Axially chiral BINIM and Ni(II)-catalyzed asymmetric chlorination of 3-substituted oxindoles

Article abstract of DOI:10.1016/j.tetasy.2011.06.021

Axially chiral BINIM-Ni(II) complexes are effective catalysts in the asymmetric chlorination of 3-substituted oxindoles and give the corresponding chlorinated adducts in good yields and up to 88% ee.

Full text of DOI:10.1016/j.tetasy.2011.06.021

Tetrahedron: Asymmetry 22 (2011) 1133–1141
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Axially chiral BINIM and Ni(II)-catalyzed asymmetric chlorination
of 3-substituted oxindoles
De Wang a, Jia-Jun Jiang a, Rui Zhang a, Min Shi a,b,
⇑
a Key Laboratory for Advanced Materials and Institute of Fine Chemicals, School of Chemistry & Molecular Engineering, East China University of Science and Technology,
130 Mei Long Lu, Shanghai 200237, China
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Axially chiral BINIM–Ni(II) complexes are effective catalysts in the asymmetric chlorination of 3-substi-
tuted oxindoles and give the corresponding chlorinated adducts in good yields and up to 88% ee.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 24 May 2011
Accepted 15 June 2011
Available online 23 July 2011
1. Introduction
Schiff base ligands L1–L8 were known products, which were pre-
pared according to previously reported procedures.9 Chiral ligands
Recently, the enantioselective electrophilic chlorination of the
-position of carbonyl compounds, such as aldehydes, ketones,
L9–L12 were synthesized according to the procedures shown in
Scheme 1. Their spectroscopic data are included in Section 4.
Initial examinations using N-Boc-protected 3-phenyloxindole
13a and N-chlorosuccinimide (NCS) 14 as the substrates in the pres-
ence of axially chiral ligands L1–L12 (10 mol %) and Ni(ClO4)2ꢀ6H2O
(10 mol %) in dichloromethane (DCM) were aimed at determining
the best BINIM ligand in this reaction system; the results of these
experiments are summarized in Table 1. We found that when using
a
acyl halides, b-ketoesters, or their derivatives, to stereoselectively
construct a tertiary or quaternary stereocenter has attracted much
attention from organic chemists.1–4 In particularly, the enantiose-
lective chlorination and other functionalization methods of 3-
substituted oxindoles have been significantly developed over the
last decade for the synthesis of optically active 3,3-disubstituted
oxindole derivatives,5 since they are important structural motifs
found in a wide array of natural and biologically active molecules.6
For example, the chlorination reaction of 3-aryloxindole has been
developed by Shibata et al., who obtained the corresponding prod-
uct in moderate enantioselectivity using a dbfox-Ph/Ni complex as
the catalyst.7 In 2011, Antilla et al. reported the chiral calcium VA-
POL phosphate mediated asymmetric chlorination of 3-substituted
oxindoles, obtaining the corresponding chlorinated products in
high yields along with up to 99% ee.8 Herein, we report that axially
chiral BINIM–Ni(II) complexes are also effective catalysts in the
asymmetric chlorination of 3-substituted oxindoles to give the
corresponding chlorinated adducts in good yields and up to 88% ee.
DCM as a solvent, the corresponding a-chlorination product 15a was
obtained in moderate to high yields but with low ee values in the
presence of axially chiral ligands L1–L6 at 0 °C; in some cases, no
chiral induction was observed (Table 1, entries 1–6). Using L7 as a
chiral ligand afforded 15a in 85% yield and 43% ee (Table 1, entry
7). We found that using L8, derived from BINAM and quinoline-2-
carbaldehyde, as a chiral ligand produced 15a in 92% yield and 81%
ee (Table 1, entry 8). Since chiral ligand L9 had an ethyl group at
the 8-position of the quinoline-2-carbaldehyde, the corresponding
product 15a was obtained in 79% yield and 25% ee, presumably
due to the steric effect (Table 1, entry 9). Chiral ligands L10–L12,
whichwere derived from H8-BINAMwithquinoline-2-carbaldehyde
combined with an Ni(II) salt, are not effective chiral catalysts in this
reaction, affording 15a in lower ee values (Table 1, entries 10–12).
Having identified the best chiral ligand for this reaction, we
next examined the metal salt and temperature effect on this reac-
tion. As can be seen from Table 2, Ni(ClO4)2ꢀ6H2O or Ni(BF4)2ꢀ6H2O
combined with L8 are effective catalysts in this reaction while the
combination of Zn(OTf)2, Ni(OAc)2, AgOAc, Cu(OAc)2 or CuOTf with
L8 did not give 15a with a good ee value (Table 2, entries 1–7).
Changing the reaction temperature to ꢁ10 °C, ꢁ20 °C, or 20 °C
did not improve the ee of 15a (Table 2, entries 8–10). We also
examined other chlorinating reagents, such as trichloroquinoli-
none in this reaction. However, these did not work as well as
2. Results and discussion
Axially chiral binaphthalenediimine (BINIM) ligands (chiral
Schiff base ligands) L1–L12 were synthesized from the reaction of
commercially available (R)-1,10-binaphthyl-2,20-diamine (bina-
phthalenediamine, BINAM)or H8-BINAMwith a variety of aldehydes
in the presence of 4 Å MS in toluene or alcohol, respectively accord-
ing to the previous literature (Fig. 1). Amongst these ligands, chiral
⇑
Corresponding author.
E-mail address: Mshi@mail.sioc.ac.cn (M. Shi).
0957-4166/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2011.06.021

1134
D. Wang et al. / Tetrahedron: Asymmetry 22 (2011) 1133–1141
R3
R4
N
N
N
R2
R2
N
N
R1
R1
N
L7
R4
R3
L1: R1 = R2 = R3 =R4 = H
N
N
N
N
1
2
3
4
L2:
R = R = Cl, R =R = H
L3: R1 = R4 = Cl, R2 =R3 = H
1
2
3
4
L4:
R = OH, R = R =R = H
L5: R1 = OH, R2 = R3 = Cl, R1 = H
1
3
2
4
L6:
R = OH, R = CH3, R = R = H
L8
Ar
N
N
N
N
N
Et
Et
N
N
Ar
N
L10: Ar = C6H5
L11: Ar = 3,5-(CH3)2C6H3
L12: Ar = 3,5-(CF3)2C6H3
L9
Figure 1. Axially chiral Schiff base ligands L1–L12.
NCS under identical conditions, giving the corresponding product
in 47% yield and 32% ee.
