Fluoride ion catalyzed multicomponent reactions for efficient synthesis of 4H-chromene and N-arylquinoline derivatives in aqueous media

Article abstract of DOI:10.1016/j.tet.2008.06.061

4H-Chromene and N-arylquinoline derivatives are obtained in good to excellent yields by proceeding through a simple, mild, and efficient procedure utilizing tetrabutylammonium fluoride (TBAF) as catalyst.

Full text of DOI:10.1016/j.tet.2008.06.061

Tetrahedron 64 (2008) 9143–9149
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Fluoride ion catalyzed multicomponent reactions for efficient synthesis of
4H-chromene and N-arylquinoline derivatives in aqueous media
*
Shijay Gao, Cheng Hsuan Tsai, Chi Tseng, Ching-Fa Yao
Department of Chemistry, National Taiwan Normal University, 88 Ding-Jou Road, Section 4, Taipei 11677, Taiwan, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 9 April 2008
Received in revised form 6 June 2008
Accepted 17 June 2008
4H-Chromene and N-arylquinoline derivatives are obtained in good to excellent yields by proceeding
through a simple, mild, and efficient procedure utilizing tetrabutylammonium fluoride (TBAF) as catalyst.
Ó 2008 Published by Elsevier Ltd.
Available online 20 June 2008
1. Introduction
reported syntheses of 4H-chromene derivatives employ piperidine
and triethylamine in organic solvents.5 Other effective syntheses of
The developments of multicomponent reactions (MCRs) have
attracted much attention from the vantage point of combinatorial
and medicinal chemistry.1 Generally, the MCR strategy affords
savings in synthetic time and effort, and has significant advantages
over conventional two-component reactions in several aspects,
such as variable and high bond forming efficiency. With a small set
of start materials, very large libraries can be developed within
a short time, which can apply to research on medicinal chemistry.
The first MCR was described in 1850 by the Strecker’s synthesis of
4H-chromene derivatives employ microwave6 and electrogenerated
base.7 Recently, some two- and three-component reactions have
been catalyzed by utilizing alkyl ammonium salts,8 Re(PFO)3,9 KF–
Al2O3,10 (S)-proline,11 and (NH4)2HPO4.12 The classical procedure for
the synthesis of quinoline derivatives has been described in
Skraup,13 Doebner–Miller,14 and Combes quinoline syntheses.15
However, the synthesis of N-substituted quinoline derivative is few
in the literature. The multicomponent reaction could be also suc-
cessfully applied to various aryl aldehydes with cyclic 3-arylamino-
2-enones and malononitrile to synthesize various N-arylquinoline
derivative catalyzed by [Bmimþ][BFꢀ4 ]16 and TEBAC.17
Over the past years, tetrabutylammonium fluoride (TBAF) in or-
ganic synthesis has been widely used for most fluoride-assisted
reactions,18 deprotection of silyl groups,19 desilyation,20 and fluori-
nation.21 TBAF has beenwidely recognized as a convenient, organic-
soluble source of naked fluoride ion. It has also been widely used for
a variety of base-catalyzed reactions such as alkylation, elimination,
Michael addition, and aldol condensation.22 The potential ability of
the fluoride ion to act as a base might be predicated on considering
thestrengthof the H–F bond. Mostionic fluoridesare easytoprepare
and use and are stable overlong periods of time. Thefluoride ions are
hygroscopic, but they do not react with water and may therefore be
recovered from aqueous solution by conventional techniques. As
part of our incessant research efforts with MCR chemistry,23 we now
report a simple and efficient catalyst, TBAF, for catalyzing the syn-
theses of 4H-chromene and N-arylquinoline derivatives via a one-
pot three-component reaction in aqueous media (Scheme 1).
a
-amino acids.2a The other MCRs have been described successfully
in Hantsch’s synthesis of 1,4-dihydropyridines in 1882,2b Biginelli’s
synthesis of 3,4-dihydropyrimidin-2-ones in 1891,2c Mannich’s syn-
thesis of
synthesis of alkaloid tropinone in 1917,2e Passerini synthesis of
-acyloxycarboxamide in 1921,2f Bucherer–Bergs’s synthesis of
hydantoins in 1934,2g Ugi’s synthesis of bis-amide in 1959,2h and
Pauson–Khand’s synthesis of
-cyclopentenone in 1977.2i
b
-amino carbonyl compounds in 1912,2d Robinson’s
a
a,b
Many important heterocycle syntheses are multicomponent
reactions. Recently, the syntheses of 4H-chromene and quinoline
derivatives have attracted great interest due to biological and
pharmacological activities. The 4H-chromene derivatives show
various pharmacological properties such as spasmolytic, diuretic,
anticoagulant, anticancer, and antianaphylactic activities.3 Quino-
line derivatives are a class of important compounds, which are
widely recognized to have antitumor, antibacterial, anticancer, and
antimalarial activities.4 The known procedure for the synthesis of
4H-chromene derivatives employ a three-component reaction of
cyclic 1,3-diketones, aryl aldehydes, and malononitrile, and is per-
formed under various reaction conditions. The conventional
2. Results and discussion
Preliminary efforts were mainly focused on the evaluation of
different additives, the yields of 4H-chromene derivatives obtained
* Corresponding author. Tel.: þ886 2 29309092; fax: þ886 2 29324249.
E-mail address: cheyaocf@scc.ntnu.edu.tw (C.-F. Yao).
0040-4020/$ – see front matter Ó 2008 Published by Elsevier Ltd.
doi:10.1016/j.tet.2008.06.061

9144
S. Gao et al. / Tetrahedron 64 (2008) 9143–9149
O
O
corresponding product was obtained in 72–85% yield in presence of
NaOH, NaHCO3, Na2CO3, and K2CO3 (entries 11–14, Table 1). On the
basis of the optimization of the reaction conditions, the scope of
these fluoride anion catalyzed multicomponent reactions was ex-
plored. Not only electron-rich aryl aldehyde, but also electron-
deficient aryl aldehyde in the reactions afforded 4H-chromene
derivatives in 73–98% yields and N-arylquinoline derivatives in
88–96% yields (Table 2). The 4H-chromene and N-arylquinoline
derivatives thus formed can be obtained in pure form by recrys-
tallizing or passing the crude through a short plug of silica. As
shown in Table 2, the periods of reaction time of cyclic 1,3-dike-
tones with aryl aldehyde containing either electron-withdrawing
Ar
O
TBAF 10 mol%
5 mL H2O
CN
CN
CN
+
+
+
+
ArCHO
reflux
O
NH2
1
2
3
5
O
Ar
O
TBAF 10 mol%
5 mL H2O
CN
CN
CN
ArCHO
reflux
Ph
N
NH2
N
Ph
6
1
2
4
Scheme 1.
