Catalyst-free synthesis of 3-alkenyloxindoles from isatin-derived Morita-Baylis-Hillman carbonates

Article abstract of DOI:10.3184/174751917X14878812592652

A variety of biologically and synthetically useful 3-alkenyloxindoles were rapidly synthesised via an S_N2′-type allylic substitution reaction of isatin-derived Morita-Baylis-Hillman carbonates with sodium sulfinates. The syntheses were conducte

Full text of DOI:10.3184/174751917X14878812592652

160 RESEARCH PAPER
VOL. 41 MARCH, 160–164
JOURNAL OF CHEMICAL RESEARCH 2017
Catalyst-free synthesis of 3-alkenyloxindoles from isatin-derived Morita–
Baylis–Hillman carbonates
Lin Jianga,b*, Yong-Gen Lia, Hang Lia, Ming-Wei Yuanb, Yong-Ming Chuana, Hong-Li Lia,b and
Ming-Long Yuana,b
aSchool of Chemistry and Environment, Yunnan Minzu University, Kunming 650500, P.R. China
bEngineering Research Centre of Biopolymer Functional Materials of Yunnan, Kunming 650500, P.R. China
A variety of biologically and synthetically useful 3-alkenyloxindoles were rapidly synthesised via an S 2′-type allylic substitution reaction
of isatin-derived Morita–Baylis–Hillman carbonates with sodium sulfinates. The syntheses were conNducted under catalyst-free reaction
conditions and good to excellent product yields (up to 96%) and Z/E selectivities (up to >20:1) were obtained.
Keywords: Morita–Baylis–Hillman carbonate, 3-alkenyloxindole, allylic substitution, sulfinate, isatin
3-Alkenyloxindoles are privileged scaffolds found in a large
number of natural and synthetic compounds with remarkable
biological activities.1 Some are shown in Fig. 1. Wasalexin A was
isolated from the foliar tissue of wasabi and exhibited antifungal
activity against Phoma lingam.2 Soulieotine, isolated from the
rhizomes of Chinese traditional medicine “Souliea vaginata”,
was mainly used for its inflammatory analgesic properties.3 Of
particular pharmaceutical significance is sunitinib (SU11248),
otherwise known by its brand name Sutent. Sunitinib is a potent
orally active receptor tyrosine kinase inhibitor and is used
medically for the treatment of advanced renal cell carcinoma
and gastrointestinal stromal tumours.4
The synthetic utility of 3-alkenyloxindoles is worthy of
mention. For example, β-substituted oxindoles of type A
can be accessed by exploiting the conjugate additions of
3-alkenyloxindoles with nucleophiles [Scheme 1, Eqn (1)].5,6
Also the alkenyl motif can act as an electron-poor fragment
to take part in synergetic or stepwise cycloadditions, thus
generating structurally diverse spirocarbocyclic oxindoles
of type B [Scheme 1, Eqn (2)].7–10 Moreover, for the
3-alkenyloxindole with an alkyl group attached at the β-position
of the ylidene, γ-site activation can be realised by the vinylogous
effect and then reactions with proper electrophilic acceptors to
furnish alkylideneoxindoles of type C can be expected [Scheme
1, Eqn (3)].11–14 Owing to their diverse biological activities
and synthetic applicability, new strategies for the efficient
construction of structurally diverse 3-alkenyloxindoles are still
in great demand.
In recent years, many reports have witnessed the importance
of Morita–Baylis–Hillman (MBH) adducts or their derivatives
R2
R2
Nu
O
Nu
O
β
α
C
as electrophilic site
β
R1
Eq 1
N
N
PG
R3
PG
type A
R3
R2
R2
synergetic or stepwise
cycloadditions
R4
O
R4
Eq 2
R1
O
R1
N
N
PG
PG
MeS
type B
NEt2
O
SMe
E
R2
E
R2
N
N
H
β
α
γ
R3
R3
C
as nucleophilic site
γ
N
R1
O
F
R1
O
O
Eq 3
H
O
N
N
N
O
N
MeO
H
PG
PG
N
type C
(Nu = nucleophile; PG = protecting group; E = electrophile)
OMe
H
Sunitinib
(SU11248, Sutent)
wasalexin A
Soulieotine
Figure 1 Some biologically important 3-alkenyloxindoles.
