Ortho-olefination of arylaldehyde O-methyloximes through palladium-catalyzed C-H activation

Article abstract of DOI:10.1002/ejoc.201200393

Palladium(II)-catalyzed ortho-olefination of arylaldehyde O-methyloximes by using O-methyloxime as a directing group gave 2-alkenylarylaldehyde O-methyloximes in moderate to good yields. After various reaction parameters (catalyst, oxidant, solvent, and reaction temperature) were examined, the optimal conditions for the reaction were identified. 2-Alkenylarylaldehydes could be obtained conveniently by hydrolysis of the coupling products. The kinetic isotope effect (k_H/k_D) for the C-H bond activation was provided, and the possible mechanism of the reaction was proposed. Copyright

Full text of DOI:10.1002/ejoc.201200393

Job/Unit: O20393
/KAP1
Date: 23-04-12 15:42:40
Pages: 6
SHORT COMMUNICATION
DOI: 10.1002/ejoc.201200393
ortho-Olefination of Arylaldehyde O-Methyloximes through
Palladium-Catalyzed C–H Activation
[a]
[a]
[a,b]
Zhipeng Xu, Biao Xiang, and Peipei Sun*
Keywords: Palladium / C–H activation / Olefination / Aldehydes / Isotope effects
Palladium(II)-catalyzed ortho-olefination of arylaldehyde O-
methyloximes by using O-methyloxime as a directing group
gave 2-alkenylarylaldehyde O-methyloximes in moderate to
good yields. After various reaction parameters (catalyst, oxi- (k
dant, solvent, and reaction temperature) were examined, the
optimal conditions for the reaction were identified. 2-Alk-
enylarylaldehydes could be obtained conveniently by hy-
drolysis of the coupling products. The kinetic isotope effect
H
D
/k ) for the C–H bond activation was provided, and the
possible mechanism of the reaction was proposed.
as carboxyl,[5] acetamido, N,N-dimethylaminomethyl,
[6]
[7]
Introduction
[
8]
[9]
N-methoxyacylamino, or pyridylsulfinyl have been re-
ported. However, no palladium-catalyzed ortho-olefination
to form 2-alkenylarylaldehydes has been reported, as the
aldehyde group is not an effective directing group in Pd-
catalyzed C–H functionalization, despite the fact that Ru
and Rh complexes have been used in this transformation.
Because alkenylarene structures play an important role
in the synthesis of various fine chemicals,[ the develop-
ment of more efficient methods to construct these building
blocks has attracted much attention. In addition, the alde-
hyde group is considered to be one of the most easily trans-
formable functional groups.[ Considering the importance
of compounds with these two structural units, an efficient
approach for the synthesis of 2-alkenylarylaldehyde deriva-
tives is therefore desirable. However, to synthesize these de-
rivatives through conventional methods such as aldol con-
densation or a Wittig-type reaction from phthalaldehydes is
generally difficult, because it is challenging to control the
regioselectivity between the two aldehyde groups at dif-
ferent sites. Another method is the Mizoroki–Heck reac-
tion. Still, 2-iodo- or 2-bromobenzaldehydes are needed,
and also, some side reactions may take place on the alde-
hyde group under the basic reaction condition.
1]
[10]
[11]
2]
Arylaldehyde O-methyloxime, which can be easily prepared
by the condensation of the corresponding aldehyde and O-
methylhydroxylamine, is part of a class of protected alde-
hydes or precursors of aldehydes. Recently, palladium-cata-
[12]
[12]
[13]
lyzed ortho-acetoxylation,
acylation,
etherification,
arylation,
[14]
[15]
and bromination
of arylaldehyde O-meth-
yloximes have been developed. In these pioneer works, the
oxime group was proven to have effective directing action
to ortho C–H functionalization. Herein, we present a facile
palladium-catalyzed ortho-olefination reaction of arylal-
dehyde O-methyloximes by using O-methyloxime as a di-
recting group to form 2-alkenylarylaldehyde O-methyl-
oximes. 2-Alkenylarylaldehydes could be obtained conve-
niently from the hydrolysis of the coupling products.
