Iron-catalyzed arylalkoxycarbonylation of N -aryl acrylamides with carbazates

Article abstract of DOI:10.1021/jo402529r

A novel arylalkoxycarbonylation of N-aryl acrylamides with carbazates leading to alkoxycarbonylated oxindoles has been developed. The reported reactions employ economical and environmentally benign FeCl₂· 4H₂O as a catalyst and easil

Full text of DOI:10.1021/jo402529r

Note
pubs.acs.org/joc
Iron-Catalyzed Arylalkoxycarbonylation of N‑Aryl Acrylamides
with Carbazates
Xiangsheng Xu, Yucai Tang, Xiaoqing Li,* Guo Hong, Mingwu Fang, and Xiaohua Du*
College of Chemical Engineering and Materials Science, Zhejiang University of Technology, Hangzhou 310014, P. R. China
S
* Supporting Information
ABSTRACT: A novel arylalkoxycarbonylation of N-aryl acryl-
amides with carbazates leading to alkoxycarbonylated oxi-
ndoles has been developed. The reported reactions employ
economical and environmentally benign FeCl2·4H2O as a cata-
lyst and easily accessible and safe carbazates as alkoxycarbonyl
radical precursors.
sters are ubiquitous chemical entities that are widely
present in natural products, pharmaceuticals, functional
the corresponding sulfonated oxindoles. Our ongoing interest
in radical reactions, especially in the generation of radicals from
hydrazines,6,8n,9 prompted us to explore the application of
carbazates to the synthesis of alkoxycarbonylated oxindoles. It
was hypothesized that carbazates may act as alkoxycarbonyl
radical precursors via a similar TBHP-mediated C−N bond
cleavage (Scheme 1). Herein we report a novel and practical
method for arylalkoxycarbonylation of N-aryl acrylamides with
carbazates, which work as easily accessible and safe alk-
oxycarbonyl surrogates. The reported reactions employ
E
materials, and valuable industrial products and also serve as
vital intermediates in organic synthesis.1 Since the pioneering
work of Heck in 1974,2 palladium-catalyzed alkoxycarbonyla-
tion using CO and alcohols as the sources of ester groups has
become one of the most common and reliable methods for the
introduction of an ester group to organic molecules.3 However,
the use of prefunctionalized substrates and toxic gas reagents
and the necessity to use high-pressure equipment remain major
shortcomings of this methodology, restricting its application
in more complex organic syntheses.3 Therefore, the design of
simple, safe, and environmentally friendly CO-free strategies for
alkoxycarbonylation, particularly involving a C−H bond
functionalization process, would be highly desirable.4 Recently,
the groups of Tian5 and Taniguchi6 independently developed
two complementary new strategies for oxidative alkoxycarbo-
nylation of terminal alkenes utilizing carbazates (ROCONHNH2)
as ester group sources. Justifiably, carbazates are especially pro-
mising alkoxycarbonyl surrogates because they are usually
stable solids and are readily available. However, despite their
high potential, carbazates have rarely been applied to the con-
struction of esters.
Scheme 1. Arylalkoxycarbonylation of N-Aryl Acrylamides
with Carbazates
Recently, difunctionalization of alkenes involving direct C−H
functionalization of arenes has received increasing attention.7 In
particular, palladium-free radical-mediated difunctionalization
of N-aryl acrylamides provides a versatile strategy for the syn-
thesis of various functionalized oxindoles, including arylphos-
phorylation,8a alkylarylation,8b−f diarylation,8g arylcarbonylation,8h,i
arylnitration,8j,k aryltrifluoromethylation,8l and azidoaryla-
tion.8m Very recently, we also developed a method for aryl-
sulfonylation in the presence of a KI/18-crown-6/TBHP
catalyst system.8n In this approach, S−N bond cleavage of
sulfonylhydrazides with TBHP generates sulfonyl radicals that
are subsequently trapped by N-aryl acrylamides, thus affording
Received: November 14, 2013
© XXXX American Chemical Society
A
dx.doi.org/10.1021/jo402529r | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
economical and environmentally benign FeCl2·4H2O as the
catalyst and successfully provide access to a wide range of
alkoxycarbonylated oxindoles.
Initially, we carried out the arylalkoxycarbonylation of N-
phenylacrylamide (1a) with methyl carbazate (2a) using our
previously reported TBAI−TBHP catalyst system.9a Gratify-
ingly, the reaction in MeCN at 80 °C for 6 h afforded the
desired oxindole 3 in 32% yield (Table 1, entry 1). Screening of
arylmethoxycarbonylation process, monosubstituted olefin
(R2 = H, products 24) had no reactivity. It is worth mentioning
that product 23 had been synthesized in 58% yield via palladium-
catalyzed carboacetoxylation of N-aryl acrylamide.7c To our
delight, arylethoxycarbonylation also proceeded smoothly to
afford ethyl ester 25 in moderate yield using readily accessible
ethyl carbazate as an ethoxycarbonyl surrogate.