Scheme 1 Transformation patterns of 3-alkenyloxindoles.
a) Allylic substitution approaches of MBH carbonates or acetates
OR'
Nu
EWG
SN2'-SN2' substitution
SN2' substitution
EWG
R
EW
G
α
+
R
Nu
R
γ
Nu
product
α−
-product
γ
R' = t-butoxycarbonyl(Boc), Ac
b) This work:
O
S
Na+
2
Ar
O
MeOOC
BocO
-CO2
COOMe
O
r
A
SO2
+ t-BuONa
SN2' substitution
R
R
O
N
N
3
PG
1
PG
Scheme 2 Allylic substitution reactions of MBH carbonates or acetates with nucleophiles.
* Correspondent. E-mail: jianglin_1981@163.com

JOURNAL OF CHEMICAL RESEARCH 2017 161
Table 1 Optimisation of reaction conditionsa
as valuable synthons in chemical modifications.15–17 Among
the various transformation patterns, the allylic substitution
reactions of MBH carbonates or acetates in the presence of a
metal-free Lewis base have attracted much interest due to their
high efficiency in the construction of multifunctional molecules
in an atom-economic manner.18–21 The allylic substitution of
these MBH derivatives could follow a tandem SN2′-SN2′ or a
single SN2′ pathway to afford α- or γ-substituted products
respectively (Scheme 2a). Although numerous research results
involving both of the transformation approaches have been
reported in terms of aldehyde-derived MBH carbonates as
substrates,22–24 isatin-derived MBH carbonates are mostly
used in the tandem SN2′-SN2′ allylic substitution to generate
α-substituted oxindoles.25–27 To the best of our knowledge,
examples concerning the SN2′-type allylic substitution to form
γ-substituted 3-alkenyloxindoles from MBH carbonates of
isatins are rare.28 Here, we report the facile synthesis of sulfone-
containing 3-alkenyloxindoles 3 by γ-allylic substitution
reaction of isatin-derived MBH carbonates 1 with readily
available sodium sulfinates 2 without the aid of a catalyst
(Scheme 2b) and promising product structures are expected for
biological screening or synthetic utilisation.
MeOOC
COOMe
OR
SO2Ph
Solvent
O
+ PhSO2Na
O
Temperature
N
N
2a
3a
1a:
1a':
R = Boc
R = Ac
Entry
1
2
3
4
5
6
7c
8
Solvent
MeCN
Toluene
PhCF3
DCE
Temp./oC
Time/h
24
24
24
24
24
24
24
6
Yield/%b
89
34
25
25
25
25
25
25
25
40
50
40
40
40
30
Trace
Trace
67
73
90
86
90
92
88
CHCl3
THF
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
9
4
6
6
18
10d
11e
12f
aReaction conditions: unless otherwise noted, reactions were performed with MBH
carbonate of isatin 1a (0.2 mmol) and sodium benzenesulfinate (2a, 0.24 mmol) in solvent
(2 mL) at the indicated reaction temperature.
bIsolated yields.
Results and discussion
Initially, we selected the N-methyl MBH carbonate of isatin 1a
as the model substrate in the direct γ-allylic substitution reaction
with sodium benzenesulfinate (2a) in acetonitrile at room
temperature. To our delight, the desired γ-substituted product
3a was obtained in 89% yield after 24 h (Table 1, entry 1).
