Palladium-catalyzed intramolecular 5-exo-dig hydroarylations of N-arylpropiolamides: Thermodynamics-controlled stereoselective synthesis of 3-methyleneoxindoles

Article abstract of DOI:10.1021/jo901963g

(Chemical Equation Presented) Palladium-catalyzed intramolecular hydroarylation of N-arylpropiolamides has been developed for the stereoselective synthesis of 3-(monosubstituted methylene)oxindoles. In the presence of Pd(OAc)₂ and dppf, a varie

Full text of DOI:10.1021/jo901963g

pubs.acs.org/joc
wide range of biological and pharmacological interest.1
Palladium-Catalyzed Intramolecular 5-exo-dig
Hydroarylations of N-Arylpropiolamides:
Thermodynamics-Controlled Stereoselective
Synthesis of 3-Methyleneoxindoles
Among these efficient methods,1-4 palladium-catalyzed
C-H bond activation with a subsequent C-C bond-forming
process is particularly effective and economic (Scheme 1).2,3
Zhu and co-workers have developed a Pd(OAc)2-catalyzed
tandem process for the preparation of 3-(diarylmethylene)-
oxindoles under basic conditions using both an anilide sp2
C-H bond and an electrophile (aryl iodides) as the coupling
partners.2 We have also reported a novel protocol for
selectively constructing the 3-(disubstituted methylene)-
oxindole skeleton by palladium-catalyzed oxidative C-H
functionalization of N-arylpropiolamides with nucleo-
philes.3 However, many bioactive oxindoles involve the
(Z)-3-(monosubstituted methylene)oxindole moiety.1 Thus,
the synthesis of (Z)-3-(monosubstituted methylene)oxindo-
les by the C-H functionalization is still interesting. We
envisioned that the intramolecular hydroarylation of
N-arylpropiolamides might realize the goal.5-8 In 2000,
Fujiwara and co-workers reported the first example of
hydroarylation of arylacetylenes.5,6 Since then, considerable
efforts have been paid to the hydroarylation of alkynes, and
two processes were observed: (1) the intramolecular 6-endo-
dig hydroarylation under acidic conditions,5-7 and (2) 5-exo-
dig hydroarylation under neutral conditions.8 Fujiwara and
co-workers, for example, have described that arylalkynes
could undergo the palladium-catalyzed intramolecular
hydroarylation reaction in acids to afford the corresponding
Tao-Shan Jiang, Ri-Yuan Tang, Xing-Guo Zhang,
Xin-Hua Li, and Jin-Heng Li*
College of Chemistry and Materials Science,
Wenzhou University, Wenzhou 325035, China
jhli@hunnu.edu.cn
Received September 12, 2009
Palladium-catalyzed intramolecular hydroarylation of
N-arylpropiolamides has been developed for the stereoselec-
tive synthesis of 3-(monosubstituted methylene)oxindoles. In
the presence of Pd(OAc)2 and dppf, a variety of N-arylpro-
piolamides successfully underwent the intramolecular hydro-
arylation reaction to afford the corresponding 3-(mono-
substituted-methylene)oxindoles in moderate to excellent
yields. It is noteworthy that the stereoselectivity of the reaction
can be controlled by varying the reaction temperature.
(4) For selected papers on the other methods for the synthesis of
oxindoles see: (a) Cheung, W. S.; Patch, R. J.; Player, M. R. J. Org. Chem.
2005, 70, 3741. (b) Yanada, R.; Obika, S.; Inokuma, T.; Yanada, K.;
Yamashita, M.; Ohta, S.; Takemoto, Y. J. Org. Chem. 2005, 70, 6972.
ꢀ
(c) Couty, S.; Liegault, B.; Meyer, C.; Cossy, J. Org. Lett. 2004, 6, 2511.
(d) D’Souza, D. M.; Rominger, F.; Muller, T. J. J. Angew. Chem., Int. Ed.
€
2005, 44, 153. (e) Tang, S.; Yu, Q.-F.; Peng, P.; Li, J.-H.; Zhong, P.; Tang,
R.-Y. Org. Lett. 2007, 9, 3413. (f) Yanada, R.; Obika, S.; Oyama, M.;
Takemoto, Y. Org. Lett. 2004, 6, 2825. (g) Shintani, R.; Yamagami, T.;
Hayashi, T. Org. Lett. 2006, 8, 4799. (h) Miura, T.; Takahashi, Y.; Mur-
akami, M. Org. Lett. 2007, 8, 5075. (i) Miura, T.; Takahashi, Y.; Murakami,
M. Org. Lett. 2008, 10, 1743. (j) Mori, M.; Ban, Y. Tetrahedron Lett. 1979,
20, 1133. (k) Sun, L.; Liang, C.; Shirazian, S.; Zhou, Y.; Miller, T.; Cui, J.;
Fukuda, J. Y.; Chu, J.-Y.; Nematalla, A.; Wang, X.; Chen, H.; Sistla, A.;
Luu, T. C.; Tang, F.; Wei, J.; Tang, C. J. Med. Chem. 2003, 46, 1116.
