Site-selective synthesis of arylated pyridines by Suzuki-Miyaura reactions of 2,3,5,6-tetrachloropyridine

Article abstract of DOI:10.1016/j.tet.2015.05.114

Site-selective arylation of commercially available 2,3,5,6-tetrachloropyridine has been accomplished, using the Suzuki-Miyaura reaction. The reaction conditions were thoroughly optimized, allowing the selective synthesis of mono-, di-, tri- and tetraarylated pyridines in good to quantitative yields. In addition, we studied the electrochemical properties of selected tetraarylpyridines by DPV-measurements.

Full text of DOI:10.1016/j.tet.2015.05.114

Tetrahedron 71 (2015) 5371e5384
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Site-selective synthesis of arylated pyridines by SuzukieMiyaura
reactions of 2,3,5,6-tetrachloropyridine
,
,
Sebastian Reimann a b, Peter Ehlers a b, Silvio Parpart a, Annette Surkus b,
Anke Spannenberg b, Peter Langer a
Institut fur Chemie, Universitat Rostock, A.-Einstein-Str. 3a, 18059 Rostock, Germany
,b,
*
a
€
€
b
€
€
Leibniz-Institut fur Katalyse an der Universitat Rostock e.V., A.-Einstein-Str. 29a, 18059 Rostock, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Site-selective arylation of commercially available 2,3,5,6-tetrachloropyridine has been accomplished,
using the SuzukieMiyaura reaction. The reaction conditions were thoroughly optimized, allowing the
selective synthesis of mono-, di-, tri- and tetraarylated pyridines in good to quantitative yields. In ad-
dition, we studied the electrochemical properties of selected tetraarylpyridines by DPV-measurements.
Ó 2015 Elsevier Ltd. All rights reserved.
Received 23 April 2015
Accepted 29 May 2015
Available online 5 June 2015
Keywords:
Pyridine
SuzukieMiyaura reaction
Site-selectivity
Cross-coupling
Catalysis
1. Introduction
Owing to their widespread incorporation in biological systems
and their application in medicinal- and chemical science, pyridines
belong to one of the most studied heterocycles to date.1 In partic-
ular, pyridines are common structural motives in natural products2
and relevant pharmaceuticals3 (Fig. 1). Moreover, pyridine pos-
sessing molecules are of central importance in organometallic
chemistry and catalysis,4 as well as material science5 and supra-
molecular chemistry.6 The ubiquitous significance of pyridines in
various research areas underlines the importance and requirement
of new synthetic methodologies for the synthesis of functionalized
pyridines.
Generally, synthetic access to substituted pyridine derivatives
relies either on the functionalization of appropriate precursors and
a final ring closing step or by the systematic introduction of sub-
stituents on the preformed pyridine ring. The first strategy is mainly
based on traditional condensation reactions,7 [3þ3] aza-Diel-
seAlder and related reactions8 or transition metal based conden-
sations.9 These procedures lack mostly on the availability of only
constricted substitution pattern. The latter strategy includes, for
example, aromatic substitutions,10 direct metallation or metal-
halogen-exchange reactions11 as well as transition metal catalyzed
Fig. 1. Choice of natural products and drugs possessing a pyridine core.
* Corresponding author. Fax: þ49 (381) 4986412; e-mail address: peter.langer@
uni-rostock.de (P. Langer).
http://dx.doi.org/10.1016/j.tet.2015.05.114
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.

5372
S. Reimann et al. / Tetrahedron 71 (2015) 5371e5384
cross-coupling reactions.12 Notably, the primary selective in-
troduction of activating groups on the substrate is the main draw-
back of these procedures.
R
B(OH)2
R
Cl
Cl
Cl
Cl
i
Several research groups focused on site selective cross-coupling
reactions on heterocycles13 including ours.14 Different electron
density distribution in heterocycles allows the facile introduction of
versatile functionalities by palladium catalyzed cross-coupling re-
actions with high selectivity. Recently, we have described the syn-
thesis of pentaalkynyl-15 and pentaarylpyridines16 as well as the
synthesis of 2,3,5,6-tetraalkynyl- and tetraalkenylpyridines12c using
cheap and commercially available pentachloropyridine or 2,3,5,6-
tetrachloropyridine as substrates, respectively. These examples im-
pressively proofed the access of highly functionalized pyridines by
cross-coupling methodologies. We also reported the site-selective
synthesis of 3,4,5-trichloro-2,6-diarylpyridines from PCP.14e
+
N
N
R
R
R
1
2
Scheme 2. Synthesis of 2aem. i, 1 (1.0 equiv), boronic acid (7.0 equiv), Pd2(dba)3
(1.25 mol %), cataCXium A (5 mol %), K3PO4 (7.5 equiv), toluene, 100 ꢁC, 22 h.
Table 2
Synthesis of 2aem
2
a
Boronic acid
Yield (%)a
99
2. Results and discussion
b
c
96
94
Initially we thouroughly optimized the reaction conditions
for the synthesis of tetraarylpyridines starting from 1 (Scheme 1,
Table 1). Successfully applied conditions for the pentafold arylation
of pentachloropyridine gave only moderate yields of the desired
product (entry 1).16 In comparison to several tested bulky, electron-
rich phosphine ligands, the cataCXium A ligand17 showed in the
presence of Pd2(dba)3 the best results (entry 6). The amount of
catalyst and ligand could be reduced to 1.25 mol % of Pd2(dba)3 and
5 mol % of ligand, while further reduction to 0.5 mol % of the pal-
ladium gave a diminished yield of product 2a (entry 8). Finally,
increasing the amount of the phenylboronic acid to 7 equiv led to
a quantitative yield using toluene as solvent and K3PO4 as base.
d
e
f
90
99
84
R
B(OH)2
R
g
73
57
Cl
Cl
Cl
Cl
i
+
N
N
R
R
h
R
1
2a
Scheme 1. Optimization of the tetrafold SuzukieMiyaura reaction of 1.
i
56
75
47
Table 1
Optimizationetetrafold SuzukieMiyaura reaction of 1
Equiv of Ph-B(OH)2
Pd source (mol %)
Ligand (mol %)
Yielda [%]
j
1
2
3
4
5
6
7
8
9
5
5
5
5
5
5
5
5
7
PdCl2(CH3CN)2 (5)
PdCl2(CH3CN)2 (5)
PdCl2(CH3CN)2 (5)
PdCl2(CH3CN)2 (5)
Pd(OAc)2 (5)
Pd2(dba)3 (2.5)
Pd2(dba)3 (1.25)
Pd2(dba)3 (0.5)
Pd2(dba)3 (1.25)
SPhos (10)
XPhos (10)
cataCXium A (10)
P(Cy)3 (10)
cataCXium A (10)
cataCXium A (10)
cataCXium A (5)
cataCXium A (5)
cataCXium A (5)
51
30
68
49
43
95
97
88
99
k
l
55
60
a
Isolated yield.
With our optimized conditions in hand, various boronic acids
provided the corresponding 2,3,5,6-tetraarylpyridines in high to
quantitative yield. Boronic acids containing substituents in two- or
three-position led to lower yields (47e73%). Furthermore, n-hex-
ylboronic acid was successfully converted to the corresponding
tetraalkyl-derivative 2j in 75% yield. (Scheme 2 and Table 2).
The structure of compound 2a was additionally confirmed by X-
ray crystal analysis (Fig. 2). The phenyl rings, located opposite
to each other, are twisted out of the pyridine ring plane
m
a
Isolated yield.
Our next step was to evaluate the regioselective synthesis
of monoarylated trichloropyridines. During our optimization,
Pd(PPh3)4 proved to be the most appropriate catalyst for this re-
action, while bulkier ligands, such as SPhos19 and cataCXium A,
gave predominately tri- and tetraarylated pyridines as main
(N1eC1eC6eC7¼ꢀ37.0(2),
N1eC5eC24eC29¼67.5(2),
respectively).
C3eC4eC18eC19¼38.5(3)
and
C1eC2eC12eC13¼ꢀ68.9(2)ꢁ,

S. Reimann et al. / Tetrahedron 71 (2015) 5371e5384
5373
Table 3
Synthesis of compounds 3aek
3
a
b
c
Boronic acid
Yield (%)a
65
64
65
55
67
71
41
57
d
e
f
Fig. 2. Molecular structure of 2a. Displacement ellipsoids are drawn at the 50%
probability level.18
g
h
products. Thus, the synthesis of the desired 2,3,5-trichloro-6-
arylpyridines was accomplished by using 5 mol % of Pd(PPh3)4,
3 equiv of KF as base in toluene at 100 ꢁC (Scheme 3, Table 3). The
arylation exclusively took place at position 5. The synthesis of other
isomers was not observed.
i
j
51
54
B(OH)2
Cl
Cl
Cl
Cl
Cl
Cl
Cl
i
+
N
N
R
R
1
3
Scheme 3. Synthesis of compounds 3aek: i, 1 (1.0 equiv), boronic acid (1.1 equiv),
k
43
Pd(PPh3)4 (5.0 mol %), KF (3.0 equiv), toluene, 100 ꢁC, 22 h.
a
Isolated yield.
Using the same conditions, while adjusting the amounts of base
(KF) and boronic acid, 2,6-diarylated products could be obtained in
good yields (Scheme 4, Table 4). Arylation on position three or five
was not observed. The structure of compound 4i was in-
dependently confirmed by X-ray crystal structure analysis (Fig. 3).
Compounds 4a and 4i were chosen as model compounds for the
synthesis of tetraarylpyridines containing two different aryl moi-
eties. Using the optimized catalyst system for the tetraarylation
reaction the corresponding 2,3,5,6-tetraaryl-pyridines were syn-
thesized in excellent yields (Scheme 5, Table 5). The amounts of
base (K3PO4) and boronic acid were reduced as compared to the
synthesis of the tetraarylated pyridines.
B(OH)2
Cl
Cl
Cl
Cl
Cl
i
+
N
N
Cl
R
R
R
1
4
Scheme 4. Synthesis of compounds 4aei. i, 1 (1.0 equiv), boronic acid (2.5 equiv),
Pd(PPh3)4 (5 mol %), KF (6.0 equiv) toluene, 100 ꢁC, 22 h.
Finally, the trifold arylation of tetrachloropyridine 1 was in-
vestigated (Scheme 6, Table 6). Again, application of the cataCXium
A ligand led to the desired products in 38e58 % yield. The formation
of the corresponding 2,3,5,6-tetraarylproduct 2 as main by-product
explain the moderate yields. However, choosing other ligands like
XPhos, SPhos and P(Cy)3 or reducing the amount of the boronic
acid, temperature or reaction time resulted in no improvement of
the product yield.
compounds containing electron donating groups are cathodically
shifted, whereas compound 3f with an electron withdrawing group
is anodically shifted.
3. Conclusions
In conclusion, we developed a convenient and high yielding
protocol for the synthesis of 2,3,5,6-tetraarylpyridines from com-
mercially available 2,3,5,6-tetrachloropyridine. Furthermore, we
studied the site-selective arylation of this starting material, giving
access to mono-, di- and triarylated pyridines. The obtained prod-
ucts are useful substrates in demand for subsequent cross-coupling
reactions to construct tetraarylpyridines with two different aryl-
moieties.
The electrochemical activity of selected compounds was studied
using DPV measurements. Compounds 2a, 2b, 2d and 2e exhibit
distinct reductions within the range of ꢀ2.18 V to ꢀ2.2 V. Com-
pound 2f reveals its first reduction potential at ꢀ1.55 V and sub-
sequent reductions until ꢀ2.2 V (Fig. 4). However, the influence by
different substitution patterns can be brought into correlation with
20
the Hammett substituent constants spara
.
Thus, the potential of

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S. Reimann et al. / Tetrahedron 71 (2015) 5371e5384
Table 4
Table 5
Synthesis of compounds 4aei
Synthesis of compounds 5aef
4
a
b
c
Boronic acid
Yield (%)a
5
4
Boronic acid
Yield (%)a
90
a
a
77
77
72
b
c
a
a
a
93
98
90
d
d
71
e
f
i
i
86
97
e
f
73
77
68
a
Isolated yields.
g
h
i
69
71
R
B(OH)2
Cl
Cl
Cl
Cl
Cl
i
+
N
N
R
R
R
1
6
a
Isolated yields.
Scheme 6. Synthesis of compounds 6aee. Conditions: i, 1 (1.0 equiv), boronic acid
(3.5 equiv), Pd(dba)2 (2.5 mol %), cataCXium A (5.0 mol %), K3PO4 (5.0 equiv), toluene,
100 ꢁC, 20 h.
Table 6
Synthesis of compounds 6aee
6
a
Boronic acid
Yield (%)a
42
b
c
58
55
Fig. 3. Molecular structure of 4i. Displacement ellipsoids are drawn at the 50% prob-
ability level.18
R
d
38
41
B(OH)2
R
Cl
Ar
Cl
Ar
i
+
Ar
N
Ar
N
e
R
4a, 4i
5
a
Isolated yields.
Scheme 5. Synthesis of compounds 5aef. Conditions: i, 4a or 4i (1.0 equiv), boronic
acid (4.0 equiv), Pd(dba)2 (2.5 mol %), cataCXium A (5.0 mol %), K3PO4 (4.0 equiv),
toluene, 100 ꢁC, 22 h.
distilled by standard methods or purchased in extra dry quality
from Sigma Aldrich. Solvents for liquid chromatography and ex-
traction were always distilled prior to use (n-heptane, n-hexane,
ethyl acetate, dichloromethane). All chemicals employed, including
halogenated pyridines, ligands, boronic acids and bases, were
purchased from a commercial source (Sigma Aldrich, Alfa Aesar)
and used without further purification.
4. Experimental
4.1. General
All reactions were carried out in oven-dried pressure tubes
under argon atmosphere. Solvents for reactions were dried and

