PPh3 Mediated Reductive Annulation Reaction between Isatins and Electron Deficient Dienes to Construct Spirooxindole Compounds

Article abstract of DOI:10.1021/acs.joc.7b00595

A PPh₃ mediated reductive annulation reaction between isatins and 4,4-dicyano-2-methylenebut-3-enoates was developed. The reaction provided an alternative method for constructing five- and three-membered all-carbon spirooxindole compounds. Lith

Full text of DOI:10.1021/acs.joc.7b00595

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Article
PPh3 Mediated Reductive Annulation Reaction between Isatins and
Electron Deficient Dienes to Construct Spirooxindole Compounds
Lei Zhang, Hong Lu, Guo-Qiang Xu, Zhu-Yin Wang, and Peng-Fei Xu
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 15 May 2017
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PPh3 Mediated Reductive Annulation Reaction between Isatins and
Electron Deficient Dienes to Construct Spirooxindole Compounds
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Lei Zhang, Hong Lu, Guo-Qiang Xu, Zhu-Yin Wang and Peng-Fei Xu*
State Key Laboratory of Applied Organic Chemistry, and College of Chemistry and Chemical Engineering, Lanzhou
University, Lanzhou 730000, P. R. China
Abstract: A PPh3 mediated reductive annulation reaction between isatins and 4,4-dicyano-2-methylenebut-3-enoates was
developed. The reaction provided an alternative method for constructing five-membered and three-membered all-carbon
spirooxindole compounds. Lithium chloride as a Lewis acid played a key role in the synthesis of spirocyclopentenyl oxindole
compounds.
INTRODUCTION
Spirooxindole moiety is an important framework present in a variety of pharmaceutical molecules1 and natural products2.
As representative compounds, compound a in Scheme 1 is a natural product that contains the spirooxindole framework,
while compounds b and c are two pharmaceutical molecules which show distinct antitumor activities1 since the strained
spiro-cyclopropane at the C3 position of oxindoles plays an important role in their biological activities. So far, the
spirooxindole framework has attracted great interest from chemists due to its biological importance and the challenge of
synthesizing it3. Isatins have been widely used as raw materials in the synthesis of spirooxindole compounds4, however, to
the best of our knowledge, isatins are rarely reported as a C1 synthon in the construction of all-carbon spirooxindole
compounds5, since the deoxygenation step is needed.
In the early reports, α-dicarbonyl compounds could be reduced by phosphine6 with one of the carbonyls deoxygenated, and
a carboxylic ester could be synthesized by a reductive coupling of α-keto ester with a carboxylic acid7. It is commonly
believed that either a five-coordinate 1,3,2-dioxaphospholene intermediate or a dipolar ion (a in Scheme 2) is formed
between the α-dicarbonyl compound and phosphine8. In our preliminary study, it was found that isatins could undergo a
reductive coupling reaction at the C3 position with a carboxylic acid, and a benzoate at C3 position of isatins could be
obtained, which also proved that a Kukhtin−Ramirez intermediate was formed between the N-methyl protected isatin and
triphenylphosphine (a in Scheme 2)7c,8b. In this process, the intermediate underwent a two-step process: first, the intermediate
accepted a proton from the acid, then the carboxylic ion attacked the C-O bond of the intermediate, triphenylphosphine oxide
departed and the ester was finally formed. Considering the feature of the above reaction, this intermediate of isatins might
have potential in the synthesis of spirooxindole compounds with another synthon. With our ongoing interest in the
exploration of heterocyclic scaffold construction through organocatalysis9, we used triphenylphosphine as a deoxygenation
regent and developed a new reaction in which isatins could react directly with electron-deficient dienes and produce various
spiro-oxindole compounds.
Scheme 1. Representative natural products and pharmaceutical molecules
Scheme 2. Different PPh3 involved intermediates
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RESULTS AND DISCUSSION
In our initial investigation, ethyl 4,4-dicyano-2-methylene-3-phenylbut-3-enoate 2a10, 11, PPh3 and an N-methyl protected
isatin were used as substrates. When stoichiometric amount of PPh3 was added, a yellow solid of tetravalent phosphinium
zwitterion (b in Scheme 2) was formed immediately. An unexpected cyclopropanation compound was produced after heating
for 24 h (Table 1, entry 1). The cyclopropanation product could also be obtained with the separated tetravalent phosphinium
zwitterions and the N-methyl protected isatin under the same conditions. To improve the efficiency of this process, a series
of N-protected isatins were tested. When the electron donating group protected isatins were used, the dimerization of isatins
was observed, phosphorous ylides of isatins were also formed in the reaction system and the excessive PPh3 was consumed
by isatins. Finally, it was found that tosyl group was the best N-protection group for the reaction (Table 1, entries 1-5). The
solvents were then screened and it was found that toluene performed the best. Polar protic solvents were not favorable for
this process, and no product was observed when MeOH was used as the solvent (see Supporting Information, Table S1).
Other polar solvents showed moderate yields in this process. Further tests showed that PPh3 was the optimal trivalent
phosphorus reagent, P(NMe2)3 (Table 1, entry 6) could cause side reactions due to its high activity, PBu3 and MePh2P
produced only moderate yields (Table 1, entries 7, 8).
Table 1. Scope of N-protected isatinsa.
NC
CN
O
Ph
EtO2C
NC
CN
60 o
toluene
C
PPh3
O
+
+
+
Ph3P
O
N
R1
O
CO2Et
N
2a
R1
1
3
entry
R1
P reagent
PPh3
temp (oC)
Time (h)
drb
yieldc (%)
1
2
3
4
5
6
7
8
Me
Boc
Ac
Bn
Ts
60
60
60
60
60
0
24
24
20
42
24
1
>20:1
____
>20:1
>20:1
6:1
20
n.r.
51
73
83
32
43
51
PPh3
PPh3
PPh3
PPh3
Ts
P(NMe2)3
PBu3
6:1
Ts
60
60
6
6:1
Ts
Ph2MeP
14
6:1
aStandard procedure: substrate 1 (0.15 mmol) and substrate 2a (0.1 mmol) were added into a reaction tube containing the solvent (0.6 mL),
PR3 solution (1.5 equiv) in the solvent (0.4 mL) was then added slowly into the tube with stirring at room temperature under N2
atmosphere, and then the reaction tube was heated at 60 oC in an oil bath with the reaction monitored by TLC. bDetermined by H NMR
1
analysis. cIsolated yield of the major product.
