New shelf-stable halo- and alkoxy-substituted pyridylboronic acids and their suzuki cross-coupling reactions to yield heteroarylpyridines

Article abstract of DOI:10.1055/s-2003-39158

New shelf-stable pyridylboronic acids have been synthesized: bromine-lithium exchange followed by reaction with triisopropylborate (TIPB) yielded 2-fluoro-5-pyridylboronic acid (4), 3-bromo-5-pyridylboronic acid (5) and 2-ethoxy-5-pyridylboronic acid (6);

Full text of DOI:10.1055/s-2003-39158

PAPER
1035
New Shelf-Stable Halo- and Alkoxy-Substituted Pyridylboronic Acids and
their Suzuki Cross-Coupling Reactions to Yield Heteroarylpyridines
Shelf-Stable
H
a
alo- and
A
u
l
tuted Pyridylb
R
oronic
A
cids . Parry,a Martin R. Bryce,*a Brian Tarbitb
a
Department of Chemistry, University of Durham, Durham, DH1 3LE, England
E-mail: m.r.bryce@durham.ac.uk
b
Seal Sands Chemicals Ltd., Seal Sands, Middlesbrough, Cleveland, TS2 1UB, England
Received 6 January 2003
suitable partners in Suzuki cross-coupling reactions. Dur-
ing the preparation of this manuscript, Rault et al. reported
similar syntheses of 410 and 511 and used each of them in
a cross-coupling reaction different from those reported
Abstract: New shelf-stable pyridylboronic acids have been synthe-
sized: bromine–lithium exchange followed by reaction with triiso-
propylborate (TIPB) yielded 2-fluoro-5-pyridylboronic acid (4), 3-
bromo-5-pyridylboronic acid (5) and 2-ethoxy-5-pyridylboronic
acid (6); directed lithiation followed by reaction with trimethylbo- herein.
rate (TMB) or TIPB afforded 2-methoxy-3-pyridylboronic acid (8),
Bromine–lithium exchange reactions on 2-fluoro-5-bro-
3-bromo-6-methoxy-4-pyridylboronic acid (11) and 3-bromo-6-
ethoxy-4-pyridylboronic acid (12). Cross-coupling of pyridylbo-
ronic acids 4, 6, 8, and 11 with 3-bromoquinoline [Cs2CO3,
Pd(PPh3)2Cl2, 1,4-dioxane, 95 °C] gave pyridinylquinoline deriva-
tives 13, 15–17 in 50–77% yields: the analogous reaction of 5 was
low yielding due to further in situ reactions of the product 14. Cross-
coupling of 12 with 2-bromo-5-nitrothiophene gave 3-bromo-4-(5-
nitro-2-thienyl)-6-ethoxypyridine (18).
mopyridine (1), 3,5-dibromopyridine (2) and 2-ethoxy-5-
bromopyridine (3) were performed in diethyl ether or tet-
rahydrofuran at –78 °C using butyllithium, followed by
reaction with TIPB and aqueous workup, to afford 2-fluo-
ro-5-pyridylboronic acid (4) (51% yield), 3-bromo-5-py-
ridylboronic acid (5) (74% yield) and 2-ethoxy-5-
pyridylboronic acid (6) (61% yield) (Scheme 1).
Key words: pyridine, boronic acids, cross-coupling, Suzuki reac-
tion, heterobiaryl
In the context of biaryl and heterobiaryl synthesis, metal-
mediated cross-coupling reactions continue to be of para-
mount importance.1 Within this field the Suzuki–Miyaura
protocol for palladium-catalyzed cross-coupling of aryl/
heteroaryl boronic acids (or esters) with aryl/heteroaryl
halides (or triflates) is particularly versatile.2 Although the
use of halopyridines as cross-coupling partners is wide-
spread,1a,3 far fewer reactions of pyridylboronic acids (or
esters) have been reported.3a,4 This is no doubt partly due
to the difficulties in purification of the parent pyridylbo-
ronic acids5 which are highly polar molecules and are wa-
ter-soluble (especially 2-pyridylboronic acid which
readily deboronates)6 although a new and efficient synthe-
sis of 3-pyridylboronic acid has been published.7 3-Py-
ridylboronic acid8 and 4-pyridylboronic acid9 have also
been used as bifunctional ligands in the assembly of poly-
nuclear metal complexes, coordinating through N and O
atoms.
