NMR (75.45 MHz, CDCl3): 159.7 (C), 133.0 (CH), 132.8 (CH), 131.5
d
(CH), 122.5 (C), 122.0 (C), 114.9 (C), 114.0 (CH), 90.5 (C^), 87.0 (C^),
55.3 (MeO). Elemental analyses (%) calcd for C15H11BrO: C, 62.74; H,
3.86; found: C, 62.69; H, 3.83. MS (EI) m/z (%): 286 (100), 287 (25),
288 (99), 289 (25).
4.4.3. 4-((4-Bromophenyl)ethynyl)-N-(4-((4-nitrophenyl)thio)phe-
nyl)aniline (5c). Method B. X¼36. Eluent EtOAc/n-hexane (1:4),
Rf¼0.21. Reddish Solid. Yield: 65%. 1H NMR (300.1 MHz, CDCl3):
4.4.9. 1-Bromo-4-((4-nitrophenyl)ethynyl)benzene (8c). Method B.
X¼28. Eluent CH2Cl2/n-hexane (1:3), Rf¼0.45. Pale yellow solid.
d
8.09e8.04 (m, 2H), 7.49e7.44 (m, 6H), 7.40e7.35 (m, 2H),
Yield: 73%. 1H NMR (400.9 MHz, CDCl3):
d 8.25e8.21 (m, 2H),
7.18e7.10 (m, 6H), 6.04 (br s, 1H, NH). 13C{1H} NMR (75.45 MHz,
CDCl3): 150.0 (C) 145.0 (C), 144.1 (C), 141.8 (C), 137.0 (CH), 133.0
7.68e7.65 (m, 2H), 7.55e7.52 (m, 2H), 7.44e7.41 (m, 2H). 13C{1H}
NMR (100.8 MHz, CDCl3): 147.1 (C), 133.1 (CH), 132.2 (CH), 131.8
d
d
(CH), 132.9 (CH), 131.6 (CH), 125.7 (CH), 124.0 (CH), 122.4 (C), 122.2
(C), 120.1 (C), 118.3 (CH), 118.2 (C), 116.1 (C), 90.5 (C), 87.7 (C). Ele-
mental analyses (%) calcd for C26H17BrN2O2S: C, 62.28; H, 3.42; N,
5.59; S, 6.40; found: C, 61.88; H, 3.39; N, 5.56; S, 6.42. MS (ESI) m/z
(CH), 129.8 (C), 123.6 (CH), 121.0 (C), 93.4 (C), 88.5 (C). One C signal
was not detected. Elemental analyses (%) calcd for C14H8BrNO2: C,
55.66; H, 2.67; N, 4.64; found: C, 55.31; H, 2.69; N, 4.94. MS (EI) m/z
calcd for Mþ: 300.9738; found: 300.9697.
(%): [MþH]þ calcd 501.0272; found: 501.0279.
¼1.39 ppm.
D
4.5. General method for the CeN coupling reactions
4.4.4. 4-((4-((4-Aminophenyl)ethynyl)phenyl)thio)bezonitrile
(6a). Method A. X¼16. Colourless solid. Yield: 70%. 1H NMR
A Schlenk tube under a nitrogen atmosphere was charged with
the corresponding iododerivate (1 equiv), 4-bromoaniline
(1.1 equiv) or 1-bromo-4-iodobenzene (1 equiv), Pd(dba)2 (5 mol
%), rac-Binap (5 mol %), NatOBu (1.3e2 equiv). Subsequently, tolu-
ene (10 mL) was added and the reaction mixture was stirred for X h
at Y ꢀC. The resulting mixture was extracted with CH2Cl2 (30 mL)
and water (2ꢁ10 mL). The organic phase was dried over MgSO4. The
solution was concentrated to about 1 mL and purified by column
chromatography.
(400.9 MHz, CDCl3):
d 7.53e7.48 (m, 4H), 7.45e7.43 (m, 2H),
7.36e7.33 (m, 2H), 7.22e7.19 (m, 2H), 6.66e6.63 (m, 2H), 3.90 (br s,
2H, NH2).). 13C{1H} NMR (100.8 MHz, CDCl3):
d
147.0 (C), 145.1 (C),
133.9 (CH), 133.0 (CH), 132.5 (CH), 132.4 (CH), 130.3 (C), 127.7 (CH),
125.1 (C), 118.0 (C), 114.7 (CH), 111.9 (C), 109.0 (C), 92.4 (C^), 86.4
(C^). Elemental analyses (%) calcd for C21H14N2S: C, 77.27; H, 4.32;
N, 8.58; S, 9.82; found: C, 76.98; H, 4.52; N, 8.55; S, 9.93. MS (EI) m/z
(%): 326 (100), 327 (52), 328 (25), 329 (5).
