One-pot domino reactions for synthesis of heterocyclic[3.3.3]propellanes and spiro[cyclopenta[b]pyridine-4,2′-indenes]

Article abstract of DOI:10.1016/j.tet.2013.04.048

An efficient synthetic procedure for the functionalized heterocyclic[3.3.3]propellanes was successfully developed by one-pot domino reaction of ninhydrin, malononitrile with 3-arylamino-2-cyclohexenones and their 5,5-dimethyl derivatives in the presence o

Full text of DOI:10.1016/j.tet.2013.04.048

Tetrahedron 69 (2013) 4915e4921
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
One-pot domino reactions for synthesis of heterocyclic[3.3.3]
propellanes and spiro[cyclopenta[b]pyridine-4,20-indenes]
*
Li-Juan Zhang, Chao-Guo Yan
College of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou 225002, China
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient synthetic procedure for the functionalized heterocyclic[3.3.3]propellanes was successfully
developed by one-pot domino reaction of ninhydrin, malononitrile with 3-arylamino-2-cyclohexenones
and their 5,5-dimethyl derivatives in the presence of triethylamine in ethanol at room temperature. On
the other hand the similar one-pot reaction containing 3-arylamino-2-cyclopentenones resulted in the
functionalized spiro[cyclopenta[b]pyridine-4,20-indenes] in moderate yields.
Received 30 January 2013
Received in revised form 2 April 2013
Accepted 11 April 2013
Available online 16 April 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Domino reaction
Propellane
Spiro compound
Enaminone
Ninhydrin
1. Introduction
successfully reported the efficient synthesis of the interesting
heterocyclic[3.3.3]propellanes by the domino four-component re-
Enaminones (enamino esters) are one kind of readily obtainable
and versatile synthetic reagents, in which the nucleophilic enamine
and the electrophilic enone (ester) moieties are combined into one
molecule.1,2 These attractive features have made them as important
building blocks in current organic synthesis.3,4 Over the decades, two
particular enaminones have been widely used to design multicom-
ponent reactions and domino reactions for theconvenient synthesis of
awidevarietyofheterocycliccompounds.Thefirstkindof widely used
enaminonescouldbereadilypreparedfromthedirectcondensationof
actions of primary amines, acetylenedicarboxylate, ninhydrin and
malononitrile.14 Inspired by these results, we envisaged that the
cyclic enaminones derived from the reaction of primary amines
with cyclic diketones, such as dimedone could be utilized as readily
available building blocks for constructing functionalized cyclic
[3.3.3]propellanes with the fused cycloalkyl unit. Here we wish to
report the efficient synthesis of heterocyclic[3.3.3]propellanes and
spiro[cyclopenta[b]pyridine-4,20-indenes] via the one-pot domino
reactions of cyclic enaminones, ninhydrin, and malononitrile.
b
-dicarbonyl compounds with primary and secondary amines.5,6 The
second commonly used enaminones came from the addition of ali-
phatic and aromatic amines to the activated alkynes bearing with
carbonyl groups.7,8 We have successfully developed several new
2. Results and discussions
At first ninhydrin reacted with malononitrile in ethanol at room
temperature for about 1 h to give the Knoevenagel adduct
according to the previously established reaction conditions.14a Then
3-arylamino-5,5-dimethyl-2-cyclohexenone was added and the
reaction was finished at room temperature in about 2 h to give the
expected heterocyclic[3.3.3]propellanes 1ae1h in satisfactory
yields (Table 1, entries 1e8). By using this domino reaction pro-
cedure, the reaction was carried out in very convenient manner and
the pure products could be easily obtained after filtration of the
resulted precipitates without further purification. To demonstrate
the practical utility of the current protocol, other kinds of cyclic
enaminones, such as 3-arylamino-2-cyclohexenones were also
used in the reaction. The reaction also proceeded very smoothly to
give the heterocyclic[3.3.3]propellanes 1ie1o in good yields (Table
domino reactions by using the in situ formed b-enamino esters from
the reaction of arylamine with electron-deficient alkynes.9,10
Propellane is a special kind of annulated tricyclic system con-
nected by a carbonecarbon single bond11 and can be found as
scaffolds in many non-naturally and naturally occurring products,
such as hasubanone, Modhephene, aspidohylline, merrilactone A
(Fig. 1).12 Due to their challenging framework and broad spectra of
biological and pharmacological activities, propellanes attracted
continuous attentions as one of the synthetic targets in organic
synthesis.13 Very recently Alizadeh and his co-workers have
* Corresponding author. Tel.: þ86 514 87975531; fax: þ86 514 87975244; e-mail
address: cgyan@yzu.edu.cn (C.-G. Yan).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.04.048

4916
L.-J. Zhang, C.-G. Yan / Tetrahedron 69 (2013) 4915e4921
OMe
OHC
OMe
O
HO
O
N
O
O
HN
Me
H
O
CO2Me
O
O
OMe
H
N
OMe
Me
A: hasubanone
B: Modhephene
C: aspidohylline
D: merrilactone A
Fig. 1. Typical natural products containing propellane skeleton.
Table 1
Synthesis of functionalized heterocyclic[3.3.3]propellanes
1a-1o
Entry
Compd
R
Ar
Yield (%)
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
H
H
H
H
H
p-CH3C6H4
p-OCH3C6H4
o-OCH3C6H4
C6H5
p-ClC6H4
m-ClC6H4
p-BrC6H4
C6H4CH2
p-CH3C6H4
p-OCH3C6H4
C6H5
81
73
80
78
71
66
74
79
72
83
72
78
71
65
78
9
10
11
12
13
14
15
p-ClC6H4
p-BrC6H4
p-NO2C6H4
C6H4CH2
H
H
1, entries 9e15). Totally fifteen new heterocyclic[3.3.3]propellanes
were successfully synthesized by the domino reaction. The struc-
tures of the above prepared compounds 1ae1o were characterized
by 1H and 13C NMR, HRMS, and IR spectra and were further con-
firmed by single-crystal X-ray diffraction performed for the two
compounds 1a (Fig. 2) and 1j (Fig. 3).
also employed in the reaction and the results are summarized in
Table 2. In the presence of triethylamine the domino reaction of
ninhydrin, malononitrile, and 3-arylamino-2-cyclopentenones in
ethanol did not give the expected heterocyclic[3.3.3]propellanes,
but afforded the functionalized spiro[cyclopenta[b]pyridine-4,20-
indenes] 2ae2f in moderate yields. Their structures were estab-
lished by spectroscopic methods and X-ray diffraction de-
termination of single-crystal of spiro compound 2a (Fig. 4).
To explore the generality and scope of this domino reaction,
other enaminones, such as 3-arylamino-2-cyclopentenones were
Fig. 2. Molecular structure of compound 1a.
Fig. 3. Molecular structure of compound 1j.

