Molecular diversity of cycloaddition reactions of the functionalized pyridinium salts with 3-phenacylideneoxindoles

Article abstract of DOI:10.1016/j.tet.2013.05.034

The cycloaddition reactions of a series of functionalized pyridinium salts, which were generated from reaction of pyridine with active alkyl halides such as p-nitrobenzyl bromide, N,N-diethyl chloroacetamide and phenacyl bromides with 3-phenacylideneoxindoles in the presence of triethylamine showed very interesting molecular diversities. A series of the functionalized spiro[cyclopropane-1,3′-indolines], and 3-furan-3(2H)-ylidene)indolin-2- ones were successfully prepared depending upon the structures of the pyridinium salts and reaction conditions. The regioselectivity and stereoselectivity of the reactions as well as reaction mechanisms were briefly discussed.

Full text of DOI:10.1016/j.tet.2013.05.034

Accepted Manuscript
Molecular diversity of cycloaddition reactions of the functionalized pyridinium salts
with 3-phenacylideneoxindoles
Qin Fu, Chao-Guo Yan
PII:
S0040-4020(13)00769-2
10.1016/j.tet.2013.05.034
TET 24372
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 28 February 2013
Revised Date: 26 April 2013
Accepted Date: 13 May 2013
Please cite this article as: Fu Q, Yan C-G, Molecular diversity of cycloaddition reactions of the
functionalized pyridinium salts with 3-phenacylideneoxindoles, Tetrahedron (2013), doi: 10.1016/
j.tet.2013.05.034.
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ACCEPTED MANUSCRIPT
Molecular diversity of cycloaddition reactions of the functionalized pyridinium
salts with 3-phenacylideneoxindoles
Qin Fu, Chao-Guo Yan*
College of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou 225002, China
Tel: 86-514-87975531; Fax: 86-514-87975244; e-mail: cgyan@yzu.edu.cn
Abstract: The cycloaddition reactions of a series of functionalized pyridinium salts, which were
generated from reaction of pyridine with active alkyl halides such as p-nitrobenzyl bromide,
N,N-diethyl chloroacetamide and phenacyl bromides with 3-phenacylideneoxindoles in the
presence of triethylamine showed very interesting molecular diversities. A series of the
functionalized spiro[cyclopropane-1,3'-indolines], and 3-furan-3(2H)-ylidene)indolin-2-ones were
successfully prepared depending upon the structures of the pyridinium salts and reaction
conditions. The regioselectivity and stereoselectivity of the reactions as well as reaction
mechanisms were briefly discussed.
Keywords: heterocycle, spiro compound, pyridinium N-ylide, oxindole, cyclopropane.
1
. Introduction
The spirooxindole unit is a privileged heterocyclic motif that forms the core structure of a large
family of natural alkaloids and many pharmacological agents with important bioactivity and
1,2
interesting structural properties.
The unique structures and the highly pronounced
pharmacological activity displayed by the spirooxindoles have made them attractive synthetic
3
targets. In various heterocyclic and carbocyclic spirooxindoles, the spirocyclopentyl and
spirocyclohexyl systems, especially spiro[indoline-pyrrolines] and spiro[indoline-pyridines] have

ACCEPTED MANUSCRIPT
4
been deeply and extensively investigated. On the other hand the highly strained
spiro[cyclopropane-1,3'-indolines] have attracted limited attentions. Recently functionalized
spiro[cyclopropane-1,3'-indolines] were discovered having inotropic herbicidal properties and as
5
an HIV non-nucleoside reverse transcriptase inhibitors. spiro[cyclopropane-1,3'-indolines] were
6
also employed as building blocks for construction of more complex oxindole compounds. As a
consequence, a number of methods have been reported for the facile preparation of
spiro[cyclopropane-1,3'-indolines]. The known preparation methods included cycloaddition of
7
8
diazomethane with isatins or diazoamide with cyclic ketones, cycloaddition of sulfur ,
9
phosphrous and arsonium ylides with isatins, dialkylation of 3-acetonitriloxindole with alkyl
10
11
dibromides, reductive cyclization of Baylis–Hillman adducts of isatin and others. An
enantioselective nitrocycloproppanation of oxindoles through the direct reaction of
bromonitroalkyl derivatives and Boc-protected 3-alkylidene oxindoles were also successfully
12
developed. Recently we developed an efficient synthetic procedure for the polysubstituted
cyclopropanes via the domino reaction of in situ generated pyridinium salts with electron-deficient
1
3
olefins. Pyridinium salts have been used extensively in cycloadditions for the synthesis of the
1
4,15
fused heterocycles with a nitrogen at the point of fusion
and also been successfully employed
We envisaged that spiro[cyclopropane-1,3'-indolines]
would be synthesized by the similar reactions of in situ generated pyridinium salts with
-alkylidene oxindoles. A literature survey showed that there has been one briefly report of
formation of spiro[cyclopropane-1,3'-indolines] by the reactions of N-phenacylpyridinium salts
1
7,18
to prepare some spirooxindole systems.
3
19
with phenacylideneoxindoles, in which only few synthetic examples were provided. With the
20
aim of expanding our previous studies on the synthesis of spirooxindoles, we decided to
2

ACCEPTED MANUSCRIPT
systematically investigated the reactions of
a
series of pyridinium salts with
3
-phenacylideneoxindoles and report the interesting molecular diversities of this domino reaction.
2
. Results and Discussion
In our initial endeavour, according to our previously established reaction conditions for
13
preparation of cyclopropanes, a solution of eqular molar p-nitrobenzylpyridinium bromide (1a)
and 3-phenacylideneoxindoles (2a-2d) in ethanol with triethylamine as base catalyst was carried
out at elevated temperature for six hours. After workup, we were pleased to find that the expected
pure functionalized spiro[cyclopropane-1,3'-indolines] (3a-3d) was obtained in 65-78% yields
(Table 1, entries 1-4). It showed that this reaction is a facile protocol for synthesis of
spiro[cyclopropane-1,3'-indolines] with advantages of mild reaction conditions, easily accessible
starting material and easy purification of the products. Then under similar conditions the reactions
Table 1 Reactions of pyridinium salts with 3-phenacylideneoxindoles
Ar
Ar
O
O
E
Et N
N
R
3
R
Br
O
O
EtOH, 50

E
N
N
H
H
3
a
Entry Compd
E
R
H
Ar
Yield (%)
1
2
3
4
5
6
7
8
9
1
3a
3b
3c
3d
3e
3f
p-NO C H
C H
6
78
76
65
70
72
88
69
54
82
80
2
6
4
4
4
4
5
p-NO C H
H
p-ClC H4
6
2
2
2
6
6
6
p-NO
p-NO
C
C
H
H
F
6 5
C H
F
p-ClC
6 4
H
CON(CH
2
CH
3
)
2
CH
3
p-CH
3 6 4
C H
CON(CH CH )
CH3
F
p-ClC H4
2
3 2
6
3g
3h
3i
CON(CH CH )
2
2
2
2
3 2
C H
6 5
CON(CH
CON(CH
CON(CH
CH
CH
CH
3
3
3
)
2
)
2
)
2
F
p-ClC
6
6
H
H
4
4
Cl
Cl
p-ClC
0
3j
3 6 4
p-CH C H
a: isolate yields; b: pyridinium salt (1.1 mmol), 3-phenacylideneoxindole
(
1.0 mmol), triethylamine (0.2 mmol), EtOH (15 mL), 50°C, 6 h.
3

ACCEPTED MANUSCRIPT
of N-diethylcarbamoylmethylpyridinium bromide (1b) with various 3-phenacylideneoxindoles
also proceeded very smoothly to give the spiro[cyclopropane-1,3'-indolines] (3e-3j) in 54-88%
yields (Table 1, entries 5-10). The substituents on oxindole moiety and aryl groups showed
marginal effect on the yield of product.
The structures of the prepared spiro[cyclopropane-1,3'-indolines] were characterized with
spectroscopic methods and confirmed by the X-ray diffraction determination of single crystal 3e
1
(
Figure 1). In the H NMR spectra of spiro compounds 3a-3j, the two protons at 2,3-position of
cyclopropyl ring usually display two doublets at about 4.30 and 4.10 ppm with the vicinal
coupling constant J = 7.8Hz. It has been well known that in trans-cyclopropane the vicinal
coupling constant of the two methine protons J = 7-10Hz, while in cis-cyclopropane the vicinal
21
coupling constant J = 4-7Hz. From Figure 1 It can be seen clearly that the aroxyl group and
diethylcarbamoyl group are in trans-configuration. On the other hand the aroxyl group and the
phenyl group of oxindole moiety also exist in trans-position. It is well known that these two
2
2
groups are in cis-position in starting 3-phenacylideneoxindoles. This result undoubtedly showed
that spiro[cyclopropane-1,3'-indolines] were formed by a multistep reaction process. According to
1
the careful analysis of H NMR data and comparison with the earlier reported results we could
conclude that the two substituents at 2,3-position of cyclopropyl ring of
spiro[cyclopropane-1,3'-indolines] existed in trans-configuration. This interesting result clearly
indicated that the Michael-initiated cyclopropanation of pyridinium ylides is a diastereoselctive
reaction.
4

ACCEPTED MANUSCRIPT
Figure 1 Molecular structure of spiro compound 2e
To explore the potential of this reaction as
a
practical protocol to obtain
spiro[cyclopropane-1,3'-indolines], the triethylamine catalyzed reactions of N-phenacylpyridinium
bromide (1c) with 3-phenacylideneoxindoles were also carried out in ethanol. The outcome of this
reaction is a little surprise to us. Besides giving the normal spiro[cyclopropane-1,3'-indolines]
(4a-4g) as main products, the functionalized 3-(2-hydroxyfuran-3(2H)-ylidene)oxindoles (5a-5g)
were also produced as byproducts (Table 2, entries 1-7). In one case compound 5f became the
main product (72%). Trying to eliminate this byproduct by adjusting the reaction conditions such
as solvent, base and temperature was not successful. The reactions usually resulted in a mixture of
two products with little variable ratios. When N-p-chlorophenacylpyridinium bromide (1d) was
employed in the reactions, a mixture of spiro compounds (4h-4q) and furanylideneoxindoles
(5h-5q) were also obtained in different ratios (Table 2, entries 8-17). The structures of the
prepared compounds were characterized with spectroscopic methods and confirmed by the X-ray
1
diffraction determination of single crystals 4a (Figure 2) and 5b (Figure 3). H NMR data of the
prepared spiro[cyclopropane-1,3'-indolines] (4a-4q) also indicated that one diaseteroisomer
predominately existed in most cases, while a mixture of cis/trans-isomers existed in samples 4j
and 4m. Single crystal structure of compound 4a clearly showed that two benzoyl groups are in
trans-configuration.
5

ACCEPTED MANUSCRIPT
Table 2 Reactions of N-phenacylpyridinium bromide with 3-phenacylideneoxindoles
Ar'
Ar
Ar'
O
Ar'
O
O
O
HO
Br
O
N
Et N
3
R
R
Ar
R
EtOH, 50

