Palladium-catalyzed C-2 selective C-H olefination of pyridines

Article abstract of DOI:10.1002/adsc.201200195

A novel and efficient protocol for the C-2 selective olefination of pyridines via a palladium-catalyzed oxidative cross-coupling reaction has been developed. A wide range of pyridines and olefin substrates including acrylic ester, styrene, and acrylamide are compatible. The products are highly useful building blocks for the synthesis of bioactive alkaloid natural products and drug molecules. Copyright

Full text of DOI:10.1002/adsc.201200195

COMMUNICATIONS
DOI: 10.1002/adsc.201200195
À
Palladium-Catalyzed C-2 Selective C H Olefination of Pyridines
a
a
a
a
a
b,
Ping Wen, Yanmei Li, Kang Zhou, Chao Ma, Xiaobo Lan, Chaowei Ma, *
a,
and Guosheng Huang *
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, Peopleꢀs Republic of China
a
Fax : (+86)-0931-891-2582; phone: (+86)-0931-891-2582; e-mail: hgs@lzu.edu.cn
Xinjiang Polytechnic College Urumqi, Xinjiang 830091, Peopleꢀs Republic of China
b
Fax : (+86)-0991-773-6149; phone: (+86)-0991-773-6149; e-mail: mcw11@163.com
Received: March 10, 2012; Revised: April 25, 2012; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200195.
Abstract: A novel and efficient protocol for the C-2
selective olefination of pyridines via a palladium-
catalyzed oxidative cross-coupling reaction has
been developed. A wide range of pyridines and
olefin substrates including acrylic ester, styrene, and
acrylamide are compatible. The products are highly
useful building blocks for the synthesis of bioactive
alkaloid natural products and drug molecules.
Among CÀH activations catalyzed by various tran-
sition metals, the reactions involving Pd-catalyzed ac-
2
tivation of a C
A
H
U
G
R
N
N
(sp )ÀH bond of pyridines have been
[
12]
extensively investigated.
Recently, Yu developed
a novel Pd-catalyzed arylation and olefination at the
C-3 position of pyridines based on a ligand-assisted
[
13]
strategy. Besides, Sames also realized the C-3 or C-
4 selective arylation of pyridines containing strong
[
14]
electron-withdrawing groups. In spite of these ad-
Keywords: CÀH activation; olefin coupling part-
vances, the direct C-2ÀH activation of pyridines still
ners; olefination; palladium; pyridines
remains a significant challenge in palladium catalysis.
Interestingly, we recently have discovered for the first
time a novel ligand-free Pd-catalyzed C-2 selective
oxidation coupling reaction of pyridines with olefins
(
Scheme 1). It is more simple and tolerant compared
[2d,7b]
Pyridine moieties exist ubiquitously in biologically with previously reported methods.
active natural products, synthetic biological probes, wish to report our preliminary results on this topic.
Herein we
[
1]
drug candidates and pesticides. As was known, the
direct CÀH activation of pyridines is quite challenging
in modern organic synthesis due to their relatively
low reactivity and high Lewis basicity. Generally, this
CÀH functionalization was carried out by using deriv-
[
2]
atives (e.g., N-oxides
and N-iminopyridinium
[4]
[3]
ylides ) or in a radical-dependent fashion. Current-
ly, several groups have gained promising results on
the preparation of pyridine-containing compounds via
metal-catalyzed pyridyl CÀH functionalization, in
[6]
[
5]
which catalysts based on zirconium, ruthenium,
[7]
[8]
[9]
rhodium, iridium, and silver were already em-
ployed. In addition, the pioneering works reported by
Hiyama and Nakao have independently demonstrated
not only the selective activation of the C-2 of pyri-
dines, but also achieved the alkylation of pyridines
with unprecedented C-4 selectivity in the presence of Scheme 1. Distinct olefination of pyridines.
Lewis acids and N-heterocyclic carbene nickel com-
[10]
plexes. Recently, Hou’s group realized an interest-
ing C-2ÀH bond addition of pyridines to olefins by
Initially, we examined the C-2 selective olefination
scandium catalysis, which was an efficient and general of pyridine 1 with n-butyl acrylate 2. The model reac-
[
11]
protocol for the ortho-alkylation of pyridines.
tion of pyridine (2.0 mmol) and n-butyl acrylate
0.5 mmol) in the presence of Pd(OAc) (10 mol%),
(
ACHTUNGTRENNUNG
2
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
ÞÞ
These are not the final page numbers!