L.-J. Zhang, C.-G. Yan / Tetrahedron 69 (2013) 4915e4921
4917
Table 2
The domino reactions of different cyclic enaminones could give
heterocyclic[3.3.3]propellanes and spiro[cyclopenta[b]pyridine-
4,20-indenes] under similar reaction conditions. Though the exact
mechanism is not investigated in detail, a possible reaction mech-
anism for the formation of two kinds of products was proposed in
Scheme 1, which was on the basis of the Alizadeh’s recently pub-
lished works14 and the similar multicomponent reactions of
malononitirile.15 At first a base catalyzed condensation of ninhydrin
with malononitrile produced the adduct (E). Secondly Michael
addition of cyclic enaminone to adduct (E) afforded the in-
termediate (F). Then the reaction could proceed further according
to two paths. On the path a, the intramolecular addition of aryla-
mino group of 3-arylamino-2-cyclohexenones and their 5,5-
dimethyl derivatives to one of carbonyl group of ninhydrin unit to
give the hydroxyl intermediate (G) with formation of nitrogen-
containing five-member ring. In the presence of triethylamine,
the deprotonated anion of intermediate (G) attacked the cyano
group to give an imine intermediate (H) with formation of oxygen-
containing five-member ring. At last the tautomerization of imino
group to amino group resulted in the heterocyclic[3.3.3]propellane
1. On the path b, arylamino group of 3-arylamino-2-cyclopen-
tanones did not firstly attack the carbonyl group, while added to
cyano group to form a cyclic imine intermediate (I), which in turn
transferred to spiro compound 2 though the iminoeamino tauto-
merization. The reasons for 3-arylamino-2-cyclopentanones and 3-
arylamino-2-cyclohexanones showing different reactivities might
be due to the steric effects of cyclopentyl and cyclohexyl units.
In conclusion, an efficient synthetic procedure for the func-
tionalized heterocyclic[3.3.3]propellanes as well as spiro[cyclo-
penta[b]pyridine-4,20-indenes] was successfully developed by one-
pot domino reaction of ninhydrin, malononitrile with cyclic
enaminones. The scope and limitation of this domino reaction was
established and the reaction mechanism was briefly discussed. This
protocol has advantages of mild reaction conditions, easily acces-
sible starting material, and easy purification of the products, which
makes it a useful and attractive method for the synthesis of the
Synthesis of spiro[cyclopenta[b]pyridine-4,20-indenes] 2ae2f
2a-2f
Entry
Compd
Ar
Yield (%)
1
2
3
4
5
6
2a
2b
2c
2d
2e
2f
p-CH3C6H4
p-OCH3C6H4
o-OCH3C6H4
p-ClC6H4
m-ClC6H4
p-BrC6H4
73
64
78
61
66
63
Fig. 4. Molecular structure of compound 2a.
Scheme 1. The proposed formation mechanism of compounds 1 and 2.

4918
L.-J. Zhang, C.-G. Yan / Tetrahedron 69 (2013) 4915e4921
complex propellanes in synthetic medicinal chemistry. Further
expansion of the reaction scope and synthetic applications of this
methodology are in progress in our laboratory.
1183, 1145, 1089, 1066, 1042, 1019, 993, 961, 920, 885, 868, 830, 779,
758, 718 cmꢁ1 1H NMR (600 MHz, DMSO-d6)
: 8.63 (s, 1H, ArH),
;
d
7.85 (d, J¼7.8 Hz, 1H, ArH), 7.68 (t, J¼7.8 Hz, 1H, ArH), 7.62e7.58 (m,
2H, NH2), 7.53 (t, J¼7.2 Hz, 1H, ArH), 7.18 (t, J¼7.8 Hz, 1H, ArH), 7.10
(d, J¼8.4 Hz, 1H, ArH), 6.74 (d, J¼7.8 Hz, 1H, ArH), 5.95 (s, 1H, ArH),
3.23 (s, 3H, OCH3), 2.26 (d, J¼16.2 Hz, 1H, CH2), 2.11 (d, J¼17.4 Hz,
1H, CH2), 1.98 (d, J¼16.2 Hz, 1H, CH2), 1.85 (d, J¼16.8 Hz, 1H, CH2),
3. Experimental section
3.1. Reagents and apparatus
0.98 (s, 3H, CH3), 0.88 (s, 3H, CH3); 13C NMR (150 MHz, DMSO-d6)
d:
All reagents and solvents were commercial available with ana-
lytical grade and used as received. Cyclic enaminones were pre-
pared by the condensation of cyclic diketones with arylamines
according to the published methods.16 Evaporation removal of or-
ganic solvents was carried out with a rotary evaporator in con-
junction with a water aspirator. Melting points were taken on a hot-
plate microscope apparatus and without calibrating. 1H and 13C
NMR spectra were recorded on 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 spectrom-
194.4, 189.6, 165.5, 155.9, 148.3, 135.2, 134.1, 131.2, 130.9, 130.6,
124.9, 123.7, 122.7, 120.8, 112.8, 112.7, 112.2, 99.0, 97.7, 63.5, 55.2,
50.6, 36.1, 33.8, 28.9, 26.7, 21.9; MS (m/z): HRMS (ESI) calcd for
C27H23NaN3O4 ([MþNa]þ): 476.1581, found: 476.1587.
3.2.4. Heterocyclic[3.3.3]propellanes (1d). Yellow solid, 78%, mp
208e210 ꢀC; IR (KBr)
y: 2960, 2936, 2878, 2335, 2257, 2194, 2026,
1713, 1599, 1542, 1496, 1462, 1425, 1407, 1387, 1325, 1276, 1234,
1203, 1182, 1139, 1088, 1010, 968, 922, 886, 867, 825, 780, 765, 728,
701 cmꢁ1; 1H NMR (600 MHz, DMSO-d6)
d: 8.84 (s,1H, ArH), 7.88 (d,
eter. X-ray data were collected on
diffractometer.
a
Bruker Smart APEX-2
J¼7.8 Hz, 1H, ArH), 7.73 (t, J¼7.8 Hz, 1H, ArH), 7.65 (t, J¼7.8 Hz, 1H,
ArH), 7.56e7.53 (m, 3H, ArH), 7.30 (s, 2H, NH2), 6.82 (d, J¼7.8 Hz,1H,
ArH), 5.94 (s, 1H, ArH), 2.53 (d, J¼16.8 Hz, 1H, CH2), 2.29 (d,
J¼15.6 Hz, 1H, CH2), 1.92 (d, J¼15.6 Hz, 1H, CH2), 1.75 (d, J¼16.8 Hz,
1H, CH2), 0.98 (s, 3H, CH3), 0.93 (s, 3H, CH3); 13C NMR (150 MHz,
3.2. General procedure for the preparation of heterocyclic
[3.3.3]propellanes (1ae1o) from one-pot domino reaction of
ninhydrin, malononitrile, and cyclic enaminones
DMSO-d6) d: 194.0, 189.9, 164.2, 147.9, 135.7, 134.7, 134.1, 131.0,
129.4, 129.3, 128.8, 125.2, 124.0, 112.8, 99.4, 98.1, 63.7, 50.6, 36.9,
34.1, 29.8, 25.9, 21.9; MS (m/z): HRMS (ESI) calcd for C26H21NaN3O3
([MþNa]þ): 446.1475, found: 446.1481.