The generality of this reductive cyclopropanation was further explored under the optimized conditions. A variety of
substituted dienes 2 (Table 2) were tested to react with N-tosyl protected isatin. Dienes 2 with the electron-donating and
electron-withdrawing group substituted phenyls performed differently in this cyclopropanation reaction. Dienes 2 with
Table 2. The substrate scope of the cyclopropanation reactiona
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entry
R2
R3
H (1a)
H
time (h)
20
drb
yieldc (%)
3a, 83
3b, 75
3c, 90
3d, 83
3e, 80
3f, 66
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Ph (2a)
6:1
2
2-MeC6H4 (2b)
3-MeC6H4 (2c)
4-MeC6H4 (2d)
4-OMeC6H4 (2e)
2-FC6H4 (2f)
2-ClC6H4 (2g)
3-ClC6H4 (2h)
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>20:1
10:1
10:1
H
72
3g, 57
3h, 60
H
20
9
4-ClC6H4 (2i)
4-BrC6H4 (2j)
4-t-BuC6H4 (2k)
3,4-diMe C6H3 (2l)
Ph (2a)
H
72
20
6
8:1
3i, 60
3j, 52
3k, 92
3l, 95
3m, 96
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H
>20:1
>20:1
>20:1
>20:1
10:1
H
H
20
4
5-Cl (1b)
5-Me (1c)
Ph (2a)
20
3n, 83
aUnless noted otherwise, the reaction is operated under the standard procedure A in the Experimental Section. Determined by H NMR
b
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analysis. cIsolated yield of the major product.
electron-donating group substituted phenyls afforded the products in high yields (Table 2, entries 11, 12), while those with
electron- deficient aryl groups provided moderate yields (Table 2, entries 8-10). Due to the steric hindrance, dienes 2 with
the ortho–substituted phenyls afforded the products in low yields (Table 2, entries 2, 6, 7), no cyclopropanation product was
isolated with 1-napth-phenyl diene 2; the furyl substituted diene 2 produced a mixture of cyclporpanation products with dr
ratio 1:1, which could not be separated by silicagel column. Dienes 2 with meta- and para- substituted phenyls did not show
any difference in the cyclopropanation reaction (Table 2, entries 8, 9). The substituent effect of isatins 1 was also
investigated. Electron poor isatin produced the product in excellent yield (Table 2, entry 13), the electron rich group
substituted isatin 1 also showed good activity in the process (Table 2, entry 14), we believed that isatins with
electron-withdrawing groups could form the intermediates8b more easily and therefore caused less side reactions of isatins.
Table 3. Screening of additives
entry
1
R1
additives (equiv)
LiCl (0.2)
solvent
toluene
temp (oC)
70
time (h)
20
yielda (%)
18
Me
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Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
LiCl (0.2)
LiCl (2.0)
LiBr (2.0)
LiBF4 (2.0)
LiOH (2.0)
LiCl (3.0)
LiCl (3.0)
LiCl (3.0)
LiCl (3.0)
toluene
toluene
toluene
toluene
toluene
toluene
DCE
70
20
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20
20
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55
66
65
21
N.R.
68
83
57
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100
100
10
aIsolated yield of the major product.
When we were optimizing the conditions for the cyclopropanation process, several Lewis acids were also tested to
improve the yield. However, when anhydrous LiCl was used as an additive, the expected cyclopropanation did not occur, a
cyclopentene annulation product was produced instead. Further research showed that only lithium salt was favorable for this
reaction, other Lewis acids such as Scandium trifluoromethanesulfonate and Magnesium trifluoromethanesulfonate only
gave cyclopropanation products. It’s probably because the coordination between lithium and PPh3 was weaker than those
between other Lewis acids and PPh3. With this interesting result obtained, we started to optimize the conditions of this [4+1]
annulation reaction. It was found that the excessive amount of lithium salt was needed to improve the yield (Table 3), DCE
was the optimal solvent, and 80 oC was the most favorable temperature. Only small amount of cyclopropanation product was
produced in the initial stage, under the reaction conditions, the cyclopanation product rearranged to form cyclopentene. An
array of aryl-substituted ethyl 4, 4-dicyano-2-methylene-3-phenylbut-3-enoates 2 were used to construct the cyclopentene
annulation products (Table 4). The results showed that substrates 2 with electron deficient group substituted phenyls (Table 4,
entries 4, 5) and the furan substituted substrate (Table 4, entry 6) resulted in moderate yields, while substrates 2 with electron
rich group substituted phenyls (Table 4, entries 2, 3, 7, 8) resulted in high yields, and the electron deficient substrates 2
showed lower reactivities in cyclopentene annulation processes than in the cyclopropanation reactions.
All the cyclopropanation and cyclopentene annulation products were characterized by H, 13C NMR and HRMS-ESI
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measurements. The structures of representative cyclopropanation and cyclopentene annulation products were determined by
single-crystal X-ray diffraction analysis (CCDC number 1424174 for 3j, 1424175 for 4a). The major diastereomers of
cycloprorantion compounds were made in analogy with representative 3j.
Table 4. Substrate scope of the [4+1] annulationsa
entry
R2
R3
yieldb（%）
4a, 83
1
2
3
4
5
6
7
8
9
Ph (2a)
H (1a)
4-Me-C6H4 (2d)
4-OMe-C6H4 (2e)
3-Cl-C6H4 (2h)
3-Br-C6H4 (2o)
2-furyl (2p)
4-t-Bu-C6H4 (2k)
3,4-diMe-C6H3 (2l)
Ph
H
4d, 77
4e, 78
H
H
4h, 60
4o, 65
H
H
4p, 58
4k, 76
4l, 70
H
H
5-Cl (1b)
4m, 86
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Ph
5-Me (1c)
4n, 81
4
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aUnless noted otherwise, the reaction was operated under the standard procedure B in the Experimental section. bIsolated yield of the major
product.
During our study, efforts were also made to understand the reaction mechanism. The N-protected isatin and
triphenylphosphine can generate phosphorous ylide (as in Scheme 5, A), the ylide may attack substrate 2 via a tandem SN2
Michael addition to form product either 3 or 4. However, it was found that the phosphorous ylide of N-protected isatin did
not react with substrate 2 under either standard procedure A (a in Scheme 3) or standard procedure B (b in Scheme 3), and
the tetravalent phosphinium zwitterions (b in Scheme 2) did not react with benzaldehyde (c in Scheme 3), either. These
experiments demonstrated that the reaction did not occur by a phosphorous ylide intermediate mechanism or a wittig reaction
mechanism, further experiments showed that N-protected isatin reacted with 2-benzylidenemalononitrile to produce a
cyclopropanation product under the standard procedure A (d in Scheme 3), which suggested that the reaction might proceed
via a Michael addition process.
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Scheme 3. Mechanism study
Further investigation proved that the isolated cyclopropanation product could be rearranged by PPh3 in DCE, the
rearrangement reached equilibrium by using PPh3 after heating for 24 hours (a in Scheme 4). On the contrary, using both
lithium chloride and PPh3 resulted in a complete conversion, f completely disappeared even though the isolated yield of the
product g was only 28% (b in Scheme 4). No rearrangement was observed by using lithium chloride alone (c in Scheme 4).
o
The rearrangement was not observed at 60 C in the cyclopropanation process, either, the reason might be that the low
temperature was not favorable for the rearrangement. The rearrangement proceeded under the standard procedure B in a yield
of only 28% (b in Scheme 4), most of the spirocyclopropane was decomposed in this process, which proved that the main
reaction pathway of the cyclopentene product is not the rearrangement of cyclopropanation product.