(l) Wang, L.; Zhang, Y.; Hu, H.-Y.; Fun, H. K.; Xu, J.-H. J. Org. Chem.
2005, 70, 3805. (m) Kalinski, C.; Umkehrer, M.; Schmidt, J.; Ross, G.; Kolb,
J.; Burdack, C.; Hiller, W.; Hoffmann, S. D. Tetrahedron Lett. 2006, 47,
4683. (n) Xing, X.; Wu, J.; Luo, J.; Dai, W.-M. Synlett 2006, 2099. (o) Yang,
T.-M.; Liu, G. J. Comb. Chem. 2007, 9, 86. (p) Overman, L. E.; Watson, D. A.
J. Org. Chem. 2006, 71, 2587. (q) Kamijo, S.; Sasaki, Y.; Kawazawa, C.;
Schubeler, T.; Yamamoto, Y. Angew. Chem., Int. Ed. 2005, 44, 7718.
(r) Mao, Z.; Baldwin, S. W. Org. Lett. 2004, 6, 2425. (s) Hills, I. D.; Fu, G.
C. Angew. Chem., Int. Ed. 2003, 42, 3921. (t) Arumugam, V.; Routledge, A.;
Abell, C.; Balasubramanian, S. Tetrahedron Lett. 1997, 38, 6473. (u) Tei-
chert, A.; Jantos, K.; Harms, K.; Studer, A. Org. Lett. 2004, 6, 3477. (v) Park,
J. H.; Kim, E.; Chung, Y. K. Org. Lett. 2008, 10, 4719.
The construction of the oxindole skeleton is a continuing
hot topic in the field of organic chemistry1-4 as a result of a
(1) (a) Mohammadi, M; McMahon, G.; Sun, L.; Tang, C.; Hirth, P.; Yeh,
B. K.; Hubbard, S. R.; Schlessinger, J. Science 1997, 276, 955. (b) Sun, L.;
Tran, N.; Liang, C.; Tang, F.; Rice, A.; Schreck, R.; Waltz, K.; Shawver,
L. K.; McMahon, G.; Tang, C. J. Med. Chem. 1999, 42, 5120. (c) Hare, B. J.;
Walters, W. P.; Caron, P. R.; Bemis, G. W. J. Med. Chem. 2004, 47, 4731.
(d) Noble, M. E. M.; Endicott, J. A.; Johnson, L. N. Science 2004, 304, 1800.
(e) Liao, J. J.-L. J. Med. Chem. 2007, 50, 409. (f) Drugs Fut. 1990, 15, 898.
(g) Robinson, R. P.; Reiter, L. A.; Barth, W. E.; Campeta, A. M.; Cooper, K.;
Cronin, B. J.; Destito, R.; Donahue, K. M.; Falkner, F. C.; Fiese, E. F.; Johnson,
D. L.; Kuperman, A. V.; Liston, T. E.; Malloy, D.; Martin, J. J.; Mitchell, D. Y.;
Rusek, F. W.; Shamblin, S. L.; Wright, C. F. J. Med. Chem. 1996, 39, 10.
(h) Andreani, A.; Burnelli, S.; Granaiola, M.; Leoni, A.; Locatelli, A.; Morigi, R.;
Rambaldi, M.; Varoli, L.; Kunkel, M. W. J. Med. Chem. 2006, 49, 6922.
(i) Graczyk, P. P. J. Med. Chem. 2007, 50, 5773.
(5) For reviews on the intramolecular hydroarylation of alkynes, see:
(a) Jia, C.; Kitamura, T.; Fujiwara, Y. Acc. Chem. Soc. 2001, 34, 633.
(b) Nevado, C.; Echavarren, A. M. Synthesis 2005, 167. (c) Fairlamb, I. J. S.
Annu. Rep. Prog. Chem., Sect. B: Org. Chem. 2006, 102, 50.