O
O
O
N
N
N
Ar
H
H
H
4
5
Entry
Ar
R
Ar’
Compd
4a
4b
4c
Yield (%)
54
Compd
5a
Yield (%)
28
1
C
C
6
6
H
5
5
5
5
5
5
5
H
H
6 5
C H
2
3
4
5
6
7
8
9
H
p-CH
C H
5
3
C
6
H
4
48
5b
5c
31
C H
6
CH3
CH3
F
56
30
6
C H
6
p-CH C H
4d
4e
55
5d
5e
36
3 6
4
C
C
C
6
6
6
H
H
H
C
C
6
H
5
58
34
Cl
Cl
H
6
H
5
4f
—
5f
72
p-CH
C H
5
3
C
6
H
4
4
4
4g
4h
4i
62
5g
—
p-ClC H4
70
5h
5i
—
6
6
p-ClC H4
H
p-ClC H4
42
50
6
6
1
0
p-ClC
p-ClC
p-ClC
6
6
6
H
H
H
4
4
4
H
p-CH
3
C
6
H
4j
72 (5:2)
60
5j
—
1
1
2
3
4
5
6
7
CH
CH
3
3
C
6
H
5
4k
4l
5k
5l
26
1
1
1
1
1
1
p-ClC
6
H
4
43
44
p-ClC H4
CH3
F
p-CH C H
4m
4n
4o
4p
4q
32 (4:1)
76
5m
5n
5o
47
6
3
6
p-ClC H4
C H
—
6
6
5
p-ClC
p-ClC
p-ClC
6
6
6
H
H
H
4
4
4
F
p-ClC
6
H
4
4
80
—
Cl
Cl
C
6
H
5
—
5p
5q
78
p-ClC
6
H
49
32
a. isolate yields; b. pyridinium salts (1.1 mmol), 3-phenacylideneoxindole (1.0 mmol),
triethylamine (0.2 mmol), EtOH (15 mL), 50°C, 6 h.
Figure 2 Molecular structure of compound 4a
6

ACCEPTED MANUSCRIPT
Figure 3 Molecular structure of compound 5b
The formation of furanylideneoxindoles (5a-5q) in the reactions is unusual and very
interesting. To explain the formation mechanism of the two products in the reactions, a plausible
reaction mechanism was proposed in Scheme 1. At first the pyridinium salt is deprotonated by
triethylamine to give a pyridinium ylide (A). Secondly Michael addition of pyridinium ylide (A)
to 3-phenacylideneoxindole 2 undergoes in two different paths. In the path a, Michael addition of
ylide (A) to the carbon atom at 3-position of 3-phenacylideneoxindole produces the intermediate
(B). Then the intramolecular substitution of the carbanion to replace pyridine affords the final
spiro[cyclopropane-1,3'-indolines] 4. In the path b, Michael addition of ylide (A) to the exocyclic
carbon atom of 3-phenacylideneoxindole gives another intermediate (C), which in turn
transformed to a alkyleneoxindole intermediate (E) by sequential elimination of pyridine (D) and
the coupling of the carbonium cation with carbanium ion to form C=C double bond. In the
presence of triethylamine, intermediate (E) transferred to an enolate ion (G) by keto-enol
tautomerism and deprotonation process. Finally the intramolecular nucleophilic addition of
enolate ion to carbonyl group produces the furanylideneoxindole 5. 3-phenacylideneoxindoles
usually take part in the reactions at C-3 of oxindole moiety to give the versatile spirocyclic
7

ACCEPTED MANUSCRIPT
oxindoles. it is unusual to observe the reactions taking place at the exocyclic carbon atom to give
23, 24
the isatinyl substituted products.
It might be due to more steric hindrance at 3-position of
oxindole moiety, the partially reaction of carbanium ion at exocyclic carbon atom resulted in the
furanylideneoxindole 5 as byproduct. The similar reaction has been observed in the base catalyzed
addition of malononitrile to 3-phencylideneoxindoles, in which the attack of carbanion of
malononitrile at the exo-methylene atom of 3-phenacylideneoxindoles firstly gave a Michael
adduct, then this Michael adduct transfered to the furanylideneoxindoles by cycloaddition of the
25
enolized phenacyl group to one of cyano groups.
Ar'
Ar'
O
Ar
O
O
O
Ar'
O
-Py
Py
Ar
path a
path b
O
O
N
N
O
H
H
N
(B)
4
Br
O
Et N
N
N
3
H
2
O
Ar'
-HBr
Py
Ar'
O
O
Ar
(A)
O
Ar
O
-Py
Ar
O
1
Ar
O
N
N
H
H
(
C)
(D)
Et N
3
Ar
Ar'
Ar'
HO
O
O
O
EtOH
Ar
O
O
N
N
H
H
5
(E)
Scheme 1 The proposed reaction mechanism for the formation of compounds 4 and 5
In order to develop an efficient synthetic procedure for the functionalized
-(2-hydroxyfuran-3(2H)-ylidene)oxindoles, many research works were carried out. We were
3
pleased to find that under similar conditions the reactions of N-phenacyl- and
N-(4-chlorophenacyl)-4-dimethylaminopyridinium bromides (1e, 1f) with
-phenacylideneoxindole afforded predominately 3-(2-hydroxyfuran-3(2H)-ylidene)oxindoles in
3
8

ACCEPTED MANUSCRIPT
very high yields (Table 3). All the reactions proceeded very smoothly and no
spiro[cyclopropane-1,3'-indolines] were dictated in these reactions. The desired
3
-(2-hydroxyfuran-3(2H)-ylidene)oxindoles were obtained in pure form after collection of the
precipitates by filtration. In Table 3, five spiro compounds (5c, 5d, 5k, 5l, 5m) were the same
products obtained in above reactions of pyridinium salt and the last three spiro compounds (5r, 5s,
5t) were prepared in this reaction. Their structures were established by the spectroscopic methods
and the single crystal structure of compound 5l (Figure 4) was also determined by X-ray
diffraction. At present the reason for the formation of 3-(2-hydroxyfuran-3(2H)-ylidene)oxindole
as sole product in the reaction of 4-dimethylaminopyridinium salts is very clear, but the facts that
4
-dimethylaminopyridinium salts showed different reactivity to that of pyridinium salts in similar
2
6
reaction are noticed in some reported works.
Table 3 Reactions of N-phenacyl-4-dimethylaminopyridinium bromide with 3-phenacylideneoxindoles
N(CH3)
2
Ar'
Ar
Ar'
O
O
HO
Et N
3
R
Br
R
N
CH CN, rt.
3
O
O
O
N
H
N
H
Ar
5
Entry
Compd
Ar
R
Ar’
Yield (%)
1
2
3
4
5
6
7
8
5c
5d
5k
5l
C H
CH3
CH3
C H
88
80
87
83
85
80
90
92
6
5
6
5
C H
p-CH C H
6
5
3
6
4
p-ClC
p-ClC
p-ClC
6
H
4
CH
CH
CH
3
3
3
6 5
C H
6
6
H
H
4
4
p-ClC
p-CH
C H
6
H
4
5m
5r
5s
3
C
6
H
4
p-ClC H4
CH3
Cl
6
6
5
p-ClC H4
p-CH C H
6
3
6
4
5t
p-ClC
6
H
4
F
p-CH
3
C
6
H
4
a: isolate yields; b: 4-dimthylaminopyridinium salts (1.1 mmol), 3-phenacylidene
oxindole (1.0 mmol), triethylamine (0.2 mmol), EtOH (15 mL), 50°C, 6 h.
9

ACCEPTED MANUSCRIPT
Figure 4 Molecular structure of compound 5l
In conclusion we have systematically investigated the reactions of a series of pyridinium salts
with various 3-phenacylidendoxindoles and found very interesting molecular diversity of
Michael-initiated ring closure reactions of pyridinium ylides. Thus the efficient synthetic protocols
for
the
functionalized
spiro[cyclopropane-1,3'-indolines],
and
3
-furan-3(2H)-ylidene)indolin-2-ones were successfully developed. The scope and limitation of
this reaction was established and the reaction mechanism was briefly discussed. These protocols
have advantages of mild reaction conditions, easily accessible starting material and easy
purification of the products, which makes it a useful and attractive method for the synthesis of the
complex oxindole derivatives in synthetic and medicinal chemistry. Further expansion of the
reaction scope and synthetic applications of this methodology are in progress in our laboratory.
Experimental Section
All reagents and solvents were commercially available with analytical grade and used as received.
All evaporations of organic solvents were carried out with a rotary evaporator in conjunction with
a water aspirator. Melting points were taken on a hot-plate microscope apparatus and were
1
13
uncorrected. H and C NMR spectra were recorded with a Bruker AV-600 instrument. IR spectra
were obtained on a Bruker Tensor 27 spectrometer (KBr disc). HRMS were measured at Bruker
UHR-TOF maXis spectrometer. X-ray data were collected on a Bruker Smart APEX-2
diffractometer. Pyridinium salts were prepared by heating pyridine with p-nitrobenzyl bromide,
α-phenacyl bromide and N,N-diethyl chloroacetamide in acetonitrile according to the published
1
0

ACCEPTED MANUSCRIPT
13
procedure.
1
. General procedure for the preparation of spiro[cyclopropane-1,3'-indolines] 3a-3j from
the reactions of pyrididinium salts with 3-phenacylideneoxindoles: A mixture of
N-p-nitrobenzylpyridinium bromide or N-diethylcarbamoylmethylpyridinium chloride (1.1 mmol)
3
-phenacylideneoxindoles (1.0 mmol) and triethylamine (0.2 mmol) in ethanol (15mL) was stirred
at about 50°C for six hours. The resulting precipitates were collected by filtration, which were
recrystallized in a mixture of chloroform and ethanol to give pure product for analysis.
2-benzoyl-3-(4-nitrophenyl)spiro[cyclopropane-1,3'-indolin]-2'-one (3a): White solid, 78%.
m.p. 216-218� . IR (KBr): 3422, 3081, 1700, 1621, 1600, 1515, 1469, 1345, 1281, 1108, 1017,
1
9
75, 847. H NMR (600MHz, CDCl
3
) δ(ppm): 8.25 (s, 1H, NH), 8.18 (d, J = 8.4Hz, 2H, ArH) ,
7
.96 (d, J = 7.8Hz, 2H, ArH), 7.58 (t, J = 7.2Hz, 1H, ArH), 7.53 (d, J = 8.4Hz, 2H, ArH), 7.44 (t, J
7.2Hz, 2H, ArH), 7.25 (d, J = 7.8Hz, 1H, ArH), 7.19 (t, J = 7.8Hz, 1H, ArH), 6.99 (t, J = 7.2Hz,
H, ArH), 6.84 (d, J = 7.2Hz, 1H, ArH), 4.30 (d, J = 7.8Hz, 1H, CH), 4.17 (d, J = 7.8Hz, 1H, CH).
=
1
13
3
C NMR (150MHz, CDCl ) δ(ppm): 192.3, 173.9, 147.2, 141.3, 141.2, 136.7, 134.0, 130.3, 128.9,
128.5, 128.1, 125.6, 123.3, 122.6, 122.3, 110.2, 42.0, 41.0, 38.3. HRMS (ESI) Calcd. for
+
C H
23 16
N
2
NaO
4
([M+Na] ): 407.1002. Found: 407.1003.
2-(4-chlorobenzoyl)-3-(4-nitrophenyl)spiro[cyclopropane-1,3'-indolin]-2'-one (3b): White
solid, 76%. m.p. 222-224� . IR (KBr): 3444, 1721, 1671, 1629, 1525, 1469, 1047, 1349, 1191,
1
1
9
7
=
089, 1012, 842. H NMR (600MHz, CDCl
3
) δ(ppm): 8.19 (d, J = 9.0Hz, 2H, ArH), 7.90 (d, J =
.0Hz, 2H, ArH), 7.81 (s, 1H, NH), 7.52 (d, J = 8.4Hz, 2H, ArH), 7.41 (d, J = 8.4Hz, 2H, ArH),
.12 (t, J = 7.2Hz, 2H, ArH), 7.00 (t, J = 7.8Hz, 1H, ArH), 6.88 (d, J = 7.8Hz, 1H, ArH), 4.23 (d, J
1
3
3
7.8Hz, 1H, CH), 4.15 (d, J = 7.8Hz, 1H, CH). C NMR (150MHz, CDCl ) δ(ppm): 191.0,
172.9, 147.3, 140.7, 134.8, 130.2, 129.8, 129.3, 128.3, 125.3, 123.4, 122.8, 122.3, 110.0, 41.7,
+
4
0.9, 38.4. HRMS (ESI) Calcd. for C23
H15ClN
2
NaO
4
([M+Na] ): 441.0613. Found: 441.0612.
2-benzoyl-5'-fluoro-3-(4-nitrophenyl)spiro[cyclopropane-1,3'-indolin]-2'-one (3c): White
solid, 65%. m.p. 204-206� . IR (KBr): 3438, 3383, 1727, 1667, 1637, 1636, 1601, 1522, 1481,
1
1
351, 1325, 1221, 1178, 1147, 1110. H NMR (600MHz, CDCl
3
) δ(ppm): 8.19 (d, J = 7.8Hz, 2H,
ArH), 7.99 (d, J = 7.8Hz, 3H, ArH, NH), 7.61 (t, J = 7.2Hz, 1H, ArH), 7.53 (d, J = 8.4Hz, 2H,
ArH), 7.48 (t, J = 7.2Hz, 2H, ArH), 7.08 (d, J = 6.6Hz, 1H, ArH), 6.91 (t, J = 8.4Hz, 1H, ArH),
13
6
.79-6.77 (m, 1H, ArH), 4.33 (d, J = 7.8Hz, 1H, CH), 4.15 (d, J = 7.8Hz, 1H, CH) . C NMR
11

