Visible light mediated aerobic oxidative hydroxylation of 2-oxindole-3-carboxylate esters: An alternative approach to 3-hydroxy-2-oxindoles

Article abstract of DOI:10.1515/hc-2019-0114

A convenient aerobic oxidative hydroxylation of 3-substituted oxindoles under mild reaction conditions is described herein. This process was accomplished by the activation of molecular oxygen in the air in the presence of a photocatalyst under the irradiation of visible light. The desired product was delivered in up to 89% yield without the addition of base or stoichiometric oxidant.

Full text of DOI:10.1515/hc-2019-0114

Heterocycl. Commun. 2020; 26: 168–175
Communication
Open Access
JVinigseiWbalneg, SliiygitehmtermOsemdani,aXitnejiadngaLue, rJuonybi CichenoaxniddXua-DtoivngeXiha*ydroxylation
of 2-oxindole-3-carboxylate esters: an alternative
approach to 3-hydroxy-2-oxindoles
https://doi.org/10.1515/hc-2019-0114
Received June 04, 2020; accepted October 03, 2020.
in some significant transformations [6-9]. Consequently,
their construction is of interest to organic chemists.
Previously, several elegant methodologies were applied
Abstract: A convenient aerobic oxidative hydroxylation
to build 3-substituted-3-hydroxy-2-oxindoles [10-12].
of 3-substituted oxindoles under mild reaction
Transition metal catalyzed intramolecular cyclization
conditions is described herein. This process was
of α-keto aromatic amides was reported to synthesize
accomplished by the activation of molecular oxygen
these versatile building blocks [13-15], and direct addi-
in the air in the presence of a photocatalyst under the
tion to isatin derivatives was also an efficient approach
irradiation of visible light. The desired product was
[16-27]. Moreover, straightforward hydroxylation of
delivered in up to 89% yield without the addition of
3-substituted-2-oxindoles was also accomplished
base or stoichiometric oxidant.
[28-33]. However, milder, greener, and more efficient
Keywords: Visible light, Photocatalysis, Oxindole, Aerobic methods to change the substituent pattern of C-3 on
oxidation
oxindole rings are still pursued.
Recently, many outstanding groups have sought
to make use of light as a clean and abundant source
of energy for chemical transformations [34-39]. Many
reactions were carried out in the presence of oxygen
Introduction
The 3-substituted-3-hydroxy-2-oxindole framework is under mild conditions. Furthermore, as an ideal oxidant
a privileged motif that is abundant in naturally occur- molecular oxygen has already participated in the
ring alkaloids and biologically active products [1-2]. construction of a series of structurally diverse skeletons
For instance, Convolutamydine A, which is isolated through photocatalysis [34-40]. For instance, Córdova
from the marine bryozoan Amathia convolute, was accomplished the α-hydroxylation of ketones and
found to be a potent inhibitor in the differentiation of aldehydes through the utilization of molecular oxygen
HL-60 human promyelocytic leukaemia cells [3]. Dis- by photocatalysis [41-42]. In 2012, Meng and co-works
covered in Hibiscus moscheutos L methyl 2-(3-hydroxy- documented a hydroxylation of β-oxo esters catalyzed
2-oxoindolin-3-yl)acetate acted as an anti-oxidant [4]. by a phase transfer catalyst and tetraphenylporphine
(R)-(+)-3-cyanomethyl-3-hydroxyoxindole from Rheum under the irradiation of a 100W halogen lamp, in which
maximowiczii Losinsk (Polygonaceae) exhibited activa- singlet oxygen took part [43]. Recently, Xiao’s group
tion/inhibition of specific cytokines [5]. 3-Substituted- designed and synthesized a new bifunctional visible
3-hydroxy-2-oxindoles also act as synthetic precursors light photocatalyst and used it in the asymmetric aerobic
oxidation of β-ketoesters [44]. As we continue to be
interested in photochemistry, in this communication, we
developed an α-hydroxylation of 3-carboxylate oxindole
derivatives by means of photocatalysis under mild
conditions. The reaction was carried out in air under
the irradiation of a household light bulb. Compared
with previous work, this work eliminates the need for
addition of base and stoichiometric oxidant. We intended
this work to further extend the scope of our previously
developed research [45].