In the last decade, C–H bond activation catalyzed by
transition metals has become one of the most modern and
well-recognized tactics for the synthesis of many kinds of
functional compounds because of its atom- and step-econ-
[
3]
omic nature. As a powerful tool for the olefination of ar-
enes, the palladium-catalyzed intermolecular dehydro-
genative Heck reaction, which is also called the oxidative
Results and Discussion
As an initial experiment, treatment of benzaldehyde O-
methyloxime (1a) with methyl acrylate (2a) in the presence
of Pd(OAc) afforded desired product 3a (Table 1). The re-
[
4]
Heck reaction, has been developed in recent years. ortho-
Olefinations with the assistance of a directing group such
2
action could proceed in air without protection. The effects
of different palladium sources, solvents, oxidants, and tem-
perature were systematically examined. Without palladium,
the starting materials were recovered entirely (Table 1, En-
[
[
a] Jiangsu Key Laboratory of Biofunctional Materials, College of
Chemistry and Materials Science, Nanjing Normal University,
Nanjing, 210097, China
Fax: +86-25-8589-1767
E-mail: sunpeipei@njnu.edu.cn
try 1). Pd(OAc) showed evident catalytic activity to the re-
2
b] Key Laboratory of Organic Synthesis of Jiangsu Province,
College of Chemistry, Chemical Engineering and Materials
Science, Soochow University,
action and 2 mol-% of the catalyst could catalyze the reac-
tion effectively, whereas other palladium species such as
Suzhou 215123, China
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200393.
PdCl , Pd(PPh ) , and Pd nanoparticles were substantially
2
3 4
less effective (Table 1, Entries 2–5). A weakly acidic medium
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1

Job/Unit: O20393
/KAP1
Date: 23-04-12 15:42:40
Pages: 6
Z. Xu, B. Xiang, P. Sun
SHORT COMMUNICATION
was favorable to the reaction. AcOH proved to be a suitable (Table 2). All products we obtained were confirmed to be
1
solvent for this transformation, whereas the addition of a E-isomers by H NMR spectroscopy. It seems that the reac-
strong acid (TFA, pTsOH) decreased the yield substantially, tion of arylaldehyde O-methyloximes with electron-donat-
because a stronger acid might lead to the decomposition of ing groups gave higher yields than those with electron-with-
the oxime group (Table 1, Entries 6 & 7). Neutral solvents drawing groups. For example, methyl acrylate reacted
such as CH CN, toluene, DMF, DMSO, dioxane, and DCE smoothly with 4-methoxybenzaldehyde O-methyloxime and
3
were disadvantageous to the reaction (Table 1, Entries 8– 3,4-dimethoxybenzaldehyde O-methyloxime to give the or-
13). As a general oxidant and ligand, p-benzoquinone (BQ) tho-olefinated product in 89 and 93% isolated yield, respec-
also played an important role. Without BQ, only a trace tively (i.e., 3c and 3n), whereas it reacted with 4-chlorobenz-
quantity of the corresponding product was detected aldehyde O-methyloxime and 4-bromobenzaldehyde O-
(Table 1, Entry 14). Other oxidants such as Cu(OAc)2, methyloxime to provide a moderate yield of 51 and 53%,
Cu O, Ag O, Ag CO , and Na S O were less effective for
2
2
2
3
2
2
8
this reaction (Table 1, Entries 15–19). Under an Ar atmo-
sphere, the reaction gave almost the same yield as that in
air (Table 1, Entry 20). At 80 °C, the reaction was complete
in 6 h with a yield of 74%. A decrease in the reaction tem- (2 mL), and BQ (1 equiv.) in air at 80 °C for 6 h. Isolated yield
perature led to a lower conversion. However, an increase (for 3a–u) is reported (reaction times for each substrate were not
Table 2. Alkenylation of arylaldehyde O-methyloximes with alk-
enes. Reaction conditions: arylaldehyde O-methyloxime
(0.01 mmol), acetic acid
1
(
0.5 mmol), alkene 2 (1.0 mmol), Pd(OAc)
2
optimized).
in the reaction temperature above 100 °C might induce the
decomposition of the substrate and therefore reduce the
yield (Table 1, Entry 2). Taking the above into consider-
ation, the reaction efficiently proceeded when 2 mol-% of
Pd(OAc) was used in combination with BQ (1.0 equiv.) in
2
acetic acid at 80 °C.
