One-pot synthesis of substituted indolines via a copper-catalyzed sequential multicomponent/C-N coupling reaction

Article abstract of DOI:10.1016/j.tet.2010.11.094

One-pot synthesis of 2-(N-sulfonylimino)indolines has been developed. The procedure combines the copper-catalyzed three-component reaction of sulfonyl azides, o-bromophenylacetylenes, and amines and the copper-catalyzed intramolecular C-N coupling in one sequence, which afforded the products in moderate to good yields. The resulting 2-(N-sulfonylimino)indolines could be easily transformed to pharmaceutically valuable oxindoles (indolin-2-ones).

Full text of DOI:10.1016/j.tet.2010.11.094

Tetrahedron 67 (2011) 1178e1182
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
One-pot synthesis of substituted indolines via a copper-catalyzed sequential
multicomponent/CeN coupling reaction
,
,
*
Hongwei Jin a b, Bingwei Zhou b, Zhi Wu b, Yang Shen a, Yanguang Wang a
a Department of Chemistry, Zhejiang University, Hangzhou 310027, PR China
b College of Chemical Engineering and Materials Science, Zhejiang University of Technology, Hangzhou 310014, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 October 2010
Received in revised form 20 November 2010
Accepted 30 November 2010
Available online 4 December 2010
One-pot synthesis of 2-(N-sulfonylimino)indolines has been developed. The procedure combines the
copper-catalyzed three-component reaction of sulfonyl azides, o-bromophenylacetylenes, and amines
and the copper-catalyzed intramolecular CeN coupling in one sequence, which afforded the products in
moderate to good yields. The resulting 2-(N-sulfonylimino)indolines could be easily transformed to
pharmaceutically valuable oxindoles (indolin-2-ones).
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Indolines
Copper
Multicomponent reactions
CeN coupling
Cascade reactions
1. Introduction
N
R1SO2N3
(Cu)H
SO2R1
SO2R1 −N2
N
Cu(I)
base
N
C
C
N
+
R2
R2
R2
H(Cu)
In the field of organic synthesis, it would be desirable to perform
a series of simple steps in one pot,1 which would minimize the
chemicals used and waste produced, as well as the reaction time
consumed. As a result, great attention has been paid to the de-
velopment of cascade reaction. Multicomponent reactions (MCRs)
involving a cascade process with at least three different substrates
to generate complex molecular frameworks have emerged as
a powerful synthetic strategy.2
Nu
R2
H
N
SO2R1
Nu
Scheme 1. Formation of ketenimine via a the copper-catalyzed azide-alkyne cyclo-
addition (CuAAC).
Indoline and its derivatives are highly important scaffolds found
in numerous biologically active natural products.3 Consequently,
a great number of methods have been developed for construction of
this important class of compounds.4 MCRs approach to indulines
rings is rare. Ketenimine,5 as a useful intermediate, has attracted
much attention due to its easy formation, relative reactivity, and
diverse chemistry.6 The most attractive and sustainable method
generating ketenimines could be attributed to the copper-catalyzed
azide-alkyne cycloaddition (CuAAC) (Scheme 1), which was estab-
lished by Fokin et al.7 This method is suitable for MCRs. Chang,8 our
group9 and others10 developed a number of three- or four-compo-
nent reactions by trapping ketenimines generated in situ from sul-
fonyl azides and terminal alkynes via this CuAAC process. Herein, we
report our results on the copper-catalyzed three-component cas-
cade reaction of sulfonyl azides, 2-bromophenylacetylenes and
amines, which furnished 2-sulfonyliminoindolines in moderate to
good yields.
2. Results and discussion
In our primary investigations, we selected the CuI-catalyzed re-
action of p-toluenesulfonyl azide (1a), o-bromophenyl-acetylene
(2a), and m-toluidine (3a) as the model reaction (Table 1). In order to
optimize the reaction conditions, several ligands, and bases were
examined. When the reaction was conducted firstly in the presence
of0.1equivofCuIand1 equivof triethylamine(TEA)inDMSOatroom
temperature for 2 h, and then under 0.1 equiv of CuI, 0.4 equiv of N-
methylglycine11 and 2.0 equiv of K2CO3 at room temperature for 4 h,
* Corresponding author. Tel.: þ86 571 87951512; e-mail address: orgwyg@
zju.edu.cn (Y. Wang).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.11.094

H. Jin et al. / Tetrahedron 67 (2011) 1178e1182
1179
Table 1
coupling step with five representative ligands, i.e., N,N-dimethyl-
glycine,
-proline12 (Table 1, entries 3e4), N,N-dimethylethane-1,2-
diamine13 (Table 1, entry 5), 1,10-phenanthroline14 (Table 1, entry 6),
and ethyl 2-oxocyclohexanecarboxylate15 (Table 1, entry 7),
-proline
was found to be the best ligand for this intramolecular CeN coupling.