4.4.5. 4-((4-((4-Methoxyphenyl)thio)phenyl)ethynyl)aniline
4.5.1. 4-((4-((4-Bromophenyl)amino)phenyl)thio)benzonitrile
(6b). Method A. X¼36. Pale yellow solid, unstable in silica gel. Yield:
(3a). X¼24, Y¼100. Eluent EtOAc/n-hexane (1:5), Rf¼0.34. Colour-
70%. 1H NMR (400.9 MHz, CDCl3):
d
7.44e7.40 (m, 2H), 7.35e7.28
less solid. Yield: 50%. 1H NMR (200.1 MHz, CDCl3):
d 7.49e7.40

ꢀ
ꢀ
J.M. Fernandez-Hernandez et al. / Tetrahedron 71 (2015) 5506e5512
5511
(m, 6H), 7.14e7.02 (m, 6H), 5.88 (br s, 1H, NH). 13C{1H} NMR
(50.30 MHz, CDCl3): 147.4 (C),144.7 (C),140.5 (C),136.9 (CH),132.4
3.60; N, 5.60; S, 6.39. MS (EI) m/z (%): 500 (100), 501 (30), 502 (98),
503 (27), 504 (8).
d
(CH), 132.2 (CH), 126.1 (CH), 121.0 (CH), 119.7(C), 119.0 (C), 117.5
(CH), 114.6 (C), 107.9 (C). Elemental analyses (%) calcd for
4.5.7. 4-((4-((4-((4-Bromophenyl)amino)phenyl)thio)phenyl)ethy-
nyl)benzonitrile (12a). X¼72, Y¼100. Eluent EtOAc/n-hexane (1:4),
Rf¼0.37. Yellowish solid. Yield: 32%. 1H NMR (300.1 MHz, CDCl3):
C
19H13BrN2S: C, 59.85; H, 3.44; N, 7.35; S, 8.41; found: C, 59.30; H,
3.70; N, 7.08; S, 8.25. MS (EI) m/z (%): 380 (82, Mþ), 381 (26), 382
(73), 383 (23), 384 (6).
d 7.63e7.55 (m, 4H), 7.42e7.37 (m, 6H), 7.15e7.10 (m, 2H),
7.06e6.98 (m, 4H), 5.82 (br s, NH). 13C{1H} NMR (75.45 MHz,
CDCl3): 143.8 (C), 141.3 (C), 140.9 (C), 136.0 (CH), 132.4 (CH), 132.1
4.5.2. 4-Bromo-N-(4-((4-methoxyphenyl)thio)phenyl)aniline
d
(3b). X¼24, Y¼100. Eluent CH2Cl2/n-hexane (1:2), Rf¼0.33. Col-
(CH), 132.0 (CH), 132.0 (CH), 127.0 (C), 122.3 (C), 120.5 (CH), 119.0
(C), 118.5 (C), 117.7 (CH), 114.2 (C), 111.3 (C), 93.7 (C), 88.0 (C). Ele-
mental analyses (%) calcd for C27H17BrN2S: C, 67.36; H, 3.56; N, 5.82;
S, 6.66; found: C, 66.84; H, 3.67; N, 5.66; S, 6.92. HRMS (ESIþ) m/z
ourless solid. 1H NMR (400.9 MHz, CDCl3):
d 7.34e7.31 (m, 4H),
7.23e7.20 (m, 2H), 6.92e6.88 (m, 6H), 5.70 (br s, 1H, NH), 3.80 (s,
3H, MeO). 13C{1H} NMR (100.8 MHz, CDCl3):
d
159.1 (C), 141.8 (C),
141.5 (C), 133.2 (CH), 132.2 (CH), 132.1 (CH), 128.5, 126.8 (C), 119.4
(CH), 118.5(CH), 114.8 (CH), 113.1 (C), 55.3 (MeO). Elemental anal-
yses (%) calcd for C19H16BrNOS: C, 59.07; H, 4.17; N, 3.63; S, 8.30;
found: C, 59.11; H, 4.22; N, 3.48; S, 8.53. MS (EI) m/z (%): 385 (100,
Mþ), 387 (49), 388 (25), 389 (10).
