Cobalt-catalyzed cross-coupling between in situ prepared arylzinc halides and 2-chloropyrimidine or 2-chloropyrazine

Article abstract of DOI:10.1021/jo900240d

A cobalt-catalyzed cross-coupling of aryl halides with 2-chloropyrimidines or 2-chloropyrazines is reported in satisfactory to high yields. The key step of this procedure is the formation of aromatic organozinc reagents and their coupling with 2-chlorodia

Full text of DOI:10.1021/jo900240d

SCHEME 1. Direct Electrochemical Coupling Reaction
Cobalt-Catalyzed Cross-Coupling Between In
Situ Prepared Arylzinc Halides and
2-Chloropyrimidine or 2-Chloropyrazine
Jeanne-Marie Be´gouin† and Corinne Gosmini*,‡
Institut de Chimie et des Mate´riaux Paris Est, ICMPE,
CNRS-UniVersite´ Paris 12 Val de Marne, UMR7182, 2-8 rue
Henri Dunant, 94320 Thiais, France, and Laboratoire
“He´te´roe´le´ments et Coordination” Ecole Polytechnique,
CNRS, 91128 Palaiseau Cedex, France
electrochemical coupling reaction between functionalized aryl-
halides and 2-halo-pyrimidines or -pyrazines leading to 2-arylpy-
rimidines and 2-arylpyrazines (Scheme 1).3 However, electro-
chemical reactions are generally considered as being more
difficult to handle than conventional methods and electrochemi-
cal synthesis are rarely applied by organic chemists in a larger
scale. Thus, functionalized arylpyrimidines and arylpyrazines
are, in practical terms, the most often obtained using palladium
or nickel-catalyzed cross-coupling reactions involving stoichio-
metric organometallic reagents such as organomagnesium,
organozinc, organoboron (organoboronic acids and organotri-
fluoroborates), or organostannanes compounds.4 In these cross-
coupling protocols, the major difficulty lies in the preparation
of the organometallic reagent and more particularly in the case
of functionalized derivatives. Although significant advances have
been achieved, the development of new access to functionalized
aryldiazines is still a major challenge. Very recently, the
arylation of electron-deficient nitrogen heterocycles with io-
doarenes promoted by potassium terbutoxide was described
without the addition of any exogenous transition metal species.5
However, poor regioselectivity has been observed with respect
to the heteroarene. Recently, we have devised an expedient route
to functionalized biaryl and heteroaryl-aryl compounds on the
basis of cobalt catalysis associated to PPh3 as ligand.6 This
combination generates an extremely powerful catalyst for the
coupling of a large variety of aromatic reagents. However, this
protocol cannot be applied to 2-chloropyrimidine and 2-chlo-
ropyrazine as coupling partners.
corinne.gosmini@polytechnique.edu
ReceiVed February 3, 2009
A cobalt-catalyzed cross-coupling of aryl halides with
2-chloropyrimidines or 2-chloropyrazines is reported in
satisfactory to high yields. The key step of this procedure is
the formation of aromatic organozinc reagents and their
coupling with 2-chlorodiazines using the same cobalt halide
as catalyst and Zn dust under mild reaction conditions. This
new cobalt-catalyzed coupling reaction represents a practical
and interesting alternative to previously known methods for
the synthesis of 2-aryldiazines.
Alternatively, the use of cobalt as a highly reactive catalyst
for carbon-carbon forming reaction has also been demonstrated
by Cahiez,7 Knochel,8 Oshima,9 Cheng,10 and our group.11
In 2003, our group has described a very easy method to access
to substituted organozinc reagents (Scheme 2) from correspond-
ing aryl halides using CoBr2 catalysis. Aryl bromides or iodides
can be efficiently converted to the corresponding organozinc
Aryldiazines, particularly those bearing functional groups,
have been shown to possess interesting properties in pharmacol-
ogy, agrochemical, supramolecular chemistry, and material
science.1 Then, during the last decades, some research groups
have directed their work toward the development of new
synthetic methodologies. Some strategies are based on the
generation of the heterocyclic ring using ring closure reactions.2
However, these methods generally require rather high reaction
temperatures and suffer from a poor functional group tolerance.
A few years ago, our group developed a direct nickel-catalyzed
(3) Gosmini, C.; Nedelec, J. Y.; Pe´richon, J. Tetrahedron Lett. 2000, 41,
201–203.