Table 2
Fluoride ion catalyzed one-pot synthesis of 4H-chromene and N-arylquinoline
by reacting cyclic 1,3-diketones, aryl aldehydes, and malononitrile
are shown in Table 1. First, it was clearly suggested that TBAF cer-
tainly catalyzed the multicomponent reactions (compare entries 1
and 2, Table 1). It is noteworthy to observe that corresponding
product was obtained in excellent yield, no any benzylidenemalo-
nonitrile or 2,2-benzyliden-bis-(5,5-dimethyl-3-oxo-1-hydroxy-
cyclohexene) was observed. The reactions carried out by using
different ammonium halide such as chloride, bromide, and iodide
showed that the fluoride ion was more active than other halides
and the iodide anion did not avail against the reaction (entries 3–5,
Table 1). The result accords with the literature and revealed that
quaternary ammonium halides are known to give rise to an order of
nucleophilicity for the halide ions, which parallels their electro-
negativities, i.e., fluoride>chloride>bromide>iodide. We tried to
explore an effective system for multicomponent reactions by
screening other fluoride sources under the same conditions, it was
found that the fluoride ion of TBAF is the most reactive than other
fluoride sources (entries 6–10, Table 1). The corresponding product
was obtained in low yield in presence of H2SiF6 and HF–pyridine,
because these prefer to afford acidic HF molecular, not basic Fꢀ
anion (entries 9–10, Table 1). Besides the basic Fꢀ anion, the
derivativesa
Entry
1
Ar
Time (min)
30
Yieldb (%)
97
5a
5b
5c
5d
5e
5f
2
3
4
5
6
7
8
9
10
30
30
94
84
98
87
75
73
96
97
98
Cl
F
Cl
F
30
30
30
O2N
Table 1
5g
5h
5i
30
One-pot synthesis of 4H-chromene derivatives in presence of various additivesa
NO2
30
O
O
MeO
OH
CHO
additive
5 mL H2O
CN
CN
CN
+
+
30
O
O
NH2
1
2
3
5
Entry
Additive (equiv)
Time (min)
Temp (ꢁC)
5 Yieldb (%)
5j
100
1
2
3
4
5
6
7
8
d
30
30
30
30
30
30
30
30
30
30
30
30
30
30
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
57c
>99
TBAF (0.1)
TBACl (0.1)
TBABr (0.1)
TBAI (0.1)
KF (0.1)
80
73
56d
88
85
73
28e
20f
72
84
82
85
11
5k
150
76
N
H
CsF (0.1)
NH4F (0.1)
H2SiF6 (0.1)
HF–pyridine (0.1)
NaOH (0.1)
NaHCO3 (0.1)
Na2CO3 (0.1)
K2CO3 (0.1)
O
O
9
12
13
14
5l
30
10
98
97
96
10
11
12
13
14
5m
5n
O
a
Condition: the reaction was performed by using 2 mmol of 1, 2 mmol of 2, and
2 mmol of 3 in the presence of 10 mol % of additive in 5 mL H2O under reflux
condition.
300
Me2N
b
NMR yield.
c
18% Benzylidenemalononitrile was observed.
7% Benzylidenemalononitrile was observed.
32% Benzylidenemalononitrile was observed.
d
15
6a
30
96
e
f
25% Benzylidenemalononitrile was observed.

S. Gao et al. / Tetrahedron 64 (2008) 9143–9149
9145
Table 2 (continued )
are often encountered in molecules of biologically active com-
pounds. The procedures described here are simple, mild, and effi-
cient. The use of TBAF as a base has the advantages of being
economically viable and more efficient for multicomponent re-
actions in aqueous media. The reaction system can be successfully
applied to a variety of aryl aldehyde as well as isatin to synthesize
a wide variety of heterocycles in good to excellent yields.
Entry
Ar
Time (min)
120
Yieldb (%)
98
16
6b
6c
6d
6e
6f
Cl
17
30
60
97
90
88
98
F
4. Experimental
4.1. General
18
O2N
19
240
300
All Analytical thin layer chromatography was performed with
E. Merck silica gel 60F254 aluminum sheets and was visualized with
UV light. Flash column chromatography, following the method
of still, was carried out with E. Merck silica gel 60 (Kieselgel 60,
230–400 mesh) using the indicated eluents. 1H nuclear magnetic
resonance (NMR) spectra were recorded routinely with a Bruker
Avance 400 (400 MHz) spectrometer. The 1H NMR data are de-
MeO
20
OH
a
Condition: the reaction was performed by using 2 mmol of 1, 2 mmol 2, and
2 mmol of 3 or 4 in the presence of 10 mol % of TABF in 5 mL H2O under reflux
condition.
scribed as following: chemical shifts (d, given in ppm with DMSO-d6
b
Isolated yield.
(2.50 ppm) as internal reference), multiplicity (s¼singlet, d¼
doublet, t¼triplet, q¼quartet, br¼broad, m¼multiplet), coupling
constants (J, given in Hz), with integration. 13C NMR spectra were
obtained with a Bruker Avance 400 (100 MHz) spectrometer using
DMSO-d6 (39.51 ppm) as internal reference. Mass spectra were
given on a JOEL SX-102A spectrometer at an ionization potential of
70 eV and reported as mass/charge (m/z) with percent relative
abundance. High-resolution mass spectra (HRMS) were acquired
with a FINNIGAN MAT-95XL spectrometer. Solvent for extraction
and chromatography were reagent grade.
group or electron-donating group are similar (entries 1–14, Table
2). Comparatively, the rate of the reaction of cyclic 3-arylamino-2-
enones with electron-deficient aryl aldehyde is faster than with
electron-rich aryl aldehyde (entries 15–20, Table 2). In order to
extend the scope of fluoride ion catalyzed multicomponent re-
action could been also successfully applied to various isatin de-
rivatives with cyclic 1,3-diketones and malononitrile to synthesize
various spirooxindoles derivatives (Table 3). For isatin derivatives,
both isatin and N-substituted isatins could undergo multicompo-
nent reactions to give the spirochromene in 87–98% isolated yields.
The fused chromene system is the core structure of many phar-
macological and biological activities.24 The scope of fluoride ion
catalyzed-multicomponent reactions has been demonstrated by
using a wide range of aryl aldehyde as well as isatin with different
groups or substituents.
4.2. Procedures and analytical data
To a mixture of benzaldehyde (213 mg, 2 mmol), malononitrile
(133 mg, 2 mmol), 5,5-dimethyl-1,3-cyclohexanedione (295 mg,
2 mmol), and water (5 mL), TBAF$3H2O (64 mg, 0.2 mmol) was
added and the mixture was stirred under reflux condition for
30 min. After completion of reaction (monitored by NMR), the
generated solid was filtered off and recrystallized from ethyl ace-
tate to obtain 5a (499 mg, 97% isolated yield).