To confirm our suspicion that the arylalkoxycarbonylation
proceeds by a radical pathway, inter- and intramolecular kinetic
isotope effect (KIE) experiments were performed (Scheme 2),
and two primary KIEs were observed (intermolecular kH/kD =
1.0 and intramolecular kH/kD = 1.3). Moreover, the addition of
a stoichiometric amount of TEMPO indeed suppressed the
arylalkoxycarbonylation process (Scheme 2).
a
Table 1. Optimization of the Reaction Conditions
On the basis of the above experimental results, a plausible
mechanism is proposed (Scheme 3). Initially, the tert-butoxyl
and tert-butylperoxy radicals are generated via iron-catalyzed
decomposition of TBHP.10 Then, C−N bond cleavage of the
carbazate through stepwise hydrogen abstraction forms
alkoxycarbonyl radical with the release of molecular nitrogen.9
The addition of alkoxycarbonyl radical to the N-aryl acrylamide
affords alkyl radical I, which further undergoes intramolecular
radical substitution reaction to give intermediate II.8 Finally,
hydrogen abstraction of radical intermediate II by TBHP leads
to the alkoxycarbonylated oxindole.8h
In conclusion, we have discovered that carbazates can be
used as easily accessible and safe alkoxycarbonyl radical pre-
cursors for the arylalkoxycarbonylation of N-aryl acrylamides,
providing a general and practical method for the construction
of alkoxycarbonylated oxindoles. The use of economical and
environmentally benign FeCl2·4H2O as the catalyst also makes
this transformation sustainable and practical.
entry
cat. (mol %)
equiv of 2a equiv of TBHP yield (%)
1
2
3
4
5
TBAI (20)
2
2
2
2
2
2
2
2
2
2
4
4
2
2
2
2
2
2
2
2
4
6
6
8
32
0
CuBr (20)
Cu(OAc)2 (20)
FeCl3 (20)
0
0
FeCl2·4H2O (20)
FeCl2·4H2O (20)
FeCl2·4H2O (10)
FeCl2·4H2O (50)
FeCl2·4H2O (20)
FeCl2·4H2O (20)
FeCl2·4H2O (20)
FeCl2·4H2O (20)
45
20
28
47
61
64
94
92
b
6
7
8
9
10
11
12
a
Reaction conditions: 1a (0.25 mmol), 2a, catalyst, and TBHP (70%
aqueous solution) in MeCN (2.0 mL) at 80 °C for 6 h, unless
otherwise noted. H2O was used as the solvent.
b
EXPERIMENTAL SECTION
General Procedures. All of the reagents and solvents were pur-
copper and iron catalysts showed that FeCl2·4H2O was the best
(entry 5). In contrast, the reactions hardly proceeded with
CuBr, Cu(OAc)2, or FeCl3 (entries 2−4). Unfortunately, the
reaction proceeded less effectively in water (entry 6).8n,9b This
initial success prompted further elaboration of the loading of
catalyst, 2a, and TBHP (entries 7−12). To our delight, an
excellent yield could be achieved by using 20 mol % FeCl2·
4H2O, 4 equiv of 2a, and 6 equiv of TBHP (entry 11).
■
chased from commercial suppliers and used without further
purification. Melting points are uncorrected. The H NMR and 13C
1
NMR spectra were recorded at 25 °C in CDCl3 at 500 and 125 MHz,
respectively, with TMS as the internal standard. Chemical shifts (δ)
are expressed in parts per million, and coupling constants (J) are given
in hertz. High-resolution mass spectrometry (HRMS) was performed
on a TOF MS instrument with an ESI source. The N-aryl acrylamides
were synthesized according to a literature method.11
With the optimized conditions in hand, the arylmethox-
ycarbonylation of a variety of N-aryl acrylamide derivatives with
methyl carbazate was tested, and the results are summarized in
Table 2. Methyl and benzyl protecting groups on the nitrogen
atom were compatible with the reaction conditions, and the
reactions afforded the corresponding oxindoles 3 and 4 in 94
and 66% yield, respectively. However, the use of acetyl and N-
free N-aryl acrylamides resulted in complex mixtures, and no
desired products 5 and 6 were detected. The reaction was
readily extended to a variety of N-aryl acrylamides, and both
electron-donating (Me and MeO) and electron-withdrawing
(halide, CF3, CF3O, COOEt, and CN) substituents were well-
tolerated under the reaction conditions. As expected, substrates
bearing m-methyl and m-bromo substituents afforded mixtures
of two regioselective products 17/17′ and 18/18′ in ratios of
1:1 and 5:1, respectively. The existence of possible steric
hindrance arising from the presence of an ortho substituent led
to a lower yield of products 19. Notably, naphthalene and
tetrahydroquinoline derivatives underwent facile arylmethox-
ycarbonylation to furnish the expected products 20 and 21 in
moderate yields. Whereas α-substituted olefins bearing CH2OH
and CH2OAc functional groups were well-tolerated in this
Typical Procedure for the Synthesis of Alkoxycarbonylated
Oxindoles. To a stirred solution of N-aryl acrylamide (0.25 mmol),
carbazate (1.0 mmol), and FeCl2·4H2O (0.05 mmol) in MeCN (2 mL)
was added TBHP (1.5 mmol, 70% aqueous solution) at room tem-
perature. The mixture was heated at 80 °C for 6 h and then cooled to
room temperature. The excess solvent was removed under vacuum,
and the residue was directly purified by silica gel column chro-
matography (petroleum/ethyl acetate = 5:1) to afford the desired
oxindole.