(4) (a) Bonnet, V.; Mongin, F.; Tre´court, F.; Que´guiner, G.; Knochel, P.
Tetrahedron 2002, 58, 4429–4438. (b) Mongin, F.; Mojovic, L.; Guillamet, B.;
tre´court, F.; Que´guiner, G. J. Org. Chem. 2002, 67, 8991–8994. (c) Molander,
G. A.; Biolatto, B. J. Org. Chem. 2003, 68, 4302–4314. (d) Billingsley, K.;
Buchwald, S. L. J. Am. Chem. Soc. 2007, 129, 3358–336. (e) Ceide, S. C.;
Montalban, A. G. Tetrahedron Lett. 2006, 47, 4415–4418. (f) Dawood, K. M.;
Kirschning, A. Tetrahedron 2005, 61, 12121–12130. (g) Darabantu, M.; Boully,
L.; Turck, A.; Ple´, N. Tetrahedron 2005, 61, 2897–2905. (h) Itami, K.; Yamazaki,
D.; Yoshida, J.-I. J. Am. Chem. Soc. 2004, 126, 15396–15397. (i) Yanagisawa,
S.; Ueda, K.; Taniguchi, T.; Itami, K. Org. Lett. 2008, 10, 4673–4676. (j) Seggio,
A.; Jutand, A.; Priem, G.; Mongin, F. Synlett 2008, 2955, 2960. (k) Alacid, E.;
Na´jera, C. Org. Lett. 2008, 10, 5011–5014.
(5) Yanagisawa, S.; Ueda, K.; Taniguchi, T.; Itami, K. Org. Lett. 2008, 10,
4673–4676.
(6) Amatore, M.; Gosmini, C. Angew. Chem., Int. Ed 2008, 47, 2089–2092.
(7) Cahiez, G.; Chaboche, C.; Duplais, C.; Giulliani, A.; Moyeux, A. AdV.
Synth. Catal. 2008, 350, 1484–1488. (b) Cahiez, G.; Avedissian, H. Tetrahedron
Lett. 1998, 39, 6159–6162.
† ICMPE.
‡ CNRS.
(1) (a) Katritsky, A. R.; Rees, C. W. ComprehensiVe Heterocyclic Chemistry;
Pergamon: New York, 1984; Vol. 2. (b) Que´guiner, G.; Marsais, F.; Snieckus,
V.; Epsztajn, J. AdV. Heterocycl. Chem. 1991, 52, 187–304. (c) Mongin, F.;
Que´guiner, G. Tetrahedron 2001, 57, 4059–4090. (d) Turck, A.; Ple´, N.; Mongin,
F.; Que´guiner, G. Tetrahedron 2001, 57, 4489–4505.
(2) (a) Wang, T.; Cloudsdale, I. S. Synth. Commun. 1997, 27, 2521–2526.
(b) Hill, M. D.; Movassaghi, M. Chem.sEur. J. 2008, 683, 6–6844. (c) Bhatti,
I. A.; Busby, R. E.; bin Mohamed, M.; Parrick, J.; Shaw, C. J. G. J. Chem. Soc.,
Perkin Trans. 1 1997, 24, 3581–3586. (d) Cesar, J. J. Comb. Chem. 2005, 7,
517–519.
10.1021/jo900240d CCC: $40.75
Published on Web 03/23/2009
2009 American Chemical Society
J. Org. Chem. 2009, 74, 3221–3224 3221

TABLE 1. Cross-Coupling Reaction between 2-Chloropyrimidine
and Aryl Bromides or Aryl Iodides
SCHEME 2.