S. Reimann et al. / Tetrahedron 71 (2015) 5371e5384
5375
www.ccdc.cam.ac.uk/data_request/cif. Elemental Analysis (EA): C/H/
N/SeMicroanalysator TruSpec CHNS (Leco). Melting point de-
termination (mp): Micro-Hot-Stage GalenÔ III Cambridge In-
struments. The melting points have not been corrected. Thin layer
chromatography (TLC): Merck Silica 60 F254 on aluminum tin foil
from MachereyeNagel. Detection with UV light at 254 nm and/or
366 nm without dipping reagent. Column Chromatography: Sepa-
ration on Fluka silica gel 60 (0.063e0.200 mm, 70e320 mesh).
Eluents were distilled before use.
4.2. General procedure for the synthesis of 2,3,5,6-tetraaryl-
substituted pyridines 2aem
An oven-dried and argon-flushed pressure tube was charged
with 2,3,5,6-tetrachloropyridine
1
(0.25 mmol), Pd2(dba)3
(1.25 mol %), cataCXium A (5.0 mol %), boronic acid (1.8 mmol) and
K3PO4 (1.9 mmol) followed by anhydrous toluene (4.0 mL). The tube
was sealed with a Teflon valve and the reaction mixture was stirred
at 100 ꢁC for 22 h. The cooled reaction mixture was diluted with
water and extracted with CH2Cl2. The combined organic layers
were dried (Na2SO4), filtered and the filtrate was concentrated in
vacuo. The residue was purified by column chromatography.
Fig. 4. Reductive DPVs of 1, 2a, 2b, 2d, 2e and 2f in DMF (0.1 mol,Lꢀ1 TBAPF6); working
electrode: platinum; [Fc/Fcþ]¼0.6 V.
1H NMR Spectroscopy: Bruker AV 300 (300 MHz) and Bruker AV
400 (400 MHz). All NMR spectra presented in this work were
recorded in CDCl3 solution. All chemical shifts are given in ppm. All
coupling constants are indicated as J. References: TMS
4.2.1. 2,3,5,6-Tetraphenylpyridine (2a). Starting with 2,3,5,6-
tetrachloropyridine 1 (54 mg, 0.25 mmol), Pd2(dba)3 (2.9 mg,
1.25 mol %), cataCXium A (5.1 mg, 5.0 mol %), phenylboronic acid
(213 mg, 1.75 mmol), K3PO4 (398 mg, 1.88 mmol) and toluene
(4.0 mL), 2a was isolated as a colorless solid (95 mg, 99%);
(d
¼0.00 ppm) or residual CHCl3
(d
¼7.26 ppm) were taken as in-
ternal standard. Peak characterization: s¼singlet, br s¼broad sin-
glet, d¼doublet, br d¼broad doublet, t¼triplet, dd¼doublet of
doublet, q¼quartet, m¼multiplet. The spectra were measured with
a standard number of scans (NS¼32). In case of unclear assignment
all possible hydrogen atoms were stated. 13C NMR Spectroscopy:
Bruker AV 300 (75 MHz) and Bruker AV 400 (100 MHz). All NMR
spectra presented in this work were recorded in CDCl3 solution. All
chemical shifts are given in ppm. All coupling constants are in-
mp¼244e246 ꢁC. 1H NMR (300 MHz, CDCl3):
¼7.15e7.22 (m, 16H,
d
CH), 7.41e7.44 (m, 4H, CH), 7.69 (s, 1H, CH). 13C NMR (75 MHz,
CDCl3):
d¼127.2 (CH), 127.8 (CH), 127.8 (CH), 128.3 (CH), 129.5 (CH),
130.2 (CH), 134.3 (C), 139.6 (C), 139.9 (C), 141.2 (CH), 155.3 (C). IR
(ATR, cmꢀ1): ṽ¼3080 (w), 3054 (w), 3023 (w), 2927 (w), 2857 (w),
1444 (m), 1416 (s), 1386 (m), 1179 (w), 1072 (w), 1017 (w), 908 (m),
854 (w), 779 (m), 757 (s), 732 (m), 690 (s), 537 (m), 528 (m), 499
(m), 409 (w), 390 (w). GCeMS (EI, 70 eV): m/z (%): 384 (Mþ, 16), 383
(66), 382 (100), 306 (3), 305 (3), 304 (10), 303 (7), 302 (6), 276 (8),
190 (7), 189 (5), 188 (3), 183 (13), 77 (4). HRMS (ESI, 70 eV): calcd for
dicated as J. References: TMS (
d
¼0.00 ppm) or residual CHCl3
(d
¼70.00 ppm) were taken as internal standard. Peak character-
ization: d¼doublet, t¼triplet, q¼quartet. DEPT method was used
for determining the presence of primary, secondary, tertiary and
quaternary carbon atoms. All spectra were measured with a stan-
dard number of scans (NS¼256). In case of unclear assignment all
possible carbon atoms were stated. In some cases the number of
scans was increased to 2000e8000 scans in order to detect car-
bonefluorine couplings. 19F-NMR Spectroscopy: Bruker AV 300
(282 MHz). Spectra were measured with a standard number of
scans (NS¼128). Mass Spectrometry (MS): Finnigan MAT 95 XP
(electron ionization EI, 70 eV); 6890 N/5973 (Agilent), 6210 Time-
of-Flight LC/MS (Agilent). Gas Chromatography MS (GCeMS): Agi-
lent HP-5890 with an Agilent HP-5973 Mass Selective Detector (EI)
and HP-5 capillary column using helium carrier gas. Only the
measurements with an average deviation from the theoretical mass
of ꢂ2 mDa were accounted as correct. High resolution MS (HRMS
(ESI)): Agilent 1969A TOF. Only the measurements with an average
deviation from the theoretical mass of ꢂ2 mDa were accounted as
correct. Infrared Spectroscopy (IR): Nicolet 550 FTIR spectrometer
with ATR sampling technique for solids as well as liquids. Signal
characterization: w¼weak, m¼medium, s¼strong. X-ray Crystal-
lography: Data were collected on a Bruker Kappa APEX II Duo dif-
fractometer. The structure was solved by direct methods and
refined by full-matrix least-squares procedures on F2 with the
SHELXTL software package (Sheldrick, G. M. Acta Crystallogr. 2008,
A64, 112.). XP (Bruker AXS) was used for graphical representation.
CCDC 986651-986652 contain the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
C
C
29H22N ([MþH]þ): 384.17468, found 384.17447. Anal. Calcd for
29H21N (383.48): C, 90.83; H, 5.52; N, 3.65. Found: C, 90.50; H,
5.329; N, 3.431.
4.2.2. 2,3,5,6-Tetra-p-tolylpyridine (2b). Starting with 2,3,5,6-
tetrachloropyridine 1 (54 mg, 0.25 mmol), Pd2(dba)3 (2.9 mg,
1.25 mol %), cataCXium A (5.1 mg, 5.0 mol %), p-tolylboronic acid
(238 mg, 1.75 mmol), K3PO4 (398 mg, 1.88 mmol) and toluene
(4.0 mL), 2b was isolated as a colorless solid (105 mg, 96%);
mp¼284e286 ꢁC. 1H NMR (300 MHz, CDCl3):
¼2.31 (s, 6H, CH3),
d
2.34 (s, 6H, CH3), 7.03e7.17 (m,12H, CH), 7.38e7.41 (m, 4H, CH), 7.69
(s, 1H, CH). 13C NMR (75 MHz, CDCl3):
d¼21.2 (CH3), 21.3 (CH3),
128.5 (CH), 129.1 (CH), 129.3 (CH), 130.0 (CH), 133.8 (C), 136.8 (C),
137.0 (C), 137.2 (C), 137.4 (C), 141.2 (CH), 154.8 (C). IR (ATR, cmꢀ1):
ṽ¼3119 (w), 3021 (w), 2859 (w), 1607 (w), 1568 (w), 1496 (m), 1426
(s), 1380 (w), 1308 (w), 1181 (m), 1112 (m), 1089 (w), 1014 (w), 1004
(m), 926 (w), 880 (w), 818 (s), 781 (m), 728 (m), 718 (w), 681 (w),
645 (w), 621 (m), 556 (m), 530 (m), 516 (m), 462 (m), 433 (w), 408
(m), 382 (w). GCeMS (EI, 70 eV): m/z (%): 440 (Mþ, 18), 439 (72),
438 (100), 331 (4), 315 (2), 220 (3), 211 (2), 207 (3), 204 (8), 197 (7),
196 (6), 182 (4). HRMS (ESI, 70 eV): calcd for C33H30N ([MþH]þ):
440.23728, found 440.23695. Anal. Calcd for C33H29N (439.59): C,
90.83; H, 5.52. Found: C, 90.61; H, 5.950.
4.2.3. 2,3,5,6-Tetrakis(4-ethylphenyl)pyridine (2c). Starting with
2,3,5,6-tetrachloropyridine
(2.9 mg, 1.25 mol %), cataCXium
ethylphenylboronic acid (262 mg, 1.75 mmol), K3PO4 (398 mg,
1
(54 mg, 0.25 mmol), Pd2(dba)3
A
(5.1 mg, 5.0 mol %), 4-

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S. Reimann et al. / Tetrahedron 71 (2015) 5371e5384
1.88 mmol) and toluene (4.0 mL), 2c was isolated as a colorless solid
was isolated as a colorless solid (137 mg, 84%); mp¼253e254 ꢁC. 1H
(116 mg, 94%); mp¼237e239 ꢁC. 1H NMR (300 MHz, CDCl3):
d
¼1.20
NMR (300 MHz, CDCl3):
d¼7.37e7.40 (m, 4H, CH), 7.52e7.62 (m,
3
3
(t, JHeH¼7.6 Hz, 6H, CH3), 1.23 (t, JHeH¼7.6 Hz, 6H, CH3), 2.61 (q,
12H, CH), 7.80 (s, 1H, CH). 13C NMR (75 MHz, CDCl3):
d
¼124.0 (q,
3JHeH¼7.7 Hz, 4H, CH2), 2.64 (q, JHeH¼7.7 Hz, 4H, CH2), 7.05e7.20
4JCeF¼271.8 Hz, CF3), 124.1 (q, JCeF¼271.7 Hz, CF3), 125.2 (q,
3
4
(m, 12H, CH), 7.41e7.43 (m, 4H, CH), 7.71 (s, 1H, CH). 13C NMR
3JCeF¼3.6 Hz, CH), 125.8 (q, JCeF¼3.8 Hz, CH), 129.8 (CH), 130.4
3
2
2
(75 MHz, CDCl3):
d¼15.4 (CH3), 15.4 (CH3), 28.5 (CH2), 28.6 (CH2),
(CH), 130.4 (q, JCeF¼32.0 Hz, C), 130.4 (q, JCeF¼32.2 Hz, C), 134.0
127.3 (CH), 127.8 (CH), 129.4 (CH), 130.1 (CH), 133.7 (C), 137.2 (C),
137.4 (C), 141.3 (CH), 143.1 (C), 143.7 (C), 154.8 (C). IR (ATR, cmꢀ1):
ṽ¼3026 (w), 2962 (m), 2930 (m), 2872 (w),1907 (w),1609 (w),1582
(w), 1513 (w), 1499 (w), 1456 (m), 1429 (s), 1405 (m), 1383 (w), 1331
(w), 1182 (w), 1117 (w), 1004 (w), 969 (w), 834 (s), 795 (m), 626 (m),
537 (m). GCeMS (EI, 70 eV): m/z (%): 495 (Mþ, 75), 494 (100), 478
(7), 466 (9), 465 (2), 464 (5), 450 (5), 449 (3), 436 (4), 420 (3), 390
(2), 329 (2), 81 (3), 57 (4), 55 (33), 44 (4), 43 (15), 41 (4), 39 (2).
HRMS (ESI, 70 eV): calcd for C37H38N ([MþH]þ): 496.29988, found
496.3007.
(C), 141.4 (C), 142.2 (C), 142.4 (CH), 154.8 (C). 19F NMR (282.4 MHz,
CDCl3):
d
¼ꢀ62.2 (CF3), ꢀ62.2 (CF3). IR (ATR, cmꢀ1): ṽ¼2937 (w),
1617 (m), 1572 (w), 1439 (m), 1406 (m), 1322 (s), 1164 (s), 1104 (s),
1061 (s), 1014 (s), 934 (w), 843 (s), 795 (m), 714 (m), 697 (w), 630
(m), 500 (w), 470 (m), 413 (m), 402 (w). GCeMS (EI, 70 eV): m/z (%):
655 (Mþ, 51), 654 (100), 652 (6), 636 (7), 468 (5), 281 (2), 248 (3),
224 (3), 181 (3), 169 (3), 119 (4), 69 (13), 44 (12), 43 (10). HRMS (ESI,
70 eV): calcd for
C
33H18F12
N
([MþH]þ): 656.12421, found
656.12529. Anal. Calcd for C33H17F12N (655.48): C, 60.47; H, 2.61.
Found: C, 60.24; H, 2.555.
4.2.4. 2,3,5,6-Tetrakis(4-tert-butylphenyl)pyridine
(2d). Starting
4.2.7. 2,3,5,6-Tetrakis(2-methoxyphenyl)pyridine (2g). Starting with
with 2,3,5,6-tetrachloropyridine 1 (54 mg, 0.25 mmol), Pd2(dba)3
(2.9 mg, 1.25 mol %), cataCXium A (5.1 mg, 5.0 mol %), 4-tert-
butylphenylboronic acid (312 mg, 1.75 mmol), K3PO4 (398 mg,
1.88 mmol) and toluene (4.0 mL), 2d was isolated as a colorless
solid (137 mg, 90%); mp¼314e316 ꢁC. 1H NMR (300 MHz, CDCl3):
2,3,5,6-tetrachloropyridine
(2.9 mg, 1.25 mol %), cataCXium
methoxyphenylboronic acid (266 mg, 1.75 mmol), K3PO4 (398 mg,
1
(54 mg, 0.25 mmol), Pd2(dba)3
(5.1 mg, 5.0 mol %), 2-
A
1.88 mmol) and toluene (4.0 mL), 2g was isolated as a colorless solid
(73 mg, 73%); mp¼228e230 ꢁC. 1H NMR (300 MHz, CDCl3):
d¼3.34
3
d
¼1.28 (s,18H, CH3 tBu), 1.32 (s,18H, CH3 tBu), 7.16e7.31 (m,12H, CH),
(s, 6H, MeO), 3.57 (s, 6H, MeO), 6.64 (br d, JHeH¼8.3 Hz, 2H, CH),
7.42e7.46 (m, 12H, CH), 7.73 (s, 1H, CH). 13C NMR (75 MHz, CDCl3):
¼31.3 (CH3 tBu), 31.3 (CH3 tBu), 34.5 (CtBu), 34.5 (CtBu), 124.6 (CH),
6.66e7.21 (m, 12H, CH), 7.53 (dd, JHeH¼7.7 Hz, JHeH¼1.8 Hz, 2H,
3
4
d
CH), 7.80 (s, 1H, CH). 13C NMR (75 MHz, CDCl3):
d
¼54.7 (MeO), 55.0
125.1 (CH),129.1 (CH),129.8 (CH),133.7 (C),136.9 (C),137.1 (C),141.3
(CH), 150.0 (C), 150.5 (C), 154.7 (C). IR (ATR, cmꢀ1): ṽ¼3030 (w),
2962 (s), 2902 (m), 2865 (m), 1609 (w), 1584 (w), 1512 (m), 1474
(m), 1460 (m), 1430 (m), 1391 (m), 1361 (m), 1268 (m), 1204 (m),
1203 (m),1118 (s), 1015 (m),1003 (m), 927 (w), 835 (s), 794 (m), 756
(w), 667 (w), 629 (m), 580 (m), 563 (m), 508 (w), 411 (w). GCeMS
(EI, 70 eV): m/z (%): 608 (Mþ, 38), 607 (100), 606 (88), 592 (9), 591
(6), 590 (9), 576 (5), 495 (11), 494 (17), 464 (2), 289 (7), 169 (2), 165
(2), 151 (3), 145 (3), 139 (3), 125 (6), 123 (5), 111 (9), 109 (7), 105 (3),
97 (13), 95 (10), 83 (12), 81 (9), 71 (14), 69 (13), 57 (25), 55 (14), 44
(MeO), 110.4 (CH), 110.4 (CH), 119.8 (CH), 120.8 (CH), 128.2 (CH),
128.8 (CH), 129.1 (C), 130.4 (C), 131.1 (CH), 132.0 (CH), 140.8 (CH),
154.1 (C),156.2 (C). IR (ATR, cmꢀ1): ṽ¼2997 (w), 2956 (w), 2832 (m),
1599 (m), 1580 (m), 1494 (m), 1459 (m), 1434 (m), 1416 (m), 1386
(w), 1253 (m), 1180 (m), 1161 (w), 1118 (w), 1079 (m), 1023 (s), 919
(m), 805 (m), 795 (w), 754 (s), 670 (m), 643 (w), 585 (w), 500 (m),
432 (w), 385 (w). GCeMS (EI, 70 eV): m/z (%): 504 (Mþ, 16), 503
(48), 502 (35), 488 (7), 474 (15), 473 (34), 472 (100), 458 (7), 442 (9),
398 (29), 397 (12), 396 (40), 350 (4), 252 (7), 244 (5), 199 (7), 191
(6), 183 (10), 176 (6). HRMS (EI, 70 eV): calcd for C33H29NO4 (Mþ):
503.20911, found 503.20812. Anal. Calcd for C33H29NO4 (503.59): C,
78.71; H, 5.80; N, 2.78. Found: C, 78.55; H, 5.560; N, 2.734.
(12), 43 (12), 41 (19). HRMS (ESI, 70 eV): calcd for C45H54
N
([MþH]þ): 608.42508, found 608.42535.
4.2.5. 2,3,5,6-Tetrakis(4-methoxyphenyl)pyridine (2e). Starting with
2,3,5,6-tetrachloropyridine (54 mg, 0.25 mmol), Pd2(dba)3
(2.9 mg, 1.25 mol %), cataCXium (5.1 mg, 5.0 mol %), 4-
4.2.8. 2,3,5,6-Tetrakis(3-(trifluoromethyl)phenyl)pyridine
1
(2h). Starting with 2,3,5,6-tetrachloropyridine
1
(54 mg,
A
0.25 mmol), Pd2(dba)3 (2.8 mg, 1.25 mol %), cataCXium A (5.1 mg,
5.0 mol %), 3-(trifluoromethyl)phenylboronic acid (333 mg,
1.75 mmol), K3PO4 (398 mg, 1.88 mmol) and toluene (4.0 mL), 2h
was isolated as a colorless solid (93 mg, 57%); mp¼119e121 ꢁC. 1H
methoxyphenyl-boronic acid (266 mg, 1.75 mmol), K3PO4
(398 mg, 1.88 mmol) and toluene (4.0 mL), 2e was isolated as
a colorless solid (125 mg, 99%); mp¼246e248 ꢁC. 1H NMR
(300 MHz, CDCl3):
d
¼3.78 (s, 6H, MeO), 3.80 (s, 6H, MeO),
NMR (300 MHz, CDCl3):
d
¼7.39e7.65 (m, 16H, CH), 7.85 (s, 1H, CH).
4
6.75e6.85 (m, 8H, CH), 7.15e7.20 (m, 4H, CH), 7.41e7.46 (m, 4H,
13C NMR (75 MHz, CDCl3):
d
¼123.7 (q, JCeF¼274.3 Hz, CF3), 123.7
3
CH), 7.64 (s, 1H, CH). 13C NMR (75 MHz, CDCl3):
d¼55.2 (MeO), 55.2
(q, JCeF¼272.3 Hz, CF3), 124.7 (q, JCeF¼4.1 Hz, CH), 125.1 (q,
4
(MeO), 113.2 (CH), 113.8 (CH), 130.6 (CH), 131.4 (CH), 132.3 (C), 133.1
(C), 141.1 (CH), 147.0 (C), 154.3 (C), 158.7 (C), 159.2 (C). IR (ATR,
cmꢀ1): ṽ¼3085 (w), 2990 (w), 2954 (w), 2834 (w), 2536 (w), 1605
(s), 1576 (s), 1512 (s), 1426 (s), 1292 (s), 1244 (s), 1208 (m), 1168 (s),
1110 (m), 1030 (s), 998 (m), 829 (s), 804 (m), 786 (m), 738 (w), 667
(m), 616 (m), 561 (m), 530 (w), 491 (m), 415 (w). GCeMS (EI, 70 eV):
m/z (%): 504 (Mþ, 29), 503 (100), 502 (94), 488 (5), 458 (6), 415 (6),
329 (4), 252 (9), 244 (8), 214 (13), 207 (10), 198 (7), 192 (20), 187
(11), 185 (14), 183 (16), 180 (10), 178 (13), 176 (24), 171 (34), 170 (17),
158 (21), 157 (9), 140 (6), 120 (6). HRMS (ESI, 70 eV): calcd for
3JCeF¼3.8 Hz, CH),126.2 (q, 3JCeF¼3.8 Hz, CH),127.0 (q, 3JCeF¼4.0 Hz,
2
CH), 128.7 (CH), 129.3 (CH), 130.6 (q, JCeF¼32.9 Hz, C), 131.3 (q,
2JCeF¼32.9 Hz, C), 132.8 (CH), 133.2 (CH), 134.0 (C), 139.2 (C), 139.4
(C), 140.9 (CH), 154.8 (C). 19F NMR (282.4 MHz, CDCl3):
d¼ꢀ62.5
(CF3), ꢀ62.6 (CF3). IR (ATR, cmꢀ1): ṽ¼1411 (m), 1374 (w), 1324 (s),
1276 (w),1250 (m),1213 (w),1180 (m),1214 (m),1180 (m),1162 (m),
1069 (s), 1001 (m), 899 (m), 836 (m), 802 (s), 727 (m), 700 (s), 536
(m), 465 (m), 436 (m), 416 (w), 399 (w). GCeMS (EI, 70 eV): m/z (%):
655 (Mþ, 61), 654 (100), 652 (2), 544 (12), 488 (4), 468 (4), 281 (2),
207 (3), 137 (2), 125 (3), 123 (3), 111 (5), 109 (5), 95 (6), 81 (6), 71 (8),
69 (10), 57 (15), 55 (10), 43 (11), 41 (11), 39 (5). HRMS (ESI, 70 eV):
calcd for C33H18F12N ([MþH]þ): 656.12421, found 656.12419. Anal.
Calcd for C33H17F12N (655.48): C, 60.47; H, 2.61. Found: C, 60.67; H,
2.232.
C
C
33H30NO4 ([MþH]þ): 504.21693, found 504.21764. Anal. Calcd for
33H29NO4 (503.59): C, 78.71; H, 5.80. Found: C, 78.65; H, 5.802.
4.2.6. 2,3,5,6-Tetrakis(4-(trifluoromethyl)phenyl)pyridine
(2f). Starting with 2,3,5,6-tetrachloropyridine (54 mg,
1
0.25 mmol), Pd2(dba)3 (2.9 mg, 1.25 mol %), cataCXium A (5.1 mg,
5.0 mol %), 4-(trifluoromethyl)phenylboronic acid (332 mg,
1.75 mmol), K3PO4 (398 mg, 1.88 mmol) and toluene (4.0 mL), 2f
4.2.9. 2,3,5,6-Tetrakis(biphenyl-3-yl)pyridine (2i). Starting with
2,3,5,6-tetrachloropyridine
1 (54 mg, 0.25 mmol), Pd2(dba)3
(2.9 mg, 1.25 mol %), cataCXium A (5.1 mg, 5.0 mol %), biphenyl-3-