Methyl 2-(1,3-Dimethyl-2-oxoindolin-3-yl)acetate (3).12 Pale-
yellow oil (54.7 mg, 94%); 1H NMR (500 MHz, CDCl3) δ 7.27
(td, J = 7.5, 1.2 Hz, 1H), 7.19 (dd, J = 7.3, 0.5 Hz, 1H), 7.04 (td, J =
7.6, 0.9 Hz, 1H), 6.86 (d, J = 7.8 Hz, 1H), 3.46 (s, 3H), 3.26 (s, 3H),
3.01 (d, J = 16.4 Hz, 1H), 2.85 (d, J = 16.4 Hz, 1H), 1.38 (s, 3H); 13C
NMR (125 MHz, CDCl3) δ 179.8, 170.2, 143.5, 132.8, 128.0, 122.2,
122.2, 108.0, 51.4, 45.4, 41.3, 26.2, 24.1.
Methyl 2-(1-Benzyl-3-methyl-2-oxoindolin-3-yl)acetate (4).13
Pale-yellow oil (50.9 mg, 66%); 1H NMR (500 MHz, CDCl3) δ
7.36 (d, J = 7.2 Hz, 2H), 7.31 (t, J = 7.5 Hz, 2H), 7.25 (t, J = 7.2 Hz,
1H), 7.19 (d, J = 7.8 Hz, 1H), 7.14 (td, J = 7.7, 1.1 Hz, 1H), 7.00
(t, J = 7.5 Hz, 1H), 6.73 (d, J = 7.8 Hz, 1H), 5.00−4.91 (m, 2H), 3.41
(s, 3H), 3.09 (d, J = 16.3 Hz, 1H), 2.90 (d, J = 16.3 Hz, 1H), 1.43
(s, 3H); 13C NMR (125 MHz, CDCl3) δ 179.8, 170.1, 142.5, 136.0,
B
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Note
a
Table 2. Scope of the Reaction with N-Aryl Acrylamides
a
Reaction conditions: N-aryl acrylamide 1 (0.25 mmol), 2 (1.0 mmol), FeCl2·4H2O (20 mol %), and TBHP (6 equiv, 70% aqueous solution) in
b
1
MeCN (2.0 mL) at 80 °C for 6 h. The ratio of isomers was determined by H NMR spectroscopy of the isolated product.
132.9, 128.6, 127.9, 127.4, 127.3, 122.3, 122.2, 109.1, 51.4, 45.5, 43.9,
41.2, 24.8.
Methyl 2-(1,3,5-Trimethyl-2-oxoindolin-3-yl)acetate (7). Pale-
yellow oil (38.8 mg, 63%); 1H NMR (500 MHz, CDCl3) δ 7.07
C
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Note
Methyl 2-(5-Methoxy-1,3-dimethyl-2-oxoindolin-3-yl)acetate (8).
Pale-yellow oil (58.5 mg, 89%); H NMR (500 MHz, CDCl3) δ 6.83
Scheme 2. Control Experiments
1
(d, J = 2.3 Hz, 1H), 6.79 (dd, J = 8.4, 2.4 Hz, 1H), 6.76 (d, J = 8.4 Hz,
1H), 3.79 (s, 3H), 3.48 (s, 3H), 3.23 (s, 3H), 3.00 (d, J = 16.5 Hz,
1H), 2.83 (d, J = 16.5 Hz, 1H), 1.37 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 179.5, 170.2, 155.9, 137.1, 134.4, 112.0, 110.2, 108.3, 55.8,
51.5, 45.8, 41.3, 26.4, 24.2; HRMS (ESI) calcd for C14H18NO4 ([M +
H]+) 264.1236, found 264.1233.
Methyl 2-(5-Fluoro-1,3-dimethyl-2-oxoindolin-3-yl)acetate (9).
1
Colorless oil (45.8 mg, 73%); H NMR (500 MHz, CDCl3) δ 6.98
(dd, J = 9.9, 1.7 Hz, 1H), 6.95 (d, J = 1.4 Hz, 1H), 6.80−6.75 (m, 1H),
3.49 (s, 3H), 3.25 (s, 3H), 3.01 (d, J = 16.7 Hz, 1H), 2.84 (d, J =
16.7 Hz, 1H), 1.38 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 179.6,
170.1, 159.3 (d, J = 238.9 Hz), 139.6 (d, J = 1.75 Hz), 134.7 (d, J =
7.75 Hz), 114.3 (d, J = 23.4 Hz), 110.7 (d, J = 24.8 Hz), 108.6 (d, J =
8.1 Hz), 51.7, 45.9, 41.2, 26.5, 24.1; HRMS (ESI) calcd for
C13H15FNO3 ([M + H]+) 252.1036, found 252.1034.
