Efficient asymmetric Michael reaction of 2-oxindole-3-carboxylate esters with maleimides catalyzed by cinchonidine

Article abstract of DOI:10.1016/j.tet.2014.03.065

A highly efficient enantioselective Michael reaction of 2-oxindole-3-carboxylate esters with N-maleimides catalyzed by commercially available cinchonidine was described. The desired adducts, containing a quaternary center at the C3-position and a vicinal tertiary center, were obtained in excellent yields (up to 99%), good enantioselectivities (up to 85% ee), and diastereoselectivities (dr>90:10) in the presence of 0.05-5 mol % catalyst loading.

Full text of DOI:10.1016/j.tet.2014.03.065

Tetrahedron 70 (2014) 3478e3484
Contents lists available at ScienceDirect
Tetrahedron
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Efficient asymmetric Michael reaction of 2-oxindole-3-carboxylate
esters with maleimides catalyzed by cinchonidine
,
,
,
,
*
Jing Zhou a b, Li-Na Jia a b, Lin Peng a, Qi-Lin Wang a b, Fang Tian a, Xiao-Ying Xu a
,
Li-Xin Wang a
,
*
a Key Laboratory of Asymmetric Synthesis and Chirotechnology of Sichuan Province, Chengdu Institute of Organic Chemistry,
Chinese Academy of Sciences, Chengdu 610041, China
b University of Chinese Academy of Sciences, Beijing, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A highly efficient enantioselective Michael reaction of 2-oxindole-3-carboxylate esters with N-mal-
eimides catalyzed by commercially available cinchonidine was described. The desired adducts, con-
taining a quaternary center at the C3-position and a vicinal tertiary center, were obtained in excellent
yields (up to 99%), good enantioselectivities (up to 85% ee), and diastereoselectivities (dr>90:10) in the
presence of 0.05e5 mol % catalyst loading.
Received 15 December 2013
Received in revised form 9 March 2014
Accepted 19 March 2014
Available online 26 March 2014
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
2-Oxindole-3-carboxylate esters
Maleimides
Michael reaction
Cinchonidine
1. Introduction
oxindoles and more than 10 mol % catalyst was needed in most
cases. To the best of our knowledge, the reaction of 3-carboxylate
Optically active 3,3-disubstituted oxindole skeletons constitute
important structural motifs in a variety of natural products and
biologically active drugs.1 For the significance of those molecules,
a variety of organocatalytic asymmetric protocols have been de-
veloped, such as Michael additions,2 aldol reactions,3 Mannich re-
actions,4 alkylations,5 aminooxygenations6 etc. Among them,
Michael addition of 3-substituted oxindoles to appropriate elec-
trophiles has been considered as a generally applied and feasible
way to access chiral 3,3-disubstituted oxindoles.7 Additionally,
maleimides have been extensively applied in asymmetric organo-
catalysis to construct chiral succinimide derivatives, which are core
structural units found in natural products and some clinical drug
candidates.8 As a result, the addition of 3-substituted oxindoles to
maleimides has drawn chemists’ attentions. In 2010, Yuan and co-
workers first reported Michael addition of 3-substituted oxindoles
to N-maleimides catalyzed by chiral tertiary amine thioureas in
excellent results.2g Later, bicyclic guanidines9 and didodecyl proli-
nol TMS-ether10 were also used in this transformation. All the re-
ported strategies involved only 3-alkyl- or 3-aryl-substituted
esters substituted oxindoles with maleimides has not been re-
ported.11 It is still desirable and useful to develop new protocols
catalyzed by simple, cheap, commercially available catalysts to af-
ford new kinds of chiral 3,3-disubstituted oxindoles with succini-
mides and adjacent quaternary and tertiary stereocenters.
Over the past decades, cinchona alkaloids are widely used as
chiral organic catalysts in asymmetric catalysis. In our previous
work, we have successfully applied cinchona alkaloids and their
derivatives in some asymmetric catalyses, especially in asymmetric
Michael addition and cyclization of maleimides,12 and for the
construction of oxindole motifs with quaternary stereocenters.13
Inspired by those achievements, we envisioned that the addition
of 3-carboxylate ester substituted oxindoles to maleimides may be
realized in the presence of cinchona alkaloids, in which the tertiary
amine group would activate the oxindoles and the hydroxyl group
would activate the maleimides through hydrogen bondings. Thus
the synergistic interactions would ensure high stereoselectivity,
affording the corresponding optically active 3,3-disubstituted
oxindoles with contiguous quaternary and tertiary stereocenters
(Scheme 1). As a part of our continuing interests in asymmetric
syntheses,14 herein, we wish to report the first asymmetric Michael
addition of 3-carboxylate ester substituted oxindoles to maleimides
catalyzed by simple and commercially available cinchona alkaloids
(Fig. 1).
* Corresponding authors. Tel./fax: þ86 28 85255208; e-mail addresses: wlxioc@
cioc.ac.cn (L.-X. Wang), xuxy@cioc.ac.cn (X.-Y. Xu).
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.03.065

J. Zhou et al. / Tetrahedron 70 (2014) 3478e3484
3479
ee). Halohydrocarbon and hydrocarbon solvents such as CH2Cl2,
CHCl3, toluene gave moderate enantioselectivities (53e58% ee,
Table 1, entries 1e6), and strong polar solvent DMF gave poor
enantioselectivity (10% ee, Table 1, entry 11). CHCl3 gave the highest
enantioselectivity with excellent yield (58% ee, 96% yield, Table 1,
entry 2) and was chosen as the most suitable solvent. Other com-
mercially available cinchona alkaloids were also evaluated in CHCl3.
Cinchonidine turned out to be the most effective catalyst with 99%
yield and 63% ee (Table 1, entry 12). Further improvement could be
achieved by lowering the reaction temperature (Table 1, entries
15e17). On lowering the temperature to ꢀ35 ꢁC, the enantiose-
lectivity increased to 73% ee with 99% yield in an acceptable re-
action time (Table 1, entry 17).
Scheme 1. Strategy for the construction of 3,3-disubstitued oxindoles.
To further improve the enantioselectivity, molar ratio, concen-
trations of reactants and catalyst loadings were studied, and the
results were presented in Table 2. Increasing or lowering the molar
ratio significantly increased the reaction rate, while slightly af-
fected the dr and ee values (Table 2, entries 1 and 2). Increasing or
lowering the concentration of substrates has slight effect on the
reaction time, yields, and enantioselectivities (Table 2, entries 3 and
4). The enantioselectivity could be further improved to 75% ee with
5 mol % catalyst 3b (Table 2, entry 5), and further lowering the
catalyst loading decreased the enantioselectivities. It was worth
noting that the introduction of carboxylate substituents at C3-
position of oxindoles greatly increased the reactivity and only
0.05 mol % 3b was sufficient to afford the reaction in high yield
(99%) with 68% ee (Table 2, entry 9).2g,9e11 On the basis of those
screenings, a set of optimal reaction conditions were established:
0.2 mmol 2a and 0.2 mmol 3a in 1.0 mL CHCl3 with 5 mol % of
cinchonidine at ꢀ35 ꢁC.
Fig. 1. Screened catalysts.
