Squaramide-catalyzed diastereo- and enantioselective Michael addition of 3-substituted oxindoles to nitroalkenes

Article abstract of DOI:10.1016/j.tetasy.2012.06.018

An efficient diastereo- and enantioselective Michael addition of 3-substituted oxindoles onto nitroalkenes catalyzed by a bifunctional chiral squaramide catalyst has been developed. This organocatalytic reaction with 2 mol % of catalyst proceeded smoothly

Full text of DOI:10.1016/j.tetasy.2012.06.018

Tetrahedron: Asymmetry 23 (2012) 972–980
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Squaramide-catalyzed diastereo- and enantioselective Michael addition
of 3-substituted oxindoles to nitroalkenes
⇑
Wen Yang, Jingsi Wang, Da-Ming Du
School of Chemical Engineering and Environment, Beijing Institute of Technology, Beijing 100081, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 10 May 2012
Accepted 25 June 2012
An efficient diastereo- and enantioselective Michael addition of 3-substituted oxindoles onto nitroal-
kenes catalyzed by a bifunctional chiral squaramide catalyst has been developed. This organocatalytic
reaction with 2 mol % of catalyst proceeded smoothly to afford 3,3-disubstituted oxindoles in high yields
with good diastereoselectivities and enantioselectivities (up to 98:2 dr, 88% ee).
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
dine-derived phosphoramide-catalyzed highly enantioselective
Michael addition of unprotected 3-substituted oxindoles to nitroal-
Hydrogen bonding as an activating force is widespread in
organocatalysis.1 As a novel type of hydrogen-bonding donor
organocatalyst, chiral squaramide is being increasingly utilized.2
After the pioneering work reported by Rawal, many chiral squara-
mide catalysts have been developed and successfully applied in
various asymmetric reactions.3 In recent years, our group has also
conducted research in this area.4 Oxindoles, especially those with a
quaternary stereocenter at the 3-position, are important structural
motifs in numerous biologically and pharmaceutically active natu-
ral alkaloids.5 In this context, various catalytic enantioselective ap-
proaches to oxindoles have been developed.6 As a continuation of
research on asymmetric catalysis using squaramide catalysts, we
attempted to develop a squaramide-catalyzed asymmetric Michael
addition of 3-substituted oxindoles to nitroalkenes, which would
provide straightforward access to synthetically useful b-aminoox-
indoles bearing adjacent quaternary–tertiary stereocenters. To
date, several efficient catalytic enantioselective methods to per-
form this reaction have been reported.7 Barbas III et al. first re-
ported the highly asymmetric Michael addition of N-Boc
protected 3-alkyloxindoles to nitroalkenes catalyzed by chiral thio-
ureas,7a while Shibasaki et al. independently developed efficient
homodinuclear Mn(III)2–Schiff base complexes to promote this
reaction.7b In the same year, Maruoka described chiral quaternary
ammonium salts for the Michael addition of N-Boc protected 3-
aryloxindoles to nitroalkenes in a water-rich solvent.7c Subse-
quently, Cheng et al. reported the addition of 3-methyl-N-pheny-
loxindole to nitroalkenes catalyzed by a simple alkyl-substituted
bifunctional thiourea,7d and Yuan developed a chiral Ni(OAc)2–dia-
mine complex catalyst for 3-alkyloxindoles bearing an N-carbonyl
group.7e Impressively, Zhou and co-workers reported a cinchoni-
kenes with a wide scope toward substrates.7f During the prepara-
tion of this manuscript, Enders et al. reported the asymmetric
Michael addition of N-Boc protected oxindoles to nitroalkenes cat-
alyzed by a chiral secondary amine.7g Despite these achievements,
the development of other new, efficient catalytic systems with low
catalyst loading is still needed. Herein we report the asymmetric
Michael addition of 3-substituted oxindoles to nitroalkenes cata-
lyzed by chiral squaramide catalysts.
2. Results and discussion
Initially, 5 mol % squaramide catalyst I was employed to pro-
mote the Michael addition of oxindole 1a with b-nitrostyrene 2a
in CH2Cl2 at ꢀ20 °C. The reaction proceeded well for 12 h to furnish
the corresponding adduct 3aa in 90% yield with 80% ee. Encouraged
by the promising result, we prepared a small library of squaramide
catalysts IꢀIX (Fig. 1) and evaluated their catalytic performance in
this Michael addition. As shown in Table 1, all of squaramide cata-
lysts screened could promote the reaction efficiently. Squaramide II
with 4-CF3 substitution on the aromatic ring gave comparable dia-
stereoselectivity but lower enantioselectivity (Table 1, entry 2).
When squaramides III and IV bearing a piperidinyl group were
examined, better enantioselectivities (84% ee and 85% ee, respec-
tively) were obtained (Table 1, entries 3 and 4). Both squaramides
V and VI derived from cinchona alkaloid only gave moderate
enantioselectivities (Table 1, entries 5 and 6). Subsequently, three
C2-symmetric squaramides VIIꢀIX were tested, but no obviously
superior result was obtained (Table 1, entries 7ꢀ9). It should be
noted that quinine/hydroquinine-derived squaramides VIII and IX
slightly improved enantioselectivity but decreased diastereoselec-
tivity. Based on a comprehensive consideration of yield, enantiose-
lectivity, and diastereoselectivity, squaramide III was selected as
the best catalyst for the optimization of reaction conditions.
⇑
Corresponding author. Tel./fax: +86 10 68914985.
E-mail address: dudm@bit.edu.cn (D.-M. Du).
0957-4166/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2012.06.018

W. Yang et al. / Tetrahedron: Asymmetry 23 (2012) 972–980
973
O
O
O
O
Ar
N
H
N
H
Ar
N
H
N
H
N
N
I: Ar = 3,5-(CF3)2C6H3
II: Ar = 4-CF3C6H4
III: Ar = 3,5-(CF3)2C6H3
IV: Ar = 4-CF3C6H4
O
O
O
O
H
Ar
Ar
N
H
N
H
HN
N
H
HN
N
OMe
R
OMe
N
N
VI: Ar = 3,5-(CF3)2C6H3
V: Ar = 3,5-(CF3)2C6H3
O
O
O
O
R
H
N
N
N
NH
HN
N
H
N
H
H
N
N
OMe
MeO
N
VIII: R = vinyl
IX: R = ethyl
VII
Figure 1. Squaramide catalysts IꢀIX.
Table 1
Screening of squaramide catalystsa
Ph
Me
Me
∗
NO2
5 mol % I-IX
CH2Cl2, -20 oC, 12 h
∗
NO2
O
O
+
Ph
N
N
Boc
Boc
2a
1a
3aa
Entry
Catalyst
Yieldb (%)
drc
eed (%)
1
2
3
4
5
6
7
8
9
I
II
90
95
98
93
94
88
90
95
94
98:2
96:4
97:3
95:5
95:5
96:4
92:8
86:14
83:17
80
68
84
85
66
III
IV
V
VI
VII
VIII
IX
ꢀ58
80
86
89
a
b
c
Reactions were carried out with oxindole 1a (0.2 mmol) and b-nitrostyrene 2a (0.2 mmol) in CH2Cl2 (0.5 mL).
Isolated yield after column chromatography purification.
Determined by chiral HPLC analysis.
d
Enantiomeric excess for the major diastereomer was determined by chiral HPLC analysis.