Table 1. Optimization of the reaction conditions.[a]
Entry
Catalyst
–
Oxidant
Solvent
Yield [%][b]
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
BQ
BQ
BQ
BQ
BQ
BQ
BQ
BQ
BQ
BQ
BQ
BQ
BQ
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
NR
74 (41, 69, 53)[
trace
c]
Pd(OAc)
PdCl
Pd(PPh
nano-Pd
2
2
3
)
4
trace
trace
[
d]
e]
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
2
57
43[
2
2
2
2
2
2
2
2
2
2
2
2
2
2
CH
3
CN
NR
NR
NR
NR
NR
NR
trace
15
toluene
DMF
DMSO
dioxane
DCE
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
1
1
1
1
1
1
1
1
1
1
2
–
Cu(OAc)
2
Cu
Ag
2
O
O
21
12
2
Ag
Na
BQ
2
CO
3
trace
NR
2
S
2
O
8
[
f]
72
[
a] Reaction conditions: benzaldehyde O-methyloxime (1a,
.5 mmol), methyl acrylate (2a, 1.0 mmol), catalyst (0.01 mmol),
solvent (2 mL), and oxidant (1 equiv.) in air at 80 °C for 6 h.
b] Isolated yield; NR = no reaction. [c] Reaction proceeded at 60,
00, and 120 °C, respectively. [d] TFA (1.0 equiv.) was added.
0
[
1
[e] pTsOH (1.0 equiv.) was added. [f] Under an Ar atmosphere.
With the optimized reaction conditions established, we
examined the reactions between various substituted aryl-
aldehyde O-methyloximes and acrylates or acrylonitrile
2
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20393
/KAP1
Date: 23-04-12 15:42:40
Pages: 6
ortho-Olefination of Arylaldehyde O-Methyloximes
respectively (i.e., 3d and 3i). Unfortunately, the reaction of
a substrate containing a strong electron-withdrawing sub-
stituent such as NO only gave a trace amount of the prod-
2
uct. These results may be attributed to the fact that an elec-
tron-withdrawing group substituted on the aromatic ring of
the substrate disfavors the formation of a cyclopalladated
intermediate. Regarding the reaction of meta-substituted
arylaldehyde O-methyloximes, which might have two C–H
bond activation sites (C2 and C6), only ortho-olefinated
products at C6 were isolated (i.e., 3e, 3g, 3p, 3r, and 3u).
Scheme 1. Isotope effect.
This regioselectivity was generally attributed to the steric to form aryl palladium intermediate A.[21] Acetate or BQ
effect of the substituent at the C3 position instead of the might act as a ligand coordinating to palladium. Afterward,
electronic nature of the substrate.[ Furthermore, it is wor- the ligand in intermediate A interchanges with an olefin to
thy to note that chloride and bromide groups on the aro- form B, which is followed by insertion of the C=C bond
matic ring were tolerated, and the surviving C–Cl or C– into the Ar–Pd bond. Subsequent β-hydroelimination and
Br bond could be further transformed into different useful reductive elimination results in the generation of the prod-
functional groups (i.e., 3d, 3g, 3h, 3i, and 3o). The reaction uct and liberation of acetic acid and a palladium(0) species.
of the phenol substrate also gave a good yield (i.e., 3j), Finally, the released palladium(0) can be reoxidized by BQ
which accounted for an excellent functional group tolerance to regenerate palladium(II), which can continue the cata-
of this reaction even under the oxidizing reaction condi- lytic cycle.
16]
tions. With methyl, ethyl, and tert-butyl acrylate, as well
as acrylonitrile, the corresponding coupling products were
obtained in moderate to good yields. Unfortunately, almost
no desired product was obtained when styrene was em-
ployed under the reaction conditions, because the acetoxyl-
[
17]
ation of styrene occurred under the acidic conditions.
To understand the catalytic process of this reaction, a
kinetic isotope effect was investigated by using 2-deuterio-
benzaldehyde O-methyloxime (1a-D) to react with 2a to
form 3a and 3a-D (Scheme 1). The k /k ratio was deter-
H
D
[
18]
mined to be 0.96, which indicated that the palladium(II)-
catalyzed C–H bond cleavage of benzaldehyde O-methylox-
ime (1a) does not occur in the rate-determining step. We
presume that the C–H activation might proceed via an
[19]
agostic intermediate or a concerted metalation deproton-
[
20]
ation.
A possible mechanism for this palladium(II)-catalyzed
olefination reaction is proposed in Scheme 2, although de-
tails await further investigation. The reaction is probably
initiated by oxime-coordinated ortho-selective cyclomet-
Scheme 2. Proposed reaction mechanism.