We then systematically screened the reaction parameters to
identify more productive reaction conditions. To test the solvent
effect, toluene, benzotrifluoride, 1,2-dichloroethane (DCE),
chloroform and tetrahydrofuran (THF) were each used. As
illustrated in Table 1, toluene and benzotrifluoride gave poor
yields (34% and 30%, Table 1, entries 2 and 3). DCE and
chloroform afforded only trace amounts of the final product
(Table 1, entries 4 and 5). Although 67% yield was obtained
in THF (Table 1, entry 6), the initially used acetonitrile was an
optimal candidate. The leaving groups were also examined. As
expected, a lower yield was delivered when the MBH acetate
of isatin 1a′ was used (73%, Table 1, entry 7), indicating the
effect of leaving group ability on the reactivity of this allylic
cMBH acetate of isatin 1a′ was used.
d2a (0.3 mmol) was used.
eSolvent (4 mL) was used.
fSolvent (8 mL) was used.
Table 2 Substrate scope of the γ-allylic substitution reactiona
GWE
EWG
4
SO2Ar
OBoc
O
5
6
R
R
O
+ ArSO2Na
MeCN, 40 oC, 6 h
N
N
7
PG
PG
2a
2b
Ar = Ph
Ar = p-MeC6H4
3
1
Entry R(1)
PG(1) EWG
Ar(2)
COOMe Ph
COOMe Ph
Yield/%b
92 (3a)
88 (3b)
93 (3c)
Z/Ec,d
19:1
19:1
19:1
1
H (1a)
Me
Me
Me
Me
Me
Me
2
3
4
5
4-Br (1b)
5-F (1c)
5-Cl (1d)
6-Br (1e)
7-Cl (1f)
COOMe Ph
COOMe Ph
COOMe Ph
COOMe Ph
COOMe Ph
COOMe Ph
COOMe Ph
COOMe Ph
COOMe Ph
96 (3d) >20:1
substitution. Subsequently, we performed
a temperature
84 (3e)
93 (3f)
81 (3g)
79 (3h)
90 (3i)
85 (3j)
82 (3k)
>20:1
15:1
12:1
19:1
10:1
12:1
>20:1
10:1
−
screening. It was revealed that when the reaction temperature
6
o
was raised to 40 C, a significantly shortened reaction time
7
5-MeO (1g) Me
was observed in spite of approximately the same yield (90%,
Table 1, entry 8). However, the yield dropped slightly at even
higher temperature (86%, Table 1, entry 9). Furthermore,
increasing the amount of sodium benzenesulfinate (2a) to 1.5
equiv. compared to 1a seemed to give no increase in product
yield (90%, Table 1, entry 10). Finally, we turned our attention
to the substrate concentration. Pleasingly, it was found that the
yield could be improved to 92% if the starting concentration
of 1a was decreased to 0.05 M (Table 1, entry 11). By contrast,
further diluting the starting concentration of 1a gave a lower
yield (88%, Table 1, entry 12) along with a sluggish reaction.
It is noteworthy that all the attempted reaction conditions gave
very good Z/E selectivities (≥19:1). Collectively, the optimised
reaction should be carried out by using the MBH carbonate of
isatin 1a (0.2 mmol) and sodium benzenesulfinate (2a, 0.24
mmol) in acetonitrile (4 mL) at 40 oC for 6 h.
8
9
5-Me (1h)
H (1i)
Me
Bn
Ac
Boc
Me
Me
Me
10
11
12
13
14f
H (1j)
H (1k)
H (1a)
5-NO2 (1m)
H (1n)
COOMe p-MeC6H4 84 (3l)
COOMe Ph
NDe (3m)
NDe (3n)
CN Ph
−
aReaction conditions: reactions were performed with MBH carbonates of isatins 1
(0.2 mmol) and sodium sulfinates 2 (0.24 mmol) in MeCN (4 mL) at 40 oC for 6 h.
bIsolated yields.
cOlefin geometry of 3h was determined to be Z by 2D ROESY analysis (see ESI) and the
other products were assigned by analogy.
dDetermined by 1H NMR analysis of the crude reaction mixture (see ESI).