Scheme 4. Rearrangement investigation
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Based on this study and the early related reports5, 8, a reasonable mechanism for the cyclopropanation and [4+1] type
annulation process was proposed. First, isatins and triphenylphosphine form the unstable intermediate A in the solvent. In the
cyclopropanation process, A reacts with substrate 2 by a Michael addition process to produce the carbanion C, C then
undergoes the replacement reaction via an intramolecular SN2 process, where the C-O bond is broken and triphenylphosphine
oxide departs, and the cyclopropanation product is formed. In the [4+1] type annulation process，the carbanion C formed
after the Michael addition is stabilized by Li+ to afford the new carbanion D (E-isomer is favorable), an intramolecular SN2
process occurs in D with the C3 position on the indole ring of A attacked by Li+-activated diene, then triphenylphosphine
oxide departs and the cyclopentene annulation product is formed. In the Li+ promoted rearrangement process, PPh3 attacks
the electron deficient olefinic bond of cyclopropanation product to form carbanion E, then another intramolecular SN2
process occurs in E with the C-C bond of cyclopropane attacked and the ring is opened, PPh3 is then eliminated and the
cyclopentene is obtained. According to our study, the cyclopentene product is mainly produced via carbanion D, not
carbanion E.
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Scheme 5. Proposed mechanism
CONCLUSION
In conclusion, we have developed an alternative method to construct spirocyclopropyl oxindole compounds and
spirocyclopentenyl oxindole compounds. PPh3 acted as a reductant and activated electronic deficient olefinic bonds in the
rearrangement process. Lithium chloride as a Lewis acid activated 4,4-dicyano-2-methylenebut-3-enoates in the [4+1]
annulation process. In addition, a plausible reaction mechanism was proposed, and the key intermediate of this reaction was
proved to be the Kukhtin−Ramirez intermediate.
EXPERIMENTAL SECTION
All reagents were purchased from commercial vendors and used as received unless otherwise noted. 1,2-dichloroethane
was dried over P2O5 for 12 hours prior to use. Toluene was dried over sodium. 1H, 13C, and 31P NMR spectra were recorded
on a Bruker JNM-ECS 400M. 1H NMR chemical shifts are given in ppm with respect to the solvent residual peak (CDCl3, δ
= 7.26 ppm), 13CNMR shifts are given in ppm with respect to CDCl3 (δ = 77.2 ppm), and 31P shifts are given in ppm with
respect to an external sample of 85% H3PO4 (δ = 0.0 ppm). HRMS spectra were acquired in the ESI mode (positive ion) with
the mass analyzer of Obitrap used. Coupling constants are reported as J-values in Hz. Column chromatography was
performed using 200-300 mesh silica gel as the stationary phase. 4,4-dicyano-2-methylenebut-3-enoate 2 was prepared
according to a procedure in the literature11a. N-tosyl protected isatin 1 was prepared according to the procedure below: isatin
(1.47 g) was dissolved in DMF (10 ml) in a 50 ml round-bottom flask at 0 oC, and sodium hydride (0.48 g) was added slowly
into the flask, after stirring for 1 h, tosyl chloride (2.28 g) was added slowly into this flask, the mixture was then stirred for 3
o
h at room temperature, then the flask was heated at 70 C for 8 h, removed from the heat and cooled down to room
temperature, water was then added into the mixture and the product was precipitated, filtrated under reduced pressure and
washed with EtOH and Et2O. N-tosyl protected isatin was obtained in 90% yield.
Standard procedure A: N-tosyl protected isatin 1 (0.15 mmol) and 4,4-dicyano-2-methylenebut-3-enoate 2 (0.1 mmol)
o
were added into toluene (1 mL) in a reaction tube, PPh3 (0.15 mmol) was then added, and the reaction was heated at 60 C
under N2 atmosphere and monitored by TLC until the starting material disappeared. The solvent was removed under reduced
pressure, and the residue was isolated by silica gel column chromatography (petroleum ether/ethyl acetate 5:1) to give
product 3.
Standard procedure B: N-tosyl protected isatin (0.15 mmol) and 4,4-dicyano-2-methylenebut-3-enoate (0.1 mmol) were
added into DCE (1 mL) in a flask, PPh3 (0.15 mmol) and LiCl (0.3 mmol) were then added, and the reactions was heated at
o
80 C under N2 atmosphere for 20 h. The solvent was removed and the residue was isolated by silica gel column
chromatography (petroleum ether/ethyl acetate 4:1) to give product 4.
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Ethyl 2-(2,2-dicyano-1-phenylvinyl)-2'-oxo-1'-tosylspiro[cyclopropane-1,3'-indoline]-2-carboxylate (3a) white solid, 44.5mg，83% yield;
mp 88−90 oC; IR (KBr) cm-1: 2983, 2230, 1734, 1597, 1462, 1380, 1254, 1238, 1190, 1177, 1086, 961, 910, 734, 665, 575, 542, 1H NMR
(400 MHz, CDCl3, TMS) : δ 8.11 (d, 2H, J = 8.3 Hz), 8.08 (d, 1H, J = 8.8 Hz), 7.46−7.42 (m, 2H), 7.54−7.49 (m, 5H), 7.39 (d, 1H, J = 7.0
Hz), 7.37 (d, 1H, J = 6.5 Hz), 7.14 (t, 1H, J = 7.6 Hz) , 4.39−4.18 (m, 2H, CH2), 2.76 (d, 1H, J = 5.6 Hz), 2.49 (s, 3H), 1.71(d, 1H, J = 5.5
Hz), 1.19 (t, 3H, J = 7.1 Hz); 13C NMR (100 MHz, CDCl3, TMS): δ 170.3, 169.8, 164.1, 146.5, 140.7, 134.8, 134.1, 132.1, 129.8, 129.7,
129.0, 128.8，128.2, 124.6, 123.9, 122.8, 113.8, 112.3, 111.8, 90.6, 64.0, 47.0, 44.2, 27.5, 21.8, 13.9; HRMS (ESI) Calcd for
C30H23N3O5S1Na1 [M+Na]+ : 560.1251; found : 560.1245.
Ethyl 2-(2, 2-dicyano-1-(o-tolyl)vinyl)-2'-oxo-1'-tosylspiro[cyclopropane-1,3'-indoline]-2-carboxylate (3b) white solid, 41.3mg, 75%
yield; mp 158−160 oC; IR (KBr) cm-1: 2925, 2853, 2232, 1733, 1598, 1462, 1381, 1253, 1238, 1190, 1177, 1086, 910, 733, 665, 575, 542
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cm-1; H NMR (400 MHz, CDCl3, TMS): δ 8.14 (d, 1H, J = 8.2 Hz), 8.08 (d, 1H, J = 8.1 Hz), 7.67 (d, 1H, J = 7.3 Hz), 7.45 (d, 2H, J =
8.2Hz), 7.39 (t, 3H, J = 8.0 Hz), 7.25 (t, 2H, J = 8.0 Hz), 7.13 (t, 1H, J = 7.6 Hz), 4.35−4.15 (m, 2H, CH2), 2.71 (d, 1H, J = 5.6 Hz), 2.19 (s,
3H), 2.48 (s, 3H, CH3), 1.80 (d, 1H, J =5.6 Hz), 1.19 (t, 3H, J = 7.2 Hz); 13C NMR (100 MHz, CDCl3, TMS): δ 171.4, 170.2, 163.7, 146.5,
140.6, 134.6, 134.1,131.2, 131.1, 130.1, 129.9, 129.8, 128.9, 128.1, 124.48, 124.46, 122.8, 122.7, 113.8, 111.7, 111.5, 94.6, 63.9, 47.6,
44.2, 25.6, 21.8, 20.0,13.8; HRMS (ESI) calcd for C31H26N3O5S1 [M+H]+ : 552.1588; found: 552.1583.