2. Results and discussion
The initial investigation to validate our hypothesis started with
the reaction of 2-oxindoline-3-carboxylate 1a with N-phenyl mal-
eimide 2a catalyzed by 20 mol % cinchonine in DCM at room
temperature. The reaction took place smoothly to afford the desired
product in 95% yield and 55% ee (Table 1, entry 1). Inspired by this
result, a series of solvents were investigated and the results were
listed in Table 1. This transformation was carried out well in all
solvents except strong polar solvent DMF and gave good to excel-
lent yields (64e98%) and moderate enantioselectivities (45e58%
Table 2
Optimization of reaction conditionsa
Table 1
Optimization of reaction conditionsa
Entry Cat. loading (mol %) 1a/2a Time (h) Yieldb (%) drc
eed (%)
1
2
20
20
20
20
5
0.5
0.1
0.05
0.05
1:2
2:1
1:1
1:1
1:1
1:1
1:1
1:1
1:2
1
1
15
15
18
24
5 days
10 days
8 days
94
99
99
97
93
92
99
56
99
89:11 74
89:11 74
89:11 73
89:11 75
89:11 75
89:11 73
88:12 72
81:19 55
87:13 68
3e
4f
5
Entry Cat. Solvent
Temp (ꢁC) Time (h) Yieldb (%) drc
eed (%)
1
2
3
4
5
6
7
8
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3b
3c
3d
3b
3b
3b
CH2Cl2
CHCl3
DCE
Cyclohexane
PhCH3
Mesitylene
Et2O
25
25
25
25
25
25
25
25
25
25
25
25
25
25
50
2
2
2
2
2
2
2
2
2
2
2
2
2
2
1
5
13
95
96
98
72
97
95
89
97
92
64
34
99
99
99
97
99
99
83:17 55e
80:20 58e
82:18 55e
79:21 53e
76:24 54e
77:24 53e
76:25 57e
74:26 52e
75:25 50e
78:22 45e
52:48 10e
80:20 63
75:25 53
72:28 48e
79:21 60
82:18 68
88:12 73
6
7
8
9
a
Unless otherwise noted, reactions were conducted with 0.2 mmol scale, and
catalyst 3b in CHCl3 (1.0 mL).
b
THF
Isolated yields.
Determined by chiral HPLC analysis.
The major diastereomers, determined by chiral HPLC analysis.
0.5 mL CHCl3 was used.
c
9
EtOAc
CH3CN
DMF
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
d
10
11
12
13
14
15
16
17
e
f
2.0 mL CHCl3 was used.
Under the optimal reaction conditions, the generality of 1a and
various maleimides 2 was further studied and the results were
listed in Table 3. A wide range of N-aromatic (2aei) and aliphatic
(2jel) maleimides worked well with 1a, and all the cases afforded
excellent yields and moderate to good enantioselectivities (93e99%
yield, 63e85% ee). N-Aliphatic maleimides afforded relatively
higher enantioselectivity compared with their N-aromatic coun-
terparts (Table 3, entries 10e12 vs 1e9).
ꢀ15
ꢀ35
a
Unless otherwise noted, reactions were conducted with 0.2 mmol 1a, 0.2 mmol
2a, 20 mol % 3, in 1.0 mL solvent.
b
Isolated yields.
Determined by chiral HPLC analysis.
The major diastereomers, determined by chiral HPLC analysis.
Contrary configuration.
c
d
e

3480
J. Zhou et al. / Tetrahedron 70 (2014) 3478e3484
Table 3
entries 6 and 7). N-Isobutyl oxindole provided a moderate yield and
slightly poor dr and ee due to the larger steric hindrance (Table 4,
entry 8). The absolute configuration was determined by an X-ray
analysis of the single crystal of 4e, which was assigned as (C6S, C7S)
(Fig. 2).15
Asymmetric Michael reaction of 1a with different N-substituted maleimidesa
Entry
2
R
4
Yieldb (%)
drc
9.0:1e
eed (%)
1
2
3
4
5
6
7
8
2a
2b
2c
2d
2e
2f
2g
2h
2i
C6H5
4a
4b
4c
4d
4e
4f
4g
4h
4i
93
99
99
99
99
99
99
99
99
99
99
99
75
77
76
75
74
63
70
80
83
82
85
79
4-CH3C6H4
4-CH3OC6H4
4-FC6H4
4-ClC6H4
4-NO2C6H4
3-FC6H4
3-NO2C6H4
2-FC6H4
CH3
8.1:1
9.0:1e
10.1:1
10.1:1
7.3:1
7.7:1e
5.5:1e
9.0:1
9
10
11
12
2j
2k
2l
4j
4k
4l
6.3:1e
6.7:1e
7.1:1e
Bn
eCHPh2
a
Fig. 2. X-ray crystal structure of product 4e.
Unless otherwise noted, reactions were conducted with 0.2 mmol 1, 0.2 mmol 2,
5 mol % 3b, in 1.0 mL CHCl3.
b
Based on the experimental results and the observed absolute
configuration of 4e, a plausible transition state model of this pro-
tocol is illustrated in Fig. 3, in which the cinchonidine catalyst ac-
tivates both the oxindole in its enol form and the carbonyl group of
maleimide through hydrogen bonding. Thus the enolate would
attack the maleimide from Si face, affording the corresponding
product with (S,S)-configuration.
Isolated yields.
Determined by chiral HPLC analysis.
c
d
The major diastereomers, determined by chiral HPLC analysis.
e
Determined by 1H NMR.
Subsequently, the scope of various oxindoles 1bei was also
studied and the resulted were shown in Table 4. The substituents of
oxindoles 1 have obvious effects on the reactivities, yields, and
enantioselectivities. Different substituents on the aromatic ring of
oxindoles afforded the desired products in good yields and ac-
ceptable enantioselectivities (90e92% yield, 59e73% ee, Table 4,
entries 1e5). Additionally, we also examined the effects of N-
substituted oxindoles. The introduction of larger substituents on
nitrogen atom decreased the reactivities, and 20 mol % catalyst 3b
and room temperature were required. N-Propyl and N-allyl oxin-
doles gave good yields and moderate enantioselectivities (Table 4,
Fig. 3. Plausible transition state model.
Table 4
Asymmetric Michael addition of different oxindoles with maleimide 2aa
3. Conclusion
In conclusion, we have developed a highly efficient organo-
catalytic Michael addition of 2-oxindole-3-carboxylates to mal-
eimides catalyzed by simple, cheap, and commercially available
cinchonidine. The desired 3,3-disubstituted oxindoles with con-
tiguous quaternary and tertiary stereocenters were obtained in
excellent yields (up to 99%), good diastereo- (dr>90:10) and ac-
ceptable enantioselectivities (up to 85% ee). This protocol featured
with low catalyst loading and provided a potential method for the
construction of 3,3-disubstituted oxindoles and chiral
succinimides.
Entry R1, R2, R3
Time (h)
4
Yieldb (%) drc
eed (%)
1e
2
H, Me, Me (1b)
5-F, Et, Me (1c)
24
48
48
48
48
2
4m 90
4n 90
4o 91
4p 92
4q 92
4r 82
4s 90
4t 51
5.7:1g 73
8.2:1g 73
8.4:1g 71
>99:1 59
6.5:1g 69
2.33:1 58
3.3:1 63
1.3:1g 41
3
4
5-Br, Et, Me (1d)
4-Cl, Et, Me (1e)
6-Br, Et, Me (1f)
H, Et, n-Pr (1g)
H, Et, eCH2eCH]CH2 (1h)
H, Et, i-Bu (1i)
5
4. Experimental section
4.1. General method
6f
7f
8f
2
120
a
Unless otherwise noted, reactions were conducted with 0.2 mmol 1a, 0.2 mmol
2a, and catalyst 3b in 1.0 mL CHCl3.