15m, 15n and 15o were obtained in good yields along with low
ee values (7–15% ee), perhaps due to the electronic property of
R1 and R2 (Table 3, entries 12–14). It is plausible that the elimina-
tion and rebounding of the Cl anion can cause racemization, but we
think that the electronic effect plays a more important role in this
reaction because when R1 and R2 are both electron-rich groups, the
ee values decreased significantly. When R2 is an aliphatic group
(R2 = Me), the reaction also proceeded efficiently to afford the
corresponding product 15l in 86% yield and 20% ee (Table 3, entry
11). Changing the N-Boc-protecting group to an N-phenyl or N-
benzyl group provided the corresponding products 15p and 15q
in 47% yield and 52% yield, respectively, with no ee value, thus sug-
gesting that the carbonyl group in the N-Boc-protecting group
plays a significant role in this reaction (Table 4, entries 15 and
16). The spectroscopic data are summarized in Section 4 and their
absolute configurations have been assigned as (R) by comparison of
the sign of the specific rotation with the literature values.7,8
The possible transition state for this asymmetric chlorination of
3-substituted oxindole can be explained as the approach of NCS to-
wards the hexacoordinated Ni(II) complex and 3-substituted oxin-
dole as illustrated in Figure 2. The enolized 3-substituted oxindoles
could react with NCS from the Re face to form the (R)-products in
accordance with the experimental results.
Examination of the solvent effect revealed that in acetonitrile,
the desired product 15a could be obtained in >99% yield along with
85% ee and using other solvents such as DCE, THF, toluene or CHCl3
gave 15a in lower ee values under otherwise identical conditions
(Table 3, entries 1–6). We considered that the protic solvents
may enhance the stability of the transition state of this asymmetric
chlorination and can provide a hydrogen bond from a protic sol-
vent with the substrate, which may cause some unexpected result
for the reaction. Thus, we added 0.1 equiv of tert-butanol,
CF3CH2OH (TFE) or (CF3)2CHOH (HFIP) as an additive into the reac-
tion system using acetonitrile as the solvent. However, we found
that these additives did not improve the reaction outcomes (Ta-
ble 3, entries 7–9). When the addition of NCS was divided into
three portions, the desired product 15a was formed in 90% yield
and 55% ee (Table 3, entry 10).
With the determination of the optimal reaction conditions, the
generality of this L8/Ni(II)-catalyzed asymmetric chlorination is
examined using a variety of N-Boc-protected 3-aryloxindoles 13.
The results are summarized in Table 4. All reactions proceeded
smoothly to give the corresponding products 3 in good yields
and moderate to good ee values under the optimal conditions (Ta-
ble 3). Whether R1 is an electron-donating or -withdrawing group
on electron-rich or -deficient aromatic rings, the reactions pro-
ceeded smoothly to give the corresponding adducts 15b–15k in
good yields and 55–88% ee values, respectively (Table 3, entries
1–10). Only in the cases of N-Boc-protected 3-aryloxindoles 13m,
13n and 13o in which R1 is CH3O, H and CH3, respectively, and
R2 is a para-methylphenyl group, the corresponding adducts
3. Conclusion
In conclusion, axially chiral C2-symmetric BINIM L8 prepared
from BINAM with quinoline-2-carbaldehyde was found to be a rea-
sonably effective chiral ligand for the Ni(II)-promoted asymmetric
chlorination of 3-substituted oxindoles to give the corresponding

D. Wang et al. / Tetrahedron: Asymmetry 22 (2011) 1133–1141
1135
NH2
NH2
N
N
4Å MS
EtOH, reflux
X
X
+
OHC
X
L9: X = Et, yield: 87%
ArB(OH)2 (3.0 equiv)
Br
Ar
Pd(OAc)2 (10 mol %)
dppb (20 mol %)
NH2
NH2
NH2
NH2
Ba(OH)2·8H2O (4.0 equiv)
NBS (2.1 equiv)
THF, 0 oC, 2 h
DME/H2O = 10/1, reflux, 48 h
NH2
Br
NH2
Ar
Ar = C6H5, yield: 81%
yield: 75%
Ar = 3,5-(CH3)2C6H3, yield:
69%
Ar = 3,5-(CF3)2C6H3, yield: 81%
Ar
Ar
N
N
NH2
4Å MS
toluene, reflux
+
OHC
N
N
N
NH2
Ar
Ar
L10: Ar = C6H5, yield: 83%
L11: Ar = 3,5-(CH3)2C6H3, yield: 78%
L12: Ar = 3,5-(CF3)2C6H3, yield: 86%
Scheme 1. Synthesis of ligands L9–L12.
adducts in good yields and moderate to good enantioselectivities.
Efforts are currently underway to elucidate the mechanistic details
of this asymmetric chlorination of 3-substituted oxindoles and to
disclose the exact structure of the active species in this catalytic
system.
essary. Commercially obtained reagents were used without further
purification. All reactions were monitored by TLC with Huanghai
60F254 silica gel coated plates. Flash column chromatography was
carried out using 300–400 mesh silica gel at increased pressure.
All chlorinations were performed under argon using standard
Schlenk techniques. The enantiomeric purities of compounds
15a–q were determined by HPLC analysis using a chiral stationary
phase column [column, Daicel Co. Chiralcel AD, AS, IC, OD and Re-
gis (S,S)-Whelk-O1] and the absolute configuration of the major
enantiomer was assigned according to the sign of the specific rota-
tion. 3-Substituted oxindoles 13a–q were synthesized according to
the previous literature.10
4. Experimental section
4.1. General methods
Melting points were obtained with a Yanagimoto micro melting
point apparatus and are uncorrected. Optical rotations were deter-
mined in a solution of CHCl3 at 20 °C by using a Perkin–Elmer-341
MC polarimeter; [a .
]D-values are given in units of 10ꢁ1 deg cm2 gꢁ1
4.2. Typical procedure for the preparation of ligands L9–L12
1H NMR spectra were recorded on a Bruker AM-300 or Bruker AM-
400 spectrometer for solution in CDCl3 with tetramethylsilane
(TMS) as internal standard; J-values are given in Hertz. 19F spectra
were recorded on a Bruker AM-300 and AM-400 spectrophotome-
ters with complete proton decoupling spectrophotometers. Mass
spectra were recorded by EI, ESI, MALDI and HRMS was measured
on an HP-5989 instrument. Infrared spectra were recorded on a
Ligand L9 was prepared by stirring (R)-BINAM (286 mg,
1.0 mmol), 8-ethylquinoline-2-carbaldehyde (389 mg, 2.1 mmol)
and 4 Å MS (200 mg) in ethanol (30 mL) for 24 h at reflux. The
hot solvent was then removed by filtration, after which an extra
10 mL ethanol were added to wash the filtration cake. The gray so-
lid was redissolved in DCM (20 mL). After stirring for another 0.5 h,
the 4 Å MS were filtered and the solvent was removed from the
flask under reduced pressure to give the crude product. After a sin-
Perkin–Elmer PE-983 spectrometer with absorption in cmꢁ1
Organic solvents used were dried by standard methods when nec-
.

1136
D. Wang et al. / Tetrahedron: Asymmetry 22 (2011) 1133–1141
Table 1
Screening of chiral ligands for the asymmetric chlorination of 3-phenyloxindole 13a
Ph
Ph
Cl
Ni(ClO4)2·6H2O (10 mol %),
L (10 mol %)
O
O
NCS
+
DCM, 4Å MS , 0 oC, 1 h
N
N
Boc
Boc
14
15a
13a
Entrya
Ligand
Yieldb (%)
eec (%)
15a
15a
1
2
3
4
5
6
7
8
9
L1
L2
L3
L4
L5
L6
L7
L8
57
63
99
76
65
79
85
92
79
92
90
90
0
26
20
22
0
16
43
81
25
10
7
L9
10
11
12
L10
L11
L12
7
a
Reaction conditions: 13a (0.1 mmol), 14 (0.12 mmol), Ni(ClO4)2ꢀ6H2O (10 mol %), ligand (10 mol %), DCM (1.0 mL), 4 Å MS
(10 mg), and the reaction was carried out at 0 °C for 1 h.
b
Isolated yield after column chromatography.