3. Conclusion
In conclusion, we have developed an efficient procedure for the
synthesis of 4H-chromene and N-arylquinoline derivatives, which
4.2.1. 2-Amino-7,7-dimethyl-5-oxo-4-phenyl-5,6,7,8-tetrahydro-
4H-chromene-3-carbonitrile (5a)
Table 3
White solid with the melting point of 234–235 ꢁC; IR (KBr, neat)
nmax 3397, 3325, 3214, 2961, 2200, 1681, 1661, 1605, 1371, 1249,
Fluoride ion catalyzed one-post synthesis spirochromene derivativesa
R
N
1214, 1160, 1139, 1036, 696; 1H NMR (400 MHz, DMSO-d6)
d 7.28 (t,
O
O
O
O
TBAF 10 mol%
5 mL H2O
J¼7.3 Hz, 2H), 7.21–7.12 (m, 3H), 6.98 (s, 2H), 4.17 (s, 1H), 2.51 (s,
CN
CN
O
+
+
2H), 2.25 (d, J¼16.1 Hz, 1H), 2.10 (d, J¼16.1 Hz, 1H), 1.04 (s, 3H), 0.96
N
R
R1
CN
(s, 3H); 13C NMR (100 MHz, DMSO-d6)
d 195.59, 162.45, 158.47,
reflux
R1
O
R1
O
NH2
R1
144.71, 128.29, 127.11, 126.53, 119.67, 112.73, 58.23, 49.96, 38.67,
35.56, 31.77, 28.36, 26.78; HRMS (EI) m/z calcd for C18H18N2O2
(Mþ): 294.1368, found: 294.1361.
7
2
3
8
Entry
R
R1
Time (min)
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
H
Me
Boc
Benzyl
Acetyl
H
Me
Boc
Me
Me
Me
Me
Me
H
H
H
H
H
8a
8b
8c
8d
8e
8f
8g
8h
8i
30
20
10
15
60
20
20
15
20
60
97
98
91
96
90
96
97
94
96
87
4.2.2. 2-Amino-4-(4-chlorophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-
tetrahydro-4H-chromene-3-carbonitrile (5b)
White solid with the melting point of 215–216 ꢁC; IR (KBr, neat)
nmax 3395, 3322, 3257, 3214, 2964, 2193, 1741, 1684, 1655, 1605,
1368, 1214, 1041; 1H NMR (400 MHz, DMSO-d6)
2H), 7.17 (d, J¼8.4 Hz, 2H), 7.04 (s, 2H), 4.19 (s, 1H), 2.50 (s, 2H), 2.24
(d, J¼16.1 Hz, 1H), 2.10 (d, J¼16.1 Hz, 1H), 1.03 (s, 3H), 0.94 (s, 3H);
d
7.34 (d, J¼8.4 Hz,
Benzyl
Acetyl
13C NMR (100 MHz, DMSO-d6)
d 195.71, 162.65, 158.52, 143.74,
8j
131.14, 129.12, 128.30, 119.55, 112.36, 57.85, 49.97, 40.14, 35.13,
31.80, 28.32, 26.88; HRMS (EI) m/z calcd for C18H17ClN2O2 (Mþ):
328.0979, found: 328.0965.
a
Condition: the reaction was performed using 2 mmol of 7, 2 mmol of 2, and
2 mmol of 3 in the presence of 10 mol % of TBAF in 5 mL H2O under reflux condition.
b
Isolated yield.

9146
S. Gao et al. / Tetrahedron 64 (2008) 9143–9149
4.2.3. 2-Amino-4-(2-chlorophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-
tetrahydro-4H-chromene-3-carbonitrile (5c)
0.94 (s, 3H); 13C NMR (100 MHz, DMSO-d6)
d 195.65, 162.12, 158.51,
157.92, 136.84, 128.20, 119.78, 113.67, 112.99, 58.57, 54.99, 50.01,
34.75, 31.77, 28.40, 26.77; HRMS (EI) m/z calcd for C19H20N2O3
(Mþ): 324.1474, found: 324.1478.
White solid with the melting point of 191–192 ꢁC; IR (KBr, neat)
nmax 3363, 3185, 2963, 2190,1738,1683,1651,1604,1506,1371,1216,
1142, 1038, 850; 1H NMR (400 MHz, DMSO-d6)
d 7.22–7.14 (m, 2H),
7.10 (t, J¼8.8 Hz, 2H), 7.02 (s, 1H), 4.21 (s, 1H), 2.50 (s, 2H), 2.24 (d,
4.2.9. 2-Amino-4-(4-hydroxyphenyl)-7,7-dimethyl-5-oxo-5,6,7,8-
tetrahydro-4H-chromene-3-carbonitrile (5i)
J¼16.1 Hz, 1H), 2.10 (d, J¼16.1 Hz, 1H), 1.02 (s, 3H), 0.94 (s, 3H); 13
C
NMR (100 MHz, DMSO-d6)
d
196.14, 162.95, 162.59, 160.19, 158.98,
Yellow solid with the melting point of 224–226 ꢁC; IR (KBr, neat)
nmax 3478, 3315, 3160, 2962, 2202,1683,1661,1615,1592,1515,1451,
141.43, 141.40, 129.57, 129.49, 120.11, 115.60, 115.39, 113.11, 58.62,
50.46, 35.41, 32.27, 28.81, 27.33; HRMS (EI) m/z calcd for
1367, 1214, 1041, 849; 1H NMR (400 MHz, DMSO-d6)
d 9.30 (s, 1H),
C
18H17ClN2O2 (Mþ): 328.0979, found: 328.0977.
6.96–6.89 (m, 4H), 6.67 (d, J¼8.4 Hz, 2H), 4.07 (s, 1H), 2.55–2.43 (m,
2H), 2.24 (d, J¼16.1 Hz, 1H), 2.09 (d, J¼16.1 Hz, 1H), 1.03 (s, 3H), 0.95
4.2.4. 2-Amino-4-(4-fluorophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-
tetrahydro-4H-chromene-3-carbonitrile (5d)
(s, 3H); 13C NMR (100 MHz, DMSO-d6)
d 196.23, 162.53, 158.89,
156.44, 135.67, 128.63, 120.36, 115.50, 113.67, 59.34, 50.53, 40.18,
35.18, 32.25, 28.90, 27.23; HRMS (EI) m/z calcd for C18H18N2O3
(Mþ): 310.1317, found: 310.1327.