2-Oxindole-3-carboxylates 1 were prepared according to the
reported procedures5b,16,17 or similarly. N-Substituted maleimides 2
were prepared according to the literature method.18 Commercial
grade solvents were dried and purified by standard procedures as
specified in Purification of Laboratory Chemicals, 4th Ed (Armarego,
W. L. F.; Perrin, D. D. Butterworth Heinemann, 1997). Racemic
b
Isolated yields.
Determined by chiral HPLC analysis.
The major diastereomers, determined by chiral HPLC analysis.
c
d
e
0.5 mol % 3b used.
f
20 mol % 3b performed at 25 ꢁC.
g
Determined by 1H NMR.

J. Zhou et al. / Tetrahedron 70 (2014) 3478e3484
3481
products were obtained from the corresponding substrates cata-
lyzed by Et3N at room temperature. NMR spectra were recorded
with tetramethylsilane as the internal standard. 1H NMR spectra
were recorded at 300 MHz, and 13C NMR spectra were recorded at
(minor), minor diastereomer: 28.47 min (major) and 38.63 min
(minor). 1H NMR (CDCl3, 300 MHz)
(dd, J¼6.00, 18.23 Hz, 1H), 3.00 (dd, J¼9.47, 18.36 Hz, 1H), 3.24
(s, 3H), 3.78 (s, 3H), 4.21e4.30 (m, 3H), 6.88e6.94 (m, 3H),
7.08e7.14 (m, 3H), 7.28e7.30 (m, 1H), 7.35e7.38 (m, 1H); 13C NMR
d
1.25 (t, J¼6.73 Hz, 3H), 2.89
75 MHz (Bruker Avance). Chemical shifts (
per million (ppm) downfield from CDCl3 (
and relative to the central CDCl3 resonance (
d) are reported in parts
d
¼7.26 ppm) for 1H NMR
(CDCl3, 75 Hz) d 13.8, 26.6, 31.3, 44.2, 55.4, 58.9, 62.7, 108.8, 114.4,
d
¼77.0 ppm) for 13C
123.4, 124.0, 124.3, 124.8, 127.7, 129.9, 144.1, 159.5, 166.9, 171.3,
NMR spectroscopy. The following abbreviations were used to de-
scribe peak patterns where appropriate: br¼broad, s¼singlet,
d¼doublet, t¼triplet, q¼quartet, m¼multiplet. Coupling constants
were reported in Hertz (Hz). Flash column chromatography was
carried out using silica gel eluting with ethyl acetate and petroleum
ether. Reactions were monitored by TLC and visualized with ul-
traviolet light. The enantiomeric excess (ee) of the products was
determined by HPLC using Daicel Chiralpak AD-H columns with i-
PrOH/hexane as eluent.
174.3, 175.2; HRMS (ESI) calcd for
445.1376; found: 445.1385.
C
23H22N2NaO6 [MþNa]þ:
4.2.4. Ethyl (3S)-3-[(3S)-1-(4-fluorophenyl)-2,5-dioxopyrrolidin-3-
yl]-1-methyl-2-oxo-2,3-dihydro-1H-indole-3-carboxylate
(4d). White solid; 99% yield (dr¼10.1:1, 75% ee for the major
diastereomer); HPLC conditions: Chiralcel AD-H column, hexane/i-
PrOH¼50:50, flow rate 0.6 mL/min, UV detection at 220 nm,
retention time: major diastereomer: 18.82 min (major) and
59.74 min (minor), minor diastereomer: 32.62 min (major) and
4.2. General procedure for the asymmetric Michael addition
of 2-oxindole-3-carboxylate esters with maleimides
48.07 min (minor). 1H NMR (CDCl3, 300 MHz)
d
1.22 (t, J¼7.14 Hz,
3H), 2.70 (dd, J¼6.09, 18.16 Hz, 1H), 3.07 (dd, J¼8.80, 18.18 Hz, 1H),
3.23 (s, 3H), 4.20e4.30 (m, 3H), 6.90 (d, J¼7.82 Hz, 1H), 7.08e7.20
(m, 5H), 7.28 (d, J¼7.39 Hz, 1H), 7.36e7.39 (m, 1H); 13C NMR (CDCl3,
A stirred solution of catalyst 3 (0.01 mmol) and 2-oxindole-3-
carboxylate esters 1 (0.20 mmol) in CH2Cl2 (1.0 mL) was cooled to
ꢀ35 ꢁC and N-substituted maleimides 2 (0.2 mmol) were added at
the same temperature. The reaction mixture was stirred at ꢀ35 ꢁC
for the time indicated in Tables 3 and 4. The reaction solution was
concentrated in vacuo. The crude product was purified by column
chromatography on silica gel (eluent PE/EtOAc¼5:1) to afford pure
products 4.
75 Hz)
d 13.8, 26.7, 31.4, 44.2, 58.8, 62.8, 108.9, 116.0, 116.3, 123.5,
124.1, 124.9, 128.3, 130.0, 144.1, 160.5, 163.8, 166.9, 171.4, 174.9.
HRMS (ESI) calcd for C22H19FN2NaO5 [MþNa]þ: 433.1176; found:
433.1186.
4.2.5. Ethyl (3S)-3-[(3S)-1-(4-chlorophenyl)-2,5-dioxopyrrolidin-3-
yl]-1-methyl-2-oxo-2,3-dihydro-1H-indole-3-carboxylate
(4e). Colorless solid; 99% yield (dr¼10.1:1, 74% ee for the major
diastereomer); HPLC conditions: Chiralcel AD-H column, hexane/i-
PrOH¼50:50, flow rate 0.6 mL/min, UV detection at 220 nm,
retention time: major diastereomer: 21.57 min (major) and
52.46 min (minor), minor diastereomer: 33.22 min (major) and
4.2.1. Ethyl (3S)-3-[(3S)-2,5-dioxo-1-phenylpyrrolidin-3-yl]-1-
methyl-2-oxo-2,3-dihydro-1H-indole-3-carboxylate
(4a). White
solid; 93% yield (dr¼9.0:1, 75% ee for the major diastereomer);
HPLC conditions: Chiralcel AD-H column, hexane/i-PrOH¼50:50,
flow rate 0.6 mL/min, UV detection at 220 nm, retention time:
major diastereomer: 16.05 min (major) and 44.92 min (minor),
minor diastereomer: 28.06 min (major) and 34.36 min (minor). 1H
50.46 min (minor). 1H NMR (CDCl3, 300 MHz)
d
1.22 (t, J¼7.14 Hz,
3H), 2.66 (dd, J¼5.88, 18.21 Hz, 1H), 3.04 (dd, J¼9.30, 18.09 Hz, 1H),
3.23 (s, 3H), 4.20e4.29 (m, 3H), 6.89 (d, J¼7.80 Hz, 1H), 7.09e7.16
(m, 3H), 7.27 (d, J¼7.56 Hz, 1H), 7.39 (d, J¼7.17 Hz, 3H); 13C NMR
NMR (CDCl3, 300 MHz)
d
1.23 (t, J¼7.12 Hz, 3H), 2.66 (dd, J¼6.12,
18.21 Hz, 1H), 3.05 (dd, J¼9.39, 18.17 Hz, 1H), 3.23 (s, 3H), 4.20e4.32
(m, 3H), 6.90 (d, J¼7.83 Hz, 1H), 7.12e7.20 (m, 3H), 7.29e7.45 (m,
(CDCl3, 75 Hz) d 13.8, 26.7, 31.6, 44.2, 58.8, 62.8, 108.9, 123.5, 124.1,
124.8, 127.6, 127.8, 129.3, 129.8, 134.4, 144.1, 166.9, 171.4, 173.7, 174.7.