*Corresponding author: Xu-Dong Xia, Engineering Laboratory
of Chemical Resources Utilization in South Xinjiang of Xinjiang
Production and Construction Corps, College of Life Sciences, Tarim
University, Alar, Xinjiang 843300, P. R. China,
E-mail: xiaxudong_10@163.com
Jinge Wang, Siyitemer Osman, Xinjiang Lu and Junyi Chen,
Engineering Laboratory of Chemical Resources Utilization in South
Xinjiang of Xinjiang Production and Construction Corps, College of
Life Sciences, Tarim University, Alar, Xinjiang 843300, P. R. China
Open Access. © 2020 Wang et al., published by De Gruyter.ꢀ
Attribution alone 4.0 License.
ꢀThis work is licensed under the Creative Commons

J. Wang et al.: Visible light mediated aerobic oxidative hydroxylation ꢁ
ꢁ169
Results and discussion
[Ir(ppy)2(dtbbpy)]PF6, polar solvents such as DMF, DMSO,
and MeOH showed relatively low compatibility compared
Initially, the 3-substituted-2-oxindole (1a) was chosen as the with MeCN, giving the product in yields ranging from
model substrate and the reaction was first studied in the 40%-64% (entries 9-11). Only a trace amount of 2a was
presence of commonly used photosensitizers. As shown in detected when less polar solvents were employed (entries
Table 1, all of the photocatalysts tested could successfully 12-14). Fortunately, we found that CF3CH2OH markedly
give the desired product in moderate yields in the presence improved the yield of this process to 88% (entry 15).
of an O2 balloon under the irradiation of visible light Moreover, a shorter reaction time was observed when using
(entries 1-4). Among them [Ir(ppy)2(dtbbpy)]PF6 proved silica gel as an additive (entry 16), possibly because the
to be the most promising for further optimization. To our substrate was activated by H-bonding and/or the solubility
delight, changing the oxygen source from an O2 balloon to of molecular oxygen was increased [46-47].
atmosphericairdidnotsignificantlyaffectthehydroxylation
With the optimized conditions in hand, the study
efficiency (entry 2 vs entry 5). The desired product was still was then focused on extending the substrate scope. The
obtained in 70% yield. Control experiments showed that electronic effect on the benzene ring of the oxindole
photocatalyst, visible light and O2 were indispensable for moiety was first examined (Table 2, entries a-f). In general,
this transformation. No product was afforded when the substrates bearing an electron-withdrawing group
reaction was conducted in the absence of any of these three provided better results than substrates with electron-
parameters (entries 6-8). Subsequently, a variety of solvents donating groups. Specifically, when an electron-donating
were examined, and the choice of the reaction media was group such as methoxy (1c) was installed on the benzene
found to be essential for the hydroxylation. When using ring, the reaction proceeded sluggishly, and the desired
Table 1ꢂScreening the reaction conditions and control experimenta
b
Entry
1
Photosensitizer
Ru(bpy)3Cl2.6H2O
Solvent
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
DMF
Oxygen source
O2 balloon
Time (h)
Yield %
68
3
4
2
[Ir(ppy)2(dtbbpy)]PF6
[Ir(dF(CF3)ppy)2(dtbbpy)]PF6
Eosin Y
O2 balloon
72
3
O2 balloon
3
61
4
O2 balloon
air
3
69
5
[Ir(ppy)2(dtbbpy)]PF6
Without photocatalyst
[Ir(ppy)2(dtbbpy)]PF6
[Ir(ppy)2(dtbbpy)]PF6
[Ir(ppy)2(dtbbpy)]PF6
[Ir(ppy)2(dtbbpy)]PF6
[Ir(ppy)2(dtbbpy)]PF6
[Ir(ppy)2(dtbbpy)]PF6
[Ir(ppy)2(dtbbpy)]PF6
[Ir(ppy)2(dtbbpy)]PF6
[Ir(ppy)2(dtbbpy)]PF6
[Ir(ppy)2(dtbbpy)]PF6
4
