Synthesis of 1-Alkyl-3-(2-oxo-2-aryl/alkyl-ethyl)indolin-2-ones through Gold/Bronsted Acid Relay Actions: Observation of Selective C=C Bond Cleavage of Enaminones

Article abstract of DOI:10.1055/s-0036-1588820

A novel gold(I)/Bronsted acid sequential catalyzed/promoted procedure to synthesize 1-alkyl-3-(2-oxo-2-aryl/alkyl-ethyl)indolin-2-ones under mild reaction conditions is developed. This methodology is realized by relay actions of gold and a Bronsted acid in a one-pot multistep manner. The gold(I)-catalyzed chemoselective C(sp ²)-H functionalization of enaminones and Bronsted acid promoted cleavage of the C=C bond are integrated effectively. Based on the results of control experiments and ESI-MS analysis, a possible reaction mechanism is proposed.

Full text of DOI:10.1055/s-0036-1588820

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2017, 49, A–J
paper
A
en
Y. Zhao et al.
Paper
Synthesis
Synthesis of 1-Alkyl-3-(2-oxo-2-aryl/alkyl-ethyl)indolin-2-ones
through Gold/Brønsted Acid Relay Actions: Observation of
Selective C=C Bond Cleavage of Enaminones
Yulei Zhao
Yang Yuan
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Lingkai Kong
Fangfang Zhang
Yanzhong Li*
Shanghai Key Laboratory of Green Chemistry and Chemical
Processes, School of Chemistry and Molecular Engineering,
East China Normal University, 500 Dongchuan Road,
Shanghai 200241, P. R. of China
yzli@chem.ecnu.edu.cn
Received: 13.03.2017
Accepted after revision: 01.04.2017
Published online: 09.05.2017
plored. In 2016, Song and co-workers realized an elegant
Cu(II)/Fe(III)-catalyzed C=C cleavage of α,β-unsaturated car-
bonyl compounds with H-phosphonates leading to β-keto-
phosphonates (Scheme 1, a).7 Sajiki and co-workers report-
ed an excellent procedure for the Pd(0)/Cu(I)-catalyzed re-
gioselective C=C bond cleavage of cinnamaldehydes for the
preparation of aromatic aldehydes (Scheme 1, b).8 In, 1987,
Eicher and co-workers disclosed the C=C bond cleavage of
an enaminone under acidic reflux conditions,9 however,
only one example was reported.
DOI: 10.1055/s-0036-1588820; Art ID: ss-2017-h0157-op
Abstract A novel gold(I)/Brønsted acid sequential catalyzed/promoted
procedure to synthesize 1-alkyl-3-(2-oxo-2-aryl/alkyl-ethyl)indolin-2-
ones under mild reaction conditions is developed. This methodology is
realized by relay actions of gold and a Brønsted acid in a one-pot multi-
step manner. The gold(I)-catalyzed chemoselective C(sp2)-H functional-
ization of enaminones and Brønsted acid promoted cleavage of the C=C
bond are integrated effectively. Based on the results of control experi-
ments and ESI-MS analysis, a possible reaction mechanism is proposed.
As a type of α,β-unsaturated carbonyl compound,
enaminones are widely used in organic synthesis.10 As part
of our ongoing interest in the development of enaminone
chemistry,11 we previously disclosed Au-catalyzed tandem
reactions involving chemo- and diastereoselective C(sp2)–H
functionalization of relatively electron-rich enaminones for
the synthesis of pyrrolo[3,4-c]-quinolin-1-one derivatives
(Scheme 1, c).11a Interestingly, when the substituent on the
nitrogen atom of the enaminones was changed to a tosyl
group, selective C=C bond cleavage was realized to afford
1-alkyl-3-(2-oxo-2-aryl/alkyl-ethyl)indolin-2-ones (Scheme
1, d).
Herein, we report a gold(I)/Brønsted acid sequential cat-
alyzed/promoted procedure to synthesize 1-alkyl-3-(2-oxo-
2-aryl/alkyl-ethyl)indolin-2-ones. The challenges associat-
ed with this tandem reaction are as follows: (1) To realize
selective C(sp2)–H functionalization of relatively electron-
deficient enaminones over the N–H insertion reaction,12
which is usually observed in analogous procedures. (2) Se-
lective cleavage of the carbon–carbon double bond rather
than decarbonylation or decarboxylation.
Key words gold(I) catalysis, Brønsted acid promotion, C(sp2)–H func-
tionalization, carbon–carbon bond activation, one-pot synthesis
The cleavage of carbon–carbon bonds is a basic chal-
lenge in chemistry.1 Because of the weaker interactions
with metal catalysts and the lower polarization, the cleav-
age of carbon–carbon bonds is relatively difficult. With an
irreplaceable role in the petroleum industry, C–C bond
cleavage has been a topic of special interest in organic
chemistry and has attracted significant attention in recent
years. After years of development, a number of excellent ap-
proaches for the cleavage of carbon–carbon bonds,2 includ-
ing the deformylation or deacetylation of 1,3-dicarbonyl
compounds2f–h and the cleavage of carbon–carbon double
bonds, have been described in the literature. The cleavage of
carbon–carbon double bonds mainly occurs via oxidative
cleavage reactions,3 metathesis reactions,4 and so on.5 α,β-
Unsaturated carbonyl compounds are very useful building
blocks in organic synthesis. Decarbonylation or decarboxyl-
ation [cleavage of a C(sp2)–C(C=O) bond] have been widely
reported,6 but cleavage of the carbon–carbon double bond
of α,β-unsaturated carbonyl compounds was rarely ex-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

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Y. Zhao et al.
Paper
Synthesis
(a) Cu(II)/Fe(III)-Catalyzed C=C Cleavage
O
Cu(acac)2 (5 mol%)
FeCl3 (10 mol%)
DIPEA (1 equiv)
O
O
P
O
Ar1
Ar2
Ar1
+
Ar2
OEt
H
+
OEt
DCE, 90 °C, O2, 24 h
HP(=O)(COEt)2
C–P bond construction
(b) Pd/Cu(I)-Catalyzed C=C Cleavage
10% Pd/C (10 mol%)
O
CuCl (1 equiv)
morpholine (1 equiv)
O
O
H
H
Ar
+
Ar
H
H
iPrOH, 100 °C, O2, 24 h
O
(c) Our previous work: tandem C(sp2)–H funtionalization/rearrangement reaction
R1
O
N2
R3
R1
N
Brønsted
Acid
Catalysis
Gold
Catalysis
O
R3
HN
+
O
R2
N
H
N
O
R2
relatively
electron-rich
(d) This work: tandem C(sp2)–H funtionalization/C=C cleavage reaction
R1
N2
R3
NHTs
R3
O
Brønsted
Acid
Promotion
Gold
Catalysis
O
+
O
R1
N
R2
N
R2
relatively
electron-deficient
1
2
3
C–C bond construction
O
TsHN
O
R1
– N2
+ H2O
C–H functionalization
cleavage of the C=C bond
N
R2
R3
Scheme 1 Examples of C=C bond cleavage of α,β-unsaturated carbonyl compounds
Initially, our investigation began with the attempted
coupling of (Z)-4-methyl-N-(3-oxo-3-phenylprop-1-en-1-
yl)benzenesulfonamide (1a) and 5-chloro-3-diazo-1-me-
thylindolin-2-one (2a), which were readily prepared ac-
cording to the literature methods.13 Firstly, the reaction of
1a with 2a was carried out using Ph3PAuNTf2 (5 mol%) as
the catalyst in air. However, severe decomposition of 2a was
observed (Table 1, entry 1). So, we decided to add 2a in di-
chloromethane (1 mL) within two hours by using a syringe
pump and a major product was detected by TLC. Neverthe-
less, preliminary NMR characterization of the product gave
an unclean spectrum. Interestingly, when the solvents were
removed under reduced pressure in the presence of chloro-
form, a cleaner NMR spectrum was obtained. Encouraged
by this discovery, we decided to remove dichloromethane
under reduced pressure one hour after the addition of 2a.