Ethyl 2-(2, 2-dicyano-1-(m-tolyl)vinyl)-2'-oxo-1'-tosylspiro[cyclopropane-1,3'-indoline]-2-carboxylate (3c) white solid, 52.4mg, 95%
yield; mp 158−160 oC; IR (KBr) cm-1: 2983, 2961, 2257, 2230, 1734, 1598, 1463, 1381, 1239, 1190, 1177, 1086, 962, 910, 734, 665, 575,
542; 1H NMR (400 MHz, CDCl3, TMS): δ 8.11 (d, 2H, J = 8.2 Hz), 8.07 (d, 1H, J = 8.2Hz), 7.46−7 .42 (m, 2H), 7.40−7.33 (m, 4H), 7.28
(s, 2H), 7.14 (t, J = 7.6 Hz), 4.40−4.18 (m, 2H), 2.77 (d, 1H, J = 5.7 Hz), 2.49 (s, 3H), 2.44 (s, 3H), 1.73 (d, 1H, J = 5.7 Hz), 1.18 (t, 3H, J
= 7.1 Hz); 13C NMR (100 MHz, CDCl3, TMS): δ 170.3, 169.9, 164.2, 146.5, 140.6, 139.0, 134.8, 134.1, 133.0, 129.8, 128.9, 128.8, 128.5,
125.4, 124.5, 122.92, 122.87, 113.8, 112.4, 111.9, 90.4, 63.9, 47.0, 44.0, 27.5, 21.8, 21.4, 13.9; HRMS (ESI) calcd for C31H25N3O5S1Na1
[M+Na]+: 574.1407; found: 574.1403.
Ethyl 2-(2, 2-dicyano-1-(p-tolyl)vinyl)-2'-oxo-1'-tosylspiro[cyclopropane-1,3'-indoline]-2-carboxylate (3d) white solid, 45.7mg, 83%
o
yield, mp 162−164 C,IR (KBr) cm-1: 2984, 2950, 2256, 2229, 1734, 1606, 1574, 1553, 1462, 1380, 1255, 1237, 1190, 1177, 1086, 961,
909, 815, 753, 732, 665, 574, 542; 1H NMR (400 MHz, CDCl3, TMS): δ 8.11−8.06 (m, 3H), 7.44 (d, 2H, J = 8.0 Hz), 7.36−7.40 (m, 4H),
7.33 (d, 2H, J = 7.6 Hz), 7.14 (t, 1H, J = 7.5 Hz), 4.36−4.18 (m, 2H), 2.77 (d, 1H) , 2.49 (s, 3H) , 2.43 (s, 3H), 1.73 (d, 1H, J = 5.4 Hz),
1.17 (t, 3H, J = 7.0 Hz); 13C NMR (100 MHz, CDCl3, TMS): δ 170.2, 169.7, 164.3, 146.5, 143.3, 140.6, 134.0, 132.0, 129.8, 129.77, 129.7,
128.8, 128.3, 124.5, 122.91, 122.86, 113.8, 112.7, 112.0, 89.4, 63.9, 47.0, 44.0, 27.6, 21.8, 21.7, 13.9; HRMS (ESI) calcd for
C31H25N3O5S1Na1 [M+Na]+ : 574.1407; found: 574.1401.
Ethyl 2-(2,2-dicyano-1-(4-methoxyphenyl)vinyl)-2'-oxo-1'-tosylspiro[cyclopropane-1,3'-indoline]-2-carboxylate (3e) white solid ,45.3mg,
o
80% yield, mp 68−70 C,IR (KBr) cm-1: 2982, 2934, 2256, 2227, 1733, 1603, 1510, 1494, 1462, 1381, 1262, 1238, 1189, 1177, 1153,
1
1086, 1027, 961, 909, 837, 733, 665, 575, 542; H NMR (400 MHz, CDCl3, TMS): δ 8.09 (d, 2H, J = 8.4Hz), 8.06 (d, 1H, J = 8.4 Hz),
7.50 (d, 2H, J = 8.8 Hz), 7.44−7.35 (m, 4H), 7.13 (t, 1H, J = 7.6 Hz), 6.99 (d, 2H, J = 8.9 Hz), 4.37−4.16 (m, 2H), 3.87 (s, 3H), 2.78 (d, 1H,
J = 5.6 Hz), 2.48 (s, 3H), 1.74 (d, 1H, J = 5.6 Hz), 1.17 (t, 3H, J = 7.1 Hz); 13C NMR (100 MHz, CDCl3, TMS): δ 170.2, 168.7, 164.4,
162.9, 146.4, 140.6, 134.1, 131.2, 130.6, 129.7, 128.8, 127.0, 124.4, 123.0, 122.8, 114.4, 113.8, 113.0, 112.3, 87.7, 63.8, 55.5, 46.9, 43.8,
27.8, 21.7,13.9; HRMS (ESI) calcd for C31H25N3O6S1Na1 [M+Na]+: 590.1356; found : 590.1348.
Ethyl 2-(2,2-dicyano-1-(2-fluorophenyl)vinyl)-2'-oxo-1'-tosylspiro[cyclopropane-1,3'-indoline]-2-carboxylate (3f) white solid, 36.8mg,
o
66% yield, mp 163−165 C, IR (KBr) cm-1: 2984, 2926, 2257, 2232, 1736, 1610, 1462, 1381, 1254, 1238, 1190, 1177, 1154, 1087, 962,
909, 754, 733, 665, 576, 542; 1HNMR (400 MHz, CDCl3, TMS): δ 7.68 (t, 1H, J = 6.4 Hz), 7.58−7.52 (m, 1H), 7.45 (d, 2H, J = 8.2 Hz),
7.42−7.38 (m, 2H), 7.34 (t, 1H, J = 7.6 Hz), 7.19−7.12 (m, 2H), 4.33−4.20 (m, 2H), 2.76 (d, 1H, J = 5.4 Hz), 2.49 (s, 3H), 1.70 (d, 1H, J =
5.4 Hz), 1.20 (t, 3H, J = 7.2 Hz); 13C NMR (100 MHz, CDCl3, TMS): δ 170.6, 166.6, 163.1, 158.8 (d, 1JC-F = 250.4 Hz), 146.6, 140.6,
134.2, 134.1 (d, 3JC-F = 8.7 Hz), 131.7, 129.8, 128.9, 124.9 (d, 4JC-F = 3.4 Hz), 124.6, 123.2, 122.9, 122.6, 122.5, 116.2 (d, 2JC-F = 21.0
Hz), 113.8, 111.7, 111.3, 93.4, 63.7, 47.0, 44.2 26.4, 21.8, 13.9; HRMS (ESI) calcd for C30H22F1N3O5S1Na1 [M+Na]+ : 578.1156; found:
578.1149
Ethyl 2-(1-(2-chlorophenyl)-2,2-dicyanovinyl)-2'-oxo-1'-tosylspiro[cyclopropane-1,3'-indoline]-2-carboxylate (3g) white solid, 32.5mg,
57% yield, mp 164–166 oC, IR (KBr) cm-1: 2984, 2926, 2256, 2234, 1736, 1597, 1463, 1380, 1311, 1238, 1190, 1178, 1087, 962, 910, 812,
1
733, 665, 575, 541; H NMR (400 MHz, CDCl3, TMS): δ 8.13 (d, 2H, J = 8.3 Hz), 8.08 (d, 1H, J = 8.3 Hz), 7.78 (t, 1H, J = 3.0 Hz),
7.49−7.43 (m, 5H), 7.40 (d, 1H, J = 8.0 Hz), 7.33 (d, 1H, J = 7.6 Hz), 7.14 (t, 1H, J = 7.6 Hz), 4.33−4.14 (m, 2H), 2.78 (d, 1H, J = 5.9 Hz),
2.48 (s, 3H), 1.70 (d, 1H, J = 5.9 Hz) 1.19 (t, 3H, J = 7.1 Hz); 13C NMR (100 MHz, CDCl3, TMS): δ 170.5, 168.8,163.4, 146.6, 140.5,
134.0, 133.4, 133.2, 132.7, 131.3, 130.3, 129.9, 129.8, 128.9, 127.4, 124.6, 123.1, 122.8, 113.8, 111.6, 111.2, 95.2, 63.7, 47.3, 44.7, 25.8,
21.8,13.9; HRMS (ESI) calcd for C30H22Cl1N3O5S1Na1 [M+Na]+: 594.0861; found: 594.0855.