(%): [MþH]þ calcd 481.0369; found: 481.0377.
¼1.66 ppm.
D
4.5.8. 4-Bromo-N-(4-((4-((4-methoxyphenyl)ethynyl)phenyl)thio)
phenyl)aniline (12b). X¼72, Y¼80. Eluent CH2Cl2/n-hexane (1:1),
Rf¼0.4. Yellowish solid. Yield. 70%. 1H NMR (300.1 MHz, CDCl3):
d
7.46e7.43 (m, 2H), 7.41e7.35 (m, 6H), 7.14e7.11 (m, 2H), 7.03e6.98
4.5.3. 4-Bromo-N-(4-((4-nitrophenyl)thio)phenyl)aniline
(m, 4H), 6.88e6.85 (m, 2H), 5.80 (br s,1H, NH), 3.82 (s,1H, MeO). 13
C
(3c). X¼24, Y¼100. Eluent CH2Cl2/n-hexane (1:1), Rf¼0.47. Col-
{1H} NMR (75.45 MHz, CDCl3):
d
159.6 (C), 143.3 (C), 141.1 (C), 139.0
ourless solid. 1H NMR (400.9 MHz, CDCl3):
d
8.07e8.03 (m, 2H),
(C), 135.5 (CH), 133.0 (CH), 132.3 (CH), 131.8 (CH), 127.6 (CH), 123.4
(C), 120.8 (C), 120.3 (CH), 117.8 (CH), 115.3(C), 114.0 (CH), 113.9 (C),
89.7 (C), 87.8 (C), 55.3 (MeO). Elemental analyses (%) calcd for
7.44e7.42 (m, 4H), 7.08e7.04 (m, 6H), 5.91 (br s, 1H, NH). 13C{1H}
NMR (100.8 MHz, CDCl3): 150.2 (C), 145.0 (C), 144.9 (C), 140.4 (C),
d
137.0 (CH), 132.5 (CH), 125.6 (CH), 124.0 (CH), 121.1 (CH), 119.4 (C),
117.5 (CH), 114.8 (C). Elemental analyses (%) calcd for
C27H20BrNOS: C, 66.67; H, 4.14; N, 2.88; S, 6.59; found: C, 66.20; H,
4.93; N, 3.01; S, 6.10. MS (EI) m/z (%): 485 (100), 486 (37), 487 (90),
C
18H13BrN2O2S: C, 53.88; H, 3.27; N, 6.98; S, 7.99; found: C, 53.69; H,
488 (32), 489 (10).
3.34; N, 7.29; S, 8.12. HRMS (ESIþ) m/z (%): [MþH]þ calcd 400.9959;
found: 400.9951.
D
¼2.00 ppm.
4.5.9. 4-Bromo-N-(4-((4-((4-nitrophenyl)ethynyl)phenyl)thio)phe-
nyl)aniline (12c). X¼96, Y¼80. Eluent CH2Cl2/n-hexane (1:1),
Rf¼0.70. Yellow solid. Yield: 23%. 1H NMR (300.1 MHz, CDCl3):
4.5.4. 4-((4-((4-((4-Bromophenyl)amino)phenyl)ethynyl)phenyl)
thio)benzonitrile (7a). X¼42, Y¼80. Eluent CH2Cl2/n-hexane (1:1),
Rf¼0.36. Orange solid. Yield: 15%. 1H NMR (300.1 MHz, CDCl3):
d
8.21 (m, 2H), 7.63 (m, 2H), 7.42e7.39 (m, 6H), 7.12 (m, 2H), 7.03 (m,
4H), 5.85 (br s, 1H, NH). 13C{1H} NMR (75.45 MHz, CDCl3):
d 146.9
d
7.55e7.38 (m, 10H), 7.22e7.19 (m, 2H), 7.01e6.97 (m, 4H), 5.83 (s,
(C), 143.8 (C), 141.6 (C), 140.9 (C), 138.5 (CH), 136.1 (CH), 132.4 (CH),
132.18 (CH), 132.15 (CH), 130.3 (C), 126.9 (CH), 123.6 (CH), 122.2 (C),
120.6 (CH), 118.8 (C), 117.7 (CH), 114.3 (C), 94.6 (C), 87.8 (C). Ele-
mental analyses (%) calcd for C26H17BrN2O2S: C, 62.28; H, 3.42; N,
5.59; S, 6.40; found: C, 62.28; H, 3.42; N, 5.39; S, 6.28. MS (EI) m/z
(%): 501 (94), 502 (28), 503 (100), 504 (29), 505 (9).