ACCEPTED MANUSCRIPT
(
150MHz, CDCl ) δ(ppm): 191.8, 173.0, 158.5 (d, J = 239.0Hz) , 147.4, 140.5, 136.7, 136.5,
3
134.2, 130.3, 129.0, 128.5, 127.1 (d, J = 9.0Hz), 122.4, 114.6 (d, J = 25.1Hz ), 110.8 (d, J =
2 4
26.0Hz), 110.4 (d, J = 8.0Hz ), 41.9, 40.9, 39.0. HRMS (ESI) Calcd. for C23H15FN NaO
+
(
[M+Na] ): 425.0908. Found: 425.0906.
2-(4-chlorobenzoyl)-5'-fluoro-3-(4-nitrophenyl)spiro[cyclopropane-1,3'-indolin]-2'-one
(3d): White solid, 70%. m.p. 236-238� . IR (KBr): 3448, 1726, 1675, 1637, 1625, 1601, 1520,
1
1
471, 1340, 1229, 1178, 1080, 1110, 857. H NMR (600MHz, CDCl
3
) δ(ppm): 8.27 (s, 1H, NH),
8
.13 (d, J = 8.4Hz, 2H, ArH), 7.94 (d, J = 8.4Hz, 2H, ArH), 7.63 (d, J = 8.4Hz, 2H, ArH), 7.56 (d,
= 2.4Hz, J = 8.4Hz, 1H, ArH), 7.18 (dt, J = 1.8Hz, J = 8.4Hz,
1 2
H, ArH), 7.05 (dd, J = 3.6Hz, J = 7.8Hz, 1H, ArH), 4.54 (d, J = 7.8Hz, 1H, ArH), 4.28 (d, J =
J = 8.4Hz, 2H, ArH), 7.31 (dd, J
1
2
1
2
1
7
1
13
.8Hz, 1H, CH). C NMR (150MHz, CDCl ) δ(ppm): 191.0, 173.5, 159.6 (d, J = 239.6Hz), 141.4,
3
41.0, 137.8, 135.2, 134.7, 130.5, 130.2, 129.8, 125.9 (d, J = 9.0Hz), 116.0 (d, J = 23.7Hz), 111.7
2 4
(d, J = 8.1Hz), 111.4 (d, J = 26.3Hz), 41.7, 40.3, 39.0. HRMS (ESI) Calcd. for C23H14FClN NaO
+
(
[M+Na] ): 483.1470. Found: 483.1474.
N,N-diethyl-5'-methyl-3-(4-methylbenzoyl)-2'-oxospiro[cyclopropane-1,3'-indoline]-2-carb
oxamide (3e): White solid, 72%. m.p. 174-176� . IR (KBr): 3463, 2975, 1723, 1693, 1635, 1488,
1
1
8
7
2
457, 1422, 1321, 1208, 1180, 1144, 1079, 1029, 985, 822. H NMR (600MHz, CDCl
3
) δ(ppm):
.37 (s, 1H, NH), 7.72 (d, J = 7.8Hz, 2H, ArH), 7.14 (s, 2H, ArH), 7.13 (s, 1H, ArH), 7.05 (d, J =
.8Hz, 1H, ArH), 6.78 (d, J = 7.8Hz, 1H, ArH), 3.97 (d, J = 7.8Hz, 1H, CH), 3.56-3.50 (m, 2H,
2 3 3
CH), 3.24-3.15 (m, 3H, CH, CH ), 2.33 (s, 3H, CH ), 2.32 (s, 3H, CH ), 1.03 (t, J = 7.2Hz, 3H,
13
CH ), 0.95 (t, J = 7.2Hz, 3H, CH ). C NMR (150MHz, CDCl ) δ(ppm): 190.6, 173.8, 164.5,
3
3
3
1
2
4
44.3, 139.0, 133.9, 132.0, 129.4, 128.7, 128.5, 125.0, 122.6, 110.0, 42.2, 40.8, 39.7, 38.7, 35.0,
+
1.6, 21.2, 14.0, 13.1. HRMS (ESI) Calcd. for C24
H
26
N
2
NaO
3
([M+Na] ): 413.2662. Found:
13.2658.
3-(4-chlorobenzoyl)-N,N-diethyl-5'-methyl-2'-oxospiro[cyclopropane-1,3'-indoline]-2-carb
oxamide (3f): White solid, 88%. m.p. 160-162� . IR (KBr):3443, 3233, 2972, 1720, 1628, 1591,
1
1
488, 1424,1318, 1201, 1145, 1086, 1034, 911, 858. H NMR (600MHz, CDCl
3
) δ(ppm): 8.09 (s,
1
H, NH), 7.76 (d, J = 7.8Hz, 2H, ArH), 7.33 (d, J = 7.8Hz, 2H, ArH), 7.15 (s, 1H, ArH), 7.07 (d, J
7.8Hz, 1H, ArH), 6.80 (d, J = 7.8Hz, 1H, ArH), 3.95 (d, J = 7.8Hz, 1H, CH), 3.58-3.52 (m, 2H,
CH), 3.24-3.16 (m, 3H, CH, CH ), 2.32 (s, 3H, CH ), 1.04 (t, J = 7.2Hz, 3H, CH ), 0.96 (t, J =
=
2
2
3
3
1
2

ACCEPTED MANUSCRIPT
1
3
7
1
.2Hz, 3H, CH3). C NMR (150MHz, CDCl ) δ(ppm): 189.9, 173.6, 164.2, 139.9, 139.0, 134.6,
3
32.3, 129.8, 129.0, 128.9, 124.7, 122.7, 110.1, 42.2, 40.8, 39.5, 38.6, 35.0, 21.2, 14.0, 13.2.
+
HRMS (ESI) Calcd. for C23H23ClN
2
NaO
3
([M+Na] ): 433.1289. Found: 433.1290.
2-benzoyl-N,N-diethyl-5'-fluoro-2'-oxospiro[cyclopropane-1,3'-indoline]-3-carboxamide
(3g): White solid, 69%. m.p. 200-202� . IR (KBr): 3366, 3276, 3068, 2972, 2934, 1708, 1637,
1
1
1
7
=
484, 1423, 1322, 1223, 1156, 1089, 1026, 959, 832. H NMR (600MHz, CDCl
3
) δ(ppm): 8.85 (s,
H, NH), 7.80 (d, J = 7.8Hz, 2H, ArH), 7.49 (t, J = 7.8Hz, 1H, ArH), 7.35 (t, J = 7.8Hz, 1H, ArH),
.19 (dd, J = 8.4Hz, J = 2.4Hz, 1H, ArH), 6.98 (td, J = 8.4Hz, J = 2.4Hz, 1H, ArH) , 6.88 (dd, J
1
2
1
2
1
7.8Hz, J
2
= 1.8Hz, 1H, ArH), 4.03 (d, J = 7.8 Hz, 1H, CH), 3.58 (d, J = 7.8Hz, 1H, CH),
) , 1.05 (t, J = 7.2Hz, 3H,
CH ), 0.97 (t, J = 7.2Hz, 3H, CH ). C NMR (150MHz, CDCl ) δ(ppm): 190.4, 173.8, 164.0,
3
.52-3.46 (m, 1H, CH), 3.32-3.27 (m, 1H, CH), 3.26-3.22 (m, 2H, CH
2
13
3
3
3
159.8, 158.2, 137.5, 136.1, 133.6, 128.8, 128.4, 126.6, 126.5, 115.0, 114.8, 111.1, 111.0, 110.5,
+
1
10.3, 42.3, 40.9, 40.1, 38.9, 35.1, 14.2, 13.2. HRMS (ESI) Calcd. for C22
H
21FN
2
NaO
3
([M+Na] ):
4
03.1428. Found: 403.1432.
-(4-chlorobenzoyl)-N,N-diethyl-5'-fluoro-2'-oxospiro[cyclopropane-1,3'-indoline]-2-carb
3
oxamide (3h): White solid, 54%. m.p. 230-232� . IR (KBr): 3451, 2970, 1731, 1634, 1592, 1485,
1
1
419, 1223, 1183, 1148, 1091, 1016, 957, 822. H NMR (600MHz, CDCl
3
) δ(ppm): 8.34 (s, 1H,
NH), 7.75 (d, J = 7.8Hz, 2H, ArH), 7.35 (d, J = 7.8Hz, 2H, ArH), 7.20 (d, J = 8.4Hz, 1H, ArH),
.00 (t, J = 8.4Hz, 1H, ArH), 6.87 (dd, J = 7.8Hz, J = 3.6Hz, 1H, ArH), 3.99 (d, J = 7.8Hz, 1H,
CH), 3.57 (d, J = 7.8Hz, 1H, CH), 3.52-3.47 (m, 1H, CH), 3.33-3.29 (m, 1H, CH), 3.27-3.24 (m,
7
1
2
1
3
2
H, CH ), 1.07 (t, J = 7.2Hz, 3H, CH ), 1.00 (t, J = 7.2Hz, 3H, CH ). C NMR (150MHz, CDCl )
2 3 3 3
δ(ppm): 189.4, 173.5, 163.9, 159.1 (d, J = 239.6 Hz) , 140.1, 137.3, 134.4, 129.7, 129.1, 126.3 (d,
J = 9.6Hz), 115.0 (d, J = 23.9Hz), 110.9 (d, J = 7.8Hz), 110.5 (d, J = 26.3Hz) , 40.3, 41.0, 39.9,
+
3
8.8, 35.1, 14.2, 13.2. HRMS (ESI) Calcd. for C22
37.1041.
H20ClFN
2
NaO
3
([M+Na] ): 437.1039. Found:
4
5
'-chloro-3-(4-chlorobenzoyl)-N,N-diethyl-2'-oxospiro[cyclopropane-1,3'-indoline]-2-carbo
xamide (3i): White solid, 82%. m.p. 242-244� . IR (KBr): 3420, 2982, 1703, 1631, 1591, 1480,
1
1
7
1
420, 1322, 1270, 1208, 1141, 1092, 825. H NMR (600MHz, CDCl ) δ(ppm): 8.58 (s, 1H, NH),
3
.74 (d, J = 8.4Hz, 2H, ArH), 7.39 (s, 1H, ArH), 7.35 (d, J = 8.4Hz, 2H, ArH), 7.26 (d, J = 8.4Hz,
H, ArH), 6.88 (d, J = 8.4Hz, 1H, ArH), 4.00 (d, J = 7.8Hz, 1H, CH), 3.57-3.52 (m, 2H, 2CH),
1
3