(2) (a) Pinto, A.; Neuville, L.; Retailleau, P.; Zhu, J. Org. Lett. 2006, 8,
4927. (b) Pinto, A.; Neuville, L.; Zhu, J. Angew. Chem., Int. Ed. 2007, 46,
3291. (c) Pinto, A.; Neuville, L.; Zhu, J. Tetrahedron Lett. 2009, 50, 3602.
(d) Song, R.-J.; Liu, Y.; Li, R.-J.; Li, J.-H. Tetrahedron Lett. 2009, 50, 3912.
(3) (a) Tang, S.; Peng, P.; Zhong, P.; Li, J. H. J. Org. Chem. 2008, 73, 5476.
(b) Pi, S. F.; Liang, Y.; Wang, N. X.; Li, J. H. Org. Lett. 2008, 10, 1179.
(c) Tang, S.; Peng, P.; Wang, Z. Q.; Tang, B. X.; Deng, C. L.; Li, J. H.; Zhong,
P.; Wang, N. X. Org. Lett. 2008, 10, 1875. (d) Peng, P.; Tang, B.-X.; Pi, S.-F.;
Liang, Y.; Li, J.-H. J. Org. Chem. 2009, 74, 3569. (e) Tang, D.-J.; Tang, B.-X.;
Li, J.-H. J. Org. Chem. 2009, 74, 6749.
(6) For papers on palladium-catalyzed 6-endo-dig hydroarylation of
alkynes, see: (a) Jia, C.; Piao, D.; Oyamada, J.; Lu, W.; Kitamura, T.;
Fujiwara, Y. Science 2000, 287, 1992. (b) Jia, C.; Lu, W.; Oyamada, J.;
Kitamura, T.; Matsuda, K.; Irie, M.; Fujiwara, Y. J. Am. Chem. Soc. 2000,
122, 7252. (c) Jia, C.; Piao, D.; Kitamura, T.; Fujiwara, Y. J. Org. Chem.
2000, 65, 7516. (d) Lu, W.; Jia, C.; Kitamura, T.; Fujiwara, Y. Org. Lett.
2000, 2, 2927. (e) Trost, B. M.; Toste, F. D.; Greenman, K. J. Am. Chem. Soc.
2003, 125, 4518. (f) Viciu, M. S.; Stevens, E. D.; Petersen, J. L.; Nolan, S. P.
Organometallics 2004, 23, 3752. (g) Ahlquist, M.; Fabrizi, G.; Cacchi, S.;
Norrby, P.-O. J. Am. Chem. Soc. 2006, 128, 12785.
8834 J. Org. Chem. 2009, 74, 8834–8837
Published on Web 10/22/2009
DOI: 10.1021/jo901963g
r
2009 American Chemical Society

Jiang et al.
JOCNote
6-endo-dig cyclization products (eq 1 in Scheme 1).6 Recently,
Gevorgyan and Chemyak reported that under neutral con-
ditions an exclusive 5-exo-dig hydroarylation reaction of
o-alkyne biaryls could take place in the presence of
Pd(OAc)2/d-i-Prpf (1,10-bis(diisopropylphosphino)ferrocene),
providing the corresponding 5-exo-dig cyclization products
(9-benzylidene-9H-fluorene derivatives) in moderate to excel-
lent yields.8 Here, we report a simple and efficient protocol
for the stereoselective synthesis of (Z)- and (E)-3-(mono-
substituted methylene)oxindoles by Pd(OAc)2/dppf-cata-
lyzed hydroarylation of N-arylpropiolamides (eq 2 in Scheme 1).
selectivity toward (E)-2a was increased to some extent using
toluene solvent at 140 °C (entry 7). We were pleased to
discover selectivity toward (Z)-2a when the reaction tempera-
ture was decreased in toluene (entries 8-11). Whereas 100 °C
provided 83% of (Z)-2a and 15% of (E)-2a (entry 8), 80 °C
afforded the desired (Z)-2a alone in 86% yield (entry 9).
Although the target (Z)-2a was still isolated exclusively at
lower temperatures, both the conversion and yield were
reduced even prolonging the reaction time (entries 10 and
11). The structure of (Z)-2a was unambiguously assigned by
the X-ray single-crystal diffraction analysis, and the config-
uration of the trisubstituted carbon-carbon double bond was
SCHEME 1. Hydroarylation Reaction Involving a C-H Activation
Process
determined according to the authoritative 1H NMR and 13
C
NMR spectra of both (E)-2a and (E)-2b.4u,v,9
TABLE 1. Screening Conditionsa
yield (%)
The hydroarylation reaction of N-methyl-N,3-diphenyl-
propiolamide (1a) was conducted to screen the optimal
conditions, and the results are summarized in Table 1.
