Palladium-catalyzed oxidative difunctionalization of alkenes with α-carbonyl alkyl bromides initiated through a heck-type insertion: A route to indolin-2-ones

Article abstract of DOI:10.1002/anie.201402893

The oxidative interception of various σ-alkyl palladium(II) intermediates with additional reagents for the difunctionalization of alkenes is an important research area. A new palladium-catalyzed oxidative difunctionalization reaction of alkenes with α-carbonyl alkyl bromides is described, in which the σ-alkyl palladium(II) intermediate is generated through a Heck insertion and trapped using an aryl C(sp²)-H bond. This method can be applied to various α-carbonyl alkyl bromides, including primary, secondary, and tertiary α-bromoalkyl esters, ketones, and amides. Indolinone synthesis: A new palladium-catalyzed oxidative difunctionalization reaction of N-arylalkenes with primary, secondary, and tertiary α-carbonyl alkyl bromides proceeds through a radical process and provides indolin-2-ones in moderate to excellent yields. The reaction is initiated by a Heck insertion followed by interception of the σ-alkyl palladium(II) intermediate with aryl C(sp²)-H bonds. dppe=1,2-bis(diphenylphosphino)ethane.

Full text of DOI:10.1002/anie.201402893

Angewandte
Chemie
DOI: 10.1002/anie.201402893
Cross-Coupling
Palladium-Catalyzed Oxidative Difunctionalization of Alkenes with
a-Carbonyl Alkyl Bromides Initiated through a Heck-type Insertion:
A Route to Indolin-2-ones**
Jian-Hong Fan, Wen-Ting Wei, Ming-Bo Zhou, Ren-Jie Song, and Jin-Heng Li*
Abstract: The oxidative interception of various s-alkyl
palladium(II) intermediates with additional reagents for the
difunctionalization of alkenes is an important research area. A
new palladium-catalyzed oxidative difunctionalization reac-
tion of alkenes with a-carbonyl alkyl bromides is described, in
which the s-alkyl palladium(II) intermediate is generated
2
À
through a Heck insertion and trapped using an aryl C(sp ) H
bond. This method can be applied to various a-carbonyl alkyl
bromides, including primary, secondary, and tertiary a-bro-
moalkyl esters, ketones, and amides.
T
he Heck reaction has become one of the most important
synthetic methods for the formation of various carbon–
carbon bonds in organic synthesis.[1] Despite impressive
advances in this research field, Heck coupling reactions that
utilize alkyl halides, particularly tertiary alkyl halides, have
remained rare and challenging.[1–5] Such transformations are
difficult because the tertiary alkyl metal intermediate, which
is generated through tertiary alkylation with a-halocarbonyl
compounds, tends to undergo b-hydride elimination, gener-
ating a conjugated olefin.[1,6] Recently, some new strategies
have been developed using palladium,[2] cobalt,[3] nickel,[4] or
other metals[5] in catalytic systems. However, all successful
transformations are limited to the classic Heck coupling
process involving b-hydride elimination. Therefore, the
development of methods that avoid b-hydride elimination
during Heck coupling reactions with alkyl halides is desirable.
In a classic Heck coupling process, the insertion of an
alkene by the active Pd0 species and an organic electrophile
forms a s-alkyl PdII intermediate A.[1] Generally, intermediate
A undergoes b-hydride elimination to furnish an alkene. An
attractive alternative has been developed for the interception
of this s-alkyl palladium(II) intermediate A; this strategy
requires additional reagents, such as alkenes,[7] alkynes, CO,
Scheme 1. Alkene difunctionalizations that involve a Heck insertion.
or ArB(OH)2, to access diverse difunctionalized products
(Scheme 1a). However, examples of palladium(0)-catalyzed
alkene difunctionalization reactions are rare; such reports
have limited generality and often produce numerous side
products from competitive b-hydride elimination and proto-
nolysis processes. To overcome these limitations, considerable
efforts have been devoted to the palladium(II)-catalyzed
oxidative difunctionalization of alkenes. This process is
generally triggered by an organometallic reagent to form
s-alkyl palladium(II) intermediate A in the presence of
oxidants, followed by interception with another nucleophile
(often ClÀ, OÀ, or organometallic reagents).[8] However, few
methods utilizing a Heck insertion process are available for
the oxidative difunctionalization of alkenes with alkyl halides.