ACCEPTED MANUSCRIPT
13
3
.28-3.19 (m, 3H, CH, CH ), 1.06(t, J = 7.2Hz, 3H, CH ), 0.99 (t, J = 7.2Hz, 3H, CH ). C NMR
2 3 3
3
(150MHz, CDCl ) δ(ppm): 189.3, 173.3, 163.8, 130.2,139.9, 134.4,129.8, 129.2, 128.6, 128.3,
126.4, 122.7, 111.3, 42.3, 41.1, 39.8, 38.4, 35.1, 14.2, 13.2. HRMS (ESI) Calcd. for
+
C H20Cl N
22 2 2
NaO
3
([M+Na] ): 453.0743. Found: 453.0745.
5
'-chloro-N,N-diethyl-3-(4-methylbenzoyl)-2'-oxospiro[cyclopropane-1,3'-indoline]-2-car
boxamide (3j): White solid, 80%. m.p. 166-168� . IR (KBr): 3460, 2981, 2026, 1703, 1633, 1420,
1
1
322, 1271, 1208, 1141, 1085, 823. H NMR (600MHz, CDCl
3
) δ(ppm): 8.44 (s, 1H, NH), 7.69
(brs, 2H, ArH), 7.40 (s, 1H, ArH), 7.22 (brs, 1H, ArH), 7.14 (brs, 2H, ArH), 6.83 (brs, 1H, ArH),
4
.02 (d, J = 6.6Hz, 1H, CH), 3.58 (d, J = 6.6Hz, 1H, CH), 3.53 (brs, 1H, CH), 3.22 (brs, 3H, CH,
13
2 3 3 3 3
CH ), 2.33 (s, 3H, CH ), 1.05 (brs, 3H, CH ), 0.96 (brs, 3H, CH ). C NMR (150MHz, CDCl )
δ(ppm): 190.1, 173.5, 163.9, 144.7, 139.8, 133.6, 129.5, 128.5, 128.4, 128.1, 126.7, 122.6, 111.2,
+
4
4
2
3
3
2.3, 41.0, 40.1, 38.5, 35.2, 21.7, 13.1, 13.2. HRMS (ESI) Calcd. for C23
H
23ClN
2
NaO
3
([M+Na] ):
33.1289. Found: 433.1292.
. General procedure for the preparation of spiro[cyclopropane-1,3'-indolines] 4a-4q and
-furan-3(2H)-ylidene)indolin-2-ones 5a-5q from the reactions of pyrididinium salts with
-phenacylideneoxindoles:
A
mixture
of
N-phenacylpyridinium
bromide
or
N-p-chlorophenacylpyridinium chloride (1.1 mmol) 3-phenacylideneoxindoles (1.0 mmol) and
triethylamine (0.2 mmol) in ethanol (15mL) was stirred at 50°C for six hours. The resulting
precipitates were collected by filtration, which was bjected to thin-layer chromatography with a
mixture of ethyl acetate and light petroleum (V/V = 2:1) to give the pure product for analysis.
(2'-oxospiro[cyclopropane-1,3'-indoline]-2,3-diyl)bis(phenylmethanone) (4a): White solid,
54%. m.p. 176-178� . IR (KBr): 3256, 1719, 1673, 1620, 1595, 1465, 1400, 1308, 1219, 1085,
1
1
020, 936, 801. H NMR (600MHz, CDCl
3
) δ(ppm): 8.53 (s, 1H, NH), 7.96 (d, J = 7.8Hz, 2H,
ArH), 7.82 (d, J = 7.8Hz, 2H, ArH), 7.53 (t, J = 7.2Hz, 1H, ArH), 7.48 (t, J = 7.2Hz, 1H, ArH),
7
7
1
1
.40 (t, J = 7.8Hz, 2H, ArH), 7.35-7.32 (m, 3H, ArH), 7.24 (t, J = 7.2Hz, 1H, ArH), 7.03 (t, J =
.2Hz, 1H, ArH), 6.93 (d, J = 7.8Hz, 1H, ArH), 4.41 (d, J = 7.8Hz, 1H, CH), 4.17 (d, J = 7.8Hz,
1
3
3
H, CH). C NMR (150MHz, CDCl ) δ(ppm): 192.1, 190.5, 173.6, 141.7, 136.7, 136.1, 133.8,
33.6, 128.8, 128.7, 128.6, 128.4, 124.3, 122.7, 122.5, 110.7, 41.3, 39.6, 38.7. HRMS (ESI) Calcd.
+
for C24
H17NaNO
3
([M+Na] ): 390.1101. Found: 390.1103.
3-(2-hydroxy-2,5-diphenylfuran-3(2H)-ylidene)indolin-2-one (5a): Yellow solid, 28%. m.p.
1
4

ACCEPTED MANUSCRIPT
1
9
1
7
34-136� . IR (KBr): 3445, 3252, 1633, 1616, 1545, 1483, 1389, 1348, 1265, 1211, 1180, 1118,
1
69, 829. H NMR (600MHz, DMSO-d
6
) δ(ppm): 10.46 (s, 1H, NH), 8.91 (s, 1H, OH), 7.97 (s,
H, ArH), 7.79 (d, J = 7.2Hz, 2H, ArH), 7.63 (d, J = 6.0Hz, 2H, ArH), 7.52-7.47 (m, 3H, ArH),
.39-7.34 (m, 3H, ArH), 7.29 (s, 1H, ArH), 6.93 (t, J = 6.6Hz, 1H, ArH), 6.69 (d, J = 7.8Hz, 1H,
13
ArH), 6.55 (t, J = 7.8Hz, 1H, ArH). C NMR (150MHz, DMSO-d
6
) δ(ppm): 168.8, 166.7, 155.3,
1
1
40.5, 138.1, 136.1, 133.3, 131.4, 129.0, 128.4, 126.5, 125.3, 122.8, 122.7, 120.0, 117.8, 111.9,
+
08.7, 100.6. HRMS (ESI) Calcd. for C24
3
H17NNaO ([M+Na] ): 390.1101. Found: 390.1101.
2-benzoyl-3-(4-methylbenzoyl)spiro[cyclopropane-1,3'-indolin]-2'-one (4b): White solid,
48%. m.p. 192-194� . IR (KBr): 3281, 3021, 1726, 1670, 1601, 1470, 1406, 1306, 1218, 1094,
1
1
019, 921, 832. H NMR (600MHz, CDCl
3
) δ(ppm): 8.52 (s, 1H, NH), 7.96 (d, J = 7.2Hz, 2H,
ArH), 7.71 (d, J = 7.2Hz, 2H, ArH), 7.53 (t, J = 6.6Hz, 1H, ArH), 7.40 (t, J = 7.2Hz, 2H, ArH),
.32 (d, J = 7.2Hz, 1H, ArH), 7.23 (t, J = 7.8Hz, 1H, ArH), 7.13 (t, J = 7.8Hz, 2H, ArH), 7.02 (t, J
7.2Hz, 1H, ArH), 6.91 (d, J = 7.2Hz, 1H, ArH), 4.40 (d, J = 7.8Hz, 1H, CH), 4.15 (d, J = 7.8Hz,
7
=
1
3
1
1
3
3 3
H, CH), 2.31 (s, 3H, CH ). C NMR (150MHz, CDCl ) δ(ppm): 192.2, 190.1, 173.6, 144.6,
41.6, 136.8, 133.8, 129.5, 128.8, 128.7, 128.6, 128.5, 128.4, 124.4, 122.7, 122.5, 110.6, 41.3,
+
9.7, 38.8, 21.6. HRMS (ESI) Calcd. for C25
H
19NNaO
3
([M+Na] ): 404.1257. Found: 404.1260.
3-(2-hydroxy-5-phenyl-2-p-tolylfuran-3(2H)-ylidene)indolin-2-one (5b): Yellow solid, 31%.
m.p. 172-174� . IR (KBr): 3359, 1670, 1613, 1542, 1489, 1464, 1351, 1255, 1205, 1176, 1149,
1
1
099, 1061, 957, 830. H NMR (600MHz, DMSO-d
6
) δ(ppm): 10.44 (s, 1H, NH), 8.83 (s, 1H,
OH), 7.94 (s, 1H, ArH), 7.78 (d, J = 7.2Hz, 2H, ArH), 7.50-7.47 (m, 5H, ArH), 7.33 (d, J = 7.8Hz,
1H, ArH), 7.17 (d, J = 7.2Hz, 2H, ArH), 6.94 (t, J = 6.6Hz, 1H, ArH), 6.69 (d, J = 7.2Hz, 1H,
13
3 6
ArH), 6.57 (t, J = 7.2Hz, 1H, ArH), 2.26 (s, 3H, CH ). C NMR (150MHz, DMSO-d ) δ(ppm):
1
1
4
68.9, 166.6, 155.6, 140.5, 138.3, 135.3, 131.4, 129.0, 128.9, 128.7, 127.1, 127.0, 126.4, 125.3,
+
24.3, 121.8, 120.1, 114.8, 108.8, 100.6, 20.7. HRMS (ESI) Calcd. for C25
3
H19NNaO ([M+Na] ):
04.1257. Found: 404.1258.
(5'-methyl-2'-oxospiro[cyclopropane-1,3'-indoline]-2,3-diyl)bis(phenylmethanone)
(4c):
White solid, 56%. m.p. 194-196� . IR (KBr): 3202, 1712, 1674, 1625, 1593, 1486, 1448, 1331,
1
1
7
1
218, 1082, 1024, 941, 817. H NMR (600MHz, CDCl ) δ(ppm): 8.71 (s, 1H, NH), 7.95 (d, J =
3
.2Hz, 2H, ArH), 7.80 (d, J = 7.2Hz, 2H, ArH), 7.52 (t, J = 7.2Hz, 1H, ArH), 7.46 (t, J = 7.8Hz,
H, ArH), 7.39 (t, J = 7.8Hz, 2H, ArH), 7.32 (t, J = 7.8Hz, 2H, ArH), 7.11 (s, 1H, ArH), 7.03 (d, J
1
5