Methyl 2-(5-Chloro-1,3-dimethyl-2-oxoindolin-3-yl)acetate (10).
1
Pale-yellow oil (47.4 mg, 71%); H NMR (500 MHz, CDCl3) δ 7.25
(dd, J = 8.3, 2.1 Hz, 1H), 7.17 (d, J = 2.1 Hz, 1H), 6.79 (d, J = 8.3 Hz,
1H), 3.50 (s, 3H), 3.24 (s, 3H), 3.02 (d, J = 16.8 Hz, 1H), 2.84 (d, J =
16.8 Hz, 1H), 1.37 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 179.4,
170.1, 142.3, 134.7, 128.0, 127.7, 122.8, 109.0, 51.7, 45.6, 41.1, 26.5,
24.1; HRMS (ESI) calcd for C13H15ClNO3 ([M + H]+) 268.0740,
found 268.0737.
Scheme 3. Proposed Mechanism
Methyl 2-(5-Bromo-1,3-dimethyl-2-oxoindolin-3-yl)acetate (11).
1
Pale-yellow oil (56.7 mg, 73%); H NMR (500 MHz, CDCl3) δ 7.40
(dd, J = 8.2, 1.8 Hz, 1H), 7.30 (d, J = 1.8 Hz, 1H), 6.74 (d, J = 8.2 Hz,
1H), 3.50 (s, 3H), 3.24 (s, 3H), 3.02 (d, J = 16.8 Hz, 1H), 2.84 (d, J =
16.8 Hz, 1H), 1.36 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 179.3,
170.0, 142.7, 135.1, 130.9, 125.5, 114.9, 109.5, 51.6, 45.5, 41.2, 26.4,
24.1; HRMS (ESI) calcd for C13H15BrNO3 ([M + H]+) 312.0235,
found 312.0233.
Methyl 2-(5-Iodo-1,3-dimethyl-2-oxoindolin-3-yl)acetate (12).
Pale-yellow oil (68.3 mg, 76%); 1H NMR (500 MHz, CDCl3) δ
7.59 (dd, J = 8.2, 1.7 Hz, 1H), 7.46 (d, J = 1.7 Hz, 1H), 6.65 (d, J =
8.2 Hz, 1H), 3.50 (s, 3H), 3.23 (s, 3H), 3.01 (d, J = 16.8 Hz, 1H), 2.83
(d, J = 16.8 Hz, 1H), 1.36 (s, 3H); 13C NMR (125 MHz, CDCl3) δ
179.1, 170.0, 143.4, 136.9, 135.5, 131.0, 110.1, 84.8, 51.6, 45.4, 41.1,
26.4, 24.1; HRMS (ESI) calcd for C13H15INO3 ([M + H]+) 360.0097,
found 360.0093.
Methyl 2-(1,3-Dimethyl-2-oxo-5-(trifluoromethyl)indolin-3-yl)-
1
acetate (13). Pale-yellow oil (47.4 mg, 63%); H NMR (500 MHz,
CDCl3) δ 7.57 (d, J = 7.6 Hz, 1H), 7.42 (d, J = 1.1 Hz, 1H), 6.94 (d,
J = 8.2 Hz, 1H), 3.49 (s, 3H), 3.29 (s, 3H), 3.06 (d, J = 16.8 Hz, 1H),
2.91 (d, J = 16.8 Hz, 1H), 1.40 (s, 3H); 13C NMR (125 MHz, CDCl3)
δ 179.8, 170.0, 146.7, 133.6, 126.0 (q, J = 3.9 Hz), 124.6 (q, J =
32.4 Hz), 124.4 (q, J = 269.5 Hz), 119.2 (q, J = 3.6 Hz), 107.8, 51.7,
45.4, 41.2, 26.6, 24.1; HRMS (ESI) calcd for C14H15F3NO3 ([M +
H]+) 302.1004, found 302.1001.
Methyl 2-(1,3-Dimethyl-2-oxo-5-(trifluoromethoxy)indolin-3-yl)-
acetate (14). White solid (72 mg, 91%); mp 162−163 °C; 1H
NMR (500 MHz, CDCl3) δ 7.15 (dd, J = 8.4, 1.2 Hz, 1H), 7.10 (d, J =
1.1 Hz, 1H), 6.84 (d, J = 8.4 Hz, 1H), 3.49 (s, 3H), 3.26 (s, 3H), 3.01
(d, J = 16.6 Hz, 1H), 2.85 (d, J = 16.6 Hz, 1H), 1.39 (s, 3H); 13C
NMR (125 MHz, CDCl3) δ 179.5, 170.1, 144.6 (q, J = 1.9 Hz), 142.3,
134.5, 121.2, 120.5 (q, J = 254.9 Hz), 116.5, 108.4, 51.6, 45.8, 41.2,
26.5, 23.9; HRMS (ESI) calcd for C14H15F3NO4 ([M + H]+)
318.0953, found 318.0950.