eND = not detected.
f1n is a known compound.29
of isatins 1 could generally be converted within 6 h, furnishing
3-alkenyloxindoles 3 in good to excellent yields and Z/E
selectivities (Table 2, entries 1–12). For MBH carbonates
of isatins 1, different substituents on the phenyl moiety were
With the optimal reaction conditions in hand, we next
evaluated the substrate scope of the γ-allylic substitution
reaction of MBH carbonates of isatins 1 with sodium sulfinates
2. The results are summarised in Table 2. The MBH carbonates

162 JOURNAL OF CHEMICAL RESEARCH 2017
The following MBH substrates 1b–k and 1m–n were synthesised
analogously. The characterisation data of substrates 1a,32 1d,33 1f,33 1h33
and 1n29 were in agreement with those reported in the literature.
first explored to probe the reactivity (Table 2, entries 1–8).
In general, the variation of the substitution position was well
tolerated although the electronic nature of the substituents
seemed to have some effect on product yield, since those
substrates 1 equipped with halogen substituents provided
higher yields (84−96%, Table 2, entries 2–6) as compared
with their counterparts which incorporated electron-donating
substituents like a 5-methoxy or a 5-methyl group (81% and
79%, Table 2, entries 7 and 8). In addition, the MBH carbonates
1 possessing different N-substituents, such as Bn, Ac or Boc,
can react smoothly to offer 82−90% yields (Table 2, entries
9–11). Moreover, sodium p-toluenesulfinate (2b) also reacted
successfully, affording corresponding product 3l in 84% yield
(Table 2, entry 12). Unfortunately, when the MBH carbonates
of isatins 1 possessing a 5-nitro group or deriving from
acrylonitrile were investigated, some unwanted side reactions
became dominant probably owing to the excessive reactivity
(Table 2, entries 13 and 14).
In summary, we have developed a catalyst-free γ-substitution
reaction of the MBH carbonates of isatins with sodium
sulfinates. A variety of biologically and synthetically promising
3-alkenyloxindoles were rapidly synthesised in high to excellent
yields (up to 96%) and Z/E selectivities (up to >20:1). This
protocol features mild reaction conditions, easily available
starting materials and rational substrate tolerance. Moreover, it
also contributes to the research field as very few examples of the
SN2′-type allylic substitution of isatin-derived MBH carbonates
have been reported so far. Further studies on applications of the
discovery are currently underway.
1
1b: Pale yellow solid; yield 36%; m.p. 135–138 °C; H NMR (400
MHz, CDCl3): δ 7.53−7.51 (m, 1H), 7.09−7.05 (m, 2H), 6.55 (s, 1H),
6.43 (s, 1H), 3.55 (s, 3H), 3.15 (s, 3H), 1.42 (s, 9H); 13C NMR (100
MHz, CDCl3): δ 167.2, 164.8, 147.5, 138.3, 134.6, 128.0, 127.2, 126.1,
118.3, 110.7, 82.1, 52.1, 30.2, 26.3; ESI-HRMS calcd for C18H2079BrNO6
+ Na: 448.0372; found: 448.0368 ([79M + Na]+, 100%); calcd for
C18H2081BrNO6 + Na: 450.0351; found: 450.0357 ([81M + Na]+, 98%).
1c:34 White solid; yield 52%; m.p. 125–127 °C; 1H NMR (400 MHz,
CDCl3): δ 7.23−7.21 (m, 1H), 7.03−6.99 (m, 2H), 6.43 (s, 1H), 6.35 (s,
1H), 3.53 (s, 3H), 3.22 (s, 3H), 1.35 (s, 9H); MS: m/z 388 [M + Na]+.
