Selective synthesis of 3-aryl quinolin-2(1H)-ones and 3-(1-arylmethylene) oxindoles involving a 2-fold arene C-H activation process

Article abstract of DOI:10.1021/jo901314t

(Chemical Equation Presented) A novel and selective palladium-catalyzed C-H activation protocol has been developed for the synthesis of 3-aryl quinolin-2(1H)-ones and 3-(1-arylmethylene)oxindoles with use of PivOH as the switch. In the presence of Pd(OAc)

Full text of DOI:10.1021/jo901314t

pubs.acs.org/joc
Selective Synthesis of 3-Aryl Quinolin-2(1H)-ones and
3-(1-Arylmethylene)oxindoles Involving a 2-Fold Arene C-H
Activation Process
Dong-Jun Tang,† Bo-Xiao Tang,† and Jin-Heng Li*,†,‡
†Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research (Ministry of Education),
Hunan Normal University, Changsha 410081, China, and ‡College of Chemistry and Materials Science,
Wenzhou University, Wenzhou 325035, China
jhli@hunnu.edu.cn
Received June 19, 2009
A novel and selective palladium-catalyzed C-H activation protocol has been developed for the
synthesis of 3-aryl quinolin-2(1H)-ones and 3-(1-arylmethylene)oxindoles with use of PivOH as the
switch. In the presence of Pd(OAc)2, AgOAc, and PivOH, a variety of N-methyl anilides reacted with
arenes to afford the corresponding 3-aryl quinolin-2(1H)-ones in moderate yields, whereas the
selectivity was shifted toward 3-(1-arylmethylene)oxindoles in the absence of PivOH.
Introduction
tion has been given to the hydroarylation of alkynes since it
was first reported by Fujiwara.1-4 The hydroarylation of
alkynes under acidic conditions usually proceeds via the
intramolecular 6-endo-dig hydroarylation process. Fujiwara
and co-workers, for example, first found that arylalkynes
could undergo the palladium-catalyzed intramolecular
hydroarylation reaction in acids to afford the endo-six-
membered heterocycles (Scheme 1).1,2 Recently, Gevorgyan
and Chemyak reported an interesting Pd-catalyzed exclusive
5-exo-dig hydroarylation of o-alkyne biaryls under neutral
conditions. However, all the methods are limited because
they only introduced one carbon and one hydrogen atom
into a carbon-carbon triple bond to form a carbon-carbon
bond and a hydrogen-carbon bond. According to the
mechanism, a novel strategy for capturing the C-Pd
σ-bonds in intermediates B or C by other groups instead of
Palladium-catalyzed addition of an arene C-H bond to a
carbon-carbon triple bond has proven to be a powerful
carbon-carbon forming reaction.1-5 However, much atten-
(1) For reviews, 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 2006, 102, 50.
(2) For palladium-catalyzed 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. (h) Chernyak, N.; Gevorgyan, V. J. Am. Chem. Soc.
2008, 130, 5636.
(3) For other transition metal-catalyzed hydroarylation of alkynes, see:
(a) Tunge, J. A.; Foresee, L. N. Organometallics 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.;
F€urstner, 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) Yamazaki, H.; Hong, P. J. Mol. Catal.
1983, 21, 133. (m) Tokunaga, Y.; Sakakura, T.; Tanaka, M. J. Mol. Catal. 1989,
56, 305. (n) Boese, W. T.; Goldman, A. S. Organometallics 1991, 10, 782. (o)
Aulwurm, U. R.; Melchinger, J. U.; Kisch, H. Organometallics 1995, 14, 3385.
Ru: (p) Hong, P.; Cho, B.-R.; Yamazaki, H. Chem. Lett. 1979, 339. (q) Kakiuchi,
F.; Yamamoto, Y.; Chatani, N.; Murai, S. Chem. Lett. 1995, 681.
(4) For Lewis acid-catalyzed hydroarylation of alkynes, see: (a) Song, C.
E.; Jung, D.-u.; Choung, S. Y.; Roh, E. J.; Lee, S.-g. Angew. Chem., Int. Ed.
2004, 43, 6183. (b) Yoon, M. Y.; Kim, J. H.; Choi, D. S.; Shin, U. S.; Lee, J.
Y.; Song, C. E. Adv. Synth. Catal. 2007, 349, 1725.
(5) (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. (e)
Tang, S.; Peng, P.; Pi, S.-F.; Liang, Y.; Wang, N.-X.; Li, J.-H. Org. Lett.
