Synthesis of new linear poly(phenylpyridyl) chains

Article abstract of DOI:10.1016/j.tet.2011.12.074

This paper describes for the first time an efficient approach of Suzuki Miyaura cross-coupling reaction leading to new mixed linear unsymmetric phenylpyridyl chains (garlands). We have studied the synthesis of new phenylpyridyl boronic species and their reactivity with a dihalogenated bipyridine to obtain four and six unit phenylpyridines.

Full text of DOI:10.1016/j.tet.2011.12.074

Tetrahedron 68 (2012) 1910e1917
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Tetrahedron
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Synthesis of new linear poly(phenylpyridyl) chains
a
a
a
a
ꢀ
ꢀ
Serge Perato , Anne Sophie Voisin-Chiret , Jana Sopkova-de Oliveira Santos , Remi Legay ,
Hassan Oulyadi b, Sylvain Rault a
University of Caen Basse-Normandie, U.F.R. des Sciences Pharmaceutiques, Centre d’Etudes et de Recherche sur le Medicament de Normandie, UPRES EA-4258, FR CNRS INC3M,
,
*
a
ꢀ
boulevard Becquerel, 14032 Caen Cedex, France
b
ꢁ
L.C.O.B.S., I.R.C.O.F., UMR 6014 CNRS C.O.B.R.A., Rue Tesniere, F-76821 Mont Saint-Aignan, France
a r t i c l e i n f o
a b s t r a c t
Article history:
This paper describes for the first time an efficient approach of Suzuki Miyaura cross-coupling reaction
leading to new mixed linear unsymmetric phenylpyridyl chains (garlands). We have studied the syn-
thesis of new phenylpyridyl boronic species and their reactivity with a dihalogenated bipyridine to
obtain four and six unit phenylpyridines.
Received 16 November 2011
Received in revised form 15 December 2011
Accepted 28 December 2011
Available online 4 January 2012
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Boron
Cross-coupling
Palladium
Pyridine
Regioselectivity
1. Introduction
for the first time a ‘2þ2’ regiocontrolled approach. Preparation of
these bi(het)aryl boronic species as building blocks allows to con-
Conjugated systems, such as oligopyridines are widely de-
scribed in literature for their applications, including use as organic
light-emitting materials, liquid crystalline materials, effective drug
delivery agents, and highly efficient catalysts.1e3 This property has
been featured in several applications not only in organic chemistry
but also in biology. Quite recently, Hamilton et al. synthesize, as
proteineprotein interaction inhibitor, a terphenyl scaffold, which is
able to induce of apoptosis in human cancer cells.4
sider quick access to four or six unit phenylpyridines and this
strategy could be of great interest because of its possible applica-
bility to automated synthesis.
The chemical challenge will be, first, to synthesize new boronic
species, and second, to prepare new four/six unit phenylpyridyl
derivatives in order to explore the reactivity of these species. The
general ‘2þ2’ mechanism of the explored reaction is reported in
Scheme 1.
Even though symmetric conjugated systems have been exten-
sively studied and documented in literature, only few methods are
available for the synthesis of unsymmetric systems. A simple strat-
egy, efficient, and green is the SuzukieMiyaura cross-coupling re-
action (SMC).5 However the preparation of such systems requires
the implementation of highly regioselective reactions. In our labo-
ratory, we have already described a potent iterative ‘1þ1’ synthesis
of oligopyridines,6 phenylpyridines,7 and oligothienylpyridines.8
This method, named Garlanding,9 which uses bifunctional hal-
oboronic species and halides takes advantage of the nature and the
position of the halogen atom on the aromatic ring.10
2. Results
During our ongoing investigation, we first examined the re-
activity of the coupling partners with the preparation of dihalo-
phenylpyridines 3a and 3b7 obtained by the SMC reaction11
between 6-bromopyridin-3-yl boronic acid 1a10a and 6-bromo-5-
methylpyridin-3-yl boronic acid 1b6a and bromoiodotoluene 2a
as illustrated in Scheme 2.
The first results of these couplings were disappointing. The
presence of a bromine atom on the alpha position of pyridylboronic
acids 1a and 1b can explain the relative low yields for compounds
3a and 3b, because this alpha bromine atom can be the source of
a third SMC reaction leading to the formation of small amounts of
terphenylpyridines (10e15%). Modifications of the reaction condi-
tions, particularly, the use of 1,2-dimethoxyethane in place of 1,4-
dioxane allowed us to increase the yield, in the case of 3b (68%).
Now, in this paper we describe the synthesis of new boronic
species and the study of their reactivity in the SMC reaction using
* Corresponding author. Tel.: þ33 0 2 31 56 68 01; fax: þ33 0 2 31 56 68 03;
e-mail address: sylvain.rault@unicaen.fr (S. Rault).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.12.074

S. Perato et al. / Tetrahedron 68 (2012) 1910e1917
1911
Scheme 1. The ‘2þ2’ approach.
Br
H3C
B(OH)2 H3C
Br
3c: 82%
+
Cl
Cl
N
I
Cl
Cl
N
1c
2a
Br
B(OH)2
Br
3d: 83%
+
CH3
N
I
CH3
2b
N
Scheme 4. Preparation of 2-chloro-5-(4-bromo-2-methylphenyl)pyridine 3c and 2-
bromo-5-(4-bromo-3-methylphenyl)pyridine 3d. Reagents and conditions: boronic
acid 1c 1.25 equiv, Pd(PPh3)4 0.05 equiv, Na2CO3 aq 2.5 equiv, DME, reflux, 24 h.
Scheme 2. Preparation of 2-bromo-5-(4-bromo-2-methylphenyl)pyridine 3a and 2-
bromo-5-(4-bromo-2-methylphenyl)-3-methylpyridine 3b. Reagents and conditions:
boronic acids 1a,b 1.25 equiv, Pd(PPh3)4 0.05 equiv, Na2CO3 aq 2.5 equiv, 1,4-dioxanex
or DMEy, reflux, 24 h.
With these two new chlorinated species the results of halo-
genemetal exchange have not been better than the previous ones.
It is the reason why we decided to turn our efforts toward the use of
bis(pinacolato)diboron as a coupling partner with 3a and 3b in the
presence of palladium.2 We carefully followed this reaction by TLC
and 1H NMR. After 1 h of stirring at room temperature no reaction
took place. The increase of the temperature to 50 ꢀC then to reflux
of 1,4-dioxane with stirring for additional 30 min allowed for the
first time, the formation of an ester in the C(2) position, but its
reactivity was such that it reacted very quickly with the starting
material to give, as a byproduct, a dimer accompanied with a great
amount of degradation products (Scheme 5).
Then we studied the synthesis of corresponding boronic acids
4a,b starting from phenylpyridines 3a,b by using the halogen-
emetal exchange methodology experimented in our laboratory10
as illustrated in Scheme 3. Unfortunately, and after numerous tri-
t
als (nBuLi, nBuLi/TMEDA, BuLi) we did not succeed to obtain bo-
ronic acid, these reactions leading always to the formation of mono
and di-dehalogenated compounds. Due to this potential instability
of boronic acids, we chose to replace the triisopropylborate by io-
dine in order to try to trap lithiated species. In this case LCMS
analyses revealed the formation of a mixture of six compounds as
showed in Scheme 3.