S. Reimann et al. / Tetrahedron 71 (2015) 5371e5384
5377
ylboronic acid (347 mg,1.75 mmol), K3PO4 (398 mg,1.88 mmol) and
(398 mg, 1.88 mmol) and toluene (4.0 mL), 2l was isolated as
a colorless solid (86 mg, 55%); mp¼224e226 ꢁC. 1H NMR (300 MHz,
toluene (4.0 mL), 2i was isolated as a colorless solid (97 mg, 56%);
mp¼235e237 ꢁC. 1H NMR (300 MHz, CDCl3):
d
¼7.27e7.45 (m, 26H,
CDCl3):
d
¼3.66 (br s, 6H, MeO), 3.73 (s, 6H, MeO), 3.76 (br s, 6H,
CH), 7.51e7.59 (m, 6H, CH), 7.62e7.67 (m, 2H, CH), 7.73e7.74 (m, 2H,
MeO), 3.79 (br s, 6H, MeO), 6.67e6.79 (m, 8H, CH), 6.91e6.93 (m,
CH), 7.97 (s, 1H, CH). 13C NMR (75 MHz, CDCl3):
d¼126.1 (CH), 126.7
4H, CH), 7.95 (s, 1H, CH). 13C NMR (75 MHz, CDCl3):
d
¼55.7 (MeO),
(CH), 127.1 (CH), 127.1 (CH), 127.4 (CH), 128.4 (CH), 128.5 (CH), 128.5
(CH),128.5 (CH),128.7 (CH),128.7 (CH),129.0 (CH),129.1 (CH),129.5
(CH), 134.5 (C), 140.1 (C), 140.6 (C), 140.7 (C), 140.8 (CH), 141.0 (C),
141.5 (C), 155.5 (C). IR (ATR, cmꢀ1): ṽ¼3057 (w), 3029 (w), 2926 (w),
1597 (m),1572 (m),1535 (w), 1387 (m),1207 (w), 1037 (w), 893 (m),
799 (m), 750 (s), 700 (s), 617 (m), 513 (m), 442 (w). GCeMS (EI,
70 eV): m/z (%): 688 (Mþ, 36), 687 (95), 686 (100), 532 (3), 344 (3),
208 (2), 207 (9), 105 (4), 97 (2), 96 (2), 91 (11), 84 (4), 77 (4), 66 (5),
60 (4), 57 (4), 55 (4), 44 (54), 43 (12), 42 (3), 41 (5), 39 (3). HRMS
(ESI, 70 eV): calcd for C53H38N ([MþH]þ): 688.29988, found
688.30015. Anal. Calcd for C53H37N (687.87): C, 92.54; H, 5.42; N,
2.04. Found: C, 92.48; H, 5.054; N, 1.644.
55.8 (MeO), 60.4 (MeO), 60.8 (MeO), 122.9 (CH), 123.2 (CH), 123.3
(CH), 123.4 (CH), 131.5 (C), 133.1 (C), 135.7 (C), 141.2 (CH), 146.6 (C),
146.8 (C), 152.4 (C), 152.5 (C), 153.7 (C). IR (ATR, cmꢀ1): ṽ¼3074 (w),
3002 (w), 2931 (w), 2831 (m), 1599 (w), 1577 (m), 1464 (m), 1412
(s), 1384 (s), 1300 (s), 1258 (s), 1222 (s), 1169 (m), 1143 (m), 1115 (w),
1083 (m), 1051 (s), 1024 (m), 996 (m), 844 (m), 785 (s), 748 (s), 670
(m), 649 (m), 606 (w), 563 (w), 514 (w), 447 (w), 412 (w). GCeMS
(EI, 70 eV): m/z (%): 624 (Mþ, 7), 623 (17), 622 (9), 608 (17), 594 (11),
593 (36), 592 (100), 488 (9), 486 (12), 281 (6), 207 (11), 111 (6), 83
(10), 73 (8), 71 (12), 69 (15), 57 (19), 55 (16), 45 (11), 44 (36), 43 (49),
42 (9), 41 (15). HRMS (EI, 70 eV): calcd for C37H37NO8 (Mþ):
623.25137, found 623.249812. Anal. Calcd for C37H37NO8 (623.69):
C, 71.25; H, 5.98. Found: C, 70.97; H, 5.845.
4.2.10. 2,3,5,6-Tetra-n-hexylpyridine (2j). Starting with 2,3,5,6-
tetrachloropyridine 1 (54 mg, 0.25 mmol), Pd2(dba)3 (2.9 mg,
1.25 mol %), cataCXium A (5.1 mg, 5.0 mol %), n-hexylboronic acid
(228 mg, 1.75 mmol), K3PO4 (398 mg, 1.88 mmol) and toluene
4.2.13. 2,3,5,6-Tetrakis(2,3,4-trimethoxyphenyl)pyridine
(2m). Starting with 2,3,5,6-tetrachloropyridine
1
(54 mg,
0.25 mmol), Pd2(dba)3 (2.9 mg, 1.25 mol %), cataCXium A (5.1 mg,
5.0 mol %), 2,3,4-trimethoxy-phenylboronic acid (371 mg,
1.75 mmol), K3PO4 (398 mg, 1.88 mmol) and toluene (4.0 mL), 2m
was isolated as a colorless solid (112 mg, 60%); mp¼190e192 ꢁC. 1H
(4.0 mL), 2j was isolated as a colorless oil (95 mg, 75%). 1H NMR
3
(300 MHz, CDCl3):
d
¼0.92 (t, JHeH¼7.1 Hz, 6H, CH3), 0.94 (t,
3JHeH¼6.5 Hz, 6H, CH3), 1.35e1.46 (m, 24H, CH2), 1.55e1.75 (m, 8H,
CH2), 2.58 (t, 3JHeH¼7.8 Hz, 4H, CH2), 2.77 (t, 3JHeH¼7.8 Hz, 4H, CH2),
NMR (300 MHz, CDCl3):
d
¼3.59 (br s, 6H, MeO), 3.64 (br s, 6H,
7.16 (s, 1H, CH). 13C NMR (75 MHz, CDCl3):
d
¼14.1 (CH3), 14.1 (CH3),
MeO), 3.73 (br s, 6H, MeO), 3.76 (br s, 12H, MeO), 3.79 (br s, 6H,
3
3
22.6 (CH2), 22.6 (CH2), 29.3 (CH2), 29.5 (CH2), 30.2 (CH2), 30.9 (CH2),
31.7 (CH2), 31.8 (CH2), 31.8 (CH2), 34.7 (CH2), 132.2 (C), 137.6 (CH),
156.7 (C). IR (ATR, cmꢀ1): ṽ¼2955 (w), 2923 (s), 2855 (s), 1558 (m),
1450 (s), 1378 (m), 1301 (w), 1115 (w), 915 (w), 888 (w), 724 (s), 502
(w), 459 (w), 397 (w). GCeMS (EI, 70 eV): m/z (%): 416 (Mþ, 2), 415
(6), 414 (8), 386 (6), 372 (14), 358 (29), 345 (20), 344 (12), 331 (17),
330 (67), 316 (5), 302 (24), 289 (15), 288 (28), 276 (21), 275 (100),
244 (4), 204 (7), 188 (4), 172 (4), 161 (5), 160 (5), 158 (3), 43 (11).
HRMS (ESI, 70 eV): calcd for C29H54N ([MþH]þ): 416.42508, found
416.4258. Anal. Calcd for C29H53N (415.74): C, 83.78; H, 12.85; N,
3.37. Found: C, 84.11; H, 12.43; N, 2.998.
MeO), 6.44 (d, JHeH¼8.7 Hz, 2H, CH), 6.58 (d, JHeH¼8.7 Hz, 2H,
CH), 6.69 (d, 3JHeH¼8.7 Hz, 2H, CH), 7.04 (d, 3JHeH¼8.4 Hz, 2H, CH),
7.81 (s, 1H, CH). 13C NMR (75 MHz, CDCl3):
d
¼55.8 (MeO), 55.9
(MeO), 60.6 (MeO), 60.7 (MeO), 60.7 (MeO), 60.8 (MeO), 106.2 (CH),
106.8 (CH), 125.5 (CH), 125.7 (CH), 126.0 (C), 128.3 (C), 131.4 (C),
141.1 (CH), 141.7 (C), 141.8 (C),151.4 (C), 151.4 (C), 152.8 (C), 153.2 (C),
153.5 (C). IR (ATR, cmꢀ1): ṽ¼2932 (w), 2837 (w), 1598 (m), 1498
(m), 1459 (s), 1407 (s), 1374 (m), 1289 (s), 1232 (m), 1201 (m), 1170
(m), 1084 (s), 1006 (s), 920 (w), 800 (s), 699 (m), 609 (m), 436 (m).
GCeMS (EI, 70 eV): m/z (%): 744 (Mþ, 19), 743 (46), 742 (11), 730 (8),
729 (32), 728 (78), 714 (13), 713 (40), 712 (100), 696 (10), 682 (14),
666 (7), 576 (21), 356 (13), 325 (3), 281 (6), 267 (4), 207 (13), 105
(11), 84 (7), 77 (6), 69 (9), 57 (8), 44 (41), 43 (14), 41 (6). HRMS (ESI,
4.2.11. 2,3,5,6-Tetrakis(2,5-dimethoxyphenyl)pyridine (2k). Starting
with 2,3,5,6-tetrachloropyridine 1 (54 mg, 0.25 mmol), Pd2(dba)3
(2.9 mg, 1.25 mol %), cataCXium A (5.1 mg, 5.0 mol %), 2,5-
dimethoxy-phenylboronic acid (319 mg, 1.75 mmol), K3PO4
(398 mg, 1.88 mmol) and toluene (4.0 mL), 2k was isolated as
a slightly yellow solid (73 mg, 47%); mp¼244e245 ꢁC. 1H NMR
70 eV): calcd for
744.30009. Anal. Calcd for C41H45NO12 (743.80): C, 66.21; H, 6.10; N,
1.88. Found: C, 66.27; H, 6.329; N, 1.708.
C
41H46NO12 ([MþH]þ): 744.30145, found
4.3. General procedure for the synthesis of 2,3,5-trichloro-6-
aryl-substituted pyridines 3aek
(300 MHz, CDCl3):
d
¼3.32 (s, 6H, MeO), 3.54 (br s, 6H, MeO), 3.57
(br s, 6H, MeO), 3.70 (s, 6H, MeO), 6.59e6.75 (m, 10H, CH),
7.06e7.07 (m, 2H, CH), 7.82 (s, 1H, CH). 13C NMR (75 MHz, CDCl3):
An oven-dried and argon-flushed pressure tube was charged
with 2,3,5,6-tetrachloropyridine 1 (0.5 mmol), Pd(PPh3)4 (5.0 mol
%), boronic acid (0.55 mmol) and KF (1.5 mmol) followed by an-
hydrous toluene (8.0 mL). The tube was sealed with a Teflon valve
and the reaction mixture was stirred at 100 ꢁC for 22 h. The cooled
reaction mixture was diluted with water and extracted with CH2Cl2.
The combined organic layers were dried (Na2SO4), filtered and the
filtrate was concentrated in vacuo. The residue was purified by
column chromatography.
d¼55.4 (MeO), 55.7 (MeO), 55.7 (MeO), 55.8 (MeO), 111.6 (CH), 111.7
(CH), 114.0 (CH), 114.7 (CH), 116.3 (CH), 116.9 (CH), 129.4 (C), 131.0
(C), 131.9 (C), 141.0 (C), 150.6 (C), 150.8 (C), 152.9 (C), 153.4 (C). IR
(ATR, cmꢀ1): ṽ¼3052 (w), 2991 (w), 2937 (m), 2831 (m), 1607 (w),
1586 (m), 1499 (s), 1451 (s), 1430 (s), 1396 (w), 1373 (w), 1278 (m),
1233 (w), 1215 (s), 1173 (m), 1144 (m), 1071 (w), 1043 (s), 1018 (s),
873 (m), 801 (s), 729 (m), 691 (m), 501 (w), 432 (w). GCeMS (EI,
70 eV): m/z (%): 624 (Mþ, 12), 623 (28), 593 (38), 592 (100), 578 (5),
489 (13), 488 (39), 486 (26), 458 (6), 312 (7), 266 (7), 236 (8), 214
(6), 126 (3), 108 (3). HRMS (ESI, 70 eV): calcd for C37H38NO8
([MþH]þ): 624.25919, found 624.26022. Anal. Calcd for C37H37NO8
(623.69): C, 71.25; H, 5.98; N, 2.25. Found: C, 70.84; H, 5.623; N,
2.010.
4.3.1. 2,3,5-Trichloro-6-phenylpyridine (3a). Starting with 2,3,5,6-
tetrachloropyridine 1 (108 mg, 0.5 mmol), Pd(PPh3)4 (29.0 mg,
5.0 mol %), phenylboronic acid (67.0 mg, 0.55 mmol), KF (87.0 mg,
1.5 mmol) and toluene (8.0 mL), 3a was isolated as a colorless solid
(84 mg, 65%); mp¼60e61 ꢁC. 1H NMR (300 MHz, CDCl3):
4.2.12. 2,3,5,6-Tetrakis(2,3-dimethoxyphenyl)pyridine (2l). Starting
with 2,3,5,6-tetrachloropyridine 1 (54 mg, 0.25 mmol), Pd2(dba)3
(2.9 mg, 1.25 mol %), cataCXium A (5.1 mg, 5.0 mol %), 2,3-
dimethoxyphenylboronic acid (319 mg, 1.75 mmol), K3PO4
d
¼7.44e7.49 (m, 3H, CH), 7.71e7.75 (m, 2H, CH), 7.89 (s, 1H, CH). 13
C
NMR (75 MHz, CDCl3):
d
¼128.2 (CH),128.6 (C),129.0 (C),129.3 (CH),
129.6 (CH), 135.9 (C), 140.0 (CH), 146.6 (C), 154.4 (C). IR (ATR, cmꢀ1):
ṽ¼3057 (w), 2924 (w), 1523 (w), 1492 (w), 1445 (m), 1398 (s), 1376