Scheme 1
An alternative strategy involving directed metallation14
was applied for the synthesis of pyridylboronic acid deriv-
atives 8, 11, and 12. Thus, reaction of 2-methoxypyridine
7 with LDA in THF at 0 °C15 followed by addition of tri-
methylborate (TMB) and aqueous workup gave 2-meth-
oxy-3-pyridylboronic acid (8) (13% yield) (Scheme 2).
Numerous attempts to improve the yield of 8 using the
same protocol at –78 °C with lithiation in the presence of
TMB, or with prior addition of TMB, were unsuccessful.
2-Methoxy- and 2-ethoxy-5-bromopyridine (9 and 10),
respectively, were lithiated at C(4) by reaction with LDA
in THF at –78 °C,16 and then treated with triisopropylbo-
rate (TIPB) to afford 3-bromo-6-methoxy-4-pyridylbo-
ronic acid (11) (39% yield) and 3-bromo-6-ethoxy-4-
pyridylboronic acid (12) (23% yield) respectively
(Scheme 3). All the boronic acids 4–6, 8, 11, and 12 were
isolated as shelf-stable solids after straightforward work-
up procedures.17
Recent attention has been directed towards functionalized
pyridylboronic acids and esters, especially halogenated
derivatives which are shelf-stable.10–13 For example, 2-
bromo- and 2-chloro-5-pyridylboronic acids have been
synthesized independently by Rault et al.10 and by our-
selves.11 We now report new halo- and alkoxy-pyridylbo-
ronic acids 4–6, 8, 11, and 12, and establish that they are
To confirm their suitability as partners in cross-coupling
reactions, pyridylboronic acids 4–6, 8, and 11 were each
treated with 3-bromoquinoline using caesium carbonate
as base and bis(triphenylphosphino)palladium dichloride
as catalyst in 1,4-dioxane at 95 °C to give the correspond-
Synthesis 2003, No. 7, Print: 20 05 2003.
Art Id.1437-210X,E;2003,0,07,1035,1038,ftx,en;P00103SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

1036
P. R. Parry et al.
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ed with 2-bromo-5-nitrothiophene under the same
conditions to give product 18 (44% yield) (Scheme 7).
Scheme 2
Scheme 7
In summary, this paper describes new shelf-stable py-
ridylboronic acid derivatives which should prove to be
versatile as bifunctional ligands for metal complex-
ation,8,9 and reagents for the synthesis of arylpyridine and
heteroarylpyridine systems of importance as pharmaceu-
tical and agrochemical compounds1 and optoelectronic
materials.3c,18 The bromo and/or alkoxy substituents on
the pyridine ring of products 15–18 offer scope for further
synthetic transformations.
Scheme 3
ing pyridinylquinoline products (Schemes 4–6). Com-
pounds 13 and 15–17 were isolated in synthetically useful
yields (50–77%); the low yield (8%) of product 14 ob-
tained from the boronic acid 5 is due to the formation of
numerous other products (TLC evidence) which probably
arise from further couplings of the reactive bromine sub-
stituent of 14. No such couplings were observed with 17
and 18, presumably due to the steric effect of the hetero-
cyclic substituent adjacent to the bromine.
2-Fluoro-5-pyridylboronic Acid (4)
To a solution of 2-fluoro-5-bromopyridine (1) (599 mg, 3.4 mmol)
and TIPB (1.3 g, 6.9 mmol) in anhyd THF (10 mL) at –78 °C was
added n-BuLi (1.6 M in hexane, 2.2 mL, 3.5 mmol) dropwise. The
reaction mixture was stirred for 4 h at –78 °C then quenched with
H2O (10 mL) and allowed to warm to 20 °C with stirring overnight.