Li
Li
H3C
I
H
H3C
H3C
RLi
E = I2
E = I2
E = I2
+
+
+
Br
Li
Li
N
Br
N
Br
N
Br
H3C
I
H
H3C
H3C
H3C
RLi
3a
Br
N
N
I
I
N
H
N
Br
Br
H3C
Br
H3C
H3C
RLi
N
N
H
N
Scheme 3. Halogenemetal exchange reaction of compound 3a. Reagents and conditions: (1) nBuLi, or nBuLi/TMEDA, or tBuLi 1.25 equiv, THF anhyd, ꢁ78 ꢀC, 45 min; (2) I2 1.25 equiv,
THF anhyd, ꢁ78 ꢀC, 1 h; (3) hydrolysis.
The formation of such a mixture illustrates the poor stability of
lithiated intermediate and the lack of regioselectivity of the halo-
genemetal exchange.
Encouraged by this new result, we also tried the same reaction
with the two chlorinated species 3c,d and this time, we isolated
boronic esters 4c,d with moderate yields (Scheme 6).
To gain in selectivity we replaced bromine on alpha position of
pyridine by chlorine, this latter being reputed of a very less re-
activity. We prepared two new mixed phenylpyridines 3c,d by SMC
reaction between 6-chloro-3-pyridyl boronic acid 1c10 and 2-iodo-
5-bromotoluene 2a or 2-bromo-5-iodotoluene 2b (Scheme 4).
We finally prepared mono halophenylpyridines 3e and 3f with
excellent yields (80e85%) frompyridin-3-yl boronic acid 1d12 and 2-
iodo-5-bromotoluene 2a or 2-bromo-5-iodotoluene 2b (Scheme 7).
With these more simple reactants we succeeded to prepare 3-
methyl-4-pyridin-3-yl phenyl boronic acid 4e and 2-methyl-4-

1912
S. Perato et al. / Tetrahedron 68 (2012) 1910e1917
halogenated phenylpyridyl boronic esters without being bothered
by the presence of the halogen and we have overcome in this case
the lack of selectivity of the halogenemetal exchange.
Br
H3C
Br
H3C
R1
Br
a
R1
On the other hand, we succeeded the synthesis of phenylpyridyl
boronic acids by the implementation of the halogenemetal ex-
change without using of director functional groups and/or stabili-
zator of the lithiated intermediate.
O
N
B
O
N
3a: R1 = H
3b: R1 = CH3
In the second part of this study, we explored the reactivity of
boronic species 4cef by engaging them in an SMC reaction with the
5-bromo-60-iodo-3,50-dimethyl-[2,30]bipyridine 6.
Br
This bipyridine 6 was obtained from the 5-bromo-60-iodo-3,50-
dimethyl-[2,30]bipyridine 5 as we previously described7 by apply-
ing a BreI exchange that occurs exclusively at the C(2) position with
excellent yield (93%, Scheme 9). In the Garlanding concept, we
remind of the interest of using an iodinated bipyridine compared to
a brominated one: even if the alpha position of the pyridine ring is
more sensitive to a cross-coupling reaction than the beta one, the
formation of byproducts is limited by using an iodinated bipyridine
because of a better regioselectivity of the SCM reaction.
H3C
R1
N
N
R1
CH3
Br
Scheme 5. Preparation of phenylpyridyl boronic esters. Reagents and conditions: bis(pi-
nacolato)diboron 1.1 equiv, KOAC 3 equiv, PdCl2(dppf) 0.08 equiv,1,4-dioxane, reflux, 24 h.
Then, the implementation of the SMC reaction in the same
conditions as described in Scheme 2 did not allow us to obtain four
unit phenylpyridines 7cef.
The modifications of conditions we have made are the choice of
different bases. The role of base is to facilitate the slow trans-
metalation of the boronic acids in cross-coupling reaction by
forming a more reactive boronate species. In general, inorganic
bases work better, and the reactivity is in the order
Cs2CO3>CsF>K2CO3>KOAc>Na2CO3.13 Therefore, we chose to use
K3PO4 rather than Na2CO3. In these conditions, with 1.25 equiv of
boronic species 4, all desired four unit compounds 7 were obtained
predominantly (7c: 71%, 7d: 64%, 7e: 65%, 7f: 77%). The low excess
of boronic species also leads to produce a little amount of six unit
phenylpyridines 8 (8c: 19%, 8d: 21%, 8e: 17%, 8f: 8%), which has
been isolated after chromatography (Scheme 9, Table 1).
O
Br
B
H3C
H3C
O
3c
4c 50%
Cl
N
Cl
Cl
N
O
B
Br
CH3
O
CH3
4d 33%
3d
Cl
N
N
Scheme 6. Preparation of phenylpyridyl boronic esters. Reagents and conditions:
bis(pinacolato)diboron 1.1 equiv, NaOAC 3 equiv, PdCl2(dppf) 8%,1,4-dioxane, reflux, TLC.
The1Hand 13CNMRsignalsof7e,fand 8e,f werepreciselyassigned
using one and two-dimensional (COSY, HSQC, and HMBC) spectra.
Furthermore, the suitable crystals for X-ray diffraction studies
were obtained for the two four unit phenylpyridines 7e and 7f by
slow evaporation of a mixture of dichloromethane/cyclohexane (1/
5). The ORTEP diagrams of the 7e and 7f crystal structures are
shown in Fig. 1. They confirm the expected structures.
Br
B(OH)2
B(OH)2
Br
Br
3e: 80%x, 83%y
3f: 85%1, 80%y
+
+
Br
N
I
I
N
N
1d
2a
N
3. Conclusion
2b
Scheme 7. Preparation of 3-(4-bromo-2-methylphenyl)pyridine 3e, 3-(4-bromo-3-
methylphenyl)pyridine 3f. Reagents and conditions: boronic acids 1d 1.25 equiv,
Pd(PPh3)4 0.05 equiv, Na2CO3 aq 2.5 equiv, 1,4-dioxanex or DMEy, reflux, 24 h.
We have successfully synthesized four unit phenylpyridines and
four sexi unit phenylpyridines through a ‘2þ2’ approach of the SMC
reaction between new phenylpyridyl boronic species and dihalo-
genated bipyridine. These new compounds were characterized by
all the spectroscopic data and confirmed by single-crystal X-ray
diffraction studies for two four unit phenylpyridines.
pyridin-3-yl phenyl boronic acid 4f with good yields using the
classical halogenemetal exchange methodology (Scheme 8).
These linear garlands are being explored as alpha-helical mimics
for the disruption of proteineprotein interactions; our efforts in
this direction will be reported subsequently.
B(OH)2
Br
H3C
H3C
Then, on the basis of the results presented in this work, further
applications and investigations of the Garlanding approach in the
field of mechanistic and synthetic organic chemistry as well as in
biological area are currently ongoing in our laboratory.
3e
4e: 75%
N
N
Br
B(OH)2
CH3
CH3
3f
4f: 68%
4. Experimental section
4.1. General procedure
N
N
Scheme 8. Preparation of 3-methyl-4-pyridin-3-yl phenyl boronic acid 4e and 2-
methyl-4-pyridin-3-yl phenyl boronic acid 4f. Reagents and conditions: (1) nBuLi,
1.25 equiv, THF anhyd, ꢁ78 ꢀC, 1 h; (2) B(OiPr)3, 1.25 equiv, THF anhyd, ꢁ78 ꢀC, 45 min;
(3) hydrolysis.