We herein report a new oxidative method for trapping
intermediate A using a-carbonyl alkyl bromides to realize
alkene difunctionalization reactions using a Pd catalyst with
a Ag2CO3 oxidant (Scheme 1c); this method proceeds
À
À
through a tandem C Br/C H functionalization and cycliza-
tion and provides access to important indolin-2-one struc-
tures.[9]
[*] J.-H. Fan, W.-T. Wei, M.-B. Zhou, Dr. R.-J. Song, Prof. Dr. J.-H. Li
State Key Laboratory of Chemo/Biosensing and Chemometrics
College of Chemistry and Chemical Engineering, Hunan University
Changsha 410082 (China)
Initial experiments were performed on the oxidative
difunctionalization reaction of N-methyl-N-phenylmethacryl-
amide (1a) and methyl 2-bromopropanoate (2a) with a palla-
dium source, phosphine ligands, and oxidants (Table 1). The
palladium catalyst was necessary for the transformation, and
[PdCl2(MeCN)2] was the most efficient Pd source (entries 1–
6). For this process, adding a ligand improved the reaction,
and using dppe was optimal (entries 1 and 7–9). Whereas
using PPh3 or PCy3 provided product 3aa in 78% and 88%
yield, respectively (entries 1 and 7), dppe increased the yield
to 99% (entry 8). Although the reaction could proceed
E-mail: jhli@hnu.edu.cn
Prof. Dr. J.-H. Li
State Key Laboratory of Applied Organic Chemistry, Lanzhou
University
Lanzhou 730000 (China)
[**] We thank the Natural Science Foundation of China (21172060), the
Specialized Research Fund for the Doctoral Program of Higher
Education (20120161110041), and the Hunan Provincial Natural
Science Foundation of China (13JJ2018) for financial support.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201402893.
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Table 1: Optimization of the reaction conditions.[a]
Table 2: Variation of the N-arylalkene 1.[a]
Entry Palladium precursor Ligand Additive Solvent
Yield [%]
1
2
3
4
5
6
7
8
9
[PdCl2(MeCN)2]
PdCl2
Pd(OAc)2
[Pd(dba)2]
[Pd(PPh3)4]
–
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PCy3
dppe
–
dppe
dppe
dppe
dppe
dppe
dppe
dppe
dppe
dppe
dppe
dppe
dppe
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2O
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
78
72
75
15
32
0
88
99
56
21
85
6
43
0
0
0
0
[PdCl2(MeCN)2]
[PdCl2(MeCN)2]
[PdCl2(MeCN)2]
10[b] [PdCl2(MeCN)2]
11
12
[PdCl2(MeCN)2]
[PdCl2(MeCN)2]
AgOAc
Ag2CO3
–
13[c] [PdCl2(MeCN)2]
14
15
16
17
18
19
20
[PdCl2(MeCN)2]
[PdCl2(MeCN)2]
[PdCl2(MeCN)2]
[PdCl2(MeCN)2]
[PdCl2(MeCN)2]
[PdCl2(MeCN)2]
[PdCl2(MeCN)2]
Cu(OAc)2 toluene
NaOAc
CsOAc
Cs2CO3
Ag2CO3
Ag2CO3
Ag2CO3
toluene
toluene
toluene
1,4-dioxane
DMF
0
43
22
56
21[d] [PdCl2(MeCN)2]
toluene
[a] Reaction conditions: 1a (0.3 mmol), 2a (0.6 mmol), palladium
precursor (5 mol%), ligand (10 mol%), additive (2 equiv), and solvent
(2 mL) at 1008C for 12 hours. The d.r. value (1:1) was determined by
1H NMR analysis. [b] [PdCl2(MeCN)2] (2 mol%). [c] Ag2CO3 (1 equiv).
[d] At 808C. Cy=cyclohexyl, dba=dibenzylideneacetone, dppe=1,2-
bis(diphenylphosphino)ethane.
[a] Reaction conditions: 1 (0.3 mmol), 2a (0.6 mmol), [PdCl2(MeCN)2]
(5 mol%), dppe (10 mol%), Ag2CO3 (2 equiv), and toluene (2 mL) at
1008C for 12 hours. The d.r. value is given in parenthesis.
without ligands, only a moderate yield was obtained (entry 9).