Ping Wen et al.
COMMUNICATIONS
[a]
Table 1. Screening of the reaction conditions.
[b]
Entry
Catalyst
Oxidant (equiv.)
Ag CO (1.5)
Additive (equiv.)
Yield [%]
C-2
C-3
1
2
3
4
5
6
7
8
9
1
1
1
1
1
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
A
T
N
T
N
U
G
ACHTUNGTRENNUNG
3
PivOH (1)
PivOH (1)
PivOH (2)
PivOH (3)
PivOH (2)
PivOH (2)
PivOH (2)
PivOH (2.5)
PivOH (2.5)
PivOH (2.5)
PivOH (2.5)
PivOH (2.5)
PivOH (2.5)
PivOH (2.5)
17
27
39
43
46
38
47
57
61
48
58
43
52
40
15
9
7
5
5
4
7
7
8
11
6
8
7
8
2
2
2
2
2
2
2
2
2
2
2
A
H
U
G
R
N
G
AgOAc (3)
AgOAc (3)
AgOAc (3)
AgOAc (3)
AgOAc (2)
AgOAc (4)
AgOAc (3)
AgOAc (3)
AgOAc (3)
AgOAc (3)
AgOAc (3)
AgOAc (3)
AgOAc (3)
A
H
U
G
R
N
U
G
A
H
N
R
N
U
G
A
H
U
G
R
N
N
A
H
U
T
N
U
G
A
T
N
T
N
U
G
[
[
c]
A
T
N
T
E
U
G
d]
A
H
U
G
R
N
N
[
[
[
[
[
e]
0
1
2
3
4
A
H
U
G
R
N
N
f]
g]
h]
i]
PdCl2
PdCl (PhP )
3 2
A
H
U
G
R
N
U
G
2
Pd
Pd
A
T
N
T
E
N
N
(dba)
2
3
A
H
U
G
R
N
N
(OAc)
2
[
a]
Reaction conditions: butyl acrylate (0.5 mmol), pyridine (2.0 mmol), Pd
additive (1–3 equiv.) in DMF (0.8 mL) at 1408C for 20 h.
Isolated yield of C-2/C-3 products.
ACHTUNGTNERNGNU( OAc) (0.05 mmol), oxidant (1.5–3 equiv.), and
2
[
[
[
[
[
[
[
[
b]
c]
d]
e]
f]
O (1 atm) was used.
2
Pyridine (4.0 mmol).
Pyridine (6.0 mmol).
1
1
1
0 mol% PdCl was used.
0 mol% PdCl ACHTUNGTRENNUNG( PhP ) was used.
2 3 2
2
g]
h]
i]
0 mol% Pd ACHTUNGTRENNUNG( dba) was used.
2 3
Run at 1208C.
Ag CO (1.5 equiv.), and PivOH (1 equiv.) in DMF transition metal catalysis could have some influence
2
3
[
13,14]
(
0.8 mL) at 1408C for 20 h afforded the desired C-2 on the activated pyridine ring reaction,
however
olefinated product 3 in 17% yield that was obtained the addition of various ligands did not reveal any pos-
based on olefin, along with the C-3 olefinated by- itive effects on the present cross-coupling reaction
product 4 in 15% yield , which were confirmed by (see the Supporting Information). Considering that
[13]
NMR after isolation (Table 1, entry 1). When using pyridine could be used as a ligand as well, the
the less basic AgOAc instead of Ag CO , the C-2 se- amounts of pyridine were increased, and pleasingly
2
3
lective C-H olefination of pyridine was improved the yield of the C-2 product could be improved to
both in the yield and selectivity (entry 2), and only 61% (entries 9). Based on the above reaction condi-
small amounts of the C-3 by-product were detected tions, other solvents such as dioxane, DMA, DMSO,
(
9% yield). Interestingly, an excess amounts of DCE, xylene, and NMP were examined further, de-
PivOH in the current model reaction, to some extent, spite giving inferior yields or no products (also see
gave increased yield and selectivity (entries 3–5), in the Supporting Information). Other palladium sources
which use of 2.5 equivalents of PivOH constitutes an were also tested. The use of PdCl afforded the C-2
2
optimal amount of acid additive. In addition to olefinated product in 58% yield (entry 11), while
PivOH, other acids were also employed, albeit with other catalysts such as PdCl2 ACUTHNGTRENNU(NG PhP ) and Pd ACHTUNGERTNNUN(G dba) of-
3 2 2 3
lower yields (see the Supporting Information). In- fered lower yields (entries 12 and 13). Compared with
creasing the amount of silver salt did not have any ob- the result under the conditions of entry 5, the model
vious effect on the reaction (entry 7), while reducing reaction catalyzed by Pd
its amount decreased the yield of the desired product 40% yield (entry 14), suggesting that a higher reaction
entry 6). Notably, when this cross-coupling reaction temperature was beneficial for the formation of 3.
