An experimental and theoretical investigation of the regio- and stereoselectivity of the polar [3+2] cycloaddition of azomethine ylides to nitrostyrenes

Article abstract of DOI:10.1016/j.tet.2010.12.034

The regio- and stereochemical polar [3+2] cycloaddition of the azomethine ylides, which were generated in situ by the reaction of isatin derivatives and proline, with trans-β-nitrostyrene and (E)-1-phenyl-2-nitropropene were studied using experimental and

Full text of DOI:10.1016/j.tet.2010.12.034

Tetrahedron 67 (2011) 1589e1597
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An experimental and theoretical investigation of the regio- and stereoselectivity
of the polar [3þ2] cycloaddition of azomethine ylides to nitrostyrenes
Kamal Alimohammadi, Yaghoub Sarrafi *, Mahmood Tajbakhsh, Saeed Yeganegi,
Mahshid Hamzehloueian
Department of Organic Chemistry, Faculty of Chemistry, Mazandaran University, Babolsar, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
The regio- and stereochemical polar [3þ2] cycloaddition of the azomethine ylides, which were generated in
Received 16 September 2010
Received in revised form 23 November 2010
Accepted 13 December 2010
Available online 17 December 2010
situ by the reaction of isatin derivatives and proline, with trans-b-nitrostyrene and (E)-1-phenyl-2-nitro-
propene were studied using experimental and theoretical methods. In comparisonwith trans-b-nitrostyrene,
when the reactions were performed with (E)-1-phenyl-2-nitropropene, a remarkable inversion in the re-
gioselectively was observed. The regioselectivity of the reactions was investigated using global and local
reactivity indices and frontier molecular orbital (FMO) analysis at the B3LYP/6-31G(d,p) level of theory. The
effects of the electronic and steric factors on the regioselectivity of the reactions were discussed. The in-
spection of geometries and energetics of transition states revealed the importance of weak interactions in
regioselectivity of the cycloaddition reactions.
Keywords:
1,3-Dipolar cycloaddition
Azomethine ylide
DFT calculations
Spiro compounds
Pyrrolizine
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
spirooxindole moieties and theoretical investigation of all possible
regio- and stereocycloaddition channels using global and local re-
1,3-Dipolar cycloaddition of azomethine ylides to electron-de-
ficient alkenes is one of the most efficient and expedient synthetic
protocols for the construction of highly substituted pyrrolidine and
pyrrolizine rings.1 The synthesis of pyrrolidine-based heterocycles
has been the center of attraction for the past several decades be-
cause it constitutes an important class of substances with highly
pronounced biological activities.2 Nitropyrrolidines are the effec-
tive precursors for the synthesis of cephalotaxus alkaloids and
potentially useful as sources of conformationally restricted ana-
logues of dopamine.3 In addition, oxindoles derivatives, in partic-
ular 3-spirooxindoles, are the central skeleton of numerous
alkaloids and are elegant targets in organic synthesis due to their
significant biological activities.4
In the past decades, in addition to the selectivity behavior, the
understanding of the underlying principles in the polar [3þ2] cy-
cloaddition reactions has grown from a fruitful interplay between
theory and experiment and continues to present as a real chal-
lenge.5 The steric and electronic effects are two major factors can
influence the selectivity of these reactions.6 Their regio- and ste-
reochemistry may be controlled either by choosing the appropriate
dipole and dipolarophile or by controlling the reaction using
a catalyst.7 Herein we report the synthesis of nitropyrrolizines with
activity indices, frontier molecular orbital (FMO) analysis, and
corresponding transition states calculations at the B3LYP/6-31G
(d,p) level of theory.
2. Results and discussion
1,3-Dipolar cycloaddition of azomethine ylides, which were
generated in situ by the reaction of isatin derivatives 1aee and
proline 2 in ethanol at reflux, with trans-b-nitrostyrene 3 afforded
a mixture of the spirooxindolo nitropyrrolizines 4aee and 5aee in
good to excellent yields (Scheme 1). The molar ratio of regioisomers
was determined by 1H NMR spectroscopy. The reaction was found
to be relative regioselective and highly stereochemistry at the spiro
centre. It is noted that regioisomers 4aee were obtained as major
products in all cases (Table 1). Among isatin derivatives, N-meth-
ylisatin 1d gave the cycloadduct 4d as the sole product in 92% yield
(Table 1, entry 4). While compounds 4a and its regioisomer 5a were
separated by column chromatography, compounds 4b, 4c, 4e and
their corresponding regioisomers could not be separated due to
their similar Rf values in different organic solvents. However, the
pure regioisomers of 4aee were obtained by recrystallizing the
crude reaction mixture from ethanol at room temperature.
The structures and the regiochemistry of the cycloadducts were
confirmed by spectroscopic data. The 13C NMR spectrum of 4d,
showed two peaks at d 175.8 and 74.9 ppm for an oxindole carbonyl
* Corresponding author. Tel./fax: þ98 1125342350; e-mail address: ysarrafi@
umz.ac.ir (Y. Sarrafi).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.12.034

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K. Alimohammadi et al. / Tetrahedron 67 (2011) 1589e1597
Scheme 1. Regioselective synthesis of spirooxindolo nitropyrrolizines 4aee and 5aee.
The ORTEP diagram of 4c represents that, the trans-geometry
Table 1
of nitrostyrene is preserved in the product and also shows the
relative configurations at all four chiral centers. However, to ex-
amine the issue of whether the reaction is concerted or proceeds
via a stepwise diradical transition state, when benzoquinone as
a radical scavenger was added to the reaction mixture under re-
action conditions, the rate of reaction did not decrease. This is an
anticipated result on the basis of a concerted cycloaddition
reaction.
1,3-Dipolar cycloaddition reaction of isatin derivatives 1aee and proline 2 with
trans-b-nitrostyrene 3
Entry
Reactants
Products
Yielda (%)
Regioisomer ratiob (4:5)
1
2
3
4
5
1aþ2þ3
1bþ2þ3
1cþ2þ3
1dþ2þ3
1eþ2þ3
4aþ5a
4bþ5b
4cþ5c
4d
87
81
83
92
88
88:12
87:13
60:40
100:0
90:10
4eþ5e
Similarly, the reaction of (E)-1-phenyl-2-nitropropene 6, as
a substituted precursor with an electron-donor group, with the
azomethine ylide generated from 1aee and 2 afforded a mixture of
the spirooxindolo nitropyrrolizines 7aee and 8aee in good yields
(Scheme 3). The structures and the regiochemistry of the cyclo-
adducts were confirmed by spectral analysis. Interestingly, the
regioisomers 8aed were the main obtained products that their
regiochemistry is in contrast to the major products 4aed. In com-
pounds 4aee the carbon atom bearing the nitro group is bonded to
the pyrrolidine ring, whereas in products 8aee it is bonded to the
oxindole ring.
a
Combined yield of isolated cycloadducts.