In a round bottom flask a mixture of ninhydrin (1.0 mmol),
malononitrile (1.0 mmol), and triethylamine (0.1 mmol) in 5.0 mL
ethanol was stirred at room temperature for about 1 h. Then cyclic
enaminone (1.0 mmol) was added to it. The solution was stirred at
room temperature for additional 2 h. The resulting yellow pre-
cipitates were collected by filtration and washed with cold alcohol
to give the pure product.
3.2.5. Heterocyclic[3.3.3]propellanes (1e). Yellow solid, 72%, mp
222e224 ꢀC; IR (KBr)
y
: 2961, 2933, 2878, 2771, 2194, 2026, 1714,
1643, 1600, 1542, 1495, 1459, 1425, 1403, 1325, 1276, 1234, 1182,
1142, 1089, 1013, 971, 952, 921, 868, 813, 768, 750, 707 cmꢁ1 1H
NMR (600 MHz, DMSO-d6)
: 8.93 (s, 1H, ArH), 7.88 (d, J¼7.8 Hz, 1H,
;
d
3.2.1. Heterocyclic[3.3.3]propellanes (1a). Yellow solid, 81%, mp
ArH), 7.77 (t, J¼7.2 Hz, 1H, ArH), 7.67e7.63 (m, 3H, ArH), 7.33 (s, 2H,
NH2), 6.88 (d, J¼7.8 Hz, 1H, ArH), 5.93 (s, 1H, ArH), 2.53 (d,
J¼17.4 Hz, 1H, CH2), 2.28 (d, J¼15.6 Hz, 1H, CH2), 1.93 (d, J¼15.6 Hz,
1H, CH2), 1.78 (d, J¼16.8 Hz, 1H, CH2), 0.98 (s, 3H, CH3), 0.93 (s, 3H,
216e218 ꢀC; IR (KBr)
y: 3080, 2958, 2875, 2193, 1712, 1595, 1540,
1513, 1462, 1427, 1404, 1325, 1275, 1234, 1205, 1181, 1145, 1089,1011,
953, 921, 867, 810, 762, 675, 617 cmꢁ1; 1H NMR (600 MHz, DMSO-
d6)
d
: 8.83 (s, 1H, ArH), 7.88 (d, J¼7.8 Hz, 1H, ArH), 7.75 (t, J¼7.2 Hz,
CH3); 13C NMR (150 MHz, DMSO-d6)
d: 193.9, 190.0, 164.0, 147.8,
1H, ArH), 7.65 (t, J¼7.8 Hz, 1H, ArH), 7.36 (d, J¼7.2 Hz, 2H, ArH), 7.17
(s, 2H, NH2), 6.88 (d, J¼7.8 Hz, 1H, ArH), 5.94 (s, 1H, ArH), 2.50 (d,
J¼16.8 Hz, 1H, CH2), 2.41 (s, 3H, CH3), 2.28 (d, J¼15.6 Hz, 1H, CH2),
1.91 (d, J¼15.6 Hz, 1H, CH2), 1.74 (d, J¼17.4 Hz, 1H, CH2), 0.98 (s, 3H,
135.9, 134.0, 133.7, 133.5, 131.1, 129.4, 125.1, 124.1, 112.7, 99.8, 98.1,
63.7, 50.6, 36.7, 34.1, 29.8, 25.8, 21.9; MS (m/z): HRMS (ESI) calcd for
C26H20ClNaN3O3 ([MþNa]þ): 480.1085, found: 480.1091.
CH3), 0.92 (s, 3H, CH3); 13C NMR (150 MHz, DMSO-d6)
d
: 194.1,189.7,
3.2.6. Heterocyclic[3.3.3]propellanes (1f). Yellow solid, 66%, mp
164.3, 148.0, 138.4, 135.7, 134.1, 132.0, 131.0, 129.8, 129.2, 125.3,
123.9, 112.8, 112.7, 99.1, 98.0, 63.7, 50.6, 36.8, 34.0, 29.7, 25.9, 21.8,
20.8; MS (m/z): HRMS (ESI) calcd for C27H23NaN3O3 ([MþNa]þ):
460.1632, found: 460.1634.
>250 ꢀC; IR (KBr)
y: 2954, 2895, 2756, 2543, 2365, 2195, 2026, 1732,
1586, 1544, 1483, 1459, 1436, 1409, 1328, 1286, 1248, 1229, 1184,
1150, 1090, 1003, 924, 864, 821, 779, 755 cmꢁ1; 1H NMR (600 MHz,
DMSO-d6)
d
: 8.98 (s, 1H, ArH), 7.89 (d, J¼7.8 Hz, 1H, ArH), 7.77 (t,
J¼7.2 Hz, 1H, ArH), 7.68e7.62 (m, 2H, ArH), 7.58 (t, J¼7.8 Hz, 1H,
ArH), 7.46 (s, 1H, NH2), 7.24 (s, 1H, NH2), 6.85 (d, J¼7.8 Hz, 1H, ArH),
5.94 (s, 1H, ArH), 2.60 (d, J¼17.4 Hz, 1H, CH2), 2.29 (d, J¼15.6 Hz, 1H,
CH2), 1.93 (d, J¼15.6 Hz, 1H, CH2), 1.80 (d, J¼17.4 Hz, 1H, CH2), 0.99
3.2.2. Heterocyclic[3.3.3]propellanes (1b). Yellow solid, 73%, mp
184e186 ꢀC; IR (KBr)
y
: 3029, 2962, 2878, 2776, 2551, 2258, 2190,
2029, 1719, 1600, 1512, 1461, 1284, 1249, 1155, 1082, 1011, 967, 926,
819, 774, 680 cmꢁ1 1H NMR (600 MHz, DMSO-d6)
: 8.74 (s, 1H,
;
d
(s, 3H, CH3), 0.95 (s, 3H, CH3); 13C NMR (150 MHz, DMSO-d6)
d:
ArH), 7.87 (d, J¼7.2 Hz, 1H, ArH), 7.76 (t, J¼7.2 Hz, 1H, ArH), 7.65 (t,
J¼7.2 Hz, 1H, ArH), 7.19 (s, 1H, NH2), 7.09 (d, J¼7.8 Hz, 2H, ArH), 6.92
(d, J¼7.8 Hz, 1H, ArH), 5.91 (s, 1H, ArH), 3.84 (s, 3H, OCH3), 2.46 (d,
J¼17.4 Hz, 1H, CH2), 2.27 (d, J¼15.6 Hz, 1H, CH2), 1.91 (d, J¼15.6 Hz,
1H, CH2), 1.74 (d, J¼17.4 Hz, 1H, CH2), 0.98 (s, 3H, CH3), 0.92 (s, 3H,
193.9,190.2,163.9,147.8,136.2,135.8,134.1,133.4,131.1,130.9, 129.0,
128.8, 128.1, 125.0, 124.1, 112.7, 112.6, 100.1, 98.3, 63.7, 50.7, 36.7,
34.2, 29.8, 25.8, 22.0; MS (m/z): HRMS (ESI) calcd for
C26H20ClNaN3O3 ([MþNa]þ): 480.1085, found: 480.1080.