HRMS (ESI) calcd for C22H19ClN2NaO5 [MþNa]þ: 449.0880; found:
449.0872.
5H); 13C NMR (CDCl3, 75 Hz)
d 13.8, 26.7, 31.4, 44.3, 58.9, 62.7, 108.9,
123.5, 124.8, 126.4, 128.7, 129.0, 129.1, 129.9, 131.4, 144.1, 166.9,
171.4, 174.0, 174.9; HRMS (ESI) calcd for C22H20N2NaO5 [MþNa]þ:
415.1253; found: 415.1270.
4.2.6. Ethyl (3S)-1-methyl-3-[(3S)-1-(4-nitrophenyl)-2,5-
dioxopyrrolidin-3-yl]-2-oxo-2,3-dihydro-1H-indole-3-carboxylate
(4f). Colorless solid; 99% yield (dr¼7.3:1, 63% ee for the major di-
astereomer); HPLC conditions: Chiralcel AD-H column, hexane/i-
PrOH¼50:50, flow rate 0.6 mL/min, UV detection at 220 nm,
retention time: major diastereomer: 34.53 min (major) and
66.75 min (minor), minor diastereomer: 41.32 min (major) and
4.2.2. Ethyl (3S)-1-methyl-3-[(3S)-1-(4-methylphenyl)-2,5-
dioxopyrrolidin-3-yl]-2-oxo-2,3-dihydro-1H-indole-3-carboxylate
(4b). White solid; 99% yield (dr¼8.1:1, 77% ee for the major di-
astereomer); HPLC conditions: Chiralcel AD-H column, hexane/i-
PrOH¼50:50, flow rate 0.6 mL/min, UV detection at 220 nm, re-
tention time: major diastereomer: 18.10 min (major) and 37.92 min
(minor), minor diastereomer: 26.42 min (major) and 30.08 min
89.88 min (minor). 1H NMR (CDCl3, 300 MHz)
d
1.24 (t, J¼7.22 Hz,
3H), 2.86 (dd, J¼6.17, 18.26 Hz, 1H), 3.15 (dd, J¼9.42, 18.30 Hz, 1H),
3.23 (s, 3H), 4.19e4.31 (m, 3H), 6.91 (d, J¼7.82 Hz, 1H), 7.12 (t,
J¼7.59 Hz, 1H), 7.28 (d, J¼7.49 Hz, 1H), 7.39 (t, J¼7.78 Hz, 1H), 7.46
(d, J¼9.00 Hz, 2H), 8.25 (d, J¼9.02 Hz, 2H); 13C NMR (CDCl3, 75 Hz)
(minor). 1H NMR (CDCl3, 300 MHz)
d
1.23 (t, J¼7.24 Hz, 3H), 2.35
(s, 3H), 2.53 (dd, J¼5.92, 17.62 Hz, 1H), 3.01 (dd, J¼8.78, 18.11 Hz,
1H), 3.23 (s, 3H), 4.22e4.32 (m, 3H), 6.89 (d, J¼7.79 Hz, 1H),
7.05e7.15 (m, 2H), 7.23 (d, J¼8.18 Hz, 1H), 7.26e7.35 (m, 2H),
d
13.8, 26.7, 31.7, 44.2, 58.7, 62.9, 109.0, 123.4, 123.8, 124.2, 124.9,
7.36e7.38 (m, 2H); 13C NMR (CDCl3, 75 Hz)
d
13.9, 21.2, 26.7, 31.4,
127.2, 130.3, 136.9, 144.0, 146.9, 166.9, 171.4, 173.2, 174.2. HRMS (ESI)
44.3, 59.0, 62.8, 109.0, 123.5, 124.4, 124.9, 126.2, 128.9, 129.8, 130.0,
138.9, 144.2, 166.9, 171.4, 174.2, 175.1. HRMS (ESI) calcd for
calcd for C22H19N3NaO7 [MþNa]þ: 460.1121; found: 460.1124.
C
23H22N2NaO5 [MþNa]þ: 429.1426; found: 429.1432.
4.2.7. Ethyl (3S)-3-[(3S)-1-(3-fluorophenyl)-2,5-dioxopyrrolidin-3-
yl]-1-methyl-2-oxo-2,3-dihydro-1H-indole-3-carboxylate
(4g). White solid; 99% yield (dr¼7.7:1, 70% ee for the major
diastereomer); HPLC conditions: Chiralcel AD-H column, hexane/i-
PrOH¼50:50, flow rate 0.6 mL/min, UV detection at 220 nm,
retention time: major diastereomer: 16.40 min (major) and
36.60 min (minor), minor diastereomer: 23.70 min (major) and
4.2.3. Ethyl (3S)-3-[(3S)-1-(4-methoxyphenyl)-2,5-dioxopyrrolidin-
3-yl]-1-methyl-2-oxo-2,3-dihydro-1H-indole-3-carboxylate
(4c). Colorless solid; 99% yield (dr¼9.0:1, 76% ee for the major di-
astereomer); HPLC conditions: Chiralcel AD-H column, hexane/i-
PrOH¼50:50, flow rate 0.6 mL/min, UV detection at 220 nm, re-
tention time: major diastereomer: 22.17 min (major) and 48.83 min
47.80 min (minor). 1H NMR (CDCl3, 300 MHz)
d
1.22 (t, J¼7.11 Hz,

3482
J. Zhou et al. / Tetrahedron 70 (2014) 3478e3484
3H), 2.72 (dd, J¼6.15, 18.18 Hz, 1H), 3.08 (dd, J¼9.39, 18.21 Hz, 1H),
3.23 (s, 3H), 4.20e4.30 (m, 3H), 6.90 (d, J¼7.80 Hz, 1H), 7.01
(t, J¼8.79 Hz, 1H), 7.10e7.13 (m, 3H), 7.29 (d, J¼7.02 Hz, 1H),
128.5, 129.7, 135.3, 143.9, 166.9, 171.1, 174.7, 175.4; HRMS (ESI) calcd
for C23H22N2NaO5 [MþNa]þ: 429.1426; found: 429.1432.