One of the applications of this olefination reaction is to
alation on the aromatic ring with Pd(OAc) , in which acet- synthesize 2-alkenylarylaldehydes by hydrolysis of the cou-
2
ate presumably participates in aromatic proton abstraction pling products. As an example, (E)-methyl 3-{2-[(E)-(meth-
Scheme 3. Synthesis of (–)-podophyllotoxin (6) from arylaldehyde O-methyloxime.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3

Job/Unit: O20393
/KAP1
Date: 23-04-12 15:42:40
Pages: 6
Z. Xu, B. Xiang, P. Sun
2] R. C. Larock, Comprehensive Organic Transformations: A
Guide to Functional Group Preparations, Wiley-VCH, New
York, 1999.
3] a) D. Alberico, M. E. Scott, M. Lautens, Chem. Rev. 2007, 107,
SHORT COMMUNICATION
[
[
oxyimino)methyl]phenyl}acrylate (3a) was further hy-
drolyzed conveniently by treatment with HCl (2 m) to give
methyl 2-formylcinnamate (4a, Scheme 3). Multisubstituted
methyl 2-formylcinnamates are precursors to synthesize ver-
satile isobenzofurans (IBFs), which have been employed in
the synthesis of aromatic and hydroaromatic natural prod-
1
74–238; b) X. Chen, K. M. Engle, D.-H. Wang, J.-Q. Yu, An-
gew. Chem. 2009, 121, 5196; Angew. Chem. Int. Ed. 2009, 48,
094–5115; c) B. M. Rosen, K. W. Quasdorf, D. A. Wilson, N.
Zhang, A.-M. Resmerita, N. K. Garg, V. Percec, Chem. Rev.
011, 111, 1346–1416; d) C.-L. Sun, B.-J. Li, Z.-J. Shi, Chem.
5
[
22]
ucts.
synthesize the natural product (–)-podophyllotoxin,
which is an aryl tetralin lignan isolated from the American
For example, IBF could be used as a material to
2
[
23]
Rev. 2011, 111, 1293–1314; e) R. Jazzar, J. Hitce, A. Renaudat,
J. Sofack-Kreutzer, O. Baudoin, Chem. Eur. J. 2010, 16, 2654–
2672; f) C. S. Yeung, V. M. Dong, Chem. Rev. 2011, 111, 1215–
[
24]
May apple tree and which may be used in the treatment
of venereal warts, a chemotherapeutic for cancer, and as
anti-HIV agent.
1292; g) W. Shi, C. Liu, A. Lei, Chem. Soc. Rev. 2011, 40, 2761–
2776; h) C. Liu, H. Zhang, W. Shi, A. Lei, Chem. Rev. 2011,
111, 1780–1824; i) R. Jana, T. P. Pathak, M. S. Sigman, Chem.
[
25]
Rev. 2011, 111, 1417–1492; j) I. P. Beletskaya, V. P. Ananikov,
Chem. Rev. 2011, 111, 1596–1636.
Conclusions
[4] a) E. M. Beck, N. P. Grimster, R. Hatley, M. J. Gaunt, J. Am.
Chem. Soc. 2006, 128, 2528–2529; b) M. Dams, D. E. De Vos,
S. Celen, P. A. Jacobs, Angew. Chem. 2003, 115, 3636; Angew.
Chem. Int. Ed. 2003, 42, 3512–3515; c) Y. Fujiwara, I. Morit-
ani, M. Matsuda, S. Teranishi, Tetrahedron Lett. 1968, 9, 633–
In conclusion, we developed the ortho-olefination of aryl-
aldehyde O-methyloximes through Pd-catalyzed oxidative
coupling with olefins to form 2-alkenylarylaldehyde O-
methyloximes. This protocol, when followed by simple de-
protection to the coupling products, could afford 2-alkenyl-
arylaldehydes, which are important precursors for the syn-
thesis of natural products. Therefore, the present work also
provided a simple method for the synthesis of 2-alkenylaryl-
aldehydes. The mild reaction conditions provide future op-
portunities to apply this methodology in the synthesis of
natural products and medicines.
6
36; d) Y. Fujiwara, I. Noritani, S. Danno, R. Asano, S. Terani-
shi, J. Am. Chem. Soc. 1969, 91, 7166–7169; e) J. Le Bras, J.
Muzart, Chem. Rev. 2011, 111, 1170–1214; f) I. Moritanl, Y.