With the optimal catalyst in hand, we investigated several reac-
tion parameters involving solvent, catalyst loading, and tempera-
ture for the optimal conditions. The results are summarized in
Table 2. The solvent screening identified chloroform as the best
reaction medium. Variation of the solvent had a limited effect on
the process. The common solvents all gave the desired adduct

974
W. Yang et al. / Tetrahedron: Asymmetry 23 (2012) 972–980
Table 2
Optimization of the reaction conditionsa
Ph
Me
Me
NO2
NO2
III
solvent
O
O
Ph
+
N
N
Boc
Boc
2a
1a
3aa
Entry
Solvent
Loading
Temp (°C)
Time (h)
Yieldb (%)
drc
eed,e (%)
1
2
3
4
5
6
7
8
CH2Cl2
THF
PhMe
5
5
5
5
5
5
10
2
1
2
ꢀ20
ꢀ20
ꢀ20
ꢀ20
ꢀ20
ꢀ20
ꢀ20
ꢀ20
ꢀ20
ꢀ40
rt
12
12
12
12
12
12
12
12
12
36
4
98
98
96
92
99
94
98
97
78
81
93
91
97:3
98:2
96:4
94:6
97:3
97:3
98:2
98:2
94:6
92:8
58:42
93:7
84
78
77
84
85
83
85
86
83
80
22
80
MeOH
CHCl3
ClCH2CH2Cl
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
9
10
11
12
2
2
0
8
a
b
c
Unless noted otherwise, reactions were carried out with oxindole 1a (0.2 mmol) and b-nitrostyrene 2a (0.2 mmol) in solvent (0.5 mL).
Isolated yield after column chromatography purification.
Determined by chiral HPLC analysis.
d
e
Enantiomeric excess for the major diastereomer was determined by chiral HPLC analysis.
The configuration was determined by comparison of the specific rotation with literature data.7a
Table 3
Substrate scope of the catalytic asymmetric Michael addition of oxindoles to nitroalkenesa
R3
R1
R1
R2
R2
NO2
2 mol % III
NO2
O
O
R3
+
CHCl3, -20 oC, 12 h
N
N
Boc
Boc
2a-l
1a-f
3aa-fa
1
2
1
2
1a
1b
: R = Me, R = H; : R = Et, R = H;
1c: R1 = Bn, R2 = H; 1d: R1 = Ph, R2 = H;
1
2
1
2
1e
1f
: R = Me, R = F; : R = Me, R = OMe
Entry
R1
R2
R3
Product
Yieldb (%)
drc
eed,e (%)
1
2
3
4
5
6
7
8
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
OMe
F
Ph 2a
3aa
3ab
3ac
3ad
3ae
3af
3ag
3ah
3ai
3aj
3ak
3al
3ba
3ca
3da
3ea
3fa
97
95
84
95
94
94
90
92
83
86
79
33
97
95
96
96
96
98:2
97:3
97:3
98:2
79:21
87:13
74:26
88:12
90:10
84:16
94:6
86
87
79
88
64
80
85
81
76
70
76
88
87
86
44
84
79
4-MeOC6H4 2b
3,4-(MeO)2 C6H3 2c
4-MeC6H4 2d
4-FC6H4 2e
4-ClC6H4 2f
2-ClC6H4 2g
4-BrC6H4 2h
2-Furanyl 2i
2-Thienyl 2j
2-Phenylethyl 2k
Et 2l
9
10
11
12f
13
14
15
16
17
97:3
Ph 2a
Ph 2a
Ph 2a
Ph 2a
79:21
90:10
87:13
88:12
90:10
Bn
Ph
Me
Me
Ph 2a
a
b
c
d
e
f
Unless noted otherwise, reactions were carried out with oxindole 1 (0.2 mmol) and nitroalkene 2 (0.2 mmol) in CHCl3 (0.5 mL).
Isolated yield after column chromatography purification.
Determined by chiral HPLC analysis.
Enantiomeric excess for the major diastereomer was determined by chiral HPLC analysis.
The configuration was determined by comparison of the specific rotation with literature data7a–c
Reaction was performed at 0 °C for 3 d.
3aa in excellent yields, with high diastereoselectivities and good
enantioselectivities ranging from 77 to 85% (Table 2, entries
1ꢀ6). Subsequently, the effect of catalyst loading was investigated.
When the model reaction was performed with 10 or 2 mol %

W. Yang et al. / Tetrahedron: Asymmetry 23 (2012) 972–980
975
Table 4
Further investigation of substrate scope
Ph
∗
Me
Me
NO2
2 mol % III
NO2
∗
O
O
Ph
+
CHCl3
N
N
R
4a-c
R
2a
5aa-ca
4a: R = H; 4b: R = Ph; 4c: R = CO2Et
Entry
4
T (°C)
Time
Product
Yielda (%)
drb
eeb (%)
1
2
3
4
5
6
4a
4a
4a
4b
4b
4c
ꢀ20
0
rt
0
rt
3 d
5 d
36 h
3 d
24 h
12 h
5aa
5aa
5aa
5ba
5ba
5ca
Trace
45
73
Trace
91
90
—
—
89/85
85/79
—
54/76
91
60:40
61:39
—
73:27
96:4
ꢀ20
a
Isolated yield after column chromatography purification.
Determined by chiral HPLC analysis.
b
squaramide III, the excellent yield and good stereoselectivity were
maintained (Table 2, entries 7 and 8). Reducing the catalyst loading
further to 1 mol % led to a decrease in both the yield and stereose-
lectivity (Table 2, entry 9). However, neither cooling nor heating
the reaction gave a better result (Table 2, entries 10ꢀ12). It is note-
worthy that the reaction proceeded at room temperature with very
low diastereoselectivity and enantioselectivity (58:42 dr, 22% ee).
With the optimal reaction conditions established, the scope of
the asymmetric Michael addition of 3-substituted oxindoles to
nitroalkenes was explored. The results are shown in Table 3. Gen-
erally, a variety of aromatic nitroalkenes 2bꢀh with different sub-
stituents on the phenyl ring reacted smoothly with oxindole 1a to
afford the corresponding adducts in high yields with good to high
diastereoselectivities and enantioselectivities (Table 3, entries
2ꢀ8). The electronic properties of the substituent have an effect
on the diastereoselectivity. The electron-rich substrates gave much
better diastereoselectivities than those bearing electron-with-
drawing groups. When heteroaromatic nitroalkenes 2i and 2j were
used as acceptors, the desired products were obtained with good
yields and diastereoselectivities but lower enantioselectivities (Ta-
ble 3, entries 9 and 10). Aliphatic nitroalkenes 2k and 2l gave good
diastereoselectivities and enantioselectivities, but 2l showed a
much lower reactivity (Table 3, entries 11 and 12). When other
branched aliphatic nitroalkenes (R3 = i-Pr, cyclohexyl) were exam-
ined, no reactions occurred. Oxindoles 1bꢀf with different groups
were also evaluated. Oxindoles 1b and 1c with an ethyl or benzyl
group at the 3-position worked well to give the corresponding ad-
ducts in high yields and with good diastereoselectivities and
enantioselectivities (Table 3, entries 13 and 14). When oxindole
1d with a phenyl group was used, a high yield and good diastere-
oselectivity but low enantioselectivity were observed (Table 3, en-
try 15). The result indicated that this catalytic system is not
suitable for an oxindole with an aryl group at the 3-position to
achieve good enantioselectivity. Oxindoles 1e and 1f with varia-
tions on the aromatic ring gave high yields and good diastereose-
lectivities and enantioselectivities (Table 3, entries 16 and 17).