When K3PO4 (Table 1, entry 8) or Cs2CO3 (Table 1, entry 9) was used as
the base, no further improvement in yield was achieved. Changing
thesolventDMSOtoDMFalsodid notenhancetheyieldof4a(Table1,
entry 10). Prolonging the reaction time could not improve the result
(Table 1, entry 11).
Optimization of reaction conditionsa
L
Ts
TsN3
1a
NH2
1. CuI, TEA
N
L
solvent, rt, 2 h
+
N
2. CuI, ligand
base
CH3
CH3
Br
4a
3a
2a
Entry
Solvent
Ligandb
Base
Tempc (ꢀC)
Yieldd (%)
The optimized reaction conditions for the formation of 4a were
applied to a wide range of substrates. As shown in Table 2, both
aromatic (Table 2, entries 1e6 and 11e21) and aliphatic sulfonyl
azides (Table 2, entries 7e10) could work to afford the desired
products. The strong electron-withdrawing group substituted aro-
matic amines, such as 3-nitroaniline (3g) (Table 2, entry 16) and 4-
nitroanline (3h) (Table 2, entry 17), gave much lower yields than
other aromatic amines (Table 2, entries 1e15, 20, and 21). We also
examined benzyl (Table 2, entry 18) and aliphatic amines (Table 2,
entry 19), but they gave the desired products in poor yields and
required higher reaction temperature (80 ꢀC) and stronger base for
the intramolecular CeN coupling.
A plausible mechanism for this cascade process was outlined in
Scheme 2. In the presence of TEA and CuI, p-tolylsulfonyl azide (1a)
reacts with o-bromophenylacetylene (2a) to form the ketenimine
species A.7 A is quickly attacked by nucleophile 3a to generate N-
sulfonylamidine B, which easily tautomerize to more stable sul-
1
2
3
4
5
6
7
8
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
A
A
B
C
D
E
F
C
C
C
C
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K3PO4
Cs2CO3
K2CO3
K2CO3
rt
0
35
46
60
32
25
20
50
55
53
55e
60
60
60
60
60
60
60
60
60
80
9
10
11
DMSO
a
Reaction conditions: p-toluenesulfonyl azide (0.6 mmol), o-bromophenyl-
acetylene (0.5 mmol), m-toluidine (0.55 mmol), TEA (0.5 mmol), CuI (0.05 mmol),
solvent (2 mL), rt, 2 h, then CuI (0.05 mmol), ligand (0.2 mmol), base (1 mmol), 4 h.
b
Ligand: A¼N-methylglycine; B¼N,N-dimethylglycine; C¼ -proline; D¼N,N-
L
dimethylethane-1,2-diamine; E¼1,10-phenanthroline; F¼ethyl 2-oxocyclo-hexane-
carboxylate.
c
Reaction temperature refer to the intramolecular CeN coupling.
Isolated yield for 4a refer to 2a.
Intramolecular coupling reaction time: 8 h.
d
e
fonamide C. The subsequent CuI/L-proline catalyzed intramolecular
CꢁN coupling of C affords the desired product 4a.
As next step, we investigated the synthetic application of this
method by hydrolysis of the resulting 4a. Thus, 4a was treated with
concentrated hydrochloric acid under reflux condition to afford
oxindole (indolin-2-one) 5a (Scheme 3), which constitute a phar-
maceutically valuable class of biologically active compounds.16,17
we did not obtained the desired product 4a (Table 1, entry 1). How-
ever, when the intramolecular CeN coupling reaction temperature
was increased to 60 ꢀC, 4a was yielded in 35% yield (Table 1, entry 2).