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S. Reimann et al. / Tetrahedron 71 (2015) 5371e5384
(m), 1336 (m), 1315 (m), 1209 (w), 1160 (s), 1096 (s), 1097 (m), 1046
(s), 1021 (m), 898 (s), 873 (s), 778 (s), 732 (m), 694 (s), 668 (m), 597
(m), 550 (m), 484 (w), 468 (w), 407 (w). GCeMS (EI, 70 eV): m/z (%):
259 (Mþ, 89), 258 (15), 257 (91), 226 (10), 225 (9), 224 (68), 223
(156), 222 (100), 189 (17), 188 (16), 187 (48), 186 (30), 160 (7), 152
(19), 151 (24), 125 (9), 112 (11), 111 (15), 99 (10), 77 (10), 76 (10), 75
(12), 74 (13), 51 (18), 50 (13). HRMS (EI, 70 eV): calcd for C11H6Cl3N
(Mþ): 256.95603, found 256.956186 and calcd for C11H6Cl327ClN
(%): 315 (Mþ, 18), 314 (5), 313 (20), 302 (32), 301 (15), 300 (94), 299
(16), 298 (100), 285 (5), 272 (15), 270 (15), 269 (7), 200 (6), 177 (4),
151 (5), 150 (5), 117 (8), 41 (19), 39 (8). HRMS (ESI, 70 eV): calcd for
C
C
15H15Cl3N ([MþH]þ): 314.0265, found 314.0261. Anal. Calcd for
15H14Cl3N (314.64): C, 57.26; H, 4.48; N, 4.45. Found: C, 57.10; H,
4.386; N, 4.279.
4.3.5. 2,3,5-Trichloro-6-(4-ethoxyphenyl)pyridine
(3e). Starting
(Mþ):
258.95308,
11H6NCl37Cl2(Mþ): 260.95013, found 260.950344. Anal. Calcd for
11H6Cl3N (258.53): C, 51.10; H, 2.34. Found: C, 51.23; H, 2.495.
found
258.953312
and
calcd
for
with 2,3,5,6-tetrachloropyridine 1 (108 mg, 0.5 mmol), Pd(PPh3)4
(29.0 mg, 5.0 mol %), 4-ethoxyphenylboronic acid (91.3 mg,
0.55 mmol), KF (87.0 mg, 1.5 mmol) and toluene (8.0 mL), 3e was
C
C
isolated as a colorless solid (101 mg, 67%); mp¼92e93 ꢁC. 1H NMR
3
4.3.2. 2,3,5-Trichloro-6-p-tolylpyridine (3b). Starting with 2,3,5,6-
tetrachloropyridine 1 (108 mg, 0.5 mmol), Pd(PPh3)4 (29.0 mg,
5.0 mol %), p-tolylboronic acid (74.8 mg, 0.55 mmol), KF (87.0 mg,
1.5 mmol) and toluene (8.0 mL), 3b was isolated as a colorless solid
(300 MHz, CDCl3):
d
¼1.42 (t, JHeH¼7.0 Hz, 3H, CH3), 4.07 (q,
3JHeH¼7.0 Hz, 2H, CH2), 6.92e6.97 (m, 2H, CH), 7.68e7.74 (m, 2H,
CH), 7.85 (s, 1H, CH). 13C NMR (75 MHz, CDCl3):
d
¼14.7 (CH3), 63.5
(CH2), 114.0 (CH), 128.1 (C), 128.1 (C), 130.9 (CH), 140.0 (CH), 146.3
(C), 154.0 (C), 160.0 (C). IR (ATR, cmꢀ1): ṽ¼3055 (w), 2986 (w), 2928
(w), 2877 (w), 1614 (s), 1578 (m), 1506 (s), 1413 (m), 1401 (s), 1333
(m), 1298 (m), 1254 (s), 1206 (m), 1180 (m), 1160 (m), 1115 (s), 1097
(m), 1046 (s), 1010 (m), 924 (m), 903 (m), 882 (m), 840 (m), 824 (s),
798 (m), 752 (m), 666 (m), 598 (m), 504 (m), 481 (m), 440 (w), 404
(w). GCeMS (EI, 70 eV): m/z (%): 303 (Mþ, 62), 302 (10), 301 (63),
277 (33), 276 (13), 275 (98), 274 (16), 273 (100), 240 (25), 238 (36),
211 (8), 209 (11), 203 (25), 185 (4), 174 (15), 148 (5), 140 (7), 139 (5),
138 (5), 119 (3), 86 (4), 63 (5), 62 (3), 29 (10). HRMS (EI, 70 eV): calcd
for C13H10Cl3NO (Mþ): 300.98225, found 300.982496 and calcd for
(87 mg, 64%); mp¼84e86 ꢁC. 1H NMR (300 MHz, CDCl3):
¼2.40 (s,
d
3H, CH3), 7.24e7.27 (m, 2H, CH), 7.61e7.65 (m, 2H, CH), 7.87 (s, 1H,
CH). 13C NMR (75 MHz, CDCl3):
d¼21.4 (CH3), 128.4 (C), 128.6 (C),
128.9 (CH), 129.2 (CH), 133.0 (C), 139.7 (C), 139.9 (CH), 146.5 (C),
154.5 (C). IR (ATR, cmꢀ1): ṽ¼3057 (w), 2919 (w), 2851 (w), 2712 (w),
1612 (m), 1562 (m), 1505 (m), 1393 (s), 1335 (s), 1309 (m), 1207 (m),
1160 (s), 1119 (m), 1094 (s), 1044 (s), 1021 (m), 899 (s), 883 (m), 817
(s), 744 (s), 695 (m), 649 (m), 580 (m), 541 (s), 488 (s), 459 (m), 448
(w), 405 (w). GCeMS (EI, 70 eV): m/z (%): 273 (Mþ, 96), 272 (49),
271 (100), 270 (38), 238 (22), 236 (35), 235 (9), 202 (10), 201 (14),
200 (27),166 (10),164 (16),139 (10),118 (13), 99 (10), 91 (20), 75 (5),
63 (9), 51 (6), 39 (8). HRMS (ESI, 70 eV): calcd for C12H9Cl3N
([MþH]þ): 271.9795, found 271.9797. Anal. Calcd for C12H8Cl3N
(272.56): C, 52.88; H, 2.96. Found: C, 52.93; H, 2.993.
C
C
13H10Cl327ClNO (Mþ): 302.97930, found 302.979724. Anal. Calcd for
13H10Cl3NO (302.58): C, 51.60; H, 3.33; N, 4.63. Found: C, 51.70; H,
3.197; N, 4.312.
4.3.6. 2,3,5-Trichloro-6-(4-biphenyl)pyridine (3f). Starting with
4.3.3. 2,3,5-Trichloro-6-(4-ethylphenyl)pyridine (3c). Starting with
2,3,5,6-tetrachloropyridine 1 (108 mg, 0.5 mmol), Pd(PPh3)4
2,3,5,6-tetrachloropyridine
1
(108 mg, 0.5 mmol), Pd(PPh3)4
(29.0 mg, 5.0 mol %), 4-biphenylboronic acid (100.1 mg, 0.55 mmol),
(29.0 mg, 5.0 mol %), 4-ethylphenylboronic acid (82.5 mg,
KF (87.0 mg, 1.5 mmol) and toluene (8.0 mL), 3f was isolated as
a
0.55 mmol), KF (87.0 mg, 1.5 mmol) and toluene (8.0 mL), 3c was
colorless solid (119 mg, 71%); mp¼142e144 ꢁC. 1H NMR
isolated as a colorless solid (92 mg, 65%); mp¼28e29 ꢁC. 1H NMR
(300 MHz, CDCl3):
d
¼7.34e7.39 (m, 1H, CH), 7.42e7.49 (m, 2H, CH),
3
(300 MHz, CDCl3):
d
¼1.25 (t, JHeH¼7.5 Hz, 3H, CH3), 2.70 (q,
7.60e7.71 (m, 4H, CH), 7.81e7.85 (m, 2H, CH), 7.91 (s, 1H, CH). 13
NMR (75 MHz, CDCl3):
¼126.9 (CH), 127.2 (CH), 127.8 (CH), 128.6
C
3JHeH¼7.8 Hz, 2H, CH2), 7.27e7.29 (m, 2H, CH), 7.64e7.60 (m, 2H,
d
CH), 7.87 (s, 1H, CH). 13C NMR (75 MHz, CDCl3):
d¼15.4 (CH3), 28.7
(C), 128.9 (CH), 128.9 (C), 134.7 (C), 140.1 (CH), 140.3 (C), 142.4 (C),
146.7 (C), 154.0 (C). IR (ATR, cmꢀ1): ṽ¼3051 (w), 1606 (w), 1559 (w),
1510 (w), 1486 (m), 1447 (w), 1402 (s), 1346 (m), 1208 (m), 1157 (m),
1095 (m), 1042 (m), 1017 (m), 1004 (w), 902 (m), 879 (w), 846 (m),
772 (m), 740 (s), 688 (m), 663 (m), 599 (m), 562 (w), 538 (w), 484
(m), 449 (m), 396 (w). GCeMS (EI, 70 eV): m/z (%): 335 (Mþ, 98),
334 (21), 333 (100), 300 (10), 298 (16), 263 (17), 227 (23), 200 (8),
152 (11), 131 (9), 113 (9), 100 (8). HRMS (EI, 70 eV): calcd for
(CH2), 127.7 (CH), 128.4 (C), 128.6 (C), 129.3 (CH), 133.3 (C), 139.9
(CH), 146.0 (C), 146.5 (C), 154.5 (C). IR (ATR, cmꢀ1): ṽ¼3056 (w),
2965 (w), 2931 (w), 2872 (w), 1612 (w), 1505 (m), 1458 (m), 1399
(s), 1334 (m), 1302 (w), 1208 (m), 1160 (s), 1094 (m), 1042 (s), 1018
(m), 966 (w), 896 (m), 879 (m), 837 (s), 748 (s), 671 (m), 646 (m),
594 (m), 580 (m), 542 (w), 511 (w), 466 (w), 408 (w). GCeMS (EI,
70 eV): m/z (%): 287 (Mþ, 86), 286 (56), 285 (90), 284 (48), 274 (33),
273 (17), 272 (100), 271 (24), 270 (100), 269 (13), 222 (5), 202 (8),
200 (25), 187 (7), 177 (5), 164 (16), 151 (8), 117 (10), 105 (9), 99 (11),
77 (7), 75 (8), 50 (5). HRMS (EI, 70 eV): calcd for C13H10Cl3N (Mþ):
284.98733, found 284.987445 and calcd for C13H10Cl327ClN (Mþ):
286.98438, found 286.984879. Anal. Calcd for C13H10Cl3N (286.58):
C, 54.48; H, 3.52; N, 4.89. Found: C, 54.60; H, 3.339; N, 5.260.
C
C
C
C
C
17H10Cl3N (Mþ): 332.98733, found 332.986985 and calcd for
17H10Cl327ClN (Mþ): 334.98438, found 334.984192 and calcd for
17H10Cl37Cl2N (Mþ): 336.98143, found 336.981836 and calcd for
H
Cl3N (Mþ): 338.97848, found 338.979430. Anal. Calcd for
37
17 10
17H10Cl3N (334.63): C, 61.02; H, 3.01; N, 4.19. Found: C, 60.89; H,
2.827; N, 4.177.
4.3.4. 2,3,5-Trichloro-6-(4-tert-butylphenyl)pyridine (3d). Starting
with 2,3,5,6-tetrachloropyridine 1 (108 mg, 0.5 mmol), Pd(PPh3)4
(29.0 mg, 5.0 mol %), 4-tert-butylphenylboronic acid (97.9 mg,
0.55 mmol), KF (87.0 mg, 1.5 mmol) and toluene (8.0 mL), 3d was
isolated as a colorless oil (87 mg, 55%). 1H NMR (300 MHz, CDCl3):
4.3.7. 2,3,5-Trichloro-6-(4-fluorophenyl)pyridine (3g). Starting with
2,3,5,6-tetrachloropyridine
1 (108 mg, 0.5 mmol), Pd(PPh3)4
(29.0 mg, 5.0 mol %), 4-fluorophenylboronic acid (76.9 mg,
0.55 mmol), KF (87.0 mg, 1.5 mmol) and toluene (8.0 mL), 3g was
isolated as a colorless solid (57 mg, 41%); mp¼94e96 ꢁC. 1H NMR
d
¼1.33 (s, 9H, CH3 tBu), 7.45e7.48 (m, 2H, CH), 7.66e7.70 (m, 2H,
(300 MHz, CDCl3):
d
¼7.10e7.17 (m, 2H, CH), 7.68e7.76 (m, 2H, CH),
CH), 7.87 (s, 1H, CH). 13C NMR (75 MHz, CDCl3):
d
¼31.2 (CH3 tBu),
7.88 (s, 1H, CH). 13C NMR (75 MHz, CDCl3):
d
¼115.3 (d,
4
34.8 (CtBu), 125.2 (CH), 128.4 (C), 128.6 (C), 129.0 (CH), 139.9 (CH),
146.5 (C),152.8 (C), 154.4 (C). IR (ATR, cmꢀ1): ṽ¼3056 (w), 2961 (m),
2903 (w), 2868 (w), 1610 (m), 1507 (m), 1462 (w), 1403 (s), 1364
(m), 1336 (m), 1269 (m), 1206 (m), 1159 (s), 1119 (m), 1089 (m), 1043
(m), 1016 (m), 896 (m), 838 (s), 758 (m), 721 (m), 695 (m), 671 (m),
626 (m), 583 (m), 541 (m), 529 (m), 471 (w). GCeMS (EI, 70 eV): m/z
2JCeF¼21.8 Hz, CH), 128.4 (d, JCeF¼2.6 Hz, C), 128.6 (C), 129.1 (C),
131.5 (d, 2JCeF¼8.7 Hz, CH), 132.0 (C), 140.1 (CH), 146.6 (C), 153.3 (C),
163.4 (d, JCeF¼251.4 Hz, CF). 19F NMR (282.4 MHz, CDCl3):
¼ꢀ110.4
d
(F). IR (ATR, cmꢀ1): ṽ¼3063 (w), 1897 (w), 1603 (m), 1505 (m), 1407
(m),1396 (m),1332 (m),1300 (m),1231 (m),1205 (m),1167 (s),1095
(m), 1044 (m), 1014 (m), 895 (m), 834 (s), 810 (m), 751 (m), 720 (m),