Determined by H NMR spectroscopy (Ha/Ha0).
b
1
group and the spiro carbon, respectively. In the 1H NMR spectrum
of the cycloadduct 4d, a doublet at
sponding to the benzylic proton consistent with the trans dispo-
sition with the CHNO2 proton. A triplet and not a doublet at
d
4.49 ppm (J¼10.5 Hz) corre-
d
6.30 ppm, attributed to the CHNO2 proton, showing that the
correct regiochemistry of the product 4d is as shown in Scheme 1.
The stereochemical outcome of the cycloaddition was de-
termined by a single X-ray crystal structure of 5-nitroisatin cyclo-
adduct 4c (Fig. 1).8 The stereochemistry of cycloadducts is
consistent with a S-shaped ylide and subsequent cycloaddition by
an endo-transition state (pathway B, Scheme 2). However, the
cycloadduct corresponding to exo-TS was not observed.
The 1H NMR spectrum of 8aee exhibited a doublet for the
benzylic proton, while it was observed as a singlet for the 7aee. The
structure of 8a was unequivocally established by X-ray single
crystal analysis,9 which further confirmed the stereochemistry
(Fig. 2).
Notably, when 1e and proline was treated with 6, a sharp de-
crease in the regioselectivity was observed, and a 46:36:18 mixture
of 8e, exo-7e and endo-7e was obtained, respectively (Table 2, entry
5). The mixture of regio- and stereoisomers were separated and
purified by column chromatography. The geometries of exo- and
endo-isomers of 7e were determined based on 1H NMR chemical
shift. A singlet at
exo-7e, appeared at lower field compared to endo-7e (
d
5.30 ppm, attributed to the benzylic proton of
4.92 ppm)
d
due to a deshielding effect of the carbonyl group of the oxindole
ring.
3. Computational details
All calculations were performed using the Gaussian0310 suit of
programs. The full geometrical optimization of all structures and
transition states (TSs) were carried out with Density Functional
Theory (DFT) using non local B3LYP hybrid functional and 6-31G
(d,p) basis set. No symmetrical restriction was applied during
geometrical optimizations. The stability of the DFT wave functions
for selected equilibrium geometries was tested using the keyword
STABLE in Gaussian03. The nature of stationary geometries has
been characterized by calculating the frequencies in order to verify
that the transition states have one and only one imaginary fre-
quency. Also, harmonic frequencies, zero-point energies and ther-
modynamic corrections were obtained using analytical force
constants. Thermal corrections to enthalpy and entropy values
were evaluated at 298.15 K.
Fig. 1. ORTEP diagram of 4c.

K. Alimohammadi et al. / Tetrahedron 67 (2011) 1589e1597
1591
_
N
R2
O
N
R1
w-shaped ylide
X
O
R2
O
+
COOH
N
H
N
R1
Ph
O
NO2
Ph
O2N
_
nitrostyrene
pathway B
N
nitrostyrene
pathway A
R2
N
N
O
O
N
N
N
R2
R2
R1
R1
R1
s-shaped ylide
endo-TS
exo-TS
X
H
H
N
NO2
Ph
NO2
N
R2
R2
Ph
O
O
N
N
R1
R1
Scheme 2. Proposed mechanism for the cycloaddition of the azomethine ylides with nitrostyrene.
Scheme 3. Regioselective synthesis of spirooxindolo nitropyrrolizines 7aee and 8aee.
4. FMO, global, and local electrophilicity/nucleophilicity
analysis
(normal electron demand reactions), while group III is charac-
terized by the HOMOdipolarophileeLUMOdipole predominant in-
teraction (inverse electron demand reactions), and the
intermediate group II collects the reactions with significant in-
volvement of both types of the HOMOeLUMO interactions. The
HOMOeLUMO energy gap for the corresponding cases generally
determines which interaction is the most important. The lower
energy difference leads to the greater orbital interaction. In most
cases, group I is dominating. However, this changes as the
Frontier Molecular Orbital (FMO) is one of the best methods to
analyze reactions, which was mainly developed by Fukui.11
Sustman12 classified 1,3-dipolar cycloaddition reactions into
three types on the basis of the relative FMO energies between the
dipole and the dipolarophile. Group I includes the processes
controlled by the HOMOdipoleeLUMOdipolarophile interaction

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K. Alimohammadi et al. / Tetrahedron 67 (2011) 1589e1597
Table 2
1,3-Dipolar cycloaddition reaction of isatin derivatives 1aee and proline 2 with (e)-
1-phenyl-2-nitropropene 6
Entry
Reactants
Products
Yielda (%)
Regioisomer ratiob (8:7)
1
2
3
4
5
1aþ2þ6
1bþ2þ6
1cþ2þ6
1dþ2þ6
1eþ2þ6
7aþ8a
7bþ8b
8c
86
78
84
88
82
88:12
86:14
100:0
84:16
46:54c
7dþ8d
7eþ8e
a
Combined yield of isolated cycloadducts.
Determined by 1H NMR spectroscopy.
Combined yield of the exo- and endo-7e.
b
c
reaction (normal electron demand reactions). To better visualize the
FMO approach, the two possible interactions HOMOdipolarophile
eLUMOdipole and HOMOdipoleeLUMOdipolarophile for each reaction are
shown in Fig. 3. Global properties of dipole 9 and dipolarophiles 3
and 6 and MO coefficients at the reactive sites for the reactants are
shown in Tables S2 and S3 in Supplementary data, respectively.
As shown in, Fig. 3 for the dipolarophile 3 the LUMO coefficient of
C3 is 0.297 and that of C1 is ꢀ0.199 and the HOMO coefficients of
dipole 9 on the reactive sites C7 and C16 are 0.338 and ꢀ0.282, re-
spectively. Therefore, the important orbital overlap should be be-
tween C3 and C7. The analysis of the regioselectivity of the reaction 2
by FMO theory shows that the most favored largeelarge interaction
takes place between C2 of the alkene 6 and C7 of azomethine ylide 9
(Fig. 3). While for the reaction 1 DFT calculations predict the regio-
selectivity experimentally observed, for the reaction 2 it fails.
Recentstudies haveshown that thedefined global and local indices
in the context of density functional theory are powerful tools to un-
derstand the behavior of 1,3-DC reactions.14 The charge transfer ability
of a molecule in its ground state approximated by Koopmans’ theo-
rem15 can be described by the electronic chemical potential, which is
defined as the arithmetic mean of one-electron energies of the frontier
Fig. 2. ORTEP diagram of 8a.
molecular orbital HOMO and LUMO, 3H and 3L as
chemical hardness , which is a measure of the stability of a system,
may be approached in terms of 3H and 3L as
electrophilicity index , which measures the stabilization in energy
m¼(3Hþ
3L)/2. The
h
14
h¼
3L
ꢀ
3H
.