When we turned our attention to screen conditions of the CeN
Table 2
One-pot synthesis of 2-sulfonyliminoindolines 4a
R1SO2N3
R2
1. CuI, TEA
SO2R1
R2
DMSO, rt, 2 h
1
N
R3NH2
3
2. CuI/L-proline
N
K2CO3, 60oC, 4 h
Br
R3
4
2
Entry
1 (R1)
2 (R2)
3 (R3)
Yieldb (%)
1
2
3
4
5
6
7
8
1a(4-MeC6H4)
1b (2-MeC6H4)
1c (C6H5)
1d (4-ClC6H4)
1e (4-i-PrC6H4)
1f (4-MeOC6H4)
1g (n-Bu)
1h (Me)
1g
1h
1a
1a
1a
1a
1a
1a
1a
1a
2a (H)
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
3a (3-MeC6H4)
3a
3a
3a
3a
3a
3a
3a
60 (4a)
45 (4b)
40 (4c)
51 (4d)
61 (4e)
55 (4f)
72 (4g)
62 (4h)
70 (4i)
43 (4j)
45 (4k)
65 (4l)
56 (4m)
45 (4n)
60 (4o)
36 (4p)
26 (4q)
25 (4r)c
17 (4s)c
50 (4t)
43 (4u)
9
3b (4-ClC6H4)
3b
10
11
12
13
14
15
16
17
18
19
20
21
3c(4-MeOC6H4)
3d (3,5-Me2C6H3)
3e (C6H5)
3f(3-ClC6H4)
3b
3g(3-NO2C6H4)
3h (4-NO2C6H4)
3i (C6H5CH2)
3j (i-Pr)
2a
2a
2b (MeO)
2c(Cl)
1a
1a
1a
3a
3a
a
Reaction conditions: sulfonyl azides (0.6 mmol), o-bromophenylacetylenes (0.5 mmol), amines (0.55 mmol), TEA (0.5 mmol), CuI (0.05 mmol), DMSO (2 mL), rt, 2 h, then
-proline (0.2 mmol), K2CO3 (1 mmol), 60 ꢀC, 4 h.
CuI (0.05 mmol),
L
b
Isolated yields for 4 refer to o-bromophenylacetylenes.
c
For the intramolecular coupling: Cs2CO3 (1 mmol), 80 ꢀC.

1180
H. Jin et al. / Tetrahedron 67 (2011) 1178e1182
2H), 7.38 (q, J¼7.5 Hz, 2H), 7.26e7.23 (m, 4H), 7.14e7.12 (m, 3H),
6.75 (d, J¼8.0 Hz, 1H), 4.41 (s, 2H), 2.40 (s, 3H), 2.39 (s, 3H), 13C NMR
NH2
TsN3
1a
(CDCl3, 125 MHz)
d 169.6, 144.7, 142.6, 139.7, 139.4, 134.3, 129.7,
129.4, 129.2, 127.9, 127.6, 126.6, 126.1, 124.5, 124.1, 123.8, 110.5, 36.4,
21.5, 21.4; EIMS m/z 376 (Mþ); HRMS (EI) calcd for C22H20N2O2S
([M]þ), 376.1245; found, 376.1265.
NTs
CuI
+
CH3
CH3
Et3N
3a
Br
A
4.1.2. 1-(m-Tolyl)-2-(o-toluenesulfonylimino)indoline (4b). White solid;
Br
1
mp 155e156 ꢀC; H NMR (CDCl3, 500 MHz)
d
8.06 (q, J¼8.0 Hz, 1H),
2a
7.40e7.36 (m, 3H), 7.28e7.19 (m, 4H), 7.14e7.10 (m, 3H), 6.73 (d,
J¼8.0 Hz, 1H), 4.41 (s, 2H), 2.56 (s, 3H), 2.39 (s, 3H), 13C NMR (CDCl3,
N
NTs
125 MHz)
d 169.7, 144.7, 140.1, 139.7, 137.7, 134.3, 132.2, 129.7, 129.4,
HN
Br
127.9, 127.8, 127.7, 126.1, 125.5, 124.5, 124.1, 123.8, 110.5, 36.6, 21.3, 20.3;
EIMS m/z 376 (Mþ); HRMS (EI) calcd for C22H20N2O2S ([M]þ),
376.1245; found, 376.1257.
HN
CH3
Ts
Br
B
C
4.1.3. 1-(m-Tolyl)-2-(benzenesulfonylimino)indoline (4c). White solid;
CuI
1
L-proline
K2CO3
Ts
mp 128e129 ꢀC; H NMR (CDCl3, 500 MHz)
d
7.91 (t, J¼8.5 Hz, 2H),
N
7.52e7.38 (m, 5H), 7.26e7.20 (m, 1H), 7.15e7.12 (m, 3H), 6.76 (d,
J¼8.0 Hz, 1H), 4.43 (s, 2H), 2.40(s, 3H), 13C NMR (CDCl3, 125 MHz)
N
d
169.7, 144.7, 142.3, 139.7, 134.2, 132.0, 129.7, 129.4, 128.6, 128.0, 127.6,
126.5, 126.1, 124.6, 124.0, 123.9, 110.6, 36.5, 21.4; EIMS m/z 362 (Mþ);
CH3
4a
HRMS (EI) calcd for C21H18N2O2S ([M]þ), 362.1089; found, 362.1106.