Initially, a series of phosphine ligands, including PPh3
(L1), dppf (1,10-bis(diphenyphosphino)ferrocene; L2), d-
i-Prpf (L3), and tert-butyl Xphos (2-di-tert-butylphosphino-
20,40,60-triisopropylbiphenyl; L4), were tested for the reaction
of substrate 1a with Pd(OAc)2 in xylene at 120 °C (entries
1-5). Without ligands, a trace amount of the target products
was observed by GC-MS analysis together with a rather low
conversion (entry 1). To our delight, amide 1a could be
consumed completely to afford the two isomers (Z)-2a and
(E)-2a in good total yields using ligands L1-L3 (entries 2-4).
Treatment of substrate 1a with Pd(OAc)2 and L2, for in-
stance, gave the target products (Z)-2a and (E)-2a in 93%
total yield (entry 3). However, L4 has no activity for the
reaction (entry 5). Interestingly, the selectivity was shifted
toward (E)-2a at higher temperature (entries 6 and 7). At
140 °C in xylene, (E)-2a was obtained as a major product in
76% yield along with 21% yield of (Z)-2a from the reaction of
amide 1a with Pd(OAc)2 and L2 (entry 6). We found that the
entry ligand solvent T (°C) t (h) conv (%)b (Z)-2a (E)-2a
1
2
3
4
5
6
7
8
xylene
xylene
xylene
xylene
xylene
xylene
toluene
toluene
toluene
toluene
toluene
120
120
120
120
120
140
140
100
80
10
10
10
10
10
8
<5
100
100
100
<5
100
100
100
100
58
trace
32
52
trace
49
41
50
trace
76
83
15
0
L1
L2
L3
L4
L2
L2
L2
L2
L2
L2
38
trace
21
17
8
10
12
24
36
83
86
55
28
9
10
11
60
25
0
0
30
aReaction conditions: 1a (0.2 mmol), Pd(OAc)2 (5 mol %), and ligand
(5 mol %) in solvent (1 mL). bThe conversion was determined by
GC-MS analysis.
With the standard conditions in hand, both the scope of
N-arylpropiolamides and the selectivity at different tempera-
ture were investigated (Tables 2 and 3). As shown in Table 2,
the hydroarylation reactions of various N-arylpropiola-
mides at 80 °C were first examined to prepare (Z)-
3-(arylmethylene)oxindoles. In the presence of Pd(OAc)2
and dppf (L2), the analogous amides with the N-methyl
group replaced by either a benzyl or an acetyl group under-
went the hydroarylation reaction smoothly to afford the
corresponding products 2b and 2c in moderate yields (entries
1 and 2). However, N-unsubstituted propiolamide (1d)
was not suitable for the reaction under the same conditions
(entry 3). To our delight, several functional groups, such as
methoxy, methyl, fluoro, and chloro, on the aromatic ring of
N-arylpropiolamides were tolerated well. MeO-substituted
substrate 1e, for instance, smoothly underwent the reac-
tion with Pd(OAc)2 and L2 in 80% yields (entry 4).
Although substrates 1f-1i, bearing an o-methyl group
(7) For selected papers on other transition-metal-mediated 6-endo-dig
hydroarylation of alkynes, see: (a) Tunge, J. A.; Foresee, L. N. Organome-
tallics 2005, 24, 6440. (b) Soriano, E.; Marco-Contelles, J. Organometallics
2006, 25, 4542. Pt: (c) Pastine, S. J.; Youn, S. W.; Sames, D. Org. Lett. 2003,
€
5, 1055. (d) Mamane, V.; Hannen, P.; Furstner, A. Chem.;Eur. J. 2004, 10,
4556. (e) Nevado, C.; Echavarren, A. M. Chem.;Eur. J. 2005, 11, 3155. Au:
(f) Reetz, M. T.; Sommer, K. Eur. J. Org. Chem. 2003, 3485. (g) Shi, Z.; He, C.
J. Org. Chem. 2004, 69, 3669. (h) England, D. B.; Padwa, A. Org. Lett. 2008,
10, 3631. Fe: (i) Li, R.; Wang, S. R.; Lu, W. Org. Lett. 2007, 9, 2219. Re:
(j) Kuninobu, Y.; Kikuchi, K.; Tokunaga, Y.; Nishina, Y.; Takai, K. Tetrahedron
2008, 64, 5974. Rh: (k) Hong, P.; Cho, B.-R.; Yamazaki, H. Chem. Lett. 1980,
507. (l) Boese, W. T.; Goldman, A. S. Organometallics 1991, 10, 782.