However, the yield decreased from 99% to 21% at a reduced
catalyst loading of [PdCl2(MeCN)2] (2 mol%; entry 8 vs.
entry 10). Extensive screening revealed that silver salts were
crucial for the reaction (entries 8 and 11–18). A good yield
was achieved using Ag2O instead of Ag2CO3 (entry 11), but
replacing Ag2CO3 with AgOAc furnished product 3aa in low
yield (entry 12). Notably, the yield decreased from 99% to
43% when one equivalent of Ag2CO3 was used (entry 13),
and reactions in the absence of a silver salt did not generate
a detectable amount of product 3aa, even in the presence of
an oxidant (Cu(OAc)2) or various bases, including NaOAc,
CsOAc, and Cs2CO3 (entries 14–18). Previous reports indi-
cated that silver salts could be used as oxidants to trigger
radical transformations.[10] Therefore, silver salts may act as
oxidants instead of bases in this process. After varying solvent
and reaction temperature, we found that the reaction in
toluene at 1008C provided the best results (entry 8 vs.
entries 19–21).
acrylamides 1b and 1c, which bear benzyl and acetyl groups
on the nitrogen atom, respectively, reacted with methyl 2-
bromopropanoate (2a), affording the corresponding products
(3ba and 3ca) in moderate yield. Unfortunately, N-phenyl-
À
amide 1d, which contained an unprotected N H group, was
not suitable for this reaction (Product 3da). Several substitu-
ents, including Me, nBu, MeO, Cl, F, and CF3, were well
tolerated on the aryl ring of the aniline derivative (3ea–ma).
For example, N-arylacrylamides 1e–g, which bear a methyl
group at the para, meta, or ortho position, successfully
underwent the difunctionalization transformation, furnishing
the desired products (3ea–ga) in 87%, 73%, and 91% yield,
respectively. Notably, the reaction of meta-methyl-substituted
N-arylacrylamide 1 f produced a mixture of regioisomers (3 fa
1
and 3 fa’) in a 1.2:1 ratio, based on H NMR analysis of the
After the standard reaction conditions had been deter-
mined, we examined the scope of this difunctionalization
process, varying the N-arylalkene 1 and the a-carbonyl alkyl
bromide 2. As shown in Table 2, the standard conditions were
compatible with various functionalized N-arylalkenes, includ-
ing N-arylacrylamides 1b–p and N-(2-methylallyl)anilines
1q–r. In the presence of [PdCl2(MeCN)2], dppe, and Ag2CO3,
unpurified mixture. The standard reaction conditions could be
applied to halogen-substituted N-arylacrylamides, such as 1j,
1k, and 1m; these compounds were converted into products
3ja, 3ka, and 3ma in high yields. Substrates with either a Ph
or an AcO group in place of the methyl group at the 2 position
of the acrylamide moiety also performed well under the
standard conditions (3na–oa). N-Methyl-N-phenylcinnama-
2
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mide (1p), which contains an internal alkene, smoothly
underwent the difunctionalization reaction to afford product
3pa in 70% yield. Unactivated alkenes 1q–r were also
investigated under the standard conditions: They were found
to be suitable substrates for the reaction, generating 3qa and
3ra in moderate yields.
This difunctionalization method was applicable to various
a-carbonyl alkyl bromides (2b–2k), including a-bromoalkyl
amides, ketones, and esters (Table 3). Secondary a-bro-
Table 3: Variation of the a-carbonyl alkyl bromide 2.[a]
form methyl 2-(2,2,6,6-tetramethylpiperidin-1-yloxy)propa-
noate (4) in 83% yield. In the presence of 1,1-diphenylalkene
and N-arylalkene 1a or 1q, methyl 2-methyl-4,4-diphenylbut-
3-enoate (5) was obtained as the major product. Therefore, an
a-carbonyl alkyl radical is formed, and the classic Heck
reaction, which generates an unactivated alkene through
b-hydride elimination, occurs before the difunctionalization
reaction with the N-arylalkene.