Determined by chiral HPLC analysis.
c
Table 2
Examination of the metal salt and temperature effect for the asymmetric chlorination of 3-phenyloxindole 13a
Ph
Ph
Cl
Lewis acid (10 mol %),
L8 (10 mol %)
O
O
NCS
+
DCM, 4Å MS, T, 1 h
N
N
Boc
Boc
14
15a
13a
Entrya
Lewis acid
T (°C)
Yieldb (%)
eec (%)
15a
15a
1
2
3
4
5
Ni(ClO4)2ꢀ6H2O
Zn(OTf)2
Ni(OAc)2
AgOAc
Cu(OAc)2
0
0
0
0
0
92
4
64
85
Trace
74
81
15
17
24
0
6
CuOTf
0
0
7
8
9
10
Ni(BF4)2ꢀ6H2O
Ni(BF4)2ꢀ6H2O
Ni(BF4)2ꢀ6H2O
Ni(BF4)2ꢀ6H2O
0
94
88
80
68
82
81
73
55
20
ꢁ10
ꢁ20
a
Reaction conditions: 13a (0.1 mmol), 14 (0.12 mmol), metal (10 mol %), L8 (10 mol %), DCM (1.0 mL), 4 Å MS (10 mg), and
the reaction was carried out for 1 h.
b
Isolated yield after column chromatography.
Determined by chiral HPLC analysis.
c
gle recrystallization by DCM/petroleum ether to give L9 as a yellow
solid (540 mg, 87% yield).
The precursors of ligands L10–L12 were prepared form (R)-H8-
BINAM according to the literature.11 In the last step, toluene was
used instead of ethanol compared with the preparation of L9. Li-
gands L10–L12 were used directly without recrystallization.
4.2.2. Ligand L2
This is a known compound.9 Yield: (235 mg, 79%). ½a 2D0
¼
ꢂ
þ217:5 (c 0.50, CH2Cl2). 1H NMR (CDCl3, 300 MHz, TMS): d 7.02
(2H, t, J = 7.8 Hz), 7.26–7.48 (12H, m), 7.92 (2H, d, J = 7.8 Hz),
7.98 (2H, d, J = 7.8 Hz), 8.63 (2H, s).
4.2.3. Ligand L3
4.2.1. Ligand L1
This is a known compound.9 Yield: (212 mg, 71%). ½a 2D0
¼
ꢂ
This is a known compound.9 Yield: (90 mg, 39%). ½a 2D0
¼ þ161:8
ꢂ
ꢁ109:5 (c 0.50, CH2Cl2). 1H NMR (CDCl3, 300 MHz, TMS): d 6.99–
7.04 (2H, m), 7.09–7.12 (4H, m), 7.24–7.42 (8H, m), 7.90 (2H, d,
J = 7.8 Hz), 7.99 (2H, d, J = 7.8 Hz), 8.63 (2H, s).
(c 0.50, CH2Cl2). 1H NMR (CDCl3, 300 MHz, TMS): d 7.25–7.31 (8H,
m), 7.34–7.42 (10H, m), 7.90 (2H, d, J = 8.1 Hz), 7.95 (2H, d,
J = 8.1 Hz), 8.18 (2H, s).

D. Wang et al. / Tetrahedron: Asymmetry 22 (2011) 1133–1141
1137
Table 3
Optimization of reaction conditions for the asymmetric chlorination of 3-phenyloxindole 13a
Ph
Ph
Cl
Ni(BF4)2·6H2O (10 mol %),
L8 (10 mol %)
O
O
NCS
+
Solvent, additive (0.1 equiv), 4Å MS,
0 oC, 1 h
N
Boc
N
14
15a
Boc
13a
Entrya
Solvent
Additive
Yieldb (%)
eec (%)
15a
15a
1
2
3
4
5
6
7
8
DCE
THF
—
—
—
—
—
—
59
85
>99
91
76
98
92
92
92
90
51
70
85
30
37
38
75
32
80
55
CH3CN
Toluene
CHCl3
Et2O
CH3CN
CH3CN
CH3CN
CH3CN
tBuOH
TFE
HFIP
—
9
10d
TFE = CH3CH2OH, HFIP = (CF3)2CHOH.
a
Reaction conditions: 13a (0.1 mmol), 14 (0.12 mmol), Ni(BF4)2ꢀ6H2O (10 mol %), L8 (10 mol %), solvent (1.0 mL), additive
(0.1 equiv), 4 Å MS (10 mg) and the reaction was carried out for 1 h.
b
Isolated yield after column chromatography.
Determined by chiral HPLC analysis.
NCS was added for three times.
c
d
Table 4
Scope and limitations of asymmetric chlorination of 3-substituted oxindoles 13
R2
R2
Cl
Ni(BF4)2·6H2O (10 mol %),
R1
R1
L8 (10 mol %)
O
O
NCS
+
CH3CN, 4Å MS, 0 oC, 1 h
N
R3
N
14
R3
15a
13
Entrya
Oxindole 13 (R1/R2/R3)
Yieldb (%)
15
eec (%)
15d
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
13b (CH3/Ph/Boc)
13c (F/Ph/Boc)
15b, 88
15c, 99
15d, 82
15e, 92
15f, 90
15g, 90
15h, 84
15i, 93
15j, 92
15k, 78
15l, 86
15m, 83
15n, 86
15o, 83
15p, 47
15q, 52
67
88
82
74
60
75
72
85
72
52
20
15
7
13d (OCH3/Ph/Boc)
13e (H/p-FC6H4/Boc)
13f (CH3/p-FC6H4/Boc)
13g (F/p-CH3C6H4/Boc)
13h (OCH3/p-FC6H4/Boc)
13i (F/p-CH3C6H4/Boc)
13j (H/m-CH3C6H4/Boc)
13k (H/b-naphthyl/Boc)
13l (H/CH3/Boc)
13m (OCH3/p-CH3C6H4/Boc)
13n (H/p-CH3C6H4/Boc)
13o (CH3/p-CH3C6H4/Boc)
13p (H/Ph/Ph)
7
0
0
13q (H/Ph/Bn)
a
Reaction conditions: 13 (0.1 mmol), 14 (0.12 mmol), Ni(BF4)2ꢀ6H2O (10 mol %), L8 (10 mol %), CH3CN (1.0 mL), 4 Å MS
(10 mg), and the reaction was carried out at 0 °C for 1 h.
b
Isolated yield after column chromatography.
Determined by chiral HPLC analysis.
The absolute configuration of 15 has been assigned as (R)-configuration by comparison of the sign of optical rotation with
c
d
the previous literature.
4.2.4. Ligand L4
4.2.5. Ligand L5
This is a known compound.9 Yield: (212 mg, 80%). ½a 2D0
ꢂ
¼ þ509:2
This is
a
known compound.9 Yield: (160 mg, 51%).