Next, chloroform (4 mL) was added to the residue and the
reaction was stirred at room temperature. To our delight,
Figure 1 X-ray crystal structure of 3a
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

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Synthesis
Table 1 Optimization of the Reaction Conditionsa
+ SbF6
Au NCMe
–
N2
H
Ts
tBu
O
N
Cl
O
tBu
1) Cat., solvent, r.t., t [h]
P
O
+
Cl
N
2) Additive, 40 °C, 10 h
O
N
2a (0.24 mmol)
1a (0.20 mmol)
3a
A
Entry
Catalyst (mol%)
Time (h)
Solvent
Additive
Yield (%)b
c
1
2
Ph3PAuNTf2 (5)
Ph3PAuNTf2 (5)
Ph3PAuNTf2 (5)
Ph3PAuNTf2 (5)
Ph3PAuNTf2 (5)
A (5)
–
2
2
2
2
2
2
1
3
2
CH2Cl2
CH2Cl2
CH2Cl2
CHCl3
–
trace
58d
93
CHCl3
3
CHCl3
4
CHCl3
53
5
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
HClconcd
HClconcd
HClconcd
HClconcd
HClconcd
HClconcd
98
6
87
7
Ph3PAuNTf2 (2)
Ph3PAuNTf2 (2)
Ph3PAuNTf2 (2)
Ph3PAuNTf2 (2)
95
8
86
9
96
10
95e
a Reaction conditions: 2a in CH2Cl2 (1.0 mL) was added to a solution of 1a and the catalyst using a syringe pump with addition over the time listed. After 1 h,
HClconcd (12 M, 40 μL, 2.4 equiv) was added [or CH2Cl2 was replaced with CHCl3 (4 mL)].
b Yield of isolated product.
c Substrate 2a (solid) was added in one portion.
d After 2a had been added, the mixture was stirred at r.t. for 20 h.
e Reaction under a nitrogen atmosphere.
pure product 3a, which was fully confirmed by X-ray crys-
N2
TsNH2 + HCO2H
tallography analysis (Figure 1),14 was easily isolated in a
yield of 58% (entry 2). Moreover, on raising the reaction
temperature to 40 °C after the solvent was changed to chlo-
roform, the yield of 3a was increased to 93% (entry 3).
When chloroform was used as the solvent instead of CH2Cl2,
partial decomposition of the diazo compound was inevita-
ble (entry 4). In order to avoid the decomposition of the di-
azo compound and simplify operations, dichloromethane
was used as the solvent and HClconcd (40 μL, 2.4 equiv) was
subsequently added (entry 5). As we expected, the tandem
reaction took place smoothly and 3a was obtained in an ex-
cellent yield (98%). Furthermore, JohnPhos(MeCN)AuSbF6
(catalyst A) was also investigated (entry 6), but no better re-
sult was achieved. When the amount of Ph3PAuNTf2 was re-
duced to 2 mol%, the reaction proceeded successfully to af-
ford a 95% yield of 3a (entry 7). Reducing the time for the
addition of 2a led to partial decomposition and lowered the
yield to 86% (entry 8). Increasing the time to three hours
gave a similar result (entry 7 vs 9; 95% vs 96%). The use of a
nitrogen atmosphere had no significant effect on the reac-
tion outcome (entry 10).
Cl
O
N
H2O
2a
O
Ph3PAuNTf2
6
NHTs
[Au]
N
C8H9NNaO3S [M + Na]+: 222.0195
Found: 222.0198
Cl
O
+
O
2a'
O
NHTs
Ph
Ph
1a
Cl
O
O
Ph
NHTs
O
N
H
3a
LAu
Cl
C
17H14ClNNaO2 [M + Na]+: 322.0605
Found: 322.0611
N
2a''
Au(I)
H
O
OH
O
N
Ph
Ph
H2O
NHTs
Cl
NTs
Cl
O
N
O
H
With optimized reaction conditions in hand (Table 1,
entry 7), we next examined the substrate scope (Table 2). A
range of substituted diazoindolinones and enaminones
were suitable for the reaction, offering the corresponding
products 3a–q in good to excellent yields. Firstly, the R3
4a
5a
25H21ClN2NaO4S [M+Na]+: 503.0803
Found: 503.0808
C
25H23ClN2NaO5S [M+Na]+: 521.0908
Found: 521.0916
C
Scheme 2 The possible reaction mechanism
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

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Synthesis
Table 2 Reaction Scopea
R1
N2
H
H
Ts
R3
O
N
O
1) Ph3PAuNTf2, CH2Cl2, r.t.
R3
O
+
R1
N
R2
2) concd HCl (2.4 equiv), 40 °C, t (h)
O
N
R2
2 (0.24 mmol)
3
1 (0.20 mmol)
Entry
R1
Ph
R2
R3
Time (h)
Product
Yield (%)b
1
2
Me
5-Cl
5-O2N
5-F
10
10
10
10
10
10
10
79
15
15
15
15
48
10
10
10
10
3a
3b
3c
3d
3e
3f
95
71
99
87
82
86
88
71
78
85
85
74
83
93
94
90
92
Ph
Me
Me
Me
Me
Me
Me
Me
3
Ph
4
Ph
5-Br
5-H
5
Ph
6
Ph
5-Me
5-MeO
4,6-Cl2
5-Cl
5-Cl
5-Cl
5-Cl
5-Cl
5-F
7
Ph
3g
3h
3i
8
Ph
9
Ph
4-O2N(C6H4)CH2
10
11
12
13c
14
15
16
17
Ph
4-Br(C6H4)CH2
3j
Ph
Bn
3k
3l
Ph
4-Me(C6H4)CH2
t-Bu
Me
Me
Me
Me
Me
3m
3n
3o
3p
3q
4-n-Pr(C6H4)
4-n-Pr(C6H4)
4-Cl(C6H4)
4-Cl(C6H4)
5-Cl
5-F
5-Cl
a Reaction conditions: 2 in CH2Cl2 (1.0 mL) was added to a solution of 1 and Ph3PAuNTf2 (2 mol%) using a syringe pump with addition over 2 h. After 1 h, HClconcd
(40 μL, 2.4 equiv) was added.
b Yield of isolated product.
c DCE was used as the solvent and the reaction was carried out at 75 °C.