Further substrate scope with varitions on the 1-position of oxin-
dole was investigated, and the results are shown in Table 4. Unpro-
tected oxindole 4a showed much lower reactivity than Boc-
protected oxindole 1a. The reaction hardly occurred at ꢀ20 °C
but gave a moderate yield at 0 °C for 5 d (Table 4, entries 1 and
2). When the reaction was performed at room temperature, the de-
sired adduct 5aa was obtained in good yield with good enantiose-
lectivities for both diastereomers (85% ee and 79% ee, respectively),
albeit with low diastereoselectivity (Table 4, entry 3). The N-phe-
nyl protected oxindole 4b reacted with b-nitrostyrene 2a at room
temperature to give 5ba in high yield but only moderate diastere-
oselectivity and enantioselectivity (Table 4, entry 5). The results
indicated that a Boc protecting group facilitates the enolization
of oxindole to enhance its reactivity. The reaction of oxindole 4c
CF3
S
F3C
N
H
N
H
N
Ph
X
Me
Me
NO2
2 mol % X
CHCl3, -20 oC, 12 h
NO2
O
O
+
Ph
N
N
Boc
Boc
1a
2
3aa
70% yield, 84:16 dr, 87% ee
Scheme 1. Thiourea-catalyzed Michael addition of oxindole 1a to b-nitrostyrene 2a.

976
W. Yang et al. / Tetrahedron: Asymmetry 23 (2012) 972–980
and b-nitrostyrene 2a proceeded well to afford adduct 5ca in high
yield with high diastereoselectivity and enantioselectivity (Table 4,
entry 6). In addition, a control experiment with the corresponding
thiourea-based catalyst X was performed in order to compare the
differences in the catalytic activity. Under otherwise identical con-
ditions, thiourea X gave the corresponding adduct 3aa in 70% yield
with 84:16 dr and 87% ee. This result demonstrates that the
squaramide gives higher reactivity and diastereoselectivity than
the corresponding thiourea catalyst (see Scheme 1).
Based on the absolute configuration of adduct 3aa, a possible
transition state model is hypothesized and shown in Figure 2.
The squaramide III may act as a bifunctional chiral catalyst. The
squaramide moiety activates nitroalkene 2a through double
hydrogen bonding. Meanwhile, the tertiary amino moiety serves
as a base for the deprotonation of the acidic proton of the oxindole.
In the transition state, the phenyl ring faces away from the cyclo-
hexane ring of the squaramide catalyst, and the bulky Boc protect-
ing group is far from the piperidinyl group. Therefore, the proposed
transition state is favored.7a The oxindole attacks the activated
nitroalkene from the Si-face to afford the (3S,1’R)-configured ad-
duct, which is consistent with the observed result.
or a Bruker AVIII 400 M spectrometer. Chemical shifts are reported
in ppm with the internal TMS signal at 0.0 ppm as a standard. The
data are reported as follows: chemical shift (ppm), and multiplicity
(s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet or
unresolved, br s = broad singlet), coupling constant(s) in Hz, inte-
gration assignment. 13C NMR spectra were recorded at 100 MHz
spectrometer. Infrared spectra were obtained with a Perkin–Elmer
Spectrum One spectrometer. The ESI-MS spectra were obtained
with a Bruker APEX IV mass spectrometer. Optical rotations were
measured with a Krüss P8000 polarimeter at the indicated concen-
tration with units of g/100 mL. The enantiomeric excesses of the
products were determined by chiral HPLC using an Agilent 1200
LC instrument with Daicel Chiralpak columns (IB, IA or AS-H).
The absolute configurations of the known adducts were assigned
by HPLC and specific rotation comparisons with the reported da-
ta;7a–c those of unknown adducts were assigned by analogy.
4.2. Materials
3-Substituted oxindoles 1aꢀf were prepared according to the
literature procedures.8 Racemic samples of 3aaꢀfa and 5aa-ca
were prepared with 10 mol % DBU as the catalyst. The squaramide
catalysts IꢀX were prepared by following the reported
procedures.4a,4b,4f,9,10
F3C
4.3. General procedure for the Michael addition of 3-substituted
oxindoles to nitroalkenes
O
O
A mixture of 3-substituted oxindole 1 (0.2 mmol, 1.0 equiv) and
catalyst III (2 mol %) in chloroform (0.5 mL) was stirred at ꢀ20 °C
for 30 min, after which nitroalkene 2 (0.2 mmol, 1.0 equiv) was
added. After stirring at ꢀ20 °C for 12 h, the reaction mixture was
concentrated and directly purified by silica gel column chromatog-
raphy to afford a mixture of both diastereomers 3. The mixture was
analyzed to determine the diastereoselectivity and enantioselec-
tivity of the reaction by chiral HPLC. The major diastereomer was
then obtained by another column chromatography separation on
silica gel, and used for characterization.
N
H
N
H
O
F3C
N
O
t-BuO
O
H
N
N
O
H
H
Me
Ph
4.3.1. (3S)-tert-Butyl 3-methyl-3-[(1R)-2-nitro-1-phenylethyl]-
2-oxoindoline-1-carboxylate 3aa7e
Figure 2. Proposed transition state model.
The title compound 3aa (the mixture of the major and minor
diastereomer) was obtained according to the general procedure
(76.9 mg, 97% yield). It was analyzed to determine the diastereose-
lectivity and enantioselectivity of the reaction (98:2 dr, 86% ee for
the major diastereomer) by HPLC (Daicel Chiralpak IA and AS-H
column in series, n-hexane/2-propanol = 95:5, flow rate 0.5 mL/
min, detection at 254 nm), major diastereomer: tminor = 33.6 min,
tmajor = 36.4 min; minor diastereomer: tR = 28.0, 30.7 min. The ma-
jor diastereomer was purified by flash chromatography and ob-
3. Conclusion
In conclusion, we have developed an efficient squaramide-cata-
lyzed diastereo- and enantioselective Michael addition of 3-substi-
tuted oxindoles to nitroalkenes. This organocatalytic reaction with
a low catalyst loading (2 mol %) afforded the corresponding ad-
ducts in high yields with good diastereoselectivities and enantiose-
lectivities. This process provides an easy route to chiral
multifunctional oxindole derivatives bearing adjacent quater-
nary-tertiary stereocenters. Further studies on asymmetric reac-
tions catalyzed by squaramides are currently underway in our
laboratory.
tained as a white solid, mp 100ꢀ102 °C, ½a D28
¼ þ27:6 (c 1.63,
ꢁ
CH2Cl2). 1H NMR (400 MHz, CDCl3): d = 7.67 (d, J = 8.0 Hz, 1H,
ArH), 7.31 (t, J = 7.2 Hz, 1H, ArH), 7.18ꢀ7.10 (m, 4H, ArH), 7.03
(d, J = 7.6 Hz, 1H, ArH), 6.82 (d, J = 7.2 Hz, 1H, ArH), 5.04 (dd,
J1 = 12.6 Hz, J2 = 3.8 Hz, 1H, CH2), 4.90 (t, J = 12.0 Hz, 1H, CH),
3.95 (dd, J1 = 10.8 Hz, J2 = 3.6 Hz, 1H, CH2), 1.52 (s, 12 H, CH3) ppm.
4. Experimental
4.3.2. (3S)-tert-Butyl 3-[(1R)-1-(4-methoxyphenyl)-2-nitroethyl]-
3-methyl-2-oxoindoline-1-carboxylate 3ab7b
4.1. General methods
The title compound 3ab (the mixture of the major and minor
diastereomer) was obtained according to the general procedure
(81.0 mg, 95% yield). It was analyzed to determine the diastereose-
lectivity and enantioselectivity of the reaction (97:3 dr, 87% ee for
the major diastereomer) by HPLC (Daicel Chiralpak IB column, n-
hexane/2-propanol = 95:5, flow rate 1.0 mL/min, detection at
254 nm), major diastereomer: tmajor = 11.7 min, tminor = 16.4 min;
Commercially available compounds were used without further
purification, unless otherwise stated. Column chromatography
was carried out with silica gel (200ꢀ300 mesh). Melting points
were measured with an XT-4 melting point apparatus without cor-
rection. 1H NMR spectra were recorded with a Varian Mercury-plus

W. Yang et al. / Tetrahedron: Asymmetry 23 (2012) 972–980
977
minor diastereomer: tR = 9.6 min. The major diastereomer was
purified by flash chromatography and obtained as a colorless oil.
according to the general procedure (78.4 mg, 94% yield). It was
analyzed to determine the diastereoselectivity and enantioselec-
tivity of the reaction (79:21 dr, 64% ee for the major diastereomer)
by HPLC (Daicel Chiralpak IB column, n-hexane/2-propanol = 95:5,
flow rate 1.0 mL/min, detection at 254 nm), major diastereomer:
tmajor = 9.2 min, tminor = 14.0 min; minor diastereomer: tR = 8.2 min.