1H, NH). 13C{1H} NMR (75.45 MHz, CDCl3):
d 145.0 (C), 143.3 (C),
140.9 (C), 133.9 (CH), 133.1 (CH), 132.6 (CH), 132.5 (CH), 132.4 (CH),
130.8 (C), 127.8 (CH), 124.8 (C), 120.5 (CH), 118.7 (C), 116.5 (CH),
114.5(C), 114.2 (C), 109.1 (C), 91.9 (C), 87.3 (C). Elemental analyses
(%) calcd for C27H17BrN2S: C, 67.36; H, 3.56; N, 5.82; S, 6.66; found:
C, 67.76; H, 3.37; N, 5,44; S, 6.65. MS (EI) m/z (%): 480 (100), 481
(30), 482 (100), 483 (30), 484 (9).
Acknowledgements
4.5.5. 4-Bromo-N-(4-((4-((4-methoxyphenyl)thio)phenyl)ethynyl)
phenyl)aniline (7b). X¼16, Y¼80. Eluent CH2Cl2/n-hexane (1:1),
Rf¼0.53. Pale orange solid. Yield: 80%. 1H NMR (400.9 MHz, CDCl3):
ꢀ
We thank the Spanish Ministerio de Ciencia e Innovacion
ꢀ
ꢀ
(CTQ2011-24016 with FEDER support) and Fundacion Seneca
(Grant 04539/GERM/06) for financial support. J.M.F.-H. would like
to acknowledge Fundacion Seneca for a Saavedra-Fajardo reincor-
poration grant.
d
7.45e7.34 (m, 8H), 7.09e7.06 (vd, 2H, J¼8.0), 6.99e6.91 (m, 6H),
ꢀ
ꢀ
5.79 (br s, 1H, NH), 3.84 (s, 3H, MeO). 13C{1H} NMR (100.8 MHz,
CDCl3): 160.1 (C), 142.8 (C), 141.1 (C), 139.2 (C), 135.8 (CH), 132.9
d
(CH), 132.3 (CH), 131.8 (CH), 127.3 (CH), 123.3 (C), 120.7 (C), 120.2
(CH), 116.7 (CH), 115.3 (C), 115.1 (CH), 113.8 (C), 89.9 (C^), 88.0
(C^), 55.4 (MeO). Elemental analyses (%) calcd for C27H20BrNOS: C,
66.67; H, 4.14; N, 2.88; S, 6.59; found: C, 66.86; H, 4.14; N, 3.15; S,
6.73. MS (EI) m/z (%): 485 (98), 486 (28), 487 (100), 488 (29), 489
(9).
Supplementary data
Supplementary data (1H and 13C NMR spectra of the new com-
pounds) related to this article can be found at http://dx.doi.org/
10.1016/j.tet.2015.06.072.
References and notes
4.5.6. 4-Bromo-N-(4-((4-((4-nitrophenyl)thio)phenyl)ethynyl)phe-
nyl)aniline (7c). X¼24, Y¼80. Eluent CH2Cl2/n-hexane (1:1), Rf¼0.2.
1. (a) Wu, P.; Malkoch, M.; Hunt, J. N.; Vestberg, R.; Kaltgrad, E.; Finn, M. G.; Fokin,
V. V.; Sharpless, K. B.; Hawker, C. J. Chem. Commun. 2005, 5775; (b) Tang, S.;
Martinez, L. J.; Sharma, A.; Chai, M. Org. Lett. 2006, 8, 4421; (c) Haag, R.; Kratz, F.
Angew. Chem., Int. Ed. 2006, 45, 1198.
2. Astruc, D.; Boisselier, E.; Ornelas, C. Chem. Rev. 2010, 110, 1857.
3. Grabchev, I.; Chovelon, J. M.; Nedelcheva, A. J. Photochem. Photobiol., A 2006,
183, 9.
Orange solid. Yield: 35%. 1H NMR (400.9 MHz, CDCl3):
d 8.09e8.07
(m, 2H), 7.56 (vd, 2H, J¼8.0 Hz), 7.48 (vd, 2H, J¼8.0 Hz), 7.44e7.38
(m, 4H), 7.24e7.20 (m, 2H), 7.01e6.98 (m, 4H), 5.85 (br s, 1H, NH).
