Preferential oxidative addition in mixed iodo/bromo quinquephenylenes

Article abstract of DOI:10.1016/j.tet.2014.04.001

A Suzuki reaction of a diiodo monobromo quinquephenylene with an aryl boronic acid is described. With PEPPSI-IPr as catalyst the threefold coupling product is mainly obtained although only two equivalents of the boronic acid are used. This shows that the intramolecular palladium transfer is favored over the common iodo/bromo selectivity. Performing the reaction with other Pd systems shows that the product distribution is strongly catalyst dependent.

Full text of DOI:10.1016/j.tet.2014.04.001

Tetrahedron 70 (2014) 3726e3729
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Preferential oxidative addition in mixed iodo/bromo
quinquephenylenes
*
€
Daniela Schmitz, Sigurd Hoger
ꢀ
€
€
Kekule-Institut fur Organische Chemie und Biochemie, Rheinische Friedrich-Wilhelms-Universitat Bonn, Gerhard-Domagk-Str. 1, 53121 Bonn, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
A Suzuki reaction of a diiodo monobromo quinquephenylene with an aryl boronic acid is described. With
PEPPSI-IPr as catalyst the threefold coupling product is mainly obtained although only two equivalents of
the boronic acid are used. This shows that the intramolecular palladium transfer is favored over the
common iodo/bromo selectivity. Performing the reaction with other Pd systems shows that the product
distribution is strongly catalyst dependent.
Received 22 January 2014
Received in revised form 28 March 2014
Accepted 1 April 2014
Available online 13 April 2014
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Arenes
Biaryls
Catalysis
Regioselectivity
Palladium
1. Introduction
applied for the preparation of macromolecules of defined molec-
ular weight and low polydispersity and also for the preparation of
Transition-metal catalyzed arylearyl-, arylevinyl-, and
aryleethynyl coupling reactions in which an (pseudo) halogen
component reacts with an organometallic compound are of fun-
damental importance in modern synthetic chemistry.1 If multiple
halogens are present in the substrate and this is treated with only
one equivalent of the metal organic compound, statistical mixtures
are expected and often observed. Selectivity can be reached by
making use of the different reactivity of the halogens, which de-
creases in the order I>Br>Cl or by halogens of the same kind and
a different degree of activation.2 Alternatively, the coupling of ha-
logenated phenols and their subsequent transformation to triflates
allows the synthesis of unsymmetrical coupling products in good to
high yield.3
end-functionalized polymers because the polymerization proceeds
via a ‘chain-growth mechanism’ rather than via a ‘step-growth
mechanism’.7 It can be assumed that after the reductive elimination
the diffusion process of the Pd(0) species and leaving the coupling
product is slower than the oxidative addition with the nearby
carbon-halogen bond. This is in accordance with the assumption
that h
2-bound arenes are on the pathway for the oxidative addi-
tion.8 Furthermore, this concept has recently been applied for the
synthesis of shape-persistent macrocycles.9
2. Results and discussion
Here we describe the synthesis of iodo/bromo septiphenylenes
that will be useful building blocks for the preparation of clamped
oligo(phenyleneeethynyleneebutadiynylenes) and other rigid
When statistical coupling reactions between a multihalogen
compound and an organometallic coupling partner are performed
the product distribution sometimes differs from the expected
composition.4 Recent work has shown that depending on the cat-
alyst system and the specific experimental conditions, a preferred
oxidative addition with the just formed 1-aryl-n-halobenzene can
occur.5 Interestingly, this does not only apply for simple arenes but
conjugated p
-oligomers.10 Specifically, we investigated the molec-
ular elongation of 1 by iodo-selective Pd(0) catalyzed Suzuki-
coupling with two equivalents of 2 followed by the ICl mediated
iododesilylation to give 4 (Scheme 1). Compound 1 is rather easy
available from the 2,6-bis(4-iodophenyl)-4-(4-tert-butylphenyl)
pyrylium tetrafluoroborate and sodium 4-bromophenyl acetate
according to the protocol developed by Zimmermann and Fischer.11
Initial Suzuki-coupling reactions were conducted under Pd cataly-
sis by the use of PEPPSI-IPr in the presence of potassium hydrox-
ide.12,13 Contrary to our expectations, we could not observe a clean
iodo/bromo selectivity that would give 3 as major product but we
also for more extended
p
-systems, e.g., for fluorenes.6 In the syn-
thesis of conjugated polymers this concept has already been
* Corresponding author. Tel.: þ49 228 73 6127; fax: þ49 228 73 5662; e-mail
€
address: hoeger@uni-bonn.de (S. Hoger).