Fujiwara, Tetrahedron Lett. 1967, 8, 1119–1122; g) A. García-
Rubia, B. Urones, R. Gómez Arrayás, J. C. Carretero, Angew.
Chem. Int. Ed. 2011, 50, 10927–10931; h) Y. Yang, K. Cheng,
Y. Zhang, Org. Lett. 2009, 11, 5606–5609.
[
5] a) M. Miura, T. Tsuda, T. Satoh, S. Pivsa-Art, M. Nomura, J.
Org. Chem. 1998, 63, 5211–5215; b) D.-H. Wang, K. M. Engle,
B.-F. Shi, J.-Q. Yu, Science 2010, 327, 315–319; c) B.-F. Shi, Y.-
H. Zhang, J. K. Lam, D.-H. Wang, J.-Q. Yu, J. Am. Chem. Soc.
2
010, 132, 460–461; d) K. M. Engle, D.-H. Wang, J.-Q. Yu,
Angew. Chem. Int. Ed. 2010, 49, 6169–6173.
Experimental Section
[
6] a) M. D. K. Boele, G. P. F. van Strijdonck, A. H. M. de Vries,
P. C. J. Kamer, J. G. de Vries, P. W. N. M. van Leeuwen, J. Am.
Chem. Soc. 2002, 124, 1586–1587; b) T. Nishikata, B. H. Lip-
shutz, Org. Lett. 2010, 12, 1972–1975.
General Experimental Procedures for the Palladium-Catalyzed
ortho-Olefination of Arylaldehyde O-Methyloxime: Arylaldehyde O-
methyloxime (0.5 mmol), alkene (1.0 mmol), BQ (0.5 mmol),
[
7] G. Cai, Y. Fu, Y. Li, X. Wan, Z. Shi, J. Am. Chem. Soc. 2007,
2
Pd(OAc) (2.24 mg, 0.01 mmol, 2 mol-%), and acetic acid (2 mL)
129, 7666–7673.
were added in a 25-mL sealed tube with a Teflon lined cap. The
mixture was heated at 80 °C (oil bath temperature) for 6 h. After
cooling to room temperature, the solvent was removed under re-
duced pressure, and the residue was purified by a flash column
chromatography on silica gel (hexane/ethyl acetate) to give the cor-
responding product.
[8]
a) D.-D. Li, T.-T. Yuan, G.-W. Wang, Chem. Commun. 2011,
47, 12789–12791; b) J. W. Wrigglesworth, B. Cox, G. C. Lloyd-
Jones, K. I. Booker-Milburn, Org. Lett. 2011, 13, 5326–5329.
[9] M. Yu, Z. Liang, Y. Wang, Y. Zhang, J. Org. Chem. 2011, 76,
987–4994.
10] a) N. Gürbüz, I. Özdemir, B. Çetinkaya, Tetrahedron Lett.
005, 46, 2273–2277; b) D. Kalyani, A. R. Dick, W. Q. Anani,
4
[
2
Supporting Information (see footnote on the first page of this arti-
M. S. Sanford, Tetrahedron 2006, 62, 11483–11498; c) Y. Terao,
Y. Kametani, H. Wakui, T. Satoh, M. Miura, M. Nomura, Tet-
rahedron 2001, 57, 5967–5974.
cle): Experimental procedures and full characterization for all com-
1
13
pounds; copies of the H NMR and C NMR spectra for all com-
pounds.
[11] a) K. Padala, M. Jeganmohan, Org. Lett. 2012, 14, 1134–1137;
b) S. H. Park, J. Y. Kim, S. Chang, Org. Lett. 2011, 13, 2372–
2
375.
[12] L. V. Desai, H. A. Malik, M. S. Sanford, Org. Lett. 2006, 8,
141–1144.
Acknowledgments
1
[
13] a) C.-L. Sun, N. Liu, B.-J. Li, D.-G. Yu, Y. Wang, Z.-J. Shi,
Org. Lett. 2010, 12, 184–187; b) V. S. Thirunavukkarasu, K.
Parthasarathy, C.-H. Cheng, Angew. Chem. 2008, 120, 9604;
Angew. Chem. Int. Ed. 2008, 47, 9462–9465.
This work was supported by the National Natural Science Founda-
tion of China (Project 20972068), the Leading Academic Discipline
Program, 211 Project for Nanjing Normal University (the 3rd
phase), and the Priority Academic Program Development of Ji-
angsu Higher Education Institutions.