Ethyl 3-(2-Methoxy-2-oxoethyl)-1,3-dimethyl-2-oxoindoline-5-
1
carboxylate (15). White solid (43.5 mg, 57%); mp 158−159 °C; H
NMR (500 MHz, CDCl3) δ 8.04 (dd, J = 8.2, 1.7 Hz, 1H), 7.84 (d, J =
1.6 Hz, 1H), 6.90 (d, J = 8.2 Hz, 1H), 4.37 (qd, J = 7.1, 0.7 Hz, 2H),
3.47 (s, 3H), 3.30 (s, 3H), 3.08 (d, J = 16.9 Hz, 1H), 2.93 (d, J = 16.9
Hz, 1H), 1.40 (t + s, 6H); 13C NMR (125 MHz, CDCl3) δ 180.2,
170.1, 166.4, 147.8, 133.0, 130.9, 124.6, 123.2, 107.6, 60.8, 51.6, 45.2,
41.2, 26.5, 24.2, 14.4; HRMS (ESI) calcd for C16H20NO5 ([M + H]+)
306.1341, found 306.1337.
(d, J = 7.8 Hz, 1H), 7.01 (s, 1H), 6.74 (d, J = 7.9 Hz, 1H), 3.47 (s,
3H), 3.25 (s, 3H), 2.99 (d, J = 16.4 Hz, 1H), 2.83 (d, J = 16.4 Hz, 1H),
2.33 (s, 3H), 1.36 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 170.3,
141.2, 133.1, 131.8, 130.4, 128.4, 123.2, 107.9, 51.6, 45.7, 41.5, 26.4,
24.4, 21.2; HRMS (ESI) calcd for C14H18NO3 ([M + H]+) 248.1287,
found 248.1285.
Methyl 2-(5-Cyano-1,3-dimethyl-2-oxoindolin-3-yl)acetate (16).
1
Pale-yellow oil (46.4 mg, 72%); H NMR (500 MHz, CDCl3) δ 7.62
D
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Note
(d, J = 8.1 Hz, 1H), 7.45 (s, 1H), 6.94 (d, J = 8.1 Hz, 1H), 3.50 (s,
3H), 3.29 (s, 3H), 3.06 (d, J = 17.0 Hz, 1H), 2.91 (d, J = 17.0 Hz, 1H),
1.39 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 179.5, 169.9, 147.6,
134.1, 133.5, 125.4, 119.1, 108.4, 105.3, 51.7, 45.1, 41.0, 26.5, 23.9;
HRMS (ESI) calcd for C14H15N2O3 ([M + H]+) 259.1083, found
259.1080.
170.0, 169.6, 144.3, 128.8, 128.5, 123.2, 122.3, 108.1, 66.7, 51.6, 49.2,
37.3, 26.4, 20.4.
Ethyl 2-(1,3-Dimethyl-2-oxoindolin-3-yl)acetate (25).12 Pale-
yellow oil (40.1 mg, 65%); 1H NMR (500 MHz, CDCl3) δ 7.27
(td, J = 7.7, 1.0 Hz, 1H), 7.20 (d, J = 7.2 Hz, 1H), 7.04 (t, J = 7.3 Hz,
1H), 6.85 (d, J = 7.8 Hz, 1H), 3.95−3.78 (m, 2H), 3.25 (s, 3H), 3.03
(d, J = 16.2 Hz, 1H), 2.83 (d, J = 16.2 Hz, 1H), 1.38 (s, 3H), 0.99 (t,
J = 7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 179.8, 169.7, 143.6,
132.9, 128.1, 122.3, 122.3, 108.0, 60.3, 45.5, 41.7, 26.3, 24.3, 13.8.
Methyl 2-(1,3,4-Trimethyl-2-oxoindolin-3-yl)acetate (17) and
Methyl 2-(1,3,6-Trimethyl-2-oxoindolin-3-yl)acetate (17′). Pale-
1
yellow oil (39.5 mg, 64%); H NMR (500 MHz, CDCl3) δ 7.17 (d,
J = 7.8 Hz, 1H), 7.07 (d, J = 7.5 Hz, 1H), 6.86−6.79 (m, 2H), 6.72−
6.68 (m, 2H), 3.46 (d, J = 4.0 Hz, 3H), 3.38 (s, 3H), 3.24 (d, J = 3.0
Hz, 6H), 3.14 (d, J = 16.0 Hz, 1H), 3.04 (d, J = 16.0 Hz, 1H), 2.98 (d,
J = 16.3 Hz, 1H), 2.83 (d, J = 16.3 Hz, 1H), 2.37 (d, J = 2.4 Hz, 5H),
1.43 (s, 3H), 1.36 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 180.1,
179.8, 170.3, 170.1, 143.9, 143.6, 138.1, 133.6, 129.9, 129.5, 128.1,
127.9, 124.9, 122.8, 122.0, 109.0, 105.8, 51.4, 46.4, 45.2, 41.4, 40.6,
26.4, 26.3, 24.2, 22.2, 21.7, 18.0; HRMS (ESI) calcd for C14H18NO3
([M + H]+) 248.1287, found 248.1284.