White solid with the melting point of 210–211 ꢁC; IR (KBr, neat)
nmax 3479, 3335, 3181, 2954, 2202, 2186, 1688, 1668, 1598, 1366,
1252, 1210, 1140, 1036, 749; 1H NMR (400 MHz, DMSO-d6)
d 7.21–
7.15 (m, 2H), 7.10 (t, J¼8.6 Hz, 2H), 7.02 (s, 2H), 4.20 (s, 1H), 3.35 (s,
4.2.10. 2-Amino-7,7-dimethyl-4-(naphthalen-1-yl)-5-oxo-5,6,7,8-
tetrahydro-4H-chromene-3-carbonitrile (5j)
White solid with the melting point of 214–215 ꢁC; IR (KBr, neat)
nmax 3420, 3319, 3254, 3208, 3062, 2959, 2185, 1679, 1659, 1596,
1377, 1351, 1248, 1205, 1158, 1141, 1033, 789; 1H NMR (400 MHz,
2H), 2.50 (s, 2H), 2.24 (d, J¼16.1 Hz, 1H), 2.10 (d, J¼16.1 Hz, 1H), 1.02
(s, 3H), 0.94 (s, 3H); 13C NMR (100 MHz, DMSO-d6)
d
196.15, 162.96,
162.59, 160.19, 158.98, 141.43, 141.40, 129.57, 129.49, 120.11, 115.60,
115.39, 113.11, 58.62, 50.46, 35.41, 32.27, 28.81, 27.33.
DMSO-d6)
d
8.38 (d, J¼7.7 Hz, 1H), 7.92 (d, J¼7.7 Hz, 1H), 7.78 (d,
4.2.5. 2-Amino-4-(2-fluorophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-
tetrahydro-4H-chromene-3-carbonitrile (5e)
Yellow solid with the melting point of 232–233 ꢁC; IR (KBr, neat)
nmax 3397, 3328, 3214, 2966, 2879, 2198, 1683, 1661, 1605, 1487,
J¼8.4 Hz, 1H), 7.59–7.49 (m, 2H), 7.45 (t, J¼7.5 Hz, 1H), 7.25 (d,
J¼7.3 Hz, 1H), 6.96 (s, 2H), 2.59 (s, 2H), 2.24 (d, J¼16.1 Hz, 1H), 2.07
(d, J¼16.1 Hz, 1H), 1.06 (s, 3H), 1.00 (s, 3H); 13C NMR (100 MHz,
DMSO-d6)
d 196.22, 163.26, 158.94, 133.83, 131.25, 128.87, 127.46,
1372, 1215, 1140, 1037, 753; 1H NMR (400 MHz, DMSO-d6)
d
7.28–
126.31, 126.15, 126.07, 125.70, 124.10, 12.011, 113.94, 59.43, 50.51,
40.22, 32.32, 28.87, 27.48; HRMS (EI) m/z calcd for C22H20N2O2
(Mþ): 344.1525, found: 344.1526.
7.09 (m, 4H), 7.04 (s, 2H), 4.47 (s,1H), 3.35 (s, 2H), 2.52 (q, J¼16.8 Hz,
2H), 2.28 (d, J¼16.1 Hz, 1H), 2.10 (d, J¼16.1 Hz, 1H), 1.06 (s, 3H), 0.97
(s, 3H); 13C NMR (100 MHz, DMSO-d6)
d 195.56, 163.09, 161.16,
157.75, 131.24, 131.11, 129.68, 129.65, 128.60, 128.52, 124.39, 119.48,
115.50, 115.29, 111.38, 56.75, 49.89, 31.77, 29.83, 28.47; HRMS (EI)
m/z calcd for C18H17FN2O2 (Mþ): 312.1274, found: 312.1269.
4.2.11. 2-Amino-4-(1H-indol-3-yl)-7,7-dimethyl-5-oxo-5,6,7,8-
tetrahydro-4H-chromene-3-carbonitrile (5k)
Yellow solid with the melting point of 185–186 ꢁC; IR (KBr, neat)
nmax 3521, 3405, 3303, 3124, 2959, 2187, 1683, 1661, 1608, 1368,
4.2.6. 2-Amino-7,7-dimethyl-4-(4-nitrophenyl)-5-oxo-5,6,7,8-
tetrahydro-4H-chromene-3-carbonitrile (5f)
Yellow solid with the melting point of 151–152 ꢁC; IR (KBr, neat)
nmax 3392, 3322, 3256, 3213, 2960, 2193, 1736, 1684, 1651, 1605,
1525, 1367, 1347, 1253, 1215, 1042, 867, 827; 1H NMR (400 MHz,
1248, 1213, 1143, 1030, 742; 1H NMR (400 MHz, DMSO-d6)
d 10.85
(s, 1H), 7.39–7.31 (m, 2H), 7.14–7.12 (m, 1H), 7.05 (t, J¼7.1 Hz, 1H),
6.99–6.92 (m, 1H), 6.85 (s, 2H), 4.51 (d, J¼6.2 Hz, 1H), 2.51 (q,
J¼17.6 Hz, 2H), 2.23 (d, J¼16.1 Hz, 1H), 2.06 (d, J¼16.1 Hz, 1H), 1.02
(s, 3H), 0.87 (s, 3H); 13C NMR (100 MHz, DMSO-d6)
d 195.75, 161.67,
DMSO-d6)
d
8.17 (d, J¼8.1 Hz, 2H), 7.44 (d, J¼8.1 Hz, 2H), 7.17 (s, 2H),
158.63, 136.59, 125.34, 120.76, 120.18, 118.39, 118.35, 117.58, 112.79,
111.67, 58.64, 50.15, 39.72, 31.66, 28.50, 27.26, 26.76; HRMS (EI) m/z
calcd for C20H18N3O2 (Mþ): 332.1399, found: 332.1395.
4.36 (s, 1H), 2.50 (s, 2H), 2.26 (d, J¼15.7 Hz, 1H), 2.11 (d, J¼15.7 Hz,
1H), 1.04 (s, 3H), 0.96 (s, 3H); 13C NMR (100 MHz, DMSO-d6)
d
195.75, 163.14, 158.61, 152.29, 146.29, 128.63, 123.68, 119.32,
111.75, 57.04, 49.88, 35.68, 34.84, 28.26, 26.96; HRMS (EI) m/z calcd
4.2.12. 2-Amino-4-(benzo[d][1,3]dioxol-5-yl)-7,7-dimethyl-5-
oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (5l)
for C18H17N3O4 (Mþ): 339.1219, found: 339.1214.