2008, 10, 1179. (f) 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. (g) Tang, S.;
Peng, P.; Zhong, P.; Li, J.-H. J. Org. Chem. 2008, 73, 5476. (h) Peng, P.; Tang,
B.-X.; Pi, S.-F.; Liang, Y.; Li, J.-H. J. Org. Chem. 2009, 74, 3569.
DOI: 10.1021/jo901314t
r
Published on Web 08/04/2009
J. Org. Chem. 2009, 74, 6749–6755 6749
2009 American Chemical Society

Tang et al.
JOCArticle
SCHEME 1
TABLE 1. Screening Optimal Conditionsa
yield (%)
entry ligand
[Ag]
additive (equiv) t (°C)b 3Aa 4Aa 5Aa
1c
2
AgOAc CF3COOH (6)
AgOAc PivOH (6)
AgOAc 4-NO2C6H4CO2H 110 32
110
110 34
0
trace 0
41
10
0
0
3
4
5
6
7
8
9
AgOAc AcOH
110 trace trace 0
110 trace trace 0
AgOAc C6H5CO2H
AgOAc PivOH (6)
AgOAc PivOH (6)
AgOAc PivOH (6)
AgOAc PivOH (6)
AgOAc PivOH (6)
AgOAc PivOH (6)
AgOAc PivOH (6)
AgOAc PivOH (4)
AgOAc PivOH (1.5)
AgOAc PivOH (0.3)
AgOAc PivOH (0.1)
AgOAc
L1
L2
L3
L4
110 43
110 17
110 15
110 33
110 23
140 47
140 40
140 38
140 23
140 14
140 10
35
53
50
39
51
33
41
32
47
0
0
0
0
0
0
0
10 L5
11 L1
12d
hydrogen would be highly desirable. Zhu and co-workers have
reported an interesting palladium-catalyzed domino reaction of
arylalkynes with electrophilic aryl iodides to afford the exo-five-
membered heterocycles under basic conditions.5a-c We also
discovered that exo-five-membered heterocycles were prepared
by the palladium-catalyzed oxidative C-H functionalization of
arylalkynes with nucleophiles,5d-h and the selectivity was not
affected by the conditions (acidic or basic). Recently, transition
metal-catalyzed activation of sp2 C-H bonds of arenes have
been widely investigated, and emerged as a promising method
for carbon-carbon bond formation.6 These prompted us to
examine the feasibility of arenes as an alternative to hydrogen to
capture the C-Pd σ-bonds. After a series of trials, we were
delighted to find that selective 5-exo-dig and 6-endo-dig diaryla-
tion of N-arylpropiolamides with arenes could be conducted
successfully via a 2-fold arene C-H activation pathway, and the
switch of the selectivity is PivOH (Scheme 1).
13 L1
14 L1
15 L1
16 L1
17 L1
18 L1
19 L1
20e L1
21 L1
22 L1
trace
14
trace 25
trace 30
140 trace 0
140
59
0
AgOAc PivOCs (2)
PivOH (6)
AgOAc PivOH (6)
Ag2CO3 PivOH (6)
AgSbF6 PivOH (6)
0
0
110 trace trace 0
140
0
0
0
110 trace trace 0
110 trace trace 0
aReaction conditions: 1A (0.2 mmol), benzene 2a (60 equiv), Pd(OAc)2
(5 mol %), ligand (10 mol %), AgOAc (3 equiv), and additive under Ar
atmosphere for 24 h. Substrate 1A was consumed completely, and some
side products via the decomposition of the two C-N bonds were observed
by GC-MS analysis. bOil-bath temperature. c6Aa was isolated in 80%
yields. dPdCl2(Ph3P)2 instead of Pd(OAc)2. eWithout Pd catalysts.
instead of CF3COOH (entry 2). Identical results were ob-
served by using 4-nitrobenzoic acid (entry 3). However, both
HOAc and benzoic acid have no activity (entries 4 and 5).
Subsequently, other conditions, such as ligand and reaction
temperature, were screened to enhance the yield. Among the
ligand and temperature examination, PPh3 (L1) combined
with 140 °C gave the best results (entries 6-11). We found
that PdCl2(Ph3P)2 was less effective than the Pd(OAc)2/Ph3P
system (entry 12). It was interesting to disclose that the
amount of PivOH affected the selectivity, and the selectivity
toward the 5-exo-dig diarylation occurred along with
decreasing loading of PivOH (entries 13-17). We found that
a trace amount of the 5-exo-dig diarylation product 5Aa
was observed in the presence of 4 equiv of PivOH (entry 13),
and the yield of 5Aa was enhanced to 30% at 0.1 equiv
of PivOH (entry 16). Gratifyingly, the product 5Aa was
obtained exclusively in 59% yield without PivOH (entry 17).