½
a 2D0
ꢁ
¼ þ6:3 (c 1.08, CH2Cl2). 1H NMR (400 MHz, CDCl3): d = 7.68
(d, J = 8.0 Hz, 1H, ArH), 7.33 (t, J = 7.6 Hz, 1H, ArH), 7.18 (t,
J = 7.2 Hz, 1H, ArH), 7.02 (d, J = 7.2 Hz, 1H, ArH), 6.75 (d,
J = 8.0 Hz, 2H, ArH), 6.66 (d, J = 8.0 Hz, 2H, ArH), 5.00 (dd,
J1 = 12.6 Hz, J2 = 3.8 Hz, 1H), 4.85 (t, J = 12.0 Hz, 1H), 3.90 (dd,
J1 = 11.2 Hz, J2 = 3.6 Hz, 1H), 3.71 (s, 3H, OCH3), 1.53 (s, 9H, CH3),
1.51 (s, 3H, CH3) ppm.
½
a 2D2
ꢁ
¼ þ11:8 (c 0.97, CH2Cl2). 1H NMR (400 MHz, CDCl3): d = 7.68
(d, J = 8.4 Hz, 1H), 7.35 (dt, J1 = 8.0 Hz, J2 = 0.8 Hz, 1H, ArH), 7.21
(dt, J1 = 7.6 Hz, J2 = 0.8 Hz, 1H, ArH), 7.08 (d, J = 7.2 Hz, 1H, ArH),
6.86ꢀ6.77 (m, 4H, ArH), 5.99 (dd, J1 = 12.8 Hz, J2 = 4.4 Hz, 1H,
CH2), 4.85 (t, J = 12.0 Hz, 1H, CH), 3.96 (dd, J1 = 11.6 Hz,
J2 = 4.4 Hz, 1H, CH2), 1.54 (s, 9H, CH3), 1.52 (s, 3H, CH3) ppm. 13sC
4.3.3. (3S)-tert-Butyl 3-[(1R)-1-(3,4-dimethoxyphenyl)-2-nitro-
ethyl]-3-methyl-2-oxoindoline-1-carboxylate 3ac
1
The title compound 3ac (the mixture of the major and minor
diastereomer) was obtained according to the general procedure
(76.7 mg, 84% yield). It was analyzed to determine the diastereose-
lectivity and enantioselectivity of the reaction (97:3 dr, 79% ee for
the major diastereomer) by HPLC (Daicel Chiralpak IB column, n-
hexane/2-propanol = 95:5, flow rate 1.0 mL/min, detection at
254 nm), major diastereomer: tmajor = 19.5 min, tminor = 25.9 min;
minor diastereomer: tR = 15.4 min. The major diastereomer was
purified by flash chromatography and obtained as a yellow foam,
NMR (100 MHz, CDCl3): d = 176.6, 162.5 (d, JC-F = 246.3 Hz),
3
148.3, 139.4, 130.4 (d, JC–F = 8.1 Hz), 129.3, 128.8, 124.5, 123.3,
2
115.3, 115.1(d, JC–F = 21.3 Hz), 84.5, 75.6, 50.9, 50.2, 27.9,
20.8 ppm. IR (KBr):
m 2981, 2933, 1789, 1763, 1734, 1607, 1559,
1511, 1481, 1467, 1372, 1349, 1290, 1252, 1152, 1108, 1008,
961, 840, 757 cmꢀ1. HRMS (ESI): m/z calcd for C22H23FN2NaO5
[M+Na]+ 437.14832, found 437.14906.
4.3.6. (3S)-tert-Butyl 3-[(1R)-1-(4-chlorophenyl)-2-nitroethyl]-
3-methyl-2-oxoindoline-1-carboxylate 3af7b
mp 53ꢀ55 °C. ½a 2D2
ꢁ
¼ þ1:7 (c 2.46, CH2Cl2). 1H NMR (400 MHz,
CDCl3): d = 7.68 (d, J = 8.4 Hz, 1H, ArH), 7.34 (dt, J1 = 8.0 Hz,
J2 = 1.2 Hz, 1H, ArH), 7.20 (t, J = 7.2 Hz, 1H, ArH), 7.10 (d,
J = 7.6 Hz, 1H, ArH), 6.63 (d, J = 8.0 Hz, 1H, ArH), 6.44 (dd,
J1 = 8.4 Hz, J2 = 2.0 Hz, 1H, ArH), 6.18 (d, J = 1.6 Hz, 1H, ArH), 5.03
(dd, J1 = 12.8 Hz, J2 = 4.4 Hz, 1H, CH2), 4.85 (t, J = 12.0 Hz, 1H, CH),
3.92 (dd, J1 = 11.2 Hz, J2 = 4.4 Hz, 1H, CH2), 3.78 (s, 3H, OCH3),
3.58 (s, 3H, OCH3), 1.54 (s, 3H, CH3), 1.52 (s, 9H, CH3) ppm. 13C
NMR (100 MHz, CDCl3): d = 176.8, 148.8, 148.3, 148.2, 139.7,
129.3, 129.0, 126.1, 124.2, 123.3, 121.2, 115.3, 111.2, 110.5, 84.2,
The title compound 3af (the mixture of the major and minor
diastereomer) was obtained according to the general procedure
(81.1 mg, 94% yield). It was analyzed to determine the diastereose-
lectivity and enantioselectivity of the reaction (87:13 dr, 80% ee for
the major diastereomer) by HPLC (Daicel Chiralpak IB column, n-
hexane/2-propanol = 95:5, flow rate 1.0 mL/min, detection at
254 nm), major diastereomer: tmajor = 10.7 min, tminor = 17.7 min;
minor diastereomer: tR = 9.4 min. The major diastereomer was
purified by flash chromatography and obtained as a white solid,
75.7, 55.6, 55.4, 51.2, 50.6, 27.8, 20.7 ppm. IR (KBr):
m
2979,
mp 72ꢀ74 °C. ½a 2D0
ꢁ
¼ þ7:5 (c 1.31, CH2Cl2). 1H NMR (400 MHz,
2936, 2838, 1790, 1765, 1732, 1607, 1593, 1556, 1520, 1481,
1467, 1371, 1350, 1301, 1264, 1151, 1104, 1073, 1027, 1010,
CDCl3): d = 7.68 (d, J = 8.0 Hz, 1H, ArH), 7.35 (t, J = 8.0 Hz, 1H,
ArH), 7.21 (t, J = 7.2 Hz, 1H, ArH), 7.13ꢀ7.08 (m, 2H, ArH), 6.77
(d, J = 8.4 Hz, 2H, ArH), 4.99 (dd, J1 = 12.8 Hz, J2 = 4.0 Hz, 1H, CH2),
4.84 (t, J = 12.0 Hz, 1H, CH), 3.95 (dd, J1 = 11.2 Hz, J2 = 3.6 Hz, 1H,
CH2), 1.54 (s, 9H, CH3), 1.52 (s, 3 H, CH3) ppm.