The solvent was evaporated in vacuo and the aqueous layer was tak-
en to pH 10 with 5% NaOH and was then washed with Et2O. The
aqueous layer was then acidified to pH 4 with 48% aq HBr to pre-
cipitate compound 4 as a white solid (245 mg, 51%); mp 170–171
°C (lit.8 172 °C).
1H NMR [(CD3)2C(O)–TMS]: δ = 8.52 (d, 1 H, J = 2.0 Hz), 8.41 (s,
2 H, OH), 8.25 (m, 1 H), 7.13 (m, 1 H).
13C NMR [(CD3)2C(O)–TMS]: δ = 166.39, 164.49, 154.08, 153.97,
147.54, 147.48, 108.91, 108.62.
Scheme 4
Anal. Calcd for C5H5BFNO2 (140.9): C, 42.62; H, 3.58; N, 9.94.
Found: C, 42.32; H, 3.57; N, 9.81.
3-Bromo-5-pyridylboronic Acid (5)
To a solution of 3,5-dibromopyridine (2) (2.0 g, 8.4 mmol) in anhyd
Et2O (30 mL) at –78 °C was added n-BuLi (1.6 M in hexane, 6.0
mL, 10.0 mmol) dropwise. The reaction mixture was stirred for 2 h
at –78 °C. TIPB (3.3 g, 17.3 mmol) was then added quickly. The re-
action mixture was stirred for 2 h at –78 °C, allowed to warm to 20
°C and quenched with H2O (50 mL). After stirring overnight, work-
up as described for 4 gave 5 as a hygroscopic white solid (1.3 g,
74%); mp >300 C (lit.9 210 °C, dec.).
Scheme 5
1H NMR [(CD3)2S(O)–TMS]: δ = 8.80 (d, 1 H, J = 1.4 Hz), 8.68 (d,
1 H, J = 2.4 Hz), 8.56 (s, 2 H, OH), 8.24 (m, 1 H).
13C NMR [(CD3)2S(O)–TMS]: δ = 153.76, 152.15, 144.79, 121.38.
Anal. Calcd for C5H5BBrNO2 (201.8): C, 29.76; H, 2.50; N, 6.49.
Found: C, 29.48; H, 1.75; N, 6.77.
Scheme 6
2-Ethoxy-5-pyridylboronic Acid (6)
Following the procedure used for compound 5, 2-ethoxy-5-bro-
mopyridine (3) (200 mg, 1.0 mmol), Et2O (5 mL), n-BuLi (1.6 M in
hexane, 0.6 mL, 1.0 mmol) and TIPB (375 mg, 2.0 mmol) gave 6 as
a white solid (101 mg, 61%); mp 131–134 °C.
To establish the scope for using alternative heteroarylbro-
mides in the coupling reactions, boronic acid 12 was treat-
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Shelf-Stable Halo- and Alkoxy-Substituted Pyridylboronic Acids
1037
1H NMR [(CD3)2C(O)–TMS]: δ = 8.59 (d, 1 H, J = 1.8 Hz), 8.03
(dd, 1 H, J = 2.1, 1.8 Hz), 7.18 (s, 2 H, OH), 6.69 (d, 1 H, J = 8.1
Hz), 4.35 (q, 2 H, J = 4.2 Hz), 1.33 (t, 3 H, J = 5.1 Hz).
13C NMR [(CD3)2C(O)–TMS]: δ = 165.56, 153.79, 144.38, 110.16,
61.25, 14.27.
3-(6-Fluoro-pyridin-3-yl)-quinoline (13)
Compound 4 (100 mg, 0.7 mmol), 3-bromoquinoline (199 mg, 1.0
mmol), Pd(PPh3)2Cl2 and Cs2CO3 in dioxane were reacted accord-
ing to the general procedure. The reaction was complete in 67 h. Pu-
rification by column chromatography (CH2Cl2–EtOAc, 1:1) gave
compound 13 as a white solid (91 mg, 57%); mp 126–127 °C.
1H NMR [(CD3)2C(O)–TMS]: δ = 9.12 (d, 1 H, J = 2.4 Hz), 8.60
(m, 1 H), 8.52 (d, 1 H, J = 2.0 Hz), 8.34 (m, 1 H), 7.95 (m, 2 H),
7.68 (m, 1 H), 7.54 (m, 1 H), 7.17 (m, 1 H).