was conducted under an atmospheric pressure of Under the optimized conditions, we first explored
oxygen, the yield could be further increased from the compatibility of the olefin coupling partners, in-
ACHTUNGTNERNUNG( OAc) at 1208C gave 3 in
2
(
[
15]
46% to 57% (entry 8).
Generally, the ligand in cluding ester, amide, and aryl moieties (3a–3e), in
2
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

Palladium-Catalyzed C-2 Selective CÀH Olefination of Pyridines
Table 2. Pd-catalyzed C-2 olefination of pyridines.
[a,b]
[
a]
Reaction conditions: butyl acrylate (0.5 mmol), pyridine (4.0 mmol), Pd
0.05 mmol), AgOAc (3 equiv.), and PivOH (2.5 equiv.) in DMF (0.8 mL) at 1408C for
0 h.
Isolated yield of C-2 product.
Run at 1308C.
ACHTUNGTRENNUNG( OAc)
2
(
2
[
[
[
b]
c]
d]
6
equiv. PivOH were used.
which the acrylate with a b-substituent (3f) was inef- low to moderate yields (3g–3l), wherein pyridines
fective in this cross-coupling. Subsequently, the sub- with a methyl at C-3 or C-3/C-5 gave higher yields of
strate scope of pyridines was then investigated products than those with a methyl at C-2 or C-4. Un-
(
Table 2). Pyridines substituted with one to three expectedly, 3-methylpyridine as a coupling partner
methyl groups at different positions on the pyridyl gave a 1:1 mixture of C-2 and C-6 products 3h with-
ring could undergo the expected C-2 olefination in out selectivity. When using the pyridine with a me-
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3
ÞÞ
These are not the final page numbers!

Ping Wen et al.
COMMUNICATIONS
thoxy group at the C-2 position as coupling partner, late to give the C-2 products in good yields (3t and
the yields (3m–3o) were obviously lower than those 3u), providing the synthetic potential for additional
using C-2 substituted pyridine due to the electron re- modifications at the halogenated positions.
[
14,16]
pulsion effect.
While the electron-withdrawing
While employing pyridines with C-2ÀX (X=Br, Cl,
cyano group and ester group were contained in pyri- F) substitution, only the halogen-replaced by-products
dine, we were disappointed to find that the yield is were obtained. Furthermore, quinoline, isoquinoline
not increased (even trace) as had been observed pre- and pyrazine were also viable substrates for the C-2
[
13]
viously by Yu (3p–3s). Moreover, it is noteworthy selective CÀH olefination (3v–3x). While the pyri-
that the pyridine substituted at the C-3 position by dines with halogen atoms (F, Cl and Br) at the C-3
either chloride or fluoride reacted with n-butyl acry- and C-5 positions, surprisingly, only the C-4 selective
olefinated products were detected (s-1–s-3), demon-
strating that the electron-withdrawing effect of two
halogen atoms increased the C-4ÀH reactivity and re-
duced the coordinating capability of the nitrogen
atom with the Pd catalyst (Scheme 2).
To gain some insight into the mechanism, we car-
ried out a kinetic isotope effect study under the reac-
tion conditions to reveal that the intermolecular ki-
Scheme 2. C-4 selective olefination of pyridines.
netic isotope effect (k /K ) is 4.0 (Scheme 3).
H
D
Based on the findings, we reasoned that pyridine in-
itially coordinated with Pd via the nitrogen atom to
form the complex A, which could potentially be
changed into a p-acceptor B due to a strong “trans-
[
13,19]
effect”,
and then the CÀH cleavage would pro-
ceed has been proposed to generate Pd(II) species C
and E via a concerted metalation/deprotonation path-
[
17]
way,
which sequentially inserted into the alkene
substrate 2 to give Pd(II) intermediate D (Scheme 4).
In addition, it has previously been found that Ag(I)
salts facilitate transmetalation in cross-coupling reac-
[
18]
tions. After subsequent b-hydride elimination in D,
the desired C-2 olefinated product 3 was afforded.