960, 844, 815, 767, 640 cmꢀ1
C
.
HRMS (ESI): m/z calcd for
24H28N2NaO7 [M+Na]+ 479.17887, found 479.17867.
4.3.4. (3S)-tert-Butyl 3-[(1R)-1-(4-methylphenyl)-2-nitroethyl]-
3-methyl-2-oxoindoline-1-carboxylate 3ad
4.3.7. (3S)-tert-Butyl 3-[(1S)-1-(2-chlorophenyl)-2-nitroethyl]-
3-methyl-2-oxoindoline-1-carboxylate 3ag
The title compound 3ad (the mixture of the major and minor
diastereomer) was obtained according to the general procedure
(80.1 mg, 95% yield). It was analyzed to determine the diastereose-
lectivity and enantioselectivity of the reaction (98:2 dr, 88% ee for
the major diastereomer) by HPLC (Daicel Chiralpak IB column, n-
hexane/2-propanol = 95:5, flow rate 1.0 mL/min, detection at
254 nm), major diastereomer: tmajor = 16.6 min, tminor = 24.6 min;
minor diastereomer: tR = 14.5 min. The major diastereomer was
purified by flash chromatography and obtained as a white solid,
The title compound 3ag (the mixture of the major and minor
diastereomer) was obtained according to the general procedure
(77.3 mg, 90% yield). It was analyzed to determine the diastereose-
lectivity and enantioselectivity of the reaction (74:26 dr, 85% ee for
the major diastereomer) by HPLC (Daicel Chiralpak IA and IB col-
umn in series, n-hexane/2-propanol = 97:3, flow rate 0.5 mL/min,
detection at 254 nm), major diastereomer: tmajor = 30.8 min, tmi-
nor = 38.8 min; minor diastereomer: tR = 32.2, 34.2 min. The major
diastereomer was purified by flash chromatography and obtained
mp 86ꢀ87 °C. ½a 2D2
ꢁ
¼ þ13:0 (c 0.97, CH2Cl2). 1H NMR (400 MHz,
CDCl3): d = 7.69 (d, J = 7.6 Hz, 1H, ArH), 7.33 (t, J = 7.0 Hz, 1H,
ArH), 7.18 (t, J = 6.8 Hz, 1H, ArH), 7.01 (d, J = 6.4 Hz, 1H, ArH),
6.94 (d, J = 6.8 Hz, 2H, ArH), 6.71 (d, J = 7.2 Hz, 2H, ArH), 5.00 (dd,
J1 = 12.6 Hz, J2 = 4.0 Hz, 1H, CH2), 4.86 (t, J = 12.0 Hz, 1H, CH), 3.90
(dd, J1 = 10.8 Hz, J2 = 4.0 Hz, 1H, CH2), 2.23 (s, 3H, CH3), 1.53 (s,
9H, CH3), 1.51 (s, 3H, CH3) ppm. 13C NMR (100 MHz, CDCl3):
d = 176.8, 148.5, 139.5, 138.0, 130.8, 129.3, 129.0, 128.8, 128.6,
124.3, 123.4, 115.2, 84.2, 75.7, 50.9, 50.6, 27.9, 21.0, 20.7 ppm. IR
as a white solid, mp 116ꢀ118 °C. ½a D20
¼ þ40:8 (c 0.74, CH2Cl2).
ꢁ
1H NMR (400 MHz, CDCl3): d = 7.81 (d, J = 8.4 Hz, 1H, ArH),
7.42ꢀ7.33 (m, 3H, ArH), 7.28ꢀ7.22 (m, 2H, ArH), 7.15 (t,
J = 7.6 Hz, 1H, ArH), 6.94 (d, J = 7.6 Hz, 1H, ArH), 4.87 (t,
J = 12.8 Hz, 1H, CH), 4.78ꢀ4.72 (m, 2H, CH2), 1.64 (s, 9H, CH3),
1.39 (s, 3H, CH3) ppm. 13C NMR (100 MHz, CDCl3): d = 176.6,
148.8, 138.9, 136.5, 132.6, 130.4, 130.0, 129.4, 129.1, 128.7,
126.9, 124.9, 123.1, 115.0, 84.9, 75.2, 49.6, 44.5, 28.0, 20.9 ppm.
(KBr):
1467, 1371, 1349, 1300, 1289, 1253, 1153, 1104, 1072, 1108,
961, 844, 825, 766, 680 cmꢀ1
HRMS (ESI): m/z calcd for
23H26N2NaO5 [M+Na]+ 433.17339, found 433.17403.
m
2980, 2932, 1790, 1766, 1732, 1608, 1557, 1515, 1481,
IR (KBr):
1468, 1372, 1348, 1289, 1252, 1151, 1105, 1056, 1037, 1007,
962, 843, 775, 754, 688 cmꢀ1
HRMS (ESI): m/z calcd for
C
22H23ClN2NaO5 [M+Na]+ 453.11877, found 453.11889.
m 2981, 2934, 1790, 1760, 1733, 1607, 1558, 1480,
.
.
C
4.3.5. (3S)-tert-Butyl 3-[(1R)-1-(4-fluorophenyl)-2-nitroethyl]-
3-methyl-2-oxoindoline-1-carboxylate 3ae
4.3.8. (3S)-tert-Butyl 3-[(1R)-1-(4-bromophenyl)-2-nitroethyl]-
3-methyl-2-oxoindoline-1-carboxylate 3ah7b
The title compound 3ae (the mixture of the major and minor
diastereomer) was obtained as a white solid (mp 112ꢀ114 °C)
The title compound 3ah (the mixture of the major and minor
diastereomer) was obtained according to the general procedure

978
W. Yang et al. / Tetrahedron: Asymmetry 23 (2012) 972–980
(87.8 mg, 92% yield). It was analyzed to determine the diastereose-
lectivity and enantioselectivity of the reaction (88:12 dr, 81% ee for
the major diastereomer) by HPLC (Daicel Chiralpak IB column, n-
hexane/2-propanol = 95:5, flow rate 0.5 mL/min, detection at
254 nm), major diastereomer: tmajor = 23.2 min, tminor = 38.3 min;
minor diastereomer: tr = 20.5 min. The major diastereomer was
purified by flash chromatography and obtained as a white solid,
J2 = 7.2 Hz, 1H, CH2), 2.93ꢀ2.87 (m, 1H, CH), 2.66ꢀ2.50 (m, 2H,
CH2), 1.98ꢀ1.89 (m, 1H, CH2), 1.64 (s, 9H, CH3), 1.62ꢀ1.59 (m,
1H, CH2), 1.45 (s, 3H, CH3) ppm. 13C NMR (100 MHz, CDCl3):
d = 177.1, 148.9, 140.7, 139.0, 130.4, 128.9, 128.4, 128.3, 126.2,
124.8, 122.8, 115.3, 84.8, 76.4, 50.1, 44.3, 34.0, 30.8, 28.0,
22.7 ppm. IR (KBr):
m 3027, 2980, 2932, 2872, 1790, 1764, 1733,
1607, 1555, 1481, 1465, 1371, 1348, 1291, 1252, 1152, 1105,
mp 109ꢀ111 °C. ½a D20
ꢁ
¼ þ4:2 (c 1.57, CH2Cl2). 1H NMR (400 MHz,
1006, 963, 843, 753, 701, 679 cmꢀ1. HRMS (ESI): m/z calcd for
CDCl3): d = 7.68 (d, J = 7.6 Hz, 1H, ArH), 7.35 (t, J = 7.2 Hz, 1H,
ArH), 7.28ꢀ7.26 (m, 2H, ArH), 7.21 (t, J = 7.2 Hz, 1H, ArH), 7.09
(d, J = 7.2 Hz, 1H, ArH), 6.71 (d, J = 8.0 Hz, 2H, ArH), 4.98 (dd,
J1 = 12.8 Hz, J2 = 4.0 Hz, 1H, CH2), 4.84 (t, J = 12.0 Hz, 1H, CH),
3.93 (dd, J1 = 11.2 Hz, J2 = 4.0 Hz, 1H, CH2), 1.54 (s, 9H, CH3), 1.52
(s, 3 H, CH3) ppm.