70
6
7c
8d
air
4
0
air
4
0
air
4
0
9
air
7
44
10
11
12
13
14
15
16e
DMSO
CH3OH
CH2Cl2
THF
air
7
40
air
4
64
air
4
trace
trace
trace
88
air
4
Toluene
CF3CH2OH
CF3CH2OH
air
4
air
12
10
air
88
aA mixture of 1a (0.3 mmol) and photocatalysts (2 mol%) in solvent (3 mL, 0.1 M) were stirred at room temperature under the irra-
diation of 18 w fluorescent lamp. bIsolated yield after column chromatography. cWithout visible light. dWithout oxygen. eWith the
addition of silica gel (30 mg per 1 mL solvent). DMF: N,N-Dimethylformamide. DMSO: Dimethyl sulfoxide. THF: Tetrahydrofuran.

ꢁ
170ꢁ
J. Wang et al.: Visible light mediated aerobic oxidative hydroxylation
Table 2ꢂSubstrate scope of the photocatalytic systema
aA mixture of 1a-1o (0.5 mmol), [Ir(ppy)2(dtbbpy)]PF6 (2 mol%), and silica gel (30 mg per 1 mL solvent) in solvent (5 mL, 0.1 M)
were stirred at room temperature under the irradiation of an 18 w fluorescent lamp open to air. bIsolated yield after column
chromatography.
product was delivered in only 57% yield after 2 days. (2p) and 3-hydroxy-1-methyl-3-phenyloxindole (2q) deriva-
Moreover, the substituted position of the R1 group had a big tives in 60% and 17% yield, respectively (Scheme 1) [33].
influence on the results of the hydroxylation. For example, Subsequently, in order to test the application of the proto-
6-Br substituted oxindole carboxylate only gave 2g in 20% col we increased the reaction scale to gram scale, as shown
yield, while 4-Br substituted oxindole carboxylate (1h) in Scheme 1. When the reaction ran on a larger scale, a
did not react upon exposure to the optimized standard decrease in reaction efficiency and in yield of the hydrox-
conditions, since 1h exists exclusively in its keto form. ylated product was observed. After 48 hours the starting
However, the 7-F substituted derivative (1i) was quite material could not be completely transferred to the product,
tolerated, and the hydroxylated product 2i was afforded in and only 60% of the target molecule was obtained.
a yield of 79%. Gratifyingly, when the N-protecting group
A plausible mechanism for this transformation is
was replaced with H, Bn and PMB, the reaction proceeded outlined in Scheme 2. Based on the previous work of Xiao’s
smoothly and afforded the desired products in moderate group, there was an equilibration of the substrate (1a)
to good yields (entries j-l). In the case of 1m, with an allyl between its keto and enol form [45]. Visible light irradiation
as the protecting group, the product was obtained only in of the photocatalyst brought it to its excited state [Ir]*,
39% yield. Finally, the ester moiety was also investigated. and oxidative quenching between 1a’ and [Ir]* delivered
1n and 1o were not fully hydroxylated even after 2 days. the radical intermediate A. The reduced photocatalyst
Under the standard reaction conditions, they afforded the [Ir]- underwent a single electron transfer with oxygen to
products (2n and 2o) in 77% and 62% yields, respectively. complete the photocatalytic cycle, to obtain an oxygen
By changing the solvent to THF, the protocol could be radical anion. Thereafter, intermediate A went through a
extended to the synthesis of 3-hydroxy-3-phenyloxindole radical coupling with the oxygen radical anion, giving rise

J. Wang et al.: Visible light mediated aerobic oxidative hydroxylation ꢁ
ꢁ171
the developed protocol to be useful in the modification of
structurally significant chemicals, and further application of
this method is ongoing in our laboratory.