Based on the above results and previous reports,[4,7,8,10,11]
we propose two possible mechanisms for this system
(Scheme 2). Initially, alkyl radical A is formed by the reaction
[a] Reaction conditions: 1 (0.3 mmol), 2 (0.6 mmol), [PdCl2(MeCN)2]
(5 mol%), dppe (10 mol%), Ag2CO3 (2 equiv), and toluene (2 mL) at
1008C for 24 hours. The d.r. value is given in parenthesis. [b] 12 hours.
moalkyl amide 2b and ketones 2c and 2d smoothly reacted
with acrylamide 1a in the presence of [PdCl2(MeCN)2], dppe,
and Ag2CO3 in moderate yields (Products 3ab–ad). The
primary a-bromoalkyl ester 2e and ketones 2 f–i were trans-
formed into the desired products (3ae–i) in moderate to good
yields, and the order of their reactivity is as follows: ester>
electron-rich aryl ketone > electron-deficient aryl ketone. To
our delight, both tertiary a-bromoalkyl ester 2j and ketone
2k were compatible with the standard conditions and reacted
with acrylamides 1a, 1e, 1j, and 1s to produce products 3aj,
3ej, 3jj, 3sj, and 3ak in 62–90% yield. For example, the
reaction of ortho-SMe-substituted acrylamide 1s with sub-
strate 2j in the presence of [PdCl2(MeCN)2], dppe, and
Ag2CO3 successfully generated product 3sj in 67% yield.
To elucidate the mechanism of the current reaction, two
radical inhibitors, namely 2,2,6,6-tetramethylpiperidinyloxyl
[TEMPO; Eq. (1)] and 1,1-diphenylalkene [Eq. (2)], were
added to the difunctionalization reaction. The addition of
2.5 equivalents of TEMPO completely inhibited a reaction of
acrylamide 1a; instead, substrate 2a reacted with TEMPO to
Scheme 2. Two possible reaction mechanisms.
between methyl 2-bromopropanoate (2a) and the active
[Pd0Ln] species (generated in situ from [PdCl2(MeCN)2] and
dppe); the active [Pd0Ln] species is oxidized into a [PdIILn]
species with the aid of a AgI oxidant.[4,8,10] Intermediate A
=
then adds to the C C bond in substrate 1a, yielding radical
intermediate B. Subsequently, B cyclizes to form radical
intermediate C. Oxidation of C by the [PdIILn] species occurs
to produce cationic intermediate D.[4] Finally, intermediate D
is deprotonated, generating product 3aa.
We cannot rule out another pathway that involves a PdII/
Pd0 catalytic cycle.[10,11] The active [PdIIX2Ln] species can
initiate the reaction by ortho palladation of the aniline ring in
substrate 1a to form s-aryl palladium(II) intermediate E.
=
Carbopalladation between E and the C C bond gives s-alkyl
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[4] a) S. A. Lebedev, V. S. Lopatina, E. S. Petrov, I. P. Beletskaya, J.
Organomet. Chem. 1988, 344, 253; b) R. Matsubara, A. C.
Gutierrez, T. F. Jamison, J. Am. Chem. Soc. 2011, 133, 19020;
c) A. Millꢁn, L. ꢂlvarez de Cienfuegos, D. Miguel, A. G. Cam-
paÇa, J. M. Cuerva, Org. Lett. 2012, 14, 5984; d) C. Liu, S. Tang,
D. Liu, J. Yuan, L. Zheng, L. Meng, A. Lei, Angew. Chem. 2012,
124, 3698; Angew. Chem. Int. Ed. 2012, 51, 3638; e) A. Nakatani,
K. Hirano, T. Satoh, M. Miura, Chem. Eur. J. 2013, 19, 7691;
f) E. A. Standley, T. F. Jamison, J. Am. Chem. Soc. 2013, 135,
1585.
[5] For examples of such processes that are catalyzed by other
transition metals, see: ruthenium: a) D.-H. Lee, K.-H. Kwon,
C. S. Yi, Science 2011, 333, 1613; ruthenium or iridium: b) Q.
Liu, H. Yi, J. Liu, Y. Yang, X. Zhang, Z. Zeng, A. Lei, Chem. Eur.