Commercial reagents were used as received without additional
purification. Melting points were determined on a Kofler heating
bench.
So, we have carefully studied the synthesis of new phenylpyridyl
boronic species. On one hand we have succeeded the synthesis of

S. Perato et al. / Tetrahedron 68 (2012) 1910e1917
Br
1913
H3C
X
N
H3C
Br
N
N
R2
5
N
Br
H3C
H3C
R1
a
H3C
H3C
OR
B
N
+
N
Br
R1
R1
H3C
R1
OR
N
N
b
H3C
I
+
R2
R2
R2
X
N
X
N
X
N
N
4c-f
6
7c-f
8c-f
Scheme 9. Preparation of phenylpyridyl bipyridines 7cef. Reagents and conditions: (a) AcCl (2ꢂ1.5 equiv), NaI (2ꢂ2.5 equiv), CH3CN, reflux, 2ꢂ4 h; (b) K3PO4 aq 2.5 equiv,
Pd(PPh3)4 5%, DME, reflux, 20 h.
Table 1
Cross coupling reactions between boronic species 4cef and 5-bromo-60-iodo-3,50-dimethyl-[2,30]bipyridine 6
Phenylpyridine
R1
R2
X
Four unit phenylpyridine
Six unit phenylpyridine
Yield (%)
Conversion
rate
N
Cl
Br
N
4c
CH3
H
Cl
7c
8c
65/17
8/2
N
N
N
Cl
N
Cl
N
N
Cl
Br
N
4d
H
CH3
Cl
7d
8d
77/8
9/1
N
N
N
Cl
N
Cl
N
N
Br
H C
H C
H C
CH
N
H C
H C
4e
CH3
H
H
7e
8e
71/19
8/2
N
N
H C
N
N
N
N
Br
H C
H C
H C
H C
N
H C
4f
H
CH3
H
7f
8f
64/21
7/3
N
N
CH
N
N
CH
N
IR spectra were recorded on a PerkineElmer BX FT-IR spectro-
photometer. The band positions are given in reciprocal centimeters
(cmꢁ1).
spectrometer. Chemical shifts are expressed in parts per million
downfield from tetramethylsilane as an internal standard and
coupling constants in hertz. Chemical shift are reported in part per
million (ppm) relative to the solvent resonance.
Chromatography was carried out on a column using flash silica
gel 60 Merck (0.063e0.200 mm) as the stationary phase. The
eluting solvent indicated for each purification was determined by
1H NMR (400 MHz) and 13C NMR (100 MHz) spectra were
recorded on a JEOL Lambda 400 spectrometer. Four units 7e,f and
six units 8e,f oligophenylpyridine 1H NMR (500 MHz) and 13C NMR
(125 MHz) data were recorded on a Bruker 500 Avance III

1914
S. Perato et al. / Tetrahedron 68 (2012) 1910e1917
dimethoxyethane. The mixture was then refluxed and treated as
described in representative procedure. The crude product was
purified by column chromatography, with 99:1 cyclohexane/EtOAc
affording 3d as a white solid (3.92 g, 68%). Mp 120 ꢀC. Same ex-
perimental data described in the literature.7
4.1.3. 2-Chloro-5-(4-bromo-2-methylphenyl)pyridine 3c. Following
the procedure for phenylpyridine 3a synthesis, 2 g of 5-bromo-2-
iodotoluene (6.73 mmol) was reacted with 1.325 g of 6-chloro-3-
pyridyl boronic acid (8.42 mmol) in presence of tetrakis-(triphe-
nylphosphine)palladium(0) (389 mg, 0.34 mmol), aqueous Na2CO3
(1.785 g, 16.84 mmol), and (50 mL) of dimethoxyethane. The mix-
ture was then refluxed and treated as described in representative
procedure. The crude product was purified by column chroma-
tography, with 99:1 cyclohexane/EtOAc affording 3c as a yellow
solid (1.55 g, 82%). Mp 88 ꢀC. IR (KBr): 3062, 2959, 2917, 2863, 1928,
1581, 1562, 1547, 1452, 1349, 1140, 1104, 995, 878, 849, 827, 743, 677,
560, 540 cmꢁ1. 1H NMR (400 MHz, CDCl3):
d
8.33 (d, J¼2.4, 1H, H6),
7.59 (dd, J¼8.3, 2.4, 1H, H4), 7.46 (d, J¼1.7, 1H, H30), 7.40 (dd, J¼8.0,
2.2, 1H, H50), 7.39 (d, J¼8.0, 1H, H3), 7.05 (d, J¼8.0, 1H, H60), 2.24 (s,
3H, CH3eph). 13C NMR (100 MHz, CDCl3):
d 150.3 (C2), 149.4 (C6),
139.1 (C4),137.7 (C20),135.6 (C10),135.2 (C50),133.4 (C30),131.2 (C60),
129.3 (C50), 123.8 (C3), 122.4 (C40), 20.1 (CH3). Anal. Calcd for
C12H9NBrCl: C, 51.01; H, 3.21; N, 4.96. Found: C, 51.14; H, 3.17; N4.91.
Fig. 1. ORTEP diagrams of 7e and major conformation of 7f.
thin layer chromatography (TLC) performed on 0.2 mm precoated
plates of silica gel 60F-264 (Merck) and spots were visualized using
an ultraviolet-light lamp.
4.1.4. 2-Chloro-5-(4-bromo-3-methylphenyl)pyridine 3d. Following
the procedure for phenylpyridine 3a synthesis, 2 g of 2-bromo-5-
iodotoluene (6.73 mmol) was reacted with 1.325 g of 6-chloro-3-
pyridyl boronic acid (8.42 mmol) in presence of tetrakis-(triphe-
nylphosphine)palladium(0) (389 mg, 0.34 mmol), aqueous Na2CO3
(1.785 g, 16.84 mmol), and (50 mL) of dimethoxyethane. The mix-
ture was then refluxed and treated as described in representative
procedure. The crude product was purified by column chroma-
tography, with 99:1 cyclohexane/EtOAc affording 3c as a yellow
solid (1.58 g, 83%). Mp 98 ꢀC. IR (KBr): 3036, 2981, 2917, 1975, 1584,
1552, 1454, 1399, 1379, 1346, 1264, 1153, 1111, 1028, 1017, 877, 843,
Elemental analyses for new compounds were performed at the
‘Institut de Recherche en Chimie Organique Fine’ (Rouen). The data
for C, H, and N were within ꢃ0.4 of the theoretical values for all final
compounds.
6-Bromo-3-pyridyl boronic acid 1a,10a 6-bromo-5-methyl-3-
pyridyl boronic acid 1b,6a 6-chloro-3-pyridyl boronic acid 1c,10
and 3-pyridyl boronic acid 1d12 are prepared according to
literature.