Experimental
General procedure for the photocatalytic reaction
To a mixture of ethyl 2-oxoindoline-3-carboxylates 1a-1o
(0.5 mmol) and [Ir(ppy)2(dtbbpy)]PF6 (2 mol%, 9.1 mg) in
CF3CH2OH (5 mL) was added silica gel (30 mg/mL) at room
temperature in a 10 mL round bottom flask. The resulting
solution was stirred at a distance of 5 cm from an 18 w
fluorescent light bulb until the reaction was determined
to be completed by TLC analysis. The crude product was
purified by silica gel chromatography.
Scheme 1ꢂSubstrate scope extension and large scale reaction
Characterization Data of the Products
Ethyl 3-hydroxy-1-methyl-2-oxoindoline-3-carboxylate
(2a) [10]
White solid; 88% yield; m.p. 137~138 oC; 1H NMR (400 MHz,
CDCl3): δ = 7.38 (t, J = 7.7 Hz, 1H), 7.29 (d, J = 7.3 Hz, 1H),
7.09 (t, J = 7.5 Hz, 1H), 6.87 (d, J = 7.8 Hz, 1H), 4.61 (s, 1H),
4.28 – 4.12 (m, 2H), 3.23 (s, 3H), 1.15 (t, J = 7.1 Hz, 3H); 13C
NMR (100 MHz, CDCl3): δ = 173.1, 169.8, 144.6, 130.6, 126.9,
123.7, 123.3, 108.8, 77.3, 63.1, 26.5, 13.8; MS (EI) m/z: 235.1.
Ethyl 3-hydroxy-1,5-dimethyl-2-oxoindoline-3-
carboxylate (2b) [10]
Scheme 2ꢂProposed mechanism
to the hydroperoxide intermediate C through intermediate White solid; 77% yield; m.p. 134~136 oC; 1H NMR (400 MHz,
B. Finally, a self-oxidation between C and 1a’ furnished the CDCl3):δ=7.17(d, J=7.2Hz, 1H), 7.10(s, 1H), 6.76(d,J=7.9Hz,
desired product 2a.
1H), 4.32 (s, 1H), 4.30 – 4.11 (m, 2H), 3.22 (s, 3H), 2.33
(s, 3H), 1.17 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3):
δ = 173.0, 169.8, 142.0, 132.9, 130.7, 126.8, 124.4, 108.5, 77.4,
63.0, 26.5, 20.9, 13.7; MS (EI) m/z: 249.1.
Conclusions
In conclusion, we describe herein a mild photocatalytic
system to construct the potentially biologically important Ethyl 3-hydroxy-5-methoxy-1-methyl-2-oxoindoline-
3-carboxylate (2c)
molecules 3-ester-3-hydroxy-2-oxindoles in up to 89% yield.
Under the irradiation of visible light, the reaction was carried
1
out open to air at room temperature. Moreover, without the Light blue solid; 57% yield; m.p. 148~150 oC; H NMR
addition of base the optimized conditions were suitable for (600 MHz, CDCl3): δ = 6.95 – 6.86 (m, 2H), 6.84 – 6.75
N-allyl protected and N-H free compounds, and the process (m, 1H), 4.37 (s, 1H), 4.30 – 4.15 (m, 2H), 3.79 (s, 3H), 3.22
goes smoothly when enlarged to gram scale. We expect (s, 3H), 1.17 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3):

ꢁ
172ꢁ
J. Wang et al.: Visible light mediated aerobic oxidative hydroxylation
δ = 172.8, 169.7, 156.3, 137.8, 127.9, 115.2, 11.5, 109.3, 77.6, 1.17 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ = 172.9,
63.1, 55.7, 26.6, 13.8; MS (EI) m/z: 265.1; HRMS (ESI): m/z 169.2, 145.8, 126.1, 125.8, 125.0, 124.3, 112.4, 76.9, 63.4, 26.7,
[M + Na+] calcd for C13H15NNaO5: 288.0848; found: 288.0842. 13.8; MS (EI) m/z: 313.0; HRMS (EI): m/z [M + H+] calcd for
C12H13BrNO4: 314.0028; found: 314.0024.