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.04.001

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D. Schmitz, S. Hoger / Tetrahedron 70 (2014) 3726e3729
3727
Table 1
obtained a rather complex mixture of different coupling products
along with unreacted starting material (Scheme 2, Table 1). The
crude product was separated by column chromatography into
fractions F1eF4, and F1 (1), F2 (6) and F4 (7) are isolated as pure
compounds. Fraction F3 could only be obtained as a mixture of two
compounds; a bromo (3) and an iodo (5) functionalized twofold
substitution product. A further separation of 3 and 5 by column
chromatography is not possible due to their similar polarities.
However, the high yield of trisubstituted product 7 clearly shows
that under the applied conditions the intramolecular catalyst
transfer (probably via migration of Pd(0) from one arene to the
another arene unit of the same molecule) predominates over the
iodo/bromo selectivity. Moreover, the attempted synthesis of 3
could not be performed under these conditions since even the
fraction of the disubstituted reaction product (F3) that was ob-
tained in only 14% yield, was not pure 3, but a mixture of two
compounds (3 and 5), as mentioned before.
Ratio of column chromatography separated product fractions of Pd-catalyzed Suzuki
reactions of iodo/bromo pentaphenylene 1 and TMS substituted boronic acid 2
F1a [%] F2a [%] F3a [%] F4a [%] Yieldb [%] Ratioc
PEPPSI-IPr KOH
25
12
d
2
14
41d
71d
47
22
8
87
72
83
86:14
53:47
15:85
Pd2dba3/tBu3P K3PO4 25
Pd(PPh3)4 Cs2CO3
2
a
Yields of F1eF4 are defined relative to the starting material determined after
column chromatography.
b
Entire yields are defined as conversion relative to the boronic acid.
Ratio of F1, F2 and F4 to F3.
Under these reaction conditions F3 is isolated as pure 3, without side product 5.
c
d
3. Conclusion
To summarize, we could expand the size of the mixed iodo/
bromo compound 1 in two-steps in good yield starting from rather
easy accessible 1. The key to success was the iodo/bromo selectivity
in the Pd(0)-catalyzed Suzuki reaction. Although the concept of
preferential oxidation in Suzuki reactions under PEPPSI-IPr and
Pd2dba3/tBu3P was already described, a preferential oxidation in
mixed iodo/bromo compounds was, as far as we know, not men-
tioned before. Nevertheless, the nature of the catalyst has an
enormous influence on the product distribution and in our case we
observe a high tendency for the PEPPSI-IPr catalysts to undergo
preferential oxidative addition that overrides the conventional
iodo/bromo selectivity.