The global
electron donating ability of the 1,3-dipole decreases or the do-
nating ability of the dipolarophile increases.1d,13
The regio- and stereoselectivities of the reactions of azomethine
ylide 9 with trans-b-nitrostyrene 3 and (E)-1-phenyl-2-nitro-
propene 6 as reactions 1 and 2 were investigated by theoretical
methods (Scheme 4). The calculated HOMO and LUMO energies are
presented in Table S2 in Supplementary data.
In this study, the HOMOeLUMO energy gaps suggest that the
HOMOdipoleeLUMOdipolarophile interaction controls the cycloaddition
u
when the system acquires an additional electronic charge
environment, was given the following simple expression,
D
N from the
u¼(
m
2/2 ),15
h
in terms of the electronic chemical potential and the chemical hard-
ness. The calculated global properties , and are shown in Table S2
in Supplementary data. The electronic chemical potential, , of the
m,
h
u
m
dipole 9 is higher than the dipolarophile 3 also the electrophilicity of
dipolarophiles is greater than that of the dipole, therefore the charge
transfer takes place from the dipole to the dipolarophile.
O
O2N
+
O
CO2H
N
N
H
H
NO2
NO2
2
1
H
H
Ph
H
3
Ph
1
Ph
Me
NO2
Ph
16
O
Me
+
N
N
N
6
_
3
NO2
O2N
O2N
O2N
7
O
O
N
H
reaction 2
N
1
N
H
reaction
H
9
(P4- Me)
major
(P1- H)
major
Scheme 4. The regioselectivity channels for 1,3-DC of azomethine ylide 9 and trans-b-nitrostyrene 3 and (E)-1-phenyl-2-nitropropene 6.

K. Alimohammadi et al. / Tetrahedron 67 (2011) 1589e1597
1593
5. Energies of transition structures
0.183
(-0.279)
2
0.147
NO2
1
Me
NO2
(0.297)
0.320
(0.190)
Although the FMO theory, which is based on electronic factors
without consideration of steric factors, provides a good basis for
understanding the regioselectivity of 1,3-DC reactions, in many
cases steric factors control the regiochemistry of the reaction.5 The
regiochemistry of the reactions 1 and 2 can be explained by as-
suming both of electronic and steric factors.
0.310
(-0.199)
3 1
Ph
Ph
-2
-4
-6
-8
1.908
5.063
2.488
2.639
Previous studies on related cycloadditions have predicted con-
certed transition structures.18 Therefore, four possible transition
structures for the reaction 1, TS-1-H, TS-2-H, TS-3-H, and TS-4-H
and for the reaction 2, TS-1-Me, TS-2-Me, TS-3-Me, and TS-4-Me,
and their corresponding cycloadducts have been optimized and
characterized. The optimized geometries of endo-transition states in
each cases TS-1-H, TS-4-H, TS-1-Me, and TS-4-Me are shown in
Fig. 4 and related exo transition states TS-2-H, TS-3-H, TS-2-Me, and
TS-3-Me are represented in Supplementary data. The activation
energies, enthalpies, and Gibbs free energies as well as the reaction
energies, enthalpies, and Gibbs free energies are reported in Table 4.
In the gas phase, the activation barriers associated with the re-
action 1 are: 8.79 (Ts-1-H), 14.15 (Ts-2-H), 13.36 (Ts-3-H), and
7.76 kcal/mol (Ts-4-H). Substitution of the hydrogen atom by
a methyl group on the nitrostyrene increases the activation energies
of the cycloaddition reaction. The activation energies orders found
for the transition structures in the reactions 1 and 2 are Ts-4-H<Ts-
1-H<Ts-3-H<Ts-2-H, and Ts-4-Me<Ts-1-Me<Ts-3-Me<Ts-2-Me,
respectively. The calculated activation barriers show that the energy
of Ts-4-H is 1.03 kcal/mol lower than that of TS-1-H, favoring the
formation of the P4-H regioisomer, and for the reaction between 6
and 9, TS-4-Me is 4.09 kcal/mol lower than TS-1-Me, favoring the
formation of the P4-Me regioisomer (Table 4). The B3LYP/6-31G(d,p)
calculations for the reaction 2 successfully predict the experimen-
tally observed regioselectivity, but it fails for the reaction 1. Fur-
thermore, previous theoretical studies on 1,3-DC reactions have
pointed out that the predicted regioselectivity of this type of cy-
cloadditions is strongly dependent on the computational level
used.19 It is well known that the DFT methods are unable to estimate
the stabilization gained by weak interaction between aromatic
rings.20 However, realization of this interaction by ab initio methods
requires a computationally demanding method, such as CCSD (T)
(coupled cluster) with averylarge basis set near saturation. Recently
Tsuzuki et al. have studied the interaction energy between benzene
dimer models at CCSD(T) with a very large basis set.21 They found
that the interaction energies of parallel, T-shaped, and slipped-
parallel models are ꢀ1.48, ꢀ2.46, and ꢀ2.48 kcal/mol, respectively.
6.710
6.954
3
9
6
-0.282
0.338
(-0.002)
16
+
7
N
(-0.159)
_
O2N
O
N
H
Fig. 3. Calculated FMO energies (eV) and HOMO and LUMO Coefficients at the reactive
sites for the reactants obtained at B3LYP/6-31G(d,p).The LUMO Coefficients are given in
parenthesis.
We used the DFT-based reactivity descriptors, such as Fukui
functions and local electrophilicity indices for the interpretation of
regioselectivity. These concepts have been found to be very useful
for explaining regiochemistry in addition reactions.16ceg The local
electrophilicity index, uk, can be measured by uk u
f þk in which f þk
¼
is the Fukui function for a nucleophilic attack.16 This expression
shows that wherever fkþ has its maximum value, i.e., at the active
site of the electrophile. For these polar cycloadditions the most
favorable regioisomeric pathway corresponds to the bond-forma-
tion at the most electrophilic and nucleophilic sites of un-
symmetrical reactants. The regioselectivity of these cycloaddition
reactions can be explained using the local electrophilicity index uk
,
at the more electrophile reactant together with the nucleophilic
Fukui functions, f-k, at the less electrophilic one.
The calculated local properties of dipole 9 and dipolarophiles 3
and 6 are summarized in Table 3. For the dipole 9, C7 has a larger fkꢀ
value than C16, i.e., 0.109 and 0.088, respectively. The C3 site of
dipolarophile 3 (the b-position) presents a larger local electrophi-
licity value than C1 site. Therefore, C3 will be the preferred position
for a nucleophilic attack by C7 of the dipole 9, which is in good
agreement with the experimental observation.