7.36e7.40 (m, 2H); 13C NMR (CDCl3, 75 Hz)
d
13.8, 26.7, 31.5, 44.2,
4.2.12. Ethyl (3S)-3-[(3S)-1-(diphenylmethyl)-2,5-dioxopyrrolidin-3-
yl]-1-methyl-2-oxo-2,3-dihydro-1H-indole-3-carboxylate
(4l). White solid; 99% yield (dr¼7.1:1, 79% ee for the major
diastereomer); HPLC conditions: Chiralcel IC column, hexane/i-
PrOH¼50:50, flow rate 0.7 mL/min, UV detection at 220 nm,
retention time: major diastereomer: 59.79 min (major) and
15.29 min (minor), minor diastereomer: 32.79 min (major) and
58.8, 62.8, 109.0, 114.4, 115.9, 122.0, 123.2, 123.5, 124.1, 124.9, 130.2,
132.6, 144.1, 160.8, 164.1, 166.9, 171.4, 174.6; HRMS (ESI) calcd for
C
22H19FN2NaO5 [MþNa]þ: 433.1176; found: 433.1181.
4.2.8. Ethyl (3S)-1-methyl-3-[(3S)-1-(3-nitrophenyl)-2,5-
dioxopyrrolidin-3-yl]-1-methyl-2-oxo-2,3-dihydro-1H-indole-3-
carboxylate (4h). Colorless solid; 99% yield (dr¼5.5:1, 80% ee for the
major diastereomer); HPLC conditions: Chiralcel AD-H column,
hexane/i-PrOH¼50:50, flow rate 0.6 mL/min, UV detection at
220 nm, retention time: major diastereomer: 24.73 min (major)
and 39.47 min (minor), minor diastereomer: 27.17 min (major) and
11.63 min (minor). 1H NMR (CDCl3, 300 MHz)
d
1.21 (t, J¼7.11 Hz,
3H), 2.56 (dd, J¼5.82, 18.12 Hz, 1H), 2.94 (dd, J¼9.43, 18.20 Hz, 1H),
3.23 (s, 3H), 4.13 (dd, J¼5.97, 9.35 Hz, 1H), 4.19e4.26 (m, 2H), 6.49
(s, 1H), 6.85 (d, J¼7.79 Hz, 1H), 7.20e7.24 (m, 1H), 7.21e7.34
(m, 12H); 13C NMR (CDCl3, 75 Hz)
d 13.8, 26.6, 31.2, 43.9, 58.4, 58.8,
77.30 min (minor). 1H NMR (CDCl3, 300 MHz)
d
1.23 (t, J¼7.46 Hz,
62.6, 108.7, 123.0, 124.8, 127.7, 128.2, 128.5, 129.8, 130.1, 137.2, 144.0,
167.0, 171.3, 174.6, 175.3. HRMS (ESI) calcd for C29H26N2NaO5
[MþNa]þ: 505.1739; found: 505.1739.
3H), 2.89 (dd, J¼6.00, 18.23 Hz, 1H), 3.16 (dd, J¼9.47, 18.36 Hz, 1H),
3.25 (s, 3H), 4.21e4.32 (m, 3H), 6.93 (d, J¼7.80 Hz, 1H), 7.15
(t, J¼7.50 Hz, 1H), 7.30 (t, J¼7.43 Hz, 1H), 7.39e7.65 (m, 3H),
8.06e8.23 (m, 2H); 13C NMR (CDCl3, 75 Hz)
d
13.9, 26.8, 31.8, 44.3,
4.2.13. Methyl (3S)-3-[(3S)-2,5-dioxo-1-phenylpyrrolidin-3-yl]-1-
58.8, 62.9, 109.1, 121.6, 122.0, 123.3, 123.6, 123.9, 125.1, 129.9, 130.2,
132.3, 144.1, 148.4, 167.0, 171.5, 173.3, 174.3; HRMS (ESI) calcd for
C
methyl-2-oxo-2,3-dihydro-1H-indole-3-carboxylate
(4m). White
solid; 90% yield (dr¼5.7:1, 73% ee for the major diastereomer);
HPLC conditions: Chiralcel AD-H column, hexane/i-PrOH¼50:50,
flow rate 0.6 mL/min, UV detection at 220 nm, retention time:
major diastereomer: 19.10 min (major) and 47.07 min (minor),
minor diastereomer: 28.80 min (major) and 36.23 min (minor). 1H
22H19N3NaO7 [MþNa]þ: 460.1121; found: 460.1137.
4.2.9. Ethyl (3S)-3-[(3S)-1-(2-fluorophenyl)-2,5-dioxopyrrolidin-3-
yl]-1-methyl-2-oxo-2,3-dihydro-1H-indole-3-carboxylate
(4i). White solid; 99% yield (dr¼9.0:1, 83% ee for the major di-
astereomer); HPLC conditions: Chiralcel AD-H column, hexane/i-
PrOH¼50:50, flow rate 0.6 mL/min, UV detection at 220 nm,
retention time: major diastereomer: 15.32 min (major) and
68.97 min (minor), minor diastereomer: 27.13 min (major) and
NMR (CDCl3, 300 MHz)
d
2.60 (dd, J¼6.09, 18.18 Hz, 1H), 3.06
(dd, J¼9.36, 18.15 Hz, 1H), 3.24 (s, 3H), 3.77 (s, 3H), 4.31 (dd, J¼6.15,
9.30 Hz, 1H), 6.91 (d, J¼7.83 Hz, 1H), 7.10e7.19 (m, 3H), 7.30
(t, J¼4.23 Hz, 1H), 7.36e7.46 (m, 4H); 13C NMR (CDCl3, 75 Hz)
d 26.7,
31.3, 44.3, 53.6, 58.7, 108.9, 123.5, 124.4, 126.5, 128.6, 128.7, 129.1,
130.0, 131.4, 144.1, 167.4, 171.2, 173.9, 174.9. HRMS (ESI) calcd for
30.57 min (minor). 1H NMR (CDCl3, 300 MHz)
d
1.22 (t, J¼7.14 Hz,
3H), 2.70 (m, 1H), 3.08 (m, 1H), 3.24 (s, 3H), 4.19e4.37 (m, 3H), 6.90
C
21H18N2NaO5 [MþNa]þ: 401.1113; found: 401.1100.
(d, J¼7.77 Hz, 1H), 7.11e7.26 (m, 4H), 7.31e7.42 (m, 3H); 13C NMR
(CDCl3, 75 Hz)
d
13.8, 26.7, 31.7, 44.5, 58.8, 62.7, 108.9, 116.5, 116.7,
4.2.14. Ethyl (3S)-3-[(3S)-2,5-dioxo-1-phenylpyrrolidin-3-yl]-5-
fluoro-1-methyl-2-oxo-2,3-dihydro-1H-indole-3-carboxylate
(4n). Colorless solid; 90% yield (dr¼8.2:1, 73% ee for the major
diastereomer); HPLC conditions: Chiralcel AD-H column, hexane/i-
PrOH¼50:50, flow rate 0.6 mL/min, UV detection at 220 nm,
retention time: major diastereomer: 16.07 min (major) and
101.91 min (minor), minor diastereomer: 23.14 min (major) and
119.3, 123.5, 124.1, 124.6, 129.1, 130.0, 131.1, 144.1, 155.5, 158.8, 166.9,
173.2, 174.1. HRMS (ESI) calcd for
433.1176; found: 433.1165.