(c 0.50, CH2Cl2). 1H NMR (CDCl3, 300 MHz, TMS): d 12.12 (s, 2H), 8.69
(s, 2H), 8.13 (d, J = 9.2 Hz, 2H), 8.00 (d, J = 8 Hz, 2H), 7.67 (d,
J = 8.8 Hz, 2H), 7.50–7.46 (m, 2H), 7.33–7.27 (m, 4H), 7.23–7.19
(M, 4H), 6.82–6.78 (m, 2H), 6.73 (d, J = 8.0 Hz, 2H).
½
a 2D0
ꢂ
¼ ꢁ549:6 (c 0.50, CH2Cl2). 1H NMR (CDCl3, 300 MHz, TMS): d
7.10 (2H, d, J = 2.4 Hz), 7.17 (2H, d, J = 8.4 Hz), 7.19–7.28 (4H, m),
7.49 (2H, t, J = 5.4 Hz), 7.61 (2H, d, J = 8.1 Hz), 7.98 (2H, d,
J = 8.1 Hz), 8.11 (2H, d, J = 8.1 Hz), 8.56 (2H, s), 12.76 (2H, s).

1138
D. Wang et al. / Tetrahedron: Asymmetry 22 (2011) 1133–1141
OBut
C
OBut
N
N
N
O
N
N
C
O
O
NCS
Ni
Ni
N
N
N
O
H
N
N
Ph
O
Ph
L8
L8
Cl
N
O
Figure 2. Proposed transition state for the enantioselectivity.
4.2.6. Ligand L6
4.2.11. Ligand L11
This is
a
known compound.9 Yield: (171 mg, 66%).
Yield: (140 mg, 78%). A yellow solid, mp: 107–109 °C.
½
a 2D0
ꢂ
¼ ꢁ375:3 (c 0.50, CH2Cl2). 1H NMR (CDCl3, 300 MHz, TMS): d
½
a 2D0
ꢂ
¼ ꢁ769 (c 0.25, CHCl3). 1H NMR (CDCl3, 400 MHz, TMS): d
2.20 (6H, s), 6.62 (2H, d, J = 8.1 Hz), 6.98 (4H, d, J = 10.8 Hz),
7.22–7.30 (4H, m), 7.44 (2H, t, J = 7.5 Hz), 7.61 (2H, d, J = 8.1 Hz),
7.96 (2H, d, J = 8.4 Hz), 8.10 (2H, d, J = 8.4 Hz), 8.59 (2H, s), 11.85
(2H, s).
8.43 (s, 2H), 8.08–8.03 (m, 4H), 7.92–7.90 (m, 1H), 7.85–7.81 (m,
1H), 7.78–7.76 (m, 2H), 7.70–7.64 (m, 2H), 7.53–7.49 (m, 2H),
6.99 (s, 2H), 6.94 (s, 4H), 6.70 (s, 2H), 2.79–2.64 (m, 4H), 2.44–
2.30 (m, 4H), 2.13 (s, 12H), 1.72–1.62 (m, 8H); 13C NMR
(100 MHz, CDCl3) d 163.4, 155.1, 147.7, 139.7, 137.0, 136.2,
134.5, 133.5, 130.4, 130.3, 129.62, 129.55, 129.5, 129.4, 129.2,
128.8, 127.8, 127.7, 127.6, 127.2, 118.4, 117.4, 29.6, 27.6, 23.4,
4.2.7. Ligand L7
This is a known compound.9 Yield: (134 mg, 58%). ½a 2D0
¼ þ102
ꢂ
(c 0.25, CH2Cl2). 1H NMR (CDCl3, 300 MHz, TMS): d 7.15–7.20 (3H,
m), 7.24–7.33 (3H, m), 7.38–7.43 (4H, m), 7.45–7.52 (4H, m), 7.92
(2H, d, J = 8.1 Hz), 7.99 (2H, d, J = 8.1 Hz), 8.45 (2H, s), 8.48–7.51
(2H, m).
23.1, 21.2; IR (neat)
749 cmꢁ1; MS (ESI) m/z 801.4 (M+Na+, 100); HRMS (ESI) calcd for
56H50N4 requires (M+Na+): 801.3933, found: 801.3936.
m 2970, 1937, 1594, 1501, 1203, 829,
C
4.2.12. Ligand L12
Yield: (130 mg, 86%).
A yellow solid, mp: 119–121 °C.
4.2.8. Ligand L8
½
a 2D0
ꢂ
¼ ꢁ462 (c 0.3, CHCl3). 1H NMR (CDCl3, 300 MHz, TMS): d
This is a known compound.9 Yield: (230 mg, 82%). ½a 2D0
¼ þ16:1
ꢂ
8.39 (s, 1H), 8.19–8.13 (m, 2H), 8.03–8.01 (m, 2H), 7.95–7.90 (m,
4H), 7.83 (s, 3H), 7.79–7.65 (m, 4H), 7.59–7.51 (m, 4H), 7.44–
7.38 (m, 1H), 6.95 (s, 1H), 2.84–2.58 (m, 4H), 2.40–2.20 (m, 4H),
1.68–1.57 (m, 8H). 13C NMR (75 MHz, CDCl3) d 164.5, 154.1,
147.8, 145.6, 141.9, 137.3, 136.7, 136.5, 134.7, 131.4 (q,
J = 33.2 Hz), 130.8, 130.44, 130.37, 130.2, 130.04, 130.01, 129.7
(q, J = 3.8 Hz), 129.1, 128.9, 128.7, 127.8, 127.6 (q, J = 3.8 Hz),
126.7, 123.3 (q, J = 271.3 Hz), 119.9, 119.8, 117.7, 117.3, 29.5,
(c 0.35, CH2Cl2). 1H NMR (CDCl3, 300 MHz, TMS): d 7.29–7.43 (6H,
m), 7.51–7.64 (8H, m), 7.75 (2H, d, J = 8.1 Hz), 7.89 (2H, d,
J = 8.7 Hz), 7.95 (4H, d, J = 8.7 Hz), 8.05 (2H, d, J = 9.0 Hz), 8.63 (s,
2H).
4.2.9. Ligand L9
Yield: (540 mg, 87%).
A yellow solid, mp: 144–146 °C.
½
a 2D0
ꢂ
¼ þ225 (c 0.25, CHCl3). 1H NMR (CDCl3, 400 MHz, TMS): d
27.9, 23.1, 22.8; 19F NMR (376 MHz, CDCl3) d ꢁ67.7; IR (neat)
m
2962, 1936, 1593, 1569, 1501, 1207, 966, 844, 746 cmꢁ1; MS
(ESI) m/z 1017.3 (M+Na+, 100); HRMS calcd for C56H38F12N3
(M+Na+): 1017.2803, found: 1017.2809.