Ethyl 2-(1-(3-chlorophenyl)-2,2-dicyanovinyl)-2'-oxo-1'-tosylspiro[cyclopropane-1,3'-indoline]-2-carboxylate (3h) white solid, 34.2mg,
o
60% yield, mp 76−78 C, IR (KBr) cm-1: 2982, 2927, 2232, 1732, 1603, 1565, 1462, 1385, 1308, 1249, 1179, 1086, 960, 906, 861, 806,
754, 695, 572; 1H NMR (400 MHz, CDCl3, TMS): δ 8.12−8.07 (m, 3H), 7.53−7.51 (m, 1H), 7.49−7.44 (m, 3H), 7.42−7.38 (m, 4H), 7.16 (t,
1H, J = 7.6 Hz), 4.40−4.19 (m, 2H), 2.77 (d, 1H, J = 5.8 Hz), 2.49 (s, 3H), 1.72 (d, 1H, J = 5.8 Hz),1.20 (t, 3H, J = 7.1 Hz); 13C NMR (100
MHz, CDCl3, TMS): δ 170.3, 168.4, 163.8, 146.6, 140.6, 136.3, 136.1, 134.0, 132.0, 130.4, 130.0, 129.8, 128.8, 127.7, 126.5, 124.6, 123.1,
122.6, 113.9, 111.8, 111.4, 91.8, 64.2, 46.7, 44.4, 27.3, 21.8, 13.9; HRMS(ESI) calcd for C30H22Cl1N3O5S1Na1 [M+Na]+ : 594.0861; found:
594.0851.
Ethyl 2-(1-(4-chlorophenyl)-2,2-dicyanovinyl)-2'-oxo-1'-tosylspiro[cyclopropane-1,3'-indoline]-2-carboxylate (3i) white solid, 34.2mg,
o
1
60% yield, mp 82−84 C, IR (KBr) cm-1: 2935, 2232, 1737, 1598, 1461, 1381, 1243, 1089, 960, 909, 821, 745, 664, 573; H NMR (400
MHz, CDCl3, TMS): δ 8.10−8.06 (m, 3H), 7.49 (d, 2H, J = 8.5 Hz), 7.44−7.41 (m, 5H), 7.39−7.36 (m, 1H), 7.15 (t, 1H, J = 7.6 Hz),
4.39−4.17 (m, 2H), 2.77 (d, 1H, J = 5.7 Hz), 2.49 (s, 3H), 1.69 (d, 1H, J = 5.7 Hz), 1.19 (t, 3H, J = 7.1 Hz); 13C NMR (100 MHz, CDCl3,
TMS): δ 170.3, 168.6, 163.9, 146.6, 140.6, 138.6, 134.0, 133.0, 130.0, 129.8, 129.6, 129.4, 128.8, 124.6, 123.0, 122.6, 113.9, 112.1, 111.6,
90.9, 64.1, 46.7, 44.3, 27.4, 21.8,13.9; HRMS (ESI) calcd for C30H22Cl1N3O5S1Na1 [M+Na]+: 594.0861; found: 594.0855.
Ethyl 2-(1-(4-bromophenyl)-2,2-dicyanovinyl)-2'-oxo-1'-tosylspiro[cyclopropane-1,3'-indoline]-2-carboxylate (3j) white solid, 31.9mg,
52% yield, mp 81−84 oC, IR (KBr) cm-1: 2983，2928, 2256，2230，1735，1596，1585，1462, 1381，1237, 1177, 1086, 1010, 961, 813,
1
752, 665, 574, 542; H NMR (400 MHz, CDCl3, TMS): 8.06−8.10 (m, 3H), 7.65 (d, 2H, J = 8.32 Hz), 7.44−7.40(m, 3H), 7.39−7.34 (m,
3H), 7.14 (t, 1H, J = 7.56 Hz), 4.39−4.18 (m), 2.75 (d, J = 5.6Hz), 2.48 (s, 3H), 1.69 (d, 1H, J = 5.6 Hz), 1.19 (t, 3H, J = 7.12 Hz); 13C
NMR (100 MHz, CDCl3, TMS): δ 170.3, 168.7, 164.0, 146.6, 140.7, 134.1, 133.5, 132.4, 131.4, 130.0, 129.7, 128.8, 127.0, 124.6, 123.0,
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122.7, 113.9, 112.1, 111.6, 91.0, 64.1, 46.7, 44.4, 27.4, 21.8, 13.9; HRMS (ESI) calcd for C30H22Br1N3O5S1Na1 [M+Na]+: 638.0356; found:
638.0350.
Ethyl 2-(1-(4-(tert-butyl)phenyl)-2,2-dicyanovinyl)-2'-oxo-1'-tosylspiro[cyclopropane-1,3'-indoline]-2-carboxylate (3k) white solid,
54.5mg, 92% yield, mp 178−180 oC, IR (KBr) cm-1: 2966, 2906, 2870, 2256, 2229, 1734, 1605, 1462, 1382, 1255, 1238, 1190, 1177, 1086,
910, 734, 664, 573, 542; 1H NMR (400 MHz, CDCl3, TMS): δ 8.10 (d, 2H, J = 8.4 Hz), 8.07 (d, 1H, J = 8.4 Hz), 7.51 (d, 2H, J = 8.5 Hz),
7.46−7.41 (m, 4H), 7.40−7.37 (m, 2H), 7.14 (t, 1H, J = 7.3 Hz), 4.37−4.16 (m, 2H), 2.78 (d, 1H, J = 5.7 Hz), 2.49 (s, 3H), 1.75 (d, 1H, J =
5.7 Hz), 1.34 (s, 9H), 1.18 (t, 3H, J = 7.1 Hz); 13C NMR (100 MHz, CDCl3, TMS): δ 170.3, 169.5, 169.3, 164.3, 156.3, 146.5, 146.5, 140.7,
134.2, 131.9, 129.8, 129.7, 128.9, 128.3, 126.0, 124.5, 123.0, 123.9, 122.9, 113.8, 112.8, 112.2, 89.2, 63.9, 46.9, 44.0, 35.2, 31.0, 27.8,
21.8,13.9; HRMS (ESI) calcd for C34H31N3O5S1Na1 [M+Na]+ : 616.1877; found: 616.1873.