CH3); 13C NMR (150 MHz, DMSO-d6)
d
: 194.1, 189.7, 164.6, 159.3,
3.2.7. Heterocyclic[3.3.3]propellanes (1g). Yellow solid, 74%, mp
148.0, 135.7, 134.1, 130.9, 130.7, 127.0, 125.3, 123.9, 114.9, 114.4, 112.8,
98.9, 97.9, 63.6, 55.4, 50.6, 36.7, 33.9, 29.7, 25.9, 21.8; MS (m/z):
HRMS (ESI) calcd for C27H23NaN3O4 ([MþNa]þ): 476.1581, found:
476.1585.
228e230 ꢀC; IR (KBr)
y
: 2961, 2933, 2877, 2351, 2194, 2026, 1714,
1633, 1599, 1541, 1493, 1456, 1426, 1405, 1325, 1279, 1234, 1183,
1143, 1089, 1012, 922, 813, 780, 748 cmꢁ1 1H NMR (600 MHz,
DMSO-d6)
;
d: 8.93 (s, 1H, ArH), 7.88 (d, J¼7.8 Hz, 1H, ArH), 7.73 (t,
J¼7.2 Hz, 3H, ArH), 7.66 (t, J¼7.8 Hz, 1H, ArH), 7.26 (s, 2H, NH2), 6.88
(d, J¼7.8 Hz, 1H, ArH), 5.93 (s, 1H, ArH), 2.53 (d, J¼17.4 Hz, 1H, CH2),
2.29 (d, J¼15.6 Hz, 1H, CH2), 1.92 (d, J¼15.6 Hz, 1H, CH2), 1.79 (d,
J¼17.4 Hz, 1H, CH2), 0.98 (s, 3H, CH3), 0.93 (s, 3H, CH3); 13C NMR
3.2.3. Heterocyclic[3.3.3]propellanes (1c). Yellow solid, 80%, mp
186e188 ꢀC; IR (KBr)
y
: 2963, 2872, 2644, 2536, 2362, 2255, 2193,
2026, 1722, 1598, 1546, 1499, 1463, 1403, 1327, 1283, 1247, 1205,

L.-J. Zhang, C.-G. Yan / Tetrahedron 69 (2013) 4915e4921
4919
(150 MHz, DMSO-d6)
d
: 193.9, 190.0, 164.0, 147.8, 135.9, 134.1, 134.0,
1090, 1048, 1014, 994, 974, 946, 923, 855, 799, 769, 710 cmꢁ1
;
1H
: 8.88 (s, 1H, ArH), 7.88 (d, J¼7.8 Hz, 1H,
132.4, 131.4, 131.1, 125.1, 124.1, 122.0, 112.7, 99.8, 98.1, 63.7, 50.6,
36.8, 34.1, 29.8, 25.8, 21.9; MS (m/z): HRMS (ESI) calcd for
C26H21BrN3O3 ([MþH]þ): 502.0761, found: 502.0755.
NMR (600 MHz, DMSO-d6)
d
ArH), 7.77 (t, J¼7.2 Hz, 1H, ArH), 7.67 (t, J¼7.2 Hz, 1H, ArH), 7.63 (d,
J¼8.4 Hz, 2H, ArH), 7.35 (d, J¼7.2 Hz, 2H, NH2), 6.92 (d, J¼7.8 Hz, 1H,
ArH), 5.92 (s, 1H, ArH), 2.49e2.43 (m, 1H, CH2), 2.28e2.22 (m, 1H,
CH2), 2.18e2.14 (m, 1H, CH2), 2.06e2.02 (m, 1H, CH2), 1.88e1.76 (m,
3.2.8. Heterocyclic[3.3.3]propellanes (1h). Yellow solid, 79%, mp
196e198 ꢀC; IR (KBr)
y
: 2961, 2868, 2370, 2191, 2027, 1724, 1588,
1536, 1497, 1432, 1406, 1355, 1331, 1271, 1246, 1181, 1147, 1089, 1039,
945, 866, 833, 773, 745 cmꢁ1; 1H NMR (600 MHz, DMSO-d6)
: 8.85
2H, CH2); 13C NMR (150 MHz, DMSO-d6)
d: 194.1, 190.5, 165.5, 147.8,
135.9, 134.2, 133.6,133.5, 131.3, 131.1, 129.4, 125.2, 124.0, 112.7, 112.4,
101.2, 97.9, 63.8, 36.6, 23.3, 22.1, 21.8; MS (m/z): HRMS (ESI)
calcd for C24H16ClNaN3O3 ([MþNa]þ): 452.0772, found: 452.0778.
d
(s, 1H, ArH), 8.04 (d, J¼7.8 Hz, 1H, ArH), 7.90e7.86 (m, 2H, ArH), 7.69
(t, J¼7.2 Hz, 1H, ArH), 7.34 (d, J¼7.8 Hz, 2H, NH2), 7.30 (d, J¼7.2 Hz,
2H, ArH), 7.26 (t, J¼7.2 Hz, 1H, ArH), 5.94 (s, 1H, ArH), 5.22 (d,
J¼16.8 Hz, 1H, CH2), 4.77 (d, J¼17.4 Hz, 1H, CH2), 2.23 (d, J¼17.4 Hz,
1H, CH2), 2.13 (d, J¼15.6 Hz, 1H, CH2), 1.93 (d, J¼17.4 Hz, 1H, CH2),
3.2.13. Heterocyclic[3.3.3]propellanes (1m). Yellow solid, 71%, mp
228e230 ꢀC; IR (KBr)
y: 2949, 2878, 2775, 2555, 2347, 2194, 2026,
1717, 1632, 1598, 1542, 1492, 1458, 1409, 1323, 1296, 1266, 1240,
1196, 1147, 1089, 1070, 1048, 1011, 996, 975, 946, 922, 855, 798, 769,
1.88 (d, J¼16.2 Hz, 1H, CH2), 0.81 (s, 3H, CH3), 0.79 (s, 3H, CH3); 13
C
NMR (150 MHz, DMSO-d6)
d: 194.0, 188.7, 164.9, 148.8, 137.8, 136.4,
709 cmꢁ1; 1H NMR (600 MHz, DMSO-d6)
d: 8.88 (s,1H, ArH), 7.88 (d,
134.1, 131.0, 128.3, 127.1, 126.7, 125.0, 124.1, 113.1, 112.7, 98.1, 97.3,
63.7, 50.3, 44.9, 35.9, 33.6, 28.9, 26.7, 21.7; MS (m/z): HRMS (ESI)
calcd for C27H24N3O3 ([MþH]þ): 438.1812, found: 438.1811.