1
1e: Pale yellow solid; yield 37%; m.p. 132–134 °C; H NMR (400
MHz, CDCl3): δ 7.76 (d, J = 8.0 Hz, 1H), 7.31−7.28 (m, 2H), 6.52 (s,
1H), 6.45 (s, 1H), 3.62 (s, 3H), 3.20 (s, 3H), 1.42 (s, 9H) ; 13C NMR
(100 MHz, CDCl3): δ 167.2, 164.9, 146.6, 137.5, 136.5, 127.3, 124.4,
121.9, 113.0, 82.1, 52.1, 29.2, 26.6; ESI-HRMS calcd for C18H2079BrNO6
+ Na: 448.0372; found: 448.0377 ([79M + Na]+, 100%); calcd for
C18H2081BrNO6 + Na: 450.0351; found: 450.0353 ([81M + Na]+, 95%)
1g:34 White solid; yield 40%; m.p. 117–119 °C; 1H NMR (400 MHz,
CDCl3): δ 6.99 (s, 1H), 6.81−6.78 (m, 1H), 6.68 (d, J = 4.0 Hz, 1H),
6.48 (s, 1H), 6.39 (s, 1H), 3.68 (s, 3H), 3.55 (s, 3H), 3.14 (s, 3H), 1.35 (s,
9H); MS: m/z 400 [M + Na]+.
1
1i:35 White solid; yield 53%; m.p. 131–133 °C; H NMR (400 MHz,
CDCl3): δ 7.40−6.92 (m, 8H), 6.71 (d, J = 8.0 Hz, 1H), 6.35 (s, 1H),
6.22 (s, 1H), 5.05 (d, J = 16.0 Hz, 1H), 4.92 (d, J = 16.0 Hz, 1H), 3.57 (s,
3H), 1.38 (s, 9H); MS: m/z 446 [M + Na]+.
1j:35 White solid; yield 48%; m.p. 120–122 °C; 1H NMR (400 MHz,
CDCl3): δ 7.74 (d, J = 8.0 Hz, 1H), 7.45−7.19 (m, 3H), 6.68 (s, 1H), 6.52
(s, 1H), 3.64 (s, 3H), 2.63 (s, 3H), 1.42 (s, 9H); MS: m/z 398 [M + Na]+.
1k:35 White solid; yield 28%; m.p. 113–115 °C; 1H NMR (400 MHz,
CDCl3): δ 7.80 (d, J = 8.0 Hz, 1H), 7.39−7.35 (m, 1H), 7.12−7.07 (m,
1H), 7.01−6.98 (m, 1H), 6.65 (s, 1H), 6.52 (s, 1H), 3.61 (s, 3H), 1.65 (s,
9H), 1.43 (s, 9H); MS: m/z 456 [M + Na]+.
Experimental
Flash column chromatography was performed using silica gel (200−300
1
mesh) eluting with petroleum ether (60–90 °C)/ethyl acetate. H NMR
spectra were recorded at 400 MHz and 13C NMR spectra were recorded
at 100 MHz (Avance 400, Bruker, Faellanden, Switzerland) using
tetramethylsilane as the internal standard. Chemical shifts are reported
in ppm (δ) downfield from the solvent residual peak (CHCl3, δ 7.26)
1m:36 White solid; yield 45%; m.p. 128–130 °C; 1H NMR (400 MHz,
CDCl3): δ 8.25−8.22 (m, 2H), 6.82−6.80 (m, 1H), 6.49 (s, 1H), 6.34 (s,
1H), 3.44 (s, 3H), 1.45 (s, 9H); MS: m/z 415 [M + Na]+.
1
for H NMR and relative to the central CDCl3 resonance (δ 77.0) for
Synthesis of 3-alkenyloxindoles 3a−l; typical procedure
13C NMR spectroscopy. Coupling constants (J) are given in Hz.
Mass spectra were obtained from Agilent 1100LC/MS spectrometry
services. ESI-HRMS was recorded on a Waters SYNAPT G2 (Milford,
MA, USA). Melting points were uncorrected. Chemical reagents
were used without further purification as commercially available.