4. Experimental section
4.1. General experimental
All palladium catalyzed reactions were performed by applying
standard Schlenk techniques under Ar atmosphere and using dry
solvents (THF), if not otherwise indicated. THF was dried over
sodium and distilled and stored under argon. Chloroform was
used in p.a. quality and dichloromethane as solvent for work-up
was used after purification by distillation. All commercial avail-
able reagents were used without further purification. 1H and 13C
NMR spectra were recorded on Bruker AM 400 and AM 500
spectrometers (400 and 500 MHz for 1H; 100.6 and 125.8 MHz for
13C). Chemical shifts are given in parts per million (ppm) refer-
enced to residual 1H or 13C signals in deuterated CDCl3 (1H: 7.26,
13C: 77.0). Deuterated CDCl3 was obtained from Deutero GmbH,
Germany. Mass spectra were measured on a Bruker Daltronics
autoflex TOF/TOF (MALDI MS; matrix material: DCTB). High res-
olution mass spectra were recorded on a Bruker Daltronics
micrOTOF-Q (ESI, APCI). Thin layer chromatography was per-
formed on silica gel coated aluminum plates (MachereyeNagel,
Alugramm SIL G/UV254, 0.2 mm silica gel coating with fluores-
cence indicator). Column chromatography was performed using
Scheme 1. Synthesis of 4 in a two-step reaction sequence of an iodo-selective Suzu-
kieMiyaura coupling and subsequent ipso-substitution.
When using Pd2dba3/tBu3P as catalyst (K2PO3 as base), 3 could
be obtained in a yield of about 41%. Surprisingly the iodo
substituted side product 5 in F3 was absent according to NMR
spectroscopic and mass spectrometric analysis of the crude
product. However, still 22% of the threefold coupling product 7
indicated that the Pd(0) after the reductive elimination is still in
close proximity to the just reacted substrate. It undergoes the
intramolecular oxidative addition with rather high probability,
even though primarily an iodo/bromo selective cross coupling
reaction is favored. With Pd(PPh3)4 as catalyst and cesium car-
bonate as base, we observed an acceptable iodo/bromo selectivity
so that 3 could be isolated in 71% yield. Compound 3 was then
converted into the mixed iodo/bromo compound 4 in 95% yield.
silica gel 60 M (MachereyeNagel, 40e63 mm) as stationary phase
and dichloromethane and cyclohexane as eluent. The synthesis of
3 is performed under Pd-catalyzed conditions using PEPPSI-IPr,
Pd2dba3 and Pd(PPh3)4 as catalyst. A full characterization of 3
and further side products is given.
4.2. Preparation under PEPPSI-IPr catalyzed conditions
Compound 1 (0.100 g, 0.130 mmol), 2 (0.052 g, 0.266 mmol),
potassium hydroxide (0.044 g, 0.779 mmol) and PEPPSI-IPr
(0.004 g, 0.005 mmol) are placed in a Schlenk-tube and re-
peatedly evacuated and flushed with argon. The starting materials
are suspended in THF (5 mL) and stirred over night at 60 ꢀC. After
cooling to rt the reaction mixture is diluted with water and

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D. Schmitz, S. Hoger / Tetrahedron 70 (2014) 3726e3729
3728
Scheme 2. Variety of emerging compounds in dependence of the catalyst system. Two disubstituted reaction products (3 and 5) are possibly obtainable as fraction F3, which cannot
be further purified by standard column chromatography and therefore are combined in one fraction.
dichloromethane and the aqueous phase is extracted three times
with dichloromethane. The combined organic phase is washed
with water, sulfuric acid (10%ige), water and brine and dried over
magnesium sulfate. After removal of the solvent the crude product
is purified by column chromatography (CH/DCM 8/1) and fractions
cooled down to rt and diluted with dichloromethane and water.
The aqueous phase is extracted three times with dichloromethane
and the combined organic phase is washed with water and brine
and dried over magnesium sulfate. After removal of the solvent the
crude product is purified by column chromatography (CH/DCM 8/1)
F1 (Rf¼0.65, 25 mg, 31.8
12%), F3 (Rf¼0.48, 15 mg, 17.6
60.4 mol, 47%) are isolated as white solids.
m
mol, 25%), F2 (Rf¼0.57, 13 mg, 16.0
m
mol,
and fractions F1 (Rf¼0.65, 2 mg, 2.6
2.8
mol, 2%), F3 (Rf¼0.48, 75 mg, 92.4
10 mg, 10.9 mol, 8%) are isolated as white solids.