13C{1H} NMR (100.8 MHz, CDCl3):
d 147.8 (C), 145.5 (C), 143.3 (C),
140.8 (C), 134.2 (CH), 133.1 (CH), 132.7 (CH), 132.4 (CH),130.3 (C),
127.2 (CH), 125.1 (C), 124.1 (CH), 120.6 (CH), 116.5 (CH), 114.5 (C),
114.2 (C), 92.1 (C^), 87.3 (C^). Elemental analyses (%) calcd for
4. Zhu, M.; Yang, C. Chem. Soc. Rev. 2013, 42, 4963.
5. (a) Bunz, U. H. F. Chem. Rev. 2000, 100, 1605; (b) Palsson, L.-O.; Wang, C.; Bat-
ꢁ
sanov, A. S.; King, S. M.; Beeby, A.; Monkman, A. P.; Bryce, M. R. Chem.dEur. J.
C
26H17BrN2O2S: C, 62.28; H, 3.42; N, 5.59; S, 6.40; found: C, 62.14; H,
2010, 16, 1470.

ꢀ ꢀ
J.M. Fernandez-Hernandez et al. / Tetrahedron 71 (2015) 5506e5512
5512
6. (a) Meier, H. Angew. Chem., Int. Ed. 2005, 44, 2482; (b) Cifuentes, M. P.; Powell,
C. E.; Morrall, J. P.; McDonagh, A. M.; Lucas, N. T.; Humphrey, M. G.; Samoc,
M.; Houbrechts, S.; Asselberghs, I.; Clays, K.; Persoons, A.; Isoshima, T. J. Am.
Chem. Soc. 2006, 128, 10819; (c) Kato, T.; Mizoshita, N.; Kishimoto, K. Angew.
Chem., Int. Ed. 2006, 45, 38; (d) Fin, A.; Vargas Jentzsch, A.; Sakai, N.; Matile, S.
Angew. Chem., Int. Ed. 2012, 51, 12736; (e) Choi, H.; Baik, C.; Kang, S. O.; Ko, J.;
Lett. 2003, 5, 3297; (r) Pinchart, A.; Dallaire, C.; Gingras, M. Tetrahedron Lett.
1998, 39, 543; (s) Van Bierbeek, A.; Gingras, M. Tetrahedron Lett. 1998, 39, 6283;
(t) Tsuchida, E.; Yamamoto, K.; Oyaizu, K.; Suzuki, F.; Hay, A. S.; Wang, Z. Y.
Macromolecules 1995, 28, 409; (u) Menger, F. M.; Azov, V. A. J. Am. Chem. Soc.
2002, 124, 11159.
10. Vicente, J.; Abad, J. A.; Lopez-Nicolas, R. M. Tetrahedron 2008, 64, 6281.
11. Vicente, J.; Abad, J. A.; Lopez-Nicolas, R. M. Tetrahedron Lett. 2005, 46, 5839.
12. Palai, A. K.; Mishra, S. P.; Kumar, A.; Srivastava, R.; Kamalasanan, M. N.; Patri, M.
J. Polym. Sci., Part A: Polym. Chem. 2011, 49, 832.
€
Kang, M.-S.; Nazeeruddin, M. K.; Gratzel, M. Angew. Chem., Int. Ed. 2008, 47,
327; (f) Schubert, C.; Margraf, J. T.; Clark, T.; Guldi, D. M. Chem. Soc. Rev. 2015,
44, 988.
ꢀ
ꢀ
ꢀ
ꢀ
7. (a) Mery, D.; Astruc, D. Coord. Chem. Rev. 2006, 250, 1965; (b) Helms, B.; Frechet,
13. (a) Ballesteros, L. M.; Martín, S.; Marques-Gonzalez, S.; Lopez, M. C.; Higgins, S.
J.; Nichols, R. J.; Low, P. J.; Cea, P. J. Phys. Chem. C 2015, 119, 784; (b) Albinsson, B.;
Eng, M. P.; Pettersson, K.; Winters, M. U. Phys. Chem. Chem. Phys. 2007, 9, 5847;
(c) Jou, J.-H.; Kumar, S.; Fang, P.-H.; Venkateswararao, A.; Thomas, K. R. J.;
Shyue, J.-J.; Wang, Y.-C.; Li, T.-H.; Yu, H.-H. J. Mat. Chem. C 2015, 3, 2182; (d)
Egbe, D. A. M.; Neugebauer, H.; Sariciftci, N. S. J. Mater. Chem. 2011, 21, 1338.