S. Reimann et al. / Tetrahedron 71 (2015) 5371e5384
5379
659 (m), 580 (m), 543 (m), 500 (m), 451 (m), 421 (m), 396 (m).
GCeMS (EI, 70 eV): m/z (%): 277 (Mþ, 99), 276 (12), 275 (100), 242
(46), 241 (12), 240 (64), 239 (6), 207 (17), 206 (12), 205 (50), 204
(20), 170 (14), 169 (17), 150 (7), 145 (5), 138 (5), 121 (13), 120 (13),
119 (9),102 (8), 95 (6), 74 (7). HRMS (EI, 70 eV): calcd for C11H5Cl3FN
(Mþ): 274.94661, found 274.946744 and calcd for C11H5Cl327ClFN
(Mþ): 276.94366, found 276.943877 and calcd for C11H5Cl37Cl2FN
(Mþ): 278.94071, found 278.941109. Anal. Calcd for C11H5Cl3FN
(276.52): C, 47.78; H, 1.82; N, 5.07. Found: C, 47.75; H, 1.872; N,
4.775.
(w), 2935 (w), 2837 (w), 1521 (w), 1500 (s), 1469 (m), 118 (m), 1419
(s), 1388 (s), 1329 (m), 1271 (m), 1224 (s), 1179 (m), 1156 (m), 1085
(m),1051 (m), 1032 (s), 926 (m), 882 (m), 855 (m), 824 (m), 812 (m),
745 (m), 723 (m), 683 (m), 669 (m), 638 (w), 584 (m), 565 (m), 529
(m), 469 (m). GCeMS (EI, 70 eV): m/z (%): 319 (Mþ, 86), 318 (15), 317
(87), 304 (10), 286 (14), 285 (10), 284 (63), 283 (24), 282 (100), 281
(17), 271 (12), 269 (62), 268 (17), 267 (98), 256 (23), 255 (9), 254
(50), 252 (35), 249 (19), 248 (20), 247 (55), 246 (34), 233 (13), 232
(11), 231 (13), 226 (11), 224 (18), 211 (11), 210 (11), 208 (10), 198
(15), 196 (24), 161 (17), 135 (11), 82 (11), 54 (17), 53 (9). HRMS (ESI,
70 eV): calcd for
C
13H11Cl3NO2 ([MþH]þ): 317.98499, found
4.3.8. 2,3,5-Trichloro-6-m-tolylpyridine (3h). Starting with 2,3,5,6-
tetrachloropyridine 1 (108 mg, 0.5 mmol), Pd(PPh3)4 (29.0 mg,
5.0 mol %), 3-methylphenylboronic acid (74.8 mg, 0.55 mmol), KF
(87.0 mg, 1.5 mmol) and toluene (8.0 mL), 3h was isolated as
a colorless solid (78 mg, 57%); mp¼42e44 ꢁC. 1H NMR (300 MHz,
317.98535. Anal. Calcd for C13H10Cl3NO2 (318.58): C, 49.01; H, 3.16;
N, 4.40. Found: C, 48.79; H, 2.876; N, 4.094.
4.3.11. 2,3,5-Trichloro-6-(3,5-difluorophenyl)pyridine (3k). Starting
with 2,3,5,6-tetrachloropyridine 1 (108 mg, 0.5 mmol), Pd(PPh3)4
(29.0 mg, 5.0 mol %), 3,5-difluorophenylboronic acid (86.8 mg,
0.55 mmol), KF (87.0 mg, 1.5 mmol) and toluene (8.0 mL), 3k was
isolated as a colorless solid (63 mg, 43%); mp¼139e141 ꢁC. 1H NMR
CDCl3):
d
¼2.41 (s, 3H, CH3), 7.26e7.34 (m, 2H, CH), 7.49e7.52 (m,
2H, CH), 7.88 (s, 1H, CH). 13C NMR (75 MHz, CDCl3):
d
¼21.4 (CH3),
126.4 (CH), 128.0 (CH), 128.6 (C), 128.8 (C), 129.9 (CH), 130.3 (CH),
135.8 (C), 138.0 (C), 139.9 (CH), 146.5 (C), 154.7 (C). IR (ATR, cmꢀ1):
ṽ¼3057 (w), 2913 (m), 2857 (m), 1607 (w), 1521 (m), 1489 (m), 1421
(m), 1402 (m), 1388 (m), 1332 (s), 1195 (m), 1156 (s), 1106 (m), 1054
(s), 994 (m), 892 (m), 788 (m), 742 (m), 697 (s), 666 (s), 610 (m), 560
(s), 541 (m), 500 (w), 454 (m), 402 (w). GCeMS (EI, 70 eV): m/z (%):
273 (Mþ, 93), 272 (49), 271 (100), 270 (37), 238 (34), 237 (14), 236
(52), 235 (11), 234 (5), 202 (11), 201 (16), 200 (30), 166 (12), 165 (9),
164 (19), 139 (10), 99 (11), 91 (13), 86 (7), 82 (6), 63 (8), 39 (7).
HRMS (ESI, 70 eV): calcd for C12H9Cl3N ([MþH]þ): 271.9795, found
271.9792. Anal. Calcd for C12H8Cl3N (272.56): C, 52.88; H, 2.96; N,
5.14. Found: C, 52.50; H, 2.607; N, 4.893.
(300 MHz, CDCl3):
d
¼6.85e6.94 (m, 1H, CH), 7.27e7.30 (m, 2H, CH),
7.91 (s, 1H, CH). 13C NMR (75 MHz, CDCl3):
d
¼105.0 (dd,
2JCeF¼26.6 Hz, 2JCeF¼25.4 Hz, CH),112.6 (d, 3JCeF¼11.6 Hz, CH),112.6
(d, 2JCeF¼26.6 Hz, CH), 128.6 (C), 130.2 (C), 138.6 (dd, 3JCeF¼10.3 Hz,
4
C), 140.3 (CH), 146.9 (C), 151.6 (dd, JCeF¼3.3 Hz, C), 162.5 (dd,
3
JCeF¼248.6 Hz, JCeF¼11.3 Hz, CF), 162.6 (dd, JCeF¼248.7 Hz,
3JCeF¼11.1 Hz, CF). 19F NMR (282.4 MHz, CDCl3):
¼ꢀ108.6 (F). IR
d
(ATR, cmꢀ1): ṽ¼3088 (w), 3063 (w), 1626 (m), 1595 (m), 1525 (m),
1434 (m),1411 (m),1391 (s),1348 (m),1304 (m),1234 (m),1200 (m),
1160 (m), 1119 (s), 1099 (m), 1063 (s), 986 (s), 939 (s), 901 (m), 864
(s), 850 (s), 811 (m), 748 (m), 691 (s), 670 (m), 655 (m), 630 (m), 581
(s), 531 (m), 509 (m), 460 (m). GCeMS (EI, 70 eV): m/z (%): 295 (Mþ,
98), 294 (14), 293 (100), 260 (54), 259 (13), 258 (84), 225 (18), 224
(12), 223 (57), 222 (14), 196 (5), 188 (15), 187 (18), 168 (9), 162 (8),
129 (12), 111 (14), 98 (8), 94 (5), 88 (4), 84 (9), 81 (6), 75 (6), 74 (5),
63 (7). HRMS (EI, 70 eV): calcd for C11H4Cl3F2N (Mþ): 292.93719,
found 292.937449 and calcd for C11H4Cl327ClF2N (Mþ): 294.93424,
found 294.934554 and calcd for C11H4Cl37Cl2F2N (Mþ): 296.93129,
found 296.931821. Anal. Calcd for C11H4Cl3F2N (294.51): C, 44.86; H,
1.37; N, 4.76. Found: C, 44.49; H, 1.249; N, 4.520.
4.3.9. 2,3,5-Trichloro-6-(2-methoxyphenyl)pyridine
(3i). Starting
with 2,3,5,6-tetrachloropyridine 1 (108 mg, 0.5 mmol), Pd(PPh3)4
(29.0 mg, 5.0 mol %), 2-methoxyphenylboronic acid (83.6 mg,
0.55 mmol), KF (87.0 mg, 1.5 mmol) and toluene (8.0 mL), 3i was
isolated as a colorless oil (69 mg, 51%). 1H NMR (300 MHz, CDCl3):
d
¼3.78 (s, 3H, MeO), 6.96 (dd, 3JHeH¼8.4 Hz, 4JHeH¼0.9 Hz, 1H, CH),
3
3
4
7.04 (ddd, JHeH¼7.7 Hz, JHeH¼7.5 Hz, JHeH¼1.2 Hz, 1H, CH), 7.28
3
4
3
(dd, JHeH¼7.7 Hz, JHeH¼1.7 Hz, 1H, CH), 7.42 (ddd, JHeH¼8.4 Hz,
3JHeH¼7.8 Hz, JHeH¼1.8 Hz, 1H, CH), 7.85 (s, 1H, CH). 13C NMR
4
(75 MHz, CDCl3):
d¼55.5 (MeO), 111.0 (CH), 120.6 (CH), 125.7 (C),
4.4. General procedure for the synthesis of 3,5-dichloro-2,6-
diaryl-substituted pyridines 4aei
129.1 (C), 130.3 (CH), 130.9 (CH), 131.0 (C), 138.9 (CH), 146.2 (C),
153.9 (C), 156.7 (C). IR (ATR, cmꢀ1): ṽ¼3059 (w), 3004 (w), 2936
(w), 2727 (w), 1602 (m), 1582 (m), 1524 (m), 1493 (m), 1460 (m),
1435 (m), 1402 (s), 1329 (s), 1263 (s), 1238 (s), 1208 (m), 1157 (s),
1099 (s), 1053 (m), 1035 (s), 1023 (s), 895 (m), 792 (m), 749 (s), 667
(m), 606 (m), 556 (m), 468 (m), 436 (w), 387 (w). GCeMS (EI,
70 eV): m/z (%): 289 (Mþ, 22), 287 (22), 256 (12), 253 (21), 252
(100), 251 (13), 239 (11), 237 (18), 226 (17), 222 (18), 219 (19), 218
(15), 217 (56), 216 (17), 189 (15), 188 (11), 187 (13), 174 (17), 138 (6),
111 (11), 86 (8), 63 (12), 39 (10). HRMS (EI, 70 eV): calcd for
An oven-dried and argon-flushed pressure tube was charged
with 2,3,5,6-tetrachloropyridine 1 (0.5 mmol), Pd(PPh3)4 (5.0 mol
%), boronic acid (1.25 mmol) and KF (3.0 mmol) followed by an-
hydrous toluene (8.0 mL). The tube was sealed with a Teflon valve
and the reaction mixture was stirred at 100 ꢁC for 22 h. The cooled
reaction mixture was diluted with water and extracted with CH2Cl2.
The combined organic layers were dried (Na2SO4), filtered and the
filtrate was concentrated in vacuo. The residue was purified by
column chromatography.
C
C
C
12H8Cl3NO (Mþ): 286.96660, found 286.966752 and calcd for
12H8Cl327ClNO (Mþ): 288.96365, found 288.963947. Anal. Calcd for
12H8Cl3NO (288.56): C, 49.95; H, 2.79. Found: C, 49.96; H, 2.915.
4.4.1. 3,5-Dichloro-2,6-diphenylpyridine (4a). Starting with 2,3,5,6-
tetrachloropyridine 1 (108 mg, 0.5 mmol), Pd(PPh3)4 (29 mg,
5.0 mol %), phenylboronic acid (152 mg, 1.25 mmol), KF (174 mg,
3.0 mmol) and toluene (8.0 mL), 4a was isolated as a colorless solid
(116 mg, 77%); mp¼135e137 ꢁC. 1H NMR (300 MHz, CDCl3):
4.3.10. 2,3,5-Trichloro-6-(2,5-dimethoxyphenyl)pyridine
(3j). Starting with 2,3,5,6-tetrachloropyridine (108 mg,
0.5 mmol), Pd(PPh3)4 (29.0 mg, 5.0 mol %), 2,5-
1
dimethoxyphenylboronic acid (100.1 mg, 0.55 mmol), KF
(87.0 mg, 1.5 mmol) and toluene (8.0 mL), 3j was isolated as
a slightly yellow solid (85 mg, 54%); mp¼66e67 ꢁC. 1H NMR
d
¼7.43e7.51 (m, 6H, CH), 7.80e7.83 (m, 4H, CH), 7.94 (s, 1H, CH). 13
C
NMR (75 MHz, CDCl3):
d
¼128.0 (CH), 128.3 (C), 129.0 (CH), 129.4
(CH), 137.2 (C), 139.3 (CH), 154.2 (C). IR (ATR, cmꢀ1): ṽ¼3057 (w),
1580 (w), 1521 (w), 1446 (m), 1401 (m), 1337 (m), 1207 (m), 1159
(m), 1097 (m), 1047 (s), 1022 (w), 896 (w), 779 (m), 729 (m), 695 (s),
669 (m), 618 (s), 552 (m), 542 (m), 482 (m), 467 (m), 408 (w), 389
(w). GCeMS (EI, 70 eV): m/z (%): 300 (Mþ, 19), 299 (84), 266 (34),
265 (20), 264 (100), 229 (16), 228 (27), 227 (27), 226 (5), 202 (9),
(300 MHz, CDCl3):
d
¼3.73 (s, 3H, MeO), 3.77 (s, 3H, MeO),
6.83e6.97 (m, 3H, CH), 7.85 (s, 1H, CH). 13C NMR (75 MHz, CDCl3):
d
¼55.7 (MeO), 56.0 (MeO), 112.3 (CH), 115.5 (CH), 116.2 (CH), 126.1
(C), 129.2 (C), 131.0 (C), 138.9 (CH), 146.2 (C), 150.9 (C), 153.4 (C),
154.5 (C). IR (ATR, cmꢀ1): ṽ¼3061 (w), 3014 (w), 2999 (w), 2969