ACCEPTED MANUSCRIPT
=
7.8Hz, 1H, ArH), 6.81 (d, J = 7.8Hz, 1H, ArH), 4.38 (d, J = 7.8Hz, 1H, CH), 4.12 (d, J = 7.8Hz,
1
3
1
1
3
3 6
H, CH), 2.31 (s, 3H, CH ). C NMR (150MHz, DMSO-d ) δ(ppm): 191.9, 191.0, 172.2, 140.2,
36.3, 135.9, 134.0, 133.6, 130.4, 129.1, 128.9, 128.8, 128.0, 127.9, 124.0, 122.6, 109.8, 40.4,
+
8.5, 38.4, 20.8. HRMS (ESI) Calcd. for C25
H
19NNaO
3
([M+Na] ): 404.1257. Found: 404.1260.
3-(2-hydroxy-2,5-diphenylfuran-3(2H)-ylidene)-5-methylindolin-2-one (5c): Yellow solid,
30%. m.p. 178-180� . IR (KBr): 3404, 3196, 1658, 1614, 1580, 1484, 1449, 1386, 1324, 1255,
1
1
203, 1147, 1002, 935, 816. H NMR (600MHz, DMSO-d
6
) δ(ppm): 10.35 (s, 1H, NH), 8.88 (s,
1H, OH), 7.97 (s, 1H, ArH), 7.79 (s, 2H, ArH), 7.64 (s, 2H, ArH), 7.50 (s, 3H, ArH), 7.37 (s, 3H,
1
3
3
ArH), 7.16 (s, 1H, ArH), 6.75 (s, 1H, ArH), 6.59 (s, 1H, ArH), 1.97 (s, 3H, CH ). C NMR
6
(150MHz, DMSO-d ) δ(ppm): 169.0, 166.4, 155.3, 138.3, 138.2, 131.3, 129.0, 128.9, 128.3, 128.2,
127.5, 126.4, 125.4, 125.1, 121.7, 115.1, 111.1, 108.4, 100.6, 20.8. HRMS (ESI) Calcd. for
+
C
25
H
19NNaO
3
([M+Na] ): 404.1257. Found: 404.1259.
2-benzoyl-5'-methyl-3-(4-methylbenzoyl)spiro[cyclopropane-1,3'-indolin]-2'-one
(4d):
White solid, 55%. m.p. 216-218� . IR (KBr): 3185, 3028, 1712, 1672, 1603, 1490, 1448, 1411,
1
1
331, 1301, 1204, 1178, 1024, 808, 756. H NMR (600MHz, CDCl
3
) δ(ppm): 8.30 (s, 1H, NH),
7
.96 (d, J = 7.8Hz, 2H, ArH), 7.71 (d, J = 8.4Hz, 2H, ArH), 7.53 (t, J = 7.2Hz, 1H, ArH), 7.40 (t, J
7.8Hz, 2H, ArH), 7.14 (d, J = 7.8Hz, 2H, ArH), 7.11 (s, 1H, ArH), 7.02 (t, J = 7.8Hz, 1H, ArH),
.78 (d, J = 7.8Hz, 1H, ArH), 4.37 (d, J = 7.8Hz, 1H, CH), 4.10 (d, J = 7.8Hz, 1H, CH), 2.32 (s,
=
6
6
1
13
3 3
H, CH ). C NMR (150MHz, CDCl ) δ(ppm): 192.3, 190.2, 173.4, 144.5, 139.1, 136.9, 133.9,
33.8, 132.3, 129.5, 129.0, 128.7, 128.6, 128.5, 124.5, 123.2, 110.1, 41.3, 39.8, 38.8, 21.6, 21.3.
+
HRMS (ESI) Calcd. for C H NNaO ([M+Na] ): 418.1414. Found: 418.1416.
2
6
21
3
3-(2-hydroxy-5-phenyl-2-p-tolylfuran-3(2H)-ylidene)-5-methylindolin-2-one (5d): Yellow
solid, 36%. m.p. 190-192� . IR (KBr): 3424, 3206, 1702, 1647, 1616, 1484, 1448, 1351, 1261,
1
1
212, 1147, 1114, 1008, 936, 824. H NMR (600MHz, DMSO-d
6
) δ(ppm): 10.31 (s, 1H, NH),
8
.80 (s, 1H, OH), 7.93 (s, 1H, ArH), 7.78 (d, J = 7.2Hz, 2H, ArH), 7.51-7.47 (m, 5H, ArH), 7.21 (s,
1H, ArH), 7.17 (d, J = 7.8Hz, 2H, ArH), 6.75 (d, J = 7.8Hz, 1H, ArH), 6.57 (d, J = 7.8Hz, 1H,
13
3 3 6
ArH), 2.26 (s, 3H, CH ), 1.99 (s, 3H, CH ). C NMR (150MHz, DMSO-d ) δ(ppm): 169.0, 166.4,
155.5, 138.3, 135.4, 131.3, 129.0, 128.9, 128.8, 128.3, 127.5, 126.4, 125.3, 125.1,121.8, 114.9,
+
1
11.3, 108.4, 100.5, 20.8, 20.7. HRMS (ESI) Calcd. for C26
3
H21NNaO ([M+Na] ): 418.1414.
Found: 418.1414.
1
6

ACCEPTED MANUSCRIPT
(5'-fluoro-2'-oxospiro[cyclopropane-1,3'-indoline]-2,3-diyl)bis(phenylmethanone)
(4e):
White solid, 58%. m.p. 188-190� . IR (KBr): 3313, 3019, 1715, 1673, 1598, 1485, 1331, 1222,
1
1
184, 1151, 1017, 945, 739. H NMR (600MHz, CDCl
3
) δ(ppm): 8.84 (s, 1H, NH), 7.98 (d, J =
7
.8Hz, 2H, ArH), 7.79 (d, J = 7.2Hz, 2H, ArH), 7.56 (t, J = 7.2Hz, 1H, ArH), 7.49 (t, J = 7.2Hz,
H, ArH), 7.42 (d, J = 7.8Hz, 2H, ArH), 7.35 (t, J = 7.2Hz, 2H, ArH), 7.13 (d, J = 7.2Hz, 1H,
1
ArH), 6.96 (t, J = 7.2Hz, 1H, ArH), 6.89 (d, J = 7.8Hz, 1H, ArH), 4.42 (d, J = 7.8Hz, 1H, CH),
1
3
4
.14 (d, J = 7.8Hz, 1H, CH). C NMR (150MHz, CDCl
3
) δ(ppm): 191.9, 190.2, 173.8, 159.1 (d, J
=
238.8Hz), 137.9, 136.5, 136.0, 134.1, 133.8, 128.9, 128.7, 128.4, 125.8 (d, J = 9.2Hz), 115.4 (d,
J = 23.2Hz), 111.6 (d, J = 7.9Hz), 110.7 (d, J = 26.4Hz), 41.5, 39.9, 38.6. HRMS (ESI) Calcd. for
+
C
24
H
16FNNaO
3
([M+Na] ): 408.1006. Found: 408.1010.
5-fluoro-3-(2-hydroxy-2,5-diphenylfuran-3(2H)-ylidene)indolin-2-one (5e): Yellow solid,
3
1
1
4%. m.p. 170-172� . IR (KBr): 3404, 1717, 1671, 1604, 1537, 1479, 1388, 1347, 1287, 1252,
1
216, 1180, 1148, 936, 817. H NMR (600MHz, DMSO-d
6
) δ(ppm): 10.49 (s, 1H, NH), 9.05 (s,
H, OH), 7.95 (s, 1H, ArH), 7.82 (d, J = 7.2Hz, 2H, ArH), 7.63 (d, J = 6.6Hz, 2H, ArH), 7.54 (d, J
6.6Hz, 1H, ArH), 7.51 (d, J = 7.2Hz, 2H, ArH), 7.40 (d, J = 7.2Hz, 3H, ArH), 7.06 (d, J = 9.0Hz,
=
1
3
1
H, ArH), 6.78 (t, J = 7.2Hz, 1H, ArH), 6.67 (d, J = 7.2Hz, 1H, ArH). C NMR (150MHz,
DMSO-d
6
) δ(ppm): 168.8, 167.8, 156.8 (d, J = 231.3Hz), 157.0, 137.7, 136.7, 131.8, 129.3, 129.1,
1
2
4
28.6, 126.7, 125.2, 122.7 (d, J = 9.3Hz), 114.2, 113.2 (d, J = 23.4Hz), 111.3, 110.7 (d, J =
+
3
6.9Hz), 109.2 (d, J = 8.9Hz), 100.6. HRMS (ESI) Calcd. for C24H16FNNaO ([M+Na] ):
08.1006. Found: 408.1006.
5-chloro-3-(2-hydroxy-2,5-diphenylfuran-3(2H)-ylidene)indolin-2-one (5f): Yellow solid,
72%. m.p. 156-158� . IR (KBr): 3449, 3404, 1657, 1539, 1480, 1417, 1386, 1349, 1320, 1249,
1
1
201, 1144, 933, 814. H NMR (600MHz, DMSO-d
6
) δ(ppm): 10.60 (s, 1H, NH), 9.07 (s, 1H,
OH), 7.94 (s, 1H, ArH), 7.82 (d, J = 7.2Hz, 2H, ArH), 7.62 (d, J = 6.6Hz, 2H, ArH), 7.54 (d, J =
6
6
.6Hz, 1H, ArH), 7.50 (t, J = 7.2Hz, 2H, ArH), 7.39 (d, J = 6.6Hz, 3H, ArH), 7.31 (s, 1H, ArH),
1
3
6
.98 (d, J = 7.8Hz, 1H, ArH), 6.70 (d, J = 7.8Hz, 1H, ArH). C NMR (150MHz, DMSO-d )
δ(ppm): 168.6, 168.1, 157.4, 139.0, 137.7, 131.8, 129.3, 129.1, 128.6, 128.5, 126.7, 126.4, 125.3,
1
24.2, 123.6, 123.3, 113.6, 111.4, 110.0, 100.7. HRMS (ESI) Calcd. for C H ClNNaO
24 16
3
+
(
[M+Na] ): 424.0711. Found: 424.0710.
2
-benzoyl-5'-chloro-3-(4-methylbenzoyl)spiro[cyclopropane-1,3'-indolin]-2'-one
(4g):
1
7