The energy of TSs with suitable geometry can be affected by p/p
interaction. The optimized geometries of Ts-1-H, Ts-2-H, Ts-1-Me,
and Ts-2-Me show that the two phenyl rings are in slipped-parallel
configuration. Therefore, they can be stabilized by p/p interaction
It was found that the substitution pattern has a strong influence on
the reaction profiles.17 In comparison with 3, 6 possess an electron
releasing methyl group on C1 position that decreases the electrophi-
licityat C1 and C2 sites. Asexpected, the decrease of the electrophilicity
at C1 is greater than C2. As indicated in Table 3, the C2 site represents
a higher local electrophilicity value than C1. Therefore, C2 in 6 will be
the preferred position for a nucleophilic attack by C7 of the dipole 9. In
contrast with the reaction 1 local electrophilicity failed to correctly
predict the experimentally observed major product of the reaction 2.
about ꢀ2.48 kcal/mol. Assuming the stabilization gained by
p/p
interaction makes the energy of Ts-1-H lower than that of Ts-4-H, in
agreement with the experimentally observed major regioisomer
(P1-H). However, this correction has no effect on the energy order
of Ts-4-Me and Ts-1-Me.
In order to assess the aromaticity of the optimized TSs, the Nucleus-
independent chemical shifts (NICS)22 was computed using gauge in-
variant atomic orbital (GIAO)23 approach at the B3LYP/6-31G(d,p). The
calculated NICS values present in Table 5. All of the considered tran-
sition structures have large negative NICS values that indicate the ar-
omatic characters of TSs due to the six electrons undergoing bond
changing. In contrast, all cycloadducts have small negative NICS values.
Therefore, it can be concluded that transition states associated with
1,3-dipolar reactions between azomethine ylides and nitroalkenes
exhibit in-plane aromaticity and undergoing a concerted mechanism.
In conclusion, the regioselective polar [3þ2] cycloaddition re-
Table 3
Local properties of dipole 9 and dipolarophiles 3 and 6
Reactant
Site
f kþ
fkꢀ
uk(eV)
3
3
9
9
6
6
C1
C3
C7
C16
C1
C2
0.042
0.071
0.014
0.085
0.027
0.072
0.101
0.013
0.109
0.088
0.087
0.022
0.112
0.189
0.027
0.164
0.069
0.185
actions of the azomethine ylides with trans-b-nitrostyrene and

1594
K. Alimohammadi et al. / Tetrahedron 67 (2011) 1589e1597
Fig. 4. Selected optimized transition structures at the B3LYP/6-31G(d,p) corresponding to the regiosomeric path of the 1,3-DC reactions 1 and 2.
Table 4
(E)-1-phenyl-2-nitropropene were carried out. Experimental re-
sults have shown that the regiochemistry in these reactions is
sensitive to the substituent on the double bond of nitrostyrene. In
Calculated electronic activation energies Ea, reaction Gibbs free energies
enthalpies
enthalpies
D
G, reaction
G#, activation
DS (cal/molK) at the B3LYP/6-31G(d,p), all
D
D
H, reaction energies
DErxn, activation Gibbs free energies D
H#, and reaction entropies
comparison with trans-b-nitrostyrene, when the reactions were
energies are in kcal/mol
performed with (E)-1-phenyl-2-nitropropene, a remarkable in-
version in the regioselectively was observed.
Product
Ea
D
G
D
H
D
Erxn
D
G#
D
H#
DS
P1(TS-1)-H
P2(TS-2)-H
P3(TS-3)-H
P4(TS-4)-H
8.786 ꢀ2.208 ꢀ17.045 ꢀ16.429 22.936 8.353 ꢀ43.768
14.151 ꢀ0.902 ꢀ15.412 ꢀ14.814 26.113 12.152 ꢀ42.666
13.360 ꢀ0.084 ꢀ15.247 ꢀ14.570 27.667 13.320 ꢀ44.858
7.760 ꢀ2.870 ꢀ17.425 ꢀ16.871 22.716 7.324 ꢀ42.815
Mechanism and the regiochemistry of two reactions have studied
in terms of global and local reactivity indices, FMO analysis and
characterization of relevant transition states at the B3LYP/6-31G(d,p)
level of theory. Inspection of theoretical results indicated that in the
case of the reaction 1, the electronic factors control the regiochem-
istry of the reaction and results of FMO analysis agree with experi-
mentally favored product. While for the reaction 2 FMO analysis
failed to predict the major product, analysis of transition states en-
ergies successfully explains the experimental results.
P1(TS-1)-Me 12.034 ꢀ0.070 ꢀ14.136 ꢀ14.026 25.825 12.161 ꢀ45.828
P2(TS-2)-Me 38.504
P3(TS-3)-Me 15.757
P4(TS-4)-Me 7.945
3.360 ꢀ10.786 ꢀ10.656 51.984 38.827 ꢀ44.129
4.552 ꢀ10.034 ꢀ9.753 29.004 16.041 ꢀ48.943
1.793 ꢀ12.710 ꢀ12.828 22.274 8.044 ꢀ48.643
Table 5
Nucleus-independent chemical shifts (NICS, ppm/mol)
6. Experimental section
Ts
NICS
Product
NICS
TS-1-H
TS-2-H
TS-3-H
TS-4-H
TS-1-Me
TS-2-Me
TS-3-Me
TS-4-Me
ꢀ14.38
ꢀ13.96
ꢀ14.30
ꢀ15.67
ꢀ14.49
ꢀ13.40
ꢀ12.87
ꢀ14.71
p-1-H
p-2-H
p-3-H
p-4-H
p-1-Me
p-2-Me
p-3-Me
p-4-Me
ꢀ4.60
ꢀ4.61
ꢀ8.68
ꢀ5.03
ꢀ4.87
ꢀ4.15
ꢀ4.41
ꢀ4.28
6.1. General procedure for preparation of spirooxindolo
nitropyrrolizines 4aee and 5a,b
A mixture of isatin (0.147 g, 1 mmol), proline (0.115 g, 1 mmol),
and trans-b-nitrostyrene (0.149 g, 1 mmol) in ethanol (10 mL) was
stirred at reflux for 1e2 h. After completion of the reaction, as in-
dicated by TLC, to the solution was added water (25 mL), and the

K. Alimohammadi et al. / Tetrahedron 67 (2011) 1589e1597
1595
precipitated solid was separated by filtration to afford the corre-
sponding regioisomers of 4aee and 5aee. The molar ratio of 4aee/
5aee was determined by 1H NMR spectroscopy. The pure cyclo-
adducts 4aee were obtained by recrystallization from ethanol and
the product 5a was purified on a silica-gel plate (eluent dichloro-
methane/ethyl acetate 12:8). Notably, the products 4b and 5b could
be separated by recrystallizing the crude reaction mixture in eth-
anol owing to their different crystalline shape.