Scheme 2. Possible mechanism for the formation of 4a.
4.1.4. 1-(m-Tolyl)-2-(p-chlorobenzenesulfonylimino)indoline
(4d). White solid; mp 153e154 ꢀC; 1H NMR (CDCl3, 500 MHz)
d 7.83
(q, J¼7.0 Hz, 2H), 7.42e7.38 (m, 4H), 7.26e7.22 (m, 2H), 7.16e7.13
Ts
(m, 3H), 6.76 (d, J¼8.0 Hz, 1H), 4.43 (s, 2H), 2.40 (s, 3H), 13C NMR
O
N
HCl
N
(CDCl3, 125 MHz)
d 169.7, 144.6, 140.9, 139.8, 138.3, 134.1, 129.8,
N
129.5, 128.9, 128.0, 127.5, 126.0, 124.6, 124.1, 124.0, 110.6, 36.6, 21.4;
EIMS m/z 396 (Mþ); HRMS (EI) calcd for C21H17ClN2O2S ([M]þ),
396.0699; found, 396.0720.
reflux
CH3
50%
CH3
5a
4a
4.1.5. 1-(m-Tolyl)-2-(p-isopropylbenzenesulfonylimino)indoline
(4e). White solid; mp 118e119 ꢀC; 1H NMR (CDCl3, 500 MHz)
d 7.83
Scheme 3. Transformation of 4a.
(d, J¼8.5 Hz, 2H), 7.40e7.36 (m, 2H), 7.31e7.19 (m, 4H), 7.15e7.12
(m, 3H), 6.75 (d, J¼8.0 Hz, 1H), 4.41 (s, 2H), 2.97e2.91 (m, 1H), 2.40
3. Conclusion
(s, 1H), 1.25 (s, 3H), 1.24 (s, 3H), 13C NMR (CDCl3, 125 MHz)
d 169.7,
153.4, 144.7, 139.7, 139.6, 134.3, 129.7, 129.4, 127.9, 127.6, 126.7,
126.6, 126.1, 124.5, 124.1, 123.8, 110.5, 36.4, 34.1, 23.7, 21.3; EIMS m/z
404 (Mþ); HRMS (EI) calcd for C24H24N2O2S ([M]þ), 404.1559;
found, 404.1577.
In conclusion, we have developed a novel synthesis of 2-(N-
sulfonylimino)-indolines via a copper-catalyzed three-component
of sulfonyl azides, terminal alkynes, and amines. This one-pot ap-
proach is mild and general, and the substrates are readily available.
The resulting product could be easily transformed to pharmaceu-
tically valuable oxindoles. Further synthetic applications for this
method are under investigation in our laboratory.
4.1.6. 1-(m-Tolyl)-2-(p-methoxybenzenesulfonylimino)indoline
(4f). White solid; mp 109e110 ꢀC; 1H NMR (CDCl3, 500 MHz)
d 7.84
(d, J¼9.0 Hz, 2H), 7.40e7.36 (m, 2H), 7.26e7.19 (m, 2H), 7.14e7.12
(m, 3H), 6.92 (d, J¼9.0 Hz, 2H), 6.74 (d, J¼7.5 Hz, 1H), 4.40 (s, 2H),
4. Experimental
3.83 (s, 3H), 2.39 (s, 3H), 13C NMR (CDCl3, 125 MHz)
d 169.5, 162.4,
144.7, 139.7, 134.3, 134.2, 129.7, 129.5, 128.6, 127.9, 127.6, 126.1,
124.6, 124.1, 123.8, 113.8, 110.5, 55.6, 36.4, 21.4; EIMS m/z 392 (Mþ);
HRMS (EI) calcd for C22H20N2O3S ([M]þ), 392.1195; found, 392.1234.