Ethyl 3-hydroxy-1-methyl-2-oxo-5-(trifluoromethoxy)
indoline-3-carboxylate (2d)
Ethyl 7-fluoro-3-hydroxy-1-methyl-2-oxoindoline-3-
carboxylate (2i)
White solid; 89% yield; m.p. 77~79 o C; 1H NMR (600 MHz,
o
1
CDCl3):δ=7.27(s, 1H), 7.18(s, 1H), 6.87(d, J=8.5Hz, 1H), 4.45 White solid; 79% yield; m.p. 118~119 C; H NMR (400
(s, 1H), 4.28 – 4.17 (m, 2H), 3.25 (s, 3H), 1.17 (t, J = 7.1 Hz, 3H); MHz, CDCl3): δ = 7.20 – 6.98 (m, 3H), 4.38 (s, 1H), 4.34 –
13C NMR (100 MHz, CDCl3): δ = 173.0, 169.1, 145.0, 143.2, 4.15 (m, 2H), 3.45 (s, 3H), 1.18 (t, J = 7.0 Hz, 3H); 13C NMR
128.3, 123.7, 120.4 (d, J = 257.1 Hz), 117.8, 109.4, 77.2, 63.4, 26.7, (100 MHz, CDCl3): δ = 172.7 (s), 169.2 (s), 147.6 (d, J = 244.6
13.7; 19F NMR (376 MHz, CDCl3): δ = -58.34 (s); MS (EI) m/z: Hz), 131.1 (d, J = 8.9 Hz), 129.5 (s), 124.0 (d, J = 6.1 Hz), 119.6
+
319.1; HRMS (EI): m/z [M + NH4 ] calcd for C13H16F3N2O5: (s), 118.6 (d, J = 19.2 Hz), 77.2 (s), 63.3 (s), 29.1 (s), 13.8 (s);
337.1011; found: 337.1007.
19F NMR (376 MHz, CDCl3): δ = -135.27 – -135.69 (m); MS (EI)
m/z: 253.1; HRMS (EI): m/z [M + H+] calcd for C12H13FNO4:
254.0829; found: 254.0820.
Ethyl 5-fluoro-3-hydroxy-1-methyl-2-oxoindoline-3-
carboxylate (2e)
Ethyl 3-hydroxy-2-oxoindoline-3-carboxylate (2j)
1
Light yellow solid; 86% yield; m.p. 126~128 o C; H NMR
(600 MHz, CDCl3): δ = 7.14 – 7.06 (m, 1H), 7.04 (dd, J = 7.3, White solid; 82% yield; m.p. 147~148 o C; H NMR (600
2.2 Hz, 1H), 6.81 (dd, J = 8.5, 3.9 Hz, 1H), 4.46 (s, 1H), 4.29 – MHz, CDCl3): δ = 8.47 (s, 1H), 7.32 (t, J = 7.7 Hz, 1H), 7.28
4.18 (m, 2H), 3.23 (s, 3H), 1.18 (t, J = 7.1 Hz, 3H); 13C NMR (100 (s, 1H), 7.08 (t, J = 7.5 Hz, 1H), 6.94 (d, J = 7.7 Hz, 1H),
MHz, CDCl3): δ = 172.9 (s), 169.2 (s), 159.3 (d, J = 242.6 Hz), 4.51 (s, 1H), 4.31 – 4.14 (m, 2H), 1.18 (t, J = 7.1 Hz, 3H);
140.5 (s), 128.3 (d, J = 8.6 Hz), 116.8 (d, J = 23.5 Hz), 112.0 13C NMR (100 MHz, DMSO-d6): δ = 174.7, 169.3, 142.8,
(d, J = 25.4 Hz), 109.4 (d, J = 7.9 Hz), 77.4 (s), 63.3 (s), 26.7 130.3, 129.2, 123.9, 122.1, 110.2, 77.6, 61.3, 14.0; MS (EI)
(s), 13.8 (s). 19F NMR (376 MHz, CDCl3): δ = –118.95 – –119.07 m/z: 221.1; HRMS (EI): m/z [M + H+] calcd for C11H12NO4:
(m); MS (EI) m/z: 253.1; HRMS (EI): m/z [M + H+] calcd for 222.0766; found: 222.0762.