m
mol, 2%), F2 (Rf¼0.57, 2 mg,
m
mol, 14%) and F4 (Rf¼0.40, 53 mg,
m
m
mol, 71%) and F4 (Rf¼0.40,
m
m
4.3. Preparation under Pd2dba3 catalyzed conditions
4.5. 2-(4-Bromophenyl)-5-(4-tert-butylphenyl)-1-(4-
iodophenyl) -3-(4-(3-trimethylsilylphenyl)phenyl)benzene (6)
In a glovebox, tBu3P (0.002 g, 0.010 mmol) is placed in a Schlenk-
Tube. Compound 1 (0.100 g, 0.130 mmol), 2 (0.052 g, 0.266 mmol)
and potassium phosphate (0.082 g, 0.390 mmol) are added and
diluted with THF (5 mL). After flushing the reaction mixture with
argon for 15 min, Pd2dba3 (0.004 g, 0.004 mmol) is added and
stirred for 4 d at 50 ꢀC. After cooling down to rt, the reaction
mixture is diluted with water and dichloromethane and the
aqueous phase is extracted three times with dichloromethane. The
combined organic phase is washed with water, sulfuric acid (10%
ige), water and brine and dried over magnesium sulfate. After re-
moval of the solvent the crude product is purified by column
chromatography (CH/DCM 8/1) and fractions F1 (Rf¼0.65, 25 mg,
Mp>250 ꢀC; 1H NMR (500 MHz, CDCl3)
d 7.72e7.71 (m, 2H),
7.64e7.61 (m, 3H), 7.58e7.53 (m, 3H), 7.51e7.48 (m, 3H), 7.46 (d,
J¼8.3 Hz, 2H), 7.42 (t, J¼7.5 Hz, 1H), 7.19e7.15 (m, 4H), 6.87 (d,
J¼8.4 Hz, 2H), 6.77 (d, J¼8.4 Hz, 2H), 1.38 (s, 9H), 0.31 (s, 9H); 13C
NMR (125 MHz, CDCl3) d 150.9, 142.1, 141.2, 141.1, 141.1, 140.6, 140.3,
139.7,139.6,138.0,137.2,136.9,136.2,133.2,132.3,131.8,131.7,130.8,
130.2, 128.7, 128.1, 127.5, 126.8, 126.6, 125.9, 120.5, 92.4, 34.6, 31.3,
ꢂ
ꢁ1.1; MS (MALDI-pos, DCTB) m/z (%): 790.2 (100) [M]þ ; HRMS
calcd for C43H40BrISiH [MþH]þ 791.1200, found: 791.1168.
4.6. 1-(4-Bromophenyl)-4-(4-tert-butylphenyl)-2,6-bis(4-(3-
tri-methylsilylphenyl)phenyl)benzene (3)
31.9
m
mol, 25%), F3 (Rf¼0.48, 43 mg, 53.3
mmol, 41%) and F4
(Rf¼0.40, 25 mg, 28.4
mmol, 22%) are isolated as white solids. F2 is
Mp>250 ꢀC; 1H NMR (400 MHz, CDCl3)
d 7.74e7.72 (m, 4H), 7.66
not obtained under these reaction conditions.