4.1. General procedure for the copper-catalyzed one-pot
synthesis of 2-sulfonyliminoindolines 4
To a solution of sulfonyl azides 1 (0.6 mmol), o-bromo-phenyl-
acetylenes 2 (0.5 mmol), aromatic amines 3 (0.55 mmol), and CuI
(0.05 mmol) in DMSO (2 mL) in Schlenk tube was added TEA
(0.5 mmol) slowly via a syringe. The reaction solution was stirred at
room temperature under N2 for 2 h. The solution was then added to
4.1.7. 1-(m-Tolyl)-2-(butanesulfonylimino)indoline (4g). White solid;
mp 74e75 ꢀC; 1H NMR (CDCl3, 500 MHz)
d 7.44e7.36 (m, 2H),
7.28e7.26 (m, 1H), 7.24e7.11 (m, 4H), 6.76 (d, J¼7.5 Hz, 1H), 4.44 (s,
2H), 3.03 (t, J¼8.0 Hz, 2H), 2.43 (s, 3H),1.81e1.74 (m, 2H), 1.43e1.35 (m,
2H), 0.89 (t, J¼7.5 Hz, 3H), 13C NMR (CDCl3, 125 MHz)
d 169.4, 144.8,
CuI (0.05 mmol), K2CO3 (1 mmol), and
L-proline (0.2 mmol), and the
139.7, 134.4, 129.6, 129.4, 127.8, 127.7, 126.1, 124.5, 124.1, 123.7, 110.3,
54.1, 36.4, 25.6, 21.4, 21.3, 13.6; EIMS m/z 342 (Mþ); HRMS (EI) calcd for
C19H22N2O2S ([M]þ), 342.1402; found, 342.1420.
mixture was stirred at 60 ꢀC under N2 for 4 h. The reaction mixture
was partitioned between ethyl acetate and saturated aq NH4Cl, the
organic layer was washed with brine, dried over Na2SO4, and con-
centrated in vacuo. The residue was purified by column chromatog-
raphy on silica gel with petroleum etherand ethyl acetate (6:1 to 9:1).
4.1.8. 1-(m-Tolyl)-2-(methanesulfonylimino)indoline (4h). White solid;
mp 97e98 ꢀC; 1H NMR (CDCl3, 500 MHz)
d 7.45e7.41 (m, 1H),
7.39e7.37 (m, 1H), 7.29e7.26 (m, 1H), 7.22e7.17 (m, 3H), 7.15e7.12 (m,
4.1.1. 1-(m-Tolyl)-2-(p-toluenesulfonylimino)indoline
(4a). White
1H), 6.73 (d, J¼8.0 Hz, 1H), 4.44 (s, 2H), 2.99 (s, 3H), 2.43 (s, 3H), 13C
solid; mp 131e132 ꢀC; 1H NMR (CDCl3, 500 MHz)
d
7.79 (d, J¼8.5 Hz,
NMR (CDCl3, 125 MHz) d 169.3, 144.8, 139.8, 134.3, 129.7, 129.5, 127.9,

H. Jin et al. / Tetrahedron 67 (2011) 1178e1182
1181
127.7, 126.1, 124.5, 124.2, 123.8, 110.4, 42.5, 36.4, 21.4; EIMS m/z 300
(Mþ); HRMS (EI) calcd for C16H16N2O2S ([M]þ), 300.0932; found,
300.0945.
124.1, 110.2, 36.3, 21.5; EIMS m/z 396 (Mþ); HRMS (EI) calcd for
C21H17ClN2O2S ([M]þ), 396.0699; found, 396.0715.
4.1.16. 1-(m-Nitrophenyl)-2-(p-toluenesulfonylimino)indoline
4.1.9. 1-(p-Chlorophenyl)-2-(butanesulfonylimino)indoline
(4p). White solid; mp 151e152 ꢀC; 1H NMR (CDCl3, 500 MHz)
(4i). White solid; mp 126e127 ꢀC; 1H NMR (CDCl3, 500 MHz)
d
8.31e8.28 (m, 2H), 7.80e7.70 (m, 4H), 7.43 (d, J¼7.5 Hz, 1H),
7.29e7.24 (m, 3H), 7.21e7.17 (m, 1H), 6.79 (d, J¼8.0 Hz, 1H), 4.48 (s,
2H), 2.40 (s, 3H), 13C NMR (CDCl3, 125 MHz)
169.4, 148.9, 143.3,
d
7.54e7.51 (m, 2H), 7.38 (d, J¼7.5 Hz, 1H), 7.36e7.34 (m, 2H),
7.27e7.21 (m, 1H), 7.16e7.14 (m, 1H), 6.75 (d, J¼7.5 Hz, 1H), 4.44 (s,
2H), 3.03 (t, J¼8.0 Hz, 2H), 1.80e1.73 (m, 2H), 1.44e1.36 (m, 2H),
d
143.2, 138.7, 135.5, 133.2, 130.6, 129.4, 128.2, 126.6, 125.9, 125.0,
124.5, 123.6, 122.6, 109.9, 36.3, 21.5; EIMS m/z 407 (Mþ); HRMS (EI)
calcd for C21H17N3O4S ([M]þ), 407.0940; found, 407.0977.