Subsequently, regeneration of the active Pd(II) spe-
cies for the next catalytic cycle was accomplished by
the oxidation of Ag(I).
Scheme 3. Kinetic isotope effect.
Scheme 4. A plausible mechanism.
4
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

Palladium-Catalyzed C-2 Selective CÀH Olefination of Pyridines
In summary, relying on the Pd-catalyzed CÀH bond
activation strategy, we have developed a highly prom-
ising oxidative protocol for the C-2 selective olefina-
tion of pyridine for the first time. The substrates did
not require N-oxide processing nor use of halogen at
the C-2 position. For dihalo-substituted substrates, C-
J. Am. Chem. Soc. 2008, 130, 9254–9256; d) J. L. Wu,
X. L. Cui, L. M. Chen, Y. J. Wu, J. Am. Chem. Soc.
2
009, 131, 13888–13889; e) L. C. Campeau, S. Rous-
seaux, K. Fagnou, J. Am. Chem. Soc. 2005, 127, 18020–
8021; f) J. J. Mousseau, J. A. Bull, A. B. Charette,
1
Angew. Chem. 2010, 122, 1133–1136; Angew. Chem.
Int. Ed. 2010, 49, 1115–1118.
4
selective olefination of pyridines could be obtained,
[
[
3] A. Larivee, J. J. Mousseau, A. B. Charette, J. Am.
which are highly useful building blocks for the synthe-
sis of bioactive alkaloid natural products and drug
molecules. Further studies on mechanistic details of
this reaction are currently ongoing in our laboratory.
Chem. Soc. 2008, 130, 52–54.
4] a) S. Yanagisawa, K. Ueda, T. Taniguchi, K. Itami, Org.
Lett. 2008, 10, 4673–4676; b) O. Kobayashi, D. Uragu-
chi, T. Yamakawa, Org. Lett. 2009, 11, 2679–2689; c) M.
Li, R. Hua, Tetrahedron Lett. 2009, 50, 1478–1481.
5] R. F. Jordan, D. F. Taylor, J. Am. Chem. Soc. 1989, 111,
[
[
7
78–779.
Experimental Section
6] a) E. J. Moore, W. R. Pretzer, T. J. ꢂConnell, J. Harris,
L. LaBounty, L. Chou, S. S. Grimmer, J. Am. Chem.
Soc. 1992, 114, 5888–5890; b) S. Hori, M. Murakami, J.
Am. Chem. Soc. 2003, 125, 4720–4721; c) K. Godula, B.
Sezen, D. Sames, J. Am. Chem. Soc. 2005, 127, 3648–
3649; d) T. Kawashima, T. Takao, H. Suzuki, J. Am.
Chem. Soc. 2007, 129, 11006–11007; e) R. Grigg, V.
Savic, Tetrahedron Lett. 1997, 38, 5737–5740.
General Procedure for the Preparation of 3a–3x
To a 10-mL glass tube with branched vial equipped with
a magnetic stir bar were sequentially added Pd
11.2 mg, 10 mol%), AgOAc (252 mg, 1.5 mmol), olefin cou-
pling partner (0.5 mmol), pyridine derivative (4.0 mmol),
PivOH (127 mg) in DMF(0.8 mL). The reaction mixture was
ACHTUNGTRENNUNG( OAc)
2
(
AHCTUNGTRENNUNG
stirred at 1408C under 1 atm of oxygen (balloon pressure)
for 20 h. After cooling down, the mixture was diluted with
CH Cl , filtered and washed with distilled water and brine,
dried over sodium sulfate, and filtered. The filtrate was con-
centrated, and the residue was purified by flash column
chromatography to provide desired product using hexane-
s:EtOAc (40/1 to 1/1, depending on different substrates) as
the eluent. Compound characterization data are available in
the Supporting Information.
[7] a) J. C. Lewis, R. G. Bergman, J. A. Ellman, J. Am.
Chem. Soc. 2007, 129, 5332–5333; b) A. M. Berman,
J. C. Lewis, R. G. Bergman, J. A. Ellman, J. Am. Chem.
Soc. 2008, 130, 14926–14927; c) J.-Y. Cho, C. N. Iverson,
M. R. I. Smith, J. Am. Chem. Soc. 2000, 122, 12868–
2
2
1
2869.
[
8] a) J. Takagi, K. Sato, J. F. Hartwig, T. Ishiyama, N.