Reagents from Corresponding Arylhalides
CoBr2-Catalyzed Synthesis of Organozinc
yields vs
entry
ArX
C6H5Br
p-EtO2CC6H4Br
m-EtO2CC6H4Br
o-EtO2CC6H4Br
p-MeO2CC6H4Br
p-NCC6H4Br
reaction time (h) product No. ArX (GC) %
1
2
3
4
5
6
7
8
9
4
5
6
6
6
6
6
6
6
6
2
6
7
5
6
6
4
4
4
5
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
12
2
80 (85)
60 (70)
65 (70)
(5)
70 (80)
57 (68)
(5)
74 (80)
60 (70)
70 (80)
41 (52)
70 (85)
71 (80)
51 (71)
63 (64)
50 (52)
90 (91)
55 (60)
32 (40)
52 (60)
reagents in a single step.12 The reaction requires commercially
available zinc dust which is common activated by traces of acid
in the presence of cobalt bromide in acetonitrile at room
temperature. However, this process fails to activate less reactive
compounds such as aromatic chlorides. To circumvent the low
reactivity of aryl chlorides, a new procedure involving a cobalt
catalysis in a mixture of acetonitrile and pyridine was set up to
successfully prepare aryl zinc chlorides.13
o-NCC6H4Br
m-NCC6H4Br
p-F3CC6H4Br
10 m-F3CC6H4Br
11 p-MeCOC6H4Br
12 p-MeOC6H4Br
13 m-MeOC6H4Br
14 o-MeOC6H4Br
15 p-ClC6H4Br
16 m-ClC6H4Br
17 p-FC6H4Br
Our previous results concerning the interesting reactivity of
aryl zinc species obtained under cobalt catalysis14 led us to
surmise that 2-aryldiazines could be obtained via the cobalt-
catalyzed cross-coupling of arylzinc derivatives and 2-chloro-
pyrimides and 2-chloropyrazines under suitable conditions. The
mild reaction conditions, high chemoselectivity, and low cost
of cobalt-catalyzed cross-coupling reactions would make very
attractive this new heterocyclic reaction. Furthermore, these
reactions often require simple ligands rather than more custom-
ized, which are often used with palladium-based systems.
Herein, we wish to report a very efficient Co(II)-mediated cross-
coupling reaction devoted to the direct synthesis of 2-arylpy-
rimidines and 2-arylpyridazines using various functionalized
aromatic halides. The results of our investigations are reported
in this paper.
18 m-FC6H4Br
19 p-MeOC6H4I
20 p-EtO2CC6H4I
reported in the case of the synthesis of functionalized diaryl-
methanes, we worked out an operationally simplified Barbier-
type procedure for the synthesis of 2-arylpyrimidines due to
the lower reactivity of 2-chloropyrimidine. As previously
reported,12b the presence of allylchloride in the medium
decreases the formation of the reduction byproduct ArH in the
beginning of the reaction. The role played by this additive has
not been clarified so far. An inert atmosphere is not required in
this process as long as ArZnX is consecutively engaged in a
coupling reaction. The temperature influences the reaction rate
but not the yield. When the reaction was carried out at room
temperature for 8 h, the 2-arylpyrimidine was obtained in 70%
GC yield. The reaction rate was improved (5 h) by increasing
the reaction temperature to 50 °C.
Various 2-arylpyrimidines have been obtained using a one-
or two-step procedure, depending on the nature of the arylhalide.
With arylbromides or aryliodides, the reaction had been carried
out in the presence of the 2-chloropyrimidine at 50 °C. In these
conditions, despite the presence of the 2-chloropyrimidine, the
oxidative addition of Co(I), obtained by Co(II) reduction,
proceeds first into the C-X bond of the arylhalide, allowing
the formation of the arylzinc compound and then into the C-Cl
bond of the 2-chloropyrimidine to achieve the cross-coupling
reaction with the arylzinc halide. As the 2-chloropyrimidine is
present in the medium from the beginning of the reaction, the
arylzinc derivative is involved in the cross-coupling reaction
as soon as formed; thereby, the formation of byproduct resulting
from the reduction or the homocoupling reactions of the arylzinc
reagents is limited.
For initial studies, we first involved a two-step coupling
reaction between an aryl zinc bromide (EtOCOC6H4ZnBr) and
2-chloropyrimidine without further addition of cobalt catalyst.
In these conditions, the corresponding 2-arylpyrimidine was
obtained in good yield (80% GC yield). Then, as previously
(8) (a) Dunet, G.; Knochel, P. Synlett 2007, 1383, 1386. (b) Korn, T. J.;
Schade, M. A.; Wirth, S.; Knochel, P. Org. Lett. 2006, 8, 725–728. (c) Korn,
T. J.; Knochel, P. Angew. Chem., Int. Ed. 2005, 44, 2947–2951. (d) Reddy,
C. K.; Knochel, P. Angew. Chem., Int. Ed. 1996, 35, 1700–1701. (e) Avedissian,
H.; Berillon, L.; Cahiez, G.; Knochel, P. Tetrahedron Lett. 1998, 39, 6163–
6166.
(9) (a) Kobayashi, T.; Ohmiya, H.; Yorimitsu, H.; Oshima, K. J. Am. Chem.