Table 3 Control Reactions
Ph
O
Cl
H
Ts
+
N2
Cl
O
N
NHTs
Ph3PAuNTf2 (2 mol%)
CH2Cl2, r.t., 3.5 h
O
Ph
O
N
Cl
N
Cl
2h (1.2 equiv)
4h, 79%
1a (0.4 mmol)
Ph
O
O
Cl
Cl
NHTs
O
Ph
Catalyst
NH2
+
S
O
CH2Cl2, 40 °C
48 h
N
O
O
N
Cl
Cl
4h (0.2 mmol)
3h
TsNH2
Entry
Catalyst
Yield of 3h (%)
Yield of TsNH2 (%)
Recovery of 4h (%)
1
2
3
4
Ph3PAuNTf2 (2 mol%) HClconcd (40 μL)
HClconcd (40 μL)
73
17
58
–
67
–
26
81
41
99
HNTf2 (4 mol%), H2O (40 μL)
H2O (40 μL)
59
–
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

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Synthesis
substituent on the benzene ring of the diazoindolinones 2
was examined. Compared to electron-donating groups (3f:
R3 = Me, 86%; 3g: R3 = MeO, 88%) (entries 6 and 7), electron-
withdrawing substituents (such as, 3c: R3 = F, 99%; 3a: R3 =
Cl, 95%) (entries 3 and 1) gave much better yields. However,
with the stronger electron-withdrawing nitro group on the
phenyl ring, the desired product 3b was obtained in only
71% yield (entry 2). 5-Bromo-3-diazoindolin-2-one (R3 = Br)
gave the desired product 3d in 87% yield (entry 4). Com-
pound 3h was obtained in only 71% yield (entry 8) due to
steric effects. Subsequently, the R2 substituents on the ni-
trogen of diazoindolinones 2 were explored. Electron-with-
drawing groups such as 4-NO2 and 4-Br on the phenyl ring
were compatible in the reaction and desired products 3i
and 3j (entries 9 and 10) were obtained in 78% and 85%
yields, respectively. A 4-methylbenzyl or benzyl group on
the nitrogen atom of 2 were also applicable, offering the
target products with good yields (3k: 85%; 3l: 74%) (entries
11 and 12). However, with an electron-withdrawing R2 sub-
stituent (such as an acetyl group), no C=C cleavage product
was detected. In addition, with poorly soluble N–H diazoin-
dolinones, serious decomposition was observed and only
trace amounts of the desired products were isolated. Final-
ly, the effects of substituents on the carbonyl carbon of the
enaminones (R1) were investigated. An alkyl-substituted
enaminone (R1 = t-Bu) provided 3m in 83% yield (entry 13).
Aryl-substituted enaminones also tolerated the reaction
conditions, affording products 3n–q with excellent yields
(90–94%) (entries 14–17).
To understand the reaction mechanism, several control
experiments were conducted. When the reaction was car-
ried out with 1a and 2h at room temperature in the pres-
ence of only Au(I), the C–H insertion product 4h (E-iso-
mer)11a was successfully isolated in a yield of 79% (Table 3).
Other diazo compounds 2 were also used to prepare inter-
mediates 4, but all of them were easily converted into the
final products 3 and the corresponding pure intermediates
4 were hard to isolate. Under the standard conditions, 4h
was transformed into product 3h in 73% yield (Table 3, en-
try 1). This result suggested that 4h was a possible interme-
diate. Treatment of 4h with HClconcd (40 μL) gave 3h in 17%
yield after 48 hours (81% of 4h recovered) (entry 2). When
H2O (40 μL) and HNTf2 (4 mol%) were used in place of HCl-
(40 μL), 3h was obtained with an encouraging yield of
concd
58% (entry 3). In the presence of H2O only, the C=C bond
cleavage reaction did not occur (entry 4). These control ex-
periments indicated that the reaction should be run in the
presence of a gold catalyst, which might release the strong
Brønsted acid HNTf2.
Based on the experimental results and previously re-
ported work,11a we have proposed a possible reaction
mechanism (Scheme 2). Firstly, Au(I)-catalyzed decomposi-
tion of the diazo compound occurred (2a → 2a′). Next, nu-
cleophilic attack by the α-carbon of the enaminone 1a (Z-
isomer) on 2a′, followed by a 1,2-H shift, provided the che-
moselective C(sp2)-H functionalized intermediate 4a (E-iso-
mer). Subsequently, in the presence of the Brønsted acid,
conjugate addition of H2O to 4a occurred to furnish 5a. Fi-
nally, cleavage of the carbon–carbon bond proceeded to
form 3a and the by-product 6 (CHONHTs).
However, compound 6 could not be detected in the re-
action and only TsNH2 was obtained. In order to clarify this
result, compound 6 was prepared (Scheme 3, a)15 and sub-
jected to the standard reaction conditions. As expected, by-
product 6 was converted into TsNH2 quantitatively (Scheme
3, b).
To further clarify the reaction mechanism, ESI-MS anal-
ysis was performed during the reaction process (Scheme
2).16 After the reaction (1a with 2a, under the standard con-
ditions) had progressed for 15 minutes, a sample was taken
from the reaction mixture for ESI-MS analysis. Fortunately,
the characteristic signal [5a + Na]+ was observed. This high-
resolution mass data of the detected complex was as fol-
lows: m/z [5a + Na]+ calculated for C25H23ClN2NaO5S:
521.0908; found: 521.0916; with an error of –1.4 ppm, sug-
gesting that 5a was a possible intermediate in the forma-
tion of 3a. Simultaneously, a characteristic signal [6 + Na]+
was also obtained (m/z [6 + Na]+ calculated for C8H9NNaO3S:
222.0195; found: 222.0198; with an error of –1.0 ppm),
which implies the presence of 6 during the reaction pro-
cess, although so far it has not been isolated from the tan-
O
O
O
O
O
O
O
EtOCHO (5.0 equiv)
Na (1.5 equiv)
S
S
S
NH3•H2O (2.5 equiv)
N
H
NH2
Cl
H
(a)
THF, 0 °C to r.t.
MeOH, 40–50 °C
6
96%
94%
O
O
O
O
O
O
S
S
Ph3PAuNTf2 (0.02 equiv)
NH2
N
H
(b)
+
H
H
OH
concd HCl (40 µL)
CH2Cl2, 40 °C, overnight
6 (0.4 mmol)
99%
Scheme 3 Preparation and hydrolysis of compound 6
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

F
Y. Zhao et al.
Paper
Synthesis
dem reaction. In addition, the characteristic signals for [3a
+ Na]+ and [4a + Na]+ were also observed. These ESI-MS data
further support the possible reaction mechanism.
(Z)-4-Methyl-N-[3-oxo-3-(4-propylphenyl)prop-1-en-1-yl]ben-
zenesulfonamide (1c)
White solid; yield: 199 mg (58%); mp 107–109 °C; Rf = 0.32 (CH2Cl2–
PE, 1:1).