C
22H19FN2NaO5 [MþNa]þ:
4.2.10. Ethyl (3S)-1-methyl-3-[(3S)-1-methyl-2,5-dioxopyrrolidin-3-
yl]-2-oxo-2,3-dihydro-1H-indole-3-carboxylate (4j). Colorless solid;
99% yield (dr¼6.3:1, 82% ee for the major diastereomer); HPLC
conditions: Chiralcel IC column, hexane/i-PrOH¼50:50, flow rate
0.7 mL/min, UV detection at 220 nm, retention time: major
diastereomer: 89.67 min (major) and 31.57 min (minor), minor di-
astereomer: 34.04 min (major) and 28.61 min (minor). 1H NMR
29.71 min (minor). 1H NMR (CDCl3, 300 MHz)
3H), 2.72 (dd, J¼6.12, 18.06 Hz, 1H), 3.09 (dd, J¼9.36, 18.15 Hz, 1H),
3.22 (s, 3H), 4.22e4.30 (m, 3H), 6.81e6.85 (m, 1H), 7.07e7.12
(m, 2H), 7.17e7.26 (m, 2H), 7.37e7.46 (m, 3H); 13C NMR (CDCl3,
d
1.24 (t, J¼7.08 Hz,
75 Hz)
d 13.9, 26.9, 31.4, 44.3, 53.4, 63.0, 109.5, 112.4, 112.7, 116.5,
(CDCl3, 300 MHz)
d
1.21 (t, J¼7.11 Hz, 3H), 2.42 (dd, J¼6.18, 18.03 Hz,
126.4,128.8,129.2,140.1,157.8, 161.0,166.5,171.1,173.8,174.8. HRMS
1H), 2.88 (dd, J¼8.88,18.03 Hz,1H), 2.91 (s, 3H), 3.21 (s, 3H), 4.10 (dd,
J¼6.06, 9.09 Hz, 1H), 4.18e4.25 (m, 2H), 6.88 (d, J¼7.83 Hz, 1H), 7.08
(ESI) calcd for C22H19FN2NaO5 [MþNa]þ: 433.1176; found: 433.1189.
(t, J¼7.44 Hz, 1H), 7.20 (d, J¼6.81 Hz, 1H), 7.37 (t, J¼7.77 Hz, 1H); 13
C
4.2.15. Ethyl (3S)-5-bromo-3-[(3S)-2,5-dioxo-1-phenylpyrrolidin-3-
yl]-1-methyl-2-oxo-2,3-dihydro-1H-indole-3-carboxylate
(4o). White solid; 91% yield (dr¼8.4:1, 71% ee for the major
diastereomer); HPLC conditions: Chiralcel IC column, hexane/i-
PrOH¼50:50, flow rate 0.6 mL/min, UV detection at 220 nm,
retention time: major diastereomer: 51.45 min (major) and
27.99 min (mino3Sr), minor diastereomer: 19.59 min (major) and
NMR (CDCl3, 75 Hz)
d 13.8, 24.8, 26.7, 31.5, 44.1, 58.6, 62.7, 108.8,
123.5,124.1,124.9,129.8,144.0,166.9,171.4,175.0,175.8. HRMS (ESI)
calcd for C17H18N2NaO5 [MþNa]þ: 353.1113; found: 353.1124.
4.2.11. Ethyl (3S)-3-[(3S)-1-benzyl-2,5-dioxopyrrolidin-3-yl]-1-
methyl-2-oxo-2,3-dihydro-1H-indole-3-carboxylate
(4k). White
solid; 99% yield (dr¼6.7:1, 85% ee for the major diastereomer); HPLC
conditions: Chiralcel AD-H column, hexane/i-PrOH¼50:50, flow
rate 0.6 mL/min, UV detection at 220 nm, retention time: major di-
astereomer: 12.19 min (major) and 14.86 min (minor), minor di-
astereomer: 18.54 min (major) and 19.27 min (minor). 1H NMR
39.58 min (minor). 1H NMR (CDCl3, 300 MHz)
d
1.23 (t, J¼7.13 Hz,
3H), 2.70 (dd, J¼5.95, 18.21 Hz, 1H), 3.07(dd, J¼9.37, 18.18 Hz, 1H),
3.20 (s, 3H), 4.21e4.30 (m, 3H), 6.77 (d, J¼8.30 Hz, 1H), 7.17e7.26
(m, 2H), 7.37e7.52 (m, 5H); 13C NMR (CDCl3, 75 Hz)
d 13.9, 26.8,
31.5, 44.2, 58.8, 63.0, 110.3, 116.0, 126.6, 126.9, 127.4, 128.7, 129.2,
131.3, 132.8, 143.2, 166.4, 171.0, 173.8, 174.8; HRMS (ESI) calcd for
(CDCl3, 300 MHz)
d
1.22 (t, J¼7.14 Hz, 3H), 2.41 (dd, J¼5.67, 18.12 Hz,
1H), 2.88 (dd, J¼9.27, 18.21 Hz, 1H), 3.14 (s, 3H), 4.10 (dd, J¼5.79,
C
22H19BrN2NaO5 [MþNa]þ: 493.0375; found: 493.0385.
9.08 Hz,1H), 4.19e4.26 (m, 2H), 4.61 (m, 2H), 6.83e6.91 (m, 2H), 6.99
(d, J¼7.05 Hz, 1H), 7.19e7.34 (m, 6H); 13C NMR (CDCl3, 75 Hz)
d
13.8,
4.2.16. Ethyl (3S)-4-chloro-3-[(3S)-2,5-dioxo-1-phenylpyrrolidin-3-
yl]-1-methyl-2-oxo-2,3-dihydro-1H-indole-3-carboxylate
26.6, 31.7, 42.4, 43.8, 58.8, 62.6,108.6,123.8,124.3,124.5,127.6,127.8,

J. Zhou et al. / Tetrahedron 70 (2014) 3478e3484
3483
(4p). Yellow solid; 92% yield (dr>99:1, 59% ee for the major
diastereomer); HPLC conditions: Chiralcel AD-H column, hexane/i-
PrOH¼50:50, flow rate 0.6 mL/min, UV detection at 220 nm,
retention time: major diastereomer: 14.52 min (major) and
18.85 min (minor), minor diastereomer: 71.18 min (major) and
24.58 min (minor), minor diastereomer: 20.93 min (major) and
26.92 min (minor). 1H NMR (CDCl3, 300 MHz)
0.94e1.01 (m, 6H),
d
1.23 (t, J¼7.11 Hz, 3H), 2.20 (m, 1H), 2.80 (m, 1H), 3.07 (m, 1H), 3.47
(m, 1H), 3.55 (m, 1H), 4.19e4.27 (m, 3H), 6.90 (m, 1H), 7.10 (m, 1H),
7.18 (d, J¼7.11 Hz, 2H), 7.26e7.42 (m, 5H); 13C NMR (CDCl3, 75 Hz)
26.88 min (minor). 1H NMR (CDCl3, 300 MHz)
d
1.18 (t, J¼7.10 Hz,
d 13.8, 19.9, 20.2, 27.1, 31.7, 44.1, 47.9, 59.8, 62.7, 109.4, 123.2, 124.1,
3H), 3.19 (s, 3H), 3.41 (dd, J¼9.35, 18.66 Hz, 1H), 3.82 (dd, J¼5.61,
18.67 Hz, 1H), 4.16e4.27 (m, 2H), 4.53 (dd, J¼5.62, 9.31 Hz, 1H), 6.76
(d, J¼7.77 Hz, 1H), 7.14 (dd, J¼7.21, 25.2 Hz, 1H), 7.26 (d, J¼1.77 Hz,
125.3, 126.6, 128.7, 129.1, 130.0, 131.7, 144.2, 167.7, 171.8, 174.4, 174.9.