J¼7.8 Hz, 1H, ArH), 7.79e7.76 (m, 3H, ArH), 7.67 (t, J¼7.2 Hz, 1H,
ArH), 7.28 (d, J¼7.8 Hz, 2H, NH2), 6.92 (d, J¼7.8 Hz, 1H, ArH), 5.92 (s,
1H, ArH), 2.48e2.43 (m, 1H, CH2), 2.27e2.22 (m,1H, CH2), 2.18e2.14
(m, 1H, CH2), 2.07e2.02 (m, 1H, CH2), 1.88e1.77 (m, 2H, CH2); 13C
3.2.9. Heterocyclic[3.3.3]propellanes (1i). Yellow solid, 72%, mp
NMR (150 MHz, DMSO-d6) d: 194.1, 190.5, 165.4, 147.8, 135.9, 134.1,
222e224 ꢀC; IR (KBr)
y
: 2949, 2875, 2770, 2026, 1716, 1635, 1596,
1543, 1511, 1461, 1410, 1324, 1296, 1239, 1195, 1148, 1089, 1047, 994,
923, 854, 800, 767 cmꢁ1 1H NMR (600 MHz, DMSO-d6)
: 8.75 (s,
134.0, 132.3, 131.6, 131.1, 125.1, 124.0, 122.1, 112.7, 112.4, 101.2, 97.9,
63.8, 36.6, 23.3, 22.1, 21.8; MS (m/z): HRMS (ESI) calcd for
C24H16BrNaN3O3([MþNa]þ): 496.0267, found: 496.0269.
;
d
1H, ArH), 7.87 (d, J¼7.2 Hz,1H, ArH), 7.75 (d, J¼6.6 Hz,1H, ArH), 7.65
(t, J¼6.6 Hz, 1H, ArH), 7.35 (d, J¼6.6 Hz, 2H, ArH), 7.19 (s, 2H, NH2),
6.92 (d, J¼7.2 Hz, 1H, ArH), 5.92 (s, 1H, ArH), 2.41 (s, 3H, CH3),
2.24e2.13 (m, 3H, CH2), 2.00 (d, J¼17.4 Hz, 1H, CH2), 1.83e1.78 (m,
3.2.14. Heterocyclic[3.3.3]propellanes (1n). Yellow solid, 65%, mp
214e216 ꢀC; IR (KBr)
y
: 2950, 2883, 2195, 2026, 1727, 1597, 1558,
1524, 1500, 1436, 1404, 1345, 1328, 1296, 1264, 1249, 1192, 1173,
1146, 1111, 1087, 991, 958, 928, 902, 863, 799, 770, 746 cmꢁ1 1H
NMR (600 MHz, DMSO-d6)
: 9.14 (s, 1H, ArH), 8.40 (d, J¼8.4 Hz, 2H,
2H, CH2); 13C NMR (150 MHz, DMSO-d6)
d: 194.2,190.3,165.8, 148.0,
;
138.4, 135.7, 134.2, 132.0, 130.9, 130.1, 129.8, 129.3, 128.0, 125.3,
123.9, 112.8, 112.4, 100.5, 97.8, 63.8, 36.5, 23.4, 22.0, 21.8, 20.8; MS
(m/z): HRMS (ESI) calcd for C25H20N3O3([MþH]þ): 410.1499, found:
410.1499.
d
NH2), 7.89 (t, J¼7.8 Hz, 1H, ArH), 7.73 (t, J¼7.2 Hz, 1H, ArH),
7.68e7.64 (m, 3H, ArH), 6.86 (d, J¼7.8 Hz,1H, ArH), 5.95 (s, 1H, ArH),
2.63e2.58 (m, 1H, CH2), 2.33e2.28 (m, 1H, CH2), 2.21e2.18 (m, 1H,
CH2), 2.11e2.08 (m, 1H, CH2), 1.93e1.90 (m, 1H, CH2), 1.83e1.77
3.2.10. Heterocyclic[3.3.3]propellanes (1j). Yellow solid, 83%, mp
(m, 1H, CH2); 13C NMR (150 MHz, DMSO-d6)
d: 193.9, 191.1, 164.9,
224e226 ꢀC; IR (KBr)
y
: 2973, 2875, 2776, 2554, 2368, 2194, 2026,
1720, 1611, 1535, 1511, 1462, 1429, 1410, 1326, 1299, 1252, 1196, 1151,
1089, 1031, 997, 940, 923, 855, 801, 774 cmꢁ1 1H NMR (600 MHz,
DMSO-d6)
147.6, 146.8, 141.2, 136.1, 134.1, 131.2, 130.0, 125.0, 124.9, 124.6, 124.1,
118.6, 112.6, 112.3, 102.5, 98.5, 63.9, 36.6, 23.5, 22.2, 22.1; MS (m/z):
HRMS (ESI) calcd for C24H16NaN4O5 ([MþNa]þ): 463.1013, found:
463.1014.
;
d
: 8.70 (s, 1H, ArH), 7.87 (d, J¼7.8 Hz, 1H, ArH), 7.77 (t,
J¼7.8 Hz, 1H, ArH), 7.66 (t, J¼7.2 Hz, 1H, ArH), 7.21 (s, 2H, NH2), 7.09
(d, J¼8.4 Hz, 2H, ArH), 6.96 (d, J¼7.8 Hz, 1H, ArH), 5.91 (s, 1H, ArH),
3.84 (s, 3H, OCH3), 2.42e2.36 (m, 1H, CH2), 2.26e2.21 (m, 1H, CH2),
2.17e2.12 (m, 1H, CH2), 2.03e1.98 (m, 1H, CH2), 1.86e1.76 (m, 2H,
3.2.15. Heterocyclic[3.3.3]propellanes (1o). Yellow solid, 78%, mp
194e196 ꢀC; 1IR (KBr)
y
: 2955, 2875, 2192, 2026, 1722, 1639, 1600,
1539, 1498, 1406,1358, 1325, 1292, 1243,1194, 1146, 1089,1013, 948,
852, 800, 776, 747 cmꢁ1 1H NMR (600 MHz, DMSO-d6)
: 8.85 (s,
CH2); 13C NMR (150 MHz, DMSO-d6)
d: 194.3, 190.2, 166.0, 159.4,
;
d
140.1, 135.7, 134.2, 130.9, 130.8, 126.9, 125.3, 123.9, 114.4, 112.8,
112.4, 100.3, 97.6, 63.7, 55.4, 36.5, 23.3, 22.0, 21.7; MS (m/z): HRMS
(ESI) calcd for C25H20N3O4 ([MþH]þ): 426.1448, found: 426.1447.