Soc. 2008, 130, 11276–11277. (b) Affo, W.; Ohmiya, H.; Takuma, F.; Ikeda,
Y.; Nakamura, T.; Yorimitsu, H.; Oshima, K.; Imamura, Y.; Mizuta, T.; Miyoshi,
K. J. Am. Chem. Soc. 2006, 128, 8068–8077. (c) Ohmiya, H.; Yorimitsu, H.;
Oshima, K. Chem. Lett. 2004, 33, 1240–1241. (d) Tsuji, T.; Yorimitsu, H.;
Oshima, K. Angew. Chem., Int. Ed. 2002, 41, 4137–4139.
(10) (a) Chang, H. T.; Jeganmohan, M.; Cheng, C. H. Chem.sEur. J. 2007,
13, 4356–4363. (b) Chang, H. T.; Jayanth, T. T.; Wang, C. C.; Cheng, C. H.
J. Am. Chem. Soc. 2007, 129, 12032–12041. (c) Shukla, P.; Hsu, Y. C.; Cheng,
C. H. J. Org. Chem. 2006, 71, 655–658. (d) Wong, Y.-C.; Jayanth, T. T.; Cheng,
C.-H. Org. Lett. 2006, 8, 5613–5616. (e) Chang, K.-J.; Rayabarapu, D. K.; Cheng,
C.-H. J. Org. Chem. 2004, 69, 4781–4787. (f) Chang, K.-J.; Rayabarapu, D. K.;
Cheng, C.-H. Org. Lett. 2003, 5, 3963–3966. (g) Liu, C.-C.; Korivi, R. P.; Cheng,
C.-H. Chem.sEur. J. 2008, 14, 9503–9506. (h) Jeganmohan, M.; Cheng, C.-H.
Chem.sEur. J. 2008, 14, 10876–10886.
(11) Gosmini, C.; Be´gouin, J. M.; Moncomble, A. Chem. Commun. 2008,
3221, 3233.
(12) (a) Fillon, H.; Gosmini, C.; Pe´richon, J. J. Am. Chem. Soc. 2003, 125,
3867–3870. (b) Kazmierski, I.; Gosmini, C.; Paris, J. M.; Pe´richon, J. Tetrahedron
Lett. 2003, 44, 6417–6420.
(13) (a) Gosmini, C.; Amatore, M.; Claudel, S.; Pe´richon, J. Synlett 2005,
2171, 2174. (b) Kazmierski, I.; Gosmini, C.; Paris, J. M.; Pe´richon, J. Synlett
2006, 881, 884.
(14) (a) Amatore, M.; Gosmini, C. Chem. Commun. 2008, 5019, 5021. (b)
Kazmierski, I.; Bastienne, M.; Gosmini, C.; Paris, J. M.; Pe´richon, J. J. Org.
Chem. 2004, 69, 936–942. (c) Fillon, H.; Gosmini, C.; Pe´richon, J. Tetrahedron
2003, 59, 8199–8202.
The results obtained in acetonitrile from aryl bromides or
iodides bearing various substituents are reported in Table 1.
These results show that the expected 2-arylpyrimidines were
obtained in good yields when para- or meta-substituted aryl
bromides were used. No noticeable influence of the substituent
electronic effect was observed on the reaction parameters. To
our disappointment, except in the case of an ortho director group
3222 J. Org. Chem. Vol. 74, No. 8, 2009

TABLE 2. Cross-Coupling Reaction between 2-Chloropyrimidine
and Arylchlorides
SCHEME 3. Cross-Coupling Reaction between
2-Chloropyrimidine and 1,4-Dibromobenzene
yields vs
such as a methoxy (Table 1, entry 14), cross-coupling of aryl
halides bearing an ortho substituent resulted in poor yields of
desired product (Table 1, entries 4 and 7). However, the
formation of the arylzinc reagent took place, but no cross-
coupling reaction occurred with the 2-chloropyrimidine. Lower
yields were obtained from aryl iodides (Table 1, entries 19 and
20), probably owing to the higher reactivity of the resulting
arylzinc iodides, which favored the formation of reduction or
dimerization byproduct.
entry
ArCl
C6H5Cl
p-MeO2CC6H4Cl
m-MeO2CC6H4Cl
p-NCC6H4Cl
m-NCC6H4Cl
m-F3CC6H4Cl
p-MeCOC6H4Cl
reaction time (h) product No. ArX (GC) %
1
2
3
4
5
6
7
5
5
6
5
5
6
3
1
5
21
6
8
10
11
53 (68)
61 (70)
55 (58)
55 (61)
50 (57)
55 (60)
60 (81)
Furthermore, we noticed that, at the time of the arylzinc
formation, 4-bromoacetophenone reacted faster and gave rise
to more dimeric products that account for the shorter reaction
times (Table 1, entry 11).