J. 2013, 19, 5120; copper: c) T. Nishikata, Y. Noda, R. Fujimoto,
T. Sakashita, J. Am. Chem. Soc. 2013, 135, 16372.
palladium(II) intermediate F, which would be trapped by
a-carbonyl radical Awith the aid of the Ag0 species,[11] leading
to s-alkyl palladium(II) intermediate G. Reductive elimina-
tion of intermediate G affords the desired product 3aa and
the [Pd0Ln] species. The active [PdIIX2Ln] species is regen-
erated from the [Pd0Ln] species with the AgI salt to start a new
catalytic cycle.
In summary, the first palladium-catalyzed oxidative
difunctionalization of N-arylalkenes with a-carbonyl alkyl
bromides is reported; this reaction is initiated through a Heck
insertion and requires the addition of Ag2CO3. This trans-
À
À
formation includes tandem C Br/C H functionalization and
cyclization steps that occur through an oxidative radical
pathway. This process features a broad substrate scope and
excellent functional-group tolerance. Further extensions of
the current method and mechanistic studies are currently
underway in our laboratory.
[6] a) T. Kobayashi, H. Ohmiya, H. Yorimitsu, K. Oshima, J. Am.
Chem. Soc. 2008, 130, 11276; b) A. C. Bissember, A. Levina,
G. C. Fu, J. Am. Chem. Soc. 2012, 134, 14232.
[7] For selected examples, see: CO: a) T. Sugihara, C. Coperet, Z.
Owczarczyk, L. S. Harring, E.-i. Negishi, J. Am. Chem. Soc. 1994,
116, 7923; b) G. D. Artman III, S. M. Weinreb, Org. Lett. 2003, 5,
1523; alkyne and alkene: c) S. Schweizer, Z.-Z. Song, F. E.
Meyer, P. J. Parsons, A. de Meijere, Angew. Chem. 1999, 111,
1550; Angew. Chem. Int. Ed. 1999, 38, 1452; d) L. F. Tietze, K.
Kahle, T. Raschke, Chem. Eur. J. 2002, 8, 401; ArB(OH)2: e) L.
Liao, R. Jana, K. B. Urkalan, M. S. Sigman, J. Am. Chem. Soc.
2011, 133, 5784; f) V. Saini, M. S. Sigman, J. Am. Chem. Soc.
2012, 134, 11372; g) V. Saini, L. Liao, Q. Wang, R. Jana, M. S.
Sigman, Org. Lett. 2013, 15, 5008; h) M. S. McCammant, L. Liao,
M. S. Sigman, J. Am. Chem. Soc. 2013, 135, 4167; for selected
reviews, see: i) K. C. Nicolaou, D. J. Edmonds, P. G. Bulger,
Angew. Chem. 2006, 118, 7292; Angew. Chem. Int. Ed. 2006, 45,
7134; j) S. R. Chemler, P. H. Fuller, Chem. Soc. Rev. 2007, 36,
1153; k) J. P. Wolfe, Synlett 2008, 2913.
[8] a) R. F. Heck, J. Am. Chem. Soc. 1968, 90, 5538; b) D. Kalyani,
M. S. Sanford, J. Am. Chem. Soc. 2008, 130, 2150; c) D. Kalyani,
A. D. Satterfield, M. S. Sanford, J. Am. Chem. Soc. 2010, 132,
8419; d) Y. Tamaru, M. Hojo, H. Higashimura, Z. Yoshida,
Angew. Chem. 1986, 98, 740; Angew. Chem. Int. Ed. Engl. 1986,
25, 735; e) A. Rodriguez, W. J. Moran, Eur. J. Org. Chem. 2009,
1313; f) A. D. Satterfield, A. Kubota, M. S. Sanford, Org. Lett.
2011, 13, 1076; g) C. Zhu, J. R. Falck, Angew. Chem. 2011, 123,
6756; Angew. Chem. Int. Ed. 2011, 50, 6626; h) Y. Tamaru, M.
Hojo, S. Kawamura, Z. Yoshida, J. Org. Chem. 1986, 51, 4089;
i) K. B. Urkalan, M. S. Sigman, Angew. Chem. 2009, 121, 3192;
Angew. Chem. Int. Ed. 2009, 48, 3146; j) E. W. Werner, K. B.
Urkalan, M. S. Sigman, Org. Lett. 2010, 12, 2848.
[9] a) B. S. Jensen, CNS Drug Rev. 2002, 8, 353; b) C. Marti, E. M.