4.1.1. 2-Bromo-5-(4-bromo-2-methylphenyl)pyridine 3a. To a stir-
red solution of 6-bromo-3-pyridyl boronic acid (1.25 equiv, 847 mg,
4.20 mmol) in 1,4-dioxane (30 mL) under nitrogen were added
5-bromo-2-iodotoluene (1 g, 3.36 mmol) and tetrakis-(triphenyl-
phosphine)palladium(0) (0.05 equiv, 195 mg, 0.17 mmol). After
5 min of stirring, aqueous Na2CO3 (2.5 equiv, 892 mg, 8.42 mmol) in
5 mL of water was added. Then the mixture was heated to 80 ꢀC
until the starting material was consumed (TLC). After cooling down
to room temperature, the mixture was filtered on Celite and
washed with CH2Cl2. The aqueous layer was extracted with EtOAc
(2ꢂ50 mL). Combined organic layers were washed with saturated
aqueous solution of NaCl (50 mL), and dried over MgSO4. Solvent
was removed in vacuo and crude product was purified by column
chromatography, with 99:1 cyclohexane/EtOAc affording 3c as
a white solid (520 mg, 47%). Mp 103 ꢀC. IR (KBr): 3044, 2952, 1573,
813, 759, 681, 634, 525 cmꢁ1. 1H NMR (400 MHz, CDCl3):
d 8.57 (d,
J¼2.7, 1H, H6), 7.80 (dd, J¼8.3, 2.4, 1H, H4), 7.63 (d, J¼8.3, 1H, H50),
7.40 (s, 1H, H20), 7.39 (d, J¼8.3, 1H, H5), 7.22 (dd, J¼8.3, 2.2, 1H, H60),
2.47 (s, 3H, CH3eph). 13C NMR (100 MHz, CDCl3):
d 150.5 (C1), 147.7
(C6), 138.9 (C30), 136.9 (C4), 135.6 (C10), 134.6 (C5), 133.1 (C50), 129.3
(C20), 125.8 (C60), 125.4 (C40), 124.2 (C3), 23.1 (CH3). C12H9NBrCl: C,
51.01; H, 3.21; N, 4.96. Found: C, 50.88; H, 3.23; N, 4.91.
4.1.5. 3-(4-Bromo-2-methylphenyl)pyridine 3e. Following the pro-
cedure for phenylpyridine 3a synthesis, 1
g of 2-bromo-5-
iodotoluene (3.36 mmol) was reacted with 517 mg of 3-pyridyl
boronic acid (4.21 mmol) in presence of tetrakis-(triphenylphos-
phine)palladium(0) (195 mg, 0.17 mmol), aqueous Na2CO3 (892 mg,
8.42 mmol), and (30 mL) of 1,4-dioxane. The mixture was then
refluxed and treated as described in representative procedure. The
crude product was purified by column chromatography, with
a gradient of solvent from 9:1 to 5:5 cyclohexane/EtOAc, affording
3e as yellow oil (690 mg, 83%). IR (KBr): 3026, 2958, 2923, 1586,
1569, 1469, 1412, 1385, 1196, 1090, 998, 852, 805, 717, 558 cmꢁ1. 1H
1451, 1347, 1088, 992, 8047, 805, 740, 671, 555 cmꢁ1 1H NMR
.
(400 MHz, CDCl3):
d
8.31 (d, J¼2.9, 1H, H6), 7.54 (d, J¼8.8, 1H, H3),
7.48 (dd, J¼8.8, 2.9, 1H, H4), 7.46 (d, J¼3.9, 1H, H30), 7.40 (dd, J¼7.8,
2.0, 1H, H50), 7.05 (d, J¼7.8, 1H, H60), 2.23 (s, 3H, CH3eph). 13C NMR
(100 MHz, CDCl3):
d
150.0 (C6), 141.0 (C2), 138.9 (C4), 137.7 (C20),
NMR (400 MHz, CDCl3):
d
8.42 (d, J¼4.0, 1H, H6), 8.37 (s, 1H, H2),
135.6 (C5, C10), 133.5 (C30), 131.2 (C60), 129.4 (C50), 127.7 (C3), 122.6
(C40), 20.2 (CH3). Anal. Calcd for C12H9NBr2: C, 44.07; H, 2.77; N,
4.28. Found: C, 43.91; H, 3.97; N, 4.12.
7.42 (d, J¼7.5, 1H, H4), 7.26 (s, 1H, H30), 7.20 (d, J¼8.0, 1H, H50), 7.16
(t, J¼6.0, 1H, H5), 6.88 (d, J¼8.0, 1H, H60), 2.05 (s, 3H, CH3). 13C NMR
(100 MHz, CDCl3):
d
149.6 (C2), 148.4 (C6), 137.8 (C20), 137.0 (C10),
136.3 (C4, C3), 133.3 (C30), 131.3 (C60), 129.1 (C50), 123.0 (C5), 122.0
(C40), 20.2 (CH3). Anal. Calcd for C12H10NBr: C, 58.09; H, 4.06; N,
5.65. Found: C, 57.89; H, 4.03; N, 5.48.
4.1.2. 2-Bromo-3-methyl-5-(4-bromo-2-methylphenyl)pyridine
3b. Following the procedure for phenylpyridine 3a synthesis, 5 g of
5-bromo-2-iodotoluene (16.84 mmol) was reacted with 4.54 g of 6-
bromo-5-methyl-3-pyridyl boronic acid (21.05 mmol) in presence
of tetrakis-(triphenylphosphine)palladium(0) (973 mg, 0.84 mmol),
aqueous Na2CO3 (4.46 g, 42.10 mmol), and (100 mL) of
4.1.6. 3-(4-Bromo-3-methylphenyl)pyridine 3f. Following the pro-
cedure for phenylpyridine 3a synthesis, 1
g of 2-bromo-5-
iodotoluene (3.36 mmol) was reacted with 517 mg of 3-pyridyl

S. Perato et al. / Tetrahedron 68 (2012) 1910e1917
1915
boronic acid (4.21 mmol) in presence of tetrakis-(triphenylphos-
phine)palladium(0) (195 mg, 0.17 mmol), aqueous Na2CO3 (892 mg,
8.42 mmol), and (30 mL) of 1,4-dioxane. The mixture was then
refluxed and treated as described in representative procedure. The
crude product was purified by column chromatography, with a gra-
dient of solvent from 9:1 to 5:5 cyclohexane/EtOAc, affording 3f as
yellow oil (710 mg, 85%). IR (KBr): 3030, 2979, 2922, 2851,1588,1575,
4% aqueous NaOH solution (50 mL). The resulting aqueous layer
was collected and acidified to pH 7 by dropwise addition of 3 N HCl.
Extraction with ethyl acetate, evaporation of the organic layer and
recrystallization from ether gave product 4e as a white solid
(640 mg, 75%). Mp 211 ꢀC. IR (KBr): 3413, 3022, 2975, 1735, 1609,
1409, 1370, 1324, 1263, 1191, 1164, 1112, 1047, 767, 704 cmꢁ1 1H
.
NMR (400 MHz, CDCl3):
d
8.55 (d, J¼4.2, 1H, H6), 8.52 (s, 1H, H2),
1469, 1419, 1379, 1187, 1067, 1025, 882, 825, 801, 710, 620, 588 cmꢁ1
.