1H, ArH), 8.06 (d, J¼7.8 Hz, 1H, ArH), 7.90 (t, J¼7.2 Hz, 2H, ArH), 7.70
(t, J¼7.8 Hz, 1H, ArH), 7.36 (d, J¼7.2 Hz, 2H, NH2), 7.31 (d, J¼7.2 Hz,
2H, ArH), 7.26 (t, J¼7.2 Hz, 1H, ArH), 5.96 (s, 1H, ArH), 5.22 (d,
J¼16.2 Hz, 1H, CH2), 4.78 (d, J¼16.2 Hz, 1H, CH2), 2.35e2.31 (m, 1H,
CH2), 2.12e2.05 (m, 2H, CH2), 1.94e1.86 (m, 1H, CH2), 1.73e1.69 (m,
3.2.11. Heterocyclic[3.3.3]propellanes (1k). Yellow solid, 72%, mp
218e220 ꢀC; IR (KBr)
y
: 2948, 2879, 2759, 2546, 2357, 2342, 2256,
1H, CH2), 1.63e1.58 (m, 1H, CH2); 13C NMR (150 MHz, DMSO-d6)
d:
2193, 2026, 1718, 1598, 1545, 1496, 1463, 1410, 1347, 1323, 1297,
1270, 1240, 1196, 1145, 1089, 1047, 990, 972, 926, 854, 792, 773, 754,
194.2, 189.3, 166.2, 148.7, 137.5, 136.5, 134.2, 131.0, 128.4, 127.2,
126.9, 126.3, 125.0, 124.1, 112.7, 99.5, 97.0, 63.9, 45.1, 36.1, 23.0, 21.6,
21.0; MS (m/z): HRMS (ESI) calcd for C25H19NaN3O3 ([MþNa]þ):
432.1319, found: 432.1321.
735 cmꢁ1; 1H NMR (600 MHz, DMSO-d6)
d: 8.80 (s,1H, ArH), 7.88 (d,
J¼7.2 Hz, 1H, ArH), 7.74 (t, J¼7.8 Hz, 1H, ArH), 7.66 (t, J¼7.2 Hz, 1H,
ArH), 7.55 (d, J¼3.6 Hz, 3H, ArH), 7.32 (s, 2H, NH2), 6.88 (d, J¼7.8 Hz,
1H, ArH), 5.93 (s, 1H, ArH), 2.48e2.43 (m, 1H, CH2), 2.28e2.23 (m,
1H, CH2), 2.18e2.13 (m, 1H, CH2), 2.04e1.99 (m, 1H, CH2), 1.88e1.76
3.3. General procedure for the preparation of spiro[cyclo-
penta[b]pyridine-4,20-indenes] 2ae2f from one-pot domino
reactions of ninhydrin, malononitrile, and cyclic enaminones
(m, 2H, CH2); 13C NMR (150 MHz, DMSO-d6)
d: 194.2, 190.4, 165.7,
148.0, 135.7, 134.7, 134.2, 131.0, 129.5, 129.3, 128.9, 128.2, 125.2,
124.0, 112.8, 112.4, 100.8, 97.9, 63.8, 36.6, 23.4, 22.1, 21.8; MS (m/z):
HRMS (ESI) calcd for C24H18N3O3 ([MþH]þ): 396.1343, found:
396.1343.
In a round bottom flask a mixture of ninhydrin (1.0 mmol),
malononitrile (1.0 mmol), and triethylamine (0.1 mmol) in 5.0 mL
ethanol was stirred at room temperature for about 1 h. Then cyclic
enaminone (1.0 mmol) was added to it. The solution was stirred at
room temperature for additional 2 h. The resulting yellow pre-
cipitates were collected by filtration and washed with cold alcohol
to give the pure product.
3.2.12. Heterocyclic[3.3.3]propellanes (1l). Yellow solid, 78%, mp
236e238 ꢀC; IR (KBr)
y
: 2948, 2880, 2771, 2552, 2194, 2026, 1717,
1560, 1543, 1494, 1459, 1409, 1323, 1296, 1267, 1239, 1196, 1148,

4920
L.-J. Zhang, C.-G. Yan / Tetrahedron 69 (2013) 4915e4921
3.3.1. 2-Amino-10,30,5-trioxo-1-(4-methylphenyl)-1,10,30,5,6,7-hexahydros-
32.7, 26.4; MS (m/z): HRMS (ESI) calcd for C23H14BrNaN3O3
([MþNa]þ): 482.0111, found: 482.0106.
piro[cyclopenta[b]pyridine-4,20-indene]-3-carbonitrile (2a). Yellow
solid, 73%, mp 224e226 ꢀC; IR (KBr)
y
: 2924, 2181, 2026, 1745, 1714,
1642, 1555, 1511, 1415, 1383, 1338, 1305, 1189, 1131, 1020, 767,
744 cmꢁ1 1H NMR (600 MHz, DMSO-d6)
: 8.06 (d, J¼6.0 Hz, 4H,
ArH), 7.41e7.34 (m, 4H, ArH), 6.20 (s, 2H, NH2), 2.40 (s, 3H, CH3),
2.33 (s, 2H, CH2), 2.20 (s, 2H, CH2); 13C NMR (150 MHz, DMSO-d6)
Acknowledgements
;
d
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.
d:
200.3, 200.2, 168.4, 153.9, 140.9, 139.7, 136.9, 131.6, 130.7, 128.9,
123.1, 118.8, 112.6, 56.0, 53.3, 32.7, 26.4, 20.8; MS (m/z): HRMS (ESI)
calcd for C24H18N3O3 ([MþH]þ): 396.1343, found: 396.1338.
Supplementary data
3.3.2. 2-Amino-10,30,5-trioxo-1-(4-methoxyphenyl)-1,10,30,5,6,7-hexahydros-
piro[cyclopenta[b]pyridine-4,20-indene]-3-carbonitrile (2b). Yellow solid,
Crystallographic data 1a (CCDC 921960), 1j (CCDC 921961), and
2a (CCDC 921962) have been deposited at the Cambridge Crystal-
lographic Database Centre. These data can be obtained free of
charge via www.ccdc.ac.ck./data_request/cif. Supplementary data
related to this article can be found online at http://dx.doi.org/
10.1016/j.tet.2013.04.048.
64%, mp >250 ꢀC; IR (KBr)
y
: 3347, 2932, 2835, 2361, 2174, 2026, 1745,
1712, 1640, 1552, 1510, 1461, 1424, 1383, 1338, 1296, 1250, 1171, 1130, 1032,
845, 801, 766, 752 cmꢁ1 1H NMR (600 MHz, DMSO-d6)
: 8.06 (d,
J¼6.6 Hz, 4H, ArH), 7.39 (d, J¼7.8 Hz, 2H, ArH), 7.12 (d, J¼7.8 Hz, 2H, ArH),
6.26 (s, 2H, NH2), 3.84 (s, 3H, OCH3), 2.34 (s, 2H, CH2), 2.20 (s, 2H, CH2); 13
NMR (150 MHz, DMSO-d6) : 200.3, 200.2, 168.7, 160.1, 154.1, 140.9, 136.8,
;
d
C
d
130.4, 126.6, 123.1, 118.8, 115.3, 112.5, 55.9, 55.5, 53.4, 32.7, 26.4; MS (m/z):
References and notes
HRMS (ESI) calcd for C24H17NaN3O4 ([MþNa]þ): 434.1111, found: 434.1105.