J¼10.3 Hz, benzylic), 4.31 (AB quartet, 1H, J¼16.1 Hz, NeCHAHB),
3.36 (m, 1H, pyrrolizine), 2.95 (t, 1H, J¼7.3 Hz, pyrrolizine),
1.53e2.27 (m, 4H, pyrrolizine); 13C NMR (75 MHz, CDCl3):
d
¼175.8,
143.9, 134.6, 132.4, 130.1, 128.7, 128.6, 128.4, 128.0, 127.2, 126.3,
125.9, 124.6, 122.5, 109.9, 91.5, 75.1, 64.4, 53.4, 51.2, 43.4, 27.8, 25.7.
Anal. Calcd for C27H25N3O3: C, 73.78; H, 5.73; N, 9.56. Found: C,
73.84; H, 5.79; N, 9.51.
6.1.6. 20-Nitro-10-phenyl-10,20,50,60,70,7a0-hexahydrospiro[indoline-
6.1.1. 10-Nitro-20-phenyl-10,20,50,60,70,7a0-hexahydrospiro[indoline-
3,30-pyrrolizin]-2-one (4a). Colorless solid (0.27 g, 77%), mp:
3,30-pyrrolizin]-2-one (5a). Colorless solid (0.04 g, ꢀ110%), mp:
189e191 ꢁC; Rf (60% CH2Cl2/hexane) 0.38; IR (KBr, cm
)
n¼3220,
195e197 ꢁC (Ref. Mp: 208e210 ꢁC);1f IR (KBr, cmꢀ1
)
n
¼3198, 1710,
1731, 1553, 1369; 1H NMR (400 MHz, CDCl3):
d
¼8.03 (s, 1H, NH),
1547, 1347; 1H NMR (300 MHz, CDCl3):
d¼8.09 (s, 1H, NH), 7.59 (d,
7.48 (m, 2H, AreH), 7.40 (m, 2H, AreH), 7.33 (m, 3H, AreH), 7.11 (t,
1H, J¼8.4 Hz, AreH), 6.94 (d, 1H, J¼7.6 Hz, AreH), 5.78 (d, 1H,
J¼11.2 Hz, CHNO2), 4.14 (dt, 1H, J¼9.6, 6.4 Hz, NeCH), 3.97 (dd, 1H,
J¼10.8, 9.6 Hz, benzylic), 1.73e2.76 (m, 6H, pyrrolizine); 13C NMR
1H, J¼7.4 Hz, AreH), 7.27 (d, 1H, J¼6 Hz, AreH), 7.11 (m, 6H, AreH),
6.71 (d, 1H, J¼7.7 Hz, AreH), 6.32 (t, 1H, J¼9.8 Hz, CHNO2), 4.87 (q,
1H, J¼8.2 Hz, NeCH), 4.53 (d, 1H, J¼10.4 Hz, benzylic), 3.29 (m, 1H,
pyrrolizine), 2.90 (t, 1H, J¼7.2 Hz, pyrrolizine), 1.48e2.21 (m, 4H,
(100 MHz, CDCl3):
d
¼178.3, 141.5, 138.6, 136.6, 130.8, 129.1, 128.0,
pyrrolizine); 13C NMR (75 MHz, CDCl3):
128.6, 128.2, 128.0, 126.2, 125.1, 122.5, 110.4, 91.6, 75.2, 64.2, 53.2,
51.1, 27.8, 25.6. Anal. Calcd for C20H19N3O3: C, 68.75; H, 5.48; N,
12.03. Found: C, 68.58; H, 5.39; N, 11.94.
d
¼177.9, 141.9, 132.4, 130.1,
127.8, 126.1, 122.8, 110.9, 96.8, 73.4, 70.52, 53.5, 48.2, 31.3, 27.1. Anal.
Calcd for C20H19N3O3: C, 68.75; H, 5.48; N,12.03. Found: C, 68.87; H,
5.55; N, 12.09.
6.1.7. 5-Bromo-20-nitro-10-phenyl-10,20,50,60,70,7a0-hexahydrospiro
[indoline-3,30-pyrrolizin]-2-one (5b). Brown solid (0.04 g, 11%), mp:
6.1.2. 5-Bromo-10-nitro-20-phenyl-10,20,50,60,70,7a0-hexahydrospiro
[indoline-3,30-pyrrolizin]-2ꢀ-o1ne (4b). Brown solid (0.30 g, 70%), mp:
194e196 ꢁC; IR (KBr, cmꢀ1
)
n
¼3244, 1726, 1548, 1373; 1H NMR
201e202 ꢁC; IR (KBr, cm
)
n
¼3244, 1726, 1548, 1373; 1H NMR
(400 MHz, DMSO-d6):
d
¼10.85 (s, 1H, NH), 7.75 (d, 1H, J¼2.0 Hz,
(300 MHz, CDCl3):
d
¼8.22 (s,1H, NH), 7.71 (s, 1H, AreH), 7.39 (d,1H,
AreH), 7.56 (d, 2H, J¼7.2 Hz, AreH), 7.51 (dd, 1H, J¼6.4, 2.0 Hz,
AreH), 7.39 (t, 2H, J¼7.2 Hz, AreH), 7.30 (m, 1H, AreH), 6.86 (d, 1H,
J¼8.0 Hz, AreH), 5.78 (d, 1H, J¼11.6 Hz, CHNO2), 4.20 (dd, 1H, J¼11.6,
9.6 Hz, benzylic), 3.70 (dt, 1H, J¼9.6, 6.0 Hz, NeCH), 1.67e2.48 (m,
J¼7.8 Hz, AreH), 7.14 (m, 5H, AreH), 6.62 (d, 1H, J¼8.1 Hz, AreH),
6.26 (t, 1H, J¼9.8 Hz, CHNO2), 4.87 (m, 1H, NeCH), 4.50 (d, 1H,
J¼10.1 Hz, benzylic), 1.51e3.23 (m, 6H, pyrrolizine); 13C NMR
(75 MHz, CDCl3):
d
¼176.0, 141.0, 137.9, 133.1, 131.9, 129.0, 128.8,
6H, pyrrolizine); 13C NMR (100 MHz, DMSO-d6):
d¼177.5, 142.8,
128.2, 126.0, 115.0, 111.9, 91.3, 75.1, 64.2, 53.4, 51.1, 27.7, 25.6. Anal.
Calcd for C20H18BrN3O3: C, 56.09; H, 4.24; N, 9.81. Found: C, 56.19;
H, 4.15; N, 9.73.