7.85 (dt, J¼7.9, 1.7, 1H, H4), 7.61 (br s, 2H, H20, H60), 7.54 (dd, J¼7.8,
1H NMR (400 MHz, CDCl3):
d
8.80 (d, J¼2.9,1H, H2), 8.60 (d, J¼4.9,1H,
4.9, 1H, H5), 7.22 (d, J¼7.5, 1H, H50), 2.28 (s, 3H, CH3eph). 13C NMR
H6), 7.83 (dt, J¼7.8, 2.0,1H, H4), 7.62 (d, J¼8.8,1H, H50), 7.43 (d, J¼2.0,
(100 MHz, CDCl3): d
149.9 (C2), 148.5 (C6), 146.0 (C3), 139.7 (C10),
1H, H20), 7.35 (dd, J¼7.8, 4.9,1H, H5), 7.25 (dd, J¼8.8, 2.0,1H, H60), 2.47
138.8 (C4), 137.1 (C60), 135.6 (C40), 132.5 (C20), 134.0 (C30), 130.0
(C50), 125.0 (C5), 20.4 (CH3). Anal. Calcd for C12H12BNO2: C, 67.65; H,
5.68; N, 6.57. Found: C, 67.28; H, 5.42; N, 6.21.
(s, 3H, CH3eph). 13C NMR (100 MHz, CDCl3):
d 148.7 (C6), 148.1 (C2),
138.7 (C30), 137.0 (C10), 135.7 (C3), 134.2 (C4), 133.0 (C50), 129.5 (C20),
126.0 (C60), 125.0 (C40), 123.6 (C5), 23.1 (CH3). Anal. Calcd for
C12H10NBr: C, 58.09; H, 4.06; N, 5.65. Found: C, 57.87; H, 4.01; N, 5.44.
4.1.10. 2-Methyl-4-(pyridin-3-yl)phenyl boronic acid 4f. Following
the procedure for boronic acid 4e synthesis, 2 g of 3-(4-bromo-3-
methylphenyl)pyridine (8.06 mmol) was reacted with 4.03 mL of
nBuLi (10.07 mmol) and 2.32 mL of triisopropylborate (10.07 mmol)
in presence of THF (100 mL). The mixture was then treated as de-
scribed in representative procedure giving 4f as a white solid
(1.17 g, 68%). Mp 184 ꢀC. IR (KBr): 3406, 2956, 2922, 1607, 1431,
1400, 1312, 1276, 1240, 1187, 803, 771, 709 cmꢁ1. 1H NMR (400 MHz,
4.1.7. 2-[3-Methyl-4-(4-chloro-pyridin-3-yl)phenyl]-4,4,5,5-
tetramethyl-1,3-dioxaborolane 4c. To a stirred solution of 2-chloro-
5-(4-bromo-2-methylphenyl)pyridine 3c (1 equiv, 1 g, 3.54 mmol)
in 1,4-dioxane (50 mL) under nitrogen were added bispinacolato-
diboron (918 mg, 3.89 mmol), [1,10-bis(diphenylphosphino)ferro-
cene]palladium(II) chloride (0.08 equiv, 215 mg, 0.26 mmol) and
sodium acetate (3 equiv, 809 mg, 9.86 mmol). Then the mixture was
heated to reflux for 16 h. After cooling down to room temperature,
the mixture was filtered on Celite and washed with CH2Cl2. Solvent
were removed in vacuo and crude product was purified by chro-
matography (cyclohexane/EtOAc 98:2) affording product 4c as
white solid (580 mg, 50%). Mp 130 ꢀC. IR (KBr): 3436, 3035, 2974,
2926, 1610, 1560, 1503, 1458, 1412, 1362, 1314, 1267, 1145, 1106, 999,
855, 839, 760, 751, 676, 633, 492 cmꢁ1. 1H NMR (400 MHz, CDCl3):
CDCl3):
d
8.79 (d, J¼2.0, 1H, H2), 8.50 (dd, J¼5.0, 1.5, 1H, H6), 8.09
(dt, J¼7.5, 1.5, 1H, H4), 7.51 (dd, J¼8.0, 5.0, 1H, H5), 7.49 (s, 1H, H30),
7.46 (d, J¼8.0, 1H, H50), 7.40 (d, J¼8.0, 1H, H60), 2.42 (s, 3H, CH3eph).
13C NMR (100 MHz, CDCl3):
d
148.7 (C6), 148.3 (C2), 142.3 (C20),
138.8 (C40), 138.7 (C3), 136.5 (C4), 135.4 (C10), 133.3 (C60), 128.8
(C30), 125.5 (C5), 124.6 (C50), 22.1 (CH3). Anal. Calcd for C12H12BNO2:
C, 67.65; H, 5.68; N, 6.57. Found: C, 67.31; H, 5.39; N, 6.31.
d
8.36 (d, J¼2.4, 1H, H20), 8.75 (s, 1H, H2), 7.71 (d, J¼7.6, 1H, H6), 7.62
4.1.11. 50-Bromo-30,5-dimethyl-6-[3-methyl-4-(4-chloro-pyridin-3-
yl)pheny]-3,20-bipyridine 7c. Following the procedure for phenyl-
pyridine 3a synthesis, 500 mg of 50-bromo-30,5-dimethyl-6-iodo-
3,20-bipyridine (1.28 mmol) was reacted with 486 mg of boronic ester
4e (1.47 mmol) in presence of tetrakis-(triphenylphosphine)palla-
dium(0) (74 mg, 0.06 mmol), aqueous K3PO4 (738 mg, 3.2 mmol), and
(30 mL) of dimethoxyethane. The mixture was then refluxed and
treated as described in representative procedure. The crude product
was purified by column chromatography, with a gradient of solvent
from 9:1 to 5:5 cyclohexane/EtOAc affording 7c as a yellow solid
(390 mg, 65%), mp 178 ꢀC and a byproduct 8c as a yellow solid
(130 mg,17%). IR (KBr): 3045, 2960, 2917, 2849,1705,1597,1579,1545,
1450, 1416, 1382, 1295, 1156, 1113, 995, 923, 886, 772, 654 cmꢁ1 1H
(dd, J¼8.3, 2.4,1H, H60), 7.39 (d, J¼8.0,1H, H50), 7.21 (d, J¼7.6,1H, H5),
2.27 (s, 3H, CH3eph), 1.37 (s, 12H, CH3pinacol). 13C NMR (100 MHz,
CDCl3):
d 150.1, 149.5, 139.5, 139.2, 137.0, 136.2, 134.8, 132.5, 129.2,
123.7, 83.9, 26.9, 24.8, 20.0. Anal. Calcd for C18H21NBClO2: C, 65.59;
H, 6.42; N, 4.25. Found: C, 65.73; H, 6.37; N, 4.12.