Miyaura, Tetrahedron Lett. 2002, 43, 5649–5651;
b) I. A. I. Mkhalid, D. N. Coventry, D. Albesa-Jove,
A. S. Batsanov, J. A. K. Howard, R. N. Perutz, T. B.
Marder, Angew. Chem. 2006, 118, 503–505; Angew.
Chem. Int. Ed. 2006, 45, 489–491; c) J. M. Murphy, X.
Liao, J. F. Hartwig, J. Am. Chem. Soc. 2007, 129,
Acknowledgements
1
5434–15435; d) D. F. Fischer, R. Sarpong, J. Am.
We thank the State Key Laboratory of Applied Organic
Chemistry for financial support. We also thank our reviewers
for suggestions.
Chem. Soc. 2010, 132, 5926–5927; e) T. E. Hurst, T. K.
Macklin, M. Becker, E. Hartmann, W. Kugel, A. S. Bat-
sanov, T. B. Marder, V. Snieckus, Chem. Eur. J. 2010,
1
6, 8155–8161; f) B.-J. Li, Z.-J. Shi, Chem. Sci. 2011, 2,
4
88–493.
[
9] I. B. Seiple, S. Su, R. A. Rodriguez, R. Gianatassio, Y.
References
Fujiwara, A. L. Sobel, P. S. Baran, J. Am. Chem. Soc.
2
010, 132, 13194–13196.
[
1] a) J. P. Michael, Nat. Prod. Rep. 2005, 22, 627–646;
b) G. D. Henry, Tetrahedron 2004, 60, 6043–6061;
c) M. C. Bagley, C. Glover, E. A. Merritt, Synlett 2007,
[
10] a) Y. Nakao, K. S. Kanyiva, T. Hiyama, J. Am. Chem.
Soc. 2008, 130, 2448–2449; b) M. Tobisu, I. Hyodo, N.
Chatani, J. Am. Chem. Soc. 2009, 131, 12070–12071;
c) C. C. Tsai, W. C. Shih, C. H. Fang, C. Y. Li, T. G.
Ong, G. P. A. Yap, J. Am. Chem. Soc. 2010, 132, 11887–
11889; d) Y. Nakao, Y. Yamada, N. Kashihara, T.
Hiyama, J. Am. Chem. Soc. 2010, 132, 13666–13668.
2
459–2462; d) C. G. Arena, G. Arico, Curr. Org. Chem.
2
010, 14, 546–580; e) C. Bianchini, G. Giambastiani, L.
Luconi, A. Meli, Coord. Chem. Rev. 2010, 254, 431–
455; f) B. J. Holliday, C. A. Mirkin, Angew. Chem.
2001, 113, 2076–2097; Angew. Chem. Int. Ed. 2001, 40,
2022–2043; g) D. G. Kurth, M. Higuchi, Soft Matter
2006, 2, 915–927; h) J. S. Carey, D. Laffan, C. Thomson,
[11] B.-T. Guan, Z.-M. Hou, J. Am. Chem. Soc. 2011, 133,
18086–18089.
M. T. Williams, Org. Biomol. Chem. 2006, 4, 2337–
[12] For Pd-catalyzed intramolecular arylation of pyridines
using tethered ArX, see: a) M. Wasa, B. T. Worrell, J.-
Q. Yu, Angew. Chem. 2010, 122, 1297–1299; Angew.
Chem. Int. Ed. 2010, 49, 1275–1277; b) J. Roger, A. L.
Gottumukkala, H. Doucet, ChemCatChem 2010, 2, 20–
40; c) D. Alberico, M. E. Scott, M. Lautens, Chem. Rev.
2007, 107,174–238; d) L. Basolo, E. M. Beccalli, E. Bor-
sini, G. Broggini, Tetrahedron 2009, 65, 3486–3491.
2
3
347; i) M. Schlosser, F. Mongin, Chem. Soc. Rev. 2007,
6, 1161–1172.
[
2] For reaction of pyridine N-oxide, see: a) P. Xi, F. Yang,
S. Qin, D. Zhao, J. Lan, G. Gao, C. Hu, S. You, J. Am.
Chem. Soc. 2010, 132, 1822–1824; b) H.-Q. Do,
R. M. K. Khan, O. Daugulis, J. Am. Chem. Soc. 2008,
1
30, 15185–15192; c) S. H. Cho, S. J. Hwang, S. Chang,
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
5
ÞÞ
These are not the final page numbers!