0.90 (t, J¼8.0 Hz, 3H), 13C NMR (CDCl3, 125 MHz)
d 169.4, 144.2,
134.6, 133.0, 129.9, 128.6, 128.0, 126.0, 124.7, 124.0, 110.0, 54.1, 36.3,
25.5, 21.4, 13.6; EIMS m/z 362 (Mþ); HRMS (EI) calcd for
C18H19ClN2O2S ([M]þ), 362.0856; found, 362.0868.
4.1.17. 1-(p-Nitrophenyl)-2-(p-toluenesulfonylimino)indoline
(4q). White solid; mp 188e190 ꢀC; 1H NMR (CDCl3, 500 MHz)
4.1.10. 1-(p-Chlorophenyl)-2-(methanesulfonylimino)indoline
d
8.37 (q, J¼7.0 Hz, 2H), 7.77 (d, J¼8.5 Hz, 2H), 7.61 (q, J¼7.0 Hz, 2H),
(4j). White solid; mp 184e185 ꢀC; 1H NMR (CDCl3, 500 MHz)
7.43 (d, J¼7.5 Hz, 1H), 7.28e7.24 (m, 2H), 7.21e7.17 (m, 2H), 6.82 (d,
d
7.55e7.51 (m, 2H), 7.40e7.34 (m, 3H), 7.27e7.22 (m, 1H),
J¼8.0 Hz, 1H), 4.50 (s, 2H), 2.41 (s, 3H), 13C NMR (CDCl3, 125 MHz)
7.17e7.13 (m, 1H), 6.75 (d, J¼7.5 Hz, 1H), 4.44 (s, 2H), 3.00(s, 3H),
d
169.1, 147.2, 143.2, 140.0, 138.7, 130.0, 129.4, 128.2, 128.0, 126.6,
13C NMR (CDCl3, 125 MHz)
d
169.3, 144.3, 134.7, 132.9, 130.1, 128.7,
125.0, 124.9,124.6, 110.0, 36.4, 21.5; EIMS m/z 407 (Mþ); HRMS (ESI)
calcd for C21H18N3O4S ([MþH]þ), 408.1018; found, 408.1005.
128.1, 126.0, 124.8, 124.1, 110.1, 42.5, 36.3; EIMS m/z 320 (Mþ);
HRMS (EI) calcd for C15H13ClN2O2S ([M]þ), 320.0386; found,
320.0402.
4.1.18. 1-Benzyl-2-(p-toluenesulfonylimino)indoline (4r). White solid;
mp 128e130 ꢀC; 1H NMR (CDCl3, 500 MHz)
d
7.85 (d, J¼8.0 Hz, 2H),
4.1.11. 1-(p-Methoxyphenyl)-2-(p-toluenesulfonylimino)indoline
7.32 (d, J¼7.0 Hz, 1H), 7.28e7.19 (m, 8H), 7.10e7.06 (m, 1H), 6.89 (d,
(4k). White solid; mp 184e185 ꢀC; 1H NMR (CDCl3, 500 MHz)
J¼8.0 Hz, 1H), 5.07 (s, 2H), 4.30 (s, 2H), 2.41 (s, 3H), 13C NMR (CDCl3,
d
7.79 (d, J¼8.0 Hz, 2H), 7.37 (d, J¼8.0 Hz, 1H), 7.27e7.19 (m, 5H),
125 MHz) d 169.7, 143.1, 142.7, 139.4, 134.7, 129.3, 128.8, 128.0, 127.9,
7.14e7.12 (m, 1H), 7.01 (q, J¼7.0 Hz, 2H), 6.73 (d, J¼8.0 Hz, 1H),
126.6, 124.5, 123.7, 110.0, 45.7, 36.2, 21.5; EIMS m/z 376 (Mþ); HRMS
(ESI) calcd for C22H21N2O2S ([MþH]þ), 377.1324; found, 377.1307.
4.40 (s, 2H), 3.86 (s, 3H), 2.39 (s, 3H), 13C NMR (CDCl3, 125 MHz)
d
170.0, 159.7, 145.0, 142.7, 139.4, 129.3, 128.3, 128.0, 127.0, 126.6,
126.1, 124.6, 123.9, 115.0, 110.5, 55.6, 36.4, 21.5; EIMS m/z 392
(Mþ); HRMS (EI) calcd for C22H20N2O3S ([M]þ), 392.1195; found,
392.1209.