Carreira, Eur. J. Org. Chem. 2003, 2209; c) H. Lin, S. J.
Danishefsky, Angew. Chem. 2003, 115, 38; Angew. Chem. Int.
Ed. 2003, 42, 36; d) C. V. Galliford, K. A. Scheidt, Angew. Chem.
2007, 119, 8902; Angew. Chem. Int. Ed. 2007, 46, 8748; e) A.
Millemaggi, R. J. K. Taylor, Eur. J. Org. Chem. 2010, 4527; f) F.
Zhou, Y.-L. Liu, J. Zhou, Adv. Synth. Catal. 2010, 352, 1381;
g) S. R. S. Rudrangi, V. K. Bontha, V. R. Manda, S. Bethi, Asian
J. Res. Chem. 2011, 4, 335; h) G. Deak, M. Doda, L. Gyorgy, L.
Hazai, L. Sterk, J. Med. Chem. 1977, 20, 1384; i) A. Numata, P.
Yang, C. Takahashi, R. Fujiki, M. Nabae, E. Fujita, Chem.
Pharm. Bull. 1989, 37, 648; j) S. Hibino, T. Choshi, Nat. Prod.
Rep. 2001, 18, 66; k) A. S. Ratnayake, W. Y. Yoshida, S. L.
Mooberry, T. K. Hemscheidt, J. Org. Chem. 2001, 66, 8717;
l) B. M. Trost, J. Xie, J. D. Sieber, J. Am. Chem. Soc. 2011, 133,
20611.
Received: February 28, 2014
Revised: April 15, 2014
Published online: && &&, &&&&
Keywords: alkenes · cross-coupling · Heck reactions ·
.
indolinones · palladium
[1] a) R. F. Heck, J. P. Nolley, J. Org. Chem. 1972, 37, 2320; b) T.
Mizoroki, K. Mori, A. Ozaki, Bull. Chem. Soc. Jpn. 1971, 44, 581;
for selected reviews, see: c) A. C. Frisch, M. Beller, Angew.
Chem. 2005, 117, 680; Angew. Chem. Int. Ed. 2005, 44, 674; d) M.
Oestreich, The Mizoroki-Heck reaction, Wiley, Hoboken, NJ,
2008; e) A. Rudolph, M. Lautens, Angew. Chem. 2009, 121, 2694;
Angew. Chem. Int. Ed. 2009, 48, 2656; f) B. Karimi, H.
Behzadnia, D. Elhamifar, P. E. Akhavan, F. K. Esfahani, A.
Zamani, Synthesis 2010, 1399; g) D. Mc Cartney, P. J. Guiry,
Chem. Soc. Rev. 2011, 40, 5122; h) B. W. Glasspoole, C. M.
Crudden, Nat. Chem. 2011, 3, 912.
[2] a) M. Mori, I. Oda, Y. Ban, Tetrahedron Lett. 1982, 23, 5315;
b) G. Z. Wu, F. Lamaty, E. Negishi, J. Org. Chem. 1989, 54, 2507;
c) Y. Pan, Z. Zhang, H. Hu, Synth. Commun. 1992, 22, 2019;
d) Y. Pan, Z. Zhang, H. Hu, Synthesis 1995, 245; e) P. Kumar,
Org. Prep. Proced. Int. 1997, 29, 477; f) L. Wang, Y. Pan, X. Jiang,
H. Hu, Tetrahedron Lett. 2000, 41, 725; g) F. Glorius, Tetrahedron
Lett. 2003, 44, 5751; h) K. Higuchi, K. Sawada, H. Nambu, T.
Shogaki, Y. Kita, Org. Lett. 2003, 5, 3703; i) H. Narahashi, A.
Yamamoto, I. Shimizu, Chem. Lett. 2004, 33, 348; j) J. Terao, N.
Kambe, Bull. Chem. Soc. Jpn. 2006, 79, 663; k) L. Firmansjah,
G. C. Fu, J. Am. Chem. Soc. 2007, 129, 11340; l) S. Brꢀse, B.
Waegell, M. A. De, Synthesis 1998, 148; m) K. S. Bloome, E. J.
Alexanian, J. Am. Chem. Soc. 2010, 132, 12823; n) W. Zhou, G.