14. (a) Shirota, Y.; Kageyama, H. Chem. Rev. 2007, 107, 953; (b) Chaskar, A.; Chen, H.-
J. M. J. Adv. Synth. Catal. 2006, 348, 1125; (c) Delort, E.; Nguyen-Trung, N.-Q.;
Darbre, T.; Reymond, J.-L. J. Org. Chem. 2006, 71, 4468.
8. Peris, E. Coord. Chem. Rev. 2004, 248, 279.
9. (a) Grayson, S. M.; Frechet, J. M. J. Chem. Rev. 2001, 101, 3819; (b) Dahan, A.;
Weissberg, A.; Portnoy, M. Chem. Commun. 2003, 1206; (c) Hortholary, C.;
ꢀꢂ
ꢂ
Coudret, C. J. Org. Chem. 2003, 68, 2167; (d) Valasek, M.; Pecka, J.; Jindrich;
Calleja, G.; Craig, P. R.; Michl, J. J. Org. Chem. 2005, 70, 405; (e) Rodríguez, J. G.;
Tejedor, J. L.; Esquivias, J.; Díaz, C. Tetrahedron Lett. 2003, 44, 6375; (f) van
Heerbeek, R.; Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Reek, J. N. H. Chem. Rev.
2002, 102, 3717; (g) Binauld, S.; Damiron, D.; Connal, L. A.; Hawker, C. J.;
Drockenmuller, E. Macromol. Rapid Commun. 2011, 32, 147; (h) Franz, N.;
Kreutzer, G.; Klok, H.-A. Synlett 2006, 1793; (i) Zhang, Z. S.; Fan, E. K. J. Org.
Chem. 2005, 70, 8801; (j) Magro, G.; Donnadieu, B.; Caminade, A. M.; Majoral, J.
P. Chem.dEur. J. 2003, 9, 2151; (k) De Nicola, A.; Goeb, S.; Ziessel, R. Tetrahedron
Lett. 2004, 44, 7963; (l) Dong, T.-Y.; Lin, M.-C.; Chiang, M. Y.-N.; Wu, J.-Y. Or-
ganometallics 2004, 23, 3921; (m) Hurst, S. K.; Cifuentes, M. P.; Humphrey, M. G.
Organometallics 2002, 21, 2353; (n) Newkome, G. R.; He, E.; Moorefield, C. N.
Chem. Rev. 1999, 99, 1689; (o) Rozalska, I.; Kulyk, P.; KulszewiczBajer, I. New J.
Chem. 2004, 28, 1235; (p) Yamamoto, K.; Higuchi, M.; Shiki, S.; Tsuruta, M.;
Chiba, H. Nature 2002, 415, 509; (q) Jones, T. V.; Blatchly, R. A.; Tew, G. N. Org.
ꢃ
F.; Wong, K.-T. Adv. Mater. 2011, 23, 3876; (c) Leliege, A.; Grolleau, J.; Allain, M.;
Blanchard, P.; Demeter, D.; Rousseau, T.; Roncali, J. Chem.dEur. J. 2013, 19, 9948;
(d) Jeong, S.; Kim, M.-K.; Kim, S. H.; Hong, J.-I. Org. Electron. 2013, 14, 2497; (e)
Wang, K.; Huang, S.; Zhang, Y.; Zhao, S.; Zhang, H.; Wang, Y. Chem. Sci. 2013, 4,
3288; (f) Ye, J.; Chen, Z.; Fung, M.-K.; Zheng, C.; Ou, X.; Zhang, X.; Yuan, Y.; Lee,
C.-S. Chem. Mater. 2013, 25, 2630.
15. Klapars, A.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 14844.
16. (a) Doucet, H.; Hierso, J.-C. Angew. Chem., Int. Ed. 2007, 46, 834; (b) Sonogashira,
K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 16, 4467.
17. (a) Vasilevsky, S. F.; Klyatskaya, S. V.; Elguero, J. Tetrahedron 2004, 60, 6685; (b)
Fang, J.-K.; An, D.-L.; Wakamatsu, K.; Ishikawa, T.; Iwanaga, T.; Toyota, S.; Akita,
S.-I.; Matsuo, D.; Orita, A.; Otera, J. Tetrahedron 2010, 66, 5479.
18. (a) Takahashi, Y.; Ito, T.; Sakai, S.; Ishii, Y. J. Chem. Soc. D 1970, 1065; (b) Heck, R.
F. Palladium Reagents in Organic Synthesis; Academic Press: New York, 1985.