HRMS (ESI) calcd for C25H26N2NaO5 [MþNa]þ: 457.1739; found:
457.1729.
2H), 7.30e7.41 (m, 4H); 13C NMR (CDCl3, 75 Hz)
d 13.8, 26.8, 32.5,
40.9, 58.8, 62.7, 107.3, 124.1, 124.4, 126.3, 128.5, 129.0, 129.9, 130.6,
131.5, 145.7, 165.8, 171.4, 174.5, 174.8. HRMS (ESI) calcd for
C
Acknowledgements
22H19ClN2NaO5 [MþNa]þ: 449.0880; found: 449.0890.
This work was supported by the National Natural Science
Foundation of China (_501100001809) (No. 21272230) and Western
Light Talent Culture Project.
4.2.17. Ethyl (3S)-6-bromo-3-[(3S)-2,5-dioxo-1-phenylpyrrolidin-3-
yl]-1-methyl-2-oxo-2,3-dihydro-1H-indole-3-carboxylate
(4q). White solid; 92% yield (dr¼6.5:1, 69% ee for the major
diastereomer); HPLC conditions: Chiralcel AD-H column, hexane/i-
PrOH¼50:50, flow rate 0.6 mL/min, UV detection at 220 nm,
retention time: major diastereomer: 15.17 min (major) and
26.26 min (minor), minor diastereomer: 24.66 min (major) and
Supplementary data
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2014.03.065.
34.62 min (minor). 1H NMR (CDCl3, 300 MHz)
3H), 2.71 (dd, J¼6.09, 18.09 Hz, 1H), 3.08 (dd, J¼9.39, 18.15 Hz, 1H),
3.21 (s, 3H), 4.20e4.28 (m, 3H), 7.05 (s, 1H), 7.05e7.19 (m, 3H),
7.25e7.27 (m, 1H), 7.37e7.43 (m, 3H); 13C NMR (CDCl3, 75 Hz)
d
1.23 (t, J¼7.20 Hz,
References and notes
1. For selected reviews: (a) Lin, H.; Danishefsky, S. J. Angew. Chem., Int. Ed. 2003,
42, 36; (b) Dounay, A. B.; Overman, L. E. Chem. Rev. 2003, 103, 2945; (c) Galli-
ford, C. V.; Scheidt, K. A. Angew. Chem., Int. Ed. 2007, 46, 8748.
d
13.8, 26.8, 32.5, 40.9, 58.8, 62.7, 107.3, 124.1, 124.4, 126.3, 128.5,
2. Selected examples: (a) Kato, Y.; Furutachi, M.; Chen, Z.; Mitsunuma, H.; Mat-
sunaga, S.; Shibasaki, M. J. Am. Chem. Soc. 2009, 131, 9168; (b) Bui, T.; Syed, S.;
Barbas, C. F., III. J. Am. Soc. Chem. 2009, 131, 8758; (c) He, R.; Ding, C.; Maruoka,
K. Angew. Chem., Int. Ed. 2009, 48, 4559; (d) He, R.; Shirakawa, S.; Maruoka, K. J.
Am. Chem. Soc. 2009, 131, 16620; (e) Li, X.; Zhang, B.; Xi, Z.-G.; Luo, S.; Cheng, J.-
P. Adv. Synth. Catal. 2010, 352, 416; (f) Li, X.; Luo, S.; Cheng, J.-P. Chem.dEur. J.
2010, 16, 14290; (g) Liao, Y.-H.; Liu, X.-L.; Wu, Z.-J.; Cun, L.-F.; Zhang, X.-M.;
Yuan, W.-C. Org. Lett. 2010, 12, 2896; (h) Ding, M.; Zhou, F.; Liu, Y.-L.; Wang, C.-
H.; Zhao, X.-L.; Zhou, J. Chem. Sci. 2011, 2, 2035; (i) Han, Y.-Y.; Wu, Z.-J.; Chen,
W.-B.; Du, X.-L.; Zhang, X.-M.; Yuan, W.-C. Org. Lett. 2011, 13, 5064.
3. Selected examples: (a) Ogawa, S.; Shibata, N.; Inagaki, J.; Nakamura, S.; Toru, T.;
Shiro, M. Angew. Chem., Int. Ed. 2007, 46, 8666; (b) Kobayashi, S.; Kokubo, M.;
Kawasumi, K.; Nagano, T. Chem. Asian. J. 2010, 4, 490; (c) Shen, K.; Liu, X.;
Zheng, K.; Li, W.; Hu, X.; Lin, L.; Feng, X. Chem.dEur. J. 2010, 15, 3736.
4. Selected examples: (a) Tian, X.; Jiang, K.; Peng, J.; Du, W.; Chen, Y.-C. Org. Lett.
2008, 10, 3583; (b) Cheng, L.; Liu, L.; Jia, H.; Wang, D.; Chen, Y.-J. J. Org. Chem.
2009, 74, 4650.
129.0, 129.9, 130.6, 131.5, 145.7, 165.8, 171.4, 174.5, 174.8. HRMS (ESI)
calcd for C22H19BrN2NaO5 [MþNa]þ: 493.0375; found: 493.0385.
4.2.18. Ethyl (3S)-3-[(3S)-2,5-dioxo-1-phenylpyrrolidin-3-yl]-2-oxo-
1-propyl-2,3-dihydro-1H-indole-3-carboxylate (4r). White solid;
82% yield (dr¼2.33:1, 58% ee for the major diastereomer); HPLC
conditions: Chiralcel AD-H column, hexane/i-PrOH¼50:50, flow
rate 0.6 mL/min, UV detection at 220 nm, retention time: major
diastereomer: 15.37 min (major) and 26.82 min (minor), minor
diastereomer: 23.29 min (major) and 31.16 min (minor). 1H NMR
(CDCl3, 300 MHz)
d 0.92e1.00 (m, 3H), 1.18e1.26 (m, 3H), 1.71
(m, 2H), 2.40 (m, 1H), 3.10 (m, 1H), 3.69 (t, J¼7.15 Hz, 2H), 4.20e4.31
(m, 3H), 6.90 (d, J¼7.75 Hz, 1H), 7.08e7.10 (m, 1H), 7.15e7.20
5. Selected examples: (a) Trost, B. M.; Frederiksen, M. U. Angew. Chem., Int. Ed.
2005, 44, 308; (b) Trost, B. M.; Zhang, Y. J. Am. Chem. Soc. 2007, 129, 14548; (c)
Cui, H.-L.; Peng, J.; Feng, X.; Du, W.; Jiang, K.; Chen, Y.-C. Chem.dEur. J. 2009, 15,
1574.
6. Bui, T.; Candeias, N. R.; Barbas, C. F., III. J. Am. Chem. Soc. 2010, 132, 5574.
7. Zhou, F.; Liu, Y.-L.; Zhou, J. Adv. Synth. Catal. 2010, 352, 1381.
(m, 2H), 7.30e7.45 (m, 5H); 13C NMR (CDCl3, 75 Hz)
d 11.2,13.8, 20.6,
31.7, 42.0, 44.1, 58.8, 62.7, 109.1, 123.2, 124.3, 125.3, 126.6, 128.8,
130.1, 131.5, 143.7, 143.9, 167.1, 171.5, 174.1, 174.7. HRMS (ESI) calcd
for C24H24N2NaO5 [MþNa]þ: 443.1583; found: 443.1567.