C
24H28NaN2O5 [M+Na]+ 447.18904, found 447.18928.
4.3.12. (3S)-tert-Butyl 3-methyl-3-[(1R)-1-nitromethylpropyl]-
2-oxoindoline-1-carboxylate 3al
The title compound 3al (the mixture of the major and minor
diastereomer) was obtained as a colorless oil according to the gen-
eral procedure (22.7 mg, 33% yield). It was analyzed to determine
the diastereoselectivity and enantioselectivity of the reaction
(97:3 dr, 88% ee for the major diastereomer) by HPLC (Daicel Chir-
alpak IB column, n-hexane/2-propanol = 90:10, flow rate 0.5 mL/
min, detection at 254 nm), major diastereomer: tmajor = 10.1 min,
4.3.9. (3S)-tert-Butyl 3-[(1R)-1-(2-furanyl)-2-nitroethyl]-3-methyl-
2-oxoindoline-1-carboxylate 3ai7b
The title compound 3ai (the mixture of the major and minor
diastereomer) was obtained according to the general procedure
(64.2 mg, 83% yield). It was analyzed to determine the diastereose-
lectivity and enantioselectivity of the reaction (90:10 dr, 76% ee for
the major diastereomer) by HPLC (Daicel Chiralpak IA and IB col-
umn in series, n-hexane/2-propanol = 95:5, flow rate 0.5 mL/min,
detection at 254 nm), major diastereomer: tmajor = 29.0 min, tmi-
nor = 33.6 min; minor diastereomer: tR = 25.8, 28.1 min. The major
diastereomer was purified by flash chromatography and obtained
tminor = 11.3 min; minor diastereomer: tR = 9.3 min. ½a D28
¼ þ43:5
ꢁ
(c 1.13, CH2Cl2). 1H NMR (400 MHz, CDCl3): d = 7.86 (d, J = 8.0 Hz,
1H, ArH), 7.36ꢀ7.32 (m, 1H, ArH), 7.19 (d, J = 8.4 Hz, 2H, ArH),
4.44 (dd, J1 = 13.2 Hz, J2 = 4.8 Hz, 1H, CH2NO2), 4.32 (dd,
J1 = 13.2 Hz, J2 = 7.2 Hz, 1H, CH2NO2), 2.84ꢀ2.77 (m, 1H, CH), 1.65
(s, 9H, CH3), 1.48 (s, 3H, CH3), 1.34ꢀ1.26 (m, 2H, CH2), 0.90 (t,
J = 7.2 Hz, 3H, CH3) ppm. 13C NMR (100 MHz, CDCl3): d = 177.4,
149.0, 139.1, 130.6, 128.8, 124.8, 122.8, 115.3, 84.7, 76.0, 50.3,
as colorless oil. ½a D20
ꢁ
¼ þ48:3 (c 1.27, CH2Cl2). 1H NMR (400 MHz,
46.2, 28.0, 22.7, 21.9, 12.0 ppm. IR (KBr):
m 2977, 2937, 2879,
CDCl3): d = 7.80 (d, J = 8.4 Hz, 1H, ArH), 7.32ꢀ7.27 (m, 2H, ArH),
7.09 (t, J = 7.4 Hz, 1H, ArH), 6.66 (d, J = 7.6 Hz, 1H, ArH), 6.28 (s,
1H, ArH), 6.09 (s, 1H, ArH), 5.10 (dd, J1 = 13.2 Hz, J2 = 3.6 Hz, 1H,
CH2), 4.91 (t, J = 12.2 Hz, 1H, CH), 3.98 (dd, J1 = 11.2 Hz,
J2 = 3.6 Hz, 1H, CH2), 1.64 (s, 9H, CH3), 1.52 (s, 3H, CH3) ppm.
1790, 1762, 1733, 1607, 1556, 1481, 1464, 1371, 1346, 1290,
1251, 1151, 1007, 842, 775, 756 cmꢀ1. HRMS (ESI): m/z calcd for
C
18H24NaN2O5 [M+Na]+ 371.15774, found 371.15769.
4.3.13. (3S)-tert-Butyl 3-ethyl-3-[(1R)-2-nitro-1-phenylethyl]-2-
oxoindoline-1-carboxylate 3ba7a
4.3.10. (3S)-tert-Butyl 3-methyl-3-[(1R)-2-nitro-1-(2-thienyl)-
ethyl]-2-oxoindoline-1-carboxylate 3aj7b
The title compound 3ba (the mixture of the major and minor
diastereomer) was obtained according to the general procedure
(79.7 mg, 97% yield). It was analyzed to determine the diastereose-
lectivity and enantioselectivity of the reaction (79:21 dr, 87% ee for
the major diastereomer) by HPLC (Daicel Chiralpak IB column, n-
hexane/2-propanol = 97:3, flow rate 0.5 mL/min, detection at
254 nm), major diastereomer: tmajor = 18.5 min, tminor = 23.9 min;
minor diastereomer: tR = 15.3, 16.3 min. The major diastereomer
was purified by flash chromatography and obtained as a white so-
The title compound 3aj (the mixture of the major and minor dia-
stereomer) was obtained according to the general procedure
(69.2 mg, 86% yield). It was analyzed to determine the diastereose-
lectivity and enantioselectivity of the reaction (84:16 dr, 70% ee
for the major diastereomer) by HPLC (Daicel Chiralpak IA column,
n-hexane/2-propanol = 97:3, flow rate 0.5 mL/min, detection at
254 nm), major diastereomer: tminor = 21.1 min, tmajor = 22.8 min;
minor diastereomer: tR = 16.5, 17.1 min. The major diastereomer
was purified by flash chromatography and obtained as a colorless
lid, mp 92ꢀ94 °C. ½a D20
ꢁ
¼ þ15:5 (c 1.92, CH2Cl2). 1H NMR (400 MHz,
CDCl3): d = 7.66 (d, J = 8.4 Hz, 1H, ArH), 7.38ꢀ7.27 (m, 2H, ArH),
7.23ꢀ7.16 (m, 2H, ArH), 7.13ꢀ7.05 (m, 2H, ArH), 6.81 (d,
J = 7.2 Hz, 2H, ArH), 4.99 (dd, J1 = 12.8 Hz, J2 = 4.4 Hz, 1H, CH2),
4.88 (t, J = 12.0 Hz, 1H, CH), 3.97 (dd, J1 = 11.2 Hz, J2 = 4.4 Hz, 1H,
CH2), 2.16ꢀ2.07 (m, 1H, CH2), 2.02ꢀ1.93 (m, 1H, CH2), 1.51 (s,
9H, CH3), 0.6 (t, J = 7.2 Hz, 3H, CH3) ppm.
oil. ½a 2D0
ꢁ
¼ þ18:0 (c 1.28, CH2Cl2). 1H NMR (400 MHz, CDCl3): d =
7.76 (d, J = 8.0 Hz, 1H, ArH), 7.35 (t, J = 7.2 Hz, 1H, ArH), 7.20ꢀ7.12
(m, 2H, ArH), 7.00 (d, J = 7.2 Hz, 1H, ArH), 6.83 (d, J = 3.2 Hz, 1H,
ArH), 6.70 (s, 1H, ArH), 5.05 (dd, J1 = 12.8 Hz, J2 = 4.0 Hz, 1H, CH2),
4.80 (t, J = 12.0 Hz, 1H, CH), 4.29 (dd, J1 = 10.8 Hz, J2 = 3.2 Hz, 1H,
CH2), 1.57 (s, 9H, CH3), 1.55 (s, 3H, CH3) ppm.