ASSOCIATED CONTENT
■
S
* Supporting Information
KIE studies and copies of 1H and 13C NMR spectra for all pro-
ducts. This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
*E-mail: xqli@zjut.edu.cn.
*E-mail: duxiaohua@zjut.edu.cn.
Notes
■
Methyl 2-(4-Bromo-1,3-dimethyl-2-oxoindolin-3-yl)acetate (18)
and Methyl 2-(6-Bromo-1,3-dimethyl-2-oxoindolin-3-yl)acetate
1
(18′). Pale-yellow oil (60.8 mg, 78%); H NMR (500 MHz, CDCl3)
δ 7.19−7.10 (m, 2.1H), 7.06 (d, J = 7.8 Hz, 0.18H), 7.01 (d, J =
1.7 Hz, 0.18H), 6.82 (dd, J = 6.6, 2.0 Hz, 1H), 3.56 (s, 0.47H), 3.53
(s, 0.55H), 3.48 (s, 1H), 3.47 (s, 3H), 3.26 (s, 3H), 3.24 (s, 1H), 3.04
(d, J = 11.9 Hz, 0.63H), 3.00 (d, J = 11.4 Hz, 0.56H), 1.48 (s, 3H),
1.36 (s, 0.6H); 13C NMR (125 MHz, CDCl3) δ 179.0, 170.0, 169.7,
145.5, 144.6, 131.5, 130.4, 129.3, 126.1, 124.8, 123.3, 121.4, 117.8,
111.4, 106.9, 51.4, 47.3, 45.0, 40.9, 38.8, 26.2, 23.8, 21.1; HRMS (ESI)
calcd for C13H15BrNO3 ([M + H]+) 312.0235, found 312.0231.
Methyl 2-(7-Bromo-1,3-dimethyl-2-oxoindolin-3-yl)acetate (19).
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the National Natural Science Foundation of China
(21102130) and the Key Innovation Team of Science &
Technology in Zhejiang Province (2010R50018 and
2011R50017) for financial support.
1
Pale-yellow oil (48.9 mg, 63%); H NMR (500 MHz, CDCl3) δ 7.37
(dd, J = 8.2, 1.1 Hz, 1H), 7.09 (dd, J = 7.3, 1.0 Hz, 1H), 6.87 (dd, J =
8.0, 7.4 Hz, 1H), 3.64 (s, 3H), 3.48 (s, 3H), 3.04 (d, J = 16.6 Hz, 1H),
2.84 (d, J = 16.6 Hz, 1H), 1.35 (s, 3H); 13C NMR (125 MHz, CDCl3)
δ 180.3, 170.0, 141.0, 136.1, 133.8, 123.5, 121.1, 102.5, 51.6, 45.2, 41.5,
30.0, 24.6; HRMS (ESI) calcd for C13H15BrNO3 ([M + H]+)
312.0235, found 312.0232.
REFERENCES
■
(1) (a) Otera, J. Esterification; Wiley-VCH: Weinheim, Germany,
2003. (b) Green, T. W.; Wutz, P. G. M. In Protective Groups in Organic
Synthesis; Wiley: New York, 1991; Vol. II. (c) Sano, T.; Ohashi, K.;
Oriyama, T. Synthesis 1999, 1141.
(2) Schoenberg, A.; Bartoletti, I.; Heck, R. F. J. Org. Chem. 1974, 39,
3318.
(3) For selected reviews, see: (a) Wu, X.-F.; Neumann, H.; Beller, M.
Chem. Soc. Rev. 2011, 40, 4986. (b) Brennfuhrer, A.; Neumann, H.;
Beller, M. Angew. Chem., Int. Ed. 2009, 48, 4114. (c) Liu, Q.; Zhang,
H.; Lei, A. Angew. Chem., Int. Ed. 2011, 50, 10788.
(4) For selected examples of CO-free alkoxycarbonylation, see:
(a) Fujihara, T.; Hosoki, T.; Katafuchi, Y.; Iwai, T.; Terao, J.; Tsuji, Y.
Chem. Commun. 2012, 48, 8012. (b) Ueda, T.; Konishi, H.; Manabe,
K. Org. Lett. 2012, 14, 3100.
(5) Su, Y.; Wu, Z.; Tian, S. Chem. Commun. 2013, 49, 6528.
(6) Taniguchi, T.; Sugiura, Y.; Zaimoku, H.; Ishibashi, H. Angew.
Chem., Int. Ed. 2010, 49, 10154.
(7) (a) Mu, X.; Wu, T.; Wang, H.; Guo, Y.; Liu, G. J. Am. Chem. Soc.
2012, 134, 878. (b) Wu, T.; Mu, X.; Liu, G. Angew. Chem., Int. Ed.