The preparations of N-methylisatin,30 N-benzylisatin,30 N-tert-
butyloxycarbonylisatin30 and N-acetylisatin31 are in the literature.
A mixture of an MBH carbonate of an isatin 1 (0.2 mmol) and a sodium
sulfinate 2 (0.24 mmol) in acetonitrile (4 mL) was heated at 40 oC for
6 h. After completion, the reaction mixture was concentrated under
reduced pressure and the residue was diluted with toluene and purified
by flash column chromatography on silica gel [petroleum ether
(60–90 °C)/ethyl acetate] to afford the desired products 3a–l.
(Z)-Methyl 2-(1-methyl-2-oxoindolin-3-ylidene)-3-(phenylsulfonyl)
propanoate (3a): Yellow solid; yield 92%; m.p. 133−135 oC; 1H NMR
(400 MHz, CDCl3): δ 7.95 (d, J = 8.0 Hz, 2H), 7.62−7.57 (m, 2H),
7.50−7.46 (m, 2H), 7.34−7.31 (m, 1H), 7.01−6.97 (m, 1H), 6.72 (d,
J = 8.0 Hz, 1H), 5.43 (s, 2H), 3.98 (s, 3H), 3.04 (s, 3H); 13C NMR (100
MHz, CDCl3): δ 166.7, 166.3, 144.0, 138.4, 133.7, 131.9, 131.8, 128.9,
128.7, 128.5, 125.3, 122.6, 119.6, 108.2, 54.8, 53.0, 25.9; ESI-HRMS
calcd for C19H17NO5S + Na: 394.0725; found: 394.0722.
Synthesis of MBH carbonates of isatins;29,32−36 typical procedure
A mixture of N-methylisatin (1 mmol, 161.2 mg), methyl acrylate
(1.5 mmol, 129 mg) and 1,4-diazabicyclo[2.2.2]octane (0.05 mmol,
5.6 mg) was stirred at ambient temperature for 3−4 days. After
completion of the reaction (monitored by TLC), the reaction mixture
was diluted with ethyl acetate. The organic layer was washed
successively with 0.2 M HCl, brine and water. Then, the organic layer
was separated, dried with Na2SO4 and concentrated under reduced
pressure. The residue obtained was purified by silica gel column
chromatography using petroleum ether (60–90 °C)/ethyl acetate as
eluent to afford the desired MBH alcohol of N-methylisatin.
The MBH alcohol of N-methylisatin (1 mmol, 247.2 mg) was
added to a suspension of sodium hydride (1.5 mmol, 36 mg) in dry
CH2Cl2 (10 mL) at ambient temperature. The mixture was stirred for
15 min and then was added slowly to a solution of (Boc)2O (1.5 mmol,
327 mg) in dry CH2Cl2 (5 mL). The reaction mixture was stirred for
3−4 h. After completion (monitored by TLC), the reaction mixture
was directly filtered and the filtrate was concentrated under reduced
pressure. The residue obtained was purified by silica gel column
chromatography using petroleum ether (60–90 °C)/ethyl acetate as
eluent to afford the desired MBH carbonate 1a.
(Z)-Methyl 2-(4-bromo-1-methyl-2-oxoindolin-3-ylidene)-3-(phenyl-
o
sulfonyl)propanoate (3b): Orange solid; yield 88%; m.p. 144−145 C;
1H NMR (400 MHz, CDCl3): δ 7.93 (d, J = 8.0 Hz, 2H), 7.65 (s, 1H),
7.61−7.57 (m, 1H), 7.50−7.47 (m, 2H), 7.30 (d, J = 8.0 Hz, 1H), 6.65 (d,
J = 12.0 Hz, 1H), 5.42 (s, 2H), 3.98 (s, 3H), 3.04 (s, 3H); 13C NMR (100
MHz, CDCl3): δ 166.3, 166.0, 142.6, 138.6, 133.9, 131.7, 131.3, 130.3,
128.9, 128.2, 126.0, 120.8, 109.3, 54.9, 53.4, 26.2; ESI-HRMS calcd for
C19H1679BrNO5S + Na: 471.9830; found: 471.9833 ([79M + Na]+, 100%);
calcd for C19H1681BrNO5S + Na: 473.9810; found: 473.9815 ([81M + Na]+,
96%).