ACCEPTED MANUSCRIPT
White solid, 62%. m.p. 222-224� . IR (KBr): 3179, 3063, 3022, 2862, 1723, 1667, 1606, 1477,
1
1
445, 1327, 1221, 1088, 1023, 937, 809. H NMR (600MHz, CDCl
3
) δ(ppm): 8.56 (s, 1H, NH),
7
.99 (d, J = 7.8Hz, 2H, ArH), 7.69 (d, J = 7.8Hz, 2H, ArH), 7.56 (t, J = 7.2Hz, 1H, ArH), 7.43 (t, J
7.2Hz, 2H, ArH), 7.36 (t, J = 6.6Hz, 1H, ArH), 7.22 (d, J = 7.8Hz, 1H, ArH), 7.15 (d, J = 7.8Hz,
H, ArH), 6.86 (d, J = 8.4Hz, 1H, ArH), 4.40 (d, J = 7.8Hz, 1H, CH), 4.12 (d, J = 7.8Hz, 1H, CH),
=
2
2
1
2
13
3 3
.33 (s, 3H, CH ). C NMR (150MHz, CDCl ) δ(ppm): 191.8, 189.7, 173.4, 144.9, 140.2, 136.6,
34.0, 133.5, 129.6, 129.5, 128.8, 128.8, 128.5, 128.4, 128.2, 126.1, 123.1, 111.7, 41.1, 40.1, 38.8,
+
1.7. HRMS (ESI) Calcd. for C H ClNNaO ([M+Na] ): 438.0867. Found: 438.0870.
2
5
18
3
2-benzoyl-3-(4-chlorobenzoyl)spiro[cyclopropane-1,3'-indolin]-2'-one (4h): White solid,
7
1
2
7
0%. m.p. 208-210� . IR (KBr): 3283, 1725, 1670, 1621, 1598, 1469, 1398, 1318, 1221, 1092,
1
014, 934, 842, 740. H NMR (600MHz, CDCl ) δ(ppm): 8.65 (s, 1H, NH), 7.98 (d, J = 7.8Hz,
3
H, ArH), 7.81 (d, J = 7.8Hz, 2H, ArH), 7.49 (t, J = 7.2Hz, 1H, ArH), 7.36-7.34 (m, 4H, ArH),
.29 (d, J = 7.8Hz, 1H, ArH), 7.25 (d, J = 7.2Hz, 1H, ArH), 7.03 (t, J = 7.8Hz, 1H, ArH), 6.94 (d,
1
3
J = 7.8Hz, 1H, ArH), 4.35 (d, J = 8.4Hz, 1H, CH), 4.16 (d, J = 8.4Hz, 1H, CH). C NMR
150MHz, CDCl ) δ(ppm): 191.0, 190.4, 173.7, 141.8, 140.5, 136.0, 134.9, 133.8, 133.0, 129.1,
28.9, 128.8, 128.4, 124.1, 122.8, 122.4, 110.0, 41.3, 39.5, 38.5. HRMS (ESI) Calcd. for
(
3
1
+
24
C H16ClNNaO
3
([M+Na] ): 424.0711. Found: 424.0714.
(2'-oxospiro[cyclopropane-1,3'-indoline]-2,3-diyl)bis((4-chlorophenyl)methanone)
(4i):
White solid, 42%. m.p. 202-204� . IR (KBr): 3292, 3053, 1711, 1672, 1618, 1586, 1470, 1397,
1
1
315, 1220, 1191, 1092, 1010, 843. H NMR (600MHz, CDCl
3
) δ(ppm): 8.66 (s, 1H, NH), 7.88 (d,
J = 8.4Hz, 2H, ArH), 7.73 (d, J = 8.4Hz, 2H, ArH), 7.35 (d, J = 8.4Hz, 2H, ArH), 7.33 (d, J =
.4Hz, 2H, ArH), 7.28-7.25 (m, 2H, ArH), 7.03 (t, J = 7.8Hz, 1H, ArH), 6.95 (d, J = 7.2Hz, 1H,
8
1
3
3
ArH), 4.32 (d, J = 7.2Hz, 1H, CH), 4.11 (d, J = 7.2Hz, 1H, CH). C NMR (150MHz, CDCl )
δ(ppm): 190.8, 189.4, 173.5, 141.7, 140.6, 140.3, 134.8, 134.4, 129.9, 129.8, 129.2, 129.1, 129.0,
+
1
23.9, 122.9, 122.5, 110.9, 41.2, 39.3, 38.5. HRMS (ESI) Calcd. for C24
58.0321. Found: 458.0324.
H15Cl
2
NNaO
3
([M+Na] ):
4
3-(2,5-bis(4-chlorophenyl)-2-hydroxyfuran-3(2H)-ylidene)indolin-2-one (5i): Yellow solid,
50%. m.p. 150-152� . IR (KBr): 3438, 3168, 1658, 1611, 1571, 1542, 1485, 1406, 1352, 1266,
1
1
177, 1152, 1096, 1053, 928, 838. H NMR (600MHz, DMSO-d
6
) δ(ppm): 10.50 (s, 1H, NH),
9
.07 (s, 1H, OH), 7.96 (s, 1H, ArH), 7.81 (d, J = 8.4Hz, 2H, ArH), 7.62 (d, J = 8.4Hz, 2H, ArH),
1
8

ACCEPTED MANUSCRIPT
7
.55 (d, J = 8.4Hz, 2H, ArH), 7.44 (d, J = 8.4Hz, 2H, ArH), 7.27 (d, J = 7.2Hz, 1H, ArH), 6.98 (t,
1
3
J = 7.2Hz, 1H, ArH), 6.71 (d, J = 7.8Hz, 1H, ArH), 6.60 (t, J = 7.8Hz, 1H, ArH). C NMR
150MHz, DMSO-d ) δ(ppm): 168.7, 165.0, 154.2, 140.7, 137.0, 136.0, 133.7, 129.2, 128.6, 128.2,
27.6, 127.3, 124.2, 121.4, 120.2, 115.6, 115.5, 110.8, 109.0, 101.2. HRMS (ESI) Calcd. for
(
6
1
+
C
24
H
15Cl
2
NNaO
3
([M+Na] ): 458.0321. Found: 458.0320.
2-(4-chlorobenzoyl)-3-(4-methylbenzoyl)2-(4-chlorobenzoyl)-3-(4-methyl-benzoyl)spiro[cy
clopropane-1,3'-indolin]-2'-one (4j): White solid, 72%. m.p. 198-200� . IR (KBr): 3293, 3051,
1
1
734, 1708, 1668, 1609, 1469, 1365, 1320, 1221, 1177, 1093, 1034, 1012, 841, 749. H NMR
3
(600MHz, CDCl ) δ(ppm): E-isomer: 8.62 (s, 1H, NH), 7.88 (d, J = 7.8Hz, 2H, ArH), 7.70 (d, J =
7
.8Hz, 2H, ArH), 7.34 (d, J = 8.4Hz, 2H, ArH), 7.29 (d, J = 7.2Hz, 1H, ArH), 7.24 (d, J = 7.8Hz,
H, ArH), 7.14 (d, J = 7.8Hz, 2H, ArH), 7.03 (t, J = 7.8Hz, 1H, ArH), 6.94 (d, J = 7.8Hz, 1H,
1
ArH), 4.33 (d, J = 7.8Hz, 1H, CH), 4.14 (d, J = 7.8Hz, 1H, CH), 2.32 (s, 3H, CH
s, 1H, NH), 7.85 (d, J = 7.8Hz, 2H, ArH), 7.75 (d, J = 7.8Hz, 2H, ArH), 7.32 (d, J = 8.4Hz, 2H,
ArH), 7.17 (d, J = 7.8Hz, 1H, ArH), 4.36 (d, J = 7.8Hz, 1H, CH), 4.12 (d, J = 7.8Hz, 1H, CH),
3
); Z-isomer: 8.56
(
1
3
2
1
1
3 3
.35 (s, 3H, CH ); Z/E = 2:5; C NMR (150MHz, CDCl ) δ(ppm): 191.3, 191.0, 189.9, 189.6,
73.5, 145.0, 144.5, 141.6, 140.4, 140.2, 135.0, 134.6, 133.7, 129.9, 129.8, 129.5, 129.1, 128.7,
28.5, 124.2, 122.8, 122.5, 110.7, 41.3, 41.0, 39.7, 39.3, 38.7, 38.2, 31.7. HRMS (ESI) Calcd. for
+
C H ClNNaO ([M+Na] ): 438.0867. Found: 438.0870.
2
5
18
3
2
-benzoyl-3-(4-chlorobenzoyl)-5'-methylspiro[cyclopropane-1,3'-indolin]-2'-one
(4k):
White solid, 60%. m.p. 220-222� . IR (KBr): 3187, 3032, 1714, 1670, 1626, 1592, 1489, 1447,
1
1
329, 1301, 1205, 1092, 1020, 807. H NMR (600MHz, CDCl ) δ(ppm): 8.30 (s, 1H, NH), 7.96 (d,
3
J = 7.8Hz, 2H, ArH), 7.74 (d, J = 8.4Hz, 2H, ArH), 7.54 (t, J = 7.2Hz, 1H, ArH), 7.40 (t, J =
7
6
3
1
.2Hz, 2H, ArH), 7.32 (d, J = 8.4Hz, 2H, ArH), 7.10 (s, 1H, ArH), 7.04 (t, J = 7.2Hz, 1H, ArH),
.80 (d, J = 7.8Hz, 1H, ArH), 4.36 (d, J = 7.8Hz, 1H, CH), 4.07 (d, J = 7.8Hz, 1H, CH), 2.31 (s,
13
3 3
H, CH ). C NMR (150MHz, CDCl ) δ(ppm): 192.0, 189.6, 173.1, 140.2, 139.0, 136.7, 134.5,
34.0, 132.5, 129.8, 129.2, 128.8, 128.6, 124.1, 123.2, 110.1, 41.2, 39.4, 38.7, 21.3. HRMS (ESI)
+
Calcd. for C25
H
18ClNNaO
3
([M+Na] ): 438.0867. Found: 438.0869.
3-(2-(4-chlorophenyl)-2-hydroxy-5-phenylfuran-3(2H)-ylidene)-5-methylindol-in-2-one
(5k): Yellow solid, 26%. m.p. 196-198� . IR (KBr): 3444, 3163, 1655, 1544, 1484, 1406, 1337,
1
1
268, 1209, 1088, 1006, 936, 811. H NMR (600MHz, DMSO-d
6
) δ(ppm): 10.34 (s, 1H, NH),
1
9

ACCEPTED MANUSCRIPT
8
7
1
.89 (s, 1H, OH), 7.96 (s, 1H, ArH), 7.81 (d, J = 8.4Hz, 2H, ArH), 7.63 (d, J = 6.6Hz, 2H, ArH),
.54 (d, J = 8.4Hz, 2H, ArH), 7.37 (d, J = 7.8Hz, 3H, ArH), 7.13 (s, 1H, ArH), 6.76 (d, J = 7.8Hz,
13
3 6
H, ArH), 6.57 (d, J = 7.8Hz, 1H, ArH), 1.96(s, 3H, CH ). C NMR (150MHz, DMSO-d )
δ(ppm): 168.9, 165.0, 154.8, 138.4, 138.1, 135.8, 129.1, 129.0, 128.4, 128.3, 128.2, 127.8, 127.7,
125.4, 125.1, 121.6, 115.6, 111.3, 108.5, 101.1, 20.7. HRMS (ESI) Calcd. for C25H18ClNNaO
3
+
(
[M+Na] ): 438.0867. Found: 438.0866.
(5'-methyl-2'-oxospiro[cyclopropane-1,3'-indoline]-2,3-diyl)bis((4-chlorophenyl)methanon
e) (4l): White solid, 43%. m.p. 182-184� . IR (KBr): 3442, 1709, 1670, 1590, 1490, 1403, 1326,
1
1
202, 1092, 1042, 1012, 822, 763. H NMR (600MHz, CDCl
3
) δ(ppm): 8.25 (s, 1H, NH), 7.88 (d,
J = 8.4Hz, 2H, ArH), 7.74 (d, J = 8.4Hz, 2H, ArH), 7.35-7.33 (m, 4H, ArH), 7.06 (s, 1H, ArH),
7
.05 (d, J = 7.8Hz, 1H, ArH), 6.81 (d, J = 7.8Hz, 1H, ArH), 4.30 (d, J = 7.8Hz, 1H, CH), 4.07 (d, J
13
=
3 3
7.8Hz, 1H, CH), 2.32 (s, 3H, CH ). C NMR (150MHz, CDCl ) δ(ppm): 192.8, 189.4, 173.2,
1
4
4
40.5, 140.3, 139.1, 134.9, 134.4, 132.6, 129.9, 129.8, 129.4, 129.2, 129.1, 123.9, 123.1, 110.3,
+
1.2, 39.3, 38.5, 21.3. HRMS (ESI) Calcd. for C25
72.0478.
H
17Cl
2
NNaO
3
([M+Na] ): 472.0478. Found:
3-(2,5-bis(4-chlorophenyl)-2-hydroxyfuran-3(2H)-ylidene)-5-methylindolin-2-one
(5l):
Yellow solid, 44%. m.p. 152-154� . IR (KBr): 3435, 3199, 1653, 1545, 1485, 1405, 1338, 1266,
1
1
211, 1149, 1095, 1052, 1009, 938, 842. H NMR (600MHz, DMSO-d ) δ(ppm): 10.37 (s, 1H,
6
NH), 9.04 (s, 1H, OH), 7.95 (s, 1H, ArH), 7.81 (d, J = 8.4Hz, 2H, ArH), 7.63 (d, J = 7.8Hz, 2H,
ArH), 7.54 (d, J = 8.4Hz, 2H, ArH), 7.45 (d, J = 7.8Hz, 2H, ArH), 7.13 (s, 1H, ArH), 6.79 (d, J =
1
3
7
.8Hz, 1H, ArH), 6.69 (d, J = 7.8Hz, 1H, ArH), 1.99 (s, 3H, CH3). C NMR (150MHz, DMSO-d6)
δ(ppm): 168.8, 164.9, 154.1, 138.5, 137.1, 135.9, 133.7, 129.2, 128.5, 128.4, 128.2, 128.0, 127.6,
2 3
127.3, 125.0, 121.4, 115.8, 110.6, 108.6, 101.1, 20.8. HRMS (ESI) Calcd. for C25H17Cl NNaO
+
(
[M+Na] ): 472.0478. Found: 472.0474.
2-(4-chlorobenzoyl)-5'-methyl-3-(4-methylbenzoyl)spiro[cyclopropane-1,3'-indolin]-2'-one
(4m): White solid, 32%. m.p. 212-214� . IR (KBr): 3297, 3023, 2917, 1717, 1674, 1597, 1489,
1
1
400, 1325, 1184, 1093, 1039, 822. H NMR (600MHz, CDCl
3
) δ(ppm): E-isomer: 8.20 (s, 1H,
NH), 7.89 (d, J = 8.4Hz, 2H, ArH), 7.70 (d, J = 7.8Hz, 2H, ArH), 7.34 (d, J = 8.4Hz, 2H, ArH),
7
.16 (d, J = 7.8Hz, 2H, ArH), 7.08 (s, 1H, ArH), 7.04 (d, J = 7.8Hz, 1H, ArH), 6.80 (d, J = 7.2Hz,
H, ArH), 4.31 (d, J = 7.8Hz, 1H, CH), 4.09 (d, J = 7.8Hz, 1H, CH), 2.34 (s, 3H, CH ), 2.32 (s,
1
3
2
0