White solid with the melting point of 224–225 ꢁC; IR (KBr, neat)
nmax 3358, 3261, 3192, 2965, 2899, 2197, 1683, 1651, 1607, 1490,
1375, 1359, 1250, 1215, 1038, 561; 1H NMR (400 MHz, DMSO-d6)
4.2.7. 2-Amino-7,7-dimethyl-4-(2-nitrophenyl)-5-oxo-5,6,7,8-
tetrahydro-4H-chromene-3-carbonitrile (5g)
Yellow solid with the melting point of 233–234 ꢁC; IR (KBr, neat)
nmax 3473, 3333, 3257, 3213, 3188, 2959, 2870, 2194, 1689, 1667,
1597, 1525, 1365, 1254, 1214, 1143, 1041, 756, 736; 1H NMR
d
6.96 (s, 2H), 6.81 (d, J¼7.7 Hz, 1H), 6.65 (s, 1H), 6.61 (d, J¼7.7 Hz,
1H), 4.11 (s, 1H), 2.50 (s, 2H), 2.24 (d, J¼15.7 Hz, 1H), 2.12 (d,
J¼15.7 Hz, 1H), 1.03 (s, 3H), 0.96 (s, 3H); 13C NMR (100 MHz, DMSO-
(400 MHz, DMSO-d6)
d
7.81 (d, J¼8.1 Hz, 1H), 7.66 (t, J¼7.3 Hz, 1H),
d6) d 195.63, 162.28, 158.39, 147.15, 145.81, 138.82, 120.25, 119.63,
7.42 (t, J¼7.7 Hz, 1H), 7.35 (d, J¼8.1 Hz, 1H), 7.17 (s, 2H), 4.93 (s, 1H),
2.50 (s, 2H), 2.20 (d, J¼16.1 Hz, 1H), 2.01 (d, J¼16.1 Hz, 1H), 1.01 (s,
112.73, 107.96, 107.49, 110.83, 58.45, 50.00, 35.18, 31.75, 28.24,
26.91; HRMS (EI) m/z calcd for C19H18N2O4 (Mþ): 338.1267, found:
338.1260.
3H), 0.88 (s, 3H); 13C NMR (100 MHz, DMSO-d6)
d 195.79, 162.72,
159.17, 148.95, 138.93, 133.34, 130.26, 127.85, 123.71, 119.03, 112.30,
56.37, 49.56, 31.83, 29.94, 28.27, 26.70.
4.2.13. 2-Amino-4-(furan-2-yl)-7,7-dimethyl-5-oxo-5,6,7,8-
tetrahydro-4H-chromene-3-carbonitrile (5m)
4.2.8. 2-Amino-4-(4-methoxyphenyl)-7,7-dimethyl-5-oxo-5,6,7,8-
tetrahydro-4H-chromene-3-carbonitrile (5h)
White solid with the melting point of 226–228 ꢁC; IR (KBr, neat)
nmax 3398, 3329, 3255, 3216, 2966, 2932, 2875, 2197, 1681, 1661,
1604, 1364, 1218, 1038, 1013, 736; 1H NMR (400 MHz, DMSO-d6)
Yellow solid with the melting point of 201–202 ꢁC; IR (KBr, neat)
nmax 3352, 3188, 2967, 2194, 1684, 1655, 1606, 1509, 1371, 1256,
d
7.47 (s, 1H), 7.06 (s, 2H), 6.32 (s, 1H), 6.05 (d, J¼2.2 Hz, 1H), 4.32 (s,
1214, 1033, 844; 1H NMR (400 MHz, DMSO-d6)
d
7.05 (d, J¼8.1 Hz,
1H), 2.48 (q, J¼17.9 Hz, 2H), 2.28 (d, J¼16.1 Hz, 1H), 2.16 (d,
2H), 6.94 (s, 2H), 6.84 (d, J¼8.1 Hz, 2H), 4.12 (s, 1H), 3.71 (s, 1H), 2.50
(s, 2H), 2.24 (d, J¼16.1 Hz, 1H), 2.09 (d, J¼16.1 Hz, 1H), 1.03 (s, 3H),
J¼16.1 Hz, 1H), 1.04 (s, 3H), 0.98 (s, 3H); 13C NMR (100 MHz, DMSO-
d6)
d 195.40, 163.25, 159.30, 155.72, 141.72, 119.52, 110.43, 110.37,

S. Gao et al. / Tetrahedron 64 (2008) 9143–9149
9147
105.04, 55.44, 59.90, 39.72, 31.79, 28.99, 28.41, 26.55; HRMS (EI)
59.07, 49.15, 41.00, 31.89, 30.65, 28.90, 26.39; HRMS (EI) m/z calcd
m/z calcd for C16H16N2O3 (Mþ): 284.1161, found: 284.1167.
for C24H22N4O3 (Mþ): 414.1692, found: 414.1685.
4.2.14. 2-Amino-4-(4-(dimethylamino)phenyl)-7,7-dimethyl-5-
oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (5n)
Yellow solid with the melting point of 217–218 ꢁC; IR (KBr, neat)
nmax 3195, 2959, 2922, 2804, 2361, 2339, 2192, 1681, 1658, 1607,
1520, 1368, 1247, 1213, 1159, 1141, 1034, 826; 1H NMR (400 MHz,
4.2.19. 2-Amino-4-(4-methoxyphenyl)-7,7-dimethyl-5-oxo-1-
phenyl-1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile (6e)
White solid with the melting point of 244–245 ꢁC; IR (KBr, neat)
nmax 3459, 3332, 3219, 2991, 2956, 2836, 2177, 1464, 1645, 1590,
1564, 1508, 1412, 1374, 1256, 1239, 1177, 1143, 1030, 852, 705; 1H
DMSO-d6)
d
6.94 (d, J¼8.4 Hz, 2H), 6.87 (s, 2H), 6.63 (d, J¼8.4 Hz,
NMR (400 MHz, DMSO-d6)
d
7.63–7.51 (m, 3H), 7.39 (d, J¼7.0 Hz,
2H), 4.05 (s, 1H), 2.84 (s, 6H), 2.48 (q, J¼17.2 Hz, 2H), 2.24 (d,
2H), 7.20 (d, J¼8.4 Hz, 2H), 6.89 (d, J¼8.4 Hz, 2H), 5.26 (s, 2H), 4.42
(s, H), 3.73 (s, 3H), 2.21 (d, J¼4.4 Hz, 1H), 2.17 (d, J¼2.2 Hz, 1H), 2.00
(d, J¼16.1 Hz, 1H), 1.69 (d, J¼17.2 Hz, 1H), 0.87 (s, 3H), 0.73 (s, 3H);
J¼16.1 Hz, 1H), 2.08 (d, J¼16.1 Hz, 1H), 1.03 (s, 3H), 0.95 (s, 3H); 13
C
NMR (100 MHz, DMSO-d6)
d 195.67, 161.85, 158.35, 149.23, 132.52,
127.72,119.94,113.29,112.33, 58.98, 50.07, 40.22, 39.72, 34.57, 31.77,
28.48, 26.75; HRMS (EI) m/z calcd for C20H23N3O2 (Mþ): 337.1790,
found: 337.1798.