2011, 50, 12578. (c) Jaegli, S.; Dufour, J.; Wei, H.; Piou, T.; Duan, X.;
Vors, J.-P.; Neuville, L.; Zhu, J. Org. Lett. 2010, 12, 4498. (d) Wei, H.;
Piou, T.; Dufour, J.; Neuville, L.; Zhu, J. Org. Lett. 2011, 13, 2244.
(e) Jaegli, S.; Erb, W.; Retailleau, P.; Vors, J.-P.; Neuville, L.; Zhu, J.
Chem.Eur. J. 2010, 16, 5863. (f) Wu, T.; Mu, X.; Liu, G. Angew.
Chem., Int. Ed. 2011, 50, 12578. (g) Mu, X.; Wu, T.; Wang, H.; Guo,
Y.; Liu, G. J. Am. Chem. Soc. 2012, 134, 878. (h) Broggini, G.; Barbera,
V.; Beccalli, E. M.; Borsini, E.; Galli, S.; Lanza, G.; Zecchi, G. Adv.
Synth. Catal. 2012, 354, 159. (i) An, G.; Zhou, W.; Zhang, G.; Sun, H.;
Han, J.; Pan, Y. Org. Lett. 2010, 12, 4482. (j) Pinto, A.; Jia, Y.; Neuville,
L.; Zhu, J. Chem.Eur. J. 2007, 13, 961. (k) Han, X.; Lu, X. Org. Lett.
2009, 11, 2381.
Methyl 2-(1-Methyl-2-oxo-2,4,5,6-tetrahydro-1H-pyrrolo[3,2,1-ij]-
1
quinolin-1-yl)acetate (20). Colorless oil (27.8 mg, 43%); H NMR
(500 MHz, CDCl3) δ 7.03 (t, J = 7.6 Hz, 2H), 6.92 (t, J = 7.5 Hz, 1H),
3.78−3.72 (m, 2H), 3.48 (s, 3H), 2.97 (d, J = 16.3 Hz, 1H), 2.84 (d,
J = 16.3 Hz, 1H), 2.80 (t, J = 6.2 Hz, 2H), 2.07−1.98 (m, 2H), 1.40
(s, 3H); 13C NMR (125 MHz, CDCl3) δ 178.7, 170.4, 139.3, 131.4,
126.9, 121.8, 120.2, 120.1, 51.5, 46.7, 41.3, 38.9, 24.6, 23.8, 21.2;
HRMS (ESI) calcd for C15H18NO3 ([M + H]+) 260.1287, found
260.1285.
Methyl 2-(1,3-Dimethyl-2-oxo-2,3-dihydro-1H-benzo[g]indol-3-
yl)acetate (21). Pale-yellow oil (38.2 mg, 54%); 1H NMR (500
MHz, CDCl3) δ 7.70 (dd, J = 8.2, 0.7 Hz, 1H), 7.53−7.41 (m, 3H),
7.31 (dd, J = 7.3, 0.9 Hz, 1H), 6.99 (dd, J = 7.6, 0.7 Hz, 1H), 3.75 (d,
J = 17.0 Hz, 1H), 3.58 (s, 3H), 3.40 (s, 3H), 3.11 (d, J = 17.0 Hz, 1H),
1.57 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 173.0, 171.3, 137.7,
136.8, 133.5, 126.8, 126.5, 126.2, 122.4, 121.3, 119.4, 108.5, 51.5, 45.1,
45.0, 32.5, 29.8; HRMS (ESI) calcd for C17H18NO3 ([M + H]+)
284.1287, found 284.1284.
̈
Methyl 2-(3-(Hydroxymethyl)-1-methyl-2-oxoindolin-3-yl)acetate
1
(22). Pale-yellow oil (37.9 mg, 61%); H NMR (500 MHz, CDCl3) δ
7.32 (td, J = 7.7, 1.1 Hz, 1H), 7.22 (d, J = 7.3 Hz, 1H), 7.06 (t, J = 7.5
Hz, 1H), 6.89 (d, J = 7.8 Hz, 1H), 3.82−3.75 (m, 1H), 3.69 (d, J =
11.0 Hz, 1H), 3.48 (s, 3H), 3.26 (s, 3H), 3.21 (d, J = 16.6 Hz, 1H),
2.98 (d, J = 16.6 Hz, 1H), 2.74−2.67 (m, 1H); 13C NMR (125 MHz,
CDCl3) δ 178.5, 170.5, 144.3, 128.9, 128.8, 122.9, 122.6, 108.4, 66.7,
51.7, 51.0, 37.0, 26.3; HRMS (ESI) calcd for C13H16NO4 ([M + H]+)
250.1079, found 250.1077.
Methyl 2-(3-(Acetoxymethyl)-1-methyl-2-oxoindolin-3-yl)acetate
(23).14 Pale-yellow oil (57.4 mg, 79%); H NMR (500 MHz, CDCl3)
1
(8) For selected examples of palladium-free radical-mediated
difunctionalization of N-aryl acrylamides, see: (a) Li, Y.; Sun, M.;
Wang, H.; Tian, Q.; Yang, S. Angew. Chem., Int. Ed. 2013, 52, 3972.