Anal. Calcd for C7H10BFNO2 (167.0): C, 50.35; H, 6.04; N, 8.39.
Found: C, 50.09; H, 6.10; N, 8.26.
2-Methoxy-3-pyridylboronic Acid (8)
To a solution of 2-methoxypyridine (7) (1.2 mL, 11.4 mmol) in an-
hyd THF (10 mL) at 0 °C was added LDA (2.0 M in heptane–THF–
ethylbenzene, 6.9 mL, 13.8 mmol) dropwise. The reaction mixture
was stirred for 3 h at –78 °C, then TMB (2.4 g, 23.2 mmol) was add-
ed dropwise. The mixture was allowed to warm to 20 °C, quenched
with H2O (10 mL) and stirred overnight. Workup as for compound
4 gave 8 as a white solid (235 mg, 13%); mp 143–145 °C.
13C NMR [(CD3)2C(O)–TMS]: δ = 164.94, 162.58, 149.43, 147.99,
146.60, 146.45, 140.86, 140.78, 133.67, 132.25, 132.21, 130.00,
129.77, 129.42, 128.57, 128.09, 127.43, 110.16, 109.78.
Anal. Calcd C14H9FN2 (224.2): C, 74.99; H, 4.05; N, 12.49, Found:
C, 74.54; H, 4.16; N, 12.38.
MS(EI): m/z (%) = 224 (M+, 100).
1H NMR [(CD3)2C(O)–TMS]: δ = 8.24 (dd, 1 H, J = 2.1, 2.1 Hz),
8.12 (dd, 1 H, J = 2.1, 1.8 Hz), 7.10 (s, 2 H, OH), 7.00 (m, 1 H),
3.99 (s, 3 H).
13C NMR [(CD3)2C(O)–TMS]: δ = 168.26, 150.09, 146.70, 118.08,
53.56.
3-(5-Bromo-pyridin-3-yl)-quinoline (14)
Compound 5 (100 mg, 0.4 mmol), 3-bromoquinoline (153 mg, 0.7
mmol), Pd(PPh3)2Cl2 and Cs2CO3 in dioxane were reacted accord-
ing to the general procedure. The reaction was complete in 68 h. Pu-
rification by column chromatography (EtOAc–CH2Cl2, 7:3) gave
compound 14 as a white solid (11 mg, 8%); mp 180–182 °C.
1H NMR (CDCl3–TMS): δ = 9.07 (s, 1 H), 8.86 (s, 1 H), 8.71 (s, 1
H), 8.27 (s, 1 H), 8.11 (d, 2 H, J = 8.0 Hz), 7.86 (d, 1 H, J = 8.5 Hz),
7.73 (t, 1 H, J = 7.0 Hz), 7.58 (t, 1 H, J = 7.5 Hz).
Anal. Calcd for C6H8BNO3 (152.9): C, 47.12; H, 5.27; N, 9.16,
Found: C, 46.78; H, 5.18; N, 8.94.
3-Bromo-6-methoxy-4-pyridylboronic Acid (11)
To a solution of 5-bromo-2-methoxypyridine (9) (727 mg, 3.9
mmol) in anhyd THF (10 mL) at –78 °C was added LDA (2.0 M in
heptane–THF–ethylbenzene, 2.0 mL, 4.0 mmol) dropwise. The re-
action mixture was stirred for 1 h at –78 °C, then TIPB (1.5 g, 7.8
mmol) was added dropwise. The mixture was stirred for 1 h at –78
°C then quenched with H2O (10 mL) and allowed to warm to 20 °C
overnight. Workup as for compound 4 gave 11 as a white solid (351
mg, 39%); mp 97–99 °C.
1H NMR [(CD3)2C(O)–TMS]: δ = 8.16 (s, 1 H), 7.76 (s, 2 H, OH),
6.84 (s, 1 H), 3.85 (s, 3 H)
13C NMR [(CD3)2C(O)–TMS]: δ = 162.79, 147.44, 115.67, 114.92,
53.17.