13C NMR (100 MHz, DMSO-d6)
d 194.79, 157.74, 150.98, 149.78,
138.70, 136.30, 130.16, 12.90, 129.68, 127.78, 121.51, 113.71, 112.06,
60.80, 54.95, 49.33, 10.93, 35.45, 31.82, 29.06, 26.25; HRMS (EI) m/z
calcd for C25H25N3O2 (Mþ): 399.1947, found: 399.1943.
4.2.15. 2-Amino-7,7-dimethyl-5-oxo-1,4-diphenyl-1,4,5,6,7,8-
hexahydroquinoline-3-carbonitrile (6a)
4.2.20. 2-Amino-4-(4-hydroxyphenyl)-7,7-dimethyl-5-oxo-1-
phenyl-1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile (6f)
White solid with the melting point of 246–247 ꢁC; IR (KBr, neat)
nmax 3462, 3335, 3221, 3056, 3021, 2958, 2179, 1660, 1620, 1572,
1490, 1415, 1374, 1259, 1145, 1041, 738, 697, 575; 1H NMR (400 MHz,
Yellow solid with the melting point of 267–268 ꢁC; IR (KBr, neat)
nmax 3472, 3333, 3276, 3217, 2962, 2360, 2339, 2179, 1652, 1634,
1614,1591,1566, 1510,1415,1377,1259,1168,1041, 852, 703, 577; 1H
DMSO-d6)
d
7.66–7.51 (m, 3H), 7.46–7.25 (m, 6H), 7.19 (t, J¼6.8 Hz,
1H), 5.34 (s, 2H), 4.46 (s, 1H), 2.20 (dd, J¼16.5, 5.5 Hz, 2H), 2.00 (d,
NMR (400 MHz, DMSO-d6) d 9.22 (s, 1H), 7.64–7.49 (m, 3H), 7.37 (d,
J¼16.1 Hz, 1H), 1.71 (d, J¼17.6 Hz, 1H), 0.88 (s, 3H), 0.73 (s, 3H); 13
C
J¼6.6 Hz, 2H), 7.07 (d, J¼8.1 Hz, 2H), 6.70 (d, J¼8.4 Hz, 2H), 5.23 (s,
2H), 4.37 (s, 1H), 2.18 (d, J¼17.2 Hz, 2H), 1.99 (d, J¼16.1 Hz, 1H), 1.68
(d, J¼17.2 Hz, 1H), 0.87 (s, 3H), 0.73 (s, 3H); 13C NMR (100 MHz,
NMR (100 MHz, DMSO-d6)
d 194.88, 51.16, 150.25, 146.52, 136.27,
130.24, 129.97, 129.77, 128.43, 126.81, 126.32, 121.55, 111.73, 60.43,
49.32, 40.99, 36.39, 31.90, 29.10, 26.30; HRMS (EI) m/z calcd for
DMSO-d6) d 194.85, 155.77, 150.94, 149.64, 137.06, 136.36, 130.17,
C
24H23N3O (Mþ): 369.1841, found: 369.1845.
129.92, 129.68, 127.75, 121.61, 115.04, 112.29, 61.02, 49.39, 40.94,
35.36, 31.84, 29.08, 26.24; HRMS (EI) m/z calcd for C24H23N3O2
(Mþ): 385.1790, found: 385.1793.
4.2.16. 2-Amino-4-(4-chlorophenyl)-7,7-dimethyl-5-oxo-1-phenyl-
1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile (6b)
White solid with the melting point of 268–269 ꢁC; IR (KBr, neat)
nmax 3467, 3331, 3218, 2952, 2179, 1652, 1618, 1593, 1568, 1486,
1415,1372, 1258, 1144, 1011, 841, 696; 1H NMR (400 MHz, DMSO-d6)
4.2.21. 2-Amino-7,7-dimethyl-20,5-dioxo-5,6,7,8-tetrahydrospiro-
[chromene-4,30-indoline]-3-carbonitrile (8a)
White solid with the melting point of >300 ꢁC; IR (KBr, neat)
nmax 3380, 3316, 3141, 2960, 2929, 2885, 2193, 1723, 1683, 1658,
1605, 1471, 1349, 1327, 1223, 1166, 1055, 902, 745, 615; 1H NMR
d
7.64–7.51 (m, 3H), 7.45–7.33 (m, 4H), 7.30 (d, J¼8.4 Hz, 2H), 5.37 (s,
2H), 4.48 (s, 1H), 2.19 (d, J¼16.5 Hz, 2H), 2.00 (d, J¼15.7 Hz, 1H), 1.70
(d, J¼17.2 Hz, 1H), 0.87 (s, 3H), 0.72 (s, 3H); 13C NMR (100 MHz,
(400 MHz, DMSO-d6)
d
10.38 (s, 1H), 7.21 (s, 2H), 7.14 (t, J¼7.3 Hz,
DMSO-d6)
d
194.79, 151.23, 150.34, 145.42, 136.09, 130.78, 130.18,
1H), 6.97 (d, J¼7.3 Hz, 1H), 6.89 (t, J¼7.5 Hz, 1H), 6.78 (d, J¼7.7 Hz,
1H), 2.56 (q, J¼17.9 Hz, 2H), 2.13 (q, J¼16.1 Hz, 2H), 1.03 (s, 3H), 1.00
129.95, 129.78, 128.70, 128.32, 121.28, 111.35, 59.85, 49.24, 40.95,
35.98, 31.85, 28.98, 26.28; HRMS (EI) m/z calcd for C24H22ClN3O
(Mþ): 403.1451, found: 403.1455.
(s, 1H); 13C NMR (100 MHz, DMSO-d6)
d 194.80, 177.96, 164.08,
158.73, 142.03, 134.37, 128.11, 122.96, 121.62, 117.26, 110.77, 109.19,
57.53, 49.98, 46.79, 39.93, 31.85, 27.55, 27.00.