4.3.14. (3S)-tert-Butyl 3-benzyl-3-[(1R)-2-nitro-1-phenylethyl]-
2-oxoindoline-1-carboxylate 3ca7b
4.3.11. (3S)-tert-Butyl 3-methyl-3-[(1R)-1-nitromethyl-3-phenyl-
propyl]-2-oxoindoline-1-carboxylate 3ak
The title compound 3ca (the mixture of the major and minor
diastereomer) was obtained according to the general procedure
(89.6 mg, 95% yield). It was analyzed to determine the diastereose-
lectivity and enantioselectivity of the reaction (90:10 dr, 86% ee for
the major diastereomer) by HPLC (Daicel Chiralpak IB column, n-
hexane/2-propanol = 97:3, flow rate 0.5 mL/min, detection at
254 nm), major diastereomer: tmajor = 41.1 min, tminor = 42.6 min;
minor diastereomer: tR = 24.0, 25.6 min. The major diastereomer
was purified by flash chromatography and obtained as a colorless
The title compound 3ak (the mixture of the major and minor
diastereomer) was obtained as a colorless oil according to the gen-
eral procedure (67.2 mg, 79% yield). It was analyzed to determine
the diastereoselectivity and enantioselectivity of the reaction
(94:6 dr, 76% ee for the major diastereomer) by HPLC (Daicel Chir-
alpak IB column, n-hexane/2-propanol = 95:5, flow rate 0.5 mL/
min, detection at 254 nm), major diastereomer: tmajor = 15.0 min,
tminor = 16.6 min; minor diastereomer: tR = 12.4, 13.4 min. ½a D20
¼
ꢁ
þ27:2 (c 1.30, CH2Cl2). 1H NMR (400 MHz, CDCl3): d = 7.86 (d,
J = 8.0 Hz, 1H, ArH), 7.35ꢀ7.31 (m, 1H, ArH), 7.25 (t, J = 7.2 Hz,
2H, ArH), 7.20ꢀ7.14 (m, 3H, ArH), 7.10ꢀ7.08 (m, 2H, ArH), 4.45
(dd, J1 = 13.2 Hz, J2 = 4.8 Hz, 1H, CH2), 4.43 (dd, J1 = 13.2 Hz,
oil. ½a 2D0
ꢁ
¼ þ3:0 (c 1.22, CH2Cl2). 1H NMR (400 MHz, CDCl3):
d = 7.44ꢀ7.42 (m, 1H, ArH), 7.30ꢀ7.28 (m, 1H, ArH), 7.25ꢀ7.16
(m, 5H, ArH), 7.05ꢀ6.95 (m, 5H, ArH), 6.75 (d, J = 7.6 Hz, 2H,
ArH), 5.02ꢀ4.95 (m, 2H, CH2), 4.16 (dd, J1 = 9.0 Hz, J2 = 6.6 Hz, 1H

W. Yang et al. / Tetrahedron: Asymmetry 23 (2012) 972–980
979
CH), 3.28 (d, J = 12.8 Hz, 1H, CH2), 3.14 (d, J = 12.8 Hz, 1H, CH2),
1.45 (s, 9H, CH3) ppm.
½
a 2D5
ꢁ
¼ ꢀ27:8 (c 0.80, CH2Cl2). The mixture was analyzed to deter-
mine the diastereoselectivity and enantioselectivity (61:39 dr, 85%
ee for the major diastereomer and 79% ee for the minor diastereo-
mer) of the reaction by chiral HPLC (Daicel Chiralpak IA column, n-
hexane/2-propanol = 95:5, flow rate 1.0 mL/min, detection at
254 nm), major diastereomer: tmajor = 22.6 min, tminor = 25.7 min;
minor diastereomer: tmajor = 18.1 min, tminor = 20.4 min. 1H NMR
(400 MHz, CDCl3): d = 8.57 (s, 1H, NH), 7.27ꢀ7.23 (m, 1H, ArH),
7.20ꢀ7.13 (m, 3H), 7.07ꢀ7.03 (m, 1H, ArH), 6.97ꢀ6.94 (m, 3H,
ArH), 6.83 (d, J = 7.6 Hz, 1H, ArH), 5.06 (dd, J1 = 12.6 Hz,
J2 = 4.4 Hz, 1H), 4.93 (t, J = 12.0 Hz, 1H, CH), 3.93 (dd, J1 = 11.2 Hz,
J2 = 4.4 Hz, 1H, CH2), 1.47 (s, 3H, CH3) ppm.
4.3.15. (3R)-tert-Butyl 3-phenyl-3-[(1R)-2-nitro-1-phenylethyl]-
2-oxoindoline-1-carboxylate 3da7c
The title compound 3da (the mixture of the major and minor
diastereomer) was obtained as a white foam according to the gen-
eral procedure (88.3 mg, 96% yield). It was analyzed to determine
the diastereoselectivity and enantioselectivity of the reaction
(87:13 dr, 44% ee for the major diastereomer) by HPLC (Daicel Chir-
alpak IA column, n-hexane/2-propanol = 98:2, flow rate 0.5 mL/
min, detection at 254 nm), major diastereomer: tmajor = 21.7 min,
tminor = 19.9 min; minor diastereomer: tR = 17.3, 30.9 min.
½
a 2D0
ꢁ
¼ þ64:3 (c 2.11, CH2Cl2). 1H NMR (400 MHz, CDCl3): d = 7.70
4.4.2. 3-Methyl-3-(2-nitro-1-phenylethyl)-1-phenyl-indolin-2-
one 5ba7d
(d, J = 8.0 Hz, 1H, ArH), 7.61 (d, J = 8.4 Hz, 2H, ArH), 7.42ꢀ7.38
(m, 3H, ArH), 7.36ꢀ7.30 (m, 3H, ArH), 7.09ꢀ7.03 (m, 3H, ArH),
6.78 (d, J = 8.0 Hz, 2H, ArH), 4.98ꢀ4.87 (m, 2H, CH2), 4.74 (dd,
J1 = 11.6 Hz, J2 = 1.6 Hz, 1H, CH), 1.44 (s, 9H, CH3) ppm.