Ping Wen et al.
COMMUNICATIONS
[
13] a) M.-C. Ye, G.-L. Ga, J.-Q. Yu, J. Am. Chem. Soc.
Am. Chem. Soc. 2009, 131, 3042–3048; c) J. M. Joo,
B. B. Toure, D. Sames, J. Org. Chem. 2010, 75, 4911–
4920.
2
011, 133, 6964–6967; b) M.-C. Ye, G.-L. Gao, A. J. F.
Edmunds, P. A. Worthington, J. A. Morris, J.-Q. Yu, J.
Am. Chem. Soc. 2011, 133, 19090–19093.
14] P. F. Guo, J. M. Joo, S. Rakshit, D. Sames, J. Am. Chem.
Soc. 2011, 133, 16338–16341.
[17] a) K. M. Engle, D.-H. Wang, J.-Q. Yu, J. Am. Chem.
Soc. 2010, 132, 14137–14151; b) K. M. Engle, P. S. T.
Boun, M. Dang, J.-Q. Yu, J. Am. Chem. Soc. 2011, 133,
18183–18193; c) J. C. Lewis, R. G. Bergman, J. A.
Ellman, J. Am. Chem. Soc. 2007, 129, 5332–5333.
[
[
15] For O employed in the reaction, see: a) Y. Hatamoto,
2
S. Sakaguchi, Y. Ishii, Org. Lett. 2004, 6, 4623–4625;
b) Y. H. Xu, J. Lu, T. P. Loh, J. Am. Chem. Soc. 2009,
[
18] For an early report on the efficacy of Ag(I) in promot-
ing transmetallation, see: a) J. Uenishi, J. M. Beau,
R. W. Armstrong, Y. Kishi, J. Am. Chem. Soc. 1987,
1
31, 1372–1373; c) C. Bee, E. Leclerc, M. A. Tius, Org.
Lett. 2003, 5, 4927–4930; d) K. T. Yip, J. H. Li, O. Y.
Lee, D. Yang, Org. Lett. 2005, 7, 5717–5719; e) T. A.
Dwight, N. R. Rue, D. Charyk, R. Josselyn, B. DeBoef,
Org. Lett. 2007, 9, 3137–3139; f) B.-J. Li, S.-L. Tian, Z.
Fang, Z.-J. Shi, Angew. Chem. 2008, 120, 1131–1134;
Angew. Chem. Int. Ed. 2008, 47, 1115–1118; g) K. Ina-
moto, C. Hasegawa, J. Kawasaki, K. Hiroya, T. Doi,
Adv. Synth. Catal. 2010, 352, 2643–2655; h) S. Mori, M.
Takubo, T. Yanase, T. Maegawa, Y. Monguchi, H.
Sajiki, Adv. Synth. Catal. 2010, 352, 1630–1634; i) G.
Broggini, E. M. Beccalli, E. Borsini, A. Fasana, G.
Zecchi, Synlett 2011, 227–230.
1
09, 4756–4758; b) X. Chen, C. E. Goodhue, J.-Q. Yu,
J. Am. Chem. Soc. 2006, 128, 12634–12635; c) R. Giri,
N. Maugel, J.-J. Li, D.-H. Wang, S. P. Breazzano, L. B.
Saunders, J.-Q. Yu, J. Am. Chem. Soc. 2007, 129, 3510–
3
511; d) B. D. Dangel, K. Godula, S. W. Youn, B.
Sezen, D. Sames, J. Am. Chem. Soc. 2002, 124, 11856–
1857.
1
[
19] For comprehensive discussions on trans-effects, see:
a) J. V. Quagliano, L. Schubert, Chem. Rev. 1952, 50,
2
01–260; b) B. J. Coe, S. J. Glenwright, Coord. Chem.
Rev. 2000, 203, 5–80.
[
16] a) B. B. Toure, B. S. Lane, D. Sames, Org. Lett. 2006, 8,
1
979–1982; b) R. Goikhman, T. L. Jacques, D. Sames, J.
6
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

COMMUNICATIONS
Palladium-Catalyzed C-2 Selective CÀH Olefination of
7
Pyridines
Adv. Synth. Catal. 2012, 354, 1 – 7
Ping Wen, Yanmei Li, Kang Zhou, Chao Ma, Xiaobo Lan,
Chaowei Ma,* Guosheng Huang*
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
7
ÞÞ
These are not the final page numbers!