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Ethyl 2-(2,2-dicyano-1-(3,4-dimethylphenyl)vinyl)-2'-oxo-1'-tosylspiro[cyclopropane-1,3'-indoline]-2-carboxylate (3l) white solid,
o
53.6mg, 95% yield, mp 84−86 C, IR (KBr) cm-1: 2982, 2924, 2256, 2229, 1734, 1605, 1462, 1380, 1256, 1238, 1190, 1177, 1086, 962,
910, 814, 753, 733, 665, 574, 542; 1H NMR (400 MHz, CDCl3, TMS): δ 8.11 (d, J = 8.2 Hz), 8.06 (d, 1H, J = 8.2 Hz), 7.45 (d, 2H),
7.35−7.42 (m, 2H), 7.25 (d, 3H, J = 4.1 Hz), 7.14 (t, 1H, J = 7.6 Hz), 4.17−4.38 (m, 2H), 2.78 (d, 1H, J = 5.7 Hz), 2.49 (s, 3H) , 2.34 (s,
3H), 2.33 (s, 3H), 1.74 (d, 1H, J = 5.7 Hz), 1.17 (t, 3H, J = 7.12 Hz,); 13C NMR (100 MHz, CDCl3, TMS): δ 170.2, 169.7, 164.2, 146.4,
142.1, 140.5,137.5, 134.0, 132.3, 130.2, 129.7, 129.0, 128.7, 125.9, 124.5, 122.9, 122.8, 113.7, 112.7, 112.1, 89.1, 63.9, 47.0, 43.8, 27.6,
21.8, 20.0, 19.9, 13.9; HRMS (ESI) calcd for C32H27N3O5S1Na1 [M+Na]+: 588.1564; found: 588.1559.
Ethyl 5'-chloro-2-(2,2-dicyano-1-phenylvinyl)-2'-oxo-1'-tosylspiro[cyclopropane-1,3'-indoline]-2-carboxylate (3m) white solid, 54.8mg,
o
96% yield, mp 176−178 C, IR (KBr) cm-1: 2983, 2927, 2256, 2231, 1734, 1597, 1582, 1460, 1383, 1254, 1238, 1190, 1178, 1088, 910,
1
819, 733, 663, 581, 543; H NMR (400 MHz, CDCl3, TMS): δ 8.08 (d, 2H, J = 8.1 Hz), 8.02 (d, 1H, J = 8.7 Hz), 7.56−7.49 (m, 3H) ,
7.47−7.45 (m, 4H), 7.41−7.37 (m, 2H), 4.44−4.21 (m, 2H), 2.77 (d, 1H, J = 5.7 Hz), 2.50 (s, 3H), 1.74 (d, 1H, J = 5.7 Hz), 1.23 (t, 3H, J =
7.1 Hz); 13C NMR (100 MHz, CDCl3, TMS): δ 169.8, 169.6, 164.0, 146.8, 139.1, 134.5, 133.7, 132.3, 130.3, 129.8, 129.1, 128.9, 128.2,
124.6, 123.5, 114.9, 112.2, 111.8, 90.5, 64.3, 47.2, 43.7, 27.8, 21.8, 13.9; HRMS (ESI) calcd for C30H22Cl1N3O5S1Na1 [M+Na]+ : 594.0861;
found: 594.0853
Ethyl 2-(2,2-dicyano-1-phenylvinyl)-5'-methyl-2'-oxo-1'-tosylspiro[cyclopropane-1,3'-indoline]-2-carboxylate (3n) white solid, 45.1mg,
82% yield, mp 160−162 oC, IR (KBr) cm-1: 2961, 2927, 2257, 1754, 1719, 1596, 1485, 1383, 1262, 1237, 1191, 1178, 1021, 911, 815, 734,
664, 569, 545; 1H NMR (400 MHz, CDCl3, TMS): δ 8.09 (d, 1H, J = 8.2 Hz), 7.94 (d, 1H, J = 8.4 Hz), 7.55−7.50 (m, 5H), 7.44 (d, 2H, J
= 8.2 Hz), 7.20 (d, 1H, J = 8.4 Hz), 7.16 (s,1H), 4.40−4.18 (m, 2H), 2.74 (d, 1H, J = 5.6 Hz), 2.48 (s, 3H), 2.32 (s, 3H), 1.69 (d, 2H, J = 5.6
Hz), 1.20 (t, 3H, J = 7.1 Hz); 13C NMR (100 MHz, CDCl3, TMS): δ 170.4, 170.0, 164.2, 146.4, 138.2, 134.7, 134.3, 134.1, 132.1, 130.3,
129.8, 128.7, 128.2, 123.4, 122.8, 113.5, 112.4, 111.8, 90.4, 64.0, 46.9, 44.1, 27.5, 21.8, 21.2, 13.9; HRMS (ESI) calcd for
C31H25N3O5S1Na1 [M+Na]+ : 574.1407; found: 574.1404
Ethyl 2,2-dicyano-2'-oxo-3-phenyl-1'-tosylspiro[cyclopent[3]ene-1,3'-indoline]-4-carboxylate (4a) red solid, 44.5mg, 83% yield, mp
o
202−204 C, IR (KBr) cm-1: 2979, 2959, 2869, 2249, 2230, 1958, 1755, 1730, 1605, 1596, 1465, 1374, 1326, 1239, 1226, 1179, 1157,
1102, 1088, 1018, 962, 767, 717, 666, 572, 545; 1H NMR (400 MHz, CDCl3, TMS): δ 8.04 (d, 1H, J = 8.3 Hz), 8.00 (d, 2H, J = 8.4 Hz),
7.56−7.52 (m, 1H), 7.47−7.43 (m, 5H), 7.35−7.31 (m, 3H), 4.07 (q, 2H, J = 7.1Hz), 3.30 (dd, 2H, J = 64.3 Hz, 17.6 Hz), 2.40 (s, 3H), 1.03
(t, 3H, J = 7.1Hz); 13C NMR (100 MHz, CDCl3, TMS): δ 171.8, 162.2, 146.5, 142.7, 139.3, 135.2, 134.1, 131.7, 130.1, 130.0, 128.5, 128.1,
125.8, 124.7, 123.4, 114.4, 111.1, 110.1, 61.6, 58.1, 54.0, 42.3, 21.7, 13.6; HRMS (ESI) calcd for C30H23N3O5S1Na1 [M+Na]+ : 560.1251;
found: 560.1245.