In conclusion, we have developed a novel one-pot reac-
tion to synthesize 1-alkyl-3-(2-oxo-2-aryl/alkyl-ethyl)in-
dolin-2-ones in good to excellent yields under mild reaction
conditions. In this process, the Au(I)-catalyzed chemoselec-
tive C(sp2)–H functionalization of tosyl-substituted enami-
nones and Brønsted acid promoted selective cleavage of the
carbon–carbon double bond are integrated effectively. The
control experiments suggest that the cleavage process was
promoted by the Brønsted acid and ESI-MS analysis further
supports the proposed reaction mechanism. Further inves-
tigation of the reaction mechanism and the synthetic appli-
cations of the process are currently underway.
IR (ATR): 2960, 2930, 1633, 1577, 1360, 1234, 1164, 1088, 1011, 915,
774, 735, 665 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 11.97 (d, J = 9.6 Hz, 1 H), 7.92–7.65 (m,
4 H), 7.33 (d, J = 8.0 Hz, 2 H), 7.28–7.21 (m, 3 H), 6.18 (d, J = 8.8 Hz, 1
H), 2.63 (t, J = 7.2 Hz, 2 H), 2.42 (s, 3 H), 1.70–1.60 (m, 2 H), 0.93 (t, J =
7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 192.5, 149.0, 145.0, 142.1, 137.5,
135.7, 130.4, 129.2, 128.3, 127.2, 99.6, 38.0, 24.1, 21.5, 13.6.
HRMS (ESI): m/z [M + Na]+ calcd for C19H21NNaO3S: 366.1134; found:
366.1136.
(Z)-N-[3-(4-Chlorophenyl)-3-oxoprop-1-en-1-yl]-4-methylben-
zenesulfonamide (1d)
All reactions were performed in oven-dried glassware in air except
when otherwise noted. The reactions were monitored by TLC carried
out on Merck silica plates (silica gel 60 F254) using UV light for visual-
ization. Starting materials and reagents were purchased from com-
mercial suppliers (Acros, Sigma Aldrich and TCI Europe), which were
used without further purification unless otherwise noted. Anhydrous
CH2Cl2 and DCE were prepared by distillation from CaH2. Column
chromatographic purification of the products was carried out using
Huanghai Chemical Co. Ltd. silica gel (300–400 mesh). IR spectra were
recorded on a NICOLET iS50 FT-IR spectrophotometer. 1H and 13C
NMR spectra were recorded at 400 MHz and 100 MHz, respectively, in
CDCl3 or DMSO-d6 (containing 0.03% Me4Si). 1H NMR spectra were re-
corded with Me4Si (δ = 0.00) as the internal reference and 13C NMR
spectra were recorded with CDCl3 (δ = 77.00) or DMSO-d6 (δ = 39.52)
as the internal reference. High-resolution mass spectra were obtained
using a Bruker Maxis Impact mass spectrometer with a TOF (for EI or
ESI) or FT-ICR (for MALDI) analyzer. Single-crystal X-ray diffraction
data were collected on a Bruker SMARTAPEX diffractometer.
White solid; yield: 255 mg (76%); mp 146–148 °C; Rf = 0.30 (CH2Cl2–
PE, 1:1).
IR (ATR): 2960, 1634, 1575, 1360, 1236, 1165, 1088, 1006, 914, 772,
728, 663 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 11.88 (d, J = 10.0 Hz, 1 H), 7.90–7.65
(m, 4 H), 7.42 (d, J = 8.4 Hz, 2 H), 7.34 (d, J = 8.0 Hz, 2 H), 7.31–7.26 (m,
1 H), 6.14 (d, J = 8.8 Hz, 1 H), 2.43 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 191.4, 145.2, 142.9, 139.8, 137.3,
136.3, 130.5, 129.6, 129.4, 127.2, 99.0, 21.5.
HRMS (ESI): m/z [M + Na]+ calcd for C16H14ClNNaO3S: 358.0275;
found: 358.0276.
1-Alkyl-3-(2-oxo-2-aryl/alkyl-ethyl)indolin-2-ones 3; General Pro-
cedure
Under an atmosphere of air, to a Schlenk tube were added enaminone
1 (0.20 mmol), Ph3PAuNTf2 (3.0 mg, 0.004 mmol) and anhydrous
CH2Cl2 (2.5 mL). Next, diazooxindole 2 (0.24 mmol) in CH2Cl2 (1.0 mL)
was added over 2 h using a syringe pump. The resulting mixture was
stirred at ambient temperature for about 1 h until the enaminone 1
had disappeared by TLC analysis. HClconcd (40 μL) was added to the
mixture which was kept stirring at 40 °C for the appropriate length of
time (see Table 2). Subsequently, the reaction was cooled to r.t., PE (2
mL) was added and the mixture was directly subjected to column
chromatography for purification.
Benzenesulfonamides 1; General Procedure (Scheme 4)
1a: R1 = Ph
NHTs
O
NH2
O
NaH (2.8 equiv)
THF, 0 °C to r.t.
1b: R1 = tBu
TsCl
+
1c: R1 = 4-nPrC6H4
1d: R1 = 4-ClC6H4
R1
R1
1.0 mmol
1.1 equiv
1
Scheme 4
5-Chloro-1-methyl-3-(2-oxo-2-phenylethyl)indolin-2-one (3a)
Under an atmosphere of N2, to a Schlenk tube were added NH2-enam-
inone13a (1.0 mmol), TsCl (209.8 mg, 1.1 mmol) and anhydrous THF
(15 mL) at 0 °C. After 20 min, NaH (60%, 112.0 mg, 2.8 mmol) was
added in three portions over 0.5 h. The resulting mixture was stirred
at 0 °C for about 0.5 h until the NH2-enaminone had disappeared ac-
cording to TLC analysis. The resulting mixture was quenched with sat.
NaCl solution, and extracted with EtOAc (3 × 20 mL). The combined
organic layers were dried over anhydrous Na2SO4, filtered and con-
centrated under reduced pressure. Purification of the residue by flash
chromatography on silica gel (CH2Cl2–PE) afforded 1.
Yellowish solid; yield: 57 mg (95%); mp 103–105 °C; Rf = 0.31
(CH2Cl2–PE, 4:1).
IR (ATR): 3059, 2905, 1709, 1683, 1610, 1489, 1344, 1223, 1099, 983,
809, 759, 733, 688 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.97 (d, J = 7.6 Hz, 2 H), 7.65–7.50 (m, 1
H), 7.50–7.38 (m, 2 H), 7.35–7.20 (m, 2 H), 6.77 (d, J = 8.8 Hz, 1 H),
4.10–3.90 (m, 1 H), 3.84 (dd, J = 18.4, 2.8 Hz, 1 H), 3.41 (dd, J = 18.4,
9.2 Hz, 1 H), 3.25 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 197.3, 177.7, 143.3, 136.4, 133.96,
131.0, 129.1, 128.5, 128.3, 128.2, 125.2, 109.1, 41.1, 39.8, 26.4.