8.56 (s, 2H), 8.03–8.00, (m, 2H), 7.95–7.91 (m, 4H), 7.63–7.61 (m,
2H), 7.57–7.50 (m, 4H), 7.46–7.39 (m, 8H), 7.31–7.27 (m, 2H),
3.07–2.90 (m, 4H), 1.14–1.11 (t, J = 7.2 Hz, 6H); 13C NMR
(100 MHz, CDCl3) d 162.0, 153.7, 147.8, 146.1, 143.5, 136.4,
133.5, 132.1, 129.2, 128.7, 127.9, 127.8, 127.7, 127.3, 127.1,
4.3. Typical reaction procedure for the chlorination of 3-
substituted oxindoles
126.5, 125.4, 125.1, 118.5, 117.9, 24.1, 14.7; IR (neat)
m 2962,
1936, 1593, 1569, 1501, 1207, 966, 844, 746 cmꢁ1; MS (ESI) m/z
641.3 (M+Na+, 100); HRMS (ESI) calcd for C44H34N4 requires
(M+Na+): 641.2681, found: 641.2696.
The catalyst was prepared by stirring Ni(BF4)2ꢀ6H2O (3.4 mg,
0.01 mmol, 10 mol %), ligand L8 (5.6 mg, 0.01 mmol, 10 mol %)
and 4 Å MS (10 mg) in CH3CN (1.0 mL) for 0.5 h under argon at
room temperature. Next, the reaction mixture was cooled to 0 °C,
after which 3-substituted oxindole 13 (0.1 mmol) and NCS 14
(0.12 mmol, 1.2 equiv) were added and the resulting mixture was
stirred at 0 °C for 1 h. When the reaction was complete as moni-
tored by TLC plate, the corresponding pure adduct was purified
by column chromatography on silica gel (petroleum ether/ethyl
acetate = 20/1).
4.2.10. Ligand L10
Yield: (180 mg, 83%).
A yellow solid, mp: 132–133 °C.
½
a 2D0
ꢂ
¼ ꢁ812 (c 0.2, CHCl3). 1H NMR (CDCl3, 300 MHz, TMS): d
8.47 (s, 1H), 8.29–8.23 (m, 1H), 8.03–7.94 (m, 5H), 7.88–7.60 (m,
6H), 7.49–7.38 (m, 6H), 7.30–7.06 (m, 6H), 7.01 (s, 1H), 2.90–2.63
(m, 4H), 2.47–2.27 (m, 4H), 1.81–1.58 (m, 8H). 13C NMR (75 MHz,
CDCl3) d 163.6, 154.9, 147.6, 145.6, 139.9, 137.3, 136.2, 134.7,
133.7, 130.3, 129.9, 129.6, 129.4, 129.1, 128.7, 128.5, 127.8,
127.5, 127.2, 126.1, 118.2, 117.3, 29.6, 27.6, 23.3, 23.0; IR (neat)
4.3.1. (R)-tert-Butyl 3-chloro-2-oxo-3-phenylindoline-1-
carboxylate 15a
m
2930, 1710, 1592, 1500, 1462, 1204, 1051, 843, 745 cmꢁ1; MS
(ESI) m/z 745.3 (M+Na+, 100); HRMS (ESI) calcd for C52H42N4 re-
A pale yellow oil.8 1H NMR (400 MHz, CDCl3) d 7.98 (d,
J = 8.4 Hz, 1H), 7.52–7.50 (m, 2H), 7.48–7.42 (m, 2H), 7.38–7.35
quires (M+Na+): 745.3307, found: 745.3301.

D. Wang et al. / Tetrahedron: Asymmetry 22 (2011) 1133–1141
1139
(m, 3H), 7.30–7.26 (m, 1H), 1.62 (s, 9H); 13C NMR (100 MHz, CDCl3)
d 170.9, 149.0, 139.1, 136.3, 130.7, 129.1, 128.9, 128.6, 127.9,
J = 248.4 Hz), 148.9, 136.7, 135.4, 132.3 (d, J = 3.4 Hz), 131.5,
130.0 (d, J = 8.6 Hz), 128.4, 126.3, 115.6 (d, J = 6.8 Hz), 115.4,
85.1, 66.1, 28.0, 21.1; 19F NMR (376 MHz, CDCl3) d ꢁ112.4; IR
126.1, 125.4, 115.6, 85.2, 66.5, 28.0; IR (neat)
m 2986, 1771, 1733,
1689, 1391, 1365, 1339, 1284, 1140, 722 cmꢁ1; ½a D20
ꢂ
¼ ꢁ124 (c
(neat) m 2987, 1774, 1735, 1506, 1491, 1332, 1300, 1277, 1248,
0.05, CHCl3) for 85% ee; Chiralcel OJ-H, hexane/iPrOH = 90/10,
0.5 mL/min, 254 nm, tminor = 11.50 min, tmajor = 13.31 min.
1149, 1113 cmꢁ1; MS (EI) m/z 375 (M+, 1%), 275 (13), 240 (100),
225 (11), 212 (28), 183 (7), 57 (7); HRMS calcd for C20H19ClFNO3
(M+): 375.1037, found: 375.1039; ½a 2D0
¼ ꢁ87:0 (c 1.6, CHCl3) for
ꢂ
4.3.2. (R)-tert-Butyl 3-chloro-5-methyl-2-oxo-3-phenylindo
line-1-carboxylate 15b
60% ee; Chiralcel AS-H, hexane/iPrOH = 95/5, 0.5 mL/min, 214 nm,
tminor = 8.13 min, tmajor = 8.98 min.
A pale yellow oil. 1H NMR (400 MHz, CDCl3) d 7.78 (d, J = 8.4 Hz,
1H), 7.45–7.42 (m, 2H), 7.30–7.28 (m, 3H), 7.18–7.14 (m, 2H), 2.30
(s, 3H), 1.54 (s, 9H); 13C NMR (100 MHz, CDCl3) d 171.1, 149.0,
136.7, 136.5, 135.2, 131.3, 129.1, 128.9, 128.5, 127.8, 126.4, 115.4,
4.3.7. (R)-tert-Butyl 3-chloro-5-fluoro-3-(4-fluorophenyl)-2-
oxoindoline-1-carboxylate 15g
A pale yellow oil. 1H NMR (400 MHz, CDCl3) d 8.00 (dd, J = 8.8,
4.4 Hz, 1H), 7.51–7.47 (m, 2H), 7.20–7.13 (m, 2H), 7.09–7.05 (m,
2H), 1.62 (s, 9H); 13C NMR (100 MHz, CDCl3) d 170.4, 163.2 (d,
J = 248.8 Hz), 160.2 (d, J = 244.0 Hz), 148.8, 135.0 (d, J = 2.5 Hz),
131.6 (d, J = 3.4 Hz), 130.1 (d, J = 8.5 Hz), 129.8 (d, J = 8.5 Hz),
117.8 (d, J = 22.9 Hz), 117.4 (d, J = 7.5 Hz), 115.7 (d, J = 22.0 Hz),
113.2 (d, J = 24.8 Hz), 85.5, 65.5, 28.0; 19F NMR (376 MHz, CDCl3)
85.0, 66.8, 28.0, 21.0; IR (neat)
m 3333, 2948, 2837, 1747, 1713,
1489, 1381, 1206, 1010 cmꢁ1; MS (EI) m/z 357 (M+, 1%), 257 (20),
222 (100), 207 (13), 194 (18), 165 (7), 57 (18); HRMS calcd for
C
20H20ClNO3 (M+): 357.1132, found: 357.1136; ½a 2D0
¼ ꢁ77:7 (c
ꢂ
1.0, CHCl3) for 67% ee; Chiralcel AS-H, hexane/iPrOH = 99/1,
0.5 mL/min, 230 nm, tminor = 8.88 min, tmajor = 9.38 min.