(b) Wei, W.; Zhou, M.; Fan, J.; Liu, W.; Song, R.; Liu, Y.; Hu, M.; Xie,
P.; Li, J. Angew. Chem., Int. Ed. 2013, 52, 3638. (c) Zhou, M.; Wang,
δ 7.31 (td, J = 7.7, 1.2 Hz, 1H), 7.23 (dd, J = 7.3, 0.6 Hz, 1H), 7.04
(td, J = 7.6, 0.8 Hz, 1H), 6.88 (d, J = 7.8 Hz, 1H), 4.46 (d, J = 10.8 Hz,
1H), 4.11 (d, J = 10.8 Hz, 1H), 3.47 (s, 3H), 3.27 (s, 3H), 3.02 (q, J =
16.4 Hz, 2H), 1.94 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 176.5,
E
dx.doi.org/10.1021/jo402529r | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
C.; Song, R.; Liu, Y.; Wei, W.; Li, J. Chem. Commun. 2013, 49, 10817.
(d) Meng, Y.; Guo, L.; Wang, H.; Duan, X. Chem. Commun. 2013, 49,
7540. (e) Zhou, S.; Guo, L.; Wang, H.; Duan, X. Chem.Eur. J. 2013,
19, 12970. (f) Zhou, Z.; Hua, H.; Luo, J.; Chen, Z.; Zhou, P.; Liu, X.;
Liang, Y. Tetrahedron 2013, 69, 10030. (g) Fu, W.; Xu, F.; Fu, Y.; Zhu,
M.; Yu, J.; Xu, C.; Zou, D. J. Org. Chem. 2013, 78, 12202. (h) Zhou,
M.; Song, R.; Ouyang, X.; Liu, Y.; Wei, W.; Deng, G.; Li, J. Chem. Sci.
2013, 4, 2690. (i) Wang, H.; Guo, L.; Duan, X. Adv. Synth. Catal.
2013, 355, 2222. (j) Shen, T.; Yuan, Y.; Jiao, N. Chem. Commun. 2014,
50, 554. (k) Li, Y.; Wei, X.; Li, X.; Yang, S. Chem. Commun. 2013, 49,
11701. (l) Xu, P.; Xie, J.; Xue, Q.; Pan, C.; Cheng, Y.; Zhu, C. Chem.
Eur. J. 2013, 19, 14039. (m) Wei, X.; Li, Y.; Zhou, A.; Yang, T.; Yang,
S. Org. Lett. 2013, 15, 4158. (n) Li, X.; Xu, X.; Hu, P.; Xiao, X.; Zhou,
C. J. Org. Chem. 2013, 78, 7343.
(9) (a) Li, X.; Xu, X.; Zhou, C. Chem. Commun. 2012, 48, 12240.
(b) Li, X.; Xu, X.; Tang, Y. Org. Biomol. Chem. 2013, 11, 1739. (c) Li,
X.; Xu, X.; Shi, X. Tetrahedron Lett. 2013, 54, 3071. (d) Li, X.; Shi, X.;
Fang, M.; Xu, X. J. Org. Chem. 2013, 78, 9499. (e) Su, Y.; Sun, X.; Wu,
G.; Jiao, N. Angew. Chem., Int. Ed. 2013, 52, 9808. (f) Taniguchi, T.;
Zaimoku, H.; Ishibashi, H. Chem.Eur. J. 2011, 17, 4307.
(g) Taniguchi, T.; Idota, A.; Ishibashi, H. Org. Biomol. Chem. 2011,
9, 3151. (h) Taniguchi, T.; Idota, A.; Yokoyama, S.; Ishibashi, H.
Tetrahedron Lett. 2011, 52, 4768.
(10) Liu, W.; Li, Y.; Liu, K.; Li, Z. J. Am. Chem. Soc. 2011, 133,
10756.
(11) Fabry, D. C.; Stodulski, M.; Hoerner, S.; Gulder, T. Chem.
Eur. J. 2012, 18, 10834.
(12) Osman, F. H.; El-Samahy, F. A. Phosphorus, Sulfur Silicon Relat.
Elem. 1998, 134/135, 437.
(13) Suar
Duarte, L. E.; San
M. S.; Joseph-Nathan, P. Tetrahedron: Asymmetry 2009, 20, 2374.
(14) Jaegli, S.; Dufour, J.; Wei, H.; Piou, T.; Duan, X.; Vors, J.-P.;
Neuville, L.; Zhu, J. Org. Lett. 2010, 12, 4498.
́
ez-Castillo, O. R.; Melen
́ ́
dez-Rodríguez, M.; Castelan-
́
chez-Zavala, M.; Rivera-Becerril, E.; Morales-Ríos,
F
dx.doi.org/10.1021/jo402529r | J. Org. Chem. XXXX, XXX, XXX−XXX