(Z)-Methyl 2-(5-fluoro-1-methyl-2-oxoindolin-3-ylidene)-3-(phenyl-
o
sulfonyl)propanoate (3c): Yellow solid; yield 93%; m.p. 142−144 C;
1H NMR (400 MHz, CDCl3): δ 7.91 (d, J = 8.0 Hz, 2H), 7.59−7.56
(m, 1H), 7.48−7.45 (m, 2H), 7.42−7.40 (m, 1H), 7.04−7.00 (m, 1H),

JOURNAL OF CHEMICAL RESEARCH 2017 163
6.65−6.61 (m, 1H), 5.42 (s, 2H), 3.95 (s, 3H), 3.01 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 165.3, 165.0, 158.7, 156.5, 139.1, 137.4, 132.8,
130.7, 128.9, 127.8, 119.4, 117.4, 117.2, 112.6, 112.2, 107.6, 53.7, 52.2,
25.0; ESI-HRMS calcd for C19H16FNO5S + Na: 412.0631; found:
412.0637.
2H), 7.76 (d, J = 8.0 Hz, 1H), 7.60−7.54 (m, 2H), 7.50−7.46 (m, 2H),
7.38−7.34 (m, 1H), 7.12−7.08 (m, 1H), 5.31 (s, 2H), 4.00 (s, 3H), 1.59
(s, 9H); 13C NMR (100 MHz, CDCl3): δ 165.5, 163.2, 147.2, 138.8,
137.0, 132.7, 130.8, 128.8, 128.3, 127.8, 127.6, 123.3, 123.1, 118.7, 113.7,
112.9, 83.6, 54.0, 52.1, 28.5; ESI-HRMS calcd for C23H23NO7S + Na:
480.1093; found: 480.1099.
(Z)-Methyl 2-(5-chloro-1-methyl-2-oxoindolin-3-ylidene)-3-(phenyl-
o
sulfonyl)propanoate (3d): Yellow solid; yield 96%; m.p. 142−144 C;
(Z)-Methyl 2-(1-methyl-2-oxoindolin-3-ylidene)-3-tosylpropanoate
1H NMR (400 MHz, CDCl3): δ 7.92 (d, J = 8.0 Hz, 2H), 7.76 (s, 1H),
7.60−7.56 (m, 1H), 7.50−7.42 (m, 3H), 6.60 (d, J = 8.0 Hz, 1H), 5.41 (s,
2H), 3.97 (s, 3H), 3.02 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 166.3,
165.9, 142.9, 138.5, 134.6, 133.9, 131.0, 130.3, 128.9, 128.7, 121.3, 115.4,
109.7, 54.9, 53.3, 26.1; ESI-HRMS calcd for C19H1635ClNO5S + Na:
428.0335; found 428.0333 ([35M + Na]+, 100%); calcd for C19H1637ClNO5S
+ Na: 430.0306; found: 430.0311 ([37M +Na]+, 35%).
o
1
(3l): Yellow solid; yield 84%; m.p. 140−141 C; H NMR (400 MHz,
CDCl3): δ 7.92 (d, J = 8.0 Hz, 2H), 7.58−7.54 (m, 1H), 7.47−7.43 (m,
2H), 7.36 (s, 1H), 7.10 (d, J = 4.0 Hz, 1H), 6.58 (d, J = 8.0 Hz, 1H), 5.40
(s, 2H), 3.96 (s, 3H), 2.98 (s, 3H), 2.28 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ 166.8, 166.2, 141.8, 138.3, 132.4, 132.1, 132.0, 128.9, 128.8,
128.1, 125.9, 119.5, 108.0, 54.7, 53.0, 25.9, 21.3; ESI-HRMS calcd for
C20H19NO5S + Na: 408.0882; found: 408.0883.