d ꢁ111.7 (d, J = 2.26 Hz), ꢁ115.6 (d, J = 1.13 Hz); IR (neat)
m 2989,
4.3.3. (R)-tert-Butyl 3-chloro-5-fluoro-2-oxo-3-phenylindoline-
1-carboxylate 15c
1788, 1742, 1507, 1484, 1339, 1295, 1262, 1144, 802 cmꢁ1; MS
(EI) m/z 379 (M+, 1%), 279 (17), 244 (100), 216 (51), 188 (7), 169
(5), 57 (10); HRMS calcd for C19H16ClF2NO3 (M+): 379.0787, found:
A pale yellow oil. 1H NMR (400 MHz, CDCl3) d 8.00 (dd, J = 8.8,
4.4 Hz, 1H), 7.50–7.48 (m, 2H), 7.39–7.37 (m, 3H), 7.18–7.12 (m,
2H), 1.62 (s, 9H); 13C NMR (100 MHz, CDCl3) d 170.5, 160.2 (d,
J = 244.5 Hz), 148.9, 135.8, 135.0 (d, J = 1.8 Hz), 130.6 (d, J = 8.1 Hz),
129.4, 128.7, 127.6, 117.6 (d, J = 22.8 Hz), 117.2 (d, J = 7.7 Hz), 113.3
(d, J = 24.8 Hz), 85.3, 66.1 (d, J = 1.6 Hz), 28.0; 19F NMR (376 MHz,
379.0790; ½a 2D0
¼ ꢁ63:3 (c 1.6, CHCl3) for 75% ee; Chiralcel AD-H,
ꢂ
hexane/iPrOH = 98/2, 0.5 mL/min, 230 nm, tminor = 11.29 min,
tmajor = 13.40 min.
4.3.8. (R)-tert-Butyl 3-chloro-3-(4-fluorophenyl)-5-methoxy-2-
oxoindoline-1-carboxylate 15h
CDCl3) d ꢁ115.8; IR (neat)
m 3091, 1778, 1734, 1483, 1339, 1293,
1262, 1144, 1098 cmꢁ1; MS (EI) m/z 361 (M+, 1%), 261 (26), 226
A pale yellow oil. 1H NMR (400 MHz, CDCl3) d 7.91 (d, J = 9.2 Hz,
1H), 7.52–7.49 (m, 2H), 7.07–6.95 (m, 4H), 3.82 (s, 3H), 1.62 (s,
9H); 13C NMR (100 MHz, CDCl3) d 170.8, 163.1 (d, J = 248.5 Hz),
157.4, 148.9, 132.3, 132.2 (d, J = 3.0 Hz), 130.0 (d, J = 7.7 Hz),
129.5, 116.6 (d, J = 40.9 Hz), 115.6, 115.4, 111.2, 85.1, 66.1, 55.7,
(100), 198 (16), 170 (7), 57 (69), 41 (10); HRMS calcd for
C
19H17ClFNO3 (M+): 361.0881, found: 361.0886. ½a 2D0
¼ ꢁ96:7 (c
ꢂ
1.7, CHCl3) for 88% ee; Chiralcel AS-H, hexane/iPrOH = 95/5, 0.5 mL/
min, 214 nm, tminor = 8.48 min, tmajor = 8.93 min.
28.0; 19F NMR (376 MHz, CDCl3) d ꢁ112.3; IR (neat)
m 3111,
4.3.4. (R)-tert-Butyl 3-chloro-5-methoxy-2-oxo-3-
1770, 1726, 1687, 1485, 1333, 1295, 1278, 1249, 1148 cmꢁ1; MS
(EI) m/z 391 (M+, 2%), 291 (38), 256 (100), 242 (5), 228 (20), 213
(10), 185 (13), 57 (10); HRMS calcd for C20H19ClFNO4 (M+):
phenylindoline-1-carboxylate 15d
A pale yellow oil.8 1H NMR (400 MHz, CDCl3) d 7.91 (d,
J = 9.2 Hz, 1H), 7.53–7.50 (m, 2H), 7.38–7.36 (m, 3H), 7.00–6.95
(m, 2H), 3.81 (s, 3H), 1.61 (s, 9H); 13C NMR (100 MHz, CDCl3) d
171.0, 157.4, 149.0, 136.3, 132.3, 129.9, 129.1, 128.6, 127.8,
391.0987, found: 391.0995; ½a D20
¼ ꢁ106:9 (c 1.65, CHCl3) for 72%
ꢂ
ee; Chiralcel OD-H, hexane/iPrOH = 98/2, 0.7 mL/min, 230 nm,
tmajor = 7.68 min, tminor = 8.43 min.
116.7, 116.3, 111.2, 84.9, 66.8, 55.8, 28.0; IR (neat)
m 2982 1774,
1732, 1488, 1334, 1294, 1277, 1248, 1148, 1101, 1036,
4.3.9. (R)-tert-Butyl 3-chloro-5-fluoro-2-oxo-3-(p-
tolyl)indoline-1-carboxylate 15i
1002 cmꢁ1; ½a 2D0
ꢂ
¼ ꢁ101:3 (c 1.35, CHCl3) for 82% ee; Chiralcel
OJ-H, hexane/iPrOH = 90/10, 0.5 mL/min, 230 nm, tmajor = 14.42 -
min, tminor = 18.53 min.
A pale yellow oil. 1H NMR (400 MHz, CDCl3) d 7.99 (dd, J = 9.2,
4.4 Hz, 1H), 7.37 (d, J = 8.8, 2H), 7.19–7.13 (m, 4H), 2.35 (s, 3H),
1.61 (s, 9H); 13C NMR (100 MHz, CDCl3) d 170.7, 160.1 (d,
J = 243.9 Hz), 149.0, 139.5, 135.0, 132.8, 132.8, 130.7 (d,
J = 9.2 Hz), 129.4, 127.6, 117.5 (d, J = 22.4 Hz), 117.2 (d,
J = 7.8 Hz), 113.3 (d, J = 24.7 Hz), 85.3, 66.1, 28.0, 21.1; 19F NMR
4.3.5. (R)-tert-Butyl 3-chloro-3-(4-fluorophenyl)-2-oxoindoline-
1-carboxylate 15e
A pale yellow oil. 1H NMR (400 MHz, CDCl3) d 7.99 (d, J = 8.0 Hz,
1H), 7.52–7.42 (m, 4H), 7.31–7.28 (m, 1H), 7.07–7.02 (m, 2H), 1.62
(s, 9H); 13C NMR (100 MHz, CDCl3) d 170.8, 163.1 (d, J = 247.5 Hz),
148.9, 139.1, 132.2 (d, J = 2.7 Hz), 130.9, 130.0 (d, J = 9.1 Hz), 128.5,
125.7 (d, J = 57.6 Hz), 115.7, 115.6, 115.4, 85.3, 65.8, 28.0; 19F NMR
(376 MHz, CDCl3) d -115.9; IR (neat)
m 2988, 1780, 1734, 1483,
1340, 1294, 1262, 1144, 1096 cmꢁ1; MS (EI) m/z 375 (M+, 1%),
275 (17), 240 (100), 212 (13), 57 (15); HRMS calcd for
C
20H19ClFNO3 (M+): 375.1037, found: 375.1039; ½a 2D0
¼ ꢁ87:0 (c
ꢂ
(376 MHz, CDCl3) d ꢁ112.2; IR (neat)
m
2984, 1777, 1733, 1507,
1.45, CHCl3) for 85% ee; Chiralcel AD-H, hexane/iPrOH = 98/2,
0.5 mL/min, 214 nm, tminor = 10.23 min, tmajor = 11.73 min.