4.1.8. 2-[2-Methyl-4-(4-chloro-pyridin-3-yl)phenyl]-4,4,5,5-
tetramethyl-1,3-dioxaborolane 4d. To a stirred solution of 2-chloro-
5-(4-bromo-3-methylphenyl)pyridine 3d (1 equiv, 1 g, 3.54 mmol)
in 1,4-dioxane (50 mL) under nitrogen were added bispinacolato-
diboron (918 mg, 3.89 mmol), [1,10-bis(diphenylphosphino)ferro-
cene]palladium(II) chloride (0.08 equiv, 215 mg, 0.26 mmol) and
sodium acetate (3 equiv, 809 mg, 9.86 mmol). Then the mixture was
heated to reflux for 16 h. After cooling down to room temperature,
the mixture was filtered on Celite and washed with CH2Cl2. Solvent
were removed in vacuo and crude product was purified by chro-
matography (cyclohexane/EtOAc 98:2) affording product 4d as
white solid (390 mg, 33%). Mp 101 ꢀC. IR (KBr): 3469, 3414, 2977,
2925,1608,1584,1567,1508,1458,1380,1358,1347,1271,1139,1108,
1074, 1048, 962, 856, 820, 754, 661, 499 cmꢁ1. 1H NMR (400 MHz,
NMR (400 MHz, CDCl3):
d
8.69 (d, J¼2.0, 1H), 8.63 (d, J¼2.2, 1H), 8.43
(d, J¼2.4,1H, H2000), 7.81 (s, 2H, H6, H40), 7.68 (dd, J¼8.1, 2.4,1H, H6000),
7.55 (s, 1H, H200), 7.48 (dd, J¼7.8, 1.2, 1H, H600), 7.42 (d, J¼8.3,1H, H5000),
7.30 (d, J¼7.8,1H, H500), 2.49 (s, 3H), 2.46 (s, 3H), 2.35 (s, 3H).13C NMR
(100 MHz, CDCl3): d 157.6, 153.9, 150.1, 149.7, 148.4, 146.8, 141.0, 140.3,
139.3, 139.1, 136.5, 136.0, 135.7, 133.3, 133.1, 131.3, 130.7, 129.5, 126.8,
123.7, 119.6, 20.4, 20.1, 19.9. Anal. Calcd for C24H19N3BrCl: C, 62.02; H,
4.12; N, 9.04. Found: C, 61.94; H, 4.08; N, 8.96.
CDCl3):
d
8.60 (d, J¼2.7, 1H, H20), 7.86 (d, J¼7.8, 1H, H6), 7.84 (dd,
J¼8.5, 2.7,1H, H60), 7.38 (d, J¼8.3,1H, H50), 7.35e7.33 (m, 2H, H3, H5),
4.1.12. 5’-Bromo-3’,5-dimethyl-6-[2-methyl-4-(4-chloro-pyridin-3-
yl)pheny]-3,2’-bipyridine 7d. Following the procedure for phenyl-
pyridine 3a synthesis, 250 mg of 50-bromo-30,5-dimethyl-6-iodo-
3,20-bipyridine(0.64mmol)wasreactedwith264mgofboronicester
4e (0.80 mmol) in presence of tetrakis-(triphenylphosphine)palla-
dium(0) (37 mg, 0.03 mmol), aqueous K3PO4 (369 mg,1.6 mmol), and
(15 mL) of dimethoxyethane. The mixture was then refluxed and
treated as described in representative procedure. The crude product
was purified by column chromatography, with a gradient of solvent
from 9:1 to 5:5 cyclohexane/EtOAc affording 7d as a yellow solid
(230mg, 77%), mp190ꢀC anda byproduct8das ayellowsolid(30 mg,
8%). IR (KBr): 3038, 2963, 2921, 1953, 1638, 1612, 1600, 1555, 1451,
1416, 1383, 1353, 1108, 1021, 901, 838, 763, 735, 688 cmꢁ1. 1H NMR
2.61 (s, 3H, CH3eph), 1.36 (s, 12H, CH3pinacol). 13C NMR (100 MHz,
CDCl3):
d 150.4, 148.0, 145.9, 138.5, 137.2, 136.8, 135.5, 128.3, 124.1,
123.2, 83.6, 25.0, 24.9, 22.3. Anal. Calcd for C18H21NBClO2: C, 65.59;
H, 6.42; N, 4.25. Found: C, 65.63; H, 6.51; N, 4.27.
4.1.9. 3-Methyl-4-(pyridin-3-yl)phenyl boronic acid 4e. To a slurry
of 2.5M of nBuLi (1.25 equiv, 2.01 mL, 5.04 mmol) in anhydrous THF
(100 mL), cooled at ꢁ78 ꢀC, was added a solution 3-(4-bromo-2-
methylphenyl)pyridine (1 g, 4.03 mmol) in THF (25 mL). The mix-
ture was allowed to react at this temperature for over 60 min. A
solution of triisopropylborate (1.25 equiv, 1.16 mL, 5.04 mmol) was
then added and left to react for 45 min. The mixture was allowed to
warm to room temperature and was quenched by slow addition of
(400 MHz, CDCl3):
d
8.68 (d, J¼2.2, 1H), 8.66 (d, J¼2.7, 1H), 8.64 (d,

1916
S. Perato et al. / Tetrahedron 68 (2012) 1910e1917
J¼2.2, 1H), 7.89 (dd, J¼8.3, 2.4, 1H, H6000), 7.82 (s, 2H, H4, H40), 7.49 (s,
1H, H300), 7.47 (d, J¼7.8, 1H, H500), 7.42 (d, J¼8.3, 1H, H5000), 7.33 (d,
J¼7.8, 1H, H600), 2.47 (s, 3H), 2.23 (s, 3H), 2.22 (s, 3H). 13C NMR
J¼1.4, 1H), 7.68 (dd, J¼8.0, 2.4, 2H), 7.59e7.56 (m, 3H), 7.51 (d, J¼7.8,
1H), 7.45e7.41 (m, 2H), 7.35 (d, J¼7.5, 1H), 7.31 (d, J¼7.8 1H), 2.56 (s,
3H), 2.52 (s, 3H), 2.39 (s, 3H), 2.36 (s, 3H). 13C NMR (100 MHz,
(100 MHz, CDCl3):
d
158.6,154.0,150.3,148.3,148.0,146.6,141.0,140.1,
CDCl3): d 157.4, 154.4, 150.3, 150.1, 149.7, 149.6, 147.0, 145.8, 140.5,
138.3,137.2, 136.9,136.2, 135.4, 134.0, 133.1, 131.4, 129.5,128.9, 124.4,
124.2, 119.7, 19.9, 19.6, 19.1 Anal. Calcd for C24H19N3BrCl: C, 62.02; H,
4.12; N, 9.04. Found: C, 61.97; H, 4.15; N, 8.93.
139.3, 139.2, 137.5, 137.1, 136.7, 136.5, 136.1, 135.7, 135.0, 134.9, 134.4,
131.4, 131.3, 130.7, 130.6, 130.1, 129.6, 129.4, 127.9, 126.8, 124.9,
123.8, 123.7, 20.6, 20.4, 20.2, 20.1. Anal. Calcd for C36H28N4Cl2: C,
73.59; H, 4.80; N, 9.54. Found: C, 73.28; H, 4.88; N, 9.43.