According to the general procedure, the reaction was performed
with 3-methyl-1-phenyloxindole 4b (44.7 mg, 0.2 mmol) and b-
nitrostyrene 2a (35.8 mg, 0.24 mmol) at room temperature for
24 h. The mixture was concentrated and directly purified by silica
gel column chromatography to afford a mixture of the major and
minor diastereomer 5ba (68.0 mg, 91% yield). White solid, mp
4.3.16. (3S)-tert-Butyl 5-methoxy-3-methyl-3-[(R)-2-nitro-1-
phenylethyl]-2-oxoindoline-1-carboxylate 3ea7b
112ꢀ114 °C. ½a 2D8
¼ þ5:8 (c 2.11, CH2Cl2). The mixture was ana-
ꢁ
The title compound 3ea (the mixture of the major and minor
diastereomer) was obtained according to the general procedure
(81.9 mg, 96% yield). It was analyzed to determine the diastereose-
lectivity and enantioselectivity of the reaction (88:12 dr, 84% ee for
the major diastereomer) by HPLC (Daicel Chiralpak IB column, n-
hexane/2-propanol = 85:15, flow rate 0.5 mL/min, detection at
254 nm), major diastereomer: tmajor = 13.4 min, tminor = 27.6 min;
minor diastereomer: tR = 11.9 min. The major diastereomer was
purified by flash chromatography and obtained as a white solid,
lyzed to determine the diastereoselectivity and enantioselectivity
(73:27 dr, 54% ee for the major diastereomer and 76% ee for the
minor diastereomer) of the reaction by chiral HPLC (Daicel Chir-
alpak IA column, n-hexane/2-propanol = 85:15, flow rate 1.0 mL/
min, detection at 254 nm), major diastereomer: tmajor = 21.5 min,
tminor = 8.4 min; minor diastereomer: tmajor = 7.0 min, tminor = 11.6 -
min). 1H NMR (400 MHz, CDCl3): d = 7.38ꢀ7.31 (m, 3H, ArH),
7.24ꢀ7.19 (m, 3H, ArH), 7.16ꢀ7.10 (m, 3H, ArH), 6.83 (d,
J = 7.6 Hz, 2H, ArH), 6.75 (d, J = 7.2 Hz, 2H, ArH), 6.55 (d,
J = 7.2 Hz, 1H, ArH), 5.16 (dd, J1 = 12.4 Hz, J2 = 4.8 Hz, 1H, CH2),
4.98 (dd, J1 = 12.4 Hz, J2 = 11.2 Hz, 1H, CH2), 4.09 (dd, J1 = 11.2 Hz,
J2 = 4.8 Hz, 1H, CH), 1.64 (s, 3H) ppm.
mp 139ꢀ140 °C. ½a D28
ꢁ
¼ ꢀ5:1 (c 1.50, CH2Cl2). 1H NMR (400 MHz,
CDCl3): d = 7.62 (d, J = 8.8 Hz, 1H, ArH), 7.23ꢀ7.14 (m, 3H, ArH),
6.89 (d, J = 7.2 Hz, 2H, ArH), 6.83 (dd, J1 = 8.8 Hz, J2 = 2.4 Hz, 1H,
ArH), 6.48 (d, J = 2.4 Hz, 1H, ArH), 5.05 (dd, J1 = 12.8 Hz,
J2 = 4.4 Hz, 1H, CH2), 4.91 (dd, J1 = 12.8 Hz, J2 = 11.2 Hz, 1H, CH2),
3.91 (dd, J1 = 11.2 Hz, J2 = 4.4 Hz, 1H, CH), 3.76 (s, 3H, OCH3), 1.53
(s, 9H, CH3), 1.50 (s, 3H, CH3) ppm.
4.4.3. (3S)-Ethyl 3-methyl-3-[(1R)-2-nitro-1-phenylethyl]-2-
oxoindoline-1-carboxylate 5ca7e
According to the general procedure, the reaction was performed
with ethyl 3-methyl-2-oxoindoline-1-carboxylate 4c (43.8 mg,
0.2 mmol) and b-nitrostyrene 2a (29.8 mg, 0.2 mmol) at ꢀ20 °C
for 12 h. The mixture was concentrated and directly purified by sil-
ica gel column chromatography to afford a mixture of the major
and minor diastereomer 5ca (66.3 mg, 90% yield). White solid,
4.3.17. (3S)-tert-Butyl 5-fluoro-3-methyl-3-[(R)-2-nitro-1-phenyl-
ethyl]-2-oxoindoline-1-carboxylate 3fa7b
The title compound 3fa (the mixture of the major and minor
diastereomer) was obtained according to the general procedure
(79.6 mg, 95% yield). It was analyzed to determine the diastereose-
lectivity and enantioselectivity of the reaction (90:10 dr, 79% ee for
the major diastereomer) by HPLC (Daicel Chiralpak IB column, n-
hexane/2-propanol = 90:10, flow rate 0.8 mL/min, detection at
254 nm), major diastereomer: tmajor = 9.0 min, tminor = 14.1 min;
minor diastereomer: tR = 7.5, 8.1 min. The major diastereomer
was purified by flash chromatography and obtained as a white so-
mp 102ꢀ104 °C. ½a D28
¼ þ18:4 (c 3.06, CH2Cl2). The mixture was
ꢁ
analyzed to determine the diastereoselectivity and enantioselec-
tivity (96:4 dr, 91% ee for the major diastereomer) of the reaction
by chiral HPLC (Daicel Chiralpak IA column, n-hexane/2-propa-
nol = 95:5, flow rate 1.0 mL/min, detection at 254 nm), major
diastereomer: tmajor = 15.2 min, tminor = 12.9 min; minor diastereo-
mer: tR = 9.6 min). 1H NMR (400 MHz, CDCl3): d = 7.76 (d, J =
8.4 Hz, 1H, ArH), 7.34ꢀ7.28 (m, 1H, ArH), 7.20 (t, J = 7.2 Hz, 2H,
ArH), 7.13 (t, J = 7.2 Hz, 2H, ArH), 7.03 (d, J = 7.2 Hz, 1H, ArH),
6.85 (d, J = 7.2 Hz, 2H, ArH), 5.02 (dd, J1 = 12.8 Hz, J2 = 4.4 Hz, 1H,
CH2NO2), 4.91 (dd, J1 = 12.8 Hz, J2 = 11.2 Hz, 1H, CH2NO2), 4.34 (q,
J = 7.2 Hz, 2H, CH2), 3.96 (dd, J1 = 11.2 Hz, J2 = 4.4 Hz, 1H, CH),
1.53 (s, 3H, CH3), 1.35 (t, J = 7.2 Hz, 3H, CH3) ppm.
lid, mp 105ꢀ107 °C. ½a D28
ꢁ
¼ þ28:6 (c 1.52, CH2Cl2). 1H NMR
(400 MHz, CDCl3): d = 7.70ꢀ7.67 (m, 1H, ArH), 7.24ꢀ7.14 (m, 3H,
ArH), 7.02 (dt, J1 = 8.8 Hz, J2 = 2.0 Hz, 1H, Ar), 6.87 (d, J = 7.6 Hz,
2H, Ar), 6.67 (dd, J1 = 8.0 Hz, J2 = 2.4 Hz, 1H, Ar), 5.06 (dd,
J1 = 12.8 Hz, J2 = 4.4 Hz, 1H, CH2), 4.91 (dd, J1 = 12.8 Hz,
J2 = 11.2 Hz, 1H, CH2), 3.93 (dd, J1 = 10.8 Hz, J2 = 4.0 Hz, 1H, CH),
1.53 (s, 9H, CH3), 1.51 (s, 3H, CH3) ppm.
4.4. Further investigation of substrate scope
Acknowledgments
4.4.1. 3-Methyl-3-(2-nitro-1-phenylethyl)indolin-2-one 5aa7f
According to the general procedure, the reaction was performed
with 3-methyl oxindole 4a (58.9 mg, 0.4 mmol) and b-nitrostyrene
2a (59.6 mg, 0.4 mmol) at room temperature for 36 h. The mixture
was concentrated and directly purified by silica gel column chro-
matography to afford a mixture of the major and minor diastereo-
mer 5aa (86.6 mg, 73% yield). White foam, mp 62ꢀ64 °C.
We are grateful for financial support from the National Natural
Science Foundation of China (Grant No. 21072020), the Science and
Technology Innovation Program of Beijing Institute of Technology
(Grant No. 2011CX01008) and the Development Program for Dis-
tinguished Young and Middle-aged Teachers of Beijing Institute
of Technology.

980
W. Yang et al. / Tetrahedron: Asymmetry 23 (2012) 972–980
Catal. 2011, 353, 1241–1246; (c) Yang, W.; Du, D.-M. Chem. Commun. 2011, 47,
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