It is noted that PivOCs has no effect on the reaction (entry 18),
and no product was observed in the absence of Pd or Ag
catalysts (entries 19 and 20). Finally, two other Ag salts were
tested, and they were less effective (entries 21 and 22).
Results and Discussion
The reaction of N-methyl-N,3-diphenylpropiolamide (1A)
with benzene (2a) was carried out to optimize the reaction
conditions (Table 1). Our investigation began with an
attempt at diarylation of amide 1A with 60 equiv of benzene
(2a), 5 mol % of Pd(OAc)2, 3 equiv of AgOAc, and 6 equiv of
CF3COOH at 110 °C. However, only 1-methyl-4-phenylqui-
nolin-2(1H)-one (6Aa),
the reported hydroarylation product, was isolated in 80%
yield (entry 1). To our delight, the target product 3Aa was
obtained in 34% yield along with 41% yield of another
hydropivaloyloxylation product 4Aa with use of PivOH
(6) For selected reviews, see: (a) Alberico, D.; Scott, M. E.; Lautens, M.
Chem. Rev. 2007, 107, 174. (b) Campeau, L.-C.; Fagnou, K. Chem. Commun.
2006, 1253. (c) Beccalli, E. M.; Gianluigi Broggini, G.; Martinelli, M.;
Sottocornola, S. Chem. Rev. 2007, 107, 5318.
With the optimal conditions in hand, we decided to
explore the anilide scope for the 6-endo-dig diarylation
6750 J. Org. Chem. Vol. 74, No. 17, 2009

Tang et al.
JOCArticle
TABLE 2. Pd(OAc)2-Catalyzed Selective 6-endo-dig Diarylation in the Presence of PivOHa
aReaction conditions: 1 (0.2 mmol), benzene 2a (60 equiv), Pd(OAc)2 (5 mol %), PPh3 (L1; 10 mol %), AgOAc (3 equiv), and PivOH (6 equiv) at
140 °C under argon atmosphere for 24 h. bSubstrate 1 was consumed completely, and some side products via the decomposition of the two C-N bonds
were observed by GC-MS analysis.
reaction with benzene (2a) first (Table 2). The results demon-
strated that the analogous amides with the N-methyl group
replaced by either a hydrogen atom or an acetyl group were
unsuitable substrates (entries 1 and 2). Consequently, a
variety of N-methyl anilides 1D-P were investigated in the
presence of Pd(OAc)2, AgOAc, and PivOH (entries 3-15).
We were pleased to find that several functional groups, such
as methyl, methoxy, fluoro, or chloro groups, on the
N-aromatic ring were perfectly tolerated, but both the iodo
group and the steric hindrance effect disfavored the reaction
(entries 3-9). While substrate 1D bearing a methyl at the
para-position gave the corresponding products 3Da in 51%
yield and 4Da in 36% yield under the standard conditions
(entry 3), substrate 1F having an o-methyl group reduced the
yield of the desired product 3Fa to 34% together with the
product 4Fa in 44% yield (entry 5). It is worthy noting that
the 6-positon arene C-H activated product 3Ea is selectively
obtained from N-methyl-3-phenyl-N-m-tolylpropiolamide
(1E) (entry 4). The results revealed that the properties of
halide groups affected the yields of the products 3, with the
order of the yields being F > Cl > I (entries 7-9). Sub-
stitutents at the terminal alkyne moiety of N-methyl-N-
phenylpropiolamides were also evaluated. It was found that
both para- and meta-substituted aryl groups, either electron
J. Org. Chem. Vol. 74, No. 17, 2009 6751

Tang et al.
JOCArticle
SCHEME 2. Cyclization Reactions of Amide 1A with Toluene (2b)
deficient or electron rich, were effective for the reaction in
good total yields under the standard conditions (entries 10-
12 and 14), but o-methoxyphenyl and alkyl groups have no
activity (entries 13 and 15). Amide 1M bearing a p-methoxy-
phenyl group, for example, was treated with benzene (2a),
Pd(OAc)2, AgOAc, and PivOHto afford a 49% yield of the
target product 3Ma and 43% yield of 4Ma (entry 12), and
74% total yield was still achieved from substrate 1O with a
p-acetylphenyl group (entry 14).