1. (a) The Chemistry of Enamines; Rappoport, Z., Ed.; John Wiley & Sons: New York,
NY, 1994, Part 1; (b) Lue, P.; Greenhill, J. V. Adv. Heterocycl. Chem. 1997, 67,
0
0
0 0
3.3.3. 2-Amino-1,3 ,5-trioxo-1-(2-methoxyphenyl)-1,1 ,3 ,5,6,7-hexahydrospiro
ꢀ
ꢀ
207e343; (c) Granik, V.; Makarov, V.; Parkanyi, C. Adv. Heterocycl. Chem. 1998, 72,
283e359; (d) Elassara, A. Z.; El-Khair, A. A. Tetrahedron 2003, 59, 8463e8480.
2. (a) Greenhill, J. V. Chem. Soc. Rev. 1977, 6, 277e294; (b) Stanovnik, B.; Svete, J.
Chem. Rev. 2004, 104, 2433e2480; (c) Negri, G.; Kascheres, C.; Kascheres, A. J.
J. Heterocycl. Chem. 2004, 41, 461e491.
3. (a) Katritzky, A. R.; Hayden, A. E.; Kirichenko, K.; Pelphrey, P.; Ji, Y. J. Org.
Chem. 2004, 69, 5108e5111; (b) Cunha, S.; Damasceno, F.; Ferrari, J. Tetra-
hedron Lett. 2007, 48, 5795e5798; (c) Kikuchi, S.; Iwai, M.; Murayama, H.;
Fukuzaka, S. Tetrahedron Lett. 2008, 49, 114e116.
[cyclopenta[b]pyridine-4,20-indene]-3-carbonitrile (2c). Yellow solid,
78%, mp >250 ꢀC; IR (KBr)
y
: 2927, 2372, 2344, 2182, 2025, 1747,
1718,1652, 1548,1497,1462,1420, 1385, 1337,1275, 1233,1116,1041,
791, 754 cmꢁ1 1H NMR (600 MHz, DMSO-d6)
: 8.06 (s, 4H, ArH),
7.56e7.13 (m, 4H, ArH), 6.24 (s, 2H, NH2), 3.86 (s, 3H, OCH3),
2.35e2.17 (m, 4H, CH2); 13C NMR (150 MHz, DMSO-d6)
: 200.5,
;
d
d
200.1, 168.8, 156.0, 154.1, 141.1, 140.8, 136.8, 136.7, 132.0, 130.6, 123.1,
122.2, 121.3, 118.9, 113.3, 112.7, 56.1, 55.8, 32.6, 25.8; MS (m/z):
HRMS (ESI) calcd for C24H17NaN3O4 ([MþNa]þ): 434.1111, found:
434.1102.
4. (a) Vohra, R. K.; Bruneau, C.; Renaud, J. Adv. Synth. Catal. 2006, 348,
2571e2574; (b) Kumar, A.; Maurya, R. A. Tetrahedron 2008, 64, 3477e3482; (c)
Moreau, J.; Duboc, A.; Hubert, C.; Hurvois, J.-P.; Renaud, J. L. Tetrahedron Lett.
2007, 48, 8647e8650; (d) Sirijindalert, H.; Hansuthirakul, K.; Rashatasakhon,
P.; Sukwattanasinitt, M.; Ajavakom, A. Tetrahedron 2010, 66, 5161e5167.
5. (a) Rechsteiner, B.; Texier-Boullet, F.; Hamelin, J. Tetrahedron Lett. 1993, 34,
5071e5074; (b) Valduga, C. J.; Squizani, A.; Braibante, H. S.; Braibante, M. E. F.
Synthesis 1998, 1019e1022; (c) Arcadi, A.; Bianchi, G.; Di Giuseppe, S.; Marinelli,
F. Green Chem. 2003, 64e67; (d) Khosropour, A. R.; Khodaei, M. M.; Kookha-
zadeh, M. Tetrahedron Lett. 2004, 45, 1725e1728.
6. (a) Kim, Y. W.; Niphakis, M. J.; Georg, G. I. J. Org. Chem. 2012, 77, 9496e9503; (b)
Li, L.; Zhao, M. N.; Ren, Z. H.; Li, J. L.; Guan, Z. H. Org. Lett. 2012, 14, 3506e3509;
(c) Wang, H. Y.; Li, L. L.; Lin, W.; Xu, P.; Huang, Z. B.; Shi, D. Q. Org. Lett. 2012, 14,
4598e4601; (d) Jiang, B.; Li, Q. Y.; Tu, S. J.; Li, G. G. Org. Lett. 2012, 14,
5210e5213.
3.3.4. 2-Amino-10,30,5-trioxo-1-(4-chlorophenyl)-1,10,30,5,6,7-hexahydros-
piro[cyclopenta[b]pyridine-4,20-indene]-3-carbonitrile (2d). Yellow
solid, 61%, mp >250 ꢀC; IR (KBr)
y
: 2925, 2371, 2346, 2172, 2026,
1708, 1643, 1414, 1383, 1189, 1133, 1015, 816, 754 cmꢁ1 1H NMR
(600 MHz, DMSO-d6)
: 8.06 (d, J¼6.0 Hz, 4H, ArH), 7.64 (s, 2H,
ArH), 7.51 (s, 2H, ArH), 6.41 (s, 2H, NH2), 2.36 (s, 2H, CH2), 2.21 (s,
2H, CH2); 13C NMR (150 MHz, DMSO-d6)
: 200.2, 168.0, 153.8,
;
d
d
7. (a) Glotova, T.; Dvorko, M.; Ushakov, I.; Chipanina, N.; Kazheva, O.; Chekhlov, A.;
Dyachenko, O.; Gusarova, N.; Trofimov, B. Tetrahedron 2009, 65, 9814e9818; (b)
Ziyaei-Halimehjani, A.; Saidi, M. R. Tetrahedron Lett. 2008, 49, 1244e1248; (c) Li,
X.; Wang, J. Y.; Yu, W.; Wu, L. M. Tetrahedron 2009, 65, 1140e1146; (d) Yavari, I.;
Bayat, M. J.; Sirouspour, M.; Souri, S. Tetrahedron 2010, 66, 7995e7999.
8. (a) Cao, H.; Jiang, H. F.; Qi, C. R.; Yao, W. J.; Chen, H. J. Tetrahedron Lett. 2009, 50,
1209e1214; (b) Liu, W. B.; Jiang, H. F.; Zhu, S. F.; Wang, W. Tetrahedron 2009, 65,
7985e7988; (c) Jiang, H. F.; Li, J. H.; Chen, Z. W. Tetrahedron 2010, 66,
9721e9728; (d) Zhu, Q.; Jiang, H. F.; Li, J.; Liu, S.; Xia, C.; Zhang, M. J. Comb.
Chem. 2009, 11, 685e696.