Ethyl 2,2-dicyano-2'-oxo-3-(p-tolyl)-1'-tosylspiro[cyclopent[3]ene-1,3'-indoline]-4-carboxylate (4d) red solid 42.4mg, 77% yield, mp
64−66 oC, IR (KBr) cm-1: 2983, 2925, 2257, 1754, 1717, 1603, 1475, 1383, 1237, 1191, 1178, 1150, 1088, 1018, 959, 911, 815, 733, 661,
569, 544; 1H NMR (400 MHz, CDCl3, TMS): δ 8.04 (d, 1H, J = 8.2 Hz), 7.99 (d, 2H, J = 8.4 Hz), 7.69−7.67 (m, 1H), 7.53 (td,1H, J = 8.3
Hz, 1.0 Hz), 7.36−7.30(m, 5H), 7.24 (d, 2H, 9.0 Hz), 4.09 (q, 2H, J = 7.1 Hz), 3.28 (dd, 2H, J = 17. 6 Hz, 68.7 Hz), 2.40 (s, 3H), 2.38 (s,
3H), 1.08 (t, 3H, J = 7.2 Hz); 13C NMR (100 MHz, CDCl3, TMS): δ 171.8, 162.2, 146.4, 143.0, 140.4, 139.2, 134.5, 134.1, 131.7, 130.0,
129.2, 128.2, 128.1, 127.2, 125.7, 124.7, 123.5, 114.4, 111.1, 110.2, 61.5, 58.0, 53.9, 42.3, 21.7, 21.4, 13.7; HRMS (ESI) calcd for
C31H25N3O5S1Na1 [M+Na]+ : 574.1407; found: 574.1400.
Ethyl 2,2-dicyano-3-(4-methoxyphenyl)-2'-oxo-1'-tosylspiro[cyclopent[3]ene-1,3'-indoline]-4-carboxylate (4e) yellow solid, 44.2mg,
o
78% yield, mp 44−46 C, IR (KBr) cm-1 :2982, 2961, 2257, 2227, 1754, 1728, 1605, 1511, 1463, 1383, 1295, 1253, 1237, 1178, 1151,
1088, 1024, 960, 910, 841, 813, 733, 661, 569, 544; 1H NMR (400 MHz, CDCl3, TMS): δ 8.04 ( d, 1H, J = 8.3Hz ), 7.99 ( d, 2H, J = 8.4
Hz ), 7.67( dd, 1H, J = 0.9 Hz, 7.7 Hz ), 7.53 ( td, 1H, J = 1.2 Hz, 8.2 Hz), 7.43−7.41 (m, 2H ), 7.33−7.29 ( m, 3H ), 6.95 ( d, 2H, J = 8.8
Hz ), 4.10 (q, 2H, J = 7.1 Hz ), 3.83 (s, 3H ), 3.37 ( dd, 2H, J = 68.7 Hz, 17.6 Hz ), 2.40 ( s, 3H ), 1.11( t, 3H, J = 7.2 Hz ); 13C NMR (100
MHz, CDCl3, TMS): δ 171.8, 162.4, 161.1, 146.5, 142.9, 139.3, 134.2, 133.9, 131.7, 130.1, 130.0, 128.1, 125.7, 124.7, 123.6, 122.3, 114.4,
114.0, 61.6, 58.0, 55.3, 42.4, 21.8, 18.4, 13.8; HRMS (ESI) calcd for C31H25N3O6S1Na1 [M+Na]+: 590.1356; found: 590.1348.
Ethyl 3-(3-chlorophenyl)-2,2-dicyano-2'-oxo-1'-tosylspiro[cyclopent[3]ene-1,3'-indoline]-4-carboxylate (4h) red solid, 34.2mg, 60%
o
yield, mp 60−62 C,IR (KBr) cm-1: 2926, 2256, 2234, 1736, 1597, 1463, 1380, 1238, 1178, 1087, 962, 910, 812, 733, 665, 575, 541; 1H
NMR (400 MHz, CDCl3, TMS): δ 8.04 (d, 1H, J = 8.3Hz), 8.00 (d, 2H, J = 8.4 Hz), 7.69 (d, 1H, J = 7.69 Hz), 7.55 (td, 1H, J = 7.3 Hz,
1.0Hz), 7.46−7.44 (m, 2H), 7.42−7.38 (m, 1H), 7.36−7.32 (m, 4H), 4.09 (q, 2H, J = 7.12 Hz), 3.38 (dd, 2H, J = 56.5 Hz, 17.7 Hz), 2.40 (s,
3H), 1.07 (t, 3H, J = 7.16 Hz); 13C NMR (100MHz, CDCl3, TMS): δ 171.8, 161.8, 146.6, 141.0, 139.3, 136.6, 134.0, 131.89, 131.86, 130.3,
130.1, 129.9, 128.7, 128.1, 126.4, 125.8, 124.8, 122.9, 114.4, 110.9, 109.9, 61.8, 58.2, 53.7, 42.2, 21.8, 13.6; HRMS (ESI) calcd for
C30H22Cl1N3O5S1Na1 [M+Na]+ : 594.0861; found: 594.0853.
Ethyl 3-(3-bromophenyl)-2,2-dicyano-2'-oxo-1'-tosylspiro[cyclopent[3]ene-1,3'-indoline]-4-carboxylate (4o) red solid, 39.9mg, 65%
o
yield, mp 62−66 C, IR (KBr) cm-1: 2983, 2926, 2258, 1763, 1720, 1599, 1464, 1384, 1237, 1191, 1179, 1151, 1088, 959, 910, 732, 661,
569, 544; 1H NMR (400 MHz, CDCl3, TMS): δ 8.04 (d, 1H, J = 8.3 Hz), 8.00 (d, 2H, J = 8.4 Hz), 7.69 (d, 1H, J = 7.6 Hz), 7.61−7.59 (m,
2H) , 7.55 (td, 1H, J = 8.4 Hz, 11.3 Hz), 7.41−7.39 (m, 1H), 7.36−7.31 (m,4H), 4.08 (q, 2H, J = 7.1 Hz), 3.37 (dd, 2H, J = 17.5 Hz, 70.2
Hz) , 2.41 (s, 3H), 1.33 (s, 9H), 1.03 (t, 3H, J = 7.1 Hz); 13C NMR (100 MHz, CDCl3, TMS): δ 171.8, 161.8, 146.6, 140.9, 139.4, 136.3,
134.0, 133.3, 132.1, 131.9, 131.5, 130.1, 130.1, 128.2, 126.8, 125.8, 124.8, 122.9, 114.4, 110.9, 109.9, 61.8, 58.2, 53.7, 42.2, 21.8, 13.6;
HRMS (ESI) calcd for C30H22Br1N3O5S1Na1 [M+Na]+ : 638.0356; found: 638.0348
Ethyl 2,2-dicyano-3-(furan-2-yl)-2'-oxo-1'-tosylspiro[cyclopent[3]ene-1,3'-indoline]-4-carboxylate (4p) red liquid, 30.5mg, 58% yield,
IR (KBr) cm-1: 2959, 2926, 2256, 2228, 1752, 1723, 1607, 1598, 1460, 1382, 1236, 1187, 1157, 1087, 910, 734, 661, 568, 543; 1H NMR
(400 MHz, CDCl3, TMS): δ 8.06 (d, 1H, J = 8.2 Hz), 7.99 (d, 2H, J = 8.4 Hz), 7.75 (d, 1H, J = 3.6 Hz), 7.66 (dd, 1H, J = 0.7 Hz, 7.7 Hz),
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7.51−7.58 (m, 2H), 7.29−7.34 (m, 3H), 4.24−4.32 (m, 2H ), 3.39 (dd, J = 17.9 Hz, 32.7 Hz ), 2.41 (s, 3H ), 1.31 (t, 3H, J = 7.1 Hz ); 13C
NMR (100 MHz, CDCl3, TMS): δ 171.8, 162.2, 149.5, 146.4, 145.1, 144.0, 143.0, 139.5, 134.0, 131.8, 131.1, 130.0, 128.4, 128.3, 125.6,