Next, 5-exo-dig diarylation of N-arylpropiolamides with
benzene (1a) was evaluated with Pd(OAc)2, PPh3, and AgOAc
in the absence of PivOH (Table 2). We found that sub-
strates 1B and 1C were still unsuitable for the 5-exo-dig
diarylation reaction under the standard conditions (entries 1
and 2). However, N-methyl-substituted substrate 1D under-
went the 5-exo-dig diarylation reaction with Pd(OAc)2, PPh3,
and AgOAc smoothly to afford the corresponding 5-exo-dig
product 5Da in 65% yield (entry 3). Identical results were
obtained from the reactions of amides 1E-I, 1M, and 1O,
bearing electron-donating or electron-withdrawing groups on
the aryl moiety, under the same conditions (entries 4-10), but
5-exo-dig diarylation of N-methyl-N-phenyloct-2-ynamide 1P
was unsuccessful (entry 11). Substrate 1F bearing an o-methyl
group, for instance, was treated Pd(OAc)2, PPh3 and AgOAc
efficiently to afford the target product 5Fa in moderate yield
(entry 5). To our delight, the standard conditions were also
compatible with amides 1H and 1I with a halo-substituted aryl
group (entries 7 and 8).
(Scheme 3). We found that without arenes a mixture of
products, including the hydropivaloyloxylation product 4Aa
and the decomposition products, were observed by GC-MS
analysis from the reaction of substrate 1A with Pd(OAc)2,
AgOAc, and PivOH (eq 4 in Scheme 3). The product 4 can be
obtained without arenes, which suggests the competition be-
tween the C-H activation and the hydropivaloyloxylation
reaction in the present 6-endo-dig diarylation process. For the
6-endo-dig diarylation reaction, intermolecular and intra-
molecular kinetic isotope effects of 3.2 and 1.6, respectively,
were found, which is among the range of the C-H activa-
tion.3a,6,7 On the other hand, we found that the hydrogen/
deuterium kinetic isotope effects for the 5-exo-dig diarylation
reaction were 1 (intermolecular) and 2.1 (intramolecular). This
result indicated that the C-H functionalization was not the
rate-determining step of this present process, and the mechan-
ism of C-H activation was incompatible with the SEAr
mechanism.3a,5-7
Consequently, the possible mechanisms as outlined in
Scheme 4 were proposed on the basis of the reported
mechanism and the present results.1-8 The reaction of Pd
(7) For selected papers on the kinetic isotope effect studies, see: (a) Shue,
R. S. J. Am. Chem. Soc. 1971, 93, 7116. (b) Boele, M. D. K.; van Strijdonck,
G. P. F.; de Vries, A. H. M.; Kamer, P. C. J.; de Vries, J. G.; van Leeuwen, P.
W. N. M. J. Am. Chem. Soc. 2002, 124, 1586. (c) Hennessy, E. J.; Buchwald,
S. L. J. Am. Chem. Soc. 2003, 125, 12084. (d) Tunge, A. A.; Foresee, L. N.
Organometallics 2005, 24, 6640. (e) Campeau, L.-C.; Parisien, M.; Jean, A.;
Fagnou, K. J. Am. Chem. Soc. 2006, 128, 581. (f) Garcꢀıa-Cuadrado, D.; de
Mendoza, P.; Braga, A. A. C.; Maseras, F.; Echavarren, A. M. J. Am. Chem.
Soc. 2007, 129, 6880.
(8) (a) Davies, D.; Donald, S. M. A.; Macgregor, S. A. J. Am. Chem. Soc.
2005, 127, 13754. (b) Lafrance, M.; Fagnou, K. J. Am. Chem. Soc. 2006, 128,
16496. (c) Lebrasseur, N.; Larrosa, I. J. Am. Chem. Soc. 2008, 130, 2926. (d)
Gorelsky, S. I.; Lapointe, D.; Fagnou, K. J. Am. Chem. Soc. 2008, 130,
10848. (e) Lafrance, M.; Lapointe, D.; Fagnou, K. Tetrahedron 2008, 64,
Another arene, toluene (2b), was also tested under the
standard conditions. As shown in Scheme 2, the reaction of
N-methyl-N,3-diphenylpropiolamide (1A) with toluene (2b),
Pd(OAc)2, AgOAc, and PivOH was carried out smoothly to
afford the corresponding product 3Ab in 27% yield (p/m =
2:1; eq 1 in Scheme 2), and the 5-exo-dig product 5Ab was
isolated in 47% yield without PivOH (p/m = 2:1; eq 2 in
Scheme 2) (Table 3). However, the reactions of amide 1A
with p-xylene (2c) or anisole (2d) were unsuccessful under the
same conditions (eq 3 in Scheme 2).