Starting materials 1a,b17 are known compounds and the spectroscop-
ic data are in agreement with those previously reported. The analyti-
cal data of products 1c,d are as follows.
HRMS (ESI): m/z [M + Na]+ calcd for C17H14ClNNaO2: 322.0605; found:
322.0613.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

G
Y. Zhao et al.
Paper
Synthesis
1-Methyl-5-nitro-3-(2-oxo-2-phenylethyl)indolin-2-one (3b)
HRMS (ESI): m/z [M + Na]+ calcd for C17H15NNaO2: 288.0995; found:
288.1001.
Yellow solid; yield: 44 mg (71%); mp 153–155 °C; Rf = 0.30 (CH2Cl2–
EtOAc, 100:1).
1,5-Dimethyl-3-(2-oxo-2-phenylethyl)indolin-2-one (3f)
IR (ATR): 3064, 2923, 1720, 1683, 1613, 1515, 1495, 1329, 1293, 1067,
752, 745, 690 cm–1
.
Yellowish solid; yield: 48 mg (86%); mp 117–119 °C; Rf = 0.33
(CH2Cl2–PE, 4:1).
1H NMR (400 MHz, CDCl3): δ = 8.27 (d, J = 8.4 Hz, 1 H), 8.11 (s, 1 H),
7.96 (d, J = 7.6 Hz, 2 H), 7.66–7.54 (m, 1 H), 7.54–7.40 (m, 2 H), 6.95
(d, J = 8.4 Hz, 1 H), 4.01 (d, J = 7.2 Hz, 1 H), 3.94 (dd, J = 18.8, 2.8 Hz, 1
H), 3.62 (dd, J = 18.4, 7.6 Hz, 1 H), 3.36 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 196.6, 178.1, 150.5, 143.5, 136.0,
134.0, 129.8, 129.0, 128.4, 125.7, 119.9, 107.6, 40.8, 39.1, 26.6.
IR (ATR): 2916, 1702, 1684, 1578, 1497, 1349, 1223, 1092, 986, 807,
767, 731, 687 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.99 (d, J = 7.6 Hz, 2 H), 7.64–7.53 (m, 1
H), 7.51–7.42 (m, 2 H), 7.07 (br s, 2 H), 6.75 (d, J = 8.4 Hz, 1 H), 4.06 (d,
J = 8.0 Hz, 1 H), 3.83 (dd, J = 18.4, 2.8 Hz, 1 H), 3.38 (dd, J = 18.4, 9.6 Hz,
1 H), 3.25 (s, 3 H), 2.28 (s, 3 H).
HRMS (ESI): m/z [M + Na]+ calcd for C17H14N2NaO4: 333.0846; found:
333.0848.
13C NMR (100 MHz, CDCl3): δ = 197.7, 178.2, 142.3, 136.7, 133.8,
132.4, 129.5, 129.0, 128.6, 128.5, 125.6, 108.0, 41.1, 40.1, 26.3, 20.9.
5-Fluoro-1-methyl-3-(2-oxo-2-phenylethyl)indolin-2-one (3c)
HRMS (ESI): m/z [M + Na]+ calcd for C18H17NNaO2: 302.1151; found:
302.1158.
White solid; yield: 56 mg (99%); mp 81–83 °C; Rf = 0.32 (CH2Cl2–PE,
4:1).
5-Methoxy-1-methyl-3-(2-oxo-2-phenylethyl)indolin-2-one (3g)
IR (ATR): 3061, 2916, 1706, 1684, 1492, 1449, 1351, 1221, 1122, 895,
809, 768, 732, 688 cm–1
.
White solid; yield: 52 mg (88%); mp 114–116 °C; Rf = 0.28 (CH2Cl2–
EtOAc, 60:1).
1H NMR (400 MHz, CDCl3): δ = 7.96 (d, J = 8.0 Hz, 2 H), 7.63–7.52 (m, 1
H), 7.51–7.35 (m, 2 H), 7.02 (d, J = 7.6 Hz, 1 H), 6.99–6.89 (m, 1 H),
6.81–6.68 (m, 1 H), 4.03 (d, J = 8.4 Hz, 1 H), 3.83 (dd, J = 18.4, 2.4 Hz, 1
H), 3.37 (dd, J = 18.4, 9.2 Hz, 1 H), 3.24 (s, 3 H).
IR (ATR): 3256, 3065, 1683, 1598, 1497, 1334, 1294, 1158, 1030, 814,
767, 688, 665 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.97 (d, J = 7.6 Hz, 2 H), 7.63–7.52 (m, 1
H), 7.52–7.41 (m, 2 H), 6.89 (s, 1 H), 6.83–6.72 (m, 2 H), 4.04 (d, J = 7.2
Hz, 1 H), 3.82 (dd, J = 18.4, 2.8 Hz, 1 H), 3.73 (s, 3 H), 3.39 (dd, J = 18.4,
9.2 Hz, 1 H), 3.24 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 197.4, 177.8, 159.6 (d, JC–F = 239.9 Hz),
140.7, 136.5, 133.9, 131.0 (d, JC–F = 8.7 Hz), 129.0, 128.4, 114.4 (d, JC–F
=
23.5 Hz), 113.0 (d, JC–F = 25.2 Hz), 108.5 (d, JC–F = 8.2 Hz), 41.4, 39.8,
13C NMR (100 MHz, CDCl3): δ = 197.6, 177.8, 156.3, 138.1, 136.5,
133.7, 130.6, 128.9, 128.3, 112.5, 112.1, 108.4, 55.7, 41.4, 39.9, 26.2.
26.4.
HRMS (ESI): m/z [M + Na]+ calcd for C17H14FNNaO2: 306.0901; found:
HRMS (ESI): m/z [M + Na]+ calcd for C18H17NNaO3: 318.1101; found:
306.0905.
318.1101.
5-Bromo-1-methyl-3-(2-oxo-2-phenylethyl)indolin-2-one (3d)
Yellowish solid; yield: 60 mg (87%); mp 138–140 °C; Rf = 0.32
4,6-Dichloro-1-methyl-3-(2-oxo-2-phenylethyl)indolin-2-one (3h)
(CH2Cl2–PE, 4:1).
White solid; yield: 48 mg (71%); mp 138–140 °C; Rf = 0.30 (CH2Cl2–PE,
3:1).
IR (ATR): 3060, 2915, 1708, 1683, 1607, 1488, 1343, 1223, 1097, 808,
759, 734, 689 cm–1
.
IR (ATR): 3063, 1720, 1685, 1606, 1580, 1347, 1290, 1213, 1080, 1022,
972, 835, 735, 720, 689 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.10–7.92 (m, 2 H), 7.65–7.55 (m, 1 H),
7.52–7.45 (m, 2 H), 7.44–7.35 (m, 2 H), 6.74 (d, J = 8.0 Hz, 1 H), 4.04
(dd, J = 8.8, 2.8 Hz, 1 H), 3.85 (dd, J = 18.4, 3.2 Hz, 1 H), 3.42 (dd, J =
18.4, 9.2 Hz, 1 H), 3.25 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 197.2, 177.7, 143.9, 136.5, 134.0,
131.5, 131.3, 129.1, 128.5, 128.0, 115.5, 109.7, 41.1, 39.8, 26.4.