[
14] C.-W. Chan, Z. Zhou, A. S. C. Chan, W.-Y. Yu, Org. Lett. 2010,
12, 3926–3929.
[15] E. Dubost, C. Fossey, T. Cailly, S. Rault, F. Fabis, J. Org. Chem.
[
1] a) A. C. Grimsdale, K. L. Chan, R. E. Martin, P. G. Jokisz,
A. B. Holmes, Chem. Rev. 2009, 109, 897–1091; b) Y. Kong,
Y. J. Fu, Y. G. Zu, W. Liu, W. Wang, X. Hua, M. Yang, Food
Chem. 2009, 117, 152–159; c) X. Hua, Y. J. Fu, Y. G. Zu, N.
Wu, Y. Kong, J. Li, X. Peng, T. Efferth, J. Pharm. Biomed.
Anal. 2010, 52, 273–279; d) S. R. Marder, B. Kippelen, A. K. Y.
Jen, N. Peyghambarian, Nature 1997, 388, 845–851.
2011, 76, 6414–6420.
[16] a) R. E. Maleczka, F. Shi, D. Holmes, M. R. Smith, J. Am.
Chem. Soc. 2003, 125, 7792–7793; b) K. Orito, A. Horibata, T.
Nakamura, H. Ushito, H. Nagasaki, M. Yuguchi, S. Yamash-
ita, M. Tokuda, J. Am. Chem. Soc. 2004, 126, 14342–14343.
[17] T. Yamane, K. Kikukawa, M. Takagi, T. Matsuda, Tetrahedron
1973, 29, 955–962.
4
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20393
/KAP1
Date: 23-04-12 15:42:40
Pages: 6
ortho-Olefination of Arylaldehyde O-Methyloximes
1
[
[
[
18] The ratio was obtained by H NMR spectroscopy; see the Sup-
[23] D. B. Berkowitz, S. Choi, J.-H. Maeng, J. Org. Chem. 2000, 65,
porting Information.
847–860.
19] D. L. Davies, S. M. A. Donald, S. A. Macgregor, J. Am. Chem.
Soc. 2005, 127, 13754–13755.
20] a) S. I. Gorelsky, D. Lapointe, K. Fagnou, J. Am. Chem. Soc.
[
[
24] M. L. S. King, M. M. Sullivan, Science 1946, 104, 244–245.
25] a) U. Claesson, A. Lassus, H. Happonen, L. Hogstrom, A.
Siboulet, Int. J. STD AIDS 1996, 7, 429–434; b) Y. Damayan-
thi, J. W. Lown, Curr. Med. Chem. 1998, 5, 205–252; c) C. T. L.
Lee, V. C. K. Lin, S. X. Zhang, X. K. Zhu, D. VanVliet, H.
Hu, S. A. Beers, Z. Q. Wang, L. M. Cosentino, S. L. Morris-
Natschke, Bioorg. Med. Chem. Lett. 1997, 7, 2897–2902.
Received: March 28, 2012
2
008, 130, 10848–10849; b) M. Lafrance, C. N. Rowley, T. K.
Woo, K. Fagnou, J. Am. Chem. Soc. 2006, 128, 8754–8756;
c) H.-Y. Sun, S. I. Gorelsky, D. R. Stuart, L.-C. Campeau, K.
Fagnou, J. Org. Chem. 2010, 75, 8180–8189.
[
[
21] K. M. Engle, D.-H. Wang, J.-Q. Yu, J. Am. Chem. Soc. 2010,
132, 14137–14151.
Published Online: ᭿
22] S. K. Meegalla, R. Rodrigo, J. Org. Chem. 1991, 56, 1882–1888.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5

Job/Unit: O20393
/KAP1
Date: 23-04-12 15:42:40
Pages: 6
Z. Xu, B. Xiang, P. Sun
SHORT COMMUNICATION
C–H Activation
Z. Xu, B. Xiang, P. Sun .................... 1–6
ortho-Olefination of Arylaldehyde O-
Methyloximes through Palladium-Cata-
lyzed C–H Activation
2
-Alkenylarylaldehyde
O-methyloximes
directing group in moderate to good yields.
Hydrolysis of the coupling products con-
veniently gave 2-alkenylarylaldehydes.
were obtained through palladium(II)-cata-
lyzed ortho-olefination of arylaldehyde O-
methyloximes by using O-methyloxime as a
Keywords: Palladium / C–H activation /
Olefination / Aldehydes / Isotope effects
6
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0