137.5, 134.0, 129.2, 129.1, 128.1, 127.9, 125.5, 114.1, 112.8, 95.3, 73.1,
70.7, 51.5, 48.2, 30.1, 27.2. Anal. Calcd for C20H18BrN3O3: C, 56.09; H,
4.24; N, 9.81. Found: C, 56.01; H, 4.17; N, 9.76.
6.1.3. 10,5-Dinitro-20-phenyl-10,20,50,60,70,7a0-hexahydrospiro[indo-
6.2. General procedure for preparation of spirooxindolo
nitropyrrolizines 7aee and 8aee
line-3,30-pyrrolizin]-2-one ꢀ(14c). Yellow solid (0.20 g, 50%), mp:
253e255 ꢁC; IR (KBr, cm
)
n
¼3296, 1725, 1548, 1334; 1H NMR
(300 MHz, DMSO-d6):
d
¼11.00 (s, 1H, NH), 8.95 (s, 1H, AreH), 8.17
A mixture of isatin (0.147 g, 1 mmol), proline (0.115 g, 1 mmol),
and (E)-1-phenyl-2-nitropropene (0.163 g, 1 mmol) in ethanol
(10 mL) was stirred at reflux for 1e2 h. After completion of the re-
action, as indicated by TLC, to the solution was added water (25 mL),
and the precipitated solid was separated by filtration, which con-
tained mixture of two regioisomers 7aee and 8aee. The molar ratio
of 8aee/7aee was determined by 1H NMR spectroscopy. However,
the pure cycloadducts 8aee was obtained by recrystallization from
ethanol and the products 7aee were purified on a silica-gel plate or
column chromatography(eluent hexane/ethyl acetate 1:1).
(d, 1H, J¼8.7 Hz, AreH), 7.17 (br s, 6H, AreH), 6.82 (d, 1H, J¼8.6 Hz,
AreH), 6.40 (t, 1H, J¼10.1 Hz, CHNO2), 4.85 (d, 1H, J¼11 Hz, ben-
zylic), 4.60 (q,1H, J¼8.1 Hz, NeCH), 3.43 (m,1H, pyrrolizine), 2.62 (t,
1H, J¼6 Hz, pyrrolizine), 1.44e2.01 (m, 4H, pyrrolizine); 13C NMR
(75 MHz, DMSO-d6):
d
¼178.1, 149.9, 142.7, 133.3, 128.9, 128.6, 128.2,
127.6, 126.2, 123.8, 110.3, 90.3, 74.7, 63.7, 53.3, 51.0, 28.2, 25.6. Anal.
Calcd for C20H18N4O5: C, 60.91; H, 4.60; N, 14.21. Found: C, 60.99; H,
4.71; N, 14.13.
6.1.4. 1-Methyl-10-nitro-20-phenyl-10,20,50,60,70,7a0-hexahydrospiro
[indoline-3,30-pyrrolizin]-2-one (4d). Colorless solid (0.33 g, 92%),
6.2.1. 10-Methyl-10-nitro-20-phenyl-10,20,50,60,70,7a0-hexahydrospiro
mp: 194e195 ꢁC; IR (KBr, cmꢀ1
)
n
¼1701, 1536, 1375; 1H NMR
[indoline-3,30-pyrrolizin]-2-one (7a). White solid (0.04 g, 10%), mp:
(300 MHz, CDCl3):
d¼7.60 (d, 1H, J¼7.4 Hz, AreH), 7.30 (m,1H, AreH),
191e192 ꢁC; Rf (50% ethyl acetate/hexane) 0.32; IR (KBr, cmꢀ1
)
7.12 (m, 6H, AreH), 6.63 (d, 1H, J¼7.8 Hz, AreH), 6.35 (t, 1H, J¼9.9 Hz,
CHNO2), 4.95 (q, 1H, J¼8.1 Hz, NeCH), 4.53 (d, 1H, J¼10.5 Hz, ben-
zylic), 3.30 (m, 1H, pyrrolizine), 2.95 (s, 3H, NeCH3), 2.91 (m, 1H,
pyrrolizine), 1.46e2.23 (m, 4H, pyrrolizine); 13C NMR (75 MHz,
n
¼3241, 1719, 1543, 1345; 1H NMR (400 MHz, DMSO-d6):
¼10.6 (s,
d
1H, NH), 7.59 (d,1H, J¼7.6 Hz, AreH), 7.11e7.23 (m, 6H, AreH), 6.97 (t,
3H, J¼6.8 Hz, AreH), 5.24 (s,1H, benzylic), 4.33 (dd,1H, J¼8.4, 5.6 Hz,
NeCH),1.83e3.30(m, 4H,pyrrolizine),1.75(s, 3H, CH3NO2),1.19e1.71
CDCl3):
d
¼175.8, 144.7, 132.4, 130.2, 128.4, 128.2, 127.9, 125.7, 124.5,
(m, 2H, pyrrolizine); 13C NMR (100 MHz, DMSO-d6):
d¼178.5, 143.1,
122.5, 108.6, 91.8, 74.9, 64.3, 53.2, 51.3, 27.8, 25.8, 25.6. Anal. Calcd for
C21H21N3O3: C, 69.41; H, 5.82; N, 11.56. Found: C, 69.35; H, 5.89; N,
11.64.
131.0, 130.3, 130.1, 129.0, 128.6, 128.3, 126.0, 122.2, 110.2, 101.8, 73.9,
73.7, 59.1, 49.1, 27.6, 25.1, 23.8. Anal. Calcd for C21H21N3O3: C, 69.41; H,
5.82; N, 11.56. Found: C, 69.56; H, 5.75; N, 11.61.