4.2.17. 2-Amino-4-(4-fluorophenyl)-7,7-dimethyl-5-oxo-1-phenyl-
1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile (6c)
4.2.22. 2-Amino-10,7,7-trimethyl-20,5-dioxo-5,6,7,8-
Yellow solid with the melting point of 260–261 ꢁC; IR (KBr, neat)
nmax 3455, 3339, 3210, 2959, 2361, 2339, 2177, 1640, 1592, 1557,
1505, 1417, 1371, 1257, 1216, 1153, 1045, 849, 702; 1H NMR
tetrahydrospiro[chromene-4,30-indoline]-3-carbonitrile (8b)
White solid with the melting point of 265–266 ꢁC; IR (KBr, neat)
nmax 3461, 3371, 3298, 3247, 3167, 2959, 2892, 2870, 2195, 1712,
1669, 1609, 1493, 1471, 1353, 1323, 1222, 1052, 904, 744, 562, 542;
(400 MHz, DMSO-d6)
d
7.64–7.51 (m, 3H), 7.40 (d, J¼7.0 Hz, 2H),
7.30 (dd, J¼8.4, 5.9 Hz, 2H), 7.14 (t, J¼8.8 Hz, 2H), 5.34 (s, 2H), 4.48
(s, 1H), 2.19 (d, J¼16.8 Hz, 2H), 2.00 (d, J¼16.1 Hz, 1H), 1.70 (d,
J¼17.2 Hz, 1H), 0.87 (s, 3H), 0.72 (s, 3H); 13C NMR (100 MHz, DMSO-
1H NMR (400 MHz, DMSO-d6)
d
7.29–7.22 (m, 3H), 7.20 (d, J¼7.0 Hz,
1H), 7.01–6.95 (m, 2H), 3.13 (s, 3H), 2.57 (s, 2H), 2.15 (d, J¼15.7 Hz,
1H), 2.08 (d, J¼15.7 Hz, 1H), 1.03 (s, 3H), 0.99 (s, 3H); 13C NMR
d6)
d
194.81, 161.98, 159.57, 151.15, 150.16, 142.66, 136.14, 130.17,
(100 MHz, DMSO-d6) d 194.88, 176.54, 164.25, 158.88, 143.57,
129.92, 129.76, 128.63, 128.55, 121.34, 115.11, 114.90, 111.66, 60.24,
133.54, 128.40, 122.76, 122.43, 117.19, 110.74, 108.17, 57.07, 49.96,
46.47, 31.96, 27.53, 27.07, 26.36; HRMS (EI) m/z calcd for C20H19N3O3
(Mþ): 349.1426, found: 349.1422.
49.27, 40.95, 35.74, 31.84, 28.98, 26.26; HRMS (EI) m/z calcd for
C
24H22FN3O (Mþ): 387.1747, found: 387.1741.
4.2.18. 2-Amino-7,7-dimethyl-4-(4-nitrophenyl)-5-oxo-1-phenyl-
1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile (6d)
4.2.23. tert-Butyl 2-amino-3-cyano-7,7-dimethyl-20,5-dioxo-
5,6,7,8-tetrahydrospiro[chromene-4,30-indoline]-
Yellow solid with the melting point of 275–276 ꢁC; IR (KBr, neat)
nmax 3460, 3321, 3218, 3070, 2959, 2180, 1651, 1620, 1592, 1565,
1519, 1374, 1346, 1258, 1146, 1042, 872, 697; 1H NMR (400 MHz,
10-carboxylate (8c)
White solid with the melting point of >300 ꢁC; IR (KBr, neat)
nmax 3379, 3328, 3247, 3205, 2961, 2937, 2870, 2196, 1791, 1673,
1601, 1479, 1466, 1352, 1311, 1248, 1149, 1053, 857, 841, 750, 560; 1H
DMSO-d6)
d
8.22 (d, J¼8.8 Hz, 2H), 7.65–7.52 (m, 5H), 7.46 (d,
J¼7.0 Hz, 2H), 5.47 (s, 2H), 4.62 (s, 1H), 2.20 (d, J¼16.5 Hz, 2H), 2.01
(d, J¼16.8 Hz, 1H), 1.73 (d, J¼17.6 Hz, 1H), 0.88 (s, 3H), 0.73 (s, 3H);
NMR (400 MHz, DMSO-d6)
d
7.74 (d, J¼8.4 Hz, 1H), 7.44 (s, 2H),
7.35–7.28 (m, 1H), 7.14 (d, J¼3.7 Hz, 2H), 2.60 (s, 2H), 2.16 (q,
13C NMR (100 MHz, DMSO-d6)
d 194.79, 153.88, 151.45, 150.97,
J¼16.1 Hz, 2H), 1.58 (s, 9H), 1.04 (s, 3H), 1.01 (s, 3H); 13C NMR
146.08, 135.92, 130.21, 130.01, 129.88, 128.14, 123.81, 121.05, 110.68,
(100 MHz, DMSO-d6) d 195.64, 175.49, 165.15, 159.15, 149.14, 139.43,

9148
S. Gao et al. / Tetrahedron 64 (2008) 9143–9149
132.86, 129.09, 125.26, 123.84, 117.50, 114.78, 111.36, 84.22, 57.77,
50.10, 47.72, 40.28, 32.55, 28.17, 28.01, 27.61; HRMS (EI) m/z calcd
for C24H25N3O5 (Mþ): 435.1794, found: 435.1818.
4.2.29. 2-Amino-10-benzyl-20,5-dioxo-5,6,7,8-tetrahydrospiro-
[chromene-4,30-indoline]-3-carbonitrile (8i)
White solid with the melting point of 284–285 ꢁC; IR (KBr, neat)
nmax 3375, 3291, 3176, 2195, 1694, 1683, 1667, 1605, 1488, 1466,
1348, 1313, 1213, 1173, 1075, 1012, 942, 881, 867, 748, 707, 689, 615,
4.2.24. 2-Amino-10-benzyl-7,7-dimethyl-20,5-dioxo-5,6,7,8-
tetrahydrospiro[chromene-4,30-indoline]-3-carbonitrile (8d)
Yellow solid with the melting point of 285–286 ꢁC; IR (KBr, neat)
nmax 3387, 3322, 3248, 3207, 2964, 2922, 2878, 2197, 1715, 1681,
1661, 1600, 1487, 1467, 1352, 1220, 1167, 1051, 749; 1H NMR
538; 1H NMR (400 MHz, DMSO-d6)
d
7.49 (d, J¼7.3 Hz, 2H), 7.34–
7.22 (m, 5H), 7.16–7.08 (m, 2H), 6.95 (t, J¼7.3 Hz, 1H), 6.68 (d,
J¼7.7 Hz, 1H), 4.90 (q, J¼16.5 Hz, 2H), 2.77–2.63 (m, 2H), 2.34–2.18
(m, 2H), 1.95 (quint, J¼6.2 Hz, 2H); 13C NMR (100 MHz, DMSO-d6)
(400 MHz, DMSO-d6)
d
7.49 (d, J¼7.3 Hz, 2H), 7.33–7.23 (m, 5H), 7.13
d 195.11, 176.77, 166.36, 158.77, 142.56, 136.16, 133.70, 128.31, 128.18,
(t, J¼7.7 Hz, 1H), 7.08 (d, J¼7.3 Hz, 1H), 6.96 (t, J¼7.3 Hz, 1H), 6.68 (d,
J¼7.7 Hz,1H), 4.90 (q, J¼16.1 Hz, 2H), 2.60 (q, J¼17.9 Hz, 2H), 2.17 (q,
J¼16.1 Hz, 2H), 1.05 (s, 3H), 1.02 (s, 3H); 13C NMR (100 MHz, DMSO-
127.09, 123.08, 122.46, 117.36, 111.71, 108.74, 57.27, 46.63, 43.31,
36.29, 26.77, 19.74; HRMS (EI) m/z calcd for C24H19N3O3 (Mþ):
397.1426, found: 397.1422.
d6)
d 195.01, 176.70, 164.48, 158.94, 142.61, 136.12, 133.58, 128.34,
128.24, 127.13, 127.08, 122.92, 122.54, 117.36, 110.67, 108.87, 57.28,
49.93, 46.60, 43.34, 39.98, 31.94, 27.60, 27.03; HRMS (EI) m/z calcd
for C26H23N3O3 (Mþ): 425.1739, found: 425.1736.