13C NMR (CDCl3–TMS): δ = 149.20, 147.79, 146.87 (2 C), 145.44,
136.12, 133.10, 129.39, 128.38 (3 C), 127.11, 126.60 (2 C).
MS (EI): m/z (%) = 284 (M+, 100%).
HRMS: m/z calcd for C14H9BrN2, 283.99491; found, 283.99310.
3-(6-Ethoxy-pyridin-3-yl)-quinoline (15)
Compound 6 (12 mg, 0.07 mmol), 3-bromoquinoline (21 mg, 0.1
mmol), Pd(PPh3)2Cl2 and Cs2CO3 in dioxane were reacted accord-
ing to the general procedure. The reaction was complete in 63 h. Pu-
rification by column chromatography (CH2Cl2–EtOAc, 9:1) gave
compound 15 as a white solid (10 mg, 59%); mp 104–105 °C.
1H NMR [(CD3)2C(O)–TMS]: δ = 9.21 (d, 1 H, J = 2.5 Hz), 8.63 (d,
1 H, J = 2.0 Hz), 8.54 (d, 1 H, J = 2.0 Hz), 8.16 (dd, 1 H, J = 2.8,
2.5 Hz), 8.05 (m, 2 H), 7.76 (m, 1 H), 7.64 (m, 1 H), 6.93 (d, 1 H,
J = 8.0 Hz), 4.43 (q, 2 H, J = 7.0 Hz), 1.39 (t, 3 H, J = 7.0 Hz).
Anal. Calcd for C6H7BBrNO3 (231.8): C, 31.08; H, 3.04; N, 6.04.
Found: C, 31.09; H, 2.90; N, 6.00.
3-Bromo-6-ethoxy-4-pyridylboronic Acid (12)
13C NMR [(CD3)2C(O)–TMS]: δ = 164.95, 150.34, 148.58, 146.66,
138.81, 133.38, 131.82 (2C), 130.36 (2C), 129.30, 128.11, 127.87,
122.31, 62.62, 15.18
Following the procedure used for compound 12, 5-bromo-2-ethox-
ypyridine (10) (261 mg, 1.3 mmol), THF (10 mL) and LDA (2.0 M
in heptane–THF–ethylbenzene, 0.8 mL, 1.5 mmol) gave 12 as a
white solid (74 mg, 23%); mp 103–105 °C.
MS(EI): m/z (%) = 250 (M+, 55), 235 (100).
1H NMR [(CD3)2C(O)–TMS]: δ = 8.15 (s, 1 H), 7.70 (s, 2 H, OH),
6.81 (s, 1 H), 4.30 (q, 2 H, J = 7.2 Hz), 1.32 (t, 3 H, J = 6.8 Hz).
HRMS: m/z calcd for C16H14N2O, 250.11061; found, 250.11059.
13C NMR [(CD3)2C(O)–TMS]: δ = 162.48, 147.45, 115.86, 114.67,
3-(2-Methoxy-pyridin-3-yl)-quinoline (16)
Compound 8 (100 mg, 0.7 mmol), 3-bromoquinoline (153 mg, 0.7
mmol), Pd(PPh3)2Cl2 and Cs2CO3 in dioxane were reacted accord-
ing to the general procedure. The reaction was complete in 95 h. Pu-
rification by column chromatography (CH2Cl2–EtOAc, 1:1) gave
compound 15 as a white solid (86 mg, 77%); mp 89–90 °C.
1H NMR [(CD3)2C(O)–TMS]: δ = 9.12 (d, 1 H, J = 2.0 Hz), 8.48 (d,
1 H, J = 2.0 Hz), 8.26 (dd, 1 H, J = 2.0, 2.0 Hz), 8.08 (m, 1 H), 8.01
(m, 1 H), 7.95 (dd, 1 H, J = 2.0, 2.0 Hz), 7.78 (m, 1 H), 7.64 (m, 1
H), 7.16 (m, 1 H), 3.98 (s, 3 H).
61.72, 14.15
Anal. Calcd for C7H9BBrNO3 (245.9): C, 34.20; H, 3.69; N, 5.70.