(d, J¼8.3 Hz, 2H), 7.58 (d, J¼7.7 Hz, 2H), 7.52e7.46 (m, 8H), 7.43 (t,
J¼7.5 Hz, 2H), 7.21 (d, J¼8.1 Hz, 4H), 7.18 (d, J¼8.4 Hz, 2H), 6.84 (d,
J¼8.3 Hz, 2H), 1.39 (s, 9H), 0.32 (s, 18H); 13C NMR (125 MHz, CDCl3)
4.4. Preparation under Pd(PPh3)4 catalyzed conditions
A solution of 1 (0.100 g, 0.130 mmol), 2 (0.052 g, 0.266 mmol)
and cesium carbonate (0.148 g, 0.455 mmol) in THF (4 mL) and
water (1 mL) is placed in a Schlenk-tube, degassed by flushing the
reaction mixture with argon and subsequently Pd(PPh3)4 (2.3 mg,
d 150.7, 141.9, 141.0, 140.5, 140.5, 139.8, 139.5, 138.4, 137.4, 136.4,
133.4, 132.3, 131.8, 130.7, 130.3, 128.4, 128.1, 127.6, 126.8, 126.6,
125.8, 120.3, 34.6, 31.4, ꢁ1.1; MS (MALDI-pos, DCTB) m/z (%): 812.3
ꢂ
(100) [M]þ ; HRMS calcd for C52H53BrSi2Na [MþNa]þ 835.2749,
2.0
m
mol) is added. After 4 d stirring at 60 ꢀC the reaction mixture is
found: 835.2761.

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D. Schmitz, S. Hoger / Tetrahedron 70 (2014) 3726e3729
3729
4.7. 1-(4-tert-Butylphenyl)-3,4,5-tris(4-(3-
Supplementary data
trimethylsilylphenyl) phenyl)benzene (7)
1H NMR, 13C NMR and MALDI MS spectra of all new compounds.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2014.04.001.
Mp 246 ꢀC; 1H NMR (500 MHz, CDCl3) ppm 7.77 (s, 2H), 7.72e7.71
(m, 2H), 7.70e7.68 (m, 3H), 7.57e7.55 (m, 2H), 7.54e7.51 (m, 3H),
7.50e7.44 (m, 7H), 7.41 (t, J¼7.5 Hz, 2H), 7.39e7.34 (m, 3H), 7.28 (d,
J¼8.5 Hz, 4H), 7.05 (d, J¼8.5 Hz, 2H),1.40 (s, 9H), 0.30 (s,18H), 0.28 (s,
9H); 13C NMR (125 MHz, CDCl3)
d 150.6, 142.1, 140.9, 140.9, 140.9,
References and notes
140.2, 139.9, 139.7, 139.3, 138.6, 138.3, 137.5, 137.4, 132.2, 132.1, 131.8,
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ꢂ
34.6, 31.4, ꢁ1.1; MS (MALDI-pos, DCTB) m/z (%): 882.5 (100) [M]þ
;
HRMS calcd for C61H66Si3Na [MþNa]þ 905.4365, found: 905.4360.
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iodophenyl)phenyl)benzene (4)
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iodine monochloride in dichloromethane (1 M, 1.50 mL, 1.50 mmol) is
added at 0 ꢀC. The reaction mixture is stirred for 1.5 h at 0 ꢀC before
being quenched with a saturated solution of sodium sulfite. The
aqueous phase is extracted three times with dichloromethane and the
combined organic phase is washed with water and brine and dried
over magnesium sulfate. After removal of the solvent under reduced
pressure the crude product is purified by column chromatography
(CH/DCM 7/1, Rf¼0.62) and 4(0.326mg, 0.354mmol,95%)isisolatedas
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CDCl3)
d
7.95 (t, J¼1.7 Hz, 2H), 7.71 (s, 2H), 7.68e7.64(m, 4H), 7.56e7.54
(m, 2H), 7.51 (d, J¼8.5 Hz, 2H), 7.42 (d, J¼8.4 Hz, 4H), 7.21e7.14 (m, 8H),
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€
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€
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31.4;MS(MALDI-pos,DCTB)m/z(%): 920.0 (100) [M]þ ;HRMScalcdfor
C
46H35BrI2Na [MþNa]þ 942.9904, found: 942.9887.
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Acknowledgements
We acknowledge financial support by the VolkswagenStiftung,
the Deutsche Forschungsgemeinschaft (SFB 624) and the Fonds der
Chemischen Industrie.
13. The reaction conditions including bases were chosen according to previous
conditions in our laboratory. A full screening of the parameter space was not
performed.