1H NMR (400 MHz, CDCl3): δ = 7.90 (d, J = 7.6 Hz, 2 H), 7.65–7.50 (m, 1
H), 7.50–7.35 (m, 2 H), 6.95 (d, J = 1.2 Hz, 1 H), 6.80 (d, J = 1.2 Hz, 1 H),
4.26 (dd, J = 19.2, 5.2 Hz, 1 H), 3.90–3.40 (m, 2 H), 3.29 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 196.9, 177.3, 147.7, 136.3, 134.9,
133.9, 130.4, 129.0, 128.4, 124.4, 122.6, 107.8, 41.5, 36.9, 26.7.
HRMS (ESI): m/z [M + Na]+ calcd for C17H14BrNNaO2: 366.0100; found:
366.0110.
HRMS (ESI): m/z [M + Na]+ calcd for C17H13Cl2NNaO: 356.0216; found:
356.0222.
1-Methyl-3-(2-oxo-2-phenylethyl)indolin-2-one (3e)
5-Chloro-1-(4-nitrobenzyl)-3-(2-oxo-2-phenylethyl)indolin-2-one
(3i)
Yellowish solid; yield: 42 mg (82%); mp 107–109 °C; Rf = 0.30
(CH2Cl2–PE, 4:1).
Yellowish solid; yield: 66 mg (78%); mp 200–202 °C; Rf = 0.30
(CH2Cl2–PE, 8:1).
IR (ATR): 3055, 2916, 1705, 1686, 1470, 1347, 1265, 1223, 1088, 731,
701, 689 cm–1
.
IR (ATR): 3065, 1713, 1685, 1609, 1519, 1485, 1342, 1218, 1163, 812,
736, 689 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.98 (d, J = 7.6 Hz, 2 H), 7.63–7.54 (m, 1
H), 7.52–7.41 (m, 2 H), 7.34–7.20 (m, 2 H), 7.05–6.95 (m, 1 H), 6.86 (d,
J = 7.6 Hz, 1 H), 4.08 (d, J = 8.0 Hz, 1 H), 3.90–3.75 (m, 1 H), 3.39 (dd,
J = 18.0, 9.2 Hz, 1 H), 3.27 (s, 3 H).
1H NMR (400 MHz, DMSO-d6): δ = 8.23 (d, J = 8.4 Hz, 2 H), 8.02 (d, J =
7.2 Hz, 2 H), 7.75–7.63 (m, 3 H), 7.59–7.48 (m, 2 H), 7.44 (s, 1 H), 7.23
(d, J = 7.2 Hz, 1 H), 6.86 (d, J = 8.0 Hz, 1 H), 5.25–5.00 (m, 2 H), 4.25–
4.00 (m, 2 H), 3.85 (dd, J = 18.8, 5.2 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 197.6, 178.3, 144.7, 136.7, 133.8,
13C NMR (100 MHz, DMSO-d6): δ = 197.9, 177.6, 147.4, 144.8, 142.6,
136.3, 134.1, 131.8, 129.2, 128.8, 128.6, 127.6, 126.6, 124.1, 124.0,
110.2, 42.4, 41.0, 38.0.
129.5, 129.0, 128.5, 128.4, 124.7, 122.8, 108.3, 41.1, 40.0, 26.3.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

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Y. Zhao et al.
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Synthesis
HRMS (ESI): m/z [M + Na]+ calcd for C23H17ClN2NaO4: 443.0769;
13C NMR (100 MHz, CDCl3): δ = 213.6, 177.9, 143.4, 131.1, 128.3,
found: 443.0772.
128.2, 124.7, 109.1, 43.9, 41.1, 38.0, 26.3.
HRMS (ESI): m/z [M + Na]+ calcd for C15H18ClNNaO2: 302.0918; found:
302.0910.
1-(4-Bromobenzyl)-5-chloro-3-(2-oxo-2-phenylethyl)indolin-2-
one (3j)
Yellowish solid; yield: 77 mg (85%); mp 223–225 °C; Rf = 0.26
(CH2Cl2–PE, 1:1).
5-Fluoro-1-methyl-3-[2-oxo-2-(4-propylphenyl)ethyl]indolin-2-
one (3n)
IR (ATR): 3063, 1712, 1686, 1611, 1485, 1362, 1220, 812, 800, 752,
Yellowish solid, yield: 60 mg (93%); mp 71–73 °C; Rf = 0.35 (CH2Cl2).
684 cm–1
.
IR (ATR): 2959, 1708, 1680, 1606, 1492, 1350, 1224, 1121, 988, 805,
1H NMR (400 MHz, CDCl3): δ = 7.99 (d, J = 7.6 Hz, 2 H), 7.62–7.56 (m, 1
H), 7.55–7.43 (m, 4 H), 7.26–7.20 (m, 3 H), 7.13 (d, J = 8.0 Hz, 1 H),
6.60 (d, J = 8.4 Hz, 1 H), 5.10–4.80 (m, 2 H), 4.08 (d, J = 6.4 Hz, 1 H),
3.90 (dd, J = 18.4, 2.8 Hz, 1 H), 3.55 (dd, J = 18.4, 8.0 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 197.0, 177.9, 142.2, 136.4, 134.9,
134.1, 132.4, 131.0, 129.4, 129.2, 128.6, 128.5, 128.3, 125.2, 122.1,
110.1, 43.5, 41.3, 39.6.
735, 689 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.89 (d, J = 7.6 Hz, 2 H), 7.27 (d, J = 7.6
Hz, 2 H), 7.08–7.00 (m, 1 H), 7.00–6.90 (m, 1 H), 6.76 (dd, J = 8.4, 4.0
Hz, 1 H), 4.04 (d, J = 8.0 Hz, 1 H), 3.82 (ddd, J = 18.4, 2.8, 0.8 Hz, 1 H),
3.36 (ddd, J = 18.0, 9.2, 0.8 Hz, 1 H), 3.25 (s, 3 H), 2.64 (t, J = 7.6 Hz, 2
H), 1.75–1.60 (m, 2 H), 0.93 (td, J = 7.2, 0.8 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 197.0, 177.9, 159.6 (d, JC–F = 239.9 Hz),
149.5, 140.6 (d, JC–F = 1.9 Hz), 134.2, 131.1 (d, JC–F = 8.7 Hz), 129.1,
HRMS (ESI): m/z [M + Na]+ calcd for C23H17BrClNNaO2: 476.0023;
found: 476.0024.
128.6, 114.4 (d, JC–F = 23.4 Hz), 113.1 (d, JC–F = 25.2 Hz), 108.5 (d, JC–F =
8.3 Hz), 41.5, 39.7, 37.9, 26.3, 24.0, 13.5.
HRMS (ESI): m/z [M + Na]+ calcd for C20H20FNNaO2: 348.1370; found:
1-Benzyl-5-chloro-3-(2-oxo-2-phenylethyl)indolin-2-one (3k)
348.1376.