Found: C, 34.90; H, 3.25; N, 5.90.
Cross-Coupling Reactions; General Procedure
The boronic acid (1.0 equiv.), 3-bromoquinoline (or for compound
18 2-bromo-5-nitrothiophene) (1.2–1.8 equiv), and Pd(PPh3)2Cl2 (5
mol%) were sequentially added to degassed 1,4-dioxane (10 mL)
and the mixture was stirred at 20 °C for 30 min. Degassed aqueous
Cs2CO3 solution (1 M, 3.0 equiv) was added and the reaction mix-
ture was heated under nitrogen at 95 °C until TLC monitoring
showed that the reaction had finished. Solvent was removed in vac-
uo then EtOAc was added and the organic layer was washed with
brine, separated, and dried over MgSO4. The product was purified
by chromatography on a silica gel column.
13C NMR [(CD3)2C(O)–TMS]: δ = 161.21, 151.35, 147.52, 147.03,
139.33, 135.42, 130.25, 129.64, 129.33, 128.44, 128.06, 127.00,
121.40, 117.77, 53.21.
MS(EI): m/z (%) = 236 (M+, 100).
HRMS: m/z calcd for C15H12N2O, 236.09496; found, 236.09500.
Synthesis 2003, No. 7, 1035–1038 ISSN 0039-7881 © Thieme Stuttgart · New York

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P. R. Parry et al.
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3-(5-Bromo-2-methoxy-pyridin-4-yl)-quinoline (17)
Horsburgh, L. E.; Sheridan, A. K.; Monkman, A. P.; Samuel,
I. D. W. Adv. Mater. 2000, 12, 217. (d)Ng, S.-C.;Lu, H.-F.;
Chan, H. S. O.; Fujii, A.; Laga, T.; Yoshino, K. Adv. Mater.
2000, 12, 1122. (e) Wang, C.; Kilitziraki, M.; Palsson,
L.-O.; Bryce, M. R.; Monkman, A. P.; Samuel, I. D. W. Adv.
Funct. Mater. 2001, 11, 47. (f) Feuerstein, M.; Laurenti, D.;
Bougeant, C.; Doucet, H.; Santelli, M. Chem. Commun.
2001, 325. (g) Monkman, A. P.; Palsson, L.-O.; Higgins, R.
W. T.; Wang, C.; Bryce, M. R.; Batsanov, A. S.; Howard, J.
A. K. J. Am. Chem. Soc. 2002, 124, 6049.
Compound 11 (100 mg, 0.4 mmol), 3-bromoquinoline (123 mg, 0.6
mmol), Pd(PPh3)2Cl2 and Cs2CO3 in dioxane were reacted accord-
ing to the general procedure. The reaction was complete in 98 h. Pu-
rification by column chromatography (CH2Cl2–EtOAc, 9:1) gave
compound 17 as a white solid (68 mg, 50%); mp 120–123 °C.
1H NMR [(CD3)2C(O)–TMS]: δ = 9.14 (d, 1 H, J = 2.0 Hz), 8.54 (d,
1 H, J = 2.4 Hz), 8.33 (d, 1 H, J = 2.8 Hz), 8.12 (d, 1 H, J = 2.4 Hz),
8.09 (m, 1 H), 8.03 (m, 1 H), 7.81 (m, 1 H), 7.65 (m, 1 H), 3.99 (s,
3 H).
(4) (a) Thompson, W. J.; Jones, J. H.; Lyle, P. A.; Thies, J. E. J.
Org. Chem. 1988, 53, 2052. (b) Oh-e, T.; Miyaura, N.;
Suzuki, A. J. Org. Chem. 1993, 58, 2201. (c) Li, J. J.; Yue,
W. S. Tetrahedron Lett. 1999, 40, 4507. (d) Lehmann, U.;
Henze, O.; Schlüter, A. D. Chem.–Eur. J. 1999, 5, 854.
(5) Fischer, F. C.; Havinger, E. Recl. Trav. Chim. Pays-Bas
1965, 84, 439.