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S. Reimann et al. / Tetrahedron 71 (2015) 5371e5384
201 (9), 149 (5), 136 (9), 132 (12), 126 (19), 125 (6), 114 (15), 101 (10),
100 (8), 99 (5), 77 (10), 75 (7), 74 (6). HRMS (EI, 70 eV): calcd for
C
C
C
360.0548, found 360.0553. Anal. Calcd for C19H15Cl2NO2 (360.23):
C, 63.35; H, 4.20; N, 3.89. Found: C, 63.45; H, 3.883; N, 3.649.
17H11Cl2N (Mþ): 299.02631, found 299.02622 and calcd for
17H11Cl37ClN (Mþ): 301.02336, found 301.02362. Anal. Calcd for
17H11Cl2N (300.18): C, 68.02; H, 3.69; N, 4.67. Found: C, 67.98; H,
4.4.5. 3,5-Dichloro-2,6-bis(4-ethoxyphenyl)pyridine (4e). Starting
with 2,3,5,6-tetrachloropyridine 1 (108 mg, 0.5 mmol), Pd(PPh3)4
(29 mg, 5.0 mol %), 4-ethoxyphenyl-boronic acid (207 mg,
1.25 mmol), KF (174 mg, 3.0 mmol) and toluene (8.0 mL), 4e was
3.585; N, 4.742.
4.4.2. 3,5-Dichloro-2,6-di-p-tolylpyridine
(4b). Starting
with
isolated as a colorless solid (142 mg, 73%); mp¼97e99 ꢁC. 1H NMR
3
2,3,5,6-tetrachloropyridine
1
(108 mg, 0.5 mmol), Pd(PPh3)4
(300 MHz, CDCl3):
d
¼1.42 (t, JHeH¼7.4 Hz, 6H, CH3), 4.07 (q,
(29 mg, 5.0 mol %), p-tolylboronic acid (170 mg, 1.25 mmol), KF
(174 mg, 3.0 mmol) and toluene (8.0 mL), 4b was isolated as a col-
orless solid (122 mg, 77%); mp¼134e136 ꢁC. 1H NMR (300 MHz,
3JHeH¼7.5 Hz, 4H, CH2), 6.92e6.97 (m, 4H, CH), 7.74e7.79 (m, 4H,
CH), 7.85 (s, 1H, CH). 13C NMR (75 MHz, CDCl3):
d
¼14.8 (CH3), 63.5
(CH2), 113.9 (CH), 127.3 (C), 129.7 (CH), 130.9 (C), 139.3 (CH), 153.6
(C),159.6 (C). IR (ATR, cmꢀ1): ṽ¼3067 (w), 2980 (m), 2928 (w), 2869
(w), 1611 (m), 1578 (m), 1506 (m), 1410 (m), 1389 (s), 1353 (w), 1314
(m), 1297 (m), 1247 (s), 1172 (m), 1110 (m), 1080 (m), 1050 (s), 1006
(w), 951 (w), 921 (m), 892 (m), 821 (s), 797 (m), 731 (m), 673 (m),
600 (m), 529 (m), 506 (m), 476 (m), 410 (w). GCeMS (EI, 70 eV): m/z
(%): 388 (Mþ, 24), 387 (100), 359 (11), 333 (28), 332 (12), 331 (43),
330 (5), 296 (20), 261 (6), 260 (3), 232 (6), 231 (4), 214 (4), 203 (4),
202 (4), 176 (4), 165 (11), 148 (4), 113 (3), 29 (10). HRMS (EI, 70 eV):
calcd for C21H19Cl2NO2 (Mþ): 387.07874, found 387.076976 and
calcd for C21H19Cl37ClNO2 (Mþ): 389.07579, found 389.076421.
CDCl3):
d
¼2.41 (s, 6H, CH3), 7.25e7.28 (m, 4H, CH), 7.69e7.73 (m,
4H, CH), 7.90 (s, 1H, CH). 13C NMR (75 MHz, CDCl3):
d
¼21.3 (CH3),
127.8 (C), 128.7 (CH), 129.3 (CH), 134.4 (C), 139.0 (C), 139.2 (CH),
154.0 (C). IR (ATR, cmꢀ1): ṽ¼3060 (w), 2917 (w), 1896 (w), 1784 (w),
1647 (w), 1610 (w), 1504 (m), 1435 (m), 1417 (m), 1402 (m), 1373
(w), 1354 (m), 1309 (m), 1252 (w), 1200 (m), 1109 (m), 1080 (s), 1010
(m), 957 (m), 874 (m), 817 (s), 755 (m), 716 (s), 638 (m), 592 (m),
512 (m), 487 (m), 454 (m), 389 (w). GCeMS (EI, 70 eV): m/z (%): 328
(Mþ, 27), 327 (100), 326 (11), 294 (18), 293 (13), 292 (59), 257 (7),
256 (7), 241 (11), 240 (10), 164 (9), 139 (13), 127 (8), 121 (6), 91 (8).
HRMS (EI, 70 eV): calcd for C19H15Cl2N (Mþ): 327.05761, found
327.057624 and calcd for C19H15Cl37ClN (Mþ): 329.05466, found
329.055034.
4.4.6. 3,5-Dichloro-2,6-bis(4-fluorophenyl)pyridine
(4f). Starting
with 2,3,5,6-tetrachloropyridine 1 (108 mg, 0.5 mmol), Pd(PPh3)4
(29 mg, 5.0 mol %), 4-fluorophenyl-boronic acid (175 mg,
1.25 mmol), KF (174 mg, 3.0 mmol) and toluene (8.0 mL), 4f was
isolated as a colorless solid (129 mg, 77%); mp¼146e148 ꢁC. 1H
4.4.3. 3,5-Dichloro-2,6-bis(4-ethylphenyl)pyridine
(4c). Starting
with 2,3,5,6-tetrachloropyridine 1 (108 mg, 0.5 mmol), Pd(PPh3)4
(29 mg, 5.0 mol %), 4-ethylphenyl-boronic acid (187 mg,
1.25 mmol), KF (174 mg, 3.0 mmol) and toluene (8.0 mL), 4c was
NMR (300 MHz, CDCl3):
d
¼7.10e7.18 (m, 4H, CH), 7.75e7.81 (m, 4H,
CH), 7.92 (s, 1H, CH). 13C NMR (75 MHz, CDCl3):
d
¼115.1 (d,
isolated as a colorless solid (128 mg, 72%); mp¼50e52 ꢁC. 1H NMR
2JCeF¼22.1 Hz, CH), 128.3 (C), 131.4 (d, JCeF¼8.2 Hz, CH), 133.1 (d,
3
3
(300 MHz, CDCl3):
d
¼1.29 (t, JHeH¼7.9 Hz, 6H, CH3), 2.71 (q,
4JCeF¼2.9 Hz, C), 139.5 (CH), 153.1 (C), 163.3 (d, 1JCeF¼249.4 Hz, CF).
3JHeH¼7.7 Hz, 4H, CH2), 7.30e7.33 (m, 4H, CH), 7.75e7.79 (m, 4H,
19F NMR (282.4 MHz, CDCl3):
d
¼ꢀ111.3 (F). IR (ATR, cmꢀ1): ṽ¼3066
CH), 7.92 (s, 1H, CH). 13C NMR (75 MHz, CDCl3):
d¼15.4 (CH3), 28.7
(w), 1889 (w), 1600 (s), 1501 (s), 1439 (s), 1416 (s), 1399 (s), 1347
(m), 1299 (m), 1225 (s), 1155 (s), 1110 (m), 1081 (s), 1015 (m), 954
(w), 880 (m), 834 (s), 806 (s), 762 (s), 660 (m), 597 (m), 529 (m),
482 (s), 455 (m), 415 (m). GCeMS (EI, 70 eV): m/z (%): 336 (Mþ, 22),
335 (100), 302 (26), 301 (16), 300 (77), 265 (20), 264 (18), 263 (17),
245 (8), 244 (5), 238 (9), 237 (5), 167 (5), 154 (12), 150 (9), 145 (4),
144 (24), 140 (5), 132 (8), 123 (6), 122 (7), 118 (5), 98 (3), 94 (6), 75
(7), 74 (4), 57 (2). HRMS (EI, 70 eV): calcd for C17H9Cl2F2N (Mþ):
(CH2), 127.5 (CH), 127.8 (C), 129.4 (CH), 134.7 (C), 139.2 (CH), 145.3
(C), 154.0 (C). IR (ATR, cmꢀ1): ṽ¼3027 (w), 2960 (m), 2930 (w), 2867
(w), 1914 (w), 1610 (m), 1503 (m), 1419 (s), 1404 (s), 1351 (m), 1199
(m), 1107 (m), 1118 (m), 1030 (m), 1020 (m), 965 (w), 874 (m), 840
(s), 763 (s), 660 (m), 637 (m), 592 (w), 553 (w), 513 (w), 486 (m),
455 (w), 386 (w). GCeMS (EI, 70 eV): m/z (%): 356 (Mþ, 43), 355
(100), 354 (34), 342 (32), 341 (13), 340 (52), 326 (5), 325 (7), 290
(4), 254 (5), 163 (10), 162 (13), 126 (3), 120 (3), 89 (3). HRMS (EI,
70 eV): calcd for C21H19Cl2N (Mþ): 355.08891, found 355.088200
335.00746, found 335.007509 and calcd for C17H9Cl37ClF2N (Mþ):
37
337.00451, found 337.004698 and calcd for C
H
Cl2F2N (Mþ):
17
9
and calcd for C21H19Cl37ClN (Mþ): 357.08596, found 357.085937
339.00156, found 339.002442. Anal. Calcd for C17H9Cl2F2N
(336.16): C, 60.74; H, 2.70; N, 4.17. Found: C, 60.59; H, 2.600; N,
4.281.
37
and calcd for C21
H
Cl2N (Mþ): 359.08301, found 359.083695. Anal.
19
Calcd for C21H19Cl2N (356.29): C, 70.79; H, 5.38; N, 3.93. Found: C,
70.71; H, 5.107; N, 4.068.
4.4.7. 3,5-Dichloro-2,6-bis(4-(trifluoromethoxy)phenyl)pyridine
4.4.4. 3,5-Dichloro-2,6-bis(4-methoxyphenyl)pyridine (4d). Starting
with 2,3,5,6-tetrachloropyridine 1 (108 mg, 0.5 mmol), Pd(PPh3)4
(29 mg, 5.0 mol %), 4-methoxy-phenylboronic acid (189 mg,
1.25 mmol), KF (174 mg, 3.0 mmol) and toluene (8.0 mL), 4d was
isolated as a colorless solid (128 mg, 71%); mp¼174e176 ꢁC. 1H NMR
(4g). Starting with 2,3,5,6-tetrachloropyridine
1
(108 mg,
0.5 mmol), Pd(PPh3)4 (29 mg, 5.0 mol %), 4-(trifluoro-methoxy)
phenylboronic acid (257 mg, 1.25 mmol), KF (174 mg, 3.0 mmol)
and toluene (8.0 mL), 4g was isolated as a colorless solid (159 mg,
68%); mp¼60e62 ꢁC. 1H NMR (300 MHz, CDCl3):
¼7.28e7.31 (m,
d
(300 MHz, CDCl3):
d
¼3.78 (s, 6H, MeO), 6.89e6.92 (m, 4H, CH),
4H, CH), 7.79e7.85 (m, 4H, CH), 7.95 (s, 1H, CH). 13C NMR (75 MHz,
7.70e7.73 (m, 4H, CH), 7.80 (s, 1H, CH). 13C NMR (75 MHz, CDCl3):
CDCl3):
d
¼120.3 (q, 1JCeF¼259.5 Hz, CF3), 120.4 (CH), 128.7 (C), 131.1
3
d
¼55.3 (MeO),113.4 (CH), 127.4 (C),129.8 (C), 130.9 (CH),139.9 (CH),
(CH), 135.5 (C), 139.7 (CH), 149.8 (q, JCeF¼1.8 Hz, C), 152.9 (C). 19
F
153.5 (C), 160.2 (C). IR (ATR, cmꢀ1): ṽ¼3054 (w), 3005 (w), 2834
(w), 2034 (w), 1609 (s), 1579 (m), 1504 (m), 1451 (m), 1421 (s), 1406
(s), 1355 (m), 1304 (m), 1243 (s), 1174 (s), 1080 (m), 1024 (s), 1005
(m), 829 (s), 788 (w), 763 (m), 631 (m), 537 (m), 448 (m), 434 (m),
415 (w). GCeMS (EI, 70 eV): m/z (%): 360 (Mþ, 24), 359 (100), 318
(5), 316 (8), 309 (13), 274 (5), 246 (4), 203 (4), 202 (4), 180 (12), 162
(2), 158 (2), 147 (2), 141 (2), 123 (2), 113 (3), 107 (3), 101 (2), 87 (2),
75 (2), 63 (2). HRMS (ESI, 70 eV): calcd for C19H16Cl2NO2 ([MþH]þ):
NMR (282.4 MHz, CDCl3):
d
¼ꢀ57.3 (CF3). IR (ATR, cmꢀ1): ṽ¼3055
(w), 1901 (w), 1608 (m), 1503 (m), 1403 (m), 1301 (m), 1205 (s), 1168
(s), 1109 (s), 1046 (m), 1029 (w), 1014 (m), 923 (m), 899 (m), 875
(m), 808 (m), 767 (m), 754 (m), 668 (m), 603 (m), 532 (m), 389 (w).
GCeMS (EI, 70 eV): m/z (%): 468 (Mþ, 23), 467 (100), 434 (23), 433
(14), 432 (65), 400 (2), 397 (6), 384 (5), 382 (8), 335 (7), 311 (6), 300
(6), 210 (4), 202 (4), 123 (3), 113 (5), 87 (3), 69 (22). HRMS (ESI,
70 eV): calcd for C19H10Cl2F6NO2 ([MþH]þ): 467.9987, found

S. Reimann et al. / Tetrahedron 71 (2015) 5371e5384
5381
467.9997. Anal. Calcd for C19H9Cl2F6NO2 (468.18): C, 48.74; H, 1.94;
N, 2.99. Found: C, 48.66; H, 1.861; N, 2.949.
7.73 (s, 1H, CH). 13C NMR (100 MHz, CDCl3):
d
¼55.2 (MeO), 113.8
(CH), 127.6 (CH), 127.8 (CH), 130.1 (CH), 130.6 (CH), 131.9 (C), 133.9
(C), 140.1 (C), 140.9 (CH), 154.9 (C), 158.9 (C). IR (ATR, cmꢀ1):
ṽ¼3055 (w), 3032 (w), 3003 (w), 2951 (w), 2930 (w), 2835 (w),
1606 (m), 1574 (m), 1511 (s), 1458 (m), 1428 (s), 1405 (m), 1387 (m),
1290 (m), 1248 (s), 1176 (s), 1030 (m), 1017 (m), 918 (m), 831 (s), 762
(m), 750 (m), 695 (s), 660 (m), 560 (m), 548 (m), 537 (m), 518 (m),
417 (w). GCeMS (EI, 70 eV): m/z (%): 444 (Mþ, 23), 443 (86), 442
(100), 428 (3), 399 (9), 398 (8), 355 (7), 354 (4), 222 (4), 177 (5), 176
(3), 171 (3), 164 (2). HRMS (EI, 70 eV): calcd for C31H24NO2 (Mþ):
442.18016, found 442.18055. Anal. Calcd for C31H25NO2 (443.53): C,
83.95; H, 5.68; N, 3.16. Found: C, 83.87; H, 5.576; N, 3.061.
4.4.8. 3,5-Dichloro-2,6-di-m-tolylpyridine
(4h). Starting
with
2,3,5,6-tetrachloropyridine (108 mg, 0.5 mmol), Pd(PPh3)4
1
(29 mg, 5.0 mol %), m-tolylboronic acid (170 mg, 1.25 mmol), KF
(174 mg, 3.0 mmol) and toluene (8.0 mL), 4h was isolated as a col-
orless solid (113 mg, 69%); mp¼81e83 ꢁC. 1H NMR (300 MHz,
CDCl3):
d
¼2.44 (s, 6H, CH3), 7.26e7.40 (m, 4H, CH), 7.60e7.61 (m,
4H, CH), 7.93 (s, 1H, CH). 13C NMR (75 MHz, CDCl3):
d
¼21.5 (CH3),
126.5 (CH), 127.8 (CH), 128.3 (C), 129.8 (CH), 130.0 (C), 137.2 (C),
137.7 (C), 139.1 (C). IR (ATR, cmꢀ1): ṽ¼2914 (w), 1788 (w), 1529 (m),
1408 (m), 1340 (m), 1201 (w), 1110 (w), 1088 (m), 1037 (s), 993 (w),
923 (m), 886 (m), 814 (m), 785 (m), 747 (s), 697 (s), 652 (w), 532
(w), 512 (w), 502 (m), 457 (m), 430 (w). GCeMS (EI, 70 eV): m/z (%):
328 (Mþ, 27), 327 (100), 326 (11), 294 (34), 293 (22), 292 (96), 256
(11), 255 (8), 241 (14), 240 (12), 227 (5), 163 (12), 139 (16), 138 (6),
127 (12), 120 (11), 115 (9), 114 (6), 113 (5), 91 (7), 89 (5), 87 (3), 65
(7), 63 (5), 51 (3), 39 (5). HRMS (EI, 70 eV): calcd for C19H15Cl2N
(Mþ): 327.05761, found 327.057678 and calcd for C19H15Cl37ClN
(Mþ): 329.05466, found 329.055137. Anal. Calcd for C19H15Cl2N
(328.29): C, 69.52; H, 4.61; N, 4.27. Found: C, 69.55; H, 4.507; N,
4.310.
4.5.2. 3,5-Bis(4-(trifluoromethyl)phenyl)-2,6-diphenylpyridine
(5b). Starting with 3,5-dichloro-2,6-diphenylpyridine 4a (100 mg,
0.33 mmol), Pd(dba)2 (4.7 mg, 2.5 mol %), cataCXium A (5.9 mg,
5.0 mol %), 4-(trifluoromethyl)-phenylboronic acid (252 mg,
1.32 mmol), K3PO4 (282 mg, 1.32 mmol) and toluene (4.0 mL), 5b
was isolated as a colorless solid (159 mg, 93%); mp¼188e189 ꢁC. 1H
NMR (400 MHz, CDCl3):
d
¼7.25e7.30 (m, 6H, CH), 7.39 (d,
3JHeH¼8.1 Hz, 4H, CH), 7.43e7.48 (m, 4H, CH), 7.55e7.58 (m, 4H,
CH), 7.74 (s, 1H, CH). 13C NMR (100 MHz, CDCl3):
d
¼124.3 (q,
1JCeF¼272.4 Hz, CF3), 125.4 (q, JCeF¼3.7 Hz, CH), 128.1 (CH), 128.3
3
2
(CH), 129.6 (q, JCeF¼32.5 Hz, C), 129.8 (CH), 130.1 (CH), 133.0 (C),
4.4.9. 3,5-Dichloro-2,6-bis(3-methoxyphenyl)pyridine (4i). Starting
with 2,3,5,6-tetrachloropyridine 1 (108 mg, 0.5 mmol), Pd(PPh3)4
(29 mg, 5.0 mol %), 3-methoxyphenylboronic acid (189 mg,
1.25 mmol), KF (174 mg, 3.0 mmol) and toluene (8.0 mL), 4i was
isolated as a colorless solid (128 mg, 71%); mp¼152e154 ꢁC. 1H
139.1 (C), 140.9 (C), 143.1 (C), 156.1 (CH). 19F NMR (282.4 MHz,
CDCl3):
d
¼ꢀ62.1 (CF3). IR (ATR, cmꢀ1): ṽ¼3058 (w), 3039 (w), 2931
(w), 1617 (m),1574 (w), 1518 (w), 1491 (w), 1430 (m), 1403 (m), 1321
(s), 1244 (w), 1165 (m), 1108 (m), 1065 (s), 1016 (s), 1004 (m), 956
(w), 908 (w), 843 (s), 805 (w), 843 (s), 778 (m), 760 (m), 718 (m),
696 (s), 628 (s), 604 (m), 547 (w), 484 (w), 409 (w), 381 (w). GCeMS
(EI, 70 eV): m/z (%): 519 (Mþ, 58), 518 (100), 500 (4), 420 (5), 371 (2),
250 (6), 214 (4), 190 (4), 189 (2), 176 (2). HRMS (EI, 70 eV): calcd for
NMR (400 MHz, CDCl3):
d
¼3.83 (s, 6H, MeO), 6.95e6.98 (m, 2H,
CH), 7.29e7.30 (m, 2H, CH), 7.34e7.36 (m, 4H, CH), 7.91 (s, 1H, CH).
13C NMR (100 MHz, CDCl3):
d¼55.3 (MeO), 114.8 (CH), 115.1 (CH),
121.9 (CH), 128.5 (C), 129.1 (CH), 138.5 (C), 139.3 (CH), 153.9 (C),
159.2 (C). IR (ATR, cmꢀ1): ṽ¼3002 (w), 2961 (w), 2924 (w), 2830
(w), 1952 (w), 1740 (w), 1598 (m), 1587 (m), 1493 (m), 1458 (m),
1415 (s), 1317 (m), 1272 (m), 1176 (m), 1033 (m), 993 (w), 895 (m),
870 (m), 796 (m), 762 (m), 703 (s), 524 (m), 469 (w), 434 (w).
GCeMS (EI, 70 eV): m/z (%): 360 (Mþ, 77), 359 (78), 358 (100), 332
(11), 331 (20), 330 (21), 329 (26), 328 (8), 272 (3), 250 (3), 238 (3),
215 (4), 214 (4), 202 (4), 180 (9), 125 (2), 114 (2), 113 (4), 101 (4), 75
C
31H18F6N (Mþ): 518.13380, found 518.13388.
4.5.3. 3,5-Di(biphenyl-4-yl)-2,6-diphenylpyridine
(5c). Starting
with 3,5-dichloro-2,6-diphenylpyridine 4a (100 mg, 0.33 mmol),
Pd(dba)2 (4.7 mg, 2.5 mol %), cataCXium A (5.9 mg, 5.0 mol %), bi-
phenyl-4-ylboronic acid (263 mg, 1.32 mmol), K3PO4 (282 mg,
1.32 mmol) and toluene (4.0 mL), 5c was isolated as a colorless solid
(173 mg, 98%); mp¼264e266 ꢁC. 1H NMR (300 MHz, CDCl3):
(2). HRMS (ESI, 70 eV): calcd for
360.05526, found 360.0551. Anal. Calcd for C19H15Cl2NO2 (360.23):
C, 63.35; H, 4.20; N, 3.89. Found: C, 63.46; H, 4.211; N, 3.923.
C
19H16Cl2NO2 ([MþH]þ):
d
¼7.25e7.29 (m, 6H, CH), 7.33e7.37 (m, 6H, CH), 7.40e7.45 (m, 4H,
CH), 7.53e7.62 (m, 12H, CH), 7.86 (s, 1H, CH). 13C NMR (75 MHz,
CDCl3):
¼127.0 (CH), 127.0 (CH), 127.4 (CH), 127.9 (CH), 127.9 (CH),
d
128.8 (CH), 130.0 (CH), 130.2 (CH), 134.0 (C), 138.5 (C), 139.7 (C),
140.0 (C), 140.4 (C), 141.2 (CH), 155.3 (C). IR (ATR, cmꢀ1): ṽ¼3081
(w), 3031 (w), 2217 (w), 1580 (w), 1488 (m), 1428 (m), 1401 (m),
1383 (m), 1263 (m), 1205 (m), 1183 (m), 1163 (m), 1121 (m), 1099
(m),1074 (m),1017 (w),1004 (m), 917 (m), 836 (s), 807 (w), 784 (m),
762 (s), 749 (m), 724 (s), 697 (m), 643 (m), 624 (m), 560 (w), 526
(w), 511 (w), 488 (m), 455 (w), 438 (w), 418 (w), 410 (w), 382 (w).
GCeMS (EI, 70 eV): m/z (%): 536 (Mþ, 12), 535 (36), 534 (39), 246
(2), 172 (4), 154 (2), 143 (6), 129 (35), 125 (2), 115 (11), 112 (7), 111
(4), 110 (5), 101 (10), 98 (10), 97 (8), 96 (3), 89 (5), 88 (3), 87 (17), 85
(11), 84 (11), 83 (15), 73 (88), 71 (30), 70 (11), 69 (24), 67 (6), 61 (11),
60 (100), 59 (6), 57 (40), 56 (13), 55 (32), 54 (4), 46 (7), 45 (29), 44
(35), 43 (38), 42 (11), 41 (34), 40 (8), 39 (9). HRMS (ESI, 70 eV): calcd
for C41H30N ([MþH]þ): 536.23728, found 536.2371.
4.5. General procedure for the synthesis of 2,3,5,6-tetraaryl-
substituted pyridines 5aef
An oven-dried and argon-flushed pressure tube was charged
with the appropriate 3,5-dichloro-2,6-diaryl-substituted pyridine
4a or 4i (0.33 mmol), Pd(dba)2 (2.5 mol %), cataCXium A (5.0 mol %),
boronic acid (1.3 mmol) and K3PO4 (1.3 mmol) followed by anhy-
drous toluene (4.0 mL). The tube was sealed with a Teflon valve and
the reaction mixture was stirred at 100 ꢁC for 22 h. The cooled
reaction mixture was diluted with water and extracted with CH2Cl2.
The combined organic layers were dried (Na2SO4), filtered and the
filtrate was concentrated in vacuo. The residue was purified by
column chromatography.
4.5.1. 3,5-Bis(4-methoxyphenyl)-2,6-diphenylpyridine (5a). Starting
with 3,5-dichloro-2,6-diphenylpyridine 4a (100 mg, 0.33 mmol),
Pd(dba)2 (4.7 mg, 2.5 mol %), cataCXium A (5.9 mg, 5.0 mol %), 4-
methoxyphenyl-boronic acid (202 mg, 1.32 mmol), K3PO4
(282 mg, 1.32 mmol) and toluene (4.0 mL), 5a was isolated as
a colorless solid (131 mg, 90%); mp¼204e206 ꢁC. 1H NMR
4.5.4. 3,5-Bis(2-methoxyphenyl)-2,6-diphenylpyridine (5d). Starting
with 3,5-dichloro-2,6-diphenylpyridine 4a (100 mg, 0.33 mmol),
Pd(dba)2 (4.7 mg, 2.5 mol %), cataCXium A (5.9 mg, 5.0 mol %), 2-
methoxyphenylboronic acid (202 mg, 1.32 mmol), K3PO4 (282 mg,
1.32 mmol) and toluene (4.0 mL), 5d was isolated as a colorless
solid (131 mg, 90%); mp¼179e181 ꢁC. 1H NMR (400 MHz, CDCl3):
(400 MHz, CDCl3):
d
¼3.80 (s, 6H, MeO), 6.83e6.85 (m, 4H, CH),
d
¼3.38 (s, 6H, MeO), 6.77e6.80 (m, 2H, CH), 6.97 (ddd,
3 4
7.18e7.21 (m, 4H, CH), 7.24e7.28 (m, 6H, CH), 7.51e7.54 (m, 4H, CH),
3JHeH¼8.3 Hz, JHeH¼7.5 Hz, JHeH¼1.2 Hz, 2H, CH), 7.20e7.22 (m,