4.1.19. 1-iso-Propyl-2-(p-toluenesulfonylimino)indoline (4s). White
solid; mp 116e117 ꢀC; 1H NMR (CDCl3, 500 MHz)
d
7.87 (t, J¼8.5 Hz,
2H), 7.33e7.25 (m, 4H), 7.15 (d, J¼8.0 Hz, 1H), 7.11e7.07 (m, 1H),
5.00e4.97 (m, 1H), 4.18 (s, 2H), 2.41 (s, 3H), 1.48 (d, J¼7.0 Hz, 6H),
4.1.12. 1-(3,5-Dimethylphenyl)-2-(p-toluenesulfonylimino)indoline
13C NMR (CDCl3, 125 MHz)
d 169.3, 142.6, 142.4, 139.6, 129.3, 127.7,
(4l). White solid; mp 158e159 ꢀC; 1H NMR (CDCl3, 500 MHz)
d
7.80
127.0, 126.6, 124.6, 123.2, 111.3, 67.1, 45.9, 36.2, 21.5, 18.9; EIMS m/z
328 (Mþ); HRMS (ESI) calcd for C18H23N2O2S ([MþH]þ), 329.1324;
found, 329.1323.
(d, J¼8.0 Hz, 2H), 7.36 (d, J¼7.5 Hz, 1H), 7.26e7.18 (m, 3H), 7.13e7.10
(m, 1H), 7.06 (s, 1H), 6.93 (s, 2H), 6.74 (d, J¼8.0 Hz, 1H), 4.39 (s, 2H),
2.39 (s, 3H), 2.35 (s, 6H), 13C NMR (CDCl3, 125 MHz)
d 169.7, 144.8,
142.6, 139.5, 139.4, 134.2, 130.6, 129.2, 127.9, 126.6, 124.6, 124.5,
123.8,110.6, 36.4, 21.5, 21.3; EIMS m/z 390 (Mþ); HRMS (EI) calcd for
C23H22N2O2S ([M]þ), 390.1402; found, 390.1416.
4.1.20. 1-(m-Tolyl)-2-(p-toluenesulfonylimino)-5-methoxyindo-line
(4t). White solid; mp 182e184 ꢀC; 1H NMR (CDCl3, 500 MHz)
d 7.79
(d, J¼8.5 Hz, 2H), 7.38 (t, J¼7.5 Hz, 1H), 7.26e7.21 (m, 3H), 7.14e7.11
(m, 2H), 6.96 (t, J¼1.0 Hz, 1H), 6.74e6.71 (m, 1H), 6.66 (d, J¼9.0 Hz,
1H), 4.37 (s, 2H), 3.79 (s, 3H), 2.39 (s, 3H), 2.38 (s, 3H), 13C NMR
4.1.13. 1-Phenyl-2-(p-toluenesulfonylimino)indoline (4m). White solid;
1
mp 160e161 ꢀC; H NMR (CDCl3, 500 MHz)
d
7.78 (d, J¼8.0 Hz, 2H),
(CDCl3, 125 MHz) d 169.1, 156.9, 142.5, 139.6, 139.5, 138.2, 134.4,
7.45e7.43 (m, 1H), 7.39e7.33 (m, 3H), 7.26e7.19 (m, 3H), 7.15e7.11 (m,
129.5, 129.3, 129.2, 127.4, 126.5, 123.9, 112.7, 111.2, 110.9, 55.8, 36.6,
21.4, 21.3; EIMS m/z 406 (Mþ); HRMS (ESI) calcd for C23H23N2O3S
([MþH]þ), 407.1429; found, 407.1427.
1H), 6.75 (d, J¼8.0 Hz, 1H), 4.43 (s, 2H), 2.38 (s, 3H), 13C NMR (CDCl3,
125 MHz)
d 169.6, 144.6, 142.6, 139.3, 134.4, 129.6, 129.2, 128.8, 127.9,
127.1, 126.5, 126.1, 124.6, 123.9, 110.4, 36.4, 21.5; EIMS m/z 362 (Mþ);
HRMS (ESI) calcd for C21H19N2O2S ([MþH]þ), 363.1167; found,
363.1166.