6.1.5. 1-Benzyl-10-nitro-20-phenyl-10,20,50,60,70,7a0-hexahydrospiro[in-
6.2.2. 5-Bromo-10-methyl-10-nitro-20-phenyl-10,20,50,60,70,7a0-hexahy-
drospiro[indoline-3,30-pyrrolizin]-2-one (7b). Cream solid (0.05 g,
11%), mp: 168e169 ꢁC; Rf (50% ethyl acetate/hexane) 0.35; IR (KBr,
doline-3,30-pyrrolizin]-2-ꢀon1 e (4e). Cream solid (0.35 g, 79%), mp:
205e207 ꢁC; IR (KBr, cm
)
n
¼1719, 1543, 1372; 1H NMR (300 MHz,
CDCl3):
d
¼7.66 (d, 1H, J¼7.4 Hz, AreH), 7.06e7.24 (m, 10H, AreH),
cmꢀ1
)
n
¼3214, 1719, 1554, 1361; 1H NMR (400 MHz, DMSO-d6):
6.40e6.54 (m, 3H, AreH, 1H, CHNO2), 5.12 (AB quartet, 1H,
J¼16.1 Hz, NeCHAHB), 4.99 (q, 1H, J¼8.2 Hz, NeCH), 4.66 (d, 1H,
d
¼10.8 (s, 1H, NH), 7.84 (d, 1H, J¼2 Hz, AreH), 7.38(dd, 1H, J¼8.0,
2 Hz, AreH), 7.24 (m, 3H, AreH), 7.15 (m, 2H, AreH), 6.69 (d, 1H,

1596
K. Alimohammadi et al. / Tetrahedron 67 (2011) 1589e1597
J¼8.4 Hz, AreH), 5.22 (s, 1H, benzylic), 4.32 (dd, 1H, J¼8.0, 6 Hz,
NeCH), 1.67e3.32 (m, 4H), 1.74 (s, 3H, CH3NO2),1.23e1.70 (m, 2H,
benzylic), 4.18 (br s, 1H, NeCH), 2.40 (br s, 2H, pyrrolizine), 1.85 (br
s, 2H, pyrrolizine), 1.72 (br s, 3H, CH3NO2, 2H, pyrrolizine); 13C NMR
pyrrolizine); 13C NMR (100 MHz, DMSO-d6):
d¼178.0, 142.4, 133.2,
(125 MHz, DMSO-d6):
d
¼176.5, 142.8, 135.5, 134.1, 131.5, 129.6,
133.1, 130.1, 129.1, 128.8, 128.4, 126.1, 114.0, 112.2, 101.3, 74.0, 73.7,
59.0, 48.9, 27.6, 25.1, 23.8. Anal. Calcd for C21H20BrN3O3: C, 57.02; H,
4.56; N, 9.50. Found: C, 56.91; H, 4.42; N, 9.58.
128.9, 128.5, 127.7, 114.2, 112.8, 102.6, 76.5, 67.4, 55.4, 48.0, 31.4,
28.3, 20.1. Anal. Calcd for C21H20BrN3O3: C, 57.02; H, 4.56; N, 9.50.
Found: C, 57.21; H, 4.47; N, 9.41.
6.2.3. 1,10-Dimethyl-10-nitro-20-phenyl-10,20,50,60,70,7a0-hexahy-
drospiro[indoline-3,30-pyrrolizin]-2-one (7d). Cream solid (0.05 g,
14%), mp: 168e170 ꢁC; Rf (50% ethyl acetate/hexane) 0.40; IR (KBr,
6.2.8. 20-Methyl-20,5-dinitro-10-phenyl-10,20,50,60,70,7a0-hexahy-
drospiro[indoline-3,30-pyrrolizin]-2-ꢀon1e (8c). Yellow solid (0.34 g,
84%), mp: 186e188 ꢁC; IR (KBr, cm
)
n
¼3191, 1737, 1541, 1338; 1
H
cmꢀ1
)
n
¼1724, 1543, 1350; 1H NMR (500 MHz, DMSO-d6):
d
¼7.66
NMR (500 MHz, DMSO-d6):
d
¼11.37 (s, 1H, NH), 8.26 (dd, 1H, J¼9.0,
(d, 1H, J¼7.5 Hz, AreH), 7.29 (t, 1H, J¼7.7 Hz, AreH), 7.19 (m, 3H,
AreH), 7.05 (m, 3H, AreH), 6.91 (d, 1H, J¼7.8 Hz, AreH), 5.26 (s, 1H,
benzylic), 4.36 (dd, 1H, J¼8.0, 5.6 Hz, NeCH), 3.29 (m, 2H, pyrroli-
zine), 3.10 (s, 3H, NeCH3), 1.84e2.19 (m, 2H, pyrrolizine), 1.76 (s, 3H
CH3NO2), 1.23e1.74 (m, 2H, pyrrolizine); 13C NMR (125 MHz,
2.0 Hz, AreH), 8.20 (d, 1H, J¼1.5 Hz, AreH), 7.57 (d, 1H, J¼7.5 Hz,
AreH), 7.30e7.38 (m, 3H, AreH), 7.05 (d, 1H, J¼8.6 Hz, AreH), 4.37
(d, 1H, J¼10.2 Hz, benzylic), 4.26 (m, 1H, NeCH),1.80e2.57 (m, 5H,
pyrrolizine), 1.73 (s, 3H, CH3NO2),1.67 (m, 1H, pyrrolizine); 13C NMR
(125 MHz, DMSO-d6):
d
¼177.3, 149.9, 142.9, 135.0, 131.4, 129.1,
DMSO-d6):
d
¼176.9, 144.8, 133.6, 130.8, 130.4, 129.5, 128.8, 126.3,
128.7,128.5,126.0,122.2,111.3,102.9, 76.2, 67.4, 55.9, 47.9, 31.7, 28.3,
20.0. Anal. Calcd for C21H20N4O5: C, 61.76; H, 4.94; N, 13.72. Found:
C, 61.93; H, 4.81; N, 13.58.
126.1, 123.4, 109.7, 102.2, 74.2, 74.0, 59.6, 49.7, 28.1, 26.7, 25.6, 24.2.
Anal. Calcd for C22H23N3O3: C, 70.01; H, 6.14; N, 11.13. Found: C,
70.14; H, 6.19; N, 11.22.
6.2.9. 1,20-Dimethyl-20-nitro-10-phenyl-10,20,50,60,70,7a0-hexahy-
6.2.4. 1-Benzyl-10-methyl-10-nitro-20-phenyl-10,20,50,60,70,7a0-hexahy-
drospiro[indoline-3,30-pyrrolizin]-2-ꢀo1ne (8d). Cream solid (0.28 g,
drospiro[indoline-3,30-pyrrolizin]-2-one
(exo-7e). White
solid
74%), mp: 173e175 ꢁC; IR (KBr, cm
)
n
¼1711, 1534, 1352; 1H NMR
(0.13 g, 30%), mp: 149e151 ꢁC; Rf (25% ethyl acetate/hexane) 0.72;
(500 MHz, DMSO-d6):
d
¼7.60 (t, 3H, J¼7.0 Hz, AreH), 7.29e7.39 (m,
IR (KBr, cmꢀ1
)
n
¼1715, 1534, 1358; 1H NMR (400 MHz, DMSO-d6):
4H, AreH), 7.08 (t, 1H, J¼7.5 Hz, AreH), 7.02 (d, 1H, J¼7.8 Hz, AreH),
4.41 (d, 1H, J¼10.2 Hz, benzylic), 4.22 (m, 1H, NeCH), 3.16 (s, 3H,
NeCH3), 1.76e2.50 (m, 5H, pyrrolizine), 1.74 (s, 3H, CH3NO2),1.68
d¼7.69 (d, 1H, J¼7.2 Hz, AreH), 7.02e7.33 (m, 12H, AreH), 6.84 (d,
1H, J¼8.0 Hz, AreH), 5.3 (s, 1H, benzylic), 4.98 (AB quartet, 1H,
J¼15.6 Hz, NeCHAHB), 4.79 (AB quartet, 1H, J¼15.6 Hz, NeCHAHB),
4.40 (dd, 1H, J¼8.0, 6.0 Hz, NeCH), 1.87e3.28 (m, 4H, pyrrolizine),
1.82 (s, 3H, CH3NO2),1.24e1.77 (m, 2H, pyrrolizine); 13C NMR
(m, 1H, pyrrolizine); 13C NMR (125 MHz, DMSO-d6):
d¼175.2, 144.8,
135.6, 131.5, 131.2, 129.0, 128.5, 127.0, 124.5, 122.9, 109.8, 102.3, 76.3,
67.5, 55.6, 48.0, 31.6, 28.3, 27.3, 20.1. Anal. Calcd for C22H23N3O3: C,
70.01; H, 6.14; N, 11.13. Found: C, 70.13; H, 6.29; N, 11.22.