13C NMR [(CD3)2C(O)–TMS]: δ = 160.32, 151.04, 147.73, 147.17,
141.32, 135.92, 130.01, 129.35, 128.81, 128.57, 127.94, 127.15,
123.56, 112.09, 53.78.
MS(EI): m/z (%) = 314 (M+, 100).
HRMS: m/z calcd for C15H11BrN2O, 314.00547; found, 314.00539.
(6) Fischer, F. C.; Havinger, E. Recueil 1974, 93, 21.
(7) (a) Cai, D.; Larsen, R. D.; Reider, P. J. Tetrahedron Lett.
2002, 43, 4285. (b) Li, W.; Nelson, D. J.; Jensen, M. S.;
Hoerrner, R. S.; Cai, D.; Larsen, R. D.; Reider, P. J. J. Org.
Chem. 2002, 67, 5394. (c) Matondo, H.; Ouhaja, N.; Souirti,
S.; Baboulène, M. Main Group Metal Chem. 2002, 25, 163;
this article states that 2-pyridylboronic acid and 3-
pyridylboronic acid have been obtained from the
corresponding pyridyl Grignard reagent and
trimethylsilylborate although details are not given.
(8) Droes, R.; Nardin, G.; Randaccio, L.; Tauzher, G.; Vuano, S.
Inorg. Chem. 1997, 36, 2463.
(9) Dreos, R.; Nardin, G.; Randaccio, L.; Siega, P.; Tauzher, G.;
Vrdoljak, V. Inorg. Chem. 2001, 40, 5536.
3-Bromo-4-(5-nitro-2-thienyl)-6-ethoxypyridine (18)
Compound 12 (20 mg, 0.08 mmol), 2-bromo-5-nitrothiophene (20
mg, 0.1 mmol), Pd(PPh3)2Cl2 and Cs2CO3 in dioxane were reacted
according to the general procedure. The reaction was complete in 59
h. Purification by column chromatography (CH2Cl2) gave com-
pound 18 as a yellow solid (11 mg, 44%); mp 84–86 °C.
1H NMR [(CD3)2C(O)–TMS]: 8.32 (s, 1 H), 7.99 (d, 1 H, J = 4.0
Hz), 7.51 (d, 1 H, J = 4.5 Hz), 6.96 (s, 1 H), 4.25 (q, 2 H, J = 4.5
Hz), 1.24 (t, 3 H, J = 7.0 Hz).
13C NMR [(CD3)2C(O)–TMS]: δ = 163.80, 152.95, 150.44, 145.21,
142.44, 129.32, 129.00, 112.96, 110.31, 62.57, 14.10.
HRMS: m/z calcd for C11H9BrN2O3S, 327.95173; found,
327.95169.
(10) Bouillon, A.; Lancelot, J.-C.; Collot, V.; Bovy, P. R.; Rault,
S. Tetrahedron 2002, 58, 2885.
(11) Bouillon, A.; Lancelot, J.-C.; Collot, V.; Bovy, P. R.; Rault,
S. Tetrahedron 2002, 58, 3323.
Acknowledgement
(12) Bouillon, A.; Lancelot, J.-C.; Collot, V.; Bovy, P. R.; Rault,
S. Tetrahedron 2002, 58, 4368.
We thank Seal Sands Chemicals Ltd. for funding this work.
(13) Parry, P. R.; Wang, C.; Batsanov, A. S.; Bryce, M. R.;
Tarbit, B. J. Org. Chem. 2002, 67, 7541.
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(b) Anctil, E. J.-G.; Snieckus, V. J. Organomet. Chem. 2002,
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(15) Comins, D. L.; LaMunyon, D. H. Tetrahedron Lett. 1998,
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(1) (a) Review: Stanforth, S. P. Tetrahedron 1998, 54, 263.
(b) Suzuki, A. In Metal-Catalyzed Cross-Coupling
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(17) Compounds 5 and 12 could not be obtained analytically
pure. As noted by other workers,7,9 it is not unusual for
arylboronic acids to give unsatisfactory elemental analysis.
This can arise if they are hygroscopic or exist as a mixture of
the free acid and the anhydride.
(18) Shirota, Y. J. Mater. Chem. 2000, 10, 1.
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