5382
S. Reimann et al. / Tetrahedron 71 (2015) 5371e5384
6H, CH), 7.26e7.31 (m, 4H, CH), 7.48e7.52 (m, 4H, CH), 7.74 (s, 1H,
CH). 13C NMR (100 MHz, CDCl3):
¼55.0 (MeO), 111.1 (CH), 120.8
100 ꢁC for 20 h. The cooled reaction mixture was diluted with water
and extracted with CH2Cl2. The combined organic layers were dried
(Na2SO4), filtered and the filtrate was concentrated in vacuo. The
residue was purified by column chromatography.
d
(CH), 127.4 (CH), 127.4 (CH), 128.9 (C), 129.0 (CH), 129.0 (CH),130.6
(C), 131.4 (CH), 141.0 (C), 142.2 (CH), 156.0 (C), 156.2 (C). IR (ATR,
cmꢀ1): ṽ¼3079 (w), 3055 (w), 2951 (w), 2929 (w), 2832 (w), 1651
(w), 1598 (m), 1493 (m), 1418 (m), 1383 (m), 1280 (m), 1242 (m),
1180 (m), 1160 (m), 1024 (m), 1002 (m), 917 (m), 787 (m), 766 (m),
749 (s), 698 (s), 680 (m), 558 (m), 542 (m), 515 (m), 494 (m). GCeMS
(EI, 70 eV): m/z (%): 444 (Mþ, 26), 443 (87), 442 (100), 428 (11), 427
(4), 426 (8), 413 (10), 412 (31), 411 (2), 396 (15), 384 (3), 380 (3), 366
(3), 350 (5), 336 (2), 320 (4), 307 (2), 198 (2), 183 (13), 177 (4), 176
(3), 170 (2), 169 (2). HRMS (ESI, 70 eV): calcd for C31H26NO2
([MþH]þ): 444.19581, found 444.19648.
4.6.1. 3-Chloro-2,5,6-triphenylpyridine (6a). Starting with 2,3,5,6-
tetrachloropyridine 1 (54 mg, 0.25 mmol), Pd(dba)2 (3.6 mg,
2.5 mol %), cataCXium A (5.1 mg, 5.0 mol %), phenylboronic acid
(107 mg, 0.88 mmol), K3PO4 (265 mg, 1.25 mmol) and toluene
(4.0 mL), 6a was isolated as a colorless solid (36 mg, 42%);
mp¼174e176 ꢁC. 1H NMR (300 MHz, CDCl3):
¼7.11e7.25 (m, 8H,
d
CH), 7.30e7.44 (m, 5H, CH), 7.77 (s, 1H, CH), 7.79e7.83 (m, 2H, CH).
13C NMR (75 MHz, CDCl3):
d¼127.7 (CH), 127.9 (CH), 128.0 (CH),
128.0 (CH), 128.3 (C), 128.5 (CH), 128.8 (CH), 129.4 (CH), 129.6 (CH),
130.0 (CH), 135.7 (C), 138.0 (C), 138.4 (C), 139.1 (C), 140.1 (CH), 154.4
(C), 154.9 (C). IR (ATR, cmꢀ1): ṽ¼3054 (w), 3029 (w), 1598 (w), 1566
(w),1528 (w), 1489 (w), 1420 (m),1365 (m),1304 (w), 1175 (w), 1114
(m), 1014 (s), 906 (m), 767 (m), 757 (m), 721 (m), 695 (s), 665 (m),
624 (m), 608 (m), 546 (m), 504 (m), 419 (w). GCeMS (EI, 70 eV): m/z
(%): 342 (Mþ, 45), 341 (61), 340 (100), 305 (9), 304 (14), 303 (7), 302
(5), 276 (4), 227 (10), 202 (8), 201 (5), 200 (6), 153 (9), 152 (8), 151
(8), 77 (3). HRMS (ESI, 70 eV): calcd for C23H17ClN ([MþH]þ):
342.1044, found 342.1044.
4.5.5. 3,5-Diphenyl-2,6-bis(3-methoxyphenyl)pyridine (5e). Starting
with 3,5-dichloro-2,6-bis(3-methoxyphenyl)pyridine 4i (119 mg,
0.33 mmol), Pd(dba)2 (4.7 mg, 2.5 mol %), cataCXium A (5.9 mg,
5.0 mol %), phenylboronic acid (161 mg,1.32 mmol), K3PO4 (282 mg,
1.32 mmol) and toluene (4.0 mL), 5e was isolated as a colorless solid
(126 mg, 86%); mp¼105e107 ꢁC. 1H NMR (400 MHz, CDCl3):
¼3.62
d
(s, 6H, MeO), 6.79e6.82 (m, 2H, CH), 7.03e7.17 (m, 6H, CH),
7.27e7.32 (m, 10H, CH), 7.77 (s, 1H, CH). 13C NMR (100 MHz, CDCl3):
d¼55.1 (MeO), 114.3 (CH), 115.2 (CH), 122.8 (CH), 127.3 (CH), 128.4
(CH),128.8 (CH),129.5 (CH), 134.5 (C),139.7 (C),141.1 (C),141.2 (CH),
155.0 (C),159.0 (C). IR (ATR, cmꢀ1): ṽ¼3010 (w), 2959 (w), 2938 (w),
2832 (w), 1598 (m), 1574 (m), 1523 (w), 1418 (m), 1381 (m), 1287
(m), 1271 (m), 1241 (m), 1202 (m), 1180 (m), 1154 (m), 1031 (m),
1007 (w), 994 (m), 906 (m), 864 (m), 782 (s), 768 (s), 733 (m), 694
(s), 652 (m), 526 (m), 484 (w), 442 (w), 398 (w). GCeMS (EI, 70 eV):
m/z (%): 444 (Mþ, 15), 443 (65), 442 (100), 427 (3), 426 (3), 400 (3),
399 (7), 398 (4), 384 (3), 368 (2), 366 (2), 355 (4), 354 (3), 183 (8),
177 (4), 176 (3), 171 (3), 164 (2), 158 (2). HRMS (ESI, 70 eV): calcd for
4.6.2. 3-Chloro-2,5,6-tris(4-methoxyphenyl)pyridine (6b). Starting
with 2,3,5,6-tetrachloropyridine 1 (54 mg, 0.25 mmol), Pd(dba)2
(3.6 mg, 2.5 mol %), cataCXium
A (5.1 mg, 5.0 mol %), 4-
methoxyphenylboronic acid (132 mg, 0.88 mmol), K3PO4
(265 mg, 1.25 mmol) and toluene (4.0 mL), 6b was isolated as
a colorless solid (63 mg, 58%); mp¼123e125 ꢁC. 1H NMR (300 MHz,
CDCl3):
d
¼3.76 (s, 3H, MeO), 3.80 (br s, 3H, MeO), 3.85 (s, 3H, MeO),
6.73e6.85 (m, 4H, CH), 6.96e7.00 (m, 2H, CH), 7.10e7.15 (m, 2H,
CH), 7.32e7.37 (m, 2H, CH), 7.73 (s, 1H, CH), 7.83e7.87 (m, 3H, CH).
C
31H26NO2 ([MþH]þ): 444.19581, found 444.19667.
13C NMR (75 MHz, CDCl3):
d
¼55.2 (MeO), 55.2 (MeO), 55.3 (MeO),
4.5.6. 3,5-Bis(4-(trifluoromethyl)phenyl)-2,6-bis(3-methoxyphenyl)
pyridine (5f). Starting with 3,5-dichloro-2,6-bis(3-
113.3 (CH), 113.3 (CH), 114.0 (CH), 127.4 (C), 130.5 (CH), 130.6 (C),
131.0 (CH),131.3 (CH),131.8 (C),134.5 (C),140.0 (CH),142.0 (C),153.3
(C), 154.3 (C), 159.1 (C), 159.4 (C), 160.0 (C). IR (ATR, cmꢀ1): ṽ¼3000
(w), 2957 (w), 2931 (w), 2836 (w),1606 (s),1515 (m),1426 (m),1403
(m), 1370 (m), 1292 (s), 1244 (s), 1172 (s), 1108 (m), 1029 (m), 1003
(m), 906 (m), 830 (s), 779 (s), 728 (m), 659 (m), 605 (s), 535 (s), 489
(w), 450 (w), 416 (w). GCeMS (EI, 70 eV): m/z (%): 432 (Mþ, 56), 431
(93), 430 (100), 416 (6), 415 (2), 389 (4), 388 (4), 387 (9), 373 (2),
344 (4), 278 (2), 266 (2), 265 (2), 216 (5), 198 (2), 177 (2),176 (2), 168
methoxyphenyl)-pyridine 4i (119 mg, 0.33 mmol), Pd(dba)2
(4.7 mg, 2.5 mol %), cataCXium A (5.9 mg, 5.0 mol %), 4-(tri-
fluoromethyl)phenylboronic acid (251 mg, 1.32 mmol), K3PO4
(282 mg, 1.32 mmol) and toluene (4.0 mL), 5f was isolated as
a
colorless solid (185 mg, 97%); mp¼143e144 ꢁC. 1H NMR
(400 MHz, CDCl3):
d
¼3.65 (s, 6H, MeO), 6.83e6.86 (m, 2H, CH),
6.99e7.03 (m, 4H, CH), 7.15e7.19 (m, 2H, CH), 7.40e7.41 (m, 4H, CH),
7.57e7.59 (m, 4H, CH), 7.75 (s, 1H, CH). 13C NMR (100 MHz, CDCl3):
(2),145 (2), 139 (3), 133 (4). HRMS (EI, 70 eV): calcd for C26H22ClNO3
37
d
¼55.1 (MeO), 114.5 (CH), 115.3 (CH), 122.7 (CH), 124.2 (q,
(Mþ): 431.12827, found 431.12737 and calcd for C26
433.12532, found 433.12537.
H
ClO3N (Mþ):
22
3
1JCeF¼272.3 Hz, CF3), 125.4 (q, JCeF¼4.2 Hz, CH), 129.1 (CH), 129.6
2
(q, JCeF¼32.5 Hz, C), 129.8 (CH), 133.1 (C), 140.3 (C), 140.8 (CH),
143.2 (C), 155.8 (C), 159.2 (C). 19F NMR (282.4 MHz, CDCl3):
d
¼ꢀ62.2
4.6.3. 3-Chloro-2,5,6-tris(3-methoxyphenyl)pyridine (6c). Starting
with 2,3,5,6-tetrachloropyridine 1 (54 mg, 0.25 mmol), Pd(dba)2
(CF3). IR (ATR, cmꢀ1): ṽ¼3055 (w), 3063 (w), 3007 (w), 2936 (w),
2840 (w), 1606 (m), 1578 (m), 1529 (w), 1488 (w), 1402 (w), 1386
(w), 1322 (s), 1288 (m), 1219 (m), 1160 (m), 1122 (s), 1109 (m), 1066
(s), 1018 (m), 1006 (m), 906 (m), 881 (m), 846 (s), 777 (m), 730 (m),
715 (s), 696 (m), 687 (m), 642 (m), 607 (m), 571 (w), 553 (w), 511
(w), 476 (w), 445 (w), 405 (w). GCeMS (EI, 70 eV): m/z (%): 580 (Mþ,
15), 579 (60), 578 (100), 536 (3), 535 (8), 534 (5), 520 (2), 491 (4),
280 (4), 217 (3), 211 (2), 183 (2), 176 (2). HRMS (ESI, 70 eV): calcd for
(3.6 mg, 2.5 mol %), cataCXium
A (5.1 mg, 5.0 mol %), 3-
methoxyphenylboronic acid (132 mg, 0.88 mmol), K3PO4
(265 mg, 1.25 mmol) and toluene (4.0 mL), 6c was isolated as
a colorless solid (71 mg, 55%); mp¼122e124 ꢁC. 1H NMR (300 MHz,
CDCl3):
d
¼3.51 (s, 3H, MeO), 3.54 (s, 3H, MeO), 3.74 (s, 3H, MeO),
6.63e6.74 (m, 4H, CH), 6.85e6.91 (m, 3H, CH), 7.00e7.12 (m, 2H,
CH), 7.24e7.36 (m, 3H, CH), 7.72 (s, 1H, CH). 13C NMR (75 MHz,
C
33H24F6NO2 ([MþH]þ): 580.17028, found 580.17057.
CDCl3):
d¼55.0 (MeO), 55.1 (MeO), 55.3 (MeO), 113.6 (CH), 114.3
(CH), 114.5 (CH), 114.7 (CH), 114.9 (CH), 115.1 (CH), 121.7 (CH), 122.0
(CH), 122.4 (CH), 128.3 (C), 128.8 (CH), 128.9 (CH), 129.5 (CH), 135.6
(C), 139.2 (C), 139.7 (C), 140.0 (CH), 140.3 (C), 154.1 (C), 154.6 (C),
159.1 (C), 159.2 (C), 159.4 (C). IR (ATR, cmꢀ1): ṽ¼3079 (w), 3056 (w),
3011 (w), 2837 (w), 1585 (s), 1568 (s), 1528 (m), 1492 (m), 1462 (m),
1426 (s), 1360 (s), 1316 (m), 1286 (m), 1250 (m), 1225 (m), 1170 (m),
1111 (m), 1083 (w), 1039 (s), 1026 (s), 992 (w), 859 (m), 840 (w), 799
(w), 786 (s), 769 (s), 713 (m), 703 (s), 690 (m), 666 (m), 626 (w), 557
(m), 511 (m), 495 (m), 420 (w). GCeMS (EI, 70 eV): m/z (%): 432
4.6. General procedure for the synthesis of 3-chloro-2,5,6-
triaryl-substituted pyridines 35aee
An oven-dried and argon-flushed pressure tube was charged
with 2,3,5,6-tetrachloropyridine 1 (0.25 mmol), Pd(dba)2 (2.5 mol
%), cataCXium A (5.0 mol %), boronic acid (0.9 mmol) and K3PO4
(1.25 mmol), followed by anhydrous toluene (4.0 mL). The tube was
sealed with a Teflon valve and the reaction mixture was stirred at