ꢀ
6015. (f) Stuart, D. R.; Fagnou, K. Science 2007, 316, 1172. (g) Cardenas, D.
J.; Martın-Matute, B.; Echavarren, A. M. J. Am. Chem. Soc. 2006, 128, 5033.
´
(h) Pascual, S.; de Mendoza, P.; Braga a, A. A.C.; Maseras, F.; Echavarren,
A. M. Tetrahedron 2008, 64, 6021. (i) Potavathri, S.; Dumas, A. S.; Dwight, T.
A.; Naumiec, G. R.; Hammann, J. M.; DeBoef, B. Tetrahedron Lett. 2008, 49,
4050 and references cited therein. (j) Chen, X.; Goodhue, C. E.; Yu, J.-Q. J. Am.
Chem. Soc. 2006, 128, 12634. (k) Giri, R.; Maugel, N.; Li, J.-J.; Wang, D.-H.;
Breazzano, S. P.; Saunders, L. B.; Yu, J.-Q. J. Am. Chem. Soc. 2007, 129, 3510.
(l) Li, J.-J.; Mei, T.-S.; Yu, J.-Q. Angew. Chem., Int. Ed. 2008, 47, 6452.
(9) Wang, Z.; Fan, R.; Wu, J. Adv. Synth. Catal. 2007, 349, 1943.
To elucidate the mechanism, some controlled experiments,
including the kinetic isotope effect experiments, were conducted
6752 J. Org. Chem. Vol. 74, No. 17, 2009

Tang et al.
JOCArticle
TABLE 3. Pd(OAc)2-Catalyzed Selective 5-exo-dig Diarylation in the Absence of PivOHa
aReaction conditions: 1 (0.2 mmol), benzene 2a (60 equiv), Pd(OAc)2 (5 mol %), PPh3 (L1; 10 mol %), AgOAc (3 equiv), and PivOH (6 equiv) at 140
°C under argon atmosphere for 24 h. bSubstrate 1 was consumed completely, and some side products via the decomposition of the two
C-N bonds were observed by GC-MS analysis.
with ArH affords intermediate
D
with the aid of
In summary, we describe here the first example of selec-
tively constructing 3-aryl quinolin-2(1H)-ones and 3-(1-
arylmethylene)oxindoles via a Pd(OAc)2-catalyzed 2-fold
arene C-H activation/annulation of the N-arylpropiola-
mide process. A mechanism has also been proposed for this
transformation on the basis of the observed values of kinetic
isotope effects.
AgOAc.6,8 Subsequently, two pathways may take place: (1)
amide-assisted o-C-H activation of the anilide is induced by
intermediate E in the presence of in situ generated pivalate
(by the action of acetate anion), followed by trans-carbopal-
ladation2a across the triple bond, which might lead to the
6-endo-dig intermediate G. Reductive elimination of inter-
mediate G provides the corresponding products 3 and re-
generates the active Pd(0) species. (2) A complex of
intermediate D with a triple bond occurs to yield the 5-exo-
dig intermediate H, followed by cis-addition to give inter-
mediate I. Intermediate I undergoes the second C-H activa-
tion/cyclization reaction to afford the product 5, which may
undergo the same process as those of Zhu according to the
kinetic isotope effect experiments.5a-c Under basic condi-
tions, another F f J pathway cannot be ruled out on the base
of the kinetic isotope effect experiments, and the 5-exo-dig
intermediate J may undergo the same process as those of
Zhu5a-c to afford the product 5.
Experimental Section
Typical Experimental Procedure for the Pd(OAc)2-Catalyzed
Selective 6-endo-dig Diarylation in the Presence of PivOH.
A mixture of aniline 1 (0.2 mmol), arene 2 (60 equiv), Pd(OAc)2
(5 mol %), PPh3 (10 mol %), AgOAc (3 equiv), and PivOH
(6 equiv) was stirred in a Schlenk tube at 140 °C for the indicated
time until complete consumption of starting material as mon-
itored by TLC and GC-MS analysis. After the reaction was
finished, the mixture was poured into diethyl ether, which was
washed with brine. The aqueous layer was extracted with diethyl
ether and the combined organic layer was dried over anhydrous
J. Org. Chem. Vol. 74, No. 17, 2009 6753

Tang et al.