(100 MHz, DMSO-d6):
d
¼176.5, 143.6, 136.3, 133.0, 130.4, 129.1,
129.0, 128.4, 127.9, 127.8, 125.9, 123.1, 109.9, 101.5, 73.9, 73.8, 59.2,
49.1, 43.2, 27.7, 25.1, 23.9. Anal. Calcd for C28H27N3O3: C, 74.15; H,
6.00; N, 9.27. Found: C, 74.01; H, 5.89; N, 9.35.
6.2.10. 1-Benzyl-20-methyl-20-nitro-10-phenyl-10,20,50,60,70,7a0-hex-
ahydrospiro[indoline-3,30-pyrrolizin]-2-one
(8e). Yellow
solid
(0.17 g, 38%), mp: 85e87 ꢁC; IR (KBr, cmꢀ1
)
n
¼1715, 1534, 1364; 1H
6.2.5. 1-Benzyl-10-methyl-10-nitro-20-phenyl-10,20,50,60,70,7a0-hexahy-
drospiro[indoline-3,30-pyrrolizin]-2-one (endo-7e). Cream solid
(0.07 g, 15%), mp: 185e187 ꢁC; Rf (25% ethyl acetate/hexane) 0.38;
NMR (400 MHz, DMSO-d6):
d
¼7.63 (m, 3H, AreH), 7.26e7.40 (m, 9H,
AreH), 7.07 (t,1H, J¼7.2 Hz, AreH), 6.86 (d,1H, J¼7.6 Hz, AreH), 5.02
(AB quartet,1H, J¼16 Hz, NeCHAHB), 4.89 (AB quartet,1H, J¼15.6 Hz,
NeCHAHB), 4.46 (d, 1H, J¼10.4 Hz, benzylic), 4.23 (m, 1H, NeCH),
1.86e2.52 (m, 4H, pyrrolizine), 1.83 (s, 3H, CH3NO2),1.73 (m, 2H,
IR (KBr, cmꢀ1
)
n
¼1709, 1539, 1347; 1H NMR (400 MHz, DMSO-d6):
d¼7.60 (d, 1H, J¼7.2 Hz, AreH), 7.03e7.27 (m, 12H, AreH), 6.64 (d,
1H, J¼7.2 Hz, AreH), 4.92 (s, 1H, benzylic), 4.83 (AB quartet, 1H,
J¼15.6 Hz, NeCHAHB), 4.76 (AB quartet, 1H, J¼15.6 Hz, NeCHAHB),
4.45 (dd, 1H, J¼9.6, 6.0 Hz, NeCH), 2.03e2.63 (m, 4H, pyrrolizine),
1.98 (s, 3H, CH3NO2), 1.81e1.96 (m, 2H, pyrrolizine); 13C NMR
pyrrolizine); 13C NMR (100 MHz, DMSO-d6):
d¼175.2, 143.4, 136.5,
135.1, 131.2, 130.7, 129.1, 128.6, 128.2, 127.9, 127.4, 126.8, 124.3, 122.6,
110.1, 101.8, 75.8, 67.2, 55.2, 47.5, 43.5, 31.2, 27.9, 19.9. Anal. Calcd for
C28H27N3O3: C, 74.15; H, 6.00; N, 9.27. Found: C, 74.01; H, 6.17; N, 9.20.
(100 MHz, DMSO-d6):
d
¼176.5, 142.3, 136.2, 132.1, 131.0, 130.3,
129.6, 129.0, 128.7, 128.6, 127.8, 127.7, 124.2, 123.7, 109.6, 96.1, 76.3,
73.5, 65.3, 46.8, 43.4, 27.7, 27.6, 19.9. Anal. Calcd for C28H27N3O3: C,
74.15; H, 6.00; N, 9.27. Found: C, 74.09; H, 6.05; N, 9.24.
Acknowledgements
The authors acknowledge the University of Mazandaran for
financial support of this research.
6.2.6. 20-Methyl-20-nitro-10-phenyl-10,20,50,60,70,7a0-hexahydrospiro
[indoline-3,30-pyrrolizin]-2-one (8a). White solid (0.27 g, 76%), mp:
Supplementary data
196e198 ꢁC; IR (KBr, cmꢀ1
)
n
¼3246, 1732, 1547, 1352; 1H NMR
(500 MHz, DMSO-d6):
d
¼10.54(s,1H,NH),7.54(d, 2H, J¼7.6 Hz, AreH),
Experimental procedure, copies of 1H and 13C NMR spectra for
all compounds, X-ray crystallographic data, Cartesian coordinates,
total energy, and number of imaginary frequencies. Supplementary
data associated with this article can be found in online version at
doi:10.1016/j.tet.2010.12.034.
7.53 (d, 1H, J¼7.6 Hz, AreH), 7.25e7.37 (m, 4H, AreH), 7.00 (t, 1H,
J¼7.6 Hz, AreH), 6.81 (d, 1H, J¼7.7 Hz, AreH), 4.39 (d, 1H, J¼10.2 Hz,
benzylic), 4.18 (m,1H, NeCH),1.74e2.50 (m, 5H, pyrrolizine),1.74 (s, 3H,
CH3NO2),1.66 (m, 1H); 13C NMR (125 MHz, DMSO-d6):
d¼176.9, 143.5,
135.6,131.5,131.1,129.0,128.5,127.4,125.2,122.2,110.9,102.3, 76.4, 67.5,
55.6, 47.9, 31.7, 28.3, 20.0. Anal. Calcd for C21H21N3O3: C, 69.41; H, 5.82;
N, 11.56. Found: C, 69.54; H, 5.68; N, 11.64.
References and notes
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