White solid; yield: 64 mg (85%); mp 182–184 °C; Rf = 0.30 (CH2Cl2–PE,
3:2).
5-Chloro-1-methyl-3-[2-oxo-2-(4-propylphenyl)ethyl]indolin-2-
one (3o)
IR (ATR): 2915, 1708, 1688, 1610, 1487, 1350, 1220, 1178, 801, 754,
740, 723, 699, 687 cm–1
.
Yellowish solid, yield: 64 mg (94%); mp 101–103 °C; Rf = 0.35 (CH2Cl2).
1H NMR (400 MHz, CDCl3): δ = 8.05–7.96 (m, 2 H), 7.65–7.56 (m, 1 H),
7.54–7.45 (m, 2 H), 7.37–7.32 (m, 4 H), 7.32–7.27 (m, 1 H), 7.26–7.22
(m, 1 H), 7.12 (dd, J = 8.4, 2.0 Hz, 1 H), 6.64 (d, J = 8.4 Hz, 1 H), 4.97 (s,
2 H), 4.13 (dd, J = 8.8, 2.8 Hz, 1 H), 3.91 (dd, J = 18.4, 2.8 Hz, 1 H), 3.51
(dd, J = 18.4, 8.8 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 197.1, 177.9, 142.4, 136.5, 135.9,
134.0, 131.1, 129.2, 129.1, 128.6, 128.32, 128.28, 128.1, 127.6, 125.2,
110.2, 44.1, 41.2, 39.8.
IR (ATR): 2959, 1710, 1680, 1607, 1490, 1343, 1100, 986, 807, 735,
705 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.89 (d, J = 8.0 Hz, 2 H), 7.40–7.20 (m, 4
H), 6.77 (d, J = 8.8 Hz, 1 H), 4.03 (d, J = 7.6 Hz, 1 H), 3.82 (dd, J = 18.4,
2.4 Hz, 1 H), 3.39 (dd, J = 18.4, 9.2 Hz, 1 H), 3.26 (s, 3 H), 2.64 (t, J = 7.6
Hz, 2 H), 1.70–1.60 (m, 2 H), 0.94 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 196.9, 177.9, 149.6, 143.3, 134.3,
131.2, 129.2, 128.6, 128.3, 128.2, 125.3, 109.1, 41.2, 39.7, 38.0, 26.4,
24.0, 13.6.
HRMS (ESI): m/z [M + Na]+ calcd for C23H18ClNNaO2: 398.0918; found:
398.0920.
HRMS (ESI): m/z [M + Na]+ calcd for C20H20ClNNaO2: 364.1075; found:
364.1075.
5-Chloro-1-(4-methylbenzyl)-3-(2-oxo-2-phenylethyl)indolin-2-
one (3l)
White solid; yield: 58 mg (74%); mp 206–208 °C; Rf = 0.30 (CH2Cl2–PE,
4:1).
3-[2-(4-chlorophenyl)-2-oxoethyl]-5-fluoro-1-methylindolin-2-
one (3p)
IR (ATR): 3063, 1716, 1670, 1486, 1363, 1219, 803, 757, 686 cm–1
.
White solid, yield: 57 mg (90%); mp 139–141 °C; Rf = 0.35 (CH2Cl2).
1H NMR (400 MHz, CDCl3): δ = 8.00 (d, J = 7.6 Hz, 2 H), 7.65–7.55 (m, 1
H), 7.54–7.35 (m, 2 H), 7.25–7.17 (m, 3 H), 7.16–7.08 (m, 3 H), 6.65 (d,
J = 8.4 Hz, 1 H), 4.92 (s, 2 H), 4.12 (dd, J = 8.4, 2.4 Hz, 1 H), 3.90 (dd, J =
18.4, 2.8 Hz, 1 H), 3.48 (dd, J = 18.8, 9.2 Hz, 1 H), 2.33 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 197.2, 177.9, 142.5, 137.9, 136.5,
134.0, 132.8, 131.1, 129.9, 129.1, 128.6, 128.3, 127.7, 125.2, 110.3,
43.8, 41.2, 39.9, 21.0.
IR (ATR): 2905, 1708, 1686, 1589, 1493, 1352, 1221, 1092, 987, 819,
688 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.00–7.85 (m, 2 H), 7.55–7.40 (m, 2 H),
7.06–6.92 (m, 2 H), 6.77 (dd, J = 8.4, 4.0 Hz, 1 H), 4.03 (dd, J = 9.2, 2.4
Hz, 1 H), 3.81 (dd, J = 18.4, 3.2 Hz, 1 H), 3.35 (dd, J = 18.4, 9.2 Hz, 1 H),
3.26 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 196.2, 177.7, 159.7 (d, JC–F = 239.9 Hz),
140.7 (d, JC–F =2.0 Hz), 140.5, 134.8, 130.8 (d, JC–F = 8.7 Hz), 129.9,
HRMS (ESI): m/z [M + Na]+ calcd for C24H20ClNNaO2: 412.1075; found:
412.1086.
129.4, 114.6 (d, JC–F = 23.5 Hz), 113.1 (d, JC–F = 25.2 Hz), 108.7 (d, JC–F =
8.2 Hz), 41.4, 39.9, 26.4.
HRMS (ESI): m/z [M + Na]+ calcd for C17H13FClNNaO2: 340.0511;
found: 340.0515.
5-Chloro-3-(3,3-dimethyl-2-oxobutyl)-1-methylindolin-2-one
(3m)
Yellow oil; yield: 46 mg (83%); Rf = 0.33 (CH2Cl2–PE, 3:1).
IR (ATR): 2968, 1703, 1610, 1490, 1343, 1101, 1070, 811, 735, 656 cm–1
.
5-Chloro-3-[2-(4-chlorophenyl)-2-oxoethyl]-1-methylindolin-2-
one (3q)
1H NMR (400 MHz, CDCl3): δ = 7.17 (d, J = 8.0 Hz, 1 H), 7.04 (s, 1 H),
6.68 (d, J = 8.4 Hz, 1 H), 3.76 (d, J = 6.8 Hz, 1 H), 3.25 (dd, J = 18.8, 2.8
Hz, 1 H), 3.15 (s, 3 H), 2.89 (dd, J = 18.4, 8.8 Hz, 1 H), 1.10 (s, 9 H).
Yellowish solid, yield: 61 mg (92%); mp 149–151 °C; Rf = 0.35
(CH2Cl2).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

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Y. Zhao et al.
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Synthesis
IR (ATR): 2907, 1709, 1684, 1588, 1489, 1344, 1221, 1092, 986, 812,
736, 651 cm–1
1H NMR (400 MHz, CDCl3): δ = 7.91 (d, J = 8.4 Hz, 2 H), 7.45 (d, J = 8.4
Hz, 2 H), 7.35–7.15 (m, 2 H), 6.78 (d, J = 8.0 Hz, 1 H), 4.02 (d, J = 7.2 Hz,
1 H), 3.81 (dd, J = 18.4, 2.4 Hz, 1 H), 3.38 (dd, J = 18.4, 8.8 Hz, 1 H), 3.26
(s, 3 H).