An, G. Zhang, J. Han, Y. Pan, Org. Biomol. Chem. 2011, 9, 5833;
o) K. S. Bloome, R. L. McMahen, E. J. Alexanian, J. Am. Chem.
Soc. 2011, 133, 20146; p) Z. Yang, J. Zhou, J. Am. Chem. Soc.
2012, 134, 11833.
[3] a) Y. Ikeda, T. Nakamura, H. Yorimitsu, K. Oshima, J. Am.
Chem. Soc. 2002, 124, 6514; b) T. Fujioka, T. Nakamura, H.
Yorimitsu, K. Oshima, Org. Lett. 2002, 4, 2257; c) Y. Ikeda, H.
Yorimitsu, H. Shinokubo, K. Oshima, Adv. Synth. Catal. 2004,
346, 1631; d) W. Affo, H. Ohmiya, T. Fujioka, Y. Ikeda, T.
Nakamura, H. Yorimitsu, K. Oshima, Y. Imamura, T. Mizuta, K.
Miyoshi, J. Am. Chem. Soc. 2006, 128, 8068; e) M. E. Weiss,
L. M. Kreis, A. Lauber, E. M. Carreira, Angew. Chem. 2011, 123,
11321; Angew. Chem. Int. Ed. 2011, 50, 11125.
[10] For selected reviews on the use of Ag salts in organic synthesis,
see: a) M. Naodovic, H. Yamamoto, Chem. Rev. 2008, 108, 3132;
b) J.-M. Weibel, A. Blanc, P. Pale, Chem. Rev. 2008, 108, 3149;
4
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Angewandte
Chemie
c) M. ꢂlvarez-Corral, M. MuÇoz-Dorado, I. Rodrꢃguez-Garcꢃa,
Chem. Rev. 2008, 108, 3174; d) Silver in Organic Chemistry (Ed.:
M. Harmata), Wiley, Hoboken, NJ, 2010.
Hirano, T. Satoh, M. Miura, J. Org. Chem. 2010, 75, 5421; e) A.
Ashimori, B. Bachand, L. E. Overman, D. J. Poon, J. Am. Chem.
Soc. 1998, 120, 6477; f) C. Li, T. Yano, N. Ishida, M. Murakami,
Angew. Chem. 2013, 125, 9983; Angew. Chem. Int. Ed. 2013, 52,
9801; g) S. Islam, I. Larrosa, Chem. Eur. J. 2013, 19, 15093;
h) E. J. Choi, E. Kim, Y. Lee, A. Jo, S. B. Park, Angew. Chem.
2014, 126, 1370; Angew. Chem. Int. Ed. 2014, 53, 1346.
[11] a) X. Wu, Y. Zhao, H. Ge, J. Am. Chem. Soc. 2014, 136, 1789;
generally, PdII/AgI-catalyzed oxidative reactions proceed
through a PdII/Pd0 process; see: b) D. R. Stuart, E. Villemure,
K. Fagnou, J. Am. Chem. Soc. 2007, 129, 12072; c) Z. Liang, J.
Zhao, Y. Zhang, J. Org. Chem. 2010, 75, 170; d) M. Miyasaka, K.
Angew. Chem. Int. Ed. 2014, 53, 1 – 6
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
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.
Angewandte
Communications
Communications
Cross-Coupling
J.-H. Fan, W.-T. Wei, M.-B. Zhou,
R.-J. Song, J.-H. Li*
&&&& — &&&&
Palladium-Catalyzed Oxidative
Difunctionalization of Alkenes with a-
Carbonyl Alkyl Bromides Initiated
through a Heck-type Insertion: A Route to
Indolin-2-ones
Indolinone synthesis: A new palladium-
catalyzed oxidative difunctionalization
reaction of N-arylalkenes with primary,
secondary, and tertiary a-carbonyl alkyl
bromides proceeds through a radical
process and provides indolin-2-ones in
moderate to excellent yields. The reaction
is initiated by a Heck insertion followed
by interception of the s-alkyl palladi-
2
À
um(II) intermediate with aryl C(sp ) H
bonds. dppe=1,2-bis(diphenylphosphi-
no)ethane.
6
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ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2014, 53, 1 – 6
These are not the final page numbers!