(m) Aulwurm, U. R.; Melchinger, J. U.; Kisch, H. Organometallics 1995, 14,
3385. Ru: (n) Hong, P.; Cho, B.-R.; Yamazaki, H. Chem. Lett. 1979, 339.
(o) Kakiuchi, F.; Yamamoto, Y.; Chatani, N.; Murai, S. Chem. Lett. 1995, 681.
Lewis acid: (p) Song, C. E.; Jung, D.-u.; Choung, S. Y.; Roh, E. J.; Lee, S.-g.
Angew. Chem., Int. Ed. 2004, 43, 6183. (q) Yoon, M. Y.; Kim, J. H.; Choi, D. S.;
Shin, U. S.; Lee, J. Y.; Song, C. E. Adv. Synth. Catal. 2007, 349, 1725.
(8) (a) Chernyak, N.; Gevorgyan, V. J. Am. Chem. Soc. 2008, 130, 5636.
(b) Chernyak, N.; Gevorgyan, V. Adv. Synth. Catal. 2009, 351, 1101.
(9) The selectivity toward the E-isomer under the optimized conditions
(entry 7 in Table 1) is higher than that of eq 3 because isomerization of olefins
to the E-isomer can take place in the presence of Pd(II); see: Yu, J.; Gaunt,
M. J.; Spencer, J. B. J. Org. Chem. 2002, 67, 4627.
J. Org. Chem. Vol. 74, No. 22, 2009 8835

Jiang et al.
JOCNote
TABLE 2. Palladium-Catalyzed 5-exo-dig Hydroarylation Reactions of N-Arylpropiolamides (1) at 80 °Ca
aReaction conditions: 1 (0.2 mmol), Pd(OAc)2 (5 mol %), and L2 (5 mol %) in toluene (1 mL) at 80 °C for 12 h. bFor 36 h. cAt 120 °C for 12 h.
dAt 120 °C for 24 h.
1b with Pd(OAc)2 and L2 at 140 °C afforded a mixture of
or electron-withdrawing groups, afforded a mixture of Z-
(Z)-2b and (E)-2b, and (E)-2b was the major product in 59%
yield along with 30% of (Z)-2b (entry 1). Identical results
were observed from the reactions of other substrates 1e-1f
and 1m (entries 2-5).
and E-isomers, the total yields are still satisfactory
(entries 5-8). Substituents at the terminal alkyne were
subsequently investigated (entries 9-14). The results de-
monstrated that the property of substituents affected the
reaction to some extent. Substrate 1j with a 4-MeC6H4
group was successfully reacted with Pd(OAc)2 and L2 in
81% yield (entry 9), whereas propiolamide 1k having a
stronger electron-donating group, a 4-MeOC6H4 group,
afforded only 31% yield (entry 10). We were pleased to
find that substrates 1l and 1m, bearing electron-deficient
groups, displayed higher activity under the standard
conditions (entries 11 and 12). It is noteworthy that amide
1n with a furan-2-yl group is still a suitable substrate for
the reaction (entry 13). However, substrate 1o bearing an
aliphatic group was less efficient, affording 2o in a low
yield (entry 14).
To elucidate the mechanism, the reaction of (Z)-2a was
heated in toluene at 140 °C (eq 3 in Scheme 2). The result
showed that the Z-isomer could be converted to the E-isomer
at higher temperature without catalysts. After 10 h, (E)-2a
was isolated in 75% yield and (Z)-2a was recovered in 21%
yield.9 The results of computational study revealed that the
energies of (Z)-2a and (E)-2a are -20205.207 and -20205.053 eV,
respectively, and the energy difference is only 3.562 kcal/mol
(calculated by the HF method in the Gaussian program).
Therefore, (E)-2a could be obtained easily from (Z)-2a at
140 °C. The deuterium-labeled experiment was also carried
out in toluene at 80 °C, affording the H- and D-substituted
products (Z)-3a-D1 (eq 4 in Scheme 2).10 The results
As shown in Table 3, the reaction at 140 °C was explored to
shift the stereoselectivity toward (E)-3-(monosubstituted
methylene)oxindoles. As expected, treatment of substrate
(10) See Supporting Information for detailed results.
8836 J. Org. Chem. Vol. 74, No. 22, 2009

Jiang et al.