4.1.13. 5’-Bromo-3’,5-dimethyl-6-(3-methyl-4-pyridin-3-ylphenyl)-
3,2’-bipyridine 7e. Following the procedure for phenylpyridine 3a
synthesis, 1 g of 50-bromo-30,5-dimethyl-6-iodo-3,20-bipyridine
(2.56 mmol) was reacted with 683 mg of boronic acid 4e (3.20 mmol)
in presence of tetrakis-(triphenylphosphine)palladium(0) (148 mg,
0.13 mmol), aqueous K3PO4 (1.476 g, 6.41 mmol), and (30 mL) of
dimethoxyethane. The mixture was then refluxed and treated as
described in representative procedure. The crude product was pu-
rified by column chromatography, with a gradient of solvent from
8:2 to 5:5 cyclohexane/EtOAc affording 7e as a yellow solid (790 mg,
71%), mp 147 ꢀC and a byproduct 8e as a beige solid (253 mg,19%). IR
(KBr): 3024, 3006, 2924, 2857,1592,1554,1451,1437,1414,1381,1311,
1190,1136,1117,1072, 997, 922, 909, 888, 851, 806, 776, 715, 695, 616,
4.1.16. 5’-[2-Methyl-4-(4-chloro-pyridin-3-yl)phenyl]-3’,5-dimethyl-
6-[2-methyl-4-(4-chloro-pyridin-3-yl)phenyl]-3,2’-bipyridine
8d. Yellow solid mp 218 ꢀC. IR (KBr): 3041, 2972, 2919, 2855, 1623,
1590, 1564, 1442, 1412, 1360, 1099, 1029, 1001, 888, 827, 783, 755,
678, 517 cmꢁ1. 1H NMR (400 MHz, CDCl3):
d
8.80 (d, J¼1.7, 1H), 8.67
(d, J¼2.0, 2H), 8.61 (d, J¼2.0, 1H), 7.93 (d, J¼2.0, 1H), 7.92 (d, J¼2.4,
1H), 7.89 (d, J¼2.7,1H), 7.70 (s,1H), 7.52e7.47 (m, 4H), 7.45e7.36 (m,
4H), 2.56 (s, 3H), 2.45 (s, 3H), 2.26 (s, 3H), 2.25 (s, 3H). 13C NMR
(100 MHz, CDCl3):
d 158.3, 154.1, 150.5, 150.2, 148.0, 147.9, 147.3,
146.8, 140.2, 139.2, 138.4, 137.9, 137.1, 137.0, 136.9, 136.7, 136.3, 136.1,
135.7,135.4,135.0,134.7,131.3,130.8,130.7,129.5,129.2,128.9,124.7,
124.4, 124.2, 124.1, 20.6, 20.1, 19.6, 19.1. Anal. Calcd for C36H28N4Cl2:
C, 73.59; H, 4.80; N, 9.54. Found: C, 73.76; H, 4.84; N, 9.38.
539, 500 cmꢁ1 1H NMR (500 MHz, CDCl3):
d
8.69 (d, J¼2.0, 1H, H2),
8.65 (d, J¼2.0, 1H, H2000), 8.62 (d, J¼2.0, 1H, H60), 8.61 (dd, J¼7.8, 3.0,
1H, H6000), 7.81 (d, J¼2.0, 1H, H4), 7.80 (d, J¼2.0, 1H, H40), 7.70 (dt,
J¼7.8, 2.0,1H, H4000), 7.54 (s,1H, H200), 7.47 (d, J¼7.0,1H, H600), 7.37 (dd,
J¼7.8, 4.8, 1H, H5000), 7.31 (d, J¼7.8, 1H, H500), 2.49 (s, 3H, CH3), 2.45 (s,
4.1.17. 5’-(3-Methyl-4-pyridin-3-ylphenyl)-3’,5-dimethyl-6-(3-
methyl-4-pyridin-3-ylphenyl)-3,2’-bipyridine 8e. Beige solid mp
150 ꢀC. IR (KBr): 3024, 2955, 2921, 2856, 1592, 1562, 1455, 1408,
1382, 1144, 1027, 1000, 909, 835, 808, 777, 716, 541 cmꢁ1. 1H NMR
3H, CH3 ), 2.35 (s, 3H, CH300). 13C NMR (125 MHz, CDCl3):
d 158.0 (C6),
0
154.0 (C20), 149.9 (C2000), 148.4 (C60), 148.2 (C6000), 146.8 (C2), 141.0
(C40), 140.0 (C100), 139.1 (C4), 138.0 (C400), 137.2 (C3000), 136.6 (C4000),
135.7 (C300),133.7 (C3),133.2 (C30),131.2 (C200),130.8 (C5),129.7 (C500),
126.7 (C600), 123.1 (C5000), 119.7 (C50), 20.5 (CH300), 20.2 (CH3), 20.0
(CH300). Anal. Calcd for C24H20N3Br: C, 66.98; H, 4.68; N, 9.76. Found:
C, 66.62; H, 4.24; N, 9.35.
(500 MHz, CDCl3):
d
8.85 (d, J¼2.0, 1H, H60), 8.78 (d, J¼2.0, 1H, H2),
8.66 (s, 2H, H200, H200000), 8.63 (dt, J¼5.2, 1.6, 2H, H400, H400000), 7.91 (d,
J¼1.6, 1H, H4), 7.87 (d, J¼1.6, 1H, H40), 7.73 (s, 1H, H600), 7.71 (s, 1H,
H600000), 7.59 (s, 1H, H2000), 7.57 (s, 1H, H20000), 7.57e7.55 (m, 1H, H6000),
7.50 (d, J¼8.0, 1H, H60000), 7.42e7.38 (m, 2H, H500, H500000), 7.37 (d,
J¼7.6, 1H, H5000), 7.33 (d, J¼7.6, 1H, H50000), 2.59 (s, 3H, CH3 ), 2.55 (s,
0
3H, CH3), 2.42 (s, 3H, CH3000), 2.39 (s, 3H, CH30000). 13C NMR (125 MHz,
4.1.14. 5’-Bromo-3’,5-dimethyl-6-(2-methyl-4-pyridin-3-ylphenyl)-
3,2’-bipyridine 7f. Following the procedure for phenylpyridine 3a
synthesis, 1 g of 50-bromo-30,5-dimethyl-6-iodo-3,20-bipyridine
(2.56 mmol) was reacted with 683 mg of boronic acid 4f
(3.20 mmol) in presence of tetrakis-(triphenylphosphine)palla-
dium(0) (148 mg, 0.13 mmol), aqueous K3PO4 (1.476 g, 6.41 mmol),
and (30 mL) of dimethoxyethane. The mixture was then refluxed
and treated as described in representative procedure. The crude
product was purified by column chromatography, with a gradient
of solvent from 8:2 to 5:5 cyclohexane/EtOAc affording 7f as a pale
yellow solid (710 mg, 64%), mp 164 ꢀC and a byproduct 8f as a white
solid (270 mg, 20%). IR (KBr): 3022, 2980, 2958, 2923, 2858, 1598,
1574, 1553, 1451, 1417, 1382, 1188, 1137, 1115, 1065, 1021, 999, 907,
874, 802, 763, 706, 678, 619, 565 cmꢁ1. 1H NMR (500 MHz, CDCl3):
CDCl3): d
157.5 (C6), 154.2 (C20), 149.8 (C200000), 149.7 (C200), 148.2
(C400000), 148.1 (C400), 146.9 (C2), 145.7 (C60), 140.0 (C10000), 139.1 (C4),
137.9 (C4000), 137.7 (C40000), 137.1 (C1000, C100000), 137.0 (C40), 136.7 (C100),
136.4 (C600000, C600, C3000), 135.6 (C30000), 134.9 (C5’), 134.3 (C3), 131.1
(C20000, C30), 130.6 (C5000, C5), 129.5 (C50000), 129.2 (C2000), 126.6 (C60000),
0
124.7 (C6000), 123.0 (C500, C500000), 20.5 (CH3 ), 20.5 (CH30000), 20.5
0
(CH3 ), 20.5 (CH3). Anal. Calcd for C36H30N4: C, 83.37; H, 5.83; N,
10.80. Found: C, 83.02; H, 5.55; N, 10.66.
4.1.18. 5’-(2-Methyl-4-pyridin-3-ylphenyl)-3’,5-dimethyl-6-(2-
methyl-4-pyridin-3-ylphenyl)-3,2’-bipyridine 8f. White solid. Mp
177 ꢀC. IR (KBr): 3022, 2956, 2920, 2858, 1588, 1571, 1456, 1419,
1379, 1184, 1129, 1071, 1021, 995, 882, 841, 805, 710, 616, 531 cmꢁ1
.