1
C12H13FNO4: 254.0829; found: 254.0827.
Ethyl 1-benzyl-3-hydroxy-2-oxoindoline-3-carboxylate
(2k) [10]
Ethyl 5-bromo-3-hydroxy-1-methyl-2-oxoindoline-3-
carboxylate (2f)
Light blue solid; 79% yield; m.p. 140~143 oC; 1H NMR (400
White solid; 84% yield; m.p. 150~153 o C; H NMR (600 MHz, CDCl3): δ = 7.46 – 7.27 (m, 7H), 7.06 (t, J = 7.6 Hz,
MHz, CDCl3): δ = 7.54 – 7.49 (m, 1H), 7.40 (s, 1H), 6.76 1H), 6.71 (d, J = 7.6 Hz, 1H), 5.19 (d, J = 15.9 Hz, 1H), 4.68
(d, J = 8.3 Hz, 1H), 4.38 (s, 1H), 4.31 – 4.16 (m, 2H), 3.22 (d,J=16.0Hz,1H),4.39(s,1H),4.36–4.26(m,1H),4.24–4.08
(s, 3H), 1.19 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): (m, 1H), 1.20 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3):
δ = 172.6, 169.1, 143.6, 133.4, 128.7, 127.0, 115.8, 110.3, 77.1, δ = 173.3, 169.7, 143.5, 135.0, 130.5, 128.6, 127.6, 126.9, 123.7,
63.4, 26.7, 13.8; MS (EI) m/z: 313.0; HRMS (EI): m/z [M + H+] 123.3, 109.8, 77.4, 63.2, 43.7, 13.7; MS (EI) m/z: 311.1.
calcd for C12H13BrNO4: 314.0028; found: 314.0022.
1
Ethyl 3-hydroxy-1-(4-methoxybenzyl)-2-oxoindoline-
3-carboxylate (2l)
Ethyl 6-bromo-3-hydroxy-1-methyl-2-oxoindoline-3-
carboxylate (2g)
o
1
Light blue solid; 74% yield; m.p. 131~132 C; H NMR
Light blue solid; 20% yield; m.p. 155~156 o C; H NMR (600 MHz, CDCl3): δ = 7.28 (d, J = 7.5 Hz, 1H), 7.25
(400 MHz, CDCl3): δ = 7.23 (s, 1H), 7.14 (d, J = 7.8 Hz, 1H), (d, J = 8.4 Hz, 3H), 7.05 (t, J = 7.6 Hz, 1H), 6.84 (d, J = 8.6 Hz,
7.03 (s, 1H), 4.34 (s, 1H), 4.28 – 4.16 (m, 2H), 3.22 (s, 3H), 2H), 6.73 (d, J = 7.9 Hz, 1H), 5.10 (d, J = 15.6 Hz, 1H), 4.63
1

J. Wang et al.: Visible light mediated aerobic oxidative hydroxylation ꢁ
ꢁ173
(d, J = 15.6 Hz, 1H), 4.37 (s, 1H), 4.34 – 4.27 (m, 1H), 6.97 (t, J = 7.5 Hz, 1H), 6.91 (d, J = 7.7 Hz, 1H), 6.67 – 6.61
4.22 – 4.12 (m, 1H), 3.78 (s, 3H), 1.19 (t, J = 7.1 Hz, 3H); 13 (m, 1H); 13C NMR (125 MHz, DMSO-d6): δ = 178.5,
C
NMR (100 MHz, CDCl3): δ = 173.2, 169.7, 158.9, 143.5, 130.4, 141.9, 141.5, 133.7, 129.2, 128.0, 127.4, 125.4, 124.8, 122.0,
128.3, 126.9, 126.9, 123.6, 123.2, 114.0, 109.8, 77.4, 63.1, 55.1, 109.8, 77.3.