SCHEME 4. Cross-Coupling Reaction between
p-Iodoanisole and 2-Chloropyrazine
The cross-coupling between ethyl para-bromobenzoate and
a functionalized chloropyrimidine such as the 4-chloro-2-
methylthiopyrimidine gave the ethyl 4-[2-(methylthio) pyrimi-
din-4-yl]benzoate (19) in 75% yield.
The cross-coupling reaction with the 1,4-dibromobenzene was
achieved with a slight modification of the reaction conditions
(Scheme 3); increasing the amount of zinc allowed the formation
of a dizinc compound that reacted with 2 equiv of 2-chloropy-
rimidine, leading to the expected disubstituted product with a
51% yield.
TABLE 3. Cross-Coupling Reaction between Arylchlorides or
Arylbromides and 2-Chloropyrazine
Modifications of the coupling reaction conditions were
required to allow the use of less reactive compounds such as
aryl chlorides. Moreover, 2-chloropyrimidine being more reac-
tive than aryl chlorides, the cross-coupling cannot occur under
a Barbier-type procedure. Alternatively, the cross-coupling was
achieved in a two-step procedure in a mixture of acetonitrile-
pyridine at 50 °C. Actually, the formation of arylzinc compounds
from aryl chlorides was only successful in this mixture as
previously described.13a The addition of pyridine allows the
stabilization of Co(I) and, thus, the activation of poorly reactive
aromatic halides. Therefore, it was necessary to form the arylzinc
reagent in a first step before adding the 2-chloropyrimidine in
the reaction medium to achieve the cross-coupling reaction.
On the basis of these observations, the process was finally
extended to aryl chlorides. The cross-coupling reaction was
efficient, with aryl chlorides bearing an electron-withdrawing
group (Table 2).
Satisfactory yields were observed from arylchlorides substi-
tuted by various functional groups in meta- and para-positions.
Because of the lower reactivity of arylzinc chlorides, lower
yields were observed compared to the corresponding arylbro-
mides. In addition, increased Co(I) stabilization by pyridine
contributes to its decreased reactivity.
The process was finally extended to 2-chloropyrazine.
Because this compound is more reactive than 2-chloropyrimidine
regarding the oxidative addition of Co(I) into the C-Cl bond,
the reaction could be carried out in a Barbier-type procedure
only with electron-rich aryliodides. In this manner, p-iodoanisole
could be 69% coupled (Scheme 4).
reaction time
of coupling (h) product No. ArX (GC) %
yields vs
entry
ArX
1
2
3
4
5
6
7
8
p-EtO2CC6H4Br
p-MeO2CC6H4Br
p-NCC6H4Br
p-F3CC6H4Br
p-MeOC6H4Br
m-MeOC6H4Br
p-MeC6H4Br
p-ClC6H4Br
p-F3CC6H4Cl
p-NCC6H4Cl
3
6
5
5
1
7
2
5
5
22
23
24
25
26
27
28
29
25
24
23
55 (63)
59 (62)
58 (67)
58 (66)
80 (86)
57 (64)
60 (78)
50 (55)
60 (65)
90 (95)
60 (88)
9
10
11′
4
12
p-MeO2CC6H4Cl
depend on the nature of the halogen. However, we noticed that
the use of an excess of arylhalide (1.3 equiv) versus the
2-chloropyrazine was necessary contrary to the 2-chloropyri-
midine.
In conclusion, we reported in this paper an efficient cross-
coupling of functionalized aryl halides and 2-chlorodiazines such
as 2-chloropyrimidine and 2-chloropyrazine via an intermediate
aryl zinc species using an eco-friendly and inexpensive cobalt
catalyst without ligand. Depending on the nature of the substrate
involved, this process even allows the synthesis of a wide variety
of 2-aryldiazines in a Barbier fashion for more convenience.