1467, 1340, 1287, 1249, 1144, 1093 cmꢁ1; MS (EI) m/z 361 (M+,
1%), 261 (18), 226 (100), 198 (9), 170 (4), 57 (11); HRMS calcd for
C
19H17ClFNO3 (M+): 361.0881, found: 361.0889; ½a 2D0
ꢂ
¼ ꢁ107:9 (c
4.3.10. (R)-tert-Butyl 3-chloro-2-oxo-3-(m-tolyl)indoline-1-
carboxylate 15j
1.5, CHCl3) for 74% ee; Chiralcel AS-H, hexane/iPrOH = 99/1,
0.3 mL/min, 254 nm, tminor = 13.04 min, tmajor = 13.88 min.
A pale yellow oil. 1H NMR (400 MHz, CDCl3) d 7.98 (d, J = 8.0 Hz,
1H), 7.47–7.40 (m, 2H), 7.35 (s, 1H), 7.30–7.23 (m, 3H), 7.17–7.15
(m, 1H), 2.35 (s, 3H), 1.62 (s, 9H); 13C NMR (100 MHz, CDCl3) d
171.0, 149.0, 139.1, 138.4, 136.2, 130.6, 129.9, 129.1, 128.5,
128.4, 126.1, 125.4, 124.8, 115.6, 85.1, 66.6, 28.0, 21.5; IR (neat)
4.3.6. (R)-tert-Butyl 3-chloro-3-(4-fluorophenyl)-5-methyl-2-
oxoindoline-1-carboxylate 15f
A pale yellow oil. 1H NMR (400 MHz, CDCl3) d 7.85 (d, J = 8.4 Hz,
1H), 7.52–7.48 (m, 2H), 7.27–7.22 (m, 2H), 7.07–7.03 (m, 2H), 2.39
(s, 3H), 1.62 (s, 9H); 13C NMR (100 MHz, CDCl3) d 170.9, 163.1 (d,
m
2984, 1771, 1734, 1490, 1332, 1278, 1152 cmꢁ1; MS (ESI) m/z:
380.1 [M+Na+] HRMS calcd for C20H20ClNO3 (M+Na+): 380.1029,

1140
D. Wang et al. / Tetrahedron: Asymmetry 22 (2011) 1133–1141
found: 380.1029; ½a D20
ꢂ
¼ ꢁ2:2 (c 1.5, CHCl3) for 72% ee; Chiralcel
0.70, CHCl3), for 7% ee; Chiralcel AS-H, hexane/iPrOH = 95/5,
0.5 mL/min, 214 nm, tminor = 8.08 min, tmajor = 8.53 min.
IC-H, hexane/iPrOH = 98/2, 0.7 mL/min, 230 nm, tminor = 10.43 min,
tmajor = 11.53 min.
4.3.16. (R)-3-Chloro-1,3-diphenylindolin-2-one 15p
4.3.11. (R)-tert-Butyl 3-chloro-3-(naphthalen-2-yl)-2-oxoind
oline-1-carboxylate 15k
A pale yellow solid. 1H NMR (400 MHz, CDCl3) d 7.64–7.62 (m,
2H), 7.55–7.47 (m, 3H), 7.45–7.31 (m, 7H), 7.22–7.18 (m, 1H),
6.90 (d, J = 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 172.6, 142.8,
136.7, 133.8, 130.3, 130.1, 129.7, 129.0, 128.6, 128.5, 127.6,
A pale yellow solid. Mp: 146.1–147.0 °C; 1H NMR (400 MHz,
CDCl3) d 8.03 (dd, J = 8.8, 1.2 Hz, 1H), 7.88–7.74 (m, 5H), 7.53–7.48
(m, 4H), 7.34–7.30 (m, 1H), 1.62 (s, 9H); 13C NMR (100 MHz, CDCl3)
d 170.9, 148.9, 139.2, 133.6, 133.2, 132.5, 130.8, 128.8, 128.7, 128.5,
127.6, 127.3, 127.2, 126.6, 126.2, 125.5, 125.1, 115.7, 85.2, 66.8,
126.5, 126.3, 124.0, 110.2, 66.4; IR (neat)
m 2991, 1742, 1611,
1499, 1466, 1367, 1255, 1167, 1023, 796 cmꢁ1; MS (ESI) m/z
319.9 (M+H+, 100); HRMS calcd for C21H14ClNO (M+H+):
320.0837, found: 320.0845; Chiralcel AD-H, hexane/iPrOH = 90/
10, 0.7 mL/min, 230 nm, tminor = 12.72 min, tmajor = 18.92 min.
28.0; IR (neat)
m 3128, 1770, 1731, 1689, 1337, 1287, 1251, 1141,
1090, 757 cmꢁ1; MS (EI) m/z 393 (M+, 1%), 316 (4), 293 (8), 259
(100), 230 (63), 215 (7), 202 (7), 57 (6); HRMS calcd for C23H20ClNO3
(M+): 393.1132, found: 393.1139; ½a 2D0
ꢂ
¼ ꢁ45:9 (c 1.5, CHCl3) for
4.3.17. (R)-1-Benzyl-3-chloro-3-phenylindolin-2-one 15q
A pale yellow oil. 1H NMR (400 MHz, CDCl3) d 7.58–7.56 (m,
2H), 7.42 (m, 5H), 7.32–7.24 (m, 5H), 7.14–7.10 (m, 1H); 6.79–
6.77 (d, J = 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 173.6, 141.9,
136.6, 135.1, 130.3, 128.9, 128.6, 127.8, 127.5, 127.3, 127.13,
52% ee; Chiralcel IC-H, hexane/iPrOH = 98/2, 0.7 mL/min, 230 nm,
tminor = 10.43 min, tmajor = 11.53 min.