43.2, 13.7; MS (EI) m/z: 341.1; HRMS (ESI): m/z [M + Na+]
calcd for C19H19NNaO5: 364.1161; found: 364.1155.
3-Hydroxy-1-methyl-3-phenylindolin-2-one (2q)[33]
1
Ethyl 1-allyl-3-hydroxy-2-oxoindoline-3-carboxylate (2m) White solid; 17% yield; H NMR (500 MHz, DMSO-d6):
δ = 7.35 (t, J = 7.7 Hz, 1H), 7.32 – 7.24 (m, 5H), 7.14
1
White solid; 39% yield; m.p. 136~137 o C; H NMR (600 (d, J = 7.2 Hz, 1H), 7.09 (d, J = 7.8 Hz, 1H), 7.05 (t, J = 7.5 Hz, 1H),
MHz, CDCl3): δ = 7.34 (t, J = 7.8 Hz, 1H), 7.29 (d, J = 7.4 Hz, 6.69 (s, 1H), 3.16 (s, 3H); 13C NMR (125 MHz, DMSO-d6):
1H), 7.08 (t, J = 7.5 Hz, 1H), 6.84 (d, J = 7.8 Hz, 1H), 5.90 – δ = 176.7, 143.4, 141.3, 133.0, 129.4, 128.1, 127.5, 125.5, 124.3,
5.80 (m, 1H), 5.29 – 5.18 (m, 2H), 4.49 (d, J = 16.8 Hz, 1H), 122.7, 108.8, 77.0, 26.1.
4.32 – 4.12 (m, 4H), 1.16 (t, J = 7.1 Hz, 3H); 13C NMR (100
MHz, CDCl3): δ = 172.9, 169.7, 143.6, 130.5, 130.4, 126.8, Acknowledgements: We are grateful to the National
123.7, 123.3, 117.1, 109.6, 77.4, 63.2, 42.3, 13.7; MS (EI) m/z: Natural Science Foundation of China (No. 21862018), and
261.1; HRMS (ESI): m/z [M + Na+] calcd for C14H15NNaO4: Tarim University (TDZKJC201701) for financial support for
284.0899; found: 284.0893.
this research.
Conflict of interest: The authors state no conflict of
interest.
Isobutyl 3-hydroxy-1-methyl-2-oxoindoline-3-
carboxylate (2n)
o
1
Light blue solid; 77% yield; m.p. 70~72 C; H NMR (600
MHz, CDCl3): δ = 7.38 (t, J = 7.8 Hz, 1H), 7.28 (d, J = 7.4
Hz, 1H), 7.09 (t, J = 7.5 Hz, 1H), 6.88 (d, J = 7.8 Hz, 1H), 4.32
(s,1H),3.94(p,J=10.5Hz,2H),3.24(s,3H),1.87–1.75(m,1H),
0.72 (t, J = 6.7 Hz, 6H); 13C NMR (100 MHz, CDCl3): δ = 173.1,
169.7, 144.4, 130.5, 127.0, 123.6, 123.2, 108.7, 77.4, 72.4, 27.5,
26.5, 18.4; MS (EI) m/z: 263.1; HRMS (ESI): m/z [M + Na+]
calcd for C14H17NNaO4: 286.1055; found: 286.1050.
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1
Light blue solid; 62% yield; m.p. 116~118 C; H NMR
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