Supporting Information
.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1588820.
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References
13C NMR (100 MHz, CDCl3): δ = 196.1, 177.6, 143.4, 140.6, 134.8,
(1) (a) Chen, F.; Wang, T.; Jiao, N. Chem. Rev. 2014, 114, 8613.
(b) Rybtchinski, B.; Milstein, D. Angew. Chem. Int. Ed. 1999, 38,
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1759.
130.9, 129.9, 129.5, 128.5, 128.3, 125.2, 109.2, 41.1, 39.8, 26.4.
HRMS (ESI): m/z [M + Na]+ calcd for C17H13Cl2NNaO2: 356.0216;
found: 356.0217.
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(E)-N-[2-(4,6-Dichloro-1-methyl-2-oxoindolin-3-yl)-3-oxo-3-
phenylprop-1-en-1-yl]-4-methylbenzenesulfonamide (4h)
In air, to a Schlenk tube were added enaminone 1a (120.6 mg, 0.40
mmol), Ph3PAuNTf2 (5.9 mg, 0.008 mmol) and anhydrous CH2Cl2 (5
mL). Next, diazooxindole 2h (116.2 mg, 0.48 mmol) in CH2Cl2 (3.0 mL)
was added over 3 h using a syringe pump. The resulting mixture was
stirred at ambient temperature for 0.5 h until enaminone 1a had dis-
appeared according to TLC analysis. Subsequently, the mixture was
subjected to flash column chromatography for purification directly,
using CH2Cl2–acetone (15:0 to 15:1, v/v) as the eluent.
Yellowish solid, yield: 163 mg (79%); mp 125–127 °C; Rf = 0.26
(CH2Cl2–acetone, 15:1).
IR (ATR): 3175, 3061, 1719, 1701, 1607, 1349, 1267, 1089, 873, 840,
746, 718, 703, 670 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 11.84 (br s, 1 H), 7.73 (d, J = 8.0 Hz,
2 H), 7.63–7.55 (m, 1 H), 7.55–7.44 (m, 4 H), 7.40–7.30 (m, 3 H), 7.17
(s, 1 H), 7.04 (s, 1 H), 4.87 (s, 1 H), 3.18 (s, 3 H), 2.44 (s, 3 H).
13C NMR (100 MHz, DMSO-d6): δ = 194.3, 174.8, 148.0, 145.1, 138.2,
137.3, 133.8, 132.2, 130.7, 129.2, 129.0, 128.9, 126.8, 124.3, 121.5,
114.8, 108.2, 43.2, 26.8, 21.0.
(5) (a) Takemori, T.; Inagaki, A.; Suzuki, H. J. Am. Chem. Soc. 2001,
123, 1762. (b) de Boer, J. W.; Brinksma, J.; Browne, W. R.;
Meetsma, A.; Alsters, P. L.; Hage, R.; Feringa, B. L. J. Am. Chem.
Soc. 2005, 127, 7990. (c) Neisius, N. M.; Plietker, B. J. Org. Chem.
2008, 73, 3218. For Diels–Alder-type cleavage, see: (d) Remy, R.;
Bochet, C. G. Chem. Rev. 2016, 116, 9816. (e) Song, L.; Zhu, G.;
Liu, Y.; Liu, B.; Qin, S. J. Am. Chem. Soc. 2015, 137, 13706.
(6) For decarbonylation, see: (a) Fristrup, P.; Kreis, M.; Palmelund,
A.; Norrby, P. O.; Madsen, R. J. Am. Chem. Soc. 2008, 130, 5206.
(b) Arisawa, M.; Kuwajima, M.; Toriyama, F.; Li, G.; Yamaguchi,
M. Org. Lett. 2012, 14, 3804. (c) Gutmann, B.; Elsner, P.; Glasnov,
T.; Roberge, T. D. M.; Kappe, C. O. Angew. Chem. Int. Ed. 2014, 53,
11557. For decarboxylation, see: (d) Zhang, P.; Zhang, L.; Gao,
Y.; Xu, J.; Fang, H.; Tang, G.; Zhao, Y. Chem. Commun. 2015, 51,
7839. (e) Zhou, M.; Chen, M.; Zhou, Y.; Yang, K.; Su, J.; Du, J.;
Song, Q. Org. Lett. 2015, 17, 1786. (f) Zhou, M.; Zhou, Y.; Song, Q.
Chem. Eur. J. 2015, 21, 10654.
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(8) Hattori, T.; Takakura, R.; Ichikawa, T.; Sawama, Y.; Monguchi, Y.;
Sajiki, H. J. Org. Chem. 2016, 81, 2737.
(9) Eicher, T.; Graf, R.; Konzmann, H.; Pick, R. Synthesis 1987, 887.
(10) For reviews, see: (a) Greenhill, J. V. Chem. Soc. Rev. 1977, 6, 277.
(b) Stanovnik, B.; Svete, J. Chem. Rev. 2004, 104, 2433. (c) Elassar,
A.-Z. A.; El-Khair, A. A. Tetrahedron 2003, 59, 8463. (d) Cao, S.;
Jing, Y.; Liu, Y.; Wan, J. Chin. J. Org. Chem. 2014, 34, 876.
(e) Dar’in, D. V.; Lobanov, P. S. Russ. Chem. Rev. 2015, 84, 601.
HRMS (ESI): m/z [M + Na]+ calcd for C25H20Cl2N2NaO4S: 537.0413;
found: 537.0417.
4-Methylbenzenesulfonamide (TsNH2);18 Hydrolysis of Compound
6
In air, to a Schlenk tube were added compound 6 (79.7 mg, 0.40
mmol),15 Ph3PAuNTf2 (5.9 mg, 0.02 equiv), anhydrous CH2Cl2 (6 mL)
and HClconcd (12 M, 40 μL, 2.4 equiv). The resulting mixture was
stirred at 40 °C overnight (about 10 h). Subsequently, the reaction
was cooled to r.t., and the mixture was subjected to flash column
chromatography for purification directly, using CH2Cl2–EtOAc as the
eluent.
White solid, yield: 67.6 mg (99%); Rf = 0.28 (CH2Cl2–EtOAc, 60:1).
IR (ATR): 3355, 3260, 1529, 1301, 1160, 1098, 905, 817, 704 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.82 (d, J = 7.6 Hz, 2 H), 7.31 (d, J = 8.0
Hz, 2 H), 4.98 (s, 2 H), 2.43 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 143.9, 139.4, 129.9, 126.7, 21.2.
HRMS (ESI): m/z [M + Na]+ calcd for C7H9NNaO2S: 194.0246; found:
194.0243.
Funding Information
We thank the National Natural Science Foundation of China (Grant
No. 21272074) and the Program for Changjiang Scholars and Innova-
tive Research Team in University (PCSIRT) for financial support.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

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Y. Zhao et al.
Paper
Synthesis
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graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/getstructures.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J