4.3.12. (R)-tert-Butyl 3-chloro-3-methyl-2-oxoindoline-1-
carboxylate 15l
127.08, 126.0, 123.7, 110.0, 66.3, 44.2; IR (neat)
m 3032, 1733,
A colourless oil.8 1H NMR (400 MHz, CDCl3) d 7.81 (d, J = 8.0 Hz,
1H), 7.40–7.38 (m, 1H), 7.33–7.29 (m, 1H), 7.19–7.14 (m, 1H), 1.88,
(s, 3H), 1.58 (s, 9H); 13C NMR (100 MHz, CDCl3) d 172.3, 148.9,
138.2, 130.5, 129.8, 125.2, 123.8, 115.5, 85.0, 61.9, 28.0, 26.4; IR
1612, 1488, 1358, 1189, 1030, 798, 694 cmꢁ1; MS (ESI) m/z 334.0
(M+H+, 100); HRMS calcd for C21H16ClNO (M+H+): 334.0993,
found: 334.0993; Chiralcel AS-H, hexane/iPrOH = 80/20, 0.7 mL/
min, 214 nm, tminor = 11.29 min, tmajor = 12.45 min.
(neat)
m 2983, 1779, 1734, 1609, 1370, 1343, 1289, 1249, 1149,
842 cmꢁ1; ½a 2D5
ꢂ
¼ ꢁ15:6 (c 1.26, CHCl3) (20% ee); Chiralcel AS-H,
Acknowledgements
hexane/iPrOH = 200/1, 0.5 mL/min, 214 nm, tminor = 10.15 min,
tmajor = 10.62 min.
We thank the Shanghai Municipal Committee of Science and
Technology (08dj1400100-2), National Basic Research Program of
China (973)-2010CB833302, the Fundamental Research Funds for
the Central Universities and the National Natural Science Founda-
tion of China for financial support (21072206, 20472096,
20872162, 20672127, 20821002 and 20732008).
4.3.13. (R)-tert-Butyl 3-chloro-5-methoxy-2-oxo-3-(p-tolyl)
indoline-1-carboxylate 15m
A pale yellow oil. 1H NMR (400 MHz, CDCl3) d 7.90 (d, J = 4.4 Hz,
1H), 7.39 (d, J = 4.4 Hz, 2H), 7.18–7.16 (m, 2H), 6.99–6.95 (m, 2H),
3.81 (s, 3H), 2.34 (s, 3H), 1.61 (s, 9H); 13C NMR (100 MHz, CDCl3) d
171.1, 157.3, 149.1, 139.3, 133.3, 132.3, 130.0, 129.3, 127.8, 116.7,
References
116.3, 111.2, 84.8, 66.8, 55.7, 28.0, 21.1; IR (neat)
m 2930, 1774,
1723, 1489, 1333, 1294, 1277, 1248, 1148, 1100 cmꢁ1; MS (EI)
m/z 387 (M+, 1%), 316 (4), 287 (26), 252 (100), 237 (5), 224 (11),
210 (11), 181 (6), 57 (7); HRMS calcd for C21H22ClNO4 (M+):
1. (a) March, J. Advanced Organic Chemistry: Reactions, Mechanisms and Structure,
4th ed.; Wiley: New York, 1992; (b) De Kimpe, N.; Verhé, R. The Chemistry of
Haloketones, -Haloaldehydes, and -Haloimines; Wiley: New York, 1990.
a-
a
a
2. For metal Lewis acid catalyzed chlorination, see: (a) Hintermann, L.; Togni, A.
Helv. Chim. Acta 2000, 83, 2425–2435; (b) Marigo, M.; Kumaragurubaran, N.;
Jørgensen, K. A. Chem. Eur. J. 2004, 10, 2133–2137; (c) Bernardi, L.; Jørgensen, K.
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Y.; Hayase, S.; Itoh, T. Chem. Lett. 2010, 39, 466–467.
387.1237, found: 387.1243; ½a D20
¼ ꢁ14:9 (c 1.50, CHCl3), for 72%
ꢂ
ee; Regis (S,S)-Whelk-O1, hexane/iPrOH = 98/2, 0.6 mL/min,
214 nm, tmajor = 22.78 min, tminor = 37.48 min.
3. For organocatalyzed chlorinations, see: (a) Wack, H.; Taggi, E. A.; Hafez, A. M.;
Drury, W. J., III; Lectka, T. J. Am. Chem. Soc. 2001, 123, 1531–1532; (b) France, S.;
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T.; Candeias, N. R.; Barbas, C. F., III J. Am. Chem. Soc. 2010, 132, 5574–5575; (b)
Mouri, S.; Chen, Z.; Mitsunuma, H.; Furutachi, M.; Matsunaga, S.; Shibasaki, M.
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Buchwald, S. L. J. Am. Chem. Soc. 2009, 131, 9900–9901; (d) He, R.; Shirakawa,
S.; Maruoka, K. J. Am. Chem. Soc. 2009, 131, 16620–16621; (e) He, R.; Ding, C.;
Maruoka, K. Angew. Chem., Int. Ed. 2009, 48, 4559–4561; (f) Kato, Y.; Furutachi,
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4.3.14. (R)-tert-Butyl 3-chloro-2-oxo-3-(p-tolyl)indoline-1-
carboxylate 15n
A pale yellow oil. 1H NMR (400 MHz, CDCl3) d 7.98 (d, J = 8.4 Hz,
1H), 7.47–7.38 (m, 4H), 7.30–7.28 (m, 1H), 7.17 (d, J = 8.4 Hz, 2H),
2.34 (s, 3H), 1.62 (s, 9H); 13C NMR (100 MHz, CDCl3) d 171.0, 149.0,
139.2, 139.1, 133.4, 130.6 129.2, 129.0, 127.8, 126.1, 125.3, 115.6,
85.0, 66.5, 28.0, 21.1; IR (neat)
m 2975, 1778, 1729, 1478, 1467,
1341, 1288, 1249, 1145, 1093 cmꢁ1; MS (EI) m/z 357 (M+, 1%),
257 (17), 222 (100), 194 (9), 57 (12); HRMS calcd for C20H20ClNO3
(M+): 357.1132, found: 357.1139; ½a 2D0
¼ ꢁ4:2 (c 1.50, CHCl3), for
ꢂ
7% ee; Chiralcel AS-H, hexane/iPrOH = 95/5, 0.5 mL/min, 214 nm,
tminor = 8.48 min, tmajor = 8.93 min.
4.3.15. (R)-tert-Butyl 3-chloro-5-methyl-2-oxo-3-(p-tolyl)
indoline-1-carboxylate 15o
A pale yellow oil. 1H NMR (400 MHz, CDCl3) d 7.84 (d, J = 8.4 Hz,
1H), 7.39 (d, J = 8.4 Hz, 2H), 7.22–7.17(m, 4H), 2.37 (s, 3H), 2.34 (s,
3H), 1.61 (s, 9H); 13C NMR (100 MHz, CDCl3) d 171.2, 149.1, 139.2,
136.7, 135.2, 133.5, 131.3, 129.2, 128.9, 127.8, 126.4, 115.4, 84.9,
66.8, 28.0, 21.1, 21.0; IR (neat)
m 2982, 1776, 1733, 1490, 1333,
1298, 1276, 1248, 1150, 1108 cmꢁ1; MS (EI) m/z 371 (M+, 1%),
271 (17), 236 (100), 208 (16), 194 (11), 57 (11); HRMS calcd for
C
21H22ClNO3 (M+): 371.1288, found: 371.1292; ½a 2D0
¼ ꢁ4:6 (c
ꢂ

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