(Z)-Methyl 2-(6-bromo-1-methyl-2-oxoindolin-3-ylidene)-3-(phenyl-
o
sulfonyl)propanoate (3e): Orange solid; yield 84%; m.p. 150−152 C;
This work was supported by the National Natural Science
Foundation of China (21302163) and the Graduate Students
Innovation Foundation of Yunnan Minzu University
(2016YJCXS24).
1H NMR (400 MHz, CDCl3): δ 7.91 (d, J = 8.0 Hz, 2H), 7.59−7.52 (m,
2H), 7.49−7.45 (m, 2H), 7.11 (d, J = 8.0 Hz, 1H), 6.87 (s, 1H), 5.39 (s,
2H), 3.95 (s, 3H), 3.01 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 166.6,
166.2, 145.2, 138.4, 133.9, 131.3, 129.3, 129.0, 128.9, 126.9, 126.2, 125.6,
118.6, 111.8, 54.9, 53.3, 26.1; ESI-HRMS calcd for C19H1679BrNO5S
+ Na: 471.9830; found: 471.9838 ([79M + Na]+, 100%); calcd for
C19H1681BrNO5S + Na: 473.9810; found: 473.9813 ([81M +Na]+, 98%).
(Z)-Methyl 2-(7-chloro-1-methyl-2-oxoindolin-3-ylidene)-3-(phenyl-
Electronic Supplementary Information
The ESI (NMR spectra of compounds 3a–l and details of the
stereochemical study) is available through
stl.publisher.ingentaconnect.com/content/stl/jcr/supp-data.
o
sulfonyl)propanoate (3f): Yellow solid; yield 93%; m.p. 144−145 C;
1H NMR (400 MHz, CDCl3): δ 7.93 (d, J = 8.0 Hz, 2H), 7.61−7.57 (m,
1H), 7.50−7.44 (m, 3H), 7.22 (d, J = 8.0 Hz, 1H), 6.90−6.86 (m, 1H),
5.38 (s, 2H), 3.97 (s, 3H), 3.40 (s, 3H); 13C NMR (100 MHz, CDCl3): δ
166.7, 166.6, 139.6, 138.5, 133.9, 130.2, 130.1, 128.9, 128.9, 123.6, 123.3,
122.3, 115.9, 55.2, 53.3, 29.5; ESI-HRMS calcd for C19H1635ClNO5S
+ Na: 428.0335; found: 428.0335 ([35M + Na]+, 100%); calcd for
C19H1637ClNO5S + Na: 430.0306; found: 430.0301 ([37M + Na]+, 32%).
(Z)-Methyl 2-(5-methoxy-1-methyl-2-oxoindolin-3-ylidene)-3-(phenyl-
sulfonyl)propanoate (3g): Yellow solid; yield 81%; m.p. 157−158 oC;
1H NMR (400 MHz, CDCl3): δ 8.02 (d, J = 8.0 Hz, 2H), 7.68−7.65 (m,
1H), 7.58−7.54 (m, 2H), 7.36−7.34 (m, 1H), 6.95 (d, J = 8.0 Hz, 1H), 6.69
(d, J = 8.0 Hz, 1H), 5.52 (s, 2H), 4.06 (s, 3H), 3.86 (s, 3H), 3.09 (s, 3H);
13C NMR (100 MHz, CDCl3): δ 166.7, 166.2, 155.7, 138.4, 138.0, 133.8,
132.3, 128.9, 128.8, 120.4, 116.9, 112.4, 108.6, 55.9, 54.7, 53.2, 26.0; ESI-
HRMS calcd for C20H19NO6S + H: 402.1011; found: 402.1014.
Received 9 November 2016; accepted 7 February 2017
Paper 1604419 DOI: 10.3184/174751917X14878812592652
Published online: 28 February 2017
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