4.1.21. -(m-Tolyl)-2-(p-toluenesulfonylimino)-5-chloroindoline
(4u). White solid; mp 152e154 ꢀC; 1H NMR (CDCl3, 500 MHz)
d
7.77 (d, J¼8.5 Hz, 2H), 7.38 (t, J¼8.0 Hz, 1H), 7.34 (s, 1H), 7.27e7.23
(m, 3H), 7.17 (q, J¼8.5 Hz, 1H), 7.11e7.09 (m, 2H), 6.66 (d, J¼8.5 Hz,
1H), 4.40 (s, 2H), 2.38 (s, 6H), 13C NMR (CDCl3, 125 MHz)
169.0,
4.1.14. 1-(m-Chlorophenyl)-2-(p-toluenesulfonylimino)indoline
(4n). White solid; mp 118e119 ꢀC; 1H NMR (CDCl3, 500 MHz)
d
7.79
d
(d, J¼8.0 Hz, 2H), 7.48e7.36 (m, 4H), 7.29e7.22 (m, 4H), 7.17e7.13
143.2, 142.7, 139.8, 133.9, 129.8, 129.5, 129.2, 127.9, 127.7, 127.4,
126.5, 124.8, 123.9, 111.3, 36.2, 21.3; EIMS m/z 410 (Mþ); HRMS (ESI)
calcd for C22H20ClN2O2S ([MþH]þ), 411.0934; found, 411.0931.
(m, 1H), 6.77 (d, J¼8.0 Hz, 1H), 4.43 (s, 2H), 2.40 (s, 3H), 13C NMR
(CDCl3, 125 MHz)
d 169.5, 144.0, 142.9, 139.1, 135.5, 135.2, 130.7,
129.4, 129.2, 128.1, 127.5, 126.6, 126.0, 125.5, 124.8, 124.2,110.3, 36.4,
21.6; EIMS m/z 396 (Mþ); HRMS (EI) calcd for C21H17ClN2O2S ([M]þ),
396.0699; found, 396.0710.
4.2. Procedure for transformation of 2-iminoindoline 4a to
oxindole 5a
4.1.15. 1-(p-Chlorophenyl)-2-(p-toluenesulfonylimino)indoline
A solution of 4a (188 mg, 0.5 mmol) in concentrated HCl (20 mL)
was refluxed for 12 h. The reaction mixture was diluted with CH2Cl2
(20 mL). The organic layer was washed with water, dried over an-
hydrous Na2SO4, and concentrated in vacuo. The residue was puri-
fied by column chromatography on silica gel with petroleum ether
and ethylacetate(6:1) to provide pure 5a as awhite solid (50% yield).
(4o). White solid; mp 185e186 ꢀC; 1H NMR (CDCl3, 500 MHz)
d 7.78
(d, J¼8.0 Hz, 2H), 7.48 (q, J¼6.5 Hz, 2H), 7.31e7.29 (m, 2H),
7.27e7.22 (m, 3H), 7.16e7.14 (m, 1H), 6.75 (d, J¼8.0 Hz, 1H), 4.43 (s,
2H), 2.40 (s, 3H), 13C NMR (CDCl3, 125 MHz)
d 169.5, 144.1, 142.8,
139.0, 134.6, 132.8, 129.9, 129.3, 128.5, 128.0, 126.6, 126.0, 124.7,

1182
H. Jin et al. / Tetrahedron 67 (2011) 1178e1182
J. P. J. Am. Chem. Soc. 2004, 126, 13906; (h) Ganton, M. D.; Kerr, M. A. Org. Lett.
Mp 108e110 ꢀC; 1H NMR (CDCl3, 500 MHz)
d
7.41 (t, J¼7.5 Hz, 1H),
2005, 7, 4777; (i) Yip, K.-T.; Yand, M.; Law, K.-L.; Zhu, N.-Y.; Yang, D. J. Am. Chem.
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7.31 (d, J¼7.0 Hz,1H), 7.26e7.18 (m, 4H), 7.07 (t, J¼7.5 Hz,1H), 6.77 (d,
J¼8.0 Hz, 1H), 3.71 (s, 2H), 2.42 (s, 3H), 13C NMR (CDCl3, 125 MHz)
d
174.5, 145.4, 139.7, 134.4, 129.5, 129.0, 127.8, 127.3, 124.6, 124.3,
ꢀ
123.7, 122.7, 109.5, 36.1, 21.4; EIMS m/z 223 (Mþ); HRMS (ESI) calcd
for C15H14NO ([MþH]þ), 224.1075; found, 224.1073.
(m) Houlden, C. E.; Bailey, C. D.; Ford, J. G.; Gagne, M. R.; Lloyd-Jones, G. C.;
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Robichaud, A. J. Tetrahedron 2010, 66, 573.
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1921, 4, 887.
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Acknowledgements
We thank the National Natural Science Foundation of China (No.
20872128) as well as the Scientific Research Fund of Educational
Bureau of Zhejiang Province (20070304) for financial support of
this work.
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Supplementary data
Supplementary data associated with this article can be found in
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