JOCArticle
SCHEME 3. Some Controlled Reactions Including the Kinetic Isotope Effect Experiments
(m, 6H), 3.85 (s, 3H); 13C NMR (125 MHz) δ 161.8, 147.7,
139.5, 136.3, 135.9, 132,0, 130.6, 130.3, 129.9, 128.5, 127.9,
SCHEME 4. Possible Mechanisms
127.5, 127.4, 126.8, 121.9, 121.5, 114.0, 29.7; IR (KBr, cm-1
)
1635, 1587; LRMS (EI, 70 eV) m/z (%) 311 (Mþ, 49), 310 (100),
267 (11).
(E)-2-(N-Methyl-N-phenylcarbamoyl)-1-phenylvinyl pivalate
1
(4Aa): yellow oil; H NMR (500 MHz) δ 7.41 (t, J = 7.5 Hz,
2H), 7.34-7.26 (m, 7H), 6.01 (s, 1H), 3.34 (s, 3H), 1.44 (s, 9H);
13C NMR (125 MHz) δ 175.7, 163.9, 153.9, 143.7, 134.6, 129.8,
129.5, 128.5, 127.3, 127.0, 126.8, 125.5, 108.6, 39.2, 36.9, 27.2;
IR (KBr, cm-1) 1752, 1667, 1630; LRMS (EI, 70 eV) m/z (%)
252 (Mþ - PivO, 10), 236 (48), 43 (100); HRMS (EI) for
C21H23NO3 (Mþ) calcd 337.1678, found 337.1676.
Typical Experimental Procedure for the Pd(OAc)2-Catalyzed
Selective 5-exo-dig Diarylation in the Absence of PivOH. A
mixture of aniline 1 (0.2 mmol), arene 2 (60 equiv), Pd(OAc)2
(5 mol %), PPh3 (10 mol %), and AgOAc (3 equiv) was stirred in
a Schlenk tube at 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 poured into diethyl ether, which was washed with brine.
The aqueous layer was extracted with diethyl ether and the
combined organic layer was dried over anhydrous Na2SO4 and
evaporated under vacuum. The residue was purified by flash
column chromatography (hexane/ethyl acetate) to afford the
product 5.
1-Methyl-3-(diphenylmethylene)indolin-2-one (5Aa):5 yellow
Na2SO4 and evaporated under vacuum. The residue was pur-
ified by flash column chromatography (hexane/ethyl acetate) to
afford products 3 and 4.
1
solid; H NMR (500 MHz) δ 7.44-7.42 (m, 3H), 7.40-7.32
(m, 7H), 7.17 (t, J = 8.0 Hz, 1H), 6.77 (d, J = 7.5 Hz, 1H), 6.68
1-Methyl-3,4-diphenylquinolin-2(1H)-one (3Aa):9 yellow
solid, mp 192.7-194.3 °C (uncorrected); 1H NMR (500 MHz)
δ 7.57 (t, J = 10.0 Hz, 1H), 7.46 (d, J = 10.0 Hz, 1H), 7.44-7.29
(m, 2H), 7.27-7.25 (m, 2H), 7.16-714 (m, 2H), 7.13-7.09
(t, J = 7.5 Hz, 1H), 6.43 (d, J = 8.0 Hz, 1H), 3.21 (s, 3H); 13
C
NMR (125 MHz) δ 166.8, 154.6, 143.3, 141.3, 140.0, 130.0,
129.3, 129.2, 129.1, 128.9, 128.8, 128.5, 127.8, 123.3, 123.2,
121.4, 107.7, 25.9; LRMS (EI, 70 eV) m/z (%) 310 (Mþ - 1, 100).
6754 J. Org. Chem. Vol. 74, No. 17, 2009

Tang et al.
JOCArticle
Acknowledgment. We thank the New Century Excellent
Talents in University (No. NCET-06-0711), Zhejiang
Provincial Natural Science Foundation of China (No.
Y407116), Specialized Research Fund for the Doctoral
Program of Higher Education (No. 20060542007),
National Natural Science Foundation of China (No.
20872112), and Scientific Research Fund of Hunan
Provincial Education Department (No 08A037) for finan-
cial support.
Supporting Information Available: General experimental
procedures, compounds characterization data for 3, 4, 5, and 6,
and copies of spectra. This material is available free of charge via
the Internet at http://pubs.acs.org.
J. Org. Chem. Vol. 74, No. 17, 2009 6755