JOCNote
TABLE 3. Palladium-Catalyzed Hydroarylation Reactions at 140 °Ca
SCHEME 3. Possible Mechanism
the desired products (Z)-2 and/or (E)-2. The products (Z)-2
can be converted to (E)-2 under thermodynamics control.
Another route cannot be rule out: HPd(OAc)Ln is generated
in situ from the reaction of Pd(OAc)2 with ligand,11 followed
by cis-hydropalladation of alkyne to afford intermediate
D. Sequential C-H activation/reductive elimination of
intermediate D gives the product (Z)-2.
In summary, we have developed a novel and facile
method for the stereoselective synthesis of 3-(mono-
substituted methylene)oxindoles in moderate to excellent
yields by Pd(OAc)2/dppf (L2)-catalyzed 5-exo-dig hydroary-
lation of N-arylpropiolamides. Importantly, we found that
the stereoselectivity of the products was thermodynamics-
controlled, which provided an attractive route to the conver-
sion of (Z)-olefins into (E)-olefins in organic synthesis.
Experimental Section
aReaction conditions: 1 (0.2 mmol), Pd(OAc)2 (5 mol %) and L2
(5 mol %) in toluene (1 mL) at 140 °C for 12 h.
Typical Experimental Procedure for the Palladium-Catalyzed
Intramolecular Hydroarylation of N-Arylpropiolamides (1). To a
flame-dried Schlenk tube was added N-arylpropiolamides 1
(0.2 mmol), Pd(OAc)2 (5 mol %), dppf (10 mol %), and toluene
(1 mL). The mixture was stirred at the indicated temperature
(80 or 140 °C) for the indicated time until complete consumption
of starting material as monitored by TLC and GC-MS analysis.
After the reaction was finished, the mixture was filtered by a crude
column with ethyl acetate as eluent and evaporated in vacuum. The
residue was purified by flash column chromatography on a silica gel
using EtOAc/petroleum ether (1:15) as eluent to give the product 2.
(Z)-1-Acetyl-3-benzylideneindolin-2-one (2c). Yellow solid,
mp 104.1-106.3 °C. 1H NMR (300 MHz, CDCl3) δ: 8.32
(d, J=8.2 Hz, 1H), 7.90 (s, 1H), 7.73-7.65 (m, 3H), 7.51-7.47
SCHEME 2. Controlled Reactions
(m, 3H), 7.36-7.27 (m, 1H), 7.05-7.03 (m, 1H), 2.75 (s, 3H). 13
C
NMR (75 MHz, CDCl3) δ: 170.9, 168.6, 140.2, 138.7, 134.4, 131.8,
130.3, 130.1, 129.2, 128.8, 128.4, 124.5, 122.1, 116.7, 26.9. IR
(KBr, cm-1): 2915, 1684, 1595, 1449, 1114. LRMS (EI, 70 eV) m/z
(%): 263 (Mþ, 32), 221 (100), 220 (67), 144 (39). HRMS (ESI)
C17H13NO2Na [M þ Na]þ: calcd 286.0843, found 286.0840.
Acknowledgment. We thank authors thank the National
Natural Science Foundation of China (No. 20872112), Program
of Science and Technology of Wenzhou (No. G20090080),
Zhejiang Provincial Natural Science Foundation of China
(Nos. Y407116 and Y4080169), and Wenzhou University
(No. 2007L004) for financial support.
suggested that the deuterium atom of methylene was from
the ortho-position of anilide via a Pd-catalyzed aromatic
C-H activation pathway.
Two possible mechanisms were proposed as outlined in
Scheme 3 on the basis of the reported mechanism and the
present results.5-9,11 Sequential C-H activation/complexa-
tion with alkyne affords intermediate B, followed by cis-
and/or trans-addition to yield intermediates (Z)-C and/or
(E)-C.9 Protonation of intermediates C takes place to give
Supporting Information Available: Analytical data and
spectra (1H and 13C NMR) for all products 2; X-ray data of 2a;
typical procedure for the Pd-catalyzed hydroarylation reactions.
This material is available free of charge via the Internet at http://
pubs.acs.org.
(11) (a) Hatano, M.; Terada, M.; Mikami, K. Angew. Chem., Int. Ed.
2001, 40, 249. (b) Amatore, C.; Jutant, A.; Meyer, G.; Carelli, I.; Chiarotto, I.
Eur. J. Inorg. Chem. 2000, 1855.
J. Org. Chem. Vol. 74, No. 22, 2009 8837