4.2.30. 10-Acetyl-2-amino-20,5-dioxo-5,6,7,8-tetrahydrospiro-
[chromene-4,30-indoline]-3-carbonitrile (8j)
White solid with the melting point of 272–273 ꢁC; IR (KBr, neat)
nmax 3594, 3533, 3318, 3183, 2204, 1755, 1722, 1678, 1658, 1603,
1465, 1423, 1372, 1350, 1334, 1305, 1211, 1172, 1073, 1014, 759, 599;
4.2.25. 10-Acetyl-2-amino-7,7-dimethyl-20,5-dioxo-5,6,7,8-
tetrahydrospiro[chromene-4,30-indoline]-3-carbonitrile (8e)
Yellow solid with the melting point of 249–250 ꢁC; IR (KBr, neat)
nmax 3409, 3327, 3247, 3199, 2967, 2900, 2190, 1715, 1683, 1661,
1593, 1464, 1352, 1266, 1167, 1046, 969, 907, 796, 763, 597, 560, 512;
1H NMR (400 MHz, DMSO-d6)
d
8.07 (d, J¼8.1 Hz, 1H), 7.50 (s, 2H),
7.32 (t, J¼7.3 Hz, 1H), 7.24–7.17 (m, 2H), 2.78–2.64 (m, 2H), 2.57 (s,
3H), 2.34–2.18 (m, 2H), 1.99–1.90 (m, 2H); 13C NMR (100 MHz,
DMSO-d6)
d 195.52, 177.95, 170.31, 166.80, 158.53, 139.16, 132.86,
1H NMR (400 MHz, DMSO-d6)
d
8.07 (d, J¼8.4 Hz, 1H), 7.52 (s, 2H),
128.61, 125.50, 123.55, 116.98, 115.24, 111.95, 57.10, 47.51, 35.88,
26.60, 25.93, 19.67.
7.35–7.30 (m, 1H), 7.20 (d, J¼3.7 Hz, 2H), 2.62 (d, J¼1.5 Hz, 2H), 2.57
(s, 3H), 2.17 (q, J¼16.3 Hz, 2H), 1.04 (s, 3H), 1.01 (s, 3H); 13C NMR
(100 MHz, DMSO-d6)
d 195.34, 177.86, 170.26, 164.85, 158.66,
Acknowledgements
139.20, 132.69, 128.64, 125.52, 123.33, 116.92, 115.33, 110.84, 57.03,
49.48, 47.44, 39.72, 32.07, 27.50, 27.03, 25.89; HRMS (EI) m/z calcd
for C21H19N3O4 (Mþ): 377.1376, found: 377.1372.
Financial support of this work by the National Science Council of
the Republic of China is gratefully acknowledged.
4.2.26. 2-Amino-20,5-dioxo-5,6,7,8-tetrahydrospiro[chromene-
4,30-indoline]-3-carbonitrile (8f)
White solid with the melting point of 276–277 ꢁC; IR (KBr, neat)
nmax 3370, 3298, 3131, 2191, 1705, 1683, 1652, 1606, 1466, 1353,
1334, 1316, 1210, 1194, 1076, 1011, 763, 680; 1H NMR (400 MHz,
Supplementary data
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2008.06.061.
DMSO-d6)
J¼7.0 Hz, 1H), 6.88 (t, J¼7.3 Hz, 1H), 2.68–2.62 (m, 2H), 2.30–2.15
(m, 2H), 1.96–1.87 (m, 2H); 13C NMR (100 MHz, DMSO-d6)
194.94,
178.08, 165.98, 158.60, 141.98, 134.51, 128.09, 123.15, 121.59, 117.30,
111.87, 109.10, 57.58, 46.87, 36.35, 26.71, 19.76; HRMS (EI) m/z calcd
for C17H13N3O3 (Mþ): 307.0957, found: 307.0964.
d
10.38 (s, 1H), 7.20 (s, 2H), 7.13 (t, J¼7.5 Hz, 1H), 7.00 (d,
References and notes
d
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4.2.27. 2-Amino-10-methyl-20,5-dioxo-5,6,7,8-tetrahydrospiro-
[chromene-4,30-indoline]-3-carbonitrile (8g)
White solid with the melting point of 277–278 ꢁC; IR (KBr, neat)
nmax 3566, 3468, 3357, 3302, 3151, 2962, 2195,1705,1675,1645,1602,
1492,1470,1424,1350,1309,1215,1075,1012, 758, 686, 540; 1H NMR
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d
7.27–7.22 (m, 3H), 7.07 (d, J¼7.3 Hz, 1H),
7.00–6.94 (m, 2H), 3.13 (s, 3H), 2.69–2.64 (m, 2H), 2.28–2.13 (m, 2H),
1.92 (quint, J¼6.2 Hz, 2H); 13C NMR (100 MHz, DMSO-d6)
d 194.96,
176.60, 166.12, 158.72, 143.49, 133.66, 128.33, 122.91, 122.35, 117.18,
111.81, 108.05, 46.52, 36.30, 26.71, 26.32, 19.73; HRMS (EI) m/z calcd
for C18H15N3O3 (Mþ): 321.1113, found: 321.1106.
4.2.28. tert-Butyl 2-amino-3-cyano-20,5-dioxo-5,6,7,8-tetra-
hydrospiro[chromene-4,30-indoline]-10-carboxylate (8h)
White solid with the melting point of 296–297 ꢁC; IR (KBr, neat)
nmax 3323, 3188, 2981, 2197, 1791, 1730, 1683, 1602, 1479, 1351, 1310,
1250, 1148,1073, 1009, 839, 757, 538; 1H NMR (400 MHz, DMSO-d6)
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d
7.72 (d, J¼8.1 Hz, 1H), 7.43 (s, 2H), 7.31 (td, J¼7.5, 1.5 Hz, 1H), 7.19–
7.11 (m, 2H), 2.69 (t, J¼5.9 Hz, 2H), 2.32–2.16 (m, 2H), 1.94 (quint,
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d 195.28, 175.03,
166.54,158.48,148.68,138.89,132.48,128.52,124.69, 123.52,117.03,
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