9. (a)Sun,J.;Xia,E.Y.;Wu,Q.;Yan,C.G.Org.Lett.2010,12,3678e3681; (b) Sun, J.;Sun, Y.;
Gao, H.; Yan, C. G. Eur. J. Org. Chem. 2011, 6952e6956; (c) Sun, J.; Xia, E. Y.; Wu, Q.; Yan,
C. G. ACS Comb. Sci. 2011,13, 421e426; (d) Sun, J.; Sun, Y.; Gao, H.; Yan, C. G. Eur. J. Org.
Chem. 2012, 1976e1983; (e) Sun, J.; Sun, Y.; Gong, H.; Xue, Y. J.; Yan, C. G. Org. Lett.
2012, 14, 5172e5175.
10. (a) Sun, J.; Sun, Y.; Xia, E. Y.; Yan, C. G. ACS Comb. Sci. 2011, 13, 436e441; (b) Sun,
J.; Sun, Y.; Gao, H.; Yan, C. G. Synthesis 2012, 1069e1073; (c) Sun, Y.; Sun, J.; Yan,
C. G. Mol. Divers. 2012, 16, 163e171; (d) Zhang, L. L.; Sun, J.; Yan, C. G. Tetra-
hedron Lett. 2012, 53, 6965e6967.
11. (a) Kinsberg, D. Acc. Chem. Res. 1974, 7, 286e293; (b) Wiberg, K. B. Chem. Rev.
1989, 89, 975e983; (c) Ainoliisa, J. P.; Ari, M. P. K. Tetrahedron 2005, 61,
8769e8807.
140.9, 136.9, 134.7, 133.3, 131.3, 130.2, 123.1, 118.7, 112.8, 56.1, 53.3,
32.7, 26.4; MS (m/z): HRMS (ESI) calcd for C23H14ClNaN3O3
([MþNa]þ): 438.0616, found: 438.0612.
3.3.5. 2-Amino-10,30,5-trioxo-1-(3-chlorophenyl)-1,10,30,5,6,7-hexahydros-
piro[cyclopenta[b]pyridine-4,20-indene]-3-carbonitrile (2e). Yellow
solid, 66%, mp >250 ꢀC; IR (KBr)
y: 3338, 2933, 2375, 2347, 2181,
2026,1747, 1718, 1644, 1623, 1591, 1554, 1476,1417, 1380,1336, 1308,
1256, 1161, 1130, 1097, 1077, 1042, 881, 811, 787, 752, 717 cmꢁ1; 1H
NMR (600 MHz, DMSO-d6)
ArH), 6.47 (s, 2H, NH2), 2.41 (s, 1H, CH2), 2.33 (s, 1H, CH2), 2.21 (s,
2H, CH2); 13C NMR (150 MHz, DMSO-d6)
: 200.2,168.0,153.7,140.9,
d: 8.07 (s, 4H, ArH), 7.65e7.44 (m, 4H,
d
140.8, 136.9, 135.7, 134.1, 131.5, 130.3, 129.6, 128.2, 123.1, 118.7, 112.9,
56.2, 53.3, 32.7, 26.4; MS (m/z): HRMS (ESI) calcd for
C23H14ClNaN3O3 ([MþNa]þ): 438.0616, found: 438.0611.
3.3.6. 2-Amino-10,30,5-trioxo-1-(4-bromophenyl)-1,10,30,5,6,7-hexahydros-
12. (a) Ibuka, T.; Tanaka, K.; Inubushi, Y. Chem. Pharm. Bull. 1974, 22, 782e796; (b)
Lee, H.-Y.; Kim, D.-I.; Kim, S. J. Chem. Soc., Chem. Commun. 1996, 1539e1540; (c)
Zu, L.; Boal, B. W.; Garg, N. K. J. Am. Chem. Soc. 2011, 133, 8877e8879; (d) Jian-
Mei, H.; Ritsuko, Y.; Chun-shu, Y.; Fukuyama, Y. Tetrahedron Lett. 2000, 41,
6111e6114.
piro[cyclopenta[b]pyridine-4,20-indene]-3-carbonitrile (2f). Yellow
solid, 63%, mp >250 ꢀC; IR (KBr)
y: 3371, 2933, 2373, 2345, 2174,
2026, 1743, 1709, 1666, 1624, 1543, 1486, 1427, 1376, 1346, 1274,
1239, 1132, 1044, 1011, 824, 794, 772, 752 cmꢁ1; 1H NMR (600 MHz,
€
13. (a) Weniges, K.; Guenther, P.; Kasel, W.; Hubertus, G.; Gunther, P. Angew. Chem.,
Int. Ed. Engl. 1981, 20, 960e961; (b) Huang, J.-M.; Yang, C.-S.; Tanaka, M.; Fu-
kuyama, Y. Tetrahedron 2001, 57, 4691e4698; (c) Nicolaou, K. C.; Snyder, S. A.;
Montagnon, T.; Vassilikogiannakis, G. Angew. Chem., Int. Ed. 2002, 41,
1668e1698; (d) Trost, B. M.; Shi, Y. J. Am. Chem. Soc. 1991, 113, 701e703; (e)
Asahi, K.; Nishino, H. Tetrahedron 2008, 64, 1620e1634.
DMSO-d6)
7.44 (d, J¼8.4 Hz, 2H, ArH), 6.45 (s, 2H, NH2), 2.36 (s, 2H, CH2), 2.21
(s, 2H, CH2); 13C NMR (150 MHz, DMSO-d6)
: 200.2, 168.0, 153.7,
140.9, 136.9, 133.7, 133.2, 131.5, 123.4, 123.1, 118.7, 112.8, 56.1, 53.3,
d
: 8.06 (d, J¼5.4 Hz, 4H, ArH), 7.78 (d, J¼7.8 Hz, 2H, ArH),
d

L.-J. Zhang, C.-G. Yan / Tetrahedron 69 (2013) 4915e4921
4921
14. (a) Alizadeh, A.; Rezvanian, A.; Zhu, L. G. J. Org. Chem. 2012, 77, 4385e4390; (b)
Rezvanian, A.; Alizadeh, A. Tetrahedron 2012, 68, 10164e10168; (c) Alizadeh, A.;
Rezvanian, A.; Zhu, L. G. Synlett 2012, 2526e2530.
15. (a) Evdokimov, N. M.; Magedov, I. V.; Kireev, A. S.; Kornienko, A. Org. Lett. 2006,
8, 899e902; (b) Kumar, D.; Reddy, V. B.; Mishra, B. G.; Rana, R. K.; Nadagoudac,
M. N.; Varmac, R. S. Tetrahedron 2007, 63, 3093e3097; (c) Evdokimov, N. M.;
Kireev, A. S.; Yakovenko, A. A.; Antipin, M. Y.; Magedov, I. V.; Kornienko, A. J.
Org. Chem. 2007, 72, 3443e3453.
16. (a) Tietcheu, C.; Garcia, C.; Gardette, D.; Dugat, D.; Gramain, J. J. Heterocycl.
Chem. 2002, 39, 965e973; (b) Sorensen, U. S.; Pombo-Villar, E. Helv. Chim. Acta
2004, 87, 82e89; (c) Epifano, F.; Genovese, S.; Curini, M. Tetrahedron Lett. 2007,
48, 2717e2720.