125.0, 123.2, 119.3, 114.3, 112.9, 113.4, 110.7, 61.8, 57.6, 50.5, 42.8, 21.8, 14.1; HRMS (ESI) calcd for C28H21N3O6S1Na1
[M+Na]+ :550.1043; found: 550.1037
Ethyl 3-(4-(tert-butyl)phenyl)-2,2-dicyano-2'-oxo-1'-tosylspiro[cyclopent[3]ene-1,3'-indoline]-4-carboxylate (4k) red solid, 54.5mg,
92% yield, mp 62−64 oC, IR (KBr) cm-1: 2965, 2869, 2257, 1754, 1718, 1603, 1464, 1384, 1237, 1179, 1150, 1088, 1017, 958, 910, 733,
661, 568, 543; 1H NMR (400 MHz, CDCl3, TMS): δ 8.04 (d, 1H, J = 8.3 Hz), 8.00 (d, 2H, J = 8.4 Hz), 7.68 (d, 1H, J = 7.16 Hz), 7.53 (td,
1H, J = 8.0 Hz, 1.0 Hz), 7.42 (dd, 4H, J = 8.4 Hz, 22.6 Hz), 7.35−7.30 (m, 3H), 4.07 (q, 2H, J = 7.1 Hz), 3.37 (dd, 2H, J = 17.5 Hz, 70.2
Hz), 2.40 (s, 3H), 1.33 (s, 9H), 1.03 (t, 3H, J = 7.1 Hz, CH3); 13C NMR (100 MHz, CDCl3, TMS): δ 171.8, 162.3, 153.5, 146.4, 143.0,
139.3, 134.5, 134.1, 131.7, 130.0, 128.1, 127.1, 125.7, 125.4, 124.7, 123.6, 114.4, 111.2, 110.3, 61.5, 58.0, 53.9, 42.3, 31.1, 21.8, 13.5 ;
HRMS (ESI) calcd for C34H31N3O5S1Na1 [M+Na]+ : 616.1877; found : 616.1873
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Ethyl 2,2-dicyano-3-(3,4-dimethylphenyl)-2'-oxo-1'-tosylspiro[cyclopent[3]ene-1,3'-indoline]-4-carboxylate (4l) red solid, 53.6mg, 95%
yield, mp 61−63 oC, IR (KBr) cm-1: 2981, 2924, 2257, 1756, 1723, 1603, 1464, 1384, 1327, 1238, 1191, 1178, 1151, 1088, 1039, 959, 911,
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813, 729, 681, 661, 570, 544; H NMR (400 MHz, CDCl3, TMS): δ 8.04 (d, 1H, J = 8.3Hz), 8.00 (d, 2H, J = 8.3 Hz), 7.68 (d, 1H, J =
7.3Hz) , 7.55−7.51 (m, 1H), 7.34−7.30 (m, 3H), 7.21−7.19 (m, 3H), 4.09 (q, 2H, J = 7.1 Hz), 3.36 (dd, 2H, J = 71.0 Hz, 17.5 Hz), 2.40 (s,
3H), 2.28 (s, 6H), 1.09 (t, 3H, J = 7.1 Hz),13C NMR (100 MHz, CDCl3, TMS): δ 171.8, 162.3, 146.4, 143.1, 139.21, 139.16, 136.8, 136.1,
134.1, 131.7, 130.0, 129.7, 129.3, 128.1, 127.6, 125.72, 125.70, 124.7, 123.6, 114.4, 111.2, 110.3, 61.5, 58.1, 53.9, 42.3, 21.7, 19.8, 13.7;
HRMS (ESI) calcd for C32H27N3O5S1Na1 [M+Na]+ : 588.1564; found: 588.1561;
Ethyl 5'-chloro-2,2-dicyano-2'-oxo-3-phenyl-1'-tosylspiro[cyclopent[3]ene-1,3'-indoline]-4-carboxylate (4m) red solid, 49.1mg, 86%
o
yield, mp 58−60 C, IR (KBr) cm-1: 2983, 2929, 2366, 2258, 1889, 1757, 1717, 1656, 1596, 1463, 1444, 1385, 1341, 1283, 1236, 1179,
1191, 1155, 1109, 1088, 1021, 958, 911, 814, 734, 700, 663, 581, 553, 544; 1H NMR (400 MHz, CDCl3, TMS): δ 8.00 (d, 1H, J = 8.9 Hz,
1H), 7.97 (d, 2H, J = 8.4 Hz), 7.66 (d, 1H, J = 2.08 Hz), 7.53−7.50 (m, 1H), 7.47−7.44(m, 5H), 7.34 (d, 2H, J = 8.2 Hz), 4.07 (q, 2H, J =
7.1 Hz), 3.38 (dd, 2H, J = 71.1 Hz, 17.1 Hz), 2.40 (s, 3H), 1.04 (t, 3H, J = 7.1 Hz); 13C NMR (100 MHz, CDCl3, TMS): δ 171.2, 161.9,
146.8, 142.6, 137.7, 134.9, 133.7, 131.8, 131.4, 130.2, 130.1, 130.0, 128.6, 128.3, 128.1, 125.1, 125.0, 115.0, 110.8, 109.8, 61.6, 57.8, 53.8,
42.1, 21.8, 13.6; HRMS (ESI) calcd for C30H22Cl1N3O5S1Na1 [M+Na]+: 594.0861; found: 594.0871
Ethyl 2,2-dicyano-5'-methyl-2'-oxo-3-phenyl-1'-tosylspiro[cyclopent[3]ene-1,3'-indoline]-4-carboxylate (4n) red solid, 44.6mg, 81%
o
yield, mp 54−56 C,IR (KBr) cm-1: 3061, 2982, 2961, 2927, 2871, 2257, 2231, 1754, 1719, 1656, 1596, 1485, 1444, 1383, 1340, 1298,
1262, 1237, 1191, 1178, 1155, 1113, 1089, 1021, 958, 911, 847, 815, 734, 699, 664, 569, 545; 1H NMR (400 MHz, CDCl3, TMS): δ 7.98
(d, 1H, J = 8.4 Hz), 7.90 (d, 2H, J = 8.4 Hz), 7.48 (s, 1H), 7.47−7.42 (m, 5H), 7.33−7.31 (m, 3H), 4.07 (q, 2H, J = 7.1 Hz), 3.36 (dd, 2H, J
= 59.9 Hz, 17.6 Hz), 2.41 (s, 3H), 2.39 (s, 3H), 1.04 (t, 3H, J = 7.1 Hz); 13C NMR (100 MHz, CDCl3, TMS): δ 172.0, 162.2, 146.4, 142.9,
136.9, 135.8, 135.1, 134.2, 132.3, 130.4, 130.1, 130.0, 128.6, 128.4, 128.1, 125.3, 123.3, 114.2, 111.2, 110.2, 61.6, 58.2, 54.0, 42.4, 21.8,
21.2,13.6; HRMS (ESI) calcd for C31H25N3O5S1Na1 [M+Na]+ :574.1407; found: 574.1398
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website with control experiments, NMR
spectra, X-ray data (CIF).
AUTHOR INFORMATION
Corresponding Author
*E-mail: xupf@lzu.edu.cn
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We are grateful to the NSFC (21372105, 21632003 and 21572087), and the “111” program from the MOE of P. R. China for financial
support.
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