S. Reimann et al. / Tetrahedron 71 (2015) 5371e5384
5383
(Mþ, 48), 431 (70), 430 (100), 416 (6), 415 (5), 401 (5), 344 (2), 278
Supplementary data
(2), 266 (2), 265 (2), 215 (3), 169 (2), 161 (2), 145 (4), 133 (4), 119 (2).
HRMS (ESI, 70 eV): calcd for C26H23ClNO3 ([MþH]þ): 432.13628,
found 432.1361. Anal. Calcd for C26H22ClNO3 (431.91): C, 72.30; H,
5.13; N, 3.24. Found: C, 72.06; H, 4.989; N, 2.915.
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2015.05.114.
References and notes
4.6.4. 3-Chloro-2,5,6-tris(2-methoxyphenyl)pyridine (6d). Starting
with 2,3,5,6-tetrachloropyridine 1 (54 mg, 0.25 mmol), Pd(dba)2
1. (a) Jones, G. In Comprehensive Heterocyclic Chemistry II; Katritzky, A. R., Rees, C.
W., Scriven, E. F. V., Mc Killop, A., Eds.; Pergamon: Oxford, UK, 1996; Vol. 5,
pp 167e243; (b) Hill, M. D. Chem.dEur. J. 2010, 16, 12052e12062; (c) Carey, J. S.;
Laffan, D.; Thomson, C.; Williams, M. T. Org. Biomol. Chem. 2006, 4, 2337e2342.
(3.6 mg, 2.5 mol %), cataCXium
A (5.1 mg, 5.0 mol %), 2-
methoxyphenylboronic acid (132 mg, 0.88 mmol), K3PO4
(265 mg, 1.25 mmol) and toluene (4.0 mL), 6d was isolated as
a colorless solid (41 mg, 38%); mp¼48e50 ꢁC. 1H NMR (300 MHz,
€
2. (a) Rompp Lexikon Naturstoffe; Steglich, W., Fugmann, B., Lang-Fugmann, S.,
Eds.; Thieme: Stuttgart, Germany, 1997; (b) Ma, X.; Gang, D. R. Nat. Prod. Rep.
2005, 22, 627e644; (c) Deininger, M. W. N.; Druker, B. J. Pharmacol. Rev. 2003,
55, 401e423.
CDCl3):
d
¼3.33 (s, 3H, MeO), 3.60 (br s, 3H, MeO), 3.85 (s, 3H, MeO),
6.59e6.62 (m, 1H, CH), 6.79e6.83 (m, 2H, CH), 6.89e7.08 (m, 4H,
CH), 7.14e7.23 (m, 2H, CH), 7.36e7.47 (m, 3H, CH), 7.81 (s, 1H, CH).
3. (a) Pharmaceutical Substances, 4th ed.; Kleemann, A., Engel, J., Kutscher, B.,
Reichert, D., Eds.; Thieme: Stuttgart, Germany, 2000; (b) Balasubramanian, M.;
Keay, J. G. In Comprehensive Hetreocyclic Chemistry II; Katritzky, A. R., Rees, C. W.
, Scriven, E. F. V., Mc Killop, A., Eds.; Pergamon: Oxford, UK, 1996; Vol. 5,
pp 245e300; (c) O’Hagen, D. Nat. Prod. Rep. 2000, 17, 435e446; (d) Cui, J. J.;
13C NMR (75 MHz, CDCl3):
d¼54.7 (MeO), 55.0 (MeO), 55.5 (MeO),
110.3 (CH), 110.3 (CH), 111.0 (CH), 119.9 (CH), 120.3 (CH), 120.5 (CH),
127.5 (C), 128.1 (C), 128.9 (CH), 129.2 (CH), 129.4 (C), 130.0 (CH),
130.9 (CH), 131.1 (CH), 131.6 (CH), 134.0 (C), 138.8 (CH), 153.4 (C),
153.9 (C), 154.0 (C), 156.0 (C), 156.1 (C), 157.1 (C). IR (ATR, cmꢀ1):
ṽ¼3000 (w), 2918 (w), 2849 (w), 2833 (w),1600 (m),1580 (m),1529
(m), 1491 (m), 1459 (m), 1434 (m), 1417 (m), 1364 (m), 1272 (m),
1243 (s), 1179 (m), 1120 (m), 1100 (m), 1014 (s), 906 (m), 803 (m),
748 (s), 726 (s), 656 (m), 626 (w), 505 (m), 469 (m), 388 (m).
GCeMS (EI, 70 eV): m/z (%): 432 (Mþ, 15), 431 (31), 430 (19), 416 (3),
402 (22), 401 (13), 400 (49), 398 (5), 397 (28), 396 (100), 386 (6),
380 (7), 378 (4), 370 (6), 364 (5), 350 (8), 326 (30), 324 (22), 320 (9),
288 (5), 209 (3), 208 (7), 153 (8), 145 (11), 132 (4). HRMS (EI, 70 eV):
ꢀ
Tran-Dube, M.; Shen, H.; Nambu, M.; Kung, P.-P.; Pairish, M.; Jia, L.; Meng, J.;
Funk, L.; Botrous, I.; McTigue, M.; Grodsky, N.; Ryan, K.; Padrique, E.; Alton, G.;
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Omura, S. J. Org. Chem. 1995, 60, 8126e8127; (f) Trecourt, F.; Gervais, B.; Mallet,
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M.; Queguiner, G. J. Org. Chem. 1996, 61, 1673e1676; (g) Sammakia, T.; Stan-
geland, E. L.; Whitcomb, M. C. Org. Lett. 2002, 4, 2385e2388; (h) Naito, Y.;
Takagi, T.; Yoshikawa, T. Mol. Cell. Pharmacol. 2010, 2, 53e60.
4. (a) Durola, F.; Sauvage, J. P.; Wenger, O. S. Chem. Commun. 2006, 171e173; (b)
Verma, A. K.; Jha, R. R.; Chaudhary, R.; Tiwari, R. K.; Danodia, A. K. Adv. Synth.
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Am. Chem. Soc. 2004, 126, 6554e6555.
5. (a) Zhou, G.; Wong, W.-Y.; Yang, X. Chem.dAsian J. 2011, 6, 1706e1727; (b)
Baxter, P. N. W. J. Org. Chem. 2004, 69, 1813e1821; (c) Cowley, M. J.; Adams, R.
W.; Atkinson, K. D.; Cockett, M. C. R.; Duckett, S. B.; Green, G. G. R.; Lohamn, J.
A. B.; Kerssebaum, R.; Kilgour, D.; Mewis, R. E. J. Am. Chem. Soc. 2011, 133,
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8614e8617.
calcd for C26H22ClNO3 (Mþ): 431.12827, found 431.12754 and calcd
37
for C
H
ClNO3 (Mþ): 433.12532, found 433.12562.
26 22
4.6.5. 3-Chloro-2,5,6-tris(2,5-dimethoxyphenyl)pyridine
(6e). Starting with 2,3,5,6-tetrachloropyridine (54 mg,
1
6. (a) Supramolecular Chemistry: Concepts and Perspectives; Lehn, J.-M., Ed.; Wiley-
VCH: Weinheim, Germany, 1995; (b) Modern Terpyridine Chemistry; Schubert,
U. S., Hofmeier, H., Newkome, G. R., Eds.; Wiley-VCH: Weinheim, Germany,
2006; (c) Wise, M. D.; Ruggi, A.; Pascu, M.; Scopelliti, R.; Severin, K. Chem. Sci.
0.25 mmol), Pd(dba)2 (3.6 mg, 2.5 mol %), cataCXium A (5.1 mg,
5.0 mol %), 2,5-dimethoxyphenylboronic acid (159 mg, 0.88 mmol),
K3PO4 (265 mg, 1.25 mmol) and toluene (4.0 mL), 6e was isolated as
a slightly yellow solid (54 mg, 41%); mp¼152e154 ꢁC. 1H NMR
€
2013, 4, 1658e1664; (d) Wu, D.; Zhi, L.; Bodwell, G. J.; Cui, G.; Tsao, N.; Mullen,
K. Angew. Chem., Int. Ed. 2007, 46, 5417e5420; (e) Wang, J.-L.; Li, X.; Lu, X.;
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kome, G. R. J. Am. Chem. Soc. 2011, 133, 11450e11453.
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Zimmer, R. Eur. J. Org. Chem. 2011, 6070e6077; (b) Ohashi, M.; Takeda, I.; Ikawa,
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Angew. Chem., Int. Ed. Engl. 1978, 17, 505e515; (d) Heller, B.; Hapke, M. Chem.
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9. (a) Yamamoto, S.-I.; Okamoto, K.; Murakoso, M.; Kuninobu, Y.; Takai, K. Org. Lett.
2012, 14, 3182e3185; (b) Allais, C.; Lieby-Muller, F.; Constantieux, T.; Rodriguez,
J. Adv. Synth. Catal. 2012, 354, 2537e2544.
10. (a) Sandford, G.; Slater, R.; Yufit, D. S.; Howard, J. A. K.; Vong, A. J. Org. Chem.
2005, 70, 7208e7216; (b) Schmidt, A.; Mordhorst, T.; Nieger, M. Org. Biomol.
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11. (a) Masson, E.; Marzi, E.; Cottet, F.; Bobbio, C.; Schlosser, M.; Gros, P. C.; Fort, Y.
(300 MHz, CDCl3):
d
¼3.31 (s, 3H, MeO), 3.54 (s, 3H, MeO), 3.59 (s,
3H, MeO), 3.68 (s, 3H, MeO), 3.77 (br s, 3H, MeO), 3.79 (s, 3H, MeO),
6.56e6.59 (m, 2H, CH), 6.70e6.75 (m, 3H, CH), 6.91e6.92 (m, 2H,
CH), 6.98e7.02 (m, 2H, CH), 7.84 (s, 1H, CH). 13C NMR (75 MHz,
€
CDCl3):
d
¼55.3 (MeO), 55.5 (MeO), 55.5 (MeO), 55.6 (MeO), 55.6
€
(MeO), 56.1 (MeO), 111.4 (CH), 111.6 (CH), 112.3 (CH), 114.4 (CH),
114.7 (CH), 115.2 (CH), 116.0 (CH), 116.2 (CH), 116.6 (CH), 127.7 (C),
128.6 (C), 129.8 (C), 129.9 (C), 133.8 (C), 138.9 (CH), 150.2 (C), 150.4
(C), 151.3 (C), 152.8 (C), 153.1 (C), 153.2 (C), 153.3 (C), 153.5 (C). IR
(ATR, cmꢀ1): ṽ¼3070 (w), 2996 (m), 2934 (w), 2832 (w), 1586 (w),
1531 (w), 1497 (s), 1456 (s), 1415 (m), 1361 (m), 1308 (m), 1272 (s),
1214 (s), 1177 (s), 1148 (m), 1095 (m),1049 (s), 1022 (s), 861 (m), 803
(s), 755 (m), 722 (m), 696 (m), 681 (m), 666 (m), 600 (w), 504 (w),
480 (w), 404 (w). GCeMS (EI, 70 eV): m/z (%): 522 (Mþ, 18), 521
(48), 520 (11), 492 (30), 491 (23), 490 (74), 487 (31), 486 (100), 484
(5), 460 (9), 456 (11), 446 (5), 430 (9), 388 (18), 387 (15), 386 (61),
385 (9), 384 (26), 261 (14), 228 (3), 220 (5), 213 (5), 205 (5), 187 (3),
ꢀ
ꢀ
ꢀ
Eur. J. Org. Chem. 2009, 4199e4209; (b) Mongin, F.; Queguiner, G. Tetrahedron
2001, 57, 4059e4090; (c) Manolikakes, S. M.; Barl, N. M.; Samann, C.; Knochel, P.
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€
12. (a) Bera, M. K.; Hommes, P.; Reissig, H.-U. Chem.dEur. J. 2011, 17, 11838e11843;
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2007, 17, 2643e2648.
176 (5), 161 (3). HRMS (EI, 70 eV): calcd for C29H28ClNO6 (Mþ):
37
521.15997, found 521.15991 and calcd for C
523.15702, found 523.15832.
H
ClNO6 (Mþ):
29 28
Acknowledgements
13. (a) Rossi, R.; Bellina, F.; Lessi, M. Adv. Synth. Catal. 2012, 354, 1181e1255; (b)
Financial support by the state Mecklenburg-Vorpommern
(scholarship of the Interdisciplinary faculty of the University of
Rostock/Dept. LL&M for S.R.) is gratefully acknowledged. Further-
more we would like to thank Prof. R. Ludwig (IfCh University of
€
Schroter, S.; Stock, C.; Bach, T. Tetrahedron 2005, 61, 2245e2267; (c) Fairlamb, I.
J. S. Chem. Soc. Rev. 2007, 36, 1036e1045.
14. (a) Dang, T. T.; Villinger, A.; Langer, P. Adv. Synth. Catal. 2008, 350, 2109e2128;
(b) Tengho Toguem, S.-M.-; Knepper, I.; Ehlers, P.; Dang, T. T.; Patonay, T.;
Langer, P. Adv. Synth. Catal. 2012, 354, 1819e1828; (c) Hung, T. Q.; Dang, T. T.;
Villinger, A.; Sung, T. V.; Langer, P. Org. Biomol. Chem. 2012, 10, 9041e9044; (d)
Malik, I.; Ahmed, Z.; Reimann, S.; Ali, I.; Villinger, A.; Langer, P. Eur. J. Org. Chem.
€
Rostock) and Prof. O. Kuhn (IfPh University of Rostock) for scientific
discussion.

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tallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
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