1H NMR (500 MHz, CDCl3):
d
8.91 (s, 2H, H200, H200000), 8.79 (s, 1H,
d
8.90 (d, J¼2.0, 1H, H2000), 8.68 (d, J¼2.0, 1H, H2), 8.64 (d, J¼2.0, 1H,
H2), 8.61 (s, 3H, H6’, H400, H400000), 7.94 (d, J¼8.0, 2H, H600, H600000), 7.93
H60), 8.61 (d, J¼4.9, 1H, H6000), 7.93 (dt, J¼7.8, 2.0, 1H, H4000), 7.82 (s,
2H, H4, H40), 7.53 (s, 1H, H300), 7.50 (d, J¼7.8, 1H, H500), 7.39 (dd,
(s, 1H, H4), 7.67 (s, 1H, H4’), 7.56e7.51 (m, 4H, H4000, H5000, H30000
,
H50000), 7.41 (d, J¼8.0, 1H, H6000), 7.41e7.40 (m, 2H, H500, H500000), 7.38
J¼7.8, 4.9, 1H, H5000), 7.33 (d, J¼6.8, 1H, H600), 2.47 (s, 3H, CH3 ), 2.24
(d, J¼8.0, 1H, H60000), 2.55 (s, 3H, CH3 ), 2.45 (s, 3H, CH3000), 2.27 (s, 3H,
0
0
(s, 3H, CH3), 2.22 (s, 3H, CH3eph). 13C NMR (125 MHz, CDCl3):
CH3), 2.24 (s, 3H, CH3 ). 13C NMR (125 MHz, CDCl3):
d 158.5 (C6),
0000
d
159.0 (C6), 154.2 (C20), 148.7 (C6000), 148.5 (C60, C2000), 146.8 (C2),
154.1 (C20), 148.6 (C400000), 148.4 (C400), 148.3 (C200000, C200), 147.5 (C60),
146.8 (C2), 139.9 (C10000), 139.3 (C4’), 138.5 (C4), 137.7 (C100), 137.6
(C1000), 137.5 (C40000), 136.8 (C20000), 136.6 (C2000, C100000), 136.1 (C4000),
135.9 (C5’), 134.7 (C3), 134.4 (C600000, C600), 131.4 (C5), 130.8 (C30),
130.7 (C6000), 129.4 (C60000, C3000), 129.1 (C30000), 124.9 (C5000), 124.6
141.2 (C40), 139.9 (C100), 138.4 (C4), 137.8 (C400), 136.8 (C200), 136.6
(C3000), 134.5 (C4000), 134.1 (C3), 133.3 (C30), 131.6 (C5), 129.5 (C600),
129.3 (C300), 124.7 (C500), 123.7 (C5000), 119.8 (C50), 20.1 (CH3 ), 19.8
0
(CH300), 19.3 (CH3). Anal. Calcd for C24H20N3Br: C, 66.98; H, 4.68; N,
0
9.76. Found: C, 66.68; H, 4.31; N, 9.43.
(C50000), 123.6 (C500000, C500), 20.7 (CH3000), 20.2 (CH3 ), 19.7 (CH30000), 19.1
(CH3). Anal. Calcd for C36H30N4: C, 83.37; H, 5.83; N,10.80. Found: C,
83.12; H, 5.45; N, 10.54.
4.1.15. 5’-[3-Methyl-4-(4-chloro-pyridin-3-yl)phenyl]-3’,5-dimethyl-
6-[3-methyl-4-(4-chloro-pyridin-3-yl)phenyl]-3,2’-bipyridine
8c. Yellow solid mp 206 ꢀC. IR (KBr): 3030, 2963, 2923, 2850, 1618,
1582, 1555, 1456, 1423, 1357, 1103, 1032, 998, 896, 828, 779, 763,
Supplementary data
749, 699, 510 cmꢁ1. 1H NMR (400 MHz, CDCl3):
d
8.84 (d, J¼1.7, 1H),
Crystallographic data (excluding structure factors) for the
structures of compounds 7e and 7f in this paper have been
8.78 (d, J¼1.7, 1H), 8.44e8.43 (m, 2H), 7.91 (d, J¼1.7, 1H), 7.87 (d,

S. Perato et al. / Tetrahedron 68 (2012) 1910e1917
1917
5. (a) Suzuki, A. Angew. Chem., Int. Ed. 2011, 50, 6722e6737; (b) Hosmane, N. S.
Boron Science: New Technologies and Applications; CRC: Boca Raton, FL, 2012;
741e806.
deposited with the Cambridge Crystallographic Data Centre as
supplementary publication nos. CCDC 814118 and 814119. Copies of
the data can be obtained, free of charge, on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK, (fax: þ44 (0) 1223 336033 or
e-mail: deposit@ccdc.cam.ac.Uk).
ꢁ
6. (a) Burzicki, G.; Voisin-Chiret, A. S.; Sopkova-de Oliveira Santos, J.; Rault, S.
ꢁ
Tetrahedron 2009, 65, 5413e5417; (b) Burzicki, G.; Voisin-Chiret, A. S.; Sopkova-
de Oliveira Santos, J.; Rault, S. Synthesis 2010, 16, 2804e2810.
7. Voisin-Chiret, A. S.; Muraglia, M.; Burzicki, G.; Perato, S.; Sopkova-de Oliveira
ꢀ
Santos, J.; Franchini, C.; Rault, S. Tetrahedron 2010, 66, 8000e8005.
ꢀ
8. De Giorgi, M.; Voisin-Chiret, A. S.; Sopkova-de Oliveira Santos, J.; Corbo, F.;
Acknowledgements
Franchini, C.; Rault, S. Tetrahedron 2011, 67, 6145e6154.
9. Voisin-Chiret, A. S.; Bouillon, A.; Burzicki, G.; Celant, M.; Legay, R.; El-Kashef, H.;
ꢀ
The authors gratefully acknowledge for the financial support
from the ‘ CRUNCHOrga’ (Centre de Recherche Universitaire Nor-
mand de Chimie Organique), ERDF funding (ISCE-Chem & INTER-
Rault, S. Tetrahedron 2009, 65, 607e612.
10. (a) Bouillon, A.; Lancelot, J. C.; Collot, V.; Bovy, P. R.; Rault, S. Tetrahedron 2002,
58, 2885e2890; (b) Bouillon, A.; Lancelot, J. C.; Collot, V.; Bovy, P. R.; Rault, S.
Tetrahedron 2002, 58, 3323e3328; (c) Bouillon, A.; Lancelot, J. C.; Collot, V.;
Bovy, P. R.; Rault, S. Tetrahedron 2002, 58, 4369e4373; (d) Bouillon, A.; Lancelot,
J. C.; Collot, V.; Bovy, P. R.; Rault, S. Tetrahedron 2003, 59, 10043e10049; (e)
Voisin, A. S.; Bouillon, A.; Berenguer, I.; Lancelot, J. C.; Lesnard, A.; Rault, S.
ꢀ
REG IVa program) and the ‘ Region Basse-Normandie’.
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