The tolerance of our protocol toward a wide variety of functional
groups enables the synthesis of a broad spectrum of valuable
compounds. This versatile process compares favorably with
other procedures that use palladium or nickel catalysis. Further
studies are in progress to extend this process to other azines
and heterocycles.
In the case of arylbromides and arylchlorides, the cross-
coupling could be conducted in a two-step procedure. As
highlighted in Table 3, the corresponding 2-arylpyrazines were
obtained in satisfactory yields, which do not seem to greatly
J. Org. Chem. Vol. 74, No. 8, 2009 3223

and coupling product were measured by GC (addition of iodine)
using an internal reference (dodecane, 200 µL). The reaction mixture
was poured into a saturated aqueous solution of NH4Cl and extracted
with dichloromethane. The organic layer was washed with a
saturated aqueous solution of NaCl and dried over MgSO4.
Evaporation of solvent and purification by column chromatography
on silica gel (pentane/diethyl ether or pentane/dichloromethane)
afforded the coupling product. Representative experimental data
from the synthesis of 4-pyrimidin-2-ylbenzoic acid ethyl ester (2):
1H NMR (300 MHz, CDCl3) δ/ppm 1.43 (t, J ) 7.1 Hz, 3H), 4.42
(q, J ) 7.1 Hz, 2H), 7.25 (t, J ) 4.8 Hz, 1H), 8.17 (d, J ) 8.6 Hz,
2H), 8.53 (d, J ) 8.6 Hz, 2H), 8.85 (d, J ) 4.8 Hz, 2H). 13C NMR
(75 MHz, CDCl3) δ/ppm 14.4 (CH3), 61.2 (CH2), 119.7 (CH), 128.1
(2CH), 129.8 (2CH), 132.3 (C), 141.4 (C), 157.4 (2CH), 163.8 (C),
166.4 (C). HRMS Calcd for C13H12N2O2, 228.0899; found, 228.0899.
Experimental Section
General Procedure for the Synthesis of 2-Arylpyrimidines
or 2-Arylpyrazines in a Barbier Procedure. To a solution of
CoBr2 (10 mol %, 0.75 mmol, 165 mg) and zinc powder (20 mmol,
1.3 g) in acetonitrile (6 mL) were successively added at room
temperature allylchloride (3 mmol, 250 µL) and trifluoroacetic acid
(100 µL), causing an immediate rise in temperature and color
change to dark gray. After stirring the resulting mixture for 3 min,
aryl bromide or iodide (7.5 mmol) and 2-chloropyrimidine (10
mmol, 1.15 g) or 2-chloropyrazine (7.5 mmol, 0.66 mL) were added.
The medium was then stirred at 50 °C until aryl halide was
consumed.
General Procedure for Synthesis of 2-Arylpyrimidines or
2-Arylpyrazines in a Two-Step Procedure. (a). Synthesis of
ArZnX. To a solution of CoBr2 (10 mol %, 0.75 mmol, 165 mg)
and zinc powder (20 mmol, 1.3 g) in acetonitrile (6 mL) were
successively added at room temperature allylchloride (3 mmol, 250
µL) and trifluoroacetic acid (100 µL), causing an immediate rise
in temperature and color change to dark gray. After stirring the
resulting mixture for 3 min, aryl halide (7.5 mmol) was added (in
the case of aryl chloride, supplementary CoBr2 (23 mol %, 1.7
mmol, 372 mg) and pyridine (4 mL) were added). The medium
was then stirred at room temperature until complete conversion of
aryl halide.
Acknowledgment. The CNRS and the Ministe`re de l’Enseigne-
ment Supe´rieur et de la Recherche are acknowledged for
financial support.
Supporting Information Available: Characterization data
1
(IR, H and 13C NMR, spectroscopic data, and HMRS) of the
products: 2, 3, 6, 8, 9, 10, 11, 13, 14, 16, 17, 18, 19, 20, 21, 22,
1
24, 25, 27. Copies of H and 13C NMR spectra of all products
(b). Cross-Coupling Reaction. 2-Chloropyrimidine (10 mmol,
1.15 g) or 2-chloropyrazine (5 mmol, 0.45 mL) was added and the
medium was stirred at 50 °C until ArZnCl or ArZnBr was
consumed. In all cases, the amounts of the corresponding ArZnX
listed in Tables 13. This material is available free of charge via
the Internet at http://pubs.acs.org.
JO900240D
3224 J. Org. Chem. Vol. 74, No. 8, 2009