ACCEPTED MANUSCRIPT
3
7
3
1
1
H, CH ). Z-isomer: 8.16 (s, 1H, NH), 7.85 (d, J = 7.8Hz, 2H, ArH), 7.75 (d, J = 7.8Hz, 2H, ArH),
3
.18 (d, J = 8.4Hz, 2H, ArH), 4.34 (d, J = 7.8Hz, 1H, CH), 4.07 (d, J = 7.8Hz, 1H, CH), 2.36 (s,
13
3 3 3
H, CH ), 2.31 (s, 3H, CH ); Z/E = 1:4. C NMR (150MHz, CDCl ) δ(ppm): 191.5, 191.1, 190.2,
89.8, 173.7, 144.9, 144.7, 140.3, 140.1, 139.5, 135.0, 134.6, 134.2, 133.7, 132.3, 129.9, 129.8,
29.5, 129.3, 129.1, 128.7, 128.6, 124.2, 122.9, 110.7, 41.4, 41.2, 39.5, 39.2, 38.7, 38.6, 21.7, 21.3.
+
HRMS (ESI) Calcd. for C26
H
20ClNNaO
3
([M+Na] ): 452.1024. Found: 452.1025.
3-(5-(4-chlorophenyl)-2-hydroxy-2-p-tolylfuran-3(2H)-ylidene)-5-methylindolin-2-one
(5m): Yellow solid, 47%. m.p. 188-190� . IR (KBr): 3440, 3220, 1654, 1571, 1543, 1482, 1406,
1
1
1
7
6
383, 1334, 1266, 1220, 1150, 1111, 1090, 935, 811. H NMR (600MHz, DMSO-d
6
) δ(ppm):
0.33 (s, 1H, NH), 8.83 (s, 1H, OH), 7.94 (s, 1H, ArH), 7.80 (d, J = 8.4Hz, 2H, ArH), 7.54 (d, J =
.8Hz, 2H, ArH), 7.50 (d, J = 7.8Hz, 2H, ArH), 7.19 (d, J = 8.4Hz, 2H, ArH), 7.16 (s, 1H, ArH),
.76 (d, J = 7.2Hz, 1H, ArH), 6.57 (d, J = 7.8Hz, 1H, ArH), 2.26 (s, 3H, CH
3
), 1.98 (s, 3H, CH
3
).
13
C NMR (150MHz, DMSO-d
6
) δ(ppm): 168.9, 165.0, 155.0, 138.3, 135.7, 135.3, 129.1, 128.8,
128.4, 128.1, 127.9, 127.8, 127.7, 125.3, 121.7, 115.5, 111.4, 108.4, 105.4, 101.0, 20.8, 20.7.
+
HRMS (ESI) Calcd. for C26
H
20ClNNaO
3
([M+Na] ): 452.1024. Found: 452.1022.
2-benzoyl-3-(4-chlorobenzoyl)-5'-fluorospiro[cyclopropane-1,3'-indolin]-2'-one (4n): White
solid, 76%. m.p. 204-206� . IR (KBr): 3444, 3013, 1725, 1696, 1665, 1589, 1484, 1401, 1329,
1
1
229, 1183, 1150, 1091, 1036, 949, 850. H NMR (600MHz, CDCl ) δ(ppm): 8.63 (s, 1H, NH),
3
7
.92 (d, J = 8.4Hz, 2H, ArH), 7.79 (d, J = 7.8Hz, 2H, ArH), 7.51 (t, J = 7.2Hz, 1H, ArH), 7.40 (t, J
=
8.4Hz, 2H, ArH), 7.37 (d, J = 7.2Hz, 2H, ArH), 7.11 (d, J = 7.8Hz, 1H, ArH), 6.98 (t, J = 8.4Hz,
1H, ArH), 6.89 (d, J = 7.8Hz, 1H, ArH), 4.36 (d, J = 7.8Hz, 1H, CH), 4.12 (d, J = 7.8Hz, 1H, CH).
1
3
C NMR (150MHz, CDCl
35.9, 134.8, 133.9, 130.0, 129.2, 128.9, 12.84, 125.6 (d, J = 7.1Hz), 115.5 (d, J = 24.3Hz), 111.4
15FClNNaO
3
) δ(ppm): 190.7, 190.0, 173.4, 159.1 (d, J = 239.3Hz), 140.7, 137.6,
1
(d, J = 8.1Hz), 110.8 (d, J = 25.3Hz), 41.4, 40.0, 38.5. HRMS (ESI) Calcd. for C24
H
3
+
(
[M+Na] ): 442.0617. Found: 442.0619.
(5'-fluoro-2'-oxospiro[cyclopropane-1,3'-indoline]-2,3-diyl)bis((4-chlorophenyl)methanone)
(4o): White solid, 80%. m.p. 200-202� . IR (KBr): 3251, 1721, 1677, 1587, 1480, 1400, 1324,
1
1
224, 1179, 1092, 1011, 841, 811. H NMR (600MHz, CDCl ) δ(ppm): 8.07 (s, 1H, NH), 7.93 (d,
3
J = 8.4Hz, 2H, ArH), 7.74 (d, J = 8.4Hz, 2H, ArH), 7.42 (t, J = 8.4Hz, 2H, ArH), 7.37 (t, J =
.4Hz, 2H, ArH), 7.10 (d, J = 8.4Hz, 1H, ArH), 6.98 (t, J = 8.4Hz, 1H, ArH), 6.86 (d, J = 7.8Hz,
8
2
1

ACCEPTED MANUSCRIPT
13
1
H, ArH), 4.35 (d, J = 7.8Hz, 1H, CH), 4.08 (d, J = 7.8Hz, 1H, CH). C NMR (150MHz, CDCl )
3
δ(ppm): 190.5, 188.9, 173.0, 159.1 (d, J = 239.7Hz), 140.9, 140.5, 137.4, 134.7, 134.2, 130.0,
129.7, 129.5, 129.3, 125.4 (d, J = 7.5Hz), 115.5 (d, J = 23.7Hz), 111.2 (d, J = 8.1Hz), 110.9 (d, J =
+
26.3Hz), 41.2, 39.8, 38.5. HRMS (ESI) Calcd. for C24
H14FCl
2
NNaO
3
([M+Na] ): 476.0227.
Found: 476.0229.
-chloro-3-(5-(4-chlorophenyl)-2-hydroxy-2-phenylfuran-3(2H)-ylidene)indolin-2-one (5p):
5
Yellow solid, 78%. m.p. 180-182� . IR (KBr): 3440, 3178, 1660, 1591, 1542, 1489, 1449, 1408,
1
1
340, 1239, 1170, 1112, 1081, 981, 813. H NMR (600MHz, DMSO-d ) δ(ppm): 10.63 (s, 1H,
6
NH), 9.11 (s, 1H, OH), 7.96 (s, 1H, ArH), 7.85 (d, J = 7.2Hz, 2H, ArH), 7.62 (d, J = 7.2Hz, 2H,
ArH), 7.56 (d, J = 7.2Hz, 2H, ArH), 7.39 (brs, 3H, ArH), 7.30 (s, 1H, ArH), 6.99 (d, J = 7.2Hz, 1H,
13
ArH), 6.70 (d, J = 7.2Hz, 1H, ArH). C NMR (150MHz, DMSO-d ) δ(ppm): 168.5, 166.6, 156.9,
6
139.1, 137.6, 136.3, 129.3, 129.2, 128.5, 128.4, 127.4, 126.5, 125.3, 124.2, 123.7, 123.1, 114.1,
+
1
11.5, 110.1, 101.2. C24
H
15Cl
2
NNaO
3
([M+Na] ): 458.0321. Found: 458.0322.
(5'-chloro-2'-oxospiro[cyclopropane-1,3'-indoline]-2,3-diyl)bis((4-chlorophenyl)methanone)
(4q): White solid, 49%. m.p. 210-212� . IR (KBr): 3290, 3049, 1721, 1672, 1618, 1594, 1472,
1
1
399, 1315, 1220, 1191, 1092, 1020, 843. H NMR (600MHz, CDCl
3
) δ(ppm): 8.34 (s, 1H, NH),
7
.92 (d, J = 8.4Hz, 2H, ArH), 7.73 (d, J = 8.4Hz, 2H, ArH), 7.42 (d, J = 8.4Hz, 2H, ArH), 7.36 (d,
J = 8.4Hz, 2H, ArH), 7.32 (d, J = 7.8Hz, 1H, ArH), 7.25 (d, J = 7.8Hz, 1H, ArH), 6.88 (d, J =
1
3
7
.8Hz, 1H, ArH), 4.33 (d, J = 7.8Hz, 1H, CH), 4.09 (d, J = 7.8Hz, 1H, CH). C NMR (150MHz,
CDCl ) δ(ppm): 190.5, 188.8, 172.9, 140.9, 140.6, 140.0, 134.7, 134.2, 130.1, 129.7, 129.3, 129.2,
29.0, 128.5, 125.6, 123.1, 111.7, 40.9, 39.8, 38.5. HRMS (ESI) Calcd. for C H Cl NNaO
3
1
2
4
14
3
3
+
(
[M+Na] ): 491.9931. Found: 491.9932.
-(2,5-bis(4-chlorophenyl)-2-hydroxyfuran-3(2H)-ylidene)-5-chloroindolin-2-one
3
(5q):
Yellow solid, 32%. m.p. 184-186� . IR (KBr): 3399, 3194, 1659, 1611, 1537, 1481, 1446, 1348,
1
1
250, 1203, 1169, 1110, 1075, 975, 815. H NMR (600MHz, DMSO-d
6
) δ(ppm): 10.64 (s, 1H,
NH), 9.24 (s, 1H, OH), 7.95 (s, 1H, ArH), 7.84 (d, J = 7.8Hz, 2H, ArH), 7.62 (d, J = 7.8Hz, 2H,
ArH), 7.56 (d, J = 8.4Hz, 2H, ArH), 7.47 (d, J = 8.4Hz, 2H, ArH), 7.27 (s, 1H, ArH), 7.00 (s, 1H,
13
ArH), 6.72 (d, J = 7.8Hz, 1H, ArH). C NMR (150MHz, DMSO-d ) δ(ppm): 168.7, 164.7, 154.0,
6
138.4, 137.0, 135.7, 133.5, 129.0, 128.4, 128.3, 128.0, 127.8, 127.5, 127.2, 124.8, 121.3, 115.6,
+
1
10.4, 108.5, 101.0. HRMS (ESI) Calcd. for C24
H
14Cl
3
NNaO
3
([M+Na] ): 491.9931. Found:
2
2