8. For recently selected examples of maleimides used in organic synthesis: (a)
Cabrera, S.; Arrayas, R. G.; Carretero, J. C. J. Am. Chem. Soc. 2005, 127, 16394; (b)
Shen, J.; Nguyen, T. T.; Goh, Y.-P.; Ye, W.; Fu, X.; Xu, J.; Tan, C.-H. J. Am. Chem. Soc.
2006, 128, 13692; (c) Zu, L.; Xie, H.; Li, H.; Wang, J.; Jiang, W.; Wang, W. Adv.
4.2.19. Ethyl (3S)-3-[(3S)-2,5-dioxo-1-phenylpyrrolidin-3-yl]-2-oxo-
1-(prop-2-en-1-yl)-2,3-dihydro-1H-indole-3-carboxylate
(4s). White solid; 90% yield (dr¼3.3:1, 63% ee for the major
diastereomer); HPLC conditions: Chiralcel AD-H column, hexane/i-
PrOH¼50:50, flow rate 0.6 mL/min, UV detection at 220 nm,
retention time: major diastereomer: 15.28 min (major) and
27.42 min (minor), minor diastereomer: 36.85 min (major) and
ꢀ
Synth. Catal. 2007, 349, 1882; (d) Najera, C.; Retamosa, M. G.; Sansano, J. M. Org.
Lett. 2007, 9, 4025; (e) Soh, J. Y.-T.; Tan, C.-H. J. Am. Chem. Soc. 2009, 131, 6904.
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Chem. Commun. 2012, 5124.
10. (a) Wang, C.; Yang, X.-N.; Enders, D. Chem.dEur. J. 2012, 18, 4832; (b) Yang, X.-
N.; Wang, C.; Ni, Q.-J.; Enders, D. Synthesis 2012, 44, 2601.
11. Chen, X.-J.; Zhu, W.; Qian, W.-K.; Feng, E.-J.; Zhou, Y.; Wang, J.-F.; Jiang, H.-L.;
29.52 min (minor). 1H NMR (CDCl3, 300 MHz)
d
1.24 (t, J¼7.11 Hz,
Yao, Z.-J.; Liu, H. Adv. Synth. Catal. 2012, 354, 2151.
3H), 2.79 (dd, J¼6.09, 18.26 Hz, 1H), 3.08 (dd, J¼9.29, 18.15 Hz, 1H),
4.20e4.35 (m, 5H), 5.17e5.27 (m, 2H), 5.80 (m, 1H), 6.87
(d, J¼7.77 Hz, 1H), 7.08e7.20 (m, 3H), 7.31e7.42 (m, 5H); 13C NMR
12. (a) Bai, J.-F.; Peng, L.; Wang, L.-L.; Wang, L.-X.; Xu, X.-Y. Tetrahedron 2010, 66,
8928; (b) Bai, J.-F.; Xu, X.-Y.; Huang, Q.-C.; Peng, L.; Wang, L.-X. Tetrahedron Lett.
2010, 51, 2803; (c) Bai, J.-F.; Wang, L.-L.; Peng, L.; Guo, Y.-L.; Ming, J.-N.; Wang,
F.-Y.; Xu, X.-Y.; Wang, L.-X. Eur. J. Org. Chem. 2011, 23, 4472; (d) Bai, J.-F.; Wang,
L.-L.; Peng, L.; Guo, Y.-L.; Jia, L.-N.; Tian, F.; He, G.-Y.; Xu, X.-Y.; Wang, L.-X. J. Org.
Chem. 2012, 77, 2947.
13. (a) Wang, L.-L.; Peng, L.; Bai, J.-F.; Huang, Q.-C.; Xu, X.-Y.; Wang, L.-X. Chem.
Commun. 2010, 8064; (b) Wang, L.-L.; Bai, J.-F.; Peng, L.; Qi, L.-W.; Jia, L.-N.; Guo,
Y.-L.; Luo, X.-Y.; Xu, X.-Y.; Wang, L.-X. Chem. Commun. 2012, 5175; (c) Wang, L.-
L.; Peng, L.; Bai, J.-F.; Jia, L.-N.; Luo, X.-Y.; Huang, Q.-C.; Xu, X.-Y.; Wang, L.-X.
Chem. Commun. 2011, 5593.
14. (a) Fu, J.-Y.; Yang, Q.-C.; Wang, Q.-L.; Ming, J.-N.; Wang, F.-Y.; Xu, X.-Y.; Wang, L.-
X. J. Org. Chem. 2011, 76, 4661; (b) Peng, L.; Wang, L.-L.; Bai, J.-F.; Jia, L.-N.; Guo,
Y.-L.; Luo, X.-Y.; Wang, F.-Y.; Xu, X.-Y.; Wang, L.-X. Org. Biomol. Chem. 2011, 9,
4774; (c) Jia, L.-N.; Peng, L.; Wang, L.-L.; Bai, J.-F.; Fu, J.-Y.; Huang, Q.-C.; Xu, X.-
Y.; Wang, L.-X. Lett. Org. Chem. 2011, 8, 352; (d) Guo, Y.-L.; Bai, J.-F.; Peng, L.;
Wang, L.-L.; Jia, L.-N.; Luo, X.-Y.; Tian, F.; Xu, X.-Y.; Wang, L.-X. J. Org. Chem. 2012,
77, 8338.
(CDCl3, 75 Hz)
d 13.8, 31.5, 42.5, 44.1, 58.8, 62.7, 109.8, 117.8, 123.3,
124.1,125.1,126.5,128.6,129.0,130.0,130.5,131.5, 143.5,167.0,171.3,
174.3, 174.8. HRMS (ESI) calcd for
441.1426; found: 441.1402.
C
24H22N2NaO5 [MþNa]þ:
4.2.20. Ethyl (3S)-1-(butan-2-yl)-3-[(3S)-2,5-dioxo-1-
phenylpyrrolidin-3-yl]-2-oxo-2,3-dihydro-1H-indole-3-carboxylate
(4t). White solid; 51% yield (dr¼1.3:1, 41% ee for the major
diastereomer); HPLC conditions: Chiralcel AD-H column, hexane/i-
PrOH¼50:50, flow rate 0.6 mL/min, UV detection at 220 nm,
retention time: major diastereomer: 13.68 min (major) and

3484
J. Zhou et al. / Tetrahedron 70 (2014) 3478e3484
15. See the Supplementary data for details of crystallographic data and the CCDC
number is 978474.
17. Schultz, A. G.; Hagmann, W. K. J. Org. Chem. 1978, 43, 4231; Brown, D. S.; Elliott,
M. C.; Moody, C. J.; Mowlem, T. J.; Marino, J. P., Jr.; Padwa, A. J. Org. Chem. 1994,
16. (a) Radul, O. M.; Zhungietu, G. I.; Rekhter, M. A.; Bukhanyuk, S. M. Khim. Ge-
terotsikl. Soedin. 1983, 3, 353; (b) Shimazawa, R.; Kuriyama, M.; Shirai, R. Bioorg.
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59, 2447.
18. Cava, M. P.; Deana, A. A.; Muth, K.; Mitchell, M. J. Org. Synth. 1937, 5, 944 1961,
41, 93.