ACCEPTED MANUSCRIPT
491.9926.
3
. General procedure for the preparation of 3-furan-3(2H)-ylidene)indolin-2-ones from the
reactions of N-phenacyl-4-dimethylaminopyrididinium salts with 3-phenacylideneoxindoles:
mixture of N-phenacyl-4-dimethylaminopyridinium bromide or N-p-chlorophenacyl-
-dimethylaminopyridinium chloride (1.1 mmol) 3-phenacylideneoxindoles (1.0 mmol) and
A
4
triethylamine (0.2 mmol) in acetonitrile (10mL) was stirred at room temperature for six hours. The
resulting precipitates were collected by filtration, which was collected by filtration and washed
with cold ethanol to give pure product for analysis.
3-(5-(4-chlorophenyl)-2-hydroxy-2-phenylfuran-3(2H)-ylidene)-5-methylindolin-2-one (5r):
Red solid, 80%. m.p. 216-218� . IR (KBr): 3433, 2025, 1671, 1569, 1545, 1481, 1454, 1427, 1405,
1
1
383, 1346, 1322, 1257, 1196, 1151, 1085, 1067, 1007, 933, 880, 821, 802, 767, 733, 699, 644. H
NMR (600MHz, DMSO-d
6
) δ(ppm): 10.36 (s, 1H, NH), 9.01 (s, 1H, OH), 7.99 (s, 1H, CH), 7.81
(d, J = 8.4Hz, 2H, ArH), 7.65 (d, J = 7.2Hz, 2H, ArH), 7.54 (d, J = 8.4Hz, 2H, ArH), 7.38 (q, J =
7
1
1
.8Hz, 3H, ArH), 7.14 (s, 1H, ArH), 6.76 (d, J = 7.8Hz, 1H, ArH), 6.58 (d, J = 7.8Hz, 1H, ArH),
13
6
.97 (s, 3H, CH3). C NMR (150MHz, DMSO-d ) δ(ppm): 168.9, 165.2, 154.8, 138.3, 138.1,
35.8, 129.1, 129.0, 128.4, 128.3, 128.2, 127.6, 125.4, 125.0, 121.7, 115.3, 108.4, 101.0,20.7.
+
HRMS (ESI) Calcd. for C25
H
18ClNNaO
3
([M+Na] ): 438.0867. Found: 438.0865.
5-chloro-3-(5-(4-chlorophenyl)-2-hydroxy-2-p-tolylfuran-3(2H)-ylidene)indolin-2-one (5s):
Red solid, 90%. m.p. 194-196� . IR (KBr): 3445, 2025, 1666, 1570, 1543, 1485, 1445, 1407, 1347,
1
1
222, 1183, 1110, 1091, 1055, 1010, 982, 932, 872, 835, 812, 718, 693, 652. H NMR (600MHz,
DMSO-d ) δ(ppm): 10.62 (s, 1H, NH), 9.05 (s, 1H, OH), 7.95 (s, 1H, CH), 7.84 (d, J = 7.8Hz, 2H,
6
ArH), 7.65 (d, J = 8.4Hz, 2H, ArH), 7.50 (d, J = 7.8Hz, 2H, ArH), 7.36 (s, 1H, ArH), 7.20 (d, J =
1
3
7
.8Hz, 1H, ArH), 6.70 (d, J = 7.8Hz, 1H, ArH), 2.28 (s, 3H, CH3). C NMR (150MHz, DMSO-d
6
)
δ(ppm): 168.5, 166.6, 157.1, 139.1, 136.3, 134.7, 129.2, 129.0, 128.5, 127.5, 126.5, 125.2, 124.2,
2 3
123.8, 123.2, 113.9, 111.6, 110.0, 101.1, 20.7. HRMS (ESI) Calcd. for C25H17Cl NNaO
+
(
[M+Na] ): 472.0478. Found: 472.0485.
3-(5-(4-chlorophenyl)-2-hydroxy-2-p-tolylfuran-3(2H)-ylidene)-5-fluoroindolin-2-one(5t):
Red solid, 92%. m.p. 176-178� . IR (KBr): 3615, 3438, 2025, 1655, 1570, 1543, 1481, 1408, 1383,
1351, 1290, 1263, 1243, 1186, 1149, 1112, 1092, 1055, 1011, 992, 938, 866, 834, 810, 698, 654,
1
6
25. H NMR (600MHz, DMSO-d
6
) δ(ppm): 10.50 (s, 1H, NH), 9.03 (s, 1H, OH), 7.95 (s, 1H,
2
3

ACCEPTED MANUSCRIPT
CH), 7.83 (d, J = 7.8Hz, 2H, ArH), 7.55 (d, J = 8.4Hz, 2H, ArH), 7.50 (d, J = 7.8Hz, 2H, ArH),
7
1
.20 (d, J = 7.8Hz, 2H, ArH), 7.09 (d, J = 9.6Hz, 1H, ArH), 6.80 (t, J = 8.4Hz, 1H, ArH), 6.68(mix,
13
H, ArH), 2.28 (s, 3H, CH3). C NMR (150MHz, DMSO-d
19.7Hz), 138.7, 136.8, 136.2, 134.8, 129.2, 129.1, 128.4, 127.5, 125.2, 122.7(d, J = 9.0Hz),
14.7(d, J = 11.6Hz), 113.3(d, J = 24.0Hz), 111.6, 110.9, 109.2(d, J = 7.5Hz), 101.1, 20.7. HRMS
6
) δ(ppm): 168.8, 166.3, 157.2(d, J =
1
1
+
(
ESI) Calcd. for C25
3
H17ClFNNaO ([M+Na] ): 456.0773. Found: 456.0775.
Acknowledgment: This work was financially supported by the National Natural Science
Foundation of China (Grant No. 21172189) and the Priority Academic Program Development of
Jiangsu Higher Education Institutions.
Supporting Information: Crystallographic data 3e (CCDC 906554), 4a (CCDC 904920), 5b
(
CCDC 904921), and 5l (CCDC 906832) have been deposited at the Cambridge Crystallographic
Database Centre.
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2
6

ACCEPTED MANUSCRIPT
Graphic abstract:
Molecular diversity of cycloaddition reactions of functionalized pyridinium salts
with 3-phenacylideneoxindoles
Qin Fu, Chao-Guo Yan
2
7

ACCEPTED MANUSCRIPT
Molecular diversity of cycloaddition reactions of the functionalized pyridinium
salts with 3-phenacylideneoxindoles
Qin Fu, Chao-Guo Yan*
Supporting Information
General Experimental Methods and Characterization of compounds
H NMR and 13C NMR of the preparaed compounds
2-15
1
16-53
X-Ray Crystallographic Data: CIF in separate file.
Crystallographic data 3e (CCDC 906554), 4a (CCDC 904920), 5b (CCDC 904921), and 5l
(
CCDC 906832) have been deposited vat the Cambridge Crystallographic Database Centre and is
available on request from the Director, CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK
http//www.ccdc.cam.ac.uk).
(

ACCEPTED MANUSCRIPT
Experimental Section
All reagents and solvents were commercial available with analytical grade and used as received. All
evaporations of organic solvents were carried out with a rotary evaporator in conjunction with a
water aspirator. Melting points were taken on a hot-plate microscope apparatus and were
1
13
uncorrected. H and C NMR spectra were recorded with a Bruker AV-600 instrument. IR spectra
were obtained on a Bruker Tensor 27 spectrometer (KBr disc). HRMS were measured at AB 5800
MALDI-TOF/TOF instrument. X-ray data were collected on a Bruker Smart APEX-2
diffractometer. Pyridinium salts were prepared by heating pyridine with p-nitrobenzyl bromide,
α-phenacyl bromide, and N,N-diethyl chloroacetamide in acetonitrile according to the published
procedure.
1
. General procedure for the preparation of spiro[cyclopropane-1,3'-indolines] 3a-3j from
the reactions of pyrididinium salts with 3-phenacylideneoxindoles: A mixture of
N-p-nitrobenzylpyridinium bromide or N-diethylcarbamoylmethylpyridinium chloride (1.1 mmol)
3
-phenacylideneoxindoles (1.0 mmol) and triethylamine (0.2 mmol) in ethanol (15mL) was stirred
at about 50°C for six hours. The resulting precipitates were collected by filtration, which were
recrystallized in a mixture of chloroform and ethanol to give pure product for analysis.
2-benzoyl-3-(4-nitrophenyl)spiro[cyclopropane-1,3'-indolin]-2'-one (3a):
O N
2
White solid, 78%. m.p. 216-218°C. IR (KBr): 3422, 3081, 1700, 1621,
1
1600, 1515, 1469, 1345, 1281, 1108, 1017, 975, 847. H NMR
3
(600MHz, CDCl ) δ(ppm): 8.25 (s, 1H, NH), 8.18 (d, J = 8.4Hz, 2H,
ArH) , 7.96 (d, J = 7.8Hz, 2H, ArH), 7.58 (t, J = 7.2Hz, 1H, ArH),
7.53 (d, J = 8.4Hz, 2H, ArH), 7.44 (t, J = 7.2Hz, 2H, ArH), 7.25 (d, J
O
O
N
=
7.8Hz, 1H, ArH), 7.19 (t, J = 7.8Hz, 1H, ArH), 6.99 (t, J = 7.2Hz,
H
1
H, ArH), 6.84 (d, J = 7.2Hz, 1H, ArH), 4.30 (d, J = 7.8Hz, 1H, CH),
13
4
1
3
.17 (d, J = 7.8Hz, 1H, CH). C NMR (150MHz, CDCl ) δ(ppm): 192.3, 173.9, 147.2, 141.3,
41.2, 136.7, 134.0, 130.3, 128.9, 128.5, 128.1, 125.6, 123.3, 122.6, 122.3, 110.2, 42.0, 41.0, 38.3.
+
HRMS (ESI) Calcd. for C23
H
16
N
2
NaO
4
([M+Na] ): 407.1002. Found: 407.1003.
2-(4-chlorobenzoyl)-3-(4-nitrophenyl)spiro[cyclopropane-1,3'-indolin]-2'-one (3b):
Cl
White solid, 76%. m.p. 222-224°C. IR (KBr): 3444, 1721, 1671, 1629,
O N
2
1
1
525, 1469, 1047, 1349, 1191, 1089, 1012, 842. H NMR (600MHz,
CDCl
ArH), 7.81 (s, 1H, NH), 7.52 (d, J = 8.4Hz, 2H, ArH), 7.41 (d, J =
.4Hz, 2H, ArH), 7.12 (t, J = 7.2Hz, 2H, ArH), 7.00 (t, J = 7.8Hz, 1H,
ArH), 6.88 (d, J = 7.8Hz, 1H, ArH), 4.23 (d, J = 7.8Hz, 1H, CH), 4.15
3
) δ(ppm): 8.19 (d, J = 9.0Hz, 2H, ArH), 7.90 (d, J = 9.0Hz, 2H,
O
8
O
N
1
3
H
3
(d, J = 7.8Hz, 1H, CH). C NMR (150MHz, CDCl ) δ(ppm): 191.0,
2